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Biomedical subjects

R Becher

Publications and source records attributed to R Becher.

186 records · Page 11Linked to original sources

Molecular analysis of an ataxia telangiectasia T-cell clone with a chromosomal translocation t(14;18)--evidence for a breakpoint in the T-cell receptor delta-chain gene.

We established a clonal T-cell line with a reciprocal chromosomal translocation t(14;18)(q11;q23) from a patient with ataxia telangiectasia (AT) and T-cell chronic lymphocytic leukemia (T-CLL). The tumor cells and the derived T-cell line were compared with respect to phenotype, karyotype, and rearrangement pattern. Restriction fragment analyses of the T-cell receptor (TCR)-delta gene, which is located within the TCR-alpha gene on chromosome 14q11, indicated that the breakpoint is located within the TCR-delta locus, splitting the TCR-delta gene between the variable and joining segments. This specific chromosomal translocation was only detected in the derived T-cell line and may be involved in the genesis of T-cell malignancies in AT.

Ataxia Telangiectasia↗

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↗

Expression of CYP2B1 in freshly isolated and proliferating cultures of epithelial rat lung cells.

Bronchiolar Clara cells and alveolar type 2 cells of the lung are known to express relatively high levels of P450 enzymes compared to other pulmonary cells. Populations of enriched type 2 cells and Clara cells were isolated from rat lung by a procedure including lung perfusion, protease digestion, centrifugal elutriation, and differential attachment. Alveolar macrophages were removed by lavage. The purity of the type 2 cell-enriched population was approximately 90%, and the purity of the Clara cell-enriched population was 40-50%. Both type 2 cells and the cells of the Clara cell-enriched population proliferated in culture. CYP2B1 mRNA was expressed approximately to the same level in type 2 cells and the Clara cell-enriched population. The mRNA levels remained roughly constant for both cell types throughout the culture period, except for an early transient reduction. The apoenzyme level of CYP2B1 was 2-3 times higher in freshly isolated cells of the Clara cell-enriched population than in the type 2 cells. Both epithelial cell types showed decreased level of CYP2B1 apoenzyme in culture. The differences in the CYP2B1 mRNA and apoenzyme expression levels in freshly isolated cells and cultured cells suggest the existence of a post-transcriptional regulatory mechanism for CYP2B1 expression in lung cells. The characterization of specific functions of lung cells in culture, such as P450 gene expression, provides necessary information for the use of the cells in in vitro pulmonary toxicology.

Animals↗

Differential distribution and increased levels of ras proteins during lung development.

Differential localization of ras proteins and variations in their levels may be of importance during lung growth and differentiation. Abundant cell proliferation occurs during development of the fetal rat lung. As assessed by flow cytometry the proliferative activity declined near birth, followed by a gradual increase in cellular proliferation during the subsequent 8 days and a decline to basal levels by 15 to 18 days of age. During this period of substantial variations in proliferative activity, differences in both the protein content and localization of the different ras proteins were observed. The content of N- and K-ras proteins in lung homogenates increased 5 to 6-fold in rats 20 days or older, compared to fetal levels. The protein levels of the ras proteins remained elevated when cellular proliferation decreased to basal levels. As determined by immunohistochemistry, the localization of N-ras protein was restricted to keratin expressing cells of bronchiolar structures, apparently mainly ciliated cells. In contrast, K-ras was found in alveolar cells, probably type I and type 2 cells. H-ras, but not K- or N-ras, was localized to nonepithelial cells. Thus, different ras proteins were localized to different regions of the lung and increased in abundance during postnatal development.

Animals↗

Gradient centrifugation analysis of steroid-hormone binding in human malignant melanoma.

Vertical tube rotor sucrose gradient centrifugation in the presence of the protease inhibitor sodium molybdate provide to give a deeper insight into the steroid hormone receptor status of human malignant melanoma (MM) as did previous studies using dextran-coated charcoal procedure only. As compared to endocrine dependent breast cancer, the oestrogen binding capacity of MM is low. Although in some biopsies fairly high concentrations of progestin binders were detected, the sedimentation properties were not receptor typic. Androgen binding was found to be negligible. In contrast, the presence of glucocorticoid receptors is a common feature of human MM. A human MM cell line was demonstrated to contain glucocorticoid receptors only.

Adult↗

Chronic nausea as the leading symptom: an indication for double-contrast examination of the upper intestinal tract following normal gastroscopy.

We report a patient with chronic nausea as the leading symptom of a primary carcinoma of the duodenum located at the flexura duodeno-jejunalis. The tumour was not reached at gastroscopy, which was performed twice. Since this area usually cannot be seen upon gastroscopy or upon small bowel enteroclysma according to Sellink, a double-contrast investigation of the upper gastrointestinal tract using a hypotonic agent should be performed when nausea persists although gastroscopy is normal.

Adenocarcinoma↗