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Biomedical subjects

A Pawlowski

Publications and source records attributed to A Pawlowski.

At least 37 records · Page 2Linked to original sources

Human melanocytic naevi. I. Electron microscopy and 3-dimensional computer reconstruction of naevi and basement membrane zone from ultrathin serial sections.

Ultrastructural studies were carried out to investigate epidermal and dermal components of human naevi. Serial sections from forty-three acquired human melanocytic naevi were examined in the electron microscope. Control naevi were obtained from guinea pigs, and melanoma from human subjects and guinea pigs. It was found that the epidermal melanocytes which form naevus nests, do not "drop down" and penetrate into the dermis, but remain in continuity with the epidermis. The naevus "nests" actually remain as part of the epidermis and are contained by the basement membrane derived from the epidermal-dermal junction. The three-dimensional aspect of naevus protrusion into the dermis was confirmed by computer reconstruction throughout the ribbons of serial sections for all forty-three biopsies examined. The results indicate that the present differentiation of melanocytic naevi into junctional, compound, dermal and blue naevus is not adequate.

Animals↗

Human melanocytic naevi. III. Immunofluorescence and immunoelectron microscopy of the basement membrane zone.

Serum pemphigoid antibody (BPA) was used to demonstrate the intraepidermal location of human pigmented naevi. Immunofluorescence was predominant along the epidermal-dermal junction and around the naevus nests seemingly located in the dermis. Serial sections showed that these naevus nests were intraepidermal. The immuno-gold labelling technique for electron microscopy, was improved by using uranyl acetate with no osmium tetroxide or lead citrate. Hemidesmosomes were absent from the epidermal-dermal junction apposed to naevus nests. Gold labelling occurred in patches of particles along the lamina densa. The number of gold particles per micron length of lamina densa were quantitated. Immunofluorescence microscopy and immuno-gold electron microscopy confirmed the intraepidermal location of pigmented naevi.

Antibodies↗

Nevi and melanoma induced by chemical carcinogens in laboratory animals: similarities and differences with human lesions.

The isolation of benzo(a)pyrene (BP) from coal tar, and the synthesis of dibenzanthracene (DBA), methylcholanthrene (MCA), and dimethylbenzanthracene (DMBA) in the 1930's, facilitated the induction of epidermal tumors in experimental animals. It was soon found that chemical carcinogens affect not only keratinocytes, but also the melanocytes (Szabo 1953). "Painting" the skin of small laboratory animals, with carcinogens, became the principal method of studying the mechanisms of chemical carcinogenesis (Yuspa et al. 1976a). Pigmented nevi and melanoma are perhaps two of the most interesting problems in dermatology, oncology and pathology. Questions related to histogenesis, classification, diagnosis, treatment and eventual prevention remain unanswered. A substantial amount of our work is used to support most of the main points regarding the development of nevi and melanoma in laboratory animals.

9,10-Dimethyl-1,2-benzanthracene↗

Guinea pig cutaneous nevi transplanted to athymic nude mice: a potential model for benign and malignant melanocytic lesions.

Junctional and compound pigmented nevi, induced by 9,10-dimethyl-1,2-benzanthracene in the skin of albino guinea pigs, were transplanted as split- and full-thickness grafts to athymic nude mice. This experiment was designed as a feasibility study to establish a model in which junctional nevi could be kept outside the donor organism for prolonged periods. Different methods of securing grafts and promoting their survival were used in 19 mice. Mice died or were killed between 15 and 178 days after grafting. Histology revealed that the grafts survived in 11 mice. Nevus cells were found in six mice. The time from grafting to the observation of nevus cells did not exceed 68 days. All nevi showed slight to advanced features of degeneration and disappearance. Poor survival of the guinea pig epidermal portion of the graft and a host cellular reaction appeared to be the main reasons why nevi had a tendency to disappear from the athymic nude mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗

Skin melanoma induced by 7,12-dimethylbenzanthracene in albino guinea pigs and its similarities to skin melanoma of humans.

A model for a metastasizing melanoma was developed, and its characteristics were established. Sixty-five albino guinea pigs were painted with 7,12-dimethylbenzanthracene in acetone. There was evidence that, after 18 months, 40% of the animals developed melanomas. Melanomas arose by a malignant transformation of junctional nevus cells and/or by transformation of amelanotic melanocytes. Metastases to the skin and internal organs were multiple and eventually fatal for the animals. Histology and electron microscopy of induced melanomas were reviewed in detail. Clinical and histological events leading to development of melanoma in albino guinea pigs were found to be similar to human melanomas in a number of aspects. Fragments of melanomas were successfully transplanted to "nude" mice and healthy albino guinea pigs. The described model could be used for study of the various cellular and tissue events which precede nevus, lentigo maligna, and melanoma formation. It could also be useful in studying carcinogenic potential, for studying development of metastases, and presumably for trials of treatment.

9,10-Dimethyl-1,2-benzanthracene↗

The effects of hyalurodinase upon tumor formation in BALB/c mice painted with 7,12-dimethylbenz-(a)anthracene.

Experiments were performed to investigate the effects of hyaluronidase on chemical carcinogenesis. Two experiments were carried out using BALB/c mice. In the first experiment the mice were divided into three groups, viz. (1) painted with 7,12-dimethylbenz(a)anthracene (DMBA), (2) injected with hyaluronidase and painted with DMBA and (3) injected with saline and painted with DMBA. In the second experiment the mice were divided into three groups: (1) painted with DMBA, (2) injected with hyaluronidase and painted with DMBA and (3) injected with heat-inactivated hyaluronidase and painted with DMBA. The tumor incidence and size of tumors were significantly lower in the group treated with hyaluronidase than in the other groups. The latent period was increased. The mitotic index of the skin adjacent to the tumors at the end of the experiment was decreased. These studies show that hyaluronidase can act as an anticarcinogenic agent.

9,10-Dimethyl-1,2-benzanthracene↗

Heterotransplantation of human basal cell carcinomas in "nude" mice.

Human basal cell carcinomas, obtained from 10 subjects were transplanted to 25 "nude" mice. Two methods of transplantation were used and compared. Grafting gave better results than subcutaneous implantation. Tumor cells were identified in 5 mice, however only 2 of them developed lesions with histology similar to human basal cell carcinoma. Grafts, in which tumors developed, were obtained from superficial basal cell carcinoma. No reasons for the cause of the low percentage of successful transplantation and slow rates of growth of the transplants are found; however, possible immunological, vascular and environmental factors are discussed.

Animals↗

The use of freeze-fracture and negative staining techniques to study the ultrastructure of melanosomes isolated from B16 melanoma.

Freeze-fracture negative staining methods were used to investigate the structure of melanosomes isolated from B16 melanoma. The findings demonstrated the presence of a melanosomal double-layered membrane. Negative staining procedure showed that the melanosomal membrane is sometimes ruptured, displaced or peeled off during the purification process. Fractured melanosomes showed melanin spheres with a mean diameter of 24 nm. This compares with a mean diameter of 26 nm for the melanin spheres revealed by negative staining. The granular appearance of fractured mature melanosomes is due to the fracture following a random path between melanin spheres.

Animals↗

Junctional and compound pigmented nevi induced by 9, 10-dimethyl-1,2-benzanthracene in skin of albino guinea pigs.

Seventy albino guinea pigs were used in the experiment to investigate the influence of 9,10-dimethyl-1,2-benzanthracene on amelanotic melanocytes. A field 5 sq cm was marked on the flank of each animal. Hairs from these fields were clipped twice a week and painted for 20 consecutive weeks with 0.3 ml of 1% 9,10-dimethyl-1,2-benzanthracene in acetone. During the 1-year observation period, pigmented sports appeared in 40 animals. Biopsies were taken under local anesthesia, and sections were prepared for light and electron microscopic observations. Melanin formation of unknown mechanism took place in the epidermal melanocytes and in the melanocytes from the outer root sheath. These melanocytes also formed junctional and compound nevi; serial sections revealed various stages of pigmented nevi development. Schwann cells did not participate in the formation of nevi. Evidence is presented that 9,10-dimethyl-1,2-benzanthracene can convert amelanotic melanocytes into melanin-producing cells in the albino guinea pig skin. In addition, this system produces an animal model for the development of junctional and compound nevi.

9,10-Dimethyl-1,2-benzanthracene↗