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Biomedical subjects

S Thakur

Publications and source records attributed to S Thakur.

At least 37 records · Page 2Linked to original sources

Positive regulation of the BRCA1 promoter.

Inherited mutations in the BRCA1 gene, presumably leading to loss of function, confer susceptibility to breast and ovarian neoplasms and are thought to be responsible for approximately 2.5-5% of all breast cancers. It has been suggested that alternative mechanisms, such as disruption of transcription, may also be involved in the suppression of BRCA1 gene expression/function in breast cancers. Therefore, we initiated studies on the BRCA1 transcriptional promoter. Utilizing systematic promoter deletions and transient transfection assays, a 36-base pair region was determined to be important for the positive regulation of BRCA1 transcription. Deletion of this positive regulatory region resulted in a significant loss of promoter activity. Utilizing DNA binding assays, proteins with specific affinities for the positive regulatory region were detected. Disruption of the DNA-protein complexes could affect normal BRCA1 transcription and may contribute to breast cancer susceptibility.

Breast Neoplasms↗

Recovery from prolonged metabolic acidosis due to accidental ethylene glycol poisoning.

In this report, we describe a case of accidental ethylene glycol poisoning in a 90-year-old woman. Despite a delay in diagnosis and treatment of over 24 hours, this patient recovered completely from profound and lengthy metabolic acidosis. She is therefore the oldest known survivor of severe ethylene glycol intoxication. We review 79 additional cases of ethylene glycol intoxication reported in the literature since 1976 and comment on diagnostic, therapeutic and prognostic features of this form of poisoning.

Acidosis↗

Differential effects of chemical and mechanical colonic irritation on behavioral pain response to intraperitoneal acetic acid in mice.

Abdominal contractions are a viscerosomatic reflex response to noxious colorectal irritation in rats. In this study we characterize the modulating effect of chemical and mechanical colonic irritation on this reflex response to peritoneal irritation induced by diluted acetic acid (HAc) in conscious C57BL/6N mice. Pain responses were scored by counting the number of abdominal contractions during the 30-min period after intraperitoneal (i.p.) injection of either vehicle or HAc. Abdominal contractions were induced by 0.6% but not by 0.3% HAc. Chemical irritation of the colon by intraluminal 25% turpentine did not produce abdominal contractions by itself, but significantly increased the effect of both 0.3 and 0.6% i.p. HAc, administered 60 min after the luminal stimulus. Mechanical stimulation of the anorectum and colon by insertion of a balloon did not modify the effect of 0.6% HAc, while the insertion plus the inflation to 0.1 and 0.2 ml (30 s on/30 s off for 10 min) reduced the response to i.p. HAc by 35 and 88%, respectively. This inhibitory effect was reversed by naloxone (5 mg/kg, s.c.) pretreatment, while naloxone alone did not modify the effect of 0.6% HAc. These results demonstrate that chemical irritation of visceral afferents in the colonic mucosa and peritoneum of mice interact to enhance viscerosomatic pain responses, while the activation of colonic mechanoreceptors inhibits peritoneal irritation-induced pain responses and induces a freezing behavior by a naloxone-sensitive mechanism.

Abdominal Muscles↗

Lipid profile in chronic renal failure at a moderate altitude of 2250 m.

There is no statistically significant difference between the two groups (CRF and control) as regard the serum lipid values regardless of the severity, age and etiology. The dyslipidemia in present study not correlate with the risk of developing cardiovascular disease reinforcing the earlier finding of increased levels of HDL-c at higher altitudes. Still in practice the lipid profile should be estimated in all patients and those found to be inappropriately high with increased cardiovascular risk should be treated as recommended in the general population.

Adult↗

Localization of BRCA1 and a splice variant identifies the nuclear localization signal.

Inherited mutations in BRCA1 confer susceptibility to breast and ovarian neoplasms. However, the function of BRCA1 and the role of BRCA1 in noninherited cancer remain unknown. Characterization of alternately spliced forms of BRCA1 may identify functional regions; thus, we constructed expression vectors of BRCA1 and a splice variant lacking exon 11, designated BRCA1 delta 672-4095. Immunofluorescence studies indicate nuclear localization of BRCA1 but cytoplasmic localization of BRCA1 delta 672-4095. Two putative nuclear localization signals (designated NLS1 and NLS2) were identified in exon 11; immunofluorescence studies indicate that only NLS1 is required for nuclear localization. RNA analysis indicates the expression of multiple, tissue-specific forms of BRCA1 RNAs; protein analysis with multiple antibodies suggests that at least three BRCA1 isoforms are expressed, including those lacking exon 11. The results suggest that BRCA1 is a nuclear protein and raise the possibility that splicing is one form of regulation of BRCA1 function by alteration of the subcellular localization of expressed proteins.

3T3 Cells↗

Brainstem auditory evoked response in neonates with birth asphyxia.

OBJECTIVE: To determine the brainstem auditory evoked response (BAER) abnormalities and their reversibility in neonates with birth asphyxia. DESIGN: Prospective case control study. SETTING: Tertiary care teaching hospital. METHODS: 30 term Neonates with 5-min Apgar < 6 and hypoxic ischemic encephalopathy (HIE) underwent BAER testing with follow up at 3 months. An equal number of normal term neonates served as controls. RESULTS: 13 out of 30 (43.3%) neonates with birth asphyxia showed some abnormality in BAER wave form. The commonest type of BAER abnormalities seen were transient prolongation of latencies of various waves (69.2%) and prolonged interside latency difference (69.2%). Other abnormalities observed were prolonged interwave interval (23.1%) and prolonged interside interval difference (7.7%). Abnormalities in BAER were significantly associated with stages of HIE and duration of neurological abnormalities more than 5 days. On follow up of 16 cases at 3 months of age, BAER abnormalities reverted back to normal in all the neonates. The Denver Developmental Screening Test (DENVER II) was suspect in 4 cases but the BAER was normal. CONCLUSION: BAER abnormalities in asphyxic neonates are transient and revert back to normal at 3 months of age. BAER does not appear to be a useful tool for early detection of neurological handicaps.

Analysis of Variance↗

Tuberculous duodenal obstruction--a case report.

Proximal duodenal obstruction due to tuberculosis can masquarade as duodenal ulcer. Although commonest cause of duodenal obstruction is ulcer, other causes must be considered, particularly tuberculosis which is common in tropics.

Adult↗

"Significance of serum gamma glutamyl transpeptidase in cholestatic jaundice".

In conclusion, our study showed that serum G.G.T rises in cholestasis, and the rise is significantly higher in extraphepatic cholestasis as compared to intrahepatic cholestasis. Serum G.G.T has not shown any superiority over alkaline phosphatase in the evaluation of cholestatic liver disease. However, two considerations must caution against the use of serum G.G.T. alone for evaluation of hepatobiliary disease. The first of these is the lack of specificity for hepatobiliary disease. Serum G.G.T. activity can be elevated in some non-hepatic disorders such as acute pancreatitis, congestive cardiac failure, myocardial infarction, diabetes mellitus and alcoholism. Determination of serum G.G.T. in these patients is of no value. Second, the possibility that changes in serum G.G.T. activity results from drug administration in man.

Alkaline Phosphatase↗

Regulation of nerve growth factor mRNA by interleukin-1 in rat hippocampal astrocytes is mediated by NFkappaB.

Cytokines such as interleukin-1beta (Il-1) are produced in the brain during development and during inflammatory processes that result from lesions or disease. One function of Il-1 in the brain appears to be the stimulation of astrocytes to proliferate and produce a variety of cytokines and trophic factors, including nerve growth factor. The mechanisms by which Il-1 exerts its actions on astrocytes remain poorly defined. We present evidence that this cytokine elicits activation of the NFkappaB transcription factor and that this transcription factor mediates effects of Il-1 on nerve growth factor mRNA expression. Elucidation of the processes by which cytokines activate astrocytes and influence trophic factor expression may provide insight into mechanisms governing inflammatory processes within the central nervous system.

Animals↗

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition.

The role of oxidative stress as a mechanism of hepatic injury caused by isoniazid (INH) was investigated in young growing rats. The interaction of moderate and severe degree of protein-energy malnutrition (PEM) was also investigated. Hepatic injury was produced by giving 50 mg/kg/day of INH for 2 weeks. Liver showed kupffer cell hyperplasia along with patchy sinusoidal congestion in hematoxylin (H) and eosin (E) staining. However, diffuse microglobules of oil red O' positive fat globules could be demonstrated in frozen sections stained with oil red O'. The concomitant elevation of serum ALT/AST added support to the histopathologic injury. Electronmicroscopic analysis revealed the proliferation of rough endoplasmic reticulum in INH-treated groups. The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism. Glutathione reductase activity was elevated concomitantly in both the tissues. A significant decrease in the activity of glutathione peroxidase and catalase is again indicative of diminished capacity to handle the disposal of hydrogen peroxide (H2O2) and lipid peroxides. All these alterations indicated that the damage to the liver cell could well be operating through the inefficient disposal of superoxides (O-2) and H2O2. A profound decrease in the protective mechanism further aggravated the picture in moderate and severe PEM, which was observed with INH alone.

Animals↗

Unusual diversity of human rotavirus G and P genotypes in India.

Between April and December 1993, we determined P and G genotypes of group A rotavirus strains obtained from children admitted to diarrhea treatment centers in five Indian cities. From a total of 63 rotavirus-positive specimens, we identified 10 different strains with five different G genotypes and four distinct P types by using reverse transcription-PCR. The common worldwide strains G1P8, G2P4, G3P8, and G4P8 were underrepresented among Indian children (33%), whereas strains of P type 6 (G1P6, G2P6, G3P6, G4P6, and G9P6), which primarily infect asymptomatic newborns but are rare in children with diarrhea were common in India (43%). Of these, G9P6, a strain not previously reported to be found in children with diarrhea, was the most prevalent (22%). Eleven percent of the strains were nontypeable, and another 11% of the specimens had mixed infections. Using digoxigenin-labeled, genotype-specific hybridization probes, we confirmed all G9 strains and mixed infections tested and identified three nontypeable strains (one G9 and two P8). The epidemiological significance of G9 rotavirus strains, if confirmed in other settings, may have important implications for vaccine development.

Base Sequence↗

Protein-energy malnutrition and oxidative injury in growing rats.

1. Weaning rats were fed ad libitum isocaloric diets containing 5% and 20% casein based proteins. 5% protein diet was protein deficient diet. Pair fed rats with the 5% protein group were maintained simultaneously on 20% protein diet but the amount restricted to the amount taken up by PEM group. 2. Glutathione, antioxidative enzymes, lipid peroxidation and histopathological studies in liver and only glutathione and antioxidative enzymes in blood were carried out. 3. Rats fed the 5% protein diet developed a severe protein energy malnutrition (PEM) whereas those on pair-fed diet developed mild to moderate PEM. 4. Glutathione related thiols superoxide dismutase, glutathione peroxidase, catalase and glutathione-Stransferase with (1 Chloro 2,4-dinitro benzene (CDNB) substrate) were decreased in liver with concomitant increase of lipid peroxidation in severe PEM. In blood glutathione, glutathione peroxidase and catalase were decreased while superoxide dismutase was increased in severe PEM group. 5. Mild to moderate PEM (pair-fed group) also resulted in similar changes in liver except glutathione peroxidase, lipid peroxidation in liver and superoxide dismutase in blood. 6. Hepatic injury was detectable only in the severe PEM group. 7. Oxidative-stress and hepatic injury occurred in severe PEM and to a lesser degree in mild to moderate PEM.

Animals↗

Perinatal mortality in urban slums in Lucknow.

OBJECTIVES: To determine the perinatal mortality rate (PNMR) in the urban slums of Lucknow DESIGN: Cross-sectional survey. SETTING: Twenty five Anganwadi centres of urban Lucknow, with a population of 25,901. METHODS: Data was collected on birth and early neonatal deaths, gestational age of the neonate (determined at birth) and maternal variables like socio-economic status, maternal age, parity, and bad obstetrical history from January 1992 to March 1993. RESULTS: There were 966 births with a still-birth rate of 37.2 and PNMR of 59.0 per 1000. The relative risk of perinatal mortality with lower socio-economic status was 1.87, bad obstetrical history 2.18, and gestational age < 37 weeks 1.95. CONCLUSIONS: Further reduction in PNMR may be possible with focussed medical services to women of low socio-economic status having bad obstetrical history and those delivering before term.

Cross-Sectional Studies↗

Poncet's disease--case report.

Poncet's disease is a rare polyarthritis occurring in patients with tuberculous infection. We describe two cases of polyarthritis, one secondary to pulmonary tuberculosis, the other secondary to tuberculous infection of lymph nodes. In both cases the arthritis rapidly subsided with chemotherapy.

Adult↗