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Biomedical subjects

B Bhattacharya

Publications and source records attributed to B Bhattacharya.

At least 19 recordsLinked to original sources

Serum zinc level : a possible index in the pathogenesis of peptic ulcer syndrome.

The present investigation shows a possible correlation between serum zinc level and peptic ulcer disease/syndrome and a plausible mechanism for the finding. Clinicopathological study of patients with peptic ulcer diseases followed by confirmed endoscopic findings shows a significant low serum zinc level, 0.846 +/- 0.15 ug/ ml +/- S.D. (P < 0.001) with an exception of approx. 10% of the patients. To understand the cellular mechanism of low zinc levels in serum, tissue zinc content of gastric mucosa was determined. A significant increased value (P < 0.01) of zinc content in gastric mucosa of patients with peptic ulcer diathesis was noted. Carbonic anhydrase, a major zinc containing enzyme was also determined in erythrocytes. However, no change of erythrocyte carbonic anhydrase content was noted. To assess the nutritional status of the patients in relation to the low serum zinc value, serum albumin level was also determined. The low serum zinc level of the peptic ulcer patients is possibly due to the positive shift for the zinc from serum to the gastric mucosa.

Carbonic Anhydrases

Proximate determinants of fertility in eastern Uttar Pradesh.

Our main objective here is to examine and discuss the effects of some sociocultural and economic factors on the proximate determinants of fertility in rural areas of eastern Uttar Pradesh (population more than 40 million persons). The region is known for its present demographic trends because the crude birth, death, and infant mortality rates are among the highest for India. The determinants considered are age at marriage of female, postpartum amenorrhea (PPA), fecundability and sterility, and menopause. The sociocultural and economic factors studied are caste, education, breast-feeding status, and social status of the currently married females in the reproductive age group. The study population is predominantly Hindu, among whom caste is a strong indicator of socioeconomic conditions. The average age of the female at return marriage (RM) is below 18 years in each religion or caste group but has been increasing over time. Median durations of breast feeding and PPA differ significantly among various socioeconomic and demographic subgroups. These are longest in scheduled castes and shortest in upper-caste Hindus. As the social status of the household increases, the median durations of breast feeding and PPA decrease. The estimates of fecundability consistently decrease with age, whereas those of sterility increase with age after 35 years. The smallest estimate of sterility is 4%, corresponding to the 25-30-year age group in each religion or caste group. Occurrence of menopause is rare before age 35, and it increases with the age of the female irrespective of religion or caste. However, the risk is minimum for females in upper castes and maximum for those in scheduled castes.

Adolescent

Efficacy and safety of oral iron chelating agent deferiprone in beta-thalassemia and hemoglobin E-beta thalassemia.

OBJECTIVES: To assess efficacy and safety of oral iron chelating agent deferiprone (DFP) in patients with beta thalassemia and hemoglobin E-beta thalassemia. DESIGN: Non-randomized study. SETTING: Hematology Out-Patient Department. SUBJECTS: Forty-one patients of beta thalassemia and hemoglobin E-beta thalassemia. INTERVENTIONS: DFP was given to 20 patients, 10 patients of beta thalassemia and 10 with hemoglobin E-beta thalassemia; the rest were taken as controls. RESULTS: A significant fall in serum ferritin was observed in the study group along with rise in urinary iron excretion (p < 0.05). Adverse effects of DFP were nausea and vomiting (30%), significant arthropathy requiring stopping of the drug (30%), and reversible neutropenia in one patient. All these complications could be managed easily with medical supervision and no death or permanent disability was seen. CONCLUSIONS: DFP is an effective and fairly well tolerated oral iron chelating agent. The side effects that occur can be tackled easily if monitored properly.

Administration, Oral

Intellectual functions in childhood malignant disorders.

Our study was designed to compare the intellectual functions in 35 children with lymphoreticular malignancies (ALL or NHL) who had received CNS directed therapy (Group A), with those in 21 patients with solid tumors (Group B). Intellectual assessment was done using the Malin's modification for Indian children of the Wechsler's intelligence scale. Using 5 verbal and performance subscales each, the verbal IQ, performance IQ and full scale IQ were derived. The mean VIQ, PIQ and FIQ were comparable in the two groups with the differences not being statistically significant. However, the dispersion of IQ scores was greater in Group A with a larger number of subjects having scores of < 80. Similarly, the scores obtained in the arithmetic, digit-span, picture completion and block design subscales were lower in Group A. Mean IQ scores were significantly lower in children over the age of 10 years at diagnosis. Sex duration since diagnosis, disease free survival and treatment variables did not affect IQ scores. In conclusion, a cross-sectional evaluation of intellectual functions has revealed only minimal differences in children treated with chemotherapy and CNS directed therapy (ITMTX and RT) in comparison to those treated with chemotherapy alone.

Adolescent

Acetylcholinesterase characteristics of termite queen exposed to anticholinesterase compounds.

A regional profile of AChE activity was noted in the Indian termite queen Odontotermes redemanni with the head recording the higher and body the lower range of activity. The enzyme characteristics such as substrate and temperature optima were more or less similar while pH requirement for optimum AChE activity varied from 7.0 to 7.6 In vitro inhibition of head and body AChE was studied using pure and commercial anticholinesterase compounds. Interestingly, the commercial formulations like Metacid-50 and Carbaryl are potent enough at 1 x 10(-8) M to produce 50% in vitro inhibition of AChE of head and body regions within 15 min of preincubation. A 20 min of preincubation (t0.5) was necessary to record 50% in vitro inhibition of AChE with known and pure anticholinesterase compounds such as DFP (3.5 x 10(-10) M) and physostigmine (3.6 x 10(-10) M). It is surmised that (a) the response of the head and body AChE to the commercial formulations of the insecticides may be used as a reliable and sensitive bioindicator of pesticidal contamination of the terrestrial environment and (b) termite control may be successfully done with the application of organophosphate or carbamate compounds.

Acetylcholinesterase

Post-transcriptional regulation of tubulin mRNA in developing rat brain.

The transcriptional activity of tubulin genes during synaptogenesis in developing rat brain has been examined by 'nuclear run off assay'. For both alpha and beta tubulin genes, the relative rates of transcription were found to be high during the early phase of synaptogenesis (postnatal days 1-5) and declined 20-50% by the end of synaptogenesis (postnatal days 15-20). Comparison of the developmental alterations in the rates of transcription of both alpha and beta tubulin mRNA with the level of polysomal tubulin mRNA shows that the age related decline (70-80%) in the level of polysomal tubulin mRNA during synaptogenesis is much too large compared to the 20-25% decline in their transcription rates suggesting that tubulin mRNA levels in developing rat brain are regulated post-transcriptionally.

Aging

Tubulin gene expression during synaptogenesis in rat, mouse and chick brain.

Studies on tubulin gene expression in brains from three different species, viz rat, mouse and chick, varying with respect to their periods of synaptogenesis, show that the rise and fall in the level of tubulin during synaptogenesis is closely parallel to that of tubulin mRNA. In all three species, the onset of synaptogenesis is accompanied by a dramatic rise in the level of tubulin which continues till the midphase and then declines to adult level by the end of synaptogenesis. The chick alpha- and beta-tubulin coding region probes, pT1 and pT2, which have a 80-90% homology with rat/mouse sequences, were employed to determine the overall levels of alpha- and beta-tubulin mRNA in all samples. Quantitation of tubulin mRNA by dot hybridization revealed a closely parallel change in the levels of both alpha- and beta-tubulin mRNA. In analogy with that of tubulin, the mRNA levels in rat and mouse brain increased progressively from birth till postnatal day 5 and that in the chick brain increased from day 7 till day 11 of embryonic development. In all three cases, the peak levels of tubulin mRNA corresponded closely with the midphase of synaptogenesis and declined almost to adult levels by the end of synaptogenesis. The sudden decline in the level of tubulin as well as its mRNA during the middle of synaptogenesis suggests that the repression of tubulin gene expression is neither due to cessation of cell division nor cell differentiation. Instead, it is likely to be due to the autoregulatory property of tubulin which leads to rapid turnover of its own mRNA when a sufficient level of intracellular tubulin accumulates during the midphase of synaptogenesis.

Animals

Tropomyosins of human mammary epithelial cells: consistent defects of expression in mammary carcinoma cell lines.

Suppression of synthesis of specific tropomyosin (TM) isoforms occurs commonly in human, murine, and avian fibroblasts transformed by retroviral oncogenes or other modalities. The resulting deficiency or altered distribution of TMs may predispose the cells to microfilament instability and contribute to expression of the transformed phenotype. In this study we have asked whether defects in TM expression had relevance to human neoplasia, which arises most often in cells of the epithelial lineage rather than in fibroblasts and often is unrelated to demonstrable expression of oncogenes. TMs were characterized in normal primary human mammary epithelial cells (HMEC) and in an immortalized nontumorigenic cell line derived from them. Seven TM isoforms were identified in primary HMEC, two of which may be unique to epithelial cells. Immortalized nontumorigenic HMEC expressed the same array of isoforms. Of six established human breast carcinoma cell lines studied, all failed to express the Mr 39,000 TM isoform and five of six also lacked expression of either the Mr 38,000 or 35,000 isoform. Northern blot analysis with probes specific for the 1.1-kilobase mRNA of fibroblast TM1 detected a mRNA of this size in normal HMEC. This mRNA, which probably encodes the Mr 39,000 TM missing from all the carcinoma lines, was absent from five of the six breast cancer cell lines. These results indicate that abnormalities in TM expression in neoplastic cells are not limited to fibroblasts. The high frequency and consistent nature of such abnormalities among cell lines derived from human breast cancer raises the possibility that such abnormalities in expression of a major cytoskeletal protein may play a role in human neoplasia.

Actins

Disordered metabolism of microfilament proteins, tropomyosin and actin, in mouse mammary epithelial cells expressing the Ha-ras oncogene.

Synthesis of 37- and 41-kD tropomyosins (TM) is suppressed in fibroblasts expressing transforming oncogenes, which may contribute to the deranged microfilament structure seen in such cells (Cooper et al., Mol. Cell. Biol. 5, 972, 1985). To determine whether TM metabolism was also deranged when epithelial cells expressed a transforming oncogene, we studied cultured mouse mammary epithelial cells which express the activated c-Ha-ras oncogene either constitutively or through glucocorticoid activation of the oncogene linked to a mouse mammary tumor virus (MMTV) promoter. The epithelial cells expressed three major TM species, one at 37 kD and two at 35 kD, but lacked expression of a 41 kD TM typically found in fibroblasts. In oncogene-expressing cells synthesis of the 37 kD TM was not suppressed but synthesis of actin was increased 2-fold. Actin entered the cytoskeleton (CSK) normally, but TM accumulated in the CSK with a 50% reduction from normal in TM:actin ratio. Thus, in both epithelial cells and fibroblasts expressing transforming ras oncogenes, the metabolism of TM and actin is disordered so as to produce TM-deficient cytoskeletal structures which may be functionally or structurally defective. However, the result is achieved by different effects on metabolism of these proteins in the two cell types, suggesting that cellular responses to oncogene actions may be conditioned by the state of cell differentiation.

Actins

Suppression of synthesis and utilization of tropomyosin in mouse and rat fibroblasts by transforming growth factor alpha: a pathway in oncogene action.

Two events which commonly occur during transformation of murine and avian fibroblasts by retroviral oncogenes are production of transforming growth factor alpha (TGF-alpha) and suppression of tropomyosin synthesis. TGF has been proposed as a mediator of transformation through autocrine stimulation. Suppression of tropomyosin synthesis may contribute to the transformed phenotype through destabilization of actin microfilaments and cytoskeletal derangement. To determine whether suppression of tropomyosin synthesis might be a consequence of the action of TGF-alpha we studied tropomyosin synthesis in rat (normal rat kidney) and mouse (NIH3T3) fibroblasts treated with TGF-alpha. In a serum-containing system, addition of TGF-alpha or epidermal growth factor to normal rat kidney monolayers in subnanomolar concentrations induced morphological changes consistent with transformation. These changes were accompanied by prominent suppression of synthesis of Mr 36,000 and 39,000 tropomyosins. Similar suppression was observed in NIH3T3 cells. Inhibition of tropomyosin synthesis began almost immediately after addition of TGF-alpha and became progressively more pronounced during the succeeding 48 h. Suppression of tropomyosin synthesis was correlated with reduced expression of 1.1- and 1.8-kilobase tropomyosin mRNAs in both TGF-treated normal rat kidney cells and v-Ki-ras-transformed NIH3T3 cells. Rapid onset of a specific block in utilization of newly synthesized tropomyosin for formation of cytoskeletal elements was also demonstrated following TGF-alpha treatment. The evidence suggests that this block may be a specific effect of TGF-alpha treatment and that reduced expression of tropomyosin gene products may be either an independent event or a regulatory consequence of the block to utilization. The data support the conclusion that suppression of tropomyosin synthesis in cells transformed by a number of retroviral oncogenes results from the autocrine action of TGF-alpha.

Animals

Regulation of alpha- and beta-tubulin mRNAs in rat brain during synaptogenesis.

Developmental alterations in alpha- and beta-tubulin mRNA in polysomes from brains of -3 days (fetal) to 30-day-old rats were quantitated by using well-characterized chicken alpha- and beta-tubulin cDNA probes, pT1 and pT2 having 80-90% homology with rat sequences. Northern blot analysis revealed a single major (greater than 95%) 1.8 kb mRNA for both alpha- and beta-tubulin. Quantitation by slot hybridization indicates a virtually coordinate expression of alpha- and beta-tubulin mRNA with a maximal level around day 5 after birth, which represents the mid-phase of synaptogenesis.

Animals

Identification and characterization of the nonphosphorylated precursor of pp17, a phosphoprotein associated with phorbol ester induction of growth arrest and monocytic differentiation in HL-60 promyelocytic leukemia cells.

Treatment of HL-60 promyelocytic leukemia cells with the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), causes rapid phosphorylation and dephosphorylation of pp17, a 17-20-kDa, pI 5.5 cytosolic protein, as an early event in a response sequence leading to growth arrest and terminal differentiation into monocytes (Feuerstein, N., and Cooper, H. L., (1984) J. Biol. Chem. 259, 2782-2788). In the present study, we have identified the nonphosphorylated precursor to pp17 by tryptic peptide mapping of single proteins recovered from two-dimensional gels. The pI of the precursor, p17, was 5.9, and the apparent Mr of both p17 and pp17 was 18,400 by SDS-polyacrylamide gel electrophoresis (one dimension). p17 was shown to be a major cytosolic protein, comprising about 0.5% of steady state labeled protein in that fraction. Both p17 and pp17 were found exclusively in the cytosol (detergent-released SOL) and were not detected in membranes, cytoskeleton, or nuclei. In untreated cells, about 90% of the protein was present in the nonphosphorylated form. Upon TPA treatment, pre-existing p17 was rapidly phosphorylated to pp17. After 15 min, the two forms were nearly equal in quantity. This corresponds to phosphorylation, within that period, of about 0.2% of total cytosolic protein, represented by a single species. The maximum level of pp17 was reached within 1 h, with pp17 exceeding p17 by about 25%. Quantitatively, therefore, the phosphorylation of p17 to pp17 is one of the most prominent early biochemical responses to TPA treatment. Available data indicate that p17 predominates in rapidly proliferating cells, while phosphorylation to pp17 occurs where cell growth is modified by TPA or other agents. Thus, the p17/pp17 system is potentially a major mechanism for intracellular propagation of growth regulatory signals. We propose the name, prosolin, for this prominent cytosolic protein.

Carrier Proteins