[Lipoprotein (a) in coronary heart disease and myocardial infarction].
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Coronary Disease↗
Biomedical subjects
G Klein
Publications and source records attributed to G Klein.
Epstein-Barr virus susceptibility of normal human B lymphocyte populations.
Human blood and tonsil B lymphocytes were fractionated on density gradients and tested for virus binding and penetration into the cells. Epstein-Barr Virus (EBV) transformation was detected by immunofluorescence staining for EBV-determined nuclear antigen (EBNA). EBV bound to and penetrated all B cell populations, but only the high density populations were transformed. Activated B lymphocytes were found in the low density fractions and these cells were resistant to EBV infection. Infected and noninfected B lymphocytes were density-analyzed during in vitro culture. A spontaneous, not virus-induced, density decrease was found to precede the production of EBNA. Cells remaining at high density never expressed EBNA. The results suggest that EBV can transform only small resting B lymphocytes and that a virus-independent activation of the infected cells induces the EBNA production and transformation.
Antigens, Viral↗
High resolution banding analysis of the involvement of strain BALB/c- and AKR-derived chromosomes No. 15 in plasmacytoma-specific translocations.
Plasmacytomas were induced in (BALB/c X AKR 6;15) X BALB/c backcross mice where one of the BALB/c-derived chromosomes No. 15 was replaced by the AKR(6;15)-derived Robertsonian 6;15 chromosome. (BALB/c X AKR 6;15)F2 mice that were homozygous for Rb 6;15 were mated to BALB/c mice. Plasmacytomas were induced in the progeny by intraperitoneal injection of pristane. The cytogenetic marker permitted the distinctive identification of the two chromosome 15 homologues, including the distal segment involved in the plasmacytoma-specific translocations. 7 of the 10 plasmacytomas contained the typical t(12;15) translocation. The BALB/c-derived 15 chromosome served as the donor of the translocated segment in six of them. In the seventh, the Rb 6;15 chromosome of the AKR strain was the donor. The remaining three tumors contained the same type of intrachromosomal rearrangement. It arose by the pericentric inversion of the Rb 6;15 chromosome, leading to a variant plasmacytoma-associated rcpt (6;15) translocation. Unlike the usual 6;15 variant that arises by a reciprocal exchange between two separate chromosomes, it was generated by an exchange of the distal segments of a single chromosomal element. High resolution banding analysis of the tumors showed that all translocated breakpoints on chromosomes 15, 12, and 6 were identical with the previously described breakpoints characteristic for the typical 12;15 and the variant 6;15 translocation in murine plasmacytomas. It is known that the distal segment of chromosome 15 carries the c-myc oncogene (23). The PC-associated translocations cut across the 5'-exon of c-myc in the majority of the cases (24,26). The severed oncogene is transposed to the Ig-region on the recipient chromosome. Since the BALB/c strain is highly sensitive to PC-induction, we were interested to examine the question whether its chromosome 15 is preferred as the oncogene donor in AKR X BALB/c backcross mice that carry cytogenetically distinguishable 15 chromosomes. Our results show that this is not the case, since the same segment of the AKR-derived chromosome 15 could also serve in the same capacity. This is in contrast with T cell leukemogenesis where we have previously found that the trisomization-associated duplication of chromosome 15 occurred in a highly asymmetrical fashion, depending on the donor strain of No. 15 (9-11).
Animals↗
Torbjörn Caspersson: some personal perspectives.
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Cell Biology↗
c-myc Involvement in chromosomal translocations in mice and men.
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Animals↗
Novel concept for a mucosal adhesive ointment.
Conventional adhesive ointments cause irritation to the mucous membranes. Therefore, a novel mucosal adhesive ointment based partly on neutralized polymethacrylic acid methyl ester was formulated. The flow curves of the ointment vehicle showed pseudoplastic properties. The rheological behavior as well as the adhesion on the mucosal membrane could be varied by the type and concentration of the polymer used and the base used for neutralization. During clinical studies, the ointment vehicle as well as a tretinoin (vitamin A acid) preparation for the treatment of lichen planus did not cause any local irritation or systemic side effects. Both vehicle and preparation were found to be pleasant for the patients to use. The new system of the mucosal adhesive ointment is not limited to the incorporation of tretinoin as the active agent; combined with other drugs the system could be applied to all types of mucosal membranes.
Adhesiveness↗
Correlation between tumorigenicity and banding pattern of chromosome 15 in murine T-cell leukemia cells and hybrids of normal and malignant cells.
The most common chromosomal aberration in murine T-cell lymphomas is trisomy of chromosome 15. It has now been shown that the chromosomal region 15E exhibits a variant early replication banding pattern after 5-bromo-deoxyuridine labeling during part of the preceding S-phase. This variation is restricted to T-cell tumors. Plasmacytomas bearing the specific translocation t(12;15) show a normal early replication banding pattern of chromosome 15. In T-cell tumors all three chromosomes 15 of one cell are of the same variant banding type. In hybrids between tumor and nontumor cells, the number of cells expressing the variant early replication banding pattern is related to the degree of malignancy. Chromosomes 15 in one cell never expressed the variant and the normal banding pattern simultaneously. All five to six chromosomes 15 from one hybrid cell are of the same banding type irrespective of their parental origin. With respect to the type of early replication banding pattern, there is complete reversibility; tumor-parent-derived chromosomes 15 change to normal, and normal-parent-derived chromosomes 15 change to tumor.
Animals↗
EGNA-specific LIF production of human lymphocyte subsets.
Using the indirect leukocyte migration inhibition technique T cells have been identified as being responsible for Epstein-Barr virus nuclear antigen-induced specific leukocyte migration inhibitory factor production. The response was dependent on the presence of macrophages or their product, T-lymphocyte activating factor.
Antigens, Viral↗
Production of leukocyte migration inhibitory factor (LIF) in human lymphocyte subsets exposed to polyclonal activators.
Lymphocyte subsets separated on the basis of nylon-wool adherence and E and EA rosetting, and characterized for the presence of esterase-positive phagocytic cells were investigated for production of leukocyte migration inhibitory factor (LIF) in response to polyclonal T- and B-cell activators, PHA, ConA, PWM, and Epstein-Barr virus (EBV). In the nylon-passed population only the high avidity E+EA+ cells responded to ConA, PHA-induced LIF production in all E-rosetting subsets. The nylon-adherent E+ subset, which contains activated T cells, produced LIF spontaneously. B cells produced LIF when exposed to PWM or uv-inactivated EBV. In accordance with the known T-cell dependence of PWM activation, LIF was detected only in supernatants of reconstituted populations containing both B and T cells. In contrast, uv-inactivated EBV, devoid of transforming potential, elicited LIF production in the pure B-cell population. LIF production in response to polyclonal activators seemed to be independent of accessory cells since reconstitution with autologous macrophages or semipurified monokine, high-molecular-weight Interleukin 1 (IL-1), did not alter the results.
B-Lymphocytes↗
T-cell-dependent hybrid resistance against a natural killer-resistant Moloney virus-induced lymphoma (YWA): in vitro generation of cytotoxic lymphocytes.
A Moloney leukemia virus-induced lymphoma of the A.SW strain, YWA, was used to generate cytotoxic cells in vitro. Cocultivation of spleen cells from in vivo primed syngeneic and semisyngeneic mice with X-irradiated YWA tumor cells for 5 days resulted in a strong killing activity against YWA. The cytotoxicity was H-2 restricted and mediated by Thy-1.2-positive lymphocytes. F1 hybrids with variable degrees of natural resistance to the YWA tumor in vivo all generated cytotoxic cells after secondary stimulation in vitro but showed differences in optimal responder:stimulator requirements.
Animals↗
Natural killer cell sensitivity of human lymphoid lines of B-cell origin does not correlate with tumorigenicity or with the expression of certain differentiation markers.
Human B-cell lines derived from normal donors (LCL) or from Burkitt lymphomas (BL) were compared for their sensitivity to natural (NK) and interferon (IFN)-activated (IAK) cytotoxicity, mediated by effector cells from normal human blood. In four cases, a BL and an LCL line were derived from the same donor and had been kept in culture for the same period of time. The BL series included both Epstein-Barr virus (EBV)-carrying and EBV-negative lymphoma lines. The latter were compared with their own EBV-converted, Epstein-Barr nuclear antigen (EBNA)- and EBV-DNA-positive sublines, established by in vitro infection with two different viral substrains. LCL and BL lines from the same donor were lysed with equal efficiency by both NK and IAK effectors. There was no relationship between the NK sensitivity and the nude mouse tumorigenicity of different EBV-converted Ramos sublines, or the expression of differentiation markers such as insulin receptor, surface IgD, and the B2 surface antigen. Moreover, EBV-converted sublines of BJAB differed in their NK sensitivity, in spite of closely similar expression of these markers. NK-sensitive Ramos and BJAB sublines induced a stronger proliferative response upon confrontation with allogeneic lymphocytes than their NK-resistant counterparts. This suggests that the target cell may play an active role in triggering the lytic interaction. There was no correlation between this property and any of the other parameters studied.
B-Lymphocytes↗
Immune resistance of semisyngeneic F1 hybrid mice to lymphoma grafts differs from natural hybrid resistance in its genetic pattern.
Resistance of semisygeneic F1 hybrid mice immunized three times with irradiated tumor cells was compared to the genetic pattern of natural hybrid resistance to challenge with live tumor cells. Syngeneic mice responded equally well to immunization with all five hemopoietic tumor lines tested as the naturally much more highly resistant F1 hybrids. Natural hybrid resistance was found to be severely reduced by sublethal irradiation with 4 Gy, in contrast to hybrid resistance to parental bone marrow.
Animals↗
Detection of an Epstein-Barr virus-associated membrane antigen in Epstein-Barr virus-transformed nonproducer cells by leukocyte migration inhibition and blocking antibody.
Soluble membrane fractions derived from Raji cells trigger lymphocytes of Epstein-Barr virus (EBV)-seropositive, but not EBV-seronegative, individuals to release a lymphokine that inhibits leukocyte migration. The reaction can be blocked by the sera of patients with EBV-DNA-carrying tumors, Burkitt lymphoma, or nasopharyngeal carcinoma. Absorption of these sera with EBV-positive, but not EBV-negative, cells abrogates their blocking activity. These findings suggest that the antigen responsible for the leukocyte migration inhibition reaction is an EBV-encoded or an EBV-induced membrane component. The antigen is not identical with EBV-associated nuclear antigen or any other known antibody-detected EBV antigen.
Antigens, Surface↗
Antibodies against a synthetic peptide identify the Epstein-Barr virus-determined nuclear antigen.
Five peptides corresponding to amino acid sequences predicted from all three reading frames of the nucleotide sequence of the third internal repeat array (IR3) of the Epstein-Barr virus (EBV) genome were synthesized chemically. All five peptides elicited antipeptide antibodies in rabbits. The antiserum raised against a 14-residue copolymer of glycine and alanine gave brilliant EBV-specific nuclear staining in the anticomplement immunofluorescence (ACIF) assay, in line with the original definition of the EBV-determined nuclear antigen (EBNA) [Reedman, B. M. & Klein, G. (1973) Int. J. Cancer 11, 499-520]. Eight EBNA and EBV DNA-carrying lines showed nuclear staining with the antipeptide antibody, whereas five EBV DNA negative lines failed to stain. The staining pattern was more discretely punctate than the finely dispersed diffuse EBNA staining obtained with human antisera. Human EBV antibody-positive but not EBV-negative sera reacted with the synthetic peptide in an ELISA test. The peptide-specific antibodies were purified from the sera of healthy EBV-seropositive persons by affinity chromatography with the peptide. They gave an EBV-specific, brilliant punctate nuclear ACIF staining similar to that of the rabbit antipeptide antibodies. It was concluded that the glycine-alanine structure encoded by the IR3 region contains a native determinant of EBNA, detected by the ACIF test. Immunoblotting with the rabbit and human peptide-specific antibodies identified poly-peptides that varied between 70 and 92 kilodaltons in size in different EBV-positive cell lines, corresponding closely to a previously identified variation pattern in the size of EBNA. In addition, rabbit antipeptide antibodies identified two cellular polypeptides, 44 and 49 kilodaltons in size.
Amino Acid Sequence↗
Hemizygous interstitial deletion of chromosome 15 (band D) in three translocation-negative murine plasmacytomas.
Three murine plasmacytomas that were exceptional in lacking the characteristic (12;15) or (6;15) translocations were studied by G banding and high-resolution banding. One of every two chromosomes 15 (two of four in tetraploid tumors) was shortened in all three tumors. High-resolution banding analysis revealed that this was due to an interstitial deletion in the 15D band region. The two breaks responsible for the deletion have been tentatively localized to the interface of bands D2/3' and within band D2. One of the three plasmacytomas, ABPC45, had a rearranged c-myc gene. All three tumors contained a greater abundance of 2.4-kilobase myc RNA transcripts than normal spleen or thymus. The c-myc gene is located in the 15 D2/3 band region. We suggest that it may have joined the centromeric portion in the deletion plasmacytomas. This transposition may have led to its constitutive activation, as in the more frequent translocation-carrying plasmacytomas.
Animals↗
Oncogene activation and tumor progression.
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Animals↗
Floating pulmonary embolus: unusual cause of recurrent syncope.
A 69-year old woman was admitted because of recurrent syncopal episodes. In hospital, she had repeated attacks of near fainting or syncope when she was turned into the left decubitus position. Continuous arterial pressure monitoring revealed that severe hypotension initiated these events. Secondarily, the heart rate dropped markedly. The symptoms quickly reversed when the patient was turned back into the supine or right decubitus position. Angiography revealed a large, riding and partly floating pulmonary embolus that obstructed the pulmonary circulation to a variable degree, apparently influenced by the patient's body position. During subsequent emergency surgery the angiographic findings were confirmed. It appears that the severe hypotensive episodes were caused by intermittent high degree obstruction of the pulmonary circulation by the floating pulmonary embolus, a mechanism that, to our knowledge, has not previously been described as a cause of recurrent syncope.
Aged↗
Interaction between Epstein-Barr virus-determined nuclear antigen (EBNA) and the viral DNA.
Epstein-Barr virus (EBV) nuclear antigen (EBNA) was purified from the Burkitt lymphoma line Raji and its EBV DNA-binding properties were characterized. EBNA binding protected fragments of about 30 bp of B95-8 cell-derived EBV DNA from an excess of DNase I. Human anti-EBNA antibodies prevented DNA binding. Purified extracts from EBNA-negative cells did not protect EBV DNA against DNase I digestion. Mapping of the EBV DNA fragments protected from endonuclease (EcoRI, HindIII, SalI) digestion revealed many binding sites. Similar results were obtained following mixing of crude cell extracts and HindIII-digested fragments of EBV DNA and subsequent immunoprecipitation of the EBNA-DNA complex. In experiments involving the analysis of EBV DNA, fragments were protected from DNase I digestion by purified EBNA.
Antigens, Viral↗