Development of a disease-specific instrument to measure quality of life in patients with alopecia areata

Alopecia areata (AA) is a common hair loss disorder that frequently follows a chronic course. Although AA is apparently associated with disturbance of quality of life (QoL), no disease-specific instrument to measure the QoL has been developed. This study was conducted to develop a disease-specific self-administered instrument to measure AA patients' QoL (AAQ). A two-step cross-sectional study was conducted. Items were generated from qualitative interviews with five patients with AA (two men and three women, age 28±6.4 years). Then, a preliminary questionnaire was produced and delivered to the patients (n=122). The AAQ was examined in terms of statistical performance. The AAQ included 7 items in the following three subscales: 'restriction of activity', 'concealment' and 'adaptation'. The reliability of internal consistency was fair with Cronbach's alpha coefficients of 0.59-81 for each subscale. Confirmatory factor analysis and correlation analysis demonstrated that the AAQ had good construct validity. Interestingly, the AAQ was only correlated with subjective severity scores as rated by the patients, but not with objective disease severity assessed by investigators.     

Cilostazol, a phosphodiesterase inhibitor, prevents no-reflow and hemorrhage in mice with focal cerebral ischemia

Background and PurposeThe Cilostazol Stroke Prevention Study II has shown a similar efficacy in stroke prevention but markedly fewer hemorrhagic events with the phosphodiesterase inhibitor cilostazol versus aspirin. The purpose of this study is therefore to investigate how cilostazol affects cerebral hemodynamics and whether it prevents hemorrhagic transformation induced by recombinant tissue plasminogen activator (rtPA) in a mouse model of focal ischemia/reperfusion. Particular emphasis will be placed on the plasma-microvessel interface.MethodsAfter receiving food containing 0.3% cilostazol or standard food for 7 days, adult C57BL/6 J mice were subjected to middle cerebral artery occlusion/reperfusion with or without rtPA (10 mg/kg) intravenously administered prior to reperfusion. Cerebral blood flow was monitored at several time points by laser speckle imaging in the 24 hour period post reperfusion, before neurobehavioral and histological assessment. The long-term effect of cilostazol on cerebral ischemia was analyzed in the non-rtPA cohort.ResultsIn the non-rtPA cohort, pretreatment by cilostazol significantly decreased the endothelial expression of adhesion molecules (P-selectin and intercellular adhesion molecule-1) and prevented platelet aggregation and leukocyte plugging in the microvessels after cerebral ischemia/reperfusion in the acute phase. Cilostazol significantly reduced mortality rate and improved motor function at 7 days post-ischemia/reperfusion. In the rtPA cohort, cilostazol significantly suppressed edema formation and hemorrhagic transformation with reduced density of microglial cells positive for matrix metalloproteinase-9 in the cerebral cortex and the striatum. In both cohorts, cilostazol significantly suppressed focal no-reflow, mitigated cerebral infarct, and improved neurological outcome.ConclusionsCilostazol may possess protective properties against cerebral ischemic injury by preventing no-reflow and hemorrhagic transformation, via maintenance of microvascular integrity.     

Auditory thalamic reticular nucleus of the rat: anatomical nodes for modulation of auditory and cross-modal sensory processing in the loop connectivity between the cortex and thalamus

The auditory sector of the thalamic reticular nucleus (TRN) plays a pivotal role in gain and/or gate control of auditory input relayed from the thalamus to cortex. The TRN is also likely involved in cross-modal sensory processing for attentional gating function. In the present study, we anatomically examined how cortical and thalamic afferents intersect in the auditory TRN with regard to these two functional pathways. Iontophoretic injections of biocytin into subregions of the auditory TRN, which were made with the guidance of electrophysiological recording of auditory response, resulted in retrograde labeling of cortical and thalamic cells, indicating the sources of afferents to the TRN. Cortical afferents from area Te1 (temporal cortex, area 1), which contains the primary and anterior auditory fields, topographically intersected thalamic afferents from the ventral division of the medial geniculate nucleus at the subregions of the auditory TRN, suggesting tonotopically organized convergence of afferents, although they innervated a given small part of the TRN from large parts. In the caudodorsal and rostroventral parts of the auditory TRN, cortical afferents from nonprimary visual and somatosensory areas intersected thalamic afferents from auditory, visual, and somatosensory nuclei. Furthermore, afferents from the caudal insular cortex and the parvicellular part of the ventral posterior thalamic nucleus, which are associated with visceral processing, converged to the rostroventral end of the auditory TRN. The results suggest that the auditory TRN consists of anatomical nodes that mediate tonotopic and/or cross-modal modulation of auditory and other sensory processing in the loop connectivity between the cortex and thalamus.     

Time-course of health status in patients with rheumatoid arthritis during the first year of treatment with infliximab

Objectives

A longitudinal study was performed to examine changes in health status in comparison with rheumatoid arthritis (RA) inflammation in patients with RA during the first 54 weeks of infliximab (IFX) treatment.

Methods

Health status in active RA patients (n = 13) was assessed monthly using the Arthritis Impact Measurement Scale 2 (AIMS2) and the VAS-GH during the first year of IFX treatment. Simultaneously, RA activity was assessed using inflammation markers, MMP-3 and the Disease Activity Score in 28 joints (DAS-28) based on CRP [DAS-28(CRP)] and ESR[DAS-28(ESR)].

Results

Serum CRP and ESR decreased significantly from 2.14 ± 0.52 mg/dL and 56.9 ± 6.96 mm/h, respectively, at baseline to 0.24 ± 0.11 mg/dL and 31.6 ± 4.39 mm/h, respectively, at 2 weeks after initiation of IFX. Other inflammatory markers and MMP-3 were also suppressed significantly after 2 weeks of IFX treatment. DAS-28(CRP) and DAS-28(ESR) were also significantly decreased after 2 weeks and suppression of both DAS values remained significant until 54 weeks of IFX treatment. After initiation of IFX, patient-reported general health also showed a significant improvement based on the changes in the six summary component scores on the AIMS2 (physical, affect, symptom, role, social interaction, and patient satisfaction). These scores all improved progressively until 14–18 weeks after initiation of IFX treatment, and then exhibited a temporary but insignificant exacerbation. The six components of the physical score also improved in a time-dependent manner until 14–18 weeks, but the scores for walking and bending, hand and finger function, arm function, self-care, and household tasks showed significant exacerbation at 22–30 weeks. The score for mobility level did not show this change.

Conclusion

IFX treatment significantly improved both RA disease activity and health status in active RA patients. Time-dependent improvement of ADL until 14–18 weeks after initiation of IFX treatment, as reflected in the six components of the physical score, might have contributed to the temporary exacerbation of health status thereafter in these patients.     

Altered expression of occludin and tight junction formation in psoriasis

Abstract In simple epithelia, tight junctions are well developed and have barrier and fence functions. On the other hand, tight junctions are less developed in stratified epithelia. In the rodent epidermis, only maculae occludentes (i.e. focal strands or spot tight junctions) are observed in the most superficial zone of the granular cell layer. Occludin is an integral membrane protein, and is localized at tight junctions in simple epithelia. In normal epidermis, occludin is expressed at the maculae occludentes in the granular cell layer, indicating that it is associated with keratinocyte differentiation. Thus, we examined occludin expression in psoriasis, in which differentiation of keratinocytes is impaired. In psoriasis, occludin was expressed more broadly in the upper epidermis than in normal epidermis. In addition, immunoelectron microscopy showed occludin to be concentrated on the maculae occludentes in the spinous layer of psoriatic skin. These findings indicate that occludin and the formation of tight junctions are related to the proliferation and differentiation of keratinocytes, and to the pathogenesis of psoriasis. Received: 21 August 2000 / Revised: 10 December 2000 / Accepted: 3 February 2001     

Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer

We previously identified three novel HLA-A24-restricted epitope peptides, which were derived from three cancer-testis antigens, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), as targets for cancer vaccination against esophageal squamous cell carcinoma (ESCC). To examine the safety, immunogenicity, and antitumor effect of vaccine treatment using a combination of these three peptides, 10 HLA-A2402-positive advanced ESCC patients who failed to standard therapy were enrolled in a phase I clinical trial. Each of the three peptides (1 mg each) was intradermally administered with 1 mL of incomplete Freund's adjuvant to the neck in three separate regions weekly for 5 weeks. The cancer vaccination therapy was well tolerated without any treatment-associated adverse events of grade 3 or 4. The TTK-, LY6K-, and/or IMP-3-specific T-cell immune responses were observed by enzyme-linked immunospot assay in peripheral blood lymphocytes obtained from nine of the 10 ESCC patients after their vaccination. The median survival time after the vaccination was 6.6 months. The vaccination could induce good clinical responses in 50% of the 10 patients. One patient experienced a complete response in hepatic metastasis lasting 7 months, one showed objective responses in all lung metastasis lesions, and three patients revealed a stable disease condition for at least 2.5 months. The cancer vaccine therapy using these three peptides demonstrated satisfactory safety and good immunogenicity as well as promising disease control rate, and therefore warrants further clinical studies. ( Cancer Sci 2009)     

The expression of differentiation markers in aquaporin-3 deficient epidermis

Aquaporin-3 (AQP3) is a water/glycerol transporting protein expressed strongly at the plasma membrane of keratinocytes. There is evidence for involvement of AQP3-facilitated water and glycerol transport in keratinocyte migration and proliferation, respectively. Here, we investigated the involvement of AQP3 in keratinocyte differentiation. Studies were done using AQP3 knockout mice, primary cultures of mouse keratinocytes (AQP3 knockout), neonatal human keratinocytes (AQP3 knockdown), and human skin. Cells were cultured with high Ca²⁺ or 1α,25-dihydroxyvitamin D₃ (VD₃) to induce differentiation. The expression of differentiation marker proteins and differentiating responses were comparable in control and AQP3-knockout or knockdown keratinocytes. Topical application of all-trans retinoic acid (RA), a known regulator of keratinocyte differentiation and proliferation, induced comparable expression of differentiation marker proteins in wildtype and AQP3 null epidermis, though with impaired RA-induced proliferation in AQP3 null mice. Immunostaining of human and mouse epidermis showed greater AQP3 expression in cells undergoing proliferation than differentiation. Our results showed little influence of AQP3 on keratinocyte differentiation, and provide further support for the proposed involvement of AQP3-facilitated cell proliferation.