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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 19 recordsLinked to original sources
PubMed1992

Assembly and secretion of fibrinogen. Degradation of individual chains.

Hep G2 cells produce surplus A alpha and gamma fibrinogen chains. These excess chains, which are not secreted, exist primarily as free gamma chains and as an A alpha-gamma complex. We have determined the intracellular location and the degradative fate of these polypeptides by treatment with endoglycosidase-H and by inhibiting lysosomal enzyme activity, using NH4Cl, chloroquine, and leupeptin. Free gamma chain and the gamma component of A alpha-gamma are both cleaved by endoglycosidase-H, indicating that the gamma chains accumulate in a pre-Golgi compartment. Lysosomal enzyme inhibitors did not affect the disappearance of free gamma chains but inhibited A alpha-gamma by 50%, suggesting that A alpha-gamma is degraded in lysosomes. The degradative fate of individual chains was determined in transfected COS cells which express but do not secrete single chains. Leupeptin did not affect B beta chain degradation, had very little affect on gamma chain, but markedly inhibited A alpha chain degradation. Antibody to immunoglobulin heavy chain-binding protein (GRP 78) co-immunoprecipitated B beta but not A alpha or gamma chains. Preferential binding of heavy chain-binding protein to B beta was also noted in Hep G2 cells and in chicken hepatocytes. Taken together these studies indicate that B beta and gamma chains are degraded in the endoplasmic reticulum, but only B beta is bound to BiP. By contrast A alpha chains and the A alpha-gamma complex undergo lysosomal degradation.

Ammonium Chloride↗
PubMed1992

Reversible dimer dissociation of tubulin S and tubulin detected by fluorescence anisotropy.

Concentration-dependent dissociation of dimers of goat brain tubulin S and tubulin was studied by fluorescence anisotropy. Upon dilution, assembly-competent fluorescein 5'-maleimide labeled dimers of tubulin S and tubulin show a progressive decrease in fluorescence anisotropy. That this lowering of anisotropy results from the dissociation of tubulin S dimers into monomers was shown by dilution experiments with unlabeled homologous and heterologous proteins. A nonlinear least-squares fit of the data gave a dissociation constant of 7.1 x 10(-8) M for tubulin S compared to 7.2 x 10(-7) M for tubulin at 25 degrees C in 0.1 M PEM buffer, pH 7.0. van't Hoff plots of dimer-monomer dissociation of tubulin S and tubulin also show considerable differences in delta H and delta S. Effects of ionic strength and colchicine on the equilibrium constants are also substantially different for tubulin and tubulin S. The implications of these observations on the influence of C-terminal tails on tubulin structure are discussed.

Animals↗
PubMed1992

Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase.

The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a key mediator of the antiviral and antiproliferative effects of interferons (IFNs). Studies examining the physiological function of the kinase suggest that it participates in cell growth and differentiation by regulating protein synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in malignant transformation, suggesting that dsRNA-PK may function as a suppressor of cell proliferation and tumorigenesis.

Amino Acid Sequence↗
PubMed1992

Multiphasic denaturation of the lambda repressor by urea and its implications for the repressor structure.

Urea denaturation of the lambda repressor has been studied by fluorescence and circular dichroic spectroscopies. Three phases of denaturation could be detected which we have assigned to part of the C-terminal domain, N-terminal domain and subunit dissociation coupled with further denaturation of the rest of the C-terminal domain at increasing urea concentrations. Acrylamide quenching suggests that at least one of the three tryptophan residues of the lambda repressor is in a different environment and its emission maximum is considerably blue-shifted. The transition in low urea concentration (midpoint approximately 2 M) affects the environment of this tryptophan residue, which is located in the C-terminal domain. Removal of the hinge and the N-terminal domain shifts this transition towards even lower urea concentrations, indicating the presence of interaction between hinge on N-terminal and C-terminal domains in the intact repressor.

DNA-Binding Proteins↗
PubMed1992

An operator-induced conformational change in the C-terminal domain of the lambda repressor.

4,4'-bis(1-anilino-8-naphthalenesulfonic acid (Bis-ANS), an environment-sensitive fluorescent probe for hydrophobic region of proteins, binds specifically to the C-terminal domain of lambda repressor. The binding is characterized by positive cooperativity, the magnitude of which is dependent on protein concentration in the concentration range where dimeric repressor aggregates to a tetramer. In this range, positive cooperativity becomes more pronounced at higher protein concentrations. This suggests a preferential binding of Bis-ANS to the dimeric form of the repressor. Binding of single operator OR1 to the N-terminal domain of the repressor causes enhancement of fluorescence of the C-terminal domain bound Bis-ANS. The binding of single operator OR1 also leads to quenching of fluorescence of tryptophan residues, all of which are located in the hinge or the C-terminal domain. Thus two different fluorescent probes indicate an operator-induced conformational change which affects the C-terminal domain. The significance of this conformational change with respect to the function of lambda repressor has been discussed.

Anilino Naphthalenesulfonates↗
PubMed1992

The cytoplasmic domain of tissue factor is phosphorylated by a protein kinase C-dependent mechanism.

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cellular receptor and cofactor for the activation of the plasma protease factor VII. TF activity in both monocytes and endothelial cells is regulated by various cytokines and mitogens, including the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA). Three TF constructs (full-length human, a cytoplasmic domain deletion mutant, and a human-rat TF chimera), expressed in a human kidney cell line, were used to examine the in vivo phosphorylation state of TF after PMA treatment. The cytoplasmic domains of both rat and human TF were rapidly phosphorylated after cells were treated with 10-100 nM PMA. This response was completely abolished by preincubating cells with staurosporine, the potent PKC inhibitor, prior to PMA treatment. Localization of the phosphorylation site(s) to the cytoplasmic domain was demonstrated using a deletion mutant of TF and by CNBr digestion at the single methionine residue (Met-210) in the TF sequence. The rat TF cytoplasmic domain was phosphorylated to a higher specific activity than the human TF cytoplasmic domain. Phosphoamino acid analysis of the chimeric TF revealed both phosphothreonine and phosphoserine, whereas human TF contained only phosphoserine. Thus both potential phosphoacceptor sites are phosphorylated in the rat TF cytoplasmic domain. Alignment of TF cDNA sequences of mouse, rat, rabbit, and man revealed that the phosphoacceptor site (X-S*/T*-P-X, where asterisk indicates the phosphorylated residue) in the cytoplasmic domain has been conserved through evolution.

Alkaloids↗
PubMed1992

Relationship of hypolipidemic and antineoplastic activities of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes, cyanoboranes, and related derivatives.

A series of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes and cyanoboranes were synthesized. These compounds have potent hypolipidemic effects, antineoplastic and antiinflammatory activities in rodents. Furthermore, they demonstrated potent cyctotoxicity against standard human tissue culture lines. The compounds which afforded the best hypolipidemic activity, i.e. greater than 40% reduction of serum cholesterol and triglyceride levels, were diphenyl-(4-methylphenyl)-phosphine borane and triphenylphosphine carboxyborane. Other derivatives demonstrated more potent antineoplastic activity against the Ehrlich ascites carcinoma growth including triphenylphosphine cyanoborane, 2-amino-4-methyl-pyridine cyanoborane and 2-amino-pyridine cyanoborane. Most of the derivatives showed good activity against murine L1210 lymphoid leukemia, Tmolt3 human leukemia, uterine HeLaS cells, and human glioma cell growth. Select compounds were active against colon adenocarcinoma, KB nasopharynx, lung bronchogenic and osteosarcoma cell growth. Tricyclohexyl- and triphenylphosphine boranes and the carboxy derivatives of the latter borane demonstrated good antiinflammatory activity.

Animals↗
PubMed1992

Immunobiological studies on experimental visceral leishmaniasis. II. Adherent cell-mediated down-regulation of delayed-type hypersensitivity response and up-regulation of B cell activation.

Visceral leishmaniasis or kala-azar is characterized by a variety of immunopathological consequences in man. The most remarkable of these are the depression of cell-mediated immunity and polyclonal B cell activation. The consequences observed in man could be induced in a murine model by inoculating the causative agent, Leishmania donovani. The cell-mediated response was studied in this murine model in terms of the delayed-type hypersensitivity (DTH) response toward leishmania antigen in a progressive infection. BALB/b (H-2b) mice showed progressive enhancement in the DTH response, whereas BALB/c (H-2d) mice showed strong DTH at the onset which gradually disappeared (defined as DTH-negative phase) and reappeared again at the later stage of infection. Adoptive transfer of enriched populations of splenic T cells from infected BALB/c mice together with parasite antigen into the footpad of syngenic normal recipients produced a dramatic enhancement in the DTH response, except at the onset of the DTH-negative phase. These observations indicate that adherent cells have a role in suppression of the cell-mediated immune response and also that another mechanism operates at the onset of the DTH-negative phase. This DTH-negative phase was not caused by depletion of DTH-mediating cells from the repertoire, but rather by suppression mediated by a subset of T cell evolved in the course of infection. Characterization on the basis of lymphokine production of the T cells mediating the DTH response and of T cells mediating suppression of the DTH response showed them to be of Th1 and Th2 type, respectively. Studies also indicated that at the onset and the later stages of infection suppression was mediated by adherent cells, but at the onset of DTH-negative phase, in particular, suppression was mediated by Th2 cells. Furthermore, experiments also showed that adherent cells from infected mice gained another property, that of driving B cells, in a T cell-dependent manner.

Animals↗
PubMed1992

NMR studies of erythrocytes immobilized in agarose and alginate gels.

31P and 13C NMR were used to study the energy metabolism in perfused, human erythrocytes. The erythrocytes were immobilized in agarose threads, Ca- or Ba-alginate beads, and Ba-alginate-coated agarose threads. Erythrocytes were easily washed out from the agarose threads, but not from alginate-containing gels. Various small molecules, such as hypophosphite, dimethyl methylphosphonate, and methylphosphonate, were taken up from the perfusion medium in a normal manner. In addition, the 2,3-bisphosphoglycerate (2,3-DPG) chemical shifts were sensitive to the oxygen partial pressure suggesting that O2 molecules were diffusing through the gel and modifying the binding of 2,3-DPG to hemoglobin. A combination of inosine and pyruvate stimulated the synthesis of 2,3-DPG, but only if inorganic phosphate was present in the perfusion medium. Inosine only resulted in a dramatic rise in the intracellular sugarphosphate concentrations. Furthermore, [2-13C]glucose was converted to [2-13C]lactate by immobilized cells at a rate which was comparable to that in a control suspension. In summary, immobilization in Ba-alginate-coated agarose threads was an efficient way of trapping human erythrocytes for whole cell NMR investigations.

Alginates↗
PubMed1992

Fluid intake patterns in schizophrenia and normal controls.

1. Patterns of fluid intake and urine output was examined in schizophrenia and normal controls. 2. Fluid intake and urine output were significantly higher in schizophrenic patients. 3. Bouts of drinking correlated significantly with fluid intake but did not differ significantly between schizophrenic patients and normal controls. 4. Schizophrenic patients drink more per bout compared to normal controls.

Adult↗
PubMed1992

Percutaneous catheter drainage of amoebic liver abscess.

Fifteen patients with amoebic liver abscesses underwent percutaneous catheter drainage under ultrasonographic guidance. Thirteen patients had solitary abscesses (right lobe 12, left lobe 1), two had associated subdiaphragmatic collections, while two patients had multiple abscesses. The indications for the drainage included lack of response to medical therapy: imminent rupture in five cases; ruptured liver abscesses in three; enlarging abscesses after hospitalization in three; persistent symptoms in two; and large left lobe abscesses in two. The volume of the abscesses before drainage was 102-1008 ml (mean 432 ml). Pigtail catheters (8 F) were used in nine of the patients and 12 F sump catheters in six. When multiple abscesses and associated subdiaphragmatic collection were present, each was drained separately. The catheters were removed (mean 7 days, range 3-20 days) when patients became apyrexial, catheter drainage was less than 10 ml in 24 h and cavitogram showed a negligible cavity (mean residual volume 5.5 ml, range 3-15 ml). Complications included minor blood loss through the catheter for 12 h in one patient and reappearance of the abscess in another requiring further drainage. Our experience suggests that catheter drainage of amoebic liver abscesses in selected cases is safe and effective, and results in prompt and early resolution of the abscess cavity with restoration of normal parenchyma.

Adolescent↗
PubMed1992

Indomethacin-loaded microspheres: design and preparation by a multiple-emulsification technique and their in vitro evaluation.

A new oral controlled-release drug delivery system was developed with two polymers using a multiple-emulsification technique. Powdered drug was dispersed in methyl cellulose sol, which was emulsified in ethyl cellulose solution in ethyl acetate. The primary emulsion thus formed was reemulsified in aqueous medium. During this phase, discrete microspheres were formed under optimized conditions. The size distribution of the microspheres was investigated, and scanning electron microscopy revealed the surface topography of the microspheres. The in vitro drug release followed first-order diffusion-controlled dissolution. More than 85% of the drug was released over 6 hr at pH 6.2 for all dissolution batches.

Administration, Oral↗
PubMed1992

The prevalence of diagnosed systemic lupus erythematosus in whites and Indian Asian immigrants in Leicester city, UK.

The prevalence of diagnosed systemic lupus erythematosus (SLE) during 1989 in the adult Indian Asian and White populations of the city of Leicester has been determined. Fifty cases (19 Asian, 31 White) fulfilling the 1982 revised ARA criteria for SLE were identified from a population of 191,469 (37,684 Asian, 153,785 White). Five different sources were used to ascertain cases. The overall prevalence of SLE in Whites was 20.2 per 100,000. Asians of both sexes had a significantly higher prevalence than Whites. Prevalence in males was 31.5 and 7.0 per 100,000 in Asians and Whites respectively; in females the figures were 69.7 and 31.7 per 100,000. Overall, lupus was 3.0 times more common in Asians than Whites. This is the first prevalence study of SLE in Indian Asians and suggests that, like the Black races and the Chinese, they have a greater frequency of SLE than Whites.

Adult↗
PubMed1992

Idiopathic inflammatory myopathy: clinicopathological observations in the Indian population.

The present study attempts to investigate the pathological basis of the two clinically different forms of idiopathic inflammatory myopathy (IIM) namely, polymyositis (PM) and dermatomyositis (DM). Clinicopathological analysis of 73 cases showed that muscle fibre necrosis and regeneration were more frequent in PM than in DM, the latter being significantly so (P < 0.05). On the other hand, vasculitis was more associated with DM while perifascicular atrophy of the muscle fibres was confined to it. Vasculitis was present in eight cases. Its incidence in patients with myositis with systemic connective tissue disease (4/9) was significantly more than in other PM and DM patients (P < 0.01). An equally significant higher frequency of perimysial inflammatory infiltrate was also seen in the former as compared to the latter. Interestingly, idiopathic DM affected men as often as women and juvenile IIM affected boys more frequently than girls. A female predilection was noted in the remaining groups of IIM. These observations indicate that there may be some basic immunopathogenetic differences between polymyositis and dermatomyositis as well as between idiopathic PM/DM and that associated with systemic connective tissue diseases. Though the number of patients studied is small, the absence of female predilection in idiopathic DM and juvenile IIM may be peculiar to the IIM in the tropics.

Adolescent↗
PubMed1992

Inadvertent duodenal stenting: a case report.

A Gianturco type metallic stent placed in the common bile duct migrated into the duodenum. The device remains in situ, and has caused no ill-effects to date. This raises the possibility that such stents may be deployed in the gastrointestinal tract.

Cholestasis↗