Biomedical subjects
K LaBresh
Publications and source records attributed to K LaBresh.
Cellular transformation by a unique isolate of human papillomavirus type 11.
Infection with human papillomavirus type 11 (HPV 11) is associated with benign epithelial proliferations and rarely with malignant and metastasizing tumors. Because of the biological diversity displayed in tissues infected with HPV 11, we have examined the capacity of various isolates of HPV 11 to transform cultured cells and compared their molecular differences by DNA sequence analysis. Five isolates of HPV 11 were examined for their ability to transform primary neonatal rat kidney epithelial cells and NIH 3T3 mouse fibroblasts in DNA transfection experiments using calcium phosphate precipitation. Included in these studies are the prototype isolate from a laryngeal papilloma (HPV 11P); HPV 11VC from a verrucous carcinoma of the penis; HPV 11Epi from the viral episomes of a primary squamous cell carcinoma; and two integrated genomes (HPV 11Int 1 and HPV 11Int 2) of the metastases. Only HPV 11VC cotransfected with the oncogene Ha-ras transformed neonatal rat kidney epithelial cells with an efficiency comparable to that of HPV 16 DNA. HPV 11VC DNA alone transformed NIH 3T3 cells. Analysis of the DNA sequence of HPV 11P and 11VC revealed 16 single nucleotide changes in the upstream regulatory region and open reading frames E1, E2, E4, and E5, five resulting in amino acid substitutions. This is the first demonstration of cellular transformation by a natural isolate HPV 11 DNA in vitro and illustrates that minimal changes in the DNA sequence of certain viruses confer oncogenicity to what are normally nontransforming viruses.
Hemodynamic effects of potentially useful antineoplastic agents.
Adenosine (Ado) and Ado analogues produce multiple hemodynamic effects including coronary vasodilation, bradycardia, alterations in left ventricular contractility, and peripheral vasodilation or vasoconstriction depending on the vascular bed. The intact anesthetized Sprague-Dawley rat was examined in relation to electrocardiogram and blood pressure alterations induced by a series of potentially useful antineoplastic agents that are purine or pyrimidine analogues as part of a preclinical evaluation of these agents. The drugs tested were arabinosyladenine and its 5'-monophosphate derivative arabinosyladenine-5'-monophosphate (ara-AMP), the 2-fluoro derivative of ara-AMP, the pyrazolo[4,3-d]pyrimidines (formycin and formycin B), 8-azaadenosine, 6-methylmercaptopurine riboside, tricyclic nucleoside-5'-monophosphate, 5-fluorouracil, arabinosylcytosine, and 3-deazauridine. Those Ado analogues subject to deamination by adenosine deaminase (ADA) were also studied in the intact Sprague-Dawley rat after pretreatment with the ADA inhibitor 2'-deoxycoformycin. The results indicate that these agents have significant hemodynamic effects and should alert clinicians to potential adverse reactions when infusing these drugs.