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Biomedical subjects

L Slater

Publications and source records attributed to L Slater.

At least 37 records · Page 2Linked to original sources
PubMed1986

The effect of hydrocortisone on the production of gamma-interferon and other lymphokines by human peripheral blood mononuclear cells.

Concentrations of hydrocortisone as low as 0.08 microgram/ml significantly reduced the yields of gamma-interferon (IFN-gamma) when phytohemagglutinin (PHA) or concanavalin A (ConA) were used as inducers; however, when staphylococcal enterotoxin A was utilized, higher concentrations (5.0 micrograms/ml) were required to achieve the same effect. Yields of interleukin-2 (IL-2) and lymphotoxin were also found to be sensitive to the effects of the steroids, but expressions of TAC antigen was not generally affected by these agents. In contrast to the effects of steroids on cell proliferation, lymphokine production remained suppressed after steroid withdrawal. Hydrocortisone appeared to influence the concentrations of cyclic nucleotides following lectin stimulation, but attempts to correct these alterations or to add exogenous IL-2 failed to restore lymphokine production to normal levels. Addition of the calcium ionophore A23187 partially restored IFN-gamma production. We conclude that the effects of corticosteroids on the yields of lymphokines, including IFN-gamma, are profound. The depression of lymphokine production appears to be associated with a number of alterations in the cell, including depression of protein synthesis, alterations in cyclic nucleotides, and diminution of the production of cofactors necessary for IFN-gamma production. Enhancement of the flux of calcium into the cell may restore some of the ability to produce IFN-gamma.

Antigens, Surface↗
PubMed1984

Immunological events in new onset diabetes.

Data from our laboratory are reviewed showing that both cell-mediated cytotoxicity, complement-dependent antibody-mediated cytotoxicity, antibody-dependent cellular cytotoxicity, and complement-augmented antibody-dependent cellular cytotoxicity may provide mechanisms which kill pancreatic islets during pathogenesis of insulin-dependent (type I) diabetes. Xenogenic test systems employing dispersed rat islet target cells were employed. Most of the findings were reversible during clinical remission of diabetes.

Animals↗
PubMed1984

Immunological analysis in familial common variable immunodeficiency.

Immunological and genetic studies were performed in nine members from three generations of the family of a patient with common variable immunodeficiency (CVI). Two additional symptomatic members (mother and grandmother) had CVI. Among other six asymptomatic members, two had CVI and one had selective IgA deficiency. The proportions of monoclonal antibody defined total T cells (Leu 1+), helper phenotype (Leu 3+) suppressor phenotype (Leu 2+) T cells, natural killer cells (Leu 7+) and surface Ig+ B cells and proliferative response to phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and in mixed lymphocyte reaction (MLR) were comparable to controls. Addition of purified interleukin-2 (IL-2) resulted in augmentation of PHA-induced proliferation of T lymphocytes similar to that seen in the controls, however with IL-2 freshly isolated T cells in the absence of PHA demonstrated markedly increased proliferative response, suggesting the presence of in vivo activated T cells. Study of HLA phenotype did not reveal any linkage. This study demonstrates the genetic nature, possibly autosomal dominant inheritance, of common variable immunodeficiency; however the immunodeficiency is not linked to any specific HLA antigen.

Adolescent↗
PubMed1984

Home versus hospital phototherapy for term infants with hyperbilirubinemia: a comparative study.

Twenty-five term infants with hyperbilirubinemia were selected for phototherapy administered at home if they fulfilled clinical and laboratory criteria designed to exclude any pathologic cause of hyperbilirubinemia. Ongoing nursing surveillance of home phototherapy was provided to assure adequate nursing care. No phototherapy-related complications were noted in the study infants. Effectiveness of phototherapy at home was compared with results in a similar group of 33 infants who underwent standard hospital phototherapy. The average decrease in serum bilirubin concentration was similar for the two groups after the first day of treatment. Duration of phototherapy was longer for infants treated at home. The major motivating factor for study entry appeared to be avoidance of parent-infant separation.

Bilirubin↗
PubMed1983

Immune islet killing mechanisms associated with insulin-dependent diabetes: three rabbit antibody-mediated islet cell cytotoxicity models.

Antibody-mediated islet cell killing mechanisms have been associated with human insulin-dependent diabetes. Several types of antibody-mediated cytotoxic mechanisms exist, but only complement-dependent antibody-mediated cytotoxicity is reported for islet killing. To evaluate further islet cytotoxic antibody mechanisms, we have studied antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity using polyclonal rabbit anti-rat islet cell immune serum and 51Cr-labelled dispersed normal rat islet target cells. Maximal immune serum-mediated islet cell specific cytotoxicity was 80% for complement-dependent antibody-mediated cytotoxicity, 40% for antibody-dependent cellular cytotoxicity and 20% for complement-augmented antibody-dependent cellular cytotoxicity. The minimum serum dilution for maximal islet cell cytotoxicity was 1:100 for complement-dependent antibody-mediated cytotoxicity, 1:10 for complement-augmented antibody-dependent cellular cytotoxicity. These data indicate a unique optimal serum dilution for each of the three antibody killing mechanisms. Immune serum-mediated cytotoxicity was more specific for rat islet target cells than macrophage target cells. That antibody mediated these cytotoxic events was documented using immune serum-derived, DEAE purified immunoglobulin G which induced killing in all three antibody assays. Both antibody-dependent cellular cytotoxicity assays appear useful for studies of human diabetes, since human non-T mononuclear cells are cytotoxic to islet cells. These results suggest that for studies of potential islet cell killing mechanisms in insulin-dependent diabetes, specific xenogeneic assays exist not only for complement-dependent antibody-mediated islet cytotoxicity, but also for antibody-dependent cellular cytotoxicity and complement augmented antibody-dependent cellular cytotoxicity.

Adolescent↗
PubMed1983

Immune islet killing mechanisms associated with insulin-dependent diabetes: in vitro expression of cellular and antibody-mediated islet cell cytotoxicity in humans.

Because immune mechanisms are associated with insulin-dependent diabetes, multiple organ specific and xenogeneic cytotoxicity assays were developed. Human cellular and antibody effector systems were incubated with 51Cr-labeled dispersed normal rat islet target cells. In eight of 11 diabetic patients, nonenriched mononuclear cells incubated with islet target cells were more cytotoxic than cells from age- and sex-matched controls (p less than 0.01). When non-T cell-enriched mononuclear cells were used at diabetes onset, seven of 11 patients' cells showed excessive islet cytotoxicity (p less than 0.05). In four patients showing elevated cytotoxicity at diabetes onset, cytotoxicity decreased to control levels during diabetes remission. Islet specificity was suggested in that mononuclear cells derived from diabetic subjects did not mediate cytotoxicity against rat spleen or macrophage target cells. Three cytotoxic antibody mechanisms were also evaluated. C-dependent antibody-mediated cytotoxicity with the use of patient serum-coated islet target cells was elevated above control levels in four of 14 patients. Antibody-dependent cellular cytotoxicity exceeded control values in only two of 16 patients, although four assay systems were evaluated. C-augmented antibody-dependent cellular cytotoxicity was elevated in three of 14 patients. No differences were observed for antibody-mediated mechanisms in four patients evaluated at both diabetes onset and remission. Cytotoxic antibody was present in only about one-half of the patients showing increased cellular cytotoxicity, whereas most patients expressing increased cytotoxic antibody had cellular cytotoxicity. Islet cell cytotoxicity assays with the use of effector systems from patients with recent onset insulin-dependent diabetes suggest that direct cellular cytotoxicity is more active than antibody-mediated cytotoxic mechanisms, and that cellular cytotoxicity can correlate with disease activity.

Adolescent↗
PubMed1982

Volume regulation of human peripheral blood lymphocytes and stimulated proliferation of volume-adapted cells.

Human peripheral blood lymphocytes exposed to hypotonic media (Ca/Mg-free, room temp.) first swell and then shrink. This shrinking response is characterized by a simple exponential with a half-time of 1.44 +/- 0.60 min (n = 11) and its extent but not the half-time for a given hypotonicity is influenced by [K+]0. Using K-selective electrodes, we observe a change in [K+]0 when cells are diluted into hypotonic media. A half-time of 1.55 +/- 0.06 min (n = 4) was obtained. A similar half-time was obtained by assay of total cell K using atomic absorption spectroscopy. At all osmolarities [K+]i was decreased from control values and was constant as [K+]0 was increased. Short-term incubation with ouabain (10(-4) M) had no effect. Decreasing osmolarities progressively inhibited phytohemagglutinin-stimulated DNA synthesis, yet cell number and viability remained unaltered. Our evidence indicates that the volume response is mediated by a change in the passive permeability of the plasma membrane to K and/or to the accompanying anions, and that the consequently volume-adapted cells are growth-inhibited.

Cell Division↗
PubMed1979

Inactivators of fibroblast interferon found in human serum.

Investigation of the inactivators of fibroblast interferon has shown that those substances could be identified in every specimen of serum taken from normal individuals. These inactivators were found to destroy a mean of 82% of the interferon antiviral activity beyond that caused by the effects of temperature alone. The inactivators exerted no effect at 4 degrees C but were found in a variety of animal as well as human sera. Although slight differences were found to exist in the extent of inactivation when comparing normal human serum to serum from patients (i) receiving chronic hemodialysis, (ii) with jaundice, or (iii) with underlying malignancies, the differences did not appear to be clinically significant. In exploring the nature of the substances, we found that both dialyzable and non-dialyzable inactivators exist, but the former appear to be the major factors responsible for the unwanted process.

Blood↗
PubMed1979

Immunosuppressive therapy of ocular disease.

Care and caution are required in using immunosuppressive agents to combat sight-threatening ocular disease. Informed consent of the patient and the active participation of a knowledgeable internist are mandatory in view of the known potential consequences of therapy. These consequences or side effects include specific and general problems, and before initiating therapy the cost/benefit ratio must be considered. Although the most commonly used agents are nonspecific, some drugs appear more beneficial in certain conditions than others, as is the case of chlorambucil in Behcet disease. It is a policy at the Uveitis Clinic of the University of California, Irvine, to institute immunosuppressive therapy early enough for conservation of useful vision, yet late enough so that it is clear that moderate to heavy steroid therapy cannot prevent blindness. In the event of failure of the "conventional" immunosuppressive therapy, plasmapheresis may prove a helpful adjunct.

Adult↗
PubMed1975

IgG, IgA and IgM by formylated rocket immunoelectrophoresis.

Formylated rocket electrophoresis has been investigated as a means of measuring the serum immunoglobulins IgG, IgA, and IgM. This procedure is simpler to carry out than carbamylation. Comparison of formylated rocket results with those from the automated immunoprecipitin (A.I.P.) system and single radial immunodiffusion (S.R.D.) gives correlation coefficients of 0.92 to 0.98 and reproducibility comparable with the AI.P. system and better than S.R.D. The procedure is recommended for use in laboratories when the number of requests for immunoglobulins does not warrant a specific protein analyser.

Formaldehyde↗