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B Opalka

Publications and source records attributed to B Opalka.

68 records · Page 4Linked to original sources

Breakpoint localization within the M-bcr and clinical course do not correlate in patients with chronic myelogenous leukemia undergoing alfa interferon therapy.

The breakpoint localization was analyzed in 61 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia to compare the breakpoint localization and clinical course. All patients were treated with interferon alfa (IFN alpha) or IFN alpha plus IFN gamma at the time of the study. Thirty-three of the patients had been pretreated with other cytostatic drugs. Sixty-nine per cent of the breakpoints were located in the 5' region of the major breakpoint cluster region (M-bcr), 29% in the 3' part. There was no significant difference between these two groups with respect to response to IFN(s), clinical course or conversion to blast crisis, nor survival.

Chromosome Fragility↗

Treatment of chronic myelogenous leukemia with interferons alpha and gamma.

A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.

Adult↗

DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b.

Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls.

Bone Marrow↗

A PvuII polymorphism of the bcr region in patients with hematopoietic disorders and their families.

The BCR gene on chromosome 22 has received increasing attention because of its involvement in the Philadelphia (Ph') translocation. For most restriction enzymes, this locus has been found to be nonpolymorphic. Two alleles have only been found when Taql-digested DNA is hybridized to a 5' bcr-specific probe. We describe another two-allele polymorphism detected by the same probe in PvuII-digested DNA. The polymorphism is characterized by an additional PvuII site in the bcr region: this causes the appearance of an additional band of about 2.3 kb or 2.5 kb besides a 4.8-kb fragment in hybridizations with the 5' bcr or a 3' bcr probe. The incidence of the second allele is very low. It has only been found in some patients with hematopoietic malignancies and in a group of volunteers having a leukemia patient in their families.

Deoxyribonucleases, Type II Site-Specific↗

Genome structure of adenovirus 12 host range mutants adapted to growth in simian Vero cells.

Mutants of adenovirus type 12 adapted to growth in Vero cells were studied by restriction enzyme and sequence analysis. Plaque-purified mutants were isolated either after long-term passage of the virus in Vero cells (CS-1, CL-1) or from Vero cells transfected with viral DNA (11-g, 12-k). The plaque-forming activity of these mutants was equal or even slightly higher in Vero cells than in HeLa cells, whereas the activity of wild-type virus in HeLa cells exceeded that in Vero cells by about one to two orders of magnitude. All mutants tested had an insertion of variable length consisting of adenoviral sequences at the right end of the viral genome. Sizes of the insertions were determined to be 294 bp (CS-1, 12-k), 560 (11-g), or 180 bp (CL-1). Additional insertions of multiple size and less than equimolar amount were detected and seem to exist in some of the viral particles. Furthermore, all four mutants tested showed an identical 69-bp deletion in the first exon of the E1a gene.

Adenoviridae↗

Definition of a region required for transformation in E1a of adenovirus 12.

In order to define functionally important regions of the E1 a gene of adenovirus 12 (Ad12), a number of Ad12 mutants were studied. These mutants share an identical 69-bp deletion in the first exon of E1a as well as duplications of a long terminal repeat sequence at the end of the Ad12 genome. The mutants are fully competent for replication and growth in their normal hosts and have a host range extended to include the Vero cell line of African green monkey origin. The partially deleted E1a can stimulate the expression of all early adenoviral genes as well as the cellular heat shock gene, the transcription of which is stimulated by Ad5 E1a. However, plasmids containing the deleted E1a plus wild type E1b were unable to effect a transformation of either primary rat embryo fibroblasts or on an established cell line following transfection. Further, the mutant viruses were defective in generating tumors in newborn hamsters. We conclude that the deleted sequence of E1a described here is critical for transformation by E1a but is not necessary for multiplication of the virus or the transcriptional activating function of the gene.

Adenovirus Early Proteins↗

Interferon alfa-2b in the treatment of chronic myelogenous leukemia.

Thirty-six patients with Philadelphia chromosome-positive CML were treated with interferon alfa-2b for at least 3 months. Thirty-two of the patients had chronic phase disease and four had acute phase disease, one in blast crisis. Patients initially received a daily dose of 4 megaunits/m2 administered subcutaneously; outpatient self administration followed at a dosage decreased in accordance with serially determined blood cell counts. Treatment was continued for 0.5 to 15 months, with a median duration of 7 months. No complete remission was achieved, but hematologic remission occurred in 21 (58%) patients, with partial hematologic remission in an additional 12 (33%). All four patients with acute phase disease failed to respond. Adverse reactions were only significant during the first days of treatment and did not interfere with self administration of the drug. Interferon alfa-2b may prove to be an important alternative therapeutic modality in chronic phase CML.

Adolescent↗

Evidence for a new lymphocyte-stimulating determinant (Lsd) detected by alloreactive T cell lines.

Three alloreactive T cell clones are described which reveal a new lymphocyte-stimulating determinant (Lsd) controlled by a gene on chromosome 1 of the mouse but different from and possibly centromeric to Mls. Two clones were originally isolated as anti-H-2b-specific and showed and retained cross-reactivity to Lsd (clone OD3, BALB/c anti-C57BL/6; clone KB37, B10.BR anti-C57BL/10). The third clone (BD7, C57BL/6 anti-CBA/J) was probably originally directed against Lsd. So far, Lsd is only characterized by stimulation of T cell proliferation, and its physiological function is not yet known.

Animals↗

Characterization of the cytolytic activity of a cloned antigen-specific T suppressor cell derived from a tolerant CBA/J mouse.

The antigen-specific T suppressor cell clone HF1 isolated from a CBA/J mouse made tolerant by low doses of bovine serum albumin has suppressive and cytolytic activity. The analysis of the latter gave the following results. Natural killer (NK)-sensitive YAC-1 (H-2a) and RBL-5 (H-2b) target cells are lysed whereas other NK targets, like EL4 (H-2b) or the human K562 cell line are resistant. Cytolytic activity is not antibody mediated. Its inhibition by sugar phosphate or monoclonal antibodies against LFA-1 antigens is such that HF1 can neither by typed as T killer nor as NK cells. It seems to represent a distinct T lymphocyte type.

Animals↗

Antigen-dependent, H-2-restricted cytolytic and noncytolytic T cell lines with specificity for minor histocompatibility antigens.

Several cloned T cell lines were isolated from primed mixed lymphocyte cultures immunized against minor histocompatibility antigens. These lines were selected with irradiated stimulator cells as antigen and require restimulation at intervals to keep growing. They are responsive, as measured by proliferation, to interleukin 2 (T cell growth factor) but cannot be grown in it continuously. These T cell lines have either the H-2d or H-2k haplotype. They all show exquisite H-2 restriction and minor histocompatibility antigen specificity. We did not observe any alloreactivity on 8 different H-2 haplotypes. For the H-2k T cell lines, the restriction element could be mapped to either the K or D end of the H-2 complex. No I-A-restricted cell line was found. It is of interest that all these T cell lines need the presence of T cells in the irradiated stimulator cell population. This suggests a more complex interaction between irradiated stimulators and responder T cells than just H-2K- or D-restricted antigen interaction. This recognition, though necessary, does not seem sufficient to induce the T cell clones to proliferate.

Animals↗

Prognostic impact of interferon alpha-induced cytogenetic remission in chronic myelogenous leukaemia: long-term follow-up.

To evaluate the long-term impact of the reduction of Philadelphia chromosome (Ph)-positive metaphases by treatment of chronic myelogenous leukaemia (CML) with interferon (IFN) alpha, we examined the outcome of 62 patients who had been enrolled between 1984 and 1990 into 2 IFN trials at our institution. As best cytogenetic response, 9 patients had achieved a complete remission and an additional 9 patients a partial remission. The remaining 44 patients had obtained either a minimal (n=29) or no cytogenetic response (n=15). Of the total of 62 patients, 9 were still on schedule and responsive to IFN in January 1995, including 7 patients in ongoing complete cytogenetic remission. The overall 5-year survival rate after a median follow-up from diagnosis of 51 months (range 3-102 months) was 62% and the median survival was reached at month 87. The effect of cytogenetic remission on survival was examined by "landmark" studies showing a significant survival advantage for patients with karyotype responses. In conclusion, in the patients studied, cytogenetic improvement was found to translate into improved survival expectancy. Long-term control by IFN alpha of CML, however, was restricted to a small minority of patients, predominantly to those attaining a complete suppression of the leukaemic cell clone as judged by cytogenetic criteria.

Actuarial Analysis↗