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S Basu

Publications and source records attributed to S Basu.

At least 235 records · Page 13Linked to original sources
PubMed1997

Characterization of tumor necrosis factor-deficient mice.

Although tumor necrosis factor (TNF) initially came to prominence because of its anti-tumor activity, most attention is now focused on its proinflammatory actions. TNF appears to play a critical role in both early and late events involved in inflammation, from localizing the noxious agent and amplifying the cellular and mediator responses at the local site and systemically, to editing (e.g., apoptosis) injured cells or effete immune cells and repairing inflammatory damage. We have generated mice deficient in TNF (TNF-/- mice) and have begun to examine the multiple functions attributed to TNF. TNF-/- mice develop normally and have no gross structural or morphological abnormalities. As predicted, they are highly susceptible to challenge with an infectious agent (Candida albicans), are resistant to the lethality of minute doses of lipopolysaccharide (LPS) following D-galactosamine treatment, have a deficiency in granuloma development, and do not form germinal centers after immunization. Phagocytic activity of macrophages appears relatively normal, as do T cell functions, as measured by proliferation, cytokine release, and cytotoxicity. B cell response to thymus-independent antigens is normal, but the Ig response to thymus-dependent antigen is reduced. Surprisingly, cytokine production induced by LPS appears essentially intact, with the exception of reduced colony-stimulating factor activity. Other unexpected findings coming from our initial analysis are as follows. (i) TNF has low toxicity in TNF-/- mice. (ii) TNF-/- mice show an anomalous late response to heat-killed Corynebacterium parvum. In contrast to the prompt response (granuloma formation, hepatosplenomegaly) and subsequent resolution phase in C. parvum-injected TNF+/+ mice, similarly treated TNF-/- mice show little or no initial response, but then develop a vigorous, disorganized inflammatory response leading to death. These results suggest that TNF has an essential homeostatic role in limiting the extent and duration of an inflammatory process-i.e., an anti-inflammatory function. (iii) In contrast to the expectation that TNF+/+ mice and TNF+/- mice would have identical phenotypes, TNF+/- mice showed increased susceptibility to high-dose LPS lethality, increased susceptibility to Candida challenge, and delayed resolution of the C. parvum-induced inflammatory process, indicating a strong gene dose requirement for different actions of TNF.

Animals↗
PubMed1997

Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial.

BACKGROUND: Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS: This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS: Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Administration, Oral↗
PubMed1997

A Model for Detachment of a Partially Wetting Drop from a Solid Surface by Shear Flow

Liquid drop detachment from a solid surface by simple shear flow is modeled based on the experimental observations available in the literature. A liquid drop adhered to a solid surface deforms in the presence of a simple shear flow to form an advancing and a receding dynamic contact angle. The drop slides on the solid surface when the drag due to the shearing fluid overcomes the retentive force due to the contact angle hysteresis. A drop having an equilibrium contact angle, thetae , approaching 180&deg; detaches from the solid surface at the onset of its sliding motion. However, a drop with thetae much lower than 180&deg; slides on the solid surface and will not detach. With further increase in the shear rate, the sliding drop detaches from the solid surface when the lift force equals the adhesive, gravitational, and buoyancy forces of the drop. Based on this premise, an approximate mathematical model for the detachment of a partially wetting drop is constructed. The experimental results available in the literature for Pristane and Squalane drop detachment are compared for slide and lift as the mode of detachment. The critical shear rate for the detachment of Pristane drops, having thetae of 175&deg;, is predicted well by the model where sliding as the mode of detachment is assumed, whereas the experimental data for Squalane drops, having thetae of 126&deg;, is well predicted by the model where lift is considered the mode of detachment.

Journal Article↗
PubMed1997

Transformed and immortalized cellular uptake of oligodeoxynucleoside phosphorothioates, 3'-alkylamino oligodeoxynucleotides, 2'-O-methyl oligoribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids.

Direct quantitative comparisons of cellular uptake across a wide variety of analogs and cell types are necessary for the design of oligonucleotide diagnostic and therapeutic applications. This work reports quantitative cellular uptake and nuclear localization of [14C]oligodeoxynucleoside phosphorothioates (PS), 3'-alkylamino oligodeoxynucleoside phosphodiesters (PO-NH2), 2'-O-methyl oligoribonucleoside phosphodiesters (2OM), peptide nucleic acids (PNA), and oligodeoxynucleoside methylphosphonates (MP) in several transformed or immortalized cell lines. All analogs demonstrated active cellular uptake in that intracellular concentrations greatly exceeded the extracellular 1 microM concentration within 1-3 hr. However, by 9-24 hr, cellular accumulations of PS exceeded those of PO-NH2 and 2OM by 3- to 5-fold, PNA by 6- to 7-fold, and MP by 8- to 10-fold. Similar results were observed in two transformed cell lines, HL-60 leukocytes and H-ras transformed fibroblasts, using three different heterogeneous sequences. H-ras and IGF-1R transformed fibroblasts had a 2- to 5-fold higher uptake of all analogs than non-transformed immortalized fibroblasts. Nuclear levels of the PO-NH2, PS, and MP analogs were approximately 25% of total cellular uptake, while nuclear percentages of 2OM and PNA were less than 20%, suggesting some differences in nuclear localization among the analogs. These observations provide a direct quantitative comparison of cellular uptake as a function of oligonucleotide modification, and imply that transformation enhances cellular uptake. From the perspective of therapy and diagnosis, clear trade-offs were apparent between efficiency of uptake on the one hand, and nuclease resistance and hybridization strength on the other.

3T3 Cells↗
PubMed1997

Kinase suppressor of Ras is ceramide-activated protein kinase.

A proline-directed serine/threonine ceramide-activated protein (CAP) kinase mediates transmembrane signaling through the sphingomyelin pathway. CAP kinase reportedly initiates proinflammatory TNF alpha action by phosphorylating and activating Raf-1. The present studies delineate kinase suppressor of Ras (KSR), identified genetically in Caenorhabditis elegans and Drosophila, as CAP kinase. Mouse KSR, like CAP kinase, renatures and autophosphorylates as a 100-kDa membrane-bound polypeptide. KSR overexpression constitutively activates Raf-1. TNF alpha or ceramide analogs markedly enhance KSR autophosphorylation and its ability to complex with, phosphorylate, and activate Raf-1. In vitro, low nanomolar concentrations of natural ceramide stimulate KSR to autophosphorylate, and transactivate Raf-1. Other lipid second messengers were ineffective. Moreover, Thr269 the Raf-1 site phosphorylated by CAP kinase, is also recognized by KSR. Thus, by previously established criteria, KSR appears to be CAP kinase.

Amino Acid Sequence↗
PubMed1997

Temperature and salt dependence of higher order structure formation by antisense c-myc and c-myb phosphorothioate oligodeoxyribonucleotides containing tetraguanylate tracts.

The use of complementary RNA or DNA sequences to selectively interfere with the utilization of mRNA of a target gene is an attractive therapeutic strategy. Two well-studied targets for oligonucleotide therapy are the c-mycand c-mybproto-oncogenes. It has been reported that sequences which contain four contiguous Gs can elicit a non-antisense response, due to the formation of a homotetrameric G quartet structure. Therefore, it was of interest to determine whether anti-c-mycand anti-c-mybphosphorothioate DNAs including tetraguanylate form higher order structures under physiologically relevant salt conditions and temperature. First, the identity of the higher order structure was established and was found to be a tetraplex. Employing intracellular (high K+), extracellular (low K+) and normal saline (no K+) salt mixtures, native gel electrophoresis revealed no tetraplex formation at 37 degrees C, the physiologically relevant temperature. On the other hand, tetraplex structure formation was observed at 4 and 23 degrees C. Hence, the potential for these sequences to form tetraplex structures at lower temperatures may not be relevant for their activity in cells and animals at physiological temperature.

Animals↗
PubMed1997

Role of double-stranded RNA-activated protein kinase in human hematological malignancies.

The double-stranded RNA (dsRNA)-activated protein kinase (PKR) is one of many genes induced by IFN. The PKR sequentially undergoes autophosphorylation and activation on binding to dsRNA. Previous studies have shown that PKR may be an important factor in the regulation of viral and cellular protein synthesis. Recent studies suggest that PKR may function as a tumor suppressor gene. The role of PKR in various human leukemic cells was therefore investigated. PKR mRNA levels by reverse transcription-PCR, protein expression by Western blot and FACScan analysis, and activity by phosphorylation status were studied. The expression of a known inhibitor of PKR, p58, was also investigated at mRNA and protein levels. A total of 24 samples from normal mononuclear cells (MNCs), 26 samples of acute lymphoblastic leukemia, 26 samples of acute myelogenous leukemia, 32 samples of chronic lymphocytic leukemia, and 5 samples of hairy cell leukemia was investigated. Mean mRNA levels were increased in acute lymphoblastic leukemia and acute myelogenous leukemia and decreased in chronic lymphocytic leukemia compared to normal MNCs. The mRNA levels in hairy cell leukemia were similar to those of normal MNCs. PKR protein was detectable in normal MNCs and leukemic cell extracts, and on FACScan analysis, more than 70% of cells stained positive for PKR. PKR activity was detectable in all samples investigated and was enhanced 4-23-fold in the presence of the synthetic dsRNA, poly(I) x poly(C). Protein expression of a known PKR inhibitor, p58, was barely detectable in normal MNCs and leukemic cells, with high expression in the HeLa cell line. These findings provide no evidence to support the hypothesis that PKR acts as a tumor suppressor in human leukemic cells.

Gene Expression Regulation, Enzymologic↗
PubMed1997

Mapping regions of herpes simplex virus type 1 glycoprotein I required for formation of the viral Fc receptor for monomeric IgG.

Glycoprotein E (gE) and glycoprotein I (gI) of herpes simplex virus type 1 (HSV-1) form a complex that binds the Fc domain of monomeric IgG. In this study, we used two approaches to map the regions of gI-1 required for formation of the HSV-1 Fc receptor for monomeric IgG. First, we constructed six plasmids encoding gD-1/gI-1 fusion proteins. Each fusion protein contains a large gI-1 peptide inserted into the ectodomain of gD-1. gD-1/gI-1 fusion proteins were coexpressed with gE-1 using a transfection-infection assay in which cells were transfected with individual fusion protein constructs and then infected with a gE+/gI- virus. Cells were then assayed for monomeric IgG binding using immunofluorescence microscopy. Transfection-infection with two of six fusion proteins conferred monomeric IgG binding activity to cells, whereas cells infected with gE+/gI- virus alone failed to bind IgG monomers. The smallest gI-1 peptide to confer monomeric IgG binding activity contained amino acids 43 to 192. To more precisely map the region of gI-1 required for monomeric IgG binding, we constructed a panel of 10 gI-1 linker insertion mutants. Transfection-infection studies identified two mutants containing linker insertions at gI-1 amino acids 128 and 145, which failed to bind monomeric IgG. The other eight mutants demonstrated wild-type IgG binding activity. Taken together, these results indicate that the region of gI-1 between amino acids 128 and 145 is required for formation of the HSV-1 Fc receptor for monomeric IgG.

Animals↗
PubMed1997

Immunization with immune complex alters the repertoire of antigen-reactive B cells in the germinal centers.

The differentiation of memory B cells in germinal centers (GC) is selectively enhanced upon administration of antigen-antibody complexes. To characterize the repertoire of this response, we examined the rearranged immunoglobulin heavy chain variable (V(H)) genes from mouse splenic GC after a single immunization with either antigen, nitrophenyl (NP) hapten coupled to keyhole limpet hemocyanin, or with a preformed complex of antigen with a monoclonal anti-NP antibody of gamma1 isotype. Among antigen-immunized mice, NP-reactive GC B cell populations in the antigen-induced GC consisted mostly of cells expressing the canonical V186.2 gene which contained, on average, 0.8 point mutations/V(H) gene by day 8 after immunization. These results are indicative of the beginning of somatic hypermutation and consistent with previously published analyses of NP antigen-driven GC. In contrast, the NP-specific B cells in GC that were elicited by administration of immune complex represented a heterogeneous cell population expressing nine different germ-line segments of the V186.2/V3 (J558) gene family, i.e. V23, V24.8, C1H4, V3, CH10, V165.1, V102, V671.5 and V186.2. Moreover, the average frequency of mutations in these genes was 1.7, reaching up to 4 mutations/V(H) in some GC. Administration of the antigen NP in complex with specific antibody apparently alters the process of interclonal competition in the GC and results in loss of dominance by V186.2+ cells and nearly stochastic representation of diverse clonotypes. These results suggest an important feedback regulation of the B cell repertoire by antibody and indicate a role for immune complexes in the activation of somatic hypermutation.

Animals↗
PubMed1997

Primary adenocarcinoma of the stomach associated with peripheral neurofibromatosis: report of a case.

A 55-year old man with von Recklinghausen's disease was admitted to our hospital for investigation of weight loss, anorexia, and abdominal discomfort. Endoscopy findings revealed impairment in the extendability of the stomach by air, and barium meal studies showed a well-contracted stomach. On exploratory laparotomy, the whole of the stomach was found to be grossly shrunken with thickening of the walls suggesting a "linitis plastica" stomach. Histological findings confirmed stage III poorly differentiated diffuse infiltrative adenocarcinoma of the stomach. This report describes a rare case of "linitis plastica" stomach in a patient with peripheral neurofibromatosis (NF-1) indicating that the NF-1 disorder does not spare an individual from other common neoplastic disorders.

Adenocarcinoma↗
PubMed1997

Hepatotoxicity of diazepam. Structural and trace metal studies in rat.

Studies of effects of diazepam on liver parenchyma are very scanty. In this study, adult albino rats were treated with diazepam in two different doses (0.25 mg and 0.30 mg/kg body wt) daily for 30 and 60 d. Through light microscopy and electron microscopy, prenecrotic and necrotic changes were noted in the high-dose group. Trace metal analysis indicated that zinc (Zn) was reduced by 30 and 60 day under both the doses, whereas iron (Fe) and copper (Cu) were reduced significantly in these groups only after 60 d of treatment. This reduction in metal contents may have some correlations with necrotic changes in liver parenchyma.

Animals↗
PubMed1997

Novel 29 kDa heparin-binding lectin from human foetal brain.

Heparin inhibitable lectins are physiologically important because of their interactions with extracellular matrix and with other cell surface glycoconjugates. However, due to the unstable nature of these animal lectins, it becomes necessary to purify them in the shortest possible time. In the present study, a chromatographic procedure was developed to separate heparin inhibitable lectin activity. Lectin activities from human foetal brain were separated on a Q-Sepharose column employing different equilibration conditions. When proteins were loaded on to a phosphate-buffered saline (PBS) equilibrated column and eluted with salt gradient, only one lectin peak was obtained. However, when proteins were loaded on to a hypotonic equilibrated column and eluted with a salt gradient, four lectin peaks were obtained. The lectin peak obtained from the PBS equilibrated column was characterized as heparin inhibitable lectin. On SDS-PAGE analysis, it gave a single band of 29 kDa. For optimum lectin activity, a pH of around 7.0 was required. Lectin activity was stimulated by Mn++; amino acid composition was different from other known lectins. The lectin was particularly rich in acidic amino acids. Regional distribution of 29 kDa lectin in different foetal brain regions gave the highest content in the cerebral cortex, showing a caudoroastral distribution. Determination of the subcellular distribution of the lectin in the foetal cerebral cortex gave the highest value with a mitochondrial fraction.

Animals↗
PubMed1997

Delta13-reductase dependent metabolism of prostaglandins in the mammalian brain and eye.

This paper describes the distribution of NAD+-dependent 15-hydroxy prostaglandin dehydrogenase (delta13-reductase) in the mammalian brain and eye tissues. In addition, an NADH-dependent 15-ketoprostaglandin delta13-reductase (15-PGDH) activity was determined in the brain and eye tissue of some species. The rabbit brain and eye tissues were obtained after arterial perfusion with PBS buffer while the monkey, bovine and porcine tissues were obtained without any treatment. [3H]-PGF2alpha or [3H]-15-keto-17-phenyl-18,19,20-trinor-PGF2alpha1-1-isopropy l ester was incubated with different eye tissue preparations under various conditions. No 15-PGDH activity was observed in the monkey brain while 14% of exogenous PGF2alpha was metabolized to its 15-keto-13,14-dihydro-metabolite by the porcine brain. The 15-PGDH activity in the monkey eye tissue was undetectable. Both brain and different eye tissues hydrolysed 15-keto-17-phenyl-18,19,20-trinor-PGF2alpha-1-isopropyl ester to its free acid and the free acid was further metabolized to 15-keto-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF2alpha by the reduction of 13,14-double bond indicating the presence of a delta13-reductase in these tissues. These data suggest that besides the presence of esterases the mammalian brain and eye tissues possess variable amounts of delta13-reductase in spite of their low 15-PGDH activity which may be of importance in physiology and drug metabolism of these tissues.

Animals↗
PubMed1997

Chaos game representation of proteins.

The present report proposes a new method for the chaos game representation (CGR) of different families of proteins. Using concatenated amino acid sequences of proteins belonging to a particular family and a 12-sided regular polygon, each vertex of which represents a group of amino acid residues leading to conservative substitutions, the method can generate the CGR of the family and allows pictorial representation of the pattern characterizing the family. An estimation of the percentages of points plotted in different segments of the CGR (grid points) allows quantification of the nonrandomness of the CGR patterns generated. The CGRs of different protein families exhibited distinct visually identifiable patterns. This implies that different functional classes of proteins follow specific statistical biases in the distribution of different mono-, di-, tri-, or higher order peptides along their primary sequences. The potential of grid counts as the discriminative and diagnostic signature of a family of proteins is discussed.

Algorithms↗
PubMed1997

Studies on 'zinc deficiency syndrome' in black bengal goats (Capra hircus) fed with fodder (Andropogon gayanus) grown on soil treated with an excess of calcium and phosphorus fertilizer.

Overliming and excessive application of superphosphate caused a zinc deficiency in the soil and so reduced the uptake of zinc by fodder plants. Bucks reared on such fodder had significantly (p < 0.01) less zinc in their hair compared with controls and suffered from 'conditioned zinc deficiency syndrome' with a significant (p < 0.01) loss of body weight, stunted growth, alopecia, lethargy, abnormal (kyphotic) gait, anorexia, digestive and respiratory problems. Oral supplementation with zinc sulphate very rapidly improved these conditions to near normality. Histological examination of samples of skin and testis from the zinc-deficient bucks revealed formation of excessive keratin, retention of nuclei in the stratum corneum and reduction in the width of the stratum granulosum in the skin, while samples of testis indicated degenerative changes, including atrophy of the seminiferous tubules, hyperplasia of the germinal epithelium and thickening of the walls of blood vessels.

Alopecia↗
PubMed1997

Activities of glycolipid glycosyltransferases and sialidases during the early development of Xenopus laevis.

The activities of glycosyltransferases and sialidases, together with the ganglioside content and distribution, have been extensively studied in mammals, while the informations on tissues of other animals, including amphibian, are scarce. In this paper we present data on the activities of SAT-1, SAT-2, SAT-4, SAT-5, GlcNAcT-1, GalNAcT-1, GalT-6, and sialidases studied in Xenopus laevis embryos at different stages of development. The highest activity was found at days 4 and 5 of embryogenesis for glycosyltransferases and sialidases respectively; a tentative correlation between the in vitro activity of these enzymes and the content of neutral and acidic glycolipids is discussed.

Animals↗
PubMed1997

Alteration of dopamine D2 receptors in human malignant stomach tissue.

Dopamine is an important enteric neurotransmitter with a wide spectrum of physiological actions on the gastrointestinal tract. In addition, it showed inhibition of malignant cell proliferation as well as a protective influence on experimental carcinogenesis in the gastrointestinal tract of murine hosts. It is well established that dopamine acts on target cells through specific receptors. Therefore the status of dopamine receptors in malignant tumors of the stomach has been evaluated. Normal, benign, and malignant stomach tissue showed the presence of high-affinity D2 dopamine receptors. The concentration (Bmax) and affinity (Kd) of dopamine binding sites in normal and benign tumor tissues were similar. In malignant stomach tissue Bmax showed a significant decrease compared to normal and benign controls; however, Kd was similar. This alteration of dopamine receptors may be of significance in understanding the etiopathogenesis of gastric cancer at the level of peripheral neurotransmitters. Rational use of dopamine receptor antagonists for various stomach diseases may be suggested.

Adenocarcinoma↗