Significant increase in the prevalence of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, particularly the USA300 variant ΨUSA300, in the Japanese community.

IMPORTANCE: USA300 is an MRSA clone producing PVL, a toxin associated with SSTIs. ΨUSA300 is a USA300 variant recently identified in Japan by Takadama et al. (15). Here, we found that the prevalence rate of PVL-positive MRSA in S. aureus was elevated in the Japanese community, and ΨUSA300 accounted for most of them. ΨUSA300 strains have been isolated from several areas in Japan and were associated with deep-seated SSTIs. This study highlighted the emerging threat posed by ΨUSA300 in Japan.

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.

Enhanced TARC production by dust-mite allergens and its modulation by immunosuppressive drugs in PBMCs from patients with atopic dermatitis.

BACKGROUND: Thymus and activation regulated chemokine (TARC) is a CC chemokine that attracts CCR4+ T cells. We reported previously that TARC is an important chemokine that defines Th2 imbalance in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: This study was undertaken to clarify TARC producing cells in peripheral blood mononuclear cells (PBMCs), the regulation of dust mite-allergen clude extract (DME) and different immunosuppressive drugs (Tacrolimus (FK506), cyclosporine (CsA), dexamethasone (Dex)) on TARC production by peripheral PBMCs from AD patients in vitro. METHODS: Monocyte derived dendritic cells (MoDCs) were generated from and TARC mRNA levels were examined and comapared with those from T cells in PBMCs from AD patients. PBMCs were cultured with or without DME and/or immunosuppressive drugs (Tacrolimus, CsA, Dex) for 7 days and TARC levels were measured. RESULTS: PBMCs from AD patients which were cultured with DME stimulation for 7 days showed significantly higher levels of TARC production than those from healthy controls. RT-PCR demonstrated that TARC mRNA was expressed in CD4+ T cells, CD8+ T cells and MoDCs. Tacrolimus, CsA and Dex individually suppressed TARC production by PBMCs from AD patients which were co-cultured with DME for 7 days. Gel shift analysis revealed differential inhibitory effects of these immunosuppressive drugs on NFkappaB activity in PBMCs from AD patients. CONCLUSION: Our data demonstrate that TARC producing cells are MoDCs, T cells as well as epidermal keratinocytes in AD. We suggest that MoDCs might regulate the immune responses by attracting T cells and CD25+ T cells in the pathogenesis of AD. We also showed the important role of DME on TARC production and the inhibitory effect of the immunosuppressive drugs on TARC production by PBMCs from AD patients, that can regulate ongoing immune responses in the pathogenesis of AD.

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.

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. TARC mRNA was expressed in epidermal keratinocytes, dermal endothelial cells and infiltrating cells. CCR4 mRNA was expressed in dermal endothelial cells and infiltrating cells. In acute AD lesional skin, there were more positive cells, and the staining intensity was stronger than in chronic lesions (p<0.05). The distribution of positive cells was as follows: In the epidermis, keratinocytes in the basal layer showed the strongest staining, and keratinocytes in the spinous layer showed moderate staining; the superficial area showed faint staining. In the dermis, infiltrating cells located in the superficial area of the dermis showed the strongest staining, positive staining intensity became weaker and the percentage of positive cells became less as the location became deeper. There were no positive cells in normal skin. These data further substantiate the role of TARC/CCR4 in the pathogenesis of AD.

Hydration structure of CO2-absorbed 2-aminoethanol studied by neutron diffraction with the 14N/15N isotopic substitution method.

Neutron diffraction measurements were carried out for CO2-absorbed aqueous 11 mol % 2-aminoethanol (MEA) D2O solutions (corresponding to 30 wt % MEA solution) in order to obtain information on both the intramolecular structure and intermolecular hydration structure of the MEA carbamate molecule in the aqueous solution. Neutron scattering cross sections observed for (MEA)0.11(D2O)0.89, (MEA)0.11(D2O)0.89(CO2)0.06, and (MEA)0.11(D2O)0.89(DCl)0.11 solutions with different (14)N/(15)N ratios were used to derive the first-order difference function, ΔN(Q), which involves environmental structural information around the nitrogen atom of the MEA molecule. Intramolecular geometry and intermolecular hydration structure of MEA, protonated MEA (MEAD(+)), and MEA carbamate (MEA-CO2) molecules were obtained through the least-squares fitting of the observed Δ(N)(Q) in the high-Q region and the intermolecular difference function, Δ(N)(inter)(Q), respectively. In the aqueous solution, the MEA molecule takes the gauche conformation (dihedral angle, ∠NCCO = 45 ± 3°), suggesting that an intramolecular hydrogen bond is formed. On the other hand, values of the dihedral angle ∠NCCO determined for MEAD(+) and MEA-CO2 molecules were 193 ± 4° and 214 ± 8°, respectively. These results imply that the intermolecular hydrogen bonds are dominated for MEAD(+) and MEA-CO2 molecules. The intermolecular nearest neighbor N···O(D2O) distance for the MEA molecule was determined to be 3.13 ± 0.01 Å, which suggests weak intermolecular interaction between the amino-nitrogen atom of MEA and water molecules in the first hydration shell. The nearest-neighbor N···O(D2O) distances for MEAD(+) and MEA-CO2 molecules, 2.79 ± 0.03 and 2.87 ± 0.04 Å, clearly indicate strong hydrogen bonds are formed among the amino group of these molecules and neighboring water molecules.

Direct amination of azoles via catalytic C-H, N-H coupling.

C-H, N-H Coupling of azoles takes place with several amines in the presence of a copper catalyst to undergo amination at the 2-position. The reaction of benzothiazole with N-methylaniline in the presence of sodium acetate and 20 mol % Cu(OAc)(2) in xylene under an oxygen atmosphere afforded the aminated product in 81% yield.

A case of anti-p200 pemphigoid with autoantibodies against both a novel 200-kD dermal antigen and the 290-kD epidermolysis bullosa acquisita antigen.

BACKGROUND: Anti-p200 pemphigoid with autoantibodies against the 200-kD dermal antigen has recently been identified. OBJECTIVES: Our patient showed small and tense blisters on her face and trunk. METHODS: Immunoblotting (IB), using extracts of normal human epidermis and dermal skin, and immunoelectron microscopy (IEM), using normal human skin, were performed using the patient's serum. RESULTS: IB analysis showed that the patient's serum did not react with 180-kD bullous pemphigoid (BP180) or BP230 antigens; however, IgG autoantibodies in the patient's serum reacted with a 200-kD dermal antigen as well as the 290-kD epidermolysis bullosa acquisita (EBA) antigen. IEM showed that IgG antibodies in the patient's serum bound to the lamina lucida, as well as both the lamina densa and sublamina densa. After the treatment with prednisolone, the 290-kD protein reactivity decreased rapidly; however, the 200-kD protein band was still observed. CONCLUSION: We describe a rare case with immunoreactive autoantibodies against both a novel dermal 200-kD autoantigen and the 290-kD EBA antigen.