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Biomedical subjects

N Basu

Publications and source records attributed to N Basu.

At least 19 recordsLinked to original sources
PubMed2003

The effects of stress on the association between hsp70 and the glucocorticoid receptor in rainbow trout.

The purpose of this study was to characterize the association between hepatic heat shock protein 70 (hsp70) and the glucocorticoid receptor in rainbow trout that were exposed to heat stress, cortisol, and beta-naphthoflavone. This study is the first to document that the glucocorticoid receptor complex in rainbow trout hepatic tissues contains hsp70. Heat stress significantly increased levels of total cellular hsp70, and by discerning the association of hsp70 with the glucocorticoid receptor, we demonstrated that heat stress significantly increased the amount of hsp70 not bound to the glucocorticoid receptor, while significantly decreasing the amount of hsp70 bound to the glucocorticoid receptor. By calculating the ratio of hsp70 bound to the glucocorticoid receptor, to the total number of glucocorticoid receptors, stress (heat stress and cortisol-treatment) promoted the association of hsp70 with the glucocorticoid receptor. These findings demonstrate a functional and structural link between hsp70 and the glucocorticoid receptor in rainbow trout, and raise questions regarding the existence of a complex, interrelated stress response that spans all levels of biological organization within the whole animal.

Animals↗
PubMed2002

Heat shock protein genes and their functional significance in fish.

Despite decades of intensive investigation, important questions remain regarding the functional, ecological, and evolutionary roles of heat shock proteins. In this paper, we discuss the utility of fish as a model system to address these questions, and review the relevant studies of heat shock protein genes and the regulation of their expression in fish. Although molecular studies of the heat shock proteins in fish are still in their early descriptive phase, data are rapidly being collected. More is known about the biotic and abiotic factors regulating heat shock proteins. We briefly review these studies and focus on the role of heat shock proteins in development, their regulation by the endocrine system, and their importance in fish in nature. Functional genomics approaches will provide the tools necessary to gain a comprehensive understanding of the significance of heat shock proteins in the cellular stress response, in the physiological processes at higher levels of organization, and in the whole animal in its natural environment.

Adaptation, Physiological↗
PubMed2002

Management of patients aged >60 years with malignant glioma: good clinical status and radiotherapy determine outcome.

Many clinical trials have shown that the most important prognostic variable in patients with malignant glioma is advanced age. However, can some patients aged >60 years still have relatively good outcomes with conventional surgical and radiotherapeutic treatment? A previous audit of practice (1983-89) suggested that functional status was an important prognostic variable in the elderly. We have reviewed a further cohort (1989-96) to evaluate changes in practice and outcomes given advances in neuroimaging, neurosurgery and radiotherapy. The major findings in this series of 80 patients aged over 60 years with a histological diagnosis of supratentorial malignant glioma were: (i) There was a relationship between management undertaken and clinical status of the patients (p < 0.01), i.e. patients in good grade generally had tumour debulking and radiotherapy, whilst those in poor grade generally had only biopsy. (ii) There was a significant increase in survival of patients in the second period who received surgical debulking and post-operative radiotherapy (from a median of 23 to 41 weeks (p < 0.05). (iii) It is likely that case selection accounted for much of this improvement since there was a direct relationship between median survival time and good clinical grade using the WHO performance scale. (iv) A shorter radiotherapy course (30 Gy in six fractions) was as efficacious as a conventional course (60 Gy in 30 fractions), and those patients having radiotherapy survived significantly longer than those not having this treatment (p = 0.001). This study has again demonstrated the importance of preoperative clinical grade and radiotherapy treatment in determining outcomes in patients >60 years. To put these data in a societal context a recent prospective multicentre audit of patients with malignant glioma in Scotland, and another audit from our unit, showed that between 24 and 65% of patients aged >60 years, with a CT diagnosis of malignant glioma do not undergo either surgery or radiotherapy. Advanced age per se should not be a bar to interventional treatment in patients aged >60 years with suspected malignant glioma.

Age Factors↗
PubMed2002

Urinary citrate excretion in idiopathic nephrolithiasis.

OBJECTIVE: To determine urinary citrate excretion in children with nephrolithiasis and normal controls. DESIGN: Prospective. SETTING: Tertiary care center in New Delhi. METHODS: This study was done on 50 children, below the age of 12 years, with idiopathic urinary calculi and 150 age and weight matched controls. The children were divided into 3 groups: Group 1 (1-4 years), Group 2 (5-8 years) and Group 3 (9-12 years). Urinary citrate was estimated in a 24-hour urine sample using colorimetric method. The stones removed from these children were also analysed. RESULTS: There was a preponderance of urinary stones in males; the highest incidence being in Group 1. Excretion of citrate in 24-hour urine sample was significantly lower in patients compared to controls, for males in all age groups and for females in Group 3. However, there was no statistically significant difference in the urinary citrate value between males and females in a given age group for either controls or patients. The urinary citrate excretion increased with age in patients and controls, but the levels in patients were lower. Depending upon the constituents, four types of stones were identified, calcium phosphate, calcium oxalate, uric acid and magnesium ammonium phosphate. Nine stones had at least more than one major constituent. Hypocitraturia was detected in 43 percent cases. The incidence was 76 percent for calcium phosphate, 87 percent for calcium oxalate, 40 percent for uric acid stones and 50 percent for magnesium ammonium phosphate. CONCLUSION: This study shows that low urinary citrate is associated with urinary stones in children, especially in endemic areas, in the absence of obvious etiological factors. Urinary citrate excretion should be determined in all children with nephrolithiasis.

Case-Control Studies↗
PubMed2001

The effects of cortisol on heat shock protein 70 levels in two fish species.

We studied the relationship between heat stress (2 h, +12 degrees ) and increased levels of circulating cortisol (50 microg cortisol/g body weight) on heat shock protein 70 (hsp70) levels in liver and gill tissues of rainbow trout (Oncorhynchus mykiss) and tilapia (Oreochromis mossambicus). The administration of cortisol by intraperitoneal injection (no heat stress) did not alter tissue hsp70 levels compared to sham implanted (no heat stress) trout and tilapia. We found elevated levels of cortisol significantly suppressed the heat stress-induced levels of hepatic hsp70 by 34.2% and 31.0%, 3 and 24 h post-heat stress, respectively, compared to sham implanted trout. Additionally, elevated levels of cortisol significantly suppressed the heat stress-induced levels of gill hsp70 by 66.2% in trout (3 h post stress) and 26.7% in tilapia (4 h post stress), compared to sham implanted fish. These results suggest that cortisol may be mediating hsp70 levels in fish tissues following times of physiological stress, and that the neuroendocrine and cellular stress responses may be functionally related in these two different species of fish.

Animals↗
PubMed2001

Ethoxyresorufin-O-deethylase induction in trout exposed to mixtures of polycyclic aromatic hydrocarbons.

This study investigated whether ethoxyresorufin-O-deethylase (EROD) activity in rainbow trout exposed to mixtures of polycyclic aromatic hydrocarbons (PAHs) could be predicted from induction equivalency factors (IEF). The test PAHs were classified into strong and weak inducers on the basis of similar exposure-response curves. Induction equivalency factors of strong inducers, based on benzo[k]fluoranthene (BkF) as the reference compound, ranged from 0.03 to 0.16. Trout exposed to mixtures of strong inducers (2, 4, and 6 equipotent parts) at 0.32-, 1.0-, or 3.2-nM BkF-equivalents showed exposure-dependent increases in EROD activity, consistent with an additive interaction. The extent of activity did not vary greatly among mixtures and single PAHs at a given induction equivalent quantity (IEQ). Induction equivalency factors could not be calculated for weak inducers because the range of induction was too low. Hence, each weak inducer was added to mixtures at concentrations that induced EROD activity fivefold. These mixtures appeared additive because binary and quaternary mixtures caused about 10- and 20-fold induction, respectively. Strong inducers mixed the same way also showed additivity. In contrast, EROD induction by mixtures containing both strong and weak PAHs was 800 to 900% greater than expected, suggesting synergistic interactions. Therefore, if mixtures are composed of PAHs that behave similarly, IEFs may be a suitable approach for assessing risk. However, for mixtures that contain PAHs of differing potency and efficacy, bioassays will be a more reliable measure of risk than IEFs.

Animals↗
PubMed2001

Spinocerebellar ataxia--type 6.

Fifty six years lady presented with pure cerebellar ataxia with positive family history from paternal side presented to our clinic. DNA screening found to be SCA6. This is the first case report of SCA6 from India.

Female↗
PubMed1999

Glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) by the human UDP-glucuronosyltransferases encoded at the UGT1 locus.

7-Ethyl-10-hydroxycamptothecin (SN-38) is a very promising anticancer drug used for the treatment of metastatic colonrectal cancer. SN-38 is the active metabolite of irinotecan, a semisynthetic anticancer drug derived from 20(S)camptothecin. In this study, we examined the potential for each of the UGT1-encoded isoforms (UGT1A1 and UGT1A3 through UGT1A10) to glucuronidate SN-38. The amount of specific protein for each isoform was determined by Western blot analysis. Although UGT1A1 was previously shown to metabolize this drug, the results of this study show that UGT1A7 glucuronidates this chemical at a 9- to 21-fold higher level at pH 6. 4 and pH 7.6, respectively, than that by UGT1A1. The activity of UGT1A7 is from 8.4- to 19-fold higher at pH 6.4 and 12- to 40-fold higher at pH 7.6 than that by the other 7 UGT1 encoded isoforms. UGT1A7 glucuronidates SN-38 with an apparent Km of 5 microM. Hence, the distribution of this isoform in the gastrointestinal tract has the potential to impact the effectiveness of this chemotherapeutic agent.

Animals↗
PubMed1999

Glucuronidation of benzidine and its metabolites by cDNA-expressed human UDP-glucuronosyltransferases and pH stability of glucuronides.

Although glucuronidation is considered a necessary step in aromatic amine-induced bladder cancer, the specific enzymes involved are not known. This study assessed the capacity of five different human recombinant UDP-glucuronosyltransferases expressed in COS-1 cells to glucuronidate benzidine, its metabolites and 4-aminobiphenyl. [(14)C]UDP-glucuronic acid was used as co-substrate. UGT1A1, UGT1A4 and UGT1A9 each metabolized all of the aromatic amines. UGT1A9 exhibited the highest relative rates of metabolism with preference for the two hydroxamic acids, N-hydroxy-N-acetylbenzidine and N-hydroxy-N,N'-diacetylbenzidine. UGT1A9 metabolized 4-aminobiphenyl approximately 50% faster than benzidine or N-acetylbenzidine. UGT1A4 N-glucuronidated N'-hydroxy- N-acetylbenzidine at the highest relative rate compared with the other transferases. UGT1A6 was effective in metabolizing only four of the eight aromatic amines tested. UGT1A1 demonstrated more extensive metabolism of the hydroxamic acid, N-hydroxy-N,N'-diacetylbenzidine, and the ring oxidation product, 3-OH-N,N'-diacetylbenzidine, than it did for the other six amines. UGT2B7 was the only product of the UGT2 gene family examined and it metabolized all the aromatic amines at similar low relative levels compared with a preferred substrate, 4-OH-estrone. The K(m) values for N-acetylbenzidine metabolism by UGT1A1 and UGT1A4 were 0.37 +/- 0.14 and 1.8 +/- 0.4 mM, respectively. The O-glucuronide of 3-OH-N,N'-diacetylbenzidine was not hydrolyzed during a 24 h 37 degrees C incubation at either pH 5. 5 or 7.4. Likewise, the O-glucuronide of 3-OH-benzidine was stable at pH 7.4, with 52% remaining at pH 5.5 after 24 h. These results suggest the following relative ranking of transferase metabolism: UGT1A9 > UGT1A4 > > UGT2B7 > UGT1A6 approximately UGT1A1. The relative pH stability of O-glucuronides is consistent with a role in detoxification and excretion of aromatic amines, while the acid lability of N-glucuronides is consistent with delivery of these amines to the bladder epithelium for activation, resulting in DNA adducts which may lead to mutations.

Base Sequence↗
PubMed1997

Inactivation of glyceraldehyde-3-phosphate dehydrogenase of human malignant cells by methylglyoxal.

The effect of methylglyoxal on the activity of glyceraldehyde-3-phosphate dehydrogenase (GA3PD) of several normal human tissues and benign and malignant tumors has been tested. Methylglyoxal inactivated GA3PD of all the malignant cells (47 samples) and the degree of inactivation was in the range of 25-90%, but it had no inhibitory effect on this enzyme from several normal cells (24 samples) and benign tumors (13 samples). When the effect of methylglyoxal on other two dehydrogenases namely glucose 6-phosphate dehydrogenase (G6PD) and L-lactic dehydrogenase (LDH) of similar cells was tested as controls it has been observed that methylglyoxal has some inactivating effect on G6PD of all the normal, benign and malignant samples tested, whereas, LDH remained completely unaffected. These studies indicate that the inactivating effect of methylglyoxal on GA3PD specifically of the malignant cells may be a common feature of all the malignant cells, and this phenomenon can be used as a simple and rapid device for the detection of malignancy.

Carcinoma, Squamous Cell↗
PubMed1997

Profile of electrocardiographic changes in Duchenne muscular dystrophy.

Cardiac changes often culminating in cardiac failure are at times a dramatic cause of death in patients of Duchenne muscular dystrophy. These changes are probably invariable in such cases though they may escape detection in early stages by clinical examination or radiological investigation. Electrocardiography serves as a sensitive, non-invasive and inexpensive tool to detect these changes. Fifty-four cases of Duchenne muscular dystrophy were studied clinically and were confirmed by biochemical and electroneuromyographic studies. They were then subjected to electrocardiographic studies. A number of electrocardiographic changes were observed, like tachycardia in 77.77%, deep Q in leads I, aVL, V6 in 53.70%, prolonged VAT in 37.03%, deep Q in leads II, III, aVF in 29.62% and prolonged Q-Tc interval in 25.92% cases. Some of these were distinctive enough to warrant attention for cases of Duchenne muscular dystrophy.

Adult↗
PubMed1997

Cell mediated immune status in malignancy--pretherapy and post-therapy assessment.

Twenty-eight cases of malignancies of different kinds were studied to assess T-cell activity and population before and after institution of therapy. Fifteen cases were diagnosed as non-metastasising squamous cell carcinoma of larynx, pharynx, laryngopharynx, hypopharynx and tonsils. Seven cases were non-metastasising infiltrating duct carcinoma of breast and 6 cases were non-Hodgkin's lymphoma (NHL). It was observed that 3 out of 15 cases (20%) of squamous cell carcinoma cases were Mantoux test (MT) negative with a T-cell population of less than 40%, 2 out of 7 cases (28.6%) of infiltrating duct carcinoma of breast were MT negative with a T-cell population of less than 40% and 3 out of 6 cases (50%) of NHL were MT negative with a T-cell population of less than 40%. The normal controls, consisting of apparently normal healthy adults, had a T-cell population of more than 40% and were all MT positive. The patients who showed a negative skin test and a T-cell population less than 40% were further subjected to assessment of T-cell population and activity after appropriate therapy, and clinical cure of the disease. It was observed that 2 out of 3 cases (66.66%) of squamous cell carcinomas, 2 out of 2 cases (100%) of adenocarcinomas and one out of 3 cases (33.33%) of NHL showed positive conversion with a T-cell population of more than 40%.

Adult↗