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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 883 records · Page 49Linked to original sources
PubMed1981

Somatic cell hybrid analyses of hematopoietic differentiation.

A differentiated cell expresses an entire set of specialized features. Somatic cell hybridization provides a method to examine control of gene regulation. We studied the expression of tissue-specific features in hybrids between human promyelocytes (HL-60) and human Burkitt's lymphoma cells (P3HR-1). Two hybrid lines, HP-1 and HP-2, and 18 hybrid clones were established and confirmed by karyotype, isozyme, and surface antigen analyses. The hybrids extinguished the 10 myeloid (HL-60) features that we examined including myeloid morphology, histochemistry, and functions that included response to colony-stimulating factor and ability to differentiate to granulocytes or macrophages. In contrast, the hybrids synthesized immunoglobulin and expressed Epstein-Barr nuclear, early, and viral capsid antigens similar to the P3HR-1 lymphoid parental line. Results are contrasted to the findings when P3HR-1 lymphocytes are fused to human erythroid-myeloid cells (K562). Taken together, our results suggest that phenotypic differences between human myeloid and lymphoid cells in the hematopoietic lineage involve mutually exclusive programs and may possibly be mediated by the activity of diffusible, transacting molecules.

Antigens, Viral↗
PubMed1981

Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by clinical, virological, and immunopathological studies.

Multiple methods, pedigree analysis, clinical evaluation, and Epstein-Barr virus (EBV)-specific serology, EBV DNA hybridization of tissues to probe for viral genome, staining of touch imprints for EBV nuclear-associated antigen, establishment of spontaneous infected B-cell lines from peripheral blood or tissues, examination of peripheral blood smears, and hematopathology studies, were used to study seven patients with the X-linked lymphoproliferative syndrome and seven additional patients with life-threatening EBV-associated diseases. These studies demonstrated EBV in the tissues of all 14 patients and immunodeficient antibody responses to EBV were documented. This virus can produce various life-threatening lymphoproliferative diseases in a variety of immunodeficient patients.

Adolescent↗
PubMed1981

Documentation of Epstein-Barr virus infection in immunodeficient patients with life-threatening lymphoproliferative diseases by Epstein-Barr virus complementary RNA/DNA and viral DNA/DNA hybridization.

Tissues from patients thought to have Epstein-Barr virus (EBV)-induced lymphoproliferative diseases were probed for EBV genomes using 2 independent hybridization techniques. Tissues from six patients with the X-linked lymphoproliferative syndrome, all five renal allograft recipients with immunoblastic sarcoma, and eight patients with diverse types of immunodeficiency and lymphoproliferative diseases such as fatal infectious mononucleosis or malignant lymphoma associated with antecedent immunodeficiency contained significant numbers of EBV genome equivalents per cell. The use of 2 hybridization probes is recommended to confirm the presence of EBV genomes. The finding of significant numbers of EBV genomes in tissues from patients with immunodeficiency suggests that EBV is the etiological agent of the associated lymphoproliferative diseases.

Adolescent↗
PubMed1981

Diverse familial malignant tumors and Epstein-Barr virus.

Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had borderline hypo-immunoglobulin A, died of glioblastoma multiforme in 1977, and at autopsy, had adenomatous colonic polyps. His eldest brother has normal immunoglobulin levels, but developed immune thrombocytopenia in 1973 and had elevated EBV antibody titers in 1980. Another brother had hypo-immunoglobulin A, thymoma in 1965, and adenomas and adenocarcinoma of the colon. Two other brothers succumbed to glioblastoma in 1968 and 1969. The father of the proband had bronchiectasis in 1952, hypo-immunoglobulin M documented in 1972, and elevated EBV antibody titers 5 years preceding development of a malignant lymphoma. The latter contained 10 EBV genome equivalents/cell by EBV viral DNA/DNA reassociation kinetics analysis. The proband's grandmother had died of an immunoglobulin G-secreting myeloma in 1977, and his grandfather had borderline low immunoglobulin M, elevated EBV antibody titers, and hypopharyngeal carcinoma in 1980. Predisposition to oncogenesis in this family was probably inherited.

Adenocarcinoma↗
PubMed1981

Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus.

Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is invariable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.

Adolescent↗
PubMed1981

Cell-mediated immune reactions in three patients with malignant lymphoproliferative diseases in remission and abnormally high Epstein-Barr virus antibody titers.

Two patients with Hodgkin's disease in remission and one chronic lymphatic leukemia patient with extraordinarily high anti-Epstein-Barr virus (EBV) (viral capsid antigen) antibody titers (greater than 10,000) were selected to study a spectrum of cell-mediated immune responses, including natural killer, interferon-boosted killer, antibody-dependent lymphocytotoxicity, and T-cell-mediated reactions. The purpose was to compare these reactions in patients with immunosuppression and a high EBV load who can hold their EBV-carrying cells under control with the corresponding reactions in patients with EBV-carrying lymphoproliferative disease. In contrast to the latter group, the three patients of the present study showed a less profound and less general suppression of the immune responses. Multiple effector mechanisms probably safeguard against the proliferation of EBV-transformed B-cells. Clinically manifest EBV-carrying lymphoproliferative disease occurs only in very severe immunodeficiencies effecting multiple effectors.

Adolescent↗
PubMed1980

In vitro NK-activity and in vivo resistance to leukemia: studies of beige, beige//nude and wild-type hosts on C57BL background.

The bg mutation in C57BL mice causes a partial impairment of NK activity, and has therefore been proposed as a model to evaluate the in vivo function of NK cells. In the present report, we studied natural resistance against the ascitic lines of one chemically and two virally induced syngeneic leukemias in C57BL bg/bg mice and their phenotypically normal heterozygous +/bg 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 18-30 h after i.v. injection. Direct splenic killing of 51Cr-labelled leukemia cells was also studied in vitro, and was found to be severely depressed in bg/bg compared to +/bg. This natural killer activity was independent of adherent cells and showed a rapid, but transient, increase after inoculation of the tumor cell doses used in the transplantation tests. It was also possible to study the bg mutation in T-cell-free mice, by combining it with the nu mutation on a C57BL 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 tumors is discussed.

Animals↗
PubMed1980

Interferon suppresses antigen- and mitogen-induced leukocyte migration inhibition.

Although first recognized by its effect on virus-cell interactions, interferon (IFN) has a variety of other effects. It can affect cell proliferation, modify the immune response at several levels, enhance the cytotoxic action of lymphocytes, suppress antibody formation and inhibit the development of delayed-type hypersensitivity (DTH) reactions. Therefore we have now tested the effect of interferon on leukocyte migration inhibition (LMI), regarded as the counterpart in vitro of DTH in humans. We have found that IFN suppresses both mitogen-and antigen-induced LMI, acting directly on the granulocytes but also affecting the lymphokine production of the lymphocytes.

Antigens↗
PubMed1980

Chromosome analyses of lymphoid cell lines derived from patients with chronic lymphocytic leukemia.

To study chromosome complements of chronic lymphocytic leukemia cells, six Epstein-Barr virus-transformed lymphoid lines were established from two patients with this disease who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). Immunoglobulin and G6PD were used as markers of the leukemic versus normal cell origin of the cell lines. The two lines, derived from putative normal cells, had no chromosomal changes. In contrast, chomosome abnormalities were found in each of the four cell lines of presumed leukemic cell origin. Although the chromosome aberrations are not as specific as the Philadelphia chromosome, there appears to be non-random involvement in chronic lymphocytic leukemia of some chromosomes, such as the No. 12.

Cell Line↗
PubMed1980

Establishment of a lymphoid cell line from leukemic cells of a patient with chronic lymphocytic leukemia.

Two lymphoid cell lines were established from a patient with chronic lymphocytic leukemia by infecting blood cells with Epstein-Barr virus (EBV). Studies of morphology, glucose-6-phosphate dehydrogenase, malic enzyme, immunoglobulin, and chromosomes of the two lines indicated that one of them originated from leukemic cells while the other arose from residual normal blood cells. The morphology and capacity for immunoglobulin secretion in the line that arose from leukemic cells were similar to those found in EVB-carrying lymphoblastoid cell lines grown from patients without neoplasia and differed from those seen in fresh chronic lymphocytic leukemia cells. These observations suggest that the introduction of EBV into the leukemic cells may have caused them to differentiate in a fashion similar to that noted in normal B cells after exposure to EBV.

Cell Line↗