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Biomedical subjects

M R Mickey

Publications and source records attributed to M R Mickey.

At least 109 records · Page 6Linked to original sources

Three-point association of HLA-A,B,Bf haplotypes deduced in 200 parents of 100 families.

The association of HLA-A and -B antigens with Bf alleles was investigated in 200 parents from 100 unrelated families. There were significant associations between HLA-A3 and Bf-F, B7 and Bf-S, B8 and Bf-S, B12 and Bf-F, and BW 35 and Bf-F. Three-point HLA-A,B,Bf haplotype frequencies, linkage disequilibrium parameters, and chi-square values were determined both from the genotype and from the phenotype data. Although the HLA-B,Bf associations involve antigens that are also present in the highly associated A,B and B,D haplotypes of the Caucasian population, there was--with the possible exception of HLA-A3,B7,Bf-S--no significant three-point association for HLA-A,B,Bf.

Adult↗

B-lymphocyte haplotypes in asthma families.

Thirty families in whom at least one member had asthma were typed for five new B-lymphocyte specificities, as well as the antigens of the A and B loci of HLA. The B-cell reactions were consistent with the concept that they were determined by genes linked to the HLA-A and HLA-B loci. Between 22 HLA-identical siblings and 16 two-haplotype different siblings, a significant difference in concordance of reactions for the B-cell groups was noted. The data obtained were most compatible with B-groups 1 and 2 being determined by one locus and B-groups 3, 4, and 5 by another locus. The superhaplotypes of HLA-A, HL-B, and B-cell loci 1 and 2 were then determined. The most striking linkages noted were for the second B-cell locus and the HLA-B locus: B-cell group 3 with HLA-B12, B-cell group 4 with HLA-B7, and B-cell group 5 with HLA-B8, B17, and Bw35.

Asthma↗

Calculations on long-term graft and patient survival in human kidney transplantation.

Long-term survival rates of human kidney transplants were found to decline at constant rates following the second year after transplantation. The slopes of decline were statistically significantly different for cadaver, parent-to-child, and HLA-identifical sibling transplants, resulting in graft survival half-life times during the constant risk phase of 7.5, 11, and 34 years, respectively. The corresponding patient survival half-life times were 12, 19, and 36 years, respectively. A highly significant difference in long-term survival risk was found when seven transplant centers that had been selected on the basis of their good 1-year graft survival results were compared with seven centers known to have a poor 1-year survival rate. The cadaver graft half-life times during the constant risk phase were 3.3 years for the "poor" centers and 8.7 years for the "good" centers. Thus, although histocompatibility obviously is a main factor in determining long-term survival risk, additional factors such as clinical treatment regimen appear to be influential. Knowledge of the long-term risk constants for the different transplant categories can be applied for the projection of success rates as well as retransplant and dialysis needs.

Cadaver↗

The role of B-lymphocyte antigens in MLC stimulation.

A total of 950 MLC combinations were set up out of which 259 were classified as low MLC response. An attempt was made to predict which of the combinations would give low response by matching the B-lymphocyte specificities and the HLA-A and -B antigens. A statistically significant prediction of a low response was noted for the B-lymphocyte specificities as well as for HLA-A and -B antigens. The fraction of the low response, which was correctly found, was, however, greater with the B-cell specificities than the HLA-A and -B locus antigens. It is concluded that the B-lymphocyte specificities may be either identical or closely linked to the DW specificities. To what extent they are associated with the strong transplantation antigens of man remains to be determined.

B-Lymphocytes↗

B-lymphocyte alloantigens in Caucasians.

Human B lymphocytes have been shown to have at least five polymorphic specificities defined by 32 antisera. The antisera were produced by absorption with pooled platelets to remove HLA activity and were selected out of over 400 tested sera. The sera that defined the five specificities had high correlation coefficients within a group (generally in the range of 0.6-0.9). As shown by the fit in the Hardy-Weinberg equilibrium, the five specificities appear to be determined by alleles at one genetic locus. No association between these specificities and HLA was noted.

Alleles↗

Hyperlipidemia in pediatric hemodialysis and renal transplant patients. Associated with coronary artery disease.

Fasting serum cholesterol and serum triglyceride levels were determined in 15 maintenance hemodialysis (MH) and 35 renal transplant (RT) patients. Fourteen of 15 MH patients (93%) had elevated triglyceride levels (greater than 140 mg/100 ml) compared to 11 of 35 RT recipients (31%) (P less than .001). Two of 15 MH patients (13%) had elevated cholesterol levels (greater than 230 mg/100 ml), compared to 18 of 35 RT recipients (51%) (P = .03). In MH patients, a positive correlation was noted between serum triglyceride levels and carbohydrate intake (P = .03). Autopsy material from 12 children who underwent MH or RT was compared to material from 16 age-matched controls; an increased collagenous content of intima, a possible early indicator of coronary artery disease, was noted more frequently (P less than .006) in index patients compared to controls. Our data demonstrate that hyperlipidemia is a frequent finding in pediatric patients treated with MH and RT, and may be associated with premature coronary artery disease.

Adolescent↗

Defective T cell function in atopic dermatitis.

The cellular immune system of 37 patients with atopic dermatitis (AD) was assessed by measuring peripheral blood T and B cells and the in vitro lymphocyte response to graded doses of phytohemagglutinin (PHA) (background and 6 concentrations of PHA from 100 to 1.6 mug). These were then correlated with clinical severity, ecosinophil counts, and serum IgE levels. The IgE levels (1,482 IU +/- 252 SEM), eosinophil counts (977 +/- 143), and absolute number of B cells (958 +/- 123) were significantly (p less than 0.05) higher than in age-matched controls (70 IU +/- 28, 182 +/- 79, and 480 +/- 60, respectively), and each significantly (p less than 0.05) correlated with the clinical severity. By contrast, percent B lymphocytes (20 +/- 1), percent (51 +/- 2) and total (2,357 +/- 217) T cells did not differ from controls. Eleven patients had low percent T cells (less than 40%); clinical and laboratory evaluation in these patients did not differ from the remaining 26. Lymphocytes from AD patients had higher background deoxyribonucleic acid (DNA) synthesis than controls (suggestive of increased number of B cells) and significantly depressed responses at the low PHA concentrations (6.3, 3.1, and 1.6 mug), which significantly correlated (p less than 0.05) inversely with IgE levels. These studies suggest a subtle defect in T lymphocyte function leading to increased B cells and increased IgE production.

Adolescent↗

Intact humoral and cell-mediated immunity in chronic marijuana smoking.

The immune system of 12 healthy chronic marijuana-smoking adults was evaluated while they smoked marijuana daily for 64 consecutive days under controlled hospitalized conditions. Studies included enumeration of B and T cell subpopulations, lymphocyte proliferative responses to PHA and to allogeneic cells, and serum immunoglobulin levels. Percent B cells, initially low in 2 patients, became normal. Baseline total B cells, determined either by surface immunoglobulins (338 cells/mm3 +/- 60 SEM) or complement receptors (162 cells/mms +/- 27) were significantly (p less than 0.05) less than control but increased to normal (485 +/- 97 and 239 +/- 47) over time. Percent T cells, initially low (less than 40%) in 4 patients, became normal. Baseline T cells (951 cells/mm3 +/- 70 SEM), significantly lower than controls (2,010 +/- 210, p less than 0.05), increased to normal by day 63 (1,875 +/- 281). In vitro lymphocyte response to graded doses of PHA and to allogeneic cells was normal initially and did not change over time. Serum IgG (1,064 +/- 33), IgA (166 +/- 13), and IgM (96 +/- 6) were normal. Serum IgE levels increased in 4 subjects without evidence of allergy. Short-term chronic marijuana use does not have a substantial adverse effect on B or T cells of young healthy adults.

Adult↗

Interaction analysis of selective and nonselective cell-mediated cytotoxicity.

The coexistence of selective and nonselective cytotoxic cells in effector suspensions required a method of separating the two effects before specificities in cell-mediated cytotoxicity could be investigated. A method of analysis was derived which used the average cytotoxicity for each effector and target to estimate selective and nonselective cytotoxic effects. The analysis clearly detected specificity in tests of cell-mediated lympholysis, and application to tests of cell-mediated cytotoxicity on cultured human tumor cells showed that selective reactions were found.

Cell Separation↗

Humoral sensitization in parous women: cytotoxic antibodies to non HL-A antigens.

From sera of parous women, we selected 100 samples that lacked cytotoxic antibodies to human peripheral lymphocytes from at least 80 unrelated persons. These sera were then reacted with a panel of 17 cultured human lymphoid cells in the complement-dependent cytotoxic test. Forty-six sera contained cytotoxic antibodies apparently directed to an antigenic system distinct from HL-A antigens, and other known cell surface markers. Rabbit serum was the most efficient source of complement with these cytotoxic antibodies which did not appear to be directed to tumor associated antigens: in fact, no lysis of melanoma cells or leukemic cells could be detected. Ten specificities could be identified which were represented on the cultured human lymphoid cells in various combinations. It is suggested that antigens detected by this approach may be similar to the Ia antigens of the mouse.

Antibody Formation↗

An application of long-term frequency analysis in measuring drug-specific alterations in the EEG of the cat.

A method is described for the quantitative measurement of "drug-specific" effects on the EEG of the cat. These effects are dose-related and are independent of the normal sources of EEG variation associated with the sleep-waking cycle. Drug-induced changes are expressed as characteristic alterations in frequency spectra and the time courses of these effects are followed for 5 h following administration of the test compounds. Atropine sulfate (0.5 and 2.0 mg/kg) and physostigmine salicylate (0.05 and 0.20 mg/kg) were administered to three unanesthetized and unrestrained cats and a broad-band frequency analysis was performed on the spontaneous brain electrical activity recorded from the prepyriform cortex, ventral hippocampus, lateral geniculate nucleus and the midbrain reticular formation. The resulting data were used as input to discriminant and canonical statistical analysis programs employed to abstract "drug-specific" patterns of frequency change. It was found that both atropine and physostigmine produce alterations in EEG frequency spectra which are clearly distinct from those patterns associated with the sleep-waking cycle and thus neither compound results in what has been characterized as an "EEG-behavioral dissociation".

Animals↗

Defective monocyte function in patients with genitourinary carcinoma.

An assay allowing quantitation of monocyte function, i.e., chemotaxis, was used to study the activity of monocytes in patients with neoplasms of the urinary tract. Twenty-four subjects with various stages of renal carcinoma exhibited a mean chemotactic defect of 34% (P less than 0.005) as compared to normal controls and patients hospitalized with nonneoplastic diseases. Twelve persons with transitional cell carcinoma of the bladder had a 29.8% (P less than 0.01) mean chemotactic defect as compared to the controls. There was no correlation between tumor stage and degree of chemotactic defect;--J Natl Cancer Inst 55: 1047-1054, 1975.

Adenocarcinoma↗

Posterior subcapsular cataracts: posttransplantation in children.

Posterior subcapsular cataracts (PSC) were noted in 41 of 69 (60%) recipients of renal allografts. The PSC were noted during the first posttransplant year (Group 1) in 21 (30%) recipients and after the first posttransplant (Group 2) year in 20 (30%) recipients. The dosage of prednisone during the first posttransplant year corrected for patient weight showed a significant correlation with the development of PSC during the first posttransplant year. The severity of the PSC were correlated with time of onset and prednisone dosage. Four recipients in Group 1 required cataract extraction to obtain sufficient vision to facilitate school work.

Adolescent↗

Comparison of kidney transplant survival among transplant centers.

Human kidney transplant survival rates at 1 year were compared among centers according to the transplantation activity as measured by the number of renal transplants performed. Statistical methods are described by which a fair assessment can be made of the outcome when small numbers of grafts are involved. The method should also be useful in evaluating subsets of patients in any given center under different treatment protocols. No evidence was found that survival rates of cadaver donor transplants were lower at the smaller centers. Other factors besides size of centers are probably of greater importance in influencing transplant survival rates.

Cadaver↗