The immunohistochemical localization of lysozyme in human axillary apocrine glands.

Lysozyme has been observed in intraluminal secretory products of apocrine glands in specimens of normal human axillary skin. Lysozyme was also observed in an occasional apocrine secretory cell, as well as in leukocytes within vascular lumina and dermal histiocytes. Lysozyme was not observed in sebaceous glands, eccrine glands, or cells of the epidermis. These observations support an epithelial origin of cutaneous lysozyme and suggest a means of further characterization of the origin and/or differentiation of tumors of appendageal origin.

The relationship between tyrosinase activity and skin color in human foreskins.

Tyrosinase activity was assayed in black and white human foreskin samples by measuring both the hydroxylation of tyrosine to dopa (tyrosine hydroxylase activity) and the conversion of [14C]tyrosine to [14C]melanin (melanin synthesis assay). Enzyme activity was found both in the particulate (75%) and soluble (25%) fractions of the cell. Membrane-bound tyrosinase was readily solubilized by either zwitter-ionic or nonionic detergents. The anionic detergent, sodium cholate, inhibited enzyme activity. Tyrosinase activity in black foreskin homogenates averaged almost three times that in white skin samples (33.8 pmols 3H2O/h/mg skin in black and 12.71 pmoles 3H2O/h/mg skin in white skin), although considerable overlap in activities existed among the two groups. Tyrosinase activities measured with two separate assays, tyrosine hydroxylase and [14C]melanin assays, were similar, suggesting that tyrosine hydroxylase activity is tightly coupled to melanin synthesis. Tyrosinase activity determined by either assay method generally correlated with skin melanin content. Kinetic analysis of tyrosinase from black and white foreskin revealed a Km for tyrosine of 2.5 X 10(-4) M in both skin types. Immunotitration experiments suggested that the difference in tyrosinase activities between white and black skin may be due, not only to different amounts of enzyme present in the melanocytes, but also possibly to differences in the catalytic activities of the enzyme found in melanocytes of black and white skin.

Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes.

Variations in human pigmentation among different racial groups are due to differences in the production and deposition of melanin in the skin. Although melanin synthesis is known to be controlled by the rate-limiting enzyme tyrosinase, the role of this enzyme as the principal determinant of skin pigmentation is unclear. Results from studies with human melanocyte cultures derived from different racial skin types reveal an excellent correlation between the melanin content of melanocyte cultures and the in situ activity of tyrosinase. Melanocytes derived from black skin have up to 10 times more tyrosinase activity and produce up to 10 times more melanin than melanocytes derived from white skin. However, the higher level of tyrosinase activity in melanocytes derived from black skin is not due to a greater abundance of tyrosinase. Results from immunotitration experiments and Western immunoblots reveal that the number of tyrosinase molecules present in white-skin melanocytes may equal the number found in highly pigmented black skin types. Moreover, approximately equivalent levels of tyrosinase mRNA are present in white and black skin cell strains. In contrast, melanocytes derived from red-haired neonates with low tyrosinase activity contain low numbers of tyrosinase molecules and low levels of tyrosinase mRNA. These results show that tyrosinase activity and melanin production in most light-skinned people is controlled primarily by a post-translational regulation of pre-existing enzyme and not by regulating tyrosinase gene activity. In contrast, melanocytes from red-haired (type I) people have low levels of tyrosinase protein and mRNA, suggesting that transcriptional activity of the tyrosinase gene is suppressed.

Epithelioid cell histiocytoma. A report of 10 cases including a new cellular variant.

Epithelioid cell histiocytoma is a recently recognized lesion that is considered to be a variant of cutaneous fibrous histiocytoma (dermatofibroma). Ten cases are presented, including their light microscopic, immunohistochemical, and ultrastructural features. Eight of the cases are similar to those previously reported, presenting as elevated nodules arising on the extremities and composed of epithelioid histiocytes with overlying epidermal effacement. Two of the cases were composed of cells with the same morphologic and immunohistochemical characteristics as typical epithelioid cell histiocytoma, including factor XIIIa positivity, but these arose in the reticular dermis and exhibited prominent cellularity.

Identification of T-lymphocytes and T-subsets in human tonsil using monoclonal antibodies and the immunoperoxidase technic.

A study was performed using monoclonal antibodies and the immunoperoxidase technic to identify T-cells and T-subsets in human tonsil sections. The in situ topographic identification of T-cells, helper cells, and suppressor cells was achieved. This model may therefore be applied to other normal lymphoid tissues. Its potential pathologic importance lies in the fact that certain disorders may be associated with depletion of lymphocyte subsets from their normal areas of "homing," and that lymphoma cells may mirror their putative normal counterparts in their selective metastatic migration pattern. The improved knowledge of normal lymphocyte subset microenvironment afforded by this technic may therefore be of value in applied pathology.

Academic manpower in dermatology.

A survey showed that there were 338 strict or geographic full-time dermatologist faculty members in the United States. Ninety-six percent of these 338 faculty members were located at the 72 schools of medicine with residency training programs in dermatology or at the 21 approved residency training programs in dermatology, not affiliated with colleges of medicine. The 42 schools of medicine without approved residency training programs in dermatology reported only 11 full-time dermatologist faculty (3% of the total). Women constituted 7% of the faculty, while foreign medical graduates constituted 9%. More than one third of faculty were trained at the institution in which they currently serve. Approximately one third were likewise trained at four major teaching institutions.

Identification of T cell in parapsoriasis infiltrates. Use of an anti-human T-cell serum and the immunoperoxidase technique.

"Parapsoriasis" is a term used to include a heterogeneous group of conditions, one variant of which, at least, eventuates in mycosis fungoides in a substantial percentage of cases. The T-cell origin of mycosis fungoides is well established. The lack of similar information on lymphoid cell types in parapsoriasis prompted an immunoperoxidase study using a specific antihuman T-cell serum in a group of seven patients with parapsoriasis. Our findings demonstrated a preponderantly T-cell infiltrate in the categories of parapsoriasis examined.

Pigmented lesions in actinically damaged skin. Histopathologic comparison of biopsy and excisional specimens.

BACKGROUND AND DESIGN: A consecutive sample of 46 cases was collected for comparative histologic evaluation. Results of incisional biopsies of cutaneous pigmented lesions interpreted as lentigo maligna, melanoma in situ, or invasive melanoma, and those suggestive, but not diagnostic, of melanoma were collected. Those lesions that were on actinically damaged skin and in which biopsy was followed by complete excision within 6 months were included. Incisional biopsies that removed greater than 50% of the surface area of the lesion were excluded. RESULTS: Of the excisional specimens, 40% demonstrated histopathologic features more pronounced than those in the biopsy specimens. Areas of invasive melanoma not detected in the biopsy specimens were observed in 20% of the excisional specimens. Accurate diagnosis based on small biopsy specimens was not always possible because of the absence of a classic lentigo maligna histologic pattern in many cases. The most frequent deviation from the pattern was the presence of lentiginous epidermal hyperplasia within these lesions. CONCLUSIONS: These results suggest that limited sampling may be inadequate for an accurate diagnosis of pigmented melanocytic lesions on actinically damaged skin. Areas chosen for biopsy may not contain the most advanced areas histologically and may fail to detect foci of invasive melanoma elsewhere within the lesion.

Involvement of the p16INK4 (CDKN2) gene in familial melanoma.

Recent work on the molecular genetics of familial melanoma has suggested that the p16 kinase inhibitor gene (CDKN2) is one of the genes causing familial melanoma. Evidence for the candidacy of the p16 gene as a familial melanoma gene is summarized and the characteristics of this class of cell cycle control proteins are reviewed.

OKT 6-positive cells: their demonstration in human thymus, and the effect of fixation on the immunoperoxidase reaction.

Human thymocytes at an intermediate stage of differentiation were demonstrated in situ in tissue sections of thymus using the mouse monoclonal antibody OKT 6 THY (Ortho Immunobiology Ltd, Raritan, NJ) and the immunoperoxidase technique. These cells were found to reside mainly within the thymic cortex. The effects of on-slide fixation on the ease of demonstration of the antigen involved were assessed. The choice of fixative was found to have a marked effect, acetone and paraformaldehyde producing the most satisfactory results.

The management of congenital pigmented nevi.

Congenital nevi (CN) can be recognized at birth or shortly thereafter. In adults, only those nevi over 5 cm in diameter can be assumed to be congenital in the absence of documentation in infancy. CN cannot be identified with certainty by histological examination, nor can melanomas be presumed to originate from CN on the basis of histologic findings. Up to 5% of patients with large CN (as defined by the National Institutes of Health (NIH) consensus information) will develop melanoma, and 80% of these will appear before the age of seven years. Increased risk of melanoma from smaller CN has not been substantiated. Although total excision of large CN immediately following birth would reduce the approximate 5% risk for melanoma from these lesions, because of the complexity of the procedure, large lesion removal is seldom completed prior to the ages of 7 to 10 years, and nevus cells frequently remain at the base of the excision with resultant negligible risk reduction. Melanoma risk from large CN is predominantly risk of melanoma in childhood. CN do not contribute significantly to risk for adult melanoma. Sunburn constitutes the most important reducible risk factor for adult melanoma. Ultimately, the greatest hazard of large CN is not melanoma risk but cosmetic deformity.