Anthony A. Gaspari

CD40 Expression by human fibroblasts

The purpose of this study was to determine whether human fibroblasts express CD40, a 50-kDa member of the tumor necrosis factor-alpha-receptor superfamily. CD40 is an important mitogenic receptor on B lymphocytes which regulates B lymphocyte proliferation and differentiation. Interestingly, CD40 mRNA was detected in human lung, gingival, synovial, dermal (foreskin), and spleen fibroblasts using the reverse-transcriptase polymerase chain reaction. Moreover, the CD40 protein was detected on cultured human fibroblasts using anti-CD40 mAbs (G28-5, EA-5) and flow cytometry and on fibroblasts in dermal tissue sections via in situ staining. In contrast to B lymphocytes, where CD40 expression is unregulated both by interleukin-4 and interferon (IFN-gamma), CD40 expression on cultured human fibroblasts could only be upregulated by IFN-gamma. IFN-gamma induced a 10-fold increase in CD40 mRNA and protein levels. Furthermore, via a two-color staining technique for CD40 expression and DNA content, IFN-gamma not only upregulated CD40 expression on cultured human fibroblasts, but also shifted fibroblasts into the G0/G1 phase of the cell cycle. This observation suggested that nonproliferating fibroblasts might display elevated levels of CD40. To test this hypothesis, CD40 expression was analyzed on fibroblasts in log phase growth vs fibroblasts which had reached confluency and were nonproliferating. Interestingly, confluent fibroblasts expressed higher levels of CD40 than fibroblasts in log phase growth. These data suggest that CD40 expression by human fibroblasts is related to cell growth. In summary, this report is the first to demonstrate that human fibroblasts from a variety of tissues display CD40. While the function of CD40 on fibroblasts is not yet known, it may facilitate fibroblast proliferation, an event important for tissue repair, and may facilitate inflammation via interaction with T lymphocytes and mast cells, which display the CD40 ligand.

Cutaneous reactions to recombinant cytokine therapy

Cytokines are critical to several fundamental homeostatic mechanisms such as fever, acute phase reactions, wound healing, hematopoiesis, inflammation, cellular and humoral immune responses, and tumor regression. As a result of advances in recombinant DNA technology, recombinant cytokines are available as therapeutic agents. They have been used for metastatic cancers and immunodeficiencies, as a therapy for naturally occurring or drug-induced anemias or leukopenias, and they have also been applied to some cutaneous disorders. Cytokine therapy can result in toxic reactions that affect many organ systems, especially the skin. These reactions are common and diverse, ranging from minor injection site reactions, pruritus, and flushing to life-threatening autoimmune disorders, severe erythroderma, or bullous skin reactions. This review focuses on the major cytokines that are in current clinical use or under investigation and describes the cutaneous complications of these agents.

Recombinant human antibody single chain variable fragments reactive with Candida albicans surface antigens.

A combinatorial phage display library expressing human immunoglobulin heavy and light chain variable regions was used to identify phage clones capable of binding to the surface of Candida albicans blastoconidia. Single chain antibody variable fragments (scFv) derived from three clones detected C. albicans antigens by indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and Western blotting. The antigens detected were conserved among different strains of C. albicans and several other Candida species. Two scFv clones detected antigens specifically expressed by C. albicans blastoconidia; the third detected antigens in both blastoconidia and filamentous forms of C. albicans. The antigens containing the epitopes recognized by all three scFv could be extracted from blastoconidia by dithiothreitol, suggesting attachment to the cell wall via sulfhydryl bonds. Epitope detection by the scFv was sensitive to treatment of C. albicans blastoconidia with sodium periodate, but not proteinase K, indicating the cognate epitopes were composed of carbohydrate. Antigenic determinants for each of the three scFv were detected by immunohistochemical staining of skin sections from a model of cutaneous candidiasis, demonstrating expression in vivo. Through selection for the ability to bind intact organisms, the phage display system provides a means to rapidly identify monoclonal binding ligands to Candida surface antigens. Being entirely human, mature antibodies generated from the scFv have potential utility in the treatment of candidiasis.

Identification of HHV-8 DNA in the skin lesions of Kaposi’s sarcoma in an immunosuppressed patient with bullous pemphigoid☆☆☆★

Kaposis sarcoma rarely occurs as an opportunistic tumor in iatrogenically immunosuppressed patients. We describe the clinical presentation, treatment of Kaposis sarcoma skin lesions in an immunosuppressed patient with bullous pemphigoid. Using the polymerase chain reaction, HHV-8 DNA was detected in two separate Kaposis sarcoma lesions but not in control tissues. The amplified DNA fragments derived from our patients Kaposis sarcoma skin lesions contained unique point mutations that distinguished the virus isolated from Kaposis sarcoma lesions derived from other patients. This is the first demonstration that HHV-8 DNA is associated with Kaposis sarcoma skin lesions in an HIV-negative, immunosuppressed patient with bullous pemphigoid. HHV-8 is probably a common latent herpesvirus that is activated by immunosuppressive therapy in genetically predisposed patients and may be involved in the pathogenesis of Kaposis sarcoma.

Follicular mycosis fungoides: a case report and review of the literature

Background: Follicular mycosis fungoides is an unusual variant of mycosis fungoides (MF). Unlike classic MF where atypical lymphocytes show a predilection for the epidermis (epidermotropism), follicular MF displays a malignant lymphocytic infiltrate tropic for hair follicles (folliculotropism). This malignant lymphocytic infiltrate results in follicular disruption typically manifesting clinically as plaques, comedones and follicular papules.

Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

Background: Thalidomide is an anti‐inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti‐inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor‐alfa (TNF‐α) production by monocytes. However, its mechanism of action in the skin is not known.

THE ROLE OF KERATINOCYTES IN THE PATHOPHYSIOLOGY OF CONTACT DERMATITIS

Industrialization has greatly increased exposure to chemicals, pollutants, and noxious substances, both at home and in the workplace. This trend of increasing chemical exposure continues as reliance on technology deepens. The initial barrier against these substances is the skin. In the majority of individuals, this defense is sufficient and acts without adverse effects. As exposure to chemicals becomes more widespread and frequent, the incidence of pathologic responses to this exposure in the population has increased dramatically. In 1990, the National Center for Health Statistics reported that eczematous dermatitis was one of the most common specific dermatoses encountered in the outpatient setting. 1 It is estimated that dermatitis as a result of incidental or inadvertent exposure to occupational hazards accounts for 30% of all occupational disease. More than 90% of cases described are due to irritant contact dermatitis (ICD) or allergic contact dermatitis (ACD). 85 In a study done in Denmark, hyperkeratotic hand eczema alone was estimated to affect 2.5% of Danish workers on permanent disability at a national cost of

Drug Treatment of Skin and Soft Tissue Infections in Elderly Long-Term Care Residents

15 million per year. 89 A direct extrapolation to the United States, based on population alone, would imply an impact of nearly

Roquinimex-induced graft-versus-host reaction after autologous bone marrow transplantation

750 million per year solely for hand eczema. Thus, contact dermatitis is a disorder of significant economic dimension. This article seeks to outline the various contact dermatitides, then compare the features of ICD and ACD, and lastly to outline the immune mechanisms of contact dermatitis, with special emphasis on the role of keratinocytes.

Contact allergy to ophthalmic dipivalyl epinephrine hydrochloride: demonstration by patch testing

SummaryNursing home-acquired skin and soft tissue infections are common, with an estimated prevalence of approximately 5%. Such infections can be a cause of significant morbidity. The types of organisms that cause primary skin and soft tissue infections in the elderly are diverse, and include bacterial, viral and fungal infections, as well as infestations with scabies or lice. In the elderly, these infections or infestations may present with atypical signs and symptoms, so a high index of suspicion is necessary. These skin and soft tissue infections may complicate an underlying chronic skin disorder (such as a decubitus ulcer), further altering their clinical presentation.Treatment of skin infections and infestations is based on the appropriate diagnostic tests. Once the diagnosis has been confirmed, treatment with the standard drug therapy is usually associated with a favourable clinical outcome. This article summarises the major skin and soft tissue infections in the elderly, and the appropriate drug therapy, with emphasis on special considerations for long-term care residents and the unique environment of the nursing home that allows for the emergence of resistant organisms. These factors make the management of skin and soft tissue infections in this population unique and challenging.