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Biomedical subjects

M Mendelsohn

Publications and source records attributed to M Mendelsohn.

At least 55 records · Page 3Linked to original sources

Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors.

Human mononuclear cells were previously shown to produce interferon-alpha (IFN) during 14 hr assays using herpes simplex virus type-1 infected fibroblasts [NK(HSV-FS)]. In this study, we have compared the effectors responsible for mediating NK(HSV-FS) cytolytic activity to those which produce IFN-alpha. Both activities were found to reside in non-adherent fractions, negative for non-specific esterase-staining cells. Like cells mediating NK cytolytic activity, IFN-alpha producing cells were found in light density Percoll gradient fractions. However, although NK(HSV-FS) and IFN production were largely overlapping, peak IFN production was consistently found in fractions slightly less dense than peak NK(HSV-FS) activity. IFN production was greatly augmented in fractions enriched for dendritic cells on hypertonic metrizamide gradients. The cells which produce IFN-alpha were phenotypically distinct from cytolytic NK effector cells: they lacked the Leu-11, Leu-7 and NKH1 cell surface markers shown to be present on both NK(HSV-FS) and NK(K562) effector cells. In addition, the IFN-alpha producing cells were found to be negative for a number of other markers characteristic of T cells, B cells or macrophages but were positive for Ia and HLA. The cells which produced IFN in response to UV-inactivated HSV antigen and to HSV-infected Raji cells were also found to be Leu-11 negative, and Ia positive. We conclude that the cells which produce IFN in response to HSV are a light density, Ia positive population which are distinct from NK cytolytic effector cells and co-purify with cells bearing a dendritic morphology. These results support our earlier findings that NK(HSV-FS) activity and IFN production are independent of one another and can segregate independently in vivo.

Antibodies, Monoclonal↗

Human natural killer cells limit replication of herpes simplex virus type 1 in vitro.

Studies were undertaken to determine whether natural killer (NK) cells could inhibit the replication of herpes simplex virus type 1 (HSV-1) in culture. In the absence of effector cells, HSV-1 was found to replicate in fibroblasts with up to a 100-fold increase in virus titer from 4 to 16 hr after incubation at 37 degrees C. Human peripheral blood mononuclear cells were found to limit virus replication in a dose-dependent manner, with the greatest inhibition being observed at the highest concentration evaluated: i.e., an effector:target ratio of 800:1. The antiviral effect was not observed when nonactivated or virus-activated mononuclear cells were added to the virus preparations at the end (instead of the beginning) of the assay period, indicating that the observed effect was not due to a nonspecific toxicity of soluble factors released from freeze-thawed effectors. Neither was inhibition of HSV-1 replication due to the generation of interferon (IFN) during the NK assay, because the addition of anti-IFN did not abrogate the antiviral effect. Thus, the inhibition of viral replication was most likely due to a cytotoxic effector rather than to release of soluble factors. The effector cells responsible for limiting HSV-1 replication were shown to be NK cells by a number of criteria. Mononuclear cells from both HSV-1 seropositive and seronegative donors limited virus replication; their activity could be boosted by pretreatment of effector cells with IFN; the effector cells which limited virus replication were found in Percoll gradient fractions enriched for large granular lymphocytes; and the effector cells shared the cell surface phenotype of NK cells--they were enriched in populations depleted of T cells by panning with Leu-4 and were depleted of activity by treatment with the anti-NK antibody Leu-11b plus complement. We conclude that human NK cells are capable of recognizing and lysing HSV-1-infected target cells before infectious virus progeny are generated. These results suggest that NK cells, acting early in the course of an infection, might serve to limit HSV-1 replication and therefore reduce the virus load in the host before the development of the adaptive immune response and clearance of the infection.

Antibody-Dependent Cell Cytotoxicity↗

Flow cytometry of mammalian sperm: progress in DNA and morphology measurement.

Variability in DNA content and head shape of mammalian sperm are potentially useful markers for flow cytometric monitoring of genetic damage in spermatogenic cells. The high refractive index and extreme flatness of the sperm heads produce an optical effect which interferes with DNA measurements in flow cytometers which have dye excitation and fluorescence light collection normal to the axis of flow. Orientation of sperm in flow controls this effect and results in coefficients of variation of 2.5% and 4.2%, respectively, for DNA measurements of mouse and human sperm. Alternatively, the optical effect can be used to generate shape-related information. Measurements on randomly oriented sperm from three mammalian species using a pair of fluorescence detectors indicate that large shape differences are detectable. Acriflavine-Feulgen stained sperm nuclei are significantly bleached during flow cytometric measurements at power levels routinely used in many flow cytometers. Dual beam studies of this phenomenon indicate it may be useful in detecting abnormally shaped sperm.

Animals↗

The Disruptive Behavior Scale: an objective assessment of unmanageable social behavior in adolescents.

The Disruptive Behavior Scale, a 26-item behavioral checklist, provides an objective measure of socially unacceptable public secondary school behavior and may prove to be of value in determining public school exit and reentry plans for disruptive adolescents. The checklist may be completed in 15-25 minutes and does not require direct administration. Test-retest reliability scores were significant (p less than .05) for all items; item-whole test scores were significant for all but 2 items. Both initial and replication validity studies that involved comparisons between public school students and adolescents expelled from public schools yielded significant differences (p less than .05) in the expected direction.

Adolescent↗

Postnatal fall and rise of circulating 25-hydroxyvitamin D in the rat*.

Plasma 25-hydroxyvitamin D levels (5 to 6 ng. per millilter at birth) decreased significantly at age 12 days (1to 2 ng. per millilter) in rat neonates. At 3 to 4 weeksof age, the plasma concentrations of 25-hydroxyvitamin D had risen to birth levels or higher. Chromatography of lipid extracts of neonatal tissues following in vivo administration of 'H-25-hydroxyvitamin D' from the milk of mothers who had been given 'H vitamin D' intravenously. Following intraperitoneal injection of equal (or 3-fold larger doses to older pups) doses of 'H-25-hydroxycholecalciferol, the half-lives of 'H in plasma were 2.9 to 3.0 days and 2.8 to 3.05 days in young and oldersuckling pups, respectively. These data collectively suggest that young suckling rats,unlike weaning rats, do not receive and/or produce sufficient 25-hydroxyvitamin D to maintain the blood concentration observed at birth.

Age Factors↗