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Biomedical subjects

R Goswami

Publications and source records attributed to R Goswami.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

Functional analysis of glucocorticoid and insulin response sequences in the rat insulin-like growth factor-binding protein-1 promoter.

Insulin-like growth factor-binding protein-1 (IGFBP-1) is produced by the liver and regulated by glucocorticoids and insulin at the level of gene transcription. To identify DNA sequences mediating the effects of glucocorticoids and insulin on IGFBP-1 promoter activity we created luciferase reporter gene constructs and performed transfection studies in H4IIE hepatoma cells. Initial studies confirmed that the IGFBP-1 promoter is functional when inserted in the correct orientation, but not in the reverse orientation. Dexamethasone (DEX) increased promoter activity 10-fold, and insulin reversed this effect of DEX by 85% at 8 h. The effects of DEX were abolished when constructs were truncated to 89 bases from the RNA cap site, and DNase footprinting with the DNA-binding domain of the human glucocorticoid receptor identified an imperfect palindrome containing two receptor-binding sites separated by three nucleotides typical of a glucocorticoid response element (GRE) at this location. Mutation of either binding site (or half-site) disrupted the effects of DEX, confirming that this sequence functions as a GRE. Two other regions of the promoter also footprinted with the glucocorticoid receptor protein and contained sequences consistent with glucocorticoid receptor-binding sites; however, neither of these footprints contained the full structure expected of a functional GRE, and neither mutation nor deletion of these other sequences altered the effects of DEX on promoter activity. To identify the DNA sequences required for the effects of insulin on glucocorticoid-stimulated promoter activity, we created internal deletions throughout the IGFBP-1 promoter region. Deletion of the 22-basepair (bp) sequence immediately 5' from the GRE disrupted the effect of insulin and appeared to increase basal promoter activity at least 2-fold in each of eight experiments (P < 0.001 vs. intact promoter). This region of the IGFBP-1 promoter contains a 19-bp palindrome (CAAAACAAACTTATTTTG) that overlaps the 5'-end of the GRE and is fully conserved in the human IGFBP-1 promoter. Each half of this palindrome resembles previously identified insulin response sequences, and deletion/mutation analysis suggests that each half may contribute to the effects of insulin on promoter activity. Gel shift studies confirmed that this palindrome binds H4IIE nuclear proteins. In summary, we have identified a GRE in the 5'-promoter region of the rat IGFBP-1 gene approximately 90 bp up-stream from the RNA cap site as well as a contiguous 22-bp region that plays a critical role in mediating the effects of insulin on glucocorticoid-stimulated promoter activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Changing trends in twinning.

Birth statistics (on 13,887.943 births) from 11 Indian States indicate a fall in the dizygotic twinning rate and a rise in the monozygotic twinning rate over the decade between 1982 and 1991. These figures seem to reverse the trend of the period 1960-1982. One plausible explanation is offered by the age-data on mothers, which indicate that twins of different sex are more frequently born to mothers above the age of 35. Since extensive family planning measures have reduced the upper age-limit of mothers, the birth-rate of twins of different sex has also fallen. Due to the increased proportion of twins of the same sex, Weinberg's differential method will therefore report a decline in the dizygotic twinning rate, wherever the mean age of mothers has fallen (i.e. most mothers do not reproduce after the age of 35).

Adult↗

Synthesis and substance P antagonist activity of naphthimidazolium derivatives.

The synthesis of unsymmetrical naphth[2,3-d]imidazolium and bridged naphth[2,3-d]imidazolium derivatives and their substance P (SP) antagonist activity are described. All compounds were evaluated for their ability to displace SP from neurokinin-1 (NK-1) receptor sites using standard receptor binding methodology (rat forebrain membrane). 1,3-Diethyl-2-[3-(1,3-dihydro-1,3,3-timethyl-2H-indol-2-ylidene) -1-propenyl]-1H-naphth[2,3-d]imidazolium chloride (7a), a representative compound in this series, was further evaluated for SP antagonist activity in a guinea pig ileum contractility assay. In vivo SP antagonist activity of 7a was demonstrated using SP-induced salivation and paw edema models performed in rats.

Animals↗

Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrimido[1,2-a]benzimidazoles.

Several heterosteroids containing a dihydroethisterone skeleton were prepared and shown to displace substance P in a receptor binding assay. Further biochemical (kinetic and Scatchard analyses) and pharmacological evaluation (substance P-induced plasma extravasation and salivation in the rat) of a representative example in this series (5a) established that these compounds are competitive antagonists at the substance P receptor.

Androstanes↗

Effect of bromhexeine on sputum amoxycillin levels in lower respiratory infections.

Bromhexeine has been widely used as an adjunct in the management of lower respiratory infections and is useful in altering the physical characteristics of sputum. Its effect on the sputum penetration of an antibiotic has been sparsely studied. The present study highlights the improvement in sputum amoxycillin (amoxy) levels when a combination tablet, amoxy 500 mg plus bromhexeine 8 mg, is administered as compared to plain amoxy 500 mg. Sputum amoxy levels were significantly higher in the combination group (0.674 +/- 0.588 micrograms ml-1) as compared to 0.272 +/- 0.19 micrograms ml-1 in the amoxy group (P = 0.028). The clinical responses assessed by the physician as well as the patient were significantly better in the amoxy plus bromhexeine group as compared to the amoxy group. The radiological and bacteriological responses were similar in both groups. There was no increase in the side-effects due to bromhexeine and, overall, its use can be recommended in the treatment of acute lower respiratory infections.

Adult↗

Effect of zinc ions on the biochemical behavior of simian virus 40 small-t antigen expressed in bacteria.

The simian virus 40 small-t antigen contains 10 cysteine residues, 6 of which are organized in two CysXCysXXCys clusters. Mutation of individual Cys residues in the two clusters or mutation of specific residues found between these clusters causes pronounced instability of the protein in animal cells. Protein instability correlates with failure of the bacterially expressed mutant proteins to bind zinc ions, an interaction which allows purification of large amounts of small-t antigen in monomeric form.

Amino Acid Sequence↗