Search PubMed⌕ Search

Biomedical subjects

R Nigam

Publications and source records attributed to R Nigam.

At least 19 recordsLinked to original sources
PubMed2006

Algorithm for perturbing thermodynamically infeasible metabolic networks.

Networks of reactions inside the cell are constrained by the laws of mass and energy balance. The second law of thermodynamics further constrains the topology of the metabolic network, by disallowing interactions that can sustain themselves when they are isolated from the rest of the network. We present an algorithm that identifies such subnetworks and makes them feasible by deleting reactions. This perturbs the network topology, but preserves the optimality of the mass balance solutions. This method has been applied to a full network of Escherichia coli.

Algorithms↗
PubMed2005

Application of foraminifers in ecotoxicology: retrospect, perspect and prospect.

In view of the extensive use of foraminifers for the pollution monitoring especially their unmatched utility in deciphering the temporal variation in the type and concentration of pollutants at a given location, the literature dealing with the application of foraminifers for pollution studies has been reviewed. The pollution monitoring through foraminifers started with attribution of peculiar foraminiferal features at any location to the circumstantial presence of pollutants at that site. These peculiar features of the foraminifers in polluted areas included, variation in the abundance of total, calcareous and agglutinated foraminifers, species diversity, abnormal tests, etc. The abnormalities of tests included stunted growth, abraded margins, dissolved ornamentations, etc. Initially, much attention was paid to the effects of sewage pollution on the foraminifers but later on all kinds of human induced as well as natural pollutants came under the preview of foraminiferologists working on pollution aspects. The advantage of application of foraminifers, over other chemical and biological techniques, for pollution monitoring lies in their potentiality to decipher temporal variation in type and concentration of pollutants at any site even in the absence of pre-pollution studies, based on the recovery of foraminifers from the sediment core samples. Realizing the potential application of characteristic foraminiferal features from the polluted areas to decipher the variation in introduction and concentration of pollutants at any given location with time, efforts were made to characterize the specific types of foraminiferal features to the specific pollutants. It was at this point that the need of culture studies was widely felt which resulted in numerous lab and field culture studies where foraminifers were subjected to specific pollutants in order to document their response to these pollutants and to develop effective foraminiferal proxies for pollution monitoring through time. Such studies are still going on and it is felt that culture studies need to be supplemented with advanced crystallographic and molecular studies in order to find the mechanism through which foraminifers respond to the pollutants.

Animals↗
PubMed2005

A pivoting algorithm for metabolic networks in the presence of thermodynamic constraints.

A linear programming algorithm is presented to constructively compute thermodynamically feasible fluxes and change in chemical potentials of reactions for a metabolic network. It is based on physical laws of mass conservation and the second law of thermodynamics that all chemical reactions should satisfy. As a demonstration, the algorithm has been applied to the core metabolic pathway of E. coli.

Algorithms↗
PubMed2004

Foraminifers as indicators of marine pollution: a culture experiment with Rosalina leei.

In order to develop a viable foraminiferal proxy for heavy metal pollutants, juvenile specimens of Rosalina leei were subjected to different mercury concentrations (0-180 ng/l). Initially considerable growth was observed in specimens kept in saline water having a mercury concentration up to 100 ng/l. But with the gradual increase in concentration of mercury the growth rate started decreasing. Total growth achieved was significantly lower in case of specimens kept at relatively higher mercury concentrations then those maintained in normal saline water. The most significant result of this experiment was the addition of abnormal chambers in the specimens kept at higher mercury concentration. Later the specimens kept at highest concentration (180 ng/l) were subjected to progressively increasing concentration of mercury to see the further effects and it was found that the specimens were still living at as high a mercury concentration as 260 ng/l although there was no growth.

Cell Culture Techniques↗
PubMed2003

Prevalence of adrenal antibodies in Addison's disease among north Indian Caucasians.

OBJECTIVE: The prevalence of antibodies in different organ-specific autoimmune diseases can vary depending on the racial group studied. Data on the prevalence of antibodies against steroidogenic enzymes in Addison's disease is available only for white Caucasians. We have evaluated the frequency of antibodies against adrenal cytoplasm, 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzyme in a cohort of Indian patients with Addison's disease of idiopathic and granulomatous aetiology. DESIGN: Study of all patients with Addison's disease on whom serum samples were available (84% of total), presenting to the Endocrinology Department in a teaching hospital in India, between 1990 and 1999. PATIENTS: Thirty-eight patients with Addison's disease (19 idiopathic, 19 granulomatous). METHODS: A radiobinding assay using in vitro transcribed and translated recombinant human 35S-labelled 21-hydroxylase, 17-alpha-hydroxylase and side-chain cleavage enzymes was utilized to detect the respective antibodies. Adrenal cytoplasmic antibodies were measured by indirect immunofluorescence on cryostatic sections of human adrenal cortex. RESULTS: Of the 19 patients with idiopathic Addison's disease, adrenal cytoplasmic antibodies were present in five (26%) patients, while 21-hydroxylase antibodies were present in four (21%) subjects. The frequency of 21-hydroxylase antibodies was similar among patients with isolated idiopathic Addison's disease (3/13, 23%), and those associated with other organ-specific autoimmune diseases (1/6, 17%). 17-alpha-hydroxylase and side-chain cleavage antibodies were present in four (21%) and three (16%) patients, respectively. Overall, at least one of the three antibodies was present in eight (42%) subjects. All four female patients with premature ovarian failure had antibodies against 17-alpha-hydroxylase and/or side-chain cleavage enzyme. Two (11%) patients with granulomatous Addison's disease had adrenal antibodies. Of these, one patient with enlarged and calcified adrenal gland secondary to tuberculosis had a high titre of antibodies against all three steroidogenic enzymes. CONCLUSIONS: Antibodies to 21-hydroxylase enzyme are less frequent in idiopathic Addison's disease in north Indians, when compared with other Caucasians. In contrast, the prevalence of 17-alpha-hydroxylase and side-chain cleavage enzyme antibodies is similar to those reported. High titre antibodies against steroidogenic enzymes may occasionally be present in patients with clinical evidence of tuberculous Addison's disease.

Addison Disease↗
PubMed2001

Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on treatment with selective serotonin reuptake inhibitor antidepressants.

BACKGROUND: Patients with depressive disorders smoke tobacco more often than the population at large and find quitting more difficult. Furthermore, when they quit smoking, they are more likely to suffer a relapse of depression. We evaluated the addition of bupropion sustained release (SR) for smoking cessation among patients with a history of depressive disorders being maintained in a euthymic state with selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD: Twenty-five adults with DSM-IV major depressive disorder or depressive disorder NOS currently receiving SSRI maintenance treatment and smoking > or = 15 cigarettes per day participated in the 9-week study. Bupropion SR, 150 mg/day, was added to SSRI treatment and increased to 300 mg/day. Subjects were counseled on smoking cessation measures and chose a target quit date 2 or 4 weeks after the initiation of bupropion SR. Self-reported smoking status, expired carbon monoxide (CO) measurements, Hamilton Rating Scales for Depression and Anxiety scores, and weight were measured at each visit. Subjects were abstinent if they reported not smoking during the prior 7 days, confirmed with an expired-air CO value of < or = 10 ppm. RESULTS: Eight (32%) of 25 subjects were abstinent after 9 weeks. At 3-month follow-up, 3 subjects remained abstinent, 3 relapsed, and 2 were lost to follow-up. Eleven subjects (44%) were nonresponders, and 6 (24%) dropped out prior to 3 weeks of treatment due to side effects (N = 3) or were lost to follow-up (N = 3). Mean weight gain was approximately 0.5 lb (0.2 kg) for those completing 9 weeks of bupropion SR treatment. During the 9-week study and the 3-month follow-up, there was no evidence of emergent depression in any subject. Four subjects (16%) spontaneously reported an improvement in SSRI-associated sexual dysfunction. CONCLUSION: These open data suggest modest effectiveness for and the safety of bupropion SR as a smoking cessation agent in individuals with depression maintained on treatment with SSRIs. Minimal weight gain, lack of emergent depressive episodes, and improvement of SSRI-associated sexual dysfunction are added advantages.

Adolescent↗
PubMed2001

Hypoglycemic effect of Hibiscus rosa sinensis L. leaf extract in glucose and streptozotocin induced hyperglycemic rats.

Investigations were carried out to evaluate the effect of aqueous extract of H. rosa sinensis leaves on blood glucose level and glucose tolerance using Wistar rats. Repeated administration of the extract (once a day for seven consecutive days), at an oral dose equivalent to 250 mg kg(-1), significantly improved glucose tolerance in rats. The peak blood glucose level was obtained at 30 min of glucose load (2 g kg(-1)), thereafter a decreasing trend was recorded up to 120 min. The data exhibit that repeated ingestion of the reference drug tolbutamide, a sulphonylurea and the extract brings about 2-3 fold decrease in blood glucose concentration as compared to single oral treatment. The results clearly indicate that tolbutamide improves the glucose tolerance by 91% and extract does so only by 47%. At 250 mg kg(-1), the efficacy of the extract was 51.5% of tolbutamide (100mg kg(-1)). In streptozotocin diabetic rats, no significant effect was observed with the extract, while glibenclamide significantly lowered the glucose level up to 7 hr. These data suggest that hypoglycemic activity of H. rosa sinensis leaf extract is comparable to tolbutamide and not to glibenclamide treatment.

Animals↗
PubMed2000

Genomic organization, chromosomal localization, and expression of the murine RAB3D gene.

Rab proteins, members of the Ras superfamily of small GTPases, play regulatory roles in intercompartmental vesicular transport. Each step of traffic seems to require the participation of at least one distinct Rab, with the Rab3 subfamily involved in stimulated exocytosis. We report our studies on the murine rab3D gene, one of the four mammalian Rab3 isoforms. We located this gene on chromosome 13, region A(2-3). The rab3D gene consists of 5 exons spanning 10.6 kb, and the structural gene is contained in exons 2 through 5 with one canonical GTP-binding motif in each exon. Organization of the rab3D gene is identical to that of rab3A but different from other rab genes. Alternative poly-A(+) signals in the 3' untranslated region account for the identities of multiple transcripts detected by Northern blot analysis. Rab3D is expressed in all tissues studied, predominantly in heart, lung, and liver, and binding sites for multiple transcription factors are found in the TATA-less promoter region.

Animals↗
PubMed2000

Numerical Simulations of Oscillation Modes of the Solar Convection Zone.

We use the three-dimensional hydrodynamic code of Stein & Nordlund to realistically simulate the upper layers of the solar convection zone in order to study physical characteristics of solar oscillations. Our first result is that the properties of oscillation modes in the simulation closely match the observed properties. Recent observations from the Solar and Heliospheric Observatory (SOHO)/Michelson Doppler Imager (MDI) and Global Oscillations Network Group have confirmed the asymmetry of solar oscillation line profiles, initially discovered by Duvall et al. In this Letter, we compare the line profiles in the power spectra of the Doppler velocity and continuum intensity oscillations from the SOHO/MDI observations with the simulation. We also compare the phase differences between the velocity and intensity data. We have found that the simulated line profiles are asymmetric and have the same asymmetry reversal between velocity and intensity as observed. The phase difference between the velocity and intensity signals is negative at low frequencies, and phase jumps in the vicinity of modes are also observed. Thus, our numerical model reproduces the basic observed properties of solar oscillations and allows us to study the physical properties which are not observed.

Journal Article↗
PubMed2000

Androgen receptor mutations in prostate cancer.

We analyzed the frequency and relevance of mutations in the coding region of the androgen receptor (AR) in genomic DNA extracted from 137 specimens of prostate cancer. The specimens were obtained from the primary tumors of patients affected by stage B disease [15 nonmicrodissected (group 1A) and 84 microdissected (group 1B)] and from the metastatic deposits of individuals with stage D1 disease [8 nonmicrodissected (group 2A) and 30 microdissected (group 2B)] who had not undergone androgen ablation therapy. The study was conducted by PCR-single strand conformational polymorphism (SSCP) analysis of exons 2-8 in the four groups and direct sequence analysis of exon 1 in group 1B. As positive and negative controls, we used genomic DNA extracted from genital skin fibroblasts of patients affected by various forms of androgen resistance with known mutations in the AR. To control for genetic instability, PCR-SSCP analysis of exon 2 of the human progesterone receptor was carried out on each specimen. The overall number of mutations detected was 11 (8%). No mutations were detected in any of the 99 patients with stage B disease. Eleven mutations were detected in exons 2-8 in 8 of the 38 patients with stage D1 disease (all in group 2B). Simultaneous analysis of exon 2 of the progesterone receptor was carried out, and no SSCP changes were identified. These data suggest that AR mutations are rare and presumably do not play a role in the initial phase of prostatic carcinogenesis. The presence of a significant number of AR mutations in metastatic disease indicates that mutations of this molecule may play a role in the most advanced phases of the natural history of this disease, either by facilitating growth or acquisition of the metastatic phenotype.

Humans↗
PubMed1998

h1- and h2-calponins are not essential for norepinephrine- or sodium fluoride-induced contraction of rat aortic smooth muscle.

To investigate the controversial issue concerning the role of calponin in smooth muscle contraction, this study examined the relationship between smooth muscle calponin and the contraction of aortic rings from different strains of rats: Sprague-Dawley (SD), Wistar, and Wistar Kyoto (WKY). Western blot analysis demonstrated that h1- and h2-calponins are present in aortic smooth muscle from adult SD rats but not Wistar or WKY rats. Nevertheless, h1-calponin is detectable in stomach from Wistar rats, although at a much lower level compared with that in the SD rat stomach. This suggests that a repressed expression of the gene, instead of a simple null mutation, may have caused its absence from the aortic smooth muscle. Despite the presence or absence of calponin, the aortic smooth muscles from the different strains of rats all develop contractions in response to the physiological agonist norepinephrine (NE) and following activation with the plasma membrane receptor-independent NaF induction. The data indicate that h1- and h2-calponins are not essential for NE- and NaF-induced contractions in aortic smooth muscle. The calponin-positive adult SD rat aorta was found to be more sensitive in contractile response to NE and NaF inductions compared with the calponin-negative rat aortae. This may imply a potential modulator function of calponin in the contraction of smooth muscle, whereas other contractile protein isoform differences between these rat strains may also play a role.

Animals↗
PubMed1996

Isoform-specific biotransformation of glyceryl trinitrate by rat aortic glutathione S-transferases.

The objective of this study was to purify and characterize rat aortic glutathione S-transferases (GSTs) and to assess their role in the biotransformation of the nitrovasodilator, glyceryl trinitrate (GTN). Two class alpha GSTs (Ya and Yc) a class mu GST (Yb2) and a class pi GST (Yp) were identified in rat aortic cytosol. Partial purification of three of these (Yb2, Yc and Yp) was achieved by affinity chromatography with S-hexylglutathione agarose. Further purification by cation- and anion-exchange chromatography resulted in the purification of GST Yc and GST Yb2/Yp to apparent homogeneity, a purification of 200- and 110-fold, respectively. Purified GST Yc and Yb2/Yp mediated GTN biotransformation with similar rates. GST activity and GTN biotransformation by rat aortic cytosol and affinity-purified GSTs were highly sensitive to inhibition by the class mu selective inhibitors Basilen Blue and bromosulfophthalein. Removal of GST Yb2 from rat aortic cytosol by immunoprecipitation resulted in marked inhibition of GST activity and GTN biotransformation. We conclude that the GSTs account for the major portion of GTN biotransformation in rat aortic cytosol, and that this is primarily attributable to the GST Yb2 isoform.

Animals↗
PubMed1995

The effects of speech output technology in the learning of graphic symbols.

The effects of auditory stimuli in the form of synthetic speech output on the learning of graphic symbols were evaluated. Three adults with severe to profound mental retardation and communication impairments were taught to point to lexigrams when presented with words under two conditions. In the first condition, participants used a voice output communication aid to receive synthetic speech as antecedent and consequent stimuli. In the second condition, with a nonelectronic communications board, participants did not receive synthetic speech. A parallel treatments design was used to evaluate the effects of the synthetic speech output as an added component of the augmentative and alternative communication system. The 3 participants reached criterion when not provided with the auditory stimuli. Although 2 participants also reached criterion when not provided with the auditory stimuli, the addition of auditory stimuli resulted in more efficient learning and a decreased error rate. Maintenance results, however, indicated no differences between conditions. Finding suggest that auditory stimuli in the form of synthetic speech contribute to the efficient acquisition of graphic communication symbols.

Acoustic Stimulation↗
PubMed1994

Biotransformation of organic nitrates and vascular smooth muscle cell function.

The organic nitrates are interesting examples of drugs that undergo biotransformation at their site of action to generate the active form of the drug. Furthermore, tolerance to the vasodilator effects of organic nitrates is associated with impairment of this metabolic activation process. Despite considerable research effort, the intracellular processes and the chemical reaction pathways by which organic nitrates are converted to their active form are still unresolved. This review by Brian Bennett and colleagues summarizes the characteristics of organic-nitrate biotransformation in vascular smooth muscle, the difficulties encountered when assessing this biotransformation, and the evidence for the role of two identified vascular biotransformation systems (glutathione-S-transferases and the cytochrome P450 system) in the metabolic activation of organic nitrates.

Animals↗
PubMed1993

Effect of inhibitors of glutathione S-transferase on glyceryl trinitrate activity in isolated rat aorta.

We investigated the role of glutathione S-transferases (enzymes known to biotransform organic nitrates) in the vascular action of glyceryl trinitrate (GTN). Relaxation of phenylephrine-contracted rat aortic strips was assessed in the presence or absence of the glutathione S-transferase inhibitors Basilen Blue, bromosulfophthalein, Rose Bengal, hematin, chlorotriphenyltin, and (octyloxy)benzoylvinylglutathione. Whereas none of the inhibitors increased the EC50 for GTN relaxation, glutathione S-transferase activity in the 100,000 x g supernatant fraction of rat aorta was inhibited markedly by most of the inhibitors. In addition, GTN-stimulated activation of aortic guanylyl cyclase in broken-cell preparations was attenuated by all of the glutathione S-transferase inhibitors, suggesting a direct inhibitory action on guanylyl cyclase. In other experiments using aortic strips preexposed to phenylephrine, the inhibitors had no effect on GTN-induced cyclic GMP accumulation or on vascular biotransformation of GTN. In contrast, both Basilen Blue and bromosulfophthalein significantly inhibited GTN-induced relaxation of K(+)-contracted aortic strips, and Basilen Blue significantly inhibited GTN biotransformation in aortic strips preexposed to 25 mM K+. This may be due to a more favourable electrochemical gradient for entry of the inhibitors into membrane-depolarized tissues. We conclude that vascular glutathione S-transferases play a role in mediating the vasodilator actions of GTN in intact tissues in vitro, but that this appears to depend upon the nature of the contractile agent used in such studies.

Animals↗
PubMed1992

Episodic release of luteinizing hormone and testosterone in Surti and Marwari bucks younger than one year of age.

Studies on the episodic release of luteinizing hormone (LH) and testosterone in Surti (n=2) and Marwari (n=2) bucks younger than one year of age (6 to 8 months) were carried out by collecting blood plasma during the breeding season. The studies revealed that definite pulsatile releases of LH and testosterone occur in both breeds of bucks. The overall number of LH and testosterone pluses over a 24 hour period was 9.1+/-1.00 and 7.5+/-0.28, respectively. The peak, basal and mean LH and testosterone concentrations did not show significant differences between the two breeds. The duration and interval of LH and testosterone pulses differed during light and dark hours. The time interval between LH peak followed by the testosterone peak was significantly (P<0.05) longer during the night than the day hours for both the breeds. The physiological basis of the findings are discussed.

Journal Article↗
PubMed1992

Treatment of dual diagnosis patients: a relapse prevention group approach.

The authors describe the successful use of an adjunctive group psychotherapy for substance-abusing patients with major psychiatric disorders (bipolar, schizophrenia, schizoaffective, psychotic depression, and atypical psychosis). The group utilizes a psychoeducational approach that focuses on substance abuse causes and consequences, principles of recovery, and relapse prevention strategies. Eight patients with prolonged histories of abuse of cocaine, alcohol, marijuana, or other drugs were enrolled in this weekly group treatment at a community mental health center drug treatment program, while continuing in treatment with their current case manager or primary therapist. Six of the eight patients achieved periods of stable abstinence, documented by self-report, urine toxicology screens, continued group attendance, and improved social functioning. Case examples are utilized to illustrate the group process.

Adult↗