Nobuyoshi Shimizu's research while affiliated with Okayama Rosai Hospital and other places

Publications (782)

Article
Objective: Inflammation-based prognostic scores including the Glasgow Prognostic Scores (GPS), Modified GPS, Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Lymphocyte-to-monocyte ratio (LMR), Prognostic index (PI), and Prognostic nutrition index (PNI) are associated with survival in surgically treated patients with malign...
Article
We report the case of a patient with lymphohistiocytoid mesothelioma (LHM). A 73-year-old man was referred to our hospital because of pleural effusion seen on chest radiographs. He had been exposed to asbestos during power distribution work. Computed tomography (CT) images of the chest showed thickening of the left parietal pleura. Biopsy with a th...
Article
We have developed a convenient multicolor fluorescent in situ hybridization (FISH) (five-, four-, three-, and two-color FISHs) for detecting specific genes/DNA segments on the human chromosomes. As a foundation of multicolor FISH, we first isolated 80 bacterial artificial chromosome (BAC) probes that specifically detect the peri-centromeres (peri-C...
Article
We previously isolated PARKIN (PARK2) as a gene responsible for a unique sort of Parkinson disease, namely Autosomal Recessive Juvenile Parkinsonism (ARJP). In this study, we surveyed all the available literature describing PARK2 gene/Parkin protein mutations found in Parkinson disease patients. Only carefully evaluated data were deposited in the g...
Article
Full-text available
Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of...
Article
Full-text available
We previously established three mouse cell lines (Aire+TEC1, Aire+TEC2 and Aire+DC) from the medullary thymic epithelial cells (mTECs) and dendritic cells (mDCs). These cells constitutively expressed “autoimmune regulator (Aire) gene” and they exhibited various features of self antigen-presenting cells (self-APCs) present in the thymic medullary re...
Article
Background Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1–20.9% and 5.8–13.0% in AD and non-AD...
Article
Full-text available
Commensal bacteria in gastrointestinal tracts are reported to function as an environmental factor to regulate intestinal inflammation and immune responses. However, it remains largely unknown whether such bacterial function exerts any effect on other immune organs distant from the intestine. In this study, the influence of commensal bacteria in the...
Data
Full-text available
Sequencing of the human Y chromosome has uncovered the peculiarities of the genomic organization of a heterogametic sex chromosome of old evolutionary age, and has led to many insights into the evolutionary changes that occurred during its long history. We have studied the genomic organization of the medaka fish Y chromosome, which is one of the yo...
Article
Resveratrol was glucosylated to its 3- and 4'-β-glucosides by cultured cells of Phytolacca americana. On the other hand, cultured P. americana cells glucosylated pterostilbene to its 4'-β-glucoside. P. americana cells converted piceatannol into its 4'-β-glucoside. The 3- and 4'-β-glucosides of resveratrol were further glucosylated to 3- and 4'-β-ma...
Article
Resveratrol was glucosylated to its 3- and 4'-β-glucosides by the glucosyltransferase PaGT3 from Phytolacca americana expressed in Bacillus subtilis. PaGT3 glucosylated pterostilbene to its 4'-β-glucoside. Piceatannol was converted into its 4'-β-glucoside by PaGT3. Resveratrol 3-β-glucoside showed the inhibitory action of adhesion, migration, and i...
Article
Down syndrome (DS), also known as Trisomy 21, is the most common chromosome aneuploidy in live-born children and displays a complicated symptom. To date, several kinds of mouse models have been generated to understand the molecular pathology of DS, yet the gene dosage effects and gene(s)-phenotype(s) correlation are not well understood. In this stu...
Article
Full-text available
Although mutations of autoimmune regulator (AIRE) gene are responsible for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), presenting a wide spectrum of many characteristic and non-characteristic clinical features, some patients lack AIRE gene mutations. Therefore, something other than a mutation, such as dysregulation of A...
Article
Recently, we isolated 4 distinct kinds of single chain antibody against human EGF receptor (EGFR) after screening the Keio phage display scFv library by using two methods of target-guided proximity labeling. In the current study, these monovalent scFv antibodies were converted to bivalent IgGs of humanized forms (hIgGs) by recombinant technology us...
Article
抄録 限局性悪性胸膜中皮腫(LMM)は非常に稀な疾患である.びまん性悪性胸膜中皮腫(DMM)との関連が解明されておらず,標準治療は確立されていない.症例は65歳男性.石綿曝露歴があり,咳嗽が出現し,胸部単純X線写真にて左上肺野に異常影を指摘された.胸部CTおよびMRIでは,比較的境界明瞭で内部不均一な胸壁を取り囲む7 cm大の腫瘤を認めた.組織針による生検にて上皮型胸膜中皮腫と診断された.PETおよび胸腔鏡所見より限局性と考え,浸潤の疑われた胸壁とともに腫瘤摘出術を施行したが,術後6ヵ月目に胸壁に再発し,放射線・化学療法中である.結語:本症例の再発形式は局所再発であったが,通常のDMMと異なり,播種癒合しびまん性に進展した可能性も否定できなかった.既報告ではLMMはDMMに比較して予後はよい...
Article
Through the comprehensive analysis of the genomic DNA sequence of human chromosome 22, we identified a novel gene of 702kb encoding a big protein of 2481 amino acid residues, and named it as TPRBK (TPR containing big gene cloned at Keio). A novel protein TPRBK possesses 25 units of the TPR motif, which has been known to associate with a diverse ran...
Article
The precise control of spatiotemporal expression of target genes is crucial when establishing transgenic animals, and the introduction of genes for fluorescent marker proteins is inevitable for accelerating research at molecular levels. To assist this, we constructed a novel dual promoter expression vector for two independent reporter genes, green...
Article
We have developed a graphical image database CancerProView (URL: http://cancerproview.dmb.med.keio.ac.jp/php/cpv.html) to assist the search for alterations of the motifs/domains in the cancer-related proteins that are caused by mutations in the corresponding genes. For the CancerProView, we have collected various kinds of data on 180 cancer-related...
Article
One-year follow-up results on Japan’s first bilateral living-donor lobar lung transplantation concern a 24-year-old woman who had become ventilator-dependent due to severe bronchiectasis associated with primary ciliary dyskinesia. Surgery was conducted using her sister’s right lower lobe and her mother’s left lower lobe. Total forced vital capacity...
Article
Objective. To evaluate the outcome of surgical treatment for malignant pleural mesothelioma (MPM). Subjects. A total of 264 cases of MPM from 2007 through 2013 from Rosai Hospital were reported. Of these, I examined 60 patients treated surgically. Results. The 56 men and 4 women had a mean age of 65 years old. Histological diagnoses were as follows...
Article
Full-text available
Isolation of short, tandem repeat sequences from mayfly Rhithrogena japonica Uéno 1928 has been carried out by probing the multicopy DNA regions using labeled total genomic DNA. Several microsatellites comprised of pyrimidine/purine-biased (Pyr/Pur) repeating units (CT, TCTG, and TCTCTG) and two minisatellites were identified. No locus containing (...
Article
Interleukin-18 (IL-18) is a potent proinflammatory cytokine that augments both innate and acquired immune responses. It is also a crucial regulator of lymphocyte production of interferon-γ (IFN-γ), which can promote acute cellular rejection of transplanted solid organs. To evaluate the role of IL-18 in liver transplantation, we constructed an adeno...
Article
We recently constructed the scFv-displaying phage library with extremely high repertoire and have successfully utilized for screening scFv antibodies against various proteins, polysaccharides and glyco-lipids. Here, we developed a new screening strategy to isolate scFv antibodies against cell surface EGF receptor (EGFR). For this, we applied two sl...
Article
In the human thymus, AIRE (autoimmune regulator) gene is expressed in a very limited type of medullary thymic epithelial cells (mTECs) and no cognate cell lines are available, hence the molecular analysis of AIRE gene function has been difficult. To improve this situation, we attempted to isolate Aire-expressing cells and established three cell lin...
Article
Full-text available
In the mechanism of thymus-induced central tolerance, the transcription factor Aire has been demonstrated to promote the expression of a wide range of peripheral organ-specific antigens (Ags) in the medullary thymic epithelial cells (mTECs), which serve as self-Ags in negative selection. We examined the expression of desmoglein 3 (Dsg3), the autoan...
Article
Full-text available
We recently identified a novel gene, named GOLSYN/Syntabulin, on human chromosome 8q23.2. In neurons, GOLSYN/Syntabulin functions as a molecule linking syntaxin 1-containing vesicles to kinesin, and thus plays an essential role in the transport of vesicles and mitochondria along neuronal processes. GOLSYN/Syntabulin is ubiquitously ex-pressed in mo...
Article
YPEL5 is a member of the YPEL gene family that is highly conserved in the eukaryotic species and apparently involved in a certain cell division-related function. In this study, we examined the functional and phylogenetic aspects of YPEL5 protein in more detail. During cell cycle, YPEL5 protein was detected at different subcellular localizations; at...
Article
Full-text available
Fungal diseases in immunocompromised hosts pose significant threats to their prognoses. An accurate diagnosis and identification of the fungal pathogens causing the infection are critical to determine the proper therapeutic interventions, but these are often not achieved, due to difficulties with isolation and morphological identification. In an ef...
Article
KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi...
Article
Chinese hamster ovary (CHO) cells are widely used for the stable production of recombinant proteins. Gene amplification techniques are frequently used to improve of protein production, and the dihydrofolate reductase (DHFR) gene amplification system is most widely used in the CHO cell line. We previously constructed a CHO genomic bacterial artifici...
Article
目的:悪性腹膜中皮腫の臨床像を胸膜中皮腫と比較し明らかにする.対象:1993~2009年3月までに診断・治療した悪性腹膜中皮腫12例と胸膜中皮腫96例を対象とした.結果:悪性腹膜中皮腫は,胸膜中皮腫と比較して,女性の比率が高く,上皮型が多く,治療は化学療法が中心であった.職業歴,石綿肺や胸膜プラークの合併より石綿ばく露の強い関与が窺われ,胸膜中皮腫と比較しても,短期間に高濃度のばく露例が多かった.予後は,悪性腹膜中皮腫および胸膜中皮腫の生存期間中央値は12.0ヵ月であり,同等に予後不良の疾患であった.結語:悪性腹膜中皮腫は女性が多く,上皮型が主であった.石綿ばく露が強く関与しており,石綿ばく露歴,腹水貯留がある場合には鑑別疾患のひとつと考えられた.治療に関しては,解剖学的に根治手術は困難であ...
Article
Unlabelled: During vertebrate embryogenesis, the liver develops at a precise location along the endodermal primitive gut tube because of signaling delivered by adjacent mesodermal tissues. Although several signaling molecules have been associated with liver formation, the molecular mechanism that regulates liver specification is still unclear. We...
Data
Exon-intron architecture of putative genes in BAC clone Mj024A04. Exon-intron architectures predicted by GENSCAN are shown.
Data
27 putative genes with nearest homologues in the BAC clone Mj024A04. The BLASTP top hits and the E-values are shown.
Data
Full-text available
Southern blot hybridization of putative genes for detection of CpG-methylation. Kuruma shrimp genomic DNA (20 μg) was digested completely, electrophoresed and blotted. Hybridization and washing were performed under low stringency condition at 42°C. The restriction enzymes that were used are indicated by their initials (M; MspI, H; HpaII). The putat...
Data
Full-text available
DNA fingerprints of kuruma shrimp BAC clones. 3 BAC clones from each hybridization positive groups (represented by positive probes at the top of each figures) and negative (neg) group were randomly selected. BAC DNA of all clones and Mj024A04 (B) were digested with EcoRI and HindIII.
Data
Full-text available
Phylogenetic tree of BIR domains of BIRPs. BIR domains in the putative IAP genes found in Mj024A04 were compared with BIR domains from several organisms. Amino acid sequences of putative IAP gene 01, 06 and 24 were predicted by GENSCAN [42]. Each BIR domains was identified using InterProScan (version 22.0) [44]. Multiple sequence alignment and the...
Data
Primers used in this study. The orientation (forward or reverse) of all primers is indicated by 'f' or 'r' in the end of each primer name. Primers whose name is 'Gene--f or r' were used for PCR detection of each putative gene fragment from BAC clones. Primers for quantitative PCR of 4 putative genes (gene 01, 09, 16 and 27) in the BAC clone Mj024A0...
Data
BAC genotyping using three microsatellite markers (MS02, 33 and 64) in Mj024A04. Genotypes representing the same size as the three microsatellite markers were taken as the same group. One base difference was regarded as experimental error.
Data
Full-text available
Calculation of the number of genotypes in shrimp genomes. Possible numbers of total genotypes were calculated using recursive formula for the marginal distribution and observed number of different genotypes. X-axis indicates the number of genotypes (θ). Y-axis indicates log-likelihood function of each given number of genotype. 90% and 95% confidenc...
Data
Full-text available
Schematic representation and frequency of BAC clones that hybridized with probe F, M and R. Number and percentage of positive clones in each group are shown. Data were based on the hybridization results for 381 clones in MjBL2 Plate 24. Location of each probes used in this study is indicated by red boxes.
Data
BAC-ends anchored gene homologues identified by BLAST search. The significant matches (E-value < 0.1) of BAC-End-Sequences against public databases are shown in the list.
Article
Full-text available
During the development of the vertebrate nervous system, mitosis of neural progenitor cells takes place near the lumen, the apical side of the neural tube, through a characteristic movement of nuclei known as interkinetic nuclear migration (INM). Furthermore, during the proliferative period, neural progenitor cells exhibit planar cell divisions to...
Article
Full-text available
Higher crustaceans (class Malacostraca) represent the most species-rich and morphologically diverse group of non-insect arthropods and many of its members are commercially important. Although the crustacean DNA sequence information is growing exponentially, little is known about the genome organization of Malacostraca. Here, we constructed a bacter...
Article
The Tn-antigen, GalNAcα-Ser/Thr, is a tumour-associated carbohydrate antigen that may provide a sensitive and specific marker for pre-clinical detection of carcinoma and a target for cancer therapies. We recently reported that MLS128 monoclonal antibody treatment significantly inhibited colon and breast cancer cell growth. On the basis of our obser...
Article
Chinese hamster ovary (CHO) cell lines are widely used for scientific research and biotechnology. A CHO genomic bacterial artificial chromosome (BAC) library was constructed from a mouse dihydrofolate reductase (DHFR) gene-amplified CHO DR1000L-4N cell line for genome-wide analysis of CHO cell lines. The CHO BAC library consisted of 122,281 clones...
Article
Objective. We examined the clinical features and prognosis of malignant pleural mesothelioma. Subjects. From 1993 to 2008. 81 patients from the Main Center for Asbestos-related Disease for Diagnosis and Treatment, Okayama Rosai Hospital, were enrolled. Results. Of the 81 patients, 74 were men and 7 were women with an average age of 66.0 years old....
Article
Aromatase is a steroidogenic enzyme catalyzing the production of estrogens and is important for the proper development and function of the reproductive system. The lineage of cyp19a1 (ovarian-type aromatase)-expressing cells in the developing gonad was analyzed using a transgenic medaka (Oryzias latipes) that recapitulates endogenous cyp19a1 expres...
Article
Spinocerebellar ataxia type 31 (SCA31) is an adult-onset autosomal-dominant neurodegenerative disorder showing progressive cerebellar ataxia mainly affecting Purkinje cells. The SCA31 critical region was tracked down to a 900 kb interval in chromosome 16q22.1, where the disease shows a strong founder effect. By performing comprehensive Southern blo...
Article
方法:1993~2008年の期間に,24例の胸膜中皮腫に胸膜肺全摘術を施行した.そのうち再発した10例を対象とし検討した.結果:性別内訳は,男性9例,女性1例で,平均年齢は62.3歳(54~75歳)であった.組織型は上皮型7例,肉腫型2例,二相型1例であった.臨床病期は,II期が8例,III期が2例で,病理病期は,II期が2例,III期が8例であった.術後補助療法は,化学療法が2例に,放射線療法が1例に行われた.再発までの期間は,平均8.5ヵ月(1~17ヵ月)で,再発部位は,8例は局所再発で,2例が遠隔転移であった.全例に化学療法が行われ,Pemetrexedが3例に,Gemcitabineが7例に使用された.24例の無病生存期間中央値は13.2ヵ月で,再発例は7.0ヵ月であった.再発からの...
Article
Parkin mutations are responsible for the pathogenesis of autosomal-recessive juvenile parkinsonism (AR-JP). On initial screening of Japanese patients with AR-JP, we had found that approximately half of the parkin mutations are deletions occurring between exons 2 and 5, forming a deletion hot spot. In this study, we investigated the deletion breakpo...
Article
The thymus is an organ where T lymphocytes develop. Thymus development requires interactions of cells derived from three germ layers. However, the molecular mechanisms that control thymus development are not fully understood. To identify the genes that regulate thymus development, we previously carried out a large-scale screening for ethylnitrosour...
Article
This cover is specifically designed to celebrate the 2nd European Congress of Immunology (www.eci-berlin2009.com), to be held September 13–16, 2009 in Berlin. The cover consists of a collage of images from Iwanami et al. (pp 2606–2616) with Berlin's historic Bradenburg Gate, Brandenburger Tor, in the forefront (image of the Brandenburg Gate r Image...
Data
The sequence of pc/glis3 cDNA and its deduced protein. The pc/glis3 cDNA sequence is shown in the upper line and its deduced amino acid sequence in the lower line. The exon boundaries are indicated by color: the 3′ end of the exon in front is in red and the 5′ end of the exon behind is in blue. The position of the probe used for northern hybridizat...
Data
The phylogenetic tree constructed for Kruppel-like transcription factors Shown are pc/glis3 (AB353137), glis1a (AB353139), glis1b (AB353140), and glis2 (AB353141) from medaka; Glis1 (NP_671754), Glis2 (Q8VDL9), Glis3 (ABI31654), Gli1 (P47806), Gli2 (NP_001074594), Gli3 (Q61602), Zic1 (AAH6024), Zic2 (Q62520), and Zic3 (Q62521) from the mouse; and C...
Data
Structure and expression of pc/glis3 mRNA (A) Structure of the pc/glis3 mRNA The structure of the WT and pc pc/glis3 mRNA is described in detail in the legend to Fig. 1G. (B) RT-PCR of the 3′ region of pc/glis3 mRNA An exon 4 fragment was amplified from both the WT and pc mutant medaka by RT-PCR with the primer set described in the text and detaile...
Data
Analysis of pc/glis3 mRNA expression (A) RT-PCR of wild-type (WT, left) and the pc mutant (right) pc/glis3 mRNA. pc/glis3 mRNA was not detectable in the pc mutant using the PCR primers 5′-GTTTGAAGGCTGCAAGAAGGCATT-3′ (sense) and 5′-CTTGCGTAACTGTCGCTCTTG-3′ (antisense), which would amplify the 3′ region of the transcript (271 bp). RFX3 is a neighbori...
Data
RT-PCR of the 3′ region of pc/glis3 mRNA (A) The regions targeted for PCR amplification (B) RT-PCR of WT and mutant mRNA (C) Genomic PCR of the regions corresponding to those amplified by RT-PCR Primers used: (1) 5′-TTTACCACTGGGAAGCAAAGC-3′/5′-GCATGAAACTCTGCGGTATATC-3′ (2)5′-TGAGTGTTGCAACAGGCCATC-3′ /5′-CAGCATCTTCCTGGACTGTGG-3′ (3)5′-TTTGAAGGCTGCAA...
Article
目的:アスベスト関連肺癌(以下,石綿肺癌)およびじん肺肺癌について検討した.対象と方法:1998~2008年の期間に当院で診断・治療した症例について検討した.比較対照は,同時期の石綿肺癌,じん肺肺癌を除いた肺癌(以下,その他肺癌)とした.結果:石綿肺癌は98例,じん肺肺癌は28例,その他肺癌は491例であった.石綿肺癌とじん肺肺癌の臨床病理学的比較において,組織型と臨床病期に有意差を認めた.手術症例の検討では,じん肺肺癌は,肺葉切除が少なく,予後も不良であった.石綿肺癌,じん肺肺癌およびその他の肺癌の予後は,生存期間中央値は20.4ヵ月,16.2ヵ月および19.2ヵ月で有意差は認めなかった.全症例を対象とした多変量解析では,石綿ばく露歴およびじん肺の合併は予後因子でなかった.結論:石綿肺癌お...
Article
The periodontal ligament (PDL) is a strong connective tissue that surrounds the tooth root, absorbs occlusal forces, and functions as a sense organ. PDL originated from dental follicle (DF), which possessed mesenchymal progenitors in the developing tooth germ. However, as specific marker genes for PDL and DF are currently unavailable, the molecular...
Article
T-antigen (Galbeta1-3GalNAc-Thr/Ser) also known as Thomsen-Friedenreich (TF) antigen is the core 1 structure of O-linked mucin type glycans. In normal epithelium, the disaccharide structure is masked by terminal carbohydrate moieties, but is uncovered in most primary and metastatic epithelial malignant tumors. For the purpose of establishing cancer...
Article
Full-text available
Loss-of-function mutations in the FLG (filaggrin) gene cause the semidominant keratinizing disorder ichthyosis vulgaris and convey major genetic risk for atopic dermatitis (eczema), eczema-associated asthma and other allergic phenotypes. Several low-frequency FLG null alleles occur in Europeans and Asians, with a cumulative frequency of approximate...
Article
Object. Characteristics and prognosis of patients with asbestos-related lung cancer were evaluated. Methods. We evaluated 98 patients with asbestos-related lung cancer treated in the period 1998-2007 in Okayama Rosai Hospital. Results. The patients consisted of 92 men and 6 women. The mean age, the age of first exposure to asbestos, the period of e...
Data
Full-text available