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Effects of upper dorsal sympathectomy on esophageal motility in humans. To evaluate the role of the sympathetic nervous system in modulating esophageal motility, esophageal manometry was performed on two groups of patients who underwent upper dorsal sympathectomy for relief of palmar hyperhydrosis. In six patients sympathectomy was done by the supraclavicular approach, with removal of T2 and T3 ganglia. Manometry was performed before the operation and three weeks after it. In seven other patients sympathectomy was done by the axillary approach, with removal of T2-T4 ganglia. Manometry in this group was performed 28.4 +/- 22.4 months after the operation. Fifteen individuals with an intact sympathetic system served as controls. Manometric parameters evaluated were esophageal contraction amplitude and duration and lower esophageal sphincter pressure. The difference between the results obtained in the pre- and postoperative periods in the first group was not statistically significant. The differences between the two patient groups and between the patient groups and the control group were not statistically significant either. We conclude that upper dorsal sympathectomy does not affect esophageal motility in man.
Semantic feature production norms for a large set of objects and events. Semantic features produced by speakers of a language when given a word corresponding to a concept have provided insight into numerous behavioral phenomena concerning semantic representation in language-impaired and -unimpaired speakers. A number of theories concerning the organization of semantic memory have used features as their starting point. Here, we provide a set of feature norms collected from approximately 280 participants for a total of 456 words (169 nouns referring to objects, 71 nouns referring to events, and 216 verbs referring to events). Whereas a number of feature norms for object concepts already exist, we provide the first set of norms for event concepts. We have used these norms (for both objects and events) in research addressing questions concerning the similarities and differences between the semantic representation of objects and events and in research concerning the interface between semantics and syntax, given that events can be expressed in language as nouns or verbs. Some of this research is summarized here. These norms may be downloaded from www.psychonomic.org/archive.
In vitro and in vivo effects of tachykinins on immune cell function in guinea pig airways. The effects of sensory neuropeptides substance P (SP) and neurokinin A (NKA) on immune cell recruitment and macrophage activation were determined. Guinea pigs exposed to capsaicin aerosol exhibited eosinophil and neutrophil influx into their bronchoalveolar lavage (BAL) fluid 24 h after treatment; SP aerosol elicited eosinophil influx, whereas NKA aerosol exposure caused neutrophil recruitment. Inhalation of capsaicin, NKA or SP aerosols also enhanced superoxide production induced by zymosan in cultured alveolar macrophages. Incubation of alveolar macrophages with SP or NKA in culture for the same time (24 h) did not potentiate the response to zymosan. Hence, tachykinin-mediated airway effects may not be the result of direct actions on target cells but rather involve alternate mechanisms and mediators which do not necessarily reflect in vitro data.
Development of the Eating Choices Index (ECI): a four-item index to measure healthiness of diet. Current indices of diet quality generally include intakes of specific foods or nutrients. We sought to develop an index that discriminates healthy and unhealthy eating choices for use in large surveys as a short questionnaire and as a measure in existing studies with adequate dietary data. The Eating Choices Index (ECI) score included four components: (i) consumption of breakfast, (ii) consumption of two portions of fruit per day, (iii) type of milk consumed and (iv) type of bread consumed, each providing a score from 1 to 5. In analysis of 5 d food records, the ECI score was examined in relation to macronutrients, fibre, vitamin C, Fe, Ca and folate using Pearson correlations. Variation with sex, BMI, socio-economic status, marital status, smoking status and physical activity were also investigated. Medical Research Council National Survey of Health and Development. Individuals (n 2256) aged 43 years. The ECI score (mean 12·3 (sd 3·5)) was significantly positively associated with protein, carbohydrate, fibre, vitamin C, Fe, Ca and folate (r = 0·2-0·5; P < 0·001) and significantly negatively associated with fat intake (r = -0·2; P < 0·001); ECI scores were not correlated with total energy intake. Individuals with a lower ECI score were more likely to be men (P < 0·001), overweight or obese (P < 0·001), have lower socio-economic status (P < 0·001), smoke more (P < 0·001) and be less physically active (P < 0·001). ECI scores correlated with nutrient profiles consistent with a healthy diet. It provides a simple method to rank diet healthiness in large observational studies.
Instantaneous Decrease in Left Ventricular Afterload during Transcatheter Aortic Valve Implantation Results in Immediate Changes in Left Ventricular Strain. Severe aortic stenosis causes chronic increased afterload on the left ventricle (LV) resulting in myocardial hypertrophy and ultimately dysfunction if left untreated. Transcatheter aortic valve implantation (TAVI) immediately decreases the afterload on the LV by reducing the pressure gradient through the aortic valve. In our study, we aim to evaluate immediate changes in LV mechanics using intra-procedural transesophageal echocardiography (TEE) to assess circumferential and radial strain via speckle tracking. Intra-operative TEE was performed during TAVI for 53 patients (mean age 84 ± 8 years). Two-dimensional images in the transgastric view were acquired at the level of the papillary muscle. Circumferential and radial strain was calculated using speckle tracking with Philips Qlab software. Global LV afterload was measured by calculating valvulo-arterial impedance (Zva). Immediately post-TAVI, there was a change in both radial strain rate (Pre: 0.73 ± 0.04 vs. Post: 0.88 ± 0.04 per second, P < 0.001) and circumferential strain rate (-0.53 ± 0.04 (pre) vs. -0.74 ± 0.04 (post) per second, P < 0.001). There was also an immediate improvement in circumferential global strain parameters (-14.5 ± 5% (pre) vs. -16.0 ± 4.7% (post), P < 0.05), whereas there was no significant change seen in global radial strain (15.6 ± 0.8% (pre) vs. 15.2 ± 0.9% (post), P = 0.69). No significant change was seen in LV ejection fraction (51.5 ± 14.2% (pre) vs. 52.1 ± 14.0% (post), P = 0.77). Speckle tracking using TEE images is feasible and identifies significant improvements in LV strain and strain rate immediately following TAVI that is not detected by conventional measure of LV function.
Large-scale inhomogeneities may improve the cosmic concordance of supernovae. We reanalyze the supernova data from the Union Compilation including the weak-lensing effects caused by inhomogeneities. We compute the lensing probability distribution function for each background solution described by the parameters Ω(M), Ω(Λ), and w in the presence of inhomogeneities, approximately modeled with a single-mass population of halos. We then perform a likelihood analysis in the parameter space of Friedmann-Lemaître-Robertson-Walker models and compare our results with the standard approach. We find that the inclusion of lensing can move the best-fit model significantly towards the cosmic concordance of the flat Lambda-Cold Dark Matter model, improving the agreement with the constraints coming from the cosmic microwave background and baryon acoustic oscillations.
Occupational Exposure to Respirable Dust, Respirable Crystalline Silica and Diesel Engine Exhaust Emissions in the London Tunnelling Environment. Personal 8-h shift exposure to respirable dust, diesel engine exhaust emissions (DEEE) (as respirable elemental carbon), and respirable crystalline silica of workers involved in constructing an underground metro railway tunnel was assessed. Black carbon (BC) concentrations were also assessed using a MicroAeth AE51. During sprayed concrete lining (SCL) activities in the tunnel, the geometric mean (GM) respirable dust exposure level was 0.91mg m(-3), with the highest exposure measured on a back-up sprayer (3.20mg m(-3)). The GM respirable crystalline silica concentration for SCL workers was 0.03mg m(-3), with the highest measurement also for the back-up sprayer (0.24mg m(-3)). During tunnel boring machine (TBM) activities, the GM respirable dust concentration was 0.54mg m(-3). The GM respirable elemental carbon concentration for all the TBM operators was 18 µg m(-3); with the highest concentration measured on a segment lifter. The BC concentrations were higher in the SCL environment in comparison to the TBM environment (daily GM 18-54 µg m(-3) versus 3-6 µg m(-3)). This small-scale monitoring campaign provides additional personal data on exposures experienced by underground tunnel construction workers.
Abortion, autonomy and prenatal diagnosis. The principle of patient self-determination has assumed central importance in British medical law in recent years. This article considers whether this increasingly strong commitment to patient autonomy has any resonance for abortion law. In particular, this article explores the possibility that the priority currently accorded to autonomous decision making may be in tension with the Abortion Act's requirement that a woman's reasons for seeking to terminate her pregnancy be judged acceptable by two medical practitioners. Moreover, interest in the moral legitimacy of a woman's reasons for wanting to terminate her pregnancy seems to be intensifying. Concerns arising from the increasing availability of precise prenatal tests have led to suggestions that access to abortion should be further restricted in order to prevent the cavalier use of abortion for reasons that might seem trivial or misguided. Using abortion following prenatal diagnosis as an example, this article considers whether it is anomalous for the common law's vigorous protection of an individual's freedom to make irrational or morally objectionable choices about his or her medical treatment to coexist with demands for further restriction of the acceptable grounds for abortion.
Effects of signal sequences and folding accessory proteins on extracellular expression of carboxypeptidase Y in recombinant Saccharomyces cerevisiae. Carboxypeptidase Y (CPY) is a yeast vacuolar protease with useful applications including C-terminal sequencing of peptides and terminal modification of target proteins. To overexpress CPY with the pro-sequence (proCPY) encoded by the Saccharomyces cerevisiae PRC1 gene in recombinant S. cerevisiae, the proCPY gene was combined with the gene coding for a signal sequence of S. cerevisiae mating factor α (MFα), invertase (SUC2), or Kluyveromyces marxianus inulinase (INU1). Among the three constructs, the MFα signal sequence gave the best specific activity of extracellular CPY. To enhance the CPY expression level, folding accessory proteins of Kar2p, Pdi1p and Ero1p located in the S. cerevisiae endoplasmic reticulum were expressed individually and combinatorially. A single expression of Kar2p led to a 28 % enhancement in extracellular CPY activity, relative to the control strain of S. cerevisiae CEN.PK2-1D/p426Gal1-MFαCPY. Coexpression of Kar2p, Pdi1p and Ero1p gave a synergistic effect on CPY expression, of which activity was 1.7 times higher than that of the control strain. This work showed that engineering of signal sequences and protein-folding proteins would be helpful to overexpress yeast proteins of interest.
Indications of breast preserving surgery without radiation. Breast preserving surgery has become a standard therapy for early breast cancer. Breast conserving therapy with radiation has been recognized as a standard strategy, because of the low incidence of local failure and minimal postoperative deformity compared with that of quadrantectomy without radiation. Among cases treated with breast preserving surgery, surgical resection alone may be sufficient for local control. We have experienced 11 cases of local failure from 108 cases who were treated with quadrantectomy. The ability of local control with quadrantectomy was analized. Among 11 cases with local failure, 3 cases had an apparently small resection area, and 3 cases had multiple tumors. In the other five cases, intraductal component was observed in primary tumor, 2 out of the five cases had EIC, and 3 of the five cases relapsed around the areola. After close analysis and modification of indication criteria, we could reduce the recurrence rate of late 66 cases to less than 2%. For local failure cases, seven cases were treated with total mastectomy, 4 with partial mastectomy, and no further relapse resulted. Our data indicated that quadrantectomy is effective and safe for local control if its indication is carefully determined.
An allelic variant of the 6A gene for human surfactant protein A. Two human surfactant protein A (SP-A) cDNA clones (1A and 6A) encoding human SP-A genes have previously been identified and characterized by our laboratory. The present study was undertaken to assess potential heterogeneity in the 6A locus among specimens from white adults and infants with respiratory distress syndrome (RDS) as well as black adults. The entire and/or a portion of the published SP-A gene was amplified from different genomic DNAs using the polymerase chain reaction (PCR), cloned, and sequenced. The data revealed the presence of a variant (6A1) of the 6A gene with characteristics of the 1A gene. The most notable changes were a one-base change in exon 1 and an 11-base insertion in the 3' untranslated region (3'UT). Both changes are found in 1A gene. Analysis of the reverse-transcribed (RT) PCR products from lung mRNAs using 6A specific oligos showed that the 6A1 variant is transcribed. The prevalence of each SP-A allele was then assessed in a group of 20 Nigerian Blacks and 43 Whites (26 infants with RDS and 17 adults). Although the data did not reach statistical significance, a trend was shown where the 6A/6A genotype appeared with higher frequency in Blacks.
Reward circuitry function in autism during face anticipation and outcomes. The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary outcomes, participants with ASDs showed hyperactivation in left midfrontal and anterior cingulate gyrus. Groups did not differ in nucleus accumbens responses to faces. The ASD group demonstrated hyperactivation in bilateral amygdala during face anticipation that predicted social symptom severity and in bilateral insular cortex during face outcomes. These results add to the growing body of evidence that autism is characterized by altered functioning of reward circuitry. Additionally, atypical amygdala activation during the processing of social rewards may contribute to the development or expression of autistic features.
[Accelerated hyperfractionated radiotherapy combined with simultaneous chemotherapy in locally advanced pharyngeal and oral carcinomas]. To evaluate the feasibility and effectiveness of a concurrent radio-chemotherapy regimen for locally advanced carcinomas of the pharynx and floor of the mouth. Since January 1990, 97 patients with locally advanced carcinomas of the naso-, oro-, hypopharynx and the oral cavity in UICC stages III and IV were treated according to an accelerated hyperfractionated radiotherapy schedule with concurrent chemotherapy. The primary tumor and positive lymph nodes received a total dose of 72 Gy in 6 weeks. In the first 3 weeks, large fields were irradiated 5 times per week with 2 Gy per fraction. Thereafter, treatment was accelerated, giving 2 daily fractions of 1.4 Gy with minimal intervals of 6 hours. Target volumes were reduced after 49.6 and 59.4 Gy, excluding clinically uninvolved lymph node regions of low and high risk. On day 1, 350 mg/m2 5-FU and 50 mg/m2 folinic acid were given as intravenous bolus followed by continuous infusion of 350 mg/m2 5-FU and 100 mg/m2 folinic acid, days 1 to 5. 10 mg/m2 mitomycin C was given on day 5 and 36 of the treatment. Salvage surgery was offered for residual disease 5 to 6 weeks after the end of radiotherapy. 70 male, 27 female; age: 27 to 81 years; T2/T3/T4: 7/30/60; N0/N1/N2/N3: 20/18/53/6; nasopharynx/oropharynx/hypopharynx/oral cavity: 16/33/36/12. Median follow-up is 26 months. Overall survival and recurrence-free survival at 2 years were Overall survival and recurrence-free survival at 2 years were 68 +/- 5% and 74 +/- 5%. Multivariate analysis revealed a significant influence of the geometric mean neck node diameter or the N-stage on loco-regional control and survival. T-stage, tumor volume, or tumor localisation did not become significant. Acute toxicity of this schedule was acceptable but required optimised supportive care. Treatment related grade 4+ late toxicity of mucosa, soft tissue and bone were observed with a cumulative frequency of 13% at 2 years. Two patients died during a phase of severe leuko- or thrombocytopenia. This phase I to II trial shows favourable results using an intensified treatment radio-chemotherapy protocol. A phase III study is now planned, comparing this regime with an accelerated hyperfractionated radio-therapy alone to an increased total dose of 77.6 Gy.
Rethinking measurement of neighborhood in the context of health research. Systematic social observations have been gaining increasing recognition in neighborhood and health research as a way of measuring neighborhood attributes hypothesized to affect residents' well-being. Despite the growing popularity of this methodology, there has not been a critical discussion of potential shortcomings of this approach. This paper reviews some of the challenges and limitations in the systematic social observations methodology. We especially differentiate between limitations related to the methodology itself and challenges the approach presents for researchers in the field. We conclude by offering directions for future research utilizing this technique.
Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data. We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation.
Image generation and handedness: is the hemi-imagery method valid for studying the hemisphere imagery generation process? The validity of the proposal by Shuren et al. (Neuropsychologia, 1996, 34, 491-492) that there is some relation between handedness and hemi-imagers was investigated by means of the hemi-imagery test. Two-hundred and two subjects were asked to image one-half of an object and to report which half (left or right) they saw. The analyses, based on criteria identical to those of Shuren et al., did not replicate their findings that subjects were more likely to image the right half of objects than the left, and that right handers are right hemi-imagers. Rather, our subjects were more inclined to image the left half than the right, and no relation between handedness score and right hemi-imagers was found. It is suggested that the reading habits of the different cultures of the groups of subjects may account for this discrepancy.
Remodeling of endosomes during lysosome biogenesis involves 'kiss and run' fusion events regulated by rab5. The small GTPase rab5 has been shown to play key roles in the function of both endocytic and phagocytic organelles. Although these organelles share several additional common features, different processes have been proposed to explain their biogenesis. In the present study, we provide evidence that lysosome biogenesis involves mechanisms similar to those previously described for the formation of phagolysosomes. Transient interactions ('kiss and run') between endocytic organelles are shown to occur during lysosome biogenesis. These interactions are regulated initially by the GTPase activity of rab5, as demonstrated by the loss of size-selective fusion between endosomes in cells expressing a GTPase-deficient mutant of rab5. Endocytic compartments in these cells sequentially display properties of early and late endosomes. However, the formation of lysosomes and the sorting of endocytic solute materials to small electron dense vacuoles are not affected by the rab5 mutation. Together, our results indicate that endosome maturation occurs during the early part of lysosome biogenesis. This process involves transient fusion events regulated, in part, by the small GTPase rab5.
Foot lesions in diabetic patients: pathogenesis and management. Vascular disease is the major factor in the development of many lesions in diabetics, although the independent role of neuropathy has been increasingly recognized. The major problem in assessment is to decide the severity of ischaemia and neuropathy present in a particular patient. Healing after local surgery can be expected in those lesions which are painless, and peripheral (that is, are situated on the toes or forefoot), especially if the ankle pulses are present. Operation must provide adequate drainage and wound care must be meticulous. The problem of prevention of recurrences remains unsolved, but recurrences can probably be delayed or prevented by a careful follow-up.
Combined endovascular and open repair of a penetrating innominate artery and tracheal injury. Endovascular therapy affords the opportunity to decrease surgical morbidity and improve operative planning in complex penetrating injuries of the chest. In this case report we describe a hemodynamically stable patient with a single gunshot wound to the base of the neck (zone I), with combined vascular and tracheal injuries. We present a novel approach to the repair of this type of injury using combined endovascular and open techniques.
Atraumatic restorative treatment with resin-modified glass ionomer material: short-term results of a pilot study. The aim of this study was to assess the feasibility of the resin-modified glass ionomer (RMGI) material in atraumatic restorative treatment (ART) approach and compare RMGI with the high-strength traditional glass ionomer cement (GIC) in permanent teeth with one or more surface-carious cavities. This study was conducted in a village school in rural southeastern Anatolia, Turkey. The RMGI and GIC restorations with the ART technique were placed randomly employing a split mouth design. In addition, the ART approach was used when necessary for both primary and/or permanent teeth with no pulpal involvement and no perceived pain before treatment. Ninety-one fillings were placed on contralateral molar pairs of 37 children. Baseline and 6-month evaluation of the fillings were made with the classic ART, modified Ryge and USPHS criteria. Based on the ART criteria, 100% of RMGI and 92.4% of GIC restorations were classified as successful after 6 months, and the difference between the 2 groups was statistically significant (p=0.009). While marginal discoloration was the commonest failure in the RMGI group according to both the modified Ryge and USPHS criteria, unsatisfactory surface texture and low anatomic form were the commonly seen failures in the ART technique. Generally, for each rating system, RMGI exhibited better clinical performance than GIC in all categories, except for marginal discoloration. Results based on the 6-month evaluation show that RMGI can be an alternative material to the GIC.
Gene flow vs. pollution pressure: genetic diversity of Mytilus galloprovincialis in eastern Adriatic. Environmental pollution may modify all the evolutionary processes involved in shaping the genetic patterns of exposed populations. In order to evaluate the pollution impact on the genetic diversity of Mediterranean mussel Mytilus galloprovincialis ten populations inhabiting differently polluted sites along the eastern Adriatic coast, from pristine bays to heavily trafficked harbours, were studied. Pollution pressure was assessed through an integrated study of biological effects and responses across different levels of biological organization. Eight microsatellite markers were analysed to assess genetic diversity of investigated populations. Both the principal component analysis (PCA) of the biomarker data set as well as the biomarker response index (BRI) confirmed substantial pollution pressure at the highly polluted sites, and very low pollution exposure at the three reference sites. Very shallow genetic differentiation was found in respect to maritime distances or pollution status, and this was attributed to a high gene flow among the populations. However, populations inhabiting polluted sites exhibited higher levels of genetic diversity and evolutionary mechanisms underlying this phenomenon are discussed.
The Uganda I/CDC strain of Plasmodium malariae in Aotus lemurinus griseimembra monkeys. Two lines of the Uganda I/CDC strain of Plasmodium malariae were studied in splenectomized Aotus lemurinus griseimembra monkeys. A line initially adapted to these monkeys from an infected chimpanzee failed to produce high-level parasite counts or mosquito infection in 13 of this type of monkey during 16 linear passages. Another line, originally adapted from the chimpanzee to Aotus azarae boliviensis, after 7 linear passages in 3 different types of Aotus was then passaged to 14 splenectomized A. lemurinus griseimembra. Geometric mean maximum parasitemia in these monkeys was 18,400/mm3. Mosquito infections were readily obtained during the period just after the parasite count rose above 1,000/mm3. Anopheles freeborni, An. stephensi, An. dirus, and 2 strains of An. gambiae supported the development of the parasite to the presence of sporozoites in the salivary glands. Two attempts to transmit the strain to other splenectomized A. lemurinus griseimembra by sporozoite inoculation were unsuccessful.
[Non-Convulsive Status Epilepticus Caused by Hyponatremia in an Elderly Woman: A Case Report]. We report the case of a 67-year-old woman with non-convulsive status epilepticus (NCSE) due to hyponatremia. She had a history of psychogenic polydipsia but not epilepsy. She was admitted to our hospital with dysbulia. On admission, she was confused and disoriented (Glasgow Coma Scale: 6, E1V1M4). Magnetic resonance imaging of the brain showed no abnormalities. Laboratory test showed hyponatremia (Na<sup>+</sup> level: 115 mEq/L). The electroencephalography (EEG) showed a generalized slow wave of 5 Hz during recording. The slow wave was promptly suppressed by diazepam and levetiracetam administered intravenously and orally, respectively. After the hyponatremia was treated the seizures stopped and did not reoccur, even after cessation of the anticonvulsant drugs. The patient was discharged with no neurological deficits. Few reports have described this condition. Here we discuss the diagnosis and treatment of NCSE due to hyponatremia. (Received May 31, 2016; Accepted December 12, 2016; Published April 1, 2017).
Epidemiology of pollution-induced airway disease: urban/rural differences in East and West Germany. The prevalence of asthma and allergic disorders was assessed in 9-11 year-old children in Leipzig and Halle in East Germany, as well as in Munich, West Germany. Both East German cities are heavily polluted due to private burning of coal and industrial emissions, while Munich has low smoke emissions but heavy road traffic. All fourth grade pupils in Munich were compared with those in Leipzig and Halle. Non-specific airway disease (bronchitis), cough, and autumn/winter nasal symptoms were most prevalent in Leipzig and Halle. Hay fever and skin test reactivity to aeroallergens were higher in West Germany compared with East Germany. Furthermore, the prevalence of asthma was also higher in the West German study area. Increased skin prick test reactivity in the West explained the increased prevalence of asthma. Longitudinal analysis showed increased respiratory symptoms on days with high mean levels of sulphur dioxide and oxides of nitrogen, as well as on days with a high peak level of 10 mu respirable particles (PM10) in East Germany. The effects of these pollutants were additive. Exposure to heavy road traffic in Munich was related to decreased pulmonary function and non-specific airway symptoms, but not to allergic sensitization and asthma.
Employment after spinal cord injury: the impact of government policies in Canada. The British Columbia Paraplegic Association (BCPA) sought a research partnership to evaluate where its activities should be focused. A survey of members with disabilities of the BCPA included questions on employment and identified three priorities related to employment. These were the need for assistance in finding appropriate work, the impact of policies of government and insurance agencies, and attitudes of employers. This paper examines the social and political environment related to employment following spinal cord injury in British Columbia, Canada. There is no coherent set of goals underlying government employment and income programs in Canada. Incremental development of particular employment and income programs during the 20th century led to a patchwork of policies and programs, which deal with people differently according to the cause of their disability. Federal and provincial governments have attempted to educate employers and reduce barriers to employment of those with disabilities by focusing on anti-discrimination legislation and individual rights (e.g. the Employment Equity Act and the Canadian Human Rights Act). However, people with disabilities face non-accommodating environments, inadequate income support, lack of opportunities and little political influence which stem from an unfair distribution of societal resources, not from discrimination. Joint efforts of the BCPA and other disability organizations are likely to have the most impact on legislative changes.
Skin targeting of resveratrol utilizing solid lipid nanoparticle-engrossed gel for chemically induced irritant contact dermatitis. Irritant contact dermatitis (ICD) is a chronic and relapsing skin disease with severe eczematous lesions. Despite its growing prevalence, therapeutic treatments remain limited. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation, and increase in transepidermal water loss. An innovative dermal treatment is essential to reduce the side effects of corticosteroids. Topical resveratrol (RES), although effective for ICD, is a challenging molecule due to low solubility and poor bioavailability. The objective of this work was to build RES-loaded solid lipid nanoparticles (RES-SLNs) with skin targeting. For this purpose, RES-SLNs were prepared using the probe ultrasonication method utilizing Precirol ATO 5 and Tween 20. The RES-SLNs were evaluated for particle size, entrapment efficiency (EE), and transmission electron microscopy (TEM) studies. Further, RES-SLNs were incorporated into Carbopol gel and investigated for ex vivo skin permeation, deposition study on human cadaver skin, and finally skin irritation study on New Zealand White rabbits. It was further assessed for possible beneficial effects on ICD using BALB/c mice. RES-SLN showed mean size below 100 nm and 68-89% EE. TEM studies confirmed spherical particles in the nanometer range. An ex vivo study of RES-SLN-loaded gel exhibited controlled drug release up to 24 h; similarly, in vitro drug deposition studies showed potential of skin targeting with no skin irritation. RES-SLN gel confirmed competent suppression of ear swelling and reduction in skin water content in the BALB/c mouse model of ICD when compared to marketed gel. Thus, the formulated RES-SLN gel would be a safe and effective alternative to conventional vehicles for treatment of ICD.
[Evaluation of results of therapy with cast removable partial prosthesis. I. Significance of the residual teeth]. On the basis of results from follow-up examinations in patients with removable cast partial prostheses, the author points to injuries to the remaining teeth which are attributable above all to errors of indication, insufficient preliminary measures, and inadequate metaphylaxis.
A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells. The molecular interaction of secreted granzyme B-serglycin complexes with target cells remains undefined. Targets exposed to double-labeled granzyme B-serglycin complexes show solely the uptake of granzyme B. An in vitro model demonstrates the exchange of the granzyme from serglycin to immobilized, sulfated glycosaminoglycans. Using a combination of cell binding and internalization assays, granzyme B was found to exchange to sulfated glycosaminoglycans and, depending on the cell type, to higher affinity sites. Apoptosis induced by purified granzyme B and cytotoxic T-cells was diminished in targets with reduced cell surface glycosaminoglycan content. A mechanism of delivery is proposed entailing electrostatic transfer of granzyme B from serglycin to cell surface proteins.
A Chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis induces the expression of erythropoietin in cultured Hep3B cells. Danggui Buxue Tang (DBT), a Chinese medicinal decoction used commonly for treating women's ailments, contains Radix Astragali (RA) and Radix Angelicae Sinensis (RAS). According to Chinese medicinal theory, this decoction is to nourish the blood function; this, however, has not been demonstrated on the molecular level. In order to reveal the hematopoietic effect of this decoction, DBT was applied to cultured Hep3B human hepatocellular carcinoma cells. The treatment of DBT induced mRNA expression of erythropoietin (EPO) in a dose-dependent manner and peaked at approximately 2.5-fold induction. The secreted EPO in cultured Hep3B cells was quantified by ELISA: the treatment of DBT potentiated the effect of hypoxia-induced EPO expression in the cultured cells. In addition, the DBT-induced EPO expression could be abolished by pre-treatment with U0126, a mitogen-activated kinase inhibitor. The current results verified the hematopoietic function of this ancient herbal decoction.
Flow injection of the lock mass standard for accurate mass measurement in electrospray ionization time-of-flight mass spectrometry coupled with liquid chromatography. A method of flow injection of the lock mass for accurate mass measurement using electrospray ionization time-of-flight mass spectrometry is described. The reference compound is introduced in the chromatographic effluent via a six-port valve placed post-column, prior to the split connector. Flow injection is performed in such a way that the reference elution peak is superimposed in the total ion current and partially overlaps that of the investigated analyte, allowing independent ionization of the two compounds and thus accurate mass measurement with no ion suppression effects. Different lock mass molecules can be injected in a single analytical run to target various analytes. The performance of this methodology is demonstrated in both isocratic and gradient liquid chromatography modes. The molecular ion of the flow-injected lock mass could also be used as a reference for mass measurement of the in-source fragments of the analytes. Good mass accuracy, within 4 mDa of the theoretical values, was obtained.
Covalent protein adduct formation and protein cross-linking resulting from the maillard reaction between cyclotene and a model food protein. Covalent Maillard products of the reactions of carbonyl compounds with proteins are often described in the literature, but, until recently, evidence for their existence has been indirect. Cyclotene (2-hydroxy-3-methylcyclopent-2-enone), a common flavor compound, was incubated with a model food protein, ribonuclease, and found to cross-link the protein. Size exclusion high-performance liquid chromatrography and electrospray mass spectrometry of the early stages of the reaction provide strong evidence for covalent adducts that we believe to be intermediates in the cross-linking reaction.
Titration studies on the active sites of pig heart lipoamide dehydrogenase and yeast glutathione reductase as monitored by the charge transfer absorbance. Macroscopic pKa values associated with the influence of pH on the visible spectrum of 2-electron reduced pig heart lipoamide dehydrogenase and yeast glutathione reductase have been determined by monitoring changes in the principal flavin band near 460 nm and the charge transfer band at 540 nm. The ionization of at least three active site amino acid side chains can influence the spectra over the range of pH studied: the two nascent thiols (interchange thiol and electron transfer thiol) and the histidine residue which acts as the base catalyst in lipoamide dehydrogenase and the acid catalyst in glutathione reductase thiol-disulfide interchange reactions. These systems are analogous to, but more complex than, those in glyceraldehyde-3-phosphate dehydrogenase and papain where a single thiol and a histidine residue in a relatively apolar milieu form a thiolate-imidazolium ion pair which is favored over the thiol-imidazole prototropic tautomer. In an effort to more nearly mimic the papain titrations, the macroscopic pKa values were determined on reduced glutathione reductase which had been monoalkylated with iodoacetamide under conditions known to favor the reaction of the interchange thiol by at least 10 to 1 (Arscott, L. D., Thorpe, C., and Williams, C. H., Jr. (1981) Biochemistry 20, 1513-1520). Like papain and glyceraldehyde-3-phosphate dehydrogenase, alkylated glutathione reductase showed two macroscopic pKa values, at pH 3.7 and pH 9.1, and by analogy, these were associated primarily with the thiol and the imidazole, respectively. Results with the native enzymes depended on the wavelength monitored. Glutathione reductase had pKa values at 4.8, 7.1, and 9.2 when monitored at 540 nm and 5.1 and 8.2 when monitored at 462 nm. Lipoamide dehydrogenase had pKa values at 4.4 and 8.7 when monitored at 529 nm and 3.9, 7.0, and 9.3 when monitored at 455 nm.
Selfish sentinels in cooperative mammals. Like humans engaged in risky activities, group members of some animal societies take turns acting as sentinels. Explanations of the evolution of sentinel behavior have frequently relied on kin selection or reciprocal altruism, but recent models suggest that guarding may be an individual's optimal activity once its stomach is full if no other animal is on guard. This paper provides support for this last explanation by showing that, in groups of meerkats (Suricata suricatta), animals guard from safe sites, and solitary individuals as well as group members spend part of their time on guard. Though individuals seldom take successive guarding bouts, there is no regular rota, and the provision of food increases contributions to guarding and reduces the latency between bouts by the same individual.
Suppressor cells in the human maternal-fetal relationship. The mixed lymphocyte culture (MLC) of maternal and newborn (cord) cells is significantly weaker than that of father-newborn and control-newborn cultures. This hyporeactivity was found not to be due to an impaired function or tolerance of either the maternal or neonatal cells. We investigated the possibility that a specific, in vivo-induced suppressor cell was active in the diminished maternal-newborn reaction. Suppressor cells were found to be active in both the stimulating and responding populations in the unidirectional MLC. The removal of TG cells from the responding (maternal or newborn) population resulted in an increase of reactivity specific for the corresponding stimulating population (newborn or maternal). The suppressor activity within the stimulating population was carried out by a radiosensitive cell, which did not require proliferation to exert its effect. We suggest that the observed hyporeactivity of maternal-newborn mixed lymphocyte cultures is due to the modulation of the reaction by specific, in vivo-induced suppressor cells.
[The content of DNA, RNA and protein and the wet weight:DNA, the protein:DNA and the RNA:DNA ratio in 19 different tissues of bovine fetuses of different body weight]. In 3 groups of fetuses (n = 6 each) of cattle with a body mass of 4.18 +/- 2.1 (about 160 days old), of 9.72 +/- 0.97 (about 200 days old) and of 17.12 +/- 2.61 kg (about 230 days old) the content of DNA, RNA and protein in 19 different tissues was analysed. The wet weight:DNA-, the protein:DNA- and the RNA:DNA-ratios were calculated. The growth of the different tissues in the mentioned period of the development of the fetuses by hyperplasia and hypertrophy is discussed.
Early development of new cardiovascular risk factors in the systemic vasculitides. To analyse the frequency and predictors of new-onset cardiovascular (CV) risk factors in patients with anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and giant cell arteritis (GCA). We analysed the frequency and predictors of new-onset hypertension and/or diabetes mellitus (HTN/DM) amongst patients with AAV or GCA recruited in the Diagnostic and Classification of Vasculitis (DCVAS) study. Patients with pre-existing HTN/DM were excluded. We included 873 patients with AAV (506 GPA, 183 MPA, 184 EGPA), and 443 with GCA. Patients with GCA were more likely female (68% vs. 52%; p<0.001) and older (71.33±8.65 vs. 52.80±16.48; p<0.001) compared to patients with AAV. HTN/DM developed within 6 months of diagnosis in 9% of patients with AAV (6% in GPA, 21% in MPA, 3% in EGPA) and 6% of patients with GCA, p=0.15. Rise in creatinine/reduced glomerular filtration rate and/or anaemia (OR 3.98, 95% CI 2.09-7.59, p<0.001) and diagnosis (MPA: OR 2.42, 95%CI 1.52-3.83, p<0.001 and GCA: OR 2.12, 95%CI 1.34-3.38, p=0.001 vs. GPA) were significantly associated with the occurrence of HTN/DM after adjusting for age, sex, ethnicity, and smoking status. We developed and validated a predictive score to discriminate patients according to the risk of developing HTN/DM within 6 months from diagnosis. Despite different epidemiological and clinical characteristics, new CV risk factors occur equally in the early stages of AAV and GCA. Renal function and type of diagnosis are associated with the occurrence of HTN/DM. We developed a simple predictive score for the risk-stratification of patients.
Critical tests of the anthelmintic febantel in the horse: activity of a paste formulation alone or with a trichlorfon paste. Critical tests were carried out in 10 horses to evaluate the antiparasitic activity of febantel given alone or with trichlorfon. Paste formulations were administered intraorally at dose levels of 6 mg of febantel (active ingredient)/kg and 35 mg of trichlorfon (active ingredient)/kg. In 5 tests with febantel alone, removal of 100% was recorded for mature or immature Parascaris equorum from 2 infected horses. Strongylus vulgaris from 4 infected horses, S edentatus from 5 infected horses, and mature Oxyuris equi from 1 infected horse; and removal of 96% was recorded for small strogyles from 1 horse tested, and bots in 5 infected horses were not affected. In 5 horses treated with both compounds, removal of 100% was recorded for mature P equorum from 2 infected horses, immature P equorum from 1 infected horse, S vulgaris from 5 infected horses, Sedentatus from 5 infected horses, mature O equi from 2 infected horses, immature O equi from 1 horse tested, 2nd Gasterophilus intestin-equi from 1 infected horse, 2nd-instar C nasalis from 1 infected horse, and 3rd-instar C nasalis from 4 infected horses. Removal of 98% was recorded for small strongyles from 1 horse tested, and removal of 65% to 100% for 3rd-instar C intestinalis from 5 infected horses. In the aggregate, removal of 3rd-instar C intestinalis was 99%. Untoward effects of treatment were quite limited. Only a transient softening of feces in 1 of 5 horses given the trichlorfon paste plus the febantel paste was recorded.
[A comparison study of cognitive-behavioral therapy alone versus combination with tapered hypnotic agents in patients with chronic insomnia]. Objective: To investigate the efficacy of cognitive-behavioral therapy for insomnia (CBT-i) or combination with tapered hypnotic agents. Methods: Seventy-five patients were randomized into either CBT-i group (n=37) or combination group (n=38). The duration of treatment lasted for 8 weeks. The efficacy was evaluated by Pittsburgh sleep quality index (PSQI), Beck depression index (BDI) , Beck anxiety inventory (BAI) and sleep diary variables at baseline, middle and end of treatment. Results: (1)Compared with the results at baseline, the total scores of PSQI,BDI and BAI in both groups significantly decreased at the end of treatment: CBT-i group, PSQI (4.7±2.5) vs. (12.9±3.5); BDI (3.2±4.4) vs. (9.7±6.4); BAI (4.2±5.6) vs. (10.7±8.1); and combination group, PSQI (5.8±2.8) vs. (13.9±3.1); BDI (4.5±4.8) vs. (13.8±8.7); BAI (4.4±4.0) vs. (14.1±6.3) (all P<0.01). (2) Compared with the results at baseline, subjective sleep quality (SQ), sleep onset latency (SOL), sleep efficiency (SE), sleep disturbance (SD) and used sleep medication (USM) in PSQI in combination group significantly decreased at week 4 and 8 (all P<0.05) . The total sleep time (TST) and daytime dysfunction (DF) in PSQI significantly decreased at week 8 (both P<0.05) . (3) Compared with combination group, improvement of SOL and SE in CBT-i group was superior (both P=0.01). Conclusions: CBT-i for chronic insomnia is effective in both CBT-i alone and combination with tapered hypnotic agents. CBT-i group is superior in improving SOL and SE. Combination regimen in our study can significantly reduce the doses of medication.
Optimization of methane production in anaerobic co-digestion of poultry litter and wheat straw at different percentages of total solid and volatile solid using a developed response surface model. Poultry litter (PL) can be good feedstock for biogas production using anaerobic digestion. In this study, methane production from batch co-digestion of PL and wheat straw (WS) was investigated for two factors, i.e., total solid (2%, 5%, and 10%) and volatile solid (0, 25, and 50% of WS), constituting a 3 × 3 experimental design. The results showed that the maximum specific methane volume [197 mL (g VS)(‑1)] was achieved at 50% VS from WS at 5% TS level. It was estimated that the inhibitory threshold of free ammonia was about 289 mg L(--1), beyond which reduction of methanogenic activity by at least 54% was observed. The specific methane volume and COD removal can be expressed using two response surface models (R(2) = 0.9570 and 0.9704, respectively). Analysis of variance of the experimental results indicated that the C/N ratio was the most significant factor influencing the specific methane volume and COD removal in the co-digestion of these two materials.
The impact of the Massachusetts Managed Mental Health/Substance Abuse Program on outpatient mental health clinics. Medicaid managed care initiatives pose special challenges to outpatient providers. During the first two full years of the Massachusetts Mental Health/Substance Abuse initiative, an analysis of cost and utilization data showed that outpatient mental health utilization and expenditures dropped slightly, although far less than did expenditures and utilization for inpatient facilities. In a telephone survey of a stratified random sample of outpatient providers, they reported that access, appropriate utilization, quality of care, the severity of their clients and aftercare coordination increased, while length of stay for these clients decreased. In their clinical practices, agencies shifted toward more emphasis on group and family care and brief therapies. As organizations, they made substantial operational changes. As a result, some agencies did better, while others did worse, under this new system.
Violent behaviour from young adults and the parents of paediatric patients in the emergency department. Violence in healthcare is a significant issue and one that is increasing in prevalence globally. Nurses have been identified as the professional group at most risk, with patients the main source of this violence. The aim of this study was to describe the experiences of Australian ED nurses with episodes of patient-related violence from young adults (16-25years of age) and the parents of paediatric patients. Data analysis of semi-structured interviews led to the identification of antecedents to episodes of violence and behaviours specific to these two groups of interest. These behaviours included: "performing" and attention-seeking behaviours and violent behaviours including both verbal and physical abuse. Antecedents discussed by participants included: parental emotions and alcohol and substance abuse. Overall the results speak to a working environment where participants regularly feel unsafe. Violence in the ED is perceived to occur frequently and to such an extent that participants have become resigned to expect and accept it as part of their job. The role played by distinct groups such as young adults and the parents of paediatric patients must be acknowledged and this knowledge used along with other known risk factors to help identify patients at risk of potential violence.
Prognostic importance of plasma lipoprotein-analyses in patients with unstable coronary artery disease. The lipoprotein (Lp) pattern was analysed in patients with suspected unstable coronary artery disease (UCAD), to compare the pattern as a prognostic instrument regarding subsequent coronary events with smoking, hypertension, diabetes mellitus and with the result of an early exercise test. Included were 295 patients with UCAD. Blood samples for Lp values were obtained in the acute phase and after one year. Apolipoprotein-A1, Apolipoprotein-B (Apo-B), Lipoprotein(a) (Lp[a]) HDL-Cholesterol, Cholesterol (Chol) and Triglycerides (TG). were estimated in serum. During the 1-year follow-up coronary events (myocardial infarction, cardiac death, coronary artery by-pass surgery) occurred in 48 patients. The severity of CAD, overweight, smoking and beta-blockade influenced the Lp-pattern. Chol-, TG- and Apo-B-levels were highest in the group with a coronary event. Apo-B turned out to be the second best predictive variable in multiple regression analysis, in men. In women no such analysis was done because of very few coronary events during follow-up. Nevertheless, the exercise test variables, ST depression and pain were more predictive of coronary events than Apo-B in men.
The ontogeny of the somatotropic axis in Hereford calves from birth to one year of age and its response to administration of exogenous bovine somatotropin. Administration of exogenous bovine ST (bST) increases growth rate, feed efficiency, and carcass quality in beef cattle. The magnitude of response to bST in beef cattle is variable and related to the age of the animal. Our objective was to determine the response of the somatotropic axis, in particular IGF-I, IGFBP-2, and IGFBP-3, to bST treatment from birth to 1 yr of age. Blood samples were collected before and after a single injection of bST (500 mg) every 50 d from birth to 1 yr of age in male and female Hereford calves. Body weights and serum concentrations of ST, IGF-I, IGFBP-2, and IGFBP-3 were determined. At birth, serum concentrations of ST, IGF-I, and IGFBP-3 increased (P < 0.05) following bST treatment. From 50 to 350 d of age, average concentrations of ST and IGF-I were greater (P < 0.05) in males, whereas IGFBP-2 concentrations were greater (P < 0.05) in females. No gender differences in IGFBP-3 concentrations were observed. Following bST treatment, IGF-I increased (P < 0.05) from 50 to 350 d of age, IGFBP-2 decreased (P < 0.05) from 50 to 200 d of age, and IGFBP-3 increased (P < 0.05) at 250 d of age. At 250 d of age, baseline concentrations of IGFBP-2 decreased (P < 0.05). Due to the positive response of IGFBP-3 and decreased baseline IGFBP-2 at 250 d of age, we conclude that this is an age at which the somatotropic axis is most responsive to exogenous bST, and it therefore may be an appropriate age to begin bST treatment in beef calves to realize the positive influence of bST on BW gain, feed efficiency, and carcass composition.
NucleiNet: A convolutional encoder-decoder network for bio-image denoising. Generic and scalable data analysis procedures are highly demanded by the increasing number of multi-dimensional biomedical data. However, especially for time-lapse biological data, the high level of noise prevents for automated high-throughput analysis methods. The rapid developing of machine-learning methods and particularly deep-learning methods provide new tools and methodologies that can help in the denoising of such data. Using a convolutional encoder-decoder network, one can provide a scalable bio-image platform, called NucleiNet, to automatically segment, classify and track cell nuclei. The proposed method can achieve 0.99 F-score and 0.99 pixel-wise accuracy on C. elegans dataset, which means that over 99% of nuclei can be successfully detected with no merging nuclei found.
[Longitudinal study on the body mass index (BMI) of dialysis patients]. Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years, 43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data.
Endocrine response to acute cold exposure by lactating and non-lactating Norway rats. Plasma levels of corticosterone, prolactin and thyroxine (T4) were measured in lactating and non-lactating Norway rats at 22 degrees C and 4 degrees C. Acute cold exposure increased corticosterone secretion in all groups, although non-lactating female levels rose higher than those of mother rats. While prolactin levels are unaffected by acute cold exposure in non-lactating females, mothers with their litters had lower prolactin levels in the cold. T4 levels increased during cold exposure in lactating females, suggesting that the low T4 levels observed during lactation may not be due to lactational competition for available iodine.
Ultrastructure of mesangial type III collagen deposition in a patient with IgA nephropathy. We report a case of IgA nephropathy with focal and segmental deposition of type III collagen in mesangium, confirmed by immunohistochemical and electron microscopic methods. Tissue negative staining showed that focal and segmental fibrotic lesions in the mesangial area consisted of disarrayed or curled striated collagen fibers and striated membranous structures. Diabetes mellitus, hypertension, and advanced glomerular sclerosis were absent in this case, and mesangial cells surrounding the type III collagen showed vacuolar degeneration revealed by electron microscopy. Production of type III collagen may be the marker for phenotypic change of mesangial cells in immune-mediated glomerular diseases.
Fine needle aspiration biopsy of the penis: transitional cell carcinoma of the urinary bladder with mucinous differentiation. We report a case of transitional cell carcinoma of the urinary bladder metastatic to the penis. The diagnosis was established by fine needle aspiration biopsy (FNAB). Malignant cells showed mucinous differentiation. Ancillary studies carried out in the FNA material as well as in the primary bladder carcinoma suggested transitional cell carcinoma with mucinous differentiation. FNAB proved to be effective in diagnosing a secondary neoplasm to the penis. Mucoid differentiation of urothelial cells can be seen in FNAB specimens and might pose a problem in differential diagnosis.
Bodily communication and personality. Fifteen measures of non-verbal communication were coded from videotaped interactions between a female confederate and 18-21 year old female subjects (n = 46). Three measures of extraversion and neuroticism had previously been taken from the subjects, as was a measure of IQ. Correlation and factor analysis revealed significant relationships between certain of the variables. Extraversion was strongly associated with speaking more; a teacher's rating of neuroticism was associated with touching the self, pausing during conversation, and an absence of expressive gesture; lower IQ was associated with smiling while listening; and self-report personality questionnaire neuroticism was associated with gaze aversion.
In vivo effects of different antispasmodic drugs on the rat bladder contractions induced by topically applied KCl. The model originally proposed by Postius and Szelenyi for in vivo screening of spasmolytic compounds on the rat urinary bladder, has been modified and tested to verify its predictivity. The topically applied KCl induced reproducible contractions of the bladder that were dose dependently inhibited by i.v. administration of calcium antagonists like nifedipine, nicardipine, and verapamil. The other spasmolytics tested (oxybutynin, terodiline, flavoxate, and papaverine), showed a non-dose-related inhibition of the contractions. The in vivo potency of the calcium antagonists was related to their in vitro activity on the agonist-induced contractions of rat bladder strips, whereas the activity of the other spasmolytics appeared higher than that predicted on the basis of their in vitro efficacy. Nicardipine showed a dose-dependent inhibition of KCl-induced contractions also after oral administration, whereas oxybutynin and papaverine behaved as after i.v. administration. The described model represents, therefore, a good, quantitative, and reproducible tool of screening at the bladder level only for antispasmodic drugs endowed with strong calcium antagonistic activity.
Gamma Knife Radiosurgery in the Treatment of Brain Tumors. Stereotactic radiosurgery with the Gamma Knife produces highly localized radiobiologic effects. Typical doses range from 12 to 25 Gy at the target periphery, with higher doses within the target. Treatment generally is well tolerated. Indications for treatment include vascular malformations and primary and metastatic tumors, both benign and malignant, involving the brain. Shrinkage of treated tumors tends to be slow, and stabilization of previously expanding tumor masses occurs in the vast majority of cases. Prospective trials are now being performed to determine the proper place of this technique in managing tumors involving the brainstem and other areas of the brain.
Serum miRNAs Signature Plays an Important Role in Keloid Disease. The molecular mechanism underlying the pathogenesis of keloid is largely unknown. MicroRNA (miRNA) is a class of small regulatory RNA that has emerged as a group of posttranscriptional gene repressors, participating in diverse pathophysiological processes of skin diseases. We investigated the expression profiles of miRNAs in the sera of patients to decipher the complicated factors involved in the development of keloid disease. MiRNA expression profiling in the sera from 9 keloid patients and 7 normal controls were characterized using a miRNA microarray containing established human mature and precursor miRNA sequences. Quantitative real-time PCR was performed to confirm the expression of miRNAs. The putative targets of differentially expressed miRNAs were functionally annotated by bioinformatics. MiRNA microarray analysis identified 37 differentially expressed miRNAs (17 upregulated and 20 downregulated) in keloid patients, compared to the healthy controls. Functional annotations revealed that the targets of those differentially expressed miRNAs were enriched in signaling pathways essential for scar formation and wound healing. The expression profiling of miRNAs is altered in the keloid, providing a clue for the molecular mechanisms underlying its initiation and progression. MiRNAs may partly contribute to the etiology of keloids by affecting the critical signaling pathways relevant to keloid pathogenesis.
Difficulties with emotion regulation mediate the relationship between borderline personality disorder symptom severity and interpersonal problems. Problems with interpersonal functioning and difficulties with emotion regulation are core characteristics of borderline personality disorder (BPD). Little is known, however, about the interrelationship between these areas of dysfunction in accounting for BPD symptom severity. The present study examines a model of the relationship between difficulties with emotion regulation and interpersonal dysfunction in a community sample of adults (n = 124) with the full range of BPD symptoms. Results showed that difficulties with emotion regulation fully mediated the relationship between BPD symptom severity and interpersonal dysfunction. An alternative model indicated that interpersonal problems partially mediated the relationship between difficulties with emotion regulation and BPD symptom severity. These findings support existing theories of BPD, which propose that difficulties with emotion regulation may account for the types of interpersonal problems experienced by individuals with BPD and suggest further examination of the possibility that interpersonal dysfunction may worsen these individuals' difficulties with emotion regulation.
Assessment and 2-year follow-up of some factors associated with severity of respiratory infections in early childhood. To assess the effect of some factors on the severity of acute respiratory infection (ARI) in children. In a case control study, children with pneumonia were matched with controls who had upper respiratory infection. They were compared in respect of nutrition, household crowding and smoke pollution, and the presence of current viral respiratory infection. Both cohorts were followed up for 18-24 months to determine if there was a difference in subsequent respiratory sequelae. Primary health care-based cohorts of peri-urban township children. Forty-eight children < 3 years of age with pneumonia (index cases) were matched by age and presentation time with controls who suffered only from upper respiratory infection. All came from underprivileged communities. Index cases were selected as they presented and the study was conducted between February 1988 and June 1991. Any difference between index cases and controls in respect of the four factors listed under 'Design'. Follow-up home visits determined whether subsequent sequelae of the two grades of ARI were different. The presence of current viral infection at entry to the study was evident in 21 of those with pneumonia and 12 controls (difference between groups = 19.15%, 95% confidence intervals 0.25 - 38.05, P = 0.052). Overcrowding in the home was comparable. Index homes were occupied by a mean of 3.57 (SD 1.54) children and 5.26 (SD 4.84) adults, control homes by 3.51 (SD 1.80) children and 4.36 (SD 2.02) adults. Occupancy of the room in which the child slept was also not significantly different: index group mean 4.23 (SD 1.55) and controls 4.02 (SD 1.38) (mean difference 0.21, 95% Cl 0.378 - 0.798, P = 0.485). Correlation of bedroom crowding with young age (< 1 year) or weight-for-age centiles was not significant in either cohort (r < 0.3 in all). The prevalence of viral infection was not increased by degree of crowding in either group (P = 0.636). Domestic smoke pollution was similar: cigarette smoking occurred in 75% of index homes and 69% of control homes. Wood or coal fires were used in 19% of index and 14% of control homes. The nutritional status of both groups proved to be similar. Fifteen per cent of index children and 12% of controls had weight-for-age centiles < or = 10th centile (difference = 3.26%, 95% Cl -10.72 - 17.24, P = 0.649). Two-year home follow-up visits were completed in 75% of the index and 69% of the control group. The balance were followed up for 18 months. There was no difference between index and control children in the recurrence of respiratory symptoms (P = 0.664) or need to visit a health facility (P = 0.302). Factors shown elsewhere to contribute to the acquisition or severity of ARI could not be demonstrated as important in this study. The children with pneumonia and their matched controls with upper respiratory infections came from equally overcrowded and smoke-filled homes, had comparable nutritional status which was not markedly poor, and had an equal incidence of current viral infection. Subsequent ill-health was not found to be greater in the pneumonia group.
CDC grand rounds: childhood obesity in the United States. In the United States, childhood obesity affects approximately 12.5 million children and teens (17% of that population). Changes in obesity prevalence from the 1960s show a rapid increase in the 1980s and 1990s, when obesity prevalence among children and teens tripled, from nearly 5% to approximately 15% (Figure 1). During the past 10 years, the rapid increase in obesity has slowed and might have leveled. However, among the heaviest boys, a significant increase in obesity has been observed, with the heaviest getting even heavier. Moreover, substantial racial/ethnic disparities exist, with Hispanic boys and non-Hispanic black girls disproportionately affected by obesity (Figure 2). Also, older children and teens are more likely to be obese compared with preschoolers.
Expression of CD95 ligand in melanocytic lesions as a diagnostic marker. CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on target cells. It has recently been reported that melanoma cells in vivo express a significant amount of CD95L, thereby being immediately able to kill CD95-bearing immunocompetent cells specific for cancer antigens, which infiltrate the lesions. In this study, we employed immunohistochemistry using an antibody directed against CD95L to investigate at which stage the melanoma CD95L expression is turned on. Skin biopsies of 49 lesions from 46 patients were assessed. These included benign and dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level 2 or 3), advance-phase melanomas (Clark's level 4 or 5) and lymph node metastases. CD95L was expressed in all of the advance-phase melanomas as well as lymph node metastases of cutaneous origin, whereas neither melanoma in situ, benign naevi nor dysplastic naevi reacted positively with the antibody. To investigate a link between positivity and tumour size, the data were analysed on the basis of Breslow thickness, and indicated that expression was observed only when tumours were thicker than 0.75 mm. We next compared expression of CD95L and HMB-45. CD95L was positive only in melanomas in a more advanced phase than stage I, whereas HMB-45 was not only expressed in melanoma cells but also in benign pigmented naevi. This indicated the advantage of CD95L staining to diagnose melanoma. The present study indicates the significant correlation between tumorigenicity and expression of CD95L, and thereby raises the possibility that CD95L may be a useful diagnostic marker for malignant melanomas.
A simple unified approach for estimating natural direct and indirect effects. An important problem within both epidemiology and many social sciences is to break down the effect of a given treatment into different causal pathways and to quantify the importance of each pathway. Formal mediation analysis based on counterfactuals is a key tool when addressing this problem. During the last decade, the theoretical framework for mediation analysis has been greatly extended to enable the use of arbitrary statistical models for outcome and mediator. However, the researcher attempting to use these techniques in practice will often find implementation a daunting task, as it tends to require special statistical programming. In this paper, the authors introduce a simple procedure based on marginal structural models that directly parameterize the natural direct and indirect effects of interest. It tends to produce more parsimonious results than current techniques, greatly simplifies testing for the presence of a direct or an indirect effect, and has the advantage that it can be conducted in standard software. However, its simplicity comes at the price of relying on correct specification of models for the distribution of mediator (and exposure) and accepting some loss of precision compared with more complex methods. Web Appendixes 1 and 2, which are posted on the Journal's Web site (http://aje.oupjournals.org/), contain implementation examples in SAS software (SAS Institute, Inc., Cary, North Carolina) and R language (R Foundation for Statistical Computing, Vienna, Austria).
[An antitumor effect of oncolytic adenovirus capable of selectively replicating in CEA-expressing cancer cells and its enhancement by 5-FU]. In recent years, many have focused on the use of oncolytic virus capable of lysing cancer cells by a cancer-selective replication for a new treatment modality of cancer. In the present study, we used oncolytic adenovirus, AdCEAp/Rep, genetically modified to selectively replicate in CEA-expressing cancer cells, and investigated whether AdCEAp/Rep could induce selective cytotoxicity to CEA expressing cancer cells, and where the AdCEAp/Rep induced cytotoxic effect could be enhanced by 5 FU in using human gastric cancer cell lines, MKN45 (CEA-positive) and MKN74 (CEA-negative). The results showed that AdCEAp/Rep showed cytotoxicity against MKN45 in a dose-dependent manner, while it did not against MKN74. Furthermore, 5-FU remarkably enhanced AdCEAp/Rep-induced cytotoxicity against MKN45 by being added 3 days after adenovirus infection. These findings strongly suggest that AdCEAp/Rep may be applicable as a new therapeutic agent for clinical cancers expressing CEA in combination with chemotherapeutic agents such as 5-FU.
Increased indoor thoron concentrations and implication to inhalation dosimetry. Increased concentrations of thoron (220Rn) and its progenies were recently measured in traditional residential dwellings and gave rise to concern about thoron dose assessment. A compartment model for the attached and unattached thoron progenies in the human body by inhalation was adapted, applied to individual measurements and examined in regard to model parameters. It was found that the lung dose is the dominant contribution to the thoron effective dose in spite of the transfer of 212Pb to other tissue. The organ equivalent dose and effective dose coefficients may change by about a factor of 2 within the 0.0-0.2 range of the unattached fraction. A decrease of the dissolution half-life of the inhaled particles in the lungs by a factor of 10 results in a decrease of the effective dose by <50%. Individual measurements of total concentration and unattached fraction result in a mean dose conversion factor of 1.3 Sv per Jhm(-3) and a mean annual dose to the residents of 11 mSv for permanent stay.
Complications of orthodontic treatment. Certain complications and limitations have been associated with orthodontic treatment. The current literature obviously has not addressed all complications, but the following review highlights interesting findings and studies that may improve understanding and management of root resorption, ankylosis, implants, periodontal damage, instability, and relapse.
Retention and chemistry of aluminium in groundwater discharge areas. The concentration of different fractions of Al were measured in seven micro (3-4 m(2)) discharge areas using extraction methods on the upper layer of the soil. The areas were situated in two catchments subjected to different levels of acidic deposition. The Al fractions were determined by separate extractions with 1m KCl, 0.5 m CuCl(2) and 0.2 m (NH(4))(2)C(2)O(4). The fractions associated with the different extraction reagents are preferentially exchangeable, organically bound and amorphous hydroxide, although a complete separation cannot be made. The total amount of Al was determined after dry ashing. The results show that the levels of total Al in the peat were high when compared to ombrotrophic peatlands. The quantity and characteristics of the organic material and the acidity of the soils in the discharge zone could be decisive in determining which fractions of Al occur. The high levels of total Al in the soil indicate that the discharge zone could be an important trap for the element.
Endovascular treatment of intracranial infectious aneurysms. Intracranial infectious aneurysm (IIA) accounts for less than 5% of all intracranial aneurysms. The aim of this study was to evaluate the role of endovascular treatment for IIA. During a 14-year period, 15 patients (age range, 2-68 years; mean, 42.8 years) with 17 aneurysms were diagnosed with IIA and treated via an endovascular route at our institution. The IIA diagnosis was based on clinical and laboratory findings of infection, echocardiography results, and digital subtraction angiography that were collected retrospectively. All patients were clinically and radiologically followed. The modified Rankin scale was used to evaluate clinical outcome. Among 15 patients, 12 presented with ruptured aneurysms (7 intraparenchymal hematoma, 4 subarachnoid hemorrhage, 1 subdural hematoma), 2 with cerebral infarcts, and 1 with pansinusitis and epidural abscess. All but one aneurysm were distally located in intracranial circulation, 14 were in anterior, and the remaining 3 were in posterior circulation. The final diagnosis was based on aneurysm morphology, location, and clinical laboratory findings. Endovascular treatment was scheduled initially for all IIAs; 13 of 17 IIAs underwent endovascular parent vessel occlusion, 3 underwent spontaneous parent vessel occlusion while waiting for intervention, and the remaining patient was treated by intrasaccular coil occlusion. There were no instances of perioperative neurological complications. Late clinical and radiological outcomes included absence of endovascular treatment related to mortality and aneurysm recurrence. Endovascular treatment may be performed safely at the time of diagnosis for at least symptomatic IIAs under the protective effect of antibiotic treatment.
Critical incident. An ethical dilemma. The purpose of this critical incident analysis is to demonstrate how knowledge of legal, moral and ethical issues has affected my nursing practice. This is a personal journey--an exploration of my own values and beliefs. The piece demonstrates how reviewing the literature has changed my stance on the issues discussed. Consequently, the piece is written in the first person, but references are used to substantiate my findings.
Numerical judgments by chimpanzees (Pan troglodytes) in a token economy. We presented four chimpanzees with a series of tasks that involved comparing two token sets or comparing a token set to a quantity of food. Selected tokens could be exchanged for food items on a one-to-one basis. Chimpanzees successfully selected the larger numerical set for comparisons of 1 to 5 items when both sets were visible and when sets were presented through one-by-one addition of tokens into two opaque containers. Two of four chimpanzees used the number of tokens and food items to guide responding in all conditions, rather than relying on token color, size, total amount, or duration of set presentation. These results demonstrate that judgments of simultaneous and sequential sets of stimuli are made by some chimpanzees on the basis of the numerousness of sets rather than other non-numerical dimensions. The tokens were treated as equivalent to food items on the basis of their numerousness, and the chimpanzees maximized reward by choosing the larger number of items in all situations.
Hand grip strength and incident ADL disability in elderly Mexican Americans over a seven-year period. Little is known about muscle strength as a predictor of disability among older Mexican Americans. The aim of this study was to examine the association between hand grip strength and 7-year incidence of ADL disability in older Mexican American men and women. A 7-year prospective cohort study of 2493 non-institutionalized Mexican American men and women aged 65 or older residing in five south-western states. Maximal hand grip strength test, body mass index, cognitive function, activities of daily living, self-reports of medical conditions (arthritis, diabetes, heart attack, stroke, cancer, hip fracture), and depressive symptoms were obtained. In a Cox proportional regression analysis, there was a linear relationship between hand grip strength at baseline and risk of incident ADL disability over a 7-year follow-up. Among non-disabled men at baseline, the hazard ratio of any new ADL limitation was 1.90 (95% CI 1.14-3.17) for those in the lowest quartile, when compared with men in the highest hand grip strength quartile, after controlling for age, marital status, medical conditions, high depressive symptoms, MMSE score, and BMI at baseline. Among non-disabled women at baseline, the hazard ratio of any new ADL limitation was 2.28 (95% CI 1.59-3.27) for those in the lowest quartile, when compared with women in the highest hand grip strength quartile. Hand grip strength is an independent predictor of ADL disability among older Mexican American men and women. The hand grip strength test is an easy, reliable, valid, inexpensive method of screening to identify older adults at risk of disability.
Reduced expression of syndecan-1 in human hepatocellular carcinoma with high metastatic potential. Syndecans comprise a gene family of transmembrane proteoglycans that regulate cellular behavior through interactions with various effectors, including heparin-binding growth factors and insoluble matrix components. Syndecan-1, the most extensively studied, localizes in epithelial cells and has been shown to present in normal hepatocytes. However, little is known about the change of syndecan-1 expression in human hepatocellular carcinoma (HCC). We investigated syndecan-1-protein expression by immunohistochemistry in 57 HCC tissue samples. Syndecan-1 gene expression was also determined. Syndecan-1 protein was expressed in cytoplasm and cell membrane of the hepatocytes and in the bile duct epithelial cells of liver with underlying hepatitis and cirrhosis. Conversely, among 57 HCC tissues, 39 HCC (68.4%) showed negative staining; 50% of well-differentiated HCC showed positive staining, whereas 82.4% of poorly differentiated HCC were negative. Loss of syndecan-1-protein expression was more prevalent in HCC with intra-hepatic metastasis (85.2%) than those without metastasis (48.0%). Similarly, syndecan-1 expression was significantly reduced in HCC with extra-hepatic metastasis (91.7%) as compared with the HCC without extra-hepatic metastasis (62.2%). The gene expression of syndecan-1 was significantly lower in HCC tissue than that in non-tumoral liver tissue. In 2 human HCC cell lines with poorly differentiated phenotype, HLE and HLF, syndecan-1 expression was markedly decreased both at the mRNA and the protein levels. These results suggest that the loss of syndecan-1 expression is a characteristic feature of HCC with high metastatic potential.
Homotopic stimulation can reduce the area of allodynia in patients with neuropathic pain. Allodynia is a common, troublesome feature of neuropathic pain conditions. In a previous study of postherpetic neuralgia we observed that repeated tactile stimulation appeared to reduce the size of the area of allodynia in some patients. We have undertaken a pragmatic clinical study to characterise this phenomenon in neuropathic pain patients with a range of different aetiologies. Neuropathic pain patients with a discrete area of tactile allodynia were recruited (n=20). We assessed the sensitive area using punctate and dynamic tactile stimuli, and thermal quantitative sensory testing. On two separate testing visits, the patients had repeated (10x over 1 min) noxious heat or cotton bud strokes applied to the affected site or contralaterally. Tactile stimulation of the affected area evoked pain (median 7 NRS) and a reduction (>30%) in the area of allodynia in 9/18 patients (maximum -48+/-9%, after 20 min), although the intensity of allodynic pain was unchanged. This effect persisted for over 1h and was present the following day in all patients tested (n=5/5). No subjects showed an increase in area after allodynic stimulation. There was no change in heat pain threshold at a distant site following allodynic stimulation, suggesting no activation of diffuse noxious inhibitory control. Repeated thermal noxious stimulation (median NRS 7) could also elicit changes (>30%) in the area of allodynia in some patients (reductions in 7/20, increases in 3/20). Thus, we have found that a brief period of homotopic painful stimulation can reduce the area of allodynia in around half of patients with established neuropathic pains.
The Influence of prolonged beta-blockers treatment on male rabbit's sexual behavior and penile microcirculation. The aim of the study was to assess the effect of the prolonged intake of three beta-blocking drugs (propranolol, metoprolol and nebivolol) on the sexual behavior and penile microcirculation of rabbits. Drugs were administered p.o. for 9 weeks and every three weeks in each group (n=13) one subgroup (n=7) performed behavioral tests, whereas in the second subgroup (n=6) penile microcirculation was measured with a laser Doppler flowmeter. The copulation studies revealed significant impairment of sexual function only in the propranolol treated group. The measured behavioral parameters suggest that at a given dose propranolol affects more performance rather than arousal aspects of rabbits' sexual behavior. In the course of the whole study no significant difference was observed among groups in penile blood flow. The data indicate that among the beta-blockers given only propranolol interferes with sexual behavior, and that beta-blockers do not appear to have a negative effect on penile microcirculation.
Purification and characterization of estrogen-2/4-hydroxylase activity from rabbit hypothalami: peroxidase-mediated catechol estrogen formation. Estrogen-2/4-hydroxylase (E-2/4-H) activity of rabbit hypothalamic tissue was previously found to be localized in the soluble subcellular fraction. In the present study, the enzymatic activity responsible for catechol estrogen formation in this subcellular fraction of the rabbit hypothalamus was purified by ammonium sulfate fractionation, ion exchange chromatography, and chromatofocusing. E-2/4-H activity was found to be associated with a group of hemoproteins with peroxidase activity. The characteristics of this hypothalamic E-2/4-H activity were reestablished in light of a peroxidatic mechanism for catechol estrogen formation. Organic hydroperoxides stimulated E-2/4-H activity, presumably by serving as oxidizing cosubstrate required for peroxidase-mediated reactions. E-2/4-H activity in a 17,500 X g supernatant of hypothalamic tissue was linear with time for at least 10 min and with protein concentration to at least 100 micrograms/150 microliter. It displayed a pH optimum of 6 and an apparent Michaelis-Menten constant (Km) of 32 microM with respect to estradiol. The amounts of 4-hydroxyestradiol formed were comparable to those of 2-hydroxyestradiol. The characteristics established in this study for the peroxidase-type E-2/4-H were distinct from those of the particulate, NADPH-dependent 2-hydroxylases found in rat liver and in porcine blastocyst and ovary. These differences provide a basis for differentiating between the two types of enzymatic activity that can lead to catechol estrogen formation in vitro.
Cutaneous facial sinus tract of dental origin. Cutaneous sinus tract on the head and neck area in a child may originate from dental disease. A high degree of clinical suspicion and complementary tests are often needed, as the diagnosis is usually not straight forward. Anatomical correlation is also useful in tracing the affected tooth or teeth. We present the case of a boy with a facial sinus tract that originated from periapical abscesses of maxillary molars.
Albiglutide: a unique GLP-1 receptor agonist. Albiglutide is a long acting GLP-1 receptor agonist (GLP-1 RA) administered by weekly injection. Area covered: The pharmacokinetic and pharmacodynamic properties of albiglutide and its clinical effects are discussed. The review encompassed a search of PubMed and a thorough analysis of the European Union and US Food and Drug Administration approval documents. Expert opinion: Albiglutide has a chemical structure quite distinct from that of other marketed GLP-1 RAs. The agent has less gastrointestinal side effects than other comparable GLP-1 RAs and is safe in patients with renal failure. As a sole treatment for diabetes and used with other hypoglycemic agents, it achieves a lowering of HbA1c of up to 1%, less than several competitor GLP-1 RAs. The benefit on weight reduction is minimal compared to other GLP-1 RAs. There exists concern about an imbalance of pancreatitis cases in the approval program as well as injection site reactions which led to discontinuance of therapy in up to 2% of participants. A large long term study now underway will determine if albiglutide, with its lower level of GI intolerance, has a place in the treatment of patients with increased risk of cardiovascular events.
Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein. Human protein arginine N-methyltransferase 2 (PRMT2, HRMT1L1) is a protein that belongs to the arginine methyltransferase family, and it has diverse roles in transcriptional regulation through different mechanisms depending on its binding partners. In this study, we provide evidences for the negative effect of PRMT2 on breast cancer cell proliferation in vitro and in vivo. Morever, cyclin D1, one of the key modulators of cell cycle, was found to be downregulated by PRMT2, and PRMT2 was further shown to suppress the estrogen receptor α-binding affinity to the activator protein-1 (AP-1) site in cyclin D1 promoter through indirect binding with AP-1 site, resulting in the inhibition of cyclin D1 promoter activity in MCF-7 cells. Furthermore, a positive correlation between the expression of PRMT2 and cyclin D1 was confirmed in the breast cancer tissues by using tissue microarray assay. In addition, PRMT2 was found to show a high absent percentage in breast caner cell nuclei and the nuclear loss ratio of PRMT2 was demonstrated to positively correlate with cyclin D1 expression and the increasing tumor grade of invasive ductal carcinoma. Those results offer an essential insight into the effect of PRMT2 on breast carcinogenesis, and PRMT2 nuclear loss might be an important biological marker for the diagnosis of breast cancer.
Neurokinin(3) receptors couple to the activation of neuronal nitric-oxide synthase in stably transfected Chinese hamster ovary cells. Several physiological effects induced by activation of neurokinin(3) (NK(3)) receptors are mediated by the production of nitric oxide (NO). We investigated the intracellular coupling of NK(3) receptors to NO synthase (NOS) using a Chinese hamster ovary cell line that was stably transfected with both the NK(3) receptor and type I (neuronal) NOS. NOS activity in the transfected cell line was assayed directly, by measuring the formation of L-citrulline, another product of NOS, as well as indirectly, by measuring the production of cGMP in cultured rat fetal lung fibroblasts (RFL-6 cells). MePhe(7)-neurokinin B (NKB) stimulation of L-[(3)H]citrulline production was concentration-dependent and yielded a two-site model for the concentration-response relationship. The production of L-citrulline in response to two other tachykinins, substance P or neurokinin A, revealed only a one-site nature of the response. The production of cGMP in response to MePhe(7)-NKB had an EC(50) value that corresponded to the high-potency component of MePhe(7)-NKB-induced production of L-[(3)H]citrulline. Agonist-induced calcium signaling was also concentration-dependent, and the acute increase in the production of cGMP by MePhe(7)-NKB (0.1 nM) was dependent on the release of calcium from intracellular stores. Results of this study provide the first direct evidence that NK(3) receptors couple to the generation of NO within the same cell.
[Scientific background and clinical implementation: three new proposals in coloproctology]. The Authors underline three clinical problems in coloproctology: the surgical access to the anal canal, the lacking aspects of the actual classification of hemorrhoids, the difficult choice of the surgical treatment in case of coexisting III degrees and IV degrees degree of hemorrhoids. They propose a new anal retractor which enables the surgeon to better calibrate all the surgical procedures inside the anal canal and to operate alone without the help of another operator. A new computerized software is able to rapidly guarantee a numeric score for hemorrhoids which is repetable before and after treatment of the disease. The Authors present a new surgical technique defined of transfixed stichtes for the resolution of the most advanced stage of hemorrhoids. The new anal retractor was used in fifthy consecutive patients operated on for proctological problems. A quickly computerized score coming from the new classification PATE 2000 Sorrento was evaluated in one hundred patients, while the surgical technique of transfixed stichtes was utilized in fifthy. All the surgical procedures performed with the new device were concluded without complications. The highest values of the score from PATE 2000 Sorrento always fit with the surgical treatment of the disease, while transfixed stitches gave dysuria in five patients, but a better quality of life was referred by 38 over 50 patients treated. The Authors underline in this paper the results of the clinical implementation of these three new solutions in colon-proctology.
[Sequential changes of various parameters of arterial blood samples]. Since the values of various parameters in arterial blood samples changes with time, they should be measured without delay. There are some situations, however, where it is quite difficult to carry out the measurement immediately. In this study, we aim to obtain a series of parameters by which we can estimate true values from stale blood samples. Arterial blood gases (PaCO2, PaO2, pH), electrolytes, blood sugar and lactate were measured at 0 min, 30 min, 60 min after collecting the samples. Cytometry was done at 0 min. We calculated proton ion concentration ([H+]) and oxygen content (CaO2). Relationships between the change of various parameters in arterial blood samples and the numbers of red blood cell (RBC), white blood cell (WBC) and platelet were analyzed using multiple regression analysis. The values of PaCO2, lactate and [H+] increased, and those of PaO2, blood sugar and CaO2 decreased with time. Electrolytes changed little. There were significant relationships between the number of RBC and the change of blood sugar, and between the number of WBC and the change of CaO2 value. From these result, we found a series of expression by which we can estimate appropriate values from stale blood samples.
Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest. This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a -6 degrees head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 +/- 158 vs. 663 +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by approximately 16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.
Alpha-benzoin oxime in higher oxidation state 3d metal cluster chemistry: structural and magnetic study of a new Mn(III)(9) complex. The initial employment of alpha-benzoin oxime (bzoxH(2)) in higher oxidation state 3d metal cluster chemistry has provided access to a new enneanuclear Mn(III) complex with an unprecedented metal-core topology consisting of two triangular [Mn(3)(mu(3)-Omicron(2-))(mu-OmicronNu)(3)](4+) fragments connected by a linear [Mn(3)(mu-OmicronNu)(6)](3+) unit. The Mn(III)(9) cluster is antiferromagnetically coupled and has an S = 3 spin ground state.
HIV-1 variants in South and South-East Asia. HIV spread in South and South-East Asia is most alarming, and genetic variability of HIV-1 is an important consideration in vaccine development. In this study, we examined the third variable (V3) region of env gene of HIV-1 variants prevalent in Thailand, Malaysia, India, and the Philippines. By phylogenetic tree analyses, an HIV-1 variant from an injecting drug user (IDU) in Thailand belonged to subtype B, and HIV-1 variants from 2 IDUs in Malaysia were classified into 2 subtypes, B and E. One HIV-1 variant from a male homosexual in the Philippines belonged to subtype B. Out of 8 HIV-1 variants from sexually transmitted disease patients in India, 7 belonged to subtype C, and one to subtype A. Although the total number of individuals examined in this study was limited, 4 HIV-1 subtypes were found in South and South-East Asia and large international movements of HIV-1-infected individuals in this region could induce global dissemination of these HIV-1 variants.
Primary diffuse leptomeningeal gliomatosis mimicking tuberculous meningitis. Primary diffuse leptomeningeal gliomatosis is a disease with an aggressive course that can result in death. To date, 82 cases have been reported. Here, the case of a 3-year-old male patient presenting with strabismus, headache, and restlessness is reported. Physical examination revealed paralysis of the left abducens nerve, neck stiffness, and bilateral papilledema. Tuberculous meningitis was tentatively diagnosed, and antituberculosis treatment was initiated when cranial imaging revealed contrast enhancement around the basal cistern. Craniocervical magnetic resonance imaging (MRI) was performed when there was no response to treatment, and it revealed diffuse leptomeningeal contrast enhancement around the basilar cistern, in the supratentorial and infratentorial compartments, and in the spinal region. Primary diffuse leptomeningeal gliomatosis was diagnosed by a meningeal biopsy.
Environmental factors in the development of autism spectrum disorders: A reply to Sealey et al. (2016). Sealey et al. have reviewed the available evidence on environmental factors that may predispose the development of autism spectrum disorders (ASD) in vulnerable populations. The authors identify exposure to vaccines, pesticides, and air pollutants as potential contributors. The author of this correspondence has previously proposed elsewhere that exposure to increasing levels of the agricultural and environmental pollutant, nitrous oxide (N2O), may be the dominant etiology of ASD and other neurodevelopmental disorders. N2O is thought to target the opioidergic system, including the Ƙ-opioid receptor (KOR). Exposure to thimerosal-containing vaccines may disrupt the activity of several endogenous targets as has been shown, principally including μ-opioid receptor (MOR). Given the antagonistic actions of the MOR and KOR, dysregulation of MOR may leave the heightened dynorphin/KOR system unchecked, possibly inducing a negative emotional state that is characteristic of ASD. Future attention may need to be focused on understanding on how early-life mercury exposures, such as in vaccines, may or may not reveal a gestational opiate dependence induced from other ASD-implicated environmental factors.
Bessel-Gauss pulse as an appropriate mathematical model for optically realizable localized waves. We show that the field of the optically feasible luminal localized wave solutions of the scalar homogeneous wave equation can be modeled by means of Bessel-Gauss pulses. As the Bessel-Gauss pulses have a closed-form expression, this fact may be of great value in numerical simulations of various experimental situations.
[In utero macrocephaly as clinical manifestation of glutaric aciduria type I. Report of a novel mutation]. Macrocephaly is a pivotal clinical sign, associated with multiple neurological diseases, particularly neurometabolical ones, such as the glutaric aciduria type I (GA I). This aciduria resulting from the genetical deficiency of the enzyme glutaryl-CoA dehydrogenase (GCDH). Is a relatively common cause of acute metabolic brain damage in early childhood. We report on one case of GA I, with early manifestations since fetal period and a novel mutation. Our patient was referred due macrocephaly in utero and occipitofrontal head circumference above the 98 percentile for chronologic age during first few months of life, hypotonia and development delay. The metabolic investigations of organic acids in urine and acylcarnitine profile in blood, the brain magnetic resonance and the molecular analyses of the glutaryl-CoA deshidrogenase gene, confirm the diagnosis. The molecular analysis allowed to identify one previously described mutation A293T and a novel mutation IVS5-2 A>G. It is important the recognition of in utero macrocephaly as a sign to early diagnosis of glutaric aciduria type I to initiate specific therapy to prevent the encephalopathic crises and minimize brain damage in patients who are already neurologically impaired.
Leaching of endocrine disrupting chemicals from marine microplastics and mesoplastics under common life stress conditions. Microplastics (MPs) and mesoplastics are able to sorb harmful substances and often contain additives, e.g., endocrine disrupting chemicals (EDCs), that can cause adverse effects to organisms. The present study aims to determine EDC concentrations and their endocrine activities in leachates of field-collected marine MPs and mesoplastics under stress conditions that are known to occur during the plastic life cycle. Estrogens were the dominant EDCs on plastic particles and were either concentrated from the surrounding water or originated from plastic manufacturing. Bisphenol A had the highest detection frequency (75%) with an average concentration of 475 ± 882 μg/kg, followed by bisphenol S, octylphenol and nonylphenol. Moreover, smaller marine MPs leached greater quantities of EDCs because the sorption from surrounding seawater is more efficient for smaller particles. It was found that normal life stresses such as microwaving (MW) and autoclaving (AC) can decrease EDC concentrations, but solar irradiation (solar) can increase EDC concentrations in leachates. Even though organisms with higher metabolic ability exhibited greater estrogenic effects, the comprehensive toxicity of plastic leachates after common life treatments was still limited (below the EC10 value) if 0.1% is taken as the EDC uptake from plastic. In future studies, the accurate contribution of plastic bound EDCs needs to be further explored, and the monitoring of MPs and mesoplastics in the human diet remains important because the concentrations of these plastics may change in the future.
The shape-maintaining component of halobacterium salinarium: a cell surface glycoprotein. Halobacterium salinarium lacks the rigid peptidogylcan layer necessary for shape-maintenance in most bacteria. Instead, the major cell surface component is a high-molecular-weight glycoprotein resembling those found on the surface of eukaryotic cells. The glycoprotein is extremely acidic and has carbohydrate units attached via both N- and O-glycosidis linkages. Evidence has been obtained that demonstrates that the glycoprotein forms a rigid structural matrix at the cell surface and is responsible for maintenance of the characteristic rod-shaped morphology of these organisms.
Multinodular cutaneous spread in neuroendocrine tumor of the breast : an unusual presentation. Carcinoid tumors are the most common type of neuroendocrine tumors with an incidence of 1.5 per 100 000 of the population. Skin manifestations of carcinoid tumors include those associated with the carcinoid syndrome and sequelae from metastatic disease. Carcinoid tumors in the breast, which were first described in 1977, are rare and may present either as primary or metastatic lesions. The existence of primary breast carcinoid tumors is controversial, however, and, if they do exist, would account for <1% of primary breast cancers. We report the case of a 76-year-old woman who presented to the M.D. Anderson Cancer Center with a long-standing history of a breast lump. Core biopsy of the mass and left axillary lymph node aspiration revealed neuroendocrine tumor of the breast, which stained positive for synaptophysin and chromogranin. Subsequently, the patient developed a left-sided pleural effusion, and a further work-up revealed metastases to the lung parenchyma and pleural space. Three years after her diagnosis, she complained of a persistent, erythematous thickening of skin over the surface of her left inferior breast, which had been present for 1 year. On examination, multiple erythematous grouped nodules arranged in an oval pattern were present. A punch biopsy from one of the nodules revealed invasive low-grade carcinoma with neuroendocrine features similar to those in her prior breast core biopsy. The tumor was seen to be infiltrating the dermis. This is a unique case of a neuroendocrine tumor of the breast with cutaneous spread. The number of reported cases of neuroendocrine tumors with cutaneous involvement remains small.
Radiation oncology outpatients' patterns of life expectancy discussions. To describe the (a) number and type of cancer care providers that radiation oncology outpatients report discussing life expectancy with, and (b) perceptions of the acceptability and utility of life expectancy information. A cross-sectional survey of patients receiving radiotherapy was undertaken in four treatment centres. Patients indicated whether they had discussed life expectancy with a cancer doctor (i.e., medical oncologists, radiation oncologists, surgeon, haematologists) and/or other cancer care provider (i.e., general practitioner, radiation therapist, nurse); and acceptability and utility of information. Of 207 respondents, 133 (64%) had discussed life expectancy with at least one provider. General practitioners (GPs) were the most frequent source of information. Of those who had discussed life expectancy, half (n = 110/207) perceived cancer would not impact life expectancy. Information was easy to understand (91%), discussed sensitively (90%), helped plan for future (83%) and gave them certainty (86%). The information made 11% feel overloaded and 34% feel anxious. Two-thirds of respondents had discussed life expectancy with at least one cancer care provider. Providers from the range of disciplines involved in cancer care need to be skilled at communicating life expectancy information and recognising the adverse impact this may have on some patients.
Haemostasis in normal pregnancy: a balancing act? Pregnancy is a risk factor for venous thrombosis and the incidence of venous thromboembolism during normal pregnancy is 6-fold higher during pregnancy than in the general female population of child-bearing age. This incidence is, however, remarkably low given the increases in markers of haemostatic activation observed during normal pregnancy. During normal healthy pregnancy there are substantial changes in the haemostatic system, many of which are procoagulant and supposed to be in preparation for the haemostatic challenge of delivery. Normal haemostasis requires a balance between coagulation and fibrinolysis to maintain the integrity of the vasculature, and complex physiological changes are evident during pregnancy which appear to ensure a constant coagulation/fibrinolysis balance. This balance is maintained, at least partly, by an increase in fibrinolytic activity, but decreases in other factors such as factor XI and monocyte tissue factor expression may also serve to counterbalance procoagulant changes.
Increased plasma catecholamines in high renin hypertension. Plasma catecholamines, indexes of sympathetic nervous tonicity, were measured simultaneously with renin both supine and after standing plus furosemide in patients with primary hypertension and normotensive volunteers. Seventy percent of hypertensive patients with high renin levels had increased catecholamines compared with a 14% incidence in the combined group with low and normal renin (P less than 0.001). Basal catecholamines were related directly to renin in the hypertensive patients and to blood pressure in the normal (P less than 0.05), but not in the high and low renin subgroups, and inversely to percent increase of catecholamines after standing plus furosemide in hypertensive and normotensive patients (P less than 0.01). Sympathetic nervous hypertonicity may be responsible for the elevation of blood pressure and for the activation of the renin-angiotensin system in patients with high renin hypertension.
Community- versus nosocomial-acquired severe sepsis and septic shock in patients admitted to a tertiary intensive care in Saudi Arabia, etiology and outcome. Sepsis syndrome is a major worldwide cause of morbidity and mortality. While community-acquired severe sepsis and septic shock constitutes a major cause of admission to the intensive care unit, hospital-acquired severe sepsis and septic shock remain major preventable causes of ICU admission. This study evaluates the rate, etiology, complication and outcome of community- and hospital-acquired sepsis in a tertiary care hospital in Saudi Arabia. This is a retrospective evaluation of all admissions with severe sepsis and septic shock to a general intensive care unit over a period of six months. A total number of 96 patients were included, which represented 15% of the total number of admissions during the study period. The mean age was 57.4 (SD 21). Sixty percent of cases were due to hospital-acquired infections, and 40% were community-acquired. The majority of the infections acquired in the hospital occurred in medical wards and intensive care units (27% and 21%, respectively). At least one co-morbid condition was present in 94% of the sample patients, with cardiovascular disease and diabetes being the most frequently encountered disorders (58%). Both community and hospital-acquired severe sepsis and septic shock carry very high mortality (58%). The ICU length of stay was significantly longer for hospital and ICU acquired infections. Both community and hospital-acquired infections carry high mortality. Hospital-acquired severe sepsis is frequent in medical wards and ICUs, and measures to further evaluate risk factors are prudent.
Dignity commission chair pushes for HCA regulation. The co-chair of the commission on improving dignity in care has vowed to champion the work of healthcare assistants and join calls for them to be regulated alongside nurses.
Enhancement of the dissolution profile of Tenoxicam by a solid dispersion technique and its analytical evaluation using HPLC. The aim of the present study was to improve the dissolution, and therefore the bioavailability, of poorly water-soluble tenoxicam. Solid dispersions consisting of tenoxicam with two different types of polymers were prepared. The first type were PVP(30) and β-cyclodextrin and the second type were two superdisintegrants, explotab and croscarmellose sodium. A solid dispersion with an explotab ratio of 1:1 (F(8)) had the best dissolution profile compared to all of the prepared solid dispersions as well as the pure drug, which was then formulated into tablets (T(2)F(8)). T(2)F(8) had far better dissolution than commercial tablets, releasing only 28.3% of the drug, while T(2)F(8) exhibited 96.5% drug release in 20 min. T(2)F(8) was subjected to analytical validation as well as stability studies. The formulation was found to be stable after storage at 40°C for one month, 40°C and 75% relative humidity (40°C/75% RH) for one month, and 60°C for 15 days; this was confirmed by the absence of degraded product prepared in the laboratory by refluxing the drug with 1 N NaOH for 15 min. Infrared (IR) spectroscopy and differential scanning calorimetry (DSC) were performed on T(2)F(8) to identify physicochemical interactions between the drug and carrier, hence its effect on dissolution. A simple and rapid HPLC method was also developed to determine tenoxicam in human plasma and was then used in a pharmacokinetic study. Plasma samples were analyzed on a C(18) column with a mobile phase of 0.02 M sodium acetate:acetonitrile: methanol (7:2.5:0.5, v/v/v) and UV detection at 375 nm. The linear range of the plasma concentration was 1-16 μg/mL with a detection limit of 158 ng/mL. Within-day and between-day precision expressed as the relative standard deviation was less than 2%. The proposed method was successfully used in a bioequivalence study in healthy volunteers and mean pharmacokinetic parameters were calculated.
A modified fluid percussion device. This report examines a modified fluid percussion device with specific improvements made to address deficiencies found in previously reported devices. These improvements include the use of a cylindrical saline reservoir made of stainless steel, placement of the reservoir in a 15-degree head-up position for the easy release of air bubbles, placement of the fluid flushing outlet and the pressure transducer close to the piston on the same plane, with both perpendicular to the direction of the piston, and adjustable reservoir volume to vary the waveform of the pressure pulse, and a metallic central injury screw secured to the animal's skull over the exposed dura. Using this device, midline fluid percussion (MFP) and lateral fluid percussion (LFP) injuries were performed in 70 rats. Histopathologic findings included diffuse axonal injury in the MFP model and cortical contusion in the LFP model. Survival rate was 41.4% in MFP animals and 100% in LFM animals when the device settings were 178 mm3 of the cylindrical reservoir and 50 degrees-60 degrees in height of the pendulum. Our results suggest that this modified fluid percussion device may offer significant improvements over previously reported fluid percussion models for use in experimental head injury.
A 36 month comparative trial of methotrexate and gold sodium thiomalate in the treatment of early active and erosive rheumatoid arthritis. To compare the safety and efficacy of methotrexate (MTX) and gold sodium thiomalate (GSTM) in patients with active early erosive rheumatoid arthritis (RA) during 3 yr. A total of 174 patients from two centres were randomly assigned to receive weekly i.m. injections of either 15 mg MTX or 50 mg GSTM for 1 yr in a double-blind fashion. Thereafter, the study was continued as an open prospective trial for an additional 2 yr with the same dose of MTX and half of the GSTM dose. Clinical and laboratory evaluations were carried out at baseline and at months 6, 12, 18, 24 and 36 in all patients, including withdrawals. An intention-to-treat analysis revealed inactivation ['clinical remission': no swollen/tender joints, erythrocyte sedimentation rate (ESR) of < 20 mm/h in males and < 30 mm in females, no corticosteroids within the last 4 weeks] in 33.3% of MTX patients and 37.9% of GSTM patients. The mean time to inactivation was insignificantly shorter with GSTM (MTX: 12.1 months; GSTM: 9.1 months; P = 0.06). At least marked improvement (> 50% reduction of the number of swollen/tender joints and of the ESR) was found in 78.2% (MTX) and 87.4% (GSTM). Withdrawal from the study due to toxicity was recorded in 16.1% of MTX and 52.9% of GSTM patients after a mean time of 30.6 and 6.1 months, respectively (P = 0.0001). In MTX and GSTM non-completers, inactivation was recorded in 24.2 and 54.7% of all patients. Among completers (54 and 34 patients, respectively), significant improvement compared to baseline was noted in all seven clinical variables (morning stiffness, overall joint pain, count of tender/swollen joints, Lansbury articular score, functional score and grip strength), ESR and C-reactive protein without significant intergroup differences. The steroid-sparing effect appeared more pronounced with GSTM. Over 36 months, treatment with MTX or GSTM induces inactivation ('clinical remission') of early and erosive RA in about one-third and at least marked improvement in four-fifths of patients (intention-to-treat analysis). Patients withdrawn from MTX or GSTM due to toxicity develop a clinical remission from the disease; this occurred more often with GSTM. Tolerability is significantly better with MTX.
Eliminating interferences in a compendial test for oxidizable substances in water. The United States Pharmacopoeia (USP) uses acidified potassium permanganate to test for dissolved organics in pharmaceutical-grade water. In the test, a standard permanganate concentration is added to a boiling, acidified water sample. Visually inspecting the sample for residual permanganate determines whether the sample passes (pink color remains) or fails (pink color disappears) the test. The permanganate redox chemistry is complex, however, and test samples are prone to developing suspended particulate and colors other than pink. Forming hazy or off-colored solutions interferes with the subjective end point determination according to the USP test. We report two alternative end point determinations that essentially eliminate interferences from the compendial test method. The first alternative involves recording a uv-visible spectrum of the reduced permanganate test solution. Residual permanganate shows three distinct absorbance maxima at 510, 526, and 545 nm. It is straightforward to differentiate the characteristic permanganate fingerprint from the broad, lower-wavelength extinction that results from interfering substances. The second alternative involves filtering the reduced permanganate test solution through sintered glass. This filtration step removes manganese oxides and other colloidal particles that contribute to haze and off color formation in test samples. Visually inspecting the filtrate for residual pink color remains the end point determination for the test method. A third alternative method, namely spectrophotometric determination of permanganate loss rate constants is not a suitable alternative owing to a strong dependence of permanganate reduction rate on organic substrate structure.
LmrCD is a major multidrug resistance transporter in Lactococcus lactis. When Lactococcus lactis is challenged with drugs it displays a multidrug resistance (MDR) phenotype. In silico analysis of the genome of L. lactis indicates the presence of at least 40 putative MDR transporters, of which only four, i.e. the ABC transporters LmrA, LmrC and LmrD, and the major facilitator LmrP, have been experimentally associated with the MDR. To understand the molecular basis of the MDR phenotype in L. lactis, we have performed a global transcriptome analysis comparing four independently isolated drug-resistant strains of L. lactis with the wild-type strain. The results show a strong and consistent upregulation of the lmrC and lmrD genes in all four strains, while the mRNA levels of other putative MDR transporters were not significantly altered. Deletion of lmrCD renders L. lactis sensitive to several toxic compounds, and this phenotype is associated with a reduced ability to secrete these compounds. Another gene, which is strongly upregulated in all mutant strains, specifies LmrR (YdaF), a local transcriptional repressor of lmrCD that belongs to the PadR family of transcriptional regulators and that binds to the promoter region of lmrCD. These results demonstrate that the heterodimeric MDR ABC transporter LmrCD is a major determinant of both acquired and intrinsic drug resistance of L. lactis.
[Screening up-regulated genes in hepatic stellate cells treated with PDGF-BB using suppression subtractive hybridization technique]. To construct a subtractive cDNAs library of up-regulated genes in rat hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor (PDGF)-BB by suppression subtractive hybridization (SSH) technique, to clone the up-regulated genes associated with its regulation effects, and to elucidate the mechanism of the molecular biology of hepatic fibrosis involved in PDGF-BB. The mRNA was isolated from HSCs stimulated with PDGF-BB and controlled with identical cells untreated with PDGF-BB, and then the cDNAs were synthesized. The cDNAs were designated as tester and driver. After being digested by restriction enzyme Rsa I, small-sized cDNAs were obtained. Tester cDNA was then divided into two groups and ligated to the specific adaptor 1 and adaptor 2, individually. After tester cDNA was hybridized with driver cDNA twice and underwent two times of nested PCR, the amplified cDNA fragments were subcloned into pGEM-Teasy vectors to set up the subtractive library. Amplification of the library was carried out with E. coli strain DH5alpha. The cDNA was sequenced and analyzed in GenBank with Blast search after PCR. The subtractive cDNAs library of up-regulated genes in HSCs stimulated with PDGF-BB was constructed successfully. The amplified library contained 102 positive clones. Colony PCR showed that 93 clones contained 200-1000 bp inserts. Sequence analysis was performed in 31 clones randomly, and the full length sequences were obtained with bioinformatics method and searched for homologous DNA sequence from GenBank; altogether 13 coding sequences were obtained, which were known ones. The genes mainly included voltage-dependent anion channel (VDAC), heat shock protein 47 and RAN-member RAS oncogene family genes. Acting as one of the most effective mitogens, PDGF-BB up-regulated some gene expressions during stimulation of the HSCs, including some cell growth associated proteins, some proteins participating in intracellular metabolism and some molecular chaperone proteins. This work brings some new clues for studying the molecular biological mechanism involved in the up-regulated genes in PDGF-BB transactivated HSCs in hepatic fibrosis.
Age-dependent changes in damage processes of hair cuticle. Human hair cuticle is always exposed to various stresses and then gradually lost in daily life. There are two typical patterns of cuticle damage: type L, where the cell membrane complex, the structure located between cuticle cells, is split and the cuticle lifts up, and type E, where the fragile substructure of the cuticle cell (endocuticle) is damaged so that its rugged residue is exposed. We previously reported that type L damage preferentially occurs in the case of Japanese females in their 20s to 40s. This study aims to elucidate the age-dependent change of cuticle and its effect on hair properties. Hair fibers collected from Japanese females (ranging from 10 to 70 years old) were evaluated in the aspects of inclination for each type of damage, resistance of cuticle against grooming stresses and content of fatty acid 18-MEA on hair surface. It was revealed that the dominant damage pattern shifts from type L to E with aging. Furthermore, the cuticle becomes gradually less resistant to daily grooming stress. The dominance of type E damage accelerates cuticle loss. Reduction of 18-MEA on weathered hair is accelerated with aging on elder hair. It has been reported that various age-dependent changes of whole hair shaft, such as diameter, density, elasticity, etc., occur in the age range of 40s and 50s. In this study, it was revealed that cuticle becomes more fragile and the hair surface properties deteriorate in the same age range.
Six cases of Lactobacillus bacteraemia: identification of organisms and antibiotic susceptibility and therapy. Six cases of bacteraemia in hospitalized patients, 5 with a depressed immune status, were caused by lactobacilli. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins and API 50 CH carbohydrate patterns assigned the causative agents to the species Lactobacillus rhamnosus, Lactobacillus curvatus, Lactobacillus delbrueckii subsp. lactis and Lactobacillus paracasei subsp. paracasei.
Bacterial ghosts as drug carrier and targeting vehicles. A novel system for the packaging of drugs as well as vaccines is presented. Bacterial ghosts are intact, non-denatured bacterial envelopes that are created by lysis of bacteria through the expression of cloned phage PhiX174 gene E. Inhibition of induced E-mediated lysis by MgSO(4), harvesting of cells by centrifugation, and resuspension in low-ionic-strength buffers leads to rapid, violent lysis and results in empty bacterial envelopes with large (approximately 1 microm in diameter) openings. The construction of plasmid pAV1, which encodes a streptavidin fusion protein with an N-terminal membrane anchor sequence, allows the loading of the inner side of the cytoplasmic membrane with streptavidin. The functionality and efficacy of binding of even large biotinylated compounds in such streptavidin ghosts (SA-ghosts) was assessed using the enzyme alkaline phosphatase. The successful binding of biotinylated fluorescent dextran, as well as fluorescent DNA complexed with biotinylated polylysine, was demonstrated microscopically. The display by bacterial ghosts of morphological and antigenic surface structures of their living counterparts permits their attachment to target tissues such as the mucosal surfaces of the gastrointestinal and respiratory tract, and their uptake by phagocytes and M cells. In consequence, SA-ghosts are proposed as drug carriers for site-specific drug delivery.
Ascorbate/Fe(3+)-induced peroxidation and inhibition of the binding of A1 adenosine receptor ligands in rat brain membranes. The effect of peroxidation induced by the ascorbate/Fe3+ system on the binding properties of the A1 adenosine receptor, was studied in rat brain membranes, using the agonist, [3H]R-N6-phenylisopropyladenosine ([3H]R-PIA), and the antagonist, [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX). For the agonist, as well as for the antagonist, the number of binding sites (Bmax) was significantly (P < 0.05) reduced after pretreatment of the membranes with ascorbate/Fe3+. The affinity of the agonist for the binding sites was not statistically modified (P > 0.05) after ascorbate/Fe3+ pretreatment, whereas the Kd value of the antagonist was increased (P < 0.05) by a factor of 2. Ascorbate/Fe3+ pretreatment affected agonist binding in the presence of GTP in a similar way as that observed in the absence of GTP, suggesting that peroxidation also affects agonist binding to A1 adenosine receptors uncoupled to G-proteins. The results suggest that when brain membranes suffer free radical oxidative damage, the adenosine modulation of neuronal activity through A1 receptors could be less efficient.

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