Expression of the GLI2 oncogene and its isoforms in human basal cell carcinoma.

Background: Mutations of the patched (Ptc) gene, a developmental regulator implicated in the signalling pathway via sonic hedgehog (Shh) and smoothened (Smo), play an essential pathogenic role in the development of basal cell carcinomas (BCCs). We previously reported the upregulation of Shh signal transducers, including Ptc, Smo and hedgehog-interacting protein, in BCCs. In vertebrates, specific downstream effectors in the Shh signalling pathway include three zinc-finger transcription factors, Gli1, Gli2 and Gli3.

Detection of herpes virus genomes in skin lesions from patients with Behçet's disease and other related inflammatory diseases.

Although the aetiology of Behçet's disease is still poorly understood, viral infection has long been postulated as one of the factors. To investigate the relationship between herpes viruses and Behçet's disease, we used polymerase chain reaction to detect herpes simplex virus 1 (HSV-1) and 2 (HSV-2), and human herpes virus 6 (HHV-6) and 7 (HHV-7) DNA in samples of lesional tissues from patients with Behçet's disease and other related inflammatory disorders. Four cases were positive for HSV-1; 1 of 11 Behçet's disease cases, 2 of 3 Sweet's disease cases and 1 of 3 erythema nodosum cases.

Demonstration of TARC and CCR4 mRNA expression and distribution using in situ RT-PCR in the lesional skin of atopic dermatitis.

Thymus- and activation-regulated chemokine (TARC/CCL17) and its receptor, CC chemokine receptor 4 (CCR4), have been proven to be involved in a number of allergic diseases, especially atopic dermatitis (AD). The purpose of this study was to examine the expression and distribution of TARC and CCR4 mRNAs in samples of AD (n=15, acute lesions 8, chronic lesions 7) and normal skin (n=6). The expression and distribution of TARC and CCR4 mRNAs were detected with the in situ reverse transcription (RT) -polymerase chain reaction (PCR) technique.

Attenuation of airway hyperresponsiveness in a murine asthma model by neutralization of granulocyte-macrophage colony-stimulating factor (GM-CSF).

Asthma is recognized as an inflammatory disease in which various cytokines are involved. Among these, granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to play a critical role in the survival of eosinophils and in the activation of antigen-presenting cells (APC). We studied the effects of neutralization of GM-CSF in a murine model of asthma, to elucidate its role in enhanced airway responsiveness and in airway inflammation.

Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides.

Background: Mycosis fungoides (MF) belongs to cutaneous T-cell lymphoma and is clinically divided into 3 stages: patch, plaque, and tumor stage. Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the CC chemokines and is a chemoattractant for CC chemokine receptor 4 (CCR4)- and CC chemokine receptor 8 (CCR8)-expressing cells.

Objective: In this study, we examined the involvement of TARC among patients with each stage of MF.

TGF-beta1-mediated regulation of thymus and activation-regulated chemokine (TARC/CCL17) synthesis and secretion by HaCaT cells co-stimulated with TNF-alpha and IFN-gamma.

Thymus and activation-regulated chemokine (TARC/CCL17) contributes not only to the recruitment of leukocytes, but is also involved in immune disorders, such as atopic dermatitis (AD) and bronchial asthma. We have previously reported that the levels of TARC were high in patients with AD and that lesional epidermis were strongly immunoreactive for TARC. In this paper, the effects of transforming growth factor (TGF)-beta(1) on the expression of TARC/CCL17 were examined in HaCaT cells, a human keratinocytes (KCs) cell line, co-stimulated with TNF-alpha and IFN-gamma.

Lack of association of TNF-238A and -308A in Japanese patients with psoriasis vulgaris, psoriatic arthritis and generalized pustular psoriasis.

Tumor necrosis factor (TNF)-alpha is one of the proinflammatory cytokines and immunomodulators, and has an important pathogenetic role in psoriasis. The TNF-alpha gene (TNFA) is in the human leukocyte antigen (HLA) class III locus on chromosome 6, which might be related to the pathogenesis of psoriasis. It has been suggested that some polymorphisms of the TNFA gene promoter, especially G to A conversions at nt-238 and -308 (TNF-238A and -308A), may be associated with psoriasis in Caucasians.

Different properties of three isoforms (alpha, beta, and gamma) of transcription factor AP-2 in the expression of human keratinocyte genes.

The transcription factor AP-2/promoter system is essential for gene expression associated with ectodermal development, particularly in the neural crest and skin. Three AP-2 isoforms, alpha, beta, and gamma, exhibit a highly homologous structure, but their functions are considered to be different. Here, we report on the role of each AP-2 isoform in complex keratinocyte biology including proliferation, differentiation, and carcinogenesis.

Hypersensitivity to mosquito bites with natural-killer cell lymphocytosis: the possible implication of Epstein-Barr virus reactivation.

Hypersensitivity to mosquito bites (HMB) has been recognized as one of the wide variety of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders, some of which overlap with chronic active EBV infection and hydroa vacciniforme. It frequently predisposes to hemophagocytic syndrome or lymphoid malignancy with a clonal EBV replication. Here we report an 8-year-old Japanese boy who presented with a 3-year history of HMB.

Biphasic cytokine expression by T cell clones from patients with atopic dermatitis with different incubation periods and strengths of stimuli.

It has been proposed that T helper (Th) 2 cells play a key role in the pathogenesis of atopic dermatitis (AD) because of clinical and experimental findings including hyper IgE, eosinophilia and Th2 type cytokine overexpression, etc. In contrast, several observations such as Th1 type cytokine detection in chronic lesions and histological features resembling allergic contact dermatitis suggest that Th1 rather than Th2 cells are important for the pathogenesis of skin lesions. In order to clarify this paradox, we investigated the function of T cell clones established from AD patients.

Electromechanical delay after ACL reconstruction: an innovative method for investigating central and peripheral contributions.

Objectives: The purpose of this study was to investigate the electromechanical properties of atrophied muscle in patients with anterior cruciate ligament (ACL) reconstruction and to examine the relationship of changes in these properties for a voluntarily elicited maximal isometric contraction and peripherally stimulated twitch contraction.

Background: It is not known if, following ACL reconstruction, a prolonged reaction time to a sudden stimulus is due to impaired proprioception in the knee joint, a prolonged processing interval in the central nervous system, or a greater elasticity in the series elastic component of the quadriceps femoris.

Methods: Seventeen patients were recruited 2 to 3 months following a unilateral ACL reconstruction.

Skin inflammation during contact hypersensitivity is mediated by early recruitment of CD8+ T cytotoxic 1 cells inducing keratinocyte apoptosis.

Contact hypersensitivity (CHS) is a T cell-mediated, Ag-specific skin inflammation induced by skin exposure to haptens in sensitized individuals. Th1/T cytotoxic 1 cells are effector cells of CHS, whereas Th2/T regulatory CD4(+) T cells have down-regulating properties. We have previously shown that CHS to 2,4-dinitrofluorobenzene is mediated by specific CD8(+) effector cells, whose cytolytic activity is mandatory for induction of skin inflammation.

Neutrophilic eccrine hidradenitis in actinic reticuloid syndrome.

Neutrophilic eccrine hidradenitis (NEH) is a rare, transient complication, which usually occurs in patients with leukemia receiving various chemotherapeutic regimens. However, similar eruptions have been observed in other conditions, including HIV-positive patients, and are often preceded by the onset of malignancies. We report the first case of NEH arising in a patient with actinic reticuloid syndrome who had been treated with methotrexate.

Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma.

Background: Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC.

Treatment of recurrent auricle pseudocyst with intralesional injection of minocycline: a report of two cases.

Pseudocyst of the auricle (PCA) is characterized by asymptomatic and fluctuant swelling of the external ear and frequent relapses despite various therapeutic approaches. We describe two patients with recurrent PCA who were successfully treated with intralesional injection of 1 mg/mL of minocycline hydrochloride (minocycline), 2 or 3 times at 2-week intervals. Intralesional injection of minocycline may be a new therapeutic choice for conservative management of PCA, especially in recurrent cases.

Effects of collagen matrix containing transforming growth factor (TGF)-beta(1) on wound contraction.

We evaluated the effectiveness of transforming growth factor (TGF)-beta(1) on wound contraction, both alone and in combination with collagen matrix, using an in vivo delayed wound healing type model. To clarify the mechanisms involved in the effectiveness of TGF-beta(1), we also used a fibroblast-populated collagen gel contraction in vitro model. Although we found that TGF-beta(1) significantly accelerated contraction of the fibroblast-populated collagen gel in vitro, we demonstrated that both collagen matrix alone and 1.

Characterization of a novel mammalian SUMO-1/Smt3-specific isopeptidase, a homologue of rat axam, which is an axin-binding protein promoting beta-catenin degradation.

A novel SUMO-1/Smt3-specific isopeptidase, SMT3IP2/Axam2 (Smt3-specific isopeptidase 2), was cloned and characterized. The catalytic domains in the carboxyl-terminal region were very much similar to those of other SUMO-1/Smt3-specific proteases, but the amino-terminal part was quite different. The enzyme specifically bound to Smt3a and Smt3b but not to SUMO-1.

The latency pattern of Epstein-Barr virus infection and viral IL-10 expression in cutaneous natural killer/T-cell lymphomas.

The nasal type, extranodal natural killer or T(NK/T)-cell lymphoma is usually associated with latent Epstein-Barr virus (EBV) infection. In order to elucidate the EBV gene expression patterns in vivo, we examined eight patients with cutaneous EBV-related NK/T-cell lymphomas, including six patients with a NK-cell phenotype and two patients with a T-cell phenotype. The implication of EBV in the skin lesions was determined by the presence of EBV-DNA, EBV-encoded nuclear RNA (EBER) and a clonality of EBV-DNA fragments containing the terminal repeats.

The main factor causing prolonged reaction time on force producing process following anterior cruciate ligament reconstruction.

This study investigated the electromechanical properties of atrophied human quadriceps femoris muscle during a voluntarily elicited maximal isometric contraction (MVC) and a peripherally stimulated twitch contraction. Nineteen patients were recruited 2-3 months following a unilateral anterior cruciate ligament (ACL) reconstruction. Both the involved leg as well as the uninvolved leg were studied.

Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid.

Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade.

Subcorneal pustular dermatosis-type IgA pemphigus induced by thiol drugs.

We report a case of subcorneal pustular dermatosis (SPD)-type IgA pemphigus arising in a 49 year-old woman with rheumatoid arthritis who had been treated with chrysotherapy. Scaly erythemic plaques containing vesicles and pustules occurred on her chest and abdomen during the course of anti-rheumatic treatments using prednisolone at 11 mg/day and thiol compounds (bucillamine and gold sodium thiomalate). Histological investigations revealed subcorneal pustules containing many neutrophils and a few acantholytic cells, and intercellular IgA deposits at the upper epidermis of the eruptions without any other immunoglobulins and complement component C3.

Dermal fibroblasts are one of the therapeutic targets for topical application of 1alpha,25-dihydroxyvitamin D3: the possible involvement of transforming growth factor-beta induction.

Background: Transforming growth factor (TGF) -beta has been suggested to be an effective inhibitor for abnormal keratinocyte growth in psoriasis. As a majority of the secreted TGF-beta are biologically latent complexes, activation is essential for TGF-beta-mediated cellular responses in vitro and in vivo. Objectives Here we report the response of the TGF-beta regulation system to 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], an active vitamin D3 analogue Patients/methods We studied two types of fibroblasts derived from normal and psoriatic lesional skin, using an enzyme-linked immunosorbent assay and Northern blotting techniques.

Transcriptional factor AP-2gamma increases human cystatin A gene transcription of keratinocytes.

The transcriptional activator protein-2 (AP-2) has been suggested to participate in keratinocyte gene regulation. Cystatin A, a cysteine proteinase inhibitor, is one of the cornified cell envelope constituents and is expressed in the upper epidermis. We report AP-2-dependent transcriptional regulation of cystatin A gene expression of keratinocytes.

Meningioma with granulofilamentous inclusions.

The authors report a case of intracranial meningioma with granulofilamentous inclusions. A 50-year-old man had right trigeminal neuralgia due to trigeminal nerve compression by a petroclival tumor and received tumor resection. Microscopically, tumor cells containing eccentric nuclei and intracytoplasmic hyaline inclusions were arranged in sheets and whorls.