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Biomedical subjects

L Patel

Publications and source records attributed to L Patel.

At least 73 records · Page 4Linked to original sources
PubMed1990

The effect of prostaglandin synthetase inhibitors on human preovulatory follicular fluid prostaglandin, thromboxane, and leukotriene concentrations.

This study evaluates the eicosanoid concentration in luteinized unruptured follicles (LUFs) on the ovaries of patients who had been treated with inhibitors of prostaglandin synthetase. Indomethacin, bromfenac, or azapropazone (or a placebo) was administered orally to 41 women during the periovulatory period. Follicular development was monitored by serial ultrasound examinations, and the onset of ovulation was regulated by an injection of hCG. Follicular fluid was aspirated during sterilization by minilaparotomy, which was performed just before the expected time of ovulation. Prostaglandin E2 and PGF2 alpha levels in the fluid were significantly reduced by indomethacin and bromfenac compared to those after placebo treatment. Bromfenac also reduced the follicular fluid leukotriene B4 level. Therefore, the development of luteinized unruptured follicles after treatment with nonsteroidal antiinflammatory drugs appears to be associated with a significant decrease in the synthesis of ovarian eicosanoids.

Adult↗
PubMed1989

Production of epoxygenase metabolite by human reproductive tissues.

Human amnion, trophoblast and umbilical vein endothelial cells synthesise an arachidonic acid metabolite which is neither a lipoxygenase nor a cyclo-oxygenase product. It is sensitive to stimulants and inhibitors of the cytochrome-P450-dependent epoxygenase system and co-migrates on HPLC with 14,15-epoxyeicosatrienoic acid (14,15-EET), which is an epoxygenase product. The function of 14,15-EET in these reproductive tissues is unknown, but it may be involved in the maintenance of vascular function.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Ovarian follicular fluid eicosanoid concentrations during the pre-ovulatory period in humans.

Prostaglandins are involved in ovulation and in every mammal studied so far, ovulation has been inhibited by prostaglandin inhibition. Information regarding the role of leukotrienes and thromboxanes in ovulation is more limited. In order to study the production of eicosanoids in human pre-ovulatory follicular fluid, follicular aspiration was timed by means of serial ultrasound scans and human chorionic gonadotrophin (hCG) to be immediately pre-ovulatory. 11 women were studied and the eicosanoids measured by radioimmunoassay (RIA). The follicular fluid was found to contain leukotrienes (LT) B4, LTC4 (D4, E4), prostaglandin (PG) E2, PGF2 alpha 6 keto PGF1 alpha k and thromboxane (TX) B2. This is the first published report of leukotrienes in human follicular fluid in spontaneous cycles, and is one of the few reports showing prostaglandins and thromboxanes. The significance of demonstrating leukotrienes in human follicular fluid is discussed as is the correlation between individual eicosanoids in the human ovary.

Dinoprostone↗
PubMed1987

lac permease of Escherichia coli: arginine-302 as a component of the postulated proton relay.

The lac permease of Escherichia coli was modified by site-directed mutagenesis such that Arg-302 in putative helix IX was replaced with Leu. In addition, Ser-300 (helix IX) was replaced with Ala, and Lys-319 in putative helix X was replaced with Leu. Permease with Leu at position 302 manifests properties that are similar to those of permease with Arg in place of His-322 [Püttner, I. B., Sarkar, H. K., Poonian, M. S., & Kaback, H. R. (1986) Biochemistry 25, 4483]. Thus, permease with Leu-302 is markedly defective in active lactose transport, efflux, exchange, and counterflow but catalyzes downhill influx of lactose at high substrate concentrations without H+ translocation. In contrast, permease molecules with Ala at position 300 or Leu at position 319 catalyze lactose/H+ symport in a manner indistinguishable from that of wild-type permease. By molecular modeling, Arg-302 may be positioned in helix IX so that it faces the postulated His-322/Glu-325 ion pair in helix X. In this manner, the guanidino group in Arg-302 may interact with the imidazole of His-322 and thereby play a role in the H+ relay suggested to be involved in lactose/H+ symport [Carrasco, N., Antes, L. M., Poonian, M. S., & Kaback, H. R. (1986) Biochemistry 25, 4486].

Amino Acid Sequence↗
PubMed1984

Cytochrome o type oxidase from Escherichia coli. Characterization of the enzyme and mechanism of electrochemical proton gradient generation.

Cytochrome o type oxidase purified from the membrane of Escherichia coli consists of four polypeptides (Mr 66000, 35000, 22000, and 17000), and the monomeric form predominates in octyl beta-D-glucopyranoside. The oxidase complex contains two b-type cytochromes (b-558 and b-563) and 2 mol of heme/mol of enzyme. Cytochrome o utilizes ubiquinol-1 and a number of other artificial electron donors as substrates but does not oxidize reduced cytochrome c or ferrocyanide. Activity is highly dependent upon exogenous phospholipids and/or Tween 20, and the quinone analogues 2-heptyl-4-hydroxyquinoline N-oxide and 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole are potent inhibitors. Proteoliposomes were formed by detergent dilution or dialysis in the presence of the oxidase and phospholipids, followed by freeze-thaw/sonication. Vesicles formed by this means are unilamellar and contain a random distribution of 85-90-A intramembranous particles on the convex and concave fracture surfaces. During oxidase turnover, the reconstituted system generates a proton electrochemical gradient (interior negative and alkaline) of -115 to -140 mV; however, respiratory control is minimal (i.e., respiratory control ratios of about 1.5 are observed). By using a glass electrode to measure changes in external pH and the fluorescence of entrapped 8-hydroxy-1,3,6-pyrenetrisulfonate to measure changes in internal pH, it is apparent that during ubiquinol oxidation, protons are released on the external surface of the membrane and consumed on the internal surface. In contrast, with N,N,N',-N'-tetramethyl-p-phenylenediamine, an electron donor that carries few protons at neutral pH, little change in external pH is observed until the protonophore carbonyl cyanide m-chlorophenylhydrazone is added, at which point the medium becomes alkaline. The results taken as a whole are consistent with the concept that oxidase turnover generates an electrical potential (interior negative) due to vectorial electron flow from the outer to the inner surface of the membrane. The pH gradient (interior alkaline), on the other hand, appears to result from scalar (i.e., nonvectorial) reactions that consume and release protons at the inner and/or outer surfaces of the membrane, respectively. In other words, cytochrome o oxidase from Escherichia coli does not appear to catalyze vectorial proton translocation.

Cell Membrane↗
PubMed1984

Nadolol binding to human serum proteins.

Nadolol protein binding was measured in serum from 95 healthy subjects. Binding was found to range between 4 and 27%, with a mean of 14 +/- 4% (s.d.). There was a small but significant correlation found between the degree of nadolol binding and the serum alpha-1-acid glycoprotein concentration. However it was concluded that changes in the serum protein binding of nadolol were unlikely to give rise to any untoward clinical effects.

Adrenergic beta-Antagonists↗
PubMed1983

The effect of a new antiarrhythmic agent, flecainide acetate, on systolic time intervals.

We investigated the effect of flecainide on systolic time intervals in 6 healthy subjects. A randomized, double blind, cross-over study was designed using flecainide (2 mg/kg), propranolol (0.2 mg/kg) or saline. In comparison with placebo, flecainide increased heart rate, diastolic BP, QT-Index, QS2-Index, PEP, and reduced LVET-Index (p less than 0.05). It caused a significant increase in PR interval, QRS duration, and PEP/LVET (p less than 0.01). Propranolol, compared with placebo, decreased heart rate and systolic BP (p less than 0.05). It increased PR interval, PEP, and PEP/LVET ratio (p less than 0.05). In comparison with propranolol, flecainide increased heart rate and QRS duration (p less than 0.01, p less than 0.001 respectively). It increased diastolic BP, PR interval, QS2-Index, PEP, and PEP/LVET ratio, and decreased LVET-Index (p less than 0.05). These changes in STI induced by flecainide may be produced by depression of myocardial contractility. Intraventricular conduction delay may be an additional contributing factor.

Adult↗
PubMed1983

Reconstitution of active transport in proteoliposomes containing cytochrome o oxidase and lac carrier protein purified from Escherichia coli.

Most active transport across the bacterial cell membrane is driven by a proton electrochemical gradient (delta-muH+, interior negative and alkaline) generated via electron transfer through a membrane-bound respiratory chain. This phenomenon is now reproduced in vitro with proteoliposomes containing only two proteins purified from the membrane of Escherichia coli. An o-type cytochrome oxidase was extracted from membranes of a cytochrome d terminal oxidase mutant with octyl beta-D-glucopyranoside after sequential treatment with urea and cholate and was purified to homogeneity by ion-exchange chromatography. The purified oxidase contains four polypeptides (MrS 66,000, 35,000, 22,000, and 17,000), two b-type cytochromes (b558 and b563), and 16-17 nmol of heme b per mg of protein, and it catalyzes the oxidation of ubiquinol and other electron donors with specific activities 20- to 30-fold higher than crude membranes. The lac carrier protein was purified as described. Proteoliposomes were formed in the presence of the oxidase and lac carrier protein by detergent dilution, followed by freeze-thaw/sonication. The system generates a delta-muH+ (interior negative and alkaline) with ubiquinol as electron donor and the magnitude of delta-muH+ is dependent on the concentration of cytochrome o in the proteoliposomes. Furthermore, the proteoliposomes transport lactose against a concentration gradient to an extent that is commensurate with the magnitude of delta-muH+ generated. The results provide powerful additional support for the "chemiosmotic hypothesis" and demonstrate that purified lac carrier protein retains the ability to function in a physiological manner.

Biological Transport, Active↗
PubMed1983

Membrane potential in anaerobically growing Staphylococcus aureus and its relationship to gentamicin uptake.

The electrical potential (delta psi) across the cytoplasmic membranes of Staphylococcus aureus cells growing under aerobic and anaerobic conditions was determined by measuring the equilibrium distribution of [3H]tetraphenyl phosphonium. In conjunction, gentamicin uptake and killing were studied in the same cells under identical conditions. Under aerobic conditions, delta psi was -169 mV, gentamicin uptake was readily demonstrable, and the number of viable cells decreased by almost four orders of magnitude in the presence of antibiotic. In contrast, delta psi was -142 mV anaerobically, gentamicin uptake was essentially nonexistent, and the aminoglycoside had no effect on viability. Remarkably, when the ionophore nigericin was added under anaerobic conditions, delta psi increased to the level observed aerobically, gentamicin uptake tripled to about 18% of the aerobic level, and viability decreased by one order of magnitude. The results are consistent with other observations (Mates et al., Proc. Natl. Acad. Sci. U.S.A. 79:6693-6697, 1982), indicating that the relationship between delta psi and gentamicin uptake is gated, and suggest that diminution of delta psi may be an important factor in aminoglycoside resistance under anaerobic conditions.

Anaerobiosis↗
PubMed1982

Direct measurement of lactose/proton symport in Escherichia coli membrane vesicles: further evidence for the involvement of histidine residue(s).

Addition of lactose to Escherichia coli ML 308-225 membrane vesicles under nonenergized conditions induces transient alkalinization of the medium, and the initial rate of proton influx is stimulated by valinomycin and abolished by nigericin or carbonyl cyanide m-chlorophenylhydrazone. A functional lac y gene product is absolutely required as the effect is not observed in ML 308-225 vesicles treated with N-ethylmaleimide nor with vesicles from uninduced Escherichia coli ML 30. Furthermore, the magnitude of the phenomenon is enhanced about 3-fold in vesicles from Escherichia coli T206, which contain amplified levels of the lac carrier protein. Kinetic parameters for lactose-induced proton influx are the same as those determined for lactose-facilitated diffusion, and quantitative comparison of the initial rates of the two fluxes indicates that the stoichiometry between protons and lactose is 1:1. Treatment of ML 308-225 vesicles with diethyl pyrocarbonate causes inactivation of lactose-induced proton influx. Remarkably, however, treatment with the histidine reagent enhances the rate of lactose-facilitated diffusion in a manner suggesting that the altered lac carrier catalyzes lactose influx without the symport of protons. The results are consistent with the hypothesis that acylation of a histidyl residue(s) in the lac carrier protein dissociates lactose influx from proton influx and indicate that this residue(s) play(s) an important role in the pathway of proton translocation.

Biological Transport↗
PubMed1982

Lactose-proton symport by purified lac carrier protein.

The lac carrier protein of Escherichia coli was purified by an improved procedure and its activity assayed by a rapid filter method. Following reconstitution of the carrier by octyl glucoside dilution, proteoliposomes were concentrated by filtration on a microporous filter. Lactose accumulation by adsorbed or entrapped proteoliposomes is driven by an artificially imposed pH gradient (interior alkaline), by a membrane potential (interior negative), or by a combination of both forces. Activity is almost completely abolished by the protonophore carbonyl cyanide m-chlorophenylhydrazone or by the competitive inhibitor thiodigalactoside. Addition of lactose to proteoliposomes under appropriate conditions results in alkalinization of the external medium. This effect is not observed with liposomes devoid of lac carrier or in the presence of proton conducting agents. The results provide a strong indication that the lac gamma gene product is the only protein in the cytoplasmic membrane of Escherichia coli required for lactose-proton symport.

Biological Transport↗
PubMed1982

A method for rapid, continuous monitoring of solute uptake and binding.

A method has been developed for dynamically monitoring the free concentration of diffusible, tritiated solutes. The technique utilizes particles of a solid scintillator microencapsulated in gel beads that are permeable to diffusible label. Since tritium beta radioactivity has an effective range in water of only a few micrometers, only label that is free to diffuse through the gel can excite the scintillator, while sequestered label is effectively excluded. Thus, the scintillation light output monitors the freely diffusible concentration of label exclusively. A simple, preliminary encapsulation technique is described and tested, and the theory behind the method is discussed with regard to the time resolution attainable for a given label concentration and type of encapsulation. The feasibility of the method is demonstrated by measuring the uptake of [3H]tetraphenylphosphonium by Escherichia coli membrane vesicles in response to the generation of a membrane potential (interior negative).

Glucose↗
PubMed1982

Beta-adrenoceptor blockade and migraine.

Except for propranolol, no other Beta-blocker has been studied thoroughly in the prophylaxis of migraine. Of those studied, propranolol, atenolol and timolol were shown to be useful in double-blind clinical trials. The mode, or even the site of action of these drugs in unknown. Possible mechanisms of action are peripheral vascular effects, a central action, 5-HT antagonism, an anxiolytic effect and a multifactorial action. The only common property of the successful drugs is lack of partial agonist activity and their profiles do not fully support any of the above hypotheses. Trials of drugs in the prophylaxis of migraine have in general been unsatisfactory due to the difficulty in controlling many variables. Beta-blockers with differing properties offer an opportunity to define the properties necessary for anti-migraine activity and perhaps shed light on the pathogenesis of migraine.

Adrenergic beta-Antagonists↗
PubMed1982

Membrane potential and gentamicin uptake in Staphylococcus aureus.

At pH 5.0, the electrical potential (delta psi, interior negative) across the plasma membrane of Staphylococcus aureus exhibits a minimum of -85 to -90 mV; the pH gradient (delta pH, interior alkaline) across the membrane approximates a maximum of about -100 mV. Under these conditions, uptake of the aminoglycoside gentamicin is negligible, and viability of the organism is not impaired by the antibiotic. In contrast, at pH 7.5, at which delta psi is about -130 mV and delta pH is 0, gentamicin uptake is observed and the drug markedly decreases viability. Dramatically, when the ionophore nigericin is added at pH 5.0, gentamicin uptake is induced, there is a striking decrease in viability, and the effect is associated with an increase in delta psi at the expense of delta pH. Consistently, valinomycin, which dissipates delta psi in the presence of potassium, abolishes gentamicin uptake and killing. In addition, from pH 5.0 to pH 7.5, there is a direct relationship between the magnitude of delta psi and both gentamicin uptake and its bactericidal effect. However, a threshold delta psi of -75 to -90 mV is apparently necessary to initiate uptake and killing. These observations provide a strong indication that delta psi plays a critical role in the uptake and antibacterial action of gentamicin and suggest that nigericin-like ionophores may be clinically useful in synergy with aminoglycosides.

Biological Transport, Active↗