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Biomedical subjects

M Gupta

Publications and source records attributed to M Gupta.

At least 55 records · Page 3Linked to original sources

Role of nitric oxide in experimental models of psychosis in rats.

The aim of our study was to investigate the effects of the NO precursor L-arginine and the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NORAG) on amphetamine-induced stereotypy, haloperidol-induced catalepsy and conditioned avoidance response (CAR) in rats. Amphetamine (3 mg/kg i.p.) was used for the induction of stereotypy, while for the induction of catalepsy and CAR, haloperidol (2 mg/kg i.p.) was used. This study was divided into 2 parts--acute administration of L-arginine (150 mg/kg i.p.) and L-NOARG (50 mg/kg i.p.) and chronic administration of L-arginine (150 mg/kg/day i.p.) and L-NOARG (50 mg/kglday i.p.) for 5 days. We found that L-arginine inhibited amphetamine-induced stereotypy and haloperidol-induced catalepsy, but intensified CAR. On the other hand, L-NOARG intensified stereotypy and catalepsy but inhibited CAR. Also, there was no significant difference between the scores of acute and chronic administration of L-arginine and L-NOARG. It is concluded from our study that nitric oxide produces conflicting results on various models of psychosis. L-arginine might be useful as an antipsychotic without causing extrapyramidal symptoms.

Animals↗

Deficiency of the 50 kDa dystrophin-associated-glycoprotein (adhalin) in an Indian autosomal recessive limb girdle muscular dystrophy patient : immunochemical analysis and clinical aspects.

Abnormalities of dystrophin are a common cause of muscular dystrophy and testing for dystrophin gene or protein has become a part of routine diagnostic evaluation of patients who present with progressive proximal muscle weakness, high serum creatine kinase concentrations, and histopathological evidence of a dystrophic process. Patients who have no dystrophin abnormalities are assumed to have autosomal recessive muscular dystrophy. In a family consisting of 5 sibs, 2 mentally normal brothers presented with abnormal gait and protrusion of chest and hips. Muscle biopsy from one of them showed dystrophic changes and reduced patchy binding of dystrophin. No detectable deletion was observed in the patient's DNA and his brother with cDMD probes. Dystrophin associated proteins, beta-dystroglycan showed discontinuous immunostaining in the sarcolemma and alpha-sarcoglycan (adhalin) was totally absent, while beta-, gamma-, and delta-sarcoglycans were highly reduced. Immunoblot analysis showed dystrophin of normal molecular weight but of decreased quantity, beta-dystroglycan was reduced by about 37% while alpha-sarcoglycan was completely absent. This study is a first attempt for a systematic clinical, genetic and molecular investigation of the autosomal recessive LGMD in India.

Adolescent↗

Lipid peroxidation and antioxidant enzymes in coronary and peripheral artery disease.

There is a strong co-relation in between the levels of blood lipids in patients of different subgroups of CAD, however this is not present in the case of subgroups of patients in PAD. Moreover levels of MDA and antioxidant enzymes are also significantly altered in the subgroups of CAD but the correlation is weak in that of PAD. Thus these values may serve as a clinical support for experimental data and supplementary information regarding atheromatous disease.

Adult↗

Treatment refusal in the involuntarily hospitalized psychiatric population: Canadian policy and practice.

Policies governing coercive psychiatric interventions must be scrutinized to ensure they are not only beneficent but just. Within Canada, in seven of ten provinces, persons may be detained in hospital against their will for dangerousness due to mental disorder but, if capable of making treatment decisions, may refuse treatment for the very illness that led to detention. In examining this issue, the purpose of this paper is threefold. First, it will demonstrate that treatment refusal amongst involuntarily hospitalized psychiatric patients has arisen from a recent separation, in law, of hospitalization from treatment. Second, it will argue that legal provisions that allow the detention of psychiatric patients prior to assessment of their treatment decision-making capacity discriminate against the mentally ill and undermine health service delivery. Finally, this paper will propose that a more just policy would allow involuntary hospitalization of only those patients who are both incapable of making treatment decisions and harmful to themselves or others.

Canada↗

Long-term results of the treatment of complete distal ureteral stenosis using a cutting balloon catheter device.

PURPOSE: We evaluated the long-term efficacy of endoscopic treatment of complete distal ureteral stenosis using a cutting balloon catheter. MATERIALS AND METHODS: We performed a total of 10 procedures in 9 patients with complete distal ureteral stenosis at or near the ureterovesical junction. Depending on presenting anatomy cases were treated with a retrograde only (6), antegrade only (1) or combined antegrade and retrograde (3) endoscopic technique. RESULTS: At a mean followup of 36 months (range 24 to 43) 9 of the 10 procedures (90%) were successful. Stenosis recurred in 1 of the 9 patients (10%) but a repeat procedure was successful. There were no intraoperative complications and no procedures required open surgical conversion. Although all patients noticed a various degree of hematuria postoperatively, none required blood transfusion or further intervention. Mean hospitalization was 1.1 days. CONCLUSIONS: Endoscopic repair of distal ureteral stenosis using a cutting balloon catheter is a viable option in patients with complete ureteral obstruction. This technique results in low morbidity, a short hospital stay and excellent long-term patency. Endoscopic treatment using a cutting balloon catheter may be a therapeutic option in many patients with complete distal ureteral obstruction at or near the ureterovesical junction.

Adult↗

Creutzfeldt-Jakob disease : report of 10 cases from North India.

Creutzfeldt-Jakob disease (CJD) is increasingly being reported over the last three decades as a result of heightened awareness of the disease. Various studies have reported annual incidence of 0.5-1.5 cases of CJD per million of general population. In India, the disease is still under reported. Over the period spanning from 1968-1997, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore recorded 69 cases of CJD from different parts of India in the CJD registry. This paper describes the clinical experience with cases of CJD managed at the Department of Neurology, G.B. Pant Hospital, New Delhi from 1990-1998. In this series, the mean age of the patients was 53.80 (+/- 7.32) years and there were 5 females and 5 males. Myoclonus was present in all the cases and abnormal behaviour with or without other features was the presenting complaint in 7 of the 10 patients, while one patient of CJD had cerebellar ataxia as the presenting feature. One patient with occipital variant of CJD presented with acute onset cortical blindness and myoclonic jerks. One of the patients had acute psychosis precipitated by emotional stress at the onset. Extrapyramidal features were noted in 7 of the 10 patients before death. The mean duration of symptoms from the onset of disease to death was 6.6 (+/- 6.11) months. Classical EEG changes were observed in all the patients, except in one possible case of occipital variant of CJD, where we did not have access to EEG record. Brain biopsy could be undertaken in 3 patients, and in 2 patients the features of subacute spongiform encephalopathy (SSE) were noted.

Adult↗

Topiramate: a new safe and effective antiepileptic.

Twenty patients of either sex, with refractory partial epilepsy with or without secondary generalisation were entered in an open label study to evaluate the efficacy and safety of topiramate in them. Topiramate was used as an adjunctive therapy with an initial starting dose of 50 mg/day. The dose was then titrated upwards with increments of 50 mg per week, till a time the most effective and the best tolerated dose was reached. This most effective/tolerated dose was then continued for 6 months. Of the 17 patients entering the maintenance phase, 4 patients (24%) became seizure free, while a total of 14 patients (83%) out of 17 cases responded with a reduction in monthly seizures rate by 50% or more. Mean reduction of 68.9% was observed in monthly seizure rate during the maintenance phase. The median effective dose of topiramate was 600 mg per day. Five patients dropped out of the study due to adverse events such as anxiety, aggressiveness, rash, lethargy, etc. The central nervous system (CNS) related side effects such as dizziness, headache, and tremor were reported, which are commonly seen with other presently available antiepileptics like carbamazepine, phenytoin sodium, sodium valproate, etc, as well. Most adverse events, however, were mild and transient and did not interfere with the day to day activity of the patients. Topiramate was not associated with any abnormality in laboratory or neurological examination findings. The excellent response with topiramate therapy in Indian patients, uncontrolled with the available antiepileptics, as well as its good safety profile endorse the international efficacious and safe image of topiramate.

Adolescent↗

Expression of angiotensin II type I receptor on erythroid progenitors of patients with post transplant erythrocytosis.

BACKGROUND: The pathogenesis of posttransplant erythrocytosis (PTE) has been elusive. Angiotensin converting enzyme inhibitors (ACEI) are efficacious in lowering the hematocrit of patients with PTE and angiotensin II (AII) type I receptors (AT1R) were recently detected on red blood cell precursors, burst-forming unit-erythroid- (BFU-E) derived cells. The purpose of this study was to determine whether there is increased expression of the AT1R on BFU-E-derived cells of patients with PTE, which might contribute to the pathogenesis of PTE. METHODS: Twelve healthy volunteers and 25 transplant recipients (13 patients with and 12 without PTE) were studied. BFU-E from peripheral blood were cultured in methylcellulose and BFU-E-derived colonies were harvested on day 10. Western blotting was used to detect AT1R and erythropoietin receptor (EpoR) expression. Intracellular free calcium in response to AII and erythropoietin (Epo) was measured with digital video imaging. RESULTS: There were no differences between transplant patients, with and without PTE, with respect to weight, age, sex, blood pressure, serum creatinine, circulating renin, angiotensin II, and Epo levels. Hematocrit, red blood cell number, BFU-E-derived colony number,and size were significantly increased in PTE compared with other two groups. AT1R expression was increased by 44% on the erythroid progenitors of PTE versus non posttransplant erythrocytosis patients and by 32% in PTE patients versus normal volunteers. AT1R expression correlated significantly with the hematocrit in PTE (Spearman r=0.68, P=0.01). In contrast, EpoR expression was equivalent in all groups. The AT1R was functional since a significant increase in [Ca(i)] was observed in Fura-2 loaded day 10 cells when stimulated with AII (182%, P<0.0001). CONCLUSION: An increase in AT1R density was observed in erythroid precursors of transplant patients with PTE compared to those without PTE and normal volunteers, and the level of AT1R expression in PTE correlated significantly with the hematocrit. In contrast, EpoR expression was not different in PTE compared with non posttransplant erythrocytosis or normal controls. This study supports a role for the AT1 receptor signaling pathway in the pathogenesis of PTE.

Angiotensin-Converting Enzyme Inhibitors↗

Protein kinase-A dependent phosphorylation of transcription enhancer factor-1 represses its DNA-binding activity but enhances its gene activation ability.

The cAMP-dependent signaling pathway has been implicated in cardiac cell growth/differentiation and muscle gene transcription. Previously, we have identified a cAMP-inducible E-box/M-CAT hybrid motif in the cardiac alpha-myosin heavy chain (alpha-MHC) gene promoter. The two factors, TEF-1 and Max, that bind to this motif are found to physically associate with each other and exert a positive cooperative effect for gene regulation. Here we show that TEF-1, but not Max, is a substrate for protein kinase-A (PK-A)-dependent phosphorylation. TEF-1 is phosphorylated by PK-A at residue serine-102. This post-translational modification of TEF-1 repressed its DNA-binding activity, but not its ability to interact with the Max protein. Replacement of serine-102 in TEF-1 by a neutral or a charged amino acid did not abolish its DNA-binding ability, suggesting that changing a charge at the 102 amino-acid position of TEF-1 was not sufficient to inhibit its DNA-binding activity. We also show that PK-A response of the alpha-MHC gene is stimulated by the presence of wild-type TEF-1 but not by mutant TEF-1 having serine-102 replaced by alanine, suggesting that phosphorylation at this residue accounts for the cAMP/PK-A response of the gene. Thus, these data demonstrate that TEF-1 is a direct target of cAMP/PK-A signaling in cardiac myocytes.

Amino Acid Sequence↗

TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha.

TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the 3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To determine the functional significance of this interaction, we used homologous recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce significantly more TNF-alpha protein than wild-type controls. The half-life of TNF-alpha transcripts is similar in wild-type and TIA-1(-/-) macrophages, indicating that TIA-1 does not regulate transcript stability. Rather, the absence of TIA-1 significantly increases the proportion of TNF-alpha transcripts that associate with polysomes, suggesting that TIA-1 normally functions as a translational silencer. TIA-1 does not appear to regulate the production of interleukin 1 beta, granulocyte-macrophage colony-stimulating factor or interferon gamma, indicating that its effects are, at least partially, transcript specific. Mice lacking TIA-1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress.

3' Untranslated Regions↗

A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene.

Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length cDNA encodes a predicted protein of 806 amino acids that contains a leucine zipper motif. This protein, termed HAF for hypoxia-associated factor, binds to a 17-base pair (bp) region of the erythropoietin promoter, which was shown earlier to participate in hypoxia-induced expression of the erythropoietin gene. In Hep3B cells, clones modified to express HAF antisense RNA showed an attenuated response to hypoxia-mediated induction of both erythropoietin and vascular endothelial growth factor transcription. HAF showed sequence-specific interaction with a DNA element in the 5' untranslated region of VEGF gene. The HAF 2.6-kilobase (kb) messenger RNA (mRNA) is expressed in most adult tissues. The highest expression occurs in fetal liver and the least in adult liver. HAF is the murine homolog of Sart-1, a 125-kd human protein expressed in the nuclei of normal and malignant cells. (Blood. 2000;96:491-497)

Animals↗

Antitumor activity of methanolic extract of Cassia fistula L. seed against Ehrlich ascites carcinoma.

Effects of methanolic extract (ME) of Cassia fistula seed on the growth of Ehrlich ascites carcinoma (EAC) and on the life span of tumor bearing mice were studied. ME treatment showed an increase of life span, and a decrease in the tumor volume and viable tumor cell count in the EAC tumor hosts. Cytological studies have revealed a reduction in the mitotic activity, and the appearance of membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells. Improvement in the hematological parameters following ME treatment, like hemoglobin content, red blood cell count and bone marrow cell count of the tumor bearing mice have also been observed. The results of the present study suggest that ME of C. fistula seed has an antitumor activity.

Animals↗

The vitamin D3 analog EB 1089 enhances the antiproliferative and apoptotic effects of adriamycin in MCF-7 breast tumor cells.

Exposure of MCF-7 breast tumor cells to the vitamin D3 analog, EB 1089 enhances the response to adriamycin. Clonogenic survival studies indicate that EB 1089 shifts the dose-response curve for sensitivity to adriamycin by approximately six-fold in p53 wild-type MCF-7 cells; comparative studies in MCF-7 cells with a temperature-sensitive dominant negative p53 mutation show less than a two-fold shift in adriamycin sensitivity in the presence of EB 1089. The combination of EB 1089 with adriamycin also promotes apoptotic cell death in the p53 wild-type MCF-7 cells but not in the MCF-7 cells expressing mutant p53. EB 1089 treatment blocks the increase in p21waf1/cip1 levels induced by adriamycin and interferes with induction of MAP kinase activity by ionizing radiation, effects which could be related to the capacity of EB 1089 to promote secretion of insulin-like growth factor binding protein. Taken together with our previous findings that EB 1089 enhances breast tumor cell sensitivity to ionizing radiation, there studies further support the concept that vitamin D3 analogs could have utility in combination with conventional chemotherapy and/or radiotherapy in the treatment of breast cancer.

Anti-Bacterial Agents↗