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Biomedical subjects

M Fishman

Publications and source records attributed to M Fishman.

At least 19 recordsLinked to original sources
PubMed1991

Cytolytic activities of activated macrophages versus paraformaldehyde-fixed macrophages; soluble versus membrane-associated TNF.

Membrane-associated tumor necrosis factor (TNF) and soluble TNF were compared as to their lytic activities, and as to the kinetics of their expression by macrophages activated with LPS and/or IFN-gamma in the presence or absence of cycloheximide. EL 4 tumor cells, resistant and sensitive to lysis by recombinant TNF or membrane-associated TNF (paraformaldehyde (PF)-fixed activated macrophages) were used as targets. In the presence of cycloheximide the TNF-resistant S-EL4 cells were lysed by both TNFs. PF-fixed macrophages was cytolytic after 1 hr activation but not after 3 or more hours of activation. Their activity was totally inhibited by anti-TNF antibodies and was a composite of transmembrane (integral) TNF and soluble TNF conjugated to macrophage membrane TNF receptors. Treatment of the macrophages with glycine pH 3.0 buffer dissociated the conjugated TNF without affecting the integral membrane TNF. When macrophages were activated with LPS +/- IFN-gamma in the presence of cycloheximide or activated just with IFN-gamma their activity after fixation with paraformaldehyde was no longer detected. Nonfixed macrophages under these conditions still remained cytotoxic. Tumor cell susceptibility to membrane-associated TNF activity, in contrast to recombinant (soluble) TNF, was greatly reduced in the presence of nicotinamide, an inhibitor of ADP-ribosyltransferase, suggesting that the mechanisms of lysis by these TNFs may be different. The lytic activity of both TNFs was found to be receptor-dependent in that tumor cells, whose TNF binding sites were "down-regulated" by TPA, were rendered resistant to lysis by both membrane-associated and soluble TNFs.

Animals↗
PubMed1990

Tumor necrosis factor-alpha analyzed within individual macrophages by combined immunocytochemistry and computer-aided image analysis.

Immunocytochemical staining procedures were combined with computer-aided image analysis to quantitate the relative intracellular production of tumor necrosis factor-alpha (TNF) within individual macrophages. Optimal conditions for time and methods for the activation of TNF production, fixation of cells for optimal immunocytochemical staining, and image analysis methods were determined. Thioglycolate elicited peritoneal macrophages were readily activated to significantly increased levels of intracellular TNF, as early as 1 hr after activation with lypopolysaccharide (LPS) + interferon-gamma: maximum intracellular TNF was evident after 2-3 hr. Both LPS and interferon-gamma was necessary to increase intracellular TNF. Normal alveolar macrophages also readily produced increased intracellular TNF, but normal peritoneal and splenic macrophages were poorly activated to TNF production. Acid stripping of receptor bound TNF allowed discrimination between intracellular TNF/integral membrane TNF, and TNF-receptor-bound TNF. Results stress the importance of studying these TNF forms early after activation. Applications for TNF quantitation by these means are discussed.

Animals↗
PubMed1990

TPA induction of EL4 resistance to macrophage-released TNF: role of ADP-ribosylation in tumoricidal activities of TNF and other factors.

Activated macrophages synthesize and release numerous tumoricidal soluble factors that can be divided into receptor- or nonreceptor-dependent agents. Tumor necrosis factor (TNF) would be an example of the former. In our experimental model the killing of EL4 thymoma cells by syngeneic activated macrophages involves, but not exclusively, TNF. Our results show that approximately 50% of the anti-EL4 activity expressed by macrophages can be specifically inhibited with rabbit anti-mouse TNF antibody. EL4 variants resistant to the lytic activity of TNF were still susceptible to macrophage-mediated lysis. A tumor-promoting phorbol ester, TPA, rendered TNF-sensitive and -insensitive EL4 cells resistant to M phi-mediated lysis. However, TPA down-regulated TNF-specific binding sites on both TNF-sensitive and -resistant cell surface membranes, suggesting that resistance to TNF involves postligand:receptor events. Tumor cell G-protein involvement (ADP-ribosylation), as a result of TNF-TNF receptor interactions, was investigated. The results showed that pertussis toxin was cytotoxic against TNF-sensitive and -resistant EL4 cells but not against TPA-treated target cells. Inhibitors of ADP-ribosyltransferase inhibited pertussis toxin cytotoxicity and macrophage-mediated lysis but did not interfere with recombinant TNF lytic activity.

Animals↗
PubMed1990

Binding of polymyxin B to rat alveolar macrophages.

The specific binding of radiolabeled polymyxin B (PmB) to rat alveolar macrophages was investigated. PmB retained its ability to inhibit lipopolysaccharide-induced tumor necrosis factor production by macrophages as long as one of five amino groups on PmB was unbound. Binding was saturable and temperature- and time-dependent, reaching steady state by 30 min at 37 degrees C and by 18 h at 4 degrees C. Macrophages had approximately 1.6 X 10(7) (Kd = 0.28 nM) PmB binding sites per cell. Lipid A had no appreciable effect on the number of sites. Binding did not occur to rat platelets, L929 fibroblast cells, a rat thymoma cell line, or precursor monocytic and myeloid cell lines. Precursor cells activated with 12-O-tetradecanoylphorbol-13-acetate acquired binding similar to that seen in alveolar macrophages, but L929 fibroblasts did not. Binding sites were sensitive to trypsin but not to phospholipase C. PmB may interact with specific binding sites involved in lipopolysaccharide-induced activation, production, or release of tumor necrosis factor by macrophages, inhibiting the effects of lipopolysaccharide on macrophages.

Animals↗
PubMed1989

Polymyxin B prevents lipopolysaccharide-induced release of tumor necrosis factor-alpha from alveolar macrophages.

Polymyxin B (PmB) blocks many of the toxic effects of lipopolysaccharide by mechanisms that are not yet understood. The production of tumor necrosis factor-alpha (TNF-alpha) by isolated rat alveolar macrophages in response to lipopolysaccharide and macrophage-activating factor was blocked by PmB at concentrations of 100, 10, and 1 micrograms/ml. Gentamicin enhanced rather than inhibited TNF production at the 100-micrograms/ml concentrations and had no effect at low concentration. Similar inhibitory effects were induced by PmB in an in vivo model in which rat macrophage TNF production was stimulated by intratracheally injected lipopolysaccharide. Because many of the effects of lipopolysaccharide are mediated by TNF, this inhibition provides a mechanism to explain the protection afforded by PmB against lipopolysaccharide-induced toxicity.

Animals↗
PubMed1979

Visual loss and foveal lesions in Usher's syndrome.

Forty-eight patients with Usher's syndrome were assess for the degree of visual loss, extent of lens opacities, and presence of foveal lesions. Twenty-one patients (44%) showed either atrophic or cystic-appearing bilateral foveal changes. Despite having foveal lesions and variable degrees of lens opacities most patients maintained central visual acuity of 20/60 or better until their middle 30s.

Adolescent↗
PubMed1978

Multiple ocular anomalies associated with maternal LSD ingestion.

Severe ocular malformations, including microphthalmos, intraocular cartilage, cataract, persistent hyperplastic primary vitreous, and retinal dysplasia, occurred in a premature baby girl. The mother had ingested LSD during the first trimester of pregnancy. To our knowledge, this is the third case reported of ocular teratogenesis associated with maternal LSD ingestion. Further cases must be documented to establish an actual cause and effect relationship between the drug and the induced malformations.

Abnormalities, Drug-Induced↗
PubMed1978

Vitelliform lesions associated with retinal pigment epithelial detachment.

Two patients with bilateral vitelliform macular lesions had normal electro-oculogram findings. The fluorescein angiograms showed retinal pigment epithelial detachment. Detachment of the retinal pigment epithelium associated with lipid and/or protein accumulation within the subpigment epithelial space represents another mechanism by which a lesion ophthalmoscopically similar to that seen in classical Best's disease can be produced.

Adult↗
PubMed1977

Pseudovitelliform macular degeneration.

Three patients with vitelliform-like macular lesions had normal electroooculogram (EOG) light-peak/dark-trough ratios, unlike typical cases of vitelliform dystrophy (Best macular dystrophy). Leakage of fluorescein dye from perifoveal cappillaries implicated an increased permeability of these vessels as the probable cause for the vitelliform-appearing lesions. All patients with vitelliform lesions demonstrating normal EOG ratios should have an evaluation by fluorescein angiography to rule out a diagnosis of what we prefer to call pseudovitelliform macular degeneration.

Aged↗
PubMed1977

Macular lesions associated with retinitis pigmentosa.

Of 31 patients with retinitis pigmentosa, 18 (58%) had lesions of the retinal pigmentary epithelium within the maculae of both eyes. Six of the 31 patients (19%) showed macular cysts or holes (five bilateral, one unilateral) without angiographic evidence of leakage from perifoveal capillaries, while seven patients (23%) had macular cysts in both eyes associated with cystoid macular edema evident by fluorescein angiography. We believe that the macular cysts or holes were caused by changes at the vitreoretinal interface, eg, vitreous traction and preretinal membranes. Other pathologic sequences may also be responsible, such as an intrinsic increase in the permeability of retinal capillaries.

Adolescent↗
PubMed1977

Foveal lesions seen in retinitis pigmentosa.

A total of 110 patients with retinitis pigmentosa were prospectively and consecutively evaluated for the presence of foveal lesions. Of these 69 (63 percent) patients showed one of two types of separate and distinct bilateral foveal lesions. Forty-seven (43 percent) patients had atrophic-appearing lesions of the retinal pigment epithelium within the fovea of both eyes, and an additional 22 (20 percent) patients showed bitalteral foveal cysts or partial-thickness holes. Of the 22 patients in this last group, 16 showed cystoid macular edema evident on fluorescein angiography.

Aged↗
PubMed1976

The electro-oculogram in diffuse (familial) drusen.

Twelve patients with diffuse drusen of Bruch membrane had their condition evaluated by electro-oculography (EOG). All had normal EOG light-peak/dark-trough ratios, which suggests that the disease does not involve a diffuse functional abnormality of the retinal pigment epithelium. This finding is in contrast to the abnormal EOG ratios reported in patients with fundus flavimaculatus. Categorizing these two diseases along with fundus albipunctatus as flecked retina syndrome should be continued on the basis of the somewhat similar morphologic appearance of the lesions, rather than because of similar results on functional testing.

Adult↗