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Biomedical subjects

R Barr

Publications and source records attributed to R Barr.

At least 73 records · Page 4Linked to original sources

An analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels.

There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

Animals↗

Immunopathology of cutaneous human lupus erythematosus defined by murine monoclonal antibodies.

Skin biopsy specimens obtained from involved skin from sixteen patients with systemic and discoid lupus erythematosus were studied. Murine monoclonal antibodies with a biotin-avidin-horseradish peroxidase staining system were used. The findings consisted of a marked reduction in the number of epidermal Langerhans cells defined by surface antigens, reduced HLA-DR (Ia-like) antigens on the surface of dermal capillary endothelium, and mononuclear cell infiltrates characterized by a predominance of helper T lymphocytes and an increase in the number of mononuclear phagocytic cells. B lymphocytes were rarely identified. The number of T lymphocytes within the dermis correlated inversely with both the number of HLA-DR-positive epidermal Langerhans cells (p less than 0.01) and the HLA-DR staining of dermal capillary endothelium (p less than 0.01). These findings suggest that a T lymphocyte-mediated immune response associated with a reduction in Langerhans cells and capillary endothelium HLA-DR antigens is involved in the inflammatory process of lupus erythematosus skin.

Adult↗

Neuroendocrine carcinoma of the skin: an immunohistochemical study of tumor markers and neuroendocrine products.

Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells.

Adenocarcinoma↗

Oxidation of reduced pyridine nucleotides by plasma membranes of soybean hypocotyl.

Highly purified plasma membranes isolated from soybean hypocotyls by free-flow electrophoresis or by a two-phase polymer separation system oxidize reduced pyridine nucleotides, NADH or NADPH, at rates of 2-5 nanomoles/mg protein/min. These rates are not influenced by mitochondrial inhibitors or by inhibitors of the alternate respiratory pathway. The NADH oxidase has a Km of 200 microM NADH. The enzyme activity is stimulated by Ca2+ and Mg2+ ions. The function of this enzyme is unknown at present, but it may represent a redox-controlled proton pump linked to acidification.

Calcium↗

Approaches to the measurement of the in vivo response to factor VIII concentrate infusion.

The in vivo response to the infusion of 12 lots of Factor VIII Concentrate was determined in a five Centre collaborative study. The principal aim of the study was to compare the responses obtained, after infusion into a single haemophiliac, of several lots of Factor VIII Concentrate made by a newly licensed process with those obtained after the infusion of several lots of Factor VIII Concentrate made by a previous process. Factor VIII Concentrates made by two other manufacturers were also evaluated. There was considerable inter-laboratory variation in the results obtained for the Factor VIII:C content of both the Factor VIII Concentrates and the ex vivo plasma samples. However, on pooling the data, the mean in vivo recovery was not statistically different from the expected response based on the potency assigned by the manufacturers. These data indicate that the results from a single laboratory may not be reliable in ascertaining either the in vitro or the in vivo potency of a particular lot of Factor VIII Concentrate and suggest that in the absence of a Factor VIII inhibitor, the in vitro and in vivo potency of a particular lot of Factor VIII Concentrate should be ascertained by several laboratories and the results pooled. Such pooled information then can be used to predict reliably the in vivo recovery of factor VIII: C activity without resorting to a formal in vivo response study.

Blood Coagulation Tests↗

Evidence for Ca++-calmodulin control of transplasmalemma electron transport in carrot cells.

Cultured carrot cells exhibit transmembrane ferricyanide reduction through a plasma membrane redox system, which may be associated with an iron reduction and uptake system in plant roots. Here we provide evidence for the inhibition of transplasma membrane ferricyanide reduction by four different Ca2+-calmodulin type antagonists, calmidazolium, trifluoperazine, pimozide and fluphenazine. These compounds inhibit in low concentrations (approximately 5-10 microM) in a time-dependent manner. Higher concentrations (50-100 microM) are required to inhibit transmembrane ferricyanide reduction in 10 min rather than in 30 min. The permeable calcium chelator, TMB-8, also inhibits transmembrane ferricyanide reduction in carrot cells. Since the redox system is controlled by hormones, the effects of anticalmodulin agents on hormone response may be mediated through the redox system.

Calcium↗

Transmembrane ferricyanide reduction in carrot cells.

Carrot cells (Daucus carota) grown in tissue culture are capable of reducing the non-permeable electron acceptor, ferricyanide, with concomitant proton extrusion from the cell. Optimum conditions for transmembrane ferricyanide reduction include a pH of 7.0-7.5 in a medium containing 10 mM each KCl, NaCl and CaCl2. Data are shown to prove that transmembrane ferricyanide reduction is an enzymatic process. It does not depend on the secretion of phenolics from the cell within the time limits of the assay (10 min). The presence of broken cells and cell fragments are excluded on the basis of stimulation or only slight inhibition by mitochondrial inhibitors. However, transmembrane ferricyanide reduction by carrot cells is inhibited about 50% by various glycolysis inhibitors, which are presumed to reduce the internal levels of NADH. Treatment of cells with p-diazoniumbenzenesulfonic acid, a non-permeant membrane modifying agent, also inhibits transmembrane ferricyanide reduction more than 90%. The data presented support the existence of a transplasma membrane redox system in carrot cells.

Cell Membrane↗

Decreased NADH-oxidoreductase activities as an early response in rat liver to the carcinogen 2-acetylaminofluorene.

Reduced nicotinamide adenine dinucleotide (NADH):ferricyanide reductase and DT-diaphorase specific activity in total homogenates of rat liver are markedly decreased as a very early biochemical event of hepatocarcinogenesis induced by the carcinogen 2-acetylaminofluorene (AAF). A 50 to 75% decrease in NADH:ferricyanide reductase was observed after 1 day of AAF (0.025% in the diet) feeding and persisted throughout a 7-week continuum of AAF administration. Carcinogen added directly to cell extracts had no effect. Similar results were obtained with single injections of either AAF or diethylnitrosamine. Xanthine dehydrogenase was also reduced in liver following AAF administration to nearly the same extent as NADH:ferricyanide reductase and DT-diaphorase. Total NADH-cytochrome c reductase and mitochondrial activity as estimated from succinic dehydrogenase were not affected by carcinogen administration relative to basal dietary controls. The reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase that functions in drug detoxification was elevated. With livers of animals fed 4-acetamidophenol, a hepatotoxin chemically related to AAF, small decreases were noted in NADH:ferricyanide reductase, but not in xanthine dehydrogenase nor in DT-diaphorase. Initial lowering of these activities in the livers of the carcinogen-treated animals is preceded by or concomitant with a reduction in the levels of extramitochondrial pyridine nucleotides known from other studies to result from DNA damage.

2-Acetylaminofluorene↗

An electrogenic proton pump associated with the Golgi apparatus of mouse liver driven by NADH and ATP.

Golgi-apparatus membranes, isolated from mouse liver, pump protons inwards, when supplied with NADH or ATP. The acidification of Golgi-apparatus cisternae and vesicles was detected with neutral red, a permeant dye, as a difference in absorbance at 550 nm minus that at 600 nm. The maximum rates detected with NADH and ATP were between 0.0006-0.0009 and 0.0030-0.0050 delta OD units/mg of protein/min, respectively, at pH 7.5. The outside buffer used was a bovine serum albumin suspension. The acidification of Golgi apparatus was inhibited from 45 to 100% by ionophores and from 22 to 100% by uncouplers. The results implicate both ATP and a redox system coupled to NADH oxidation in the acidification of Golgi-apparatus membranes.

Adenosine Triphosphate↗

A Calcium-Selective Site in Photosystem II of Spinach Chloroplasts.

After acid-treatment of spinach (Spinacia oleracea) chloroplasts, various partial electron transport reactions are inactivated from 25 to 75%. Divalent cations in concentrations from 10 to 50 millimolar can partially restore electron transport rates. Two cation-specific sites have been found in photosystem II: one on the 3-(3,4-dichlorophenyl)-1, 1-dimethylurea-insensitive silicomolybdate pathway, which responds better to restoration by Mg(2+) than by Ca(2+) ions, the other on the forward pathway to photosystem I, located on the 2,5-dimethylbenzoquinone pathway. This site is selectively restored by Ca(2+) ions. When protonated chloroplasts are treated with N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aziridine, a carboxyl group modifying reagent, presumed to react with glutamic and aspartic acid residues of proteins, restoration of electron transport at the Ca(2+)-selective site on the 2,5-dimethylbenzoquinone pathway is impaired, while no difference in restoration is seen at the Mg(2+) site on the 3-(3,4-dichlorophenyl)-1,1-dimethylurea-insensitive silicomolybdate pathway.Trypsin treatment of chloroplasts modifies the light-harvesting pigment-protein complex, destroys the dibromothymoquinone-insensitive 2,5-dimethyl-benzoquinone reduction, but does not interfere with the partial restoration of activity of this pathway by Ca(2+) ions, implying that the selective Ca(2+) effect on photosystem II (selective Ca(2+) site) is different from its effects as a divalent cation on the light-harvesting pigment-protein complex involved in the excitation energy distribution between the two photosystems.

Journal Article↗

Parental representations of transsexuals.

The parental representations of 30 male-to-female transsexuals were rated using a measure of fundamental parental dimensions and shown to be of acceptable validity as a measure both of perceived and actual parental characteristics. Scores on that measure were compared separately against scores returned by matched male and female controls. The transsexuals did not differ from the male controls in their scoring of their mothers but did score their fathers as less caring and more overprotective. These differences were weaker for the comparisons made against the female controls. Item analyses suggested that the greater paternal "overprotection" experienced by transsexuals was due to their fathers being perceived as offering less encouragement to their sons' independence and autonomy. Several interpretations of the findings are considered.

Female↗

Ferricyanide Reduction in Photosystem II of Spinach Chloroplasts.

Ferricyanide can be reduced in Photosystem II of spinach chloroplasts at 2 separate sites, both of which are sensitive to 3-(3,4-dichlorophenyl)-1,1-dimethylurea, but only one of which is sensitive to dibromothymoquinone. Data presented in this paper emphasize ferricyanide site II of Photosystem II, which is sensitive to thiol inhibition and may reflect a cyclic pathway around Photosystem II. Ferricyanide reduction sites 1 and 2 also differ from each other in fractions isolated from discontinuous sucrose gradients, from fragmented chloroplasts, and upon trypsin treatment. Sucrose density gradient centrifugation shows that ferricyanide reduction site 1 activity at pH 6 decreases from 30 to 50% in various isolated fractions, while the dibromothymoquinone-insensitive activity at pH 8 (site 2) is stimulated from 15 to 35%.Fragmentation of chloroplasts also stimulates ferricyanide site II activity, but trypsin treatment destroys ferricyanide reduction site II completely in 6 minutes. Ferricyanide reduction site 1 still retains 50% activity at this point. The meaning of these differences is discussed in terms of the physical location of these two sites on the thylakoid membrane.

Journal Article↗

Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro.

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet-associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.

Adult↗