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Biomedical subjects

S D Sharma

Publications and source records attributed to S D Sharma.

At least 109 records · Page 6Linked to original sources
PubMed1985

Inhibition of aflatoxin B1-hepatocarcinogenesis in rats by beta-naphthoflavone.

Effects of beta-naphthoflavone (beta NF) on the activity of hepatic microsomal aflatoxin B1 (AFB1)-4-hydroxylase - the cytochrome P-450-dependent enzyme system which catalyzes the metabolism of AFB1 to AFM1 - and on AFB1-induced in vivo hepatocarcinogenesis were investigated in weanling male Fischer rats. A single i.p. injection of beta NF in doses of 20 mg/kg and 150 mg/kg induced AFB1-4-hydroxylase 3- and 4-fold, respectively, 48 h post injection. Feeding of diet containing 0.01% beta NF for a period of 9-weeks induced AFB1-4-hydroxylase approximately 2-fold. AFB1, given by intubation in a dose of 25 micrograms five times/week for 8 weeks, produced 42 weeks later a 100% incidence of liver lesions (neoplastic foci, nodules or tumors), but feeding beta-NF in diet at a concentration of 0.015% for one week prior to and during the 8 weeks of AFB1 treatment inhibited AFB1 hepatocarcinogenesis by approximately 75%. These results are in accord with the suggestion that AFB1-4-hydroxylase induction may be associated with the inhibition of AFB1 carcinogenesis, possibly occurring as a consequence of accelerated detoxification of AFB1 via its conversion to AFM1.

Aflatoxin B1↗
PubMed1985

Detection of Toxoplasma gondii antigens by a dot-immunobinding technique.

A sensitive assay for the detection of antigens of Toxoplasma gondii by spotting samples directly onto nitrocellulose paper was developed. The sensitivity ranged from 10 to 40 pg of antigen diluted in phosphate-buffered saline and 40 to 130 pg of antigen diluted in normal mouse serum, normal human serum, or human cerebrospinal fluid. T. gondii antigen in serum samples taken from mice infected with T. gondii was detectable by day 2 of infection. Antigen was also detectable in cerebrospinal fluid samples taken from four of six infants congenitally infected with T. gondii and in serum samples from two of these infants.

Animals↗
PubMed1985

In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii.

Administration of recombinant interleukin 2 (rIL 2) resulted in a significant (p less than 0.01) decrease in mortality in mice infected with a dose of Toxoplasma gondii that killed 100% of untreated mice. Mice treated with rIL 2 had a significantly (less than 0.005) lower numbers of cysts in the brains. The protection afforded by rIL 2 could not be correlated with increased antibody synthesis or be explained by increased macrophage killing in the treated mice. Mice treated with rIL 2 after Toxoplasma infection demonstrated increased natural killer (NK) cell activity compared with either Toxoplasma-infected or rIL 2-treated mice. rIL 2 failed to reverse the suppressed proliferative response of lymphocytes to concanavalin A and lipopolysaccharide in mice acutely infected with a virulent strain of T. gondii. These results reveal that rIL 2 may have a remarkably protective effect against intracellular parasites.

Animals↗
PubMed1984

Regulation of natural killer cell activity by anti-I-region monoclonal antibodies.

The effects of a monoclonal antibody directed against immune response gene products on mouse NK activity were examined. In vivo administration of an anti-I-Ak antibody to C3H/He (H-2k) mice modulated their peritoneal cell (PC) and spleen cell (SC) natural killer (NK) activity against YAC-1 lymphoma target cells in vitro. No such effect was observed when BALB/c (H-2d) mice were treated with this antibody. Administration of anti-I-Ak antibody to mice before and after infection with Toxoplasma or treatment with poly(I:C) leads to suppression of NK activity in comparison to NK activity of mice infected with Toxoplasma or injected with poly(I:C) alone. A similar treatment regimen with M5/114 antibody which reacts with I-Ab, I-Ad, I-Ed, and I-Ek molecules resulted in decreased NK activity in B10.D2 (H-2d) but not in B10.BR (H-2k) mice. Serum and cell culture supernatant interferon (IFN) concentrations were not altered as a result of anti-I-Ak treatment. Removal of adherent cells did not restore NK activity of anti-I-Ak-treated Toxoplasma-infected mice to levels obtained with mice infected with Toxoplasma. In contrast, depletion of Ly 2.1+ cells from nylon-wool nonadherent SC of mice treated with anti-I-Ak antibody, before and after infection with Toxoplasma, resulted in restoration of NK activity to the same level as that observed in Toxoplasma-infected mice.

Animals↗
PubMed1984

Enhancement of human natural killer cell activity by subcellular components of Toxoplasma gondii.

The ability of sonicates and subcellular fractions of the intracellular parasite Toxoplasma gondii to enhance in vitro human natural killer (NK) cell activity was examined. Incubation of nylon-wool-non-adherent human peripheral blood lymphocytes (PBL) with sonicates of T. gondii for 18-72 hr resulted in increased NK activity against an NK-sensitive, as well as an insensitive, target cell. Single-cell assays revealed that augmentation of NK activity was not due to an increased binding of K562 target cells to effector cells. Differential centrifugation studies indicated that NK-augmenting activity was distributed in membrane-enriched and cytoplasmic fractions. This activity was found to be resistant to treatment with ribonuclease (RNase) and deoxyribonuclease (DNase), but susceptible to proteolysis. Antibodies present in the serum of humans infected with Toxoplasma blocked the NK cell-augmenting effect of the membrane-enriched fractions. Enhancement of NK activity by PBL incubated with Toxoplasma sonicate was accompanied by a concomitant increase in interferon (IFN), but not of interleukin 2 (IL-2), levels in supernatants of the cell cultures.

Adult↗
PubMed1984

The role of fibrinolysis in the therapy of peripheral vascular disease.

In vivo thrombolytic studies in stumptailed monkeys indicated that pentoxifylline potentiates thrombolysis induced by urokinase activated human plasmin. Pentoxifylline as well as prostaglandin E1 released plasminogen activators and activated the fibrinolysin system. From this point of view pentoxifylline and prostaglandin E1 synergized with each other. Pentoxifylline potentiated the thrombolytic effect of prostaglandin E1 in vivo.

Alprostadil↗
PubMed1984

Effects of lysosomotropic amines on human polymorphonuclear leucocyte function.

Lysosomotropic agents interfere with lysosome function. We studied the effects of the lysosomotropic amines: lidocaine, diphenylamine and dansylcadaverine on several functions of human polymorphonuclear leucocytes (PMN): enzyme release, phagosome-lysosome fusion, superoxide anion generation upon stimulation with opsonized bacteria, and phagocytosis and killing of opsonized Staphylococcus aureus. Lidocaine depressed all cellular functions tested. Diphenylamine reduced enzyme release and phagosome-lysosome fusion in phagocytosing PMN. This was accompanied by an increase in superoxide anion generation. Dansylcadaverine enhanced enzyme release and phagosome-lysosome fusion, and reduced superoxide anion generation. Neither of these two agents influenced bacterial uptake; bacterial killing was impaired only in dansylcadaverine treated cells. Cadaverine, an analogue that does not penetrate cells, had no effect on any of the functions tested.

Amines↗
PubMed1984

Determination of aromatic amino acids by ion-pair reversed-phase liquid chromatography in human sera from healthy and phenylketonuric individuals.

A simple chromatographic procedure is described for simultaneous analysis of aromatic amino acids in serum samples obtained from normal individuals and from phenylketonuric patients. Quantitative measurement of phenylalanine, tyrosine, histidine and tryptophan is made in samples as small as 10 microliter after deproteinization with trichloroacetic acid. With phenoxyacetic acid as the internal standard, samples are analyzed by reversed-phase chromatography isocratically by an ion-pairing agent in the eluent, and the amino acids are detected with the UV detector at 210nm. Total analysis time was about 30 minutes. Using this method in serum samples from phenylketonuric patients phenylalanine was increased (as expected), and histidine was decreased, at a statistically significant level.

Amino Acids↗
PubMed1983

Leiomyoma of the palate.

Leiomyoma, a benign neoplasm of smooth muscle cell origin, has been documented infrequently in the oral cavity. It may arise wherever unstriated muscle is present including the arterial wall (Cherrick et al., 1973). The most common site is the uterus, followed by the wall of the alimentary canal and in subcutaneous tissue (McCaffrey et al., 1978). A search of the literature revealed 51 cases of oral leiomyomas. Cherrick et al. (1973) reviewed 35 cases, including seven of their own. Galili and Shteyer (1974) summarized the clinical data of 42 cases of oral leiomyomas reported since 1884. We can find only nine more reported cases of leiomyoma in the oral cavity: one each by Rhatigan and Kim (1976), Shirota et al. (1976), Kelly and Harrigan (1977), Schweigel (1980), Davis (1980) and Mechlin et al. (1980); and three cases by Damm and Neville (1979). The common sites in the oral cavity are the tongue and cheek but its occurrence on the palate is rare for out of the 51 cases of oral leiomyomas, only 10 involved the palate (one case each was reported by Fein, 1905; Kist and Bhaskar, 1964; Garrett, 1969; Galili and Shteyer, 1974; Rhatigan and Kim, 1976; and Davis, 1980; and four cases by Cherrick et al., 1973). Its rarity and large size make the tumour worth reporting.

Adult↗
PubMed1983

Augmentation of NK cell activity by soluble and particulate fractions of Toxoplasma gondii.

The ability of sonicates of Toxoplasma gondii and of subcellular fractions of the organism to enhance natural killer (NK) cell activity in mice was examined. Treatment of BALB/c mice with the sonicate preparations enhanced peritoneal and splenic NK activity to the level obtained with intact tachyzoites. Similar augmentation of NK activity in A/J, C57BL/6, and C3H/HeJ mice was also observed. Administration of Toxoplasma sonicate intraperitoneally, intravenously, or subcutaneously enhanced both peritoneal and splenic NK activity. Treatment of mice with a sonicate of L929 fibroblast failed to enhance their NK activity. Concentrations of sonicates ranging from 400 to 4 micrograms of protein enhanced both peritoneal and splenic NK activity. Both the soluble and particulate fractions of the sonicate obtained by differential centrifugation were capable of enhancing peritoneal NK activity, whereas splenic NK activity was enhanced only by the particulate fraction. Heat, protease, and sodium periodate treatment of the Toxoplasma sonicate completely abolished its capacity to augment NK activity. Gel filtration studies revealed that the NK augmenting activity of the Toxoplasma sonicate is distributed over a wide molecular weight range.

Animals↗
PubMed1983

In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.

Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.

Ammonia-Lyases↗
PubMed1983

Inhibition of human natural killer activity by lysosomotropic agents.

We have examined the effect of three lysosomotropic amines on human NK cell activity. Dansylcadaverine (DCA), diphenylamine (DPA), and lidocaine (LID) inhibited NK activity of nylon wool-purified and large granular lymphocyte (LGL)-enriched cell preparations. Cadaverine (CAD), an analog of DCA that does not affect lysosomal function, had no effect on NK activity. Binding of the K562 target cells to effector cells, as assessed in a single cell assay, was not inhibited by DCA, DPA, or LID. Cytotoxicity was inhibited by DCA and DPA only when these drugs were added within 5 min after the initiation of NK assays. In contrast, LID inhibited NK activity even when added 60 min after the addition of effector cells to target cells. All three amines that inhibited NK activity also reduced the intracellular concentration of the lysosomal enzyme beta-glucuronidase without affecting the activity of the cytoplasmic enzyme lactate dehydrogenase. Kinetic analysis revealed that LID inhibited both the maximum velocity (Vmax) of the cytotoxicity reaction as well as the affinity constant (Km); whereas DCA and DPA only inhibited Vmax.

Adult↗
PubMed1983

Western Blot analysis of the antigens of Toxoplasma gondii recognized by human IgM and IgG antibodies.

Western Blot analysis revealed that both IgM and IgG antibodies present in the sera of humans infected with Toxoplasma gondii recognize three major antigens with apparent m.w. of 32,000, 22,000, and 6000, respectively. In addition, IgG antibodies recognized at least 17 other antigenic components. After subcellular fractionation, enrichment of the three major antigens recognized by IgM and IgG antibodies by the membrane fraction was observed. Solubilization of membrane-enriched preparations with a mixture of sodium dodecyl sulfate and sodium deoxycholate did not reveal any new antigenic structures that reacted with IgM or IgG antibodies. Treatment of Toxoplasma lysate preparations and various fractions obtained after differential centrifugation with NaIO4 diminished the reactivity of the antigens with both IgM and IgG antibodies. Lipase treatment had no effect on the number or nature of antigens recognized by IgM antibody. Treatment with pronase and trypsin eliminated the 32,000 and 22,000 m.w. antigenic components detected by IgM antibodies, whereas such treatment had no effect on the 6000 m.w. component. Periodic acid-Schiff staining of polyacrylamide gels of Toxoplasma sonicates revealed the presence of three components corresponding to m.w. of 62,000, 45,000, and 6000, respectively. At least 15 components, including the 6000 m.w. component, directly bound concanavalin A.

Animals↗