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Biomedical subjects

B Lambert

Publications and source records attributed to B Lambert.

At least 199 records · Page 11Linked to original sources

Effects of cancer chemotherapeutic agents on testicular DNA synthesis in the rat. Evaluation of a short-term test for studies of the genetic toxicity of chemicals and drugs in vivo.

Changes in the rate of testicular DNA synthesis in the rat were studied at various times after single doses of 12 cancer chemotherapeutic agents. The animals were given intravenous injections of [14C]thymidine and [3H]thymidine 24 and 3 h, resp., before they were killed. By combining measurements of the free serum radioactivity and the testicular incorporation of the differentially labelled precursor, different response patterns were obtained for agents with different modes of action. The DNA-damaging agents cyclophosphamide, chlorambucil, thio-TEPA, busulphan, CCNU and procarbacine, after some delay, caused a decrease of testicular thymidine incorporation and a corresponding increase of free serum radioactivity. The non-DNA-damaging agents 5-fluorouracil, methotrexate, hydroxyurea and cytosine arabinoside had a rapid effect on testicular thymidine incorporation and produced diverse response patterns different from that of the DNA-damaging agents. Actinomycin D and also vinblastine caused changes in testicular thymidine incorporation and showed response patterns different from those of the other agents. These results show that simple measurements of testicular DNA synthesis may provide useful information for the evaluation of genotoxic effects of chemical compounds and may help one to distinguish between DNA-damaging agents and metabolic inhibitors of DNA synthesis.

Animals↗

Unusual XX/XY chimerism.

Apparently identical twin boys are both XX/XY and have two populations, A1 and B, of cells in their peripheral blood. Chimerism in somatic tissue outside the blood cells can be demonstrated in only one of the twins. From analysis of chromosomes and many gene markers the mechanism of origin of the unusual twins remains unclear.

ABO Blood-Group System↗

Age-related decrease of ultraviolet light-induced DNA repair synthesis in human peripheral leukocytes.

The capacity for ultraviolet light-induced DNA repair synthesis, studied in peripheral leukocytes from 58 healthy subjects 13 to 94 years old, was found to vary greatly between individuals. A negative, statistically significant correlation was obtained between age and this synthesis, indicating a decrease in repair capacity with age. An age-related decrease in DNA repair may increase the susceptibility of cells to agents causing DNA damage, i.e. carcinogens and certain cytostatic drugs.

Adolescent↗

DNA synthesis in subpopulations of blood mononuclear leucocytes in human subjects after vaccination against yellow fever.

After vaccination of five volunteers with yellow fever live vaccine, blood mononuclear cells were isolated and labelled with 3H-thymidine at intervals. DNA synthesis was measured by scintillation counting and autoradiography of rosetted cells. Rosetting with sheep erythrocytes (E-RFC) identified T cells, and such erythrocytes coated with IgM antibodies and complement (EAC-RFC) identified B cells and monocytes. DNA synthesis in the total mononuclear cell fraction, as well as in subfractions enriched in or deprived of E-RFC, displayed a sharp increase on day 10--11 after vaccination, remained high on day 13--14, and then returned to the prevaccination level. There was a corresponding morphological transformation, measured by size distribution and number of nucleoli per cell. The major fraction of DNA-synthesizing cells before, during and after the peak of activity was found among non-rosette-forming cells. However, during the activity peak the numbers and proportion of DNA-synthesizing E-RFC were increased while the response with regard to EAC-RFC was not obvious. Thus within a complex cellular response a transient T-cell response was identified.

Adult↗

Effect of carbenoxolone on lipolysis in rat adipose tissue.

Carbenoxolone slightly but significantly decreased the release of FFA from rat epididymal fat pads. The antilipolytic action of carbenoxolone was not blocked by 10(-3)M 3-isobutyl-1-methylxanthine, a potent inhibitor of phosphodiesterase. The findings suggest that carbenoxolone exerts its antilipolytic activity by acting on adenylate cyclase, thereby decreasing cyclic AMP concentrations and the activity of the hormone-sensitive lipase in adipose tissue.

Adipose Tissue↗

Sister chromatid exchanges in lymphocyte cultures of patients receiving chemotherapy for malignant disorders.

The frequency of sister chromatid exchange (SCE) was studied in peripheral lymphocytes of patients receiving chemotherapy for various malignant disorders. Significantly increased SCE frequencies were recorded in six patients 2-7 weeks after CCNU treatment and in one patient 2 weeks after melphalan treatment. One patient treated with prednimustine and one treated with DTIC had SCE frequencies just within the upper limit of the control range 1-2 weeks after therapy. Normal SCE frequencies were recorded in nine patients studied at times varying from 3 days to several weeks after administration of cytostatic courses involving 5-fluorouracil, vincristine, adriamycin, cyclophosphamide, bleomycin, thioTEPA, methotrexate, and prednimustine. Radiotherapy could not be causally related to increased SCE frequencies in any of the patients. The results indicate that CCNU and melphalan, in contrast to several other chemotherapeutic agents, induce very long-lived DNA lesions, which may be of crucial importance for the development of secondary neoplasms.

Adolescent↗

Sister chromatid exchanges in lymphocytes from psoriasis patients treated with 8-methoxypsoralen and longwave ultraviolet light.

The frequency of sister chromatid exchanges (SCE) was analysed in peripheral lymphocytes from patients receiving 8-methoxypsoralen (8-MOP) and longwave ultraviolet light (UVA) against psoriasis. The average SCE frequency in 14 patients after 3-10 weeks of clinical treatment did not differ statistically from that before treatment. UVA irradiation in vitro of blood from patients receiving 8-MOP caused a significant increase in the number of SCE. Such an increase was not observed after systemic administration of 8-MOP excluding UVA irradiation in vitro, nor after UVA irradiation in vitro in the absence of 8-MOP. Thus, the combination of oral 8-MOP administration and subsequent UVA irradiation in vitro promotes SCE in peripheral lymphocytes. However, this effect is not seen after clinical irradiation to the skin in vivo. The reason for this may be that the accumulated dose of UVA light in circulating lymphocytes, even after several weeks of clinical therapy, is not large enough to produce a significant amount of DNA damage leading to SCE, or else that DNA damage caused by the treatment is efficiency repaired during the intervals between treatments.

Adolescent↗

Chromosome aberrations and sister-chromatid exchange in workers in chemical laboratories and a rotoprinting factory and in children of women laboratory workers.

Cultured lymphocytes from 73 workers in chemical laboratories and the printing industry were found to have a significantly increased frequency of chromatid and isochromatid breaks, in comparison with 49 control subjects (42 adults and 7 children). An increase of the same magnitude was also found in 14 children, aged 4 days--11 yr, of 11 women laboratory workers who had worked during pregnancy. A significant correlation between age and frequency of chromosome aberrations was noted for both the exposed and control children but not for the adults. The frequency of sister-chromomatid exchange was significantly increased in 12 technicians working in laboratories performing hormone analysis. 4 children of 2 female technicians working during pregnancy also had a significnatly increased frequency of sister-chromatid exchange. The cause and biological significance of these findings are not yet known.

Adolescent↗

Male pseudohermaphroditism: diagnosis in cell culture.

Testicular feminization is a classic form of complete male pseudohermaphroditism. The individuals have a normal XY karyotype but unambiguously female external genitalia. They have congenital complete insensitivity to androgen due to an X-linked mutation. In four patients (from tow families with several affected members) with the typical phenotype of testicular feminization, a severe deficit of specific androgen-binding activity was detected in cultured fibroblasts from labium majus skin. Measurement of this activity in genital skin fibroblasts improves the differential diagnosis in patients with complete or imcomplete male pseudohermaphroditism before puberty.

Adolescent↗

Ultraviolet-induced DNA-repair synthesis in lymphocytes from patients with chronic lymphatic leukemia.

Ultraviolet-induced DNA-repair synthesis was studied in peripheral lymphocytes from 10 patients with chronic lymphatic leukemia (CLL). An ultraviolet-dose curve was established for each patient and compared with curves for healthy individuals. The same level of DNA-repair synthesis was recorded in CLL and normal lymphocytes. This contrasts with a report from another laboratory. Evidence is presented of the necessity of inhibiting replicative DNA-synthesis with hydroxyurea in order to adequately estimate the DNA-repair synthesis.

Aged↗