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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 325 records · Page 18Linked to original sources
PubMed1986

Differential effect of cyclosporin-A on the mixed-lymphocyte culture-induced proliferative and cytotoxic responses of T lymphocytes with different cell densities.

We have analyzed the effect of cyclosporin-A (CsA) on the proliferative and cytotoxic responses induced by mixed-lymphocyte cultures (MLC-s) on low and high density T lymphocytes. Allogeneic stimulation had a different impact on the two subsets. Proliferative and cytotoxic responses were inversely correlated; i.e., high density cells proliferated but exerted low levels of cytotoxicity while the lytic activity of the low density subset was stronger and the proliferation was weak. CsA impaired the proliferative and cytotoxic responses of the high density T lymphocytes but influenced less markedly the response of the low density cells. In both subsets CsA inhibited the MLC-induced interleukin 2 (IL-2) production. The generation of specific cytotoxicity was markedly suppressed by CsA, whereas the generation of anomalous activity was less affected. Addition of exogenous IL-2 to the CsA-containing cultures fully restored the proliferation and the generation of nonspecific cytotoxicity. In contrast, addition of interferon gamma (IFN-gamma) restored neither of these responses. However, for complete restoration of the stimulation-specific cytotoxicity, addition of both lymphokines was required. Taken together these results suggest that the CsA-induced suppression of the lymphokine production has different consequences in the low and high density subsets; the expression of anomalous and specific cytotoxicities require different signals; CsA interferes with several steps in the T-cell activation.

Cyclosporins↗
PubMed1986

Cytotoxic factor produced by human blood lymphocytes of low density upon exposure to autologous B cells.

The mechanism of cytolysis by natural killer cells has been shown to involve a soluble lytic factor - the natural killer cytotoxic factor (NKCF). We have investigated the generation of NKCF on exposure of subpopulations of human blood lymphocytes to autologous B lymphocytes and EBV infected B lymphocytes (BEBV), and the sensitivity of these lymphocytes to the cytotoxic factor. We present evidence that the low density lymphocytes representing majority of NK cells, can be stimulated to produce NKCF by the autologous B/BEBV cells. Allogeneic B/BEBV cells did not induce NKCF production. Recognition of the autologous B/BEBV cells did not seem to involve Dr antigens. Although the autologous B/BEBV cells could stimulate NKCF production, the NKCF was lytic only to K562 targets. The autologous B/BEBV cells could neither be lysed by the factor produced, nor could these cells absorb the factor.

Antibodies, Monoclonal↗
PubMed1986

Human T-cell leukemia virus-associated nuclear antigen (HTLV-NA).

Replication-competent retroviruses are not known to encode or induce nuclear antigens that are immunogenic in their natural hosts. We describe here the detection of a human T-lymphotropic virus (type I and type II) associated nuclear antigen (HTLV-NA) by an anticomplement immunofluorescence assay. Antibody to HTLV-NA is detected in 18 of 68 (26%) HTLV-I seropositives.

Antigens, Viral↗
PubMed1986

Differentiation-dependent sensitivity of human B-cell-derived lines to major histocompatibility complex-restricted T-cell cytotoxicity.

Sets of Burkitt lymphoma lines and Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) derived from the same individuals were compared for sensitivity to cytotoxic T-lymphocyte (CTL) clones. Major histocompatibility complex class I antigen-restricted CTL clones were generated by stimulating the lymphocytes of an EBV-seropositive individual with the autologous LCL. One clone (BK-20) lysed the autologous and allogeneic HLA-A11-expressing LCLs but not mitogen-induced B lymphoblasts. Thus the clone was selectively cytotoxic for LCLs. Allospecific CTL clones directed against the HLA-A11 antigen were generated from an EBV-seronegative individual. One clone (WP-36) was selectively cytotoxic for the appropriate allospecific LCL, whereas another clone (WP-21) lysed also T and B lymphoblasts. None of the four Burkitt lymphoma lines established in parallel with the CTL-sensitive LCLs were lysed. Two of the Burkitt lymphoma lines were EBV-negative, and EBV-positive sublines were derived from these by in vitro infection. One but not the other of the two convertants became sensitive to all three types of CTL clones. The CTL-sensitive converted line had also acquired some LCL characteristics: increased cell size, aggregation, and a shift in several of the B-cell-specific surface markers. The CTL-resistant convertant expressed EBV antigens but showed no phenotypic change. These findings suggest that the cellular phenotype plays a decisive role in the sensitivity of B-cell-derived lines to the lytic effect of LCL-selective autologous and allogeneic CTLs.

Antigens, Surface↗
PubMed1986

Effect of intraperitoneal insulin on solute kinetics in CAPD: insulin kinetics in CAPD.

The authors evaluated the transport kinetics of insulin and inulin administered intraperitoneally to six diabetic patients undergoing continuous ambulatory peritoneal dialysis. The mass transfer coefficients (MTC) calculated from dialysate to blood for 1.5% and 4.25% dextrose dialysate were (ml/min): insulin 2.9 +/- 0.9, 2.0 +/- 0.5; inulin 3.3 +/- 1.4; 2.9 +/- 1.7, respectively. The MTC for inulin calculated from blood to dialysate was 2.0 +/- 0.7 ml/min. Because insulin disappears from the peritoneal cavity at a rate similar to inulin, it suggests that insulin transport can be defined by diffusion. The derived MTC values for glucose were not altered by the addition of intraperitoneal insulin. The derived MTCs for eight diabetic to thirteen nondiabetic patients were compared. The MTC derived for urea was less among the diabetics (16.6 +/- 2.2 vs. 24.6 +/- 2.6 p less than 0.05), but there were no differences for creatinine, uric acid, glucose, inulin, and protein. The derived values were found to be normally distributed and patients in the upper quartile for one solute were generally in the upper quartile for other solutes.

Ascitic Fluid↗
PubMed1986

Calcium carbonate precipitation in bicarbonate hemodialysis.

Calcium carbonate has been observed to precipitate in the fluid pathway of dialysate delivery systems dispensing bicarbonate-containing dialysates. Such precipitation can occlude the fluid pathway, leading to system malfunction and increased maintenance requirements. We show that commercial supplies of sodium bicarbonate are contaminated by trace amounts of sodium carbonate. This contamination may result in immediate precipitation of calcium carbonate on formulation of the dialysate, since bicarbonate-containing dialysates, as formulated, are metastable with respect to calcium carbonate. Sparging of the bicarbonate-containing concentrate with carbon dioxide converts any carbonate to bicarbonate, thus avoiding the formation of precipitates on addition of calcium ions.

Bicarbonates↗
PubMed1986

Unstable bladder in children: functional evaluation by modified voiding cystourethrography.

A slightly modified technique for voiding cystourethrography was applied in 100 patients between 4 and 15 years of age and used to study uninhibited detrusor contractions in the so-called unstable bladder syndrome. Uninhibited detrusor contractions result in a slowing or cessation of the flow of contrast material into the bladder and a simultaneous minimal or marked opening of the bladder neck, with variable filling of the posterior urethra. Comparison of the radiologic findings with the results of urodynamic studies demonstrated an overall accuracy of 92%, sensitivity of 93%, and specificity of 90.7% for the radiologic technique.

Adolescent↗
PubMed1986

Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal.

Alprazolam treatment is effective for panic disorder, but its major disadvantages include possible dependence and withdrawal symptoms upon discontinuation. The authors report three cases in which carbamazepine, a clinically effective anticonvulsant without abuse potential, successfully attenuated alprazolam withdrawal symptoms.

Adult↗
PubMed1986

Effects of disinfectants in renal dialysis patients.

Patients receiving hemodialysis therapy risk exposure to both disinfectants and sterilants. Dialysis equipment is disinfected periodically with strong solutions of hypochlorite or formaldehyde. More recently, reuse of dialyzers has introduced the use of additional sterilants, such as hydrogen peroxide and peracetic acid. The use of these sterilants is recognized by the center staffs and the home patient as a potential risk, and residue tests are carried out for the presence of these sterilants at the ppm level. Gross hemolysis resulting from accidental hypochlorite infusion has led to cardiac arrest, probably as a result of hyperkalemia. Formaldehyde is commonly used in 4% solutions to sterilize the fluid paths of dialysis controllers and to sterilize dialyzers before reuse. It can react with red cell antigenic surfaces leading to the formation of anti-N antibodies. Such reactions probably do not occur with hypochlorite or chloramines. The major exposure risk is the low concentration of disinfectant found in municipal water used to prepare 450 L dialysate weekly. With thrice-weekly treatment schedules, the quality requirements for water used to make this solution must be met rigorously. Standards for water used in the preparation of dialysate have recently been proposed but not all patients are treated with dialysate meeting such standards. The introduction of sterilants via tap water is insidious and has led to more pervasive consequences. Both chlorine and chloramines, at concentrations found in potable water, are strong oxidants that cause extensive protein denaturation and hemolysis. Oxidation of the Fe2+ in hemoglobin to Fe3+ forms methemoglobin, which is incapable of carrying either O2 or CO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloramines↗
PubMed1986

Suppression of T-cell response in autologous mixed lymphocyte-tumor culture by large granular lymphocytes.

The role of large granular lymphocytes (LGL) in the autologous mixed lymphocyte-tumor culture (MLTC) was studied in cancer patients with malignant pleural effusions. When blood lymphocytes were cocultured in vitro with autologous tumor cells freshly isolated from carcinomatous pleural effusions, [3H]thymidine incorporation was weakly stimulated on day 6 in 6 of 30 samples. Removal of LGL from the responder population by treatment with the Leu-7 or Leu-11b monoclonal antibody plus complement (C') induced or augmented the proliferative response. LGL and small T-lymphocytes were isolated by discontinuous Percoll gradient centrifugation and tested separately for the proliferative response to autologous tumor. T-cells proliferated in 24 of 30 cases, while LGL showed no proliferation. Addition of LGL to autologous mixed T-cell-tumor cultures suppressed the proliferation of T-cells. LGL, however, did not inhibit T-cell proliferation induced by alloantigens and lectins. The suppressive activity of Percoll-purified LGL was not reduced by OKT3 plus C' treatment, but it was totally abrogated by Leu-11b plus C'. Supernatants produced by 24-hour culture of LGL with autologous tumor contained soluble factors that suppressed the autologous MLTC without killing the autologous tumor or T-blasts. The LGL-mediated suppression was not abolished by anti-interferon-alpha or anti-interferon-gamma antibody. Activation of T-cells in the autologous MLTC induced lytic potential restricted to autologous tumor. In the presence of LGL, T-cells failed to develop autotumor killing activity. Once autotumor killer T-cells were generated in autologous MLTC, their cytotoxicity was no longer inhibited by LGL. These results indicate that LGL from patients with carcinomatous pleural effusions suppress the capacity of autotumor-recognizing T-lymphocytes to proliferate and develop autotumor cytotoxicity in the autologous MLTC. This could explain why fresh T-cells have no cytolytic activity to autologous tumor.

Adenocarcinoma↗
PubMed1986

Conditioned tumorigenicity of activated oncogenes.

Virally transduced oncogenes (v-onc) have a restricted target cell spectrum. They transform only a small part of the cell types in which they are expressed. Temperature-sensitive (ts) mutant studies have shown that some of them may act by blocking specific steps of maturation. If the cell can bypass the block, e.g., by a temporary switch off of the temperature-sensitive transforming protein, reexpression of the oncogene product at the permissive temperature may be unable to restore the transformed phenotype. Consideration of these facts, together with evidence concerning the reversion of the transformed phenotype and the suppression of tumorigenicity in hybrids derived from the fusion of normal and malignant cells, leads to the concept of "conditioned tumorigenicity." It states that the transforming and/or tumorigenic effect of a given oncogene, activated by structural or by regulatory changes, is restricted to specific and often quite narrow differentiation or maturation windows within each susceptible lineage. A similar restriction seems to apply to oncogenes activated by chromosomal translocation. The regular juxtaposition of the c-myc gene to one of the three immunoglobulin loci in Burkitt's lymphoma, mouse plasmacytoma, and rat immunocytoma is a case in point. The myc-carrying chromosome can break at many different places, within, upstream, or downstream of the gene, but not within its coding exons. This suggests that the break occurs at random and the myc protein plays an essential role in the selective, i.e., tumorigenic process. If so, other oncogenes should be equally transposable to the "Ig hot spots" during the long series of cell divisions in the preneoplastic target cell population that characterizes the prehistory of both BL and MPC. In other human B-cell leukemias and lymphomas, other (e.g., 11;14 and 14;18) translocations have been found, confirming that this can actually occur, but only in histologically different neoplasms. The exclusive involvement of myc in BL and MPC must be relatable to the specific functional features of the precursor cells and to the normal role of the myc protein. Recent evidence indicates that the myc gene is regularly turned off before or at the time when the cell enters a pathway that is programmed to lead it towards a resting Go state. Clonally expanded B-cells are believed to turn into resting memory cells upon waning of the antigenic stimulus. The normal, nontranslocated myc allele is regularly switched off in both BL and MPC, indicating that the cell has already obeyed a program involving the down-regulation of myc.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Human peripheral blood mononuclear cells (PBM) cultured in serum-free medium. III. Morphological study of an in vitro microcytotoxicity model.

An in vitro tumor immunity model is suggested. Interactions between lymphocytes and macrophages in serum-free medium are being studied as well as the effect induced upon these interactions by the addition of heterologous and homologous tumor cells. In our model, the tumor cells seem to be approached by the lymphocytes before any contact with the macrophages and then presented to the latter. The macrophages may then acquire an "activated" structure and display cytotoxic properties. A pattern of in vitro cellular immunity is obtained. This description may serve as a model for further study and understanding of the process of tumor immunity. It is suggested that in contrast to generally accepted models of cellular immunology, lymphocytes can interact directly with antigen complexes and present them to macrophages. The latter would in turn be activated, become cytotoxic and produce or accumulate immune globulins. These cells seem to be an in vitro analog of the recently described tumor infiltrating lymphocytes (TIL) which reside in vivo within spontaneous tumors.

Cell Communication↗
PubMed1986

Common bile duct obstruction caused by hydatid daughter cysts--management by endoscopic retrograde sphincterotomy.

Four patients with cholestatic jaundice due to ruptured hydatid liver cyst into the biliary tract underwent endoscopic retrograde sphincterotomy with clearance of the bile ducts. Prompt relief of jaundice followed the produced and no complications occurred. After the procedure all patients received medical treatment (Mebendazole) for 3-4 months and were well at a mean follow-up of 8 months. We conclude that endoscopic retrograde sphincterotomy is a safe and effective treatment for cholestatic jaundice caused by hydatid daughter cysts obstructing the bile ducts. This method may serve as an alternative to surgery in selected, high risk, patients.

Adult↗
PubMed1985

Natural cytotoxicity of human blood monocytes and natural killer cells and their cytotoxic factors: discriminating effects of actinomycin D.

The effect of actinomycin D on target susceptibility to human blood natural killer (NK) cells and monocytes was analysed in direct cell-mediated and their cytotoxic factor-mediated cytotoxicity assays. Treatment of K562 cells with actinomycin D reduced their susceptibility to lysis by non-adherent lymphocytes and Percoll-purified large granular lymphocytes (LGL) in a 4-hr 51Cr-release assay, without affecting their sensitivity to monocytes purified by adherence to autologous serum-coated plastic surfaces. The drug treatment caused no shift in the kinetics of cytotoxicity. In the target binding assay LGL formed fewer conjugates with actinomycin-D-treated K562 cells than with untreated ones, while the binding of monocytes to targets was not reduced by the drug treatment of K562 cells. The cold target competition assay revealed that actinomycin-D-treated cold K562 cells showed less successful inhibition than untreated cold K562 cells. Lymphocytes and monocytes could be induced to release soluble cytotoxic factors, termed natural killer cytotoxic factors (NKCF) and monocyte cytotoxic factors (MCF), respectively, when co-cultured with K562 cells. Both cytotoxic factors lysed NK-sensitive target cells in a 48-hr assay. Actinomycin-D-treated K562 cells reduced or abolished the ability to stimulate the release of NKCF from lymphocytes, whereas they induced MCF secretion from monocytes as effectively as untreated ones. On the other hand, actinomycin D treatment of K562 cells enhanced their susceptibility to NKCF and MCF. This actinomycin-D-induced augmentation of target sensitivity to the cytotoxic factors was restricted to NK-sensitive target cells (K562 and Molt-4). NK-resistant target cells (Raji, YAC-I, EL4 and T blasts) were not lysed by NKCF and MCF even after they were treated with actinomycin D. The capacity of K562 cells to bind NKCF and MCF was not altered by actinomycin D. Treatment of the adherent cell population with OKMI or Leu-MI plus complement abrogated both cell-mediated cytotoxicity and MCF production, while Leu-IIb plus complement was ineffective. These results suggest that the effect of actinomycin-D treatment can be used to distinguish the two distinct types of blood mononuclear cells with natural cytotoxicity, NK cells and monocytes, and that each effector type recognizes different plasma membrane moieties of NK target cells, although the cytotoxic factors released from each effector cell similarly bind to and lyse the target cells.

Animals↗