Biomedical subjects
Publications and source records attributed to V Kaushal.
Infectious diarrhoea is one of the most common illness affecting mankind. Recent advancement have led to detailed understanding of causative agents and the pathogenesis of the infections. Fluid and electrolyte replacement remains the most important aspect of treatment. The role of antimicrobial agents is discussed.
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The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product.
The gene, DTP, coding for diadenosine 5',5'''-P1, P4-tetraphosphate (Ap4A) phosphorylase was isolated from a Saccharomyces cerevisiae genomic DNA library in lambda gt11. In yeast and Escherichia coli transformed with the multicopy vector, YEp352, containing the cloned DTP gene, the Ap4A phosphorylase was produced at levels nine- to 17-fold higher than in untransformed hosts. The nucleotide (nt) sequence was determined. The gene codes for a polypeptide chain of 321 amino acids (aa). Two-aa sequence motifs of possible significance were identified: a potential adenine nt binding site and a potential phosphorylation site. The DTP gene is located on yeast chromosome III and is present as a single copy. Although multicopy vector expression increased the Ap4A phosphorylase activity ninefold above the endogenous activity in transformed yeast, the intracellular concentration of Ap4A did not decrease and the growth rate of the yeast was unchanged.
We analysed the dose-volume distribution in normal brain in eight patients undergoing localized external beam radiotherapy for brain tumours. The results have been represented as integral dose-volume histograms and show that large volumes of normal brain receive clinically significant doses of radiation. A mean of 43% (range 24%-57%) of normal brain volume received more than 50% and a mean of 22% (range 9%-38%) received more than 85% of the maximum tumour dose. The amount of normal brain irradiated increased with enlarging target volume. With the use of customized shielding blocks the mean volume reduction of normal brain receiving more than 50% and 85% maximum tumour dose was 178 ml (median 183 ml; range 89-244 ml) and 110 ml (median 110 ml; 40-179 ml) respectively. This represents an average reduction of 13% and 8% of normal brain volume. Although clinically important this may not be sufficient for a significant improvement in therapeutic ratio.
Diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) phosphorylase has been isolated previously using classical protein isolation techniques [A. Guranowski and S. Blanquet (1985) J. Biol. Chem. 260, 3542-3547]. A protein A-Sepharose immunoaffinity column was prepared to simplify the purification procedure. The immunoaffinity column was prepared using specific polyclonal antibodies to Ap4A phosphorylase covalently coupled to protein A-Sepharose with dimethyl pimelimidate by a modification of the procedure of C. Schneider et al. [(1982) J. Biol. Chem. 257, 10,766-10,769]. The specific activity of the immunoaffinity-purified enzyme showed an increase equivalent to the specific activity obtained by chromatography on DEAE-cellulose and hydroxyapatite columns.
Seventy-eight patients with carcinoma of the penis treated over a period of twelve years (1972-1983) were retrospectively analyzed. According to Jackson's clinical staging, 18.0 per cent were in stage I, 20.5 in stage II, 26.9 in stage III, and 34.6 per cent in stage IV. Some early-stage patients (12 with stage I and 4 with stage II) were primarily treated by external irradiation to a dose of 55 Gy/5 week/25 fr. Thirteen of these 16 patients had local control with preservation of the organ. The remaining patients with stage II were treated by partial or total penectomy. In stage III penectomy with inguinopelvic lymph node dissection was done. Stage IV patients received palliative irradiation and/or chemotherapy. There years' disease-free survival (including salvage surgery) was 93 per cent in stage I, 62.5 per cent in stage II and 38 per cent in stage III.
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Linear standard curves were obtained for 1 to 10 micrograms of bovine serum albumin measured in the presence of 50 mM Mes, Mops, Pipes, Caps, Bes, Hepes, Heppso, and Tes zwitterionic buffers using bicinchoninic acid for detection. The zwitterionic buffers Ada, Tricine, and Bicine that strongly bind Cu2+. Tris, and Bistris, each at 50 mM, inhibited color development to prevent quantitative measurement of protein mass.
Experience with 200 cases of testicular tumors seen over a period of 10 years has been presented. Modes of presentation, response to treatment, and patterns of failure have been analyzed in 186 cases of germ cell tumors. The role of radiation in the overall management of seminomas is reaffirmed, and the need for adjuvant radiation to the supraclavicular region and mediastinum is demonstrated in Stage II cases of seminoma. Results of treatment with radiation alone or combined with chemotherapy were not encouraging in nonseminomas in the current series. The advantages of an aggressive multimodal approach with judicious combination of surgery, radiation treatment, and combination chemotherapy have been discussed, with review of relevant literature.
The incidence of congenital dysplasia of the hip in Northern India is 0.8% in infants born in two hospital maternity units which are interested in detecting this condition.
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OBJECTIVE: To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis. DESIGN: One-year, randomized, placebo-controlled trial. SUBJECTS: 83 patients with severe ulcerative colitis were enrolled. Fifty patients who relapsed within two months on corticosteroid withdrawal were randomized into two groups. The azathioprine group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and oral azathioprine (2 mg/Kg/day). The placebo group received oral sulfasalazine (6-8 g/day), oral prednisolone (1 mg/Kg/day) and placebo. Corticosteroids were tapered over 12-16 weeks. RESULTS: Five patients (2 in azathioprine group, 3 in placebo group) dropped out of the study. Three patients in the azathioprine group had side effects. The number of patients going into complete remission and partial remission was not significantly different in the two groups. The proportion of relapses in the azathioprine group was lower than in the placebo group (p < 0.05). CONCLUSIONS: In patients with ulcerative colitis, azathioprine had no effect in achieving remission, when given in combination with prednisolone; however, it lowers the proportion of relapses. Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal.
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