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9451197 | Management of established osteoporosis. | Osteoporosis is established when certain types of fractures occur or a reliable form of bone densiometry detects low bone mass. The treatment of established osteoporosis is undertaken with a number of choices. The goals of therapy are to stabilize the patient's condition and to prevent fractures. Generally, this means preventing further osteoporosis and, if possible, increasing bone mineral density. Estrogen, calcitonin, alendronate, etidronate, exercise, and calcium with vitamin D are the most available therapies in the United States. Other therapies are discussed. |
9451198 | Emotional adjustment to a chronic illness. | The emotional reaction to the diagnosis of a chronic illness can be a greater challenge than coping with the physical manifestations of the illness. This article describes and explains the determinants of the emotional reaction to the diagnosis of a chronic illness: (1) personality before the illness; (2) unresolved anger or grief from the past; (3) the suddenness, extent, and duration of life-style changes mandated by the illness; (4) familial and individual resources for dealing with stress; (5) stages of individual and family life cycle; (6) previous experience with illness or crisis; and (7) codependency in the family system. Also discussed are the stages of integrating grief process with the benefits and pitfalls of each stage and signs of acceptance. The benefits and necessity of going through the grief process are explored. People who receive diagnoses of chronic illness may find their emotional reaction more disabling than the illness itself until they go through the adjustment process to embrace the new person they have e through the illness. |
9451199 | Appropriate laboratory testing in rheumatic diseases. | The diagnosis and management of systemic rheumatic disease is predominantly based on clinical parameters. Nevertheless, specific laboratory diagnostic tests may often be critically helpful, for example, in ruling out septic and crystal-induced arthritis in the differential diagnosis of acute monoarthritis. In the evaluation of patients with polyarticular rheumatic disease syndromes, autoimmune testing may be helpful to corroborate the clinical diagnosis of such diverse illnesses as rheumatoid arthritis, systemic lupus erythematosus, Lyme disease, and anticardiolipin syndrome. |
9451230 | [Breast feeding and length of hospitalization]. | One of the important tasks for a nurse is to insure that the newborn receives all the nourishment that it needs. A well fed baby is healthier, experiences a shorter hospital stay and develops a stronger bond with its mother. To prove this point a study was performed on a group of low birth weight newborns (free of other pathological symptoms) pare nutrition against hospitalization time. 85 children of both sexes were divided into 3 groups: premature but of normal gestational size, premature but small for gestational size, and full term but small for gestational size; all had a birth weight superior to 2 kilos and were examined postpartum on their first and third week. The groups were then subdivided into 2 groups: one received only artificial milk formula and the other group received their mothers' milk through a bottle. The children that drank the maternal milk required fewer days in the hospital (18 +/- 6 days versus 27 +/- 7 days for those drinking only formula) and had a smaller percentage of weight loss after birth (3.7 +/- 2.0% versus 5.2 +/- 2.9%), demonstrating a significant difference in their overall health. |
9451231 | [The patient with a tracheostomy]. | For the treatment of certain specific diseases, a tracheostomy is a required procedure in order to keep the patient's air passageways open. The nurse's care must ensure this permeability is maintained and infections avoided while serving to aid both the patient and his/her family to adapt as best as possible to the conditions caused by the intervention. Treatment Plan details will be drawn up based on each individual patient's diagnosis. |
9451228 | Heart health: rehabilitation. | Cardiac rehabilitation is the sum of activities necessary to enable patients with heart disease to achieve their optimal physical, mental, social and economic state, so that they may, by their own efforts, regain as normal as possible a place in munity and lead an active and productive life (World Health Organization 1993). It is a multidisciplinary, multifaceted approach with an overall aim of improving the short-term recovery of patients and encouraging long-term lifestyle changes in relation to adverse risk factors (Horgan et al 1992). This clearly indicates the holistic nature of the rehabilitation process, where all aspects of a person's life need to be considered, and where emphasis is on the contribution of the individual towards his or her own recovery. |
9451235 | [Distribution of time spent by nurses in primary health care teams]. | The time nurses spend on two activities is measured; one being the time spent in consulting offices by Primary Assistance Health Care Team members; and the second being the total time dedicated to house calls. This distribution time study has three focuses: observational, cross-sectional and descriptive. This study showed that more than one fourth of a nurse's time is spent carrying out technical procedures on patients, another fourth part is used filling out administrative documents, another fourth part corresponds to preventative medicine and health education activities, all of which leaves very little time for an independent professional role pared to an interdependent role. |
9451237 | [Non-comparative evaluation of a new hydrofiber dressing in the treatment of vascular ulcers]. | To evaluate the performance of the hydrofiber dressing in the treatment of leg ulcers. |
9451238 | [Hospital infections in intensive care units]. | A study done on acquired infections by patients in an intensive care unit. Data pared with other studies and concrete factors such as the incidence of naso tracheal intubations infections are looked at to determine the principal risk factors involved. |
9451239 | [Continuing education. Menopause, 2. Health education in menopause]. | This is the second part of the article published in the preceding magazine issue. "Revista ROL de Enfermería Number 230:72-77". This section presents a number of adequate preventative measures so that a woman may live through her climacteric period in as healthy a way as possible. |
9451260 | Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. | To evaluate the safety of withholding anticoagulant treatment from patients with clinically suspected deep vein thrombosis but normal findings pression ultrasonography. |
9451261 | Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. | To investigate the relation of infant feeding practice to childhood respiratory illness, growth, position, and blood pressure. |
9451262 | Preventing fatal diseases increases healthcare costs: cause elimination life table approach. | To examine whether elimination of fatal diseases will increase healthcare costs. |
9451263 | First sexual intercourse: age, coercion, and later regrets reported by a birth cohort. | To investigate how age at first sexual intercourse is related to the reported circumstances and to determine how these corresponded to views in early adulthood about its timing. |
9451264 | Can primary prevention or selective screening for melanoma be more precisely targeted through general practice? A prospective study to validate a self administered risk score. | To establish whether a questionnaire incorporating MacKie's risk factor flow chart can identify patients at high risk for melanoma so that they can be targeted for primary and secondary prevention. To validate the risk score derived from the questionnaire and test the feasibility of pletion paring patients' self reported skin characteristics with a skin examination performed by an experienced general practitioner. |
9451304 | A national survey of board-certified emergency physicians: quality of care and practice structure issues. | The opinions and experiences of board-certified emergency physicians regarding employment structure and finances, professional society policies, and quality of patient care have never been formally studied. A survey questionnaire was sent to a random sample of 1,050 emergency physicians certified by the American Board of Emergency Medicine. The survey contained 29 multiple choice questions. Of the 1,050, 465 (44.3%) of the surveys were returned. Respondents averaged 13.5 years of emergency medicine practice, 83% were members of the American College of Emergency Physicians, and 44% were emergency medicine residency trained. Seventy-five percent felt they had been financially exploited by the emergency department contract holder and 49% considered leaving their employer because of unfair business practices. Fifteen percent have been terminated without due process/peer review, and 11% have been forced to leave a position, move, or pensation because of pete clauses. The majority reported encountering instances of substandard emergency medical care, monly in settings with multihospital pany coverage. The majority also believe their specialty societies should address issues of employment structure and quality of patient care standards. |
9451305 | Effect of routine pulse oximetry measurements on ED triage classification. | Pulse oximetry monly used to rapidly determine oxygen saturation and is incorporated in emergency triage as a screening for potential plications. This study examined the effect of routine pulse oximetry measurements on emergency department (ED) triage classification. Using a portable pulse oximeter, oxygen saturation of 1,235 adults presenting to a university-based, urban ED was obtained and each patient was assigned a classification of severity based on a standard 1-to-4 scale before and after the measurement. According to data obtained, a small but statistically significant group (2.8%) benefitted from the routine use of pulse oximetry in an emergency triage system and only 40% of these patients required admission or extended care. Although this group is small in number, the potential consequences of missing a hypoxic condition could be devastating for the individual patient. Since pulse oximetry is presently an inexpensive technology, it would seem to be a worthwhile screening tool for emergency triage. |
9451306 | Correlation between triage nurse and physician ordering of ED tests. | Triage nurse ordering of tests can reduce patient time in the emergency department. This benefit must be balanced with the extra expense and potential morbidity of unnecessary tests. This study examined whether triage nurse ordering of lab tests and X-rays correlated with physician ordering. In Phase I, a prospective study, triage pleted an order form for each patient triaged during randomly selected 2-hour blocks over a 3-week period. In Phase II, Phase I was repeated with test ordering guidelines derived from Phase I results. Correlations of nurse and physician orders were analyzed by kappa statistics and paired t tests. In Phase I, 176 patients were enrolled of a possible 204 (82%). In Phase II, 350 patients were enrolled of a possible 418 (84%). The percentage of nurse overordering of tests in Phase I was 35%; In Phase II, it was 34% (P NS). Kappa values were determined for blood testing (Phase I, 0.48; Phase II, 0.54 [P = .048]), for X-ray (Phase I, 0.68; Phase II, 0.65 [P = .523]), for urinalysis (Phase I, 0.76; Phase II, 0.67 [P = .338]), and for electrocardiogram (Phase I, 0.78; Phase II, 0.77 [P = .438]). The improved lab correlation in Phase II resulted from the nurses ordering fewer tests (P = .046). Nurses deviated from the test ordering guidelines in 37% of patients. Triage nurse ordering of X-rays, electrocardiogram, and urinalysis has moderate to substantial correlation with physician ordering. Correlation of triage nurse and physician ordering of tests can be improved with the use of test ordering guidelines. |
9451307 | Cardiac arrests witnessed by EMS personnel in a multitiered system: epidemiology and outcome. | The purpose of the study was to determine the epidemiology and the etiology of cardiac arrests witnessed by emergency medical services (EMS) personnel and the survival from resuscitation according to the Utstein style. Consecutive prehospital cardiac arrests witnessed by EMS personnel in the Helsinki City EMS system between January 1, 1994 and December 31, 1995 were included in this prospective cohort study. A total of 809 cardiac arrests were registered during the study period, 108 (13.3%) of which were EMS-witnessed. The incidence of EMS-witnessed cardiac arrests was 1.8 per 1,000 urgent calls per year. Resuscitation was attempted in 94 patients, 45 of whom (47.9%) were hospitalized alive and 15 of whom (16.0%) were discharged. Fourteen of the survivors were discharged with overall performance category I or II. Cardiac etiology was verified in 60 (55.6%) cases. In multivariate analysis, initial rhythm of ventricular fibrillation and cardiac etiology remained independent factors of survival. These results indicate that overall survival rates in EMS-witnessed cardiac arrests have remained low but those who survive are discharged without major neurological sequelae. Noncardiac etiology accounts for 45% of cases and seems to be a major determinant of low overall survival rates. |
9451308 | Mild protective and resuscitative hypothermia for asphyxial cardiac arrest in rats. | It has been shown in dogs that mild hypothermia (34 degrees C) during or immediately after ventricular fibrillation cardiac arrest can improve cerebral e. The effect of mild hypothermia on e after 8 minutes of asphyxiation (5 minutes' cardiac arrest) was studied for the first time in rats. Restoration of spontaneous circulation was with external cardiopulmonary resuscitation and observation to 72 hours. Three groups of 10 rats each were studied. At 72 hours pared with the normothermic control group 1, final overall performance categories (OPC) and neurological deficit scores (NDS) were numerically better in the resuscitative (post-arrest) hypothermia group 2 and significantly better in the protective (pre-intra-arrest) hypothermia group 3 (P < .05). Total brain histopathological damage scores (HDS) were 17 +/- 5 in group 1, 14 +/- 6 in group 2 (NS), and 6 +/- 2 in group 3 (P < .001 versus group 1). HDS correlated with OPC (r = .6, P < .05) and NDS (r = .7, P < .05). Mild hypothermia improved cerebral e after asphyxial cardiac arrest in rats, more when induced before than after arrest. The model's insult is within the therapeutic window, which makes it also suitable for screening other cerebral resuscitation potentials. |
9451309 | The computed tomography appearance of recurrent and chronic appendicitis. | The objective of this study was to puted tomography (CT) appearance of recurrent and chronic appendicitis. In 100 consecutive appendiceal CT examinations of proven appendicitis, 18 patients met criteria for recurrent (multiple discrete episodes) or chronic (continuous symptoms > 3 weeks, pathological findings) appendicitis. CT findings were reviewed. Ten patients had recurrent appendicitis, 3 had chronic appendicitis, 3 had both, and 2 had pathological chronic appendicitis. CT findings in 18 recurrent/chronic cases were identical to 82 acute appendicitis cases, including pericecal stranding (both 100%), dilated (> 6 mm) appendix (88.9% versus 93.9%), apical thickening (66.7% versus 69.5%), adenopathy (66.7% versus 61.0%), appendolith(s) (50% versus 42.7%), arrowhead (27.8% versus 22.0%), abscess (11.1% versus 11.0%), phlegmon (11.1% versus 6.1%), and fluid (5.6% versus 19.5%). CT findings in recurrent and chronic appendicitis are the same as those in acute appendicitis. Appendiceal CT can be beneficial for evaluating patients with suspected recurrent or chronic appendicitis. |
9451310 | Information sharing can reduce laboratory use by emergency physicians. | This study analyzed the effect information sharing through physician profiling would have on emergency physician behavior. It is a before-and-after audit of laboratory use in munity hospital. A 9-month control period was followed by a 15-month period in which the physicians' laboratory use was presented and discussed at monthly meetings. The laboratory use decreased 17.8%, from a mean of 2.36 studies per patient during the control period to 1.94 during the final quarter of the study. The actual laboratory costs per month decreased 17.7%, from a mean of $32,415 per month to $26,687 per month. There was only one possible adverse e out of 34,320 patients seen. There were no adverse changes in other quality improvement indicators. Information sharing can result in a decrease in the number and cost of laboratories studies ordered by emergency physicians without an adverse change in routine quality improvement indicators. |
9451311 | Wound infection rate and irrigation pressure of two potential new wound irrigation devices: the port and the cap. | The objectives of this study were to determine the speed of irrigation and the infection rate of two new irrigation devices. In the clinical portion of this two-part study, 208 patients with traumatic wounds were randomized to one of two new irrigation device groups, the cap/bottle or the port/bag, to determine irrigation times and plication rates. Wounds were irrigated in less than 4 minutes in 97% of patients using a mean of 786 mL. bined plication rates were: port group, 1 of 99 (1%); cap group, 4 of 108 (4%), P = .356. In part II, 9 male and 8 female medical volunteers were timed in the delivery of 250 mL of saline into a graduated cylinder, using four different irrigation set-ups. Mean time for 250 mL and calculated stream pressures (psi) were: (1) cap/bottle, 12.9 seconds, 1.5 psi; (2) port/bag, 11.2 seconds, 2.0 psi; (3) syringe/catheter, 113.2 seconds, 8.2 psi; and (4) syringe/needle, 175.4 seconds, 7.3 psi (time and psi: P < .05 for all parisons except cap versus port). Rapid irrigation and infection parable with standard devices used in wound irrigation suggest that the new devices may prove to be valuable tools in emergent wound care. |
9451312 | Age-related differences in diagnoses within the elderly population. | The mon diagnoses of elderly patients in the emergency department (ED) pared among three age subgroups: 65 to 74, 75 to 84, and 85 and older. puterized billing records for patient visits to 10 northern New Jersey hospital EDs for the years 1985 to 1991 were retrospectively analyzed. The most frequently occurring ICD-9-CM codes for elderly patients pared among the three age subgroups. Elderly prised 174, 146 (14% of the total) patient visits. The 176,146 patient visits were assigned 259,440 ICD-9-CM codes. The mon ICD-9-CM codes for medical diagnoses included chest pain, cardiac dysrhythmias, congestive heart failure, syncope, abdominal pain, and dyspnea. Fractures, particularly of the lower limb and upper limb; contusions; open wounds, particularly of the head, neck, and trunk; and falls were among the mon trauma diagnoses. The proportions in the three age subgroups of each diagnosis were statistically significantly different, except for cardiac arrest and contusions of the trunk and of multiple sites. The diagnoses with clinically significant higher relative risks in older age subgroups were atrial fibrillation, congestive heart failure, syncope, hypovolemia/dehydration, gastrointestinal hemorrhage, dyspnea, pneumonia, pulmonary edema, cerebrovascular accident, septicemia, urinary tract infection, fractures, and open wounds of the head, neck, trunk, particularly the scalp, and falls. Clinically significant lower relative risks were found in older age subgroups for chest pain, acute myocardial infarction, hypertension, angina, chronic airway obstruction not elsewhere classified, epistaxis, contusions of the upper limb, and open wounds of the finger. |
9451313 | Painless acute aortic dissection presenting as left lower extremity numbness. | Acute aortic dissection may have variable presentations, making the diagnosis clinically challenging. Acute neurologic syndromes secondary to dissection of the aorta are mon. However, including aortic dissection in the differential diagnosis is imperative. This report describes the first reported case of an acute thoracic aortic dissection presenting with the plaint of unilateral lower extremity numbness. Peripheral ischemic neuropathy as the result of vascular occlusion is mon. The pathophysiology and clinical manifestations of ischemic neuropathies in the setting of acute aortic dissection are discussed. |
9451314 | Fractures and other injuries from falls after an ice storm. | This is a retrospective review of all patients seen at an urban emergency department for 9 days after an ice storm because of a fall on ice. Date of presentation, age, sex, and anatomic location and type of injury were tabulated. Risk factors for fractures were identified. A total of 327 injuries were identified in 259 patients. Back injury was mon (19.3%). Ninety-one patients sustained 93 fractures. Ankle fractures were mon (24.7%), followed by fractures of wrist (19.4%) and hip (14.0%). Ankle fractures were mon than other studies of falls after a snow storm. Fracture was significantly related to age (P = .0001). There was a trend for women to sustain fractures (P = .07). Unlike other mass casualty events, fractures and injuries peaked on the 5th and 6th day after the storm, allowing adequate time for mobilizing resources to care for the injured. |
9451315 | Critical care provided in an urban emergency department. | The emergency department (ED) provides a substantial amount of critical care. The purpose of this study was to quantitate the critical care provided in an urban ED. The study was performed at a large urban hospital with an annual ED volume of 70,000 patients. All patients requiring critical care in the ED or hospital were prospectively observed between September 1 and November 30, 1993. Patients requiring recovery room care or neonatal intensive care were excluded. Data collected included age, disposition, length of stay, triage acuity assignment in the ED, primary diagnosis, and critical care procedures. During the study, 11,989 patients were examined in the ED with 500 (5%) requiring admission, 340 (3%) requiring a critical care intervention, and 96 (1%) being admitted to an intensive care unit (ICU). Ten percent of patients receiving critical care in the ED were admitted to the floor for lack of bed space. Triage assignment of emergent life-threatening or urgent potentially life-threatening condition predicted critical care need and waiting time to examination. The spectrum of critical care procedures performed in the ED and ICU were similar except for advanced life support intervention, which was mon in the ED (17 versus 3), and arterial line placement, which was mon in the ICU (14 versus 1). The spectrum of diagnoses reflected the age of patients with cardiovascular illnesses (33%), metabolic illnesses (18%), and trauma mon in adults (age > or = 17) and infectious illnesses (46%) or metabolic illnesses (21%) mon in pediatric patients. Overall, 14% of adult critical care, 23% of pediatric critical care, and 15% of all critical care provided in the areas studied occurred in the ED. A significant proportion of critical care is provided in the ED, and triage acuity assignment reflects this need. A significant proportion of critically ill patients was admitted to the floor for lack of bed space, which highlights the financial constraints in urban hospitals such as the one studied. |
9451316 | Need for law enforcement in cases of intimate partner violence in a university ED. | The purpose of this study was to quantify the proportion of men and women seen in a university emergency department (ED) for treatment of injuries resulting from intimate partner violence (IPV) that require reports to law enforcement authorities. A total of 1,516 adult ED patients were asked plete a written survey instrument; 1,003 patients pleted the survey. Two percent of patients reported they presented to the ED for treatment of injuries resulting from IPV. Three percent reported IPV within the last year, and 10% reported that they had ever been physically abused by a partner. Six percent of respondents reported that they had ever been threatened with a gun or knife by a partner, 2% within the past year. Only the lifetime prevalence of IPV was significantly greater among female patients, 15% versus 6% (P < .001). Approximately 2% of our ED patients require law enforcement intervention for IPV. |
9451318 | Coping with pediatric death in the ED by learning from parental experience. | The death of a pediatric patient in the emergency department generates an intense emotional response in the physician and staff. A majority of emergency physicians describe this as the most stressful event in emergency medicine. Few emergency physicians are instructed in plexities of dealing with the death of a child. The authors have developed a teaching module that introduces aspects of pediatric death-telling through the eyes of parents who have personally experienced the death of a child. |
9451319 | The acute asthmatic patient in the ED: to admit or discharge. | Treating asthma in the emergency department (ED) always involves the potentially difficult decision as to whether to discharge the patient, to continue treatment, or to admit to the hospital. The following are useful guidelines. (1) The duration of the bronchospasm, frequency of visits, history of previous endotracheal intubation, pulse rate, and accessory muscle use are findings affecting successful discharge from the ED. (2) Patients with peak expiratory flow rate (PEFR) of < 20% and who do not respond to inhalant therapy, with PEFR values persisting at < 40% of predicted, will require 4 or more days to resolve and should be admitted to the hospital. (3) Patients with a PEFR between 40% and 70% of predicted after initial inhalant therapy may well be responsive to steroids in the ED, but an ED will adequately need to care for the patient for 5 to 12 hours while waiting for the onset of action of glucocorticoids. Discharged with glucocorticoids, this group has a 6% relapse rate within 10 days of the ED visit. (4) Patients with a PEFR of > or = 70% have a 14% relapse rate after discharge without glucocorticoids. Other reasons to consider admission are pneumonia, barotrauma, lability, prominent psychiatric difficulties, poor access to medications, poor educability, fear of steroids, patients on glucocorticoids or those who have recently stopped glucocorticoids, and evening discharges of patients from the ED, which all predispose to relapses of acute asthma. To decrease the relapse rate, provocative factors should be reviewed with the patient, as well as access to medication and use of spacers, inhaler techniques, PEFR meters, self-management plans, and referral to a defined appointment at 24 to 48 hours of the ED visit. |
9451320 | Algorithms for diagnosing some electrolyte disorders. | The differential diagnosis of electrolyte disorders has traditionally been framed in terms of pathophysiology, and analysis of clinical problems has usually proceeded in the same way. However, easier access to rapid-response laboratory analysis has prompted physicians who encounter patients with serious electrolyte abnormalities to try to establish the cause by quickly obtaining further simple tests. In that vein, this article and the algorithms that are presented are intended to assist the preliminary laboratory differential diagnosis of low and high serum levels of sodium, potassium, and calcium. |
9451322 | The cost-effective use of nebulized racemic epinephrine in the treatment of croup. | Recent studies have shown that discharging to home an emergency department (ED) patient with croup if the patient is clinically stable 3 to 4 hours after being treated with nebulized racemic epinephrine (NRE) is safe and cost-effective. The objective of this study was to determine if EDs in our geographic area are using NRE cost-effectively in the management of croup. A survey was mailed to the ED medical directors of 23 hospitals in Ohio, Kentucky, and Indiana within a 150-mile radius of our teaching/referral children's hospital. All the hospitals surveyed munity hospitals with EDs and in-patient pediatric units. The survey presented a 2-year-old with a croup-like illness and stridor at rest whom they have just treated with NRE and dexamethasone. The medical directors were asked what their disposition would be once the NRE therapy has pleted: automatically admit, transfer, discharge immediately, or observe for 3 to 4 hours and if stable at that time discharge to home with follow-up. Seven (30%) indicated they would automatically pared with 16 (70%) who indicated they would observe for 3 to 4 hours (P = .06). This article discusses potential reasons that 30% of the ED medical directors in our geographic area would automatically admit these patients rather than observe for signs of improvement that could lead to safe discharge and resultant cost savings. |
9451323 | Waiver of informed consent: a survey of emergency medicine patients. | Changes to Federal regulations pertaining to waiver of informed consent for acute care research were debated by the research and munities for more than 2 years before being finalized in October of 1996. Input from the general public was limited. This survey investigated the opinions of emergency medicine patients concerning waiver of informed consent for acute care research. A convenience sample of 212 patients were approached at a tertiary care academic urban emergency department. Seventy-three percent approved of waiver of informed consent if the absolute risks were minimal (50% if the absolute risks were greater than minimal but the incremental risks were minimal). Educational status and certain aspects of the patient's current health status (but not age, race, or gender) significantly affected the results. While most emergency medicine patients would want to be enrolled in a study if they had a serious illness and were unable to give informed consent, a significant percentage of patients would not want to be enrolled regardless of the degree of risk or availability of a family member to speak on their behalf. Waiver of informed consent for emergency research is an ethical dilemma pitting individual rights against societal needs and physician parentalism. A better understanding of what patients consider appropriate may help in resolving this dilemma. |
9451324 | The impact of National Health Insurance on the volume and severity of emergency department use. | National Health Insurance (NHI) was introduced in Taiwan on March 1, 1995. To evaluate the Influence of NHI on the volume and severity of emergency department (ED) visits, a retrospective analysis was conducted. The results showed that NHI did not result in a substantial increase in ED volume (P > .05), but the severity as measured by triage nurses did increase (P < .01). There was no change in the number of admissions to the intensive care units of patients transferred from smaller hospitals, but its percentage significantly decreased (P < .05), which may be a result of the significant increase in the total number of interhospital transfers. It was hypothesized that the universal coverage and a copayment contributed to these changes. |
9451336 | Immunotherapy, including gene therapy, for metastatic melanoma. | Current standard therapy for distant metastatic melanoma is ineffective and promises the quality of a patient's life. Immunotherapy is briefly reviewed in relation to its many forms: from local non-specific to the more recent specific vaccines, including those using specific melanoma peptides (e.g. from the proteins encoded by melanoma-associated gene (MAGE)) and those involving genetically transduced autologous melanoma cells using retroviral vectors in vitro. The mode of action of genetically transduced melanoma cells incorporating the granulocyte macrophage colony stimulating factor (GM-CSF) gene (GVAX) is presented as a paradigm for cytokine-mediated strategies. Trials of GVAX and other cytokine gene strategies are under way in Brisbane, Boston and Amsterdam, and some interim perspectives on the clinical es and immunological mechanisms involved are sketched. Some of pounding problems in immunotherapeutic strategies for cancer are identified, and possible adjunct manoeuvres for ing them are discussed. |
9451337 | Trends in survival from colonic cancer: the impact of subspecialization. | Data from population-based registries have demonstrated a recent increase in case survival for colonic cancer which has been attributed to earlier diagnosis. The present study was performed to identify time trends in case survival for patients with colonic cancer in a single institution, and to identify factors associated with any such improvement. |
9451338 | Where the sun never shines: anorectal melanoma. | Melanoma occurring in the anorectal region is recognized to be an mon tumour with a poor prognosis. Queensland has the highest incidence rate of cutaneous melanoma in the world. The purpose of the present study was to determine if the very high incidence of cutaneous melanoma in Queensland has any bearing on the incidence of anorectal melanoma, and pare this with published studies from other parts of the world. An assessment of the authors' results in the treatment of anorectal melanoma was made by a review of patients presenting during the last decade throughout Queensland. |
9451339 | Independently predictive prognostic variables after resection for colorectal carcinoma. | Clinical variables such as surgical orbidity and follow-up have been claimed to influence ultimate survival in patients who have resection for colorectal cancer. It is unclear whether the effect of clinical covariates is confounding or independent. We have attempted to build prehensive model, which is capable of testing the dependence and importance of prognostic factors. |
9451340 | Renal parenchyma-sparing surgery in carcinoma. | There is controversy regarding the role of renal-sparing surgery in patients with kidney cancer who have a functioning contralateral kidney. |
9451341 | Fifteen-year experience of testicular neoplasm in a regional centre. | During a 15-year period from 1980 to 1995, 63 patients from the Geelong region of Victoria presented with germ cell neoplasm. |
9451343 | Food bolus intestinal obstruction in a Chinese population. | The aim of the present study was to review the authors' experience of the diagnosis and management of food bolus obstruction in a Chinese population. |
9451342 | The relationship of cervical lymph node metastases to primary sites of carcinoma of the upper aerodigestive tract: a pathological study. | Therapeutic and elective dissection of the neck is accepted management in the treatment of squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT). Accurate histological assessment of the levels of involvement of cervical metastatic spread from different sites within the UADT has allowed the increasing use of less than radical procedures, with associated reduced morbidity. |
9451344 | The unreamed tibial rod in open tibial fractures. | Open tibial fractures may be managed surgically by either external fixation or the intramedullary rod. If a rod is used, the delayed removal of the locking screws has been advocated to enhance fracture healing. The aim of the present study was to report the results of closed unreamed locked tibial rods in open fractures and evaluate the effect of locking screw removal. |
9451345 | Growth disturbances associated with untreated benign bone cysts. | The occurrence of benign bone cysts adjacent to an active physis may be associated with a physeal arrest. That arrest may result from physeal penetration of the cysts itself, secondary pathologic fracture or the result of surgical curettage. |
9451346 | Comparison of the effect of two heights of glycine irrigation solution on serum sodium and osmolality during transurethral resection of the prostate. | The absorption of sodium-deficient, hypotonic irrigation solution is believed to contribute, in certain cases, to hyponatraemia and hypo-osmolality and, in severe cases, to the so-called transurethral resection of the prostate (TURP) syndrome. |
9451347 | The temporalis muscle flap in intraoral reconstruction. | Reconstruction following excision of intraoral tumours presents a challenge to the head and neck surgeon. The purpose of hte present study was to review the authors' initial experience with the temporalis muscle flap. |
9451348 | Does a teaching programme in day surgery impact on efficiency and quality of care? | Recent medical advances have led to an explosion in the use of day surgery, making traditional teaching untenable and necessitating a transfer of undergraduate teaching programmes into the day surgery setting. concerns have been raised about the impact of teaching on efficiency and quality of care in this environment. |
9451349 | He who cannot take part in the friendly meal is half cut off from the society of man. | The history of oesophageal surgery is reviewed with particular reference to the early history of ingested foreign bodies, oesophagotomy and oesophageal stricture. Some emphasis is placed on those conditions, which are of particular significance in childhood. A brief mention is also made of the history of carcinoma fo the oesophagus. |
9451365 | Preserving the diabetic kidney. | End stage renal disease is an mon problem among both type 2 and type 1 diabetic patients. It is possible to halt or delay the progression from microalbuminuria to proteinuria to end stage renal disease through early screening and aggressive control of blood pressure, blood glucose, and the appropriate use of angiotensin-converting enzyme inhibitors. |
9451368 | Why family physicians deliver babies. | Numerous factors have been hypothesized to explain the steady decline of family physicians providing maternity care. Rather than exploring reasons for departure, we sought to learn why many family physicians choose to deliver babies. |
9451369 | Esophagogastroduodenoscopy performed by a family physician. A case series of 793 procedures. | Primary care physicians are performing an increasing number of gastrointestinal endoscopies. The purpose of this research is to present a large case series of diagnostic esophagogastroduodenoscopies (EGDs) performed by a family physician in a solo rural practice. |
9451370 | The consultation and referral process. A report from NEON. Northeastern Ohio Network Research Group. | Consultation and referral are ponents of the practice of primary care. Despite this, little is known about the factors that contribute to the success of a referral. We examined the short-term es munication between family physicians and consultants during the referral process. |
9451371 | The family APGAR and psychosocial problems in children: a report from ASPN and PROS. | Our study examined whether the lack of social support as measured by the Family APGAR was related to parents' and physicians' identification of child psychosocial problems and sociodemographic and symptom characteristics of the children screened. |
9451372 | Women's interest in natural family planning. | In the United States, approximately 4% of women of reproductive age use natural family planning (NFP) to avoid pregnancy. It is unclear whether this low number is related to a lack of available information, women's lack of interest, or other factors. Our study examined women's interest in using NFP either to e pregnant or to avoid it. |
9451373 | Variations in approaching the diagnosis of depression: a guided focus group study. | Primary care physicians are often held to the same standard of performance as mental health specialists, yet they face special challenges in recognizing and treating depression. The purpose of this study was to explore the range of approaches to diagnose depression. |
9451374 | Chromium picolinate supplementation for diabetes mellitus. | Chromium picolinate is a widely available nutritional supplement marketed for a plethora of afflictions. There is some evidence, including results from human studies, that it has a role in glucose homeostasis. We report the case of a 28-year-old woman with an 18-year history of type 1 diabetes mellitus whose glycosylated hemoglobin (Hb A1c) declined from 11.3% to 7.9% 3 months after initiation of chromium picolinate, 200 micrograms 3 times daily. Chromium picolinate continues to fall squarely within the scope of "alternative medicine," with both unproven benefits and unknown risks. It deserves closer scrutiny with additional prospective, randomized, double-blind, placebo-controlled trials to evaluate its efficacy in improving es in patients with diabetes. A brief review of the literature was done to assist physicians who are being called upon to counsel and treat patients who are engaging in alternative therapies. |
9451377 | Nursing management and healthcare in Slovenia. | Nursing management and healthcare in Slovenia are undergoing rapid change as the country es independent. Nursing is changing the rigid hierarchy of health service and implementing professional development. Nurses are striving to e key players in delivery, decision making, and policy setting to ensure quality healthcare. |
9451379 | Will nursing administration programs survive in the 21st century? | Why are graduate nursing administration (MSN/A) program enrollments declining? Do these programs truly meet the needs of potential students? Will they help them to be effective and innovative partners on the healthcare management team? The authors explore reasons for the decline in MSN/A enrollments, potential negative es, and currently available alternative educational choices. They then suggest MSN/A program redesign and other courses of actions. Nurse administrators and nurse educators must be aware of these trends and have equal input into the creation of a viable MSN/A program that will be able to survive in the 21st century. |
9451380 | The Professional Transitions Workshop. Cornerstones of practice. | The Professional Transitions Workshop is a new program that integrates the Professional Advancement Program (clinical ladder) and the Professional Model of Practice (primary nursing). Together, these two programs provide the philosophical and structural foundations of professional practice and empower nurses to articulate the defining features of their clinical experiences. Educating staff members about these programs emphasizes critical thinking and storytelling as important skills for the professional nurse. The authors describe the advantages, processes, and es of this change. |
9451381 | Performance improvement with patient service partners. | Once the decision is made to use a patient-focused care delivery system, a variety of methods can be used to successfully design the model. The author describes the process used by a multilevel, multidisciplinary team at munity hospital to design and implement a Service Partner role that would meet and exceed customer expectations. Demonstrated performance improvements included increased patient satisfaction, productive labor dollar savings, and improvements in the work environment for staff members. |
9451382 | Rating nursing performance based on behaviors. | If used effectively, performance appraisal systems keep employees focused on the vision and mission of the organization. Appraisal tools firmly grounded in desired behaviors can be effective in improving performance. The authors describe the steps and development of a Behavior Anchored Rating Scale (BARS) for registered nurses and give readers information for developing behaviorally based evaluation tools. |
9451383 | Work complexity assessment. Decision support data to address cost and culture issues. | Nurse administrators, in response to budget imperatives, have made decisions that, rather than solve their difficulties, magnify them. Finding solutions that address cost as well as culture changes in nursing is crucial if we are to remain financially and professionally viable. In this article, the authors describe a tool for reconstructing reality for both cost reduction and relationship development. |
9451384 | Mediation: a response to aid-in-dying and the Supreme Court decision. | The recent U.S. Supreme Court decision concerning aid-in-dying has drawn attention to plexity of end-of-life care. The authors summarize the recent Supreme Court's decision and the problems surrounding plex issue. A case study is provided to demonstrate how mediation facilitates collaborative problem solving. Finally, the authors demonstrate how nurse leaders can apply this three-stage process and its attendant principles to facilitate ethical decision making in end-of-life care. |
9451388 | Breast cancer mortality trends in Australia: 1921 to 1994. | To analyse breast cancer mortality trends in Australia and to see if mammographic screening has yet led to a reduction in mortality. |
9451389 | Shared antenatal care fails to rate well with women of non-English-speaking backgrounds. | pare the views of women from non-English-speaking backgrounds who received antenatal care at a public hospital clinic with those whose care was shared between a public hospital clinic and a general practitioner. |
9451390 | Factitious quinine-induced thrombocytopenia. | A 57-year-old man presented on multiple occasions to various hospitals with thrombocytopenia plaints of easy bleeding. Despite his repeated denials of quinine use, laboratory investigations confirmed a diagnosis of quinine-induced thrombocytopenia. He appeared to have factitious disorder and to have discovered a novel means of precipitating symptoms. |
9451391 | Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of Australia and New Zealand. | Evidence shows that patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of 55 mm Hg or less will have longer life expectancy if given supplemental oxygen to keep the PaO2 above 60 mm Hg, preferably for longer than 15 hours a day, including sleep. There is some evidence for improved quality of life. It is reasonable to offer this therapy for other lung diseases which cause chronic hypoxaemia, and there are also less well defined indications for supplemental oxygen during exercise, sleep and air travel. |
9451393 | Graduates of the University of Tasmania Medical School: career achievements 10 to 23 years after graduation. | To assess the postgraduate achievements of graduates of the University of Tasmania Medical School. |
9451407 | Patterns of disease and HIV testing at sexually transmitted disease clinics. | To measure the occurrence of sexually transmitted diseases (STDs) and of HIV testing in a population of STD clinic attenders and the associations of these with age, gender, ethnicity, intravenous drug use, sexual practices and other STDs. |
9451408 | Osteitis--an under-recognised association with seronegative spondyloarthropathy? | To emphasise osteitis as a feature of the spondyloarthritides. |
9451409 | Assessing glycaemic control in diabetes: relationships between fructosamine and HbA1C. | Glycated haemoglobin (HbA1C) has e the internationally established method of assessing long term glycaemic control in people with diabetes. In New Zealand the measurement of glycated albumin (fructosamine), which is substantially cheaper than HbA1C has been widely adopted. In this study we have sought to determine if the value of HbA1C can be reliably estimated from knowledge of plasma fructosamine. |
9451410 | Spinal injuries in New Zealand rugby and rugby league--a twenty year survey. | To establish trends in frequency of serious spinal cord injuries in rugby and rugby league over a 20 year period and to elucidate patterns of injury from retrospective analysis of cases admitted to New Zealand's two spinal injuries units. |
9451411 | Aging, dementia and care: setting limits on the allocation of health care resources to the aged. | This article explores the ethical dimensions behind care of the elderly and considers whether younger people should be given priority over the aged in the provision of health care resources. It is argued that age is a relevant consideration in decisions concerning the allocation of health care. The notions of a 'natural life span' and a 'tolerable death' are discussed and on this basis I conclude that while the interests and claims of the elderly must be protected, the use of unlimited resources in the pursuit of life extending measures cannot be justified. When traditional ethical principles are applied to care of the aged they have to be viewed in a modified fashion. The nature of dementia is such that integrity in caregiving has to take account of the patient's premorbid self. I argue that the morally appropriate response to demented patients excludes acute-care, life-extending medicine, but neither does it advocate active euthanasia. The aim is to find a middle ground between treating the demented too aggressively and failing to give them sufficient treatment. |
9451421 | The management of crisis in sickle cell disease. | The symptoms and signs of sickle cell disease are exacerbated in times of crisis, characterized by tissue infarction or worsening anaemia. Prompt medical intervention is required in these distressing situations to provide relief fort to the patient. Effective analgesia is crucial in treating the painful crisis of sickle cell disease. The haemoglobinopathy may cause hyposthenuria with reduced ability to excrete the sodium load in normal saline. A 5% dextrose solution or 5% dextrose in 25% normal saline is therefore mended for intravenous hydration. As the leading cause of morbidity and mortality in sickle cell disease, infections call for vigorous antibiotic therapy. Oxygen administration should be reserved for hypoxic patients, and blood transfusion given only when really indicated. Acute chest syndrome and cerebrovascular accidents are plications of sickle cell disease whereas priapism can cause important long-term sequelae; all deserve urgent attention. In the long prehensive care is cost-effective in reducing the frequency and adverse effects of sickle cell crisis. |
9451417 | Growth kinetics of the granulosa cell population in ovarian follicles: an approach by mathematical modelling. | This paper describes, from a mathematical viewpoint, the cellular changes in the granulosa of ovarian follicles during their terminal development. A dynamic model takes into account the processes of (1) cell division, (2) exit from the cell cycle towards differentiation, and (3) apoptotic cell death. Proliferative cells leave the cycle in an irreversible way. The risk of entering apoptosis applies to non-cycling cells. Changes in the cell numbers and in the growth fraction are derived from differential equations. The transitions between the different cell states are ruled by time-dependent rates. Numerical applications of the model concern ovulating and degenerating ovarian follicles in the ewe. The main feature of the ovulating case is the progressive exhaustion of the partment for the benefit of the non-cycling cells. From an initial mainly proliferative state the granulosa progressively switches to a highly differentiated state, so that the growth fraction continuously decreases. In the atretic cases, the pattern of changes in the total viable cell number is influenced by the follicular age at the onset of the apoptotic process and by the intensity of the cell death rate. As apoptosis affects the non-cycling cells, the growth fraction is no longer strictly decreasing. The sensitivity of the model to the parameters is studied in a more general framework than the granulosa cell population. |
9451422 | Variation in cell yield and proliferative activity of positive selected human CD34+ bone marrow cells along the circadian time scale. | Variations in cell yield and proliferative activity of human bone marrow (BM) progenitor cells were determined with flow cytometry along the 24-h (circadian) time scale. Equal volumes of BM were aspirated every 5 h, altogether 5 times in 5 healthy men. An average 6-fold higher yield of positive selected CD34+ cells occurred in each subject when BM was aspirated during the daytime and late afternoon, while a lower yield occurred during the night. Using all CD34+ cell yield data normalized to percentage of mean, a significant time-effect was found by ANOVA (p = 0.02) and a significant circadian rhythm was detected by the least-squares fit of a 24 h cosine (p = 0.02). The 95% confidence limits of the acrophase (time of highest values) puted to be at midday between 10:24 and 14:48 h. A highly significant correlation (p = 0.001) was found between proliferation of positive selected CD34+ cells and the more mature myeloid precursor cells from the same BM aspirates, suggesting mon temporal pattern along the circadian time scale. However, no correlation was demonstrated between proliferation and cell yield of CD34+ selected cells, suggesting that mechanisms other than variation in proliferation may cause the circadian rhythm in stem cell yield. These circadian variations in stem cell yield and proliferation suggest that proper timing within 24 h may potentially be important regarding e from progenitor cell harvesting and treatment with haematopoietic growth factors. |
9451418 | A polymerase chain reaction assay for simultaneous detection and quantitation of proto-oncogene and GAPD mRNAs in different cell growth rates. | A reverse transcriptase followed by a polymerase chain-reaction (RT-PCR) assay was developed for the simultaneous detection and quantitation of proto-oncogene (c-fos and c-myc) mRNAs using an internal standard mRNA glyceraldehyde-6-phosphate dehydrogenase (GAPD). Total cellular RNA was reverse transcribed and PCR amplified with oligonucleotide primers specific to GAPD and either c-fos or c-myc genes. In contrast to Northern blot analysis, the RT-PCR assay is rapid and sensitive enough to quantitate specific proto-oncogene levels from as little as 12-25 ng of total cellular RNA. The reliability of the assay was tested by measuring c-fos and c-myc expression in C3H 10T1/2 mouse embryo fibroblast cells under two different growth states: (a) quiescent cell entry into the proliferative cycle, and (b) plateau phase. Furthermore, the assay was used in measuring variations in c-fos or c-myc expression in HA-1 hamster cells following exposure to the cellular stressing agent, nitric oxide. In serum-stimulated cells, the RT-PCR measurements of transient increase in c-fos (16-fold at 30 min) and c-myc (10-fold at 1 h) mRNA levels parable to previously reported results in the literature using a Northern blotting assay. In addition, a two- to fivefold increase in c-fos mRNA levels was observed in plateau phase cells pared to log phase growth. Furthermore, a transient increase in c-fos mRNA levels (threefold at 2 h) was also observed following cells' exposure to the stressing agent nitric oxide. These results suggest that the multiplex RT-PCR assay represents a significant improvement over current methods to quantitate specific cellular mRNAs under different growth conditions or following environmental insults. |
9451423 | Lectin-induced increase in clonogenic growth of haematopoietic progenitor cells. | The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p < 0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with D-galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation. |
9451424 | Decreased expression of c-myc oncoprotein by peripheral blood mononuclear cells in thalassaemia patients receiving desferrioxamine. | Desferrioxamine (DFX) is an iron chelation agent widely used in the treatment of transfusional iron overload in patients with thalassaemia major and other severe refractory anaemias. DFX has been shown to induce inhibition of DNA synthesis and apoptosis in vitro; however, the molecular targets of DFX action are not well known. The c-myc proto-oncogene is involved in a number of cellular processes including proliferation, differentiation and apoptotic cell death. We have examined the expression of c-myc in peripheral blood mononuclear cells from 71 patients with homozygous beta-thalassaemia in regular transfusion and iron chelation therapy with DFX, 5 non-transfusion, non-chelation-dependent thalassaemic patients, and 15 healthy volunteers using an APAAP immunocytochemical method. We have found that mononuclear cells from thalassaemic patients receiving DFX express significantly lower levels of c-myc pared to control healthy volunteers or thalassaemics receiving no DFX. In vitro treatment of HL60 or K562 leukaemic cells with 100 microliters DFX also induced a rapid decrease in c-myc mRNA and protein levels, followed by apoptosis and inhibition of DNA synthesis. These effects were blocked by simultaneous addition of ferric chloride. Our data suggest that deprivation of cellular iron induces downregulation of c-myc expression in vitro and in vivo and may influence haemopoietic cell growth and survival. |
9451425 | African iron overload and hepatocellular carcinoma (HA-7-0-080). | Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, iron overload in Africa is not thought to be etiologically related to this malignancy. To determine if African iron overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular iron. Subjects were stratified according to hepatocellular iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with iron overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between iron overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with iron overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without iron overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that iron overload may be a risk factor for hepatocellular carcinoma in Africa. |
9451420 | A novel growth stimulating activity from BRL-3A cell conditioned medium. | The R- cell line is a 3T3-like cell line originating from mouse embryos with a homozygous disruption of the type 1 insulin-like growth factor receptor (IGF-IR) genes. Although R- cells cannot grow at all in serum-free medium (SFM) supplemented by several known growth factors, either singly or bination, they are able to grow in 10% serum, albeit at a reduced rate. These findings suggested that serum contains an unknown, or unidentified, growth factor that can promote cell growth even in cells devoid of IGF-IRs. In an effort to identify such growth factor, we searched, using R- cells, for a growth and DNA synthesis stimulating activity in SFM conditioned by different cell lines. We found that the BRL-3A cell line secreted an activity capable of stimulating DNA synthesis and cell proliferation in R- cells. This activity (which is concentration-dependent) can be collected and concentrated by ultrafiltration, it is heat-labile, proteinase K-sensitive and has a size larger than 10 kDa. Because of the resistance of R1 cells to stimulation by known growth factors, we believe that this activity is due to a novel polypeptide secreted by BRL-3A cells. Further characterization of the ponent(s) is in progress. |
9451426 | Impact of clinical and morphological variables in classification and regression tree-based survival (CART) analysis of CML with special emphasis on dynamic features. | To determine parameters of predictive value in CML, a retrospective clinico-pathological study was performed. This included laboratory data and (pretreatment) bone marrow biopsies of 120 patients with a monotherapy by busulfan (BU) and 50 patients with interferon-alpha 2b (IFN) treatment. Median survival in the BU group was 39 months and in the IFN-treated patients 65 months. Morphological features (CD61-positive megakaryocytes, argyrophilic fibres, pseudo-Gaucher cells) were evaluated by morphometry. Additionally, we measured the incidence of apoptosis (in situ end-labelling technique) and the expression of the proliferating cell nuclear antigen (PCNA). The ratio between the proliferative and apoptotic cell fraction was coined leukaemia turnover index (LTI). In order to estimate the impact of clinical and various morphological as well as dynamic features of prognostic significance, a multivariate analysis was carried out using the classification and regression tree approach (CART). Discrimination of single disease parameters revealed that fibrosis remained the most significant variable for survival in both therapeutic groups. Indicators of myeloid metaplasia such as occurrence of erythro-normoblasts and/or splenomegaly were important clinical parameters for prognosis. Inclusion of morphological as well as dynamic disease features in risk classification resulted in a substantial improvement of prognostic pared to other predictive scores which could be demonstrated by means of ROC-analysis. |
9451427 | Clinico-prognostic relevance of quantitative immunophenotyping in B-cell chronic lymphocytic leukemia with emphasis on the expression of CD20 antigen and surface immunoglobulins. | Expression of CD20, evaluated as antibody binding capacity (ABC) (i.e. absolute number of molecules of antibody per cell), was analyzed using flow cytometry on leukemic cells of 93 previously untreated patients, all fulfilling strict criteria of "immunologically typical" (i.e. CD5+, CD23+) B-cell chronic lymphocytic leukemia (CLL). Although changes of CD20 antigen density did not correlate with clinical parameters representative of either tumor mass (i.e. clinical stage, histological pattern of bone marrow involvement, absolute peripheral blood lymphocytosis) or disease progression (i.e. lymphocyte doubling time), a trend toward a better life-expectancy was observed in the low CD20 expression pared with the high CD20 expression group (p = 0.05; relative risk of death, 0.51, 95% confidence interval, 0.24-1.04). Given the correlation between CD20 ABC and mean fluorescence intensity (MFI) of light chain (LC) surface immunoglobulins (Sm Ig) (r = 0.481, p < 0.0001), as well as the impact of MFI of Sm Ig LC on overall survival (p = 0.01; relative risk of death 0.44; 95% confidence interval, 0.10 to 0.76), we tried to verify whether bination of B-cell markers, evaluated in a quantitative manner, could have additive prognostic properties. To this purpose we gave a value of 1 or 0 to each B-cell marker according to whether it was expressed at a low (i.e. CD20 ABC < 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig < 100) or high (i.e. CD20 ABC > or = 17.9 x 10(3) molecules/cell, MFI of LC Sm Ig > or = 100) level thus allowing patient stratification into two groups with scores of 2 and 0-1, respectively. Survival of patients who scored 2 was significantly longer respectively. Survival of patients who scored 2 was significantly longer than that of patients who scored 0-1 (p = 0.02; relative risk of death, 0.44; 95% confidence interval, 0.22-0.72). However, when quantitative changes of CD20 antigen and LC Sm Ig expression, either alone or bination, were simultaneously analyzed in a Cox model which included usual clinico-hematological features, only absolute peripheral blood lymphocytosis (p = 0.0001) and Binet clinical stages (p = 0.0001) maintained their prognostic power unmodified. Although variability of CD20 and Sm Ig expression make it possible to appreciate biological heterogeneity of B-cell CLL better, however, they cannot substitute well-established clinico-hematological features in the prognostic assessment of B-CLL patients. |
9451419 | WR-1065, an active metabolite of the cytoprotector amifostine, affects phosphorylation of topoisomerase II alpha leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells. | The effects of WR-1065 (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) II alpha activity, and topo II alpha phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. Exposure of CHO cells to 0.4 microM of WR-1065 for 30 min did not effect cell cycle progression nor topo II alpha activity and phosphorylation status. However, concentrations ranging from 4 microM to 4 mM were equally effective in significantly altering these three end points. Cell cycle progression was analysed by flow cytometry. Following a 30 min exposure to this range of concentrations, cells redistributed throughout the cell cycle with the most prominent changes being an accumulation of cells in G2. Topo II alpha activity was measured using a kinetoplast DNA (kDNA) decatenation assay. Enzyme activity was reduced by 50% relative to control levels throughout the 4 microM to 4 mM dose range tested. Likewise, topo II alpha phosphorylation levels, analysed using an immunoprecipitation assay and an antibody specific to the 170 kDa band of topo II, decreased between 42% to 48% of control levels. Inhibition of topo II alpha activity in cells exposed to WR-1065 is consistent with the associated observation of WR-1065 mediated cell cycle progression delay and build-up of cells in the G2 phase of the cell cycle. |
9451428 | Delineation of erythropoiesis in normal and malignant bone marrow using monoclonal antibody AS-E1 directed against transferrin receptors (CD71). | We have delineated the partment in normal and malignant bone marrow (BM) by using the monoclonal antibody (mAb) AS-E1 directed against the transferrin receptor by flow cytometric (FCM) analysis. In normal BM we found a bimodal expression in antigen density with a minor subset (approximately 3%) expressing AS-E1high and a larger subset (approximately 15%) expressing AS-E1low. By fluorescence activated cell sorting, morphological examination of smears stained by immunocytochemistry and by BFU-E assays the AS-E1high fraction was shown to contain cells of erythroid origin (proerythroblasts, basophilic erythroblasts and polychromatic erythroblasts), whereas the AS-E1low fraction consisted mainly of promyelocytes and myelocytes. In patients with malignant hematological disorders we found a more pronounced heterogeneity in the density and the degree of AS-E1low pared to normal BM, and to further characterize the AS-E1low cells in patients and to exclude that this broad reactivity interfered with the identification of the AS-E1high cells, we employed triple-color FCM assays with mAbs directed against the myeloid surface markers CD13 and CD66 in addition to AS-E1. In all patients we found that 80-90% of the AS-E1low cells co-expressed CD13 and/or CD66 and thus were of myeloid origin. Finally, we evaluated 2 methods for determination of the AS-E1high subset and found an assay involving forward light scatter and logAS-E1 density to be sufficient. We conclude that AS-E1high is a valid FCM marker for the normal erythropoiesis. |
9451434 | Secondary structures in d(CGG) and d(CCG) repeat tracts. | Several studies have been made to elucidate the nature of secondary structures in the single strands of d(CGG).d(CCG) repeat tracts but with conflicting conclusions. Here, we review this work and attempt e towards consensus. Some investigators find that the G-rich strand forms hairpins. Of these, some conclude that pairing is in the alignment d(GGC).d(GGC) with two Watson-Crick bonds and one G.G bond per duplex repeat, others conclude that the alignment is d(GCG).d(GCG) with two G.G bonds and one C.C bond per duplex repeat. Others find quadruplex formation and conclude that this is in the latter alignment with two G4-quartets per quadruplex repeat and C.C bonds. We investigate why these different results were obtained and conclude that quadruplexes are likely to form under physiological conditions. We argue that they are probably bonded in the alignment d(GGC).d(GGC) with one G4-quartet and two C.G.C.G. quartets per quadruplex repeat. The C-rich strand does not appear to form quadruplexes under physiological conditions but forms hairpins. Apparently, short hairpins adopt the alignment d(CCG).d(CCG) with mismatched cytosine residues stacked into the helix but with 15 or more repeat units, the dominant form is a distorted hairpin aligned as d(GCC).d(GCC) with unpaired cytosine residues possibly turned outwards and stacked in the minor groove. |
9451435 | Evidence for two preferred hairpin folding patterns in d(CGG).d(CCG) repeat tracts in vivo. | Unusual DNA secondary structures have been implicated in the expansion of trinucleotide repeat tracts that has been found to be responsible for a growing number of human inherited disorders and folate-sensitive fragile chromosome sites. By inserting trinucleotide repeat sequences into a palindromic clamp in lambda phage we are able to investigate their tendencies to form hairpins in vivo in any particular alignment and with odd or even numbers of repeat units in the hairpin. We previously showed that with d(CAG).d(CTG) repeat tracts there was a markedly greater tendency to form hairpins with even numbers of repeat units than with odd numbers, whereas d(GAC).d(GTC) repeats showed no such alternation despite having the same position. We expected that d(CGG).d(CCG) repeats, might show the same pattern as d(CAG).(CTG) repeats since they are also involved in trinucleotide repeat expansion disorders. The pattern was not so clear and we wondered whether this might be because d(CGG).d(CCG) repeats have more than one possible alignment in which they could self-anneal. We now present results for all three alignments, which suggest that while even-membered hairpins are preferred in the frame d(CGG).d(CCG), hairpins with odd numbers of trinucleotides are more stable in the frame d(GGC).d(GCC). In both cases the base-pair predicted to close the terminal loop of unpaired bases is 5'C.3'G which has previously been found to be a favoured loop-closing pair. |
9451436 | The hydrophobic domains in the carboxyl-terminal signal for GPI modification and in the amino-terminal leader peptide have similar structural requirements. | Proteins having a glycosyl-phosphatidylinositol (GPI) membrane anchor are synthesized with a carboxyl-terminal signal that is cleaved in the endoplasmic reticulum prior to GPI modification. The signal is characterized by a moderately hydrophobic domain downstream from the cleavage/modification site. The essential features of this domain were characterized using a truncated version of folate receptor (FR) type beta (FR-beta delta 5) in which its five carboxyl-terminal amino acid residues were deleted without affecting the efficiency of GPI modification. The amino acids at various positions in the hydrophobic domain were systematically altered and the extent of GPI modification of the binant proteins was determined by measuring [3H]folic acid binding at the cell surface, by Western blot analysis and from the sensitivity of the proteins to phosphatidylinositol-specific phospholipase C (PI-PLC). The results indicate that a threshold level of hydrophobicity exists at a single position below which the efficiency of GPI modification decreases with increasing hydrophilicity. Further, the hydrophobic domain is characterized by a hydrophobicity profile and not merely a minimum overall hydrophobicity. Thus, a leucine-rich core hydrophobic segment of six to eight amino acid residues is more sensitive to relatively small hydrophilic pared to its flanking regions and such mutations could pensated by a hydrophobic substitution elsewhere within this core segment. Such a hydrophobicity profile is characteristic of the amino-terminal leader peptide. When the entire hydrophobic domain of the leader peptide of FR-beta (12 amino acid residues) was substituted with the hydrophobic domain of the GPI signal (13 amino acids), it was possible to obtain expression of FR-beta on the cell surface. In this construct, point mutations in the core hydrophobic segment and in the flanking regions within the substituting peptide produced a similar pattern of effects on the cell surface receptor pared to the corresponding mutations in the GPI signal of FR-beta. The results suggest mon principles may govern interactions of the hydrophobic domains of the GPI signal and the leader peptide with the endoplasmic reticulum. |
9451437 | Towards an atomic model of the thick filaments of muscle. | The thick filaments of muscle and non-muscle cells are polymers of myosin molecules whose energy-transducing heads lie on the filament surface, where they interact with actin to generate force. A key structural question is how the myosin heads are arranged in the relaxed state, and how this arrangement changes on activation of contraction. We have fitted the atomic structure of the myosin head to the three-dimensional structure of myosin filaments of tarantula muscle determined by electron microscopy to produce a near-atomic model of the head arrangement. A good fit is obtained only when the two heads from a myosin molecule run along the helical tracks antiparallel to each other. Oppositely oriented heads from axially adjacent molecules in a helix interact with each other, with their nucleotide-binding pockets opposed. This arrangement, supported also by crosslinking evidence, suggests a simple mechanism for the stabilization of myosin head helices in relaxed muscle via the formation of intermolecular "dimers" of heads from axially adjacent myosin molecules. |
9451438 | Mammalian RNA polymerase I exists as a holoenzyme with associated basal transcription factors. | Transcription initiation of ribosomal RNA genes requires RNA polymerase I (Pol I) and auxiliary factors which either bind directly to the rDNA promoter, e.g. TIF-IB/SL1 and UBF, or are assembled into productive transcription plexes via interaction with Pol I, e.g. TIF-IA, and TIF-IC. Here we show that ponents required for specific rDNA transcription initiation are capable of physical interaction with Pol I in the absence of DNA and can be co-immunoprecipitated with antibodies against defined subunits of murine Pol I. Sucrose gradient centrifugation and fractionation on gel filtration columns reveals that approximately 10% of cellular Pol I elutes as a plex with an apparent molecular mass of > 2000 kDa. The large Pol plex contains saturating levels of TIF-IA, TIF-IB and UBF, but limiting amounts of TIF-IC. In support of the existence of a plex between Pol I and basal factors, the plex is transcriptionally active plementation with TIF-IC. The results suggest that, analogous to class II gene transcription, a plex, the "Pol I holoenzyme", exists that appears to be the petent form of Pol I. |
9451440 | Stalling of human DNA (cytosine-5) methyltransferase at single-strand conformers from a site of dynamic mutation. | Single-strand conformers (SSCs) from the C-rich strand of the triplet repeat at the FMR-1 locus are rapidly and selectively methylated by the human DNA (cytosine-5) methyltransferase. The apparent affinity of the enzyme for the FMR-1 SSC is about tenfold higher than it is for a control Watson-Crick paired duplex. The de novo methylation rate for the SSC is over 150-fold higher than the de novo rate for the control duplex. Methylation of what is generally called a hemi-methylated duplex occurs with a rate enhancement of over 100-fold, while methylation of what can be viewed as a hemi-methylated FMR-1 SSC is actually slower than the de novo rate. The pronounced inhibition of the methyltransferase by the methylated SSC suggests that the enzyme has a higher affinity for the methylated product of its reaction with the SSC than it has for the unmethylated SSC substrate. Gel retardation studies show that the methyltransferase binds selectively to SSCs from the C-rich strand of the FMR-1 triplet repeat. This suggests a two-step stalling process in which the human methyltransferase first selectively methlyates and subsequently stalls at the C-rich strand SSC. Stalling may reflect the inability of the enzyme to release a DNA product that is fixed in a conformation resembling its transition state by the unusual structure of the substrate. In particular, the data suggest that DNA methyltransferase may physically participate in biological processes that lead to dynamic mutation at FMR-1. In general, the data raise the possibility that a two-step stalling process occurs at secondary structures associated with chromosome instability, chromosome remodelling, viral replication or viral integration and may account for the local hypermethylation and global hypomethylation associated with viral and non-viral tumorigenesis. |
9451441 | Transfer protein TraM stimulates TraI-catalyzed cleavage of the transfer origin of plasmid R1 in vivo. | Factors contributing directly to the cleavage of the conjugative transfer origin of plasmid R1 in Escherichia coli were investigated. The essential transfer protein TraM was identified as a necessary positive effector of the catalytic activity of TraI relaxase at the R1 transfer origin in the absence of protein TraY. The stimulatory effect of TraM on the cleavage reaction in vivo correlated with the capacity of TraM to bind origin DNA. TraM was shown to be essential for heterologous mobilization of binant origin DNA. The requirement for TraM to promote mobilization was distinct from the protein's positive effect on transfer gene regulation. Chimeric traM alleles, fusing heterologous amino and carboxyl coding sequences from the traM genes of the R1 and the IncFI plasmid P307, were used to localize the specificity determinant of TraM's DNA binding activity. Use of the chimeric alleles also revealed that the requirement for TraM in mobilization is origin specific but transfer system independent. No evidence was found for a plasmid specific activity of TraM at a stage in the transfer process subsequent to the initial cleavage of origin DNA. In light of TraM's regulatory functions in transfer gene expression, we propose that TraM could control conjugative DNA processing in response to intracellular levels of transfer proteins. |
9451439 | Ligand- and DNA-induced dissociation of RXR tetramers. | Unliganded bacterially expressed RXR alpha lacking the N-terminal region AB (apo-RXR alpha delta AB) was found in solution as an apparent mixture of 165 kDa tetramers and 42 kDa monomers which could be quantitatively separated by gel filtration and non-denaturing gel electrophoresis. Under identical conditions both liganded (holo-) and apo-RAR alpha delta AB were present as single monomeric species. apo-RXR alpha delta AB tetramers, as well as dimers of the apo-RXR ligand binding domain (apo-LBD), dissociated readily into monomers when exposed to their cognate ligand 9-cis retinoic acid (9c-RA). The apo-RXR alpha delta AB tetramer bound only transiently to a cognate DR1 response element, and was converted into DR1-apo-RXR alpha delta AB plexes indistinguishable from those generated by cooperative DNA binding of apo-RXR alpha delta AB monomers. In the absence of DNA, the addition of 9c-RA greatly accelerated the formation of heterodimers with the apo-RAR alpha delta AB heterodimerization partner. No RXR alpha delta AB or RAR alpha delta AB homodimers could be observed in solution, but upon mixing of the two receptor monomers stable heterodimers could be isolated which bound to DR5 response elements in a highly cooperative manner. In these heterodimers, RXR alpha delta AB interacted with its cognate ligand as efficiently as in RXR alpha delta AB homodimers. The presence of ligand did not alter the stability of RXR alpha delta AB homodimer or RXR alpha delta AB-RAR alpha delta AB plexes on DR1 and DR5 response elements, respectively. These in vitro data support a model in which RXR tetramers could serve as an inactive pool with the dual function of: (i) rapidly supplying large amounts of RXR heterodimerization partners upon 9c-RA generation; and (ii) allowing RXR homodimer formation on "accessible" cognate response elements in the absence of 9c-RA. These events may represent a ligand-dependent regulatory mechanism controlling the availability of the promiscuous RXR dimerization partner that is engaged in multiple nuclear receptor signalling pathways. |
9451442 | Analysis of hapten binding and catalytic determinants in a family of catalytic antibodies. | We report here the cloning and kinetic analysis of a family of catalytic antibodies raised against mon transition state (TS) analog hapten, which accelerate a unimolecular oxy-Cope rearrangement. Sequence analysis revealed close homologies among the heavy chains of the catalytically active members of this set of antibodies, which derive mainly from a single germline gene, whereas the light chains can be traced back to several different, but related germline genes. The requirements for hapten binding and catalytic activity were determined by the construction of hybrid antibodies. Characterization of the latter antibodies again indicates a strong conservation of binding site structure among the catalytically active clones. The heavy chain was found to be the determining factor for catalytic efficiency, while the light chain exerted a smaller modulating effect that depended on light chain gene usage and somatic mutations. Within the heavy chain, the catalytic activity of a clone, but not hapten binding affinity, depended on the sequence of the plementarity determining region (CDR). No correlation between high affinity for the hapten and high rate enhancement was found in the oxy-Cope system, a result that stands in contrast to the expectations from transition state theory. A mechanistic explanation for this observation is provided based on the three-dimensional crystal structure of the most active antibody, AZ-28, plex with the hapten. This study demonstrates the utility of catalytic antibodies in examining the relationship between binding energy and catalysis in the evolution of biological catalysis, as well as expanding our understanding of the molecular basis of an immune response. |
9451443 | The human proteasomal subunit HsC8 induces ring formation of other alpha-type subunits. | The eukaryotic 20 S proteasome is a barrel-shaped plex, made up of four seven-membered rings. The outer and inner rings contain seven different alpha and beta-type subunits, respectively, each subunit located at a defined position. Recently, we have reported that the binant human alpha-type subunit C8 (HsC8) assembles into a heptameric ring-like structure by itself. In the present study we show that the two naturally neighboring alpha-type subunits of HsC8, HsPROS30 and HsPROS27, do not form plexes by themselves, but only dimers. This indicates that the propensity to form homo-oligomeric rings is not a general feature among human alpha-type subunits. However, coexpression of HsC8 and either of these neighbor alpha-type subunits results in the formation of hetero-oligomeric plexes, resembling the HsC8 ring-like structure. The ratio between the two types of subunits in the plexes is surprisingly heterogeneous, varying from very high to very low HsC8 content. The three tested alpha-type subunits thus apparently lack binding sites that selectively interact with a specific neighboring subunit. This suggests that the correct positioning of the different alpha-type subunits in the eukaryotic 20 S proteasome is not dictated by the alpha-type subunits themselves, but rather by the interaction with specific beta-type subunits. |
9451444 | The solution structure of functionally active human proliferating cell nuclear antigen determined by small-angle neutron scattering. | The function of proliferating cell nuclear antigen (PCNA) in DNA replication and repair is to form a sliding clamp with replication factor C (RF-C) tethering DNA polymerase delta or epsilon to DNA. In addition, PCNA has been found to interact directly with various proteins involved in cell cycle regulation. The crystal structure of yeast PCNA shows that the protein forms a homotrimeric ring lining a hole through which double-stranded DNA can thread, thus forming a moving platform for DNA synthesis. Human and yeast PCNA are highly conserved at a structural and functional level. We determined the solution structure of functionally active human PCNA by small-angle neutron scattering. Our measurements strongly support a trimeric ring-like structure of functionally active PCNA in solution, and the data are in good agreement with model calculations based on the crystal structure from yeast PCNA. The human PCNA used in the small-angle neutron scattering experiments was active before and after the measurements in a RF-C independent and a RF-C dependent assay suggesting that the trimeric structure is the in vivo functional form. |
9451445 | Unfolding of apomyoglobin from Aplysia limacina: the effect of salt and pH on the cooperativity of folding. | The equilibrium unfolding pathway of Aplysia apomyoglobin has been studied under various solvent conditions. The protein exhibits a single unfolding transition in acid in contrast to the two transitions observed for the mammalian apomyoglobins with which it shares mon fold but a low level of sequence identity (24%). This acid-unfolded species has considerable residual structure as evidenced by both tryptophan fluorescence and far-UV CD spectroscopy. It remains 40% alpha-helical under low salt conditions (2 mM citrate, 4 degrees C); the folded form is 65% helical. A similar species is observed for the mammalian globins in mild acid conditions. Titration with GdnHCl at pH 7 reveals two unfolding transitions, the first mon features with that observed in acid and the second resulting in pletely unfolded state. Under the same conditions, urea unfolds the pletely in an apparently single cooperative transition. Assuming a simple three-state model (F<-->I<-->U), data from GdnHCl and urea titrations over a range of pH conditions were used to derive values for the apparent stability (delta Gw(app) and solvent accessibility (n(app)) of the folded (F) and intermediate (I) forms of the protein. Urea titrations were then repeated over a range of KCl concentrations in order to understand the contribution of Cl- to the different unfolding activity of GdnHCl. A three-state scheme is justified when changes in delta G(w(app)) occur without changes in n(app). The change in free energy of folding of I<-->F (delta Gw(F/I)) decreases to 0 at pH 4 as expected from the acid unfolding curve. delta Gw(I/U) reaches its maximum at pH 4.5, the isoelectric point of the protein. Variations of this value with pH and chloride are as much as 3 kcal mol-1 and correlate closely with changes in n(app) although there is no change in the alpha-helical content of I across the pH range. This observation is interpreted here as a deviation of the unfolding of the I state of Aplysia apomyoglobin from a cooperative behaviour. |
9451446 | Kinetic refolding of beta-lactoglobulin. Studies by synchrotron X-ray scattering, and circular dichroism, absorption and fluorescence spectroscopy. | beta-Lactoglobulin (beta LG) is a predominantly beta-sheet protein with a markedly high helical propensity and forms non-native alpha-helical intermediate in the refolding process. We measured the refolding reaction of beta LG with various techniques and characterized the folding kinetics and the structure of the intermediate formed within the burst phase of measurements, i.e. the burst-phase intermediate. Time-resolved stopped-flow X-ray scattering measurements using the integral intensity of scattering show that beta LG forms pact, globular structure within 30 ms of refolding. The averaged radius of gyration within 100 ms is only 1.1 times larger than that in the native state, ensuring that the burst-phase intermediate pact. The presence of a maximum peak in a Kratky plot shows a globular shape attained within 100 ms of refolding. Stopped-flow circular dichroism, tryptophan absorption and fluorescence spectroscopy show that pronounced secondary structure regains rapidly in the burst phase with concurrent non-native alpha-helix formation, and that the paction process is panied by annealing of non-native secondary structure and slow acquisition of tertiary structure. These findings strongly suggest that paction and secondary structure formation in protein folding are quite rapid processes, taking place within a millisecond time-scale. The structure of the burst-phase intermediate in beta LG refolding was characterized as having pact size, a globular shape, a hydrophobic core, substantial beta-sheets and remarkable non-native alpha-helical structure, but little tertiary structure. These results suggest that both local interactions and non-local hydrophobic interactions are dominant forces early in protein folding. The interplay of local and non-local interactions throughout folding processes is important in understanding the mechanisms of protein folding. |
9451447 | Integrins in morphogenesis and signaling. | Integrins are a family of heterodimeric transmembrane receptors that provide a physical and biochemical bridge ponents of the extracellular matrix and the intracellular physiological environment. Binding of integrins to their ligands results in the formation of cytoplasmic multi-protein posed of both cytoskeletal and signaling molecules. position and activity of these assemblies is regulated by the nature of integrin-ligand interactions, as well as by intracellular regulators that include tyrosine kinases and phosphatases, PKC, and small GTPases. Integrin-mediated cellular physiological responses include the activation of signal transduction, cytoskeletal rearrangements, and co-regulation of growth factor activities. These bined with integrin-mediated cell adhesion, play a major role in tissue morphogenesis and developmental processes. |
9451448 | Receptor protein tyrosine phosphatases: involvement in cell-cell interaction and signaling. | Receptor protein tyrosine phosphatases (RPTPs) represent a relatively new family of cell-surface receptors consisting of a variable, putative ligand-binding ectodomain followed by a single transmembrane segment and one or two intracellular catalytic domains. The RPTPs are thought to transduce extracellular signals by dephosphorylating tyrosine-phosphorylated intracellular substrates. As such, they are the enzymatic counterparts of the well studied receptor tyrosine kinases. However, little is known about the signaling mechanisms and biological functions of the RPTPs. Recent studies show that the extracellular domain of certain RPTPs can mediate either homophilic or heterophilic interactions and suggest a role in cadherin-mediated cell-cell adhesion, possibly via an action on catenins. This review will focus on the role of RPTPs in cell-cell interaction and the possible biological implications. |