Mark Allen Everett

Demonstration in situ of “T” Cells and “T” Cell Subsets in Lichen Planus using Monoclonal Antibodies

This report describes the in situ demonstration of “T” lymphocytes and “T” lymphocyte subsets in tissue sections using a case of lichen planus as a model. The technique utilized is the indirect immunoperoxidase method with monoclonal antibodies to “T” cells and “T” cell subsets. In the case examined a predominance of helper “T” cells was found. The potential application of this method in the immunopathology of skin and internal organs is discussed.

Demonstration of OKT 6—reactive cells in mycosis fungoides

Infiltrates of five cases of mycosis fungoides (MF) were studied for the presence of cells reactive with a monoclonal antibody, OKT 6, which detects an antigen present on relatively immature thymocytes and Langerhans cells. In situ immunohistochemical staining was used for their demonstration. OKT 6-reactive cells formed a definite component of the dermal infiltrates of all patients examined. In three patients who showed numerous Pautrier microabscesses on routine histologic examination, OKT 6-positive cells were found to form a component of these abscesses. OKT 6-reactive cells have also recently been shown to be present in varying numbers in the dermal infiltrates of large plaque (atrophic) parapsoriasis (LPAP), a condition which may terminate in MF. The significance of these findings is discussed.

Absence of Epstein-Barr virus in lymphoepitheliomalike carcinoma of the skin : Polymerase chain reaction evidence and review of five cases

Lymphoepithelioma is a lymphocyte-rich, poorly differentiated, nonkeratinizing carcinoma of the nasopharynx with distinctive clinical, epidemiologic, and etiologic features. Histologically and immunophenotypically identical tumors arising outside the nasopharynx are designated lymphoepitheliomalike carcinomas (LELCs), and have been described in the gastrointestinal tract, lung, salivary glands, thymus, and increasingly in the skin. Despite similarities between LELC and nasopharyngeal lymphoepithelioma, there is growing evidence that they are etiologically distinct. Serologic studies and molecular techniques have consistently demonstrated an etiopathologic association between Epstein-Barr virus (EBV) and lymphoepithelioma and LELC of several locations, including stomach, salivary gland, lung, and thymus. Though histologically similar. lymphoepitheliomalike carcinoma of the skin (LELCS) does not contain EBV DNA by RNA in situ hybridization. Recently, techniques for polymerase chain reaction (PCR) using fixed tissue have been described that to our knowledge have not been applied to LELCS. We studied five cases of LELCS, taking advantage of the higher sensitivity of PCR to evaluate the role, if any, of EBV specifically in the pathogenesis of LELCS.

In situ demonstration of T cell subsets in atrophic parapsoriasis

It has been demonstrated recently in mycosis fungoides and lichen planus that T lymphocyte subsets may be identified in cutaneous lymphocytic infiltrates using the immunoperoxidase technic in conjunction with monoclonal antibodies produced by the technic of Kohler and Milstein. This communication describes the application of this technic to cutaneous lymphoid infiltrates of parapsoriasis in which T cell predominance has been demonstrated previously. The lymphoid infiltrates of six patients with atrophic parapsoriasis were examined by the indirect immunoperoxidase technic using monoclonal antibodies (from two commercial sources) directed against helper and suppressor T cell subsets. Both helper and suppressor cells (as defined by a positive reaction with monoclonal antibodies) could be identified in cutaneous infiltrates. Helper cells predominated, but in varying degrees among patients. The relevance of these findings in relation to the possible development of clinical mycosis fungoides from atrophic parapsoriasis is discussed. In addition, factors causing difficulty in the consistent identification of cell subtypes are discussed. These factors suggest that in the present state of imperfection, difficulty will be experienced in using this technic for the accurate quantification of percentages of lymphocyte subsets in tissue sections.U

In situ demonstration of OKT 6-positive cells in cutaneous lymphoid infiltrates

A monoclonal antibody, OKT 6, has been developed against an antigen which is expressed by immature T cells as part of their normal intrathymic differentiation, but not by mature peripheral T cells. It was though that a search for the expression of such an antigen might be worthwhile in prelymphomatous conditions. This communication describes the investigation of lymphocytic infiltrates of atropic parapsoriasis, lymphomatoid papulosis, and a small group of miscellaneous skin conditions with OKT 6 and the immunoperoxidase technic. OKT 6-positive cells were identified in the dermis in varying numbers in four cases of atrophic parapsoriasis and in one case of lymphomatoid papulosis, but not in any of the other disorders. Positive epidermal staining was noted in all tissues examined. The pattern obtained suggested that epidermal dendritic cells may react with OKT 6. The findings indicate that OKT 6-positive cells may be found outside the thymus in certain conditions. The observations in epidermis cast doubt on the exact nature of the positively reacting cells observed in dermis, suggesting that may either be immature thymocytes or possibly Langerhans cells.

Hormonal stimulation of tyrosinase activity in human foreskin organ cultures

SummaryA human foreskin organ culture system has been developed to study the response of human skin to hormonal stimulation. Foreskins are maintained in culture on floating plastic supports which allows the epidermal surface to be exposed to air while the dermis is bathed in nutrient medium. Both black and white human foreskins can be maintained in organ culture for at least 1 wk with no change in the tissue structure or cell viability as determined by histochemical staining and by dopa reaction staining. Tyrosinase activity in both black and white human foreskin cultures decays markedly during the first 2 d of culture to a new steady state level which remains stable throughout the culture period. Both black and white foreskin cultures consistently demonstrate 2- to 10-fold increases in tyrosinase activity when treated with theophylline (1 mM). Approximately 90% of all skin cultures examined showed an increase in enzyme activity when treated with this phosphodiesterase inhibitor. Dibutyryl cAMP (0.1 mM) and [Nle4, D-phe7]-alpha MSH (10−8M), were also found to markedly stimulate tyrosinase activity in some skin cultures, whereas alpha-MSH and prostaglandin E1 produced only an inconsistent and small increase in the activity of the enzyme. Histamine (1 μM), vitamin D3 (1 μM), and retinoic acid (1μM) failed to stimulate tyrosinase activity in either white or black foreskin cultures. This hormone-responsive organ culture system can be utilized to characterize the molecular processes responsible for the regulation of tyrosinase and pigmentation in human skin.

OKT 9 reactivity in mycosis fungoides and large plaque (atrophic) parapsoriasis

A monoclonal antibody OKT 9 which detects a determinant expressed by a variety of proliferating cell types has been recently developed. This antibody was used in conjunction with the immunoperoxidase technique to study the cutaneous lymphoid infiltrates of nine patients with mycosis fungoides, one patient with lymphomatoid papulosis, two patients with Sézary syndrome, and ten patients with large plaque atrophic parapsoriasis (a condition which may terminate in overt mycosis fungoides.) OKT 9 reactive cells were identified in all cases of mycosis fungoides examined, in one case of lymphomatoid papulosis, one of two cases of Sézary syndrome, and one of ten cases of large plaque atrophic parapsoriasis. These results suggest that further studies using OKT 9 should be performed to assess whether OKT 9 reactivity may be used as a prognostic marker in cutaneous lymphomas and prelymphomas.

OKT 9 reactive cells in mycosis fungoides

The development of tnonoclonal antibodies to T cells and T cell subsets (Kung et al. 1979, Reinherz et al. 1979) has provided a potentially powerful tool for the phenotypie analysis of lymphocyte subpopulations in a variety of diseases. During their normal intrathytnic differentiation (Reinherz et al. 1980), Ihymocytes lose certain antigens (T9, 6, 10) and gaiti others (T4, 5, 8, and 3). (Table 1). The analysis of cell suspensions by using monoclonal antibodies directed to these differentiation antigens has resulted in the demonstration of a predominately immalute phcnotype (TIO positive or ITO and 19 positive) in human T eell acute leukemias (Reinherz et al. 1980). In contrast, an early stttdy in Sezary syndrome using monoclonal antibodies directed against mature 1 cell antigens has indicated a mature phenotype of the cells coneerncd (Greaves et al. 198 I). T9, which is expressed and lost early in thymie differentiation (Rcinberz et al. 1980) is probably not in fact specific for immature T cells, bul may also be expressed by malignant cells of non T lineage (Greaves et al. 1981).

Papillomatous melanocytic nevi: an estrogen related phenomenon

A prospective two‐month epidemiologic and histologic study of all melanocytic nevi biopsied (n = 434) at the University of Oklahoma Health Center was undertaken. Melanocytic nevi with papillomatous features (PAP) (n=50) were found to occur predominantly in females (females = 44, males = 6; p < 0.01 adjusted for sex distribution of all melanocytic nevi). Immunohistochemical analysis of melanocytic nevi revealed concordance between PAP and intracytoplasmic nevocellular staining for estrogen‐inducible pS2 protein. Melanocytic nevi without papillomatous features failed to stain for pS2 protein. These results suggest a hormone responsivness exclusive of patient sex which may influence the pathogenesis of these distinctive melanocytic nevi.

Jean Louis Alibert, The Father of French Dermatology

lean Louis Marc Alibert (Fig, ]), the fourth of eight children, was born on May 2, 1768, on rue basse St. Jean (now rue Alibert) in Villefranche de Rouergue, a southwestern French town with a population of 8,000. His father, Pierre, was a well-known local magistrate. At age five, Alibert began school at a celebrated local religious institution run by the Fathers of Christian Doctrine, where he studied classics. After deciding upon the priesthood for a career, he moved at the age ot 18 to their seminary at Toulouse for his novitiate. There, 3 years later, the Church lands were appropriated (1789). Secularization of much of the clergy was accomplished under the law of August 17, 1792, when all religious orders were dispersed. Alibert, forced to abandon his religious vocation, began teaching in a local school.