Biomedical subjects
Publications and source records attributed to E Solomon.
Segregation of biliverdin reductase (BLVR) in 11 independent human-mouse hybrids confirms the assignment to chromosome 7 in man and gives a regional localization of 7pter----7q22. Isoelectric focusing of BLVR reveals genetically determined variation among inbred strains of mice.
The plasminogen activators (PAs) are serine proteinases which convert the inactive proenzyme plasminogen into plasmin, a proteinase associated with processes such as fibrinolysis and tissue remodelling. There are two immunologically distinct types of PA: tissue-type (t-PA), the main form involved in thrombolysis, and urokinase-type (u-PA), primarily involved in tissue degradation. Two or possibly more genes encode PA activity, and one locus has been provisionally assigned to chromosome 6 in man. We have isolated cDNA clones which encompass the entire coding sequence of the t-PA gene, and have used these to probe DNA on Southern blots isolated from 18 independent human-rodent somatic cell hybrid lines. The presence of the human gene for t-PA showed complete concordance with human chromosome 8 in the hybrids. In addition, the cDNA clones recognize a restriction fragment length polymorphism, where the two common alleles each have a frequency of approximately 0.5. t-PA and u-PA activities have been found in a wide variety of malignant cells, where they are thought to play a role in metastatic invasion of normal tissue. The results reported here will enable us to investigate whether genetic changes associated with the chromosome encoding t-PA are associated with altered t-PA expression in neoplasia.
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Hybrids formed between human acute lymphoblastic leukemia (ALL) cells and mouse myeloma have been used to determine the chromosomal location of genes required for the expression of several monoclonal antibody (mAb)-defined cell surface antigens on ALL cells. Cloned hybrids were tested for antibody binding, immunoprecipitation of the relevant protein, chromosome isoenzyme markers and karyotype. Two antigens of those studies could be definitively mapped, OKT10/p45 to chromosome 4 and BA-2/p24 to chromosome 12. mAb BA-2 reacts with the same protein as another mAb designated 609-29 (anti-teratocarcinoma). Reactivity with the latter mAb has been previously shown to segregate with chromosome 12.
The dominant selectable gene, Ecogpt, has been introduced, by the calcium phosphate precipitation technique, into normal human fibroblasts, along with the SV40 early region genes. In one transfectant clone, integration of these sequences into human chromosome 17 was demonstrated by the construction of human-mouse somatic cell hybrids, selected for by growth in medium containing mycophenolic acid and xanthine. A whole cell hybrid, made between the human transfectant and a mouse L cell, was used as donor of the Ecogpt-carrying human chromosome 17 to 'tribrids' growing in suspension, made by whole cell fusion between a mouse thymoma cell line, and to microcell hybrids made with a mouse teratocarcinoma cell line. Two tribrids contained karyotypically normal human chromosomes 17 and a small number of other human chromosomes, while a third tribrid had a portion of the long arm of chromosome 17 translocated to mouse as its only human genetic material. Two independent microcell hybrids contained a normal chromosome 17 and no other human chromosome on a mouse teratocarcinoma background. These experiments demonstrate the ability to construct human-mouse somatic cell hybrids using a dominant selection system. By applying this approach it should be possible to select for a wide range of different human chromosomes in whole cell and microcell hybrids. In particular, transfer of single human chromosomes to mouse teratocarcinoma cells will allow examination of developmentally regulated human gene sequences after differentiation of such hybrids.
We have mapped two new genes to chromosome 11 which control the cell-surface expression of two distinct antigens defined by monoclonal antibodies. One of the antigens has a general tissue distribution and is associated with a molecular complex of two polypeptides of 80,000 dalton and 40,000 dalton molecular weight. The second antigen has a restricted tissue distribution and is carried on a polypeptide of 100,000 daltons. We have used a combination of genetic and biochemical techniques to demonstrate that these new markers are distinct from the antigens defined by the monoclonal antibodies F10.44.2 and W6/34 which are also encoded by genes on chromosome 11. It is concluded that human chromosome 11 carries at least four distinct genes controlling cell-surface antigen expression.
Somatic cell hybrids have been constructed between a thymidine kinase-deficient mouse cell line and blood leukocytes from a patient with acute promyelocytic leukemia showing the 15q+;17q- chromosome translocation frequently associated with this disease. One hybrid contains the 15q+ translocation chromosome and very little other human material. We have shown that the c-fes oncogene, which has been mapped to chromosome 15, is not present in this hybrid and, therefore, probably is translocated to the 17q- chromosome. Analysis of the genetic markers present in this hybrid has enabled a more precise localization of the translocation breakpoints on chromosomes 15 and 17. Our experiments also have enabled an ordering and more precise mapping of several genetic markers on chromosomes 15 and 17.
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Certain predictors are traditionally presumed to be reliable measures for selection of candidates for general dentistry training programs. The purpose of this study was to assess the relative value of academic standing, letters of recommendation, and personal interview impressions by comparing them with performance during training. Predictor data were collected from the application files of all postdoctoral trainees in the advanced general dentistry training program at the Eastern Dental Center of the past ten years (N = 154). However, only 102 postdoctoral students had information available for all three predictor criteria. Performance was rated subjectively on completion of training by two faculty members on a six-point rating scale. The highest correlations between predictors and performance were to academic achievement (r = 0.347). Weaker, though statistically significant, correlations were found for the personal interview (r = 0.206) and letters of recommendation (r = 0.192). Although these predictor criteria will continue to be used in the selection of candidates, administrators and selection committees must be aware of the limitations of such criteria in predicting performance.
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