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Biomedical subjects

A Chauhan

Publications and source records attributed to A Chauhan.

At least 109 records · Page 6Linked to original sources
PubMed1993

Amyloid beta-protein stimulates casein kinase I and casein kinase II activities.

Amyloid beta-protein (A beta) is the major protein of cerebrovascular and plaque amyloid in Alzheimer's disease (AD). Extensive evidence has demonstrated abnormal protein phosphorylation in this disease. We investigated the effect of synthetic A beta with the amino-acid sequence corresponding to cerebrovascular A beta and plaque A beta on the activities of casein kinase I (CK I) and casein kinase II (CK II). These enzymes were purified from bovine brain and casein was used as a substrate. A beta was found to stimulate markedly CK I- and CK II-mediated phosphorylation of casein in a concentration-dependent manner. The effect of plaque A beta was considerably higher than that of cerebrovascular A beta. Heparin, which is known to be a specific inhibitor of CK II, completely inhibited A beta-stimulated CK II activity. A beta itself was not a substrate for casein kinases. These findings were confirmed using other substrates for CK I and CK II. The experiments with synthetic CK II-substrate peptide (Leu-Glu-Leu-Ser-Asp-Asp-Asp-Asp-Glu) and the phosphorylation of erythrocyte membrane proteins by intrinsic membrane-bound CK I in erythrocytes showed marked stimulation in activities of casein kinases in the presence of A beta 1-40 or blocked A beta. We propose that A beta, by stimulating casein kinases, may contribute to abnormal protein phosphorylation in AD, in particular to increased phosphorylation of microtubule-associated proteins, leading to the neurofibrillary tangles formation and neurodegeneration in this disease. Interaction of A beta with protein kinases, thus, may characterize the beginning of the disease.

Amino Acid Sequence↗
PubMed1993

Activation of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate.

Phosphatidylinositol 3-kinase (PI 3-kinase) was partially purified from rat liver cytosol and used to synthesize phosphatidylinositol 3,4,5-trisphosphate (PIP3), using phosphatidylinositol 4,5-bisphosphate (PIP2) as a substrate. Purified PIP3 (free of chromatographic oxalate) activated protein kinase C (PKC) in the presence of phosphatidylserine and calcium (PKC -cofactors) in a concentration-dependent manner. In the absence of these cofactors, effect of PIP3 was not observed. Comparison of the effects of PIP3 and PIP2 on PKC activity indicates that PIP3 is a more potent PKC-activator than PIP2. The affinity of PKC to PIP3 was 4 fold higher than that to PIP2 (KPIP3 = 0.022 and KPIP2 = 0.087 mol %), while its maximal velocity (Vmax) was similar to that of PIP2-stimulated PKC activity (0.4 - 0.5 mumol/mg/min). These results suggest a physiological role for PIP3 in signal transduction, and support the previous finding (Chauhan et al. (1991) Arch. Biochem. Biophys. 287,283) that PKC-activation by phosphoinositides increases with the state of phosphorylation of these lipids. We propose that PIP3 by activating PKC may initiate a cascade of events from PIP3-->PKC- activation-->effects on other protein kinases such as MAP-kinase-->gene expression.

Animals↗
PubMed1993

Magnesium protects phosphatidylinositol-4,5-bisphosphate-mediated inactivation of casein kinase I in erythrocyte membrane.

Recent reports suggest that membrane-bound casein kinase I (MBCK I) activity in erythrocytes is inactivated by exogenously added phosphatidylinositol 4,5-bisphosphate (PIP2) (Bazenet et al. (1990) J. Biol. Chem. 265, 7369-7376; Brockman and Anderson (1991) J. Biol. Chem. 266, 2508-2512). Here we report that PIP2-mediated inhibition of MBCK I in erythrocytes is only observed if exogenous PIP2 and the kinase are allowed to interact in the absence of Mg2+. Prior incubation of PIP2 with 1 mM Mg2+ prevents the inactivation of MBCK I by PIP2. Other divalent cations (Ni2+, Co2+, Mn2+, Cd2+, Ca2+) and trivalent metal ions (La3+, Cr3+, Al3+) did not protect MBCK I from PIP2-mediated inactivation, indicating that the protective effect is specific for Mg2+ only. We propose a role of Mg2+ in the interaction of CK I with phosphoinositides, and that PIP2-mediated inhibition of protein kinase(s) may be a non-physiological phenomenon.

Animals↗
PubMed1993

Effect of oesophageal acid instillation on coronary blood flow.

To assess whether gastrointestinal factors can cause chest pain ("linked angina"), we studied the effect of oesophageal stimulation with acid on coronary blood flow in 20 syndrome X patients. Coronary blood flow velocity (CBFV) was measured with an intracoronary doppler catheter positioned in the proximal left anterior descending coronary artery. Acid stimulation produced typical anginal pain in 11 patients. Mean CBFV was significantly reduced from 7.3 (SD 4.0) to 4.4 (2.8) cm/s. Gastro-oesophageal reflux leading to reduced coronary blood flow may be a mechanism to explain linked angina.

Adult↗
PubMed1993

Hepatitis E virus transmission to a volunteer.

Hepatitis E virus (HEV) causes an enteric non-A, non-B hepatitis. The disease occurs in epidemic settings and sporadically, and viral transmission is thought to be faecal-oral. We present here a single volunteer study of HEV transmission followed by disease. Clinical and biochemical features of the infection correlated with HEV detection in the stools and sera by reverse transcription/polymerase chain amplification. IgG antibody has persisted for 2 years. The presence of HEV in serum before clinical signs appeared suggests that in endemic areas sporadic transmission of HEV may also occur parenterally.

Feces↗
PubMed1993

"Syndrome X" and coronary artery disease.

BACKGROUND: "Syndrome X" is a heterogeneous disorder that probably encompasses several disease states. The long-term prognosis in syndrome X is good, although a significant number of patients continue to experience chest pain and remain functionally limited. Several studies have reported that the development of coronary artery disease in patients with syndrome X is rare. Our experience, however, has shown that patients diagnosed as having syndrome X may develop atherosclerotic coronary artery disease over a relatively short period of time. METHODS: Three patients with syndrome X were studied with repeat coronary angiography. RESULTS AND CONCLUSIONS: We describe the development of coronary artery disease in three syndrome X patients over a relatively short time after their normal coronary angiogram. Accordingly, the physician should remain alert to this possibility.

Adult↗
PubMed1993

Effect of hyperventilation and mental stress on coronary blood flow in syndrome X.

OBJECTIVES: To assess the effect of hyperventilation and mental stress on coronary blood flow and symptom production in patients with syndrome X. DESIGN: A prospective study. Hyperventilation and mental stress tests were performed on the ward and were repeated in the cardiac catheter laboratory where coronary blood flow velocity was also measured with an intracoronary Doppler catheter in the left anterior descending coronary artery. Oesophageal manometry studies were also performed. PATIENTS: 29 patients with syndrome X (typical anginal chest pain, a positive exercise test, and normal coronary angiogram). SETTING: A regional cardiothoracic centre. RESULTS: Hyperventilation produced typical chest pain in 16 patients on the ward. 13 patients experienced their typical chest pain with mental stress test 5. Ten patients experienced chest pain with both hyperventilation and mental stress tests. This pattern was reproduced exactly when the tests were repeated in the cardiac catheter laboratory. Hyperventilation produced a significant increase in the rate-pressure product during ward and laboratory testing. There was, however, no significant change in the rate-pressure product on mental stress tests. The mean (SEM) coronary flow velocity decreased significantly on hyperventilation in the catheter laboratory from 10.0 (0.92) cm/s to 5.9 (0.72) cm/s (p < 0.001). There was also a significant reduction in the mean (SEM) coronary blood flow velocity on mental stress tests from 9.8 (0.86) cm/s to 7.4 (0.6) cm/s (p < 0.001). This reduction in flow velocity occurred in the absence of any changes in diameter of the left anterior descending artery. Further analysis showed that the coronary flow velocity was reduced significantly in only that group of patients in which hyperventilation and mental stress provoked chest pain. There was a significant increase in the arterial concentrations of noradrenaline on both hyperventilation and mental stress testing. Oesophageal manometry showed abnormalities in 17% of patients. CONCLUSIONS: Both hyperventilation and mental stress can produce chest pain in patients with syndrome X and this is associated with a reduction in coronary blood flow velocity. The results of this study suggests that this reduction in coronary flow occurs as a result of increased microvascular resistance.

Adult↗
PubMed1993

Clinical presentation and functional prognosis in syndrome X.

OBJECTIVES: To assess the effect of clinical presentation on functional prognosis in patients with syndrome X. DESIGN: A prospective study. Patients with syndrome X presenting with unstable angina and stable angina were followed up with a questionnaire to examine their functional state. PATIENTS: 41 patients with syndrome X and unstable angina and 41 patients with syndrome X and stable angina. Syndrome X was defined as typical anginal chest pain, a positive exercise test, and normal coronary angiogram. SETTING: Regional cardiothoracic centre. RESULTS: The mean follow up time was 36 (range 20-51) months for the unstable angina group and 35 (range 19-51) months for the stable angina group. No patient was lost to follow up in either group. At follow up 28 patients in the unstable angina group were pain free compared with 15 patients in the stable angina group (p = 0.008). Seven patients in the unstable angina group had further hospital admission with chest pain after the cardiac catheterisation compared wtih 12 patients in the stable angina group (NS). Seven patients in the unstable angina group believed that they had heart disease compared with 27 in the stable angina group (p < 0.001). 26 patients in the unstable angina group but only eight patients in the stable angina group were unlimited in their physical activity (p < 0.001). 12 patients in the unstable angina group compared with 27 patients in the stable angina group were unable to work normally because of chest pain (p < 0.001). The mean (SD) duration of symptoms before cardiac catheterisation was 7.9 (4.7) months in the unstable angina group and 13.4 (5.6) months in the stable angina group (p < 0.001). 10 patients in the unstable angina group and 24 patients in the stable angina group still attended hospital outpatient clinics because of chest pain (p = 0.004). 16 patients in the unstable angina group and 29 patients in the stable angina group were still taking regular antianginal medication (p < 0.001). CONCLUSIONS: Patients with syndrome X who present with unstable angina have a significantly better functional prognosis than those presenting with symptoms of stable angina. This may reflect differences in underlying pathophysiological mechanisms.

Adult↗
PubMed1993

Coronary flow reserve measurements with a new Judkins-style Doppler angiographic catheter.

The authors assessed whether measurements obtained by Judkins-style Doppler catheters are comparable to those achieved with the intracoronary Doppler technique in 42 patients with normal coronary arteries on angiography (19 syndrome X and 23 heart transplant patients). Resting coronary flow velocity and response to a hyperemic intracoronary dose of papaverine was measured with a Judkins-style, 8F Doppler-tipped catheter positioned in the left coronary ostium and a 3.6F intracoronary Doppler catheter positioned in the proximal left anterior descending artery. Mean coronary flow velocity at rest was significantly higher with the Judkins Doppler (10.1 +/- 4.6 vs 6.3 +/- 4.5 cm/sec, p < 0.01). The mean coronary flow velocity at peak hyperemia was also significantly higher with the Judkins Doppler (33.7 +/- 14.1 vs 19.7 +/- 11.5 cm/sec, p < 0.01). Coronary flow reserve was 3.57 +/- 1.3 with the Judkins Doppler and 3.47 +/- 1.2 with the intracoronary Doppler (r = 0.85). A second study was performed in 14 heart transplant patients with the intracoronary Doppler positioned in the left main coronary artery. The resting and hyperemic flow velocities were again higher with the Judkins Doppler but the differences were not statistically significant. There was again a strong correlation between the Doppler catheters for coronary flow reserve measurements. The Judkins-style Doppler technique appears to be a quick, safe, and accurate alternative to the intracoronary Doppler technique.

Cardiac Catheterization↗
PubMed1993

A new medium for rapid slide culture of tubercle bacilli.

Human blood medium (HBM) and egg enriched sheep blood medium (SBM) were evaluated to see their efficacy for primary culture of tubercle bacilli. SBM is found to be equally effective compared to HBM. Both types of media were associated with a low rate of contamination (2.75%). Availability of culture results after 7 days compared to 6 weeks on Lowenstein-Jensen media is a distinct advantage of slide culture method with a possible use in primary isolation and in evaluation of drug sensitivity pattern of Mycobacterium tuberculosis.

Animals↗
PubMed1992

Common aetiological agent for epidemic and sporadic non-A, non-B hepatitis.

Enterovirus-like particles have been reported in the acute phase of both epidemic and sporadic non-A, non-B (NANB) hepatitis. To examine whether these particles were the causative agent in the two types of disease, 29 patients with acute viral hepatitis in a north Indian epidemic outbreak and 9 with sporadic acute disease were investigated. 25 (86%) of 29 patients with epidemic hepatitis and 5 (56%) of 9 with sporadic disease were diagnosed as having enterically-transmitted-NANB hepatitis by exclusion. Virus-like particles (VLP) of 30-34 nm were detected in stool of 1 patient with epidemic and 1 with sporadic hepatitis. The VLPs crossreacted serologically and a specific IgM response was seen in acute epidemic and sporadic serum samples. After inoculation with infected stool rhesus monkeys had a mild rise in liver enzymes, and bile samples contained VLPs. These results suggest that the aetiological agent in epidemic and sporadic disease is the same.

Animals↗
PubMed1992

Coronary artery bypass grafting nine years after cardiac transplantation.

Angina and increasing exertional dyspnea developed in a 53-year-old man 9 years after cardiac transplantation. Left heart catheterization revealed severe proximal triple coronary artery disease, and he underwent surgical revascularization. Now 18 months after the operation he continues to be free of symptoms.

Coronary Angiography↗
PubMed1992

Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.

Animals↗
PubMed1992

Protamine induces autophosphorylation of protein kinase C: stimulation of protein kinase C-mediated protamine phosphorylation by histone.

Protein kinase C (PKC), a protein phosphorylating enzyme, is characterized by its need for an acidic phospholipid and for activators such as Ca2+ and diacylglycerol. The substrate commonly used in experiments with PKC is a basic protein, histone III-S, which needs the activators mentioned. However, protamine, a natural basic substrate for PKC, does not require the presence of cofactor/activator. We report here that protamine can induce the autophosphorylation of PKC in the absence of any PKC-cofactor or activator; this may represent a possible mechanism of cofactor-independent phosphorylation of this protein. It was investigated if protamine itself can act as a PKC-activator and stimulate histone phosphorylation in the manner of Ca2+ and phospholipids. Experiments however showed that protamine is not a general effector of PKC. On the contrary, histone stimulated PKC-mediated protamine phosphorylation and protamine-induced PKC-autophosphorylation. Histone alone did not induce PKC-autophosphorylation. Kinetic studies suggest that histone increases the maximal velocity (Vmax) of protamine kinase activity of PKC without affecting the affinity (Km). Other polycationic proteins such as polyarginine serine and polyarginine tyrosine were not found to influence PKC-mediated protamine phosphorylation, indicating that the observed effects are specific to histone, and are not general for all polycationic proteins. These results suggest that histone can modulate the protamine kinase activity of PKC by stimulating protamine-induced PKC-autophosphorylation.

Animals↗