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Biomedical subjects

K Mehta

Publications and source records attributed to K Mehta.

At least 37 records · Page 2Linked to original sources
PubMed1987

Treatment of hepatosplenic candidiasis with liposomal-amphotericin B.

Nine patients with hematologic malignancies developed fungal infections, predominantly involving the liver and spleen. Eight patients had biopsy-documented progressive candidiasis and one had an unclassified fungus. The patients were treated with liposomal-amphotericin B (L-AmpB) after their fungal infection progressed during treatment with standard intravenous (IV) AmpB (Fungizone; E. R. Squibb & Son, Princeton, NJ) and/or other antifungals. Eight patients (88.8%) were cured of their fungal infection, and one showed improvement after treatment. Minor acute toxicity and no chronic toxicity were associated with the administration of L-AmpB. L-AmpB is a safe and effective therapeutic method for treating fungal infections that have invaded the liver and spleen even when they are refractory to conventional anti-fungal therapy.

Adolescent↗
PubMed1987

Expression of c-fos, c-myb, and c-myc in human monocytes: correlation with monocytic differentiation.

Terminal differentiation of human monocytic leukemia cells (THP-1 cells) was associated with the induction of c-fos, the down regulation of c-myb, and no significant change in the level of c-myc expression. Gamma interferon, which resulted in a slight decrease in c-myb but no change in c-fos or c-myc expression, had a transient antiproliferative effect without a morphological or functional differentiation of THP-1 cells. Resting human peripheral blood monocytes have a high c-fos, a low c-myc, and no detectable c-myb expression. These findings suggest that a switch in c-fos/c-myb expression is associated with the terminal differentiation of cells of the monocytic lineage.

Cell Differentiation↗
PubMed1986

Amphotericin B inhibits the serum-induced expression of tissue transglutaminase in murine peritoneal macrophages.

Culture of mouse resident peritoneal macrophages (PM) in serum-containing medium causes a rapid and marked induction of the enzyme tissue transglutaminase (tissue TGase). Coculture of PM with amphotericin B (AmpB) inhibited the serum-induced expression and accumulation of tissue TGase. The AmpB-mediated inhibition of tissue TGase was specific and was due to inhibition of enzyme synthesis. The serum-dependent induction of tissue TGase was inhibited in a dose-dependent fashion, and a complete inhibition was observed at 1.5 microgram/ml dose of AmpB. The inhibition was reversible; however, the time of recovery depended on the dose and time of exposure of the cells to AmpB. The present studies suggest that AmpB-mediated inhibition of tissue TGase is due to inhibition of the uptake of serum retinoids by PM.

Amphotericin B↗
PubMed1986

Expression of tissue transglutaminase in cultured monocytic leukemia (THP-1) cells during differentiation.

Retinoic acid (RA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced differentiation of a human monocytic leukemia cell line, THP-1. RA- or TPA-treated cells stopped proliferating, became adherent to plastic surfaces, and acquired the ability to phagocytose yeast cells, plain sheep RBCs, and IgG-coated sheep RBCs. The morphological and functional changes, induced by RA or TPA, were associated with a 20-50-fold increase in cellular transglutaminase activity. This increase in enzyme activity was found to be due to the induction of a specific intracellular transglutaminase, tissue transglutaminase. The induction of tissue transglutaminase was a specific response of THP-1 cells to differentiation and was not observed with agents that did not induce their morphological or functional differentiation. Dibutyryl cyclic AMP potentiated the RA-induced expression of tissue transglutaminase. A 15-min exposure to TPA was sufficient to induce differentiation and expression of tissue transglutaminase in THP-1 cells. In contrast, RA required a continuous exposure (48 h) to induce similar changes in morphology or enzyme activity. These results support the view that differentiation of cells of the monocytic lineage is associated with an induction and accumulation of the protein cross-linking enzyme tissue transglutaminase.

Bucladesine↗
PubMed1985

Protective effect of liposomal-amphotericin B against C. albicans infection in mice.

The efficacy of free amphotericin B (AmpB) and liposomal-amphotericin B (L-AmpB) in the protection against C. albicans infection in mice was studied. Mice injected with a single dose of L-AmpB (1-4 mg/kg) two days prior to the yeast inoculation had an increased survival time when compared to animals injected with lower doses (0.8 mg/kg) of free AmpB or L-AmpB. L-AmpB (4 mg/kg of body weight) conferred protection against the fungal infection even when administered as a single dose five days prior to the yeast inoculation. A single-dose regimen of free AmpB showed a protective effect only when administered two days prior to the inoculum. When mice were challenged with larger yeast inocula, protection was seen with L-AmpB (4 mg/kg) or with multiple doses of free AmpB (0.8 mg/kg daily x 5) and not with single doses of free AmpB. In this group of mice, only animals treated with L-AmpB were microbiologically free of infection.

Amphotericin B↗
PubMed1985

Liposomal amphotericin B for the treatment of systemic fungal infections in patients with cancer: a preliminary study.

Twelve patients with hematologic malignancies complicated by fungal infections were treated with liposomal amphotericin B (L-AmpB). Nine patients were granulocytopenic; the three additional patients with normal granulocyte counts were immunosuppressed. All patients had biopsy findings or cultural evidence of the progression of their fungal infection while being treated with conventional amphotericin B. Doses of 0.8-1.0 mg/kg of L-AmpB were administered intravenously every 24-72 hr. Three patients had a complete remission, five had a partial remission, and four showed no improvements. A total of 161 doses of L-AmpB were administered. Fever and chills occurred on seven occasions. No hematologic or blood chemistry abnormalities related to L-AmpB treatment were observed.

Adolescent↗
PubMed1985

Selective toxicity and enhanced therapeutic index of liposomal polyene antibiotics in systemic fungal infections.

Incorporation of the polyene antibiotic amphotericin B (AMB) in liposomes results in a marked reduction in drug toxicity with no loss of antifungal potency. Nephrotoxicity, the dose-limiting side effect of AMB, is almost abolished when the drug is utilized in a liposomal carrier. Because of reduced toxicity, high doses of liposomal AMB can be used, resulting in superior therapy of systemic fungal infections in mice. The improved therapeutic index of liposomal AMB versus free AMB is also manifest in infected neutropenic animals. The reduced toxicity of liposomal AMB is due to a fundamental alteration in the interaction of the drug with mammalian cell membranes. AMB transfers effectively from donor liposomes to fungal cell walls and membranes and is thus toxic to fungi. By contrast, AMB does not transfer from liposomes to mammalian cells and thus is not toxic to these cells. Thus, the use of liposomal AMB may offer a marked improvement in the therapy of systemic fungal infection in cancer patients and other immunodebilitated individuals.

Amphotericin B↗
PubMed1985

Prophylaxis of murine candidiasis via application of liposome-encapsulated amphotericin B and a muramyl dipeptide analog, alone and in combination.

The present study was conducted to examine the effect of a lipophilic analog of muramyl dipeptide, 6-O-stearoyl-N-acetylmuramyl-L-alpha-aminobutyryl-D-isoglutamine (6-O-S-Abu-MDP), a macrophage activator, on the prophylactic activity of liposomal amphotericin B (L-AmpB) against disseminated candidiasis in mice. Multilamellar vesicles containing AmpB and (6-O-S-Abu)-MDP were prepared by using dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol (7:3 molar ratio). Hale-Stoner mice (6 to 8 weeks old) were injected with 7 X 10(5) CFU of Candida albicans 336 isolated from a patient. Groups of mice were injected intravenously with different doses of L-AmpB and L-(6-O-S-Abu)-MDP, individually or in combination, 2 days before challenge with C. albicans. The mice were injected with a fixed dose of L-AmpB (1.2 mg/kg in 400 mg of lipid per kg) and various doses of L-(6-O-S-Abu)-MDP (0.6, 1.2, 2, and 4 mg/kg in 400 mg of lipid per kg) or vice versa. Other control groups included untreated mice and those receiving empty liposomes (400 mg of lipid per kg), free AmpB (0.6 mg/kg), or free (6-O-S-Abu)-MDP (4 mg/kg). The mice receiving L-AmpB (1.2 mg/kg) plus L-(6-O-S-Abu)-MDP (0.6 to 4.0 mg/kg) survived up to 25 to 30 days as compared with those injected with L-AmpB alone (15 days) or with L-(6-O-S-Abu)-MDP alone (10 to 15 days). All the mice in other control groups died within 7 to 11 days. The kidney cultures of the mice that received L-AmpB (4 mg/kg) plus L-(6-O-S-Abu)-MDP (1.2 mg/kg) were free of C. albicans infection, unlike those injected with L-AmpB. Variance analysis of these findings indicates a synergistic activity between L-AmpB and L-(6-O-S-Abu)-MDP in the prophylaxis of candidiasis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Effect of liposomal amphotericin B on murine macrophages and lymphocytes.

The effect of liposome-encapsulated amphotericin B on mouse macrophages and on T- and B-lymphocyte functions in vitro was compared with that of free amphotericin B. Liposomal amphotericin B was generally less toxic than the free form of the drug. Low concentrations of free amphotericin B completely inhibited the serum-dependent induction of transglutaminase, a marker for macrophage differentiation, and production of superoxide anion by macrophages, whereas encapsulation of the drug within liposomes protected the cells from these adverse effects. Liposomal amphotericin B did not affect the blastogenic response of T cells compared with the free drug, which was inhibitory at high concentrations. Antibody production in vivo was inhibited partially by both free and liposomal amphotericin B. These results thus suggest that encapsulation of amphotericin B in liposomes reduces the immunosuppressive effects exerted by free amphotericin B. This provides further justification for therapeutic use of liposomal amphotericin B in systemic fungal infections (G. Lopez-Berestein, R. Mehta, R. L. Hopfer, K. Mills, L. Kasi, K. Mehta, V. Fainstein, M. Luna, E. M. Hersh, and R. L. Juliano, J. Infect. Dis. 147:939-945, 1983).

Acyltransferases↗
PubMed1985

Interferon-gamma requires serum retinoids to promote the expression of tissue transglutaminase in cultured human blood monocytes.

The culture of HPBM in serum-containing medium induced a large accumulation of the protein cross-linking enzyme, tissue TGase. Immune IFN enhanced the expression of tissue TGase in cultured monocytes. Enzyme-inducing activity, both in normal and IFN-treated cells, was completely blocked by depleting the serum of the lipid fraction. The readdition of retinol at a physiologic concentration (1 micron) to delipidized serum completely restored the enzyme-inducing activity in cultured monocytes. Thus, serum retinoids seem to play an important regulatory role in the expression of tissue TGase gene in differentiating human monocytes.

Acyltransferases↗
PubMed1978

Effect of borax on testis of Indian desert gerbil, Meriones hurriane Jerdon.

Borax was injected at a dose level of 250 mg/kg b. wt for 16 days (total dose 4 g/kg b. wt) s.c. to active adult male gerbils. Borax caused several degenerative changes in the testes, of which giant cell formation, pyknosis and exfoliation are prominent. The increased activity of phosphatases was also noticed.

Animals↗
PubMed1978

Immune reactions in human filariasis.

Sera from cases of elephantiasis due to Wuchereria bancrofti infection promoted an intense adhesion of peripheral blood leukocytes to W. bancrofti microfilariae in vitro. A similar adhesion was also seen using sera from some normal persons living for several years in areas where filariasis is endemic. No such adhesion was evident with sera from microfilaria carriers or from normal subjects from nonendemic areas. The adhesion was complement independent and was associated with the immunoglobulin G fraction of serum. 51Cr release studies suggested the occurrence of cell-mediated cytotoxicity to W. bancrofti microfilariae in the presence of elephantiasis serum. Microfilariae of Litomosoides carinii could be isolated free of blood cells, from the blood of infected rats. In the presence of serum, or its immunoglobulin G fraction, from patients with elephantiasis, L. carinii microfilariae adhered to human peripheral blood leukocytes or rat spleen cells.

Animals↗