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Biomedical subjects

A Robbins

Publications and source records attributed to A Robbins.

At least 91 records · Page 5Linked to original sources

Regulation of simian virus 40 early transcription in vitro by a purified tumor antigen.

Cloned DNA templates were used to direct the transcription of early and late simian virus 40 (SV40) genes by a cell-free RNA-synthesizing system. Transcription by RNA polymerase II was sensitive to low levels of alpha-amanitin and completely dependent on exogenously added DNA template. RNA products of discrete lengths were efficiently synthesized when transcription was directed by DNA restriction fragments containing promoter sequences for either early or late genes of SV40. Addition of the D2 tumor antigen to the template DNA inhibited transcription originating from the SV40 early promoter. In contrast, the D2 protein had little or no effect on the transcription from SV40 or adenovirus 2 (Ad2) late promoter sequences. When a mixture of cloned DNA containing SV40 early promoter and Ad2 late promoter was used to direct RNA synthesis, the D2 protein specifically inhibited the synthesis of SV40 early genes but not that of Ad2 late sequences. The D2 DNA binding protein also had no effect on the transcription directed by SV40 mutant templates that contain an intact early promoter sequence but lack specific tumor-antigen binding sites. We have confirmed that, under the conditions of the transcription assay, the D2 protein binds and interacts specifically with its recognition sites on wild-type template DNAs but fails to bind to mutant or Ad2 DNA templates that lack sequences containing SV40 tumor-antigen binding sites. These findings provide evidence that a direct interaction between tumor antigen and its specific binding sites on DNA is the mechanism by which the SV40 A gene autoregulates its transcription.

Antigens, Neoplasm↗

Dioxin studies.

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Dioxins↗

Male infertility.

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Environmental Exposure↗

Enzymatic activities associated with a purified simian virus 40 T antigen-related protein.

A protein antigenically related to the simian virus (SV 40) A gene product has been purified to near homogeneity from cells infected with the adenovirus-SV 40 hybrid virus Ad2(+)D2 and shown to contain ATPase (ATP phosphohydrolase, EC 3.6.1.3) and protein kinase (ATP:phosphotransferase, EC 2.7.1.37) activity. Both enzymatic activities copurify with the protein through six stages including one gel filtration column, two ion exchange columns, and a heparin affinity column. Analogous fractions from extracts of cells uninfected or infected with adenovirus 2 alone do not contain these enzymatic activities. The D2 hybrid protein resolves into two forms (I and II) during ion exchange chromatography. Form I, the major species (85%) of the D2 hybrid protein, elutes from DEAE-Sephadex in 0.37 M NaCl and is able to catalyze the hydrolysis of ATP to ADP + P(i) at a rate of 3 mumol/hr per mg. The remaining 10-15% of the D2 hybrid protein consists of form II which elutes from DEAE-Sephadex in 0.29 M NaCl and is able to hydrolyze ATP as well as to incorporate phosphorus from ATP into either the D2 hybrid protein itself or other protein acceptors such as phosvitin. Although both forms are able to bind DNA, the ATPase activity of form I cosediments with SV 40 DNA more efficiently than does the protein kinase activity of form II during glycerol gradient centrifugation. The ATPase activity of form I is efficiently inhibited by addition of anti-T gamma globulin to the reaction mixture whereas control gamma globulin has no effect. Similarly, the phosphorylation of the D2 hybrid protein by form II is inhibited by anti-T gamma globulin. By contrast, phosphorylation of phosvitin is specifically inhibited by antibody only when the immune complex is removed from the reaction mixture. Thus, it appears likely that one and possibly two enzymatic activities are carried out by the D2 hybrid protein. These findings are discussed in terms of mechanisms of SV 40 DNA replication and virally induced transformation.

Adenosine Triphosphatases↗

Arsine (arsenic hydride) poisoning in the workplace.

The National Institute for Occupational Safety and Health (NIOSH) recommends that appropriate workpractices be implemented to reduce the risk of worker exposure to arsine (AsH3) gas. There is a high potential for the generation of arsine gas when inorganic arsenic is exposed to nascent (freshly formed) hydrogen. This recommendation is based on several reports of worker exposure to arsine resulting in severe toxic effects or death. Most of the reported cases occurred when arsine was accidently generated during an industrial process. NIOSH would like to inform the occupational health community of some of the circumstances in which workers have been poisoned by arsine, with particular emphasis on the underlying mechanisms of generating the gas. We request that producers and distributors of arsenic and materials containing arsenic transmit information to their customers and employees, and that professional associations and unions inform their members. Stibine (SbH3), another toxic gas, if formed when antimony is exposed to nascent hydrogen. In most situations where arsine can be formed if antimony is present. Therefore, similar work practices should be implemented to reduce the risk of worker exposure to stibine.

Antimony↗