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Biomedical subjects

A Chauhan

Publications and source records attributed to A Chauhan.

At least 127 records · Page 7Linked to original sources
PubMed1992

Impairment of coronary flow reserve in orthotopic cardiac transplant recipients with minor coronary occlusive disease.

OBJECTIVE: Coronary occlusive disease is the major long-term complication after cardiac transplantation. The relation between minor angiographic abnormalities and myocardial perfusion has not been previously assessed in a large number of cardiac transplant patients. DESIGN: Prospective study. Coronary flow reserve was measured with an intracoronary Doppler flow probe in the proximal left anterior descending coronary artery in each patient. A dose of intracoronary papaverine producing maximal vasodilation was then administered. SETTING: A regional cardiothoracic centre and a supraregional transplant unit. PATIENTS: Seven patients with chest pain but normal coronary anatomy (controls), and 61 cardiac transplant patients between three months and 10 years after operation (median 4.5 years). Twenty one cardiac transplant patients had angiographic evidence of minor coronary occlusive disease (mean (SD) percentage stenosis diameter 23% (6%)) in a primary or secondary coronary vessel (group 1), with 12 of these in the left anterior descending coronary artery (stenosis diameter (mean (SD) 24% (8%)). The remaining 40 transplant patients had normal coronary angiograms (group 2). MAIN OUTCOME MEASURE: Coronary flow reserve was defined as the ratio of the peak flow velocity after papaverine to the resting flow velocity. RESULTS: Group 1 patients had a noticeably impaired coronary flow reserve (2.6 (1.1)) compared with control patients (3.9 (0.4), p = 0.05) and, after adjusting for year after operation, compared with group 2 patients (3.8 (1.0), p < 0.001). No other variables were associated with a reduction in coronary flow reserve. Mean resting flow velocity was similar in all three groups (controls, 7.4 (4.6) cm/s; group 1, 7.5 (5.9) cm/s; and group 2, 7.3 (3.9) cm/s). Mean peak flow velocity response to papaverine was reduced in group 1 patients (18.1 (13.5) cm/s) relative to group 2 patients (27.5 (15.4) cm/s, p = 0.05) but not controls (28.4 (15.1) cm/s, p = 0.1). CONCLUSIONS: Coronary flow reserve and the peak flow response to the coronary vascular smooth muscle relaxant papaverine are impaired in cardiac transplant patients with minor coronary occlusive disease. This disturbance of cardiac microvascular function may contribute to the late morbidity and mortality seen in cardiac transplant patients with coronary occlusive disease.

Blood Flow Velocity↗
PubMed1992

Kallmann's syndrome and dilated cardiomyopathy.

A 52-year-old male previously known to have Kallmann's syndrome was admitted with congestive cardiac failure. He was found to have a dilated cardiomyopathy and died despite medical therapy. This report is the first known case of Kallmann's syndrome and dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1991

Activation of protein kinase C by phosphatidylinositol 4,5-bisphosphate: possible involvement in Na+/H+ antiport down-regulation and cell proliferation.

Phosphatidylinositol 4,5-bisphosphate (PIP2) as well as diacylglycerol (DG) activate protein kinase C (PKC) in the presence of calcium and phosphatidylserine. The pH at half-activation (pK) is 6.2 for DG.PKC and 7.7 for PIP2.PKC. Since the second monophosphate proton in position 5 of the PIP2 inositol (i.e., the last ionizable proton) has a pK of 7.7 (Van Paridon et al., (1986) Biochim. Biophys. Acta. 877, 216), the active effector is a fully deprotonated PIP2. Activation of PKC by PIP2 thus may follow intracellular alkalinization and be tied to the down-regulation of the Na+/H+ antiport mechanism. Since alkalinization is obligatory for cell proliferation, PIP2(5-).Ca.PKC may also be the gate that opens the pathways toward this and connected cellular reactions. A PIP2 analog in which inositol carbons 2-4 and the 4-phosphate have been removed, 1-phosphatidyl-rac-glycerol-3-phosphate (PGP), is completely inactive as PKC effector; this suggests that both 4-and 5-phosphate are engaged in the PIP2(5-).Ca.PKC complex. A model of the activated kinase takes this into account.

Animals↗
PubMed1991

Interaction of protein kinase C with phosphoinositides.

Calcium/phosphatidylserine-dependent protein kinase C (PKC) is activated by phosphatidylinositol 4,5-bisphosphate (PIP2), as well as by diacylglycerol (DG) and phorbol esters. Here we report that PIP2, like DG, increases the affinity of PKC for Ca2+, and causes Ca(2+)-dependent translocation of the enzyme from the soluble to a particulate fraction (liposomes). Phosphatidylinositol 4-phosphate (PIP) also displaces phorbol ester from PKC and causes Ca(2+)-dependent translocation of the enzyme to liposomes, but is much less efficient than PIP2, and a much weaker activator, with a histone phosphorylation v(PIP)/v(PIP2) of approximately 0.15. Scatchard analysis indicates competitive inhibition between PIP and phorbol ester with Ki(PIP) = 0.26 mol% as compared with Ki(PIP2) = 0.043 mol%. No effect of phosphatidylinositol (PI) on phorbol ester binding to PKC, translocation of PKC, or activation of PKC was observed. These results suggest that both PIP and PIP2 can complex with PKC, but full activation of the enzyme takes place only when PIP is converted to PIP2. We suggest that an inositide interconversion shuttle has a role in the regulation of protein phosphorylation.

Animals↗
PubMed1991

Action of amyloid beta-protein on protein kinase C activity.

Amyloid beta-protein (A beta), the major protein of cerebrovascular and plaque amyloid in Alzheimer disease, is considered a primary factor in the pathology of this disease. The effect of synthetic A beta (1-40) on the activity of protein kinase C (PKC) was studied with histones for a substrate in a mixed micellar assay, and with calmodulin-depleted soluble brain proteins in a liposomal system. We report here that A beta affects PKC activity in a biphasic manner. An initial stimulation of PKC was noted at low concentrations of A beta (less than 2.5 microM); while PKC-inhibition was observed in a concentration-dependent manner at higher concentrations of A beta. The in vitro phosphorylation of 20, 47, and 87 kDa brain proteins (known PKC substrates) was significantly reduced by 60 microM A beta. The role of 20 kDa in memory storage, of 87 kDa in neurotransmission and neurosecretory processes, and of 47 kDa in long-term potentiation or memory is well recognized, and A beta is known to have both neurotrophic and neurotoxic effects. Since PKC plays an important role in neuronal function, it is suggested that dual modulation of PKC by A beta may be linked to its neurotrophic and neurotoxic effects. We propose that at low concentrations A beta, by stimulating PKC, may contribute to neurites generation; and at higher concentrations A beta, by inhibiting PKC activity, might lead first to memory impairment, and then to neuronal loss.

Amino Acid Sequence↗
PubMed1991

The quantitation of rabies-specific antibodies. I. Modified counter immunoelectrophoresis. A rapid and sensitive method.

Modified counter immunoelectrophoresis was standardized with respect to dilution of tissue culture antigen and indicator serum, the incubation time for neutralization and the effect of an electric current. The technique was found to be sensitive enough to detect a minimum level of antibodies (0.5 IU/ml) by using a 16 mA current per slide for 2 h, indicator serum of 15 IU/ml and the use of an antigen at a concentration of 1:35. Above all, the incubation period did not affect the neutralization of the virus. The test was also applied to the detection of rabies-specific antibody levels in 73 human sera. The test was found to be simple, quick and economical for titration of rabies antibodies.

Antibodies, Viral↗
PubMed1991

The quantitation of rabies-specific antibodies. II. Factors affecting the sensitivity of the haemagglutination inhibition test.

Various factors affecting the HAI test for the quantitation of rabies-specific antibodies have been evaluated with a view to obtaining maximum sensitivity and reproducibility in tests using tissue culture antigens prepared in vero cells and concentrated by dialysis. Goose erythrocytes treated with proteolytic enzyme bromelian at a concentration of 0.025% were much more susceptible to HA than those that were untreated or erythrocytes treated with neuraminidase. In addition, other parameters like the use of a phosphate buffered saline (PBS) as a diluent at pH 6.2, incubation at 0-4 degrees C for 1.5-3 h were found to be most critical for achieving maximum HA activity. To remove non-specific inhibitors, serum samples were treated with aerosil, acetone in combination or alone. Of the 73 serum samples tested, removal of non-specific inhibitors by aerosil alone occurred in up to 54.79% of the samples, whereas using acetone-aerosil treatment followed by adsorption with goose erythrocytes, the inhibitors were removed in 98.67% of the samples to a level that was undetectable at the 1:4 starting dilution in the HAI test.

Acetone↗
PubMed1991

The quantitation of rabies-specific antibodies. III. A comparative evaluation of modified counter immunoelectrophoresis, haemagglutination inhibition and serum neutralization titres of human sera.

The rabies-specific antibodies of 73 serum samples from vaccinated humans were determined by the modified counter immunoelectrophoresis (MCIE), and the haemagglutination inhibition test (HAI) by using the conventional serum neutralization test (SN) as a yard-stick. Both MCIE and HAI were found to be sensitive and specific for the estimation of rabies antibodies. In general, the unitages obtained by the MCIE and SN showed statistically insignificant differences (P greater than 0.05) and the correlation coefficient between the two methods was 0.697 (P less than 0.05). Although the unitage of the sera detected by HAI tests was lower by a factor of 0.155 from the unitage of SN tests, there was statistically insignificant differences between the two techniques (P greater than 0.05) with a correlation coefficient of 0.556 (P less than 0.05).

Antibodies, Viral↗
PubMed1990

Lipid activators of protein kinase C.

Among the many reported lipid activators of protein kinase C only those of high affinity can be considered true physiological effectors, at present the tumor promoters, e.g., phorbol esters; 1,2-diacyl-sn-glycerols; and phosphatidylinositol 4,5-bisphosphate. Many other compounds (including arachidonic acid) are activators at high, unphysiological concentrations only, and they seem to be sterically unsuited for bonding to the enzyme. Such pseudo-activators possibly act by scrambling the structure of the regulatory moiety of the kinase.

Animals↗
PubMed1990

Churg-Strauss vasculitis and ascaris infection.

A patient with Churg-Strauss vasculitis presenting with mononeuritis multiplex, who developed obstructive jaundice, is described. On investigation the jaundice proved to be due to ascaris infestation. As the immune abnormalities associated with ascaris infection are also typical of those seen in the Churg-Strauss syndrome it is speculated that the vasculitis occurred because of a failure to regulate the anti-ascaris immune response.

Antigen-Antibody Complex↗
PubMed1989

Phosphatidylinositol 4,5-bisphosphate competitively inhibits phorbol ester binding to protein kinase C.

Calcium phospholipid dependent protein kinase C (PKC) is activated by diacylglycerol (DG) and by phorbol esters and is recognized to be the phorbol ester receptor of cells; DG displaces phorbol ester competitively from PKC. A phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), can also activate PKC in the presence of phosphatidylserine (PS) and Ca2+ with a KPIP2 of 0.04 mol %. Preliminary experiments have suggested a common binding site for PIP2 and DG on PKC. Here, we investigate the effect of PIP2 on phorbol ester binding to PKC in a mixed micellar assay. In the presence of 20 mol % PS, PIP2 inhibited specific binding of [3H]phorbol 12,13-dibutyrate (PDBu) in a dose-dependent fashion up to 85% at 1 mol %. Inhibition of binding was more pronounced with PIP2 than with DG. Scatchard analysis indicated that the decrease in binding of PDBu in the presence of PIP2 is the result of an altered affinity for the phorbol ester rather than of a change in maximal binding. The plot of apparent dissociation constants (Kd') against PIP2 concentration was linear over a range of 0.01-1 mol % with a Ki of 0.043 mol % and confirmed the competitive nature of inhibition between PDBu and PIP2. Competition between PIP2 and phorbol ester could be demonstrated in a liposomal assay system also. These results indicate that PIP2, DG, and phorbol ester all compete for the same activator-receiving region on the regulatory moiety of protein kinase C, and they lend support to the suggestion that PIP2 is a primary activator of the enzyme.

Binding Sites↗
PubMed1988

Calcium diphosphatidate membrane traversal is inhibited by common phospholipids and cholesterol but not by plasmalogen.

Phosphatidate-mediated Ca2+ membrane traversal is inhibited by phospholipids (PL) such a phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), sphingomyelin and lysoPC, but not by PC-plasmalogen. Kinetics of Ca2+ traversal through a 'passive' bilayer consisting of OH-blocked cholesterol show competition between PC and phosphatidic acid (PA); it appears likely that a Ca(PA.PC) complex is formed which is not a transmembrane ionophore but will reduce the amount of phosphatidic acid available for the formation of the ionophore, Ca(PA)2. PS and PI may inhibit Ca2+-traversal in the same manner by forming Ca(PA.PL) complexes. We suggest that PC-plasmalogen, with one of the Ca2+-chelating ester CO groups missing, cannot engage in calcium cages, i.e., Ca(PA.PL) complexes, and thus does not interfere with Ca(PA)2 formation. Double-reciprocal plotting of Ca2+ traversal rates in cholesterol-containing liposomes vs. calcium concentration suggests that cholesterol inhibits Ca2+ traversal by competing with Ca2+ for PA. The inhibition does not seem to be caused by a restructuring or dehydration of the membrane 'hydrogen belts' affected by cholesterol; most probably, it is due to hydrogen bonding of the cholesterol-OH group to a CO group of PA; this reduces the amount of PA available for the calcium ferry. The inhibition by sphingomyelin and lysoPC may also be explained by their OH group interacting with PA via hydrogen bonding. The pH dependence of Ca2+ traversal suggests that H[Ca(PA)2]- can serve as Ca2+ cross-membrane ferry but that at physiological pH, [Ca(PA)2]2- is the predominant ionophore. In conclusion, the results indicate that Ca2+ traversal is strongly dependent on the structure of the hydrogen belts, i.e., the membrane strata occupied by hydrogen bond acceptors (CO of phospholipids) and donors (OH of cholesterol, sphingosine), and that lipid hydrogen belt structures may regulate storage and passage of Ca2+.

Binding, Competitive↗
PubMed1988

Preparation of passive bilayer liposomes.

In studies of in-membrane molecular interactions, need may arise for a matrix that cannot itself interact, except hydrophobically, with the reactants. Such a bilayer matrix should, ideally, consist of only a hydrophobic zone without ionic outer layers and without hydrogen belts (the membrane strata containing CO and OH groups). However, because of the necessity of anchoring the bilayer to its aqueous surroundings, there must be polar substituents. Hydrophilic ether groups in the form of polyoxyethylenes can provide nearly sufficient anchoring and yet not confer unwanted reactivity to the membrane since they are only very weak H-bond acceptors. The stability of the bilayer is ensured by the presence of a few percent of an amphiphile (which may be the substrate to be studied, e.g. a phospholipid) or by a free polyethylene hydroxy group far remote from the original hydrogen belt region. Our most impermeable liposomes consisted of O-methylcholesterol/O-methoxyethoxyethoxyethylcholesterol; the most readily prepared liposomes were made from O-methylcholesterol and hydroxy(ethoxy)4dodecane (Brij 30) or Triton.

Arsenazo III↗
PubMed1988

The stimulation by adrenocorticotropin of the phosphorylation of adrenal inhibitor-1: a possible role in steroidogenesis.

Adrenocorticotropin (ACTH) acts via protein kinase A and the putative phosphorylation of a regulatory protein(s). We have examined a role in this process for inhibitor-1 which, following phosphorylation by protein kinase A, inhibits a phosphoprotein phosphatase activity. In the tissues we have examined inhibitor-1 was found primarily in the cytosol (90%) with the rest in the mitochondrial pellet. The highest concentration was in the adrenal cortex. Using adrenal cortex slices, the stimulation of steroidogenesis by ACTH and dibutyryl cAMP is paralleled by a corresponding increase in the phosphorylation of inhibitor-1 and this is not affected by inhibitors of protein synthesis which inhibit the steroidogenic response. The increase in the phosphorylation of inhibitor-1 occurs in the cytosol, while that in the mitochondrial pellet is not affected. Exogenous phosphorylated inhibitor-1, however, was found to inhibit phosphoprotein phosphatase activity in the mitochondrial pellet. The results suggest that the ACTH-induced increase in phosphorylated inhibitor-1 in the cytosol can affect susceptible phosphoprotein phosphatase activity both in the cytosol and the mitochondrial pellet and, hence, the level of phosphorylation of regulatory protein(s) involved in steroidogenesis.

Adrenocorticotropic Hormone↗
PubMed1986

Phosphatidylcholine and cholesterol inhibit phosphatidate-mediated calcium traversal of liposomal bilayers.

Rates of phosphatidic acid- (PA-) mediated Ca2+-traversal are maximal in 'passive bilayers' void of lipid CO and OH groups: dietherphosphatidylcholine (diether-PC) or OH-blocked cholesterol liposomes. Phosphatidylcholine (PC) as bilayer matrix causes 99% inhibition, while 45 mol% cholesterol in passive bilayers inhibits by about 70%. Possibly, the absence of CO and OH groups causes a dehydration of the 'hydrogen belts', i.e., the membrane strata occupied by hydrogen bond acceptors (CO of phospholipids) and donors (OH of cholesterol, sphingosine) and thereby facilitates the formation of dehydrated Ca(PA)2, the ionophoric vehicle; or (our preferred explanation) PC engages in a (non-ionophoric) Ca(PA X PC) complex and thus reduces the concentration of the ionophore, while cholesterol competes with Ca2+ for the CO groups of phosphatidic acid by hydrogen-bonding. The Ca2+-traversal rates realized in bilayers with modified hydrogen belts lend support to the speculation that a Ca(PA)2 ferry may be of physiological importance, e.g., in membranes (such as myelin) containing much ether phospholipid (plasmalogen); and that Ca2+-membrane association and traversal may be controlled by the composition of the hydrogen belts.

Biological Transport↗