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Biomedical subjects

S Chakrabarti

Publications and source records attributed to S Chakrabarti.

At least 127 records · Page 7Linked to original sources
PubMed2000

Endothelins, their receptors, and retinal vascular dysfunction in galactose-fed rats.

PURPOSE: Endothelins are potent vasoactive factors that have been implicated in the pathogenesis of several vascular disorders. This study was conducted to determine the role that endothelins play in the development of retinal microangiopathy under hyperhexosemic conditions induced by galactose feeding. METHODS: Retinal blood flow was determined using Doppler sonography in galactose fed rats with or without an endothelin receptor antagonist (Bosentan) treatment and were compared to control rats after 1 and 6 months of follow-up. Levels of endothelin-1, endothelin-3, (ET-1, ET3) and receptors endothelin A, endothelin B, (ET(A), ET(B)) mRNA expression were determined by semiquantitative RT-PCR. Immunohistochemical distribution of ET-1 and ET-3, ligand binding, and autoradiography to determine ET receptor distribution were carried out. RESULTS: Retinal vasoconstriction measured by an increase in resistivity index (RI) was present in 1 month galactose feeding compared to controls, which was prevented by Bosentan treatment. After 6 months of follow up all animal groups exhibited higher RI compared to their 1 month counterpart, although they were not different from each other. Compared to the controls, after 1 month levels of mRNA for ET-1, ET-3, and ET(A) were increased in galactose-fed rats, whereas ET(B) mRNA production remained similar to controls. After 6 months, all four genes exhibited increased levels compared to the controls, and no effect of Bosentan treatment on gene expression was evident. Increased immunoreactivity of ET-1 and ET-3 was determined, as well as increased ET receptor concentration was further present in the retina of galactose-fed animals. CONCLUSION: The data suggests that endothelin production is increased under hyperhexosemic conditions and that the endothelins play an important role in regulating the hemodynamics of retinal blood flow.

Animals↗
PubMed2000

Interaction of endothelin-1 with vasoactive factors in mediating glucose-induced increased permeability in endothelial cells.

Alteration of endothelins (ET) and/or their receptors may be important in mediating vascular dysfunction in diabetes. We investigated mechanisms regulating ET-1 expression in human umbilical vein endothelial cells (HUVEC) in response to glucose and the functional significance of these mechanisms. Permeability across HUVEC, grown in medium containing either low (5 mmol/l) or high (25 mmol/l) D-glucose were investigated. L-glucose was used as a control. ET-1, ET(A), and ET(B) mRNA were assessed by semiquantitative RT-PCR. ET-1 immunoreactivity and F-actin microfilament assembly were investigated using confocal microscopy. Increased transendothelial permeability was noted in cells cultured in high glucose or when the cells grown in low (physiologic) glucose were incubated with ET-1, vascular endothelial growth factor (VEGF), or N (G) -nitro-L-arginine methyl ester but not when they were incubated with ET-3, N(G)-nitro-D-arginine methyl ester, or L-glucose. Increased permeability was associated with increased ET-1, ET(A), and ET(B) mRNA expression and augmented ET-1 immunoreactivity. High glucose induced increased permeability, increased ET-1, ET(A), and ET(B) mRNA expression. ET-1 immunoreactivity was blocked by the protein kinase C (PKC) inhibitor chelerythrine, the specific PKC isoform inhibitor 379196, VEGF-neutralizing antibody, or the ET(A) blocker TBC11251, but was not blocked by the specific ET(B) blocker BQ788 or by a VEGF-non-neutralizing antibody. Increased permeability was also associated with deranged F-actin assembly in the endothelial cells and by derangement of endothelial cell junctions as assessed by electron microscopy. Data from this study suggest that high glucose-induced increased permeability may be induced through increased ET-1 expression and disorganization of F-actin assembly. ET-1 expression and increased permeability may occur secondary to PKC isoform activation and may be modulated by VEGF and nitric oxide.

Base Sequence↗
PubMed2000

Isolation of viruses from stools in stem cell transplant recipients: a prospective surveillance study.

We prospectively examined stool specimens for enteric viruses in 75 stem cell transplant recipients (autologous 48, allogeneic 27) to determine the frequency and significance of these infections. Only six patients (8%) had a positive isolate. Five of these were allograft recipients (18%) compared to one autograft recipient (2%) (P = 0.02). Unrelated donor BMT recipients were at the highest risk for a viral isolate (OR = 10.5). Adenovirus was the commonest isolate (four patients). One patient each had an echovirus, enterovirus and small round structured virus identified. No correlation was found between the severity of gastro-intestinal symptoms and detection of a viral pathogen. There was no correlation with GVHD or CMV status. The only risk factor identified for isolation of an enterovirus was allogeneic BMT from an unrelated donor. There was a negative correlation with PBSC grafts. All the patients infected with an enteric virus had concomitant infection with other pathogens, compared to only 18% of uninfected patients (P = 0.001). The non-relapse mortality of the infected patients was 50% and only 7% in the uninfected patients (P = 0.01, OR = 12.5), although the isolated virus was the direct cause of death in one patient only. This study indicates a low rate of enteric virus isolation in recipients of PBSC grafts, both autologous and allogeneic. However, unrelated donor BMT is associated with a higher risk of enteric virus infection and an adverse outcome. Bone Marrow Transplantation (2000) 25, 277-282.

Adenoviridae↗
PubMed2000

Adenovirus infections following haematopoietic cell transplantation: is there a role for adoptive immunotherapy?

Adenovirus has been recognised as an important pathogen in BMT recipients, especially in patients with GVHD and those receiving T cell-depleted allografts. We report adenovirus infections from an ongoing surveillance study in four patients after a non-myeloablative transplant and their improved outcome following withdrawal of immunosuppression in two patients and donor lymphocyte infusion for relapsed disease in the others. We discuss the control of adenovirus infections following immune manipulations and the feasibility of adoptive immunotherapy for post-transplant adenovirus infections.

Adenoviridae Infections↗
PubMed2000

Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.

We retrospectively evaluated 75 allogeneic stem cell transplant recipients to ascertain the incidence, risk factors and outcome of infection with Clostridium difficile. Ten patients (13%) had Clostridium difficile infection at a median of 38 days (range day -6 to day +72) following the transplant. There was no difference in the duration or severity of diarrhoea in patients with Clostridium difficile infection compared to the uninfected patients and no relationship to the prior antibiotic or chemotherapy usage, age, gender, underlying disease, donor type, CMV serostatus, total body irradiation or time to engraftment. The incidence of viral infections was increased in patients infected with Clostridium difficile (7/10 vs 15/65, P = 0.005, odds ratio 7.7), but the strongest association was with GVHD >grade 2 (5/10 vs 6/65 uninfected patients, P = 0.004, odds ratio 9.8). Patients infected with Clostridium difficile also suffered a higher non-relapse mortality with 7/10 patients succumbing to either GVHD or infections, compared to 19/65 patients in the uninfected group (P = 0.02, odds ratio 5.6). Thus Clostridium difficile infections in our study had a strong association with GVHD and increased non-relapse mortality. It is possible that Clostridium difficile toxin might predispose to increased severity of GVHD leading to an adverse outcome.

Adolescent↗
PubMed2000

Augmented expression of endothelin-1, endothelin-3 and the endothelin-B receptor in breast carcinoma.

AIMS: Endothelins (ETs) are peptides expressed in many tumours which may stimulate angiogenesis and desmoplasia. Because ETs have not been extensively studied mammary neoplasia, we assessed ET protein and mRNA expression and receptor mRNA expression in normal and neoplastic breast tissues. METHODS AND RESULTS: Tissues from five normal breasts, six fibroadenomas, seven ductal carcinomas in situ (DCIS) and 25 invasive carcinomas were stained with anti-ET-1 and anti-ET-3 antibodies and analysed using a grading system. ET-1, ET-3, ETA and ETB mRNA expression was assessed by quantitative RT-PCR from eight carcinomas and five normals. Weak staining for ET-1 and ET-3 was detected in all normals. Moderate to strong staining was seen in 72% and 64% of carcinomas for ET-1 and ET-3, respectively. Most fibroadenomas showed weak positivity for ET-1 (83%) and ET-3 (67%). ET-1 and ET-3 mRNA levels were upregulated in carcinomas compared with normal breast. No ETA mRNA was not detected in any tissue. ETB mRNA was detected in normal breast and was increased in carcinomas. CONCLUSION: These results suggest that the ET system is altered in breast carcinomas and this may be of importance in the progression from in-situ to invasive carcinoma.

Blotting, Southern↗
PubMed2000

Population screening for hemochromatosis: a comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors.

Early diagnosis and treatment of hemochromatosis is essential to prevent organ damage. Screening strategies to detect early hemochromatosis include testing for iron overload and/or genetic testing. Voluntary blood donors numbering 5,211 were screened with unbound iron-binding capacity (UIBC), transferrin saturation (TS), and genetic testing for the C282Y mutation of the HFE gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound heterozygotes, 371 simple heterozygotes, and 4,755 normals. There were 5 men and 11 women homozygotes with a mean age of 42, range 28 to 57. Mean UIBC (24 +/- 7 microL) and TS (48% +/- 17%) in homozygotes were significantly different from compound heterozygotes, simple heterozygotes, and normals (ANOVA). Only 3 homozygotes had an elevated serum ferritin. Family studies found an additional 4 iron-loaded homozygotes. Optimal thresholds were < or =28 micromol/L for UIBC and > or =46% for TS. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for UIBC of 0.93 (0. 85-1.0, 95% confidence interval), and for TS of 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.

Adult↗
PubMed2000

Role of Mg2+ in the interaction of anticancer antibiotic, chromomycin A3 with DNA: does neutral antibiotic bind DNA in absence of the metal ion?

Antitumor antibiotic, Chromomycin A3 (CHR), inhibits DNA replication and transcription via reversible interaction with double stranded DNA with GC-base specificity. The interaction, at and above physiological pH, requires the presence of bivalent metal ions, such as Mg2+. Anionic antibiotic does not bind DNA in the absence of Mg2+. In this paper we have examined the structural potential of neutral CHR at pH 5.2 to bind DNA in the absence of Mg2+. We have demonstrated the ability of the neutral antibiotic to bind DNA by means of different spectroscopic techniques and evaluated the necessary thermodynamic parameters for elucidation of the molecular basis of recognition. The results are compared with the scenario when Mg2+ is present in the system, because the ultimate aim of these studies is to elucidate the role of Mg2+ in CHR-DNA recognition. Neutral CHR binds to Mg2+ with lesser affinity than its anionic form. Spectroscopic features of the drug and its Mg2+ complex indicate self association of the antibiotic in the absence and presence of Mg2+. GC-base specificity of the drug and its Mg2+ complex are retained at pH 5.2, though the modes of recognition of DNA by the two ligands are different. Minor groove width of DNA plays a role in the accommodation of the ligand(s) during the GC base specific recognition while positive charge of Mg2+ in CHR:Mg2+ complex further facilitates the association. Relatively lower affinity of the neutral drug and its Mg2+ complex for DNA can be ascribed to the self association of these ligands in the absence of DNA.

Animals↗
PubMed2000

Transmission of HIV from injecting drug users to their wives in India.

We aimed to identify factors associated with transmission of human immunodeficiency virus (HIV) from injecting drug users (IDUs) to their wives in Manipur, northeast India, where the prevalence of HIV among IDUs is 80% via a case-control study. One hundred and sixty-one HIV-infected IDUs and their wives were recruited from September 1996 to August 1997 inclusive. HIV status was determined by enzyme-linked immunosorbent assay (ELISA) plus Western blot, Interviews were administered anonymously. Regression analysis identified factors associated with transmission of HIV from IDU husbands to their non-injecting wives. Seventy-two wives (45%) were HIV-positive. Only 15% of the couples reported regular usage of condoms during intercourse. On multivariate analysis, a sexually transmitted disease (STD) in either member, reported by the husband, estimated duration of HIV in the husband for >8 years, and a history of blood transfusions were associated with infection in the wife. In conclusion, STDs are associated with transmission of HIV from husband to wife. Improved control of STDs, condom promotion, and improved blood screening are urgently needed in Manipur.

Case-Control Studies↗
PubMed2000

Therapeutic potential of endothelin receptor antagonists in diabetes.

Endothelins (ETs) are widely distributed in the body and perform several vascular and non-vascular functions. Experimental evidence indicates that abnormalities of the ET system occur in several organs affected in chronic diabetic complications. Furthermore, ET antagonists were found to prevent structural and functional changes in the target organs of chronic diabetic complications in animal models. Abnormalities of plasma ET levels have also been demonstrated in human diabetes. This review discusses the role of ET in the pathogenesis of chronic diabetic complications. The current experimental evidence suggests that ET antagonism may potentially represent an adjuvant therapeutic tool in the treatment of chronic diabetic complications.

Animals↗
PubMed2000

Endothelin receptor blockade prevents augmented extracellular matrix component mRNA expression and capillary basement membrane thickening in the retina of diabetic and galactose-fed rats.

Endothelins (ETs) are a family of vasoactive peptides that have mitogenic properties and have also been associated with altered long-term nuclear signaling. We have previously shown that mRNA levels for ET-1, ET-3, and their receptors are upregulated under hyperhexosemic conditions. In this study, an endothelin antagonist was used to assess the effects of endothelin blockage on the production of two basement membrane transcripts, fibronectin and collagen alpha1 (IV). The microvascular basement membranes were analyzed using ultrastructural morphometry. Streptozotocin-induced diabetic rats, galactose-fed rats (30% galactose in diet), and nondiabetic, non-galactose-fed control rats were studied after 1-month and 6-month follow-up. Simultaneously, similar animal groups were treated with a general ET receptor blocker (bosentan, 100 mg x kg(-1) x day(-1)) and investigated. Semiquantitative reverse transcription-polymerase chain reaction for fibronectin and collagen alpha1 (IV) was conducted after 1 month of follow-up with comparison to beta-actin housekeeping gene using slot blot hybridization and densitometry. Basement membrane thickness was assessed after 6 months of follow-up in diabetic rats, using the orthogonal intercept method. After 1 month of follow-up, increased fibronectin and collagen alpha1 (IV) mRNA were present in the retina of diabetic and galactosemic animals, and the bosentan-treated groups exhibited mRNA levels similar to the control animals. After 6 months of follow-up, diabetes and galactose feeding induced basement membrane thickening, which was partially prevented by bosentan treatment. The above findings indicate that increased production of extracellular matrix proteins leading to thickening of microvascular basement membrane, secondary to hyperhexosemia, may be mediated via augmented ET production.

Animals↗
PubMed2000

Prevalence of HCV & HBV infection amongst HIV seropositive intravenous drug users & their non-injecting wives in Manipur, India.

Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections were evaluated among 77 Manipuri couples of whom all husbands were both intravenous drug users (IDUs) and human immunodeficiency virus (HIV) positive. This study showed for the first time a high prevalence of HCV (92%) and HBV (100%) infection amongst the IDUs in Manipur. Stringent control measures to prevent the transmission of hepatitis viruses (B and C) are urgently required in Manipur.

Coitus↗
PubMed2000

Ascorbate induced cross-linking of oxyhemoglobin subunits.

Ascorbic acid during oxidation in vitro can generate H2O2 which induces non-disulphide covalent cross-linking of coincubated oxyhemoglobin. The cross-linking phenomenon mediated by H2O2 takes place possibly without the involvement of hydroxyl radicals as evident from the failure of radical scavengers like mannitol and dimethyl sulphoxide as well as metal-chelator, to inhibit the process. This pro-oxidant effect of ascorbic acid may have physiological significance in red blood cells in vivo.

Ascorbic Acid↗
PubMed2000

Endothelin-1, endothelin-3 and their receptors (endothelin(A) and endothelin(B)) in chronic renal transplant rejection in rats.

Endothelins (ET) are a family of vasoactive peptides that play an important role in several disorders affecting kidneys. In this study we investigated the expressions of ET-1, ET-3, and their receptors, ET(A) and ET(B), in a rat chronic renal transplant rejection model. Renal allografts were performed (F344 --> Lewis) with bilateral nephrectomy in recipients. For isograft control, lewis --> lewis transplantations were performed. All recipients were sacrificed 140 days after transplantation and the grafts were analyzed histologically. ET-1 and ET-3 protein expression in grafts was measured by immunohistochemistry and ELISA. Semiquantitative RT-PCR methods were used for mRNA levels of ET-1, ET-3, ET(A) and ET(B). No evidence of chronical rejection was manifested in isografts. The allografted rats showed proteinuria and increased serum creatinine levels. Histologically, renal allografts showed atrophy and sclerosis of the glomeruli, cortical scarring and vascular intimal thickening. Immunohistochemically, ET-1 and ET-3 were localized in the convoluted tubules, collecting ducts, endothelium and smooth muscle cells of the large blood vessels. Significantly increased staining for ET-1 and ET-3 were found in allografts compared to isografts. Simultaneously, ELISA for ET-1 and ET-3 showed elevated protein concentrations in allografts compared to isografts. Allografts showed significantly increased ET-1- and ET-3 mRNA compared to isografts. On the other hand, a significant down regulation of the ET(A) mRNA was noted, and the ET(B) mRNA remained unchanged. The data from the present study suggest that alteration of ET system may be of importance in the pathogenesis of chronic renal transplant rejection.

Animals↗
PubMed2000

HIV-1 subtypes in injecting drug users & their non-injecting wives in Manipur, India.

The presence of HIV-1 antibodies was determined among the injecting drug users (IDUs) and their non-injecting wives. A total of 233 (72%) were found to be HIV-1 seropositive among the 322 subjects recruited in this study between August, 1996 and September, 1997. The distribution of HIV-1 subtypes among the injecting drug users (IDUs) and their wives was determined using peptide enzyme immunoassay (EIA). Sexual transmission of HIV-1 occurred frequently (45%) from HIV-1 infected IDUs to their spouses. The majority of the subjects (167/233) were infected with subtype C followed by subtype Thai B (29/233). Subtype C was the most common among both IDUs (78%) and their wives (57%), followed by subtype Thai B (12% and 13% respectively). The distribution of subtypes was significantly different between IDUs and their wives with a lower percentage of subtype C and higher percentage of subtype D in the infected wives (P < 0.03). Discordance for subtypes transmitted from IDUs to their wives suggests the occurrence of dual and/or recombinant infection in the IDUs.

Female↗
PubMed2000

Mapping and monitoring the health and vitality of coral reefs from satellite: a biospheric approach.

Biospheric studies of coral reefs require a planetary perspective that only remote sensing from space can provide. This article reviews aspects of monitoring and mapping coral reefs using Landsat and Spot satellite images. It details design considerations for developing a sensor for equatorial orbiting spacecraft, including spectral characteristics of living corals and the spatial resolution required to map coral reef communities. Possible instrumentation choices include computer techniques, filtered imagers, push-broom spectral imagery, and a newly developed hyperspectral imaging scheme using tomographic reconstruction. We compare the salient features of each technique and describe concepts for a payload to conduct planetary-scale coral reef monitoring.

Animals↗
PubMed2000

Distribution of HIV-1 subtypes in female sex workers of Calcutta, India.

BACKGROUND & OBJECTIVES: Different routes for the transmission of HIV-1 in India have been reported and the majority of infections occurred through heterosexual route of transmission. In order to understand the dynamics of HIV-1 transmission, a systematic study was undertaken to determine the viral subtypes circulating among the female sex workers in Calcutta, India. METHODS: Peptide enzyme immunoassay (PEIA), heteroduplex mobility assay (HMA) and DNA sequence analysis were used to ascertain the HIV-1 subtypes. RESULTS: V3 serotyping of 52 HIV-1 seropositive samples identified 33 (60%) to be subtype C. A DNA fragment within C2-V3/C2-V5 regions of HIV-1 gp120 was amplified directly from the lymphocyte DNA to avoid any bias in selecting viral variants and used in HMA. Of the 40 samples analyzed, 38 (95%) belonged to subtype C and 2 were found to be non-typable. Further analysis of these 38 samples revealed that 26 (68%) had maximum homology to the C3-Indian reference strain (IND868), 11 (29%) were most homologous to C2-Zambian strain (ZM18) and 1 (3%) showed close resemblance to C1-Malawi strain (MA959). Nucleotide sequence of 11 subsamples encompassing about 325 base pairs was aligned for the Indian and other geographically distinct isolates. On distance and parsimony trees, most of the samples (8/11) clustered together as subtype C. INTERPRETATION & CONCLUSIONS: Subtype C was the major circulating HIV-1 strain in this geographical region, although variation within this subtype was also noticed. DNA sequence analysis was found to be the best method in determining the nature of the HIV-1 subtype followed by HMA and peptide enzyme immunoassay. These findings may have important implications for the design of effective vaccines in India and emphasizes the need for constant monitoring of the HIV-1 subtypes in different parts of India.

Amino Acid Sequence↗