Developmental biology. Transforming frogs and flies.
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Biomedical subjects
Publications and source records attributed to J Marsh.
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To determine how transmembrane osmotic gradients perturb the structure and dynamics of biological membranes, we examined the effects of medium dilution on the structures of osmolyte-loaded lipid vesicles. Our preparations were characterized by dynamic light scattering (DLS) and nuclear magnetic resonance (NMR) spectroscopies. Populations of Escherichia coli phosphatidylethanolamine (PE) or dioleoylphosphatidylglycerol (DOPG) vesicles prepared by the pH jump technique were variable and polymodal in size distribution. Complex and variable structural changes occurred when PE vesicles were diluted with hypotonic buffer. Such vesicles could not be used as model systems for the analysis of membrane mechanical properties. NaCl-loaded, DOPG vesicles prepared by extrusion through 100 nm (diameter) pores were reproducible and monomodal in size distribution and unilamellar, whereas those prepared by extrusion through 200-, 400-, or 600-nm pores were variable and polymodal in size distribution and/or multilamellar. Time and pressure regimes associated with osmotic lysis of extruded vesicles were defined by monitoring release of carboxyfluorescein, a self-quenching fluorescent dye. Corresponding effects of medium dilution on vesicle structure were assessed by DLS spectroscopy. These experiments and the accompanying analysis (Hallett, F.R., J. Marsh, B.G. Nickel, and J.M. Wood. 1993. Biophys. J. 64:000-000) revealed conditions under which vesicles are expected to reside in a consistently strained state.
Vesicle polydispersity and leakage of solutes from the vesicle lumen influence the measurement and analysis of osmotically induced vesicle swelling and lysis, but their effects have not been considered in previous studies of these processes. In this study, a model is developed which expressly includes polydispersity and leakage effects. The companion paper demonstrated the preparation and characterization of large unilamellar lipid vesicles. A dye release technique was employed to indicate the leakage of solutes from the vesicles during osmotic swelling. Changes in vesicle size were monitored by dynamic light scattering (DLS). In explaining the results, the model identifies three stages. The first phase involves differential increases in membrane tension with strain increasing in larger vesicles before smaller ones. In the second phase, the yield point for lysis (leakage) is reached sequentially from large sizes to small sizes. In the final phase, the lumen contents and the external medium partially equilibrate under conditions of constant membrane tension. When fit to the data, the model yields information on polydispersity-corrected values for membrane area compressibility, Young's modulus, and yield point for lysis.
This paper describes the state of documentation at the BDA Museum in 1987, when the author was appointed Museum Officer. It analyzes in some detail the approach taken in devising a new documentation system and the reasons for doing so; and describes the current documentation system used in the museum.
In order to increase awareness of strategies to prevent osteoporosis and heart disease we designed a clinic offering education and screening to all women aged 40-60 years on our practice list of 8600 patients, starting in January 1988. Screening and supervision of HRT users occurred at a weekly clinic run by the doctor and nurse. Audit in August 1991 showed that there were 260 present users of HRT (20%) of our population of 1322 women aged 40-60 years. Seventy-eight percent had taken HRT for over a year and 15% for more than 5 years. Ex-users totalled 117, of whom 52% had taken HRT for over a year and 14% for over 5 years. Examination of the clinic registers and responses to postal questionnaires showed that 681 (51.5%) of patients attended the health education clinic. Of the clinic attenders, 25% took HRT compared with 10.8% of non-attenders. Compliance with long-term therapy measured by audit of repeat prescriptions varied between 84% and 92% over a period of 5 years. Reasons for stopping treatment were anxiety over possible side-effects, especially breast cancer and dislike of bleeding.
The effect of in ovo and posthatch administration of cyclophosphamide, an immunosuppressive drug, on avian dendritic cells was examined in New Hampshire chickens. The Small Bursa line of New Hampshire chickens was more sensitive to the toxic effects of this drug than the line from which it was selected, the Lester J. Dreesen line. The bursal secretory dendritic cells, which may effect B cell differentiations, were left intact and appeared more prominent after treatment. The ellipsoid-associated cells, the dendritic cells of the spleen that bind and carry antigen, became vacuolated after treatment, but normal ellipsoid-associated cells were found within 1 wk. Ellipsoid-associated cells were able to bind and move carbon away from the ellipsoid areas of the spleen 5 wk after in ovo treatment with cyclophosphamide. However, the ability of treated birds to mount an antibody response to SRBC was compromised. The present study revealed that bursal dendritic cells were resistant to cyclophosphamide treatment during embryogenesis and the same embryonic treatment did not influence the migrating capability of ellipsoid-associated cells.
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An outbreak of haemorrhagic colitis due to Escherichia coli O157 and associated with a restaurant in Lothian, occurred in September 1990. There were 16 symptomatic cases, four of whom (all children) required dialysis. Notable features of the outbreak were the wide range of incubation periods (1-14 days), the occurrence of secondary spread through asymptomatic carriers and the prolonged period (at least seven days) during which the restaurant appears to have been the source of infection. Despite careful investigation, no single source within the restaurant was identified. The implications for public health are discussed.
A case of spontaneous subarachnoid haemorrhage occurring in association with a disorder of platelet function is described and the features of the disorder of platelet function were consistent with a storage pool deficiency. There has been no previous report of subarachnoid haemorrhage with platelet dysfunction.
24 community midwives recorded details of 783 postnatal visits over a 2 week period. The findings provide a description of postnatal visiting practice in Lothian Region, Scotland. Analysis revealed that 10 factors were significantly associated with the duration of visits. These could be grouped as follows: time consuming procedures (physical examination of the mother or baby, PKU testing), administration-related (the number of other visits that day, the need to liaise with general practitioners or health visitors, whether the mother was already known to the midwife, the time kept waiting at the house), feeding-related (the existence of feeding problems, whether the mother had breast fed previously) and delivery-related (the existence of complications during the delivery). The presence of health, social or emotional problems, or the lack of family/partner support was not associated with longer visits. The implications of these findings are discussed.
Hb. Heathrow [beta 103(G5)Phe- greater than Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormal beta chain was resolved from the normal beta chain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C- greater than G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomic beta-globin gene. This is only the third known instance of Hb Heathrow.
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Patients with diabetes and end-stage renal failure are known to have a high risk for cardiac morbidity and mortality associated with renal transplantation. The most efficient method to determine preoperative cardiac risk has not been established. To determine the effectiveness of intravenous dipyridamole thallium imaging in predicting cardiac events, 40 diabetic renal transplant candidates were studied preoperatively in a prospective trial. The study group consisted of 40 patients whose average age was 42 years (range 27 to 64); 34 (85%) were hypertensive and 21 (53%) were cigarette smokers. Cardiac history included chest pain in 6 patients and prior myocardial infarction in 3 patients. Dipyridamole thallium imaging showed reversible defects in 9 patients, fixed defects in 8 patients and normal scans in 23 patients. Dipyridamole thallium imaging was performed using 0.56 mg/kg of dipyridamole infused intravenously over 4 minutes. Cardiac events occurred only in patients with reversible thallium defects, of which there were 6. Of these 6 patients, 3 had cardiac events before transplantation and 3 had them in the early postoperative phase (within 6 weeks of surgery). Of 21 patients who underwent renal transplantation, 3 had cardiac events within 6 weeks of transplantation. The average duration of follow-up was 11 months (range 1 to 21). Thus, dipyridamole thallium imaging is an effective method of identifying renal transplant candidates likely to develop cardiac complications. Routine coronary angiography may not be necessary to screen all renal transplant candidates for coronary artery disease before surgery.
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Data was collected from patients with colonic or rectal tumours undergoing potentially curative surgery. Univariate analysis showed an association between perioperative transfusion with plasma and the earlier recurrence of tumour. Allowing for possible confounding factors the relative risk of recurrence for patients receiving plasma was 2.44 (95 per cent confidence interval = 1.10-5.46, P = 0.041) and for patients receiving whole blood or plasma, it was 2.39 (95 per cent confidence interval = 1.19-4.83, P = 0.021). The risk of recurrence for those receiving a transfusion of plasma was, therefore, more than twice that of those not given it. We were unable to demonstrate an independent harmful effect of transfusion with packed cells. These data suggest that the plasma protein, rather than the cellular component of whole blood, mediates the accelerated tumour recurrence.
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Mothers of children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) were assessed repeatedly over a period of 6 years in order to determine the psychological correlates of managing this chronic illness. Both maternal depression and overall emotional distress after the 1st year of the IDDM increased slightly with illness duration and were also influenced by other factors. Mothers' adjustment shortly after their children were diagnosed with IDDM was a strong predictor of their long-term emotional symptomatology. However, mothers' symptoms over time were not related to medical aspects of IDDM (i.e., the extent of the children's metabolic control, number of rehospitalizations, or their compliance with the medical regimen) and were also unrelated to the levels of depression or anxiety reported by their children. Mothers generally found it easier to cope with the IDDM the longer their children had the illness. However, the degree to which mothers perceived the IDDM to be bothersome or difficult to manage at any given point in time was associated with their overall levels of emotional distress.