Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast cells

Mast cells (MCs) are common components of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often accompanied by vascular changes. However, little is known about modulation of MC-derived proangiogenic factors during inflammation. In this study, we evaluated the effects of the proinflammatory mediator prostaglandin E2 (PGE2) on MC expression and release of proangiogenic factors. We report that PGE2 dose-dependently induces primary MCs to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP-1). This release of MCP-1 is complete by 2 h after PGE2 exposure, reaches levels of MCP-1 at least 15-fold higher than background, and is not accompanied by degranulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is detected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE2-induced MCP-1 secretion by approximately 60%. Agonists of PGE2 receptor subtypes revealed that the EP1 and EP3 receptors can independently mediate MCP-1 release from MCs. These observations identify PGE2-induced MCP-1 release from MCs as a pathway underlying inflammation-associated angiogenesis and extend current understanding of the activities of PGE2.     

Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with rheumatoid arthritis induces synovitis in cynomolgus monkeys

Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.     

Decreased α event-related synchronization in the left posterior temporal cortex in schizophrenia: a magnetoencephalography-beamformer study

Alpha rhythm is one of the most prominent electromagnetic changes in the brain, and electroencephalography (EEG) alpha reactivity disturbance may sometimes represent an early sign of cerebral dysfunction. Although magnetoencephalography (MEG) has a better spatial resolution than EEG, it has not extensively been used to explore alpha-power change deficits in schizophrenia as a possible neurophysiological marker of the disease. The purpose of this study was to use MEG to identify abnormalities in alpha synchronization induced by eye-closing in schizophrenia patients compared to healthy controls, and to investigate whether alpha reactivity deficits correlate with clinical features of the disorder. MEG data were recorded in 22 schizophrenia patients and 20 age- and gender-matched controls during eyes-open/eyes-closed resting states. Cortical sources of event-related synchronization (ERS) were estimated using multiple source beamformer, and BrainVoyager was used for statistic group analysis. A significant decrease in ERS in the upper alpha band (10–13 Hz) was found in the left posterior temporal region in schizophrenia patients relative to controls, and this activity showed correlation with visual memory scores. This upper alpha ERS deficit may indicate left temporal dysfunction and visual-information processing impairment in schizophrenia, and upon further confirmation it might represent a neurophysiological state marker of the disorder.     

Different distribution of Cav3.2 and Cav3.1 transcripts encoding T-type Ca(2+) channels in the embryonic heart of mice

We investigated the distribution of T-type Ca(2+) channel mRNAs in the mouse embryonic heart. Cav3.2, but not Cav3.1, was expressed in the E8.5 embryonic heart along with cardiac progenitor markers (Nkx2.5, Tbx5, Isl-1) and contractile proteins (alpha and beta MHC). In the E10.5 heart, the distribution of Cav3.1 mRNA was confirmed in the AV-canal and overlapped with that of MinK or Tbx2. Cav3.2 mRNA was observed not only in the AV-canal but also in the outflow tract, along with MinK and Isl-1, indicating the expression of Cav3.2 in the secondary heart field. Thus, Cav3.2 may contribute to the development of the outflow tract from the secondary heart field in the embryonic heart, whereas Cav3.1 may be involved in the development of the cardiac conduction-system together with Cav3.2.     

Multiple gastrointestinal stromal tumors in neurofibromatosis type 1 treated with laparoscopic surgery

Gastrointestinal stromal tumors (GISTs) have been reported to occasionally occur in patients with neurofibromatosis type 1 (NF-1), and many cases have had multiple lesions predominantly involving the small intestine. We report herein a case of multiple GISTs associated with NF-1 from whom laparoscopic surgery was beneficial. In a 79-year-old female admitted with anemia and melena, the abdominal computed tomography revealed a tumor arising from the small intestine. Laparoscopic surgery was performed, and another small tumor was revealed during laparoscopic observation. Extracorporeal partial and wedge resection of the small intestine were undertaken. Both lesions were diagnosed as typical GISTs of low risk. Laparoscopic surgery would be useful for examination and a minimally invasive approach to tumors of the small intestine, especially on cases with the possibility of multiple tumors.     

Rapid typing of influenza viruses using super high-speed quantitative real-time PCR

The development of a rapid and sensitive system for detecting influenza viruses is a high priority for controlling future epidemics and pandemics. Quantitative real-time PCR is often used for detecting various kinds of viruses; however, it requires more than 2h per run. Detection assays were performed with super high-speed RT-PCR (SHRT-PCR) developed according to a newly designed heating system. The new method uses a high-speed reaction (18s/cycle; 40 cycles in less than 20min) for typing influenza viruses. The detection limit of SHRT-PCR was 1 copy/reaction and 10(-1) plaque-forming unit/reaction for viruses in culture supernatants during 20min. Using SHRT-PCR, 86 strains of influenza viruses isolated by the Tokyo Metropolitan Institute of Public Health were tested; the results showed 100% sensitivity and specificity for each influenza A and B virus, and swine-origin influenza virus. Twenty-seven swabs collected from the pharyngeal mucosa of outpatients were also tested, showing positive signs for influenza virus on an immunochromatographic assay; the results between SHRT-PCR and immunochromatography exhibited 100% agreement for both positive and negative results. The rapid reaction time and high sensitivity of SHRT-PCR makes this technique well suited for monitoring epidemics and pre-pandemic influenza outbreaks.     

Obstructions of portal veins and tumor numbers are associated with humped hepatocellular carcinoma

Tumor protrusion in hepatocellular carcinoma (HCC) is one of the risk signs of tumor rupture. Despite curative tumor treatments, HCC recurrences sometimes occur with rapidly growing humped or ruptured HCC in small sized tumors. The aim of this study was to clarify the characteristics of humped HCC clinically and radiologically associated with tumor progression, liver damage, and treatment. The subjects were 179 consecutive HCC patients who underwent angiographic examination. Dynamic studies, using helical computed tomography and magnetic resonance imaging were assessed, and the HCC area were measured. The tumor-node-metastasis (TNM) stage differed significantly between the humped and non-humped HCC groups. Humped HCC was more frequently observed in the right lobe (29.3% of right-lobe HCCs) than in the left (10.1%; p=0.003). Analysis of recurrent HCC revealed that patients with multiple treatments of >4 sessions had more humped HCC (33.8%) than those with 1-3 sessions (16.7%; p=0.042). Multivariate regression analysis revealed that tumor invasion in the portal vein, rather than large tumor size, was significantly associated with tumor protrusion. HCC recurrence with humped HCC occurs often in patients with multiple treatments. Tumor factors of the TNM classification, especially tumor invasion in the portal vein, might be associated with the mechanisms of tumor protrusion.     

A comparison of psychiatric consultation liaison services between hospitals in the United States and Japan

The authors investigated psychiatric consultation in two hospitals, one in the United States, the other in Japan. They examined similarities and differences, and drew inferences on possible cross-cultural values and/or temporary cultural conditions. As compared with the Japanese consultation patients, the Americans had more mood disorders, including anxiety and chemical-dependency problems, in respective diagnostic classifications. Patients in the United States also showed more acute as well as more serious chronic conditions. These differences may relate to disorder base-rates in the respective countries. In general, psychosocial problems emerged as ascendant in Japan, as compared with chemical-dependency difficulties among American patients. The results are discussed in terms of current conditions in Japan that affect the mental health professions, together with attempts by Japanese clinicians to protect collective mores by ascribing causation for disorders to the individual, rather than the societal conditions often invoked in the United States.     

Clinical and Host Genetic Characteristics of Mendelian Susceptibility to Mycobacterial Diseases in Japan

Purpose  

The aim of this study is to investigate clinical characteristics and genetic backgrounds of Mendelian susceptibility to mycobacterial diseases (MSMD) in Japan.