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Biomedical subjects

S Kohl

Publications and source records attributed to S Kohl.

At least 109 records · Page 6Linked to original sources

The prevalence of neural tube defects among ethnic groups in Brooklyn, New York.

Records of almost 174,000 consecutive births at six Brooklyn hospitals during the years 1968-1976 were reviewed for congenital neural tube defects. Prevalence of anencephaly, myelomeningocele and occipital encephalocele combined was significantly higher in infants delivered to mothers born in Puerto Rico than in offspring of non-Puerto Rican whites or blacks. The association of prevalence rates with ethnicity remained significant after adjustment for several variables. However, when adjustment was made for private or service status the difference between Puerto Ricans and whites, although still appreciable, was no longer statistically significant. No significant differences in prevalence rates between whites and blacks were observed. Sex ratios of affected infants were close to unity in each ethnic group. Statistically significant associations were found between the prevalence of neural tube defects and parity, gravidity and economic status. The patterns of these associations varied among the ethnic groups. A declining trend in the prevalence of myelomeningocele was observed for all ethnic groups.

Black People↗

Indomethacin enhancement of human natural killer cytotoxicity to herpes simplex virus infected cells in vitro and in vivo.

Indomethacin, a prostaglandin synthetase inhibitor, increased human mononuclear cell (MC) natural killer cytotoxicity (NKC) to herpes simplex virus (HSV) infected cells in vitro at concentrations of 2 X 10(-10)M (p less than .025). Infant mice were significantly (p less than 0.025) protected from a lethal HSV infection by prior injection with a combination of MC and indomethacin (60.7% survival) although neither alone was protective. These results further support the probable in vivo role of NKC in protection against HSV infection, and the critical regulation of NKC by prostaglandins.

Animals↗

Leukocyte function in healthy neonates following vaginal and cesarean section deliveries.

Oxidative metabolic activities of polymorphonuclear leukocytes from cord blood of 15 full-term infants delivered by cesarean section without labor, five infants delivered by cesarean section with labor, and 15 infants delivered vaginally, as well as 35 healthy adult control subjects, were evaluated. The absolute polymorphonuclear leukocyte counts of cord blood from infants delivered vaginally and by cesarean section with labor were significantly higher when compared to cord blood APCs from infants delivered by cesarean section without labor and healthy adult control APCs. Zymosan-stimulated oxygen consumption, hexose monophosphate shunt activity, and quantitative nitroblue tetrazolium dye reduction were significantly lower in cord blood PMNLs from infants delivered vaginally and by cesarean section with labor than in cord blood PMNLs from infants delivered by cesarean section without labor or control PMNLs. Metabolic activity of PMNLs from healthy adults and infants born by cesarean section without labor did not differ significantly. This study indicates that the function of PMNLs isolated from cord blood varies with the method of delivery. These observations may explain previous discrepancies in the literature as well as the propensity of certain neonates to infection.

Cesarean Section↗

The importance of brain biopsy in suspected herpes simplex encephalitis.

In a retrospective study of 10 patients who underwent biopsies because of suspected herpes simplex encephalitis, the diagnosis was confirmed in only 3 patients. However, in 4 patients whose clinical presentations were indistinguishable from herpes simplex encephalitis, biopsy revealed other treatable conditions. These findings, together with a review of the recent literature, indicate that brain biopsy is the appropriate way to evaluate such patients.

Aged↗

Inhibition of cellular cytotoxicity of leukocytes for herpes simplex virus-infected cells in vitro and in vivo by intralipid.

The effect of intralipid, a lipid emulsion used in total parenteral nutrition, on cellular cytotoxicity for herpes simplex virus (HSV)-infected cells was analyzed. In vitro, intralipid inhibited antibody-dependent cellular cytotoxicity (ADCC) of lymphocytes, monocytes-macrophages, and polymorphonuclear leukocytes and natural killer cytotoxicity of lymphocytes for radiolabeled HSV-infected liver cells. This was due to an effect on the leukocytes, rather than on the target cells. Intralipid did not affect leukocyte viability but inhibited the expression of leukocyte Fc receptors necessary for cytotoxicity. In vivo, intralipid inhibited murine ADCC and completely nullified the protection against lethal infection with HSV in neonatal mice afforded by the administration of human leukocytes and antibody. These data suggest that high levels of circulating intralipid may interfere with antiviral immunity in humans and predispose hosts who are already compromised to severe viral infections.

Animals↗

Virus-infected colostral cell cytokine stimulation of human leukocyte natural killer cytotoxicity.

Natural killer cytotoxicity is an important antiviral defense mechanism. Human peripheral blood mononuclear cells cultured with herpes simplex virus (HSV)-infected cells produced a cytokine. This substance stimulated adult natural killer cytotoxicity from 53.0 +/- 10.5% to 79.8% (P less than 0.01) against HSV-infected target cells. These data resulted in a calculated cytokine-dependent cellular cytotoxicity (CDCC) value of 65.8%. Cytokine production was not stimulated by uninfected cells and was independent of the presence or absence of antibodies to HSV in sera of donors and mononuclear cells. Cells from human colostrum also produced an HSV-stimulated cytokine which mediated CDCC by using both adult (19.8 +/- 3.9%) and neonatal (18.6 +/- 3.4%) mononuclear effectors cells. Colostral cell cytokine production was also independent of donor HSV serology. Not all colostral cultures produced the cytokine, and in general colostrum-stimulated CDCC was lower than peripheral blood leukocyte-stimulated CDCC. Colostral cell cytokine stimulation of neonatal natural killer cytotoxicity may account in part for the increased nonspecific resistance of breast-fed infants to viral infection.

Biological Products↗

Murine cellular cytotoxicity to syngeneic and xenogeneic herpes simplex virus-infected cells.

Cellular cytotoxicity of C57BL/6 adult mice peritoneal cells to xenogeneic (Chang liver) and syngeneic (BL/6-WT3) herpes simplex virus (HSV)-infected cells was analyzed in a 6-h 51Cr release assay. There was no difference in antibody-dependent cellular cytotoxicity to either target. There was no natural killer cytotoxicity to targets with cells from uninfected mice except at very high effector cell ratios. HSV-infected (2 X 10(4) PFU intraperitoneally 1 day previously) mice mediated significantly higher antibody-dependent cellular cytotoxicity and required less antibody (10(-5) versus 10(-2) dilution), fewer cells, and less time to kill than cells from uninfected mice. HSV-infected mice mediated natural killer cytotoxicity but preferentially killed syngeneic HSV-infected cells. Stimulation of cytotoxicity was not virus specific since influenza-infected mice mediated similar levels of cytotoxicity to HSV-infected targets. There was no difference in morphology (95% macrophage) or in the percentage of FcR-positive cells, but infected mice had more peritoneal cells and generated higher levels of superoxide in response to opsonized zymosan or phorbolmyristate acetate. These data demonstrate nonspecific virus-stimulated metabolic and effector cell function which may enhance clearance of virus in an infected host.

Animals↗

Kinetics of human antibody responses to primary genital herpes simplex virus infection.

5 patients with primary genital herpes simplex virus (HSV) infection were studied prospectively for the production of serum antibody reactivity as measured by the virus micro-neutralization test (NT), micro-solid phase radioimmunometric assay (micro-SPRIA), and antibody-dependent cellular-cytotoxic (ADCC) test. ADCC antibody was detected before reactivity measured by either NT or micro-SPRIA in 2 of the patients. A 3rd patient failed to produce neutralizing antibody, whereas specific activity was detected by the other two methods. In 2 other patients a good correlation was observed for development of antibody by all three methods. There were several discordant results in the kinetics of production of antibody detected by these assays, suggesting that not all individuals produce similar types of antiviral antibody.

Adult↗

The effect of route of delivery on neonatal natural killer cytotoxicity and antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

The ability of human neonatal and adult Ficoll-hypaque purified mononuclear cells to mediate natural killer cytotoxicity (NKC) and antibody-dependent cellular-cytotoxicity (ADCC) against 51Cr labeled herpes simplex virus-infected (HSV-infected) and uninfected cells was evaluated in healthy term infants delivered vaginally or by Cesarean (C)-section without labor, and in healthy adult controls. Cord blood NKC to HSV-infected cells (12.5 +/- 7.0) was lower (P less than 0.01) than adult controls NKC (29.5 +/- 7.0). NKC to HSV-infected cells of babies delivered vaginally (16.6 +/- 3.4) was lower (P less than 0.05) than adult controls (28.4 +/- 4.2). NKC to HSV-infected cells of neonates delivered by C-section without labor (7.6 +/- 2.8) was also lower (P less than 0.001) than adult controls (30.7 +/- 4.0) and lower (P less than 0.05) than that of neonates delivered vaginally. Cord blood ADCC (43.1 +/- 9.0) was lower (P less than 0.05) than ADCC of adult controls (58 +/- 10). ADCC of neonates delivered vaginally (50 +/- 5.9) was similar to ADCC of adult controls (57.4 +/- 6.9). ADCC of neonates delivered by C-section without labor (30.4 +/- 7.2) was lower than ADCC of adult (58.5 +/- 7.4) and was lower (P less than 0.05) than ADCC of neonates delivered vaginally. These findings demonstrate that the method of delivery influences subsequent neonatal leukocyte NKC and ADCC. Further experiments will delineate the cause of these variations, which probably include labor or stress related hormonal changes in the mother or neonate.

Antibody-Dependent Cell Cytotoxicity↗

Protection of neonatal mice against herpes simplex virus infection: probable in vivo antibody-dependent cellular cytotoxicity.

Infant mice are extremely susceptible to fatal Herpes simplex virus (HSV) infection. They are unable to produce antibody to HSV, and their leukocytes cannot mediate antibody-dependent cellular cytotoxicity (ADCC) to HSV-infected cells. In order to avoid H-2-dependent effector mechanisms and instead analyze possible in vivo ADCC, a murine model employing adoptive transfer of antibody and human leukocytes was developed. Administration of either human immune globulin or leukocytes i.p. from HSV immune or nonimmune humans could not protect infant C57BL/6 mice from fatal HSV infection. In contrast, a combination of a subneutralizing dilution of globulin and leukocytes from nonimmune or immune human donors, given one day before inoculation, was highly protective against lethal HSV infection. The cells involved included lymphocytes or monocyte-macrophages. At least 5 X 10(6) viable leukocytes (or 1 X 10(6) monocyte-macrophages) and immune serum globulin concentrations as low as 10(-8) were protective. Infected cell monolayer adsorption and DEAE column fractionation demonstrated that the protection by globulin was due to specific antiviral IgG antibody. Protection was n ot seen in animals receiving virus before immune transfer. Protection did not involve synergistic viral neutralization by antibody and cells, as shown by in vitro experiments. Animals receiving globulin and cells, unlike normal infant mice, had circulating antiviral antibody and peritoneal leukocytes able to mediate ADCC to HSV-infected cells. This is the first in vivo evidence for the role of human ADCC. This model also allows for the in vivo evaluation of the ability of cells from immunocompromised humans to curb viral infection.

Animals↗

Separation of cytotoxic leukocyte populations of human peripheral blood and colostrum of PVP-silica (Percoll) density gradients.

PVP-silica (Percoll) did not inhibit antibody-dependent cellular cytotoxicity in an 18 h 51Cr-release assay. By the use of a simple discontinuous density gradient centrifugation technique, leukocytes from peripheral blood and colostrum were separated into morphologic and cytotoxic functional populations. The major cytotoxic effector cells in colostrum are lipid-free macrophages and probably a small lymphocyte subpopulation.

Antibody-Dependent Cell Cytotoxicity↗

Interferon induction of natural killer cytotoxicity in human neonates.

Low natural killer cytotoxicity has been associated with serious herpes simplex virus infections. Neonates' mononuclear cells had significantly lower NKC to HSV infected (P less than 0.001) and uninfected (P less than 0.005) target cells than did adults' MC. Under appropriate conditions, both neonates' MC to NKC was increased by exogenous human leukocyte interferon. Although neonates' and adults' MC had a similar sensitivity to interferon, there was a significant (P = 0.05) lack of consistency in neonates' MC response. Twenty-three percent (4/17) of neonates' MC samples did not respond with increased NKC in the presence of interferon, unlike adults' MC, all of which demonstrated increased NKC. Neonates' MC did not suppress adults' MC-NKC. These data demonstrate the efficacy of interferon as an NKC stimulator in the neonate, but indicate a heterogeneous response of neonatal cells. We are encouraged with the prospect of clinical trials of interferon to treat severe viral infections in neonates. We urge the inclusion of immune surveillance in these trials.

Adult↗