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Biomedical subjects

R Fishel

Publications and source records attributed to R Fishel.

80 records · Page 5Linked to original sources

Multisystem presentation of eosinophilic fasciitis.

A 20-year-old man experienced the onset of progressive scleroderma-like skin changes with eosinophilia and hypergammaglobulinaemia after strenuous military activity. A biopsy showed faciitis. Concomitant splenomegaly, polysynovitis, restrictive lung function, myositis, decrease hepatic clotting factors and proteinuria were documented. He responded well to corticosteroids, relapse upon their discontinuation and had a complete remission of both skin and systemic features while on penicillamine and azathioprine. He is new in good health and has received no medication for the past two years.

Adult↗

Biochemical studies of homologous and nonhomologous recombination in human cells.

Purified and partially purified protein fractions from human cells have been developed that promote homologous and nonhomologous recombination reactions in vitro. Homologous pairing of model DNA substrates is catalyzed by the homologous pairing protein HPP-1 in a magnesium-dependent, ATP-independent reaction that requires stoichiometric amounts of the protein. Addition of the human single-strand binding (SSB) holoprotein complex hRP-A reduces the requirement of HPP-1 in the reaction up to 20-fold. Although the combination of homologous pairing and SSB activities is similar to the bacterial strand-exchange process, the numbers, size, and requirements of the human reaction appear to preclude any detailed comparisons. We have used Z-DNA affinity chromatography as a major step in isolation of human recombination proteins and found that the activities appear to elute as a complex form in approximate multiples of 500 kDa. Associated with the homologous recombination complex is a potent blunt-end ligation activity that appears to mimic the nonhomologous joining functions that are frequently seen following transfection of DNA into mammalian cells. A simple scheme for the association of homologous and nonhomologous recombination functions in mammalian cells is discussed.

Base Sequence↗

Genomic instability: first step to carcinogenesis.

Multiple genetic alterations are commonly observed in human cancers. It has been suggested that inactivation of DNA repair pathways, which leads to an increased mutation rate and chromosomal instability, can initiate and accelerate the neoplastic process. Such a causality has been shown for DNA mismatch repair and Hereditary Nonpolyposis Colorectal Cancer (HNPCC), and evidence is accumulating that several other DNA repair pathways are frequently inactivated in different cancer types. In addition to genetic alterations, perturbations in DNA methylation patterns (epigenetic changes), which include both local hypermethylation and genome-wide hypomethylation, are frequently observed early in tumorigenesis. Therefore, genomic instability including genetic and/or epigenetic alterations may be the first step in carcinogenesis. Knowledge of these biochemical mechanisms are likely to lead to more effective cancer diagnosis and therapy.

Cell Transformation, Neoplastic↗