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Biomedical subjects

R Goswami

Publications and source records attributed to R Goswami.

At least 19 recordsLinked to original sources
PubMed1998

Insulin autoantibodies before and after carbimazole therapy in Asian Indian patients with Graves' disease.

Carbimazole therapy can induce insulin autoantibodies (IAA) in Japanese Graves' disease patients, a phenomenon possibly linked to their immunogenetic profile. This phenomenon is not observed in Caucasians. We assessed IAA levels in 114 North Indian Graves' disease patients before and after carbimazole therapy (mean duration 6.2 +/- 3.9 months). The functional significance of IAA was assessed in 46 of them by first phase (sum of +1 and +3 min) insulin response to intravenous glucose (IVGTT) and an oral glucose tolerance test (OGTT) undertaken before commencement of the carbimazole therapy. IAA were measured using a radiobinding assay and expressed as the assay precision unit, S.D. scores (S.D.S), over healthy controls. Before treatment 22 of 114 (19.3%) patients were IAA positive (mean +/- S.D., 5.9 +/- 3.2 S.D.S). After carbimazole therapy a further 11 (9.6%) showed positive for IAA (mean +/- S.D., 3.5 +/- 1 S.D.S). Of the 22 patients who were IAA positive before treatment, 12 became negative after carbimazole therapy. The fasting insulin and first phase insulin responses were similar in IAA positive and IAA negative Graves' disease patients (mean +/- S.D., 61.7 +/- 35.9 versus 88.3 +/- 46.6 pmol/l, P = 0.123 and 1127 +/- 696 versus 1033 +/- 430 pmol/l, P = 0.716, respectively). The OGTT results were comparable in the IAA positive and the IAA negative groups. Thus, North Indian Graves' disease patients, who resemble Caucasians in their HLA haplotypes, behave like Japanese in their tendency to become IAA positive with carbimazole therapy. A subset of the patients who were IAA positive before treatment also demonstrated negative IAA (12/22) after carbimazole therapy.

Adult↗
PubMed1998

Cyclic AMP protects against staurosporine and wortmannin-induced apoptosis and opioid-enhanced apoptosis in both embryonic and immortalized (F-11kappa7) neurons.

The mechanism by which opiates affect fetal development is unknown, but one potential target is the programmed cell death (apoptosis) pathway of neurons. Apoptosis was induced in both primary neuronal cultures from embryonic day 7 cerebral hemispheres of chick brain (E7CH) and the F-11kappa7 cell line (an immortalized mouse neuroblastoma x dorsal root ganglion hybrid stably transfected to overexpress kappa-opioid receptors) by either staurosporine or the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002. Cells pretreated with either the mu-specific opioid agonist morphiceptin (E7CH) or the kappa-specific opioid agonist U69,593 (F-11kappa7) for 24 h showed increased apoptosis in response to staurosporine or wortmannin when compared with non-pretreated cells. The effects of morphiceptin and U69,593 were time- and dose-dependent and antagonist-reversible, suggesting that they were receptor-mediated. Neither morphiceptin nor U69,593 by themselves had any measurable effect on cell viability or DNA fragmentation, and coaddition of opiates at the same time as staurosporine, wortmannin, or LY294002 did not enhance apoptosis. Time course studies indicated a maximal opioid effect at a time (16-24 h) when inhibition of adenylate cyclase had been maximal for many hours. Addition of dibutyryl cyclic AMP either before or at the time of opioid addition protected against apoptosis and reduced fragmentation to levels seen for staurosporine plus dibutyryl cyclic AMP alone. The specificity for cyclic AMP was confirmed by showing protection with the specific agonist Sp-adenosine 3',5'-cyclic monophosphothioate and increased killing with the antagonist Rp-adenosine 3',5'-cyclic monophosphothioate. We conclude that the opioid enhancement of apoptosis is based on the inhibition of adenylate cyclase and that the effect is time-dependent.

Androstadienes↗
PubMed1998

Prevalence and significance of steatorrhea in patients with active Graves' disease.

OBJECTIVE: The aim of this study was to determine the prevalence of steatorrhea in patients with Graves' disease and to assess its significance and correlation with changes in body mass index (BMI), coefficient of fat absorption (COFA), and pancreatic exocrine function in these patients. METHODS: Daily dietary fat intake, 24 h fecal fat, COFA, fecal chymotrypsin activity (as an index of pancreatic exocrine function), and total T3, T4, and TSH levels were assessed in 28 patients with active Graves' disease. In 24 patients, reassessment was done after attaining a euthyroid state with carbimazole therapy. RESULTS: In the thyrotoxic state, 13 of 28 patients had steatorrhea, whereas 15 had normal (<6 g/day) fat excretion (11.4 +/- 6.7 g vs 2.9 +/- 0.8 g, p = 0.0007). Daily fat intake, basal BMI, and serum T3 and T4 levels were similar in the steatorrheic and nonsteatorrheic groups. The mean COFA of the steatorrheic group was significantly lower than that of nonsteatorrheic group (91.6% +/- 4.8% vs 97.7% +/- 0.9%, respectively; p = 0.0006). In the steatorrheic group, fat excretion and COFA normalized after attainment of euthyroidism (changes in fat excretion and COFA = 7.3% +/- 6.3 g/day and 7.7% +/- 5.4%, respectively). Fecal chymotrypsin levels were similar in the steatorrheic and nonsteatorrheic thyrotoxics and in 16 healthy control subjects. The levels did not show any significant changes following attainment of euthyroid status. CONCLUSION: Steatorrhea associated with a decrease in COFA can occur in a reversible manner in 46% of patients with Graves' disease. However, steatorrhea in these patients is not linked with weight loss or with pancreatic exocrine dysfunction.

Absorption↗
PubMed1998

Observations on hepatic structure and function in fibro-calculous pancreatic diabetes (FCPD) vis-a-vis other diabetic subtypes.

Investigations of liver function and histology were undertaken in thirty four patients with Fibrocalculous Pancreatic Diabetes (FCPD). The data obtained were compared with those of similarly aged members of a diabetic control group comprising twelve patients with Protein Deficient Diabetes Mellitus (PDDM), twelve with Type 1 diabetes or Insulin Dependent Diabetes Mellitus (IDDM) and four young patients with Type 2 Diabetes of Non-Insulin Dependent Diabetes Mellitus (NIDDM). None of them had apparent past or present liver disease. Elevations of serum ALT (SGPT) and alkaline phosphatase levels were fairly common and was often associated with mild fatty changes and occasionally with focal necrosis and inflammatory changes. Cirrhosis and inflammatory changes per se were infrequent and fatty changes per se did not occur. In contrast patients belonging to the other diabetic subsets were very occasionally afflicted with hepatic abnormalities or not afflicted at all. We propose that loss of hepatotrophic actions mediated by insulin and glucagon could initiate and/or enhance hepatic abnormalities in FCPD where deficiencies of insulin and glucagon coexist.

Adolescent↗
PubMed1998

The formation of ceramide from sphingomyelin is associated with cellular apoptosis.

The apoptotic response of the immature B-cell to the cross-linking of surface IgM receptors provides a good model for cell death and we show in WEHI-231 B-cells that the time course of apoptosis corresponds to the increased formation of ceramide, as measured either by mass (using the diacylglycerol kinase method) or radiolabelling with [3H]palmitate. Inhibitors of sphingosine biosynthesis have no effect on cell death induced by anti-IgM in WEHI-231 but inhibitors of ceramidase accelerate apoptosis, suggesting that activation of sphingomyelinase is the key event in apoptosis. We have demonstrated this by in vitro assay of neutral sphingomyelinase. Apoptosis is also important in normal brain development and neuronal survival is dependent upon phosphatidylinositol 3-kinase (PI3-kinase) activation by growth factors (insulin, nerve growth factor etc.). Withdrawal of these growth factors or inhibition of PI3-kinase with wortmannin or LY294002 activated the pro-apoptotic CPP32 (Yama/Apopain/caspase 3, EC 3.4.22), activated neutral sphingomyelinase and increased ceramide formation in an immortalized dorsal root ganglion cell line F-11. Protection against apoptosis can be achieved by overexpression of the bc12 family of proteins or addition of drugs which elevate cAMP levels. cAMP protects against apoptosis induced by either wortmannin or staurosporine. The specificity for cAMP was confirmed by showing protection with the specific agonist (Sp)cAMPS and increased killing with the antagonist (Rp)cAMPS. However, cAMP did not protect against ceramide killing, suggesting that there are at least two major pathways of apoptosis in neuronal cells.

Animals↗
PubMed1997

Prevalence of enuresis and other bladder symptoms in patients with active Graves' disease.

OBJECTIVE: To determine the prevalence of bladder symptoms in patients with Graves' disease and assess their abnormalities on urodynamic studies. PATIENTS AND METHODS: The study comprised 30 consecutive patients (13 female, 17 male, mean age 31 years, SD 10) with active Graves' disease. Before and after attaining euthyroidism with carbimazole, their bladder symptoms were assessed using a questionnaire adapted from the American Urologic Association voiding symptom score, the serum levels of total triiodo-L-thyronine (T3), serum thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay, and uroflowmetry, cystometry and perineal muscle electromyography were performed. RESULTS: Twelve of the 30 patients (40%) had the onset of bladder symptoms 1-6 months after the onset of symptoms of Graves' disease; four of the 12 patients had enuresis. Urodynamic studies were possible in five patients and showed reduced flow rates in all, a significant post-void residual volume in four, and enlarged bladder capacity and increased perineal muscle electromyographic activity during the voiding phase in three. Voiding disturbances and urodynamic abnormalities resolved after attaining euthyroidism. CONCLUSION: Significant bladder symptoms can occur in about 40% of patients with active Graves' disease but resolve on euthyroidism; in some patients, urodynamic studies show significant abnormalities which are also reversible.

Adolescent↗
PubMed1997

Chronic exposure to kappa-opioids enhances the susceptibility of immortalized neurons (F-11kappa 7) to apoptosis-inducing drugs by a mechanism that may involve ceramide.

Chronic exposure of embryonic brain to opioids leads to microcephaly and developmental abnormalities. An immortalized mouse neuroblastoma x dorsal root ganglion hybrid cell line stably transfected to overexpress kappa-opioid receptors (F-11kappa7) showed complete loss of kappa-receptor binding to [3H]U69,593 after exposure to the kappa-agonist U69,593 for 24 h. U69,593 had no measurable effect on cell viability as determined by either cell viability or DNA fragmentation assays. However, when cell death (apoptosis) was induced by either staurosporine or the phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002, cells pretreated with U69,593 for 24 h showed increased apoptosis compared with untreated cells. Thus, staurosporine (50 nM), wortmannin (4 microM), and LY294002 (30 microM) treatment for 24 h induced a 50% loss of cell viability and DNA fragmentation in 24 h. U69,593 pretreatment produced the same killing at lower concentrations, namely, 20 nM staurosporine, 2 microM wortmannin, and 14 microM LY294002, respectively. The effects of U69,593 were time-, dose-, and naloxone-reversible, suggesting that they are receptor-mediated. However, coaddition of U69,593 at the same time as staurosporine, wortmannin, or LY294002 did not enhance apoptosis. All three drugs that induced apoptosis were found to increase the level of ceramide, and pretreatment with U69,593 further increased the rate of formation of ceramide, a lipid that induces apoptosis in cells. We propose that chronic exposure to kappa-receptor agonists promotes increased vulnerability of neurons to apoptosis.

Analgesics↗
PubMed1996

Remission with carbimazole therapy & assessment of T4 suppression test as an index of relapse in patients with Graves' disease in India.

This study determined the relapse rate following the use of antithyroid drugs (ATD) in patients with Graves' disease and assessed T4 suppression test as a follow up index for predicting relapse after carbimazole treatment in 21 patients who had taken 9-12 months of ATD treatment continuously with good compliance. T4 suppression test was done before stopping ATD treatment. During one year of follow up after stopping ATD therapy, 12 (57%) patients relapsed and 9 (43%) remained in remission. Six of the 12 relapses occurred in the first 3 months of stopping ATD therapy. The response following the use of carbimazole therapy was comparable to that reported from iodine sufficient western countries and may be because of the salt iodination programme in our country. T4 suppression test was normal in 14 (66%) and abnormal in 7 (34%) patients. All the patients with abnormal T4 suppression test relapsed after stopping ATD. The overall accuracy of the T4 suppression test (76%) also favourably compared with reported values of other useful but less readily available markers such as thyrotropin releasing hormone (TRH) stimulation test and thyroid receptor antibodies. Thus, in our experience antithyroid drugs were able to induce long term remission in 43 per cent patients with Graves' disease and abnormal T4 suppression test can be used as a reliable parameter for predicting relapse.

Adult↗
PubMed1996

Dyspnoea, lung function & respiratory muscle pressures in patients with Graves' disease.

To understand the pathophysiology of dyspnoea in patients with hyperthyroidism, lung function, maximum inspiratory, expiratory respiratory muscle pressures (MIP and MEP) and intensity of dyspnoea (after six minutes walking test) were recorded in 12 consecutive patients with active Graves' disease. Reassessment was done after achieving euthyroidism with 8-12 wk of carbimazole therapy. Patients covered similar distance during 6 min walking before and after carbimazole therapy. However, there was a significant reduction in dyspnoea following euthyroidism. This was accompanied by significant decrease in respiratory rate, minute ventilation, forced expiratory volume in one second (FEV1%) and improvement in the forced vital capacity (FVC). No significant changes in tidal volume (TV) and maximum-midexpiratory flow rates (MMEFR), MIP and MEP were observed. Lung function parameters, MIP and MEP did not correlate with the severity of dyspnoea. Serum T4 levels correlated inversely with the distance covered during 6 min walking test, MIP and MEP. To conclude, increased breathing effort in presence of reduced FVC may lead to dyspnoea during hyperthyroid phase in patients with active Graves' disease. Lack of correlation between the severity of dyspnoea and abnormalities in lung function suggests that other mechanisms of dyspnoea may also operate in these patients.

Adult↗
PubMed1995

Prevalence & significance of pancreatic islet cell & adrenal antibodies in patients with Graves' disease.

The prevalence of adrenocortical (ACAb), islet cell (ICAb) and thyroid microsomal (TMAb) autoantibodies was determined by indirect immunofluorescence, in 88 consecutive patients with Graves' disease. ACAb, ICAb and TMAb positivity was seen in 3 (3.3%), 10 (11%) and 66 (75%) patients respectively. Among these one patient had both ACAb and ICAb positivity. Diabetes mellitus was found to be present in two (2.3%; both ICAb positive) of the 88 patients studied. Two of the four ICAb positive patients had loss of first phase insulin response to intravenous glucose. A significant proportion of patients of Graves' disease had associated islet cell and/or adrenal autoimmunity. A high index of suspicion for associated endocrine autoimmunity should be maintained while dealing with subjects of Graves' disease.

Adrenal Cortex↗
PubMed1994

Dideoxy sequencing and structural analysis of the rat insulin-like growth factor binding protein-1 gene.

Insulin-like growth factor binding protein-1 (IGFBP-1) is an important modulator of IGF bioavailability. To facilitate studies of IGFBP-1 regulation and function in rodent models, we cloned the rat IGFBP-1 gene and analyzed its structure by dideoxy sequencing. The rat IGFBP-1 gene is relatively small (approximately 5 kb) and contains 4 exons and 3 introns, similar to the human IGFBP-1 gene.

Amino Acid Sequence↗
PubMed1994

Hypocalcemia-induced reversible hemodynamic dysfunction.

A series of three cases of 'hypocalcemic dysfunction' that reflects a range of clinical profiles from a purely calcium responsive peripheral collapse to paroxysmal nocturnal dyspnea and orthopnea is reported. The underlying diversity of clinical presentation is noteworthy, as is its prompt response to calcium therapy.

Adult↗