Franklin Pass

Identification of a novel human papilloma virus in cutaneous warts of meathandlers.

Abstract Papillomavirus DNA from common skin warts of four meathandlers has been characterized and compared to the DNA genomes of known human cutaneous papillomaviruses. Virus was purified from one of the human papilloma samples and was found to exhibit a restriction endonuclease cleavage pattern distinct from those of known human papillomaviruses (HPV). Moreover, viral DNA extracted from papillomas from the other three patients exhibited sequence homology and restriction endonuclease cleavage patterns similar to this novel viral DNA. In addition to this unique HPV, one of the patients also contained a second species of HPV which was related to, yet distinct from, HPV-2, a species of HPV associated with common cutaneous warts in man. Finally, employing the Southern transfer procedure and stringent hybridization conditions, each meathandler HPV DNA studied was found to be unrelated to the major species of bovine papillomavirus, types 1 and 2.

Sodium lauryl sulfate irritant patch tests. II. Variations of test responses among subjects and comparison to variations of allergic responses elicited by Toxicodendron extract

Inflammation was induced on the forearms of volunteers by twenty-four closed patch tests to either the irritant 10% sodium lauryl sulfate (SLS) or Toxicodendron extract. Each chemical was tested at eight sites on the ventral forearms of each volunteer in order to assess the variability of response among test sites in individual subjects. Inflammation was assessed about 10 minutes after patch tests were removed. The degree of inflammation elicited by both Toxicodendron and SLS was variable among subjects, but variation among individual test sites was much more marked in subjects tested with SLS (p less than 0.002). The marked variability of responses to irritation that occur in any single subject may explain why irritant patch test responses do not reliably identify the irritation-prone individual.

Identification of three distinct papillomavirus genomes in a single patient with epidermodysplasia verruciformis

Benign papillomas from a patient with a family history of epidermodysplasia verruciformis were examined for the presence of human papillomavirus (HPV) DNA. Employing stringent hybridization conditions that allow identification of a single type of HPV and radioactively labeled HPV-5 DNA as a probe, we have detected HPV DNA exhibiting sequence homology to HPV-5 in these tumors. Restriction endonuclease analysis of this HPV DNA confirmed its identity as HPV type 5. However, when hybridization was performed under less stringent conditions that allow all of the known types of HPV to react with the radioactively labeled HPV-5 DNA probe, two additional species of HPV DNA unrelated to HPV-5 were identified. As these two HPV types do not hybridize with HPV 1, 2, 3, or 4 under stringent conditions, they appear unique and have, as yet, not been reported to be associated with patients exhibiting epidermodysplasia verruciformis. Thus we have observed three distinct HPV species in benign papillomas from a single patient. These observations have important implications when attempting to correlate the type of HPV present in the various wart disease syndromes that have been described to date and further suggest that extreme care must be taken when analyzing carcinomas, occupying similar anatomic sites and suspected to have arisen from papillomas, for HPV species.

Biotechnology, a new industrial revolution

During the past twenty years, classic genetics has been transformed to a modem molecular science. And now we are about to witness a new step, the manipulation of genetic science to provide a technical base for industry. This new biotechnology, called recombinant DNA (rDNA) technology, is based largely upon our ability to identify specific genetic information and to transfer genetic information from one organism or cell to another. Perhaps our greatest exposure to rDNA is the pages of The Wall Street Journal touting the commercial impact upon business and investment, but it is important to focus for a moment upon the science and the potential effect upon our lives and those of our patients. Most readers have a working knowledge of rnendelian genetics and the rudiments of nucleic acid chemistry. However, few of us followed the advances leading to the discipline of rDNA or gene splicing. In the 1960s, scientists learned how genes moved from one bacterium to another by the transfer of virus-like bacteriophages or separate small circular DNA plasmids. Thus, phages and plasmids were identified as vectors for carrying genetic information. Soon investigators learned how bacteria have the capacity to clip genetic information from chromosomes and repair the resultant breaks. Over 200 bacterial enzymes have now been identified, each with a specific ability to cut and repair DNA. The final step in this process involved understanding the mechanisms of gene expression, including the identification of nucleic acid sequences that initiate and terminate protein synthesis. Put this all together and we have rDNA technology: the capacity to select a gene of specific function and transfer the gene via a vector to bacteria where large

Vaccines for latent viruses

There are two traditional ways to modify a virus for immunization: (1) kill the virus or (2) use a live, attenuated virus. There are three modern ways to prepare vaccines: (1) extract and purify a part of the virus that is immunogenic, (2) synthesize a polypeptide immunogen piece of the virus, or (3) use recombinant deoxyribonucleic acid or gene splicing to prepare an immunogenic portion of the virus. The last three produce subunit vaccines that can be made to contain no deoxyribonucleic acid. They are not infectious and are likely to be nononcogenic. Using recombinant deoxyribonucleic acid techniques, a vaccine for bovine papillomavirus has been prepared. This is in clinical trials and probably will be licensed for use in cattle in 1988. A vaccine for herpes simplex virus has been prepared using glycoprotein D from the surface of the virus. This immunizes animals but it has not reached clinical trials in humans.

Immunology of Human Papovaviruses

Papovaviruses are small, nonenveloped DNA viruses that share certain morphological features and replicative processes. The term “papova” is an acronym composed by grouping the first two letters of “human papilloma. virus,” “mouse polyoma virus,” and “simian vacuolating virus” (simian virus 40, SV40) (Melnick, 1962). The papovaviruses fall naturally into two subgroups: the larger papilloma (wart) viruses, which produce benign tumors of the skin or mucous membrane, and the smaller viruses of the SV40-polyoma subgroup, most of which cause infections of the urinary tract and are oncogenic for laboratory animals. It has been proposed that the papovaviruses be established taxonomically as a family, Papovaviridae, containing two genera, Papovavirus A (the papillomaviruses) and Papovavirus B (viruses of the SV40-polyoma subgroup), and that virus species be designated by numbers (Melnick et al., 1974). Papovavirus infections of man and their chief characteristics are listed in Table 1.