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Biomedical subjects

C Singh

Publications and source records attributed to C Singh.

At least 37 records · Page 2Linked to original sources
PubMed1996

Solvation, water permeation, and ionic selectivity of a putative model for the pore region of the voltage-gated sodium channel.

This paper describes a molecular dynamics and molecular mechanics study of the solvation and selectivity of the narrow pore and vestibule region of a model-built structure for the voltage-gated sodium channel. The particular structure used was one proposed by Guy and Durell. However, many of the features we saw would likely be shared with other possible models for this channel, such as the one proposed by Lipkind and Fozzard. It was found that the water mobility was reduced in the channel and the water orientations were significantly ordered by the channel environment. Water mobility depended on protein mobility; in a computer experiment in which the protein was artificially frozen, channel water at 300 degrees K was immobilized. Water motions were defined in significant part by a series of discrete moves from one pattern of hydrogen bonding with particular amino acids to another. However, there are so many different hydrogen bonding patterns that a description of the motion in terms of transitions among a small number of discrete states is not appropriate. In the model whose solvation we explored, several charged residues seem to play a particularly significant role in determining solvation and water motions. Based on energy minimization studies, the structure clearly shows selectivity for univalent cations over anions.

Amino Acid Sequence↗
PubMed1995

Expression of p68 in human colon cancer.

p68 is an interferon-inducible protein kinase which is a key factor in the regulation of both viral and cellular protein synthesis. Since p68 plays a central role in cellular protein synthesis, we hypothesized that it would parallel translational activity, and thereby correlate with cellular differentiation in both normal and neoplastic cell types. Using the anti-p68 monoclonal antibody, TJ4C4, we have previously noted a correlation of p68 expression with the degree of cellular differentiation in the human upper aerodigestive tract and lung. During normal human fetal development, p68 is abundantly expressed in the upper aerodigestive tract and lungs, but considerably less so in the colon. In order to determine if this fetal expression pattern correlated with the pattern seen in adult colon and colonic adenocarcinomas, we analyzed the expression pattern of p68 in 80 patients with adenocarcinoma of the colon. Using light microscopic evaluation of immunoperoxidase-stained tissue sections, a spectrum of p68 expression was noted among the tissue samples. Increased p68 levels were noted in the majority of tumors with increased cellular differentiation, and those tissues with decreased p68 were, in general, less differentiated. These data are consistent with the concept that the expression of p68 parallels the degree of cellular differentiation, and are consistent with previously reported studies using this antibody. The limited fetal expression pattern of p68 in the colon and the variable correlation of p68 with differentiation suggests that p68, as well as other translational regulators, can be important in assessing the biological potential of tumors arising in the colon.

Adenocarcinoma↗
PubMed1993

Embryo-fetal development influenced by lead exposure in iron-deficient rats.

Lead administered (250, 500, 1000 and 2000 ppm Pb as lead nitrate) through drinking water from the 6th to the 14th day of gestation in iron-deficient rats, resulted in a significantly reduced litter size, reduced fetal weight and a reduced crown-rump length, increased resorption and a higher blood-lead uptake in those groups receiving 1000 and 2000 ppm Pb. These animals also had a higher placental lead uptake. However, the level was the same in both groups. Fetal lead uptake remained the same whether or not 2000 ppm lead was given to an iron-deficient or normal iron groups of mothers. This indicates that iron-deficiency renders female rats more susceptible to inducing embryo- and feto-toxicity when given lead through their drinking water.

Animals↗
PubMed1993

Taxol and lipopolysaccharide activation of a murine macrophage cell line and induction of similar tyrosine phosphoproteins.

Taxol, a unique antimitotic drug, is thought to exert its antitumor activity by binding to and promoting the assembly of microtubules. Studies on the mechanism of action of Taxol have focused mainly on this ability to induce microtubule polymerization. Recent evidence suggests that Taxol affects novel intracellular targets within macrophages and neutrophils. To investigate further the mechanism of action of Taxol on macrophages, we have examined the pattern of tyrosine protein phosphorylation, using antiphosphotyrosine monoclonal antibodies (MAbs) in a RAW 264.7 (RAW) macrophage cell line. We found that Taxol, like lipopolysaccharides (LPS), caused a marked increase in tyrosine phosphorylation of three proteins having M(r) of 40 (p40), 41 (p41), and 43 (p43) kd in RAW cells. Immunoprecipitation of these tyrosine phosphoproteins followed by Western blotting with a microtubule-associated protein-2 (MAP-2) kinase MAb revealed that both Taxol and LPS induced the tyrosine phosphorylation of a MAP-2 kinase-like protein. In addition, MAP-2 kinase-like activity was stimulated in the presence of Taxol or LPS. Examination of cellular mRNA levels in LPS and Taxol-activated macrophages by Northern blot analysis revealed increased expression of Interleukin-1 beta, and tumor necrosis factor-alpha cytokine mRNAs. Because Taxol promotes tubulin assembly, we examined the effect of LPS on microtubule polymerization. LPS had no polymerizing activity over Taxol alone. We conclude that Taxol and LPS have a common target in macrophages that is a critical component of the signal transduction pathway that mediates LPS cellular responses.

Animals↗
PubMed1992

Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule.

In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease.

Abatacept↗
PubMed1992

Hypolipidemic activity of Achyranthus aspera Linn in normal and triton induced hyperlipemic rats.

The alcoholic extract of A. aspera, at 100 mg/kg dose lowered serum cholesterol (TC), phospholipid (PL). triglyceride (TG) and total lipids (TL) levels by 60, 51, 33 and 53% respectively in triton induced hyperlipidemic rats. The chronic administration of this drug at the same doses to normal rats for 30 days, lowered serum TC, PL, TG and TL by 56, 62, 68 and 67% respectively followed by significant reduction in the levels of hepatic lipids. The faecal excretion of cholic acid and deoxycholic acid increased by 24 and 40% respectively under the action of this drug. The possible mechanism of action of cholesterol lowering activity of A. aspera may be due to rapid excretion of bile acids causing low absorption of cholesterol.

Animals↗
PubMed1991

Lead-induced fetal nephrotoxicity in iron-deficient rats.

Lead administration (250, 500, 1000, and 2000 ppm, as lead acetate) in drinking water during fetal development (from 15 to 20 days of gestation), in normal and iron-deficient pregnant rats, revealed dose-dependent increases in the lead content of maternal blood that was more marked in iron-deficient animals. The placentae and fetuses did not show a dose-dependent increase in lead content. Lead administration revealed dose-dependent hydropic degeneration of renal proximal cells in the fetuses. The highest dose (2000 ppm lead) and iron deficiency exhibited more lead accumulation in maternal blood, placentae, and fetuses, and maximum pathologic changes in the fetal kidney when compared with the other doses and also with the fetuses of dams not deficient in iron.

Animals↗
PubMed1990

Continuous-variable quantification of dermatoglyphic whorl patterns: a statistical study of angular measurements.

Core(s) and triradii of dermatoglyphic whorl patterns were joined together to form triangles. Base angles of these triangles were measured (in degrees). The tangent angle at the lower edge of a ridge crossing the core-triradius line was also measured in degrees on each side of the whorl. Significant differences and similarities of these angles were investigated for unrelated Caucasian males and females by the use of Student's t- and Pearson's r-tests. Angular findings were related to the corresponding information provided by ridge counts. Similarities and differences between males and females are described.

Dermatoglyphics↗
PubMed1990

Studies on the antiviral activity of inorganic heteropolyanions against Semliki forest virus in vivo and vaccinia virus in vitro.

Seven new inorganic heteropolyanions were tested for their antiviral activity. One of these, sodium 12-tungstoborate, was found to protect mice from Semliki forest virus and mouse embryo fibroblast monolayers from vaccinia virus infections. In mice these heteropolyanions exhibited no synergistic antiviral activity with the interferon inducing mycoviral double-stranded RNA.

Animals↗
PubMed1989

The antioxidants as protectors of host stress organ injury in mice infected with Plasmodium berghei.

A study has been made of counteracting the stress organ injury in Plasmodium infection by means of antioxidants on the premise that free radicals are responsible for causing the injury to stress organs. This was evidenced by drastically altered biochemical parameters in liver and spleen of the host in terms of elevated levels of lipid peroxides and xanthine oxidase (XO) activity, and a fall in superoxide dismutase activity coupled with other drastic biochemical changes. The cardinal factor responsible for the above was considered to be XO which engenders free radicals purportedly responsible for the stress organ (biochemical) injury. Results demonstrate a lowering of lipid peroxide levels, xanthine oxidase activity, liver weight and modulation of protein level in liver of the host (mouse) in Plasmodium infection when treated with catechin, glutathione and propylgallate.

Animals↗