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Biomedical subjects

S Kohl

Publications and source records attributed to S Kohl.

At least 91 records · Page 5Linked to original sources
PubMed1984

Cytotoxicity of leukocytes from normal and Shigella-susceptible (opium-treated) guinea pigs against virulent Shigella sonnei.

Intraepithelial lymphocytes were collected from the ileum of adult Hartley strain guinea pigs and used as effector cells in a 60-min bactericidal assay with virulent Shigella sonnei as target cells. Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) were measured and correlated with the resistance of the animals to infection by S. sonnei. Normal guinea pig intraepithelial lymphocytes exhibited mean NKC and ADCC values of 22.8 +/- 5.0 and 34.1 +/- 13.6, respectively. These animals were resistant to oral challenge with virulent S. sonnei. Intraepithelial lymphocytes from guinea pigs which were fasted for 4 days demonstrated NKC and ADCC values similar to those of normal animals (31.0 +/- 8.1 and 41.7 +/- 6.7, respectively). These animals also were resistant to oral challenge. Intraepithelial lymphocytes from guinea pigs which were given 1 ml of deodorized tincture of opium 2 h before cell collection demonstrated deficient NKC (4.7 +/- 4.2) and ADCC (5.3 +/- 4.9) values but remained resistant to infection by S. sonnei. When guinea pigs were fasted for 4 days and given opium, deficient NKC (2.0 +/- 2.0) and ADCC (1.3 +/- 1.3) values were demonstrated; this group of animals was susceptible to infection by S. sonnei (P less than 0.04). These experiments demonstrated that opium treatment depresses one form of gut immunity. When combined with starvation, opium treatment may increase susceptibility to infection by shigellae by modulation of immunity in addition to the effects on gut motility and bacterial flora.

Animals↗
PubMed1984

Cytotoxicity of human peripheral blood and colostral leukocytes against Shigella species.

We examined the ability of human peripheral blood leukocytes to kill strains of Shigella sonnei and Shigella flexneri by using a modified bactericidal assay. Antibody-dependent cellular cytotoxicity (ADCC) was demonstrated in the presence of specific rabbit immune serum directed against S. sonnei. With peripheral blood leukocytes from adults, ADCC was found only in the mononuclear cell and purified lymphocyte populations. Monocyte-macrophages and polymorphonuclear leukocytes were unable to demonstrate ADCC. Lymphocyte ADCC, which was not affected by the addition of phenylbutazone (an inhibitor of phagocytosis), was mediated by a non-T, Fc receptor-positive, HNK-1- cell. ADCC (using antiserum directed against virulent S. sonnei) was demonstrated against virulent S. sonnei but not against virulent S. sonnei or virulent S. flexneri. In contrast to leukocytes from adults, both mononuclear and polymorphonuclear cells from neonatal cord blood and from a patient with chronic granulomatous disease mediated anti-Shigella ADCC. Breast milk leukocytes (BMLs) collected 1 to 3 days postpartum were used as effector cells against virulent S. sonnei. The entire BML population, BMLs which did not adhere to plastic and BMLs which passed through nylon wool columns mediated both natural killer cytotoxicity and ADCC. In paired experiments, natural killer cytotoxicity and ADCC were significantly lower (30 to 45% inhibition) but not ablated, when phenylbutazone was added to BMLs and nylon wool-purified BMLs (P less than 0.05). These experiments suggest that colostral leukocytes mediated both extracellular and intracellular bacteriolysis in the presence and absence of specific antiserum. These mechanisms may be active in vivo in protection against shigellosis.

Age Factors↗
PubMed1984

Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence.

Investigations of polymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an almost total deficiency of a high molecular weight glycoprotein(s) (GP138) in the granule and membrane fractions of the patient's cells, and NaB3H4-galactose oxidase labeling demonstrated the absence of a major glycoprotein complex on the surface of her PMNs. Monoclonal antibodies (MAb) were employed in flow cytometry experiments to demonstrate that two previously characterized glycoproteins (Mo1 and LFA1) were undetectable on the surface of the patient's PMNs and monocytes. Immunoprecipitation of 125I-labeled patient cells with subunit specific MAbs confirmed that the alpha-subunits of Mo1 (155 kD) and LFA1 (177 kD) and their common beta-subunit (94 kD) were totally deficient. Functional analyses of patient PMNs demonstrated severe impairment of adherence- and adhesion-dependent cell functions including spreading, aggregation, orientation in chemotactic gradients, antibody-dependent cellular cytotoxicity, and phagocytosis of particles (Oil-Red-0-paraffin, zymosan) selectively opsonized with C3-derived ligands. Patient PMNs demonstrated a normal capacity to rosette with IgG or C3b-coated sheep erythrocytes, but rosette formation with C3bi-coated erythrocytes was profoundly diminished. Adhesion-independent functions including shape change, N-formyl-methionyl-leucyl-3H-phenylalanine binding, and O-2 generation or secretion elicited by soluble stimuli were normal. Membrane fluidity, surface charge, and microtubule assembly were also normal. These findings provide new evidence that critical PMN surface glycoproteins are required to facilitate multiple adhesion-dependent cellular functions of the inflammatory response.

Adult↗
PubMed1984

Ontogeny of protection of neonatal mice from lethal herpes simplex virus infection by human leukocytes, antiviral antibody, and recombinant alpha-interferon.

We have studied the peripheral blood leukocytes from human infants in an assay involving the protection of neonatal mice from herpes simplex virus (HSV) infection by human antibody, interferon, and leukocytes. Recombinant DNA alpha-interferon (IFLrA), antibody, and Ficoll-Hypaque-purified mononuclear cells (MC) from human adults administered intraperitoneally protected neonatal mice from a lethal HSV challenge 1 day later (73.6% survival). MC obtained from human infants less than 130 days old in combination with IFLrA and antibody afforded no protection (15.2% survival; p less than 0.0005 compared to survival with adults' MC). MC from infants over 130 days protected the neonatal mice [60% survival; not significantly different from survival using adult cells, but significantly (p less than 0.0005) different than survival using MC from younger infants]. The ontogeny of MC protection parallels the clinical development of resistance of infants to HSV infection.

Animals↗
PubMed1984

Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-1/OKM-1 deficiency.

Four children with an immunodeficiency involving the absence of leukocyte membrane glycoproteins reacting with anti-LFA-1 and OKM-1 monoclonal antibodies were unable to mediate adherence-dependent leukocyte functions. Even with normal Fc receptor function, their PMN-ADCC and MC-NKC were markedly deficient. Single cell analysis demonstrated deficient antibody-mediated PMN-target cell adherence. Monoclonal antibodies against LFA-1 and OKM-1 reproduced this immunodeficiency in leukocytes from normal adults. LFA-1/OKM-1 mediates a PMN-target cell adhesive step.

Adolescent↗
PubMed1984

[Reversibility of akinetic segments in coronary heart disease].

Akinetic wall segments not exhibiting contractions following nitroglycerin administration or in a post-extrasystolic beat are usually considered to consist of scar tissue; i.e. even by re-established or improved blood supply following aorto-coronary bypass surgery no functional improvement is expected. In the present study, the pre- and postoperative ventriculograms (RAO projection) of 24 patients undergoing bypass surgery were analyzed. Ventriculography was routinely performed following sublingual nitroglycerin and a post-extrasystolic contraction. In each patient the akinetic segment had received a bypass graft which was found to be patent on reangiography. In 7 of 24 patients (29%) the formerly akinetic segment exhibited improved contraction postoperatively; in 17 patients the segment remained akinetic. Global ejection fraction rose in the group of patients with improved akinesia from 47 +/- 10 to 65 +/- 10% (p less than 0.05). In the patients with unchanged contraction pattern, ejection fraction was found to be 56 +/- 12% prior to surgery and 54 +/- 16% after surgery (n.s.). The increase in ejection fraction was more pronounced in those patients showing improvement of anterior wall akinesia (from 39 to 72%) than it was in patients exhibiting improved inferior wall akinesis (from 54 to 59%). According to these findings, the regional ejection fraction was found to be higher postoperatively in patients with former anterior wall akinesis (78%) than in those showing inferior wall contraction abnormalities (49%). End-diastolic and end-systolic left ventricular volume changes postoperatively did not reach statistical significance, although end-systolic volume showed a clear trend to decrease (preoperative: 114 +/- 54 ml/1.73 m2; postoperative: 79 +/- 29 ml/1.73 m2; n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Influence of naproxen therapy on natural killer cytotoxicity and antibody-dependent cellular cytotoxicity against cells infected with herpes simplex virus.

Natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC) represent one of the body's primary lines of defense against viral infections, including herpes simplex (HSV). This immune defense system is negatively influenced by prostaglandins. A project was undertaken to evaluate the influence of an antiprostaglandin agent in vivo on these cytotoxic effects against cells infected with HSV. Thirteen subjects without previous histories of clinical herpes simplex infection were studied during menses with and without naproxen therapy. A statistically significant augmentation (p = 0.05) of natural killer-cell function was identified in mononuclear cells during therapy. Subjects with baseline cytotoxicity of less than 45% demonstrated consistent elevations during naproxen therapy. No other significant differences could be found for mononuclear or polymorphonuclear cells with regard to NKC and ADCC. There appears to be a subset of patients who may benefit from immunologic augmentation with antiprostaglandin agents when experiencing herpes simplex virus infection.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

The effect of storage of blood on mononuclear cell antibody-dependent cellular cytotoxicity to herpes simplex virus-infected cells.

Antibody-dependent cellular cytotoxicity (ADCC) activity to herpes simplex virus-infected cells of fresh mononuclear cells was compared with the ADCC activity of mononuclear cells obtained from blood after 1, 2, and 18 hr of storage at room temperature. After 1 and 2 hr of blood storage, mononuclear cell ADCC activity decrease significantly (P less than 0.05 and P less than 0.01, respectively) and was undetectable after 18 hr of storage. The use of preservative-free heparin and various effector to target cell ratios further verified these results. There was no significant difference between natural killer cytotoxicity of mononuclear cells obtained from fresh blood compared with that obtained from blood after 1 and 2 hr of storage. These data demonstrate the importance of rapid assay of clinical specimens utilized to determine differences in ADCC activity of patient populations.

Adult↗
PubMed1983

Anti-infective therapy of infectious endocarditis.

Because of its high morbidity and mortality, endocarditis will remain an important pediatric problem. Obtaining adequate culture information prior to starting antibiotics to ensure an accurate early diagnosis coupled with aggressive medical and surgical management is likely to give the best outcome. These patients are generally best handled by a team approach with the child's primary physician, cardiologist, infectious disease consultant, and cardiovascular surgeon working in close harmony.

Anti-Bacterial Agents↗
PubMed1983

Human neonatal leukocyte interferon production and natural killer cytotoxicity in response to herpes simplex virus.

Human neonates are susceptible to severe herpes simplex virus (HSV) infection; however, the immunologic mechanisms explaining this lack of resistance remain to be defined. The ability of leukocytes from adults and neonates to produce interferon (IFN) in response to HSV challenge and to destroy HSV infected cells in the absence of antibody, termed natural killer cytotoxicity (NKC), were compared. The NKC activity of leukocytes from neonates (13.5 +/- 2.5%) was significantly lower (p less than 0.005, Mann Whitney test; p = 0.007, Students t-test) than the NKC activity of adult leukocytes (25.7 +/- 3.2%). In contrast, no significant difference was observed between IFN production by neonate (87.7 +/- 29.1 units) and adult (87.8 +/- 29.4 units) leukocytes.

Adult↗
PubMed1983

Stimulation of human natural killer cytotoxicity and protection of mice from infection due to herpes simplex virus by recombinant human leukocyte interferon.

Destruction of virus-infected cells in the absence of antibody (natural killer cytotoxicity [NKC]) has been correlated with resistance to infection due to herpes simplex virus (HSV). Two preparations of human leukocyte interferon produced by recombinant DNA bacteria--IFLrA and IFLrD--were demonstrated to increase NKC in a dose-dependent fashion in vitro. IFLrA was more potent than was IFLrD in this assay. When administered intraperitoneally in combination with human leukocytes to one-week-old mice, IFLrA and IFLrD significantly increased survival (to 47.6% [P less than 0.01] and 23.8% [P less than 0.05], respectively) after an otherwise uniformly lethal challenge of HSV. Differences between interferon immunostimulating activities at similar antiviral concentrations may be important in vivo in animals and in clinical settings.

Animals↗
PubMed1983

Cytokine-stimulated human natural killer cytotoxicity: response to rotavirus-infected cells.

The ability of rotavirus-infected cells to stimulate leukocytes to release a cytokine which enhanced the subsequent leukocyte cytotoxicity to a second set of [51Cr] labeled rotavirus-infected cells was analyzed. Human interferon increased leukocyte cytotoxicity to Simian rotavirus (SA-11)-infected target cells. Similarly, 11 of 12 supernates of SA-11-stimulated peripheral blood leukocyte cultures increased the killing of SA-11-infected cells (P less than 0.005). This resulted in a calculated cytokine-dependent cellular cytotoxicity value of 9.6 +/- 1.9%. Three of five of the supernates tested contained measurable levels of interferon (12-48 unit/ml). In contrast, SA-11-stimulated colostral leukocyte culture supernates neither increased leukocyte cytotoxicity nor contained measurable levels of interferon.

Biological Products↗
PubMed1983

Antibody-dependent leukocyte killing of Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated, yeast-like fungus which is pathogenic for man. The role of various facets of the immune response which prevent disseminated disease in most normal hosts is unclear. A chromium-release assay was developed using radiolabeled cryptococci to reexamine antibody-dependent cell-mediated killing of this fungus. For a small capsule strain this assay served as a qualitative measure of effector cell function and was correlated with an assay of lethal injury to the organism. Polymorphonuclear leukocytes rather than mononuclear cells were the most active effector cells, causing significant chromium release from the fungus at effector-to-target ratios as low as 3:1. Polymorphonuclear leukocytes and mononuclear cells from a patient with chronic granulomatous disease showed minimal antibody-dependent cell-mediated chromium release suggesting that the final fungicidal pathway may be similar in antibody-dependent and antibody-independent leukocyte killing of this organism.

Animals↗
PubMed1983

Human antibody-dependent cellular cytotoxicity and natural killer cytotoxicity to herpes simplex virus-infected autologous and allogeneic cells.

Using cultured skin shavings, human cellular cytotoxicity to uninfected and herpes simplex virus (HSV)-infected autologous and allogeneic fibroblasts and Chang liver cells was analysed in a 51Cr release assay. The effector cell requirements and characterization, time kinetics and antibody requirements were similar using each HSV-infected target cell in an antibody-dependent cellular cytotoxicity (ADCC) system. There was lower natural killer cytotoxicity (NKC) to uninfected autologous cells than unrelated cells in an 18 hr assay. NKC to infected autologous and unrelated fibroblasts was similar to that mediated against Chang liver cells. Thus NKC to uninfected fibroblasts correlated with the relationship of effector and target cells while NKC to infected cells correlated with the intrinsic lytic potential of the effector cells. The autologous system offers little advantage in the analysis of ADCC or NKC in normal individuals to virus-infected cells, but is probably crucial for the detection of HLA-restricted T-cell cytotoxicity. The demonstration of autologous anti-viral ADCC and NKC lends further credence to the in vivo importance of the mechanisms.

Antibodies↗