Focused Microarray Analysis of Peripheral Mononuclear Blood Cells from Churg–Strauss Syndrome Patients

DNA diagnostics are useful but are hampered by difficult ethical issues. Moreover, it cannot provide enough information on the environmental factors that are important for pathogenesis of certain diseases. However, this is not a problem for RNA diagnostics, which evaluate the expression of the gene in question. We here report a novel RNA diagnostics tool that can be employed with peripheral blood mononuclear cells (PBMCs). To establish this tool, we identified 290 genes that are highly expressed in normal PBMCs but not in TIG-1, a normal human fibroblast cell. These genes were entitled PREP after predominantly expressed in PBMC and included 50 uncharacterized genes. We then conducted PREP gene-focused microarray analysis on PBMCs from seven cases of Churg–Strauss syndrome (CSS), which is a small-vessel necrotizing vasculitis. We found that PREP135 (coactosin-like protein), PREP77 (prosaposin), PREP191 (cathepsin D), PREP234 (c-fgr), and PREP136 (lysozyme) were very highly up-regulated in all seven CSS patients. Another 28 genes were also up-regulated, albeit more moderately, and three were down-regulated in all CSS patients. The nature of these up- and down-regulated genes suggest that the immune systems of the patients are activated in response to invading microorganisms. These observations indicate that focused microarray analysis of PBMCs may be a practical, useful, and low-cost bedside diagnostics tool

Nature of collective decision-making by simple yes/no decision units Eisuke Hasegawa

The study of collective decision-making spans various fields such as brain and behavioural sciences, economics, management sciences, and artificial intelligence. Despite these interdisciplinary applications, little is known regarding how a group of simple 'yes/no' units, such as neurons in the brain, can select the best option among multiple options. One prerequisite for achieving such correct choices by the brain is correct evaluation of relative option quality, which enables a collective decision maker to efficiently choose the best option. Here, we applied a sensory discrimination mechanism using yes/no units with differential thresholds to a model for making a collective choice among multiple options. The performance corresponding to the correct choice was shown to be affected by various parameters. High performance can be achieved by tuning the threshold distribution with the options' quality distribution. The number of yes/no units allocated to each option and its variability profoundly affects performance. When this variability is large, a quorum decision becomes superior to a majority decision under some conditions. The general features of this collective decision-making by a group of simple yes/no units revealed in this study suggest that this mechanism may be useful in applications across various fields

Mossbauer Spectrometer for Measurements in High Magnetic Fields(Part II. Several Instruments and Techniques Developed in HFLSM)

A Mossbauer spectrometer has been designed and constructed for measurements in high magnetic fields beyond 20 T which are generated by a hybrid magnet in the High Field laboratory for Superconducting Materials at Tohoku University. Simple ways were adopted in order to avoid some obstacles for the spectroscopy. The most serious problem was electromagnetic inductions occurring at metallic components in a source drive system. It was found that the replacement of an aluminum drive-rod to a Bakelite one improved remarkably the Mossbauer spectrum. Test measurements of a-Fe at room temperature were satisfactorily performed under the magnetic fields up to 10 T. The results agreed well with the theoretical expectation

Severity-based treatment for Japanese patients with MPO-ANCA-associated vasculitis: the JMAAV study

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients’ disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity

Comparison of Mid-term Angiographic and Clinical Outcomes Following Zotarolimus-eluting Stent and Paclitaxel-eluting Stent Implantation Based on Lesion Complexity

First-generation drug-eluting stents (DESs) have reduced angiographic and clinical restenosis rates compared to bare-metal stents (BMSs). Zotarolimus-eluting stents (ZESs) are second-generation drug-eluting stents: however, the clinical efficacy of ZES implantation is unclear because late loss associated with ZESs is reportedly higher than that observed for other DESs. The aim of this study was to evaluate the clinical efficacy of ZESs compared to paclitaxel-eluting stents (PESs). We retrospectively evaluated the angiographic and clinical outcomes of 431 lesions in 342 patients treated with PESs and 153 lesions in 121 patients treated with ZESs in our hospital between May 2007 and December 2010. Follow-up angiographic examinations were performed eight months post-treatment and clinical outcomes were assessed one year after the procedure. Quantitative coronary angiographic analyses showed that late loss was significantly higher for ZESs than PESs (0.82 ± 0.73 mm vs 0.47 ± 0.68 mm; P = 0.003). However, there was no significant difference in target lesion revascularization (TLR) between the two groups (ZES: 15 lesions, 9.8% vs PES: 25 lesions, 5.8%; P = 0.092). When comparing stents according to the American College of Cardiology/American Heart Association (ACC/AHA) lesion type, the TLR rate in the ZES group was significantly lower than in the PES group (0% vs 7.0%; P = 0.038) for Type A/B1 lesions, but the TLR rate for type B2/C lesions in the ZES group was significantly higher than in the PES group (15.8% vs 5.3%; P = 0.009). Multivariate logistic regression analysis showed that dialysis (OR: 35.54; 95% CI: 3.15-400.67; P = 0.039) and pre-minimal lumen diameter (OR: 0.036; 95% CI: 0.002-0.541; P = 0.016) were independent predictors of TLR in ZES-treated lesions. However, no factors predicted TLR in PES-treated lesions. Our study demonstrated excellent outcomes with ZESs for simple lesions, but it is necessary to carefully implant ZESs in complex lesions, such as ACC/AHA type B2/C lesions

Effects of HLA-DRB1 alleles on susceptibility and clinical manifestations in Japanese patients with adult onset Still’s disease

BackgroundHLA-DRB1 alleles are major determinants of genetic predisposition to rheumatic diseases. We assessed whether DRB1 alleles are associated with susceptibility to particular clinical features of adult onset Still’s disease (AOSD) in a Japanese population by determining the DRB1 allele distributions.MethodsDRB1 genotyping of 96 patients with AOSD and 1,026 healthy controls was performed. Genomic DNA samples from the AOSD patients were also genotyped for MEFV exons 1, 2, 3, and 10 by direct sequencing.ResultsIn Japanese patients with AOSD, we observed a predisposing association of DRB1*15:01 (p = 8.60 × 10−6, corrected p (Pc) = 0.0002, odds ratio (OR) = 3.04, 95% confidence interval (95% CI) = 1.91–4.84) and DR5 serological group (p = 0.0006, OR = 2.39, 95% CI = 1.49–3.83) and a protective association of DRB1*09:01 (p = 0.0004, Pc = 0.0110, OR = 0.34, 95% CI = 0.18–0.66) with AOSD, and amino acid residues 86 and 98 of the DRβ chain were protectively associated with AOSD. MEFV variants were identified in 49 patients with AOSD (56.3%). The predisposing effect of DR5 was confirmed only in patients with AOSD who had MEFV variants and not in those without MEFV variants. Additionally, DR5 in patients with AOSD are associated with macrophage activation syndrome (MAS) and steroid pulse therapy.ConclusionThe DRB1*15:01 and DR5 are both associated with AOSD susceptibility in Japanese subjects. A protective association between the DRB1*09:01 allele and AOSD was also observed in these patients. Our data also highlight the effects of DRB1 alleles in susceptibility to AOSD

Risk Factors for Restenosis after Percutaneous Coronary Intervention with Sirolimus- and Paclitaxel-eluting Stents

To identify risk factors for restenosis after percutaneous coronary intervention with sirolimus (SES)- or paclitaxel (PES)-eluting stents. The clinical outcomes of 894 patients treated with either SES (n = 462) or PES (n = 432) between January 2005 and January 2010 were evaluated. Multivariate logistic regression analysis showed that long ( > 20mm)(odds ratio [OR], 1.87; 95% confidence interval [CI], 1.07-3.33; P = 0.03) or bent (angle > 45°) lesions (OR, 2.57; 95% CI, 1.47- 4.49; P < 0.01) were independent risk factors for restenosis with SES, and that hemodialysis (OR, 7.61; 95% CI, 2.78- 20.85; P < 0.01) and long (OR, 2.63; 95% CI, 1.18-5.84; P = 0.02) or bent lesions (OR, 3.47; 95% CI, 1.65-7.27;P < 0.01) were independent risk factors for target lesion revascularization (TLR) with SES. In contrast, no independent risk factors for restenosis and TLR were found for lesions treated with PES. The rate of TLR was significantly higher in patients on hemodialysis or in those with long lesions in the SES group (hemodialysis, 30.4% vs. 11.1%, P = 0.02; long lesions, 13.2% vs. 4.4%, P < 0.01; for SES vs. PES, respectively). Rates of restenosis and TLR were significantly higher in patients with bent lesions in the SES group (restenosis, 30.8% vs. 15.6%, P < 0.01; TLR, 20.0% vs. 5.8%, P < 0.01; for SES and PES, respectively). Most clinical studies have described better angiographic results for SES compared to PES. However, PES might result in better clinical outcomes than SES for patients on hemodialysis or for those with long or bent lesions

Results of laparoscopic subtotal cholecystectomy by laparoscopic linear stapler in difficult cases with severe cholecystitis

Laparoscopic subtotal cholecystectomy (LSC) has been recognized as a safe and feasible alternative surgical procedure for a difficult laparoscopic cholecystectomy (LC) with severe inflammation in Calot’s triangle. We compared the surgical outcomesof cholecystectomy for acute cholecystitis between standard LC and LSC using laparoscopic linear stapler. 172 patients were diagnosed as acute cholecystitis, among them, 16 patients who underwent LSC and other 156 patients who underwent standardLC were enrolled in this study. The severity grading of acute cholecystitis in LSC group was significantly higher than LC group. Operation time was longer in the LSC group than LC group. LSC had significantly more intraoperative blood loss compared to LC. However, there was no significant difference in the postoperative complications between two groups. LSC using laparoscopic linear stapler contributes surgeons avoid common bile duct injury in difficult LC