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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 757 records · Page 42Linked to original sources
PubMed1983

The Epstein-Barr virus-determined nuclear antigen: a previously identified 48K component and higher-molecular-weight forms of the antigen are structurally related.

The Epstein-Barr virus(EBV)-determined nuclear antigen (EBNA) was purified from a variety of EBV-carrying nonproducer cells. Antigen was detected by Western blotting and subsequent visualization of complexes with antiserum/protein A. All cell lines contained several EBNA components, ranging in molecular weight from 48,000 (48K) to 73K. Even higher-molecular-weight forms of EBNA-positive immunoreactivity were detected, but in much lower yield and in only some preparations (81K in Raji; 120K in Namalva and Raji). Preparations in which the 48K, 65K, 70K, or 73K polypeptides predominated had amino acid compositions with largely similar distributions for most residues. The preparations also yielded similarly sized large fragments upon proteolytic treatments. These findings suggested that all structures are related and that the 48K component may be a part of, or a degradation product from, the larger 65-73K components.

Amino Acids↗
PubMed1983

Epstein-Barr virus and tumor promoters.

Epstein-Barr virus (EBV) can be maintained in lymphoblastoid cell lines. The infection is usually latent and the lack of a fully permissive cell have made the studies of the lytic functions of the virus difficult. In these cell lines virus production can be induced by addition of phorbol esters, n-butyrate, or nucleotide analogues. These compounds have been used to study EBV in several aspects: the latent and lytic functions of EBV. The possible use of this model system as an in vitro assay for tumor promoters. The mechanism behind the tumor promoter and n-butyrate induced activation of EBV.

B-Lymphocytes↗
PubMed1983

Studies on the B lymphoblast antigen No. 1 (BB-1) on a series of Burkitt lymphoma lines differing in the expression of the EBV/C3 receptor complex.

In the Jijoye-P3HR-1 family of Burkitt lymphoma sublines, the expression of the B lymphoblast-1 antigen, BB-1, identified by the monoclonal antibody described by Yokochi and colleagues, was found to be strictly related to the expression of the EBV receptor/C3 receptor (EBVR/C3R) complex. It was absent on the receptor-negative P3HR-1 line, present in the original receptor-positive Jijoye line, and reappeared in nonvirus producer sublines derived from P3HR-1 itself. We suggest the BB-1 antigen is related to the EBVR/C3R complex in the Jijoye family, either at the level of genetic or epigenetic determination or at the level of steric interaction on the cell membrane. In all probability, however, the BB-1 antigen is not identical to the receptor itself. It is also clear that a similar relationship does not necessarily apply to other cell lines. In the course of the studies, it was accidentally discovered that propagation of the P3HR-1 cells on newborn instead of fetal calf serum induces the concomitant expression of EBV receptors, C3 receptors, and the BB-1 antigen. The mechanism of this induction is obscure; it does not appear to be related to any significant change in the frequency of virus-producing cells.

Animals↗
PubMed1983

Human monoclonal antibodies to a genus-specific chlamydial antigen, produced by EBV-transformed B cells.

Stable B cell lines producing human monoclonal antibodies to Chlamydia were established from salpingitis patients in the early convalescence phase. The antibody-producing cells were immortalized by Epstein Barr virus (EBV) transformation. Specific antibody-secreting clones were enriched by a stepwise microtiter plate cloning procedure. The selected B cell clones showed stable antibody production for more than 1 yr in continuous culture. Serologic specificity was demonstrated by micro-immunofluorescence (micro-IF) tests against a panel of Chlamydia reference strains. The antibodies were of the IgG1 subclass, and complement fixation could be demonstrated for one clone. There was no cross-reactivity against a large number of other bacteria. The monoclonal antibodies are directed against a common genus-specific surface antigen of the Chlamydia organism. Infected McCoy cells showed a brilliant, punctuated fluorescence surrounded by an inclusion membrane. Compared with conventional antisera, the monoclonal antibodies showed a clearer fluorescence pattern with very low background.

Antibodies, Bacterial↗
PubMed1983

Epstein-Barr virus-specific leukocyte migration inhibition reaction with tumor biopsy extracts: correlation with the presence of viral DNA.

The Epstein-Barr virus (EBV)-specific leukocyte migration inhibition (LMI) reaction was used to detect EBV antigens in human tumor biopsies in parallel with nuclei acid hybridization for EBV DNA. None of six EBV DNA-negative tumors gave any significant LMI reaction. Fourteen of 17 EBV DNA-positive tumors gave a significant difference between the migration of leukocytes from EBV-seropositive versus -seronegative donors. One tumor gave a borderline reaction. The two-LMI-negatives in this group had only a marginal EBV DNA content. It is suggested that the EBV-specific LMI test may be useful for detecting EBV genomes in tissue and tumor extracts.

Animals↗
PubMed1983

Induction of an activated b lymphocyte-associated surface moiety defined by the B2 monoclonal antibody by ebv conversion of an EBV-negative lymphoma line (Ramos): differential effect of transforming (B95-8) and nontransforming (P3HR-1) EBV substrains.

The expression of the B2 antigen, defined by a monoclonal antibody, was studied on Burkitt lymphoma lines, lymphoblastoid cell lines, leukemia and myeloma lines, hybrids between different hemapoetic cell lines, and EBV-converted sublines of originally EBV-negative, B2-negative B lymphoma lines. In confirmation of earlier results, the expression of B2 was found to be restricted to a relatively narrow portion of the B cell maturation pathway. Non-B cell-derived lines were uniformly negative. Hybrids derived from the fusion of highly B2-positive and B2-negative or low B2 expressing lines of B cell origin were B2-positive. In contrast, fusion of B2-positive Burkitt lymphoma lines with the primitive human erythroleukemia line K562 resulted in the complete extinction of B2 expression. These findings are in line with the expected behavior of a B cell differentiation marker. EBV conversion of the EBV-negative, B2-negative Ramos lymphoma line by the transforming B95-8 substrain of the virus regularly induced the expression of B2, whereas conversion with the nontransforming P3HR-1 substrain had no such effect, in spite of the continued presence of EBV-DNA and EBNA in both types of EBV-converted sublines. The possibility that B2 induction may reflect the action of the transforming gene(s), present in B95-8 but deleted from the P3HR-1 virus, and the implications of this possibility for the functional mapping of the EBV genome are discussed.

Animals↗
PubMed1983

Serum anti-EBV IgA is inversely related to tumor infiltration by surface IgA positive lymphocytes in nasopharyngeal carcinoma.

The mean number of tumor-infiltrating lymphoid cells with surface IgA was moderately higher in primary nasopharyngeal carcinoma (NPC) than in their neck gland metastases or in other head and neck tumors. Within the group of primary NPC, patients with large numbers of IgA positive infiltrating cells had a significantly lower mean IgA antibody titer to Epstein-Barr viral capsid antigen. It is unlikely therefore that the unique, frequent elevation of this antibody titer in NPC is due to stimulation of infiltrating IgA positive lymphoid cells among the virus-containing epithelial tumor cells.

Antibodies, Viral↗
PubMed1983

Isolation of an effective debriding agent from the stems of pineapple plants.

The stem of the pineapple plant contains, in addition to a number of proteases, particularly bromelain, a non-proteolytic component which is responsible for the complete bridement of experimental burns by an "enzymatic dissection" between the viable native and the non-viable denatured burn tissue. With very little scraping, using a tongue depressor, all of the eschar can be removed and a bed suitable for grafting results. This "Escharase" has a molecular weight of 45,000 daltons and is a trimer made up of three identical subunits weighing 15,000 daltons each; it has an isoelectric point of pH 6.04 and has no hydrolytic enzyme activity against normal protein substrates or various glycosaminoglycan substrates. It can be concentrated by membrane ultrafiltration in a molecular weight range between 30,000 and 50,000 daltons and be purified by isoelectric focusing. The biological activity of the Escharase is not dependent on sulfhydryl groups nor upon the contaminating bromelain activity. The Escharase activity varies enormously from preparation to preparation, but the ultrafiltration procedure tends to concentrate Escharase activity to a fairly constant amount.

Animals↗
PubMed1983

Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings.

Neoplastic populations from 25 cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this disease and the relationship, if any, to various clinical parameters. Intrinsic to this study was the expression of a number of B-cell antigens defined by monoclonal antibodies. These included antibodies to B1 and B2, both expressed exclusively on B lymphocytes, but with the latter probably restricted to a narrow window of differentiation, BB-1 and LB-1, both markers of activated lymphocytes, and 38.13, a monoclonal antibody raised against and recognizing an epitope expressed on Burkitt lymphoma cells. While the patterns of reactivities were complex, the cases could be classified into various groups on the basis of the phenotypes revealed. These were termed "pre-B," "early-B," "intermediate-B," "mature-B," and "secretory-B" from their patterns of immunoglobulin (Ig) isotype expression and their capacity to secrete Ig in short-term culture. Although B1 was detected on neoplastic cells from all but one case, its intensity of expression varied markedly, being strongest on the "mature-B" and "secretory-B" cases and weakest on the "pre-B" type. The expression of B2 was essentially restricted to the "intermediate-B," "mature-B," and "secretory-B" cases and was usually, but not invariably, accompanied by the coexpression of surface IgM and IgD. While expression of BB-1 was restricted to a few cases with mature features, LB-1 was more frequently detected and found predominantly on "intermediate-B" and "mature-B" cases. The 38.13 antibody was found to react weakly with a number of the populations coexpressing IgM and IgD. The export of large amounts of whole Ig was restricted to three "secretory-B" cases all of which were associated with a serum M-component corresponding to the Ig isotype secreted in vitro. In contrast, the secretion of free Ig light chains was a consistent feature of all B-LL, and the amounts detected did not vary considerably between the different types. No correlation between immunologic cell-type and the stage of the disease was apparent. Classification of the cases into "true" B-chronic lymphocytic leukemia and immunocytoma similarly revealed no strict association of these histopathologic entities with any particular phenotypic group, although those cases with the more mature features tended to be immunocytomas. The findings are discussed within the context of normal B-cell differentiation pathways.

Antibodies, Monoclonal↗
PubMed1983

Effects of ketotifen on cholinergic induced airway obstruction.

By repeated inhalant carbachol provocation tests on 13 normal and 13 asthmatic subjects, we investigated the effect of ketotifen (as compared with placebo) on the cholinergic responsiveness of the airways. In normal subjects, ketotifen reduced the slope of the linear regression lines, calculated from the airway resistance vs. the intra-pulmonary deposited amount of carbachol (reactivity). By adding a single dose of 80 mg of propranolol the bronchial reactivity was increased. Neither placebo nor ketotifen pretreatment altered the response to propranolol. In asthmatic subjects, the reactivity of the airways to carbachol was reduced after 7 days of ketotifen treatment. Propranolol increased the pre-challenge airway resistance values, and ketotifen did not reduce this bronchoconstrictive action. We could not observe any influence of ketotifen on the potentiation of the carbachol-induced bronchoconstriction. We conclude that ketotifen on the potentiation of the carbachol-induced bronchoconstriction. We conclude that ketotifen reduces the bronchial reactivity as assessed by carbachol inhalation in normal and in asthmatic subjects.

Adolescent↗
PubMed1983

[Modification of nocturnal heart rhythm disorders using oxygen therapy in patients with chronic obstructive lung disease].

In 14 patients with chronic obstructive lung disease, the effect of nocturnal oxygen therapy was evaluated. The mean flow of 100% oxygen was 2 l/min. We registered the transcutaneously measured blood gases over 10 h, beginning at 8 p.m. while patients were breathing air, the lowest value of PO2 was mean = 45 mm Hg, and while they were breathing oxygen it was mean = 57 mm Hg. Continuous electrocardiograms showed a reduction of supraventricular arrhythmias, from 180 premature beats over 10 h during inhalation of air to 86 during oxygen inhalation. In each of the 13 patients we found a decrease in frequency of premature ventricular beats (from mean = 141 to mean 54 over 10 h, i.e., from 100% to 25.5% +/- 17.1%. During the 2 h of lowest oxygen saturation, the frequency of ventricular arrhythmias was increased. We expected 20% and registered 38.8%.

Arrhythmias, Cardiac↗
PubMed1983

Genetic control of in vitro NK-activity and in vivo resistance to tumors.

Natural Killer (NK) cells are lymphocyte like cells which lack conventional B- and T-cell characteristics, and have the ability to rapidly kill certain tumor cells in vitro. Analysis of the genetic control of NK-activity in mice have provided several models to test the in vivo role of NK-cells in defence against neoplasia. Studies of certain F1-hybrid and backcross combinations have revealed a correlation between H-2 linked in vivo resistance and in vitro NK-activity against semisyngeneic transplantable tumors. The beige (bg) mutation in C57B1 mice causes a partial impairment of NK-activity, and can therefore serve to evaluate whether NK-cells can contribute to resistance against syngeneic tumors in the normal intact host. We have recently studied natural resistance against the ascitic lines of one chemically and two virally induced syngeneic leukemias in C57B1.bg/bg mice and their phenotypically normal heterozygous littermates. S.c. threshold inocula of all three leukemia lines grew faster and caused death earlier in bg/bg than in +/bg mice, and two of the lines were rejected completely at a significantly higher frequency in +/bg control animals. The +/bg mice also eliminated 125I-IdUrd-labelled leukemia cells at a faster rate than bg/bg mice, as measured by pulmonary, hepatic and splenic radioactivity retained 14-30 h after i.v. injection. The bg mutation was also possible to study in T-cell free mice, by combining it with the nu mutation on a C57B1 background. The NK-activity of such beige-nude mice was found to be partially impaired compared to nude (non-beige) or wild type animals, but higher than that of beige (non-nude) mice. Our results suggest that NK-cells may be responsible for elimination of small numbers of tumor cells in the intact syngeneic host. The further use of beige and beige-nude mice in studies of transplanted and primary, autochthonous tumors will be discussed.

Animals↗
PubMed1983

[Formulation and clinical test of a novel mucosal adhesive ointment].

A novel mucosal adhesive ointment on the base of partly neutralized polymethacrylic acid methyl ester (Eudispert) was formulated. The flow curves of the ointment show a pseudoplastic quality without any thixotropic effect. The viscosity depended on the kind and concentration of the base. During the clinical studies the pure ointment as well as a tretinoin-preparation for a lichen planus treatment showed no local irritation, good mucosal adhesion and suitable way of application for the patients.

Acrylic Resins↗
PubMed1983

Physicochemical and morphological characterization of a new allotransplantable mammary carcinoma ascites subline, TA3-St/ticol/-A.

The TA3-St/ticol ascites cell (I), immunoselected from the strain-specific TA3-St mammary carcinoma ascites cell of the strain A mouse for decreased H-2a antibody-binding capacity, underwent a spontaneous transition in vivo to a new cell line, TA3-St/ticol/-A (II). Line II was more allotransplantable than was the parental line (line I), and its absorptive capacity for anti-H-2a antibody was manyfold less than line I. Disruption of line II cells by lyophilization did not increase the absorptive capacity, in contrast to its marked enhancement in the TA3-Ha ascites cell under similar conditions. An explanation for the enhanced allotransplantability of line II may be related to either a loss of H-2a antigens or altered macromolecular structures at the cell surface: sialic acid, consisting of 93% N-glycolylneuraminic acid for line II and 9% for line I; altered chemical structures of cell surface glycoproteins, particularly a high-molecular-weight glycoprotein present in much greater proportion in line II than in line I; a macromolecular complex released by a protease from line I, but not line II; and I being agglutinable by concanavalin A, but not line II. Electron microscopy showed line II to be more pleomorphic and less rounded than was line I. Under high-resolution electron microscopy, the cell surfaces of both allotransplantable cells, lines II and I, exhibited thin filamentous material, material not observed at the surface of the nonallotransplantable TA3-St ascites cell.

Animals↗
PubMed1983

Cell surface characteristics of an allotransplantable TA3 ascites subline resulting from a process of immunoselection.

Comparison of the cell surface characteristics of the parental strain-specific TA3-St ascites cell (I) of the strain A mouse and the more allotransplantable TA3-St/ticol ascites cell (II), immunoselected for reduced absorption of anti-H-2a antibody from Cell I, revealed the following. Cell II, like Cell I, possessed no detectable epiglycanin at its surface, as neither cell absorbed more than 0.5% as much of the antiepiglycanin antibody as was absorbed by the epiglycanin-containing allotransplantable TA3-Ha ascites cell. Tritium-labeled glycoproteins, with polyacrylamide slab gel electrophoresis with sodium dodecyl sulfate and with isoelectric focusing of detergent-treated cells, exhibited marked quantitative differences, but qualitative differences were not established. Glycopeptides cleaved from each cell by proteolysis and fractionated by gel filtration gave similar elution profiles, and the column fractions possessed similar carbohydrate and amino acid compositions. Less sialic acid (170 micrograms/10(9) cells) was removed by neuraminidase from Cell II than from Cell I (270 micrograms/10(9) cells), and the compositions (9% N-glycolylneuraminic acid for Cell II and 20% for Cell I) were different. Transmission and scanning electron microscopy showed rough irregular folds and ridges on the surfaces of each cell, but Cell II appeared more pleomorphic and less rounded than did Cell I. High-resolution transmission electron microscopy showed filamentous material at the surface of Cell II, but not at the surface of Cell I.

Amino Acids↗
PubMed1983

[Livedo reticularis: dermatologic alarm signal in cold agglutinin disease].

A hitherto healthy adult man developed paroxysmal cold agglutinin disease following an infection of the upper respiratory tract with mycoplasma pneumoniae. Despite continuous blood exchange he died of massive intravascular hemolysis and uremia after 5 days. A presenting striking symptom of this rapidly fatal disease was the acute onset of generalized livedo reticularis. The disease was caused by the rare anti Pr-cold agglutinins which are capable of eliciting hemolysis even in low titers and, in the present case, at body temperature.

Adult↗