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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 397 records · Page 22Linked to original sources

Fibroblast growth factor stimulates the proliferation and differentiation of neural precursor cells in vitro.

We have developed an in vitro culture system to study the regulation of proliferation and differentiation of neural precursor cells contained within the neuroepithelium of embryonic day 10 mice. A number of soluble growth factors have been tested for their ability to regulate these early events and, of these factors, we have found that the fibroblast growth factors [FGFs] can directly stimulate the proliferation and survival of the neuroepithelial cells. At least 50% of the neuroepithelial cells divide in the presence of FGF whereas in the absence of FGF all of the cells die within 6 days of culture. At higher concentrations of FGF, the cells change from being nonadherent round cells in tight clusters into a more flattened cell type which adheres to the substratum. This morphological change is accompanied by the expression of both neurofilament and GFAP, which are definitive markers of the two major cell types in the central nervous system: neurons and glia. In addition a neuroepithelial cell line, which does not rely on FGF for survival or proliferation, expresses both of these markers in response to FGF. These results indicate that FGF is stimulating the differentiation of the neuroepithelial cells into mature neurons and glia.

Animals↗

Physiological factors in infantry operations.

Male infantry soldiers (n = 34) were studied before, during, and after a 5-day simulated combat exercise. During the exercise, subjects were rated on their field performance by senior infantry non-commissioned officers. Prior to the exercise, direct measures of body composition and maximal oxygen uptake were obtained. Before and after the exercise the Army Physical Fitness Test and various measures of anaerobic capacity (Wingate and Thorstensson tests) and muscular strength (isometric and isokinetic) were obtained. Results showed no significant decrement in field performance during the exercise. Upper-body anaerobic capacity and strength declined following the exercise, although the results for upper-body strength were not consistent on all measures. Field performance was significantly correlated with measures of upper-body anaerobic capacity and strength. Upper-body strength and anaerobic capacity appear to be important for infantry operations and subject to declines during combat operations.

Adolescent↗

Down syndrome (trisomy 21) thymuses have a decreased proportion of cells expressing high levels of TCR alpha, beta and CD3. A possible mechanism for diminished T cell function in Down syndrome.

T cell differentiation antigen expression by thymocytes from nine individuals with Down syndrome (DS) and 27 controls was examined using immunofluorescence and flow cytometry. We found no significant differences between DS and controls in the proportion of CD1+ or CD2+ cells or in the percentages of CD4-8-, CD4+8+, CD4-8+, or CD4+8- cells. However, a significantly smaller proportion of cells expressing high levels of T cell receptor alpha, beta (TCR alpha, beta) was observed in DS thymuses compared to controls (28.0% vs 47.5%, respectively; P less than or equal to 0.01). A similar observation was made for CD3, a signal-transducing complex for the TCR, where the proportion of cells expressing high levels of CD3 in DS was 24.3% compared to 53.3% for controls (P less than or equal to 0.001). These data demonstrate aberrant T cell maturation in DS. Furthermore, our observation of diminished expression of critical molecules for antigen-specific recognition by T cells suggests a possible mechanism for decreased T cell function in DS.

Antigens, CD↗

An S1 nuclease-sensitive homopurine/homopyrimidine domain in the c-Ki-ras promoter interacts with a nuclear factor.

To gain insight into the normal controls mediating expression of the c-Ki-ras protooncogene, we have identified DNA sequence elements within its promoter that are essential for transcriptional activity. Transient expression assays using the bacterial chloramphenicol acetyltransferase gene were used initially to localize regions directing primary promoter function. Stepwise deletion of 5' promoter sequences resulted in a gradual decrease in the ability to drive transcription of the reporter gene, suggesting that this promoter is composed of multiple cis-acting elements. Gel mobility-shift and DNase protection studies involving a 166-base-pair DNA fragment allowed the identification of protein-binding sites corresponding to these multiple regulatory elements. One element demonstrating particular transcriptional influence exists as a homopurine/homopyrimidine-rich region that in vitro exhibits S1 nuclease sensitivity and binds at least one nuclear protein. Data from competition binding experiments suggest that this nuclear factor may be influential in the regulation of other essential growth-control genes as well.

Animals↗

Endometrial cancer trends in England and Wales: a possible protective effect of oral contraception.

Case-control studies have shown that combined oral contraceptives (OCs) are protective against endometrial cancer. In England and Wales, OCs have been on the market for 30 years and widely used for 20 years. Trends in other known risk factors for endometrial cancer would tend to have increased its incidence in that time in women under 55 years of age. Vital statistics however show a decrease for endometrial cancer mortality (41%) and morbidity (15%) in that group. This suggests an important protective effect of OCs on this disease.

Adult↗

Percutaneous transluminal aortic valvuloplasty--the acute outcome and follow-up of 149 patients who underwent the double balloon technique.

Double balloon percutaneous transluminal aortic valvuloplasty (PTAV) was performed on 149 patients (76 male (51%), mean age 76 +/- 11 years) whose symptoms included severe congestive heart failure in 127 cases (82%), syncope in 21 (14%) and angina in six (4%). Significant changes (P less than 0.05) in peak systolic (83 +/- 36 to 38 +/- 30 mmHg) and mean gradient (68 +/- 25 to 36 +/- 21 mmHg), and aortic valve area (0.6 +/- 0.2 to 1.0 +/- 0.4 cm2) were achieved in 130/149 patients (87%). Complications included an overall in-hospital mortality of 13%, (10.0% excluding the six deaths occurring in 18 moribund patients), a neurologic deficit incidence of 3%, and surgical arterial entry site repair 3.0% (14/47) of patients. Multivariate analysis identified congestive heart failure (NYHA Class IV), left ventricular ejection fraction, cardiac output and coronary artery disease as independent variables significantly affecting in-hospital mortality. Predictors of poor long-term survival were degree of heart failure, and coronary artery disease. The cumulative probability of survival at 24 months was 52 +/- 5% (excluding non-cardiac deaths, was 66 +/- 3%). Follow-up (mean time: 16 +/- 7 months) of 130 patients discharged alive revealed 41 late deaths (26 cardiac related). Sixty-two patients (70%) were symptomatically improved; 17 patients had symptom recurrence and underwent repeat valvuloplasty, and 10 patients valve replacement. Follow-up catheterization of 18 asymptomatic patients revealed that 11 patients had silently restenosed. These data indicate that aortic valvuloplasty is a palliative therapy for elderly patients, who are poor surgical candidates, with symptomatic calcific aortic stenosis with reasonable clinical success and long-term survival when considering their clinical status, but with a significant restenosis rate.

Aged↗

Cis- and trans-acting factors involved in centromere function in Saccharomyces cerevisiae.

The function of centromeric DNA in the yeast Saccharomyces cerevisiae has been studied in detail. Twelve of the sixteen S. cerevisiae centromeres have been sequenced to date, and a consensus sequence has been identified. This sequence consists of a central region 78 to 86bp in length which is greater than 90% A + T, usually in runs of As and runs of Ts. The central region is flanked on one side by a highly conserved 8bp sequence and on the other side by a highly conserved 25bp sequence which contains partial dyad symmetry around a central C/G base pair. Mutational analyses have been used to determine the importance of each subset of the consensus sequence to centromere function. A protein which binds to the 8bp sequence and at least one that binds to the 25bp sequence have been identified. The roles of these proteins in centromere function in mitosis and meiosis are currently under investigation.

Base Sequence↗

Survival among women with cancer of the uterine cervix: influence of marital status and social class.

STUDY OBJECTIVE: The aim was to investigate whether the survival of women with cancer of the uterine cervix is associated with their marital status and social class. DESIGN: The study was a survey of survival up to 5 years from diagnosis of women with cancer of the cervix registered in the South Thames Cancer Registry, using Cox regression to adjust for marital status, social class, age, and stage at registration. Because of deficiencies in social class data held by the Registry (social class was assigned in only 51% of cases, as opposed to 93% for marital status), the findings were compared with survival data from the OPCS Longitudinal Study. SETTING: During the period of study (1977-81) the South Thames Cancer Registry covered a female population of about 3.5 million in the south east of England. PATIENTS: Data on 1728 women were analysed. MEASUREMENTS AND AND MAIN RESULTS: Apparent differences in crude survival by marital status and social class were examined. These were found to be accounted for by adjustment for age and stage. The better survival of those whose social class was unknown was found to be an artefact of the way in which cancer registries assign social class, but this did not appear to bias registry based studies of social class survival seriously. CONCLUSIONS: (1) After adjusting for age, factors affecting survival in women with cancer of the cervix, such as stage at presentation or host resistance, appear to be similarly distributed in the different marital status and social class groups; (2) for cervical cancer, the marked social class gradient and unusual marital status distribution found in cross sectional mortality data reflect the incidence of the disease, not differences in survival; (3) explanations for these patterns in incidence and mortality data are to be found in the aetiology of the disease.

Adult↗

Perceived use of health education services in a school-based clinic.

This study assessed 1087 adolescents attending public school in Grades 10, 11, 12, and perceived use of health education services in a school-based clinic. Adolescents reported the most frequent health services they would use were nutrition/body weight, sex education, and mental health services. In addition, sex differences were found for perceived health education services as more girls than boys reported they would more likely use services for nutrition/overweight and underweight, information on unwanted pregnancy, counseling, and clinics to treat the blues.

Adolescent↗

Hospital-based group smoking cessation programs.

Since 1983, a standard eight-session group smoking cessation course (Fresh Start) has been disseminated throughout Victoria by the Anti-Cancer Council of Victoria with participation of various health agencies, including hospitals. During the five years since the Fresh Start program began, 94 groups were conducted under the auspices of hospitals and there were attended by 894 smokers (43% men, 57% women). Their mean age was 40.6 years. They had smoked for an average of 20 years. Their average precourse daily consumption of cigarettes was 27.7. One year after the course, 24% of the total initial enrollment reported themselves to be not currently smoking. The more course sessions participants attended, the more likely they were to succeed in quitting.

Health Promotion↗

Bisoprolol: studies of potential interactions with theophylline and warfarin in healthy volunteers.

Many patients receiving bisoprolol treatment might also require warfarin or theophylline therapy. Two studies were carried out in healthy volunteers to investigate the possibility that bisoprolol might interact with warfarin or theophylline, both of which have low therapeutic ratios. In a balanced, two-way, crossover study, eight men and four women took bisoprolol 10 mg daily for 14 days. They were divided into two groups of six volunteers. On the tenth day of treatment, six subjects received theophylline 375 mg (Nuelin tablets) by mouth and the pharmacokinetics of theophylline were determined. After a washout period of 7 days, they also underwent determination of single-dose theophylline kinetics. The other six subjects had single-dose theophylline kinetics determined 7 days before the first dose of bisoprolol, and then again after 10 days of bisoprolol treatment. Concurrent administration of bisoprolol did not influence the tolerability of theophylline and had no significant effect on any of the pharmacokinetic parameters for theophylline. In a separate study, 12 healthy men received warfarin daily until their prothrombin times were about 1.5 x control. They then received bisoprolol 10 mg daily p.o. for 10 days; warfarin was continued until 5 days after the end of bisoprolol treatment. Bisoprolol and warfarin treatments were well tolerated, and there was no effect on prothrombin times of either starting or stopping bisoprolol treatment. These studies show no effect of bisoprolol treatment upon theophylline pharmacokinetics, and no evidence of an effect of bisoprolol upon low-level anticoagulation with warfarin. Nevertheless, care should always be taken when changes are made in the medication of patients receiving theophylline or warfarin.

Adrenergic beta-Antagonists↗