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Biomedical subjects

M Weston

Publications and source records attributed to M Weston.

At least 37 records · Page 2Linked to original sources
PubMed1993

Presentation of cytosolic antigen by HLA-DR requires a function encoded in the class II region of the MHC.

The processing pathway for the MHC class II-restricted presentation of endogenous cytosolic Ag is distinct from the class I pathway since a cytosolic form of the influenza virus A hemagglutinin, expressed by a recombinant vaccinia virus, was presented by HLA-DR in a B cell mutant lacking the TAP1 subunit of the transporter for Ag presentation (TAP). In this report, two additional B cell mutants have been used to define the requirements of this TAP1-independent processing pathway. The first mutant, .61, lacks expression of both TAP1 and TAP2 genes, and of both LMP2 and LMP7 genes encoding proteasome subunits. As expected, class I-restricted presentation of the influenza virus matrix protein was totally deficient in mutant .61. In contrast, class II-restricted presentation of both the natural cytosolic matrix and the engineered cytosolic hemagglutinin proteins was functional in mutant .61. Thus, presentation of cytosolic Ag by class II molecules is independent of both TAP subunits and of the two MHC-encoded proteasome subunits. However, this endogenous processing pathway is dependent on at least one other function encoded in the class II region of the MHC as demonstrated with the second mutant, .174, in which a large deletion eliminates all expressed class II genes. Mutant .174 transfected with HLA-DR1 genes was previously shown to be defective in the presentation of exogenous Ag but normal in the presentation of short exogenous peptides. We show here that .174(DR1) is also defective in the presentation of cytosolic matrix and hemagglutinin proteins. This similar requirement for the class II-restricted presentation of either cytosolic Ag or internalized exogenous Ag suggests that both forms of Ag are ultimately targeted to the same cellular compartment for association with class II molecules.

Antigen Presentation↗
PubMed1993

Analysis of disease progression from clinical observations of US Air Force active duty members infected with the human immunodeficiency virus: distribution of AIDS survival time from interval-censored observations.

A non-parametric estimator of the AIDS survival time (after developing AIDS) is computed for the AIDS data set from the US Air Force (USAF). Survival times are unobservable. They are censored by the screening mechanism. The Armstrong Laboratory's Epidemiologic Research Division maintains data on over 954 active duty US Air Force (USAF) individuals who tested positive for human immunodeficiency virus (HIV) antibodies. Many have been clinically evaluated seven times since 1986. The HIV-positive individual is classified in seven stages of the disease complex as time progresses. Exact times of transition from one stage to the next are unknown. It is known that transition occurred between two consecutive evaluations. The aim of this study is to analyse distributions of the times that individuals spend in each stage of the HIV disease complex. We will discuss methods used to obtain non-parametric estimators of the distribution of times that individuals spend in stage 6. Finally, it is hoped to model the median time spent in each stage of the disease. This, along with incidence and separation data, will allow the prediction of the impact of HIV disease on USAF individuals and medical care systems.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cine magnetic resonance imaging of eye movements.

Cine magnetic resonance imaging (MRI) is a technique in which multiple sequential static orbital MRI films are taken while the patient fixates a series of targets across the visual field. These are then sequenced to give a graphic animation to the eyes. The excellent soft tissue differentiation of MRI, combined with the dynamic imaging, allows rapid visualisation, and functional assessment of the extraocular muscles. Good assessment of contractility can be obtained, but the technique does not allow study of saccadic or pursuit eye movements. We have used this technique in 36 patients with a range of ocular motility disorders, including thyroid-related ophthalmopathy, blow-out fracture, post-operative lost or slipped muscle, and Duane's syndrome.

Eye Movements↗
PubMed1991

Left ventricular aneurysm and intraventricular thrombi. Investigation and surgical correlations.

Formation of a left ventricular aneurysm and intraventricular thrombus represents one of the dreaded sequelae of coronary artery disease and acute myocardial infarction. The present emphasis is to reduce the incidence by reduction of cholesterol and fats, elimination of smoking, improved detection and control of hypertension and diabetes mellitus. Earlier diagnosis is available with stress testing and other noninvasive techniques. Cardiac catheterization allows detection of occlusive lesions. The CASS and other studies increasingly prove that percutaneous angioplasty and coronary artery bypass surgery improve life expectancy and implicitly should reduce the incidence of acute myocardial infarction. In the setting of the latter, thrombolytic agents may reduce the amount of myocardial injury. Despite these measures, formation of left ventricular aneurysms remains a common occurrence. Diagnosis and management are critical issues to the cardiac surgeon.

Cardiac Catheterization↗
PubMed1990

Aortic valvoplasty: comparison of the techniques and results of transeptal and retrograde methods.

Balloon aortic valvoplasty is used in some patients with aortic valve stenosis who are unsuitable for aortic valve replacement. Complications associated with the retrograde approach can be avoided using an antegrade approach which has been less widely described. Experience of these two methods is reported and aspects of the differences in technique are emphasized. Aortic valvoplasty was attempted in 21 patients with severe aortic valve stenosis (mean gradient 65 mmHg). A significant reduction in gradient was achieved in 20 (mean reduction 59% transeptal group [four patients], 50% retrograde group [16 patients]) with symptomatic improvement in 18 patients which was maintained at follow-up (mean interval of 5.2 months, range 1-17 months) in 8/15 patients. There were only two significant, resolvable early complications and increases in aortic regurgitation were not seen. There were six late deaths but three patients improved sufficiently to undergo successful aortic valve replacement. Aortic valvoplasty provides good palliation of symptoms. In patients who are unsuitable for the retrograde approach the antegrade, transeptal approach is a satisfactory and effective alternative.

Aged↗
PubMed1989

Role of CD4 in thymocyte selection and maturation.

We examined the possible role of CD4 molecules during in vivo and in vitro fetal thymic development. Our results show that fetal thymi treated with intact anti-CD4 mAbs fail to generate CD4 single-positive T cells, while the generation of the other phenotypes remains unchanged. Most importantly, the use of F(ab')2 and Fab anti-CD4 mAb gave identical results, i.e., failure to generate CD4+/CD8- T cells, with no effect on the generation of CD4+/CD8+ T cells. Since F(ab')2 and Fab anti-CD4 fail to deplete CD4+/CD8- in adult mice, these results strongly argue that the absence of CD4+/CD8- T cells is not due to depletion, but rather, is caused by a lack of positive selection, attributable to an obstructed CD4-MHC class II interaction. Furthermore, we also observed an increase in TCR/CD3 expression after anti-CD4 (divalent or monovalent) mAb treatment. The TCR/CD3 upregulation occurs in the double-positive population, and may result from CD4 signaling after mAb engagement, or may be a consequence of the blocked CD4-class II interactions. One proposed model argues that the CD3 upregulation occurs in an effort to compensate for the reduction in avidity or signaling that is normally provided by the interaction of the CD4 accessory molecule and its ligand. As a whole, our findings advocate that CD4 molecules play a decisive role in the differentiation of thymocytes.

Animals↗
PubMed1989

Foster care for children with AIDS: a psychosocial perspective.

The first Foster Boarding Home Program for babies with AIDS in the United States was started in New York by The Leake and Watts Children's Home in 1985. The authors describe the stages of the program, the possible reasons for its remarkable success, and some general characteristics of the AIDS epidemic. They also present preliminary findings about the characteristics of the children and foster parents in this group. General psychosocial issues concerning AIDS are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Vitamin E and retinopathy of prematurity. Follow-up at one year.

Five hundred forty-five infants weighing less than 1501 g at birth were entered into a randomized, prospective study to determine the effect of high serum levels (5 mg/dL) of vitamin E used prophylactically to try to prevent or alter the natural course of retinopathy of prematurity (ROP) and its sequel, retrolental fibroplasia (RLF). Three hundred twenty-eight infants were available for the one- to two-year eye examination. Although there was a trend (P = 0.072) toward less severe RLF among vitamin E-treated infants, the incidence of RLF was 11/162 (6.8%) in the placebo treated (P) infants, and 12/166 (7.2%) in the vitamin E-treated (E) infants. The incidences of hyperopia, myopia, anisometropia, strabismus and amblyopia were also similar in both the P and E groups.

Cicatrix↗
PubMed1985

Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less.

The incidence of culture-proven neonatal sepsis and necrotizing enterocolitis (NEC) in preterm infants maintained at pharmacologic (mean 5.1 mg/dL +/- 1.45 SD) serum vitamin E levels for long periods was prospectively studied as part of a double-masked clinical trial of the effect of prophylactic vitamin E v placebo treatment on the development and course of retinopathy of prematurity (ROP). Within a few days of birth, 914 preterm infants were enrolled in the study; 545 (275 placebo-treated infants, 270 vitamin E-treated infants had birth weight of 1,500 g or less. A significant difference in incidence of neonatal sepsis (17 placebo-treated infants, 37 vitamin E-treated infants) and NEC (18 placebo-treated infants, 32 vitamin E-treated infants) was observed among infants who had been treated for eight or more days and who had developed neither sepsis nor NEC before that time. The association of vitamin E treatment with increased incidence of disease was much higher with sepsis than with NEC. The most likely reason for these observations is a pharmacologic serum vitamin E-related decrease in oxygen-dependent intracellular killing ability which results in a decreased resistance to infection in preterm infants. The data suggest that, if this occurs, it is clinically significant only in the more immature infants. In view of the known variability of absorption of oral vitamin E and the association between high serum vitamin E levels and increased incidence of sepsis and late-onset NEC reported here, it can be concluded that serum vitamin E levels must be monitored when supplemental vitamin E is administered to premature infants, especially those with birth weight 1,500 g or less. The risk-benefit ratio of long-term treatment using vitamin E at high serum levels should be clearly assessed.

Administration, Oral↗
PubMed1984

Differences in the mean fat cell diameter of males between 1 and 48 months of age.

The mean fat cell diameter was determined from measurements of abdominal adipose cells, obtained during inguinal hernia repair, of 126 white and 95 black males ranging in age from 1 through 48 months of age. The mean diameters of black and white subjects did not differ significantly, suggesting that differences in fatness among adults of these two ethnic groups have their origin beyond the age range of this study. The mean fat cell diameter increased through the 6-8 month age group, decreased until the end of the first year, and then levelled off through 48 months of age. Comparison of this curve with those for the triceps, subscapular, abdominal, and suprailiac skinfolds of the same subjects showed generally parallel courses except for the triceps, which continued to increase in size after the means of fat cell diameters and the other skinfolds had levelled off. Our data indicate that changes in body fatness on the trunk at least in the first 4 years of life may be accounted for by changes in fat cell size.

Abdominal Muscles↗
PubMed1980

Risks and benefits of bilateral nephrectomy: an analysis of 134 cases.

In a retrospective survey of 134 patients undergoing bilateral nephrectomy from 1969 to 1980 it was found that the commonest indications were hypertension (60%) and infection/reflux (22%). Operation in hypertensive dialysis patients was followed by a fall in blood pressure in 70% (SE 9%) at one and 3 months while normotensive patients having their kidneys out for other reasons had a 47% (SE 11%) incidence of hypertension at one month and 7 out of 10 were still hypertensive at 3 months. When operation was performed in transplanted patients, 7 of 10 hypertensives had a fall in pressure, one of 6 normotensive persons had an increase, an use of antihypertensive drugs fell from 13/16 to 4 of 16 patients. The mortality was 10.4% (SE 2.6%) overall, the mortality of operations which included an unplanned splenectomy was significantly higher. There were 34 other complications in 25 patients. Complications, but not deaths, were more frequent in operations performed in dialysis patients rather than at the same time as, or after, a transplant. Over 12 years the ratio of bilateral nephrectomy to renal transplant operations has fallen from 8% (1969-1971) to 18% (1978 to present). The decrease is partly due to a fall in the number of operations for hypertension in dialysis patients and may be related to the appearance of beta-blocker and new vasodilator drugs.

Blood Pressure↗