MAP7D2 is a brain expressing X-linked maternal imprinted gene in humans

Increasing evidence suggests imprinted genes influence mouse and human behaviors and cognitive functions. Unlike autosomal imprinted genes, X-linked imprinted genes are expressed in a sex-dependent manner because of male hemizygosity. Therefore, these genes could directly affect sex-specific brain functions and sex-biased vulnerability to psychiatric disorders such as autism1. Comparing lymphoblastoid cell lines (LCL) and peripheral blood mononuclear cells (PBMC) from healthy adult male and females, we identified MAP7 domain containing 2 (MAP7D2) as the first human X-linked imprinted gene. Both in LCL and PBMC, MAP7D2 expression was significantly suppressed in males by maternal imprinting. In each female LCL clone, MAP7D2 was expressed higher in paternally derived allele and was affected by X-chromosome inactivation. In female PBMC, however, reactivation of maternal MAP7D2 alleles was observed. MAP7D2 was expressed specifically in the brain among human tissues with unique isoforms. These results predict a crucial role of MAP7D2 for human sex-dependent neurobiological traits

Stabilizing synthetic data in the DNA of living organisms

Data-encoding synthetic DNA, inserted into the genome of a living organism, is thought to be more robust than the current media. Because the living genome is duplicated and copied into new generations, one of the merits of using DNA material is long-term data storage within heritable media. A disadvantage of this approach is that encoded data can be unexpectedly broken by mutation, deletion, and insertion of DNA, which occurs naturally during evolution and prolongation, or laboratory experiments. For this reason, several information theory-based approaches have been developed as an error check of broken DNA data in order to achieve data durability. These approaches cannot efficiently recover badly damaged data-encoding DNA. We recently developed a DNA data-storage approach based on the multiple sequence alignment method to achieve a high level of data durability. In this paper, we overview this technology and discuss strategies for optimal application of this approach

38-year-old woman with recurrent abdominal pain, but no fever

A 38-year-old woman presented with 2 days history of left-flank pain. She had similar episodes of abdominal pain as well as chest pain several times, but symptoms disappeared spontaneously. Each time she developed pain, there was no fever. After ruling out common causes of recurrent abdominal pain, familial Mediterranean fever (FMF) was considered as a potential diagnosis. Genetic tests revealed multiple heterozygote mutations, which may be associated with FMF. Patients with Mediterranean fever mutations may present with atypical presentations without fever, like in this case. Astute clinical suspicion is required to make an accurate diagnosis

Cytologic Analysis of Epstein-Barr Virus-Associated T/Natural Killer-Cell Lymphoproliferative Diseases

Rapid, precise diagnosis of Epstein-Barr virus-associated T lymphocyte or natural killer cell lymphoproliferative diseases is clinically important to prevent disease progression and avoid fatal outcomes for patients. In addition to detecting increased copy numbers of Epstein-Barr virus, identification of the lymphocyte subpopulation targeted by the virus infection is crucial to reaching the final diagnosis. However, these procedures are laborious and require large amounts of sample. In contrast, flowcytometric analysis may provide crucial information for initial screening of diseases using only small amounts of sample and involves little labor. In addition to the increase of a particular subpopulation, selective HLA-DR expression indicates selective activation and expansion of a virus-infected clone. Presence of a characteristic HLA-DRhigh CD5dim/negative fraction within CD8+ T lymphocytes indicates a possible diagnosis of Epstein-Barr virus-associateds hemophagocytic lymphohistiocytosis. One should note, however, that cases with familial hemophagocytic lymphohistiocytosis may exhibit a similar abnormal fraction within CD8+ T lymphocytes. These T cells are oligoclonally expanded reactive T cells expanding in response to B cells infected with Epstein-Barr virus

Human heme oxygenase-1 deficiency: A lesson on serendipity in the discovery of the novel disease

金沢大学大学院医学系研究科血管病態制御学The first case of human heme oxygenase (HO)-1 deficiency was reported by Yachie et al. at our laboratory in the Department of Pediatrics, Angiogenesis and Vascular Development, Kanazawa University Graduate School of Medical Science, in 1999. In the present paper I would like to review this novel disease. Our studies into HO-1 deficiency were called by us \u27Kanazawa version Project X\u27. From the story of our successful discovery we have learned that serendipity is a very important spiritual factor. Serendipity is the making of fortunate and unexpected discoveries by chance (from its possession by the heroes in the Persian fairy tale The Three Princes of Serendip). © 2007 Blackwell Publishing Asia

HybGFS: a hybrid method for genome-fingerprint scanning

BACKGROUND: Protein identification based on mass spectrometry (MS) has previously been performed using peptide mass fingerprinting (PMF) or tandem MS (MS/MS) database searching. However, these methods cannot identify proteins that are not already listed in existing databases. Moreover, the alternative approach of de novo sequencing requires costly equipment and the interpretation of complex MS/MS spectra. Thus, there is a need for novel high-throughput protein-identification methods that are independent of existing predefined protein databases. RESULTS: Here, we present a hybrid method for genome-fingerprint scanning, known as HybGFS. This technique combines genome sequence-based peptide MS/MS ion searching with liquid-chromatography elution-time (LC-ET) prediction, to improve the reliability of identification. The hybrid method allows the simultaneous identification and mapping of proteins without a priori information about their coding sequences. The current study used standard LC-MS/MS data to query an in silico-generated six-reading-frame translation and the enzymatic digest of an entire genome. Used in conjunction with precursor/product ion-mass searching, the LC-ETs increased confidence in the peptide-identification process and reduced the number of false-positive matches. The power of this method was demonstrated using recombinant proteins from the Escherichia coli K12 strain. CONCLUSION: The novel hybrid method described in this study will be useful for the large-scale experimental confirmation of genome coding sequences, without the need for transcriptome-level expression analysis or costly MS database searching

Natural history of medium-sized atrial septal defect in pediatric cases

AbstractBackgroundThe indication for surgical repair of atrial septal defect (ASD) is pulmonary to systemic blood flow ratio (Qp/Qs)>2.0, and therapeutic strategy depends on the facility in cases of Qp/Qs 1.5–2.0. Defect size increases with age, but hemodynamic changes of medium-sized ASD (Qp/Qs 1.5–2.0) are unknown.Methods and resultsFrom April 1, 1985 to March 31, 2008, we experienced 125 cases of cardiac catheterization for ASD. Twelve cases were re-evaluated without surgical repair. The first and second catheterizations were performed at median ages of 7 years (range, 2–13 years) and 16 years (range, 5–19 years), respectively. The mean follow-up period was 7 years. Qp/Qs increased from 1.6 to 2.0 during follow-up (p<0.05). Of four cases with Qp/Qs<1.5 at initial presentation, three had Qp/Qs≥1.5 at second inspection. Right ventricle diastolic volume (RVEDV/LVEDV) also increased.ConclusionsQp/Qs and RVEDV/LVEDV of medium-sized ASD increase together in childhood. Re-evaluation before adulthood should be considered in patients with no indications of ASD closure in childhood

The 53rd Regional Meeting of the Japan Pediatric Society in the Chubu District

学会開催報

ヘムオキシゲナーゼ1産生制御による単球機能の調節と炎症治療戦略の開発

血管傷害モデルにおいて、HO-1は酸化ストレスにより誘導される細胞傷害/細胞死を抑制することが明らかにされた。同時に、HO-1による細胞保護作用は、HO-1の発現量や発現の局在、さらに発現時間などにより精密に調節されている可能性が示唆された。特に、細胞接着に依存する細胞ではHO-1の過剰発現が細胞接着因子の発現低下と細胞死を誘導する可能性も明らかにされた。末梢血単球の内、CCR2 CD16^亜群が恒常的にHO-1を産生し、血管内皮の機能維持に重要な役割を果たしていることが明らかにされた。さらに、急性炎症性疾患ではこれらの単球亜群が増加、過度の炎症による組織/臓器傷害の抑制に関与していることが示唆された。蛋白尿を伴う糸球体傷害では、尿中蛋白量に比例して尿細管によるHO-1 mRNA発現が誘導された。種々の腎疾患の中でも、病態の差異に応じてHO-1 mRNAの局在は特徴的なパターンを示した。腎疾患におけるHO-1 mRNA発現の局在とその程度を評価することにより、新たな視点で病態解析が可能となった。慢性気道炎症では呼気中CO濃度が増加することが知られている。原発性肺高血圧症や二次性肺高血圧症症例での肺組織を用いた検討では、肺胞マクロファージのみでなく、気道壁や毛細血管内のマクロファージにおいてもHO-1蛋白発現が認められた。このことから、気道炎症を伴う種々疾患においても多様なレベルでHO-1が炎症の制御に関わっていることが示された。ステロイド投与により単球表面のHb・Hp受容体(CD163)発現が著しく増強することが明らかにされた。また、CD163発現を増強した単球はHb・Hpの取り込みが亢進、IL-10のみでなく、HO-1の産生が有意に増加した。これらの事実は、血管傷害のみでなく、気管支喘息や慢性気管支炎などの気道炎症性疾患に対しても、従来想定されていなかった機序での抗炎症効果を示すものとして極めて興味深い。現在、この点について研究を継続中である。It was shown in a vascular injury model that HO-1 inhibits cell injury/death induced by oxidative stress. At the same time, it is suggested that the cytoprotective effect of HO-1 is strictly dependent on the level, location and duration of the enzyme activity. In particular, anchorage dependent cells, such as endothelial cells, are highly sensitive to overexpression of HO-1, which lead to the loss of adhesion molecules and apoptosis.Among circulating monocytes, C16 CCR2- subpopulation is shown to produce HO-1 in vivo, playing critical role in protecting the functions of endothelial cells. Furthermore, this particular subpopulation of monocytes increases during acute inflammatory illnesses, suggesting that they play significant anti-inflammatory roles by preventing excessive tissue/organ damage.HO-1 mRNA expression within renal tubular epithelium increased in association with urinary protein levels in various glomerular injuries. However, the distribution of HO-1 mRNA varied amo ng illnesses of different pathogenesis, indicating that the pattern of HO-1 mRNA expression reflect distinct mechanisms of tissue injury in different kidney diseases.It has been shown recently that CO in expiratory air reflects inflammation of the airway. Increased levels of HO-1 protein expression were detected within in lung tissue of primary pulmonary hypertension. Major HO-1 producers were alveolar macrophages, and macrophages within capillary lumen, bronchial wall and airway. These results indicate that macrophages play anti-inflammatory roles by producing HO-1/CO within the airway at different levels.Steroid administration induced rapid and significant increase of CD163, receptors for hemoglobin/haptoglobin complex, on manocyte surfaces. These monocytes with high CD163 levels rapidly uptake Hb/Hp complex, and subsequently produced HO-1 and IL-10. These results indicate that monocyte HO-1 production is important not only for the protection of vascular endothelial cells, but unexpectedly for the maintenance of airway function. Further investigation is being performed to resolve these issues.研究課題/領域番号:16591014, 研究期間(年度):2004-2005出典：「ヘムオキシゲナーゼ1産生制御による単球機能の調節と炎症治療戦略の開発」研究成果報告書　課題番号16591014 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作