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Biomedical subjects

E Klein

Publications and source records attributed to E Klein.

At least 397 records · Page 22Linked to original sources
PubMed1983

Correlation between lymphocyte-mediated auto-tumor reactivities and clinical course. I. Evaluation of 46 patients with sarcoma.

T-cell-enriched blood lymphocyte populations from 24 osteosarcoma and 22 soft-tissue sarcoma patients were assayed at the time of surgery for proliferative response to, and/or cytotoxic potential against autologous tumor cells. Tumor-free period and survival of the patients were correlated with the results obtained in the in vitro tests. The observation time was between 18 and 118 months (mean 62) for the osteosarcoma patients and between 18 and 72 (mean 42) for the patients with soft-tissue sarcoma. In both groups tumor-free period and survival were longer for those individuals who had auto-tumor reactivity. In the non-reactive group, all patients died within 3 years. Almost all patients had cytotoxicity against K562.

Adolescent↗
PubMed1983

Correlation between lymphocyte-mediated auto-tumor reactivities and the clinical course. II. Evaluation of 69 patients with lung carcinoma.

T-cell-enriched lymphocyte populations of 69 lung carcinoma (44 squamous cell, 23 adeno-, and two large cell carcinoma) patients were investigated at the time of surgery for proliferative response to, and/or cytotoxic potential against, freshly separated autologous tumor cells. Tumor-free period and survival time of the patients were correlated with the reactivity obtained in the in vitro tests. The observation time varied between 20 and 78 months (mean 52). Tumor-free period and survival time were longer and survival rate higher in the group with lymphocyte reactivity toward their tumors. In the non-reactive group, all patients but one died within 3 years. Almost all patients had cytotoxic lymphocytes against K562, the three who did not belonging to the category with short survival time.

Adenocarcinoma↗
PubMed1983

Genetic studies on natural resistance to Moloney lymphoma (YAC) isografts. I. Introduction of a non-H-2-linked resistance gene on strain A/Sn background.

YAC is a Moloney-virus-induced lymphoma of strain A/Sn origin that is highly sensitive to natural killing (NK) in vitro and NK-mediated hybrid resistance in vivo. Previous studies have shown that hybrid resistance is under polygenic control that includes both H-2-linked and non-H-2-linked factors. For further analysis on the genetics and immunology of hybrid resistance, we are at present developing congenic resistant lines on an A/Sn strain background. Following an outcross to a strain that conveys strong hybrid resistance on the F1 offspring, the mice are challenged with small viable inocula of YAC. Survivors are backcrossed to A/Sn. This is followed by repeated YAC challenge and backcrossing. We now report the successful establishment of a first resistant strain, designated A.LRA. It is relatively resistant to small inocula of YAC cells due to a single, non-H-2-linked dominant gene introduced from the C57L strain.

Animals↗
PubMed1983

Phorbol 12,13-dibutyrate (P(Bu)2)-treated human blood mononuclear cells bind to each other.

Treatment of human blood mononuclear cells with nanomolar concentrations of phorbol 12,13-dibutyrate (P(Bu)2) induced their aggregation. The phenomenon was seen within a few minutes and reached its maximum manifestation after 20 min. At this time, 20-30% of unfractionated and nylon wool-passed mononuclear leukocytes were in the aggregates. The influence of pretreatment with 2-deoxyglucose, NaN3, EDTA, cyclohexamide, or incubation at 4 degrees C on the phenomenon indicated that it is energy and temperature dependent, requires the presence of extracellular divalent cations, and is independent of protein synthesis. Nonaggregating 2-deoxyglucose-and NaN3-pretreated cells could still bind [3H]P(Bu)2 which rules out the possibility that the phorbol ester molecule acts as a bridge between the aggregated cells. Seventeen percent of the P(Bu)2-treated T-cell population bound untreated autologous and allogeneic cells. The binding property has a certain species specificity because only 4% of the cells interacted with mouse lymphocytes. At the ultrastructural level, the intercellular binding showed broad areas of surface contact (both between lymphocytes and lymphocyte-monocyte) and "trapping" by surface processes was not seen. Aggregated cells did not show cytopathogenic changes.

Animals↗
PubMed1983

Large granular lymphocytes inhibit the in vitro growth of autologous Epstein-Barr virus-infected B cells.

The effect of lymphocyte subsets, separated on the basis of cell density, on Epstein-Barr virus (EBV)-induced B-cell proliferation was studied. The experiments were performed with lymphocytes of seropositive individuals. After 2 weeks of culture, the growth of B cells was inhibited by the T subset, which is also active in natural killer assays, i.e., the low-buoyant density lymphocyte fractions. However, if the cultures were observed for a longer time, the initial growth regressed even in cultures containing the subsets which did not have natural killing (NK) function, i.e., those with high cell density. The initial cell concentration at which the cultures were seeded determined the outcome of the experiments and the demonstration of inhibitory effects. An important difference was seen between the subsets with regard to radiosensitivity. The prompt inhibitory effect of the NK-positive subset remained after irradiation, while the function of the NK-negative one was abrogated. In the presence of the irradiated T-enriched total population, infected B cells (BEBV) grew. Consequently, the radiation-resistant effector compartment, represented by the low-density cells, was not sufficient to counteract the establishment of BEBV lines. They contributed, nevertheless, to the regression because the kinetics of B-cell growth were different in cultures containing separated high-density cells or the total population. In the former, growth continued for a longer time and complete regression occurred only in the cultures initiated with high cell concentrations. The experiments showed that two types of cells contribute to the regression of BEBV growth in cultures initiated with lymphocytes of seropositive donors. One acts promptly and is independent of cell proliferation; another is activated for proliferation by encounter with B blasts.

Cell Division↗
PubMed1983

Lymphocyte-mediated lysis of autologous and allogeneic B-cell lines in man.

The lytic potential of human blood lymphocytes was assayed against autologous and allogeneic EBV-transformed B-cell lines (LCL). The effects--if present--were very weak. Short-term interferon (IFN) treatment of the lymphocytes induced cytotoxic potential which could be manifested against autologous and allogeneic LCL. The sensitivity of the targets increased after superinfection with the P3HR-1 strain of EBV. Thus the strongest lytic effects were obtained with IFN-treated lymphocytes acting on EBV superinfected targets. Individuals with and without previous EBV encounter reacted against autologous LCL, indicating that the lysis did not represent an EBV-specific cellular memory. No evidence for alloantigen recognition emerged from the tests.

B-Lymphocytes↗
PubMed1983

Clinical implications of research on the mechanism of action of lithium.

Lithium is a unique drug in its clinical profile in psychiatry. Lithium has numerous biochemical effects, but none has yet been proven to be its mode of therapeutic action. Inhibition of noradrenaline-sensitive adenylate cyclase is reviewed as the only biochemical effect of lithium shown to occur in both animals and man at therapeutic lithium concentrations. A tetracycline antibiotic, demeclocycline, also blocks noradrenaline-sensitive adenylate cyclase. A clinical trial of demeclocycline in mania would provide a test of the adenylate cyclase theory of lithium action.

Adenylyl Cyclase Inhibitors↗
PubMed1983

The tumor promoter phorbol-12,13-dibutyrate [P(Bu)2] stimulates cytotoxic activity of human blood lymphocytes.

The tumor promoters 12-13-phorbol-dibutyrate, P(Bu)2, and 12-O-tetradecanoylphorbol-13-acetate, TPA, were shown to augment the cytotoxic potential of human blood lymphocytes with low cell density. In kinetics experiments the enhancing effect was preceded by an initial suppression lasting for about 2 hours. Admixture of mononuclear adherent cells abrogated the P(Bu)2 effect in a dose dependent way. P(Bu)2 altered the sensitivity of K562 cells to the cytotoxic effect. Short term pretreatment increased the sensitivity, but after longer pretreatment the cells became resistant. The results show that tumor promoters can influence the cytolytic system at different levels. By acting directly on the lymphocytes they potentiate the lytic function. When mixed mononuclear populations are used, this effect may be counteracted via activation of the suppressive functions of monocytes. In addition, the target cell sensitivity can also be modulated. As a result, the final outcome of phorbol treatment depends on the strength, kinetics and the mode of its effects on the interactants.

Cell Adhesion↗
PubMed1983

Effect of interferon on cell proliferation and generation of cytotoxic potential in mixed autologous and allogeneic lymphocyte cultures.

Autologous and allogeneic mixed lymphocyte cultures (AMC and MLC) were assayed for blastogenesis, generation of cytotoxic potential, and the effect of interferon (IFN-alpha) on these features. The cells of the mixed cultures lysed K562, Daudi, and autologous and allogeneic phytohaemagglutinin blasts. Stimulator-specific cytotoxicity was observed only in MLC. B blasts induced with Staphylococcus aureus were only affected in a stimulator-specific manner. Short-term IFN treatment of the MLC-derived effectors before the lytic assay enhanced the nonspecific component of cytotoxicity. Cell proliferation was considerably lower in AMC than in MLC. This was decreased when IFN-alpha was added at the initiation of the cultures. The presence of IFN influenced the generation of lytic potential. Comparison of the lysis of the different targets exerted by MLC-activated cells suggested that the specific component was more substantially elevated than the nonspecific one. It is likely that the IFN induced such modifications in the culture conditions that favoured the proliferation of the specific clone. Re-exposure of lymphocytes cultured in the presence of IFN to another dose of IFN before the assay had no influence on their lytic potential.

B-Lymphocytes↗
PubMed1983

Thyroid function after bronchography with propyliodone.

Thyroid function was studied in 27 subjects who underwent bronchography with propyliodone (18-70 ml, containing 30% of organic iodine). Sustained elevations of serum non-hormonal iodine were observed, indicating that significant amounts of propyliodone were absorbed from the bronchial tree and also that elimination may take several weeks. During the period of anaesthesia, there was an increase in thyroxine-binding globulin and all thyroid hormones which was transient and probably reflected vascular response to the anaesthetic. T4-T3 conversion was inhibited with a nadir of T3 and a peak of rT3 occurring on the 2nd day after propyliodone exposure. FT4 increased gradually during the 2 weeks after bronchography, but remained within the normal range. 6 out of the 27 patients developed pathologic T4 levels, 3 elevated T3 levels, and 2 an abnormal response to thyrotropin-releasing hormone; these changes might have been confused with hyperthyroidism. None of the patients developed clinical thyrotoxicosis; however, in patients with autonomous thyroid tissue, the same precautions should be taken with propyliodone as with other iodine-containing agents which are known to induce hyperthyroidism in this situation.

Adult↗
PubMed1983

Interpretation of lymphocytotoxicity assays and the demonstration of auto-tumor reactive lymphocytes in patients: central issues of present day tumor immunology.

The outcome of a short term cell-mediated cytotoxic assay depends on the susceptibility of the target and the activation profile of the lymphocyte population. Certain cultured cell lines are highly sensitive to the lytic effect of lymphocytes of unimmunized donors, provided they have been derived from the same species--NK effect. This cytotoxicity seems to be independent of lymphocyte receptor-target antigen interaction but is likely due to some membrane property of the target. Specificity is only on the species level. With fresh, non-cultured targets, in certain systems which operationally conform with the natural killing henomenon, antigen specific recognition defines the effect. We propose that on fresh targets, the operational NK effect, should be viewed fundamentally similar to CTL. Analysis of antigen induced cytotoxic systems suggests that the question of "specificity" on the effector level can only be asked if target cells of similar characteristics are used. Specificity at the effector level depends on the panel of targets presented. Cells with inherent sensitivity to the lytic effect of activated lymphocytes (i.e. NK sensitive cells) may be killed even if they are unrelated to the stimulus, and also such NK resistant cells which carry antigens for which the relevant receptor carrying lymphocytes are present in a sufficient number. Lysis of the latter cells can occur due to transactivation. Transactivation means that accompanying the event of antigen specific recognition in a lymphocyte population, additional cells are activated that do not participate in the specific reaction. In patients with solid tumors lymphocytes which recognize autologous tumor biopsy cells and can damage them, have been demonstrated. Auto-tumor-killer lymphocytes have been generated in conventional mixed lymphocyte cultures, using the patient's lymphocytes as responders--probably due to transactivation or in mixed lymphocyte cultures containing lymphocytes and autologous tumor cells.

Acute Disease↗
PubMed1983

The meal-related peak in plasma cortisol is not mediated by radioimmunoassayable ACTH.

There is evidence for the existence of ACTH-unrelated mechanisms in the regulation of cortisol secretion in man. The present study was designed to elucidate the interrelations between plasma ACTH and cortisol levels during the 'midday surge' in cortisol concentrations. For comparison, a 'midday surge' was imitated by infusing small amounts of ACTH in dexamethasone-suppressed subjects. The meal-related cortisol bursts were not preceded by an adequate increase in ACTH levels. In contrast, markedly elevated ACTH levels were necessary to produce a comparable cortisol peak by administration of ACTH. Apparently, the meal-related bursts in cortisol levels were not mediated by radioimmunoassayable ACTH. These findings argue against the classic concept that the adrenal cortex is inseparably linked to immediately preceding hormonal events occurring in the hypothalamo-pituitary system.

Adrenocorticotropic Hormone↗
PubMed1983

Granular activated carbon usage in chloramine removal from dialysis water.

Chloramines, oxidant compounds used in municipal drinking water as sanitizing agents, potentiate hemolytic anemia when present in dialysate. Thus far, the addition of ascorbic acid to the dialysate and the use of granular activated carbon (GAC) have been the only reliable, practical methods reported for removing chloramines. This is a report on the bench-scale testing of five kinds of GAC from three manufacturers. The performance of 100 g of each carbon was studied in a 2-in-diameter column through which feed-water containing approximately 1.5 mg/L chloramines flowed downward at an average volumetric rate of 140 ml/min. The carbons' experimental capacities for chloramines differed by as much as one order of magnitude. The experimental results were used to estimate the capacity of a 9-in-diameter, 45-in-tall column of the best carbon. These scale-up estimations indicate that this sorbent may safely last through 156 5-h dialyses.

Anemia, Hemolytic↗