A case of bleeding duodenal ulcer with pemphigus vulgaris during steroid therapy

We report a rare case of bleeding duodenal ulceration in the different form of pemphigus vulgaris (PV). A 52-year-old female was diagnosed with acute pharyngitis and administered methylprednisolone. After several days, melena and many blisters were noted on her body. Endoscopy revealed blood oozing from the second part of a duodeneal ulcer around the major duodenal papilla. After initial endoscopic hemostasis, we observed a large regional, shallow duodenal ulcer. The blisters were suspected to represent the Nikolsky’s sign. The histological findings of her skin were characterized by suprabasal acantholysis and mixed inflammatory cell infiltrates, including scattered eosinophils. There were no other significant findings on skin biopsy or by direct immunofluorescence. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein 3 autoantibodies in her serum, and the patient was finally diagnosed with mucosal-dominant PV. Although we performed multiple biopsies from the esophagus, stomach and duodenum, the samples did not contain significant findings to enable us to distinguish from pemphigus vulgaris. Corticosteroids remain an essential component of PV treatment. When clinicians encounter PV development during steroid therapy, upper gastrointestinal complications should be considered and diagnostic endoscopy conducted.     

Enhanced Ca2+-sensing receptor function in idiopathic pulmonary arterial hypertension

Rationale: A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is an important stimulus for pulmonary vasoconstriction and vascular remodeling. Increased resting [Ca(2+)](cyt) and enhanced Ca(2+) influx have been implicated in PASMC from patients with idiopathic pulmonary arterial hypertension (IPAH). Objective: We examined whether the extracellular Ca(2+)-sensing receptor (CaSR) is involved in the enhanced Ca(2+) influx and proliferation in IPAH-PASMC and whether blockade of CaSR inhibits experimental pulmonary hypertension. Methods and Results: In normal PASMC superfused with Ca(2+)-free solution, addition of 2.2 mmol/L Ca(2+) to the perfusate had little effect on [Ca(2+)](cyt). In IPAH-PASMC, however, restoration of extracellular Ca(2+) induced a significant increase in [Ca(2+)](cyt). Extracellular application of spermine also markedly raised [Ca(2+)](cyt) in IPAH-PASMC but not in normal PASMC. The calcimimetic R568 enhanced, whereas the calcilytic NPS 2143 attenuated, the extracellular Ca(2+)-induced [Ca(2+)](cyt) rise in IPAH-PASMC. Furthermore, the protein expression level of CaSR in IPAH-PASMC was greater than in normal PASMC; knockdown of CaSR in IPAH-PASMC with siRNA attenuated the extracellular Ca(2+)-mediated [Ca(2+)](cyt) increase and inhibited IPAH-PASMC proliferation. Using animal models of pulmonary hypertension, our data showed that CaSR expression and function were both enhanced in PASMC, whereas intraperitoneal injection of the calcilytic NPS 2143 prevented the development of pulmonary hypertension and right ventricular hypertrophy in rats injected with monocrotaline and mice exposed to hypoxia. Conclusions: The extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) due to upregulated CaSR is a novel pathogenic mechanism contributing to the augmented Ca(2+) influx and excessive PASMC proliferation in patients and animals with pulmonary arterial hypertension.     

Effects of a program to prevent social isolation on loneliness, depression, and subjective well-being of older adults: A randomized trial among older migrants in Japan

Social isolation among the elderly is a concern in developed countries. Using a randomized trial, this study examined the effect of a social isolation prevention program on loneliness, depression, and subjective well-being of the elderly in Japan. Among the elderly people who relocated to suburban Tokyo, 63 who responded to a pre-test were randomized and assessed 1 and 6 months after the program. Four sessions of a group-based program were designed to prevent social isolation by improving community knowledge and networking with other participants and community "gatekeepers." The Life Satisfaction Index A (LSI-A), Geriatric Depression Scale (GDS), Ando-Osada-Kodama (AOK) loneliness scale, social support, and other variables were used as outcomes of this study. A linear mixed model was used to compare 20 of the 21 people in the intervention group to 40 of the 42 in the control group, and showed that the intervention program had a significant positive effect on LSI-A, social support, and familiarity with services scores and a significant negative effect on AOK over the study period. The program had no significant effect on depression. The findings of this study suggest that programs aimed at preventing social isolation are effective when they utilize existing community resources, are tailor-made based on the specific needs of the individual, and target people who can share similar experiences.     

Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population

MicroRNA may play a role in the pathophysiology of schizophrenia. A recent meta‐analysis of genome‐wide association studies indicated a significant association between schizophrenia and a common intronic variation in MIR137HG (microRNA 137 host gene) encoding the primary microRNA‐137. To explore additional risk variations for schizophrenia, we resequenced MIR137 and performed an association analysis in 1321 Japanese individuals. By resequencing, we detected four sequence variations in the 5' and 3' flanking regions. There were no significant associations between these variations and schizophrenia. Our resequencing and association analysis of MIR137 failed to find additional risk variations for schizophrenia.     

Association of the BDNF C270T polymorphism with schizophrenia: Updated meta‐analysis

Brain‐derived neurotrophic factor (BDNF) has been suggested to play a role in the pathophysiology of schizophrenia. The C270T polymorphism (rs56164415) in the BDNF 5′‐non‐coding region has been extensively investigated for an association with schizophrenia, but with conflicting results. An updated meta‐analysis was therefore performed of 13 case–control association studies (3505 patients and 3992 controls). An association was found between the T allele and schizophrenia. The association was significant in the East Asian population, but not in the Caucasian population. It is suggested that the BDNF C270T polymorphism contributes to schizophrenia susceptibility, especially in East Asian subjects.