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1.
BMC Bioinformatics ; 20(1): 362, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253084

RESUMO

BACKGROUND: Accurate detection of polymorphisms with a next generation sequencer data is an important element of current genetic analysis. However, there is still no detection pipeline that is completely reliable. RESULT: We demonstrate two new detection methods of polymorphisms focusing on the Polymorphic Edge (PED). In the matching between two homologous sequences, the first mismatched base to appear is the SNP, or the edge of the structural variation. The first method is based on k-mers from short reads and detects polymorphic edges with k-mers for which there is no match between target and control, making it possible to detect SNPs by direct comparison of short-reads in two datasets (target and control) without a reference genome sequence. The second method is based on bidirectional alignment to detect polymorphic edges, not only SNPs but also insertions, deletions, inversions and translocations. Using these two methods, we succeed in making a high-quality comparison map between rice cultivars showing good match to the theoretical value of introgression, and in detecting specific large deletions across cultivars. CONCLUSIONS: Using Polymorphic Edge Detection (PED), the k-mer method is able to detect SNPs by direct comparison of short-reads in two datasets without genomic alignment step, and the bidirectional alignment method is able to detect SNPs and structural variations from even single-end short-reads. The PED is an efficient tool to obtain accurate data for both SNPs and structural variations. AVAILABILITY: The PED software is available at: https://github.com/akiomiyao/ped .


Assuntos
Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Software
2.
Int J Clin Oncol ; 22(2): 316-323, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27752787

RESUMO

BACKGROUND: Although liver resection combined with preoperative chemotherapy is expected to improve outcomes of patients with resectable colorectal liver metastasis (CRLM), there is as yet insufficient clinical evidence supporting the efficacy of preoperative systemic chemotherapy. The aim of this phase II study was to assess the feasibility and efficacy of preoperative FOLFOX systemic chemotherapy for patients with initially resectable CRLM. METHODS: A prospective multi-institutional phase II study was conducted to evaluate the feasibility and efficacy of preoperative chemotherapy for resectable CRLM (ClinicalTrials.gov identifier number NCT00594529). Patients were scheduled to receive 6 cycles of mFOLFOX6 therapy before liver surgery. The primary endpoint was the macroscopic curative resection rate. RESULTS: A total of 30 patients were included in this study. Two patients who were diagnosed with hepatocellular and intrahepatic cholangiocellular carcinoma based on pathology were excluded from the analysis. More than half of the patients (57 %) had solitary liver metastasis. The completion rate of preoperative chemotherapy was 64.3 % and the response rate was 53.6 %. Two patients were unable to proceed to liver resections due to disease progression and severe postoperative complications following primary tumor resection. Macroscopic curative resection was obtained in 89.3 % of eligible patients. Postoperative mortality and severe complication (≥Gr. 3) rates were 0 and 11 %, respectively. The 3-year overall and progression-free survival rates were 81.9 and 47.4 %, respectively. CONCLUSION: Our phase II study demonstrated the feasibility of liver resection combined with preoperative mFOLFOX6 therapy in patients with initially resectable CRLM. Further study is warranted to address the oncological effects of preoperative chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Terapia Combinada , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Hepatectomia , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
3.
Nucleic Acids Res ; 41(Web Server issue): W109-14, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23761449

RESUMO

Positional MEDLINE (PosMed; http://biolod.org/PosMed) is a powerful Semantic Web Association Study engine that ranks biomedical resources such as genes, metabolites, diseases and drugs, based on the statistical significance of associations between user-specified phenotypic keywords and resources connected directly or inferentially through a Semantic Web of biological databases such as MEDLINE, OMIM, pathways, co-expressions, molecular interactions and ontology terms. Since 2005, PosMed has long been used for in silico positional cloning studies to infer candidate disease-responsible genes existing within chromosomal intervals. PosMed is redesigned as a workbench to discover possible functional interpretations for numerous genetic variants found from exome sequencing of human disease samples. We also show that the association search engine enhances the value of mouse bioresources because most knockout mouse resources have no phenotypic annotation, but can be associated inferentially to phenotypes via genes and biomedical documents. For this purpose, we established text-mining rules to the biomedical documents by careful human curation work, and created a huge amount of correct linking between genes and documents. PosMed associates any phenotypic keyword to mouse resources with 20 public databases and four original data sets as of May 2013.


Assuntos
Genes , Fenótipo , Software , Animais , Interpretação Estatística de Dados , Bases de Dados Factuais , Exoma , Estudos de Associação Genética , Variação Genética , Humanos , Internet , Camundongos , Camundongos Knockout
4.
Nucleic Acids Res ; 39(Database issue): D861-70, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21076152

RESUMO

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN's original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies. Our integrated database has been implemented on the infrastructure of publication medium for databases, termed SciNetS/SciNeS, or the Scientists' Networking System, where the data and metadata are structured as a semantic web and are downloadable in various standardized formats. The top-level ontology-based implementation of mammal-related data directly integrates the representative knowledge and individual data records in existing databases to ensure advanced cross-database searches and reduced unevenness of the data management operations. Through the development of this database, we propose a novel methodology for the development of standardized comprehensive management of heterogeneous data sets in multiple databases to improve the sustainability, accessibility, utility and publicity of the data of biomedical information.


Assuntos
Bases de Dados Factuais , Bases de Dados Genéticas , Mamíferos/genética , Animais , Humanos , Internet , Mamíferos/metabolismo , Camundongos , Integração de Sistemas , Interface Usuário-Computador
5.
Rinsho Shinkeigaku ; 50(8): 581-4, 2010 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-20803969

RESUMO

We reported a 61-year-old man who had developed acute cerebellar ataxia in the trunk and the lower limbs. His chemical blood analysis showed very mild hypothyroidism and the presence of serum anti-thyroid peroxidase (TPO) antibody and anti-NH2 terminal of alpha-enolase (NAE) antibody. While cerebellar atrophy was not evident on magnetic resonance imaging (MRI) of the brain, 99mTc-ECD SPECT using the easy Z-score imaging system (eZIS) showed decreased regional cerebral blood flow (rCBF) in the vermis of cerebellum. His cerebellar ataxia improved spontaneously within three weeks. The present case is very rare and suggests that anti-NAE autoantibody may be associated with actue cerebellar ataxia.


Assuntos
Autoanticorpos/sangue , Ataxia Cerebelar/imunologia , Fosfopiruvato Hidratase/imunologia , Biomarcadores/sangue , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Hepatobiliary Pancreat Sci ; 27(8): 496-509, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32362018

RESUMO

BACKGROUND/PURPOSE: To investigate the long-term outcome and entire treatment course of patients with technically unresectable CRLM who underwent conversion hepatectomy and to examine factors associated with conversion to hepatectomy. METHODS: Recurrence and survival data with long-term follow-up were analyzed in the cohort of a multi-institutional phase II trial for technically unresectable colorectal liver metastases (the BECK study). RESULTS: A total of 22/12 patients with K-RAS wild-type/mutant tumors were treated with mFOLFOX6 + cetuximab/bevacizumab. The conversion R0/1 hepatectomy rate was significantly higher in left-sided primary tumors than in right-sided tumors (75.0% vs 30.0%, P = .022). The median follow-up was 72.6 months. The 5-year overall survival (OS) rate in the entire cohort was 48.1%. In patients who underwent R0/1 hepatectomy (n = 21), the 5-year RFS rate and OS rate were 19.1% and 66.3%, respectively. At the final follow-up, seven patients had no evidence of disease, five were alive with disease, and 20 had died from their original cancer. All 16 patients who achieved 5-year survival underwent conversion hepatectomy, and 11 of them underwent further resection for other recurrences (median: 2, range: 1-4). CONCLUSIONS: Conversion hepatectomy achieved a similar long-term survival to the results of previous studies in initially resectable patients, although many of them experienced several post-hepatectomy recurrences. Left-sided primary was found to be the predictor for conversion hepatectomy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adulto , Idoso , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila , Genes ras , Humanos , Japão , Leucovorina , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos Organoplatínicos , Prognóstico , Estudos Prospectivos , Análise de Sobrevida
7.
Neuroepidemiology ; 32(2): 101-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19039242

RESUMO

BACKGROUND: With the striking increase in the number of elderly people in Japan, dementia has not only become a medical but also a social issue. METHODS: We studied the prevalence of dementing disorders in a rural island town of Japan (Ama-cho), using a door-to-door 2-phase design. RESULTS: Of the 120 persons screened as having cognitive impairment, 104 people were diagnosed as having dementia. The prevalence (cases/100 persons aged 65 years and older) was 11.0 for all types of dementia, 7.0 for Alzheimer's disease, 1.7 for vascular dementia, 0.53 for dementia with Lewy bodies, 0.74 for Parkinson's disease dementia, 0.21 for progressive supranuclear palsy, 0.11 for frontotemporal lobar degeneration and 0.74 for other dementia. The overall prevalence was higher in women for Alzheimer's disease and Parkinson's disease dementia, and in men, for vascular dementia and dementia with Lewy bodies. CONCLUSION: We confirmed the overall prevalence of dementia in the elderly population aged 65 years and older to be 11.0. This finding is higher compared with previous reports in Japan.


Assuntos
Demência/diagnóstico , Demência/epidemiologia , Saúde da População Rural/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Masculino , Prevalência , População Rural/estatística & dados numéricos
8.
Sci Data ; 6: 190034, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30806635

RESUMO

Pigs are important, both for agriculture and as animal models for human diseases. However, due to the lack of embryonic stem cells, the possibility of genetic modification is quite limited. To overcome this limitation, induced pluripotent stem (iPS) cells have been derived from pigs. Despite the public availability of a large number of expression datasets from mice, rats, and primates-derived iPS cells, the expression profile of pig-derived iPS cells is quite limited. Furthermore, there is no dataset focused on the profiling of pig-derived iPS cell with six reprogramming factors (Oct3/4, Sox2, Klf4, c-Myc, Lin28, and Nanog). Here, we used Illumina RNA sequencing platform to characterize the mRNA expression of four-factor derived and six-factor derived pig iPS cells. We observed that the expression levels of whole genes in our established six factors derived iPS cells and parent fibroblast, and compared with that of iPS cells with four factors in public database. These data are valuable in understanding species difference in the reprogramming process of stem cells, and could help identify the key regulating genes involved in the process.


Assuntos
Perfilação da Expressão Gênica , Células-Tronco Pluripotentes Induzidas , Suínos , Animais , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Técnicas de Reprogramação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fator 4 Semelhante a Kruppel , Análise de Sequência de RNA
9.
BMC Plant Biol ; 8: 20, 2008 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-18302796

RESUMO

BACKGROUND: Information on more than 35 000 full-length Oryza sativa cDNAs, together with associated microarray gene expression data collected under various treatment conditions, has made it feasible to identify motifs that are conserved in gene promoters and may act as cis-regulatory elements with key roles under the various conditions. RESULTS: We have developed a novel tool that searches for cis-element candidates in the upstream, downstream, or coding regions of differentially regulated genes. The tool first lists cis-element candidates by motif searching based on the supposition that if there are cis-elements playing important roles in the regulation of a given set of genes, they will be statistically overrepresented and will be conserved. Then it evaluates the likelihood scores of the listed candidate motifs by association rule analysis. This strategy depends on the idea that motifs overrepresented in the promoter region could play specific roles in the regulation of expression of these genes. The tool is designed so that any biological researchers can use it easily at the publicly accessible Internet site http://hpc.irri.cgiar.org/tool/nias/ces. We evaluated the accuracy and utility of the tool by using a dataset of auxin-inducible genes that have well-studied cis-elements. The test showed the effectiveness of the tool in identifying significant relationships between cis-element candidates and related sets of genes. CONCLUSION: The tool lists possible cis-element motifs corresponding to genes of interest, and it will contribute to the deeper understanding of gene regulatory mechanisms in plants.


Assuntos
Biologia Computacional/métodos , Oryza/genética , Regiões Promotoras Genéticas/genética , Elementos Reguladores de Transcrição/genética , Sequência de Bases , DNA de Plantas/genética , Bases de Dados Factuais , Biblioteca Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico
10.
J Surg Res ; 148(2): 158-63, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18468635

RESUMO

BACKGROUND: In liver surgery, the hepatic pedicle often is clamped to reduce blood loss, and later unclamped, representing hepatic ischemia and reperfusion (I/R) with induction of hypoxia. Vascular endothelial growth factor (VEGF) expression reportedly is induced by hypoxia; further, some cancer cells express the VEGF receptor (flt-1, flk-1/KDR). We hypothesized that I/R-induced VEGF expression could enhance growth of microscopic tumor via VEGF receptors on tumor cells, thus promoting liver metastasis in a rat model. MATERIALS AND METHODS: Time-dependent VEGF expression in liver and plasma was determined by enzyme-linked immunosorbent assay in rats subjected to 60 min of 70% hepatic I/R (I/R group). Other rats given an intrasplenic inoculation of a rat colon adenocarcinoma cell line (RCH-H4) were divided 3 days later into three groups: group A, untreated; group B, sham operation; group C, 70% I/R for 60 min. Liver metastasis was evaluated on day 14. Expression of flt-1 and flk-1/KDR was examined in RCN-H4 cells, and effects of exogenous VEGF on RCN-H4 cell proliferation were determined by MTT assays. RESULTS: Hepatic VEGF expression increased significantly in the I/R group compared to the control group. Liver metastasis was more extensive in group C than in groups A and B. RCN-H4 cells expressed flt-1 and flk-1/KDR, while exogenous VEGF increased RCN-H4 cell proliferation. CONCLUSION: Hepatic ischemia reperfusion leads to induction of VEGF and this is associated with increased tumor burden in an animal model of colon cancer metastasis.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo/patologia , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/secundário , Traumatismo por Reperfusão/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica , Fígado/enzimologia , Masculino , Ratos , Ratos Endogâmicos F344 , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Surg Endosc ; 22(12): 2748-52, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18324439

RESUMO

The authors have used a modified hemi-double-stapling (HDS) technique for reconstruction after laparoscopically assisted distal gastrectomy. The stomach is resected from the greater curvature side using a linear stapler inserted into the stomach from that side at a position vertical to the line of the greater curvature. Resection of the stomach is performed by extending the resection line to the lesser curvature using laparoscopic coagulating shears. The resected specimen is examined. After placement of a purse-string suture at the duodenal stump, an anvil is inserted into the stump, and an additional suture with 2-0 silk is placed over the purse-string suture. A curved intraluminal stapler (CDH25) is inserted into the stomach through the opening made on the lesser curvature side, and the center rod of the stapler is passed through the gastric wall on the corner of the resection line at the greater curvature. Ligation with 2-0 silk is added to the center rod by suturing the gastric tissue 5-8 mm from the center rod to encircle it. The authors call this the "one-knot setup HDS," and with this method, a large-caliber anastomosis is secured. In many cases, it is difficult to observe the anastomotic site through the small incisional opening. However, under laparoscopy with the temporal abdominal wall-lift method using the Multi Flap Gate, the anastomotic site can be easily and safely observed. One-knot setup HDS combined with the temporal abdominal wall-lift method is considered a safe and simple method for performing Billroth I anastomosis in laparoscopic distal gastrectomy.


Assuntos
Parede Abdominal/cirurgia , Gastrectomia/métodos , Gastroenterostomia/métodos , Laparoscopia/métodos , Grampeamento Cirúrgico/métodos , Coto Gástrico , Humanos , Ligadura/métodos , Técnicas de Sutura
12.
Mol Cells ; 24(3): 394-408, 2007 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-18182856

RESUMO

Several genes/QTLs governing resistance/tolerance to abiotic and biotic stresses have been reported and mapped in rice. A QTL for submergence tolerance was found to be co-located with a major QTL for broad-spectrum bacterial leaf blight (bs-blb) resistance on the long arm of chromosome 5 in indica cultivars FR13A and IET8585. Using the Nipponbare (japonica) and 93-11 (indica) genome sequences, we identified, in silico, candidate genes in the chromosomal region [Kottapalli et al. (2006)]. Transcriptional profiling of FR13A and IET8585 using a rice 22K oligo array validated the above findings. Based on in silico analysis and arraying we observed that both cultivars respond to the above stresses through a common signaling system involving protein kinases, adenosine mono phosphate kinase, leucine rich repeat, PDZ/DHR/GLGF, and response regulator receiver protein. The combined approaches suggest that transcription factor EREBP on long arm of chromosome 5 regulates both submergence tolerance and blb resistance. Pyruvate decarboxylase and alcohol dehydrogenase, co-located in the same region, are candidate downstream genes for submergence tolerance at the seedling stage, and t-snare for bs-blb resistance. We also detected up-regulation of novel defense/stress-related genes including those encoding fumaryl aceto acetate (FAA) hydrolase, scramblase, and galactose oxidase, in response to the imposed stresses.


Assuntos
Genes de Plantas , Oryza/genética , Doenças das Plantas/genética , Locos de Características Quantitativas/genética , Mapeamento Cromossômico , Biologia Computacional , Regulação da Expressão Gênica de Plantas , Análise de Sequência com Séries de Oligonucleotídeos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Xanthomonas/patogenicidade
13.
Brain Res ; 1160: 1-10, 2007 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-17583678

RESUMO

The pathogenic events that lead to amyotrophic lateral sclerosis (ALS) have not been elucidated. We previously described familial amyotrophic lateral sclerosis (FALS) caused by a Leu126delTT mutation in the Cu/Zn superoxide dismutase gene (SOD1) and have produced transgenic mice (TgM) carrying the same mutation (SOD1(L126delTT) TgM), which exhibited distinct ALS-like motor symptoms and pathological findings. In this study, we analyzed gene expression in the spinal cord of SOD1(L126delTT) TgM by cDNA microarray. Eleven genes were upregulated and two genes downregulated in pre-symptomatic TgM. In post-symptomatic TgM, 54 genes were upregulated and four genes downregulated. We performed real-time polymerase chain reaction (PCR) analysis of 10 of the 54 upregulated genes in the post-symptomatic TgM. The results of real-time PCR were consistent with those obtained by microarray for micro-crystallin (Crym), heat shock protein 1 (Hspb1/HSP27), serine proteinase inhibitor clade A member 3N (Serpina3n), complement component 1q subcomponent beta polypeptide (C1qb), cathepsin H (Ctsh) and polyadenylate binding protein-interacting protein 1 (Paip1). In immunohistochemical analysis, Hsbp1/HSP27 and Ctsh expression levels were increased in reactive astrocytes at the ventral horn of the spinal cord in post-symptomatic TgM, as were Crym, some of Ctsh and Paip1 in microglial cells. Increased expression of those genes was not observed in the control mice. These four genes may be related to the pathogenesis of FALS, especially with regard to the progression of reactive astrocytes and the inflammatory response of microglial cells.


Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/fisiopatologia , Deleção de Genes , Expressão Gênica/fisiologia , Leucina/genética , Superóxido Dismutase/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Catepsina H , Catepsinas/genética , Catepsinas/metabolismo , Cristalinas/genética , Cristalinas/metabolismo , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Proteínas de Choque Térmico/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Chaperonas Moleculares , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Medula Espinal/metabolismo , Medula Espinal/patologia , Superóxido Dismutase-1 , Cristalinas mu
14.
Brain Res Mol Brain Res ; 135(1-2): 12-20, 2005 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-15857664

RESUMO

Mutation of Cu/Zn superoxide dismutase (SOD1) contributes to a portion of the cases of familial amyotrophic lateral sclerosis (FALS). We previously reported on a FALS family whose members had a mutant form of SOD1 characterized by a 2-base pair (bp) deletion at codon 126 of the SOD1 gene. To investigate the cellular consequences of this mutation, we produced transgenic mice that expressed normal and mutated copies of human SOD1: wild-type SOD1 (W), wild-type SOD1 with a FLAG epitope at C-terminal (WF), mutated SOD1 with the 2-bp deletion (D), and SOD1 with the 2-bp deletion with FLAG (DF). The mice heterozygotic for the human mutated SOD1 (D and DF) showed distinct ALS-like motor symptoms, whereas the mice heterozygotic for the normal SOD1 (W and WF) mice did not. Homozygotes of D and DF lines showed the ALS symptoms at an earlier age and died earlier than the heterozygotes. By Northern blot analysis, the mRNAs for all human SOD1s were confirmed in these lines. All the human SOD1 proteins, except the D mutant, were detectable by immunoblot. The D protein was only confirmed when it was concentrated by immunoprecipitation. Neuropathologically, loss of spinal motor neurons and reactive gliosis were common features in the symptomatic lines. The remaining motor neurons in these mice also exhibited eosinophilic inclusions. The biochemical and pathological characteristics of these mice are quite similar to those of human FALS patients with same mutation. This intriguing model will provide an important source of information of the pathogenesis of FALS.


Assuntos
Camundongos Transgênicos/fisiologia , Doença dos Neurônios Motores/genética , Mutação , Superóxido Dismutase/genética , Animais , Northern Blotting/métodos , Western Blotting/métodos , Modelos Animais de Doenças , Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Heterozigoto , Humanos , Imuno-Histoquímica/métodos , Imunoprecipitação/métodos , Corpos de Inclusão/enzimologia , Corpos de Inclusão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Doença dos Neurônios Motores/enzimologia , Doença dos Neurônios Motores/fisiopatologia , Neurônios Motores/enzimologia , Neurônios Motores/patologia , Oligopeptídeos , Peptídeos/metabolismo , RNA Mensageiro/metabolismo , Medula Espinal/enzimologia , Medula Espinal/patologia , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Fatores de Tempo
15.
Biotechnol Rep (Amst) ; 5: 105-111, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28435806

RESUMO

The icosahedral capsid structure of simian virus 40 (diameter, 45 nm) consists of 72 pentameric subunits, with each subunit formed by five VP1 molecules. Electron microscopy, immuno-gold labeling, and ζ-potential analysis showed that purified recombinant VP1 pentamers covered polystyrene beads measuring 100, 200, and 500 nm in diameter, as well as silica beads. In addition to covering spherical beads, VP1 pentamers covered cubic magnetite beads, as well as the distorted surface structures of liposomes. These findings indicate that VP1 pentamers could coat artificial beads of various shapes and sizes larger than the natural capsid. Technology based on VP1 pentamers may be useful in providing a capsid-like surface for enclosed materials, enhancing their stability and cellular uptake for drug delivery systems.

16.
J Hepatobiliary Pancreat Sci ; 22(8): 634-45, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25926024

RESUMO

BACKGROUND: Patients with colorectal liver metastasis (CRLM) might be down-staged by chemotherapy from an initially unresectable stage to a resectable stage. Because the tumor response to preoperative chemotherapy has been correlated with resection rate, the improved efficacy from the concept that only the patients without K-ras mutations receive an anti-EGFR antibody might be expected to increase the conversion rate. The purpose of this study is to evaluate the conversion rate from unresectable CRLM to complete resection. METHODS: We conducted a multi-institutional phase II trial for unresectable CRLM. Patients received mFOLFOX6 with either bevacizumab (bev) or cetuximab (cet) based on K-ras status (UMIN000004310). Planned treatment was for six cycles during which tumors were assessed for resectability every three cycles. Patients whose disease was unresectable after six cycles switched their chemotherapy regimen from mFOLFOX6 to FOLFIRI. The primary endpoint was R0 resection rate. RESULTS: Thirty-five patients with unresectable CRLM were enrolled. A total of 22/12 patients with K-ras wild-type/mutant (wt/mt) were treated with mFOLFOX6 plus cet/bev, respectively. The overall response rate was 64.7% (wt/mt; 77.3%/41.7%, P = 0.04). In 20 patients (58.8%), hepatectomy was performed according to protocol treatment, and the conversion rate was 72.7%/33.3% in wt/mt patients, respectively (P = 0.03). Finally, 23 patients (67.6%) underwent hepatectomy, and the conversion rate was 77.2%/50.0% in wt/mt patients (P = 0.09). The overall R0 resection rate was 47.1% (wt/mt; 50.0%/41.7%, P = 0.36). CONCLUSIONS: This prospective study showed that combined chemotherapy based on K-ras status can facilitate conversion to resection in patients with unresectable CRLM.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Genes ras , Hepatectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adulto , Idoso , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/uso terapêutico , Estudos Prospectivos
17.
DNA Res ; 10(6): 239-47, 2003 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-15029955

RESUMO

The NAC domain was originally characterized from consensus sequences from petunia NAM and from Arabidopsis ATAF1, ATAF2, and CUC2. Genes containing the NAC domain (NAC family genes) are plant-specific transcriptional regulators and are expressed in various developmental stages and tissues. We performed a comprehensive analysis of NAC family genes in Oryza sativa (a monocot) and Arabidopsis thaliana (a dicot). We found 75 predicted NAC proteins in full-length cDNA data sets of O. sativa (28,469 clones) and 105 in putative genes (28,581 sequences) from the A. thaliana genome. NAC domains from both predicted and known NAC family proteins were classified into two groups and 18 subgroups by sequence similarity. There were a few differences in amino acid sequences in the NAC domains between O. sativa and A. thaliana. In addition, we found 13 common sequence motifs from transcriptional activation regions in the C-terminal regions of predicted NAC proteins. These motifs probably diverged having correlations with NAC domain structures. We discuss the relationship between the structure and function of the NAC family proteins in light of our results and the published data. Our results will aid further functional analysis of NAC family genes.


Assuntos
Arabidopsis/genética , Proteínas de Bactérias , Proteínas de Ligação a DNA/genética , Genes de Plantas , Família Multigênica/genética , Oryza/genética , Fatores de Transcrição/genética , Proteínas de Arabidopsis/genética , Sequência de Bases , Clonagem Molecular , Filogenia , Estrutura Terciária de Proteína/genética , RNA de Plantas , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
18.
Rinsho Shinkeigaku ; 42(10): 954-8, 2002 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-12739386

RESUMO

We report a case of pseudomigraine with pleocytosis (PMP) characterized by temporary neurological deficits and elevated cell counts in cerebrospinal fluid (CSF). A 28-year-old woman was admitted to our hospital with a second episode of right side throbbing headache accompanied by hemianopsia without scintillating scotoma of left side, hand numbness and weakness of left hand. Two months before the admission, she experienced a first identical episode, which lasted several hours. On admission to our hospital, neurological examination showed left hemianopsia, mild left hemiparesis, dysesthesia of left hand, exceeded tendon reflex of left upper limb, stiff-neck and positive Kerning's sign. CSF examination showed mild elevation of mononuclear cell counts. No abnormal findings on brain CT and MRI (including diffusion weighted image) were observed. 99mTc-HMPAO single photon emission computed tomography (SPECT) demonstrated extensive hypoperfusion at right cerebral hemisphere, corresponding to her neurological deficits. Her electroencephalography (EEG) showed reduced amplitude on the right occipital area. The reduced amplitude of cortical component of somatosensory evoked potential (SEP) by left median nerve stimulation were observed. On the third day after the admission, her symptoms improved and cell count of CSF was normalized. One week after the onset her SEP, EEG and SPECT were normalized on their retrials. She has never recurred these symptoms. We established a diagnosed of psedomigraine with pleocytosis as the first Japanese case.


Assuntos
Leucocitose/complicações , Transtornos de Enxaqueca/complicações , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Transtornos de Enxaqueca/diagnóstico
19.
J Clin Neurol ; 8(3): 230-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23091534

RESUMO

BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder with optic nerve atrophy. Although there are no other associated neurological abnormalities in most cases of LHON, cases of "LHON plus" have been reported. CASE REPORT: The proband was a 37-year-old man who had visual and gait disturbances that had first appeared at 10 years of age. He showed horizontal gaze palsy, gaze-evoked nystagmus, dysarthria, and cerebellar ataxia. Brain and orbit MRI disclosed atrophy of the optic nerve and cerebellum, and degenerative changes in the bilateral inferior olivary nucleus. Mutational analyses of mitochondrial DNA identified the coexistence of heteroplasmic G11778A and homoplasmic T3394C mutations. CONCLUSIONS: These results suggest that the combination of G11778A and T3394C mutations leads to an atypical LHON phenotype.

20.
Intern Med ; 51(22): 3135-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23154719

RESUMO

We herein describe a rare case of ulcerative colitis associated with unilateral hypoglossal nerve palsy. A 64-year-old woman developed severe active ulcerative colitis and was treated with prednisolone. The dose of oral prednisolone was reduced to 7.5 mg/day, following which the patient noticed slight dysphagia and a speech disturbance. She was diagnosed with unilateral hypoglossal nerve palsy, which was thought to be caused by mononeuritis. She was treated with intravenous methylprednisolone at a dose of 500 mg/day, which improved the neuropathy. When the neuropathy occurred, the patient was in a mildly active stage of ulcerative colitis. We concluded that the mononeuritis observed in the present case was likely an extraintestinal manifestation of ulcerative colitis.


Assuntos
Colite Ulcerativa/complicações , Doenças do Nervo Hipoglosso/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Feminino , Humanos , Doenças do Nervo Hipoglosso/tratamento farmacológico , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico
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