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15546518 | [Study of predictive factors of severe digestive lesions due to caustics ingestion]. | Our purpose was to analyze the predictive factors of severe upper gastrointestinal injury by caustic substances in adult patients. Retrospective study between February 1995 and February 2001 of adult patients who underwent an urgent upper endoscopy due to caustic ingestion. Endoscopic caustic ingestion criteria by Zargar et al were used to determine the degree of injury. We performed a univariate study of factors associated with sever digestive injury and, lately, a logistic regression analysis of predictive factors. Sensitivity, specificity, positive and negative predictive values of these factors were calculated. One hundred and fifty nine patients were included in the study, whose mean age was 48.9 (20.1) years and 49.7% were men. The more frequent caustic ingested was lye (47.8%). A severe caustic injury was found in urgent upper endoscopy in 18.4% of patients, which was located in esophagus in 14.6%, stomach in 8.2% and duodenum in 0.6% of cases. Male sex, voluntary ingestion, oropharingeal lesions, significant clinical symptoms and dishwasher and detergents ingestion were associated with severe upper gastrointestinal tract (GIT) injury. Voluntary ingestion, oropharingeal lesions and significant clinical symptoms at admission were independent predictive factors of severe GIT injury. The existence of one of these factors had an 89.7% of sensitivity while two or more displayed a specificity of 91%. Clinical and exploratory data may determine, before upper endoscopic procedure, the probability of severe GIT injury by caustic ingestion. Therefore, these data could play a significant role in the diagnostic, prognostic and therapeutic management of caustic ingestion. |
15546517 | [Physical activity and quality of life in older adults in Spain]. | This study examined the relationship between leisure-time physical activity (LTPA) and health-related quality of life (HRQL) in the older adult population of Spain. Household cross-sectional survey on 3,066 subjects representatives of the non-institutionalized Spanish population aged 60 years and over. Data on LTPA was obtained with a structured questionnaire and HRQL was measured with the SF-36 instrument. Analyses were done through linear regression, where the dependent variable was each of the eight scales of the SF-36 and the main independent variable was LTPA. Analyses were adjusted for sociodemographic and social network variables, health habits, health services use, and chronic diseases. A total of 42.7% subjects had a sedentary activity, 54.2% light LTPA and 3% moderate/intense LTPA. As compared with sedentary activity, light LTPA was associated with a higher score in all SF-36 scales, except for the physical role and emotional role, among men and women. For subjects with light LTPA the increase in score was over 3 points in most SF-scales, which is usually considered as a clinically relevant change in HRQL. Results did not vary materially by age, level of education, obesity or chronic disease. The higher LTPA, the better HRQL (p for linear trend < 0.05 in most scales of the SF-36 questionnaire). Light LTPA is associated with better HRQL than sedentary activity. Because this association did not change with age, level of education, obesity or chronic disease, it is suggested that most older adults could improve their HRQL with, at least, a light LTPA. |
15546515 | Virtual outreach: a randomised controlled trial and economic evaluation of joint teleconferenced medical consultations. | To test the hypotheses that virtual outreach would reduce offers of hospital follow-up appointments and reduce numbers of medical interventions and investigations, reduce numbers of contacts with the health care system, have a positive impact on patient satisfaction and enablement, and lead to improvements in patient health status. To perform an economic evaluation of virtual outreach. A randomised controlled trial comparing joint teleconsultations between GPs, specialists and patients with standard outpatient referral. It was accompanied by an economic evaluation. The trial was centred on the Royal Free Hampstead NHS Trust, London, and the Royal Shrewsbury Hospital Trust in Shropshire. The project teams recruited and trained a total of 134 GPs from 29 practices and 20 consultant specialists. In total, 3170 patients were referred, of whom 2094 consented to participate in the study and were eligible for inclusion. In all, 1051 patients were randomised to the virtual outreach group and 1043 to standard outpatient appointments. The patients were followed 6 months after their index consultation. Patients randomised to virtual outreach underwent a joint teleconsultation, in which they attended the general practice surgery where they and their GP consulted with a hospital specialist via a videolink between the hospital and the practice. Outcome measures included offers of follow-up outpatient appointments, numbers of tests, investigations, procedures, treatments and contacts with primary and secondary care, patient satisfaction (Ware Specific Visit Questionnaire), enablement (Patient Enablement Instrument) and quality of life (Short Form-12 and Child Health Questionnaire). An economic evaluation of the costs and consequences of the intervention was undertaken. Sensitivity analysis was used to test the robustness of the results. Patients in the virtual outreach group were more likely to be offered a follow-up appointment. Significant differences in effects were observed between the two sites and across different specialities. Virtual outreach increased the offers of follow-up appointments more in Shrewsbury than in London, and more in ENT and orthopaedics than in the other specialities. Fewer tests and investigations were ordered in the virtual outreach group, by an average of 0.79 per patient. In the 6-month period following the index consultation, there were no significant differences overall in number of contacts with general practice, outpatient visits, accident and emergency contacts, inpatient stays, day surgery and inpatient procedures or prescriptions between the randomised groups. Tests of interaction indicated that virtual outreach decreased the number of tests and investigations, particularly in patients referred to gastroenterology, and increased the number of outpatient visits, particularly in those referred to orthopaedics. Patient satisfaction was greater after a virtual outreach consultation than after a standard outpatient consultation, with no heterogeneity between specialities or sites. However, patient enablement after the index consultation, and the physical and psychological scores of the Short Form-12 for adults and the scores on the Child Health Questionnaire for children under 16, did not differ between the randomised groups at 6 months' follow-up. NHS costs over 6 months were greater for the virtual outreach consultations than for conventional outpatients, pound 724 and pound 625 per patient, respectively. The index consultation accounted for this excess. Cost and time savings to patients were found. Estimated productivity losses were also less in the virtual outreach group. Virtual outreach consultations result in significantly higher levels of patient satisfaction than standard outpatient appointments and lead to substantial reductions in numbers of tests and investigations, but they are variably associated with increased rates of offer of follow-up according to speciality and site. Changes in costs and technological advances may improve the relative position of virtual consultations in future. The extent to which virtual outreach is implemented will probably be dependent on factors such as patient demand, costs, and the attitudes of staff working in general practice and hospital settings. Further research could involve long-term follow-up of patients in the virtual outreach trial to determine downstream outcomes and costs; further study into the effectiveness and costs of virtual outreach used for follow-up appointments, rather than first-time referrals; and whether the costs of virtual outreach could be substantially reduced without adversely affecting the quality of the consultation if nurses or other members of the primary care team were to undertake the hosting of the joint teleconsultations in place of the GP. Qualitative work into the attitudes of the patients, GPs and hospital specialists would also be valuable. |
15546516 | [Impact of metabolic syndrome in the control of blood pressure and dyslipemia]. | The objective of the study was to assess the influence of metabolic syndrome (MS) in the control of blood pressure (BP) and dyslipemia. A cross sectional study was performed with 1,320 (634 M and 686 F), 40.1 (13.3) years-old, BMI 29.8 (4.7) hypertensive non-diabetic patients. MS was diagnosed according to NCEP-ATP-III guidelines. Blood pressure control goal was BP < 140/90 mmHg. Coronary risk (CR) was calculated according to Framingham (low < 10%, intermediate 10-20% and high > 20% at 10 years). Goals of C-LDL levels were those of NCEP-ATP-III. 461 (35%) patients had MS and the remaining 859 became controls. Patients with MS had higher initial levels of hypertension and were receiving more antihypertensive drugs: 2.1 [1.3] vs. 1.7 [1.3]; p < 0.001), yet the average systolic and diastolic BP achieved and the degree of control was similar in both groups 53% vs. 52%; (p = ns). Patients with MS had higher CR at ten years than controls (10.7 [8.3] vs. 7.9 [6.8], p < 0.001) but achieved the C-LDL goals at fewer proportions than controls (57% vs. 74%; p < 0.001). In a regression analysis, patients with MS had 26% less probabilities of achieving both goals (p < 0.001). Hypertensive patients with MS have higher CR, and need more antihypertensive drugs to achieve the same BP goals. Yet it is more difficult for them to achieve LDL cholesterol goals. Patients with MS remain a target for cardiovascular prevention. |
15546510 | Immunity against mouse thymus-leukemia antigen (TL) protects against development of lymphomas induced by a chemical carcinogen, N-butyl-N-nitrosourea. | Mouse thymus-leukemia antigens (TL) are aberrantly expressed on T lymphomas in C57BL/6 (B6) and C3H/He (C3H) mice, while they are not expressed on normal T lymphocytes in these strains. When N-butyl-N-nitrosourea (NBU), a chemical carcinogen, was administered orally to B6 and C3H strains, lymphoma development was slower than in T3(b)-TL gene-transduced counterpart strains expressing TL ubiquitously as self-antigens, suggesting that anti-TL immunity may play a protective role. In addition, the development of lymphomas was slightly slower in C3H than in B6, which seems to be in accordance with the results of skin graft experiments indicating that both cellular and humoral immunities against TL were stronger in C3H than B6 mice. The interesting finding that B lymphomas derived from a T3(b)-TL transgenic strain (C3H background) expressing a very high level of TL were rejected in C3H, but not in H-2K(b) transgenic mice (C3H background), raises the possibility that TL-specific effector T cell populations are eliminated and/or energized to a certain extent by interacting with H-2K(b) molecules. |
15546509 | Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and colorectal cancer: the Fukuoka Colorectal Cancer Study. | Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating folate metabolism, which affects DNA synthesis and methylation. This study investigated the relation of MTHFR C677T and A1298C polymorphisms to colorectal cancer in a case-control study in Fukuoka, Japan. The subjects comprised 685 incident cases of histologically confirmed colorectal adenocarcinomas and 778 community controls selected randomly in the study area. The genotype was determined by the PCR-RFLP method using genomic DNA extracted from buffy coat. Alcohol use was ascertained by in-person interview. Statistical adjustment was made for gender, age class, area, and alcohol use. The MTHFR 677TT genotype was associated with a statistically significant decrease in the risk with an adjusted odds ratio of 0.69 (95% confidence interval 0.51-0.93) compared with the 677CC and 677CT combined, and the decrease was most evident in individuals with no alcohol consumption. While the A1298C polymorphism showed no measurable association with the overall risk of colorectal cancer, the 1298CC genotype was associated with a statistically significant increase in the risk when alcohol consumption was high, and was also associated with an approximately 2-fold increase in the risk of each of proximal and distal colon cancer. The findings add to evidence that individuals with the MTHFR 677TT genotype have a decreased risk of colorectal cancer in the absence of folate depletion, suggesting a protective role of folate by ensuring a sufficient thymidylate pool for DNA synthesis. Because very few individuals had the 1298CC genotype, the findings regarding the A1298C polymorphism need careful interpretation and confirmation in larger studies. |
15546508 | Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. | We determined the effects of several non-steroidal anti-inflammatory drugs (NSAIDs), aspirin (acetylsalicylic acid, ASA), indomethacin and a cyclooxygenase-2 (COX-2)-selective inhibitor (NS398), on cellular proliferation and regulation of COX-2 protein expression in endometrial cancer cells in vitro, and investigated their modes of action. All three NSAIDs markedly inhibited the proliferation of Ishikawa, HEC-1A and AN3CA endometrial cancer cell lines in a time- and concentration-dependent manner. ASA and indomethacin triggered apoptosis in cells of all three lines through release of cytosolic cytochrome c, activation of caspase-9 and-3, and cleavage of poly(ADP-ribose) polymerase (PARP), but NS398 induced minimal apoptosis only in Ishikawa cells. ASA altered the cell cycle distribution, with G2/M phase accumulation of cells, and induced overexpression of Ki-67 protein. Both ASA and indomethacin reduced the protein levels of Bcl-2 and Bcl-xl, but upregulated those of Bax and Bcl-xs. COX-2 protein expression and PGE(2) production were upregulated by ASA and indomethacin in all three cell lines. However, NS398 did not alter COX-2 protein expression or PGE(2) production in these cells. These results indicate that NSAIDs inhibit proliferation of endometrial cancer cells independently of the reduction of COX-2 protein expression. A cytochrome c-dependent apoptotic pathway and/or cell cycle arrest may contribute to the inhibitory effects of these NSAIDs. |
15546507 | Novel models for human scirrhous gastric carcinoma in vivo. | Human scirrhous gastric carcinoma, a diffusely infiltrating type of poorly differentiated gastric carcinoma also known as linitis plastica type carcinoma, is characterized by cancer cell infiltration and proliferation accompanied with extensive stromal fibrosis. We established two new gastric cancer cell lines, designated OUCM-8 and OCUM-11, which developed the characteristic biology of scirrhous gastric carcinoma upon orthotopic implantation in mice. Involvement of lymph nodes and liver metastasis was also found in both orthotopic models. Histologically, these orthotopic models showed proliferation with extensive fibrosis, resembling human scirrhous gastric cancer. Both cell lines were derived from ascites of patients with scirrhous gastric cancer. The growth of OCUM-8 and OCUM-11 cells following the addition of KGF, FGF, and EGF was increased significantly relative to untreated cells. An increase in the number of attached and spreading cells occurred following the addition of TGF-beta 1 in both cell lines. OCUM-11 cells showed microsatellite instability. Although subcutaneous scirrhous gastric cancer cells show medullary growth, most in vivo studies of scirrhous gastric cancer have used xenografted tumors implanted subcutaneously. Only in a few cases was it confirmed that these scirrhous gastric cancer cell lines retained the original histologic characteristics. Our orthotopic models should contribute to the elucidation of disease progression in situ and to the development of therapy for scirrhous gastric cancer. |
15546506 | mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers. | We previously identified 18 genes that correlated with ER positivity by adapter-tagged competitive-PCR analysis of 2412 genes in human breast cancer tissues. The aim of the present study was to determine the prognostic significance of these genes. mRNA expression levels of 12 of the above 18 genes were quantified in breast cancer tissues by real-time PCR assay, and their association with patients' prognosis (n = 110) was studied according to hormone receptor (HR) status. In addition, the genes found to influence prognosis were further investigated to examine whether their mRNA expression could be induced by estrogen in MCF-7 cells in vitro. Of the 12 genes, mRNA expression levels of two [alpha 1-antichymotrypsin (ACT) and stanniocalcin 2 (STC2)] were significantly (P = 0.002 and P = 0.007, respectively) associated with good prognosis in HR-positive (ER and/or PR positive) breast cancer patients treated with adjuvant hormone therapy. Multivariate analysis showed that ACT mRNA level, but not STC2 mRNA level, in HR-positive patients, was a significant prognostic factor (P = 0.042), which was independent of tumor size and lymph node metastases. On the other hand, mRNA expressions of ACT and STC2 were not significantly associated with prognosis in HR-negative patients. Estradiol treatment resulted in a significant increase in the mRNA levels of both ACT and STC2 in MCF-7 cells. The mRNA level of ACT, which is an estrogen-inducible gene, is a significant predictor of good prognosis in HR-positive, but not HR-negative, patients with breast cancers. Since HR-positive patients were treated with adjuvant hormone therapy, we suggest that ACT mRNA level could potentially be used as a predictor of response to hormone therapy, rather than a prognostic factor (predictor of metastatic potential). |
15546505 | Transforming growth factor-beta 1-induced apoptosis is blocked by beta 1-integrin-mediated mitogen-activated protein kinase activation in human hepatoma cells. | Growth factors and extracellular matrices cooperatively regulate cellular behavior. However, the interactions between transforming growth factor-beta 1 (TGF-beta 1) and integrins in hepatic cells are not fully understood. We investigated the effects of beta 1-integrin on TGF-beta 1-regulated growth of hepatoma cells. Human hepatoma cell lines HepG2, Huh7, and Hep3B were stably transfected with beta 1-integrin, and the parental, and mock- and beta 1-integrin-transfected hepatoma cells were treated with TGF-beta 1. Modulation of apoptosis and pathways involved in the process were investigated. TGF-beta 1 suppressed the growth of hepatoma cells, and apoptosis was observed in Hep3B and Huh7. Hepatoma cells transfected with beta 1-integrin were protected from TGF-beta 1-induced apoptosis. Mitogen-activated protein (MAP) kinase inhibitors, PD98059, SB203580, and SP600125, abolished this protective effect of beta 1-integrin, but herbimycin A and wortmannin were ineffective. Hepatoma cells overexpressing beta 1-integrin showed increased activities of MAP kinases, and TGF-beta 1 induced sustained activation of MAP kinases in these cells, but only transient activation in mock-transfected cells. These data suggest that MAP kinases activated by beta 1-integrin provide a strong anti-apoptotic signal during TGF-beta 1-induced apoptosis in human hepatoma cells. Therefore beta 1-integrin-mediated signals may contribute to the development and progression of hepatocellular carcinoma. |
15546504 | Eradication of Helicobacter pylori induces apoptosis and inhibits proliferation of heterotopic proliferative glands in infected Mongolian gerbils. | Mongolian gerbils infected with Helicobacter pylori (H. pylori ) develop heterotopic proliferative glands (HPGs) in the glandular stomach submucosa. To investigate the effects of H. pylori eradication on cell turnover in HPGs, three antibiotics, lansoprazole, amoxicillin and clarithromycin, were administered at 50 or 75 weeks after inoculation of H. pylori, and the stomachs were excised for histological examination at 1, 2, 4, 8 or 25 weeks thereafter. The HPGs were classified into gastric type (G-type) and others (GI + I-type), which included both pure intestinal (I-type) and gastric-and-intestinal mixed type (GI-type). Apoptosis and cell proliferation were evaluated by means of TUNEL assay and BrdU labeling, respectively. At 8 weeks post-eradication, apoptotic indices were significantly increased in the eradication group (G-type: 2.5%; GI + I-type: 7.2%) compared to the non-eradication group (G-type: 0.6%; GI + I-type: 2.1%: P < 0.01), while BrdU labeling indices were significantly decreased (G-type: 1.9%; GI + I-type: 6.8% as compared with 4.3% and 13.2%, respectively, P < 0.01 for both). At 25 weeks, the apoptotic indices were similarly higher [G-type: 0.4 (eradication group) vs. 0.2% (non-eradication group); GI + I-type: 5.8 vs. 1.1%, both P < 0.01], and the BrdU labeling indices (G-type: 0.8 vs. 2.2%, P < 0.01; GI + I-type: 5.1 vs. 11%, P < 0.05) continued to be lower in HPGs. Furthermore, there were highly significant reductions in the areas of HPGs at 8 and 25 weeks post-eradication. These findings demonstrated that eradication results in apoptosis and reduction of proliferation of HPGs in H. pylori-infected gerbils, these lesions thus being apparently reversible through regulation of cell kinetics. |
15546503 | Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. | BRCA1 (BReast-CAncer susceptibility gene 1) and BRCA2 are tumor suppressor genes, the mutant phenotypes of which predispose to breast and ovarian cancers. Intensive research has shown that BRCA proteins are involved in a multitude of pivotal cellular processes. In particular, both genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Recent studies suggest that BRCA proteins are required for maintenance of chromosomal stability, thereby protecting the genome from damage. New data also show that BRCAs transcriptionally regulate some genes involved in DNA repair, the cell cycle, and apoptosis. Many of these functions are mediated by a large number of cellular proteins that interact with BRCAs. The functions of BRCA proteins are also linked to distinct and specific phosphorylation events; however, the extent to which phosphorylation-activated molecular pathways contribute to tumor suppressor activity remains unclear. Finally, the reasons why mutations in BRCA genes lead to the development of breast and ovarian cancers are not clearly understood. Elucidation of the precise molecular functions of BRCAs is expected to improve our understanding of hereditary as well as sporadic mammary carcinogenesis. |
15546502 | Interferon-beta gene therapy for cancer: basic research to clinical application. | Interferon-beta gene therapy for cancer is the first such protocol developed in Japan. Here we describe the development process of our interferon-beta gene therapy from basic research to clinical application. Interestingly, the biological and biochemical characteristics of interferon-beta gene therapy through transfer of the interferon-beta gene into tumor cells by means of cationic liposomes differed from those of conventional interferon-beta protein therapy. Interferon-beta gene transfer could induce apoptosis in interferon-beta protein-resistant tumor cells, such as glioma, melanoma, and renal cell carcinoma. Induction of apoptosis was related to the level of intracellular mRNA of interferon-beta, prolongation of the phosphorylation time of molecules in the interferon-beta signal transduction pathway, such as JAK1, Trk2, and STAT1, and activation of DNase gamma. In our preclinical study we developed lyophilized cationic liposomes containing interferon-beta gene (gene drug) for clinical use and confirmed their safety. Thereafter, we performed a pilot clinical trial in patients with malignant glioma and confirmed the safety and effectiveness of this interferon-beta gene therapy. In this review we also comment on the status of gene therapy regulation in Japan. Interferon-beta gene therapy is expected to become widely available for clinical use in cancer patients, and this new strategy might be extended to molecular targeting therapy, or used in combination with cell therapy or other therapies. |
15546501 | The role of thymidine phosphorylase, an angiogenic enzyme, in tumor progression. | Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF). TP is overexpressed in various tumors and plays an important role in angiogenesis, tumor growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP. A novel, specific TP inhibitor, TPI, inhibits angiogenesis induced by overexpression of TP in KB/TP cells (human KB epidermoid carcinoma cells transfected with TP cDNA), as well as the growth and metastasis of KB/TP cells in vivo. 2-deoxy-D-ribose, the degradation product of thymidine generated by TP activity, has both angiogenic and chemotactic activity. Both 2-deoxy-D-ribose and TP inhibit a hypoxia-induced apoptotic pathway. These findings suggest that 2-deoxy-D-ribose is a downstream mediator of TP function. 2-deoxy-L-ribose, a stereoisomer of 2-deoxy-D-ribose, inhibits the promotion of angiogenesis, tumor growth and metastasis by TP. Although the mechanism of the action of 2-deoxy-D-ribose is still unknown, 2-deoxy-L-ribose may inhibit the physiological activities of 2-deoxy-D-ribose, and consequently those of TP. Inhibition of TP activity and function appears to be a promising approach for the chemotherapy of various tumors. |
15546499 | Young age: an independent risk factor for disease-free survival in women with operable breast cancer. | The incidence of breast cancer in young women (age < 35) is low. The biology of the disease in this age group is poorly understood, and there are conflicting data regarding the prognosis for these women compared to older patients. We retrospectively analyzed 2040 consecutive primary invasive breast cancer patients who underwent surgical procedures at our institution between 1990 and 1999. The younger age group was defined as patients aged <35 years at the time of diagnosis. The clinicopathological characteristics and treatment outcomes were compared between younger and older age groups. A total of 256 (12.5%) patients were aged <35. There was a significantly higher incidence of nuclear grade 3 and medullary histological-type tumors in younger patients compared to older patients. Axillary lymph node status, T stage, histological grade, c-erbB2 expression and estrogen receptor status did not differ significantly between the two age groups. Younger patients had a greater probability of recurrence and death at all time periods. Although there was no significant difference in disease-free survival between the two age groups in lymph node-negative patients, the younger group showed worse prognosis among lymph node-positive patients (p < 0.001). In multivariate analysis, young age remained a significant predictor of recurrence (p = 0.010). Young age (<35) is an independent risk factor for relapse in operable breast cancer patients. |
15546500 | Exposure to juvenile stress exacerbates the behavioural consequences of exposure to stress in the adult rat. | To examine the effects of exposure to post-weaning pre-puberty (juvenile) stress on the emotional and cognitive abilities in response to exposure to stress in adulthood, we first exposed rats to a platform stress at the age of 28 d. Two months later the rats were exposed to acute swim stress. Rats exposed to both stressors showed a higher level of anxiety (as measured both in open-field and startle response tests) than controls or rats exposed to either the juvenile or the adulthood stressor. In the Morris water-maze, rats that were exposed to both juvenile and adulthood stress performed better than the other groups. In a second experiment we verified that the effect of the juvenile stress was indeed age-dependent. One group was exposed at the age of 26-28 d and again at the age of 60 d (juvenile + adulthood stress); the other group was exposed to the first stressor at the age of 60-62 d and to the second at the age of 90 d [adulthood (60) + adulthood (90) stress]. Juvenile + adulthood stress had a significantly greater effect than exposure to stress twice in adulthood, on anxiety level and on the performance in the water-maze. Finally, in a third experiment we found that the juvenile+adulthood stress group swam faster and tended to explore the central area more than the other groups--a finding that could explain their better performance on the first trial of the spatial task. These results indicate that an exposure to a relatively brief juvenile stressful experience has profound and long-lasting effects on the ability to cope with stress in adulthood. |
15546498 | Zinc/copper imbalance reflects immune dysfunction in human leishmaniasis: an ex vivo and in vitro study. | The process of elimination of intracellular pathogens, such as Leishmania, requires a Th1 type immune response, whereas a dominant Th2 response leads to exacerbated disease. Experimental human zinc deficiency decreases Th1 but not Th2 immune response. We investigated if zinc and copper levels differ in different clinical forms of leishmaniasis, and if these trace metals might be involved in the immune response towards the parasite. Blood was collected from 31 patients with either localized cutaneous (LCL), mucosal (ML) or visceral (VL) leishmaniasis, as well as from 25 controls from endemic and non-endemic areas. Anti-Leishmania humoral and cellular immune response were evaluated by quantifying specific plasma IgG, lymphoproliferation and cytokine production, respectively. Plasma levels of Cu and Zn were quantified by atomic absorption spectrophotometry. A significant decrease in plasma Zn was observed in all three patient groups (p < 0.01 for LCL and ML, p < 0.001 for VL), as compared to controls, but only VL (7/10) and ML (1/7) patients displayed overt Zn deficiency. Plasma Cu was increased in LCL and VL (p < 0.001) but not in ML, and was strongly correlated to anti-Leishmania IgG (Spearman r = 0.65, p = 0.0028). Cu/Zn ratios were highest in patients with deficient cellular (VL<<LCL<ML) and exacerbated humoral (VL>LCL>ML) immune response. Ex vivo production of parasite-induced IFN-gamma was negatively correlated to plasma Cu levels in LCL (r = -0.57, p = 0.01). In vitro, increased Cu levels inhibited IFN-gamma production. 1. Zn deficiency in VL and ML indicate possible therapeutic administration of Zn in these severe forms of leishmaniasis. 2. Plasma Cu positively correlates to humoral immune response across patient groups. 3. Environmentally or genetically determined increases in Cu levels might augment susceptibility to infection with intracellular pathogens, by causing a decrease in IFN-gamma production. |
15546497 | Spider silks: recombinant synthesis, assembly, spinning, and engineering of synthetic proteins. | Since thousands of years humans have utilized insect silks for their own benefit and comfort. The most famous example is the use of reeled silkworm silk from Bombyx mori to produce textiles. In contrast, despite the more promising properties of their silk, spiders have not been domesticated for large-scale or even industrial applications, since farming the spiders is not commercially viable due to their highly territorial and cannibalistic nature. Before spider silks can be copied or mimicked, not only the sequence of the underlying proteins but also their functions have to be resolved. Several attempts to recombinantly produce spider silks or spider silk mimics in various expression hosts have been reported previously. A new protein engineering approach, which combines synthetic repetitive silk sequences with authentic silk domains, reveals proteins that closely resemble silk proteins and that can be produced at high yields, which provides a basis for cost-efficient large scale production of spider silk-like proteins. |
15546496 | The use of microbubbles to target drug delivery. | Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed. |
15546495 | Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats. | Reserpine, an alkaloid from Rauwolfia serpentina was widely used for its antihypertensive action in the past. In later years, its use has been reduced because of precipitation of depression and extra pyramidal symptoms due to its central action. In the present investigation, reserpine methonitrate (RMN), a novel quaternary analogue of reserpine was synthesised and evaluated biochemically for its central and peripheral amine depleting actions in rats while its influence on the blood pressure was measured in anaesthetized rats in comparison with reserpine Reserpine treatment (5 mg/kg) produced a significant increase in the urinary excretion of VMA, 5-HIAA and HVA while RMN at doses of equal to and double the equimolar doses of reserpine (5 and 10 mg/kg) produced significant increase in VMA and 5-HIAA excretion without producing any effect on HVA excretion compared to control animals. Reserpine in the dose range of 0.5 to 15 microg/kg produced significant reduction in blood pressure compared to control. RMN was also found to produce significant decrease in blood pressure at doses of 10, 25 and 50 microg/kg body weight in comparison to control. The results indicated peripheral depletion of biogenic amines by RMN without affecting the central stores of the amines. The present study clearly indicated that the quaternization of reserpine restricts its transfer across the blood-brain barrier and could be the reason for its selective peripheral action. It is also clear that the hypotensive actions of RMN could be due to peripheral depletion of catecholamines. |
15546494 | Myasthenia gravis and pregnancy: clinical implications and neonatal outcome. | The myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients. To describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome. From January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean +/- SD maternal age was 27.4 +/- 4.0 years. During pregnancy 2 women (11%) had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39%) had clinical worsening of the condition of 9 other patients (50%) remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean +/- SD gestational age of 37.5 +/- 3.0 weeks and a mean birth weight of 2710 +/- 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns. The clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population. |
15546492 | Metabolic scaling: consensus or controversy? | The relationship between body mass (M) and standard metabolic rate (B) among living organisms remains controversial, though it is widely accepted that in many cases B is approximately proportional to the three-quarters power of M. The biological significance of the straight-line plots obtained over wide ranges of species when B is plotted against log M remains a matter of debate. In this article we review the values ascribed to the gradients of such graphs (typically 0.75, according to the majority view), and we assess various attempts to explain the allometric power-law phenomenon, placing emphasis on the most recent publications. Although many of the models that have been advanced have significant attractions, none can be accepted without serious reservations, and the possibility that no one model can fit all cases has to be more seriously entertained. |
15546493 | Females do not have more injury road accidents on Friday the 13th. | This study reinvestigated the recent finding that females - but not males - die in traffic accidents on Friday the 13th more often than on other Fridays (Näyhä S: Traffic deaths and superstition on Friday the 13th. Am J Psychiatry 2002, 159: 2110-2111). The current study used matched setting and injury accident data base that is more numerous than fatality data. If such an effect would be caused by impaired psychic and psychomotor functioning due to more frequent anxiety among women, it should also appear in injury crashes. We used the national Finnish road accident database for 1989-2002. To control seasonal variation, 21 Fridays the 13th were compared in a matched design to previous and following Fridays, excluding all holidays, on number of accidents, male/female responsibility for accidents, and the number of dead, injured and overall number of active participants (drivers, pedestrians and bicyclists) as a consequence of the accident. There were no significant differences in any examined aspect of road injury accidents among the three Fridays, either in females or males. Women were not overrepresented in crashes that occurred on Fridays 13th. There is no consistent evidence for females having more road traffic crashes on Fridays the 13th, based on deaths or road accident statistics. However, this does not imply a non-existent effect of superstition related anxiety on accident risk as no exposure-to-risk data are available. People who are anxious of "Black Friday" may stay home, or at least avoid driving a car. |
15546491 | Application of methods of identifying receptor binding models and analysis of parameters. | Possible methods for distinguishing receptor binding models and analysing their parameters are considered. The conjugate gradients method is shown to be optimal for solving problems of the kind considered. Convergence with experimental data is rapidly achieved with the appropriate model but not with alternative models. Lack of convergence using the conjugate gradients method can be taken to indicate inconsistency between the receptor binding model and the experimental data. Thus, the conjugate gradients method can be used to distinguish among receptor binding models. |
15546490 | Size control in growing yeast and mammalian cells. | In a recent publication it was claimed that cultured mammalian cells, in contrast to yeasts, maintain a constant size distribution in the population without a size checkpoint. This inference may be challengeable. (1) It is argued that "weak" size control implies the existence of a checkpoint, and unfortunately the technique used by Conlon and Raff might obscure such a weak mechanism. (2) Previous investigations of size control in yeasts have shown that individual cell data, rather than means and variances of cell populations, are prerequisites for reliable interpretation. (3) No experimental data so far obtained suggest that in any cell culture a linear growth pattern in cell mass can maintain size homeostasis on its own without size control. (4) Studies on fission yeast mutants indicate that the molecular mechanisms of size control vary with genetic background, implying that no single mechanism is likely to apply to any cell type, including cultured mammalian cells, under all conditions. The claim that cultured mammalian cells maintain size homeostasis without a checkpoint needs to be re-evaluated by measurements on individual cells. |
15546489 | beta-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins. | BACKGROUND: Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar beta-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether beta-amyloid altered oxidized lipoprotein clearance via CD36. METHODS: The availability of mice genetically deficient in class A (SRAI & II) and class B (CD36) scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Abeta on: (a) cholesterol ester accumulation by GC-MS and neutral lipid staining, (b) binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c) expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Abeta-CD36 signaling altered metabolism of oxidized lipoproteins. RESULTS: In primary microglia and macrophages, Abeta inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL) in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Abeta were devoid of cholesterol ester. Pretreatment of cells with Abeta did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Abeta did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Abeta inhibited oxidized lipoprotein binding and its subsequent degradation via CD36, but not SRA, and this was independent of Abeta-CD36-signaling. Furthermore, Abeta treatment decreased CD36, but not SRA, mRNA and protein, thereby reducing cell surface expression of this oxLDL receptor. CONCLUSIONS: Together, these data demonstrate that in the presence of beta-amyloid, CD36-mediated clearance of oxidized lipoproteins is abrogated, which would promote the extracellular accumulation of these pro-inflammatory lipids and perpetuate lipid peroxidation. |
15546488 | Treatment decision-making and the form of risk communication: results of a factorial survey. | Prospective users of preventive therapies often must evaluate complex information about therapeutic risks and benefits. The purpose of this study was to evaluate the effect of relative and absolute risk information on patient decision-making in scenarios typical of health information for patients. Factorial experiments within a telephone survey of the Michigan adult, non-institutionalized, English-speaking population. Average interview lasted 23 minutes. Subjects and sample design: 952 randomly selected adults within a random-digit dial sample of Michigan households. Completion rate was 54.3%. When presented hypothetical information regarding additional risks of breast cancer from a medication to prevent a bone disease, respondents reduced their willingness to recommend a female friend take the medication compared to the baseline rate (66.8% = yes). The decrease was significantly greater with relative risk information. Additional benefit information regarding preventing heart disease from the medication increased willingness to recommend the medication to a female friend relative to the baseline scenario, but did not differ between absolute and relative risk formats. When information about both increased risk of breast cancer and reduced risk of heart disease were provided, typical respondents appeared to make rational decisions consistent with Expected Utility Theory, but the information presentation format affected choices. Those 11% - 33% making decisions contrary to the medical indications were more likely to be Hispanic, older, more educated, smokers, and to have children in the home. In scenarios typical of health risk information, relative risk information led respondents to make non-normative decisions that were "corrected" when the frame used absolute risk information. This population sample made generally rational decisions when presented with absolute risk information, even in the context of a telephone interview requiring remembering rates given. The lack of effect of gender and race suggests that a standard strategy of presenting absolute risk information may improve patient decision-making. |
15546487 | Zygapophysial joint blocks in chronic low back pain: a test of Revel's model as a screening test. | Only controlled blocks are capable of confirming the zygapophysial joints (ZJ) as the pain generator in LBP patients. However, previous workers have found that a cluster of clinical signs ("Revel's criteria"), may be valuable in predicting the results of an initial screening ZJ block. It was suggested that these clinical findings are unsuitable for diagnosis, but may be of value in selecting patients for diagnostic blocks of the lumbar ZJ's. To constitute evidence in favour of a clinical management strategy, these results need confirmation. This study evaluates the utility of 'Revel's criteria' as a screening tool for selection of chronic low back pain patients for controlled ZJ diagnostic blocks. This study utilized a prospective blinded concurrent reference standard related validity design. Consecutive chronic LBP patients completed pain drawings, psychosocial distress and disability questionnaires, received a clinical examination and lumbar zygapophysial blocks. Two reference standards were evaluated simultaneously: 1. 75% reduction of pain on a visual analogue scale (replication of previous work), and 2. abolition of the dominant or primary pain. Using "Revel's criteria" as predictors, logistic regression analyses were used to test the model. Estimates of sensitivity, specificity, predictive values and likelihood ratios for selected variables were calculated for the two proposed clinical strategies. Earlier results were not replicated. Sensitivity of "Revel's criteria" was low sensitivity (<17%), and specificity high (approximately 90%). Absence of pain with cough or sneeze just reached significance (p = 0.05) within one model. "Revel's criteria" are unsuitable as a clinical screening test to select chronic LBP patients for initial ZJ blocks. However, the criteria may have use in identifying a small subset (11%) of patients likely to respond to the initial block (specificity 93%). |
15546486 | The rehydration transcriptome of the desiccation-tolerant bryophyte Tortula ruralis: transcript classification and analysis. | The cellular response of plants to water-deficits has both economic and evolutionary importance directly affecting plant productivity in agriculture and plant survival in the natural environment. Genes induced by water-deficit stress have been successfully enumerated in plants that are relatively sensitive to cellular dehydration, however we have little knowledge as to the adaptive role of these genes in establishing tolerance to water loss at the cellular level. Our approach to address this problem has been to investigate the genetic responses of plants that are capable of tolerating extremes of dehydration, in particular the desiccation-tolerant bryophyte, Tortula ruralis. To establish a sound basis for characterizing the Tortula genome in regards to desiccation tolerance, we analyzed 10,368 expressed sequence tags (ESTs) from rehydrated rapid-dried Tortula gametophytes, a stage previously determined to exhibit the maximum stress induced change in gene expression. The 10, 368 ESTs formed 5,563 EST clusters (contig groups representing individual genes) of which 3,321 (59.7%) exhibited similarity to genes present in the public databases and 2,242 were categorized as unknowns based on protein homology scores. The 3,321 clusters were classified by function using the Gene Ontology (GO) hierarchy and the KEGG database. The results indicate that the transcriptome contains a diverse population of transcripts that reflects, as expected, a period of metabolic upheaval in the gametophyte cells. Much of the emphasis within the transcriptome is centered on the protein synthetic machinery, ion and metabolite transport, and membrane biosynthesis and repair. Rehydrating gametophytes also have an abundance of transcripts that code for enzymes involved in oxidative stress metabolism and phosphorylating activities. The functional classifications reflect a remarkable consistency with what we have previously established with regards to the metabolic activities that are important in the recovery of the gametophytes from desiccation. A comparison of the GO distribution of Tortula clusters with an identical analysis of 9,981 clusters from the desiccation sensitive bryophyte species Physcomitrella patens, revealed, and accentuated, the differences between stressed and unstressed transcriptomes. Cross species sequence comparisons indicated that on the whole the Tortula clusters were more closely related to those from Physcomitrella than Arabidopsis (complete genome BLASTx comparison) although because of the differences in the databases there were more high scoring matches to the Arabidopsis sequences. The most abundant transcripts contained within the Tortula ESTs encode Late Embryogenesis Abundant (LEA) proteins that are normally associated with drying plant tissues. This suggests that LEAs may also play a role in recovery from desiccation when water is reintroduced into a dried tissue. The establishment of a rehydration EST collection for Tortula ruralis, an important plant model for plant stress responses and vegetative desiccation tolerance, is an important step in understanding the genome level response to cellular dehydration. The type of transcript analysis performed here has laid the foundation for more detailed functional and genome level analyses of the genes involved in desiccation tolerance in plants. |
15546485 | Laboratory diagnosis and susceptibility profile of Helicobacter pylori infection in the Philippines. | Helicobacter pylori diagnosis and susceptibility profile directs the applicability of recommended treatment regimens in our setting. To our knowledge, there is no published data on the culture and local susceptibility pattern of Helicobacter pylori in the Philippines. 52 dyspeptic adult patients undergoing endoscopy from the Outpatient Gastroenterology clinic of the University of the Philippines-Philippine General Hospital underwent multiple gastric biopsy and specimens were submitted for gram stain, culture, antimicrobial sensitivity testing, rapid urease test and histology. Antimicrobial susceptibility testing was done by Epsilometer testing (Etest) method against metronidazole, clarithromycin, amoxicillin, and tetracycline. Sixty percent (60%) of the study population was positive for H. pylori infection (mean age of 44 years +/- 13), 70% were males. H. pylori culture showed a sensitivity of 45% (95% CI [29.5-62.1]), specificity of 98% (95%CI [81.5-100%]), positive likelihood ratio of 19.93 (95% CI [1.254-317.04]) and a negative likelihood ratio of 0.56 (95% CI [0.406-0.772]). All H. pylori strains isolated were sensitive to metronidazole, clarithromycin, amoxicillin and tetracycline. Knowledge of the antibiotic susceptibility patterns in our setting allows us to be more cautious in the choice of first-line agents. Information on antibiotic susceptibility profile plays an important role in empiric antibiotic treatment and management of refractive cases. |
15546484 | Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy - spatial and time dependent distribution. | Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP) and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous distribution of gene expression in the syngeneic P22 rat tumor model. |
15546483 | A national survey of the prevalence of schistosomiasis and soil transmitted helminths in Malawi. | Past estimates have put the prevalence of schistosomiasis between 40% and 50% in the Malawi population overall based on studies undertaken ten years or more ago. More recent surveys in known high risk areas find similar levels. However control measures, changing ecology and migration may have led to changes in the prevalence of schistosomiasis in different parts of Malawi. A national schistosomiasis and soil-transmitted helminth (STH) survey was undertaken to measure the distribution, prevalence and intensity of infection in November 2002. A school was selected randomly from a random sample of 30 Traditional Authorities stratified by six distinct ecological zones, and 1,664 year 3 pupils (9-10 year olds) were questioned about recent illnesses and "red urine". Samples of urine and faeces were examined for the presence of eggs using the standard Kato-Katz technique for soil-transmitted helminths and intestinal schistosomiasis and urine samples using the filtration technique for Schistosoma haematobium. The prevalence of Schistosoma mansoni is 0.4% (95% CI 0-1.3%), S. haematobium 6.9% (95% CI 1.9 - 11.9%), hookworm 1.3% (95% CI 0.4-2.3%), Ascariasis 0.5% (95% CI 0.1-1.0%) and trichuriasis 0% in year 3 pupils (modal age 10 years of age). Intensity of infection is low for all infections except for 2.5% who have high intensity S. haematobium infection. The "red urine" question is 67% sensitive and 80% specific for positive S. haematobium microscopy. The reduction in prevalences may be real as a result of recent control measures, or false if historical results were based on surveys of high risk populations. Another explanation is that this survey used an unrepresentative sample of schools. Detailed analysis suggests this is unlikely. Recommendations include the use of a 30% positive threshold for the "red urine" screening question to be used in schoolchildren in high prevalence areas. This survey, based on a national probability sample excluding the northern region lakeside area, finds much lower overall prevalence and intensity of schistosomiasis and STHs than previous estimates based on selected surveys. Disease control featuring chemotherapy may be having a profound effect. The localised nature of the distribution of the infections means that control programmes may work best if undertaken at district level or below. "Red urine" questionnaire surveys may help identify hot spots. |
15546482 | The association of patient trust and self-care among patients with diabetes mellitus. | Diabetes requires significant alterations to lifestyle and completion of self management tasks to obtain good control of disease. The objective of this study was to determine if patient trust is associated with reduced difficulty and hassles in altering lifestyle and completing self care tasks. A cross-sectional telephone survey and medical record review was performed to measure patient trust and difficulty in completing diabetes tasks among 320 medically underserved patients attending diabetes programs in rural North Carolina, USA. Diabetes tasks were measured three ways: perceived hassles of diabetic care activities, difficulty in completing diabetes-related care activities, and a global assessment of overall ability to complete diabetes care activities. The association of patient trust with self-management was examined after controlling for patient demographics, physical functioning, mental health and co-morbidities. Level of patient trust was high (median 22, possible max 25). Higher trust levels were associated with lower levels of hassles (p = 0.006) and lower difficulty in completing care activities (p = 0.001). Patients with higher trust had better global assessments of overall ability to complete diabetes care activities (p < 0.0001). Higher patient trust in physicians is associated with reduced difficulty in completing disease specific tasks by patients. Further studies are needed to determine the causal relationship of this association, the effect of trust on other outcomes, and the potential modifiability of trust. |
15546481 | Testicular seminoma after the complete remission of extragonadal yolk sac tumor : a case report. | Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31-42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor. A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma. We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis. |
15546479 | (+) MK-801 and phencyclidine induced neurotoxicity do not cause enduring behaviours resembling the positive and negative symptoms of schizophrenia in the rat. | Studies in rats and primates have demonstrated that repeated phencyclidine treatment can produce enduring cognitive deficits that may resemble the cognitive deficits seen in schizophrenia, suggesting that neurodegeneration resulting from NMDA-receptor dysfunction may be a valid model of schizophrenia. The purpose of the present experiments was to expand these findings and to determine if medium and high doses of the NMDA-antagonists phencyclidine and (+)MK-801 could produce permanent behavioural changes in animal tests with face validity for some aspects of the positive and negative symptoms of schizophrenia. Rats were treated with dose regimens of (+)MK-801 and phencyclidine known to produce mild and severe irreversible levels of neurotoxicity, and were tested 7 or 10 days after the last drug administration in the social interaction test and in standard activity cages. The rats did not show any enduring behavioural changes as a result of the treatment. The present study could therefore not provide additional evidence for the face validity of this model of schizophrenia. |
15546478 | Effects of anticancer chemotherapeutic drugs on the acetylcholine receptor-operated potassium current in guinea pig atrial myocytes. | The effects of 7 anticancer chemotherapeutic drugs on the muscarinic acetylcholine receptor-operated potassium current (I(K.ACh)) in guinea pig atrial myocytes were investigated using the whole cell patch clamp technique. Doxorubicin, pirarubicin, and mitoxantrone inhibited the carbachol-induced I(K.ACh) in a concentration-dependent manner in atrial cells at a holding potential of -40 mV. IC50 values of doxorubicin, pirarubicin, and mitoxantrone for the carbachol-induced I(K.ACh) were 7.7 microM, 3.7 microM, and 9.1 microM, respectively. Pirarubicin inhibited the adenosine-induced and the GTPgammaS-induced I(K.ACh) in a concentration-dependent manner (IC50=6.0 and 5.1 microM, respectively). Doxorubicin and mitoxantrone up to 100 microM did not have an influence on the adenosine-induced I(K.ACh). Doxorubicin did not affect the GTPgammaS-induced I(K.ACh). Mitoxantrone 100 microM inhibited the current only by 25%. For concentrations up to 100 microM, anticancer drugs that have chemical structures entirely different from that of doxorubicin, i.e., 5-fluorouracil, 6-mercaptopurine, cyclophosphamide, and actinomycin D, did not have an influence on the carbachol-induced I(K.ACh). Doxorubicin and chemically related compounds possess anticholinergic effects mediated via an inhibitory action on I(K.ACh) by different underlying molecular mechanisms. Doxorubicin and mitoxantrone may inhibit I(K.ACh) by the blockade of muscarinic receptors, whereas pirarubicin may inhibit the current not only via blocking the muscarinic receptors but also by depressing the functions of the K+ channel itself and/or GTP-binding proteins. |
15546477 | Inhibitory action of ethanol on cyclooxygenase-2 expression through suppression of the extracellular signal-related kinase-mediated pathway in rat alveolar macrophages. | The purpose of the present study was to elucidate the effects of ethanol on expression of cyclooxygenase in alveolar macrophages. Rat alveolar macrophages were collected by bronchoalveolar lavage and stimulated by lipopolysaccharide. Lipopolysaccharide-induced cyclooxygenase-2 expression and prostaglandin E2 production were inhibited by ethanol (100-200 mM) in a concentration-dependent manner. Ethanol at 100-200 mM concentration-dependently inhibited cyclooxygenase-2 mRNA expression. Lipopolysaccharide-stimulated phosphorylation of both extracellular signal-related kinase and p38 mitogen-activated protein kinase was also significantly inhibited by ethanol (50-200 mM). Cyclooxygenase-2 expression was significantly inhibited by U0126 but was not affected by SB203580. In the presence of SB203580, lipopolysaccharide-induced cyclooxygenase-2 expression was also inhibited by ethanol (50-200 mM). On the other hand, cyclooxygenase-1 was expressed constitutively in alveolar macrophages and cyclooxygenase-1 expression was affected neither by lipopolysaccharide nor ethanol. Lipopolysaccharide-induced expression of inducible nitric oxide synthase in alveolar macrophages was not affected by ethanol at 50-200 mM. These results suggest that lipopolysaccharide-induced expression of cyclooxygenase-2 is mediated by extracellular signal-related kinase but not by p38 kinase and that ethanol selectively attenuates cyclooxygenase-2 expression mainly by inhibiting activation of extracellular signal-related kinase. |
15546476 | Effect of Hibiscus rosa sinensis extract on hyperproliferation and oxidative damage caused by benzoyl peroxide and ultraviolet radiations in mouse skin. | The present study was conducted to investigate the ameliorative potential of Hibiscus rosa sinensis extract in mice skin. Combination of a single topical application of benzoyl peroxide (20 mg/0.2 ml/animal) followed by ultraviolet radiations (0.420 J/m2/s) was used to induce hyperproliferation and oxidative stress. Single benzoyl peroxide application prior to ultraviolet B radiations exposure caused significant depletion in the detoxification and antioxidant enzymes, while malondialdehyde formation, hydrogen peroxide content, ornithine decarboxylase activity and DNA synthesis were raised significantly. However, pretreatment of H. rosa sinensis extract (3.5 mg and 7 mg/ kg b.wt.) partly restored the levels of cellular protective enzymes (P<0.05). Besides, malondialdehyde formation and hydrogen peroxide content (P<0.05) were statistically significantly reduced at both doses. The ornithine decarboxylase activity and thymidine incorporation in DNA were also reduced dose dependently (P<0.05) by the plant extract. Therefore, we propose that H. rosa sinensis extract exerts a protective effect against the tumour promotion stage of cancer development. |
15546475 | Inhibition of the protease activity of the light chain of type A botulinum neurotoxin by aqueous extract from stinging nettle (Urtica dioica) leaf. | We investigated the inhibitory effect of stinging nettle leaf extract on the protease activity of botulinum neurotoxin type A and B light chains. The nettle leaf infusion was fractionated and HPLC-based enzymatic assays were performed to determine the capacity of each fraction to inhibit the protease activity of botulinum neurotoxin type A and B light chains. Assay results demonstrated that a water-soluble fraction obtained from the nettle leaf infusion inhibited type A, but did not inhibit type B light chain protease activity. The inhibition mode of water soluble fraction against protease activity of type A light chain was analyzed and found to be a non-competitive. |
15546474 | Mesenchymal stem cells: cell biology and potential use in therapy. | Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells in xeno-free environment without affecting their growth or differentiation potential. Finally, the mesenchymal stem cells seems to be hypoimmunogenic and thus allogenic mesenchymal stem cells transplantation is possible. It is envisaged that mesenchymal stem cells can be used in systemic transplantation for generalized diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues and organs in tissue engineering protocols. The results of these initial trials are very encouraging and several clinical trials are under way to study the efficacy and long-term safety of therapeutics based on mesenchymal stem cells. |
15546473 | Current in vivo assays for cutaneous toxicity: local and systemic toxicity testing. | This review provides an update on current (June 2004) in vivo assays for evaluations of local and systemic cutaneous toxicity. As the science of toxicology and safety assessment grows and evolves, an increasing number of in vitro assays and screening procedures designed to minimize the use of animals in cutaneous toxicity evaluations have been validated or are currently in development. However, in some cases, it remains necessary to evaluate the effects of new drugs or chemicals in an animal model in order to protect human health. Current regulatory requirements and study designs for local and systemic in vivo cutaneous toxicity evaluations, as well as discussions of procedures unique to cutaneous toxicity evaluation are presented in this review. |
15546460 | 'Is she experiencing any pain?': disability and the physician-patient relationship. | In this essay, I reflect on my experience as a multiple sclerosis patient in order to identify some of the unique challenges that chronic disability poses in the physician-patient relationship. I suggest that it is important to broaden the goals of the clinical encounter to incorporate personal (as opposed to simply bodily) well-being, to be aware of the manner in which chronic disability affects decisions regarding treatment, to recognize the import of physical and attitudinal barriers and to acknowledge that patients with chronic disabilities have an 'expert' knowledge of bodily experience. I also suggest that chronic disability provides an exceptional opportunity with respect to the relationship between doctors and patients. |
15546459 | Five cases of non-typhoidal Salmonella endovascular infection. | The incidence of human non-typhoidal Salmonella (NTS) infection has increased in many countries. Endovascular infection is one of the most serious forms of extraintestinal infection. Five patients with NTS endovascular infection treated at Middlemore Hospital, Auckland, New Zealand, are presented here. All persons with NTS bacteraemia who are older than 50 years and have a risk of atherosclerosis should be evaluated for possible endovascular infection. |
15546458 | Audit of community-based anticoagulant monitoring in patients with thromboembolic disease: is frequent testing necessary? | Oral anticoagulant monitoring is managed by general practitioners in Auckland. An audit of this service in 452 patients demonstrated that anticoagulant control was in line with recommended international guidelines, with 58.3% of international normalized ratio (INR) measurements in the therapeutic range. However, the frequency of testing was high, with the majority of patients (68%), including those on long-term treatment, having INR measurements at weekly intervals. We question the need for such frequent INR testing. |
15546457 | Fibrosing alveolitis in systemic sclerosis: the need for early screening and treatment. | Abnormalities in lung function occur in 70% of patients with systemic sclerosis (SSc). Fibrosing alveolitis in SSc (FASSc) is more commonly seen in the diffuse cutaneous form of SSc, particularly in the presence of antitopoisomerase antibodies (Scl70), and with the decreasing incidence of scleroderma renal crisis it is now the major cause of mortality in this patient population. Screening of patients recently diagnosed with SSc by pulmonary function tests and the performance of high resolution computed tomography when physiological abnormalities are identified has resulted in the identification of significant numbers of patients with early, asymptomatic FASSc. Whether these patients should be further investigated with a surgical lung biopsy or receive immunosuppression is unclear, because it cannot yet be reliably predicted who will develop progressive disease and the evidence to support the efficacy of treatment is not strong. The objective of the present article was to review the evidence to support the use of immunosuppressive therapy in FASSc and, based on these data, to propose an algorithm for the investigation and management of this difficult clinical problem. |
15546456 | Gene therapy: applications and progress towards the clinic. | Gene therapy was originally conceived as an approach to the treatment of genetic disease, to repair or replace a faulty gene. Subsequently, gene therapy clinical trials have been undertaken for a wide range of conditions, particularly cancer and AIDS. Overall, the results from gene therapy have been disappointing. The reasons include the following: (i) low gene transfer efficiencies and (ii) shortcomings in the identification and manipulation of appropriate target cells, including progenitor cell populations required for the maintenance of long-term effects. Today, the immense potential of gene therapy remains, but more basic research is required to improve technical aspects of this form of cellular therapy. |
15546455 | Reliability of X-rays and bone scans for the assessment of changes in skeletal metastases from breast cancer. | To examine the level of agreement among observers regarding changes between serial images of bone metastases. Thirty-five pairs of bone X-rays and 30 pairs of bone scans were selected from the files of patients with breast cancer involving the skeleton. All images in a pair were of the same site and had been taken at least 12 weeks apart. Thirteen radiologists and 14 nuclear medicine physicians examined the X-ray and bone scan pairs, respectively. Each assessed whether the changes between sequential films represented improvement, stability or worsening. Inter-observer agreement was analysed using the kappa statistic (kappa). There was only fair overall agreement among radiologists regarding changes between X-rays (kappa = 0.23), but there was substantial agreement among nuclear medicine physicians for bone scan assessments (kappa = 0.62). Neither the experience of the observers nor the time between images had a significant effect on agreement. For X-rays, agreement was poorer if the response category was 'improvement' and if the type of bone lesion was mixed lytic/sclerotic. Evaluation of serial X-rays is unreliable for determining the response of bone metastases. Scintigraphic evaluation has a higher internal validity for the determination of response, but it should not be used in isolation from other clinical data. |
15546454 | A chronic disease management programme can reduce days in hospital for patients with chronic obstructive pulmonary disease. | A steady increase in chronic obstructive pulmonary disease (COPD) admissions was addressed by enhancing primary care to provide intensive chronic disease management. To compare the effect of a disease management programme, including a COPD management guideline, a patient-specific care plan and collaboration between patients, general practitioners, practice nurses, hospital physicians and nurse specialists with conventional care, on hospital admissions and quality of life. One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records. General practices were randomized to either conventional care (CON), or the intervention (INT). Pre- and post-study assessment included spirometry, Shuttle Walk Test, Short Form-36, and the Chronic Respiratory Questionnaire (CRQ). Admission data were compared for 12 months prior to and during the trial. For respiratory conditions, mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1, whereas those for the CON group increased from 3.5 to 4.0 (group difference, P = 0.030) The INT group also showed an improvement for two dimensions of the CRQ, fatigue (P = 0.010) and mastery (P = 0.007). A chronic disease management programme for COPD patients that incorporated a variety of interventions, including pulmonary rehabilitation and implemented by primary care, reduced admissions and hospital bed days. Key elements were patient participation and information sharing among healthcare providers. |
15546453 | Unobvious wounds: the suffering of hospice patients. | The suffering of palliative care patients is ordinarily thought of in terms of symptoms, and these are identified by medical terms (pain, nausea, depression). The problematic issue of relief of patients' pain meaning the same thing as the 'relief of the suffering and distress of terminally ill patients' has been raised. The aim of this study was to estimate the frequency with which medically defined suffering matched the reported suffering of our patients. One hundred patients admitted to a hospice were asked 'In what way are you suffering?' The patients' diagnoses, their pain scores and the reasons for admission as defined by the treating clinicians were recorded. The mean age of the patients was 68 years (range 28-93 years), 92 had advanced malignant disease and 51 were women. Twenty-four patients were unable to state the reason for hospice admission, but none had any uncertainty in identifying the nature of their own suffering. There was a weak correlation between the patient's view of their suffering and the reason for admission. The identification of pain as the cause of suffering was weakly correlated with pain scores. Some patients with pain scores of 8-10/10 did not mention pain as a cause of suffering, and others with scores of 0/10 did identify pain as the cause of suffering. Asking hospice patients about suffering in a simple open-ended way can expose a different dimension of distress, and the views of the 100 patients of this study support the statement that relief of pain and relief of suffering are not the same. |
15546452 | Trust and confidence: towards mutual acceptance of ethics committee approval of multicentre studies. | To compare issues raised by Human Research Ethics Committees (HREC) during the ethics review process and to determine the length of time taken to gain HREC approval for multicentre research studies. Review and analysis of HREC documentation and correspondence for all multicentre research studies were conducted through three HREC under the auspices of Cancer Trials Australia, Melbourne, Victoria, Australia, between November 1997 and March 2001 to determine the variance of documentation, correspondence and recommendations across the three HREC and the time taken for study approval. Thirty-one projects were submitted to any two of the HREC (16 studies) or all three HREC (15 studies). The median time for study approval at an individual HREC was 75 days, but it was 111 days for approval at all participating sites. There were 554 clarifications or comments made by the reviewing HREC, the majority of which had no significant bearing on the ethical or scientific calibre of the study. There was only one study in which a significant protocol change was requested by a HREC. Multicentre study approvals are delayed when submitted to multiple HREC. The three HREC raised similar issues without substantive differences in their recommendations. A process for the mutual acceptance of HREC recommendations could facilitate multicentre research. |
15546451 | Clinical features in the emergency department can identify patients with suspected acute coronary syndromes who are safe for care in unmonitored hospital beds. | Standard practice for patients requiring hospital admission with suspected acute coronary syndromes (ACS) is admission to a monitored cardiology bed. The Western Hospital Chest Pain Protocol was developed to identify a subset of these patients who could be safely managed in an unmonitored bed. The objective of this prospective study of chest pain patients classified as 'high' or 'intermediate' risk by the Agency for Health Care Policy and Research/National Health and Medical Research Council guidelines was to further evaluate the safety of this protocol. This study was a prospective, observational, cohort study investigating the outcomes of patients admitted to hospital with suspected ACS. The primary outcome of interest was death or life-threatening arrhythmia within 24 h of hospital admission. If the Western Hospital Chest Pain Protocol had been strictly applied, there would have been one death in the group assigned to unmonitored beds (1/750; 0.13%, 95% confidence interval 0.01-0.85%) and no other life-threatening arrhythmias. There is a subgroup of patients with suspected ACS who require hospital admission who can, based on clinical and biochemical features in the emergency department, be safely assigned to unmonitored beds. |
15546434 | Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption: effects on plasma lipoprotein and carotenoid metabolism. | Regular intake of plant sterol (phytosterol)-enriched foods enhances the cholesterol lowering effect of diets. One side effect associated with plant sterol consumption is a modest reduction in plasma carotenoid concentrations. This study investigated the effect of consuming a low-fat National Cholesterol Education Programme (NCEP) Step 1 diet, including a low-fat plant sterol ester (PSE)-enriched spread on cholesterol metabolism to determine if specific dietary advice to increase daily fruit and vegetable intake could prevent reduced plasma carotenoid concentrations. In this randomised, crossover double-blind trial, 48 hypercholesterolaemic men received 21 g day(-1) of a low-fat PSE-enriched spread or placebo for 3 weeks, interrupted by 3 weeks washout. Individuals also adhered to a NCEP Step 1 diet and repeated 3-day food diaries monitored adherence. Specific advice was provided to increase dietary fruit and vegetable intakes. Fasting blood samples were collected at pre- and post-intervention for lipoprotein and carotenoid analysis. Plasma total and low-density lipoprotein (LDL) cholesterol concentrations were significantly (P <0.05) reduced, by 4.6 and 7.1%, respectively, after the PSE-enriched low-fat spread. Plasma apo B concentrations were significantly (P <0.0005) lower after the PSE spread. PSE consumption was also associated with significantly (P <0.05) lower total plasma beta-carotene concentrations, but this change was not significant after lipid standardisation. PSE consumption had no effect on retinol, alpha-carotene, gamma-tocopherol, alpha-tocopherol, lutein, zeaxanthin, beta-crypyoxanthin or lycopene concentrations. Dietary advice to increase daily fruit and vegetable consumption may be effective in preventing a reduction in plasma carotenoid concentrations previously associated with PSE consumption. Further, PSE incorporated in a low-fat spread and consumed as part of a NCEP Step 1 diet are effective in reducing total and LDL cholesterol. |
15546433 | Advice available on the Internet for people with coeliac disease: an evaluation of the quality of websites. | The Internet may be a useful resource for people with coeliac disease as a great deal of health-related information is published online. However, not all of it is accurate. It has been suggested that accurate information is most likely found on transparent sites and kitemarks are awarded on this basis. This paper examines whether the Internet is a useful resource for people with coeliac disease and whether transparency criteria can be used in identifying accurate sites. An evaluation tool was developed using selected transparency criteria and clinical guidelines for accuracy. A total of 63 websites were evaluated. In the study, 66% of the websites scored less than 50% for accuracy. This was primarily because of incomplete information but 15.9% of sites contained inaccuracies. Over 50% of sites scored less than 50% for transparency. No correlation was found between sites that scored highly for accuracy and those that scored highly for transparency. There are useful information available for people with coeliac disease but transparency criteria alone cannot be used to identify accurate sites. |
15546432 | An elemental diet for bowel obstruction in pregnancy: a case study. | Bowel obstruction is a recognised complication in pregnancy, especially in those with adhesions from previous surgery. We report a case where the use of an elemental diet was successful in avoiding surgery in a pregnant patient with recurrent conservatively managed small bowel obstruction. |
15546431 | Home enteral feeding audit. | To determine the main problems that families experience in the first month after their child is discharged from hospital on home enteral tube feeds (HETF) in terms of obtaining feed and equipment, managing tube feeding and accessing health professionals. A multiple choice/short answer questionnaire was used to interview 81 parents/carers of children aged 0-16 years discharged from a supra regional children's hospital on HETF for the first time between December 2001 and August 2003. Questions addressed issues such as: contact with the home delivery company (HDC); delivery of feed and equipment; training; ability to access help; illnesses associated with tube feeding; and understanding of procedures post-discharge. The main problems identified were: delayed first deliveries (> or =7 days post-discharge; 47%); equipment missing from the first delivery (41%); difficulty obtaining a prescription from the general practitioner (GP) (17%); changing to different equipment post-discharge with minimal training on the new equipment (26%). There were many problems with delays in delivery of equipment, incorrect equipment and changing of equipment when patients were first discharged on HETF. Significant improvements are necessary in organization of home enteral feeding systems when patients are first discharged. |
15546430 | Influence of individually estimated portion size on the assessment of nutritional risk in colorectal cancer in Portugal. | We evaluated the influence of individually estimated portion sizes on the estimate of nutrient related risk of colorectal cancer, using data from a Portuguese hospital based case-control study on diet and colorectal cancer. A total of 100 patients with colorectal adenocarcinoma (aged 15-92 years) and 211 controls (aged 36-89 years) were included. Two data sets were created for nutrient analysis, the first one allowed estimates of food intake using data on portion size as collected with visual aids during the interview. The second estimate substituted respondents' estimate with a standard portion size, as used in the semi-quantitative (SQ) food frequency approach. The two analytic approaches yielded similar energy and nutrient intakes in cases and controls. The percent range of concordance is acceptable, in the same quartile varying from 44 to 82% (mean: 56%) and very good in the same or adjacent (+/-1) quartile (mean: 91%, range: 85-97%). The two estimates lead to a similar pattern of multivariate odd's ratio, however the SQ estimates resulted in more significant findings. We conclude that little extra information is gained by including individual portion size information when assessing diet-related risk of colorectal cancer. |
15546429 | A comparison of food group variety between toddlers with and without cystic fibrosis. | To compare the food group variety and nutritional adequacy of the diet between toddlers with cystic fibrosis (CF) and age-matched controls. Subjects A clinical sample of 22 toddlers with CF (mean age=21.3 +/- 7.2 months) matched to a community sample of 22 healthy peers. The variety index for toddlers (VIT) and the mean adequacy ratio (MAR). Fruit group scores were highest for children with CF (0.95 +/- 0.13; possible range 0.00-1.00), and dairy group scores were highest for controls (0.90 +/- 0.18). All children earned the lowest scores for vegetables (CF: 0.15 +/- 0.12; controls: 0.26 +/- 0.22). No significant differences were found when comparing VIT and MAR scores by sample (P >0.05). A moderate positive relationship was found between total VIT scores and MAR scores for all children (r=0.38, P <0.05). Toddlers with CF did not achieve the 120-150% of Recommended Dietary Allowance (RDA) for energy. Toddlers with CF are consuming diets that are varied and nutritionally adequate for a healthy child. To optimize nutritional status and growth, current recommendations for toddlers with CF to eat a well-balanced diet and to exceed daily RDA for energy requirements remain key dietary issues. |
15546428 | Attitudes and barriers to dietary advice aimed at reducing risk of type 2 diabetes in first-degree relatives of patients with type 2 diabetes. | To evaluate the attitudes to and adoption of dietary advice in nondiabetic first-degree relatives of patients with type 2 diabetes and to examine barriers to adherence. One-year controlled intervention study, where treatment group (n=73) received lifestyle education. Attitudes towards dietary advice, change in dietary habits and importance of potential barriers to adherence were evaluated by questionnaires. Nondiabetic relatives (25-55 years; males and females) of individuals with type 2 diabetes were recruited. Education was based on current nutrition recommendations and aimed at improving dietary fat quality, increasing intake of fruit and vegetables, with additional advice to reduce dietary glycaemic index (GI). Attitudes and importance of barriers were classified by the intervened subjects into four categories ranging from 'No problem' to 'Yes, definitely a problem'. Dietary adherence was monitored by food frequency questionnaire at baseline and after 1 year. Participants were generally in favour of advice aimed at improving dietary fat quality. Attitudes towards advice to reduce GI varied widely. Food selection changed in accordance with predefined dietary goals. 'Forgetfulness', 'low availability in lunch restaurant' and 'lack of ideas for cooking' were barriers to adherence. Dietary advice aimed at reducing risk of type 2 diabetes was generally positively received and adopted in subjects with heredity for the disease. The most prevalent barriers reported are potentially modifiable. |
15546427 | Canadian dietitians' views and practices regarding obesity and weight management. | To provide insight into Canadian dietitians' attitudes and practices regarding obesity and weight management. Cross-sectional mail survey of a stratified random sample of members of Canadian dietetic associations. A total of 514 dietitians (74% of those surveyed), 350 (69%) of whom actively counselled overweight/obese clients. Participants received a questionnaire to assess dietitians' attitudes regarding obesity and overweight, views regarding their role in weight management, counselling practices, and the criteria used to judge success. Demographic variables were collected. Most dietitians believed that obesity contributes to morbidity and mortality, and that small weight losses produced important health benefits. However, 80% agreed that health indicators other than weight loss should be the focus of obesity management, and 55% specifically recommended that clients not weigh themselves. Instead, weight management was promoted by recommending healthy eating and increased physical activity. Three-quarters agreed that they are the profession best trained to manage obesity but two-thirds believed their time would be better spent preventing rather than managing obesity. Dietitians most valued education received from on-the-job support and mentoring from other dietitians. Participants reported wanting to learn more about motivational and behavioural modification counselling techniques. Canadian dietitians follow a lifestyle approach to weight management. Studies are required to formally assess the effectiveness of various aspects of this approach. |
15546423 | Analysis of Acanthamoeba polyphaga surface carbohydrate exposure by FITC-lectin binding and fluorescence evaluation. | Characterization of the representative protozoan Acanthamoeba polyphaga surface carbohydrate exposure by a novel combination of flow cytometry and ligand-receptor analysis. Trophozoite and cyst morphological forms were exposed to a panel of FITC-lectins. Population fluorescence associated with FITC-lectin binding to acanthamoebal surface moieties was ascertained by flow cytometry. Increasing concentrations of representative FITC-lectins, saturation binding and determination of K(d) and relative B(max) values were employed to characterize carbohydrate residue exposure. FITC-lectins specific for N-acetylglucosamine, N-acetylgalactosamine and mannose/glucose were readily bound by trophozoite and cyst surfaces. Minor incremental increases in FITC-lectin concentration resulted in significant differences in surface fluorescence intensity and supported the calculation of ligand-binding determinants, K(d) and relative B(max), which gave a trophozoite and cyst rank order of lectin affinity and surface receptor presence. Trophozoites and cysts expose similar surface carbohydrate residues, foremost amongst which is N-acetylglucosamine, in varying orientation and availability. The outlined versatile combination of flow cytometry and ligand-receptor analysis allowed the characterization of surface carbohydrate exposure by protozoan morphological forms and in turn will support a valid comparison of carbohydrate exposure by other single-cell protozoa and eucaryotic microbes analysed in the same manner. |
15546422 | Identification of early microbial colonizers in human dental biofilm. | To elucidate the first colonizers within in vivo dental biofilm and to establish potential population shifts that occur during the early phases of biofilm formation. A 'checkerboard' DNA-DNA hybridization assay was employed to identify 40 different bacterial strains. Dental biofilm samples were collected from 15 healthy subjects, 0, 2, 4 and 6 h after tooth cleaning and the composition of these samples was compared with that of whole saliva collected from the same individuals. The bacterial distribution in biofilm samples was distinct from that in saliva, confirming the selectivity of the adhesion process. In the very early stages, the predominant tooth colonizers were found to be Actinomyces species. The relative proportion of streptococci, in particular Streptococcus mitis and S. oralis, increased at the expense of Actinomyces species between 2 and 6 h while the absolute level of Actinomyces remained unaltered. Periodontal pathogens such as Tannerella forsythensis(Bacteroides forsythus), Porphyromonas gingivalis and Treponema denticola as well as Actinobacillus actinomycetemcomitans were present in extremely low levels at all the examined time intervals in this healthy group of subjects. The data provide a detailed insight into the bacterial population shifts occurring within the first few hours of biofilm formation and show that the early colonizers of the tooth surface predominantly consist of beneficial micro-organisms. The early colonizers of dental plaque are of great importance in the succession stages of biofilm formation and its overall effect on the oral health of the host. |
15546421 | Isolation of a lactic acid bacterium and yeast consortium from a fermented material of Ulva spp. (Chlorophyta). | Microbiota in a fermented culture of Ulva spp. was examined with the objective to characterize the type of fermentation and to obtain starter microbes for performing seaweed fermentation. Fermented Ulva spp. cultures which were obtained and transferred in a laboratory were examined for their microbiota. With phenotypic characterization and phylogenetic analysis based on rRNA gene nucleotide sequences, the predominant micro-organisms were identified as Lactobacillus brevis, Debaryomyces hanseni var. hansenii, and a Candida zeylanoides-related specimen, suggesting that the observed fermentation can be categorized to lactic acid and ethanol fermentation. Inoculating the individually cultured cell suspensions of the three kinds of micro-organisms with cellulase induced the fermentation in various kinds of seaweed. A microbial consortium composed of a lactic acid bacterium, L. brevis, and yeasts, D. hansenii and a C. zeylanoides-related specimen, were predominant in a fermented culture of Ulva spp. Lactic acid and ethanol fermentation could be induced in various kinds of seaweed by adding this microbial consortium along with cellulase. This is the first report of lactic acid and ethanol fermentation in seaweed, which is expected to provide a new material for food and dietary applications. |
15546420 | Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp. | To determine the effects of herbal essential oils on Trichophyton spp. growth and to evaluate the effects of Pelargonium graveolens oil and its main components citronellol and geraniol combined with ketoconazole against Trichophyton spp. Growth inhibition of six Trichophyton spp. by herbal essential oils was accessed and the combined effects of P. graveolens oil and its main components citronellol and geraniol were evaluated using a checkerboard microtitre assay against T. schoenleinii, T. erinacei and T. soudanense. The essential oil fraction of P. graveolens and its main components, geraniol and citronellol, exhibited strong synergism with ketoconazole against T. schoenleinii and T. soudanense, with fractional inhibitory concentration (FIC) indices in the range of 0.18-0.38. The antifungal effects of ketoconazole against Trichophyton spp. are enhanced significantly by administering it in combination with the essential oil fraction of P. graveolens or its main components, because of strong synergism, especially against T. soudanense and T. schoenleinii. The combination of ketoconazole and the essential oil fraction from P. graveolens or its main components for treatment of infections caused by Trichophyton species may reduce the minimum effective dose of ketoconazole, and thus minimize the side-effects of ketoconazole. |
15546419 | Relationship between inactivation kinetics of a Listeria monocytogenes suspension by chlorine and its chlorine demand. | Chlorine demand by Listeria monocytogenes cells and inactivation of L. monocytogenes by chlorine (0.6-1.0 mg l(-1)) at different temperatures (4, 20 and 30 degrees C) have been investigated in a batch reactor. Chlorine demand depended on the microbial concentration and was independent on the initial chlorine concentration and temperature. Chlorine decay was modelled by the addition of two first-order decay equations. Inactivation of L. monocytogenes by chlorine depended on the initial microbial concentration, initial chlorine concentration and temperature. A mathematical model based on a biphasic inactivation properly described survival curves of L. monocytogenes and a tertiary model was developed that satisfactorily predicted the inactivation of L. monocytogenes by different concentrations of initial chlorine at different temperatures. Both available chlorine decay and inactivation of L. monocytogenes by chlorine were biphasic and can be modelled by a two-term exponential model. The biphasic nature of survival curves of L. monocytogenes did not reflect the effect of a change of available chlorine concentration during the treatment. The microbial inactivation was caused by successive reactions that occur after the consumption of the chlorine by the bacterial cell components. |
15546418 | Characterization of Saccharomyces cerevisiae strains isolated from must of grape grown in experimental vineyard. | Isolation and characterization of indigenous Saccharomyces cerevisiae strains from 12 grape varieties grown in an experimental vineyard of Apulia. Thirty to 40 colonies from each of the 12 fermentations were obtained at the end stage of spontaneous fermentation. By using morphological and physiological methods and by the PCR analysis of internal transcribed ITS1-5,8S-ITS2, the isolates belonging to Saccharomyces genus were identified. These isolates were further characterized by amplification with S. cerevisiae species- and delta element-specific primers, thus allowing the identification of S. cerevisiae strains selected from each of the 12 fermentations. By means of RFLP analysis of mtDNA, each S. cerevisiae population isolated from a single fermentation appeared to constitute a genetically homogenous group. The comparison of the 12 cultivar-specific mtDNA RFLP patterns, allowed classifying the 12 S. cerevisiae populations into three genetically homogenous groups. The isolated strains fermented vigorously in synthetic and grape juice medium and showed high alcohol and sulphur dioxide (SO(2)) resistance and low hydrogen sulphite (H(2)S) production. The molecular analysis, in conjunction with the traditional morphological and physiological methods, was useful in discriminating at strain level the indigenous population of S. cerevisiae present in a vineyard of Apulia. The dominant S. cerevisiae strains identified in the 12 fermented musts showed potentially important oenological characteristics. The characterization of natural S. cerevisiae strains from several typical Italian grapes grown in a restricted experimental vineyard is an important step towards the preservation and exploitation of yeast biodiversity of Apulia, a relevant wine-producing region. The close relationship between the S. cerevisiae strains from different grapes grown in the same vineyard indicated that the occurrence of native strains is representative of the area rather than of the variety of grapes. |
15546417 | Fermentation conditions affecting the bacterial growth and exopolysaccharide production by Streptococcus thermophilus ST 111 in milk-based medium. | To study the effect of different fermentation conditions and to model the effect of temperature and pH on different biokinetic parameters of bacterial growth and exopolysaccharides (EPS) production of Streptococcus thermophilus ST 111 in milk-based medium. The influence of temperature and pH was studied through fermentation and modelling. Fermentations under non-pH controlled conditions with S. thermophilus ST 111 indicated that the EPS production was low in milk medium, even if additional nitrogen sources were supplemented. Under pH-controlled conditions, addition of whey protein hydrolysate to the milk medium resulted in a fivefold increase of the EPS production. This medium did not contain polysaccharides interfering with EPS isolation. Primary and secondary modelling of different fermentations revealed an optimum temperature and pH of 40 degrees C and constant pH 6.2, respectively, for growth in milk medium supplemented with whey protein hydrolysate. Maximum EPS production was observed in the range of 32-42 degrees C and constant pH 5.5-6.6. Whereas growth and maximum EPS production were clearly influenced by temperature and pH, the specific EPS production was only affected by stress conditions (T = 49 degrees C). Addition of whey protein hydrolysate to milk medium resulted in an increased growth and EPS production of S. thermophilus ST 111 under pH-controlled conditions. A modelling approach allowed studying the influence of temperature and pH on the kinetics of both growth and EPS production. The use of an appropriate milk-based medium and a combined model of temperature and pH can be of practical importance for the production of yoghurt or other fermented milks as well as for process optimization of the large-scale production of starter strains to be used for their EPS production. |
15546416 | Genetic and functional characterization of a Bacillus sp. strain excreting surfactin and antifungal metabolites partially identified as iturin-like compounds. | A bacterial strain producing antifungal compounds active against the plant pathogenic fungi Fusarium, Rhizoctonia and Sclerotinia has been characterized and shown to control Rhizoctonia root rot of soya bean. The metabolites excreted by Bacillus BNM 122 remained active after autoclaving, were resistant over a wide pH range and to hydrolytic enzymes. By (1)H-NMR and thin-layer chromatography analyses surfactin and iturin-like compounds were partially identified. Moreover, soya bean seeds bacterization with BNM 122 in a compost-based formulation was as effective controlling Rhizoctonia solani as pentachloronitrobenzene. According to its 16S rDNA sequence BNM 122 was closely related to Bacillus amyloliquefaciens and Bacillus subtilis. PCR analysis of the 16S-23S rRNA intergenic spacer region and repetitive sequence-based PCR (rep-PCR) genomic fingerprinting revealed a close genetic relationship to B. amyloliquefaciens. However, by physiological characterization using API tests, this strain resembled more B. subtilis. This is the first report describing the co-production of surfactin and iturin-like compounds by a putative strain of B. amyloliquefaciens. The synergistic effect of both lipopetides is a remarkable trait for a candidate biocontrol agent. This kind of research has relevance in order to minimize the use of synthetic fungicides and surfactants, contributing to the preservation of the environment. |
15546415 | Inhibition of the reattachment of young adult zebra mussels by single-species biofilms and associated exopolymers. | To determine the effects of single-species bacterial films and their associated extracellular products on the reattachment of young adult zebra mussels. Ten strains of bacteria were isolated from surfaces where adult zebra mussels can be found attached in nature. Single-species biofilms were developed on both glass and polystyrene using these bacteria. The reattachment of zebra mussels (i.e. with byssal threads) was compared between surfaces with and without films. Although no differences were observed in mussel reattachment between glass surfaces with and without films (P > 0.05, anova), a reduction in mussel reattachment between polystyrene surfaces with and without films was observed for seven of the 10 strains (P < or = 0.05 to <0.001, anova). Bacterial extracellular products (BEP) were isolated from five bacterial films and tested for their effects on mussel reattachment. Four of the five sets of isolated extracellular products evoked the same effects as their respective intact biofilms. We conclude that depending on the substratum, individual strains of bacteria in biofilms can inhibit the reattachment of adult zebra mussels. In some cases, BEP were the source of the inhibitory effects. The nature of the substratum on which the biofilms develop affects properties of the biofilm and its extracellular components, which subsequently influences zebra mussel reattachment. |
15546414 | Description of heterotrophic bacteria occurring in paper mills and paper products. | To isolate aerobic mesophilic bacilli and thermophilic bacteria from different paper mill samples and to evaluate their potential harmfulness. A total of 109 mesophilic and 68 thermophilic isolates were purified and characterized by automated ribotyping and partial 16S rDNA sequencing. The mesophilic isolates belonged to the genera Bacillus (13 taxa), Brevibacillus (three taxa) and Paenibacillus (five taxa). The thermophilic bacteria represented seven taxa of Bacillus, Geobacillus or Paenibacillus, four of proteobacteria and one of actinobacteria. The most frequently occurring bacteria were Bacillus cereus, B. licheniformis, Pseudoxanthomonas taiwanensis and bacteria closely related to Paenibacillus stellifer, P. turicensis or Leptothrix sp. One mill was contaminated throughout with bacteria of a novel mesophilic genus most closely related to Brevibacillus centrosporus and another with bacteria of a novel thermophilic genus most closely related to Hydrogenophilus thermoluteolus. One B. cereus isolate producing haemolytic diarrhoeal enterotoxin was detected and all the tested B. licheniformis isolates produced a metabolite toxic to boar sperm cells. The bacilli and thermophilic bacteria isolated represent species which should not present occupational hazards in paper mill environments. The most harmful bacterium detected was B. licheniformis and potentially also B. cereus. Knowledge of the microbial diversity in a paper mill provides a rational basis for development of an effective controlling programme. A database constructed from the fingerprints generated using automated ribotyping helps to identify and trace the contamination routes of bacteria occurring in paper mills. |
15546413 | Effect of microwave radiation on Bacillus subtilis spores. | To compare the killing efficacy and the effects exerted by microwaves and conventional heating on structural and molecular components of Bacillus subtilis spores. A microwave waveguide applicator was developed to generate a uniform and measurable distribution of the microwave electric-field amplitude. The applicator enabled the killing efficacy exerted by microwaves on B. subtilis spores to be evaluated in comparison with conventional heating at the same temperature value. The two treatments produced a similar kinetics of spore survival, while remarkably different effects on spore structures were seen. The cortex layer of the spores subjected to conductive heating was 10 times wider than that of the untreated spores; in contrast, the cortex of irradiated spores did not change. In addition, the heated spores were found to release appreciable amounts of dipicolinic acid (DPA) upon treatment, while extracellular DPA was completely undetectable in supernatants of the irradiated spores. These observations suggest that microwave radiation may promote the formation of stable complexes between DPA and other spore components (i.e. calcium ions); thus, making any release of DPA from irradiated spores undetectable. Indeed, while a decrease in measurable DPA concentrations was not produced by microwave radiation on pure DPA solutions, a significant lowering in DPA concentration was detected when this molecule was exposed to microwaves in the presence of either calcium ions or spore suspensions. Microwaves are as effective as conductive heating in killing B. subtilis spores, but the microwave E-field induces changes in the structural and/or molecular components of spores that differ from those attributable only to heat. This study provides information on the effect of microwaves on B. subtilis spore components. |
15546412 | Molecular diversity of tannic acid degrading bacteria isolated from tannery soil. | The aim of this study was to enrich and isolate bacteria from a tannery soil that were capable of utilizing tannic acid and gallic acid as sole source of carbon aerobically, and to characterize their diversity in order to identify efficient strains that can be used for tannin bioremediation. Bacterial strains were isolated after enrichment in minimal medium with tannic acid or gallic acid as sole carbon source. Polymerase chain reaction (PCR) restricted fragment length polymorphism of 16S rDNA [amplified ribosomal DNA restriction analysis (ARDRA)] and BOX-PCR was used to characterize their diversity. Two strains showing relatively high efficiency in degrading tannic acid and gallic acid were identified on the basis of carbon source utilization pattern (BIOLOG) and 16S rDNA sequence. Bacterial strains capable of degrading tannic acid and gallic acid could be grouped into six and seven clusters on the basis of ARDRA and BOX-PCR, respectively. On the basis of 16S rDNA sequence, the most efficient isolate degrading tannic acid belonged to Pseudomonas citronellolis, whereas the most efficient gallic acid degrader showed maximum phylogenetic relatedness to P. plecoglossicida. Aerobic tannic acid degraders such as the two strains isolated in this study can be used for tannin bioremediation, and in the study of genes involved in the production of tannase, an industrially important enzyme. |
15546411 | Penicillium chrysogenum glucose oxidase -- a study on its antifungal effects. | Purification and characterization of the high molecular mass Candida albicans-killing protein secreted by Penicillium chrysogenum. The protein was purified by a combination of ultrafiltration, chromatofocusing and gel filtration. Enzymological characteristics [relative molecular mass (M(r)) = 155 000, subunit structure alpha(2) with M(r,alpha) = 76 000, isoelectric point (pI) = 5.4] were determined using SDS-PAGE and 2D-electrophoresis. N-terminal amino acid sequencing and homology search demonstrated that the antifungal protein was the glucose oxidase (GOX) of the fungus. The enzyme was cytotoxic for a series of bacteria, yeasts and filamentous fungi. Vitamin C (1.0 mg ml(-1)) prevented oxidative cell injuries triggered by 0.004 U GOX in Emericella nidulans cultures but bovine liver catalase was ineffective even at a GOX : catalase activity ratio of 0.004 : 200 U. A secondary inhibition of growth in E. nidulans cultures by the oxygen-depleting GOX-catalase system was likely to replace the primary inhibition exerted by H(2)O(2). Penicillium chrysogenum GOX possesses similar enzymological features to those described earlier for other Penicillium GOXs. Its cytotoxicity was dependent on the inherent antioxidant potential of the test micro-organisms. Penicillium chrysogenum GOX may find future applications in glucose biosensor production, the disinfection of medical implants or in the food industry as an antimicrobial and/or preservative agent. |
15546410 | The role of host organism, transcriptional switches and reporter mechanisms in the performance of Hg-induced biosensors. | The purpose of this study was to comprehensively compare the response of nine biosensors capable of being induced by Hg. Induction by Hg was based upon the insertion of merR, merB, zntA and zntR promoter genes. LuxCDABE or lucFF reporter genes expressed luminescence, and host organisms were Escherichia coli, Vibrio anguillarum and Pseudomonas fluorescens. The role of transcriptional switches, reporter mechanism and host organism was to be investigated. All biosensors were subjected to the same assay conditions. Sensors had their own individual growth characteristics and response to the doses of Hg tested. Maximum bioluminescence response was induced by concentrations of Hg between 2.5 nm and 5 microM. E. coli pRB28 was found to detect levels of Hg as low as 1.6 nm and yet was capable of operating in a concentration range of up to 12.5 microM. The response of the sensors demonstrated their suitability for analysis under environmentally relevant concentrations. The sensitivity of the sensors, the optimum range and the expediency of the assay could not be related to a single sensor trait. It may be concluded that biosensor performance is dependent on more than one of the single factors studied. The results show that comparative testing of sensors is an important step in evaluating the relevance and performance of biosensors prior to routine environmental application. |
15546409 | Growth of enterotoxigenic Staphylococcus aureus in povi masima, a traditional Pacific island food. | To obtain preliminary data on the microbiology and hurdles to pathogen growth in the traditional Pacific Island food, povi masima, which is essentially beef brisket cured in brine. Six containers of povi masima were prepared and two were inoculated with five enterotoxigenic strains of Staphyloccocus aureus. The povi masima were divided into two lots each containing two uninoculated control and an inoculated container. Lot 1 was incubated at room temperature (20 degrees C) and lot 2 under refrigeration (4-5 degrees C) for up to 98 days. During storage, samples were removed and tested for aerobic plate count, coagulase-producing Staphylococci, Clostridium perfringens, staphylococcal enterotoxin and various chemical parameters of the food. Coagulase-producing Staphylococci and aerobic plate counts grew to high levels in both the inoculated and uninoculated lots stored at room temperature, but enterotoxin was only detected at one time point in these lots and this may represent a false positive result. The concentration of NaCl in the meat increased with time as concentrations equilibrated, and nitrite was rapidly lost in those lots stored at room temperature. Storage at 4-5 degrees C prevented proliferation of coagulase-producing Staphylococci. For safe curing and storage, this food should be kept under refrigeration as this prevented growth of staphylococci. Optimum storage would also be achieved with improved attempts to ensure equal distribution of NaCl prior to storage. Under conditions traditionally used to cure and store this food, enterotoxigenic staphylococci can grow to numbers where toxigenesis might occur, especially during the early stages of curing where the salt has not diffused from the brine into the meat. |
15546408 | Deletion of the Delta12-oleic acid desaturase gene of a nonaflatoxigenic Aspergillus parasiticus field isolate affects conidiation and sclerotial development. | To investigate how linoleic acid affects conidial production and sclerotial development in a strictly mitotic Aspergillus parasiticus field isolate as related to improving biocompetitivity of atoxigenic Aspergillus species. We disrupted A. parasiticusDelta12-oleic acid desaturase gene (odeA) responsible for the conversion of oleic acid to linoleic acid. We examined conidiation and sclerotial development of SRRC 2043 and three isogenic mutant strains deleted for the odeA gene (DeltaodeA), either with or without supplementing linoleic acid, on one complex potato dextrose agar (PDA) medium and on two defined media: nitrate-containing Czapek agar (CZ) and Cove's ammonium medium (CVN). The DeltaodeA mutants produced less conidia than the parental strain on all media. Linoleic acid supplementation (as sodium linoleate at 0.3 and 1.2 mg ml(-1)) restored the DeltaodeA conidial production comparable to or exceeding the unsupplemented parental level, and the effect was medium dependent, with the highest increase on CVN and the least on PDA. SRRC 2043 and the DeltaodeA mutants were unable to produce sclerotia on CVN. On unsupplemented PDA and CZ, DeltaodeA sclerotial mass was comparable to that of SRRC 2043, but sclerotial number increased significantly to two- to threefold. Supplementing linoleic acid to media, in general, tended to decrease wild type and DeltaodeA sclerotial mass and sclerotial number. Linoleic acid stimulates conidial production but has an inhibitory effect on sclerotial development. The relationship between the two processes in A. parasiticus is complex and affected by multiple factors, such as fatty acid composition and nitrogen source. Conditions that promote sclerotial development differ from those required to promote maximum conidial production. Manipulation of content and availability of linoleic acid at different fungal growth phases might optimize conidial and sclerotial production hence increasing the efficacy of biocompetitive Aspergillus species. |
15546407 | Development of an extensive set of 16S rDNA-targeted primers for quantification of pathogenic and indigenous bacteria in faecal samples by real-time PCR. | The microbiota of the human intestinal tract constitutes a complex ecosystem. We report the design and optimization of an extensive set of 16S rDNA-targeted species- and group-specific primers for more accurate quantification of bacteria from faecal samples with real-time PCR. A linear range of quantification between 0.1-10 pg and 10 ng of specific target genome was obtained, which corresponds to detection of ca 30-4500 to 1.9 x 10(6)-6.0 x 10(6) target bacterial genomes. Functionality of the assays was confirmed by quantification of target bacterial DNA from faecal DNA preparations of healthy volunteers and irritable bowel syndrome (IBS) patients. Additionally, spiking of faecal preparations with Helicobacter pylori, Clostridium difficile or Campylobacter jejuni was used to confirm the accurate and sensitive quantification. Real-time PCR is a very sensitive and precise technique for an extensive quantitative evaluation of gut microbiota and is feasible for detection of human pathogens from faecal samples. To design and optimize an extensive set of real-time PCR assays targeting a large group of predominant and pathogenic GI microbial species for further use in updating the current knowledge of the putative role of gut microbiota in health and disease. |
15546406 | Development of a capture/enrichment sandwich ELISA for the rapid detection of enteropathogenic and enterohaemorrhagic Escherichia coli O26 strains. | To improve the sensitivity of a monoclonal antibody (MAb 2F3) based enteropathogenic Escherichia coli (EPEC)/enterohaemorrhagic E. coli (EHEC) serogroup O26-specific sandwich ELISA (sELISA), using a capture/enrichment format of the assay. The sELISA utilized an EPEC/EHEC O26-specific MAb 2F3 as the capture reagent and an E. coli serogroup O26 lipopolysaccharide-specific polyclonal antibody in the development stage. Wells containing faeces test samples from bovine enteritis cases and agar colony sweep cultures from human diarrhoea cases, after a 2-h capture stage, were washed and enrichment of the captured cells was encouraged by addition of tryptone soya broth. After overnight incubation, the contents of each well were transferred to sterile wells and the sELISA completed. Any sELISA positive samples were then subcultured onto blood agar to recover and further characterize the positive cultures. The assay had a sensitivity of 10(3) CFU ml(-1). ELISA positive samples consisted of 21 (4.8%) of the 442 bovine and 19 (3.7%) of the 519 human samples tested, and ELISA positive EPEC/EHEC O26 strains were isolated from 11 and three of these samples respectively. The capture/enrichment method improved the sensitivity of a MAb-based sELISA for the detection of EPEC/EHEC O26 strains, and also contributed to an improved isolation rate of the organism from field samples. The application of a specific MAb in a capture/enrichment format of the sELISA, provides a prospectively suitable screening method for the detection of pathogenic bacteria from mixed culture samples. |
15546405 | Use of the 'ex vivo' test to study long-term bacterial survival on human skin and their sensitivity to antisepsis. | To determine bacterial survival on human skin and their sensitivity to antisepsis. An 'ex vivo' protocol which uses human skin samples placed into diffusion cells, and electron microscopy (EM), were used to study the growth of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa inoculated onto skin samples over a 46-h incubation period at 32 degrees C. Concurrently variation in skin pH was evaluated at different time intervals during this period. In addition the antimicrobial activity of three antiseptics against the incubated micro-organisms was assessed quantitatively with the 'ex vivo' test, while their detrimental effects against bacteria were observed by EM. All three bacteria were still present in high number after 46 h inoculation on skin, although the concentration of E. coli and S. aureus were reduced by 2.74 and 1.58 log(10) reduction, respectively, over this period of time. Electron micrographs showed clear evidence of cell division and some bacteria appeared to be embedded into the skin layers. The antiseptics tested had some antibacterial activity against bacteria incubated on skin for 3 and 10 h, and EM evidence showed some morphological damages including cellular blebbing and the presence of fibrillar material around the cells. All micro-organisms had an acidifying effect on skin samples. Here, it was shown that bacterial pathogens can survive and grow when incubated on human skin. In addition, it is possible that they can penetrate the stratum corneum, which can provide some protection against antisepsis. The apparent low bactericidal activity of biocides attributed in part to bacterial protection from skin layers is particularly important to assess in order to ensure antisepsis efficacy. |
15546404 | Predominance of Saccharomyces uvarum during spontaneous alcoholic fermentation, for three consecutive years, in an Alsatian winery. | The purpose of this study was to determine the origin of the yeasts involved in the spontaneous alcoholic fermentation of an Alsatian wine. During three successive years, must was collected at different stages of the winemaking process and fermented in the laboratory or in the cellar. Saccharomyces yeasts were sampled at the beginning and at the end of the fermentations. Saccharomyces cerevisiae clones were genetically characterized by inter-delta PCR. Non-S. cerevisiae clones were identified as Saccharomyces uvarum by PCR-RFLP on MET2 gene and characterized at the strain level by karyotyping. The composition of the Saccharomyces population in the vineyard, after crushing and in the vat was analyzed. This led to three main results. First, the vineyard Saccharomyces population was rather homogeneous. Second, new non-resident strains had appeared in the must during the winemaking process. Finally, the yeast population in the vat only consisted in S. uvarum strains. This 3-year study has enabled us to show the involvement of indigenous S. uvarum in the alcoholic fermentation. This study gives a first insight into the polymorphism of S. uvarum strains involved in a spontaneous alcoholic fermentation. |
15546403 | In situ quantification of biocide efficacy using GFP transformed Aureobasidium pullulans. | To develop a real-time in situ method to quantify loss of viability of Aureobasidium pullulans PRAFS8 cells attached to plasticized polyvinyl chloride (pPVC) with incorporated biocides, and to use the method to compare biocide efficacy in situ. A. pullulans PRAFS8, transformed with green fluorescent protein (GFP), was used to quantify the efficacy of a range of biocides incorporated into pPVC. Experimentally, it was found that a density of 1.53 x 10(6) yeast cells per cm(2) of pPVC was optimal as increasing the density of the yeast cells to 6.12 x 10(6) cm(-2) attached to pPVC containing the biocide 2-n-octyl-4-isothiazolin-3-one (OIT) decreased the rate of fluorescence loss. A strong positive correlation between fluorescence and viable yeast cell number was observed and fluorescence was used as a direct indicator of cell viability. The effectiveness of five commercial biocides, commonly incorporated into pPVC at their in-use concentrations, was tested against yeast cells attached to the pPVC surface. The loss of fluorescence and hence viability in situ was quantified using image analysis. The biocides N-(trichloromethylthio) phthalimide (NCMP), 10,10'-oxybisphenoxarsine (OBPA), OIT and 2,3,5,6-tetrachloro-4-(methylsulphonyl) pyridine (TCMP) caused complete loss of fluorescence within 30-50 h. In contrast the biocide dichloro-octyl-isothiazoline caused only 55 +/- 15% fluorescence loss after 50 h. Starvation of the yeast cells in suspension for 24 h prior to attachment reduced their initial sensitivity to OBPA, NCMP, OIT and TCMP by 15-20%, but eventually the fluorescence was also completely lost. The use of A. pullulans expressing cytosolic GFP enables the in situ quantification of loss of viability when cells are attached to pPVC with incorporated biocides. GFP fluorescence was used as a real-time indicator of cell viability and thus can be applied for direct quantification of the effectiveness of a broad range of biocides, incorporated into the polymer mass and used to protect a variety of plastics or other materials from microbial growth. |
15546402 | Bacterial population dynamics and community structure in a pharmaceutical manufacturing water supply system determined by real-time PCR and PCR-denaturing gradient gel electrophoresis. | To control bacteria in the pharmaceutical water supply system. Bacteria were enumerated by conventional culture method and fluorescent vital staining. Activated carbon treatment and storage in a tank provided favourable environments for bacterial growth. The bacterial population of the water in both the post-activated carbon treatment and the tank was analysed by denaturing gradient gel electrophoresis (DGGE) with PCR-amplified 16S rDNA fragments including V6, -7, and -8 regions. The bacterial community structure in activated carbon treated water was stable throughout the year. Several kinds of bacteria such as genus Aquaspirillum and Methylobacterium were found in the water after activated carbon treatment. The bacterial community structure was changed and other bacteria such as mycobacteria were detected after storage. Mycobacteria were quantified in water samples using real-time PCR targeting the 16S rDNA gene. Mycobacteria were also detected in tap water and their number was increased 10(3)-10(4)-fold higher after storage. These data suggest the importance of culture-independent methods for quality control of water used in pharmaceutical manufacturing. Critical steps and specified bacteria that should be controlled in the water supply system were recognized by culture-independent methods. These data will enable effective control of water used in the pharmaceutical industry. |
15546401 | Direct detection of bacterial pathogens in representative dairy products using a combined bacterial concentration-PCR approach. | To develop a simple, rapid method to concentrate and purify bacteria and their nucleic acids from complex dairy food matrices in preparation for direct pathogen detection using polymerase chain reaction (PCR). Plain non-fat yogurt and cheddar cheese were each seeded with Listeria monocytogenes or Salmonella enterica serovar. Enteritidis in the range of 10(1)-10(6) CFU per 11-g sample. Samples were then processed for bacterial concentration using high-speed centrifugation (9700 g) followed by DNA extraction, PCR amplification, and amplicon confirmation by hybridization. Bacterial recoveries after centrifugation ranged from 53 to >100% and 71 to >100% for serovar. Enteritidis and L. monocytogenes, respectively, in the non-fat yogurt samples; and from 77 to >100% and 69 to >100% for serovar. Enteritidis and L. monocytogenes, respectively, in the cheddar cheese samples. There were no significant differences in recovery efficiency at different inocula levels, and losses to discarded supernatants were always <5%, regardless of dairy product or pathogen. When followed by pathogen detection using PCR and confirmation by amplicon hybridization, detection limits of 10(3) and 10(1) CFU per 11-g sample were achieved for L. monocytogenes and serovar. Enteritidis, respectively, in both product types and without prior cultural enrichment. This study represents progress toward the rapid and efficient direct detection of pathogens from complex food matrices at detection limits approaching those that might be anticipated in naturally contaminated products. |
15546400 | Cytokines in cancer immunity and immunotherapy. | The concept that the immune system recognizes and controls cancer was first postulated over a century ago, and cancer immunity has continued to be vigorously debated and experimentally tested. Mounting evidence in humans and mice supports the involvement of cytokines in tumor initiation, growth, and metastasis. The idea that the immune system detects stressed, transformed, and frankly malignant cells underpins much of the excitement currently surrounding new cytokine therapies in cancer treatment. In this review, we define the contrasting roles that cytokines play in promoting tumor immunity, inflammation, and carcinogenesis. We also discuss the more promising aspects of clinical cytokine use in cancer patients. |
15546399 | The role of cytokine DNAs as vaccine adjuvants for optimizing cellular immune responses. | Cytokines represent a diverse group of immunologic effector and regulatory proteins that are critical components of the host response to invading pathogens. They have also been utilized as adjuvants to enhance immune responses to vaccines. In particular, plasmid cytokines have been studied extensively as candidate adjuvants for DNA vaccines in preclinical models and are now entering early-phase clinical trials. Here, we review recent advances in our understanding of cytokine biology, T-lymphocyte differentiation, and potential applications of plasmid cytokines in the rational design of improved vaccines. |
15546398 | Is targeting Toll-like receptors and their signaling pathway a useful therapeutic approach to modulating cytokine-driven inflammation? | Cytokine-driven inflammation and tissue destruction is a common theme of chronic inflammatory diseases such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, chronic obstructive pulmonary disease, and atherosclerosis. Research over the last two decades demonstrated the importance of cytokines that are not only expressed chronically but also are capable of signaling at sites of chronic inflammation. Cytokines thus regulate major pathological processes that include inflammation, angiogenesis, tissue remodeling, and fibrosis. This research led to the identification of key cytokines involved in these processes, two of which, tumor necrosis factor-alpha and interleukin-1, have also been successfully targeted in the clinic. However, what triggers and maintains cytokine gene expression in chronic inflammation remains a mystery. In this article, we review current progress in the understanding of cytokine-driven inflammation and discuss current evidence implicating Toll-like receptors (TLRs), recently identified as the receptors recognizing self versus non-self molecular patterns, in the regulation of cytokine-driven inflammation. Whether targeting TLRs and their downstream signaling pathway will prove to be a successful approach for the treatment of these devastating diseases remains to be determined. |
15546397 | The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation. | Discovery and characterization of the tumor necrosis factor (TNF) family member B-lymphocyte stimulator (BLyS) has opened a novel chapter in the role of TNF family members in the homeostatic control of lymphocyte populations. BLyS and its sister cytokine APRIL (a proliferation-inducing ligand) act primarily as soluble trimers and serve to regulate the steady-state numbers of nearly all B-cell compartments. This homeostatic regulation is accomplished through the regulation of B-cell production rates, selection thresholds, and lifespan. Differential expression of the three BLyS receptors during differentiation and activation provides related yet distinct homeostatic niches for follicular, marginal zone, and memory B-cell subsets. |
15546396 | Interleukin-10 in viral diseases and cancer: exiting the labyrinth? | Interleukin-10 (IL-10) is unique among cytokines, as it is considered both as a potent immunostimulatory and immunosuppressive factor. This complex biology has been particularly challenging when trying to define the useful or harmful role of IL-10 in chronic viral diseases and cancer. In the present review, we emphasize how these multiple roles define IL-10 as an adaptive molecule, constantly tuning the host response against dangerous and resourceful pathogens. |
15546395 | Signaling pathways in Th2 development. | In order for an immune response to be successful, it must be of the appropriate type and magnitude. Intracellular residing pathogens require a cell-mediated immune response, whereas extracellular pathogens evoke a humoral immune response. T-helper (Th) cells orchestrate the immune response and are divided into two subsets, Th1 and Th2 cells. Here, we discuss the mechanisms of Th2 development with a focus on signal transduction pathways that influence Th2 differentiation. |
15546394 | Opposing roles for IL-13 and IL-13 receptor alpha 2 in health and disease. | Interleukin (IL)-13 is a key inducer of several type-2 cytokine-dependent pathologies. It regulates inflammation, mucus production, tissue remodeling, and fibrosis. Consequently, it has become an important therapeutic target for a number of debilitating illnesses, including asthma, idiopathic pulmonary fibrosis, ulcerative colitis, as well as several other diseases in which IL-13 is believed to be overproduced. In the murine model of schistosomiasis, IL-13 has emerged as a central mediator of chronic infection-induced liver pathology. Although IL-4, IL-5, IL-10, and IL-13 each regulate distinct aspects of the granulomatous inflammatory response, IL-13 was identified as the primary mediator of liver fibrosis. Thus, elucidating the mechanisms that regulate the production and function of IL-13 has become an intensive area of research. IL-13 signaling is mediated by the type-2 IL-4 receptor, which consists of the IL-4R alpha and IL-13R alpha 1 chains. However, another IL-13-binding chain, IL-13R alpha 2, appears to strongly inhibit the activity of IL-13. Animals deficient in IL-13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection. They also develop severe IL-13-dependent fibrosis and portal hypertension and quickly succumb to the infection. Here, we summarize findings from the schistosomiasis model, which illustrate opposing activities for IL-13 and IL-13R alpha 2 in health and disease. |
15546393 | Interleukin-13 in asthma pathogenesis. | Bronchial asthma is a complex disorder that is thought to arise as a result of aberrant T-lymphocyte responses to noninfectious environmental antigens. In particular, the symptoms of asthma are closely associated with the presence of activated T-helper 2 cell (Th2) cytokine-producing cells [interleukin (IL)-4, IL-5, IL-9, and IL-13] in the airway wall. Although each of the Th2 cytokines likely contributes to the overall immune response directed against environmental antigens, a substantial body of evidence points to a singular role for IL-13 in the regulation of the allergic diathesis. Initial studies in animal models of disease provided compelling evidence that IL-13, independently of other Th2 cytokines, was both necessary and sufficient to induce all features of allergic asthma. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene with asthma and related traits. With the preponderance of evidence continuing to support a pivotal role for IL-13 in allergic disorders, attention is now turned toward understanding the mechanisms by which this cytokine may mediate the pathophysiological features of allergic disease. The emerging paradigm is that IL-13 induces features of the allergic response via a complex array of actions on resident airway cells rather than through traditional effector pathways involving eosinophils and immunoglobulin E-mediated events. In light of these recent developments, this review explores our current understanding of the singular role of IL-13 in the pathogenesis of asthma, with a particular focus on new insights into the mechanisms by which IL-13 mediates various features of asthma. |
15546392 | Issues in T-helper 1 development--resolved and unresolved. | T-helper 1 cell (Th1) development participates in immunity to many pathogens in part by providing a source of interferon (IFN)-gamma that contributes numerous protective effects. The process of Th1 development involves signals provided by antigen-presenting cells and cytokines produced in response to pathogens, with IFN-gamma itself, interleukin (IL)-12, and IL-18 each promoting the process in some way. Despite the rapid progress into mechanisms of Th1 development in recent years, there are still a number of important unresolved issues in this area. The precise sequence of effector and cellular mechanisms represents a relatively recent avenue of research but is still the subject of current debate, as is the basis of mechanisms that may stabilize a Th1 response. Another unresolved issue is the role of type I IFNs in substituting for IL-12-mediated activation of signal transducer and activator of transcription 4 (Stat4) and induction of IFN-gamma in either murine or human T cells. It is now clear that Th1 cells acquire the property of being capable of nonantigen-dependent activation through the coordinate signaling of IL-12 and IL-18, but the precise order of intracellular signaling events and the uniqueness of this pathway's reliance on the p38 mitogen-activated protein kinase (MAPK) pathway are still issues in need of resolution. Finally, the process of verifying the effects of Stat4 mutations on functional responses has led to the recognition of an unexpected action of the STAT N-domain that may apply generally to other STAT proteins as well. None of these areas is static or resolved fully, and they likely will remain topics of rapid progress. |
15546391 | Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. | Produced in response to a variety of pathogenic organisms, interleukin (IL)-12 and IL-23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses. These dimeric cytokines share a subunit, designated p40, and bind to a common receptor chain, IL-12R beta 1. The receptor for IL-12 is composed of IL-12R beta 1 and IL-12R beta 2, whereas IL-23 binds to a receptor composed of IL-12R beta 1 and IL-23R. Both cytokines activate the Janus kinases Tyk2 and Jak2, the transcription factor signal transducer and activator of transcription 4 (STAT4), as well as other STATs. A major action of IL-12 is to promote the differentiation of naive CD4+ T cells into T-helper (Th) 1 cells, which produce interferon (IFN)-gamma, and deficiency of IL-12, IL-12R subunits or STAT4 is similar in many respects. In contrast, IL-23 promotes end-stage inflammation. Targeting IL-12, IL-23, and their downstream signaling elements would therefore be logical strategies for the treatment of immune-mediated diseases. |
15546390 | Induction of allergic inflammation by interleukin-18 in experimental animal models. | Interleukin-18 (IL-18) has been regarded as a proinflammatory cytokine because of its potent interferon-gamma-inducing activity. However, mutant mice that release excess amounts of IL-18 spontaneously develop pruritic chronic dermatitis-like atopic dermatitis (AD), suggesting the importance of IL-18 for the development of AD. Intriguingly, depletion of il-18 but not stat6, an essential transcriptional factor for IL-4 signaling, rescues the mice from AD, indicating IL-18-dependent, T-helper 2 (Th2) cell-independent AD. This type of AD is classified as innate-type allergy in contrast to Th2 cell-dependent ordinary allergy. Consistent with the previous studies, mice transferred with antigen-specific Th1 cells exhibit no airway hyperresponsiveness and respiratory eosinophilic inflammation after challenge with antigen alone. However, they suffer from asthma upon challenge with antigen plus IL-18, with comparable levels of both the alterations as in those transferred with Th2 cells following challenge with antigen. The former type of asthma is categorized as Th1-associated allergy. Therefore, it is definitely necessary to evaluate whether individual allergic disorders involve either of these IL-18-mediated pathways or a Th2-mediated one. |
15546389 | The role of IL-27 in the development of T-cell responses during parasitic infections. | The recognition that CD4+ T-cell responses could be divided into at least two functional subsets either dominated by production of interferon (IFN)-gamma and associated with cell-mediated immunity (Th1) or characterized by production of interleukin (IL)-4 and IL-5 and associated with humoral immunity (Th2) provided a basis to understand the role of T cells in resistance or susceptibility to different types of pathogens. As a consequence, many studies have focused on the identification of cytokines that influence these events. For example, the development of Th1-type responses is largely dependent on IL-12. However, other cytokines also affect this process, and initial studies revealed that IL-27, a cytokine with close structural and functional similarity to IL-12, can promote Th1 responses required for immunity to Leishmania major. Subsequent work with IL-27R (WSX-1)-deficient mice infected with Toxoplasma gondii or Trypanosoma cruzi revealed that the IL-27/IL-27R system can act as a negative regulator of inflammatory T-cell responses. The aim of this review is to discuss recent studies from these laboratories on the role of IL-27 in immunity to parasitic infections in the context of previous work and to highlight the pleiotropic effects of the IL-27/IL-27R system in the development and regulation of Th1 and Th2 responses. |
15546388 | IL-12 and IL-23: master regulators of innate and adaptive immunity. | Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell-derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)-23, a new member of the IL-12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL-12 and IL-23 promote two distinct immunological pathways that have separate but complementary functions. IL-12 is required for antimicrobial responses to intracellular pathogens, whereas IL-23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression. |
15546387 | Biology of IL-21 and the IL-21 receptor. | Interleukin-21 (IL-21) is the newest member of the common gamma-chain family of cytokines, which includes IL-2, IL-4, IL-7, IL-9, IL-13, and IL-15. Its private receptor, IL-21R, has been shown to activate the Janus kinase/signal transducers and activators of transcription signaling pathway upon ligand binding. Initial studies have demonstrated that IL-21 has pleiotropic effects on the proliferation, differentiation, and effector functions of B, T, natural killer, and dendritic cells. More recently, the potential therapeutic capacity of IL-21 in the treatment of cancers has been widely investigated. The biological role of IL-21 in the immune system is complex, as IL-21 has been shown to have the ability to both promote and inhibit immune responses. Overall, the current data point to IL-21 being a novel immunomodulatory cytokine, whose regulation of any given immune response is highly dependent on the surrounding environmental context. |
15546386 | Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. | In this review, we discuss the role of cytokines and their signaling pathways in immunodeficiency. We focus primarily on severe combined immunodeficiency (SCID) diseases as the most severe forms of primary immunodeficiencies, reviewing the different genetic causes of these diseases. We focus in particular on the range of forms of SCID that result from defects in cytokine-signaling pathways. The most common form of SCID, X-linked SCID, results from mutations in the common cytokine receptor gamma-chain, which is shared by the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21, underscoring that X-linked SCID is indeed a disease of defective cytokine signaling. We also review the signaling pathways used by these cytokines and the phenotypes in humans and mice with defects in the cytokines or signaling pathways. We also briefly discuss other cytokines, such as interferon-gamma and IL-12, where mutations in the ligand or receptor or signaling components also cause clinical disease in humans. |
15546385 | Lymphotoxin and LIGHT signaling pathways and target genes. | Lymphotoxins (LT alpha and LT beta), LIGHT [homologous to LT, inducible expression, competes with herpes simplex virus (HSV) glycoprotein D for HSV entry mediator (HVEM), a receptor expressed on T lymphocytes], tumor necrosis factor (TNF), and their specific receptors LT beta R, HVEM, and TNF receptor 1 (TNFR1) and TNFR2, form the immediate family of the larger TNF superfamily. These cytokines establish a critical communication system required for the development of secondary lymphoid tissues; however, knowledge of the target genes activated by these signaling pathways is limited. Target genes regulated by the LT alpha beta-LT beta R pathway include the tissue-organizing chemokines, CXCL13, CCL19, and CCL21, which establish cytokine circuits that regulate LT expression on lymphocytes, leading to organized lymphoid tissue. Infectious disease models have revealed that LT alpha beta pathways are also important for innate and adaptive immune responses involved in host defense. Here, regulation of interferon-beta by LT beta R and TNFR signaling may play a crucial role in certain viral infections. Regulation of autoimmune regulator in the thymus via LT beta R implicates LT/LIGHT involvement in central tolerance. Dysregulated expression of LIGHT overrides peripheral tolerance leading to T-cell-driven autoimmune disease. Blockade of TNF/LT/LIGHT pathways as an intervention in controlling autoimmune diseases is attractive, but such therapy may have risks. Thus, identifying and understanding the target genes may offer an opportunity to fine-tune inhibitory interventions. |
15546384 | The role of type I interferons in non-viral infections. | For a long time, the family of type I interferons (IFN-alpha/beta) has received little attention outside the fields of virology and tumor immunology. In recent years, IFN-alpha/beta regained the interest of immunologists, due to the phenotypic and functional characterization of IFN-alpha/beta-producing cells, the definition of novel immunomodulatory functions and signaling pathways of IFN-alpha/beta, and the observation that IFN-alpha/beta not only exerts antiviral effects but is also relevant for the pathogenesis or control of certain bacterial and protozoan infections. This review summarizes the current knowledge on the production and function of IFN-alpha/beta during non-viral infections in vitro and in vivo. |
15546383 | Interferons, interferon-like cytokines, and their receptors. | Recombinant interferon-alpha (IFN-alpha) was approved by regulatory agencies in many countries in 1986. As the first biotherapeutic approved, IFN-alpha paved the way for the development of many other cytokines and growth factors. Nevertheless, understanding the functions of the multitude of human IFNs and IFN-like cytokines has just touched the surface. This review summarizes the history of the purification of human IFNs and the key aspects of our current state of knowledge of human IFN genes, proteins, and receptors. All the known IFNs and IFN-like cytokines are described [IFN-alpha, IFN-beta, IFN-epsilon, IFN-kappa, IFN-omega, IFN-delta, IFN-tau, IFN-gamma, limitin, interleukin-28A (IL-28A), IL-28B, and IL-29] as well as their receptors and signal transduction pathways. The biological activities and clinical applications of the proteins are discussed. An extensive section on the evolution of these molecules provides some new insights into the development of these proteins as major elements of innate immunity. The overall structure of the IFNs is put into perspective in relation to their receptors and functions. |
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