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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 541 records · Page 30Linked to original sources
PubMed1996

Identification and characterization of BICP27, an early protein of bovine herpesvirus 1 which may stimulate mRNA 3' processing.

Sequence analysis of the left genomic terminus of bovine herpesvirus 1 (BHV-1) revealed two convergently transcribed genes with 3' ends about 300 bp apart. The gene on the left is the previously described circ gene; that on the right was found to encode a protein of 400 amino acids which was designated BICP27 because of its homology to ICP27 (Vmw63) of herpes simplex virus 1 (HSV-1) and related proteins from other alpha- beta- and gammaherpesviruses. Rabbit antisera raised against a synthetic oligopeptide representing the amino terminus of the predicted polypeptide demonstrated the presence of BICP27 in the nuclei of infected cells by in situ immunoadsorbent assays. In Western immunoblots, BICP27 was detected as a 50 kDa BHV-1 specific protein expressed with early kinetics, in contrast to HSV-1 ICP27 which is an immediate early (IE) protein. A DNA fragment containing BICP27 coding sequences was inserted into a baculovirus genome. The recombinant BICP27 protein, identified by its reactivity with the antipeptide sera, exhibited the same electrophoretic mobility as BICP27 specified by BHV-1. Transient expression assays using target genes differing only in their poly(A) sites showed that BICP27, like its HSV-1 counterpart, may be involved in 3' processing of mRNA.

Amino Acid Sequence↗
PubMed1996

Nebulised antipseudomonal antibiotic therapy in cystic fibrosis: a meta-analysis of benefits and risks.

BACKGROUND: To establish the benefits and risks of nebulised antipseudomonal therapy in cystic fibrosis the results of relevant randomised controlled trials were combined. METHODS: The therapeutic end points compared were (a) number of pulmonary exacerbations requiring treatment with systemic antibiotics, (b) measurable alteration in respiratory tract pseudomonal load, (c) alteration in lung function on spirometric assessment, (d) development of resistance in respiratory tract Pseudomonas strains to the nebulised antipseudomonal used in each randomised controlled trial, and (e) renal and auditory impairment. RESULTS: Five studies were suitable for meta-analysis, eight others could not be included because of inadequate outcome description or the lack of appropriate randomisation. Meta-analysis shows benefit for nebulised antipseudomonal antibiotic therapy with no demonstrable adverse effect other than a possible increase in in vitro antibiotic resistance of Pseudomonas aeruginosa of the respiratory tract. CONCLUSIONS: Although inferences drawn from individual randomised controlled trials concerning the benefits and risks of this form of therapy are conflicting, pooled effect size establishes benefit with nebulised antipseudomonal antibiotic therapy and emphasises its relevance to the integration of information in other areas of controversy relating to the treatment of this disease.

Administration, Inhalation↗
PubMed1996

Stimulation of epidermal growth factor gene expression during the fetal mouse reproductive tract differentiation: role of androgen and its receptor.

We have shown previously that epidermal growth factor (EGF) plays a role in testosterone-dependent fetal Wolffian duct differentiation. To further assess the role for EGF, we determined whether EGF gene expression was modulated in response to male reproductive tract differentiation. The expression of EGF messenger RNA (mRNA) was measured by an RT-PCR assay using primer pairs spanning the coding sequence of 3228 nucleotide (nt) to 3401 nt. Using the RT-PCR reaction, an amplimer of the expected size, 173 bp, was detected in the fetal male reproductive tract. The amplimer hybridized with a radioactive probe representing an internal sequence of the amplified product and was digested by the restriction enzyme HaeIII, which has an unique cleavage site at 3365 nt. The level of EGF mRNA at different stages of sexual differentiation was measured by a newly developed quantitative competitive RNA PCR (QCPCR) assay for EGF mRNA. The assay was sensitive and reproducible within a linear range of amplification with 5 x 10(4) to 140 x 10(4) copies of mRNA. Using the quantitative competitive RNA PCR we found that the level of EGF mRNA was higher in the male reproductive tract than that in the female reproductive tract. Exposure to testosterone (40 mg/kg.day) during days 13-17 of gestation induced the Wolffian duct in the female fetuses and resulted in stimulation of EGF-mRNA expression. Similarly, an antiandrogen receptor, flutamide (100 mg/kg.day) exposure during days 13-17 of gestation inhibited male reproductive tract differentiation and resulted in inhibition of EGF-mRNA expression. Moreover, during the differentiation of the male reproductive tract there was a biphasic increase in the level of EGF-mRNA, first at day 14 of gestation, the period of onset of testicular activity and Wolffian duct morphogenesis, and second at day 18 of gestation, corresponding to onset of differentiation of the urogenital sinus, epididymal duct, and seminal vesicle. Thus, it appears that testosterone-induced male sexual differentiation is accompanied by an increase in EGF gene expression.

Androgens↗
PubMed1996

System for accurate one-dimensional gel analysis including high-resolution quantitative footprinting.

The interactive menu-driven computer program, Geltrak, displays and analyzes a one-dimensional (1-D) electrophoretic gel after digitization by either densitometry or storage-phosphor technology. The program is designed to analyze nucleic acid or protein gels in a variety of ways and includes a specific footprinting option. Overall accuracy for the entire process of 1-D electrophoretic gel band quantitation by peak profile fitting has been investigated. A standard control gel with a predetermined component ratio and minimal background was devised and subjected to electrophoresis, followed by three methods of digitization. The resulting images were analyzed by Geltrak, and their integrated peak area ratios were compared with their initial measured values. Individual band profiles from the control gel were used to develop an improved fitting function to represent the peak profile shape exactly. This function can be used in conjunction with a sophisticated profile-fitting technique to accurately predict the peak shapes from gels with background noise or overlapping bands.

DNA Footprinting↗
PubMed1996

A triphasic oral contraceptive pill, CTR-05: clinical efficacy and safety.

OBJECTIVE: The primary objective of this study was to compare the safety, contraceptive efficacy, and menstrual cycle patterns in women using triphasic oral contraceptive pills, namely CTR-05, containing 50/100/150 micrograms desogestrel and 35/30/30 micrograms ethinylestradiol, and Orthonovum777 containing 500/750/1000 micrograms norethindrone and 35/35/35 micrograms ethinylestradiol. METHOD: Forty-six female volunteers, satisfying the selection criteria, were evaluated for six cycles, in an open-label, randomized study. Volunteers using CTR-05 were studied for 13 additional cycles for efficacy and safety. RESULTS: No serious adverse effects were observed in either group. The incidences of other drug-related adverse effects, such as headache and nausea, were transient in both groups. CTR-05 did not lower levels of high density lipoprotein (HDL) cholesterol. This may be attributed to the lower androgenicity of its progestin component, desogestrel. No pregnancies were reported in either group. Clinical and laboratory parameters remained within normal limits in both groups. In the CTR-05 group, the lower dose of ethinylestradiol did not affect the safety, efficacy and acceptability of the product. CONCLUSION: Desogestrel, with little estrogenic activity and only minimal androgenic activity, leads to lipoprotein changes, resulting in a favorable cardiovascular profile, as well as minimal androgen-related effects, such as hirsutism and acne.

Adult↗
PubMed1996

Antimutagenic effects of polyphenols isolated from Terminalia bellerica myroblan in Salmonella typhimurium.

Antimutagenic effect of 2 polyphenolic fractions isolated from T. bellerica in TA98 and TA100 strains of S. typhimurium against 2AF, NPD and 4NQNO has been characterized. Both the fractions were significantly effective against S9-dependent 2AF; less effective against NPD and almost not effective against 4NQNO in TA100 strain. Using 13C-NMR spectral analysis, the TB-3 fraction, which was significantly more effective against 2AF compared to TB-4, was found to be a mixture of 3 tannins while TB-4 was non-tannin fraction. Interaction of polyphenols with S9 proteins may be the probable cause of inhibitory effect of these polyphenols, though the possibility of other mechanisms cannot be ruled out.

Antimutagenic Agents↗
PubMed1996

Effects of long-term hydralazine treatment on myocardial structure and expression of myosin isogenes in cardiac pressure overload in rats.

The long-term effects of an arterial vasodilator, hydralazine, on myocardial structure and cardiac myosin isogene expression in pressure overload in rats were investigated. Portan rats were subjected to pressure overload by partial abdominal aortic constriction in order to study the effects of a 4-week treatment with hydralazine (15 mg/kg p.o.) on hemodynamics, ventricular structure, and ventricular total RNA, DNA, protein and myosin isoform expression pattern in sham (SO) and pressure-overloaded (p.o.) rats. P.o. increased the mean arterial pressure (MAP) and systolic blood pressure (SBP) and resulted in increased ventricular weight, LV wall thickness, total RNA and protein content; however, total DNA remained unchanged. The expression of fetal isogene beta-myosin heavy chain (beta-MHC) was markedly enhanced, whereas alpha-MHC was reduced. Hydralazine (15 mg/kg p.o.) normalized MAP and SBP, but did not modulate the hypertrophic changes of pressure-overloaded myocardium. It did not prevent an increase in ventricular total RNA and protein content and antithetical expression of myosin isoforms. Overall growth rate of rats was unaffected by hydralazine treatment. These results suggest that hydralazine has no direct effect in preventing the progression of cardiac hypertrophy and expression of beta-MHC, in spite of lowering blood pressure in pressure-overloaded rats. Thus, it further reaffirms that factors other than hemodynamics may play a pivotal role in the development of cardiac hypertrophy and induction of fetal isogene expression.

Analysis of Variance↗
PubMed1996

Influence of pentoxifylline and dispirin on aggregation and deformability of erythrocytes under in vitro conditions.

Aggregation mechanism and deformability in pentoxifylline- and dispirin-treated erythrocytes are measured and compared with that of normal cells. The aggregation process is analyzed in terms of parameters which are obtained from the sequential recording of the transmitted light signal throughout the aggregate formation and sedimentation process. Erythrocyte deformability is determined by measurement of passage time through cellulose membrane. The variations in aggregation parameters in pentoxifylline-treated samples show that the formed aggregates are of larger size which sediment faster. In dispirin-treated cells, the formation of large size aggregates is delayed. The entire process is completed faster in pentoxifylline-treated compared to that of dispirin-treated cell whereas the normal sample shows an intermediate value. The deformability of erythrocytes treated with these drugs is increased.

Aspirin↗
PubMed1996

Unusual occurrence of cholera in Delhi during January 1994: epidemiological investigations.

Hundreds of laboratory-confirmed cholera cases occur every year in Delhi. However from 1965 through 1993, no cases of cholera nor carriers of Vibrio cholerae have been detected in the months January and February of all these years. Nevertheless, two cases occurred in January 1994. Both were children who acquired their infection locally. Six hundred fifty-eight rectal swabs collected from possible contacts were negative for V. cholerae. The next isolations could be made only in April, which is the usual beginning of the cholera season. The study suggests that cholera transmission can occur during the winter months in Delhi, but that it is not sustained.

Acute Disease↗
PubMed1996

Comparative antioxidant effects of beta-adrenoceptor blockers, calcium antagonists and U-74500A against iron-dependent lipid peroxidation in murine ventricular microsomal membranes.

Recently we have shown that ACE inhibitors and platelet activating factor antagonists inhibit iron-dependent lipid peroxidation in murine ventricular membranes and possess beneficial effects on ischemia and ischemia reperfusion-induced myocardial injury, which has been ascribed to their capacity to scavenge or impair oxygen free radical generation. In the present study we investigated the effects of beta-adrenoceptor blockers and calcium antagonists on iron-dependent lipid peroxidation (LPO) in murine ventricular membranes and compared them with the lazaroid U-74500A, a potent antioxidant. Fe(2+)-vitamin C induced LPO in a concentration- and time-dependent manner, measured as thiobarbituric acid reactive substances (TBARS) formation. Pretreatment of ventricular membranes with gallopamil, verapamil, propranolol and metaprolol at concentrations of 5 microM and higher inhibited Fe(2+)-vitamin C-induced LPO in a concentration-dependent manner with IC50 values of 192.8-208.3 microM; however, they were less potent than U-74500A (IC50 6.8 microM). In contrast, atenolol, timolol, diltiazem and nifedipine inhibited LPO at very high concentrations with IC50 values of 864.5-971.5 microM. Inhibition of LPO may not be due to the drugs' classical pharmacological actions, but rather to their characteristic chemical structures or physicochemical interactions with biological membranes. In view of the pathological importance of LPO in cardiac ischemic injury, inhibition of LPO by gallopamil, verapamil, propranolol and metaprolol may provide additional cardioprotective activity and thus reinforces their beneficial effects in the treatment of ischemic heart disease.

Adrenergic beta-Antagonists↗
PubMed1996

A recent case of congenital malaria in Singapore.

We report a case of congenital malaria in a 2-month-old baby girl, born in Singapore of a Singaporean mother, who presented with fever for one week, gross hepatosplenomegaly and anaemia (haemoglobin 5.6 g/dL) and thrombocytopenia. Peripheral blood films showed Plasmodium vivax. There was no local transmission at that time, but the mother had spent the first 6 months of her pregnancy in Pakistan, where she had been treated for prolonged fever at 4 months amenorrhoea with ibuprofen alone. The mother and 2 siblings were asymptomatic and repeatedly tested negative on blood films for malaria parasites, but the mother tested positive for antibodies to Plasmodium on the Fluorescent Antibody Test. The child was treated with oral chloroquine and made an uneventful recovery. We postulate that this is believed to be the first recent case of congenital malaria in Singapore since it was declared malaria free in 1982. The diagnosis should be considered in babies of mothers who have travelled to places where malaria is endemic, as maternal infection may be unrecognised, and the child may be asymptomatic at birth.

Antimalarials↗
PubMed1996

Role of noradrenaline uptake inhibition and alpha-adrenoceptors in reperfusion ventricular arrhythmias in vivo and in vitro.

In view of the importance of sympathetic nervous system in the genesis of cardiac arrhythmias during reperfusion following coronary occlusion, the role of noradrenaline uptake inhibitor desipramine in the prevention of reperfusion arrhythmias was investigated in intact rabbit heart and isolated rat heart. For both the paradigms, ischaemia was produced by coronary artery ligation for 30 min followed by reperfusion for 60 min with drug administration at the time of reperfusion. Desipramine was used at three dose levels (0.2, 0.6 and 2.0 mg/kg) in the in vivo study while in vitro it was used at a concentration of 7 microM. Further, to investigate the status of adrenergic receptors during ischaemia and reperfusion, ischaemia was simulated by superfusing lactate physiological solution in isolated rabbit aortic strip preparation, which has well characterized alpha-receptors. Cumulative dose response curves (DRC) of selective alpha 1 agonist, phenylepherine (PE) were recorded during normal, ischaemic and reperfused conditions. Desipramine showed dose dependent anti-arrhythmic effect in vivo as well as in vitro. In intact heart studies desipramine offered protection against reperfusion arrhythmias in a dose related manner i.e. 50, 67.5 and 100% whereas in isolated studies, 50% protection was observed in the overall incidence of arrhythmias. DRC of PE shifted towards right during both ischaemia and reperfusion with a significant elevation of maximal response only during reperfusion.

Adrenergic Uptake Inhibitors↗
PubMed1996

Behavioural effects of prenatal diazepam administration on anxiety patterns in rats.

Diazepam (10 mg/kg, ip) treatment was given from day 13 to 20 of gestation to pregnant rats, this being the critical period for neural development in this species. The pups born were subjected to open-field exploratory behaviour, tunnel-board exploratory behaviour, elevated zero maze behaviour and social interaction tests at 8-9 weeks of age. The results indicate that prenatal diazepam treatment induces a significant increase in open-field ambulation, grooming, scratching and licking/washing, whereas rearing and faecal dropping remain unchanged. Significant reduction in tunnel-board exploratory activity, activity on zero-maze and social interaction were also observed in the prenatally diazepam treated offsprings. The results suggests that prenatal interference in the form of diazepam leaves a lasting imprint on offsprings resulting in hyper-emotional responsiveness and anxiety state.

Animals↗