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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 361 records · Page 20Linked to original sources
PubMed1984

Lysis of tumor biopsy cells by blood lymphocyte subsets of various densities. Autologous and allogeneic studies.

Blood lymphocyte subsets of various densities from 14 healthy donors and 25 patients with solid tumors were used in tests for cytotoxicity against allogeneic or autologous tumor cells. The allogeneic combinations comprised 36 tests on 28 tumors. In these the unmanipulated total lymphocyte population was cytotoxic in one experiment. In tests with density-separated subsets, 16 experiments were positive. The lytic effect resided in the light subsets. Auto-tumor lysis was detected in 7 of 25 cases, when the total lymphocyte population was used. Eleven additional tests showed cytotoxicity with the separated subsets. The autologous tumor cells were damaged by the light lymphocytes of 15 patients. Of these patients, 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. Pretreatment of the effectors with Hu-IFN-alpha enhanced or induced cytotoxicity in the light lymphocytes, against both allogeneic and autologous tumors, while the dense subset was rarely potentiated. The autologous system may represent an immune situation and therefore it is not unexpected that the active cells should have different phenotypic characteristics from those of the operationally natural killer system.

Biopsy↗
PubMed1984

Evidence for ACTH-unrelated mechanisms in the regulation of cortisol secretion in man.

In an attempt to elucidate the significance of ACTH independent mechanisms in the regulation of cortisol secretion in man, the dynamics of plasma ACTH and cortisol levels were studied in response to different stimuli. The cortisol response to small amounts of exogenous ACTH and to insulin induced hypoglycemia was preceded by an increase in ACTH levels appropriate to explain the increase in cortisol. In contrast, after administration of methamphetamine, there was an increase in cortisol levels in the absence of any changes in ACTH concentrations. Apparently, the methamphetamine induced cortisol secretion was not mediated by radioimmunoassayable ACTH. A diurnal rhythm was observed for the responses to hypoglycemia and to methamphetamine with larger cortisol responses in the evening as compared to the forenoon. These changes were not accompanied by parallel changes in the ACTH responses. From these differences, additional evidence is provided for the importance of ACTH independent mechanisms in the regulation of cortisol secretion.

Adrenal Cortex↗
PubMed1984

Carbamazepine and haloperidol v placebo and haloperidol in excited psychoses. A controlled study.

Carbamazepine has recently been reported to have therapeutic potential in mania. We studied carbamazepine plus haloperidol v placebo plus haloperidol in excited psychoses in a controlled double-blind design. Twenty-three patients completed five weeks of carbamazepine-haloperidol therapy, and 20 patients placebo-haloperidol therapy. Brief Psychiatric Rating Scale ratings showed superior improvement in the group receiving carbamazepine plus haloperidol. This benefit was as apparent in excited schizophrenia as in mania. No unusual toxicity was observed because of the combination of haloperidol with carbamazepine.

Adult↗
PubMed1984

Purified mouse mammary tumor and lymphoid cells in immune assays.

Tumor and lymphoid cell components from primary mammary adenocarcinomas of C3H/He mice were isolated simultaneously by velocity gradients. Viable tumor cells were obtained in sufficient numbers to test their in vivo and in vitro growth. Isolated tumor cells grew in 97% of inoculated syngeneic animals. In six assays with different tumors the effects of tumor-associated lymphoid cells (TAL) on in vivo tumor growth varied, enhancing in three and delaying in two experiments. Isolated tumor cells from animals with enhancing TAL grew faster in nonirradiated mice, whereas tumor cells from animals with inhibitory TAL grew better in irradiated animals. Isolated tumor cells also proliferated in cell culture, where they averaged 35% primary plating efficiency. Separated tumor cells were used in short-term 51Cr-release assays with TAL, tumor-bearer lymph node and spleen effectors. Cytotoxicity was detected in only five of 25 assays. In no case was there killing by lymphocyte populations from normal animals. In the present report we describe a technique for the isolation of viable tumor and lymphoid cells from murine adenocarcinomas that allows study of interactions between these populations from the original tumor-bearing host.

Animals↗
PubMed1984

Effects of isolated tumor lymphocytes alone and with adherent cells.

The effect on the growth of gradient-isolated mouse mammary tumor cells of different populations of lymphoid cells were evaluated in microcytotoxicity assays. Variable effects were obtained with tumor-bearer lymph node and spleen cells: in some experiments growth stimulation occurred, whereas in others inhibition was observed. Mixed effector populations gave more regular results: adherent spleen cells added to lymph node or spleen lymphocytes inhibited tumor cell growth in six of nine experiments; inhibition occurred when either of the effector populations in the mixture was derived from the tumor-bearing mouse. Tumor-associated lymphoid cells (TAL) stimulated growth of the tumor cells in five of seven experiments. However, TAL inhibited tumor growth when combined with adherent spleen cells from tumor-bearing animals. In contrast with the peripheral lymphoid cells, admixture of control adherent cells from normal animals with TAL did not inhibit growth. No natural killer effect was seen in these growth inhibition assays. These data indicate that lymphoid populations capable of inhibiting tumor cell growth can be found in tumor-bearing animals, but such combination of active cells are not present in the tumor site.

Adenocarcinoma↗
PubMed1984

Effect of cyclo(Leu-Gly) on reserpine-induced hypomotility and increases in cortical beta-adrenergic receptors.

Previous studies have indicated that the endogenous peptide, melanotropin release inhibiting factor (MIF) and its analog cyclo(Leu-Gly) ( CLG ) facilitate dopamine (DA) receptor agonist binding and inhibit DA receptor supersensitivity induced by neuroleptics and opiates. The effect of CLG was tested on beta-adrenergic hypersensitivity induced by reserpine to ascertain whether CLG has effects on other neuronal systems besides DA. Administration of reserpine to rats induced hypomotility and enhanced binding of [3H]dihydroalprenolol (DHA) to cortical membranes. Concurrent administration of CLG blocked both the hypomotility and the enhanced [3H]DHA binding to cortical membranes. Lithium has also been shown to prevent reserpine induced hypomotility and increased cortical [3H]DHA binding. These studies suggest that CLG may be producing its effect either like lithium or by an amphetamine like action. If CLG can be shown to have lithium like activity, it could prove to be useful in the treatment of mania.

Animals↗
PubMed1984

Complement-dependent cellular cytotoxicity due to alternative pathway C3 activation by the target cell membrane.

The cytotoxic activity of human blood lymphocytes toward Raji cells was strongly elevated when human serum (HS) was included in the cytotoxicity assay. This phenomenon also occurred when the effector cells were activated by interferon (IFN). Hypogammaglobulinemic serum (HyS) and heat-inactivated serum could also augment cytotoxicity, but C3-depleted serum was inefficient. IFN treatment of Raji cells decreased their sensitivity to lysis and this effect was counteracted by addition of HS to the system. It is likely that C3 activation by, and deposition on, Raji cells when used as targets for cytotoxicity facilitate their recognition and lysis by lymphocytes. These events may represent one mechanism operating in the natural killing phenomenon.

Complement Activation↗
PubMed1984

EGNA-specific LIF production of human lymphocyte subsets.

Using the indirect leukocyte migration inhibition technique T cells have been identified as being responsible for Epstein-Barr virus nuclear antigen-induced specific leukocyte migration inhibitory factor production. The response was dependent on the presence of macrophages or their product, T-lymphocyte activating factor.

Antigens, Viral↗
PubMed1984

Production of leukocyte migration inhibitory factor (LIF) in human lymphocyte subsets exposed to polyclonal activators.

Lymphocyte subsets separated on the basis of nylon-wool adherence and E and EA rosetting, and characterized for the presence of esterase-positive phagocytic cells were investigated for production of leukocyte migration inhibitory factor (LIF) in response to polyclonal T- and B-cell activators, PHA, ConA, PWM, and Epstein-Barr virus (EBV). In the nylon-passed population only the high avidity E+EA+ cells responded to ConA, PHA-induced LIF production in all E-rosetting subsets. The nylon-adherent E+ subset, which contains activated T cells, produced LIF spontaneously. B cells produced LIF when exposed to PWM or uv-inactivated EBV. In accordance with the known T-cell dependence of PWM activation, LIF was detected only in supernatants of reconstituted populations containing both B and T cells. In contrast, uv-inactivated EBV, devoid of transforming potential, elicited LIF production in the pure B-cell population. LIF production in response to polyclonal activators seemed to be independent of accessory cells since reconstitution with autologous macrophages or semipurified monokine, high-molecular-weight Interleukin 1 (IL-1), did not alter the results.

B-Lymphocytes↗
PubMed1984

Natural killer cell sensitivity of human lymphoid lines of B-cell origin does not correlate with tumorigenicity or with the expression of certain differentiation markers.

Human B-cell lines derived from normal donors (LCL) or from Burkitt lymphomas (BL) were compared for their sensitivity to natural (NK) and interferon (IFN)-activated (IAK) cytotoxicity, mediated by effector cells from normal human blood. In four cases, a BL and an LCL line were derived from the same donor and had been kept in culture for the same period of time. The BL series included both Epstein-Barr virus (EBV)-carrying and EBV-negative lymphoma lines. The latter were compared with their own EBV-converted, Epstein-Barr nuclear antigen (EBNA)- and EBV-DNA-positive sublines, established by in vitro infection with two different viral substrains. LCL and BL lines from the same donor were lysed with equal efficiency by both NK and IAK effectors. There was no relationship between the NK sensitivity and the nude mouse tumorigenicity of different EBV-converted Ramos sublines, or the expression of differentiation markers such as insulin receptor, surface IgD, and the B2 surface antigen. Moreover, EBV-converted sublines of BJAB differed in their NK sensitivity, in spite of closely similar expression of these markers. NK-sensitive Ramos and BJAB sublines induced a stronger proliferative response upon confrontation with allogeneic lymphocytes than their NK-resistant counterparts. This suggests that the target cell may play an active role in triggering the lytic interaction. There was no correlation between this property and any of the other parameters studied.

B-Lymphocytes↗
PubMed1984

The Lyt phenotype of the T cells in an antitumor adoptive transfer differs for "parent to F1" and "parent to parent" combinations.

The T-cell subset mediating tumor graft neutralization was characterized in a methylcholanthrene (MC) tumor system. Lyt 1+ cells were critical for the successful prevention of outgrowth of the tumor cells in graft neutralization assays with irradiated recipients. Elimination of Lyt 1+ cells abolished the outgrowth inhibitory effect exerted by T-cell-enriched populations derived from syngeneic or semisyngeneic mice immunized with the H-2-carrying MC-induced M-A tumor. In accordance, lymphocyte populations containing 98% Lyt 1+ cells derived from M-A-immune mice, mediated a complete transplantation immunity against this tumor. When the immune T cells admixed to the tumor inoculum were syngeneic to the recipient (i.e., A-derived cells were transferred to A recipients, or F1 to F1), elimination of the Lyt2+ cells did not influence the potential to inhibit tumor outgrowth. The presence of Lyt 1+2- cells were thus necessary, and sufficient, in the syngenic combination. A reduction of the graft-inhibiting potential occurred after elimination of Lyt 2+ cells from the A-derived M-A immune T-cell population when the recipients were semisyngeneic (i.e., (A/Sn X A.SW)F1, (A/Sn X CBA)F1, or (A/Sn X C57B1/6)F1). Consequently, only in the semisyngeneic, but not in the syngeneic combinations, was the transfer of Lyt 2+ cells necessary for optimal graft inhibition. It can be concluded that the genotypic relation between the donor and the recipient influences the prerequisites of the tumor cell neutralization.

Animals↗
PubMed1984

Contribution of activated C3 to lymphocyte-mediated target lysis: complement-dependent cellular cytotoxicity.

Lysis of Raji cells by human lymphocytes was found to be enhanced if human serum was added to the assay. This was not due to the contribution of antibodies because hypogammaglobulinemic serum also augmented cytotoxicity. The results suggest that the mechanism of the enhancement was due to activation of C3 by the Raji cells. We assume that the cleavage products are deposited on cell surfaces in such a way that they contribute to contact between effector and target. Previous reports in two antibody-dependent cellular cytotoxicity systems provided other examples for the existence of this phenomenon.

Blood↗
PubMed1984

Ligand inhibition studies on the role of Fc receptors in antibody-dependent cell-mediated cytotoxicity.

Subjection of human peripheral blood lymphocytes to a temp shift from 4 to 37 degrees C resulted in a shedding of Fc receptors (termed FcRI) from 40-50% of FcR-positive cells followed by their re-expression within 4 hr; a phenomenon which had no effect on the cells' antibody-dependent killing capacity. Removal of lymphocytes having an immobile form of the Fc receptor resistant to the effects of the temp shift (termed FcRII), or removal of lymphocytes bearing both FcRI and FcRII, resulted in a similar amount of reduction in ADCC activity. This was attributed, therefore, to the loss of FcRII-positive cells. The influence of isolated (shedded) FcRI and Clq on ADCC activity was investigated. Soluble FcRI was shown to inhibit ADCC mediated through the immobile Fc receptors (FcRII), despite its lack of an ability to block EA rosette formation through these receptors. Clq also had a dose-dependent inhibitory effect on ADCC. These observations are consistent with earlier findings that FcRII possesses two active binding sites; and suggest that a prerequisite for killing in ADCC is the interaction of these with the C gamma 2 and C gamma 3 domains. The ability of synthetic peptides representative of human gamma 1-chain sequences to inhibit ADCC was determined, in an attempt to locate those sites within the IgG antibody Fc region involved in interaction with two FcR binding sites. Preliminary evidence was obtained to suggest that one of these is situated within the C gamma 2 domain, in the region of residues 274 (Lys)-294 (Glu).

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Limb allografts in rats immunosuppressed with cyclosporin A.

The role of cyclosporin A in transplantation of composite tissue for potential reconstructive purposes is examined in the rat hind limb transplant model. Two inbred rat strains were utilized. Brown ACI rat hind limbs were transferred to the dorsum of white Lewis rats with microvascular anastomoses. Twenty transplants were divided into four groups for postoperative immunosuppression: control, no cyclosporin; 7 days of cyclosporin; 21 days of cyclosporin; and continuous cyclosporin from 44-113 days. Hemagglutination and antibody titers were measured. Clinical evaluation and histologic examination at sacrifice were performed and rejection graded. Cyclosporin A has been successful in suppressing rejection in composite allograft transplant across defined major histocompatability barriers. Rats treated with cyclosporin A for a short period of time showed signs of rejection after discontinuation of therapy. Five animals treated continuously on cyclosporin A for up to 113 days showed no sign of rejection clinically, histologically, or immunologically.

Animals↗
PubMed1984

Effect of plasma proteins on the sieving spectra of hemofilters.

qoffxture of neutral maltodextrins with a continuous molecular weight distribution from 340 to 120,000 daltons has been used alone or in the presence of plasma to determine solute rejection by four hemofilters and the effect of plasma on such rejection. High pressure liquid chromatographic analyses were utilized to establish concentration ratios of feed and filtrate solutions over a wide molecular weight range. At equal transmembrane velocities, the boundary layer-corrected rejection of each hemofilter was determined as a function of molecular weight. The presence of plasma increased rejection by the Amicon Diafilter 30, the Hospal RP-6, and the Gambro FH202 hemofilters , but the Fresenius D-6 was virtually unaffected.

Blood↗