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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 379 records · Page 21Linked to original sources
PubMed1984

Role of dialyzer contaminants in the allergic epiphenomena of hemodialysis.

Cuprophan hollow-fiber dialyzers contain contaminants including 1,2,3-propanetriol, carbohydrates, Limulus amebocyte lysate-reactive material, and particulates. In a clinical study, the role of these substances in the allergic-type response seen in some hemodialysis patients was examined. Patients were dialyzed three times per week for 6-week intervals with each of four dialyzer preparations designed to vary the burden of contaminants presented to the patient. Predialysis eosinophil counts and serum immunoglobulin (Ig) E levels were obtained weekly. White cell and platelet counts and plasma C3a and C5a levels were measured during dialysis for each dialyzer preparation. Dialyzer preparation had no effect on predialysis eosinophil counts or IgE levels. All patients demonstrated transient leukopenia and complement activation during dialysis, the magnitudes of which were unaffected by the type of dialyzer preparation. At the levels found in the dialyzers studied, it was questioned whether water-soluble extractables or particulates play any role in the allergic epiphenomena of hemodialysis.

Cellulose↗
PubMed1984

Effects of clomipramine infusion on sleep in depressed patients.

Sleep structure of 10 endogenous depressed patients was investigated before and after clomipramine treatment. Clomipramine significantly reduced REM time, increased REM latency and induced dissociation between the tonic and phasic events of REM sleep, without affecting any of the other sleep parameters. The REM suppressing effect was most prominent on the third night after beginning treatment.

Adult↗
PubMed1984

Evidence for extrapituitary mechanisms mediating the morning peak of plasma cortisol in man.

There is evidence for the existence of ACTH unrelated mechanisms in the regulation of cortisol secretion in man. This study was designed to elucidate the interrelationship between plasma ACTH and cortisol levels during the increase in cortisol levels, which occurs during morning hours. The results were compared with those of an artificial cortisol peak induced by administration of small amounts of ACTH, and with ACTH and cortisol values during insulin-induced hypoglycemia. In these control groups, the increase in cortisol levels was preceded by a large increase in ACTH levels; in the case of the physiological morning peak there was no adequate rise in mean ACTH levels. Thus, the spontaneously occurring increments in individual ACTH levels appear to be inappropriate for the increases in cortisol. This conclusion was corroborated by the finding that oscillations of plasma cortisol concentrations, comparable to the physiological morning peak, were demonstrable in ACTH-deficient patients when they were supplied with subthreshold amounts of exogenous ACTH. These findings argue against the classic concept that the adrenal cortex is invariably linked to immediately preceding episodes of pituitary ACTH secretion.

Adrenal Cortex↗
PubMed1984

Activation of cytotoxic activity of human blood lymphocytes by tumor-promoting compounds.

Three categories of tumor promoters and chemically related but inactive substances were tested for their effect on the cytotoxic activity of human blood lymphocytes against K562 and Daudi targets. Lymphocytes incubated overnight in the presence of phorbol esters 12-O-tetradecanoylphorbol-13-acetate and phorbol-12,13-dibutyrate [P(Bu)2] had enhanced function. Incubation with 4-alpha-phorbol-12,13-didecanoate was without effect. Enhancing activity was also exerted by the indole alkaloids, teleocidin and lyngbyatoxin A, and the polyacetates, aplysiatoxin and debromoaplysiatoxin, but not by dihydroteleocidin. Only the tumor-promoting compounds activated the cytotoxic potential. The substances acted in a dose-dependent manner with optimal activity at characteristic concentrations. Overnight incubation of lymphocytes at 4 degrees did not change their spontaneous cytotoxicity but abolished the enhancing effect of P(Bu)2. Thus, P(Bu)2-induced activation occurred only on metabolically active cells. The activation did not require DNA synthesis. Similar to controls, the P(Bu)2-treated cells required divalent cations and an intact cytoskeleton in order to perform their lytic function. Experiments with the various metabolic inhibitors indicate that phorbol ester treatment does not induce an alternative cytotoxic mechanism since, as with untreated lymphocytes, P(Bu)2-activated cells require contact with the target and intact secretory functions. The enhanced cytolytic potential was not due to induction of alpha-interferon (IFN-alpha) production, as shown by the fact that the effect was not abolished by addition of anti-IFN antibodies during the P(Bu)2 treatment of lymphocytes or during the cytotoxic assay. However, the presence of antiserum against IFN reduced the cytotoxic potential of control cells, suggesting that endogenous IFN production contributes to the maintenance of lytic function in cultured cells. If this mechanism is counteracted by addition of anti-IFN serum, the phorbol esters can provide an alternative activation signal. When P(Bu)2-activated lymphocytes were subsequently treated with IFN-alpha or IFN-gamma, their lytic capacity was further increased. These results indicate that P(Bu)2 and IFN activate cytotoxic potential through different pathways.

Burkitt Lymphoma↗
PubMed1984

Experimental and clinical data for the role of NK-cells in immunosurveillance.

Blood lymphocyte subsets separated on the basis of densities from 14 healthy donors and 25 patients with solid tumors were tested for lytic effect against allogeneic or autologous tumor cells derived from surgical specimens. The allogeneic combinations comprised 36 tests on 28 tumors. In these the total lymphocyte population was cytotoxic in one experiment. On the other hand, 16 experiments with density separated subsets were positive. The lytic effect resided in the light subset. Auto-tumor lysis excreted by total lymphocyte population occurred in 7 of 25 cases. Additional 11 tests showed cytotoxicity with the separated subsets. The autologous tumor cells were damaged by the light lymphocytes of 15 patients. Among these 6 had cytotoxic cells also in the high density subset. In seven cases auto-tumor lysis was exerted only by the dense lymphocytes. Thus in 13 cases the profile of auto tumor lysis differed from that observed with the allogeneic combinations and against K562. The autologous system may represent an immune situation and therefore it may not be unexpected that a proportion of the active cells have different phenotypic characteristics compared to the operationally natural killer system.

Antibody Specificity↗
PubMed1984

Phorbol esters inhibit the functional activation of cytotoxic precursors in mixed lymphocyte cultures.

We have investigated the effect of phorbol esters on T cell activation and generation of suppressor and cytotoxic activity in mixed lymphocyte cultures (MLC). The presence of 30 nM P(Bu)2 during the sensitization phase inhibited the generation of allospecific cytotoxicity and also decreased the killing potential against NK-sensitive targets. The inhibition was not mediated by direct blocking of the lytic capacity nor by suppression of clonal expansion of cytotoxic cells through modulation of lymphokine production. The presence of P(Bu)2 enhanced cell proliferation, but inhibited the functional activation of lymphocytes and consequent generation of Dr antigen-positive T cells. Because the presence of the compound did not affect the MLC-induced generation of suppressor activity, it is likely that P(Bu)2 selectively blocks the maturation of cytotoxic precursors. Surface-marker analysis with OKT monoclonal antibodies revealed that the effects on lymphocyte activation were associated with a decrease in OKT3 and OKT4 reactivity and an increase in the percentage of OKT8-positive cells. The decrease in OKT4 reactivity was not due to selective loss of this lymphocyte subpopulation, because P(Bu)2 was equally mitogenic for the purified OKT4- and OKT8-positive subsets. The results suggest that the effect of P(Bu)2 on cell differentiation and its ability to modulate the expression of functional markers in lymphocyte subsets may interfere with T-T cell cooperation that controls the functional maturation of cytotoxic precursors.

Antigens, Surface↗
PubMed1984

T lymphocyte culture established by repeated stimulation with the autologous lymphoblastoid line. MHC class II restricted interactions with B blasts.

An OKT3+T4+T8-DR+ lymphocyte line was developed from an Epstein-Barr virus (EBV) seropositive individual by repeated stimulation in vitro with autologous EBV-infected B cells. The T cell population designated E-44 was carried for eight months in the presence of Interleukin-2 and was repeatedly tested for cytotoxicity, proliferation and lymphokine production in response to the autologous and a panel of allogenic B cells. The E-44 cells lysed the autologous lymphoblastoid cell lines (LCL) and allogenic B cell lines sharing the DR6.1 major histocompatibility complex antigen with the lymphocyte donors. The EBV genome-negative lymphoma line BJAB and its two, infected in vitro, EBV-positive sublines were lysed with similar efficiencies. Autologous Staphylococcus aureus protein A (Prot-A) induced B, but not Phytohaemagglutinin (PHA)-induced T blasts were also lysed. It is likely that E-44 recognized an antigenic component derived from the fetal calf serum in association with class II determinants expressed on the B cells. Preincubation of E-44 cells with saturating amounts of OKT3 and Leu3a monoclonal antibodies abrogated the lytic effect on the autologous LCL. Cold target competition experiments demonstrated that, within, the population, the same cells reacted with the autologous Prot-A-induced blasts, the EBV-transformed LCL, and also with Daudi (an EBV genome-positive BL line). Although Daudi was the target which was lysed with the greatest efficiency, the avidity of interaction was highest with the autologous LCL because these cells competed best. Among the cells that were sensitive for the lytic effect, only the autologous LCL and Prot-A-induced B blasts triggered release of detectable amounts of Interleukin-2 and induced proliferation of the culture. The results suggest that the affinity of interaction with the target may be decisive for the triggering of the various T cell functions.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Characterization of the phorbol 12,13-dibutyrate (P(Bu)2) induced binding between human lymphocytes.

The mechanisms, cell surface structures, and cell types involved in the phorbol 12,13-dibutyrate (P(Bu)2)-induced binding between human lymphocytes were studied. Induction of cell aggregation by 20 min treatment with P(Bu)2 required Ca2+, an intact membrane, functional microfilaments, and the possible participation of an esterase or, less likely, a protease. Trypsin-sensitive cell surface structures were needed and neuraminidase (NANase) treatment slightly increased the intercellular binding. Retinoic acid, an anti-tumor promoting agent, was inhibitory. Calmodulin-dependent processes, microtubules, phospholipid methylation, intracellular levels of cyclic adenosine monophosphate, and cellular secretion did not seem to be involved. Cell conjugation between 24 hr P(Bu)2-treated and untreated cells required participation of trypsin-sensitive cell surface structures in each of the interacting cells and NANase treatment of one partner slightly increased the intercellular binding. Thymocytes, T cells, mature B and Epstein-Barr virus-transformed B cells aggregated while pre-B, early B, and intermediate B lymphocytes derived from representative malignancies did not. The lack of aggregation was not due to the absence of phorbol ester receptors. It is concluded that the P(Bu2)-induced intercellular binding is mediated by cell surface proteins, depends on certain enzymatic activities and metabolic events and involves certain cell types.

Amino Acids↗
PubMed1983

Comparison of highly NK active human lymphocyte subsets separated by various procedures involving E, EA rosetting, density gradients and adherence to immune complexes.

Lymphocyte subsets from human blood obtained by different procedures were analyzed for cytotoxic potential and phenotypic characteristics. Nylon wool column passed lymphocytes were fractionated on the basis of: (1) E and Fc gamma receptor expression, (2) cell density and Fc gamma receptor expression, (3) Fc gamma receptor expression. The cytotoxic subsets obtained by separation on the basis of E and EA rosetting differed in their phenotypic composition from those separated on the basis of density or on immune complex monolayers. The E- Fc gamma- population contained few LGL and OKM1 positive cells. The E- Fc gamma+ population was made up almost entirely of LGL and OKM1 positive cells. The low density population was highly enriched in LGLs; among these the Fc gamma- cells were OKT3 positive. In contrast to the E- population the low dense Fc gamma+ cells were mainly LGLs and were OKM1 positive. Fc gamma+ subsets had less killer activity against Daudi cells. The choice of procedure for obtaining a strongly cytotoxic population depends on the needs of particular experiments. Separation on the basis of E rosetting gave lower cell (62%) and cytotoxic (43%) recovery and required about twice the amount of blood and twice the time, as compared with the other 2 procedures. The cell fractions obtained this way allowed characterization of several phenotypically different active populations and showed a difference in cytotoxic potential against K562 and Daudi cells. Density fractionation isolated a highly cytotoxic subset with LGL morphology but this population was still heterogeneous phenotypically. With regard to enrichment of NK activity, the immune complex monolayer attachment method was the most efficient for total cell recovery and for the time taken to perform it.

Antigen-Antibody Complex↗
PubMed1983

Expression of Helix pomatia (HP) haemagglutinin receptors on cytolytic lymphocytes activated in mixed cultures.

The expression of receptors for Helix pomatia (HP) haemagglutinin, a T cell marker, was assayed on human lymphocytes cultivated with K562 or allogeneic lymphocytes. The receptor was detected on the cells after neuraminidase treatment by reactivity with FITC conjugated HP. By affinity chromatography the lymphocyte populations were separated into 3 subsets: (1) a subset which did not attach to the lectin column; (2) and (3) two subsets attaching with different avidities, and therefore eluting with different concentrations of the lectin-binding sugar hapten. The subsets were characterized for T cell markers, HP and E receptors, the B cell marker SIg and also for Fc receptors, and were tested for lytic potential against K562 and allogeneic blasts. A high proportion of HP receptor positive T blasts did not attach to the lectin column, and thus had low avidity HP receptors, confirming that activation of T lymphocytes is accompanied by decreased expression of T markers. The passed fraction which was enriched in blasts had the strongest cytotoxic function, while the fraction rich in cells with high avidity HP receptors and containing mainly small cells, had weak activity. This was true for both the anti-K562 and allospecific activities. Thus the phenotypic characteristics of the cells exerting the two types of lytic function were similar. The distribution of the lytic potential in the three subsets correlated with the presence of E and EA receptor positive blasts.

Cells, Cultured↗
PubMed1983

Immune interferon (IFN-gamma) production in autologous mixed cultures.

T cells were exposed in vitro to autologous B cells or monocytes. Tested on the seventh day, the cultured lymphocytes lysed K562, Daudi, autologous, and allogeneic phytohemagglutinin (PHA) blasts. Autologous B blasts were not affected. The supernatants contained gamma interferon (IFN-gamma). The quantity of IFN did not correlate with the strength of the proliferative response nor with the strength of the cytotoxic potential.

Cell Division↗
PubMed1983

The role of humoral immunity and the contribution of the F1 anti-parental effect in the rejection of a Moloney leukemia virus-induced lymphoma graft.

Antibody and rejection responses against the Moloney leukemia virus-induced YAC lymphoma of A strain origin were found to be weak in A but high in (A X C57Bl)F1 hybrids. (A X C57Bl) X A backcross mice typed for expression of H-2 antigens were investigated for these responses in order to ascertain the importance of the H-2 phenotype of the host and the development of antibodies for rejection of the tumor cells. With an LD50 challenge inoculum in immunized backcross mice, the presence of anti-YAC antibodies appeared to be important for protection against the outgrowth of the tumor, particularly in the H-2a mice. None of them survived, unless antibody-positive. On the other hand, a proportion of the H-2 heterozygous mice rejected the tumor in the absence of antibodies. In the antibody-positive group a higher number of H-2 heterozygous mice survived than of H-2 homozygous mice. The results showed that both humoral and cellular responses are important for the rejection of an antigenic lymphoma and indicate the contribution of an F1 anti-parental component in the latter.

Animals↗