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Biomedical subjects

K Mehta

Publications and source records attributed to K Mehta.

At least 91 records · Page 5Linked to original sources
PubMed1989

Transglutaminase levels and immunologic functions of BCG-elicited mouse peritoneal macrophages isolated by centrifugal elutriation.

BCG-elicited mouse peritoneal macrophages were separated into three subpopulations by counterflow centrifugal elutriation. The three subpopulations were characterized on the basis of the level of a protein cross-linking enzyme, tissue transglutaminase. Subpopulation-3 consisted of large cells (greater than 95% esterase positive and greater than 90% viable) and had at least a fivefold higher transglutaminase activity (35 +/- 6 nmol/hr/mg) as compared to macrophages in subpopulation-1 (6 +/- 2 nmol/hr/mg) and at least a threefold higher enzyme activity as compared to subpopulation-2 (11 +/- 2 nmol/hr/mg). Subpopulation-3 also showed sevenfold higher phagocytosis of IgG-coated sheep red blood cells. The three subpopulations showed no difference in their ability to kill Listeria monocytogenes as determined by [3H]-thymidine release. Subpopulations-2 and -3 caused 90% inhibition of murine adenocarcinoma (EMT-6) tumor cell growth in the presence or absence of lipopolysaccharide. Subpopulation-1 had a poor ability to inhibit EMT-6 cell growth (29 +/- 12%). However, in the presence of lipopolysaccharide, this activity increased by at least threefold (92 +/- 7%). The three subpopulations showed no significant difference in their cytolytic activity against murine mastocytoma (P815) target cells in the presence or absence of lipopolysaccharide. These results suggest that tissue transglutaminase may have no significant role in bactericidal, tumoricidal, or tumoristatic function of macrophages; however, it might have some role in promoting the Fc-receptor-mediated phagocytic function of the macrophages.

Animals↗
PubMed1989

Cell-mediated immune responses to sperm antigens: effects on mouse sperm and embryos.

Sperm antigens were assessed for their ability to induce cell-mediated immune (CMI) responses. Purified fertilization antigen (FA-1), protamine, and the lithium diiodosalicylate (LIS)-solubilized sperm preparation activated presensitized lymphocytes to secrete soluble mediators that activated macrophages and significantly inhibited sperm motility and embryonic development. The FA-1, however, was the most potent antigen in inducing proliferative response as well as the release of soluble mediators. LIS-sperm preparation, which contained numerous antigens, showed the least activity. The unsensitized control spleen cells did not secrete any factor(s) when activated with the antigen. In conclusion, these results indicate that sperm antigens can specifically induce (CMI) factors that have detrimental effects on sperm motility and preimplantation embryos. These findings may have potential clinical implications for humans, especially in immunologic and unexplained infertility, recurrent abortions, and development of antisperm contraceptive vaccines.

Animals↗
PubMed1989

A case of acute monocytic leukemia with lysozyme-positive leukemic monocytes and normal serum lysozyme levels.

We report a case of acute monocytic leukemia with normal serum lysozyme but with immunoperoxidase positivity for lysozyme in the leukemic blasts. The diagnosis of acute monocytic leukemia was made on the basis of cellular morphology, immunocytochemistry and cytochemistry. Discrepancy between serum lysozyme and intracytoplasmic lysozyme has not previously been reported in the literature. Levels of serum lysozyme may be misleading in cases of acute monocytic leukemia (FAB classification M5).

Adult↗
PubMed1989

Human immunodeficiency virus-associated large-cell immunoblastic lymphoma presenting as a perianal abscess.

We report a case of perianal non-Hodgkin's lymphoma that presented as a perianal abscess in an otherwise asymptomatic intravenous drug abuser who tested positively for human immunodeficiency virus infection. Extranodal lymphoma of the anal canal is a very rare event, which has recently been described in homosexual men with the acquired immunodeficiency syndrome. This is the first report, to our knowledge, of perianal lymphoma occurring in a nonhomosexual patient with the acquired immunodeficiency syndrome.

Abscess↗
PubMed1989

Treatment of systemic fungal infections with liposomal amphotericin B.

Forty-six patients with systemic fungal infections were treated with liposomal amphotericin B. Twenty-one patients had disseminated candidiasis, 19 had aspergillosis, and the rest had a variety of other fungal infections. Forty patients failed to respond to conventional amphotericin B therapy, and 6 patients were given liposomal amphotericin B because conventional amphotericin B caused severe side effects. Twenty-four patients had a complete response, and 22 patients failed to respond. No short- or long-term toxic reactions were observed. The acute side effects such as fever, chills, and potassium loss were infrequent and milder than those commonly observed with conventional amphotericin B. No chronic renal, hematologic, or central nervous system side effects were observed. Liposomal amphotericin B therapy was effective and less toxic than conventional amphotericin B therapy.

Adolescent↗
PubMed1988

Induction of adenosine deaminase and 5' nucleotidase activity in cultured human blood monocytes and monocytic leukemia (THP-1) cells by differentiating agents.

The in vitro effect of short-term culture as well as the effect of retinol (ROH), retinoic acid (RA), muramyl dipeptide [( Abu']MDP), lipopolysaccharide (LPS), and gamma interferon (IFN-gamma) on the induction of the purine metabolic enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and 5'nucleotidase (5NT) in human peripheral blood monocytes (HPBM) was examined. HPBM isolated by centrifugal elutriation were cultured for up to 96 h. Following an initial time lag of 24 h, mean ADA activity from seven separate experiments as measured in nmoles/10(6) cells/h increased from a baseline of 31.3 +/- 9.3 to 57.8 +/- 16.4 (P less than 0.005) at 72 h and to 72 +/- 21.5 (P less than .025) by 96 h. 5NT activity increased from a baseline of 2.2 +/- 0.9 to a maximum of 44 +/- 10.1 by 72 h and then declined to 29 +/- 18 (P less than 0.005) by 96 h, while no significant change in PNP activity was observed. HPBM incubated for 3 d with optimal concentrations of LPS, RA, and IFN-gamma had increases in ADA and 5NT activity ranging from three- to 10-fold compared to HPBM cultured in media alone, whereas no effect was observed with ROH and [Abu']MDP. RA, but not ROH, significantly enhanced ADA activity in a monocytic leukemia cell (THP-1) line. Addition of RA or the tumor promoter, phorbol 12-myristic 13-acetate (PMA), to HPBM or THP-1 cells resulted in significant increases in 5NT activity with opposite effects on ADA activity. These findings suggest that the biological mechanisms associated with differentiation in normal and malignant monocytes seem to be related and that the sequence and degree to which the various differentiation agents induce the enzyme elevations are also related to the mechanisms of activation/differentiation.

5'-Nucleotidase↗
PubMed1988

Pharmacological nature of newer imidazoli(di)nes on rat anococcygeus muscle.

The Pharmacological nature of newer imidazoli(di)nes (clonidine analogs) on rat anococcygeus muscle (RA) was investigated. Clonidine analogs produced dose-dependent (1 X 10(-3) to 1 X 10(-5) M) contractions on RA. The relative affinity (pD2) values were in the rank order of ST 375 greater than ST 567 greater than ST 608 greater than CLO greater than ST 600 greater than ST 363 greater than noradrenaline (NA) greater than ST 91 greater than ST 93. The intrinsic activity (alpha E) values of ST 93, ST 91, ST 600 and clonidine were comparable to alpha E of NA while the other analogs showed lower values. The responses of the clonidine analogs and NA on RA were antagonised in the presence of phentolamine and prazosin but were unaffected by yohimbine. Propranolol, atropine, cyproheptidine, mepyramine and metiamide had no effect on the responses. Reserpine pretreatment did not inhibit the responses of clonidine analogs on RA. The data suggests that newer clonidine analogs exhibited differences for their receptor occupation and receptor activation. The excitatory effects of newer clonidine analogs on RA are mediated through the stimulation of postsynaptic alpha (alpha 1) adrenoceptors.

Animals↗
PubMed1987

Suppression of macrophage cytostatic activation by serum retinoids: a possible role for transglutaminase.

Mouse resident peritoneal macrophages, activated in vitro with murine recombinant interferon-gamma and lipopolysaccharide in the presence of sera from different sources, showed marked differences in their abilities to inhibit murine adenocarcinoma cell growth, and in induced activity of the enzyme, tissue transglutaminase. The extraction of lipids from the serum abolished its ability to induce tissue TGase activity and to inhibit cytostatic activity, but these capabilities were fully restored by readdition of all trans-retinol or all trans-retinoic acid at physiological concentrations. Addition of dansylcadaverine, a competitive inhibitor of TGase, resulted in complete recovery of macrophages from retinoid-induced suppression of cytostatic activity. These results suggest that endogenous retinoids play an important role in the regulation of macrophage-mediated cytostatic activity in a process that is independent of prostaglandin secretion but seems to involve the protein cross-linking enzyme, tissue transglutaminase.

Adenocarcinoma↗
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↗