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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 901 records · Page 50Linked to original sources

Non-random duplication of chromosome 15 in murine T-cell leukemias: further studies on translocation heterozygotes.

Four combinations of translocation heterozygotes with cytogenetically distinct chromosomes 15 were used to investigate whether the T-cell leukemia-associated duplication of chromosome 15 is a non-random or a random event. In leukemias of AKR x CBAT6T6F1 (Group 1) and C57BL x CBAT6T F1 (Group IV) crosses the duplication was non-random, affecting the AKR-derived chromosome 15 (Group 1) and CBAT6T6-derived T (14;15) 6 chromosome (Group IV), respectively. In contrast, in leukemias induced in CBA x CBA T6T6F1 combinations (Group III) - where both chromosomes 15 (normal and translocated) were CBA-derived-the duplication was random. Similarly, in the Rb6;15 x CBAT6T6F1 cross (group II) the duplication of chromosome 15 appeared to be random. The results supported the hypothesis that the genetic content of chromosome 15 rather than its translocated state is decisive for the preferential duplication of this chromosome in T-cell leukemogenesis. However, the genetic background of the strain from which chromosome 15 is derived may also influence the duplication pattern of individual tumors.

Animals↗

[Removal of infected entrapped pacemaker electrodes by continuous traction (author's transl)].

To remove an infected pacemaker system in order to control the infection is often difficult when there is extensive connective-tissue fixation of the electrode. Forced manual extraction may lead to severe complications. For this reason, operative removal, in certain circumstances involving cardiotomy under extracorporeal circulation, has been practised. An alternative is continuous traction in which the probe is attached peripherally and by continuous traction removed from its cardiac attachment. Nine patients have been treated successfully by this method. In eight the electrode was removed within 1-10 days without significant complications. In one instance the electrode-catheter tore within the superior vena cava after 18 days of continuous traction; the remaining catheter, about 12 cm long, was removed with a sling catheter.

Aged↗

[Orally active vasodilators in the management of chronic treatment-resistant cardiac failure (author's transl)].

The acute haemodynamic effects of 40 mg isosorbide dinitrate (10 subjects), 4 mg prazosin (20 subjects) and 50 mg dihydralazine (8 subjects) were compared in 24 patients with the clinical picture of chronic therapy-resistant cardiac failure (NY Heart Association stages III-IV). There was a fall in left-ventricular filling pressure of about 15% and right-atrial mean pressure of 21 and 24%, respectively, with isosorbide dinitrate and prazosin, while there was no change with dihydralazine. Cardiac output rose by 23% with dihydralazine and 20% with prazosin, but remained unchanged with isosorbide dinitrate. These data indicate that a reduction in pulmonary and systemic-venous congestion due to chronic decompensated cardiac failure can be achieved with isosorbide dinitrate and prazosin, while cardiac output can be improved only with prazosin and dihydralazine.

Adult↗

[Protective effect of ketotifen and disodium cromoglycate in bronchial challenge tests with allergens (author's transl)].

The protective effect of ketotifen and disodium cromoglycate (DSCG) was evaluated by a randomised double blind cross-over study in 15 children with allergic bronchial asthma. 13 children were allergic to house dust mite (Dermatophagoides pteronyssinus), two to grass pollen. After a positive bronchial challenge test ketotifen or DSCG was given for 4 days followed by bronchial challenge with increasing allergen concentrations. Seven patients showed better allergen tolerance after ketotifen, 5 after DSCG. Protective action against late reactions was found only in 2 children after ketotifen and one child after DSCG.

Adolescent↗

Effect of interferon-alpha 1 from E. coli on some cell functions.

Interferon-alpha 1 from Escherichia coli transformed with a hybrid plasmid containing a human leukocyte complementary DNA insert, induces resistance to virus in appropriate target cells. It also shares the following properties with natural leukocyte interferon (IFN). (i) It enhances natural killing activity of human lymphocytes, (ii) it enhances antibody-dependent cell-mediated cytotoxicity, (iii) it suppresses antigen- and mitogen-induced leukocyte migration inhibition, (iv) it inhibits growth of IFN-sensitive Burkitt lymphoma cells. Since these activities are exhibited by a cloned protein species, they are due to IFN itself and not to other human proteins.

Antibody-Dependent Cell Cytotoxicity↗

Induction of the EBV cycle in B-lymphocyte-derived lines is accompanied by increased natural killer (NK) sensitivity and the expression of EBV-related antigen(s) detected by the ADCC reaction.

Human B-lymphocyte-derived lines were forced to enter the EBV-cycle by superinfection with the P3HR-1 substrain of EBV or sodium butyrate treatment. The induced cells were used as targets for natural killing (NK) and EBV-specific, antibody-dependent cellular cytotoxicity (ADCC). Two Burkitt lymphoma lines, Raji and Daudi, and one normal adult derived lymphoblastoid cell line, NAD-7, were comparable in their ADCC-sensitivity after induction, but only the Burkitt lymphoma-derived lines showed a major increase in NK-sensitivity. The superinfection-induced membrane change, responsible for both NK and ADCC sensitivity, is an early function of the viral cycle, correlated with the appearance of early antigens (EA). Indirect evidence indicates that the NK and ADCC target sites are different but this problem requires further investigation. Sodium butyrate induced an increased NK sensitivity and EBV-related ADCC sensitivity in the Burkitt lymphoma-derived P3HR-1 line. Lymphocyte effectors from different donors showed great differences in their NK and ADCC activity. Optimal ADCC could be demonstrated with effectors that were intermediate in their NK-activity.

Antibody-Dependent Cell Cytotoxicity↗

Radiolabeling of natural adenosine triphosphatase inhibitor with phenyl (14C)isothiocyanate and study of its interaction with mitochondrial adenosine triphosphatase. Localization of inhibitor binding sites and stoichiometry of binding.

The natural ATPase inhibitor (IF1) from beef heart mitochondria was labeled with phenyl (14C)isothiocyanate [(14C)PITC]. Chemical labeling by (14C)PITC does not modify the inhibitory properties of IF1, provided the number of residues of (14C)PITC bound per molecule of IF1 is lower than five to six, which corresponds to the average labeling of roughly half of the available lysine residues in IF1. This partially labeled, fully active, IF1 was used to determine the binding stoichiometry of IF1 with respect to F1 and to localize the inhibitor binding sites in F1-ATPase. The pattern of loss of ATPase activity of F1 with increasing amounts ot (14C)PITC-IF1 indicated that the ATPase activity is fully inhibited when 1 mol of IF1 is bound to 1 mol of F1. As F1 contains at least 2 beta subunits, this points to a half-site reactivity of F1 with respect to IF1. Sites of interaction between (14C)PITC-IF1 and F1 subunits were investigated by the use of two cross-linking reagents which act as "zero length" cross-linkers, 1-ethyl-3-[(dimethylamino)propyl]carbodiimide (EDAC) and N-(ethoxycarbonyl)-2-ethoxydihydroquinoline (EEDQ); the products of cross-linking were analyzed by NaDodSO4-polyacrylamide gel electrophoresis. IF1 was found to bind preferentially to the beta subunit of F1. Among the cross-linked products formed by reaction of EDAC or EEDQ with subunits of F1, one of them, the beta gamma dimer, did not accumulate when IF1 was added to F1 prior to cross-linking.

Adenosine Triphosphate↗

Surface immunoglobulins on Burkitt's lymphoma biopsy cells from 91 patients.

One hundred and fourteen biopsies from 91 cases of African Burkitt's lymphoma were examined by immunofluorescence methods for the presence of surface-associated mu, gamma, delta, kappa and lambda chains, as well as for the Fc region of gamma chains and for beta1C. Only 5% of the biopsies were surface-Ig-negative; 18% were negative for mu chains and 61% for gamma chains. Delta chain staining was absent, or borderline in a few tumors. Mu chains, gamma chains in a few highly reactive tumors and, in many cases, the predominant light chain seemed to be clonal markers. They gave no convincing evidence of more than one cell clone, either within single tumors or within syn- or metachronous tumors in one individual. Gamma chains in moderately stained tumors, Fc and beta1C correlated with each other and the first two reactivities decreased after incubation at low pH, indicating that their presence resulted from outside coating of the cells. The results indicated that one clone of B cells is involved in Burkitt's lymphoma in the large majority of cases. This clone is in a state of differentiation at which surface delta chains are not expressed. No prognostic information resulted from the analysis of the markers studied.

Biopsy↗

Cytogenetic studies on abelson-virus-induced mouse leukemias.

The karyotype of Abelson-virus-induced murine leukemias was studied by G-banding. In contrast to the regular trisomy of chromosome 15 in most murine T-cell leukemias, Abelson leukemias were purely diploid, and remained diploid for up to seven consecutive passages in vivo. The hypothesis is advanced that integration into the recipient cell of the DNA copy of the large cellular insert, carried by the Abelson virus, may perform a function similar to the effects of gene duplication by trisomy in the more slowly developing murine leukemias.

Abelson murine leukemia virus↗

[Effect of the antirheumatic drug Sulindac on thrombocyte function (author's transl)].

The effect of a treatment with the antirheumatic drug Sulindac (from 200 to 400 mg/day over 4 weeks) on thrombocyte function (bleeding time, platelet retention, platelet aggregation induced with suitable concentrations of ADP, epinephrine, collagen and Ristocetin) on thrombocyte count and thromboplastin time was investigated in 20 patients. In 10 healthy volunteers collagen-induced platelet aggregation was measured after oral application of 200 mg Sulindac. Analysis of the data obtained by the tests revealed no unwanted or harmful effects of Sulindac on platelet functions, platelet count and prothrombin time. No significant difference between the data before and during treatment was found. No medical drop out was registrated.

Collagen↗

Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate.

Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK-sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.

Antigens, Viral↗

[Antiarrhythmic drugs in chronic ventricular extrasystole (author's transl)].

Several class I antiarrhythmic drugs were used in an intraindividual comparative study in 15 patients with chronic stable ventricular extrasystole of various origins. In a randomised sequence lidocaine, ajmalin and, in a cross-over double blind study with placebo, the new antiarrhythmic Org 6001 were tested. Propafenon was given as a final preparation. Each substance was administered parentally in therapeutic doses. A significant placebo effect could be excluded, baseline control values before administration of individual substances correlated well. Comparing mean values obtained over one hour before and after administration of the substance it was shown that the effectiveness of drugs decreased as follows: ajmalin, propafenon, lidocaine, Org 6001. Whereas suppression of extrasystole was most marked after ajmalin, propafenon showed the longest period of activity. After Org 6001 divergent activity of arrhythmia could be observed; in some patients good antiarrhythmic effects could be demonstrated. For evaluation of effectiveness and validity of new antiarrhythmic substances intraindividual comparison with placebo and well established standard antiarrhythmic drugs is advisable.

17-Ketosteroids↗

Activated T lymphocytes in infiltrates and draining lymph nodes of nasopharyngeal carcinoma.

Lymphocytes isolated from the tumors and draining lymph nodes of nasopharyngeal carcinoma (NPC) patients exhibit the following characteristics of immune activation: (1) stable E rosette formation, (2) natural attachment to various human cells, (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the NPC T cells attach in vitro to various cells they kill only EBV-genome-carrying targets. These findings suggest the occurrence of a local cellular immune response in NPC, possibly directed to EBV-determined antigens.

Cell Line↗