Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules.

We have previously reported that griseofulvin inhibits VCAM-1 expression on human vascular endothelial cells. Since griseofulvin interferes with microtubule assembly, we used colchicine as another microtubule antagonist and compared it with griseofulvin to further characterize this inhibition. By flow cytometry, colchicine inhibited VCAM-1 induction on TNFalpha-stimulated human dermal microvascular endothelial cells (HDMEC) dose-dependently.

Exacerbation of pustulosis palmaris et plantaris after topical application of metals accompanied by elevated levels of leukotriene B4 in pustules.

Background: Pustulosis palmaris et plantaris (PPP) is a chronic inflammatory disease consisting of polymorphonuclear leukocyte infiltration, and is often exacerbated by focal infections such as tonsillitis. In some cases, metal allergy has been reported.

Objective: The purpose of this study was to evaluate (1) the significance of metal allergy in the formation of pustules, and (2) the participation of leukotriene (LT) B(4) in the formation of pustules of PPP.

Granulocyte/macrophage colony-stimulating factor inhibits IL-12 production of mouse Langerhans cells.

We investigated the capacity of mouse Langerhans cells (LC) to produce IL-12, a central cytokine in a Th1 type of immune responses. We prepared purified LC (>95%) from BALB/c mouse skin by the panning method using anti-I-Ad mAb. An ELISA showed that purified LC spontaneously produced IL-12 p40, and that its production was up-regulated following simultaneous stimulation with anti-CD40 mAb and IFN-gamma.

Differential effects of cytokines and immunosuppressive drugs on CD40, B7-1, and B7-2 expression on purified epidermal Langerhans cells1.

Langerhans cells are MHC class II antigen-positive antigen-presenting cells in the epidermis. Recent studies have revealed that Langerhans cells express costimulatory molecules like B7-1 and B7-2 and the accessory molecule CD40. Although these molecules are important for the antigen-presenting function of Langerhans cells, little is known about the precise regulation of their expression on purified Langerhans cells.

Functional CD40 ligand is expressed on epidermal Langerhans cells.

Epidermal Langerhans cells (LC) are bone-marrow-derived major histocompatibility complex (MHC) class II antigen-expressing antigen-presenting cells (APC) that comprise 1-3% of total epidermal cells (EC). LC express high levels of MHC class II antigen and augment costimulatory molecules such as B7-1, B7-2 during culture. In a previous report, using purified murine LC, we showed that freshly prepared LC (fLC) do not express CD40, whereas cLC express CD40.

Polymorphisms of HLA-DM genes in Japanese patients with psoriasis vulgaris.

We analysed the polymorphisms of HLA-DM genes in 85 unrelated Japanese patients with psoriasis vulgaris and 52 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of DMA*0101 was decreased (79% vs. 89%, P < 0.

Increased numbers of CD68 antigen positive dendritic epidermal cells and upregulation of CLA (cutaneous lymphocyte-associated antigen) expression on these cells in various skin diseases.

CD68 is a myelomonocytic marker identified in human dermal macrophages. Although the existence of CD68 + dendritic epidermal cells has been reported, their characteristics have not been well elucidated. Cutaneous lymphocyte-associated antigen (CLA) is a homing receptor of cutaneous inflammatory T cells.

Kimura's disease associated with ulcerative colitis: detection of IL-5 mRNA expression of peripheral blood mononuclear cells and colon lesion.

Kimura's disease is considered to be a Th2 type allergic reaction based on the presence of eosinophilia and IgE hyperimmunoglobulinemia. We report a 26-year-old Japanese male with this disorder associated with ulcerative colitis. IL-5 is a selective stimulator for the production of eosinophilia and is considered to play an important role in Kimura's disease.

Analysis of HLA class II and TAP alleles in Japanese patients with psoriasis vulgaris.

We investigated HLA class II and transporter associated with antigen processing (TAP) alleles in eighty-five unrelated Japanese patients with psoriasis vulgaris and fifty-two healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. The frequencies of DRB1*1502 and DQB1*0601 were increased in the patient group (DRB1*1502; 21% vs 12%, p < 0.05, DQB1*0601; 35% vs.

Calcitonin gene-related peptide and Langerhans cell function.

Morphologic studies have indicated that Langerhans cells (LC) are frequently in anatomic apposition with epidermal nerves containing the neuropeptide calcitonin gene-related peptide (CGRP). Experiments were undertaken to examine whether CGRP modulates LC function. The effect of pre-exposure of LC to CGRP in vitro on alloantigen presentation and specific protein presentation to a responsive T-cell line were studied using freshly prepared murine epidermal cell populations enriched for LC content (EC) by treatment with antibody to Thy-1 and complement.

Increased pulse wave velocity and shortened pulse wave transmission time in hypertension and aging.

We measured pulse wave velocity (PWV) and pulse transmission time (PTT) in 29 patients with hypertension, ranging in age from 37 to 73 years, in a series of 36 normal subjects with the same age range, and in an additional series of 44 normal subjects aged 18-35 years. PWV increases linearly with age for both normal subjects and patients with hypertension, with a corresponding significant decrease in PTT. There was a statistically highly significant (p < 0.

Regulation of cytokine expression in macrophages and the Langerhans cell-like line XS52 by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP) inhibits antigen presentation by Langerhans cells (LC) and macrophages, and LC are anatomically associated with CGRP-containing epidermal nerves. To determine whether CGRP may produce some of its functional effects through regulation of cytokine expression, we utilized enzyme-linked immunosorbent assay (ELISA) of conditioned supernatants to examine production of interleukin (IL)-10 and IL-1 beta protein in the LC-like cell line XS52 as well as the reverse transcriptase-polymerase chain reaction (RT-PCR) to examine levels of mRNA for IL-10, IL-1 beta, and the 40-kDa subunit (p40) of IL-12. CGRP augmented the lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF) -induced release of IL-10 protein and the induced expression of IL-10 mRNA in these cells.

Study of aspartate at residue 9 of HLA-C molecules in Japanese patients with psoriasis vulgaris.

The frequency of aspartate at residue 9 (Asp-9) of HLA-C molecules was investigated among 75 Japanese patients with psoriasis vulgaris and 50 healthy controls. We developed a technique of polymerase chain reaction sequence-specific primer (PCR-SSP) amplification of genomic DNA for HLA-C alleles with a codon for Asp-9. The specificity of amplification was confirmed by direct sequencing of the amplified products and amplification from total RNA (RT-PCR).

Immunomodulatory properties of maxadilan, the vasodilator peptide from sand fly salivary gland extracts.

Sand flies are the arthropod vector of leishmaniasis and salivary gland extracts from these flies exacerbate leishmaniasis in vivo. The mechanism of exacerbation appears to be due to immunomodulatory effects of the saliva on host immune function but the active component is unknown. The following studies reveal that maxadilan, the vasodilatory peptide present in sand fly salivary gland extracts, has immunomodulatory properties.

Identification and DNA typing of two Cw7 alleles (Cw*0702 and Cw*0704) in Japanese, with the corrected sequence of Cw*0702.

Two alleles encoding HLA-Cw7 antigens, tentatively called C7J1 and C7J2, have been identified in Japanese using a PCR-SSCP method. The nucleotide sequence of full-length C7J1 cDNAs showed a high degree of homology to the reported Cw*0702 sequence except in exon 1. We then resequenced the allele carried by the cell line JY in which Cw*0702 was first identified, according to a request from the WHO Nomenclature Committee.

Modulation of Langerhans cell function by epidermal nerves.

Many if not most epidermal Langerhans cells appeared to be closely associated anatomically with calcitonin gene-related peptide (CGRP)-containing nerves as determined by confocal laser scanning microscopy. Furthermore, a small proportion of Langerhans cells had immunoreactive CGRP at or near their cell surfaces, suggesting that nerves are capable of depositing CGRP at or near Langerhans cells. CGRP inhibited Langerhans cell antigen-presenting capability for elicitation of delayed-type hypersensitivity in immunized mice to present alloantigens in the mixed epidermal cell-lymphocyte reaction and to present a protein antigen to a responsive hybridoma.

Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects.

Epidermal Langerhans cells (LC) are associated anatomically with epidermal nerves, and a product of these nerves, calcitonin gene-related peptide (CGRP), inhibits the antigen-presenting capacity of LC and macrophages. As the CGRP receptor appears to be coupled to Gs alpha protein, which in turn activates adenylate cyclase, the ability of CGRP to induce cAMP in LC was examined and correlated with functional effects. LC were isolated from murine epidermal cells using antibodies on magnetic microspheres.

Inhibition of the induction of delayed-type and contact hypersensitivity by calcitonin gene-related peptide.

Calcitonin gene-related peptide (CGRP)-containing nerves are frequently associated anatomically with epidermal Langerhans cells (LC), and LC Ag-presenting function is down-regulated by CGRP. To investigate possible regulation of cutaneous immunity by CGRP, we examined its effect on the induction of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CHS). A system of immunity to the murine spindle cell tumor S1509a (H-2a) was employed to examine induction of DTH by LC.

IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.

IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor immune responses, we examined the effect of IL-10 on LC Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). Because induction of immunity to S1509a requires exposure of LC to granulocyte-macrophage (GM)-CSF, this system also allowed us to study the regulatory interactions of GM-CSF and IL-10 on LC.

Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?

Background: Psoriasis vulgaris was reported to be associated with a specific alanine residue at position 73 of HLA-C alleles in Japanese patients.

Objective: Our purpose was to determine the role of HLA genes in susceptibility to psoriasis vulgaris in the Israeli Jewish population.

Methods: Twenty-eight Israeli patients were analyzed for their HLA class I and II specificities by means of serologic and molecular methods.

Epidermal cell presentation of tumor-associated antigens for induction of tolerance.

Intravenous administration of hapten-coupled epidermal cells (EC) induces tolerance in mice. To assess the relevance of this observation to cutaneous tumors, the ability of EC to induce tolerance to the S1509a spindle cell tumor (H-2a) was examined. ECs were prepared from CAF1 (H-2a/d) mice and the supernatant from a freeze-thaw lysate of S1509a cells was used as a source of soluble tumor-associated Ag (TAA).

Subungual pigmented nevus: evaluation of DNA ploidy in six cases.

The discrimination between subungual pigmented nevus and subungual melanoma in situ is still a clinical problem. We measured DNA ploidy in six cases of subungual melanotic lesions which exhibited the features of subungual pigmented nevus or lentigo simplex histologically. Five cases presented a diploid pattern with or without a slight increase of hyperdiploid cells.

Regulation of Langerhans cell function by nerves containing calcitonin gene-related peptide.

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated.

A survey of ciguatera: assessment of Puako, Hawaii, associated with ciguatera toxin epidemics in humans.

A survey for the assessment of the ciguatera problem has been determined in Puako, South Kohala, on the Island of Hawaii. This is in the area of persistent ciguateric outbreaks during the months of January through March, caused by a specific species of fish (Cheilinus rhodochrous, red rose wrasse, or po'ou). Analyses of algae, Gambierdiscus toxicus, and various species of fish, including herbivores and carnivores, gave positive indications of Puako as a potential ciguateric area.