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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 991 records · Page 55Linked to original sources

Relationship between Epstein-Barr virus genome number, amount of nuclear antigen, and early antigen inducibility in diploid and tetraploid lymphoma cells of related origin.

In a collection of near-diploid and near-tetraploid Raji sublines and somatic Raji/Raji hybrids a linear relationship was found between the number of Epstein-Barr virus (EBV) genome copies and the relative amount of EBV-determined nuclear antigen per cell. Inducibility of the viral cycle by iododeoxyuridine and by P3HR-1 virus superinfection coulb be related to the number of resident EBV genome copies per haploid target cell. The implications of these findings are discussed.

Antigens, Viral↗

Epstein-Barr virus-related antibody patterns in ataxia-telangiectasia.

Epstein-Barr virus-related antibody titres were determined in twenty-seven patients with ataxia-telangiectasia (AT) and twenty-two healthy members of their families, in twenty-two patients with other diseases, among them ten with Behçet's disease and ten with various primary immune deficiencies, and fifteen healthy members of their families, and in twenty-three unrelated healthy controls. The AT patients showed an increased incidence (55.6%) of high antibody titres (greater than or equal to 1:320) to viral capsid antigen (VCA), and also a high incidence (48.2%) of antibodies to Epstein-Barr virus (EBV) induced early antigens (EA), but low titres (less than 1:10) of antibodies to the EBV-associated nuclear antigen (EBNA) in 44.2% of the cases. The geometric means of anti-VCA were three-to four-fold higher, and of anti-EBNA six-fold lower, than those of the control groups. The patients with the other diseases did not differ significantly from the controls except for a higher incidence of anti-EBNA titres of less than 1:10 (38.1% vs 4--5%). AT patients with low anti-EBNA titres tended to have more advanced T cell deficiencies than AT patients with moderate anti-EBNA titres, as detected by counts of total lymphocytes and E-rosetting cells, and skin test responses. The results support the hypothesis that a functioning T cell system is required to release EBNA from EBV genome-carrying cells for initial and maintained production of anti-EBNA.

Adolescent↗

Selection of a low antigenic variant subline from the TA3St ascites carcinoma by repeated passage of antibody-coated cells through anti-immunoglobulin columns.

TA3St mouse ascites carcinoma cells of strain A origin (H-2a) were coated with anti-H-2a serum and passaged through mouse immunoglobulin-anti-immunoglobulin columns repeatedly prior to each in vivo passage. After six passages in vivo, a variant cell line emerged with significantly decreased H-2a expression and an increased ability to grow progressively across H-2 allograft barriers. Chromosome analysis of the variant cell line revealed no major changes in karyotype. The application of the method for studies on the generation of immunoresistant tumor cell variants and on the relationship between antibody-binding sites and rejection target sites is discussed.

Animals↗

Establishment of a human lymphoblastoid cell line with specific antibody production against group A streptococcal carbohydrate.

A human lymphoblastoid cell line, secreting specific antibody against Group A carbohydrate (A-CHO) was established by pre-selection of antigen binding normal human lymphocytes, followed by Epsetin Barr virus (EBV) induced immortalization. Culture supernatants were assayed for anti A-CHO antibodies by radioimmunoassay, N-acetyl-glucosamine-coupled T4-phage plaque inhibition tests and passive hemagglutination. As a rule, the supernatants contained about 10 micrograms/ml anti-A-CHO antibodies of the IgM-kappa type. The antibody was fractionated and partially purified on an N-acetyl glucosamine Sepharose 4B column with a recovery of about 3 micrograms/ml of supernatant.

Antibody Formation↗

[Exercise tolerance of patients with artificial cardiac pacemakers (author's transl)].

In order to determine their exercise tolerance, 20 patients with artificial ventricular demand pacemakers below the age of seventy were studied by bicycle ergometry. Only 30% of the patients showed a normal exercise tolerance according to the criteria by Kaltenbach, while 70% stopped the test prematurely because of leg fatigue, dyspnoe or chest pain. In terms of their exercise tolerance, there was no difference between patients who developed normal sinus rhythm or rapid atrial fibrillation during the exercise and those who remained at the fixed pacemaker rate throughout the test. It is concluded, therefore, that the exercise tolerance of pacemaker-patients is not only limited by the fixed heart rate but mainly by the underlying heart disease (coronary heart disease, cardiomyopathy, hypertensive heart disease etc.) and the general physical condition of the patients. In an age-matched control group of 20 patients 50% showed a normal exercise tolerance and the duration of exercise in this group was only slightly longer (21%) than in the pacemaker-group.

Aged↗

Establishment of specific antibody producing human lines by antigen preselection and Epstein-Barr virus (EBV)-transformation.

Specific antibody producing human cell lines were established by preselecting antigen binding B-lymphocytes and subsequently transforming ("immortalizing") them with Epstein-Barr virus (EBV). NNP-binding B-cells were isolated from the blood of three donors with high anti-NNP titers. EBV-transformation led to polyclonal cell lines that had 15-18% NNP receptor positive cells. A similar fraction of the cells produced NNP-specific plaques in the Cunningham-Szenberg assay. Unconcentrated culture media agglutinated NNP-coupled erythrocytes in up to an 1/2,048 dilution and inactivated NNP-coupled T4 bacteriophage in up to an 1/10,000 dilution. EBV-transformed but not similarly NNP-preselected lines of the same donors were completely negative in the rosette, plaque and antibody secretion tests. Supernatants of the antibody producing lines gave no reaction with the non-coupled erythrocytes or with a number of other hapten coupled controls. Anti-NNP antibodies secreted by all three preselected lines were of the IgM kappa type, which was in contrast to the sera of the donors that contained both IgM and IgG antibodies, with both light chain types. Cloning of one NNP-antibody producing line yielded 9 antibody producers out of 30. The positive clones formed NNP rosettes and plaques with 31-86% of the cells and produced anti-NNP of class IgM, Kappa. The cell culture contained 5-16 micrograms IgM/ml cell culture.

Antibody Formation↗

[Dopamine and dobutamine in the treatment of severe cardiac failure (author's transl)].

Ten patients in severe cardiac failure were treated with dopamine (4 microgram/kg . min) and dobutamine (7.5 microgram/kg.min). Both drugs brought about a similar increase in stroke volume and cardiac output of about 50% and 60%, respectively, accompanied by a fall in peripheral vascular resistance of about 33%. On dopamine the heart rate increased by 12%, but remained unaltered on dobutamine. There was a significant fall in the preload of both ventricles with dobutamine, while ventricular filling pressure during dopamine infusion was only slightly decreased, unchanged or even increased. The pulmonary (wedge) pressure during dopamine infusion averaged 9 mm Hg higher than during dobutamine (P less than 0.001). There is thus the potential danger with dopamine of aggravating pulmonary congestion. Furthermore, the improvement in cardiac function due to dopamine is at the expense of a higher oxygen demand than with dobutamine. Dobutamine is, therfore, preferable to dopamine in the treatment of advanced myocardial failure.

Adult↗

Chromosome changes (trisomy 15) in murine T-cell leukemia induced by 1,12-dimethylbenz(a)anthracene (DMBA).

The banding pattern of DMBA-induced leukemias in C57BL/6 mice revealed a very constant chromosome pattern: the presence of trisomy 15 in almost all leukemic cells. This finding strongly suggests that chromosome 15 trisomy is the first detectable specific chromosome change associated with the development of DMBA-induced T-cell lymphomas. A similar association was previously shown with regard to development of radiation-leukemia-virus-induced T-cell lymphoma. It is conceivable that in tumors of diverse etiologies common cytogenetic changes may appear in the same common target-cell precursor, by a process of the "convergent microevolution" type.

9,10-Dimethyl-1,2-benzanthracene↗

Interaction of the B95-8 and P3HR-1 substrains of Epstein-Barr virus (EBV) with peripheral human lymphocytes.

Two substrains of the Epstein-Barr virus derived from the B95-8 and P3HR-1 cell lines were studied for their interaction with human peripheral lymphocytes. It has been previously shown that B95-8 virus has and P3HR-1 virus lacks lymphocyte-transforming ("immortalizing") properties. DNA stimulation induced by B95-8 virus showed a good correlation with the number of surface Ig-positive cells. P3HR-1 virus added before B95-8 virus completely abolished the stimulation of DNA synthesis. It also prevented EBNA induction by B95-8 virus. P3HR-1 virus added after B95-8 virus diminished DNA stimulation by the latter in a time-dependent fashion. P3HR-1 virus did not inhibit DNA stimulation by phytohaemagglutinin but was inhibitory if added before a B cell mitogen (Staphylococcus Aureus). The origin of P3HR-1 virus and its relationship to the transformation process are discussed.

Antigens, Viral↗

Reduced capillary resistance in allergic patients.

Fifty four of 67 allergic children (81%) had a pathologically reduced capillary resistance (CR) of less than 16 cm Hg. Five of the 13 allergic children with normal CR were treated with corticosteroids. Prednisone improved CR in on patient for at least 24 h, and this was reflected by improvement of hemorrhagic parameters such as bleeding intensity, bleeding pattern and blood loss. There was no correlation between CR and IgE levels. 90% of the symptomatic relatives of allergic children had a reduced CR, but only 44% of asymptomatic relatives. CR presents a simple additional tool for diagnosing allergy and might give hints to the carrier state of allergy.

Adolescent↗

Antibody-dependent cellular cytotoxicity against Epstein-Barr virus-associated antigens in African patients with nasopharyngeal carcinoma.

Antibody-dependent cellular cytotoxicity (ADCC) was performed on serum samples from African patients with nasopharyngeal carcinoma (NPC) to determine whether antibody titers determined by this assay might be of prognostic value in this disease. The serum donors were divided into two groups: (1) those individuals who died within 2 years following diagnosis of NPC; and (2) individuals who responded well to therapy and surivived for more than 2 years following diagnosis. The ADCC GMT for the survivor group was significantly higher than the GMT for non-survivors (%5,410 versus 615). Interestingly, there were a number of discordant sera in the non-survivor group that had very low ADCC titers (less than 240) at diagnosis in the presence of high VCA titers. When ADCC titers were compared with anti-EA or IgA antibody titers to VCA, a statistically significant inverse correlation was noted. These data suggest that ADCC titers might be of prognostic importance in African NPC.

Africa↗

Detection of Epstein-Barr virus (EBV) DNA sequences using in situ hybridization.

In situ hybridization was used to detect Epstein-Barr virus (EBV) DNA sequences under conditions where the virus DNA is replicating spontaneously and where it is induced to do so following superinfection. The in situ reaction itself is influenced by several parameters, analogous to conventional nucleic acid hybridization, consideration of which should help to optimize the designing of in situ hybridization reactions in general. Both EBV complementary RNA (cRNA) and EBV DNA synthesized in vitro can efficiently detect the virus DNA sequences in situ. The findings presented here can therefore be utilized in both the study of EBV-cell interactions and, more generally, in studies using in situ hybridization as a general approach.

Antigens, Viral↗

Relationship between Epstein-Barr virus (EBV)-production and the loss of the EBV receptor/complement receptor complex in a series of sublines derived from the same original Burkitt's lymphoma.

Virus production, EBV (P3HR-1 substrain) superinfectability, IdUrd inducibility, EBV receptor and complement (C3) receptor expression were assessed in two independently maintained jijoye lines, the derived P3HR-1 clone that releases a growth inhibitory and cytopathic, non-transforming viral mutant, and in non-producer sublines derived from the P3HR-1 line by the spontaneous cessation of virus production. Both jijoye lines were superinfectable, inducible, and carried EBV and C3 receptors. Virus-producing P3HR-1 cells and recently derived non-producer sublines lacked EBV-receptors and C3 receptors, could not be superinfected, but were IdUrd inducible. Two long-passaged, non-producer sublines of P3HR-1 reexpressed EBV and C3 receptors to an equal degree (different in the two sublines). EBV-superinfectability became partially reestablished in the subline with the higher expression of EBV and C3 receptors. These findings support the hypothesis that the EBV-receptor/C3 receptor negativity of the producer P3HR-1 sublines and their recent non-producer derivatives is due to negative selection by the growth-inhibitory, cytopathic P3HR-1 virus variant. The closely linked disappearance and reappearance of EBV-receptors and complement receptors gives further support to the idea that these two receptors are either identical or closely linked constituents of the cell membrane.

Antigens, Viral↗

Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine C-type virus.

Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short-term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C-type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C-type virus either by repeated dosage through nude mice or by in vitro superinfection with the supernatants of nude-mouse-passaged lines. The appearance of surface-associated MuLV antigens after superinfection was confirmed in a complement-dependent cytotoxicity test. Subsequently, the NK sensitivity of each infected line was compared with its non-infected counterpart in direct cytolytic and competition assays. None of these two assay systems showed a consistent difference in NK sensitivity of infected and non-infected cell lines. These findings do not lend support to the concept tht murine C-type viral antigens are responsible for NK sensitivity.

Animals↗