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Biomedical subjects

R Barr

Publications and source records attributed to R Barr.

At least 55 records · Page 3Linked to original sources
PubMed1991

Chloroquine-sensitive transplasmalemma electron transport in Tetrahymena pyriformis: a hypothesis for control of parasite protozoa through transmembrane redox.

Plasma membrane electron transport was studied in a protozoan cell, Tetrahymena pyriformis, by assaying transmembrane ferricyanide reduction and the reduction of iron compounds. The rates of ferricyanide reduction varied between 0.5 and 2.5 mumol/g dry wt. per min, with a pH optimum at 7.0-7.5. Other active non-permeable electron acceptors, with redox potentials from +360 to -125 mV, were cytochrome c, hexaammine ruthenium chloride, ferric-EDTA, ammonium ferric citrate, and indigo di-, tri- and tetrasulfonates. It was found that Tetrahymena cells can reduce external electron acceptors with redox potentials at pH 7.0 down to -125 mV. Ferricyanide stimulates ciliary action. Transmembrane ferricyanide reduction by Tetrahymena was not inhibited by such mitochondrial inhibitors as antimycin A, 2-n-heptyl-4-hydroxyquinoline N-oxide, or potassium cyanide, but it responded to inhibitors of glycolysis. Transmembrane ferricyanide reduction by Tetrahymena appears to involve a plasma membrane electron transport chain similar to those of other animal cells. As in other cells, the transmembrane electron transport is associated with proton release which may be involved in internal pH control. The transmembrane redox system differs from that of mammalian cells in a 20-fold greater sensitivity to chloroquine and quinacrine. The Tetrahymena ferricyanide reduction is also inhibited by chlorpromazine and suramin. Sensitivity to these drugs indicates that the transplasma membrane electron transport and associated proton pumping may be a target for drugs used against malaria, Trypanosomes and other protozoa.

Animals↗
PubMed1991

The possible role of redox-associated protons in growth of plant cells.

The protons excreted by plant cells may arise by two different mechanisms: (1) by the action of the plasma membrane H(+)-ATPase and (2) by plasma membrane redox reactions. The exact proportion from each source is not known, but the plasma membrane H(+)-ATPase is, by far, the major contributor to proton efflux. There is still some questions of whether the redox-associated protons produced by NADH oxidation on the inner side of the plasma membrane traverse the membrane in a 1:1 relationship with electrons generated in the redox reactions. Membrane depolarization observed in the presence of ferricyanide reduction by plasma membranes of whole cells or tissues or the lag period between ferricyanide reduction and medium acidification argue that only scalar protons may be involved. The other major argument against tight coupling between protons and electrons involves the concept of strong charge compensation. When ferricyanide is reduced to ferrocyanide on the outside of cells or tissues, an extra negative charge arises, which is compensated for by the release of H+ or K+, so that the total ratio of increased H+ plus K+ equals the electrons transferred by transmembrane electron transport. These are strong arguments against a tight coupling between electrons and protons excreted by the plasma membrane. On the other hand, there is no question that inhibitor studies provide evidence for two mechanisms of proton generation by plasma membranes. When the H(+)-ATPase activity is totally inhibited, the addition of ferricyanide induces a burst of extra proton excretion, or vice versa, when plasma membrane redox reactions are inhibited, the H(+)-ATPase can function normally. Since plasma membrane redox reactions and associated H+ excretion are related to growth it is possible that in plants the ATPase-generated protons have a different function from redox-associated protons. The H(+)-ATPase-generated protons have been considered for many years to be necessary for cell wall expansion, allowing elongation to take place. A special function of the redox-generated protons may be in initiating proliferative cell growth, based on the presence of a hormone-stimulated NADH oxidase in membranes of soybean hypocotyls and stimulation of root growth by low concentrations of oxidants. Here we propose that this NADH oxidase and the redox protons released by its action control growth. The mechanism for this may be the evolution of protons into a special membrane domain, from which a signal to initiate cell proliferation may originate, independent of the action of the H(+)-ATPase-generated protons.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Division↗
PubMed1991

Electron and proton transport across the plasma membrane.

Transplasm membrane electron transport in both plant and animal cells activates proton release. The nature and components of the electron transport system and the mechanism by which proton release is activated remains to be discovered. Reduced pyridine nucleotides are substrates for the plasma membrane dehydrogenases. Both plant and animal membranes have unusual cyanide-insensitive oxidases so oxygen can be the natural electron acceptor. Natural ferric chelates or ferric transferrin can also act as electron acceptors. Artificial, impermeable oxidants such as ferricyanide are used to probe the activity. Since plasma membranes contain b cytochromes, flavin, iron, and quinones, components for electron transport are present but their participation, except for quinone, has not been demonstrated. Stimulation of electron transport with impermeable oxidants and hormones activates proton release from cells. In plants the electron transport and proton release is stimulated by red or blue light. Inhibitors of electron transport, such as certain antitumor drugs, inhibit proton release. With animal cells the high ratio of protons released to electrons transferred, stimulation of proton release by sodium ions, and inhibition by amilorides indicates that electron transport activates the Na+/H+ antiport. In plants part of the proton release can be achieved by activation of the H+ ATPase. A contribution to proton transfer by protonated electron carriers in the membrane has not been eliminated. In some cells transmembrane electron transport has been shown to cause cytoplasmic pH changes or to stimulate protein kinases which may be the basis for activation of proton channels in the membrane. The redox-induced proton release causes internal and external pH changes which can be related to stimulation of animal and plant cell growth by external, impermeable oxidants or by oxygen.

Adenosine Triphosphatases↗
PubMed1990

Electron donation to the plasma membrane redox system of cultured carrot cells stimulates proton release.

Membrane-permeable electron donors, duroquinol, diphenylcarbazide, pyrocatechol and tert-octylcatechol, promoted both reduction of an impermeant electron acceptor and proton transport with cultured carrot cells. These cells were preloaded with electron donors for 15, 30, 45 and 60 min. Aliquots of cells were removed at various times, washed free of excess electron donors and assayed for their effect on transplasma membrane redox with impermeable hexacyanoferrate (HCF III) as the electron acceptor and for simultaneous H+ excretion in the presence of hexacyanoferrate. All four electron donors stimulated HCF III reduction and associated H+ excretion. Below a rate of hexacyanoferrate reduction of 6 mumol/g dry wt. per min, the ratios of H+/e- were between 0.3 and 1 with low concentrations (0.1 mM) of the added electron donors. When hexacyanoferrate reduction exceeded 6 mumol/g dry wt. per min, proton release began to cascade to give ratios of 1 to 3, suggesting activation of an H(+)-ATPase or a proton transporter. This behavior by cultured carrot cells indicates that a certain threshold of proton concentration in a limited membrane domain must be reached in order for the proton channel to be opened.

Biological Transport, Active↗
PubMed1989

The effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity.

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44. Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.

Animals↗
PubMed1989

Arachidonic acid transformation is not stimulated in delayed pressure urticaria.

Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.

Adult↗
PubMed1988

The effect of platelet activating factor on electron transport of spinach chloroplasts.

It was found that platelet activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) inhibits electron transport greater than 90% in Photosystem II of spinach chloroplasts in concentrations from 2.8 to 3.5 micrograms/ml. The inhibition of the main pathway of electron transport through Photosystem II appeared to be specific for the platelet activating factor. Phorbol myristate acetate, 1,2-dipalmitin or fatty acid esters gave 17-32% inhibition in higher concentrations. The inhibition site for platelet activating factor was localized close to the reaction center of Photosystem II, based on the inhibition of the donor reaction, diphenyl carbazide----indophenol, in Tris-treated chloroplasts. Other Photosystem II reactions, H2O----silicomolybdic acid, H2O----2,5-dimethylbenzoquinone, or H2O----indophenol, were also inhibited by platelet activating factor. The present data point out the unique inhibition of Photosystem II electron transport by the platelet activating factor, but do not support the operation of a phosphoinositide cycle in chloroplasts.

Chlorophyll↗
PubMed1988

Auxin-Stimulated NADH Oxidase Purified from Plasma Membrane of Soybean.

NADH oxidation by plasma membrane vesicles purified from hypocotyls of etiolated soybean seedlings by two-phase partition was stimulated 2- to 3-fold by auxins, indole-3-acetic acid, 2,4-dichlorophenoxy acetic acid (2,4-D), and alpha-naphthaleneacetic acid. The stimulation was concentration dependent in the presence or absence of detergent with a maximum for 2,4-D at 1 micromolar. The NADH oxidation activity was solubilized with the zwitterionic detergent CHAPS and purified by ion exchange chromatography and gel filtration approximately 2000-fold over the total homogenate. Both the partially purified fraction and an active band from nondenaturing gel electrophoresis revealed the same three bands when analyzed by denaturing gel electrophoresis. When obtained from plasma membrane vesicles from the region of rapid cell elongation, the NADH oxidase complex retained auxin responsiveness throughout purification (3- to 5-fold stimulation by 1 micromolar 2,4-D).

Journal Article↗
PubMed1988

Electroretinograms in autism: a pilot study of b-wave amplitudes.

The authors recorded electroretinograms for 27 autistic patients and 20 age- and sex-matched healthy volunteers. Thirteen (48%) of the autistic patients demonstrated subnormal b-wave amplitudes, which may indicate abnormal retinal function. One patient was tested serially at two sites; his low b-wave amplitude did not vary over time or between the two sites. If this retinal finding can be confirmed at other laboratories and in larger samples of autistic patients, it might provide a marker for a specific subtype of autism.

Adolescent↗
PubMed1988

General practitioner relocation in an urban area.

One important factor affecting access to primary health care is the location of the general practitioner but it is often assumed that opportunities to influence the distribution of general practitioners are minimal owing to their low propensity to relocate. In this study in an urban area of Manchester a relatively high level of turnover over nearly five years was observed among 488 general practitioners, reflecting factors such as changes of practice within the study area (6% of general practitioners), movements to new premises without changing practice (7%), moves into (23%) and out of (20%) the study area and retirements (13%). Some characteristics of movers were examined and compared with those of other general practitioners. It is argued that levels of turnover may be predictable to some extent, but that family practitioner committees need greater knowledge of general practitioners' movements in order to influence the distribution of general practitioner services.

Career Mobility↗
PubMed1987

Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles.

To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance.

Animals↗
PubMed1987

Antiproliferative effects of suramin on lymphoid cells.

Suramin, a polyanionic drug used in the treatment of Rhodesian and Gambian trypanosomiasis and more recently in the acquired immune deficiency syndrome, is a potent inhibitor of the constitutive mammalian DNA polymerases alpha, beta, and gamma and the lymphoid-specific polymerase terminal deoxynucleotidyl transferase. To define the effect of this inhibition on cell proliferation, we studied the effect of suramin on several cell lines in culture and in mice in vivo. Suramin, at 200 micrograms/ml (which is regularly achieved in the plasma of patients), had no effect on the proliferation of 4 of 5 nonlymphoid cell lines. In contrast, exposure of 10 lymphoid cell lines to 200 micrograms/ml suramin for 4 days caused significant growth inhibition in 8 of these 10 lines. Suramin given i.p. to BALB/cBYJ mice at clinically relevant doses (15-60 mg/kg) caused profound and prolonged thymic atrophy within 5-7 days of drug administration (greater than a 90% weight loss in mice treated with 60 mg/kg). Thymic sections revealed severe cortical loss, prominence of dendritic cells, and vacuolated macrophages. Liver, peripheral blood, spleen, kidney, and total body weights were not affected. The apparent selective lymphocytotoxicity of suramin may represent an important property of this drug. We speculate that this may account for the persistent immune suppression reported in suramin-treated acquired immune deficiency syndrome patients.

Animals↗
PubMed1987

Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat.

The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.

Animals↗
PubMed1986

Redox reactions of tonoplast and plasma membranes isolated from soybean hypocotyls by free-flow electrophoresis.

Redox reactions were studied in more than 90% pure tonoplast and plasma membranes isolated by free-flow electrophoresis from soybean (Glycine max) hypocotyls. Both types of membrane contained a b-type cytochrome (alpha max = 561 nm) and a noncovalently bound flavin, two possible components of a transmembrane electron-transport chain. Isolated tonoplast and plasma membranes reduced ferricyanide, indophenol and various iron complexes with NADH or NADPH as electron donors. The redox activity was inhibited in tonoplast membranes by about 60% by 10 microM p-chloromercuribenzene sulfonate, 8% by 500 microM lanthanum nitrate and 10% by 100 microM nitrophenyl acetate. In contrast, the redox activity of isolated plasma membranes was inhibited by about 60% by 500 microM lanthanum nitrate or 100 microM nitrophenyl acetate, but only 25% by 10 microM p-chloromercuribenzene sulfonate. The results show that both tonoplast and plasma membranes of soybean contain active electron-transport systems, but that the two systems respond differently to inhibitors.

Cell Fractionation↗