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P Jain

Publications and source records attributed to P Jain.

At least 91 records · Page 5Linked to original sources
PubMed1996

Differential expression of voltage-gated K+ channel genes in left ventricular remodeled myocardium after experimental myocardial infarction.

Left ventricular (LV) remodeling after experimental myocardial infarction (MI) is associated with hypertrophy of noninfarcted myocardium and electrophysiological alterations. We have recently shown that post-MI hypertrophied LV myocytes have prolonged action potential duration (APD) and generate triggered activity from early afterdepolarizations. The prolonged APD was attributed to decreased density of the two outward K+ currents, I(to)-fast (I(to)-f) and I(to)-slow (I(to)-s), rather than changes in the density and/or kinetics of the L-type Ca2+ current. The changes in ionic current density may be related to alterations in the expression and levels of ion channel proteins. To test this hypothesis, rats underwent either left anterior descending coronary artery (LAD) ligation (post-MI group [n = 10]) or sham surgery (sham group [n = 10]). Three weeks later transcripts from the noninfarcted LV myocardium in the post-MI group (n = 6) and LV myocardium of the sham group (n = 6) were analyzed by RNase protection assay. Expressions of five K+ channel subunit mRNAs (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) reported in the rat ventricle were analyzed. Compared with the sham group, expressions of Kv1.4, Kv2.1 (putative I(to)-s), and Kv4.2 (putative I(to)-f) channel subunit mRNAs were significantly decreased by 60% (P < .03), 54% (P < .005), and 53% (P < .002), respectively, in the post-MI group. There was no significant change in the Kv1.2 and Kv1.5 mRNA levels. Western blotting demonstrated a similar decrease in the Kv2.1 and Kv4.2 immunoreactive protein levels (43% [P < .03] and 67% [P < .003], respectively [n = 4]) and no significant change in Kv1.5 immunoreactive protein level. Our results strongly correlate with the electrophysiological findings in this model and show that transcriptional regulation in the post-MI remodeled rat LV is distinct for each voltage-gated K+ channel subunit. These findings provide, at least in part, the molecular basis for the electrophysiological alterations observed in this model.

Animals↗
PubMed1996

Clinical management of asthma in the 1990s. Current therapy and new directions.

Asthma is a serious global health problem affecting nearly 100 million people worldwide. Its rising prevalence and associated morbidity and mortality are of increasing concern. Traditionally, symptomatic control of bronchoconstriction with beta 2 agonists and theophylline has been the mainstay of therapy. However, during recent years, inflammation has been recognised as the predominant cause of reversible airway obstruction and airway hyperreactivity. As a result, the emphasis in treatment has shifted to the early use of inhaled corticosteroids to control airway inflammation. beta 2 agonists are best used on an as-needed basis for the relief of acute bronchoconstriction and for the prevention of exercise-induced asthma. Sustained release theophylline or an inhaled long-acting beta 2 agonist may effectively control nocturnal symptoms. Preliminary studies involving agents active in the 5-lipoxygenase pathway as preventive therapy are encouraging. Further studies are needed to define their role in the management of asthma.

Asthma↗
PubMed1996

RU486 suppresses prolactin production in explant cultures of leiomyoma and myometrium.

OBJECTIVE: To assess the action of RU486 (mifepristone), in the presence and absence of P, on PRL production by explant cultures of leiomyoma and myometrium. DESIGN: Explant cultures using tissue from nine premenopausal women undergoing hysterectomy in the proliferative phase of the menstrual cycle; immunohistochemical staining of tissue sections from five patients for P receptor (PR) subtype. MAIN OUTCOME MEASURES: Prolactin secretion (measured by RIA), lactate dehydrogenase secretion (measured by quantitative colorimetric assay), and immunohistochemistry for PR subtype. RESULTS: Prolactin secretion was decreased in leiomyomas by RU486 at concentrations of 10(-7) M and 10(-5)M when normal serum-containing medium was used. In experiments with all detectable P removed from serum, PRL secretion was suppressed in both leiomyomas and myometrium at an RU486 concentration of 10(-7)M. Immunohistochemistry results suggest that the A form of the PR is the dominant form in both leiomyomas and myometrium. CONCLUSIONS: Prolactin production is suppressed in both leiomyomas and myometrium after treatment with RU486 in vitro, and this suppression may serve as a marker for the clinical effectiveness of agents used in the treatment of leiomyomas.

Culture Media↗
PubMed1995

Reemergence of the fetal pattern of L-type calcium channel gene expression in non infarcted myocardium during left ventricular remodeling.

The cardiac L-type voltage-dependent calcium channel (VDCC) is a critical component of cardiac action potential and excitation-contraction coupling. The objective of the present study was to examine the changes in expression in Motif IV, an alternatively spliced region of the alpha-1 subunit of the VDCC channel in postmyocardial infarction (MI) remodeled rat left ventricle. RNase protection assay was used to determine alteration in isoform expression in the noninfarcted hypertrophied ventricular myocardium 21 days post myocardial infarction. Our study demonstrates that cardiac hypertrophy is associated with significant increase in the mRNA level of the fetal isoform, with the reversion of fetal:adult isoform ratio to the fetal phenotype. Changes in isoform expression in the post-MI remodeled ventricle, not previously reported, is a pertinent genetic marker of cardiac hypertrophy.

Alternative Splicing↗
PubMed1995

Overuse of the indwelling urinary tract catheter in hospitalized medical patients.

BACKGROUND: The indwelling urinary tract catheter (IUTC) is an important aspect of medical care. We studied the prevalence of the unjustified use of the IUTC in hospitalized medical patients and identified situations associated with its unjustified use. METHODS: This prospective study involved 202 patients admitted to either the medical intensive care unit (n = 135) or the medical floors (n = 67) of a tertiary care university hospital who were catheterized during the hospital admission. An independent observer assessed the indication of initial catheterization by chart review and interview with the patient and the nurse. The need for continued catheterization was assessed daily by the same observer. The proportion of unjustified IUTC placement was determined using the study guidelines. Complications as a direct consequence of catheter use were recorded. RESULTS: Of the 202 patients who were studied, the initial indication for the placement of an IUTC was found to be unjustified in 21% (95% confidence interval [CI], 15% to 27%). Continued catheterization was unjustified in 47% (95% CI, 42% to 57%) of 912 patient-days with IUTC studied. In the medical intensive care unit, 64% (95% CI, 58% to 70%) of the total unjustified patient-days with IUTC resulted from its excessively prolonged use for monitoring urine output. Urinary incontinence was found to be the major cause of unjustified initial ([52%] 95% CI, 32% to 74%) and continued ([56%] 95% CI, 50% to 62%) use of IUTC in the noncritical care areas. Catheter-related urinary tract infection requiring intravenous antibiotics or continuous bladder irrigation with amphotericin B was observed in 5% of the patients. CONCLUSIONS: The IUTCs are significantly overused in hospitalized medical patients and careful attention to this aspect of medical care may reduce catheter-related complications by primary prevention.

Catheters, Indwelling↗
PubMed1995

Molecular cloning, expression and characterization of a ubiquitin conjugation enzyme (E2(17)kB) highly expressed in rat testis.

Ubiquitin-conjugating enzymes (E2s) play a key role in ubiquitin-mediated proteolysis by catalysing the conjugation of ubiquitin to protein substrates. We have previously reported the cDNA cloning of a 14 kDa conjugating enzyme [E2(14)k; Wing, Dumas and Banville (1992) J. Biol. Chem. 267, 6495-6501] that efficiently supported ubiquitination and protein degradation in reticulocyte extracts. Surprisingly, the structure of this E2 was markedly more similar to the Saccharomyces cerevisiae DNA repair gene RAD6, than to the S. cerevisiae UBC4/UBC5 genes which are required for the degradation of short-lived proteins and support much of the ubiquitination of yeast proteins. This suggested that mammalian homologues of UBC4/UBC5 remained to be identified. Using oligonucleotides derived from the S. cerevisiae UBC4 sequence as primers in a PCR reaction with rat muscle cDNA as a template, a 390 bp DNA fragment was amplified which predicted an amino acid sequence that was 83% identical to yeast UBC4. Screening a rat testes cDNA library identified a family of cDNAs which predicted two very similar proteins with basic pIs and molecular masses of approx. 16,700 Da. Isoform 2E was expressed in Escherichia coli and purified to homogeneity. It supported ubiquitination to reticulocyte and testis proteins more rapidly in vitro and produced larger conjugates than E2(14)k. Examination of RNA from different tissues indicated that this type of E2 was expressed in a broad spectrum of tissues but at particularly high levels in the testis. Fractionation of a testis extract by anion-exchange chromatography identified several putative ubiquitin protein ligase activities with which this E2 could interact in promoting conjugation of ubiquitin to proteins. One of these activities supported conjugation of ubiquitin to histone H2A, a substrate degraded in the ubiquitin system by a non-N-end rule mechanism. This paper reports the first cloning of a apparent mammalian homologue of S. cerevisiae UBC4/UBC5. Its high expression in testis and ability to efficiently support conjugation to testis proteins suggest that this family of E2s may play a role in the proteolysis that occurs during spermatogenesis.

Amino Acid Sequence↗
PubMed1995

Increased expression of messenger RNA for collagen type I, collagen type III, and fibronectin in myometrium of pregnancy.

OBJECTIVE: To determine the expression of the extracellular matrix proteins collagen type I, collagen type III, and fibronectin by immunohistochemistry, and the messenger RNA (mRNA) for these proteins by Northern blot analysis in the myometrium of pregnancy compared with myometrium from normal premenopausal women. METHODS: Myometrial tissue was obtained from seven pregnant women undergoing elective cesarean delivery and eight nonpregnant premenopausal women undergoing hysterectomy. Tissue was paraffin embedded and processed for RNA. Antibodies to collagen type I, collagen type III, and fibronectin were used to examine protein expression by immunohistochemistry. Complimentary DNA probes for the same proteins were used to examine mRNA expression by Northern blot analysis. RESULTS: Increased staining was seen for all three proteins in the myometrium of pregnancy. Densitometric analysis of Northern blots showed increased levels of collagen type I mRNA (P < .003), collagen type III mRNA (P < .005), and fibronectin mRNA (P < .04) in the myometrium of pregnancy compared with myometrium from nonpregnant premenopausal women. CONCLUSION: There is increased expression of both protein and mRNA for collagen type I, collagen type III, and fibronectin in the myometrium of pregnancy.

Blotting, Northern↗
PubMed1995

Silent myocardial ischemia in diabetics with normal autonomic function.

Twenty male diabetic patients (age range, 40-60 years) with normal autonomic function were studied to determine the prevalence of silent myocardial ischemia on exercise as well as ambulatory electrocardiography. The presence and extent of silent myocardial ischemia was also correlated with the severity of atherosclerotic coronary artery disease as determined by coronary angiography. A cohort of 20 matched non-diabetic patients were also included in the study. Silent myocardial ischemia was detected in 50% of the diabetic patients on exercise electrocardiography and in 35% on ambulatory electrocardiography compared with 10% and 5% in non-diabetics by the two methods, respectively (P < 0.01 and P < 0.05, respectively). On exercise testing in diabetic patients, silent myocardial ischemia was detected in 64% of the patients with three-vessel disease, 50% of the patients with two-vessel disease and 20% of the patients with one-vessel disease whereas in non-diabetic patients silent myocardial ischemia was detected in only 18% of the patients with three-vessel disease (P < 0.05) and in none of the patients with two- or one-vessel disease. On ambulatory electrocardiography, only patients (both diabetic and non-diabetic) with three-vessel disease manifested silent myocardial ischemia. Total ischemic burden was similar in both the diabetic and non-diabetic patients. We conclude that silent myocardial ischemia occurs in diabetic patients with coronary artery disease more frequently even in the absence of autonomic dysfunction and the prevalence of silent myocardial ischemia is higher in patients with severe degree of coronary artery disease.

Adult↗
PubMed1995

A new subclass of alkaloids from a dendrobatid poison frog: a structure for deoxypumiliotoxin 251H.

Deoxypumiliotoxin 251H [4], representing a new subclass of the pumiliotoxin-A class of alkaloids, has been isolated from a dendrobatid frog, Epipedobates tricolor. The structure, elucidated by nmr, gc-Ftir, and mass spectral analyses, is proposed to be an 8-methyl-6-(5-hydroxy-2-methylhexylidene)-1-azabicyclo[4.3.0]nonan e. The absolute stereochemistry and the relative configuration of the hydroxyl group are unknown.

Alkaloids↗
PubMed1995

An autosomal recessive nonsyndromic form of sensorineural hearing loss maps to 3p-DFNB6.

Autosomal recessive nonsyndromic hearing loss (ARNSHL) is the most common form of congenitally acquired inherited hearing impairment. Although numerous loci are believed to exist, only five have been identified. Using a pooled genomic DNA screening strategy, we have identified a sixth locus, DFNB6, on 3p in the interval bounded by D3S1619 and D3S1766.

Alleles↗
PubMed1995

The myometrium of postmenopausal women produces prolactin in response to human chorionic gonadotropin and alpha-subunit in vitro.

OBJECTIVES: To examine the effect of equimolar concentrations of hCG and dissociated alpha-subunit on PRL production by leiomyoma and myometrial tissue obtained from different hormonal states and to examine changes in PRL messenger RNA levels as PRL protein levels increased. DESIGN: Explant cultures of leiomyomas and myometrium were established and cultured for 96 hours. Tissue was studied from normal cycling women, postmenopausal women, pregnant women, and women undergoing GnRH agonist (GnRH-a) therapy. Cultured medium was collected at 24, 48, and 96 hours and assayed for PRL. In selected experiments, tissue was processed at 0 and 96 hours to analyze messenger RNA (mRNA) levels. RESULTS: Human chorionic gonadotropin and alpha-subunit stimulated PRL secretion in [1] explant cultures of leiomyoma and myometrium from premenopausal women, [2] cultures of tissue treated in vivo with leuprolide acetate for both leiomyoma and myometrium, and [3] myometrium obtained from postmenopausal women. Postmenopausal myometrium was significantly more responsive to stimulation. Prolactin mRNA levels were documented to increase after hormone treatment in postmenopausal myometrium. CONCLUSION: Myometrium from postmenopausal women is very responsive to hCG and alpha-subunit. There is a difference in response between tissue obtained from menopausal women and that from women undergoing GnRH-a therapy to achieve a "medical menopause" and reproductive age women. The level of endogenous gonadotropins as well as the steroid milieu may modulate myometrial PRL secretion.

Antineoplastic Agents, Hormonal↗
PubMed1995

Significance of left ventricular inflow gradients in patients with ventricular septal defect.

Hemodynamic data of 167 patients of isolated ventricular septal defect (VSD) was retrospectively analyzed for the presence of left ventricular inflow gradients. End diastolic gradients of > 5 mm Hg between the pulmonary artery wedge pressure and the left ventricular end diastolic pressure were recorded in 40 of these patients. In three of these cases, left atrium was also entered and identical pressure gradients were recorded between the left atrial pressure and the left ventricular end diastolic pressure. Two dimensional and Doppler echocardiographic or operative findings were available in 32 of the 40 patients. No statistical correlation was found between the presence and degree of left ventricular inflow gradients at end diastole and the degree of left to right shunt. Out of a total of 40 patients with left ventricular inflow gradients, gradients of 6-10 mm Hg were present in 24 patients. Echocardiographic or operative findings available in 19 of these did not show any left ventricular inflow obstruction. Enddiastolic gradients of 11-15 mm Hg were present in 14 patients. Echocardiographic or operative findings were available in 11 of these and one of these had congenital mitral stenosis at surgery. End diastolic gradients of more than 15 mm Hg were present in 2 patients and one of these had congenital mitral stenosis at surgery. Thus organic left ventricular inflow obstruction is rare with inflow mitral gradients of upto 15 mm Hg in patients of VSD.

Adolescent↗
PubMed1995

An epidemiological study of coronary heart disease in different ethnic groups in Delhi urban population.

A community based epidemiologival survey of coronary heart disease (CHD) was carried out on a random urban sample of 13,560 adults of different ethnic groups in Delhi. CHD was diagnosed either on the basis of clinical history, supported by documentary evidence of treatment in hospital/home or on the ECG evidence in accordance with Minnesota Code. The prevalence rate of CHD on clinical basis per 1000 adults was the highest in Sikhs (47.3), lowest in Muslims (22.8) and identical in Hindus (31.8) and Christians (31.2). The prevalence rate/1000 of silent CHD on the basis of ECG was high in Muslims (89.5) and Sikhs (87.3), low in Christians (25.0) and intermediate in Hindus (60.0). The Sikhs showed the highest prevalence rate of myocardial infarct (MI) (15.5) and angina (AP) (31.8) compared to other communities. The prevalence rate of CHD on clinical basis was higher in males than females in all communities. The prevalence of silent CHD was higher in females in Hindus and Sikhs but in Muslims it was higher in men (94.8) than in women (85.2). The wide variations in prevalence rates of CHD in different ethnic groups cannot be explained satisfactorily on the basis of conventional risk factors and support the multifactorial etiological character of CHD.

Adult↗
PubMed1994

Effects of Late Coronary Artery Reperfusion on Left Ventricular Remodeling Persist for 10 Weeks After Experimental Rat Myocardial Infarction and Are Associated with Improved Survival.

Objective: To test the hypothesis that coronary artery reperfusion performed too late to reduce infarct size improves survival by altering left ventricular remodeling and preventing progressive left ventricular dilation. Background: Several clinical trials have suggested that late coronary artery reperfusion without infaret size reduction is associated with a survival benefit. Although the mechanism is not known, survival benefits could be related to decreased infarct expansion associated with late coronary artery reperfusion. Decreased infarct expansion results in decreased left ventricular volume, and the resulting decreased wall stress could prevent or attenuate progressive left ventricular dilation and improve survival. Methods: Rats (n = 84) were randomized to undergo sham operation, permanent left coronary artery ligation, or 2 hours of left coronary artery ligation followed by reperfusion. Ten weeks later, hemodynandic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Results: When examined 10 weeks after experimental myocardial infarction late eperfusion's effects on left ventricular remodeling resulted in reduced left ventricular volume when compared to hearts with infarcts supplied by a permanently occluded coronary artery (1.9 +/- 0.1 ml/kg vs. 2.1 +/- 0.2 ml/kg; p < 0.01). Although there was a trend toward less thinning along (0.95 +/- 0.13 mm vs. 1.00 +/- 0.10 mm; p = NS) and less expansion (2.3 +/- 0.4 vs. 2.8 +/- 0.9; p = NS) in reperfused hearts compared to hearts with a permanently occluded coronary artery, changes in infarct shape 10 weeks after infarction were not significantly different. Reperfusion's beneficial effects on remodeling of noninfarcted myocardiurn were associated with improved survival. Mortality was higher in the permanently occluded rats than in the reperfused rats (35% vs. 12%; p < 0.05). Conclusion: Late coronary artery reperfusion has a beneficial effect on remodeling of noninfarcted myocardum that results in reduced left ventricular volume in rat hearts examined 10 weeks after infarction. These beneficial effects on left ventricular remodeling are associated with improved survival.

Journal Article↗