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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 739 records · Page 41Linked to original sources
PubMed1983

The role of humoral immunity and the contribution of the F1 anti-parental effect in the rejection of a Moloney leukemia virus-induced lymphoma graft.

Antibody and rejection responses against the Moloney leukemia virus-induced YAC lymphoma of A strain origin were found to be weak in A but high in (A X C57Bl)F1 hybrids. (A X C57Bl) X A backcross mice typed for expression of H-2 antigens were investigated for these responses in order to ascertain the importance of the H-2 phenotype of the host and the development of antibodies for rejection of the tumor cells. With an LD50 challenge inoculum in immunized backcross mice, the presence of anti-YAC antibodies appeared to be important for protection against the outgrowth of the tumor, particularly in the H-2a mice. None of them survived, unless antibody-positive. On the other hand, a proportion of the H-2 heterozygous mice rejected the tumor in the absence of antibodies. In the antibody-positive group a higher number of H-2 heterozygous mice survived than of H-2 homozygous mice. The results showed that both humoral and cellular responses are important for the rejection of an antigenic lymphoma and indicate the contribution of an F1 anti-parental component in the latter.

Animals↗
PubMed1983

Correlation between lymphocyte-mediated auto-tumor reactivities and clinical course. I. Evaluation of 46 patients with sarcoma.

T-cell-enriched blood lymphocyte populations from 24 osteosarcoma and 22 soft-tissue sarcoma patients were assayed at the time of surgery for proliferative response to, and/or cytotoxic potential against autologous tumor cells. Tumor-free period and survival of the patients were correlated with the results obtained in the in vitro tests. The observation time was between 18 and 118 months (mean 62) for the osteosarcoma patients and between 18 and 72 (mean 42) for the patients with soft-tissue sarcoma. In both groups tumor-free period and survival were longer for those individuals who had auto-tumor reactivity. In the non-reactive group, all patients died within 3 years. Almost all patients had cytotoxicity against K562.

Adolescent↗
PubMed1983

Correlation between lymphocyte-mediated auto-tumor reactivities and the clinical course. II. Evaluation of 69 patients with lung carcinoma.

T-cell-enriched lymphocyte populations of 69 lung carcinoma (44 squamous cell, 23 adeno-, and two large cell carcinoma) patients were investigated at the time of surgery for proliferative response to, and/or cytotoxic potential against, freshly separated autologous tumor cells. Tumor-free period and survival time of the patients were correlated with the reactivity obtained in the in vitro tests. The observation time varied between 20 and 78 months (mean 52). Tumor-free period and survival time were longer and survival rate higher in the group with lymphocyte reactivity toward their tumors. In the non-reactive group, all patients but one died within 3 years. Almost all patients had cytotoxic lymphocytes against K562, the three who did not belonging to the category with short survival time.

Adenocarcinoma↗
PubMed1983

Genetic studies on natural resistance to Moloney lymphoma (YAC) isografts. I. Introduction of a non-H-2-linked resistance gene on strain A/Sn background.

YAC is a Moloney-virus-induced lymphoma of strain A/Sn origin that is highly sensitive to natural killing (NK) in vitro and NK-mediated hybrid resistance in vivo. Previous studies have shown that hybrid resistance is under polygenic control that includes both H-2-linked and non-H-2-linked factors. For further analysis on the genetics and immunology of hybrid resistance, we are at present developing congenic resistant lines on an A/Sn strain background. Following an outcross to a strain that conveys strong hybrid resistance on the F1 offspring, the mice are challenged with small viable inocula of YAC. Survivors are backcrossed to A/Sn. This is followed by repeated YAC challenge and backcrossing. We now report the successful establishment of a first resistant strain, designated A.LRA. It is relatively resistant to small inocula of YAC cells due to a single, non-H-2-linked dominant gene introduced from the C57L strain.

Animals↗
PubMed1983

Phorbol 12,13-dibutyrate (P(Bu)2)-treated human blood mononuclear cells bind to each other.

Treatment of human blood mononuclear cells with nanomolar concentrations of phorbol 12,13-dibutyrate (P(Bu)2) induced their aggregation. The phenomenon was seen within a few minutes and reached its maximum manifestation after 20 min. At this time, 20-30% of unfractionated and nylon wool-passed mononuclear leukocytes were in the aggregates. The influence of pretreatment with 2-deoxyglucose, NaN3, EDTA, cyclohexamide, or incubation at 4 degrees C on the phenomenon indicated that it is energy and temperature dependent, requires the presence of extracellular divalent cations, and is independent of protein synthesis. Nonaggregating 2-deoxyglucose-and NaN3-pretreated cells could still bind [3H]P(Bu)2 which rules out the possibility that the phorbol ester molecule acts as a bridge between the aggregated cells. Seventeen percent of the P(Bu)2-treated T-cell population bound untreated autologous and allogeneic cells. The binding property has a certain species specificity because only 4% of the cells interacted with mouse lymphocytes. At the ultrastructural level, the intercellular binding showed broad areas of surface contact (both between lymphocytes and lymphocyte-monocyte) and "trapping" by surface processes was not seen. Aggregated cells did not show cytopathogenic changes.

Animals↗
PubMed1983

Low-molecular-weight (61K) mu chain in P3HR-1 cells and various derived somatic hybrids.

The expression of a truncated 61K mu chain in the Burkitt lymphoma lien P3HR-1 and a derived ouabain and TG-resistant subline, PUT, and in various somatic cell hybrids with PUT as one of their parents is described. Both PUT and P3HR-1 contain intracellular mu and kappa chains, but express no membrane immunoglobulin. Immunoprecipitation of 14C-labeled amino acid or [3H]glucosamine-labeled P3HR-1 extracts with anti-mu serum brought down the same 61K mu chain. Anti-light-chain sera did not precipitate the truncated mu chain. P3HR-1 is a clonal derivative of the Burkitt lymphoma (BL) line Jijoye. The parental Jijoye line is membrane-IgM positive and contains two normal-sized mu chains. Both are precipitable by anti-mu and anti-kappa sera. In addition, anti-mu also precipitated a 61K mu chain. A 61K mu chain was also identified in the following somatic hybrids: PICATPO, an autohybrid of two different P3HR-1 sublines, PUTRAL and PUT/ARH-77, derived from the fusion of PUT with the membrane-IgG-positive BL line Rael and the lymphoblastoid cell line (LCL) ARH-77, respectively, and the HP-1 (PUT/HL-60) hybrid, derived from the fusion of PUT with the granulocytic leukemia line, HL-60. The 61K mu chain could not be detected in some other BL/BL hybrid combinations, namely RAMPUT (PUT/Ramos) and NAMPUT (PUT/Namalva). The anti-light-chain serum (lambda or kappa) had no detectable effect on the truncated 61K mu chain in any of the cases tested, suggesting a lack of assembly between the 61K mu chain and the light chain.

Cells, Cultured↗
PubMed1983

In vitro differentiation of chronic lymphocytic leukaemia cells with a small pre-B-like phenotype.

Neoplastic populations from three cases of chronic lymphocytic leukaemia (CLL) which had features consistent with a maturation arrest at the 'small pre-B' stage are described. The cells were small and rounded with a scanty cytoplasm and stained for mu heavy chains but not light chains intracellularly while surface immunoglobulin (SmIg) was either undetectable or expressed sparsely on a minority of cells. Other features included the weak expression of B1, a lack of B2, an absence of the common acute lymphoblastic leukaemia antigen (cALLA), the presence of Ia and a variable expression of the receptors for Fc gamma and C3. Successful induction of in vitro differentiation in all three of the cases allowed the identification of a sequence of events whereby cells initially containing isolated mu heavy chains in their cytoplasm, on commencing light chain synthesis, begin to express stable SmIgM while surplus light chain is secreted without any association with the heavy chain. Although this is followed ultimately by the secretion of intact Ig effector molecules, the export of surplus light chains is apparently maintained throughout the developmental sequence. These findings are discussed with particular emphasis on their relation to normal B-cell maturation.

Aged↗
PubMed1983

Lymphocyte-mediated lysis of autologous and allogeneic B-cell lines in man.

The lytic potential of human blood lymphocytes was assayed against autologous and allogeneic EBV-transformed B-cell lines (LCL). The effects--if present--were very weak. Short-term interferon (IFN) treatment of the lymphocytes induced cytotoxic potential which could be manifested against autologous and allogeneic LCL. The sensitivity of the targets increased after superinfection with the P3HR-1 strain of EBV. Thus the strongest lytic effects were obtained with IFN-treated lymphocytes acting on EBV superinfected targets. Individuals with and without previous EBV encounter reacted against autologous LCL, indicating that the lysis did not represent an EBV-specific cellular memory. No evidence for alloantigen recognition emerged from the tests.

B-Lymphocytes↗
PubMed1983

Robertsonian translocation studies on the significance of trisomy 15 in murine T-cell leukemia.

G-banding analysis was carried out on T-cell leukemias induced in various Robertsonian mice by 7,12 dimethylbenz(a)anthracene (DMBA), N-methyl-N-nitrosourea (MNU), or Moloney virus. Trisomy 15 was the only regularly seen chromosome aberration whether chromosome No. 15 was involved in a centric fusion or not. Translocated No. 15 chromosomes were not preferentially duplicated. These results show that it is not the translocated state of chromosome No. 15 but the genetic content that is of importance in leukemia development.

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

Epstein-Barr virus markers in a series of Burkitt's lymphomas from the West Nile District, Uganda.

In an epidemiological survey in the West Nile District of Uganda, 70 pathologically confirmed BL cases were detected over a 5-yr period; this corresponded to an annual incidence rate of 1.6 per 100,000 general population or about 5 per 100,000 children in the age group 5-14 yr. Of the confirmed cases which were examined by EBV/DNA molecular hybridization, 96% were found to contain an average of 38 EBV genome equivalents per tumour cell, whereas none of the examined unconfirmed cases did. Duplicate hybridization assays in two laboratories were in close agreement. Serological testing showed that 91% of the confirmed BL cases had elevated EBV/VCA titres (greater than or equal to 160) and 64% were EA(D)-positive (greater than or equal to 10). Most of the cases with high EBV/genome content had high VCA titres, but there was a poor correlation between the two parameters among all cases. This study confirms that in high BL incidence areas the association between EBV and this lymphoma is almost constant, whereas it is exceptional in low-incidence areas. This further supports the aetiological implication of EBV in the endemicity of this tumor in equatorial Africa.

Adolescent↗
PubMed1983

Antibodies of predetermined specificity for the NH2 terminus of a cellular protein p53 react with the native molecule: evidence for the presence of different p53s.

Two synthetic peptides corresponding to residues 1-20 and 10-20, respectively, of one type of a cellular protein called "p53" have been linked to a carrier protein and injected into rabbits to raise antibodies. The antibodies obtained were capable of reacting with the native protein, as judged by an enzyme-linked immunosorbent assay, protein A-linked staining of immunoblots after NaDodSO4 gel electrophoresis, and immunoprecipitation. The immunoassay titers against the protein were lower for these antibodies than for antisera derived from immunization with purified p53. However, staining with the immunoblot method showed that the antipeptide antibodies against p53 were uniquely specific. The data suggest that at least two different types of p53 molecules occur. The cellular protein previously isolated from human cells transformed by Epstein-Barr virus and from murine tumors induced by methylcholanthrene appears to be larger than the p53 reported in relation to simian virus 40- or adenovirus-transformed cells and to some other tumors. Some interrelationships have not been excluded, but it is clear that the two protein molecules do not behave identically. The reactions of the antipeptide antibodies with the intact protein have implications in regard to protein conformations. The strict specificities of such antibodies allow the generation of distinct sets of reagents useful for quantitation, purification, and cloning.

Amino Acid Sequence↗
PubMed1983

The Epstein-Barr virus receptor is distinct from the C3 receptor.

Polyvalent serum directed against C3 receptors was employed in an attempt to block Epstein-Barr virus (EBV) binding to virus receptor-containing cell lines. The serum eliminated 90% of virus binding to Daudi and BJAB, lines which express only the C3d receptor. Raji and Ramos cells, which express the C3d, C3b and C3bi receptors, still adsorbed 70% of their virus capacity in the presence of excess antiserum. These effects were independent of the virus strain. In the light of previous reports, these data imply that, although the two receptors, EBV and C3d, are closely associated, the binding sites of EBV and complement are distinct. Additionally, an unusual EBV substrain-specific receptor found on U698 and P3HR-1/ASNP lines was shown to be independent of complement receptors.

Animals↗
PubMed1983

In vitro complement binding in human skin cells with altered differentiation.

Exposure of cytoskeletal intermediate-sized filaments (ISF) of various cell populations in normal human skin to normal human serum (NHS) results in the deposition of C3 upon these structures; this phenomenon most likely occurs antibody-independently, is initiated by Clq binding to ISF, and is followed by the activation of the classical complement pathway. In the present study we investigated the cytoplasmic C3-binding properties of skin cells undergoing altered differentiation. Incubation of cryostat skin sections of dermal melanocytic nevi with NHS and, subsequently, with fluorescein isothiocyanate-conjugated rabbit antihuman C3 resulted in a bright cytoplasmic staining of the vast majority of nevus cells. Immunoelectron microscopic studies demonstrated that ISF within nevus cells represented the only cytoplasmic C3-binding structures. In contrast, ISF within melanoma cells, basal cell carcinoma cells, and keratinocytes constituting psoriatic lesions lacked C3-binding properties. We propose that changes in structure and subunit protein composition of ISF in certain cells undergoing altered differentiation results in a decrease or loss of their C3-binding capacity.

Basal Cell Carcinoma↗
PubMed1983

Epstein-Barr virus carried by Raji cells: a mutant in early functions?

Immunoprecipitation was used to study Epstein-Barr virus-specific polypeptide synthesis in Raji cells after chemical induction of the viral cycle. The results indicate that Raji cells fail to synthesize a few early and both late polypeptides. Comparison with P3HR-1 virus superinfection experiments at different MOIs indicates that some of these early polypeptides are required for virus DNA replication. The results are compatible with what is known about the complexity of viral DNA in Raji cells.

Antigens, Viral↗