Search PubMed⌕ Search

Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 181 records · Page 10Linked to original sources
PubMed2001

Protection of sodium arsenite-induced ovarian toxicity by coadministration of L-ascorbate (vitamin C) in mature wistar strain rat.

Arsenic, a major water pollutant in India, produces toxic effects on female reproductive system in rodent models at the dose available in drinking water in arsenic-intoxicated zones. This study examines the coadministration of L-ascorbate (vitamin C) on ovarian steroidogenesis, plasma levels of gonadotrophins, brain monoamines, and ovarian as well as uterine peroxidase activities in sodium arsenite-treated rats. After sodium arsenite treatment, relative ovarian and uterine weights, ovarian Delta5-3beta-HSD and 17beta-HSD activities, plasma levels of gonadotrophins, norepinephrine levels in midbrain and diencephalon, and the activities of peroxidase in ovary and uterus were decreased significantly. On the other hand, serotonin levels in midbrain and diencephalon were increased significantly 28 days after sodium arsenite treatment at the dose of 0.4 ppm/100 g body weight/rat/day. All these parameters were protected significantly and in most cases were unchanged from control level when L-ascorbate at 25 mg/100 g body weight/rat/day was coadministered orally with sodium arsenite. This cotreatment of L-ascorbate with sodium arsenite also restored the estrous cycle in a regular manner. We concluded that L-ascorbate plays a pivotal role in maintaining normal ovarian activities and brain monoamines in arsenic-treated rats.

Animals↗
PubMed2001

Deciphering the genetic architecture of a multivariate phenotype.

A heritable multivariate quantitative phenotype comprises several correlated component phenotypes that are usually pleiotropically controlled by a set of major loci and environmental factors. One approach to decipher the genetic architecture of a multivariate phenotype, in particular to map the underlying loci, is to reduce the dimensionality of the data by means of a data reduction technique, such as principal component analysis. The extracted principal components are then analyzed in conjunction with marker data to map the underlying loci. We have examined the efficiency of this approach with and without taking into account the correlation structure of the multivariate phenotype when extracting principal components. We have assumed that genome-wide scan data on sibpairs are available for low-density (widely spaced) and high-density markers. Using extensive simulations, based on three models of the multivariate phenotype, we have shown that although ignoring the correlation structure of the multivariate phenotype does not have any serious impact on the efficiency of mapping the underlying trait loci in wide marker intervals, there is a significant adverse effect of this practice for fine-mapping. We, therefore, recommend that the correlation structure of the multivariate phenotype be carefully examined to decide on the strategy of extracting principal components for deciphering the genetic architecture of the multivariate phenotype.

Chromosome Mapping↗
PubMed2001

X-ray structure, solution properties, and biological activity profile of vanadocene(IV) acetylacetonate complex,.

The structure of [V(eta5-C5H5)2(CH3C(O)CHC(O)CH3)](O3SCF3) (1) (=[VCp2(acac)](O3SCF3)), a dual-function anti-cancer agent with anti-angiogenic and anti-mitotic properties, was determined by single-crystal X-ray diffraction. The geometry is well described as a pseudo-tetrahedral like structure with the centroids of the cyclopentadienyl rings and the two oxygen atoms of the acetylacetonate ring in the ancillary positions of the central vanadium (IV) atom. The bisector of the V(acac) fragment deviates from the C2 axis of the ligand framework by only 4 degrees, compared to a deviation of 7 degrees for the V(acac) fragment in the tetramethylethano-bridged vanadocene acetyl acetonate complex. Crystal data for 1: space group, P2(1)/c; a=7.5544(9) A, b=14.936(2) A, c=16.193(2) A, beta=102.901(2) degrees, V= 1781.0(4) A3; Z=4; R=0.0506 for 2310 reflections with I> 2sigma(I). This report also details the electron paramagnetic resonance, UV/Vis spectroscopy, electrochemical properties and the biological activity profile of this potent anti-cancer agent.

Angiogenesis Inhibitors↗
PubMed2001

Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments.

The effects of hypothyroidism on parameters of oxidative stress and on intraneuronal distribution of neurofilaments have been investigated in the developing rat brain. Progressive hypothyroidism during the first 4 weeks of postnatal development led to an increase in superoxide dismutase and catalase activity, decline in the level of glutathione and mitochondrial cytochrome c oxidase activity and increase in the level of .OH radical along with enhanced protein carbonylation and lipid peroxidation. Immunocytochemical staining of cryostat sections of normal and hypothyroid cerebella from 25 day postnatal rats with anti neurofilament (NF) light chain (L) antibody showed aberrant accumulation of neurofilaments in the perikaryon of the hypothyroid Purkinje neurons in contrast to relatively uniform distribution in the controls. The morphological and biochemical alterations in the neurons of the developing hypothyroid brain are comparable to those seen in several neurodegenerative diseases.

Animals↗
PubMed2001

Chloroplast fructose-1,6-bisphosphatase from Oryza differs in salt tolerance property from the Porteresia enzyme and is protected by osmolytes.

Salinity exerted a distinctly differential effect on fructose-1,6-bisphosphatase (EC. 3.1.3.11) isolated from salt-sensitive and salt-tolerant rice (Oryza sativa) varieties. Cytosolic and chloroplastic isoforms of the enzyme from salt-sensitive rice seedlings exhibited decreased catalytic activity during growth in the presence of salt. Furthermore, chloroplastic fructose 1,6-bisphosphatase purified from salt-sensitive (O. sativa cv. IR26) and from the wild halophytic rice Porteresia coarctata differed in their in vitro salt tolerance property although they exhibited otherwise identical biochemical and immunological properties. This decline in enzyme activity was not correlated with de novo synthesis of the chloroplastic fructose-1,6-bisphosphatase protein in the presence of salt. The inhibitory effect of increasing concentration of NaCl on in vitro enzymatic activity could be prevented by preincubation of the enzyme with a number of osmolytes with an effectiveness in the order polyol>sugars. Further, the intrinsic tryptophan fluorescence of the purified rice enzyme is altered in vitro with increasing NaCl concentration which could be prevented by preincubation with inositol. Purified chloroplastic fructose-1.6-bisphosphatase from P. coarctata however, exhibits no such inhibition of enzyme activity in vitro or alteration in tryptophan fluorescence with increasing NaCl concentration.

Journal Article↗
PubMed2001

Gramicidin A and its complexes with Cs+ and Tl+ ions in organic solvents. A study by steady state and time resolved emission spectroscopy.

Gramicidin A (gr A), a linear pentadecapeptide containing four trp residues has been studied using steady state and time resolved fluorescence (at 298 K) and phosphorescence (at 77 K) in methanol (CH3OH), ethanol (C2H5OH), dimethyl sulfoxide (DMSO), 1,4-dioxane, 2-methyl tetrahydrofuran (2-MeTHF), ethanol/benzene (C2H5OH/C6H6) mixed solvent. Similar studies have also been carried out in CH3OH containing monovalent cations K+, Cs+, Tl+ and divalent cation Ca2+. Lambda(max) of fluorescence is found to be a good signature of the different forms having double helical structure [dh (1) to dh (4)] (J. Struct. Biol. 121 (1998) 123-141). Steady state and time resolved quenching studies of gr A by KI in CH3OH and DMSO and life time of the emitting singlet states of gr A support that gr A exists as a mixture of different forms of double helical (dh) structure [dh (1) to dh (4)] in CH3OH and as a random coil structure in DMSO. This study further indicates that emitting trp residue in DMSO is better shielded than that in CH3OH. Phosphorescence spectra of gr A at 77 K in CH3OH glass suggests that gr A retains a particular conformation dh (3) in this matrix. The phosphorescence spectra of gr A [conformation dh (4)] in 2-MeTHF at 77 K is further red shifted indicating that among all the dh forms, dh (4) has the emitting trp residue in most hydrophobic environment. The hydrophobicity of the emitting tryptophan environment is thus found to be in the order: dh (1)<dh (3)<dh (4). Since 2-MeTHF forms a clear glass at low temperature, it is thus possible to study the side chain arrangement of gr A dh (4) as a function of temperature. The phosphorescence spectra in different alcohol glassy matrix are in conformity with the observation of different side chain arrangement of gr A as one changes the polarity of alcohol. Steady state and time resolved quenching studies of gr A using Cs+ ion in CH3OH at 298 K clearly demonstrate the two binding sites for the metal ions and provide the value of equilibrium constant of the 'non-emitting' complex of gr A with Cs+ ion in the ground state. The observation of distinct red shift of the (0,0) band of the phosphorescence spectra of the complexes of gr A with K+, Cs+ and Tl+ ions at 77 K compared to that in CH3OH glass confirms the metal ion induced change of conformation in dh (3). The result also suggests that the emitting trp residues in the complexes are in somewhat more hydrophobic environment compared with that in the free gr A in CH3OH glass. The triplet state life time of these complexes indicate that the heavy metal ions Cs+ and Tl+ are within a Van der Waal's distance of emitting trp residue in gr A in CH3OH glass at 77 K so that they are capable of inducing increased spin-orbit coupling due to a heavy atom effect.

Cations, Monovalent↗
PubMed2001

Identification and characterization of an excretory-secretory product from Giardia lamblia.

A 58 kDa excretory-secretory product (ESP) of Giardia lamblia has been characterized. The ESP was purified over 508-fold by a combination of ammonium sulphate precipitation and sequential chromatography on affinity matrix and a gel filtration column. The homogeneity of the purified protein was established by sodium dodecyl sulphate polyacrylamide gel electrophoresis (Mr, 58 kDa) and analytical isoelectrophoresis (pI 4.75). The purified protein was recognized by the pooled sera of G. lamblia-positive patients as well as an antiserum raised against crude Giardia extract, thus indicating it to be an immunodominant parasite product. The ESP was found to agglutinate rabbit erythrocytes. The haemagglutinating activity of this protein was inhibited strongly by thyroglobulin, fetuin, asialofetuin and monosialoganglioside but not by simple sugars. The purified protein was characterized immunochemically and was found to be heat stable as well as protease sensitive. Lectin-binding studies of the purified ESP and its sensitivity to periodic-acid silver staining as well as to metaperiodate treatment clearly indicated its glycoprotein nature. The major localization site of the ESP was found to be on the surface of the parasite as revealed by flow cytometric analysis. Further, this glycoprotein induced fluid accumulation in ligated rabbit ileal loops and revealed a positive skin permeability reaction in the rabbit.

Animals↗
PubMed2001

Immunoprotective efficacy of a purified 39 kDa nymphal antigen of Hyalomma anatolicum anatolicum.

Soluble nymphal antigens (HNAg) were purified by immunoaffinity chromatography using CNBr-activated Sepharose 4B coupled with immunoglobulin ligands from animals immunized with HNAg and 69-71% protected against challenge infestations, and 8% recovery of the purified protein (Aff-HNAg) was obtained. Following immunization of crossbred calves (Bos indicus x Bos taurus) with 1600 sg of Aff-HNAg in three divided doses, significant rejections of larvae (p<0.001, 84.2%), nymphs (p<0.05, 61.4%) and adults (p<0.05, 58.7%) were recorded. No significant changes were recorded in the engorgement weights of the larvae and nymphs, but there was a significant (p<0.05) reduction in the weight of the engorged adults. Immunization conferred a significant decrease in the numbers of resultant nymphs (p<0.001) and adults (p<0.001) that had fed on the immunized animals. SDS-PAGE analysis identified a 39 kDa protein, previously isolated from larvae of Hyalomma anatolicum anatolicum, as the antigen responsible for the induction of resistance against all the stages of the tick.

Animals↗
PubMed2001

Anti-endomysial antibody negative celiac disease: does additional serological testing help?

Anti-endomysium antibodies (AEM) fail to identify all untreated celiac disease (CD) patients. This study aims to determine if additional serology, in particular, IgA anti-tissue transglutaminase (tTG) antibodies, increases detection. Fifty-three biopsy-proven untreated CD patients (39 women, 14 men; median age 51 years) and 65 control patients with normal duodenal histology (46 women, 19 men; age range 17-90 years, median 45 years) were prospectively studied. Serum total IgA, IgA anti-tTG, IgA AEM, IgA anti-gliadin (AGA) and IgG AGA antibodies were measured. Thirteen (25%) CD patients were AEM negative. None were IgA deficient. Three AEM-negative CD patients had a raised IgA anti-tTG and IgA AGA. IgG AGA was raised in 10 AEM-negative CD patients, but also in 14/65 (22%) of controls. In conclusion, AEM-negative CD is common and detection is only modestly enhanced by testing for IgA anti-tTG antibodies. Duodenal biopsy is still recommended for the accurate diagnosis of CD.

Adult↗
PubMed2001

Gut mucosal secretion of interleukin 1beta and interleukin-8 predicts relapse in clinically inactive Crohn's disease.

Trials of maintenance therapy in Crohn's disease are often underpowered, and there is need for objective markers of relapse. We assessed the relationship of whole gut lavage fluid cytokines to relapse in inactive Crohn's disease. Fifty-four patients with inactive Crohn's disease were prospectively assessed. Inactivity was determined as a Crohn's disease activity index of <150 and whole gut lavage fluid immunoglobulin G <10 microg/ml. All patients underwent whole gut lavage with analysis of IL-1beta and IL-8. Follow up was for one year. Patients with elevated whole gut lavage fluid IL-1beta (P < 0.004) and IL-8 (P < 0.02) had greater chance of relapse. Young age, short disease duration, and fistulating disease also relapsed more frequently. Multiple regression identified IL-1beta as an independent variable. In conclusion, an elevated whole gut lavage fluid IL-1beta in inactive Crohn's disease identifies patients at high risk of relapse.

Adolescent↗
PubMed2001

Biphasic effects of selegiline on striatal dopamine: lack of effect on methamphetamine-induced dopamine depletion.

We tested the hypothesis that selegiline can attenuate dopamine depletion if administered following high doses of methamphetamine that cause neurotoxicity in the striatum. Methamphetamine produced decreases of 50% or greater in both striatal concentrations of dopamine and combined concentrations of homovanillic acid and DOPAC in mice. For animals not exposed to methamphetamine, chronic treatment with selegiline over 18 days caused biphasic effects on striatal dopamine content, with decreases, no effect, or increases observed for mice receiving treatment with 0.02, 0.2, and 2.0 mg/kg, respectively. Selegiline failed to modify methamphetamine-induced reductions in striatal dopamine content or combined concentrations of homovanillic acid and DOPAC. Significant increases in mortality following the onset of selegiline treatment (24 hours after the initial dose of methamphetamine) occurred in methamphetamine-treated mice that received saline or 2.0 mg/kg of selegiline, but not for mice treated with 0.02 or 0.2 mg/kg of selegiline. These results indicate that selegiline fails to attenuate dopamine depletion when administered chronically following exposure to methamphetamine, but may attenuate methamphetamine-induced mortality. In control animals that did not receive methamphetamine, low doses of selegiline produced decreases the concentration of striatal dopamine, while high dose treatment caused increases in striatal dopamine content.

Animals↗
PubMed2001

Selective impairment of protein kinase C isotypes in murine macrophage by Leishmania donovani.

Leishmania donovani, an obligate intracellular parasite resides and multiplies within macrophage of the reticuloendothelial system. The intracellular signalling mechanism involved in the impaired oxidative response in leishmaniasis has not yet been clearly established. Generation of superoxide anion (O2-) is supposed to be the first line of host defence during microbial invasion. We found a substantial inhibition of superoxide anion generation in parasitized macrophages, which was just the reverse in case of macrophages challenged with Lipophosphoglycan (LPG) deficient attenuated leishmanial parasite UR-6. The generation of O2- essentially needs the prior activation of protein kinase C (PKC) mediated phosphorylation events. Our study proposed that phosphorylation of 67, 54, 47 and 36 kDa proteins was attenuated during infection. This was supported by PKC activity study, where Ca-dependent PKC activity was inhibited but, Ca-independent PKC activity was enhanced. This result was further confirmed by using isotype specific pseudosubstrate inhibitors of Ca-dependent PKC beta and Ca-independent PKC zeta. Application of beta-pseudosubstrate could not alter the Ca-dependent PKC activity but zeta-pseudosubstrate inhibited the Ca-independent PKC activity in infected macrophages. Our immunoblot analysis with specific antibody against PKC beta and PKC zeta isotypes showed down regulation of PKC beta-II expression with concomitant induction of PKC zeta. Such inhibition of Ca-dependent PKC beta was reversed in macrophages treated with UR-6. Taken together, our observations revealed that infection with L. donovani selectively attenuates both the expression and activity of Ca-dependent PKC beta.

Animals↗
PubMed2001

Generation of ceramide in murine macrophages infected with Leishmania donovani alters macrophage signaling events and aids intracellular parasitic survival.

In the present study, we examined the involvement of intracellular ceramide in host pathogen interaction of BALB/c mouse peritoneal macrophages infected with the obligate intracellular protozoan, Leishmania donovani. Our findings indicate that the level of intracellular ceramide was enhanced as a result of the in vitro infection. While the elevated ceramide was largely due to de novo synthesis, activation of the sphingomyelinases was also observed. The enhanced ceramide was responsible for the downregulation of classical PKC activity, upregulation of calcium independent atypical PKC-zeta expression and activity of calcium independent PKC. Ceramide also impaired the phosphorylation of MAPK. Evidently, ceramide suppressed the generation of nitric oxide during leishmanial infection and also facilitated the survival of leishmanial parasites in the intramacrophageal milieu. These data present newer insight to the signaling events in leishmania-infected murine macrophages, which might offer ceramide as a new therapeutic target in the future.

Animals↗
PubMed2001

Respiratory syncytial virus infections in autologous blood and marrow transplant recipients with breast cancer: combination therapy with aerosolized ribavirin and parenteral immunoglobulins.

Scant data are available concerning the impact and response to therapy of respiratory syncytial virus (RSV) infections in patients undergoing autologous blood and marrow transplantation (BMT) for breast cancer. During eight winter seasons from 1992-1993 to 1999-2000, nine (4%) of 249 such patients were hospitalized with RSV infections. Six patients, including all five patients who were early post transplant in the pre-engraftment period, developed pneumonia and were treated with a combination of aerosolized ribavirin and IVIG. Among five patients with pneumonia in whom therapy was initiated prior to respiratory failure, one (20%) died. The sixth patient, in whom therapy was initiated after respiratory failure developed, also died. In total, two (1%) patients, both of whom were in the pre-engraftment period, died of progressive pneumonia. In conclusion, RSV is a significant cause of life-threatening pneumonia in autologous BMT recipients with breast cancer during the early post-transplant period, and accounted for a substantial portion of the overall transplant-related mortality, which in recent years has been minimal.

Aerosols↗
PubMed2001

Identification of a critical lysine residue at the active site in glyceraldehyde-3-phosphate dehydrogenase of Ehrlich ascites carcinoma cell. Comparison with the rabbit muscle enzyme.

The involvement of the lysine residue present at the active site of Ehrlich ascites carcinoma (EAC) cell glyceraldehyde-3-phosphate dehydrogenase (Gra3PDH) was investigated by using the lysine specific reagents trinitrobenzenesulfonic acid (TNBS) and pyridoxal phosphate (PP). Both TNBS and PP inactivated EAC cell Gra3PDH with pseudo-first-order kinetics with the rate dependent on modifier concentration. Kinetic analysis, including a Tsou plot, indicated that both TNBS and PP apparently react with one lysine residue per enzyme molecule. Two of the substrates, d-glyceraldehyde-3-phosphate and NAD, and also NADH, the product and competitive inhibitor, almost completely protected the enzyme from inactivation by TNBS. A comparative study of Gra3PDH of EAC cell and rabbit muscle indicates that the nature of active site of the enzyme is significantly different in these two cells. A double inhibition study using 5,5'-dithiobis(2-nitrobenzoic acid) and TNBS and subsequent reactivation of only the rabbit muscle enzyme by dithiothreitol suggested that a cysteine residue of this enzyme possibly reacts with TNBS. These studies on the other hand, confirm that an essential lysine residue is involved in the catalytic activity of the EAC cell enzyme. This difference in the nature of the active site of EAC cell Gra3PDH that may be related to the high glycolysis of malignant cells has been discussed.

Amino Acid Sequence↗