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Biomedical subjects

J H Epstein

Publications and source records attributed to J H Epstein.

At least 19 recordsLinked to original sources

Experimental models for primary melanoma.

The nonmelanoma skin cancers squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) are by far the most common malignancies that occur in the United States each year. The third most common skin cancer, malignant melanomas (MM), accounted for 3% of all reportable cancers in the United States in 1991. The incidence of and mortality due to MM have been increasing at an alarming rate over at least the past 4 decades. As a result of this epidemic, there have been intense efforts to develop appropriate experimental models to examine the etiology and biology of this cancer. Benign and malignant melanocytic tumors have been produced in dogs, mice, guinea pigs, hamsters and gerbils with chemical carcinogens such as 7,12 dimethyl(a)benzanthracene (DMBA) and chemical promoters. Perhaps the most extensive and thorough studies using these chemicals were accomplished in the Weiser-Maple guinea pig model, in which radial and vertical stage growth occurred similar to human MM growth patterns. However, such stimuli are unlikely to be related to the human experience. Many investigators have considered ultraviolet radiation (UVR) from the sun to be intimately involved with the melanoma epidemic. Thus, a number of models have been developed to examine this possible relationship. These have included irradiation of DMBA-induced benign melanocytic tumors in pigmented hairless mice, chemical promotion of UVR-induced tumors in haired mice and the induction of melanomas by UVR in the South American opossum. In addition, a melanocytic growth was produced with psoralens plus UVA in a haired mouse. All of these melanomas required chronic UVR exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Photoimmunology.

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Allergy and Immunology

Stimulation of ultraviolet-induced carcinogenesis by 1,3-Bis(2-chloroethyl)-1-nitrosourea.

The influence of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on ultraviolet-induced carcinogenesis was examined in hairless mouse skin in vivo. Noncarcinogenic amounts of topically applied BCNU and carcinogenic levels of UVB energy were utilized in the study. The applications of BCNU significantly accelerated the appearance and growth of the cutaneous tumors in this study. Thus, the BCNU acted as either a promoting or a cocarcinogenic agent for ultraviolet-induced cancer formation. Although the mechanism of this effect has not been established, avoidance of extensive sun exposure would probably be prudent when topical BCNU is being utilized therapeutically.

Administration, Topical

Dermatology.

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Animals

Ultrastructural study of the nuclei in premitotic and repair DNA synthesis following UVB injury.

Ultrastructural changes in nuclei synthesizing DNA were studied by cytochemical technique. Guninea pigs ears were UVB irradiated and TdR-H3 was injected intradermally into the irradiated sites 1 hr before biopsy. Areas of the epidermis containing more than 80% of cells in DNA (repair or premitotic) synthesis identified by light microscopic autoradiography were selected and cut at 600 A. The glycolmethacrylate sections were stained with uranyl acetate and lead citrate, and consecutive sections were incubated with 0.01% pronase and 0.5% RNase before staining in order to observe DNA. In cells undergoing DNA repair, the zone of DNA became discontinuous and DNA was scattered throughout the entire karyoplasm as small aggregates and fine filaments. Nuclei in S-phase showed essentially the same change, but quantitatively the disappearance of DNA from the nuclear membrane and distribution in the karyoplasm became much greater. These changes were not seen in specimens treated without cytochemical technique.

Animals

Photocarcinogenesis: a review.

Clinical observations and epidemiologic studies indicate that the sun is the primary stimus for most human skin can formation. However, investigations directly confirming this association as well as defining the action spectra, time-dose relationships, energy level requirements, etc., have been confined to animal experimentation. Studies in which gross methods are used indicate that the experimental carcinogenic action spectrum falls primarily between 280 and 320 nm. Quantitative studies and tumor promotion investigations indicate that UV-induced cancer formation begins with the initial exposure. Heat, wind, and moisture stimulate UV carcinogenesis. Also, exogenous chemicals may influence carcinogenesis as photosensitizers such as 8-MOP, as additive carcinogens as noted with DMBA, or as promoters as described for Croton oil, retinoic acid, and BCNU. Qualitative studies indicate that progressive alterations occur in the epidermal-dermal basement membrane and dermal conncecive tissue and mucopolysaccharides associated with the progressive development of epidermal cancers. Malignant melanomas have also been induced experimentally in hairless mice with UV energy. Mechanistically, immunologic alterations and effects on DNA have received the most attention. Tumor-specific antigenicity as well as antigen deletion has been demonstrated. Immune suppression by antilymphocyte serum and certain chemicals has led to stimulation of tumor development. Perhaps the most exciting new information relates to the demonstration that chronically UV-irradiated mice have not rejected highly antigenic UV-induced cancers. This indicated that UV irradiation specifically altered the immunologic responses of the animals to these tumors. Within recent years, the influence of DNA injury and repair on cutaneous carcinogenesis has received a great deal of attention. This has been partly due to the demonstration of defective repair of UV-induced DNA damage in patients with XP. The primary photosensitive problem in these patients is an inordinate sensitivity to the carcinogenic effects of sunlight. However, correlation of DNA injury and repair directly with cancer formation has not been accomplished.

Animals

Recommendations for future research on ultraviolet radiation carcinogenesis.

Recommendations for future research on photocarcinogenesis were developed during an international conference on UVR carcinogenesis. Areas covered in the recommendations include research at the molecular biology level, human (especially epidemiologic aspects), physical (including instrumentation), and biologic studies (stressing animal models). The recommendations also propose the establishment of central supply and service sources for photocarcinogenesis research as well as the establishment of interdiscipilinary training programs related to research in photocarcinogenesis.

Animals

Immunofluorescent studies of epidermal protein during UV induced carcinogenesis.

Previous studies with agar diffusion technique demonstrated that antibodies produced in rabbits by injection of urea extractable proteins of rat cornfied cells cross react with proteins extracted from normal epidermis of hairless mice using the same technique. In the present study we investigated by indirect immunofluorescence microscopy the immunoreactivity of epidermal proteins in normal and ultraviolet light (UVB) induced hyperplasia and malignant transformation. Reactivity to the antibody was seen over the entire epidermis of nontreated skin and hypertrophied epidermis which occurred at 6-8 weeks after initiation of UVB irradiation. However, the reactivity diminished when malignant changes took place in the epidermal cells. Almost complete disappearance of the immunoresponse was observed in squamous cell carcinoma produced by further UVB radiation. These results suggest that the reactivity of this urea extractable protein serves as an additional immunologic marker for normal epidermal cells. Alterations in the immunoreactivity parallels UVB induced carcinogenesis.

Animals

Solar urticaria.

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Antibodies

Photoallergy.

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Humans

Photocontact dermatitis to halogenated salicylanilides and related compounds. Our experience between 1967 and 1975.

We evaluated the role of the halogenated salicylanilides and related compounds in the development of photocontact dermatitis between 1967 and 1975 as seen at the University of California, San Francisco clinic. During this period positive photopatch tests to at least one of these chemicals were detected in 98 patients. Prior to 1967, tetrachlorosalicylanilide and the brominated salicylanilides were the most common offenders. Declines occurred in number of patients with positive photopatch tests and patch tests to these agents as well as the number of patients tested to these agents during this period; ie, almost three times as many people were tested and four times as many had positive photopatch tests in the last six months of 1967 as compared to the first nine months of 1975. The most striking reduction in numbers of patients with positive tests occurred after 1968, but the most notable reduction in the total number of positive photopatch tests occurred after 1970. We concluded that these results were most likely due to removal from the market of the more potent photosensitizing chemicals and increased physician familiarity with the disease process.

Adult