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Biomedical subjects

M Fishman

Publications and source records attributed to M Fishman.

At least 55 records · Page 3Linked to original sources
PubMed1989

The effect of phorbol esters on tumor cell sensitivity to macrophage-mediated cytostasis.

Macrophage-mediated cytostasis was measured in a mouse syngeneic system where EL4 thymoma cells were found to be inhibited by C57B1/6 mouse macrophages. When tumor cells were pretreated with TPA, they became resistant to macrophage-mediated stasis. Nonelutriated as well as elutriated cells enriched in G1/early S and late S were sensitive to macrophage-mediated stasis. However, when elutriated cells were treated with TPA, cells enriched in G1/early S were rendered resistant to the cytostatic activity of macrophages whereas cells enriched in late S were not. The TPA effect on tumor cell susceptibility to stasis was found to be reversible and a nontumor-promoting phorbol ester, alpha-PDD, was ineffective.

Animals↗
PubMed1989

Human macular pigment assessed by imaging fundus reflectometry.

A computerized, television-based, imaging fundus reflectometer was used to obtain estimates of the spatial distribution of macular pigment (xanthophylls) from seven normal subjects. Digitized images of the bleached macula of each subject were acquired at illuminating wavelengths from 462 to 697 nm. An analysis of spectral reflectances indicated that differences in short-wavelength reflectance between the foveal center and parafovea were influenced by spatial variations in melanin and oxyhemoglobin absorption as well as by the distribution of macular pigment. To provide an estimate of the spatial distribution of macular pigment alone, we have corrected fundus images obtained at 462 nm for the effect of melanin and oxyhemoglobin absorption. The spatial variation in macular pigment double density across the horizontal and vertical meridians of the retina was well described by Gaussian functions. The peak double densities for the individual subjects ranged from 0.22 to 0.45 and the standard deviations of the Gaussian functions averaged approx. 1 degree.

Adult↗
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↗
PubMed1988

Induction of EL4 cell resistance to syngeneic macrophage-mediated lysis by protein kinase C ligands; effects of cultured TPA-treated target cell and protein phosphorylation.

Pretreatment of EL4 cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) for 30 min renders them resistant to lysis by activated macrophages (M phi). This resistance was augmented two to three-fold when TPA-treated EL4 cells were incubated for 2-6 hr prior to co-culture with M phi. Preincubation of TPA-treated cells for 24 hr could result in 100% resistance. in this paper we show that an endogenous ligand for protein kinase C, oleoyl-2-acetate glycerol (OAG), was capable of inducing tumour cell resistance to M phi kill and, similar to the effects seen with TPA, OAG did not affect the selective binding of tumour cells to activated M phi. Another important observation on the mechanism of TPA induction of tumour cell resistance was that once the target cells were programmed to die after a minimal contact with activated M phi of 4-6 hr, TPA treatment was ineffective in altering the percent lysis 20 hr later. To investigate whether any possible correlation exists between TPA-induced protein phosphorylation and acquisition of resistance, EL4 cells were labelled with 32P and treated simultaneously with TPA, and cellular proteins were resolved by two-dimensional gel electrophoresis. Eight polypeptides (MW 24,000-70,000, pI 4.8-6.1) showed consistent increased phosphorylation as a result of TPA treatment. One-minute exposure with TPA resulted in enhanced phosphorylation of only four peptides (MW 39,000, 58,000, 63,000, 70,000) while all eight polypeptides showed increased phosphorylation by 10 min.

Animals↗
PubMed1987

Macular pigment and reduced foveal short-wavelength sensitivity in retinitis pigmentosa.

Some patients with retinitis pigmentosa (RP) show a reduced foveal short-wavelength sensitivity that cannot be attributed to a reduction in the sensitivity of the short-wavelength cone system. To determine whether an increased amount of macular pigment (xanthophyll) might account for this finding, we derived estimates of the two-way optical density of the macular pigment of five such RP patients as well as of five normals. The spectral reflectance of the foveal region of each subject was obtained from digitized images of the bleached fundus provided by a television-based reflectometer. The density spectra of the macular pigment, melanin, and oxygenated hemoglobin were fit by a least-squares procedure to the log of the ratio of parafoveal to foveal spectral reflectance in order to obtain a quantitative estimate of the contribution of each of these ocular pigments to foveal short-wavelength reflectance. By this analysis, the two-way densities of the macular pigment, melanin, and oxyhemoglobin of the RP patients were not significantly different from those of the normals. Therefore, the reduced foveal short-wavelength sensitivity of these patients was not due to an increased amount of macular pigment, but may result instead from morphological abnormalities in the foveal cones such that a normal amount of macular pigment screens the cones more effectively.

Adult↗
PubMed1987

Effects of maternal hydration on fetal renal pyelectasis.

Fetal renal pyelectasis is a frequent finding on routine obstetrical sonography. The cause of this pelvocalyceal dilatation is often not apparent, although urinary tract obstruction is the most important condition to be excluded. One of the many hypothetical explanations for minimal fetal renal pyelectasis suggests that aggressive maternal hydration before sonography leads to fetal diuresis with resultant pelvocalyceal dilatation. In this study, 20 pregnant volunteers underwent sonography after 10-12 hours of dehydration, after which 1,000 ml of fluid was administered and repeat sonography was performed. Despite a significant increase in the state of maternal hydration as determined by a decrease in urine specific gravity, there was no significant change in the degree of fetal renal pyelectasis before and after hydration. Therefore, pelvocalyceal dilatation identified prenatally should not be attributed to maternal hydration.

Drinking↗
PubMed1986

Oxidation of chloride and thiocyanate by isolated leukocytes.

Peroxidase-catalyzed oxidation of chloride (Cl-) and thiocyanate (SCN-) was studied using neutrophils from human blood and eosinophils and macrophages from rat peritoneal exudates. The aims were to determine whether Cl- or SCN- is preferentially oxidized and whether leukocytes oxidize SCN- to the antimicrobial oxidizing agent hypothiocyanite (OSCN-). Stimulated neutrophils produced H2O2 and secreted myeloperoxidase. Under conditions similar to those in plasma (0.14 M Cl-, 0.02-0.12 mM SCN-), myeloperoxidase catalyzed the oxidation of Cl- to hypochlorous acid (HOCl), which reacted with ammonia and amines to yield chloramines. HOCl and chloramines reacted with SCN- to yield products without oxidizing activity, so that high SCN- blocked accumulation of chloramines in the extracellular medium. Under conditions similar to those in saliva and the surface of the oral mucosa (20 mM Cl-, 0.1-3 mM SCN-), myeloperoxidase catalyzed the oxidation of SCN- to OSCN-, which accumulated in the medium to concentrations of up to 40-70 microM. Sulfonamide compounds increased the yield of stable oxidants to 0.2-0.3 mM by reacting with OSCN- to yield derivatives analogous to chloramines. Stimulated eosinophils produced H2O2 and secreted eosinophil peroxidase, which catalyzed the oxidation of SCN- to OSCN- regardless of Cl- concentration. Stimulated macrophages produced H2O2 but had low peroxidase activity. OSCN- was produced when SCN- was 0.1 mM or higher and myeloperoxidase, eosinophil peroxidase, or lactoperoxidase was added. The results indicate that SCN- rather than Cl- may be the physiologic substrate (electron donor) for eosinophil peroxidase and that OSCN- may contribute to leukocyte antimicrobial activity under conditions that favor oxidation of SCN- rather than Cl-.

Amitrole↗
PubMed1986

Induction of tumor cell resistance to macrophage-mediated lysis by preexposure to non-activated macrophages.

Thioglycollate-elicited peritoneal exudate (non-activated) macrophages do not lyse tumor cells and in contrast to activated macrophages bind less target cells. However, a non-lethal encounter of tumor cells with non-activated macrophages resulted in a pronounced effect on the subsequent tumor cell binding to and lysis by activated macrophages. Our results have shown that binding of tumor cells by non-activated macrophages was Ca2+ and temperature dependent; had a requirement for a Pronase-sensitive structure on macrophage surface membranes; was saturable; and was 2-3X less than that observed for activated macrophages. Experiments were conducted in which syngeneic tumor cells were incubated with a monolayer of non-activated macrophages and then assayed for selective binding and sensitivity to lysis. The important observations were that as a result of a 3-hr incubation with non-activated macrophages at an EC: TC ratio of 5:1 there was an increase in the number of tumor cells that bound to both activated and non-activated macrophages; a loss of selective binding in which the ratio of tumor cells bound to activated/non-activated macrophages (normally greater than 2) was lowered to 1.0; and a concomitant decrease in the susceptibility of tumor cells to macrophage-mediated cytolysis. The induction of tumor cell resistance to macrophage kill required an exposure to an excess number of non-activated macrophages, was reversible upon culturing with or without macrophages for 24 hr and required cell-cell contact. Our results reinforce the importance of selective binding between tumor cells and activated macrophages as an initial phase in tumor cell killing and also illustrates an active role for non-activated macrophages in vivo in allowing tumor cells to escape the immune surveillance by activated macrophages.

Animals↗
PubMed1986

Foveal cone pigment density difference and reflectance in retinitis pigmentosa.

Cone pigment density difference refers to a change in light absorption by cones before and after bleaching of their visual pigments. With a television ophthalmoscope image processor, we measured the foveal cone pigment density difference in patients with retinitis pigmentosa (RP), good central vision, and no clinically apparent foveal lesion. Foveal reflectance was obtained at 12 different wavelengths of illumination. Compared with similar-aged normal subjects, most patients with dominantly inherited RP had normal or minimally reduced cone pigment density difference within the central fovea, relatively lower than normal density difference at the foveal margin, and increased foveal reflectance. Compared with these normal subjects, patients with recessively inherited RP had significantly reduced cone pigment density difference within the central fovea, relatively more normal density difference at the foveal margin, and normal foveal reflectance.

Absorption↗
PubMed1986

Induction of tumor cell resistance to macrophage-mediated lysis by phorbol esters: a postbinding event.

Activated macrophages can recognize, bind to, and lyse tumor cells in an antibody-independent manner. We have found that tumor cells pretreated with phorbol esters are markedly less susceptible to macrophage-mediated cytolysis, although the initial binding step is unaffected. Tumor cells preincubated with tumor-promoting phorbol esters (10(-8)-10(-6) M) were rendered resistant to macrophage kill whereas non-tumor-promoting derivatives were inactive in protecting tumor cells against cytolysis. Inhibition of [3H]phorbol-12,13-dibutyrate binding by other phorbol esters correlated with their potency as tumor promoters and their ability to render tumor cells resistant to macrophage killing. The role of protein kinase C as the receptor to phorbol esters was implicated by inhibition of PDBu binding by phenothiazine derivatives. This suggests a possible mechanism for the resistance of phorbol ester-treated tumor cells to macrophage-mediated cytolysis.

Animals↗
PubMed1986

Foveal cone pigment density difference in the aging human eye.

Using fundus reflectometry, we have measured a decrease in the density difference of the foveal cone visual pigments with age in human subjects. This decrease is consistent with a loss of visual pigment in the retina with age. Fundus reflectance and normalized density difference spectra data are presented for these subjects. A decrease in cone pigment with age would be consistent with both anatomic studies, which indicate a loss and displacement of photoreceptors with age, and psychophysical studies, which demonstrate loss of photoreceptor function with age.

Adult↗
PubMed1986

Microbial adherence and infection--clinical relevance.

Adherence mechanisms have been described for some microbes, often in direct association with onset of infection. In other cases, the evidence is vague. This article will summarize modes of attachment, and will focus on each anatomical tract in an effort to outline the relationship between microbial adherence, host cells, foreign bodies, and infection.

Adhesiveness↗
PubMed1986

Painful sickle cell crisis: bone marrow patterns observed with MR imaging.

Eleven patients with homozygous sickle cell anemia (SCA) undergoing painful crisis were studied with magnetic resonance (MR) imaging. The signal intensity of bone marrow was diffusely decreased in the axial and peripheral skeleton on short repetition time (TR)/echo time (TE) images and long TR/TE images, which suggested hematopoietic marrow hyperplasia and was confirmed by isotope marrow scans in five patients. Focal areas of further decrease in signal intensity were seen on short TR/TE images in 12 of the 14 (86%) painful joints and three of the five (60%) painless joints. In the painful joints, these focal areas converted to high signal intensity on long TR/TE images, presumably due to edema, which suggested acute marrow infarction. In the painless joints, these low-intensity focal areas remained as low signal on long TR/TE images, which suggested absence of edema and thus areas of old infarction or fibrosis. These results indicate that MR imaging may enable differentiation between acute and chronic marrow infarcts in patients with SCA and serve as a useful guide in monitoring and directing therapy.

Adult↗
PubMed1985

Failure of sulfites to produce clinical responses in patients with systemic mastocytosis or recurrent anaphylaxis: results of a single-blind study.

Although sulfite sensitivity can precipitate asthma in a subpopulation of subjects with asthma, its role in precipitating anaphylaxis or as a nonspecific mast cell degranulator in systemic mastocytosis has not been examined. To evaluate critically the importance of sulfites in these diseases, eight patients with systemic mastocytosis and 25 patients with unexplained, recurrent anaphylaxis were challenged in a single-blind fashion; sodium bisulfite in capsules was administered in increasing doses of 1, 5, 10, 25, 50, 100, and 200 mg every 30 minutes. On separate occasions a liquid suspension of 200 mg of sodium bisulfite was administered to one patient with systemic mastocytosis and nine patients with anaphylaxis. Vital signs, pulmonary function tests, plasma histamine levels, and clinical reactions were monitored. There were no observable responses in either the mastocytosis group or in 23 of 25 patients in the anaphylaxis group. Two patients in the anaphylaxis group with initial positive challenges had similar symptoms on subsequent placebo challenge. One subject with asthma and with a history suggestive of sulfite sensitivity responded to oral challenge with 5 mg of sodium bisulfite and 100 micrograms of sodium bisulfite intradermally with a dramatic reduction in FEV, requiring treatment with bronchodilators. A comparison of baseline plasma histamine levels with those obtained after the sulfite challenge procedure in each category demonstrated a significant rise (p less than 0.05) in the systemic mastocytosis group. The overall level of significance determined by applying paired sample t tests to the histamine data from all subjects was p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Preparation of audiovisual aids for infection control education.

This article contains guidelines for selection and design of audiovisual materials pertinent to the teaching of infection control. Clarity, rate of presentation, and color are emphasized because they may correlate directly with effective presentation and learner comprehension. The use of audiovisual programs may cut presentation time in half, thereby achieving long-term cost-effectiveness. Slides project well if appropriate color combination is used, and if copy is limited to six double-spaced, very short lines. Specifications for effective use of color are summarized in the text.

Audiovisual Aids↗
PubMed1984

Increased adenosine deaminase (ADA) activity and a shift from ADA-dependent to ADA-independent phases during T-cell activation: a paradox.

During activation of WF rat splenic T-cells, a change occurs with respect to susceptibility to a toxic accumulation of adenosine or deoxyadenosine (dADO) in the presence of adenosine deaminase (ADA) blockade. Addition of nucleoside 1 hour after the initiation of a concanavalin A response in the presence of 2'deoxycoformycin (DCF) markedly inhibited the response, whereas delay of addition of the nucleoside for 24-48 hours resulted in minimal or no inhibition. Inhibition was not simply the result of prolonged incubation of cells in the presence of nucleoside and was apparently not attributable to an effect on proliferating cells. Addition of interleukin 2 (IL-2) to cultures containing DCF and dADO did not reverse the inhibitory effect, which suggests that IL-2-producing T-cells also were not the target of nucleoside toxicity. A twofold increase in ADA activity that occurred during T-cell activation was nonessential for the survival of mitogen-activated T-cells in the presence of toxic concentrations of dADO and did not account for an apparent increased resistance of these cells to nucleoside toxicity. These paradoxical observations prompted an analysis of ADA activity in various populations of activated T-cells enriched with cells in G0/G1, S, or G2+M cell-cycle phases, which indicated that increased ADA activity was not associated with a specific period during cell-cycle traverse, but, rather, coincided with cell enlargement in preparation for mitosis. In conclusion, either an early event in T-cell mitogenesis is highly susceptible to nucleoside toxicity or a mechanism independent of ADA is acquired during T-cell activation that allows proliferating T-cells to resist toxic concentrations of nucleoside.

Adenosine↗