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A K Roy

Publications and source records attributed to A K Roy.

At least 73 records · Page 4Linked to original sources
PubMed1993

A distal activation domain is critical in the regulation of the rat androgen receptor gene promoter.

The far upstream region of the rat androgen receptor (AR) gene has been cloned, and the nucleotide sequence up to -2656 bp established. Nested deletion mutants of rat AR 5' flanking sequences were ligated to the luciferase reporter gene, and their promoter activities were examined in transfected COS1 cells. Results show a critical cis-acting domain located between positions -960 and -940. Deletion of this cis element resulted in a greater than 90% decrease in the promoter activity. A nuclear protein that specifically binds to this 21-nucleotide sequence was identified by gel mobility shift analysis. The -960/-940 cis element has no identify to the binding sequence of any known transcription factor. Furthermore, the cognate binding protein is present in both rat and human (HeLa) cell nuclear extracts. We conclude that a novel trans-activator interacting at the -960/-940 region plays a critical role in the regulation of AR gene expression.

Animals↗
PubMed1993

Relative efficiency of Phyllanthus emblica fruit extract and ascorbic acid in modifying lead and aluminium-induced sister-chromatid exchanges in mouse bone marrow.

The identification of desmutagens and bioantimutagens in plants has prompted the search for additional plant extracts capable of modifying adverse cellular effects of environmental toxicants. The protective action of crude extracts of Phyllanthus emblica fruits (PFE) against lead (Pb) and aluminium (Al)-induced sister chromatid exchanges (SCEs) was studied in bone marrow cells of Mus musculus. The modifying effect of the crude extract was compared with that of comparable amounts of synthetic ascorbic acid (AA), a major component of the fruits. Oral administration of PFE or AA for 7 consecutive days before exposure of mice to the metals by intraperitoneal injections reduced the frequencies of SCEs induced by both metals. PFE afforded a more pronounced protective effect than AA in counteracting the genotoxicity induced by both Al and Pb: This difference was significant with Pb. The higher protection afforded by PFE may be attributed to the interaction of AA with other natural ingredients present in the crude fruit extract.

Alum Compounds↗
PubMed1993

Phenytoin-induced chronic hepatitis.

Phenytoin has been associated with acute hepatotoxicity. Chronic liver enzyme abnormalities associated with phenytoin have been attributed to enzyme induction. There have been no reports of phenytoin-induced chronic hepatitis. We describe an asymptomatic 52-year-old woman who received phenytoin sodium for 11 years and was found to have elevated serum aminotransferases. Assays for hepatitis A, B, and C were negative. Liver biopsy was performed and showed chronic persistent hepatitis. This documentation of phenytoin-induced chronic persistent hepatitis was proven by histology and its etiology confirmed by drug withdrawal and by rechallenge. Although uncommon, this entity is important to recognize in the differential diagnosis of asymptomatic chronic hepatic enzyme dysfunction.

Biopsy↗
PubMed1993

Zinc supplementation in protein energy malnutrition.

A pair-matched controlled study was done with 30 children (15 males, 15 females) of mild to moderate PEM in test and equal number in control groups, aged 8-24 months old. At the beginning, in both test and control groups parents were advised to provide sufficient amount of home cooked foods so that the child received on an average 100-150 Kcal/kg/day of energy and 2-3 g/kg/day of protein. Vitamin supplements were provided to all children in both groups. In addition, the test group received a supplementation of 5.625 mg of elemental zinc daily orally while controls received a placebo. Evaluation at the end of 3 months showed that children in test group had a weight gain of 3.742 +/- 0.488 kg against 2.035 +/- 0.383 kg of the control group. Similarly, weight velocity was 5.752 +/- 0.818 g/kg/day in test group against 3.153 +/- 0.617 g/kg/day of the control group. These differences in weight gain and weight velocity were highly significant (p < 0.001). Serum zinc levels, initially and at the end of study were 87.5 +/- 9.6 micrograms/dl and 121.0 +/- 10.1 micrograms/dl, respectively in test group in comparison to 91.2 +/- 9.8 micrograms/dl and 91.0 +/- 10.1 micrograms/dl in controls. This difference was also highly significant (p < 0.001). The daily total calorie intake remained comparable in both groups. Our observations suggest that zinc supplementation during nutritional rehabilitation of mild to moderate PEM hastens the recovery.

Administration, Oral↗
PubMed1993

Study of photodynamic reactions of p-nitroacetophenone using ESR and optical techniques.

The photosensitizing properties of p-nitroacetophenone (PNAP), a well-known radiosensitizer, have been studied in near UV region. The mechanism of PNAP photosensitization has been investigated by testing the efficiency of singlet oxygen production using photooxidation of 2,2,6,6-tetramethylpiperidine (TEMP) and photodegradation of guanosine. In both the cases, the enhancement effect of deuterated solvents has been observed. Results of these experiments suggest the significant role of type II mechanisms in PNAP photosensitization.

Acetophenones↗
PubMed1992

CD7 augments T cell proliferation via the interleukin-2 autocrine pathway.

The role of CD7, a T cell differentiation antigen, in T cell function is not known at present; this study evaluates the effect of anti-CD7 mAb in PMBC cultures activated with suboptimal concentrations of lectins, antigens, and anti-CD3 mAb. We found that the inclusion of anti-CD7 resulted in increased IL-2 production and IL-2R-alpha expression in these cultures. H-7, a protein kinase C (PKC) inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor, significantly suppressed the proliferation of T cells in comitogenic assays. This suggested that the comitogenic effect mediated by CD7 molecule involved both the PKC and the PTK pathways of T cell activation. These drugs appeared to affect the CD7-mediated effects by inhibiting the IL-2 autocrine pathway, especially the up-regulation of IL-2R-alpha since inhibition was not relieved with exogenous rIL-2. Taken together, our results suggest that CD7 augments T cell function by up-regulating IL-2R-alpha expression and IL-2 production via multiple pathways of protein phosphorylation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Metabolism and DNA binding of 2-nitropyrene in the rat.

2-Nitropyrene (2-NP), a contaminant of ambient air, is a potent bacterial mutagen in the Ames assay and induces leukemia/lymphoma in female Sprague-Dawley rats. To understand the mechanistic basis for its tumorigenic activity, it is essential to elucidate the metabolic pathways of 2-NP in vivo. Such knowledge will also assist in developing analytical methods for monitoring human exposure to nitropolynuclear aromatic hydrocarbons in ambient air. Thus, 2-nitro[U-4,5,9,10-14C]pyrene was synthesized and administered to male F344 rats by intragastric gavage at a dose of 30 mg (0.4 mCi/mM)/kg body weight. During the first 48 h, 57.5% of the dose was eliminated in the feces and 9.7% was eliminated in the urine. Correspondingly, after 168 h, 58.9 and 10.6% were excreted in feces and urine, respectively. Fecal metabolites (isolated amounts) included 6-hydroxy-2-acetylaminopyrene (19.5%), 6-hydroxy-2-aminopyrene (10.4%), 2-aminopyrene (10.0%), 2-acetylaminopyrene (0.8%), and unmetabolized 2-nitropyrene (10.0%). 6-Hydroxy-2-acetylaminopyrene, 6-hydroxy-2-aminopyrene, and 2-aminopyrene were identified as their acetyl derivatives by comparison of their chromatographic retention times, mass spectra, and UV spectra to those of synthetic standards. Urinary metabolites included 6-hydroxy-2-acetylaminopyrene (2.0%); glucuronide conjugates were tentatively identified (3.2%). The results of this study indicate that nitroreduction and ring oxidation are metabolic pathways in vivo. For DNA binding studies, rats were treated with 2-nitro[4,5,9,10-3H]pyrene [1.6 mg (598 mCi/mM)/kg body weight]. The levels of binding (pM bound/mg DNA) were as follows: 1.3, liver; 1.14, mammary tissue; 0.65, lung; 1.67, kidney; and 1.8, bladder. Upon high-performance liquid chromatographic analysis of the DNA hydrolysate (liver, mammary, and kidney), approximately 2.0% of the radioactivity coeluted with the synthetic markers derived from nitroreduction, N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene. Thus, simple nitroreduction of 2-NP does not significantly contribute to the total DNA binding of 2-NP metabolites in vivo. The significance of each pathway for the tumorigenic effects of 2-NP remains to be examined.

Air Pollutants↗
PubMed1992

Modification of metal-induced micronuclei formation in mouse bone marrow erythrocytes by Phyllanthus fruit extract and ascorbic acid.

The comparative efficacy of Phyllanthus emblica fruit extract, and its main constituent, ascorbic acid, in modifying the cytotoxic action of lead and aluminium was evaluated in vivo in bone marrow cells of Mus musculus. Oral administration of Phyllanthus emblica fruit extract for 7 days before exposure to the metals through intraperitoneal injections reduced the frequency of micronuclei induced by all doses of both metals. Priming with comparable doses of synthetic ascorbic acid reduced micronuclei formation induced by both doses of aluminium and only the lower dose of lead. With the higher dose of lead (20 mg/kg body wt.) priming with ascorbic acid increased the frequency of micronuclei when compared with mice administered lead alone. The greater efficacy of Phyllanthus fruit extract in alleviating metal-induced clastogenicity may be due to the combined action of all ingredients in the crude extract, rather than to ascorbic acid alone.

Aluminum↗
PubMed1992

Spatio-temporal expression of estrogen sulfotransferase within the hepatic lobule of male rats: implication of in situ estrogen inactivation in androgen action.

Estrogen sulfotransferase (EST) catalyzes transfer of the sulfate group from phosphoadenosine phosphosulfate to estrogenic steroids. Since estrogen sulfates do not bind to the estrogen receptor with high affinity, EST can control the intracellular level of the receptor-active estrogens. Androgen action in the rat liver, as indicated by the androgenic induction of alpha 2u-globulin, is inhibited by low levels of estrogens. Thus, in situ estrogen inactivation by EST is expected to increase hepatic androgen sensitivity. During the lifespan of the animal, rat liver undergoes three distinct phases of androgen sensitivity, i.e. prepubertal androgen insensitivity, androgen sensitivity after approximately 40 days of age, and androgen insensitivity during senescence (greater than 750 days). EST in the liver is expressed only after puberty, when the liver becomes androgen sensitive. Furthermore, localization of EST and its corresponding mRNA within the lobular unit of the liver demonstrates that only androgen-responsive hepatocytes located around the central vein contain immunoreactive EST and its corresponding mRNA. These temporal and spatial correlations of EST expression and hepatic androgen sensitivity support the concept that steroid-inactivating enzymes play important roles in sex hormone action.

Aging↗
PubMed1992

Estrogen sulfotransferase of the rat liver: complementary DNA cloning and age- and sex-specific regulation of messenger RNA.

Mammalian estrogen sulfotransferase (EST; EC 2.8.2.4) sulfurylates the hydroxyl group of estrogenic steroids by transferring the sulfate from a cosubstrate adenosine 3'-phosphate-5'-phosphosulfate. Sulfurylated steroids do not bind to the estrogen receptor with high affinity and, therefore, are hormonally inactive. We have purified rat liver EST and developed monoclonal antibody to this enzyme. By immunoscreening a lambda gt-11 expression library constructed from male rat liver cDNAs, the cDNA clone corresponding to EST was identified and isolated. A recombinant expression plasmid (pCMV5) containing this cDNA insert when transfected into COS-7 cells generated both immunologically and enzymatically active EST. With the help of this cDNA probe, we have explored the regulation of the EST mRNA in the liver and the possible role of this enzyme in sex hormone action. During the lifespan of male rats, only the young adult animals show hepatic androgen responsiveness. Also, estrogenic hormones strongly antagonize androgen action in the rat liver. Northern blot analysis of liver RNA derived from male rats of different ages shows that the androgen sensitivity of young adult animals is associated with a high expression of EST mRNA. During the same period, mRNA corresponding to dehydroepiandrosterone sulfotransferase is markedly (approximately 10-fold) down-regulated. Such a correlation is in concordance with the role of these enzymes in the maintenance of hepatic androgen sensitivity during young adult life by inactivating the estrogenic and sparing the androgenic steroids. Furthermore, the increase in the hepatic androgen sensitivity of androgen-treated female rats is also associated with the induction of EST.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Regulation of steroid hormone action in target cells by specific hormone-inactivating enzymes.

The target cell sensitivity of steroid hormones is determined by the concerted action of specific hormone receptors and steroid-inactivating enzymes. In recent years, a considerable amount of knowledge has been obtained on hormone receptor concentration-based target cell sensitivity. However, an equal understanding of the role of specific steroid-inactivating enzymes in hormone action is absent. This review highlights the importance of specific steroid-inactivating enzymes in the control of target cell sensitivity of mineralocorticoids, glucocorticoids, androgens, and estrogens. Two classes of enzymes that are actively involved in this process are hydroxysteroid dehydrogenases and hydroxysteroid sulfotransferases. Some of the target cells in which the critical roles of these enzymes have been extensively characterized are those of the kidney, endometrium, and liver. cDNA for many of these enzymes have already been cloned, and rapid progress in the elucidation of this component of steroid hormone action is anticipated.

17-Hydroxysteroid Dehydrogenases↗
PubMed1992

Peripartum cerebral venous thrombosis.

The clinical and computed tomography (CT) features of 25 patients with peripartum CVT are described. Majority of the patients presented in postpartum period and did not receive proper antenatal care. Headache (92%), altered sensorium (80%, seizures (76%), papilloedema (80%) and hemiplegia (52%) were the common modes of presentation. CT findings included diffuse brain oedema (52%), haemorrhagic or nonhaemorrhagic infarctions on one or both sides of brain (48%), gyral enhancement (40%) and tentorial enhancement (16%). While 15 patients made good recovery, 3 cases (12%) died during acute stage of illness.

Adult↗
PubMed1992

Neuromyotonia.

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Adult↗
PubMed1991

Identification of the major metabolites and DNA adducts formed from 2-nitropyrene in vitro.

In contrast to 1-nitropyrene (1-NP), which is the most abundant nitropolycyclic aromatic hydrocarbon in numerous environmental sources, 2-nitropyrene (2-NP) has been detected only in the ambient air and not in direct emissions. Thus, 2-NP can be used as an indicator for monitoring human exposure to nitropolynuclear aromatic hydrocarbons in ambient air. Therefore, it is essential to determine the possible metabolic pathways of 2-NP. The metabolism of 2-NP by rat liver 9000 g supernatant was investigated. Under aerobic conditions, ring oxidation to 6-hydroxy-2-nitropyrene and nitroreduction to 2-aminopyrene (2-AP) were observed. When incubations were carried out in an atmosphere of nitrogen, 2-AP was the only metabolite detected. These results are consistent with those observed with 1-NP. In vitro metabolic activation of 2-NP to DNA adducts catalyzed by xanthine oxidase was also examined. Two adducts were characterized as N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene. The presence of deoxyadenosine adduct, which is derived from the nitroreduction pathway, may contribute to the powerful direct-acting mutagenicity of 2-NP.

Animals↗