Extracorporeal photochemotherapy does not suppress T- or B-cell responses to novel or recall antigens.

Background: Extracorporeal photopheresis (ExP) is an effective therapy for several conditions including cutaneous T-cell lymphoma, scleroderma, and allograft rejection. Experimental animal models suggest that ExP may induce antigen-specific immunosuppression.

Objective: Our purpose was to determine the effect of photopheresis on humoral and cell-mediated immunity in human subjects.

Staphylococcus aureus isolation from the lesions, the hands, and anterior nares of patients with atopic dermatitis.

Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can exacerbate the disease. Some patients with atopic dermatitis may act as a reservoir for S. aureus transmission to others.

Identification and immunohistochemical localization of protein precursors to human axillary odors in apocrine glands and secretions.

Objectives: To determine the cellular localization in male and female axillary tissue for apocrine secretion odor-binding proteins 1 (ASOB1) and 2 (ASOB2) and the electrophoretic pattern of female apocrine proteins and to begin characterization of the ASOB1 protein.

Design: Immunohistochemical techniques were used with biopsy samples from axillary tissue of male and female subjects. Immunological techniques and microsequencing were used to characterize several of the proteins in male and female apocrine secretions.

S. aureus isolation from the lesions, the hands, and the anterior nares of patients with atopic dermatitis.

Staphylococcus aureus colonization is common in atopic dermatitis (AD) and can exacerbate the disease. Additionally, some evidence shows that patients with AD may act as reservoirs for S. aureus transmission to others.

Propionibacterium acnes colonization in acne and nonacne.

Propionibacterium acnes is a number of the resident bacterial flora and resides in sebaceous follicles. Age-related and body-dependent quantitative differences exist, indicating the role of sebum as an important ecological factor for P. acnes.

Does oral isotretinoin prevent Propionibacterium acnes resistance?

Oral and topical antibiotics play a major role in acne therapy. Physicians base treatment choices on personal perceptions of efficacy, cost-effectiveness or risk-benefit ratios and rarely take bacterial resistance into account. Propionibacterium acnes isolates resistant to one or more anti-acne antibiotics have been reported in Europe, the USA, Japan and New Zealand.

Pathogenesis of cutaneous T-cell lymphoma: implications for the use of recombinant cytokines and photopheresis.

Cutaneous T-cell lymphoma (CTCL) is a clonally derived, skin invasive malignancy of CD4+ cells with the phenotype of mature helper T cells. We previously demonstrated that the leukaemic form of CTCL (Sézary), is characterized by prominent immunological defects including depressed cell-mediated immunity. We also demonstrated increased production of T-helper type 2 (Th2) cytokines (IL-4, IL-5) and deficient Th1 cytokines (IL-2 and IFN-gamma) by their peripheral blood mononuclear cells (PBMC) and detected IL-4 and IL-5 mRNA within lesional skin of patients with all stages of CTCL.

Effects of topical erythromycin on ecology of aerobic cutaneous bacterial flora.

We have demonstrated previously that application of topical erythromycin, an antibiotic commonly used for the treatment of acne, results in an increased density of cutaneous erythromycin-resistant (Emr) coagulase-negative staphylococci; however, it is unknown if this increase results in an overall higher density of total cutaneous staphylococci or if upon cessation of erythromycin use, Emr coagulase-negative staphylococci remain at an increased density compared with the pretreatment density. To investigate this, 2% erythromycin or vehicle was applied to each subject's forehead (n = 225) twice a day by laboratory personnel for a period of 6 weeks. Samples were obtained for culture from the forehead, anterior nares, and back of the subjects at baseline and at weeks 6, 9, and 12 of the study.

The potential therapeutic role of interleukin-12 in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative disorder characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature T-helper (Th) cells. Sezary syndrome (SzS) represents an advanced form of CTCL associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by peripheral blood mononuclear cells (PBMCs) in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, indicating that the clonal T-cell population is likely derived from the T-helper type 2 (Th2) subset of helper T lymphocytes.

Failure to detect human T-lymphotropic virus type-I proviral DNA in cell lines and tissues from patients with cutaneous T-cell lymphoma.

Previous molecular studies investigating the presence of HTLV-I proviral DNA in cell lines and tissue samples of patients with cutaneous T-cell lymphoma (CTCL) have reported a detection rate ranging from 0-92%. Despite the lack of epidemiologic data linking HTLV-I infection with CTCL, the molecular data still invite speculation regarding the precise role of HTLV-I in the pathogenesis of CTCL. To determine the detection rate of HTLV-I proviral DNA among CTCL patients referred to our medical center, we analyzed Epstein-Barr virus-transformed cell lines established from peripheral blood of seven CTCL patients and 43 tissue samples from 22 patients with different stages of disease.

Replicate plating: does it increase reliability?

As a part of a clinical study to evaluate the antibacterial effect of a topically applied erythromycin gel, microbiological specimens were taken from two groups of patients: one group using 2% erythromycin gel and the other group using a placebo gel. These specimens were plated in triplicate using a common source on bacteriological media using standard procedures. After the appropriate incubation times, the numbers of aerobic and anaerobic organisms were counted separately from each of three plates.

Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell Lymphoma: relevance to mechanism of therapeutic action.

The anti-tumor action of many chemotherapeutic agents has recently been attributed to the induction of apoptosis in the malignant cell population. In this study, we investigated the ability of extracorporeal photopheresis (ExP) and in vitro PUVA (8-methoxy-psoralen + ultraviolet A) therapy to induce apoptosis in peripheral blood mononuclear cells from Sezary syndrome patients and normal controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood lymphocytes demonstrated two distinct cell populations within 24 h of treatment.

A human axillary odorant is carried by apolipoprotein D.

The characterization of the source of the odor in the human axillary region is not only of commercial interest but is also important biologically because axillary extracts can alter the length and timing of the female menstrual cycle. In males, the most abundant odor component is known to be E-3-methyl-2-hexenoic acid (E-3M2H), which is liberated from nonodorous apocrine secretions by axillary microorganisms. Recently, it was found that in the apocrine gland secretions, 3M2H is carried to the skin surface bound to two proteins, apocrine secretion odor-binding proteins 1 and 2 (ASOB1 and ASOB2) with apparent molecular masses of 45 kDa and 26 kDa, respectively.

Kinetic analysis of apoptosis induction in human cell lines by UVA and 8-MOP.

Whereas previous studies have indicated that DNA damage as a result of 8-methoxypsoralen (8-MOP) and UVA treatment leads to cell death, this study establishes the minimum concentrations of 8-MOP and UVA necessary to induce apoptosis in human T-lymphocytic and monocytic cell lines. In order to asses apoptosis, we used fluorescent microscopy to examine changes in light scattering as well as internucleosomal DNA fragmentation. Generation of a dose response curve showed that the minimum combination of UVA and 8-MOP that was necessary to induce greater than background levels of apoptosis within 24 h of treatment was 0.

A new method for in vivo evaluation of antimicrobial agents by translocation of complex dense populations of cutaneous bacteria.

Previously, we described methods for measuring in vivo antimicrobial activity in which the resident bacterial flora of the forearm is expanded by occlusion with an impermeable plastic film, test agents are applied and quantitative cultures are obtained at varying time points. This methodology allows for an in vivo quantitative assessment of antimicrobial effects directed against a dense flora comprised primarily of staphylococci. This method may not be applicable to situations in which there is a high density of multiple species of bacteria.

Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P.

Expression of interleukin-4 and interleukin-5 mRNA in developing cutaneous late-phase reactions.

The stimuli for the accumulation and activation of eosinophils, which are prominent components of IgE-mediated allergic late-phase reactions (LPRs), are not defined. Messenger RNA for interleukin-5 has been found in lymphocytes present in biopsy specimens of skin obtained during LPR 24 hours after antigen challenge. However, it is not known whether interleukin-5 is present to attract or activate the eosinophils that accumulate during the first 6 hours after antigen challenge when cutaneous LPRs are developing.

IL-12 reverses cytokine and immune abnormalities in Sezary syndrome.

Cutaneous T cell lymphoma is a lymphoproliferative disorder typically characterized by skin invasion of clonally derived malignant CD4+ lymphocytes that phenotypically resemble mature Th cells. Sezary syndrome (SzS) represents an advanced form of cutaneous T cell lymphoma associated with generalized erythroderma and involvement of the peripheral blood by the malignant cell population. We have previously demonstrated aberrant cytokine production by PBMC in SzS characterized by increased IL-4 and deficient IL-2 and IFN-gamma production, as well as increased expression of mRNA for IL-4 and IL-5 within active skin lesions, suggesting that the clonal T cell population is derived from the Th 2 subset of helper T lymphocytes.

Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma.

We have previously demonstrated that peripheral blood mononuclear cells from patients with Sézary syndrome, the leukemic form of cutaneous T-cell lymphoma which is accompanied by erythroderma and lymphadenopathy, have a Th2 cell cytokine [interleukin 4 (IL-4) and interleukin 5] production pattern. In this study, we extend these observations to demonstrate a correlation of the presence of a Th2 cytokine pattern with a malignant T-cell clone in different stages of cutaneous involvement among patients with cutaneous T-cell lymphoma (CTCL). Skin biopsies were obtained from 12 CTCL patients with various disease stages (three patch, three plaque, six tumor), three patients with parapsoriasis, four patients with inflammatory dermatoses, including two psoriasis and two lichen planus, and 12 normal controls.

Retroviruses and cutaneous T-cell lymphoma.

Since the discovery of the first human retrovirus, HTLV-I, and its etiologic role in ATL, the search for a retrovirus and its role in the development and progression of CTCL has been vigorously pursued and debated. Current studies in CTCL have evaluated serum antibodies to retroviral proteins, electron microscopy to identify viruslike particles, and Southern blot analysis and PCR amplification to detect proviral DNA sequences. There have been inconsistent findings within and between a variety of studies, emphasizing the need for critical evaluation of experimental methods and their potential shortcomings.

Therapeutic applications of photopheresis.

Photopheresis is a useful therapy for advanced cutaneous T-cell lymphoma, particularly for Sezary syndrome. Additional conditions in which clinical studies have suggested a therapeutic role for photopheresis include certain autoimmune diseases and reversal of rejection of solid organ allografts. Because photopheresis is extremely well tolerated and evidence is lacking for a direct immunosuppressive effect produced by this therapy, randomized trials should be pursued to determine the full spectrum of clinical benefit of this novel therapeutic modality.

Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells.

Sezary syndrome (SzS), the leukemic stage of cutaneous T-cell lymphoma (CTCL), is typically a CD4+ T-cell lympho-proliferative disease characterized by numerous immunologic abnormalities, including decreased T-cell responses to antigens and mitogens, decreased natural killer and lymphocyte-activated killer cell activities, eosinophilia, and increased levels of immunoglobulins, particularly IgE and IgA. Because this constellation of abnormalities is reminiscent of the pleiotropic in vitro activities of IL-4 and IL-5, we examined the possibility that malignant T cells in SzS may be producing increased amounts of IL-4 with a concomitant decrease in IL-2 and IFN-gamma production. Such a cytokine secretion pattern would be similar to that produced by murine Th2 cells.