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Biomedical subjects

S Kohl

Publications and source records attributed to S Kohl.

At least 73 records · Page 4Linked to original sources
PubMed1987

Defective production of antibody to herpes simplex virus in neonates: defective production of T helper lymphokine and induction of suppression.

Defective production of antibodies to herpes simplex virus (HSV) and low resistance to HSV infection in neonatal mice could be reconstituted by using macrophages from syngeneic adult mice plus concanavalin A-stimulated supernatants prepared from adult mouse spleen cells or adult human peripheral blood lymphocytes. In each supernatant, interleukin-2 (IL-2) produced by T helper cells (positive for Lyt 1.2 or OKT4) was necessary to provide reconstitution. Supernatants from neonatal mice failed to mediate reconstitution because of an age-dependent absence of production of IL-2. Although supernatants from neonatal human cell cultures contained IL-2, they failed to reconstitute production of antibody to HSV and resistance to HSV infection because of a suppressor of IL-2 activity. Early antibody production and antibody-dependent cellular effector function are important defenses against HSV infection and are critically defective in the neonate.

Animals↗
PubMed1987

Natural killer cell cytotoxicity and antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells in human pregnancy.

Natural killer cell (NKC) cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) represent the ability of human leukocyte effector cells to destroy target cells in the absence and presence of antibody, respectively. Since these immune systems play a pivotal role in the body's primary lines of defense against a variety of pathogens including herpes simplex virus (HSV), a study was undertaken to evaluate the influence of pregnancy on these systems. Eleven uncomplicated gravidas were followed serially through each trimester and compared to 11 nonpregnant female controls. Mononuclear cells were acquired by Ficoll-Hypaque centrifugation of heparinized blood. Chang liver cells infected with HSV-I were utilized as target cells in a 51Cr release assay. Mean NKC values in the pregnant patients were uniformly lower than in the controls. No similar decreases in ADCC activity were observed in a comparison between the two study populations. These data support previous observations suggesting that pregnancy represents a relatively immunocompromised state. Differences apparently exist between NKC and ADCC effector cell populations with regard to the influence of pregnancy. Although these physiologic alterations in immunoregulation may help support the fetoplacental allograph, detrimental conditions may exist regarding susceptibility to various pathogens such as HSV.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

The genetic deficiency of leukocyte surface glycoprotein Mac-1, LFA-1, p150,95 in humans is associated with defective antibody-dependent cellular cytotoxicity in vitro and defective protection against herpes simplex virus infection in vivo.

The role of the Mac-1, LFA-1, p150,95 leukocyte glycoprotein family in mediating antiviral host defense was investigated by utilizing mononuclear cells (MC) obtained from eight patients with a genetic deficiency of Mac-1, LFA-1, and p150,95, and normal MC incubated with subunit-specific monoclonal antibodies (MAb) directed against these glycoproteins. As shown with an in vitro chromium-release cytotoxicity assay to herpes simplex virus (HSV)-infected Chang liver target cells, MC of these patients with the severe phenotype or normal MC preincubated with a combination of MAb against Mac-1 glycoprotein subunits were deficient in antibody-dependent cellular cytotoxicity (ADCC). When used individually, MAb directed at LFA-1-alpha or -beta also inhibited ADCC and natural killer cytotoxicity (NKC). In a single cell agarose assay, MC of Mac-1-deficient patients formed fewer effector-target cell conjugates in the presence of specific anti-HSV antibody. To investigate the in vitro contributions of these glycoproteins to cytotoxic host defense mechanisms, two in vivo adoptive transfer models were explored in which neonatal mice are protected against a lethal HSV challenge by normal human MC plus anti-HSV antibody (in vivo ADCC) or human interferon-alpha (NKC stimulated in vivo). In each model, MC from patients with "severe" or "moderate" phenotypes of Mac-1 deficiency, or normal MC incubated with a combination of anti-LFA-alpha, Mac-1-alpha, p150,95-alpha plus -beta MAb failed to protect neonatal mice against lethal HSV infection. These studies further indicate requirements for adhesion-dependent mechanisms in the mediation of MC-ADCC, and suggest that Mac-1-dependent cellular adhesive properties are necessary for normal cytotoxic functions in vivo in experimental models of human ADCC or interferon-stimulated NKC. These findings, in addition to the recognized occurrence of severe or even lethal viral infections in some Mac-1-deficient patients, suggest that glycoproteins of the Mac-1 family may be important determinants of antiviral host defense.

Adult↗
PubMed1986

Defective production of anti-herpes simplex virus antibody by neonatal mice. Reconstitution with Ia+ macrophages and T helper lymphocytes from nonimmune adult syngeneic mice.

Both neonatal humans and mice are exquisitely susceptible to severe HSV infection. We have now documented a profound defect in the ability of neonatal C57BL/6 mice to produce anti-HSV ADCC antibody. This ability is acquired over the first 2 to 4 wk of life. Reconstitution of neonatal mice by i.p. injection of peritoneal cells from adult nonimmune syngeneic mice both affords dose-dependent protection against lethal HSV infection and reconstitutes the antibody-production defect. By cell-separation techniques (adherence, nylon wool column purification, B cell panning) and cell ablation techniques (silica treatment, irradiation, anti-T cell, anti-Ia, anti-Lyt-1.2 and anti-Lyt-2.2 monoclonal antibodies plus complement treatment) the subpopulations involved in the antibody production reconstitution of neonatal mice by adult cells were identified. These include both an Ia+, radioresistant, adherent, silica-sensitive macrophage population and a nylon wool column-purified, radiosensitive, anti-T, anti-Lyt-1.2-sensitive helper T cell population. The latter cell may be substituted for by concanavalin A-stimulated lymphokine-containing spleen cell supernatants or human recombinant IL 2. In addition to reconstitution of ADCC antibody production, the same cell populations, or cells plus lymphokine-containing supernatants or IL 2, protected the newborn mice from lethal HSV infection. Further characterization of this system and of soluble replacement factors has implications for therapy or immunoprophylaxis of human neonates with, or at risk of, HSV infection.

Aging↗
PubMed1986

Cytomegalovirus infection and fetal death in a twin. A case report.

In a diamnionic-dichorionic male twin pregnancy, one twin was stillborn, with disseminated cytomegalovirus (CMV) identified morphologically, and the other was liveborn, without clinical or laboratory evidence of CMV infection. The placenta of the affected twin had chronic villitis; that of the liveborn was normal. Although the discordance went unexplained, it illustrates the clinical variability of congenital CMV infection. Dissimilar immune responses between the affected and unaffected twin or direct extension of uterine CMV infection to only one twin may have been responsible for the discordance.

Adult↗
PubMed1985

Herpes simplex virus encephalitis during childhood: importance of brain biopsy diagnosis.

Twelve consecutive pediatric patients 1 day to 11 years of age with suspected herpes simplex virus (HSV) encephalitis underwent brain biopsy. Five were proved to have HSV encephalitis; seven had subdural empyema, malignant glioma, enteroviral encephalitis, (one each), and presumed viral encephalitis, non-HSV (four). Neither epidemiologic, clinical, nor noninvasive laboratory tests were able to help differentiate the two groups of patients. The EEG was more sensitive than the CT scan in demonstrating focal lesions in early HSV encephalitis. In patients with HSV encephalitis, the mean time from hospital admission to appropriate antiviral chemotherapy was 3 days, and the outcome of HSV encephalitis was uniformly poor. In patients with febrile encephalitis-like syndromes with CSF pleocytosis, focal neurologic signs, or other localizing test results (EEG, CT), anticipatory antiviral chemotherapy and brain biopsy are the only hope to prevent the poor outcome associated with HSV encephalitis, to exclude other treatable conditions, and to avoid multiple types of unnecessary empiric therapies.

Biopsy↗
PubMed1985

The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features.

An inherited syndrome characterized by recurrent or progressive necrotic soft-tissue infections, diminished pus formation, impaired wound healing, granulocytosis, and/or delayed umbilical cord severance was recognized in four male and four female patients. As shown with subunit-specific monoclonal antibodies in immunofluorescence flow cytometry and 125I immunoprecipitation techniques, in addition to a NaB3H4-galactose oxidase labeling assay, granulocytes, monocytes, or lymphocytes from these individuals had a "moderate" or "severe" deficiency of Mac-1, LFA-1, or p150,95 (or a combination)--three structurally related "adhesive" surface glycoproteins. Two distinct phenotypes were defined on the basis of the quantity of antigen expressed. Three patients with severe deficiency and four patients with moderate deficiency expressed less than 0.3% and 2.5%-31% of normal amounts of these molecules on granulocyte surfaces, respectively. The severity of clinical infectious complications among these patients was directly related to the degree of glycoprotein deficiency. More profound abnormalities of tissue leukocyte mobilization, granulocyte-directed migration, hyperadherence, phagocytosis of iC3b-opsonized particles, and complement- or antibody-dependent cytotoxicity were found in individuals with severe, as compared with moderate, deficiency. It is proposed that in vivo abnormalities of leukocyte mobilization reflect the critical roles of Mac-1 glycoproteins in adhesive events required for endothelial margination and tissue exudation. The recognition of phenotypic variation among patients with Mac-1, LFA-1 deficiency may be important with respect to therapeutic strategies.

Adolescent↗
PubMed1985

Leukocyte LFA-1, OKM1, p150,95 deficiency syndrome: functional and biosynthetic studies of three kindreds.

Three patients (2 female, 1 male) with recurrent infection, granulocytosis, impaired pus formation, and/or delayed umbilical cord separation were identified. Assessments of polymorphonuclear leukocytes (PMN)/monocyte function in each patient revealed profound abnormalities of adherence and adherence-dependent functions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of their PMN lysates demonstrated a deficient or absent protein(s) of 138 kilodaltons (gp 138). Na3HB4 labeling demonstrated the absence of a major cell surface glycoprotein complex in each patient. Among parental and sibling PMN suspensions, functional assessments revealed no consistent abnormalities, although variably diminished gp138 was identified by SDS-PAGE and Na3HB4 labeling. Analysis by fluorescence-activated cell sorting and monoclonal antibodies (MAb) to LFA-1 alpha, OKM1 alpha, and their common beta subunit demonstrated a severe or total deficiency of PMN/monocyte surface expression of each protein among all patients; intermediate values were observed for parental and affected sibling suspensions, findings consistent with an autosomal recessive mode of inheritance for this disorder. Cell surface labeling (125I) and immunoprecipitation with the same MAb demonstrated the absence of these glycoproteins in addition to a 150-kilodalton protein (p150,95). Identical abnormalities of surface expression of patient lymphocytes blast-transformed with phytohemagglutinin (PHA) or Epstein-Barr virus were demonstrated. Further, significantly diminished natural killer cell cytotoxicity was observed for each patient tested. PHA blast-transformed patient lymphocytes labeled with [35S]methionine demonstrated a total absence of the beta molecule but indicated the presence of an LFA-1 alpha precursor. These findings indicate that LFA-1 alpha synthesis and surface expression require beta association. It is concluded that impaired inflammatory function in this disorder is casually related to a heritable deficiency of critical "adhesive" leukocyte glycoproteins.

Adolescent↗
PubMed1985

Influence of menstrual cycle variations on natural killer cytotoxicity and antibody-dependent cellular cytotoxicity to cells infected with herpes simplex virus.

Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent the ability of human leukocytes to destroy target cells. Those systems have been shown to influence herpes simplex virus (HSV) infections. Prostaglandins are known to inhibit these nonspecific immunologic defenses. Since prostaglandin production varies with the menstrual cycle, this study was undertaken to test for variations in cytotoxic activity against HSV-infected cells during the proliferative, secretory and menstrual phases in 13 normal volunteers. NKC and ADCC activity was not statistically different between the three menstrual phases when testing was done for both mononuclear and polymorphonuclear cells from donor sera. This study suggested that NKC and ADCC cannot be used to explain anecdotal experiences suggesting menstrual variations as a triggering mechanism for HSV recurrences.

Adult↗
PubMed1984

The relative role of transplacental and milk immune transfer in protection against lethal neonatal herpes simplex virus infection in mice.

The role of passive maternal immunity in neonatal herpes simplex virus (HSV) infection is controversial. C57BL/6 mice born to HSV-immune mothers had significantly greater survival than those born to nonimmune mothers after an intraperitoneal or oral HSV challenge. In subsequent experiments with intraperitoneal and oral HSV challenge, non-immune mice that were foster fed for one week by actively or passively immunized mothers were significantly protected. Injections of passive antibody postpartum in nonimmune mother mice resulted in detectable transfer of antibody to HSV to their infant mice via breast milk. In mice, maternal breast milk, not transplacentally derived antibody, protects neonates from low-dose HSV infection.

Animals↗
PubMed1984

Analysis in human neonates of defective antibody-dependent cellular cytotoxicity and natural killer cytotoxicity to herpes simplex virus-infected cells.

Human neonatal mononuclear cells (MCs) had low antibody-dependent cellular cytotoxicity (ADCC) compared with cells from adults in a chromium-release assay against Chang liver cells infected with herpes simplex virus (HSV). Polymorphonuclear leukocyte (PMNL) ADCC of neonates was similar to that of adults. In a single-cell agarose conjugation assay IgG antibody to HSV significantly increased conjugation by adult MCs, adult PMNLs, and cord blood PMNLs but not by cord blood MCs. Expression of the high-affinity IgG Fc receptor (FcR) assayed by erythrocyte-antibody rosetting revealed significant differences between adult MC FcR and cord blood FcR. There was no difference in PMNL FcR expression. Human interferon-alpha increased neonatal MC adhesion in the presence of IgG and FcR expression, but it had no effect on MC ADCC. Defective FcR expression and target cell adhesion may partly explain low neonatal MC ADCC. In addition, cord blood cells have a lytic or recycle, as well as an adherence, defect.

Adult↗
PubMed1984

Early detection in suspected herpes simplex encephalitis.

In a retrospective study of ten patients who had brain biopsy because of suspected herpes simplex encephalitis, the diagnosis was confirmed in only three patients. However, in four patients whose clinical presentation was indistinguishable from that of 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.

Adult↗
PubMed1984

Antibody-dependent cellular cytotoxicity and natural killer cytotoxicity of peritoneal cells from nude mice to herpes simplex virus-infected cells.

Nude BALB/c mice (athymic) were more susceptible to fatal herpes simplex virus (HSV) than normal BALB/c mice (P = 0.002). The peritoneal cells of nude mice mediated levels of antibody-dependent cellular cytotoxicity (ADCC) of equal or greater magnitude than cells from normal BALB/c, heterozygote nu/+, or C57BL/6 mice. Unstimulated natural killer cytotoxicity of peritoneal cells from nude mice was higher (P less than 0.05) than that mediated by cells from C57BL/6 mice. Nude mice failed to make anti-HSV ADCC antibody 6 to 14 days post HSV inoculation, at times when nu/+, BALB/c, and C57BL/6 mice produced antibody. Passive reconstitution of nude mice with high titer intraperitoneal anti-HSV immune globulin provided circulating anti-HSV ADCC antibody and significant protection against lethal HSV infection.

Animals↗