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Biomedical subjects

S Kohl

Publications and source records attributed to S Kohl.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neonatal herpes simplex virus infection.

The incidence of genital herpes simplex virus (HSV) and neonatal HSV infection is increasing in the United States. The risk to the neonate of a woman with genital recurrences (1%-3%) versus first-episode infection (30%-50%), even when asymptomatic, has been defined. Appreciation of the subtle clinical signs, as well as more obvious cutaneous signs of neonatal infection, will lead to appropriate diagnostic evaluation (including, at times, polymerase chain-reaction assay) and therapy. Understanding the immune defects predisposing the neonate to severe HSV infection will enhance efforts to reconstitute the neonate's immune function. Maternal vaccination, chemoprophylaxis, and appropriate use of cesarean-section delivery may prevent cases of neonatal herpes now and in the future.

Diagnosis, Differential↗
PubMed1996

Interleukin-12 administered in vivo decreases human NK cell cytotoxicity and antibody-dependent cellular cytotoxicity to human immunodeficiency virus-infected cells.

Persons infected with human immunodeficiency virus (HIV) have cellular cytotoxicity defects. Interleukin (IL)-12 is a potent stimulator of cytotoxicity. Fifteen HIV-infected patients were studied in a phase 1, single-dose escalation trial of human recombinant IL-12. One day after subjects received an IL-12 dose of 300 or 1000 ng/kg, they had a reduction in absolute lymphocyte count and peripheral blood mononuclear cell recovery. In evaluable patients 24 h after IL-12 administration, there was a 31% reduction overall in NK cell cytotoxicity (NKC) to HIV-infected cells at all doses and a 52% reduction in antibody-dependent cellular cytotoxicity (ADCC) at doses of 300 and 1000 ng/kg. In vitro incubation of patients' cells with IL-12 (before IL-12 administration) for 24 h increased NKC but had no effect on ADCC. The paradoxic acute reduction in cell number and cytotoxicity in vivo may be due to NK cell trafficking or regulatory cytokine mechanisms not apparent in vitro.

Adolescent↗
PubMed1996

The clinical application of two newly developed lipid emulsions (Solipid 20% S&E) in critically ill patients.

OBJECTIVE: The clinical compatibility of two newly developed lipid emulsions based on soy oil (20%) emulsified with egg lecithin (12 g/l) or soy lecithin (15 g/l) (Solipid 20% E&S) has been compared. DESIGN: Double-blind prospective randomized study. SETTING: Intensive care unit of a university hospital. PATIENTS: 20 patients (16 men, 4 women, age 20-59 years) were entered into the study. INTERVENTIONS: One g of lipids/kg body weight per day was administered on day 1 and subsequently 2 g/kg/day on days 2-5. Blood was drawn once a day, lipids, lipoproteins, apoproteins and other routine clinical chemistry parameters were determined. RESULTS: No significant increase of total triglycerides could be observed. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoproteins A I and B usually remained below the reference ranges. Electrolytes, uric acid and glucose, blood cells, parameters of liver and kidney function, coagulation and protein metabolism did not show relevant changes; only the activity of gamma-GT in both groups--independent of the sort of lecithin--increased significantly. CONCLUSION: The results indicate adequate elimination of both tested lipid emulsions from the plasma at usual clinical conditions. Therefore Solipid 20% S&E can be used in critically ill patients.

Adult↗
PubMed1996

Interleukin-12 induces interferon-gamma expression and natural killer cytotoxicity in cord blood mononuclear cells.

Severe viral infection in newborns has been attributed to immaturity of the immune system including a defect in natural killer cytotoxicity (NKC) and decreased production of cytokines that are important for natural killer (NK) function. We investigated the induction of interferon (IFN)-gamma and activation of NK activity in adult and cord blood mononuclear cells (BMC) after IL-12 treatment. The levels of mRNA in these BMC were measured by Northern blot and reverse transcription-polymerase chain reactions using primers specific for IFN-gamma. The levels of IFN-gamma protein were measured by ELISA. In the absence of IL-12, only adult BMC spontaneously produced low levels of IFN-gamma. After IL-12 treatment, induction of IFN-gamma expression was detected as early as 4 h in both cord and adult BMC. Both cord and adult cells showed similar levels of IFN-gamma mRNA and protein expression in response to IL-12 at a concentration as low as 10 U/mL. In contrast, upon phorbol ester and ionomycin treatment, adult BMC produced more IFN-gamma mRNA than cord BMC. In a 51Cr release assay with human immunodeficiency-infected H9 cells as indicators, both cord and adult cells responded to IL-12 induction of NKC. Our findings demonstrate that cord BMC are capable of responding to IL-12 stimulation, competent in synthesizing IFN-gamma, and able to mount NKC. Thus, it appears that the deficiency in IFN-gamma production or NKC in cord cells is not due to an inherent defect in IL-12 response of the cord cells.

Base Sequence↗
PubMed1996

Characterization of natural killer and antibody-dependent cellular cytotoxicity of preterm infants against human immunodeficiency virus-infected cells.

The odds risk of vertical transmission of human immunodeficiency virus (HIV) to preterm infants is almost four times that of term infants and may relate to maternal and neonatal factors. We characterized the competence of early nonspecific cellular immunity, namely natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC), of peripheral blood mononuclear cells (PBMC) from preterm (n = 20) and term neonates (n = 28) versus adult controls against a T cell line infected with the human T cell lymphotrophic virus-III(B) using a chromium-51 release assay. PBMC from term neonates exhibited levels of NKC activity equal to adults against HIV-infected targets, yet the NKC capacity of preterm neonatal PBMC was significantly diminished. The ADCC activity of both term and preterm neonatal PBMC against HIV-infected targets was significantly less than that of adult PBMC. Overnight stimulation of a subset of samples with IL-12 augmented the NKC activity of both infant groups and adults, whereas the ADCC activity remained unchanged. These findings demonstrate that term neonates are deficient in ADCC against HIV-infected targets, whereas preterm infants are deficient in both NKC and ADCC, which may relate, in part, to the increased risk of transmission of HIV with preterm delivery. In addition, IL-12 has the potential to augment both term and preterm neonatal antiviral defense.

Adult↗
PubMed1994

Association between anti-human immunodeficiency virus type 1 (HIV-1) antibody-dependent cellular cytotoxicity antibody titers at birth and vertical transmission of HIV-1.

Because vertical transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant occurs in only 15%-35% of possible opportunities, natural immune defenses of the mother, fetus, or neonate may be protective against infection. The relation between antibody-dependent cellular cytotoxicity (ADCC) antibodies and HIV-1 infection was explored in 78 neonates born to HIV-infected women. More than 90% of sera had measurable ADCC titers against HIV-1IIIB. Infant titers were closely correlated with maternal titers but were independent of total IgG and total antibody reactive to the same strain in whole virus ELISA. At birth, mean ADCC antibody levels of infants or their mothers were the same for infants who were infected and those who ultimately seroreverted and remained healthy. ADCC antibody titers against HIV-1SF2 were weakly correlated with anti-HIV-1IIIB titers and did not predict protection from HIV-1 infection. High levels of anti-HIV-1 ADCC antibody at birth are not protective against vertical transmission of HIV-1.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1994

Human fetal antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Human fetal antibody-dependent cellular cytotoxicity (ADCC) has not been reported previously. Most investigations have failed to document any cytolytic activity among fetal lymphocytes. The purpose of this study was to investigate ADCC activity in the human fetus and identify and characterize the effector cell populations in the fetus. Fetal spleen cells were separated into single-cell suspensions and assayed with 51Cr-labeled herpes simplex 1-infected Chang liver target cells. Significant ADCC activity was detected in 19 of 26 (73%) of freshly assayed fetal spleen cell preparations from fetuses of 17-24 wk gestational age. This activity, however, was significantly less than concurrently run adult peripheral blood mononuclear cells. After plastic adherence the fetal spleen ADCC activity from nonadherent cells was not significantly different from whole spleen preparations. Surprisingly, ADCC activity in nonadherent fetal cells dropped significantly after exposure to latex beads, an effect not seen in nonadherent adult lymphocytes. Thus, either fetal monocyte-derived (macrophages) fetal spleen cells do not efficiently adhere to plastic or a unique nonadherent population of latex-sensitive immunocytes is capable of mediating ADCC activity in the fetus. We suspect the former conclusion to be the more plausible; however, fluorescence-activated cell sorter staining of fetal cells was not sufficient to confirm these suspensions by fluorescence-activated cell sorter analysis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1993

Effect of soy protein diet versus standard low fat, low cholesterol diet on lipid and lipoprotein levels in children with familial or polygenic hypercholesterolemia.

The effect on serum lipid and lipoprotein levels of a standard low fat, low cholesterol diet was compared with that of a soy protein-substituted low fat, low cholesterol diet in 23 children with familial or polygenic hypercholesterolemia: 12 boys and 11 girls (mean age, 9.3 +/- 4.5 years) were included in this outpatient program. Group 1 received the soy protein diet for 8 weeks; group 2 received the low fat, low cholesterol diet. After an interruption of 8 weeks, each group was placed on the alternate regimen. Fasting blood samples were collected at the beginning of each dietary period. During the soy protein diet, the levels of total cholesterol decreased by 16% in group 1 and 18% in group 2, and low-density lipoprotein cholesterol (LDL-C) levels decreased about 22% in group 1 and 25% in group 2. During the standard low fat, low cholesterol diet, total cholesterol and LDL-C levels were reduced by 8% and 7% in group 1 and by 12% and 13%, respectively, in group 2. The effect on LDL-C was significantly greater (p < 0.05) in the soy protein group than in the low fat, low cholesterol group. We conclude that a diet substituting soy protein for animal protein has a more beneficial short-term effect on total cholesterol and LDL-C levels in children with hypercholesterolemia than a standard low fat diet.

Adolescent↗
PubMed1993

Antibodies to epitopes of herpes simplex virus type 1 glycoprotein B (gB) in human sera: analysis of functional gB epitopes defined by inhibition of murine monoclonal antibodies.

The epitopes on herpes simplex virus (HSV) glycoprotein B (gB) recognized by sera of 23 patients with well-characterized HSV infection were studied. Twelve epitope-specific monoclonal antibodies with neutralization (NT) or antibody-dependent cellular cytotoxicity (ADCC) activities were used in competitive ELISA binding inhibition studies. The sera were additionally analyzed for homologous viral type NT, ADCC activity, and gB-reactive antibody by ELISA. Seroconversion was observed in each assay during convalescence. Relative type specificity for sera from HSV-1-infected but not from HSV-2-infected individuals was demonstrated in the ADCC assay. Sera from HSV-infected patients contained antibodies recognizing 9 of 12 epitopes, representing 5 of the 6 characterized antigenic domains of gB tested. Two of the epitopes were blocked in a type-specific fashion. The incidence of epitopic recognition increased gradually with time and was delayed compared with the detection of functional ADCC or NT activity and overall antibody recognition of gB in the ELISA.

Acute Disease↗
PubMed1993

Natural killer cytotoxicity and antibody-dependent cellular cytotoxicity of human immunodeficiency virus-infected cells by leukocytes from human neonates and adults.

In infants born to mothers infected with the human immunodeficiency virus (HIV), antibody-dependent cellular cytotoxicity (ADCC) or natural killer cytotoxicity (NKC) may either eliminate infection or ameliorate its course. We developed and standardized an assay for cytotoxicity of HIV-infected cells and studied the capacity of leukocytes from healthy neonates and adults to lyse HIV-infected cells by ADCC and NKC. The chosen target cell line, a T cell line infected with the HXB-2 clone of human T-cell lymphotrophic virus-IIIB, displayed stable surface expression of viral antigens over months of continuous culture and allowed simultaneous assessment of NKC and ADCC of effector cell populations. Conditions for optimal ADCC lysis of target cells were defined for unpurified peripheral blood mononuclear cells and purified lymphocytes and monocytes. Polymorphonuclear neutrophils from healthy adults and neonates exhibited low activity in ADCC of HIV-infected targets. Lymphocytes and monocytes from adults were found to differ in antibody dependence, kinetics, and sensitivity to latex inhibition for ADCC-mediated lysis of HIV-infected targets. Peripheral blood mononuclear cells of healthy neonates and adults displayed equivalent capacity to mediate NKC of HIV-infected targets. However, neonates' peripheral blood mononuclear cells were found to be significantly less active than adults' in ADCC lysis of HIV-infected cells. This pattern of diminished ADCC cytotoxicity with intact NKC is the opposite of that seen in HIV-infected adults. Our findings suggest that therapies designed to enhance ADCC effector cell function in the neonate may help interrupt vertical transmission of HIV.

Adult↗
PubMed1992

Persistent cerebrospinal fluid neutrophilia in delayed-onset neonatal encephalitis caused by herpes simplex virus type 2.

We describe an infant with three unusual features of perinatally acquired herpes simplex virus type 2 encephalitis: onset of illness at 34 days of age, absolute cerebrospinal fluid neutrophilia, and systemic viral dissemination after central nervous system disease. To provide early, effective antiviral therapy, clinicians should be aware of atypical presentations of serious herpes simplex virus infections.

Encephalitis↗
PubMed1992

Epitopes of herpes simplex virus type 1 glycoprotein B that bind type-common neutralizing antibodies elicit type-specific antibody-dependent cellular cytotoxicity.

A panel of 45 well-characterized monoclonal antibodies (MAbs) reactive to glycoprotein B (gB) of herpes simplex virus (HSV) type 1 was tested by ELISA and in antiviral functional assays (that included virus neutralization, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement-mediated lysis), using type 1 or 2 virus strains. All MAbs were ELISA-reactive. Eleven of the MAbs mediated neutralization and 9 mediated ADCC. All of the ADCC epitopes were contained within the amino-terminal half of the extracellular portion of gB. The ADCC reactions were strictly type 1-specific, whereas 9 of 11 neutralizing MAbs exhibited type-common activity. There was some association between the ADCC and neutralization activities, since of 12 MAbs with functional activity, 8 were positive in both assays. These results suggest that differences in the presentation of gB, and perhaps HSV-1 gB versus HSV-2 gB, on free virus and virus-infected cells determine epitope availability.

Animals↗
PubMed1992

A comparison of herpes simplex virus specific antibodies found in human milk and serum.

It is not known if milk antibody protects infants from herpes simplex virus (HSV) infection. As a first step to test this hypothesis, anti-HSV antibodies were studied in human milk. Paired serum and milk samples were analyzed for anti-HSV antibodies by ELISA, Western blot analysis (WBA), neutralization (NT) plaque assay, and antibody-dependent cellular cytotoxicity (ADCC) assay. Nineteen of the 20 serum samples showed anti-HSV activity by ELISA and ADCC, and 18 showed activity by WBA and NT. We found a significant association between the immunoassays for detection of anti-HSV antibodies in sera. Fewer of the human milk samples showed anti-HSV activity; only one milk sample was positive by ELISA and one by NT assay, four by ADCC and 12 by WBA. The milk sample from the seronegative donor was also negative. We found a poor association of antibody titers in human milk and serum antibody titers using ELISA, NT, and ADCC assays. There was a significant (p = 0.022) association between serum and milk results using WBA. Among the four assays, WBA was the most sensitive for antibody detection. It will be used in an on-going prospective study to determine the role of anti-HSV antibody in the protection against HSV infections in infants.

Antibodies, Viral↗
PubMed1992

New aspects of neonatal herpes.

Herpes simplex virus (HSV) is a rare but increasingly prevalent agent of newborn infection. Primary or first episode genital infection in the mother constitutes the greatest risk of infection in the neonate. Transplacental, HSV-specific functional antibody appears to protect infants from severe disease and may be therapeutically exploitable. Prevention of serious sequelae in the infant depends on early diagnosis and treatment of HSV-infected infants.

Antiviral Agents↗