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Biomedical subjects

M P Gupta

Publications and source records attributed to M P Gupta.

At least 19 recordsLinked to original sources
PubMed1992

Isolation and characterization of a rat ventricular cDNA expressed specifically in cardiac and skeletal muscles.

We describe the isolation of a novel cDNA named Myomy and show that its transcripts are present in skeletal and cardiac muscles as well as in differentiated Sol 8 skeletal muscle cell line. Sequence analysis revealed that neither nucleotides nor deduced protein product have any significant homology to those previously described. The encoded protein of Myomy cDNA consists of 76 amino acids and has a molecular weight of 8,000 dalton. Based on its muscle specific expression, low abundance and a higher occurrence of SP(T)XX, S(T)S(T)XX motifs, we suggest that Myomy encodes a new muscle specific transcription factor.

Amino Acid Sequence↗
PubMed1992

(+)-4 beta-hydroxyhernandulcin, a new sweet sesquiterpene from the leaves and flowers of Lippia dulcis.

From the leaves and flowers of Lippia dulcis collected in Panama, a new sweet sesquiterpene identified as (+)-4 beta-hydroxyhernandulcin [2] was isolated, accompanied by (+)-hernandulcin [1], (-)-epihernandulcin [3] (a novel natural product), and 6-methyl-5-hepten-2-one [4]. Acteoside (verbascoside) [5], a known bitter phenylpropanoid glycoside, was isolated from the flowers of L. dulcis. The structure of (+)-4 beta-hydroxyhernandulcin was established by interpretation of its spectral data.

Panama↗
PubMed1991

Egr-1, a serum-inducible zinc finger protein, regulates transcription of the rat cardiac alpha-myosin heavy chain gene.

Egr-1 is an early growth response gene that encodes a protein with three zinc fingers and is involved in transcriptional regulation. In adult heart myocytes, in contrast to c-fos and c-myc, high levels of Egr-1 mRNA expression have been shown. Here we report that Egr-1 transactivates rat cardiac alpha-MHC gene expression. In serum-starved primary cultures of 18-day-old fetal rat heart myocytes, addition of serum evoked expression of both Egr-1 and alpha-MHC gene transcripts. Inclusion of 10 microM cycloheximide in these cultures for 48 h caused a greater increase in Egr-1 mRNA, whereas the expression of alpha-MHC transcripts was ablated. To examine the involvement of Egr-1 in alpha-MHC induction, we transfected primary cultures of cardiac myocytes with plasmids pCMVEgr-1 (Egr-1 expression vector) and pMP3.3CAT containing -2.9- to +0.42-kilobase sequences of the alpha-MHC gene fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene. Cotransfection of pCMVEgr-1 stimulated expression of pMP3.3CAT 10-15-fold. Furthermore, pCMVEgr-1 also stimulated expression of the endogenous alpha-MHC gene in primary cultures of cardiac myocytes. Transactivation of pMP3.3CAT expression by pCMVEgr-1 was also observed by transfecting the myogenic cell line Sol 8, but not in L6E9 cells or in NIH3T3 fibroblasts. By creating progressive 5' deletions of the alpha-MHC gene, we found that the region extending between -1698 and -1283 base pairs is necessary for Egr-1-induced expression of the alpha-MHC/CAT construct. These results define a physiological target for the Egr-1 transcription factor and delineate a novel mechanism for regulation of the alpha-MHC gene.

Animals↗
PubMed1991

Activation of alpha-myosin heavy chain gene expression by cAMP in cultured fetal rat heart myocytes.

The effect of cAMP on cardiac myosin heavy chain (MHC) gene expression in primary cultures of 18-day-old fetal rat heart myocytes was investigated. When myocytes were treated with either 10 microM forskolin or 1 mM 8-bromo-cAMP for 48 h, the relative amount of the V1 to -V3 myosin isoform ratio increased 3-fold. The abundance of alpha-MHC mRNA was also increased 3-to-4-fold in forskolin treated vs control cells. However, no appreciable change was observed in the level of beta-MHC mRNA. In addition, a 70% increase in the transcription rate of the cardiac MHC gene was observed by nuclear run-on assay following treatment of cells with 10 microM forskolin for 12 h. These results demonstrate the preferential induction of alpha-MHC mRNA by cAMP which is, in part, mediated by transcriptional activation of the gene.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

The role of adrenergic system in regulation of cardiac myosin heavy chain gene expression.

The cardiac phenotype exhibits considerable plasticity, being under the regulation of numerous factors, such as developmental stage, functional load, as well as nutritional and hormonal states of the animal. Several lines of evidence indicate that the adrenergic nervous system plays an important role in the redistribution of myosin isoforms in the heart. For example, chemical sympathectomy favors the expression of V3 isomyosin at the expense of V1. In this study, we have examined the effect of adrenergic pathways on the expression of cardiac myosin heavy chain (MHC) genes. The level of cAMP was modulated by either adding forskolin or 8-bromo-cAMP to primary cultures of embryonic (18 d) cardiac myocytes. We have found that the level of mRNA coding for MHC-alpha was increased two- to three-fold. The effect was dose- and time-dependent and was potentiated further when the 8-Br-cAMP was given together with a phosphodiesterase inhibitor. The same changes were found in KCl arrested cells, indicating independence of contractile activity. Treatment of cells known to activate the protein kinase C (TPA) and inositol triphosphate pathways has increased the level of beta-MHC mRNA while that of alpha-MHC remained unchanged. These data lend strong support to direct effect of the adrenergic system on activity of cardiac genes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Flavonol glycosides from Monnina sylvatica.

A new kaempferol triglycoside and three known kaempferol glycosides, among them two apiosides, have been isolated from the aerial parts of Monnina sylvatica. The structures were established on the basis of acid and enzymatic hydrolysis and spectral data (UV, 1H and 13CNMR, NOE difference measurements, D/CI and FAB-MS) of the isolates and of some derivatives. The triglycoside kaempferol 3-O-beta-D-glucosyl-(1----2)-O-[alpha-L-rhamnosyl(1----6)]-beta-D- galactoside is a new natural product. The configuration of the apiosyl moiety in kaempferol 3-O-beta-D-apiosyl(1----2)-beta-D-galactoside and kaempferol 3-O-beta-D-apiosyl(1----2)-O-[alpha-L-rhamnosyl(1----6)]- beta-D-galactoside was established through NOE difference measurements on the peracetate.

Carbohydrate Sequence↗
PubMed1991

Studies on the mode of action of tolnaftate in Microsporum gypseum.

Studies were performed on the mode of action of tolnaftate and resistance to this drug in Microsporum gypseum. Cells grown in the presence of tolnaftate (at the IC 50) showed a reduced content of total phospholipids and sterols whereas there was an increase in total RNA content. Incubation of cells with tolnaftate (at 10 x MIC), followed by addition of different macromolecule precursors revealed inhibition of the biosynthesis of all macromolecules except for RNA. The activity of membrane-bound enzymes did not change on treatment with tolnaftate (10 x MIC) whereas an increase in the leakage of intracellular 32P was observed. The content of total phospholipids was higher in tolnaftate-resistant cells, whereas the content of total sterols, DNA, RNA and protein was comparable to that of susceptible cultures. Activity of phosphodiesterase decreased and 5'-nucleotidase increased in tolnaftate-resistant cells. Our results suggest that the antifungal activity of tolnaftate is due to differential action on various targets site(s) which are modified in strains resistant to the drug.

DNA, Fungal↗
PubMed1991

[Evaluation of traditional medicine: effects of Cajanus cajan L. and of Cassia fistula L. on carbohydrate metabolism in mice].

The authors report the results of pharmacologic evaluation of two medicinal plants: Cajanus cajan (L.) Millsp and Cassia fistula, which are used in Panamanian folk medicine for the treatment of diabetes. It was found that the aqueous fraction of the leaves and stems of C. cajan did not produce any hypo blood sugar effect in normoglycemic mice; instead, it produced a hyperglycemia with doses of 500 mg/kg and 1000 mg/kg (p less than 0.001). Only with a dose of 300 mg/kg a short lived decrease in the glycemia was seen at one hour. On the contrary, the folk use of the leaves of C. fistula for diabetes seems to have some correlation with the popular frek use. The aqueous fraction produced a significant decrease in the glycemia (p less than 0.001) at 4 and 24 hours with doses of 300 and 500 mg/kg, and at one and four hours after the dose of 1000 mg/kg (p less than 0.001). In the glucose tolerance test, the aqueous fraction of C. cajan produced a significant and short lasting decrease (p less than 0.05) with the dose of 300 mg/kg, while the dose of 500 mg/kg did at 0.25, 0.5 and 1 hour (p less than 0.01). The 1000 mg/kg dose produced a significant increase in glucose tolerance at 1 and 2 hours (p less than 0.05). The aqueous fraction of C. fistula produced a significant decrease (p less than 0.05) with the dose of 500 mg/kg at 0.25 and 0.5 hours. The 1000 mg/kg dose produced a significant increase (p less than 0.001) at 0.25 and 2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Antimicrobial activity of various algae of the Panamanian Atlantic coast].

The methanolic extracts in 5 of 7 alagae from the Atlantic coast of Panama: Caulerpa racemosa, Halimeda opuntia, Gelidiela acerosa, Laurencia papillosa y Acanthophora spicifera, showed antimicrobial activity against Staphylococcus aureus and Bacillus subtilis in a concentration of 50 mg/ml by the cylinder plate method. None of the algae studies showed activity against Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. The content of agar in Acanthophora spicifera was found to be the highest (33.5%) of all the species studied.

Anti-Infective Agents↗
PubMed1990

Effect of cigarette smoke inhalation on benzo[a]pyrene-induced lung carcinogenesis in vitamin A deficiency in the rat.

Vitamin A deficiency caused a significant increase (P less than 0.05) in benzo[a]pyrene (BP)-induced lung tumor incidence and tumor burden in male Wistar rats. Inhalation of cigarette smoke during initiation and post-initiation phases of carcinogenesis resulted in higher tumor burden as compared to the same observed in the animals exposed to cigarette smoke during the post-initiation phase only. Stimulation in tumor burden by cigarette smoke was increased further by vitamin A deficiency.

Administration, Inhalation↗
PubMed1990

Ethnobotanical inventory of medicinal plants used by the Guaymi Indians in western Panama. Part II.

A list of newly identified plants is presented to supplement Part I (Joly et al. (1987) Journal of Ethnopharmacology 20, 145-171). A comparative analysis is made between our work and two other recent inventories of plants used by the Guaymi Indians of Panama and Costa Rica. As in Part I, the results of a literature survey are also provided, including medicinal uses, known constituents and pharmacological effects.

Medicine, Traditional↗
PubMed1990

Cardiac sarcolemma as a possible site of action of caffeine in rat heart.

Caffeine (0.1-10 mM) produced a biphasic effect on Na(+)-K+ ATPase activity in the rat heart sarcolemmal preparations. The Na(+)-K+ ATPase activity was stimulated by about 25% at low concentrations (0.1-1 mM), whereas the enzyme was inhibited by about 25% at higher concentrations (10 mM) of caffeine. The stimulatory effect of 1 mM caffeine was associated with about 30% increase in the Vmax value for Na(+)-K+ ATPase, whereas the depressant action of 10 mM caffeine was associated with an increase of the Km value from 1.4 to 2.1 mM ATP. The Na(+)-induced Ca++ release from the sarcolemmal vesicles was stimulated with caffeine in a concentration-dependent manner; about 80% increase in the activity was observed at 0.1 mM caffeine. The apparent Ka (millimolar Na+) values for the Na(+)-induced Ca++ release were about 17 and 6 in the absence and presence of 1 mM caffeine, respectively. However, the sarcolemmal Na(+)-dependent Ca++ uptake and ATP-independent Ca++ binding were not affected, whereas the ATP-dependent Ca++ accumulation and Ca+(+)-stimulated ATPase activities were depressed by 1 to 10 mM caffeine. This agent at concentrations of 0.1 to 10 mM produced a biphasic effect on the contractile activity of the isolated perfused rat heart. The initial transient positive inotropic (30-60%) effect was followed by a sustained negative inotropic (50-80%) response of the drug; the delayed decrease in contractile force was associated with a significant increase (35-50%) in the resting tension. The initial positive inotropic effect of caffeine was dependent on the concentration of Ca++ (0.2-3 mM) in the perfusion medium; however, this response was attenuated either by lowering the concentration of Na+ from 140 to 35 mM or by different concentrations (0.5-1 mM) of amiloride in the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Alterations of phosphatidylethanolamine N-methylation in rat heart by quinidine.

To elucidate the molecular mechanism underlying the adverse depression of myocardial contractility observed during antiarrhythmic therapy of quinidine, we investigated its action on the phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17) activities of cardiac subcellular membranes. Rat heart sarcolemma, mitochondria, and microsomes (sarcoplasmic reticular fragments) were isolated, and the three catalytic sites for N-methylation activities were examined with 0.055 (site I), 10 (site II), and 150 (site III) microM concentrations of S-adenosyl-L-[methyl-3H]methionine as a methyl donor. Total methyl group incorporation into sarcolemmal phosphatidylethanolamine was depressed by 10(-6)-10(-3) M quinidine at sites II and III. The activity of site I was stimulated at low (10(-9) M) concentrations and inhibited at high concentrations of the drug. A similar behaviour was observed with procainamide, although the inhibitory effect was less pronounced and was not additive with quinidine. Quinidine-induced inhibition was associated with a depression of Vmax, while the apparent affinity for S-adenosyl-L-methionine was unaltered. Analysis of individual methylated phospholipids confirmed inhibition by quinidine at sites II and III in sarcolemma. Microsomal phosphatidylethanolamine N-methylation was affected by 10(-6) M quinidine only at site II, whereas no changes were noted in mitochondria. Quinidine also inhibited both the positive inotropic response and concomitant increase in tissue N-methylated phospholipids observed upon L-methionine perfusion of rat heart. These results suggest that quinidine alters the intramembranal level of N-methylated phospholipids, and this may serve as a biochemical mechanism contributing to its negative inotropic effect.

Animals↗
PubMed1989

Dermatomycosis in dogs.

During the routine examination of dogs for cutaneous lesions, 205 dogs were screened for fungi other than dermatophytes. Twenty-two dogs (10.8%) revealed the presence of non-dermatophytic fungi suspicious for representing the etiologic agents of the skin lesions. The fungi isolated were Alternaria sp. (2.9%), Penicillium sp. (2.4%), Aspergillus fumigatus (2.0%), Mucor sp. (1.5%), Cladosporium sp. (1.5%) and Fusarium sp. (0.5%). No dermatophyte was isolated in association with these fungi. The incidence of these infections was found to be greater in warm and humid climate.

Animals↗
PubMed1989

Activation of heart sarcoplasmic reticulum Ca++-stimulated adenosine triphosphatase by insulin.

Although insulin is known to elicit a positive inotropic effect in cardiac muscle preparations, very little is known concerning the mechanism of this action. In view of the crucial role played by the sarcoplasmic reticular (SR) calcium transport in cardiac contractile events, the effects of insulin on the pig heart SR were investigated. Insulin activated the SR Ca++-stimulated adenosine triphosphatase (ATPase) in a concentration-dependent manner (0.1 mU to 1 U/ml); maximal activation (125%) was seen at 0.1 to 1 U/ml of insulin. Kinetic studies revealed that the insulin-induced activation was due to an increase in the apparent Vmax of Ca++-stimulated ATPase without any alteration in the Km. Insulin was found to bind with SR membranes in a specific manner and this binding was rapid, saturable and displacable. The dose-related increase in the activation of Ca++-stimulated ATPase was related linearly (r = 0.98) to binding of insulin with SR membranes; 50% activation of Ca++-stimulated ATPase was found to occur at 13.5 fmol of insulin binding per mg of SR protein. When insulin was allowed to dissociate by a 100-fold dilution of the insulin-receptor complex, the activity of SR Ca++-stimulated ATPase also declined gradually. Furthermore, proteolytic digestion on the membrane with trypsin (3 micrograms/mg of protein) decreased both insulin binding as well as the increase in Ca++-stimulated ATPase activity by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1989

Clinical, haemodynamic and echocardiographic study in chronic cor pulmonale.

Thirty patients of chronic cor pulmonale were studied clinically and by chest skiagram, electrocardiography, echocardiography, pulmonary function tests, arterial blood gas analysis and, wherever possible by right heart catheterization. Pulmonary arterial pressures (PAP) correlated significantly only with cardiomegaly on skiagram and with arterial oxygen tension (PaO2). There was no significant correlation between mean PA pressures and prominent pulmonary conus on RVH by ECG, FEV1, PaCO2 or right ventricular outflow tract dimensions by echocardiography. Left ventricular function, as assessed by pulmonary capillary wedge pressure on cardiac catheterization, by LV ejection fraction and fractional shortening on echocardiography was normal in all cases except two (6.67%). There was significant increase in left ventricular posterior wall thickness in the patients studied.

Adult↗
PubMed1988

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat.

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.

Administration, Inhalation↗