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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 721 records · Page 40Linked to original sources
PubMed1983

Epstein-Barr virus-associated antibody pattern in untreated non-Hodgkin lymphoma patients. Relationship to clinical variables and lymphocyte functions.

Sera from 296 unselected and untreated patients with non-Hodgkin lymphoma (NHL) classified according to the Rappaport and the Kiel systems were analyzed for antibodies to Epstein-Barr virus (EBV). The aim of the study was to determine whether antibody spectra and titers to EBV-coded antigens correlated to clinical and immunological variables and whether the titers were of any prognostic significance. Increased antibody titers to EB viral capsid antigen (VCA) and slightly raised titers to early antigens (EA) of the diffuse (D) and restricted (R) types were noted frequently. Anti-VCA antibody titers correlated to clinical stage and age of the patients but not to histological subgroups according to the Rappaport or the Kiel classification systems. However, anti-VCA titers greater than or equal to 1:2560 were seen only in diffuse lymphomas according to the Rappaport and in non-follicle cell-derived lymphomas according to the Kiel classifications. Patients with complement-receptor-positive diffuse lymphomas had higher anti-VCA titers than complement-receptor-positive nodular cases. Anti-VCA titers also correlated positively to serum IgG levels (p less than 0.01). Total number of lymphocytes separated from peripheral blood and mitogen induced (ConA, PWM) DNA synthesis were recorded before treatment in 56 of the patients. The patients exhibited a significant lymphocytopenia as well as a significantly reduced lymphocyte response to mitogens (p less than 0.001) compared to healthy controls. Elevated anti-VCA titers and anti-EA titers correlated to a good mitogen-induced lymphocyte response (p less than 0.05). Only anti-D 1:40 at diagnosis predicted a poor prognosis.

Adolescent↗
PubMed1983

[A new, non-invasive study method for the determination of left-ventricular function in patients with coronary disease].

With the new development of the Nuclear Stethoscope-a microprocessor based cardiac scintillation probe-it is possible to determine the contractile parameters and the diastolic filling measurement of the left ventricle, after the application of Technetium 99m. Due to the high sensitivity and specificity a functional diagnosis of the left ventricle is possible to approximately 90%. The report describes our first attempts to determine the ejection fraction (EF) at rest and during exercise in 24 patients with diagnosed coronary heart disease. Of the 24 patients, 18 (75%) were already found to have abnormal, in that they did not have the expected increase in the EF. The comparison of the results from the non-invasive probe with those of the coronary angiographic findings demonstrate a good correlation Correlation coefficient r = 0.960). The determination of the EF of coronary patients at rest and especially during exercise, from the point of view of rehabilitation, is of great practical relevance, allowing the residual function of the myocardium after infarction and harmful overloading to be better defined.

Adult↗
PubMed1983

Gamma-interferon (IFN-gamma) produced during effector and target interactions renders target cells less susceptible to NK-cell-mediated lysis.

Human mitomycin C-treated PBL were mixed with cells of an NK sensitive hybrid cell line (PUTKO-I). A fraction of tumor cells survived this treatment and could be recovered from the cultures. These surviving cells were completely NK-resistant and this property persisted for 2-3 weeks after cultivation in fresh medium. Treatment of a clone (C13) of PUTKO-I with PBL-PUTKO mixed lymphocyte-tumor-cell culture (MLTC) supernatants resulted in a marked reduction in NK sensitivity after 8-12 h of treatment. The kinetics of induction of NK resistance by MLTC supernatants was similar to that of purified IFN-gamma and was faster than for IFN-alpha. The active component in the supernatants was characterized as a mixture of IFN-gamma and IFN-alpha based on neutralization of activity with specific antisera. The role of mycoplasma contamination was investigated and it was found that cell lines free of detectable mycoplasma stimulated production of NK-protective activity by PBL and this activity was neutralized by anti-IFN-gamma serum. Separation of PBL on discontinuous Percoll gradients demonstrated a correlation between the NK activity of cell fractions and their ability to produce IFN in response to tumor cells. Taken together, the selection-dependent variations in NK sensitivity, the kinetics of IFN production and induction of resistance suggest that tumor cells may be able to escape elimination by NK cells due to protection by IFN produced by the effector-cell-containing population.

Cell Line↗
PubMed1983

Enzyme-linked immunosorbent assay for the detection of Epstein-Barr virus-induced antigens and antibodies.

Two Epstein-Barr virus (EBV)-specific ELISA tests were developed. One, based on the use of crude extracts from virus producer cells highly induced in the presence of Ara C (providing EA + VCA- cells) or in the absence of the drug (providing EA + VCA + cells) is suitable for the detection of antibodies directed against antigen complexes associated with the lytic virus cycle; i.e., EA, VCA and presumably also MA. The second, performed with purified EBNA, can be used for the detection of antibodies to the transformation-associated nuclear antigen. The tests are expected to find application in the dissection of antibody responses of patients to various antigenic subcomponents, the monitoring of EBV-coded antigens during biochemical purification, and the screening of spent media from hybridoma cultures for EBV-specific antibodies.

Antibodies, Viral↗
PubMed1983

Epstein-Barr virus-specific serodiagnostic tests in carcinomas of the head and neck.

Sera from 256 patients with cancers of the head and neck were examined for their profiles of IgG and IgA antibodies to Epstein-Barr virus (EBV)-specific, viral capsid antigen (VCA), the diffuse (D) and the restricted (R) components of the early antigen (EA) complex, and the EBV-associated nuclear antigen (EBNA), in order to assess the value of these procedures in the routine diagnosis of poorly or undifferentiated nasopharyngeal carcinoma (NPC). In 13 NPC patients, the carcinoma had invaded cervical lymph nodes, and their sera revealed, in addition to high IgG anti-VCA titers, elevated levels of IgA antibodies to VCA, of IgG antibodies to D, and most also had IgA anti-D. Such profiles were seen in very few of the patients with carcinomas at other sites of the head and neck. They had not developed in four NPC patients whose tumors were limited to the postnasal space, and in three patients with other tumors at that site. Among 15 patients with cervical node metastases from occult primary tumors, 2 had EBV-specific antibody profiles compatible with NPC, 1 was judged to have NPC on clinical grounds, and the other died of a pulmonary carcinoma, or possibly pulmonary metastases. In 4 of the remaining 13 patients with occult tumors, the primary site was found outside the nasopharynx, whereas it escaped detection in the other 9. These results lend further support to the usefulness of the EBV-specific serology to clinicians in the diagnosis of NPC, especially in cases of lymph node invasion by undetected primary tumors. The data also emphasize the need of complementing the serology with the examination of biopsies for the presence of EBV deoxyribonucleic acid (DNA) or, more readily performed, EBNA-positive carcinoma cells.

Aged↗
PubMed1983

Studies on the possible chemical, immunochemical and morphological differences at the cell surfaces of immunosensitive and immunoresistant, Moloney virus-induced, lymphoma cell-lines.

Comparison was made of several cell-surface parameters in the immunosensitive, Moloney virus-induced, mouse lymphoma, YAC, and its immunoresistant variant, YACIR. The characteristics of the two cell lines appeared to be similar by most of the criteria employed. The poly(acrylamide)-gel electrophoresis (with sodium dodecyl sulfate) patterns, after staining with Coomassie Brilliant Blue, of detergent-solubilized materials, appeared to be identical. After elution from a gel filtration column, no major differences were observed in the protein profiles of material cleaved from viable cells by proteolysis. Scanning and transmission electron microscopy revealed no major differences between the YAC and YACIR cells. The concentration of the lectins, Ricinus communis agglutinin, concanavalin A, wheat-germ agglutinin, and Solanum tuberosum (potato) agglutinin, required to agglutinate viable cells of the two lines were not significantly different. Neither cell was agglutinated by the lectins from Dolichos biflorus or Vicia graminea. Significant differences were, however, observed in the concentrations of lectin from Arachis hypogaea (peanut) needed to agglutinate the two cells. Although similar amounts (184-188 micrograms/10(9) cells) of sialic acid were released from viable cells by neuraminidase (V. cholerae), striking differences were observed in the composition of this material: 48% of N-glycolylneuraminic acid for YAC and 15% for YACIR. The remainder was N-acetylneuraminic acid for each cell line.

Agglutination↗
PubMed1983

Flow karyotype analysis and fluorescence-activated sorting of Burkitt-lymphoma-associated translocation chromosomes.

Flow karyotype analysis was performed to assess the feasibility of fluorescence-activated sorting of Burkitt lymphoma (BL)-associated translocation chromosomes. The typical 14q+ chromosome in the t(8;14) and the two "variant translocations", the 2q+ in the t(2;8) and the small 22q- in the t(8;22), could be identified as single peaks within the flow karyotypes of metaphase chromosomes isolated from several different BL-lines for each translocation. The translocation chromosomes could be separated with a high degree of purity and in quantities suitable for biochemical analysis. The same analytical and preparative technique was also successfully applied to the identification and sorting of the Philadelphia (Ph1) chromosome in a 9;22 translocation-carrying CML-derived line and a familial (11;22) translocation.

Burkitt Lymphoma↗
PubMed1983

Incidence and type of tumors induced by DMBA carcinogenesis in H-2 congenic strains on a B10 background.

Five congenic strains on B10 background (B10, B10.S, B10.G, B10.BR and B10.A) were investigated for their susceptibility to tumor induction by 9,10 dimethyl-1,2 benzanthracene (DMBA). The DMBA was administered via a stomach tube five times at weekly intervals (total 5 mg). Two types of malignancies predominated: diffuse lymphocytic lymphomas with or without thymic involvement, and epidermal tumors. B10 (H-2b) was the most resistant strain when total tumor incidences were compared. B10.S (H-2s) had the highest incidence of both lymphomas and epithelial tumors and B10.G was significantly more susceptible to thymic lymphomas than B10. In B10.S mice thymic lymphomas were more frequent in males than in females, the reverse being true for tumors of epithelial origin. No correlation between tumor incidence and in vitro NK activity was demonstrated.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

[New approach in the laser therapy of nevus flammeus].

The technical properties of the flashlamp-pumped dye laser are compared with those of other lasers already used in the therapy of port-wine stains. The advantages of the dye laser seem to be evident. The main reasons are the possibility of free choice of the wavelength and the small width of beam pulse. Short term results are presented. The therapeutical value of this method will be recognized not before lang term results are available.

Evaluation Studies as Topic↗
PubMed1983

Expression of the BLA antigen, defined by the monoclonal 38.13 antibody, on Burkitt lymphoma lines, lymphoblastoid cell lines, their hybrids and other B-cell lymphomas and leukemias.

The BLA expression of eight Burkitt lymphoma lines was high, whereas it was negative in four, including the two IgG producers tested. Most lymphoblastoid cell lines (LCL) of normal origin had only a low percentage of positive cells, not significantly above background, although a few had up to 30% positives. EBV conversion of the EBV-negative Burkitt lymphoma line Ramos destabilized the high BLA expression, leading to a decrease in the average number of positive cells in the majority of the converted sublines in parallel with considerable fluctuation in antigen expression within each subline. Our group has previously shown that EBV-conversion of Ramos cells can induce certain differentiation steps (Spira et al., 1981 a). EBV-converted sublines of another EBV-negative Burkitt lymphoma, BJAB, showed a much greater stability previously and remained unchanged with regard to BLA expression in our present experiments. Eight T-cell leukemias, three myeloid leukemia lines and two diffuse histiocytic lymphomas were negative for BLA, whereas two myeloma lines were 30-40% positive. A histiocytic tumor had marginal reactions. Hybrids derived from the fusion of high with low BLA-reactive parental lines showed all three possible patterns (high, intermediate and low), provided that B-cell lines were fused with each other. Fusion of two Burkitt lymphoma lines with the K562 erythroleukemia line led to the extinction of BLA expression, as well as to the eclipse of other B-cell markers. B-lymphoma and leukemia (CLL) cells harvested directly from the patient showed a heterogeneous reactivity pattern. Strong to intermediate BLA expression was found among CLL cells and in most histological groups of B-CLL lymphomas except the centroblastic group (3/3 negatives). IgG-expressing follicular lymphomas were less reactive than IgM +/- IgD lymphomas of the same group. Immunocytomas were also low-reactive. BLA can be thus expressed on a variety of B-cell neoplasms; the degree of its expression appears to be related to the stage of differentiation.

Antibodies, Monoclonal↗
PubMed1983

Intracellular Epstein-Barr virus DNA is methylated in and around the EcoRI-J fragment in both producer and nonproducer cell lines.

Methylation patterns in intracellular Epstein-Barr virus (EBV) DNA sequences using the isoschizomers HpaII and MspI and the cloned EcoRI-J fragment as a probe have been studied. The possible role of DNA methylation in determining the producer and nonproducer status of EBV-carrying lymphoma cell lines and whether this pattern would be affected by treatment with inducers, like TPA and n-butyrate, which effectively activate the productive virus cycle in low-level producer lines, were examined. By studying intracellular EBV DNA present in total cellular DNA isolates it was concluded that (i) intracellular EBV DNA is methylated in and around the EcoRI-J fragment in both producer and nonproducer cell lines; (ii) methylation at this site is more pronounced in nonproducer cell lines as compared with producer cell lines; (iii) the cell lines studied here responded differently to chemical induction as determined by EBV-specific antigen immunofluorescence staining. However, no major differences in the methylation pattern in and around the EcoRI-J fragment could be observed before and after induction.

Animals↗
PubMed1983

Relationship between the amounts of EBV-DNA and EBNA per cell, clonability and tumorigenicity in two ebv-negative lymphoma lines and their EBV-converted sublines.

The effect of EBV-conversion of two EBV-negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between 1.1 and 4.9 times compared to the original "parental" lines. Tumorigenicity was increased in one out of 2 BJAB-derived, EBV-positive lines and in 3 of 6 Ramos-derived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV-genomes/cell, the amount of EBNA/cell and tumorigenicity.

Animals↗
PubMed1983

Immune interferon (IFN-gamma) production in autologous mixed cultures.

T cells were exposed in vitro to autologous B cells or monocytes. Tested on the seventh day, the cultured lymphocytes lysed K562, Daudi, autologous, and allogeneic phytohemagglutinin (PHA) blasts. Autologous B blasts were not affected. The supernatants contained gamma interferon (IFN-gamma). The quantity of IFN did not correlate with the strength of the proliferative response nor with the strength of the cytotoxic potential.

Cell Division↗
PubMed1983

Activation of the EBV-cycle and aggregation of human blood lymphocytes by the tumor promoters teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin.

A variety of tumor promoters such as the phorbol esters were found to be capable of inducing the viral cycle in cell lines latently infected with Epstein-Barr virus (EBV). We tested two classes of new tumor promoters; indole alkaloids and polyacetates, for their ability to induce the synthesis of the Epstein-Barr virus determined early antigen (EA) complex. Teleocidin and lyngbyatoxin A are indole alkaloids. Aplysiatoxin and debromoaplysiatoxin are polyacetates. Of these four tumor promoters all but debromoaplysiatoxin induced the synthesis of the EA complex. However, in combination with 3 mM n-butyrate, all four induced EA synthesis. The potent tumor promoters teleocidin, lyngbyatoxin A and aplysiatoxin induced maximal synthesis of EA at the concentration of 5 to 10 ng/ml, whereas the weak tumor promoter debromoaplysiatoxin required a concentration of 250 ng/ml to achieve maximal induction. Phorbol esters induce quick morphological changes and aggregation of human blood lymphocytes. The latter phenomenon has been interpreted as the expression of a "cell binding phenotype" (Patarroyo et al., in press). We showed that all four promoters induced aggregation of human lymphocytes at similar concentrations. The induction seemed to be a common effect which could be induced by both strong and weak tumor promoters.

Alkaloids↗
PubMed1983

Epstein-Barr virus (EBV)-induced lymphoproliferative disease in cotton-topped marmosets.

Six cotton-topped marmoset monkeys (Sangiunus oedipus) were inoculated with 10(5) transforming units of B95-8 virus, and two of them developed fatal lymphoproliferative disease. The EBV-carrying tumor cells from these marmosets had the following characteristics: (1) they were polyclonal by surface immunoglobulin and immunoglobulin production in vitro; (2) they had no specific chromosome abnormalities, and (3) they failed to form colonies in large percentages in agarose. It is proposed that a spectrum of phenotypes of EBV-induced lymphoproliferative diseases in the cotton-topped marmosets may be identified and are more akin to fatal infectious mononucleosis or X-linked lymphoproliferative syndrome than to Burkitt's lymphoma.

Animals↗