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J Schiller

Publications and source records attributed to J Schiller.

12 recordsLinked to original sources

Non-selective analysis of the transformation of FR3T3 rat cells by bovine papillomavirus type 1: regulations of viral transcription associated with phenotypic transformation.

Drug-resistant clones selected from FR3T3 rat cells after transfer of neo-BPV1 (Bovine Papillomavirus Type 1) DNA constructs became phenotypically transformed (focal transformation, growth in suspension and tumor formation) soon after selection (approximately 5 generations in culture). A frameshift mutation in ORF E5 abolished transformation, but did not prevent the autonomous maintenance of the DNA construct. A more complex situation was observed when the E2 transactivating function was abrogated. A minority of the E2(-)-neor clones became phenotypically transformed shortly after drug selection, but the majority maintained normal growth properties for 30 to 50 generations. The rate of viral transcription was uniformly high in cells which exhibited transformed growth properties early after selection (the E2- minority class and all the wild type transformants) and low in phenotypically normal cells (the majority of the E2- lines). The same low transcriptional activity and delayed expression of transformed growth properties had been observed after transfection of a similar construct carrying a wild type viral early region (69-T fragment), but lacking the late region. The elevated rate of viral transcription, which correlates with the immediate expression of transformation, appears therefore to require at least two distinct elements, the E2 transactivator function and sequences in the late region of the viral genome. In their absence, high transcription rates and transformation could be established only in a minority of the transfected clones, by an unknown, E2-independent mechanism. Evidence was obtained for a third transformation route which, in the absence of either E2 or the late region, led to the focal occurrence of transformed derivatives after 30 to 50 generations of normal growth, but was not associated with an overall increase in viral expression.

Animals

Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain.

The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also activate a wide range of co-transfected promoters without E2P cores to a lower extent. Analysis of multiple E2 mutants in transfected cells revealed that the C-terminal DNA binding E2 domain binds to the E2P cis sequences in the form of pre-existing nuclear dimers. The DNA binding function of E2 was required for specific trans-activation of the E2P elements, as well as for the function of the previously described C-terminal 'short E2' transrepressor. In addition to the C terminus, specific trans-activation also required an intact N-terminal half of the E2 protein. When expressed alone, the N-terminal E2 domain was found to activate heterologous promoters without E2P elements to an extent comparable to wild-type E2, and therefore represents the functional transcription activation domain of the E2 factor. In contrast to other DNA-binding activator proteins described to date, the transcriptional activation by the E2 factor can occur without specific DNA binding. Its mechanism may thus involve protein--protein interactions between common transcription factors and the N-terminal E2 domain which contains amphipathic helix motifs.

Animals

Cardiovascular disorders. Diagnostic and therapeutic implications for the podiatric medical practice.

The cardiovascular system has multiple implications in the podiatric patient. The examination should begin with a complete and careful history. The physical examination should be thorough. Noninvasive evaluation should be performed as indicated with both a static and functional component. Cardiac disease should be investigated in all patients with a history or physical findings consistent with this disorder, such as blue toe syndrome, palpitations, or chest pain.

Blood Pressure

Sclerosing cholangitis and primary biliary cirrhosis--a disease spectrum?

Sclerosing diseases of the biliary system encompass a spectrum ranging from primary sclerosing cholangitis (usually of the extrahepatic biliary tree) to primary biliary cirrhosis of the intrahepatic bile canaliculi. In a study of 35 patients with primary intra- and extrahepatic biliary sclerosis, age of onset, sex distribution, symptomatology, associated diseases, radiographic abnormalities and chemical profile were considered. The difficulty of differentiating sclerosing cholangitis and biliary cirrhosis from other causes of obstructive jaundice preoperatively was stressed, in addition to points of differential clinical and laboratory findings. The etiology of these entities as well as the possibility that they represent variant clinical manifestations of the same disease process were also considered. Mechanical and pharmacological treatment alternatives that were attempted included drainage procedures, the easiest and most widely used of which was the T-tube. However, this could prove to be a source of infection and should therefore be removed early, inasmuch as cholangitis represents a major cause of morbidity. Steroids have been used with varying effectiveness; subjective improvement was generally attained, although objective improvement has been difficult to document. When choleuretics and cholestyramine were administered, we noted significant palliation. Antibiotics were reserved for treatment of cholangitis. Until the underlying etiology of this rare malignant sclerosing process is found, only symptomatic treatment can be offered.

Adult