Inhibition of lymphocyte cytotoxicity and mitogen-induced transformation of lymphocytes by human skin homogenates.

Limitation of the inflammatory cascade has been demonstrated in man by an inhibitor(s) of the prostaglandin system and by inhibitor(s) for chemotaxis of leukocytes. Other factors may exist in vivo that inhibit other inflammatory sequences. In this report, homogenates from human skin interfered with 2 standard assays of lymphocyte function, mitogen-induced transformation and cytotoxicity while homogenates of human placenta did not. Differential centrifugation studies located inhibitory factor(s) primarily in the nuclear fractions. Therefore, reversible transitory depressions of the cell-mediated immune response that are observed concomitantly with chronic dermatoses may reflect release of inhibitory material dermatitic skin in vivo.

The quantitative distribution of gold in skin during chrysotherapy.

Gold concentrations in epidermis, dermis, and whole skin were measured by neutron activation analysis after formation of suction bullae in 8 patients who had received protracted cyrysotherapy. Epidermis contained 3% (median) of the gold content of whole skin. A direct correlation between cumulative gold dose and skin gold level was noted. These findings suggest that apparent gold concentrations in skin are influenced by the depth of the biopsy, that keratinous tissues have little affinity for gold, and that the gold storage capability of skin is not saturated by large cumulative doses of gold. The beneficial effect of gold in pemphigus may not be mediated at the site of blister formation.

Kaposi's sarcoma: absence of cytomegalovirus antigens.

Using an immunohistochemical method, we could not detect cytomegalovirus antigens in the tissue of Kaposi's sarcoma but could in the cells of control sections from tissues known to be infected by that virus. Our results are consistent with the hypothesis that high antibody titers to cytomegalovirus found in patients with Kaposi's sarcoma are not due to infection of neoplastic cells by the virus, as a secondary event; our data supports the conclusions of others that exposure to cytomegalovirus may be a primary event in the pathogenesis of Kaposi's sarcoma.

Electrophoretic patterns of proteins in cystic fibrosis sweat.

The abnormal gene product in cystic fibrosis has not been identified. We report that two-dimensional polyacrylamide gel electrophoresis of 125I-labeled sweat proteins coupled with fluorography and rare earth screen radioautography reveals an absence of an acidic protein of molecular weight 60,000 in sweat collected from 9 patients with cystic fibrosis. The protein spot was present in sweat from heterozygotes and from controls.

In vivo chemotaxis induced by polyunsaturated fatty acids.

Intradermal injection of as little as 500 ng of arachidonic acid or the metabolites from arachidonic acid incubated with soybean lipoxygenase produced infiltration of the upper dermis by polymorphonuclear leukocytes 18 hours after injection. In experiments comparing the chemotactic properties of four fatty acids in varying concentrations, oxidative products of arachidonic acid by soybean lipoxygenase were the most powerful followed by free arachidonic acid and free linoleic acid while stearic acid did not produce significant infiltration. These findings suggest that the elevated levels of free arachidonic acid and an arachidonic acid metabolite (12L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid), recently found in psoriatic epidermis, may at least in part be attracting polymorphonuclear leukocytes into psoriatic skin.

Cholestrol and cholesteryl ester content in normal and pathologic scale.

Using a sensitive new assay, we have measured the cholesteryl ester and cholesterol contents of stratum corneum from callus, normal skin, psoriatic lesions (plantar and nonplantar), and lamellar ichthyotic lesions (plantar and nonplantar). Cholesteryl ester content of normal stratum corneum was significantly higher than that of callus, suggesting that callus was not a suitable control tissue for further biochemical studies involving sterol content of stratum corneum. Both psoriatic and lamellar ichthyotic scale have increased levels of free cholesterol and decreased levels of esterified cholesterol when compared to appropriate controls.

Inhibition of cell-mediated immune reactions by an aqueous extract of normal human skin.

An aqueous extract of normal human skin has been shown to contain an inhibitor of certain cell mediated immune reactions. In this report, the effect of the inhibitor on cell membrane markers and antibody dependent cellular cytotoxicity was determined. Significant diminution of E rosette formation was demonstrated using as little as 0.6 microgram of the skin fraction (p less than .02). Fc receptors for both IgG and IgM were reduced by 46-96% of controls in the presence of the skin inhibitor. On the other hand, no effect on the detection of the complement receptor or surface immunoglobulin was observed, indicating some specificity of binding. In addition, the antibody dependent cell-mediated cytotoxic reaction was inhibited on the skin extract. It was shown that the inhibitor interacted with the lymphocytes, not the antibody or target cells. No effect was detectable when the skin fraction was added after the interactions of effector cells, antibody, and target cells had occurred. This was in contrast to PHA-induced cytotoxicity which could be inhibited following the preincubation of the lymphocytes with the mitogen. Thus there appears to be 2 mechanisms by which the skin fraction interferes with cellular responses: inhibition of antibody binding to Fc receptors, and interference with a step in cellular activation following mitogen stimulation. Analysis of the extract showed the inhibitor was inactivated by trypsin, and did not contain sialic acid, 5'-nucleotidase of beta-N-acetylglucosaminidase, and thus was not associated with membrane or lysosomal enzymes.

Detection of human papillomavirus DNA in seborrheic keratosis by polymerase chain reaction.

We searched for HPV DNA in 72 cases of seborrheic keratosis (nongenital SK 29, genital SK 43) using polymerase chain reaction. Amplification of HPV DNA was found in 24 (nongenital, 1; genital, 23). HPV DNA type 6 was present in 18 cases and type 11 in four and type 33 in two. Twenty-three (53%) cases of genital region SK and one (3%) case of nongenital region SK contained HPV DNA sequences. Histopathologically, the perinuclear vacuolization of epithelial cells, mitosis and dyskeratotic cells were more marked in HPV DNA-positive SK than those in negative SK (P < 0.01). We suppose HPV may play an important role in epidermal proliferation of SK in the genital region.

Lipase expression in human skin.

We have used a monoclonal antibody against human pancreatic lipase to study the immunohistochemical expression of lipase in formalin-fixed, paraffin-embedded biopsy specimens from normal and a variety of tumoral and inflammatory skin diseases. In normal skin, lipase is detected in the sebaceous glands and in the external root sheath of the hair follicle. Antibody to lipase might be a valuable reagent to help confirm sebaceous and follicular differentiation in adnexal tumors. Immunoreactivity to lipase is also detected within mononuclear phagocytes in situations where extracellular release of lipids occurs, such as in xanthomas or in inflammation of the fat with significant lysis of adipocytes. The antibody to lipase identifies a major protein in pilosebaceous homogenates of 42.7 kDa following immunoblotting.

Factor XIIIa in the hamartomas of tuberous sclerosis.

Factor XIII is a blood coagulation factor which may also be produced in an intracellular location. The 'a' subunit of this factor has been found in a number of different cell types and has been shown to stimulate the proliferation of fibroblasts in vitro. We have examined cutaneous, central nervous system and renal lesions from persons with tuberous sclerosis using a standard immunohistochemical assay to see if factor XIIIa is expressed in these hamartomatous growths. We found factor XIIIa in most of the stromal cells composing the skin lesions of tuberous sclerosis as well as in cells of subependymal giant cell astrocytoma of the brain and the stromal cells in renal angiomyolipoma. Expression of factor XIIIa may be of significance in the formation of fibrous growths in tuberous sclerosis.

Loss of factor XIIIa in pig dermis during tissue expansion.

Considerable evidence suggests that factor XIIIa, a blood coagulation factor, also functions in tissue repair, and specifically in the dynamic process of fibroplasia. On the other hand, the dynamic process of tissue expansion would require a loosening of the dermis, the opposite of fibroplasia. We examined the effects of tissue expansion on the expression of factor XIIIa in pig skin. Standard immunohistochemical procedures were used coupled with a rabbit antibody to factor XIIIa. In this report, we demonstrate that the normal expression of factor XIIIa in pig dermis is completely inhibited at the apex overlying the tissue expander. Factor XIIIa inhibition during expansion supports the thesis that this substance is important in the production and maintenance of fibroplasia.

Multicenter study comparing 0.05% gel formulations of desoximetasone and fluocinonide in patients with scalp psoriasis.

A double-blind, multicenter study was conducted to evaluate and compare the safety and efficacy of desoximetasone gel 0.05% and fluocinonide gel 0.05% in patients with scalp psoriasis. One hundred twenty-five patients were enrolled in this randomized, parallel-group trial. Responses based on clinical assessment in 123 patients showed that the desoximetasone gel formulation is a safe and effective treatment for psoriasis of the scalp. Although efficacy appears equivalent to that of fluocinonide gel 0.05% in treating psoriasis of the scalp, desoximetasone appears to be slightly better tolerated and better accepted cosmetically.

Quality assessment of skin biopsy specimens referred to anonymous consultants.

BACKGROUND AND DESIGN: Managed care organizations may direct dermatopathologic specimens to anonymous consultants. I hypothesized that the quality of the consultation decreases when there is no incentive for an anonymous consultant to actively pursue the dermatologist/consumer. Therefore, I examined 364 consecutive specimens that had been directed to anonymous consultants. The specimens were obtained from patients who consulted a university-based dermatology clinic or the office of a collaborating practitioner. The quality of consultation was evaluated in 5 areas: factual correctness, arguable differences in degree, evidence that the history had been read by the consultant, knowledge of dermatologic disease evident in the interpretative aspects of the report, and appropriate direct interaction with the referring physician when indicated. RESULTS: There was concordance between the interpretation by anonymous consultants and the findings of my review in 66.8% of cases that involved common dermatopathologic diagnoses. There were errors in fact in 26 cases (7.1%). There were examples of failure to correlate histologic findings with clinical history, apparent lack of understanding of dermatologic disease, and failure to resolve conflicts between the histologic pattern and the clinical information. CONCLUSIONS: I found a decrease in the quality of biopsy specimen interpretation received from anonymous consultants. Dermatologists need to maintain and/or upgrade their skills in dermatopathology to supervise the quality of interpretation obtained from anonymous consultants.

Herpetiform blisters in systemic lupus erythematosus.

Four patients with systemic lupus erythematosus (SLE) had a vesicobullous eruption that histologically resembled dermatitis herpetiformis. Immunofluorescence microscopy patterns in the skin studied in three patients, however, were characteristic of SLE. Treatment of the underlying collagen-vascular disease improved the eruption, while recurrence coincided with exacerbation of the systemic disease. This distinctive lesion is an important parameter of SLE activity.

Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS.

A 29-year-old Haitian man with the acquired immune deficiency syndrome (AIDS) developed disseminated cryptococcosis with an unusual cutaneous presentation. He had numerous hypopigmented papules over his face that clinically resembled molluscum contagiosum. To our knowledge, cutaneous cryptococcosis resembling molluscum contagiosum has not been previously reported. The patient had a T-cell defect consistent with AIDS and belonged to a high-risk group. To our knowledge, this is the second report of cutaneous cryptococcosis in a patient with AIDS.

Profitability of a university-based clinic using benchmark time lengths for clinical encounters.

Reductions in reimbursement are applied to all physicians in a region equally. However, physicians do not practice in equivalent situations. For example, there are few fiscal allowances for academic functions associated with teaching and administration. Furthermore, university-based physicians may practice in clinical venues that cannot be as efficient as nonuniversity sites. Unavoidable inefficiencies may include (1) the costs of maintaining one historical record for a large noncontiguous practice; (2) university-required holiday schedules and sick leave, making university personnel less productive; (3) noncompetitive overhead rates assigned to clinic components by university financial offices; (4) university-based accounting systems that are not designed for effective cost control and the timely generation of useful management information; and (5) poorly managed billing services. Until now, declining reimbursements have generally led to sufficient efficiencies in delivery so that revenues and expenses can be in equilibrium.

Management of pemphigus with gold compounds: a long-term follow-up report.

Fourteen of 15 patients with pemphlgus have responded successfully to systemically administered gold therapy for up to four years. Eight of the 15 (56%) are in remission, requiring no therapy (mean, 21 months). The remaining seven patients are receiving maintenance systemic gold therapy. Only one instance of toxicity was seen during maintenance therapy. The high remission rate associated with gold therapy and the infrequent side-effects during maintenance therapy suggest that systemically given gold therapy may be the treatment of choice for the management of pemphigus, following initial therapy with corticosteroids when necessary.

Carcinoembryonic antigen in benign sweat gland tumors.

Carcinoembryonic antigen was demonstrated in sweat gland adenomas by immunostaining using standard immunoperoxidase techniques. Carcinoembryonic antigen could not be found in adnexal tumors derived from the pilar and sebaceous apparatus. The demonstration of this specific antigen in certain sweat gland tumors may be helpful in the recognition and classification of these kinds of lesions.

Hereditary painful callosities.

An autosomal dominant genodermatosis that is characterized by painful callosities develops over pressure points. Histologically, these lesions are similar to epidermal nevi.

Cutaneous T-cell lymphoma associated with the acquired immunodeficiency syndrome.

Four cases of T-cell lymphoma occurring in the setting of the acquired immunodeficiency syndrome (AIDS) have been reported previously. We describe a 46-year-old man with AIDS in whom a cutaneous T-cell lymphoma with lymph node involvement developed. Immunohistochemical staining of the skin revealed the lymphoid infiltrate to be CD3+, CD4+, CD8+, and T-cell antigen receptor alpha/beta positive. Co-infection with human T-cell lymphotropic virus type I was not detected by polymerase chain reaction. Human immunodeficiency virus infection may have contributed to the development of this patient's lymphoma. This case represents the rare occurrence of cutaneous T-cell lymphoma and AIDS.