Recurrent pneumonia with mild hypogammaglobulinemia diagnosed as X-linked agammaglobulinemia in adults

<p>Abstract</p> <p>Background</p> <p>X-linked agammaglobulinemia (XLA) is a humoral immunodeficiency caused by disruption of the Bruton's tyrosine kinase (BTK) gene. Typical XLA patients suffer recurrent and severe bacterial infections in childhood.</p> <p>Methods</p> <p>Flow cytometric analysis of the peripheral monocytes using the anti-BTK antibody was used to characterize a 27 year old male patient with mild hypogammaglobulinemia (IgG, 635 mg/dl; IgM, 11 mg/dl; IgA, <5 mg/dl). He had suffered from frequent pneumonia since age 25 but had no history of frequent infections in his childhood or in adolescence. Sequencing of the BTK cDNA obtained from an Epstein–Barr virus-transformed B lymphoblastoid cell line derived from the bone marrow of the patient was performed to confirm a genetic defect.</p> <p>Results</p> <p>Flow cytometric analysis of cytoplasmic BTK protein in peripheral monocytes indicated that the patient presents a rare case of adult-onset XLA and that his mother is an XLA carrier. Sequencing of the BTK gene revealed a deletion of AG in the codon for Glu605 (AGT), resulting in an aberrant stop codon that truncates the BTK protein in its kinase domain.</p> <p>Conclusions</p> <p>This case suggests that some XLA cases may remain undiagnosed because they only show mild hypogammaglobulinemia and they lack repeated infections in childhood. Flow cytometric analysis is a powerful method to screen these patients.</p

A surgical orthodontic case with multiple tooth losstreated by bite splint with CAD/CAM method

Recently, the number of middle–aged and elderly orthognathic surgery patients with un-healthy oral conditions has been increasing. Although an interdisciplinary approach in-volving orthodontist, oral surgeon and prosthodontist is required in orthognathic surgery of these patients, deciding the jaw position after orthognathic surgery is difficult due to unhealthy oral conditions such as edentulous jaw and tooth loss. In the recently study, preoperative simulation methods for orthognathic surgery have been developed through the use of virtual reality computed technology. A male first examined at the age of 36 years and 7 months was diagnosed as having mandibular protrusion with multiple tooth loss and mandibular deviation. The patient was treatedinterdisciplinary by a team of specialists in surgical orthodontic, dental prosthetic and periodontal treatment. Using the interdisciplin-ary approach and haptic device with virtual tactile perception showed satisfactory results loss treated with orthognathic surgery

Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus Type-1 mono-infection and co-infection with hepatitis C Virus

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type-1 (HTLV-1) carriers co-infected with and hepatitis C virus (HCV) have been known to be at higher risk of their related diseases than mono-infected individuals. The recent studies clarified that IL-28B polymorphism rs8099917 is associated with not only the HCV therapeutic response by IFN, but also innate immunity and antiviral activity. The aim of our research was to clarify study whether IL-28B gene polymorphism (rs8099917) is associated with HTLV-1/HCV co-infection.</p> <p>Results</p> <p>The genotyping and viral-serological analysis for 340 individuals showed that IL-28B genotype distribution of rs8099917 SNP did not differ significantly by respective viral infection status. However, the IL-28B mRNA expression level was 3.8 fold higher in HTLV-1 mono-infection than HTLV-1/HCV co-infection. The high expression level was associated with TT (OR, 6.25), whiles the low expression was associated with co-infection of the two viruses (OR, 9.5). However, there was no association between down-regulation and ATL development (OR, 0.8).</p> <p>Conclusion</p> <p>HTLV-1 mono-infection up-regulates the expression of IL-28B transcripts in genotype-dependent manner, whiles HTLV-1/HCV co-infection down-regulates regardless of ATL development.</p

Coincidence analysis to search for inspiraling compact binaries using TAMA300 and LISM data

Japanese laser interferometric gravitational wave detectors, TAMA300 and LISM, performed a coincident observation during 2001. We perform a coincidence analysis to search for inspiraling compact binaries. The length of data used for the coincidence analysis is 275 hours when both TAMA300 and LISM detectors are operated simultaneously. TAMA300 and LISM data are analyzed by matched filtering, and candidates for gravitational wave events are obtained. If there is a true gravitational wave signal, it should appear in both data of detectors with consistent waveforms characterized by masses of stars, amplitude of the signal, the coalescence time and so on. We introduce a set of coincidence conditions of the parameters, and search for coincident events. This procedure reduces the number of fake events considerably, by a factor $\sim 10^{-4}$ compared with the number of fake events in single detector analysis. We find that the number of events after imposing the coincidence conditions is consistent with the number of accidental coincidences produced purely by noise. We thus find no evidence of gravitational wave signals. We obtain an upper limit of 0.046 /hours (CL $= 90$) to the Galactic event rate within 1kpc from the Earth. The method used in this paper can be applied straightforwardly to the case of coincidence observations with more than two detectors with arbitrary arm directions.Comment: 28 pages, 17 figures, Replaced with the version to be published in Physical Review

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

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DNAのヌクレオソーム単位での断片化はアポトーシスの特徴的変化の一つであるが,断片化の欠損するアポトーシスも報告されている。本研究では,アポトーシスの核変化誘導機序の解明のために,DNA断片化を伴わない細胞死におけるその欠損原因の解析を行った。(1)ヌクレオソーム単位でのDNA断片化欠損はネオカルチノスタチンにより誘導されたMolt-4細胞のアポトーシスにおいて認められた。この時,DNA断片化に必須であるとされているDNA fragmentation factor (DFF)はMolt-4細胞において正常に機能していたことから,DFFだけでDNA断片化の誘導を説明することはできないと考えられた。(2)イミダゾールによる細胞内酸性化はDNA断片化を抑制したが,細胞内pHの中性化により断片化誘導が認められた。このことはアポトーシスにおけるDNA断片化誘導には細胞内pHが中性付近に保持されることが必要であることを示唆する結果である。(3)亜鉛とノコギリヤシ果エキスは前立腺癌細胞株にヌクレオソーム単位でのDNA断片化を欠損した細胞死を誘導し,この時の細胞死のタイプは主としてネクローシスであった。これらの知見はアポトーシスの実行過程の解明に重要な情報を与える。Oligonucleosomal DNA fragmentation is a hallmark of apoptosis, however the fragmentation does not always occur in apoptotic cell death. In the present study, we examined the cause of no oligonucleosomal DNA fragmentation in the cell death to clarify the ladder formation mechanism during apoptosis. (1) Oligonucleosomal DNA fragmentation was not observed in neocarzinostatin (NCS)-induced apoptotic Molt-4 cells. DNA fragmentation factor (DFF), which is essential for the apoptotic ladder formation, was found to be functionally expressed in these cells, suggesting that the DFF expression is not sufficient to induce the oligonucleosomal DNA fragmentation. (2) Intracellular acidification by imidazole inhibited the formation of oligonucleosomal DNA fragmentation and the neutralization in these cells induced DNA fragmentation. This result suggests that maintaining intracellular pH in the neutral range is essential for the induction of apoptotic DNA fragmentation. (3) Zinc and the extract from S. repens induced cell death, associated with no oligonucleosomal DNA fragmentation in prostatic cancer ceH lines. Zinc and the extract-treated cells exhibited mainly necrotic features. These findings provide important information about the execution phase of apoptosis

AMPK を介した糖・脂質代謝調節に関する研究

グリセロールは肝臓における糖新生や脂質合成の材料であるため、肝臓へのグリセロール流入量の変化は様々な代謝経路に変調をきたす。アクアポリン9（AQP9）は、主に肝臓において発現が見られ、水分子のみならず、グリセロールや尿素などの低分子溶質をも透過させるチャネル型膜蛋白質である。AMP-activated protein kinase（AMPK）は生体内のエネルギーセンサーであり、糖・脂質代謝の恒常性維持に働くセリン/スレオニンキナーゼである。本研究では、AMPKの活性化剤である、5-aminoimidazole-4-carboxamide-1--D-ribonucleoside（AICAR）を、ヒト肝癌由来HepG2 細胞に作用させたところ、AQP9 mRNA の発現量が顕著に減少することを確認した。レポータージーンアッセイや転写因子forkhead boxa2（Foxa2）遺伝子をノックダウンさせた実験の結果から、Foxa2 は、AICAR によるAQP9 遺伝子発現抑制に関わる重要な転写調節因子であることを見出した。AICAR により活性化されたAMPK は、Akt のThr-308 残基とSer-473 残基のリン酸化を促し、それに伴いFoxa2 がリン酸化されて核内から核外へと移行することを明らかにした。したがって、肝臓でのグリセロール輸送の観点からAMPK によるコントロールのもとに、AQP9 は肝臓へのグリセロールの流入量を変化させ、糖・脂質代謝調節に寄与している可能性が示唆された。Change in glycerol influx into the liver causes metabolic alternations in many pathways since glycerol is a substrate forgluconeogenesis and lipogenesis in the liver. Aquaporin 9 (AQP9), a channel membrane protein, is expressed mainly in the liver andpermeable to water and small molecular weight solutes such as glycerol and urea. AMP-activated protein kinase, AMPK, functioningas a serine/threonine kinase acts as an energy sensor in the homeostasis of glyco- and lipid-metabolism. In this study, we found that5-aminoimidazole-4-carboxamide-1--D-ribonucleoside (AICAR), an AMPK activator, significantly down-regulated AQP9 mRNAexpression in human hepatoma HepG2 cells. Forkhead box a2 (Foxa2) was demonstrated to be one of the transcriptional regulatorsof AQP9 gene expression repressed by AICAR from the results of a reporter gene assay and knock-down of the Foxa2 gene bysiRNA. Activation of AMPK by AICAR promoted the phosphorylation of Akt at Thr-308 and Ser-473 residues and subsequentlyphosphorylated and excluded Foxa2 from the nucleus. These results suggest the possibility that AQP9 is under AMPK control in theinflux of glycerol into the liver and that AQP9 contributes to the glycol- and lipid-metabolism of glycerol transport in the liver