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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 415 records · Page 23Linked to original sources

On the expression of H-Y antigen in transsexuals.

Histocompatibility-Y (H-Y) antigen, the presumptive inducer of the mammalian testis, is present in the cells of normal males and not in the cells of normal females. Recent reports have implied that patients with transsexualism exhibit H-Y antigen phenotypes at variance with those of normal males and females and, thus, that H-Y serology might provide a tool for the diagnosis and study of the transsexual condition. We therefore evaluated blood and testicular cells from 21 male-to-female transsexuals using conventional and monoclonal H-Y antibodies. We found no evidence of abnormal H-Y phenotype. Five of the patients were interviewed postoperatively by two examiners and rated for the diagnosis of transsexualism. Three of the five were rated primary transsexual by one or both examiners, and two were rated secondary transsexual.

Adult↗

Aromatic L-amino acid decarboxylase: histochemical localization in rat kidney and lack of effect of dietary potassium or sodium loading on enzyme distribution.

Utilizing a mono-specific antiserum produced in rabbits to hog kidney aromatic L-amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.

Animals↗

Comparison of intravenous gamma globulin and a monoclonal anti-Fc receptor antibody as inhibitors of immune clearance in vivo in mice.

Fc-receptor-mediated clearance and nonspecific phagocytic clearance were assessed after the infusion of monomeric human IgG, heat-aggregated human IgG, and a monoclonal anti-mouse macrophage FcII receptor antibody (2.4G2) into normal mice. Each agent blocked Fc-receptor function in vivo, but 2.4G2 was much more potent per microgram than the other agents. Monomeric IgG in blocking doses did not affect other aspects of immune function. In contrast, aggregated IgG, and to a lesser extent, 2.4G2 reduced serum complement levels. In addition, these agents also caused moderate reductions in nonspecific phagocytic function. Monoclonal anti-mouse macrophage C3bi receptor antibody (Mac-1), another monoclonal antibody which binds to macrophage CR3 receptors without interfering with Fc-receptor function, also reduced serum complement and inhibited nonspecific phagocytic function. Complement depletion alone (produced by infusion of cobra venom factor) could not account for the observed changes in Fc receptor or nonspecific phagocytic function. We conclude that both monomeric IgG and anti-Fc-receptor antibodies can markedly inhibit Fc-receptor function in vivo; however, the pattern of physiologic changes produced by these agents differs.

Animals↗

Collagen and elastin synthesis in human stroma and breast carcinoma cell lines: modulation by the extracellular matrix.

The desmoplastic response to breast carcinoma is being studied. The stimulation of stromal cell proliferation by a preformed breast tumor matrix was shown. An additional mechanism for stimulating scleroprotein deposition is described here. On a per-cell basis, the synthesis of collagen and elastin was increased by 50% and 70%, respectively, in fibroblasts grown on the preformed breast tumor matrix compared to the same cells grown on plastic or on their own preformed matrix. Breast tumor cells themselves synthesized small amounts of collagen and elastin compared to fibroblasts. These levels were unchanged when breast tumor cells were grown on the preformed matrix of fibroblasts. Addition of steroid hormones to cultured cells grown on plastic or on preformed matrices in various combinations, did not change the levels of either collagen or elastin synthesis. The matrix of human breast tumor cells exerts a dual effect; it is mitogenic for fibroblasts, and also stimulates the level of collagen and elastin synthesis, events that could contribute to the formation of the desmoplastic response to human breast cancer in situ.

Breast Neoplasms↗

Postictal pulmonary edema. Report of a case.

We present a case of postictal pulmonary edema, with serial radiologic and arterial blood gas assessment as well as pulmonary function testing. A review of pertinent experimental and clinical studies and discussion of possible pathophysiologic mechanisms follows, stressing the differences in diagnostic and therapeutic approach between this entity and other forms of hypoxemic respiratory failure.

Adult↗

Specific labeling and partial inactivation of cytochrome oxidase by fluorescein mercuric acetate.

Addition of 1 eq of fluorescein mercuric acetate (FMA) to beef heart cytochrome oxidase was found to inhibit the steady-state electron transfer activity by 50%, but further additions up to 10 eq had no additional effect on activity. The partial inhibition caused by FMA is thus similar to that observed with other mercury compounds (Mann, A. J., and Auer, H. E. (1980) J. Biol. Chem. 255, 454-458). The fluorescence of FMA was quenched by a factor of 10 upon binding to cytochrome oxidase, consistent with the involvement of a sulfhydryl group. However, addition of mercuric chloride to FMA-cytochrome oxidase resulted in an increase in fluorescence, suggesting that FMA was displaced from the high affinity binding site. Cytochrome c binding to FMA-cytochrome oxidase resulted in a 10% decrease in the fluorescence, possibly caused by Forster energy transfer from FMA to the cytochrome c heme. The binding site for FMA in cytochrome oxidase was investigated by carrying out sodium dodecyl sulfate gel electrophoresis under progressively milder dissociation conditions. When FMA-cytochrome oxidase was dissociated with 3% sodium dodecyl sulfate and 6 M urea, FMA was predominantly bound to subunit II following electrophoresis. However, when the dissociation was carried out at 4 degrees C in the absence of urea with progressively smaller amounts of lithium dodecyl sulfate, the labeling of subunit II decreased and that of subunit I increased. These experiments demonstrate that mercury compounds bind to a high affinity site on cytochrome oxidase, possibly located in subunit I, but then migrate to subunit II under the normal sodium dodecyl sulfate gel electrophoresis conditions. A definitive assignment of the high affinity binding site in the native enzyme cannot be made, however, because it is possible that mercury compounds can migrate from one sulfhydryl to another under even the mildest electrophoresis conditions.

Animals↗

Neonatal lupus erythematosus. A report of three cases associated with anti-Ro/SSA antibodies.

Three patients had neonatal lupus erythematosus syndrome. All three infants were girls who presented with characteristic skin lesions but without evidence of congenital heart block. All three mothers were asymptomatic at the time of delivery and have remained so until the present time. All mothers were positive for anti-Ro/SSA antibodies, as were the infants prior to 6 months of age. Anti-La/SSB antibodies were not present in either the mothers or the infants. HLA typing revealed that two of the mothers were positive for B8 and DR3, while the third mother was positive for B8 and DR2. Two of the infants were positive for B8 and DR3, while the third infant was positive for DR2 only.

Antibodies↗

Simultaneous reticulocyte and platelet counting on a clinical flow cytometer.

Laser flow cytometric analysis is well suited to many clinical immunofluorescent and hematologic applications. One of these is automated reticulocyte and platelet enumerations. We have performed a clinical evaluation of a fluorescence laser flow cytometer reticulocyte and platelet enumeration method using the fluorochrome acridine orange. One hundred and thirty-two clinical specimens from inpatients in our comprehensive cancer center were analyzed for platelet counts and 101 samples from the same population were analyzed for reticulocyte counts by the flow cytometer and simultaneously by conventional techniques. Both the reticulocyte and platelet enumerations achieved a high degree of correlation with standard methods for the nonbone marrow-transplant patients studied (R = .989 for reticulocytes and R = .995 for platelets). Marrow transplant patients had a slightly poorer correlation coefficient for the reticulocyte enumeration (R = .923), but analysis of serial determinations of these patients' samples for reticulocyte counts revealed that results were more consistent over time with the automated method than with the traditional manual method. The laser flow cytometer fluorescence reticulocyte and platelet enumeration methods described are efficient, rapid, and reliable for platelet and reticulocyte counting.

Acridine Orange↗

Effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet on levels of serum lipids and estradiol.

Recent studies have implicated elevated levels of serum estradiol in males as the major predisposing factor for myocardial infarction, with serum cholesterol playing a secondary role. The purpose of the present study was to investigate the effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet and daily exercise on levels of serum estradiol, testosterone, and lipids in males. Twenty-one males participating in the Pritikin Longevity Center 26-day residential program volunteered for the study. During the program, serum estradiol levels were significantly reduced from 47.2 +/- 4.6 to 23.8 +/- 2.5 pg/ml (mean +/- SE) whereas serum testosterone levels were unchanged (5.1 +/- 0.3 versus 5.1 +/- 0.2 ng/ml). Total serum cholesterol levels were reduced from 229 +/- 9 to 181 +/- 7 mg/dl whereas triglyceride levels were reduced from 301 +/- 66 to 151 +/- 13 mg/dl. High-density lipoprotein-cholesterol levels fell from 41 +/- 3 to 35 +/- 1 mg/dl whereas the ratio of total cholesterol to high-density lipoprotein-cholesterol was unchanged (5.5 +/- 0.4 versus 5.1 +/- 0.3).

Blood Glucose↗

Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo[a]pyrene and testosterone.

Percutaneous absorption of chemicals is generally considered a diffusional process, with the rate-limiting barrier being the nonviable stratum corneum. Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in mammalian skin maintained as short-term organ cultures. Skin samples from mouse, rat, rabbit, guinea pig, marmoset, and man were examined. The results from studies with benzo[a]pyrene (BP) and testosterone showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous "first pass" metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and testosterone was highest in mouse skin, and significant species variations in the metabolite profiles were observed. Studies with mouse skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when KCN was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.

Administration, Topical↗

Repair of DNA alkylation adducts in mammalian cells.

Carcinogenic alkylating agents, including nitrosamines, are able to alkylate DNA at various sites. This review presents evidence of the high degree of specificity in the type of DNA damage induced by various N-nitroso compounds and in the DNA repair processes among tissues or cells of different species. The O6-alkylguanine DNA alkyltransferase activity in various human and rodent tissues is discussed as well as the detection of O6-methylguanine in human DNA, using monoclonal antibodies and radioimmunoassay. The relevance of these findings to the mechanisms of cancer induction by nitrosamines is discussed.

Alkylating Agents↗

O6-Alkylguanine DNA alkyltransferase activity in monkey, human and rat liver.

Previous studies have shown that in in vitro assays using methylated DNA substrates, human and rat liver fractions were able to catalyse the repair of the promutagenic lesion O6-methylguanine (O6-meG). These studies have been extended to include monkey liver fractions and the repair of O6-ethylguanine (O6-etG). Human and monkey liver fractions have similar capacities for the repair of O6-meG and are 8-10 times more active than rat liver fractions. In all species examined, the liver extracts showed a lower capacity to repair O6-etG and the rate of repair was dependent on the degree of modification of the DNA substrate and the protein concentration used. The in vitro metabolism of dimethylnitrosamine (DMN), an alkylating carcinogen, by liver slices, has been previously demonstrated in these three species, but the activity in monkey liver was considerably lower compared with human and rat liver. The lack of evidence of a carcinogenic effect of DMN in the monkey liver could be correlated to this low capacity to metabolise DMN and the high O6-alkylguanine-DNA alkyltransferase levels in this organ.

Animals↗