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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 811 records · Page 45Linked to original sources
PubMed1982

Epstein-Barr virus in nasopharyngeal and salivary gland carcinomas of Greenland Eskimoes.

Biopsy specimens from nasopharyngeal carcinomas (NPC) or salivary-gland carcinomas (SGC) in Greenland Eskimoes were examined for the presence of Epstein-Barr virus (EBV) DNA and sera from the patients were tested for EBV-specific antibody titres. Six out of 7 NPCs and one from an undifferentiated SGG were positive for EBV DNA. The EBV-specific antibody spectra and titres of the patients with NPC or undifferentiated SGG conformed to the results of earlier studies in other high-incidence areas.

Adult↗
PubMed1982

A 53-kilodalton protein common to chemically and virally transformed cells shows extensive sequence similarities between species.

A heat-stable DNA-binding protein with subunits of about 53 kilodaltons (kDal) was purified from two virally transformed human cell lines (Epstein-Barr virus-positive Raji and Namalwa) and two mouse tumor cell lines (methylcholanthrene-induced Meth A sarcoma and TA3 mammary carcinoma). All four 53kDal proteins showed closely related total amino acid compositions, similar peptide maps, and identical NH2-terminal amino acid sequences for 20 residues. These 53-kDal proteins are therefore evolutionarily highly conserved, independent of whether they originate from virally or chemically transformed cells. The NH2-terminal sequence and the protein chain as a whole are not hydrophobic; however, some unexpected residue distributions were observed. Comparisons with other proteins reveal no clear sequence similarity with known tumor antigen structures, homologous immunoglobulins, or some other proteins of known sequence. Epstein-Barr virus-determined nuclear antigen also appears to have a different NH2-terminal sequence. Thus, the results show that the 53-kDal proteins represent a unique protein type with little species variation; this finding suggests that these proteins must perform an important common function in different transformation systems.

Amino Acid Sequence↗
PubMed1982

Effects of n-butyrate on Epstein-Barr virus-carrying lymphoma lines.

n-Butyrate has been shown to induce Epstein-Barr virus (EBV) antigen synthesis in certain EBV-carrying lymphoma lines (Luka et al., 1979). We have studied the effect of n-butyrate on two EBV-positive Burkitt lymphoma lines by immuno-fluorescence and electron microscopy. In the producer line P3HR-1, the drug induced not only early antigen (EA) and virus capsid antigen (VCA) synthesis, as shown before, but also increased the number of cells containing virus particles. The transition from VCA expression to the formation of virus particles was much more effective in treated cells than in EBV antigen-producing cells of the same line. The productive cycle was associated with the development of characteristic morphological changes. In the non-producer Raji cells, n-butyrate induced EA in only a minor fraction of the cells. There were, however, clear signs of differentiation in the direction of plasma cells. Two days after the addition of n-butyrate 80% of the Raji cells could be classified as plasmablasts. After 72 h, 20% of the cells appeared as typical plasma cells.

Antigens, Viral↗
PubMed1982

Compartment model of prenalterol.

In previous pharmacokinetic studies in healthy subjects the time course of plasma concentration of prenalterol was described by a short distribution phase (alpha-phase) with a mean half-life of about 8 minutes and an elimination phase (beta-phase) with an average half- life of about two hours [1, 2]. The aim of this joint study was to check the pharmacokinetic data obtained after intravenous single dose administration with the computer program TOPFIT [3] using different compartment models and to test the predictive power of the chosen kinetic model for plasma concentration data after repetitive intravenous prenalterol dosing.

Adrenergic beta-Agonists↗
PubMed1982

Metabolic effects of prenalterol in healthy volunteers.

The effect of the beta 1-adrenoceptor agonist prenalterol on the metabolic parameters glucose, lactate, free fatty acids and serum-insulin were studied in 8 healthy volunteers. Prenalterol was administered intravenously in geometrically increasing doses from 5 to 80 micrograms/kg. The only metabolic effect of prenalterol that could be proved was a significant dose-dependent rise in FFA-concentration. The stimulating effect of prenalterol on lipolysis was significant not only at the time points of maximal effect following each injection, but also 30 min later. Serum-insulin-concentration and glucose- and lactate-concentration failed, however, to show a significant rise after prenalterol administration. This behaviour is a strong indication of a beta 1-selectivity of prenalterol over the whole dose range given.

Adrenergic beta-Agonists↗
PubMed1982

Quantitative comparison of Epstein-Barr virus receptor expression on sIgM and sIgG cell lines and B-cell lymphoma biopsies.

Over 50 B-cell derived lines and B-cell lymphoma and leukemia biopsies were screened for expression of the Epstein-Barr virus (EBV) receptor. The 13 sIgM-positive lines bound more than five times as much virus as the six IgG lines. Among the biopsies, the 17 sIgM, 11 sIgM and sIgD, and seven sIgG expressing biopsies were further divided according to expression of the C3 receptor. C3 receptor-positive biopsies, which expressed sIgM alone or along with sIgD, had the largest subpopulation of cells which expressed the EBV receptor (EBVR). C3 receptor-negative biopsies only expressed the EBVR on half as many cells as their C3 receptor-positive counterparts. However, the relative number of EBVR on individual EBVR-positive cells was independent of C3 receptor expression. Within the sIgG class, both C3 receptor-negative and positive cells expressed equally low levels of EBVR, both in terms of subpopulation and relative number of EBVR per positive cell. These results suggest that subpopulation expression of the EBV receptor is related to the C3 receptor but that relative number of receptors per cell is associated with sIg phenotype.

B-Lymphocytes↗
PubMed1982

Two large virion envelope glycoproteins mediate Epstein-Barr virus binding to receptor-positive cells.

The four major Epstein-Barr virion envelope components were separated by column chromatography and reconstituted into artificial liposomes. These liposomes were tested for their ability to bind selectively to Epstein-Barr virus receptor-positive cells. Only when the two high-molecular-weight glycoproteins, VE1 and VE2, were present together was a stable binding complex formed. The addition of the other virion envelope components did not increase the levels of binding. This binding was inhibited by unlabeled viable virions and by neutralizing antisera, which recognized the two components. Adsorption of viable virus was also eliminated by the antisera. The enzyme susceptibility pattern of the cell-liposome interaction is similar to that of the virus-cell interaction, thus confirming the specificity of the binding site. A model for Epstein-Barr virus binding in which VE1 and VE2 coordinately recognize the same binding site is presented.

Antibodies, Viral↗
PubMed1982

Immunization against the polyoma virus-induced tumor-specific transplantation antigen by early region mutants of the virus.

To investigate the relation between the polyoma tumor-specific transplantation antigen and the virus-coded proteins, mice were immunized by inoculation of a variety of viable polyoma virus mutants and then challenged with polyoma virus-induced tumors. Two classes of early region mutants were used. One class produces a normal small T-antigen and truncated middle and large T-antigens. The second class (hr-t mutants) forms a normal large T-antigen together with N-terminal fragments of small and middle T-antigens. All mutants, transforming as well as nontransforming, induced protection against polyoma virus tumors. However, there were quantitive differences between the mutants. The finding that an hr-t mutant could induce tumor rejection suggests that full-length middle and small T-antigens are not necessary for the induction of this response. Since intact middle T-antigen is the only virus-coded protein known to associate with the plasma membrane, the possibility must be considered that the polyoma virus tumor-specific transplantation antigen consists of cellular components.

Animals↗
PubMed1982

Immunochemical characterization of EBV antigens detected by double immunodiffusion.

Double immunodiffusion (Ouchterlony) tests gave regularly positive reactions when extracts of [35S]-methionine-labeled, n-butyrate-induced P3HR-1 cells were allowed to react with serum pools with high Epstein-Barr virus (EBV) antibody titers from Burkitt lymphoma or nasopharyngeal carcinoma patients, but not with EBV antibody-negative sera. Similarly prepared extracts of noninduced P3HR-1 cells gave no precipitation lines with the antibody-positive sera. The composition of the precipitates was analyzed by SDS-PAGE and compared with immunoprecipitates obtained by indirect immunoprecipitation in solution. Three lines precipitated on the Ouchterlony plate were analyzed; these lines were located at close (a), intermediate (b), and distant (c) positions in relation to the antigen well. Precipitate (a) contained polypeptides with molecular weights of 165,000 (165K), 152K, 138K, 134K, 103K, and 55K. Precipitate (b) contained 152K and 138K as the major components, while 55K was relatively underrepresented. Precipitate (c) contained 90K and 55K as major components, while 152K was a minor component. The method is suitable for the study of possible subtype differences between defined antigenic components of the early and late EBV-determined antigen complexes.

Antigens, Viral↗
PubMed1982

Human lymphoma-lymphoma hybrids and lymphoma-leukemia hybrids. I. Isolation, characterization, cell surface markers, and B-cell markers.

Four new somatic cell hybrids were obtained by fusion of various Burkitt's lymphoma (BL)-derived cell lines that had different selective markers: Raji-P3HR-1, Daudi-Raji, and a P3HR-1-P3HR-1 "autohybrid" derived from two P3HR-1 sublines. In addition, a hybrid was obtained between the Daudi (BL) line and the human leukemia cell line K562. The hybrids were extensively characterized by means of chromosome, isozyme, and HLA surface markers. The phenotypic differences between the parent cell lines allowed some conclusions with respect to the expression of latent Epstein-Barr virus (EBV) genomes, C3 and EBV receptors, and of immunoglobulin and beta 2-microglobulin-HLA expression as well as the influence of the leukemia cell (K562) genome on B-cell properties in the Daudi-K562 hybrid. B-cell and differentiated markers of these hybrids were characterized. High-level expression dominated for the marker C3 and EBV receptors, which showed a good correlation coefficient of 0.84, as was true for Fc receptors and surface immunoglobulin. The Daudi-K562 hybrid showed loss of all B-cell markers but retention of the leukemia cell markers (e.g., hemoglobin synthesis).

Animals↗
PubMed1982

Human lymphoma-lymphoma hybrids and lymphoma-leukemia hybrids. II. Epstein-Barr virus induction patterns.

In addition to the spontaneous expression of markers of the early and late phases of the viral cycle [Epstein-Barr virus (EBV), early viral cycle antigens (EA), and viral capsid antigen (VCA)] by a Panel of hybrid cell lines derived by fusion of human hematopoietic cell lines, the induction of these markers by three chemical inducers [5-iodo-2'-deoxyuridine, the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA), and sodium butyrate] were analyzed. A variant of the prototype producer of lytic EBV, P3HR-1 (PICAT) was observed to show consistent low spontaneous and induced production of EA and VCA as compared to the P3HR-1 line from which it was derived. An "autohybrid" (PICATPO-1) between these two lines showed a low production of VCA. Hybrids between Raji and P3HR-1 sublines (RUD-PICAT-1 and RUDPUT-2) showed reduced expression of EBV antigens. Both hybrids were capable of VCA expression, in contrast to the Raji parent that expressed EA but not VCA. A new Raji-Daudi hybrid (DITRUD-1) expressed spontaneous and induced EA and VCA at levels intermediate between its two parents. A different type of hybrid was derived from a Daudi subline and the K562 leukemia cell line (DUTKO-1) and was found to be capable of spontaneous as well as induced EA and VCA expression. Both DUTKO-1 and DITRUD-1 were similar to Daudi in their induction profile in respect to a very low response to TPA.

Animals↗
PubMed1982

Further studies on the relationship between allotransplantability and the presence of the cell surface glycoprotein epiglycanin in the TA3-MM mouse mammary carcinoma ascites cell.

The loss of strain specificity in the TA3-St mammary carcinoma ascites cell during passage in ascites form in diseased syngeneic strain A mice was confirmed by the observation that TA3-MM/2 ascites cells were capable of progressive growth in 7 foreign mouse strains. Support for the hypothesis that allotransplantability in the TA3-MM lines may be due to masking of cell surface histocompatibility H-2a antigens by large glycoprotein (epiglycanin) molecules was obtained from the finding that the capacity of the TA3-MM/2 ascites cell to absorb anti-H-2a antibody was several times less than that of the parent TA3-St ascites cell, although it was greater than the capacity of the non-strain-specific TA3-Ha line. Further support for the location of epiglycanin molecules at the cell surface was obtained by transmission electron-microscopic observation of a high concentration of filamentous structures, usually 20-40 nm long, but often extending to 200-300 nm length at the TA3-MM/2 cell surface. Similar structures were also observed at the TA3-Ha cell surface but were not observed at the surface of the TA3-St ascites cell, a cell known to contain no detectable epiglycanin. Epiglycanin molecules, obtained by two different methods from TA3-MM/1, TA3-MM/2, and TA3-Ha ascites cells, were shown to be similar with respect to their capacities to inhibit the binding of 125I-labeled epiglycanin to its antibody, induced in the rabbit by TA3-Ha ascites cells in a radioimmunoassay.

Animals↗