Search PubMed⌕ Search

Biomedical subjects

W S Clark

Publications and source records attributed to W S Clark.

70 records · Page 4Linked to original sources
PubMed1986

Hematologic correlates and the role of erythrocyte CR1 (C3b receptor) in the development of AIDS.

Circulating immune complexes (CICs) are common in patients with the acquired immunodeficiency syndrome (AIDS) as in anemia. In our previous reports, we observed that the deposition of CICs on erythrocytes via C3b receptors (CR1) resulted in a defective CIC clearing system of erythrocytes and in high membrane osmotic fragility of such erythrocytes. We investigated the functional activity of erythrocyte CR1 in 89 patients with AIDS, 41 with AIDS related complex (ARC), 102 healthy homosexual volunteers, and 37 heterosexual males, in relation to the presence of CICs, antibody to lymphadenopathy associated virus/human T lymphotropic virus-III (LAV/HTLV-III), anemia, and the direct and indirect Coombs' tests. CICs were frequently found in all groups except heterosexual males. Absence of CR1 activity was observed in 85% of patients with AIDS, and in 59% with ARC. Impaired CR1 activity also occurred in the homosexual volunteer group. Positive direct Coombs' test and the presence of CICs correlated inversely with CR1 activity while a lowered hematocrit and the presence of antibody to LAV/HTLV-III correlated directly. Neither the sera nor the eluates from erythrocytes with a positive IgG Coombs' test contained IgG antibody against erythrocytes. This suggests decremental loss of CR1 activity progressing from asymptomatic LAV/HTLV-III antibody positive homosexual volunteers to the prodromal spectrum of ARC and finally progressing to a total disappearance in overt AIDS. Of 8 homosexuals volunteers demonstrating the composite of impaired CR1 activity, positive antibody to LAV/HTLV-III, and polyvalent positive direct Coombs' test (with gamma, mu, and C3b), all developed ARC or overt AIDS within 2 years of these observations.

AIDS-Related Complex↗
PubMed1986

Relationships between C3b receptor (CR1) activity of erythrocytes and positive Coombs' tests.

Although positive direct Coombs' tests occur in most patients with active systemic lupus erythematosus (SLE), haemolytic anaemic associated with antibody to erythrocytes (E) occurs in less than 10%. Our studies show an association between positive direct Coombs' tests and both the presence of circulating immune complexes and diminished activity of the C3b receptor (CR1) of E. Data presented in this report suggest that in vivo binding of immune complexes and complement by the CR1 of E results in positive direct Coombs' tests in the absence of antibody to E. These observations explain the low frequency of haemolytic anaemia compared with the high frequency of direct positive Coombs' tests in patients with SLE.

Antibodies↗
PubMed1983

Studies on immune adherence (C3b) receptor activity of human erythrocytes: relationship between receptor activity and membrane osmotic fragility.

Although human erythrocytes (E) possess C3b receptors (C3b-R), their in vivo functions are unknown. We had observed that E from patients with immune complex diseases had defective or impaired C3b-R activity when circulating immune complexes (CIC) could be demonstrated. This phenomenon has been investigated in relation to membrane osmotic fragility of such E by a coil planet centrifugation (CPC) system. Osmotic fragility was defined by the hemolysis starting point (HSP), peak point (HPP) and end point (HEP) using NaCl osmotic gradient (150-30 mOsM) coiled tubes. It was observed that E with low C3b-R activity showed high osmotic fragility. Hemolysis of E with low C3b-R activity started at 104 +/- 8 mOsM (n = 133) compared to 97 +/- 3 mOsM (n = 18) of patients' E with normal C3b-R activity and 96 +/- 5 mOsM of E from normal healthy donors (n = 128). Furthermore, we observed that HSP shifted towards lower osmolarity with clinical and immunological improvement of disease activity after treatment with corticosteroids. When osmotic gradients were lower to 120-50 mOsM, 52 out of 116 E samples with low C3b-R activity separated into 2 E populations. In contrast, none of 18 E samples with normal C3b-R activity separated into 2 E populations. However, we observed broadened fragility patterns in these 18 E samples. Serial studies of C3b-R activity, osmotic fragility and the presence of CIC were performed in 7 patients. Improvement of disease activity was associated with increased C3b-R activity, decreased osmotic fragility and the disappearance of CIC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1982

Studies on immune adherence (C3b) receptor activity of human erythrocytes: relationship between receptor activity and presence of immune complexes in serum.

Human erythrocytes (E) have surface receptors for the third component of complement (C3b-IA receptors) which mediate immune adherence haemagglutination (IAHA). We have observed that E from patients with systemic lupus erythematosus had imparied or defective C3b receptor (C3b-R) activity when circulating immune complexes (CIC) were found in serum. This phenomenon has been investigated by a newly developed method involving competitive inhibition of IAHA in patients with immune complex diseases. IAHA involving sheep E coated with antibody and complement (EAC), and indicator human E was inhibited by lysates of E with normal C3b-R activity from healthy donors and a monkey. In contrast, the lysates of E from 95% of patients bearing CIC did not inhibit IAHA, which indicated such E had defective or impaired C3b-R activity. This phenomenon was supported by control studies in which IAHA was not inhibited by lysates of E with absent, inactivated or occupied C3b-R. In those patients, in whom CIC disappeared during immunosuppressive therapy, C3b-R activity slowly returned to normal levels. Moreover, it was observed that C3b-R activity of patients' E decreased with the reappearance of CIC during exacerbations of disease. These observations suggest that CIC are carried in vivo by the C3b-R of E as well as those of the mononuclear phagocyte system, and that the E C3b-R may also contribute to the clearance of CIC.

Animals↗
PubMedDate not supplied

Detection of circulating immune complexes: a new application of immune adherence haemagglutination.

A simple, rapid and economical method involving immune adherence haemagglutination (IAHA) has been developed for the measurement of circulating immune complexes (CIC) in human sera. Human D-positive erythrocytes with highly active C3b receptors were employed as indicator cells. The procedure can be completed within 2 h and with 25 microliters of serum. The lower limit of sensitivity of this IAHA method was 2 micrograms/ml of heat-aggregated IgG and 16 ng/ml of IgG as antigen in a complexed state with anti-IgG antibody. By applying this method, CIC were detected in sera from categories of patients in whom CIC have been reported with other methods. Studies thus far suggest that the IAHA method may be useful in detecting and quantifying CIC in the investigation of clinical syndromes in which these complexes are believed to relate to pathogenesis.

Animals↗
PubMedDate not supplied

Sonographic fetal growth curves from an indigent population in Atlanta, Georgia: I. Singleton pregnancies.

The sonographic estimation of gestational age relies on standards of normal fetal growth established in highly selective patient populations. The majority have used middle-class, Caucasian gravidas with excellent menstrual dating criteria. These reference populations differ considerably from the indigent patient population in most southern medical centers: menstrual dating is often imprecise and there is a high rate of low birthweight infants delivered. Therefore, we established models of fetal growth in a southern, indigent, predominantly black patient population. We also compare our study to other sonographic studies.

Biometry↗
PubMedDate not supplied

Accounting for dropout bias using mixed-effects models.

Treatment effects are often evaluated by comparing change over time in outcome measures. However, valid analyses of longitudinal data can be problematic when subjects discontinue (dropout) prior to completing the study. This study assessed the merits of likelihood-based repeated measures analyses (MMRM) compared with fixed-effects analysis of variance where missing values were imputed using the last observation carried forward approach (LOCF) in accounting for dropout bias. Comparisons were made in simulated data and in data from a randomized clinical trial. Subject dropout was introduced in the simulated data to generate ignorable and nonignorable missingness. Estimates of treatment group differences in mean change from baseline to endpoint from MMRM were, on average, markedly closer to the true value than estimates from LOCF in every scenario simulated. Standard errors and confidence intervals from MMRM accurately reflected the uncertainty of the estimates, whereas standard errors and confidence intervals from LOCF underestimated uncertainty.

Analysis of Variance↗
PubMedDate not supplied

Changes in plasma cholesterol levels after hospitalization for acute coronary events.

UNLABELLED: To retrospectively assess the changes in total cholesterol levels after a hospital admission for an acute coronary event, 287 patients were identified who had one isolated event: 130 patients with acute myocardial infarction, 122 patients after coronary artery bypass graft surgery, 35 patients after percutaneous transluminal coronary angioplasty. To be included, patients had to have a total cholesterol measurement within the 3 months prior to hospitalization and periodically after the acute coronary event. Total cholesterol measurements were recorded during four time periods: 0-3 months before hospital admission (baseline); and 0-3, 3-6, and 6-9 months after the hospitalization. Mean total cholesterol value was used if a patient had multiple measurements during a time period. RESULTS: There was no significant difference in the baseline total cholesterol levels among the three groups (acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty). In all three groups, there was a decrease in total cholesterol level after hospital admission compared to baseline (p < 0.0001). This decrease was significantly greater in coronary artery bypass graft surgery patients compared to the other two groups. Total cholesterol levels returned to baseline levels by 3 months after the hospitalization in all three groups. Total cholesterol decreased significantly from baseline in patients after an acute myocardial infarction; this decrease was significantly greater if they received thrombolytic therapy (p < 0.05). Total cholesterol returned to baseline 3 months after hospitalization in both groups. CONCLUSIONS: During the 3 months following hospital admission for an acute coronary event, total cholesterol levels are not representative of the patient's baseline values. Management of hypercholesterolemia in this setting requires the use of baseline (preadmission) total cholesterol values.

Aged↗