Biomedical subjects

S Sengupta

Publications and source records attributed to S Sengupta.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography by the 4-h post procedure amylase level.

BACKGROUND: Pancreatitis is the commonest and most significant complication of endoscopic retrograde cholangiopancreatography (ERCP). Early detection of post-ERCP pancreatitis would allow the safe discharge of day-case patients and targeted use of preventive therapies. Clinical diagnosis is inaccurate, and the aim of this study was to evaluate the 4-h post-ERCP hyperamylasemia as a predictor of pancreatitis. METHODS: Two hundred and sixty-three consecutive ERCPs performed at one center were prospectively analyzed, examining patient and procedure characteristics, as well as the amylase level as predictors of pancreatitis. RESULTS: Younger age (< 25 years), Sphincter of Oddi dysfunction, pancreatogram and failed cannulation were risk factors for pancreatitis; sphincterotomy conferred an increased risk, which was not statistically significant. Hyperamylasemia was a highly sensitive and moderately specific predictor of pancreatitis. A cut-off level of 1.5-fold higher than normal was useful for the exclusion of pancreatitis, while a cut-off level of threefold higher than normal was more specific, so as to target potential preventive therapies. CONCLUSIONS: The 4-h post-ERCP amylase level is a useful test to base management decisions on. It needs to be interpreted in conjunction with clinical assessment as well as identifiable risk factors related to the patient or the procedure.

Adolescent↗

PubMed2001

Uropathogenic Escherichia coli potentiates type 1 pilus-induced apoptosis by suppressing NF-kappaB.

Urinary tract infections (UTIs) are among the most common inflammatory diseases. Acute UTIs are typically caused by type 1-piliated Escherichia coli and result in urothelial apoptosis, local cytokine release, and neutrophil infiltration. To examine the urothelial apoptotic response, a human urothelial cell line was incubated with various E. coli isolates and was then characterized by flow cytometry. Uropathogenic E. coli (UPEC) induced rapid urothelial apoptosis that was strictly dependent upon interactions mediated by type 1 pili. Interestingly, nonpathogenic HB101 E. coli expressing type 1 pili induced apoptosis at approximately 50% of the level induced by UPEC, suggesting that pathogenic strains contribute to apoptosis by pilus-independent mechanisms. Consistent with this possibility, UPEC blocked activity of an NF-kappaB-dependent reporter in response to inflammatory stimuli, yet this effect was independent of functional type 1 pili and was not mediated by laboratory strains of E. coli. UPEC suppressed NF-kappaB by stabilizing IkappaBalpha, and UPEC rapidly altered cellular signaling pathways. Finally, blocking NF-kappaB activity increased the level of piliated HB101-induced apoptosis to the level of apoptosis induced by UPEC. These results suggest that UPEC blocks NF-kappaB and thereby enhances type 1 pili-induced apoptosis as a component of the uropathogenic program.

Apoptosis↗

PubMed2001

Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the toxicity of etoposide, a topo-isomerase II inhibitor.

Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm(3) in volume. Liposomal etoposide (10 mg/m(2)/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.

Animals↗

PubMed2001

Idiopathic bilateral external jugular vein thrombosis--a case report.

The authors report a patient with the rare presentation of bilateral external jugular vein thrombosis. A 45-year-old man presented with swelling over both sides of the neck and puffiness of the face. Physical examination revealed cordlike thickening of both the external jugular veins. Two-dimensional echocardiographic and Doppler studies showed thrombosis of both the external jugular veins and digital subtraction angiography (DSA) revealed nonvisualization of external jugular veins of either side. No malignancy, coagulation disorder, or any infection was demonstrable. A regular follow-up for 1 year was done, but no other cause could be found and there was no progression of the disease.

Angiography, Digital Subtraction↗

PubMed2001

The role of community advisory boards: involving communities in the informed consent process.

Ethical research involving human subjects mandates that individual informed consent be obtained from research participants or from surrogates when participants are not able to consent for themselves. The existing requirements for informed consent assume that all study participants have personal autonomy; fully comprehend the purpose, risks, and benefits of the research; and volunteer for projects that disclose all relevant information. Yet contemporary examples of lapses in the individual informed consent process have been reported. The authors propose the use of community advisory boards, which can facilitate research by providing advice about the informed consent process and the design and implementation of research protocols. These activities could help reduce the number of individual informed consent lapses, benefiting study participants and the scientific integrity of the research in question.

Advisory Committees↗

PubMed2001

Making grandma's data secure: a security architecture for home telemedicine.

Home telemedicine presents special challenges for data security and privacy. Experience in the Informatics for Diabetes Education And Telemedicine (IDEATel) project has demonstrated that data security is not a one-size-fits-all problem. The IDEATel users include elderly patients in their homes, nurse case managers, physicians, and researchers. The project supports multiple computer systems that require a variety of user interactions, including: data entry, data review, patient education, videoconferencing, and electronic monitoring. To meet these various needs, a number of different of security solutions were utilized, including: UserID/Password, PKI certificates, time-based tokens, IP filtering, VPNs, symmetric and asymmetric encryption schemes, firewalls and dedicated connections. These were combined in different ways to meet the needs of each user groups.

Aged↗

PubMed2001

Role of alphavbeta3 integrin receptors in breast tumor.

The intriguing problem of tumor metastasis involves adhesion of the metastatic cells via the integrin group of cell surface receptors to the ECM proteins of the basement membrane. Modulation of integrin family of cell surface receptors is believed to be associated with stages of tumor metastasis. In this present study, results obtained indicate that alphavbeta3 vitronectin receptors may play an important role in the malignant behaviour of human breast tumor. Alphavbeta3 integrin receptors can modulate the activity of collagenase enzyme and thereby the invasive property of breast tumor cells.

Breast Neoplasms↗

PubMed2001

Food and feeding of Amphiesma stolatum (Linnaeus 1758).

The food and feeding behaviour of Amphiesma stolatum was studied. A total of 117 snakes were examined to analyse the diet composition. Ten live snakes were maintained in enclosure for evaluating the feeding habit, choice of food and rate of assimilation. The anurans constituted the major diet of the food spectrum. In captivity, fishes (fry), amphibians and reptiles were consumed by the snakes. A. stolatum exihibited Elaphe type of hunting behaviour. In most cases the snake struck the prey at its head. The assimilation rate with frog was highest.

Amphibians↗

PubMed2000

Ethical issues in early detection of HIV infection to reduce vertical transmission.

Proposals to make prenatal HIV testing routine and universal dramatize ethical issues regarding early detection of HIV. These proposals would abolish pretest counseling and written informed consent for prenatal HIV testing. Ethical concerns include whether pregnant women are adequately informed that they may refuse such testing and whether patients have an opportunity to obtain more detailed information about the benefits and risks of HIV testing in this context. Several pertinent research questions need to be studied, including whether pregnant women find routine universal HIV testing acceptable and whether safeguards adequately protect women who receive testing. If analogous policies to enhance early detection of HIV are considered in other clinical contexts, the important clinical and ethical differences between vertical transmission and other situations of HIV transmission must be kept clearly in mind.

Breast Feeding↗

PubMed2000

Negative cross-talk between p53 and the glucocorticoid receptor and its role in neuroblastoma cells.

The tumour suppressor p53 and the glucocorticoid receptor (GR) respond to different types of stress. We found that dexamethasone-activated endogenous and exogenous GR inhibit p53-dependent functions, including transactivation, up- (Bax and p21(WAF1/CIP1)) and down- (Bcl2) regulation of endogenous genes, cell cycle arrest and apoptosis. GR forms a complex with p53 in vivo, resulting in cytoplasmic sequestration of both p53 and GR. In neuroblastoma (NB) cells, cytoplasmic retention and inactivation of wild-type p53 involves GR. p53 and GR form a complex that is dissociated by GR antagonists, resulting in accumulation of p53 in the nucleus, activation of p53-responsive genes, growth arrest and apoptosis. These results suggest that molecules that efficiently disrupt GR-p53 interactions would have a therapeutic potential for the treatment of neuroblastoma and perhaps other diseases in which p53 is sequestered by GR.

Apoptosis↗

PubMed2000

Mechanisms for the formation of protein-bound homocysteine in human plasma.

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Greater than 70% of homocysteine in circulation is protein-bound. An in vitro model system using human plasma has been developed to study mechanisms of protein-bound homocysteine formation and establish the equilibrium binding capacities of plasma for homocysteine. Addition of homocysteine to plasma caused an initial rapid displacement of cysteine and a subsequent increase in protein-bound homocysteine. This rapid reaction was followed by a slower oxygen-dependent reaction forming additional protein-bound homocysteine. To determine the equilibrium binding capacity of plasma proteins for homocysteine, plasma was treated with 0.5-10 mM dl-homocysteine for 4 h at 37 degrees C under aerobic conditions. Under these conditions the equilibrium binding capacity was 4.88 +/- 0.51 and 4.74 +/- 0.68 micromol/g protein for male (n = 10) and female (n = 10) donors, respectively. The mechanism of protein-bound homocysteine formation involves both thiol-disulfide exchange and thiol oxidation reactions. We conclude that plasma proteins have a high capacity for binding homocysteine in vitro.

Blood Proteins↗

PubMed2000

Differential effects of C-terminal molecular tagged integrase on replication competent moloney murine leukemia virus.

Moloney murine leukemia virus (M-MuLV) proviruses carrying integrase (IN) protein tagged either with a simian virus 40 (SV40) nuclear localization signal (NLS) or various antigenic epitopes were generated. Hexahistidine (His(6)), hemagluttinin (HA), or two consecutive HA sequences (2XHA) were fused to the C-terminus of IN as antigenic markers. These epitope-tagged IN proteins were stably expressed through multiple rounds of infection. The IN-His(6), IN-HA, and IN-2XHA proteins, purified from virus, could be immunoprecipitated with antibodies against His(6) and HA, respectively. An M-MuLV provirus encoding the SV40 large T antigen NLS fused to IN at the same position as the epitope tags was also passaged through cells. In contrast to the stability of the epitope tags, the SV40 NLS sequence was rapidly mutated by a frameshift mutation that introduced negatively charged amino acids into the basic NLS. The instability of the NLS suggests that the strong nuclear localization of the IN-SV40 NLS may have detrimental effects on virus assembly. These observations have implications for studying nuclear transport properties of M-MuLV and for engineering a murine-based retroviral vector for gene therapy.

Amino Acid Sequence↗

PubMed2000

Factors affecting African-American participation in AIDS research.

BACKGROUND: Although African Americans are disproportionately affected by the AIDS epidemic, they are underrepresented in AIDS research, particularly in AIDS clinical trials. This study examines a multidimensional construct of distrust and other factors that may affect willingness to participate in AIDS research. METHODS: A total of 301 African Americans (aged >/=18 years) in Durham, North Carolina participated in a cross-sectional survey. In-person interviews, 20 to 25 minutes in length, were conducted with participants. Structural equation modeling was used to develop models exploring distrust and other factors affecting willingness to participate in AIDS research among African Americans. RESULTS: Distrust was the strongest inverse predictor of willingness to participate in AIDS clinical trials. Distrust was not significantly associated with willingness to participate in AIDS surveys and educational interventions. Altruism, facilitators/barriers, religiosity, and economic group membership were also significantly associated with willingness to participate in AIDS clinical trials. Only altruism was significantly associated with willingness to participate in AIDS surveys and educational interventions. CONCLUSIONS: Distrust about research institutions is a significant barrier to recruiting African Americans in AIDS clinical trials. Issues of distrust need to be acknowledged by researchers to develop better recruitment and retention strategies when conducting AIDS clinical trials in African-American communities.

Acquired Immunodeficiency Syndrome↗

PubMed2000

NBD-isocolcemid-tubulin interaction: a novel one-step reaction involving no conformational adjustment of reactants.

Isocolcemid, a colcemid analogue in which the positions of the C-ring methoxy and carbonyl are exchanged, is virtually inactive in binding to tubulin and inhibiting the formation of microtubule assembly. We have found that the substitution of a NBD group in the side chain of the B-ring of isocolcemid can reverse the effect of these structural alterations (at the C-ring) and the newly synthesized NBD-isocolcemid restores the lost biological activity. It inhibits microtubule assembly with an IC(50) of 12 microM and competes efficiently with [(3)H]colchicine, for binding to tubulin. NBD-isocolcemid has two binding sites on tubulin; one is characterized by fast binding, whereas the binding to the other site is slow. These two sites are independent and unrelated to each other. Colchicine and its analogues compete with NBD-isocolcemid for the slow site. Association and dissociation rate constants for the fast site, obtained from the stopped-flow measurements, are (7.37 +/- 0. 70) x 10(5) M(-1) s(-1) and 7.82 +/- 2.74 s(-1), respectively. While the interaction of colchicine and its analogues with tubulin involves two steps, NBD-isocolcemid binding to tubulin at the slow site has been found to be a one-step reaction. This is evident from the linear dependence of the observed rate constant (k(obs)) with both NBD-isocolcemid and tubulin concentrations. The interaction of NBD-isocolcemid with tubulin does not involve the conformational change of NBD-isocolcemid, as is evident from the unchanged CD spectra of the drug. The absence of enhanced GTPase activity of tubulin and the native-like protease cleavage pattern of the NBD-isocolcemid-tubulin complex suggest an unaltered conformation of tubulin upon NBD-isocolcemid binding to it as well. Implications of this on the mechanism of polymerization inhibition have been discussed.

4-Chloro-7-nitrobenzofurazan↗

PubMed2000

Resonant production of topological defects

We describe a novel phenomenon in which vortices are produced due to resonant oscillations of a scalar field which is driven by a periodically varying temperature T, with T remaining much below the critical temperature T(c). Also, in a rapid heating of a localized region to a temperature below T(c), far separated vortex and antivortex can form. We compare our results with recent models of defect production during reheating after inflation. We also discuss possible experimental tests of our predictions of topological defect production without ever going through a phase transition.

Journal Article↗

PubMed2000

Tumour regression in a ligand inducible manner mediated by a chimeric tumour suppressor derived from p53.

The p53 tumour suppressor induces cell cycle arrest and apoptosis in response to cellular stresses. p53 is inactivated by various cellular and viral factors. We set out to generate regulatable p53 derivatives that are highly inducible by synthetic ligands, escape inactivation and efficiently induce apoptosis. We have generated Ligand Inducible Chimeric Tumour Suppressors (LI-CTS), that are inactive unless provided with artificial ligands. They are resistant to inactivation, due to the replacement of domains that mediate p53 inhibition by heterologous sequences. LI-CTS are activated by micromolar concentrations of ligand in a variety of cell lines. Following ligand addition, they translocate to the nucleus, activate p53 inducible genes and induce apoptosis. We have established human head and neck squamous cell carcinoma lines that stably express LI-CTS, which are inducible. These lines form tumours in nude mice in the absence of ligand. Addition of ligand inhibits tumour formation, and moreover, regresses established tumours by apoptosis. Although regulatable p53 expression has been achieved previously, our study provides the first demonstration of regulatable in vivo regression of tumours in a p53 based approach. Regulated inhibition and regression of tumours with a ligand inducible chimeric tumour suppressor could provide a novel approach to p53 based gene therapy.

Animals↗

PubMed2000

Multistage electrophoresis system for the separation of cells, particles and solutes.

It is common to operate equilibrium-based separation methods, such as distillation and extraction, as multistage unit operations, in which equilibrium is presumably achieved within each stage. Two rate-based separation processes, free electrophoresis and magnetic particle separation, have now been operated in multistage mode. Preparative free electrophoresis of particles and solutes has resisted scale-up and is confined to a narrow range of ionic compositions. Natural convection induced in electrophoresis buffers by Ohmic heating has been a strong deterrent and has led to such measures as radial electrophoresis in Couette flow, free-flow electrophoresis, low-gravity electrophoresis, density gradient electrophoresis, and reorienting density gradient electrophoresis, to name a few. The short vertical electrophoresis path exploited in the last-mentioned forms the basis for multistage electrophoresis. A thin-layer countercurrent distribution apparatus was designed and constructed so that up to 20 fractions could be collected on the basis of electrophoretic mobility by applying an electric field. The mixture to be separated starts in a bottom cavity, and successive top cavities collect fractions as separand particles or molecules are electrophoresed upward out of the bottom cavity. Mathematical models of this process were developed, and experiments were performed to verify the predictions of the models by collecting and counting particles in each cavity after fractionation.

Animals↗

PubMed2000

Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies.

Etoposide is an antineoplastic agent which acts by forming a ternary complex with topoisomerase II and DNA, causing DNA breaks and cell death. In recent studies we have demonstrated that encapsulation in liposomes increases the antitumour efficacy and reduces the adverse effects associated with etoposide. The present study was thus conducted to evaluate whether encapsulation in cationic liposomes altered the pharmacokinetics of etoposide and to study the effect of cholesterol incorporation on the stability of the liposomes. Etoposide-encapsulated unilammellar liposomes were synthesized by thin film hydration followed by extrusion. The drug was administered to Swiss albino mice at a dose of 10 mg kg(-1). The concentration of the drug in plasma was analysed at different time points till 360 min after injection, using a h.p.l.c. method. The terbium chloride-dipicolinic acid interaction method was applied to study the stability of the formulation in mouse serum and also following storage at 0( composite function)C over a period of time. The effect of the free and liposomal drug on myelosuppression was evaluated at 10 mg m(-2)and 40 mg m(-2)dose levels by quantifying blood cell counts on day 15 and day 21 following a 5 day course of therapy. Encapsulation in cationic liposomes increased the area under the concentration vs time curve to 42.98 microghml(-1)from 24.18 microghml(-1)in the case of the free drug. Half-life (beta) was 58. 62 and 186 min in the case of free and liposomal etoposide, respectively. In the stability studies, incorporation of cholesterol progressively stabilized the formulation in serum. The use of sucrose at increasing concentrations as a cryoprotectant also increased the shelf stability of the formulation at 0( composite function)C. Toxicity studies using a dose of pure drug revealed that though myelosuppression was evident in both liposomal- and free drug-treated groups on day 15 it was reversed by day 21 following initiation of therapy. The present findings suggest that liposomes could serve as an alternative mode of delivery for etoposide.

Analysis of Variance↗