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Biomedical subjects

N K Singh

Publications and source records attributed to N K Singh.

At least 19 recordsLinked to original sources
PubMed1999

Effect of malathion, an organophosphorus pesticide, on the serum proteins of Heteropneustes fossilis (BLOCH).

The use of pesticides to control pests and to increase food production is a normal process in this modern age. The objective of this study was to determine changes in different serum protein fractions caused by the action of malathion, a commonly used pesticide. We used Indian catfish, Heteropneustes fossilis. The fish were exposed to a sublethal dose of 4 mg/L of malathion for 24, 48, 72, and 96 hr. The LC50 value at 96 hr was found to be 11.676 mg/L. The results showed the formation of three low and four high mobility fractions and the disappearance of some protein fractions at different periods of exposure. The appearance of fractions A, B, and C (low-mobility proteins) may be due to altered immune responses caused by cellular damage. The appearance of new high-mobility fractions (D, E, F, and G) is possibly due to the breakdown of red blood cells and other cellular components. The findings of this study indicate that the high concentration of malathion (4 mg/L) induced more alterations in serum proteins compared with the low concentration (1.2 mg/L) used in our previous study.

Animals↗
PubMed1998

Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India.

OBJECTIVES: To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. DESIGN: Randomised, unblinded, controlled trial with 180 day follow up. SETTING: Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. SUBJECTS: People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. INTERVENTIONS: Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. MAIN OUTCOME MEASURES: Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. RESULTS: Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. CONCLUSIONS: A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar.

Adolescent↗
PubMed1998

Transcriptional activation of the Aspergillus nidulans gpdA promoter by osmotic signals.

A differentially expressed gpdA cDNA clone was isolated from NaCl-adapted Aspergillus nidulans (FGSC359) and identified as glyceraldehyde-3-phosphate dehydrogenase (gpdA) on the basis of its nucleotide sequence. The level of gpdA RNA substantially increased in cultures gradually adapted to NaCl but was greatly reduced in cultures exposed briefly to a high concentration of NaCl. A pyrG auxotroph of A. nidulans (A773) was cotransformed with a gpdA-uidA construct and a plasmid containing the Neurospora crassa pyr4 gene as a selectable marker. One pyrG+ beta-glucuronidase-positive (GUS+) transformant was selected, and stable integration of the gpdA-uidA construct into the genome was confirmed by Southern blot analysis. Gradual adaptation to increasing concentrations of NaCl resulted in an increase in GUS activity to 2.7-fold. GUS activity was reduced after a 2-h exposure of an unadapted culture to 2 M NaCl but gradually increased to a maximum of twofold after 24 h. GUS activity also increased by 8.4-fold in Na2SO4-adapted cultures, 4.9-fold in polyethylene glycol-adapted cultures, and 7.5-fold in KCl-adapted cultures. These results are consistent with the hypothesis that the A. nidulans gpdA promoter is transcriptionally activated by osmotic signals.

Adaptation, Physiological↗
PubMed1998

Effect of sublethal levels of malathion on the gills of Heteropneustes fossilis: scanning electron microscopic study.

Scanning electron microscopic studies of the gills of catfish, Heteropneustes fossilis, exposed to sublethal malathion (4 mg/L and 6 mg/L) revealed that 24-hour exposure to 4 mg/L had a mild effect. However, severe damage was found after 48- and 72-hour exposures. After a 24-hour exposure to a 6 mg/L concentration, more severe damage ensued. The microridged epithelial cells of the gill arch became perforated and the central portion of the filament appeared elevated. Numerous mucous gland openings also became visible. After 48- and 72-hour exposures, the damage and structural changes were more pronounced when compared with the 4 mg/L exposure. Enlarged mucous gland openings were found on the gill arch. The lamellar surface had many crevices, elevations and depressions. Broken microridges in the gill arch surface were visible at a 72-hour exposure. At 96 hours of exposure, structural recovery occurred to some extent in both the 4- and 6-mg/L exposures. Corrugation and dissociated epithelium along with some interlamellar bridges were evident after 72 hours of exposure to both concentrations. Such deleterious effects cause reduction in available water supply as well as available respiratory area that may result in decreased oxygen uptake. Consequently, fish may fail to get sufficient oxygen and asphyxiate.

Animals↗
PubMed1998

Profound hyponatraemia following an idiosyncratic reaction to diuretics.

A case report of a79-year-old woman with a breast adenocarcinoma who presented with clouding of consciousness and anorexia with a hyponatraemia of 97 mmol/l is described. An initial diagnosis of secretion of inappropriate antidiuretic hormone (SIADH) was made on the clinical history and a urine: plasma osmolality ratio of 2.25. Further investigation revealed the correct diagnosis of a sodium-losing state with dehydration, and that her ADH level was normal. The actual cause of her hyponatraemia was the recent prescription of a thiazide diuretic. This case illustrates the unreliability of urine: plasma osmolality ratios for the diagnosis of SIADH.

Aged↗
PubMed1997

Expression of a synthetic protein-based polymer (elastomer) gene in Aspergillus nidulans.

A gene for a synthetic protein-based polymer, G-(VPGVG)119-VPGV, coding for the EG-120mer (elastomer), was cloned into a fungal expression vector to allow constitutive expression of the polymer controlled by the gpdA (glyceraldehyde-3-phosphate dehydrogenase) promoter sequence of Aspergillus nidulans. Stable transformants of A. nidulans showed plasmid integration with varying copy number when analyzed by Southern-blot hybridization. Expression of the synthetic gene was demonstrated by Northern-blot hybridization. However, the translational efficiency for production of the polymer polypeptide was low, presumably because of certain codons in the polymer gene (CCG and GUA) that are rarely used by A. nidulans. Partial purification by reversible phase transition followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed the presence of polymer protein in a transformant that contained multiple copies of the polymer gene. This study represents the first attempt to express a synthetic gene (with no natural analog) in a fungus.

Aspergillus nidulans↗
PubMed1997

Antitumor activity studies of newly synthesized N-salicyloyl-N'-(p-hydroxybenzthioyl)hydrazine and its copper(II) complex both in vivo and in vitro.

A new ligand N-salicyloyl-N'-(p-hydroxybenzthioyl) hydrazine (H2STPH) and its Cu(II) complex [Cu(SPTH)] were prepared and characterized by analytical and physicochemical studies. In vivo antitumor activity of [Cu(STPH)] has been tested against breast tumor in C3H/J strain mice and in vitro on P-815 (murine mastocytoma) and K-562 (human erythroleukemia) cells. LD50 values were estimated at a dose level of 100 mg/kg body weight and a light microscopic study also carried out.

Animals↗
PubMed1997

Antioxidant effects of lovastatin and vitamin E on experimental atherosclerosis in rabbits.

The effects of the administration of vitamin E (10 mg/day) plus lovastatin (2 mg/day; group A, n = 10), lovastatin alone (2 mg/day; group B, n = 10), and placebo (group C, n = 10) were compared over 24 weeks in a randomized, single-blind controlled trial. All groups of rabbits received a trans fatty acid (TFA)-rich diet (5-10 g/day) for 36 weeks. Treatment with vitamin E plus lovastatin (group A) and lovastatin (group B) started after 12 weeks of administration of TFA-rich diet was associated with a significant but similar decline in serum cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in both groups at 36 weeks. Lipid peroxides and diene conjugates showed a significant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovastatin group B showed a lesser but significant decrease in lipid peroxides and diene conjugates at 36 weeks, indicating that lovastatin may have antioxidant activity. In control group C, the increase in blood lipids and oxidative stress at 36 weeks was much greater than the decrease in groups A and B. After experimental lipid peroxidation at 24 weeks in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits died due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against death due to free radical stress. Aortic lipids and sudanophilia indicating athorosclorosis were significantly lower in groups A and B than in group C. The atherosclerotic coronary plaque sizes were significantly smaller in group A (18.5 +/- 3.6 microns) than in groups B (41.6 +/- 4.2 microns) and C (85 +/- 6.7 microns). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therapy with vitamin E, as an adjunct to lipid lowering with lovastatin, can provide additional benefit in the inhibition of oxidative stress and atherosclerosis. The antioxidant activity of lovastatin has not been reported, to our knowledge.

Animals↗
PubMed1997

Prevalence and determinants of hypertension in the Indian social class and heart survey.

To determine the association of socio-economic status (SES) and prevalence of hypertension and its risk factors in a rural population, a cross sectional survey was conducted in two randomly selected villages in the Moradabad district in North India. There were 1935 residents aged over 25 (984 men and 951 women) who were randomly selected and categorised into social classes 1-4 depending upon SES based on occupation, housing conditions, land holding, total per capita income, ownership of consumer durables and education. The prevalence of hypertension diagnosed by JNC V criteria (>140/90 mm Hg) was significantly higher among social class 1 and 2 and showed positive relation with SES in both sexes. Among social class 1 and 2 subjects, there was a higher prevalence of overweight and obesity and sedentary lifestyle. Logistic regression analysis with adjustment of age showed that SES had a positive relation with hypertension (odds ratio: men 1.09, 95% CI 1.05-1.14; women 1.08, 95% CI 1.05-1.13), body mass index (odds ratio: men 1.12, 1.08-1.18; women 1.11, 1.06-1.16) and sedentary lifestyle (odds ratio: men 1.45, 1.32-1.58; women 1.38, 1.26-1.49). Only weak but significant associations were observed with smoking, alcohol and salt intake. The association of hypertension with social class was reduced after adjustment of body mass index, sedentary lifestyle, smoking and salt intake (odds ratio: men 0.96, 0.81-1.14; women 0.73, 0.54-1.04). There was an increase in the prevalence of hypertension and age-specific blood pressure (BP) with increasing age in both sexes. The overall prevalence of hypertension by WHO criteria (>160/95) was 4.6% and by JNC V criteria 20.8%, and the rates were comparable in both sexes. Social class 1 and 2 subjects in rural North India have a higher prevalence of hypertension and its risk factors of overweight and sedentary lifestyle.

Adult↗
PubMed1997

Epidemiological study of hypertension and its determinants in an urban population of North India.

OBJECTIVES: To determine age-specific prevalence of hypertension and blood pressure (BP) levels in relation to diet and lifestyle factors in North Indians. DESIGN AND SETTING: Cross-sectional survey in 20 randomly selected streets in Moradabad, North India. SUBJECTS AND METHODS: A total of 1806 subjects from North India (904 males and 902 females) age range 25-64 years. The survey methods were as follows: dietary diaries for 7 days food intake record; BP measurements; physician administered questionnaire and anthropometric measurements. Diagnosis of hypertension was based on new World Health Organization/International Society of Hypertension (WHO/ISH) criteria. Risk factors were assessed based on WHO guidelines. RESULTS: The prevalence of hypertension according to WHO/ISH criteria was 23.7% and by old WHO criteria 13.3%. In the WHO/ISH hypertensive group, isolated diastolic hypertension was present in 47.3% males and 40.6% females. Males have a slightly higher prevalence than females in the young age group, however, the prevalence rates are comparable in the older age groups. In both sexes, the prevalence rates and BP level increased with older age. Multivariate analysis revealed that age, higher body mass index, central obesity and higher socioeconomic status were independently and strongly associated with hypertension in both sexes. Higher dietary fat and salt intake and lower physical activity were weakly but significantly associated with hypertension. CONCLUSION: Association of higher socioeconmic status, higher body mass index and central obesity in North Indian adults with higher fat intake, lower physical activity and higher prevalence and level of hypertension indicate that these populations may benefit by decreasing the dietary fat intake and increasing physical activity, with an aim to decrease central obesity for decreasing hypertension in North Indians.

Adult↗
PubMed1997

Genetic and biochemical characterization of novel low molecular weight glutenin subunits in wheat (Triticum aestivum L.).

Two novel low molecular weight subunits of glutenin with relative molecular mass (M(r) values) of 30 and 32 kDa were isolated from the seeds of hexaploid wheat and characterized at genetic and biochemical levels. Among 115 Indian bread wheat cultivars analysed, 40 had a narrow doublet of the new protein bands, 69 had a wide doublet, 3 had only the faster moving band of the doublet, and the remaining 3 cultivars had only the slower moving band. These subunits could be seen in the alkylated glutenin preparations only and the genes for the faster (designated Glu-D4) and slower (designated Glu-D5) moving protein bands of the doublet were located on chromosomes 1D and 7D, respectively. Amino acid composition of the two new subunits was quite different from those of the other well-characterized gluten proteins, as the new subunits have lower amounts of proline and relatively higher amounts of glycine, aspartic acid-asparagine, cysteine, and lysine. Polyclonal antibodies raised against these polypeptides cross-reacted strongly with the major low molecular weight subunits of wheat glutenin (Glu-3 subunits), but did not cross-react with the high molecular weight glutenin subunits or monomeric gliadins. Furthermore, preliminary results on the N-terminal amino acid sequences of the new subunits show homology with the major low molecular weight glutenin subunits, suggesting an evolutionary link between the two.

Amino Acids↗
PubMed1996

Isolation and characterization of Leishmania donovani calreticulin gene and its conservation of the RNA binding activity.

Calreticulin has been implicated in multiple cell functions. Recently, we have shown that both human and simian calreticulin are RNA binding proteins and that their binding activity is due to phosphorylation. To demonstrate that the RNA binding property of calreticulin is an intrinsic part of this multi-functional molecule and is evolutionarily conserved, we isolated and characterized the calreticulin gene from the unicellular parasite, Leishmania donovani. Amino acid sequence homology between human and Leishmania calreticulin (L. d. cal) is limited, but like the human homologue, L. d. cal binds Ca+2, can be phosphorylated in vitro and binds certain RNA sequences in a phosphorylation-dependent manner. Unlike human calreticulin, L. d. cal is glycosylated and its binding to endogenous Leishmania RNA is phosphorylation-independent. The binding of L. d. cal to Leishmania RNA suggests that the RNA binding activity of calreticulin has remained evolutionarily conserved.

Amino Acid Sequence↗
PubMed1996

Inhibition of retinoic acid receptor function and retinoic acid-regulated gene expression in mouse melanoma cells by calreticulin. A potential pathway for cyclic AMP regulation of retinoid action.

Calcium is a second messenger that controls a wide variety of cellular functions. Because of its multiple actions, there is a stringent requirement for calcium homeostasis, and this is achieved in part by a system of transport and storage proteins such as calreticulin located in the endoplasmic reticulum. Calreticulin is also found in the nucleus, suggesting that it may have a role in transcriptional regulation. It has been reported that calreticulin can inhibit steroid-regulated gene transcription by preventing receptor binding to DNA. Here we report that overexpression of the calreticulin gene in B16 mouse melanoma cells resulted in a decrease in retinoic acid (RA)-stimulated reporter gene expression. Gel shift analysis showed that purified calreticulin inhibited the binding of endogenous RAR to a beta-RA response element oligonucleotide, only if added prior to the addition of the oligonucleotide. Co-immunoprecipitation studies suggest a physical interaction between RAR and calreticulin. Transfection of the calreticulin gene into B16 cells inhibited the RA induction of protein kinase Calpha, a marker of RA-induced differentiation. We also found that cyclic AMP increased the expression of calreticulin. Cyclic AMP may act to antagonize RA action by both decreasing RAR expression (Y. Xiao, D. Desai, T. Quick, and R. M. Niles, J. Cell Physiol., in press) and stimulating calreticulin levels.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Fast dissociation of phe-tRNA synthetase from Aspergillus nidulans immobilized on sepharose-6B column by NaCl.

Phenylalanyl-tRNA2) synthetase from Aspergillus nidulans was efficiently immobilised to sepharose 6B column containing phenylalanine as the ligand. NaCl was found to be a potent dissociating agent for the immobilised enzyme. While 0.5 M NaCl in discontinuous elution showed a slow impetus on dissociation giving a plateaux profile, a solution of 0.8 M NaCl made the elution rapid giving a sharp peak. On the other hand, in a gradient (continuous) elution the rapidity of dissociation was found to be enhanced with the increase in the difference of the two concentrations. The result suggests that Na+ ions interact with the protein binding site of the ligand eventually dissociating the enzyme molecule by disrupting the covalent bond without affecting its normal catalytic activity.

Aspergillus↗
PubMed1996

Isolation of differentially expressed cDNA clones from salt-adapted Aspergillus nidulans.

Differentially expressed cDNA clones were isolated from salt-adapted Aspergillus nidulans (FGSC #359). Poly (A)+ RNA from adapted mycelia was used to construct a lambda Uni-ZAP cDNA library. The library was screened with mixed subtracted cDNA probes. Three-hundred and fifty-seven positive plaques were isolated in the primary screening. Sixty-two randomly selected plaques were purified and placed into eight different cross-hybridization groups. A representative cDNA from each group was used to study expression under unadapted, salt-adapted and salt-shock conditions. These clones, representing eight different genes, displayed enhanced expression under salt stress. Exploratory nucleotide sequencing was performed, and the predicted amino-acid sequence was compared with known gene sequences in the data-bank. Five of the cDNA clones were identified as a mitochondrial (mt) ATPase beta subunit, a mt ATPase subunit 9, a mt transport protein, a ubiquitin-extension protein and a ribosomal protein. Three cDNA clones could not be identified due to lack of adequate homology with known sequences. These results suggest that at least five genes with known function in cellular processes like ATP generation and protein synthesis, and three other genes of unknown identity, are greatly induced in salt-adapted conditions.

Adenosine Triphosphatases↗
PubMed1996

Effect of treatment with magnesium and potassium on mortality and reinfarction rate of patients with suspected acute myocardial infarction.

The aim of the study was to test whether magnesium and potassium administration can decrease both early and late cardiac event rates in 355 patients with suspected acute myocardial infarction (AMI). The study was conducted by a primary and secondary care research centre as a randomized, initially double-blind comparison for 4 weeks followed by a single blind period for 2 years. Patients with definite or possible AMI and unstable angina based on World Health Organization criteria were assigned within 24 hours of infarction to different groups. Treatment was administered for 3 days through intravenous infusion with either 8.12 mmol/day Mg (group A, n = 81), 10.49 mmol/day K (group B, n = 77) 10% dextrose solution (group C, n = 87) or a placebo containing 2% dextrose solution (group D, n = 81). After discharge from the hospital all groups were advised to follow a fat-reduced diet. Groups A, B, and C were also advised to take magnesium hydroxide or potassium chloride orally. Comparison of groups A and B with group D over 2 years indicated that treatment with magnesium or potassium was associated with increased (p < 0.05) serum magnesium and potassium, and significant reduction in the incidence of cardiac events (22 and 24 vs 41 patients), total mortality (9 and 10 vs 20 deaths), and ventricular ectopics (17 and 21 vs 44), respectively, in the groups. Group C showed no significant benefit. It is possible that magnesium and potassium infusion immediately after AMI and addition of Mg and K salts to the AMI regimen may enhance tissue levels of these cations, leading to significant reduction in complications and mortality after 2 years.

Acute Disease↗
PubMed1996

Do corticosteroids influence the disease course or mortality in Guillain-Barre' syndrome?

Forty-six patients of Guillain-Barre' Syndrome were randomized to receive either prednisolone (40 mg daily for 2 weeks and then tapered off) or placebo. The patients were followed up for 6 months and were assessed on an objective scale of disability. The improvement in mean disability grade was significantly better at 2 weeks and 4 weeks in the placebo group as compared to those who received corticosteroids. The difference persisted at 24 weeks, but was statistically insignificant. A greater proportion of patients in the placebo group had improved by at least 1 disability grade at all points of time. The group of patients treated with steroids took twice as long to improve by 1 disability grade as compared to those in the placebo group. At 6 months, 41.7% of the patients in the steroid group had recovered almost completely (good outcome) as compared to 54.5% of the patients is the placebo group. Corticosteroids, therefore, do not appear to benefit GBS patients, and may in fact, delay the recovery from acute illness.

Adult↗