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Biomedical subjects

G S Rao

Publications and source records attributed to G S Rao.

At least 19 recordsLinked to original sources
PubMed1992

Chemotaxis of human blood monocytes toward endothelin-1 and the influence of calcium channel blockers.

The adherence of monocytes to the arterial endothelium followed by its migration into the arterial intima is the earliest event in atherogenesis. The vasoconstrictive peptide, Endothelin-1 (ET-1), is elevated in patients with atherosclerosis. We were interested to know whether ET-1 was a chemoattractant for blood monocytes. Using the modified membrane filter technique for chemotaxsis assessment, ET-1 increased monocyte chemotaxis in a dose-dependent manner. Ca2+ channel blockers, Nifedipine, Diltiazem and Verapamil (5 microM), reduced ET-1 chemotaxsis more than 60% (P < 0.001). Aspirin and Indomethacin (1 mM and 100 microM, respectively) reduced migration by 23% (P < 0.05). Alpha-Lipoic acid, Probucol and Neomycin (100 microM) were also migration inhibitory (37%, P < 0.01). These results suggest that ET-1 is a strong chemoattractant for blood monocytes; Ca2+ influx is probably the major stimulus for the accelerated migration induced by ET-1.

Aspirin↗
PubMed1992

Crystallization of the NAD-dependent malic enzyme from the parasitic nematode Ascaris suum.

The malic enzyme from muscle mitochondria of the parasitic nematode Ascaris suum is a tetramer of 65 kDa monomers that catalyzes the oxidative decarboxylation of malate to pyruvate and CO2 with NAD cofactor as oxidant. This malic enzyme is critical to the nematode for muscle function under anaerobic conditions. Unlike mammalian versions of the enzyme such as that found in rat liver, which require NADP as cofactor, the nematode version is an NAD-dependent enzyme. We report the crystallization of samples of the nematode enzyme at room temperature from pH 7.5 solutions of polyethylene glycol 4000 containing magnesium sulfate, NAD and sodium tartronate. Immediately upon mixing of protein and precipitant solutions, a marked precipitation of the protein occurs. Out of this precipitate, crystals appear almost immediately, most commonly in a truncated cube form that can grow to 0.5 to 0.7 mm on a cube edge in two to three days. The crystals are trigonal, space group P3(1)21 or its enantiomer, with a = b = 131.2(7) A, c = 152.6(9) A, and two monomers per asymmetric unit. Fresh crystals diffract X-radiation from a synchrotron source (lambda = 0.95 A) to about 3.0 A resolution. Rotational analysis of Patterson functions indicates that the malic enzyme tetramer has 222 symmetry.

Animals↗
PubMed1992

Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3.

It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro-Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc-L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol-water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = -22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = -178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipeptides↗
PubMed1992

Effects of active site modification and reversible dissociation on the secondary structure of triosephosphate isomerase.

Binding of ligands to the catalytic center of mammalian triosephosphate isomerase (TPI) induces a conformational change(s) that enhances the specific deamidation of Asn71 at the subunit interface. Deamidation initiates dissociation and degradation of the enzyme in vivo and in vitro. We have utilized circular dichroism spectroscopy to examine the conformational changes in the enzyme upon ligand binding and subunit dissociation/reassociation. Native TPI from rabbit, chicken, and yeast exhibit similar spectra at pH 7.5, but are substantially different at pH 9.5. Covalent reaction of the active site Glu 165 with the substrate analogue 3-chloroacetol phosphate results in a conformational change (decrease in beta-sheet) which is similar in TPI from all three species. Reversible dissociation of the dimeric enzyme in guanidine followed by dialysis, although permitting full recovery of catalytic activity, results in refolded dimers with decreased alpha-helix. These conformational changes induced by ligand binding, pH, or reversible dissociation explain, in part, the differences in the chemical and physical properties of the enzyme from the three species at alkaline pH, the increased lability of the dissociated/reassociated enzyme, and corroborate 31P NMR data on substrate-induced conformational changes. These studies also support the concept of molecular wear and tear whereby ligand binding at the catalytic center induces conformational changes that increase the probability of covalent modification and ultimate degradation of the protein.

Animals↗
PubMed1992

The management of tumours arising in the maxillary antrum.

Eighty-eight cases of tumours arising in the maxillary antrum undergoing treatment between 1967 and 1989 are reported. The series comprised 34 females and 54 males. Sixty-two patients had squamous cell carcinoma (SCC). Forty of those with SCC were treated by XRT only, four cases by surgery only, while the remaining 18 patients had surgery and post-operative XRT as a combined modality treatment. Early SCC (T2N0) was adequately controlled by radical radiotherapy alone with a 5-year survival of 69.1%. In more advanced SCC (T3N0 and (T4N0) radical radiotherapy alone was less successful with the 5-year survival falling to 19%. Combined modality treatment comprising radical surgery followed by radical postoperative radiotherapy improved 5-year survival in advanced SCC to 61%. It is therefore recommended that if patients are treated for cure, major surgery followed by radical postoperative radiotherapy is preferable in advanced squamous tumours ((T3/T4) of the maxillary antrum.

Adult↗
PubMed1992

Percutaneous absorption enhancement of leuprolide.

Chemical enhancers and vehicles were tested for their ability to improve the percutaneous absorption of leuprolide, a nonapeptide (luteinizing hormone releasing hormone analogue; MW 1209.4). In vitro permeabilities in nude mouse, snake, and cadaver skin were evaluated in either Franz diffusion cells or a Bronaugh flow-through system using an HPLC assay. Skin irritation caused by the formulations was evaluated in the rabbit. The chemical enhancer systems investigated strongly enhanced skin penetration of leuprolide. Maximum permeability enhancement of leuprolide acetate can be achieved with a nonirritating formulation containing ethanol, menthol, camphor, methyl salicylate, urea, and hydrogel. The in vitro permeability in nude mouse skin was 10 or 100 times higher than that obtained in cadaver skin, depending on the type of enhancer that was used in the formulation. Snake skin was at least 10 times less permeable than cadaver skin in this study. However, the effects of chemical enhancers on skin permeability were highly dependent on the skin model. Further, the in vitro permeability of leuprolide in the base form was 10 times higher than in the acetate form with the enhancers.

Acetates↗
PubMed1992

Trichloroethylene toxicity in mice: a biochemical, hematological and pathological assessment.

Oral administration of trichloroethylene (TCE; 0, 500, 1000 and 2000 mg/kg/day) to male mice once daily, 5 days a week for a period of 28 days, caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and characteristics proliferation of endothelial cells of hepatic sinusoids. Increase in kidney weight, glomerular nephrosis, degeneration/desquamation of tubular epithelium and characteristic amyloid deposition in glomeruli were observed only in the group of mice treated with 2000 mg/kg TCE. These changes occurred concurrently with a significant increase in total protein and free sulphydryl contents, elevated activities of acid phosphatase and catalase and decreased activity of delta-aminolevulinic acid dehydratase (delta-ALAD) indicating the sensitivity of liver and kidney as target tissues in TCE-toxicity. Hematological studies showed a significant increase in RBC counts and a reduction in WBC counts without any statistically significant change in the hemoglobin, urea nitrogen, creatinine and uric acid levels in the blood of TCE-exposed mice. A dose-related increase in cell density and acid phosphatase activity with a parallel significant decrease in the activity of delta-ALAD were observed in the bone marrow, which appear to be responsible for hematological alterations in TCE-exposed mice. The results suggest that early metabolic, pathological and hematological perturbations following a short-term exposure of TCE in mice, can provide the basis for its documented potential for chronic effects like blood dyscrasia and cancer.

Animals↗
PubMed1992

Blood basopenia as an indicator of ovulation.

Direct basophil counts were done on capillary blood samples in thirteen normal young women, during the different phases of their menstrual cycles. Mean basophil counts during the follicular and progestational phases were 36.6/cumm and 39.3/cumm respectively. A significant midcycle fall in counts of 36% and a premenstrual fall of 22% were observed. These changes are probably due to migration of the cells from the peripheral blood into the rupturing follicle of the ovary and into the ischemic premenstrual endometrium.

Adolescent↗
PubMed1991

Hematin catalysed autooxidation of hydroquinone or 1,2,4-benzenetriol.

Autooxidation of hydroquinone (HQ) or 1,2,4-benzenetriol (BT), catalysed by hemin in the presence of dithiothreitol was studied in phosphate buffered saline. Inclusion of glutamate in the above reaction mixture resulted in the formation of thiobarbituric acid reactive products (TBAR) only in an aerobic atmosphere and was linear up to 2 h. Oxygen consumption was noticed during the reaction process. The formation of TBAR was linear with the increase in concentration of heme (1-4 microM), dithiothreitol (0.2-2 mM) or BT (0.17-0.85 mM). Linearity of TBAR formation from glutamate for up to 2 h was observed during the autooxidation of BT in the presence of heme. Besides glutamate, heme concentration dependent formation of TBAR from deoxyuridine or DNA was also observed. Almost complete inhibition of TBAR formation from glutamate, deoxyuridine or DNA was observed in the presence of catalase or superoxide dismutase (SOD). The presence of thiourea or mannitol in the reaction mixture caused substantial diminution of TBAR formation. Albumin or dimethyl sulfoxide also caused partial inhibition. Complete to partial inhibition observed in the presence of oxyradical scavengers in this study indicates that hemin catalysed autooxidation of BT results in the formation of reactive oxygen radicals.

Aldehydes↗
PubMed1991

Release of 2-thiobarbituric acid reactive products from glutamate, deoxyuridine or DNA during autoxidation of dopamine in the presence of copper ions.

Cytotoxic effects of catecholamine are thought to be caused by the formation of 0-semiquinone and superoxide radicals. Dopamine in the presence of copper ions releases aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was concentration dependent of both dopamine and copper ion. Complete inhibition of formation of TBAR from glutamate, deoxyuridine or DNA was observed in the presence of thiourea and catalase. Mannitol, albumin and superoxide dismutase offered substantial protection. The present data indicate that dopamine in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release aldehydic products from glutamate, deoxyuridine or DNA capable of reacting with TBA.

Aldehydes↗
PubMed1990

Accumulation of low molecular weight (bleomycin detectable) iron in bone marrow cells of rats after benzene exposure.

An accumulation of low molecular weight (LMW) bleomycin detectable iron in the bone marrow was observed after administration of benzene (IP 0.5 ml/kg, daily) for 5 and 10 days in female albino rats. However, this LMW iron was not detectable in the bone marrow of rats from the control group. Studies of bone marrow fractionation showed that the maximum accumulation of this LMW iron was in the mitochondrial fraction. An increase in the activity of superoxide dismutase and lipid peroxidation was also noticed in the benzene exposed groups.

Animals↗
PubMed1979

Investigations on myelination in vitro. Regulation by thyroid hormone in cultures of dissociated brain cells from embryonic mice.

Cultures of dissociated brain cells from embryonic mice were used to study the influence of thyroid hormone on myelination in vitro. Synthesis of myelin-associated lipids such as cerebrosides and sulfatides was used as an index for myelination. An experimental design, in which the cells were grown on medium containing serum from a thyroidectomized calf, was employed to demonstrate the direct effect of L-3,5,3'-triiodothyronine (T3Y on the biosynthesis of myelin lipids. The cells grown in the presence of hypothyroid calf serum which contained very low levels of thyroid hormones (T4 (thyroxine), 1.2 microgram/ml; T3, less than 25 ng/100 ml) compared to normal serum (T4, 5.8 microgram/ml; T3, 110 ng/100 ml) showed a diminished synthesis of myelin-associated glycolipids. This reduced activity could be restored to normal by including T3 (13 ng/ml) in the medium.

Animals↗
PubMed1979

Uptake of L-tri-iodothyronine by isolated rat liver cells. A process partially inhibited by metabolic inhibitors; attempts to distinguish between uptake and binding to intracellular proteins.

1. Rat liver cells obtained by dispersion with collagenase were used to investigate the mode of entry of L-tri-iodothyronine into the cell. 2. The hormone was taken up very rapidly at 23 degrees C; the linear phase of uptake lasted for up to approx. 20 s. 3. A plot of the initial rates of uptake against different concentrations of L-tri-iodothyronine yielded a sigmoidal curve. The Eadie--Hofstee plot (v/[S]2 versus v) yielded two straight lines. The uptake component with an apparent Kt value of 86 +/- 15 pM was designated as system I, and the second uptake component with an apparent Kt of 726 +/- 11 pM as system II. The Hill plot for system I was not linear; the apparent Hill coefficient for system II was calculated to be 2.1.4. Uptake of L-tri-iodothyronine by system I was higher at pH 6.4 than at pH 7.4; system II was relatively insensitive to changes in the pH of the external medium. 5. Both systems exhibited a transition temperature at about 16 degrees C in the Arrhenius plot. The activation energies of the two systems below and above 16 degrees C were 72.8 and 47.7 and 54.4 and 33.1 J/mol respectively. 6. Inhibitors of cellular energy reduced the uptake by system I to a larger extent than that by system II. 7. Replacement of Na+ in the external medium by either K+ or choline led to uptake that followed normal Michaelis--Menten kinetics. 8. Thiol-group-blocking agents reduced the uptake of the hormone by both systems. 9. Treatment of liver cells with beta-glucosidase, Pronase and neuraminidase led to a decrease in the uptake of L-tri-iodothyronine by system I, whereas uptake by system II was decreased after treatment with phospholipase A2, beta-galactosidase. Pronase and neuraminidase. 10. The stereoisomer D-tri-iodothyronine (100--3000 pM) did not affect system I, but uptake by system II decreased with increasing concentration of D-tri-iodothyronine. Reverse L-tri-iodothyronine (2--100 pM) and L-thyroxine (100--3000 pM) did not influence uptake by either system. 11. Under identical conditions of incubation, the uptake of L-tri-iodothyronine was 3.7 times higher than binding to cytosol proteins. The binding was insensitive to metabolic inhibitors. The results suggest that cytosol proteins are not directly involved in the uptake of L-tri-iodothyronine. 12. Plasma-membrane vesicles also take up the hormone rapidly at 23 degrees C. Increasing the osmolarity of the external medium led to a decrease in the uptake of L-tri-iodothyronine by vesicles. 13. Uptake as a function of L-tri-iodothyronine concentration exhibited a sigmoidal curve. The Eadie--Hofstee plot showed two uptake components with apparent Kt values of 96.8 and 1581 pM. 14. The results of our study are consistent with a carrier-mediated translocation of the hormone into the cell.

Animals↗