An EcoRI polymorphism associated with a human genomic clone from band 11p13.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to V Huff.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Following acute and chronic exposures to various chemicals in vivo, the average SCE frequency in human and rabbit lymphocytes has generally been shown to decrease with time posttreatment. The rate of this decline varies, however, and little data have been published pertaining to the decrease in SCEs soon after exposure. To gain more information about the immediate decline in SCEs with time, we injected rabbits with a single dose of 35 mg/kg cyclophosphamide (CP) and determined SCE levels in circulating lymphocytes at various times 5 h to 2 weeks after treatment. We observed a rapid decline in SCE frequencies within 5 days, and by 10 days post-exposure the SCE levels were back to control values. The distribution of SCEs among cells and the number of circulating lymphocytes were also analyzed at each time. Within 2-3 days posttreatment we observed a rapid loss of cells with high SCE levels concomitantly with a rapid decline in circulating lymphocytes and a decrease in the average SCE frequency. When the number of lymphocytes began to increase, the number of cells with normal SCE values also increased. By 10-11 days after CP, the lymphocyte count had recovered, the SCE frequency had returned to control levels, and the distribution of SCEs among cells was almost identical to the control distribution. These data, in addition to published information on rabbit lymphocyte lifespan, suggest that the decline in SCE levels with time posttreatment is a function of lymphocyte turnover.
The chemotherapeutic agent cis-platinum(II)diamminedichloride (cis-PDD) has been shown to be mutagenic, teratogenic, and carcinogenic. We determined the cytogenetic effects of cis-PDD on human and rabbit lymphocytes in vitro and on rabbit marrow cells, lymph node cells, and lymphocytes in vivo. Lymphocyte cultures from two humans and one rabbit were treated in vitro with cis-PDD. For in vivo studies, five New Zealand white rabbits were given iv injections of cis-PDD. Posttreatment blood samples were withdrawn for analysis and rabbits were sacrificed at either 6 or 24 hr for cytogenetic analysis of marrow and node cells. Sister chromatid exchange (SCE) analysis of human and rabbit metaphases from lymphocytes treated in vitro showed that rabbit lymphocytes are more sensitive to SCE induction by cis-PDD. Significant increases in SCE were observed in lymphocyte cultures obtained as early as 1 hr post treatment from injected rabbits. Analysis of node, marrow, and lymphocyte metaphases from injected rabbits showed a high number of chromosome aberrations in these cells with bone marrow showing a delayed response to treatment. These results indicate that cis-PDD is clastogenic in hematopoietic tissues in vivo and that SCE methodology may be useful in monitoring patients receiving cis-PDD therapy.
In previous cytogenetic studies of rabbits injected with the clastogen, streptonigrin (SN), we observed a higher incidence of chromosome aberrations in lymph node cells than in marrow cells recovered 6 h after treatment. In this study we examined several factors that may be responsible for this difference in the incidence of lesions. Results from SN pulse-treated lymphoid and marrow cultures demonstrated that the responses were different in vitro also. In addition, at higher doses of SN, lymphoid cells displayed a greater sensitivity to the drug when treated during DNA synthesis; marrow cells showed no differences in sensitivity throughout the cell cycle. Analysis of the percentage of lymph node and marrow metaphases labeled following 2, 4, or 6 h of culture in the presence of tritiated thymidine indicated that G2 was less than 2 h in lymph node cells and approximately 4 hr in marrow cells. From these data we conclude that the difference in the incidence of lesions 6 hr after an in vivo SN exposure. However, our data also indicate that lymph node cells are innately more sensitive to the induction of lesions than are marrow cells.
Wilms' tumor (WT) is the most common renal malignancy of children. While most occur sporadically, a small percentage are familial or occur as part of a developmental syndrome. Classic WTs exhibit a triphasic histologic pattern composed of blastema, epithelium, and stroma. Occasionally, heterologous elements may also be observed. In this study we investigated a series of four WTs that occurred within a single familial aggregate and contained focal areas of neural differentiation. The tumors were evaluated histologically for the presence of neural elements and immunohistochemically for expression of neural-related markers. Genetic linkage analysis was performed on 3 of the 4 WTs. In addition to the classic triphasic histology, the WTs contained tumor rosettes (4/4), ganglion cells (2/4), foci of ganglioneuromatous differentiation (2/4), and anaplasia (1/4). Staining for chromogranin, S-100, synaptophysin, vimentin, and neuron-specific enolase was positive in all 4 tumors within the areas of neural differentiation whereas staining for CD99 (013) and glial fibrillary acidic protein was negative. Linkage analysis studies suggest that the familial predisposition gene segregating in this family is at 19q13.4. To our knowledge, this is the first reported series of WTs with neural differentiation that occurred within a single family aggregate. Genetic linkage analysis of this family is consistent with linkage to the FWT2 WT predisposition gene at 19q13.4. We propose that these tumors may represent a unique manifestation of tumor susceptibility in this family.