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  • 1
  • 2
    Keywords: CDNA ; CLONES ; BIOLOGY ; alternative splicing ; CDNAS ; ASSEMBLIES ; assembly ; ANNOTATION ; COMPLETE GENOM
    Abstract: The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for nonprotein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology
    Type of Publication: Journal article published
    PubMed ID: 15103394
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  • 3
    Publication Date: 2018-08-02
    Description: Purpose: Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS–HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. Experimental Design: Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression. Results: These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time in vivo , and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2. Conclusions: These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. Clin Cancer Res; 24(15); 3668–80. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 4
    ISSN: 1432-1920
    Keywords: Brain ; Infection ; Computed tomography ; Parasites ; Inflammation ; Sparganosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral sparganosis is a rare parasitic CNS disease, producing chronic active granulomatous inflammation. We retrospectively reviewed the clinical data, CT scans and histopathologic specimens in 34 patients with cerebral sparganosis. The majority of the patients (89%) were rural inhabitants; 75% had a history of ingestion of frogs and/or snakes. The major presenting symptoms were seizure (84%), hemiparesis (59%) and headache (56%) of chronic course. On CT scans, the disease most frequently involved the cerebral hemispheres, particularly frontoparietal lobes, with occasional extension to the external and internal capsules and basal ganglia. The cerebellum was rarely involved. Bilateral involvement was seen in 26%. The main CT findings consisted of white matter hypodensity with adjacent ventricular dilatation (88%), irregular or nodular enhancing lesion (88%), and small punctate calcifications (76%). In combination, the CT triad above appears to be specific for this disease, and was noted in 62% of cases. Of 16 follow-up CT scans, 5 (38%) showed a change in the location of the enhancing nodule. With a single CT scan, it does not appear to be possible to determine whether the worm is alive or dead, information important for deciding whether to intervene surgically. Change in the location of the enhancing nodule and/or worsening of the other CT findings on sequential CT scans would suggest that the worm is alive and that the patient is a candidate for surgery.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1920
    Keywords: Cysticercosis ; MR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary MR and CT features of neurocysticercosis are variable and depend fundametally on the stage in evolution of the infection, location, number and size of the worm. The authors retrospectively evaluated MR images obtained on a 2.0T superconducting unit in 22 neurocysticercosis patients and observed various MR features including some new findings. A variety of MR findings are presented with special reference to six case reports. The features include: (1) a large simple cyst containing both internal septations and a scolex; (2) suprasellar racemose cysts mimicking other cysts, (3) a fourth ventricular cyst readily depicted by aid of CSF flow-void in the sagittal plane; (4) degenerating cysts showing “white target” appearance; (5) granulomatous lesions having a “black target” appearance; and (6) a meningitic form showing Gd-DTPA enhancement of basal cisterns and of a subacute infarct.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1920
    Keywords: Magnetic resonance imaging ; Tuberculosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-six patients with intracranial tuberculosis (Tb) (10 with acute meningitis, 5 with chronic meningitis, 5 with meningitic sequelae and 6 with localized tuberculoma(s) were examined with MR before and after Gd-DTPA enhancement (0.1 mmol/kg), using 2.0T superconducting unit, and the images were retrospectively analyzed and compared with CT scans. Without Gd-DTPA enhancement, the MR images were generally insensitive to detection of active meningeal inflammation and granulomas. The signal intensity of granulomas was usually isointense to gray matter on both T1- and T2-weighted images, whether they were associated with diffuse meningitis or presented as localized tuberculoma(s). A few granulomas showed focal hypointensity on T2-weighted images. Calcifications seen on CT of the meningitic sequelae group usually appeared markedly hypointense on all spin-echo sequences. On Gd-DTPA enhanced T1-weighted images, abnormal meningeal enhancement indicating active inflammation was conspicuous, and the granulomas often appeared as conglomerated ring-enhancing nodules, which seems to be characteristic of granulomas. Thin rim enhancement around the suprasellar calcifications were observed in two out of 5 patients with meningitic sequelae. Compared with CT, MR detected a few more ischemic infarcts, hemorrhagic infarcts, meningeal enhancement and granulomas in the acute meningitis group, but missed small calcifications in the basal cisterns well shown on CT in the sequelae group. Otherwise, MR generally matched CT scans. MR imaging appears to be superior to CT in evaluation of active intracranial Tb only if Gd-DTPA is used, while CT is better than MR in evaluating meningitic sequelae with calcification.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1920
    Keywords: Key words Computed tomography ; head and neck ; Contrast medium ; dose ; Comparative study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adequate contrast enhancement of major neck vessels is more important than that of a tumour itself in CT of most head and neck tumours because of differentiation from neck node metastases. Our purpose was to re-evaluate the dosage of contrast medium for adequate vascular enhancement in CT of the head and neck. In a blind prospective fashion, 60 patients with a variety of head and neck lesions were randomised into three equal groups receiving 0.75, 1.0, or 1.25 ml/kg of meglumine ioglycate, 300 mg/ml. Contrast medium was administered by injector at 2 ml/s. The scan time and interscan delay were each 1 s, and total scan time 50–180 s. The scan was started immediately after administration of two-thirds of the contrast medium. The degree of vascular enhancement was assessed visually and quantitatively. We visually scored the degree of vascular enhancement as excellent (4 points), good (3), fair (2) or poor (1). For quantitative study, after measuring the CT numbers of the common or internal carotid artery (CA), internal jugular vein (IJV) and adjacent muscle at three levels, were calculated mean vessel/muscle contrast ratios. The degree of enhancement of the CA and IJV tended to increase with dose of the contrast media, but no examination was rated as showing poor enhancement in any group. The mean visual assessment scores for 0.75, 1.0, and 1.25 ml/kg were 2.7, 2.9 and 3.1, respectively; the mean ICA/muscle contrast ratios were 1.58, 1.55 and 1.63, and those of IJV/muscle 1.65, 1.59 and 1.59. There was no significant difference between visual and quantitative assessment in any group. The results suggest that 0.75 ml/kg of contrast medium appears sufficient for vascular opacification for head and neck lesions when the CT scan can be completed in about 120 s.
    Type of Medium: Electronic Resource
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  • 8
    Abstract: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the US population and is considered to be a metabolic predisposition to liver cancer. However, the role of adaptive immune responses in NAFLD-promoted HCC is largely unknown. Here we show, in mouse models and human samples, that dysregulation of lipid metabolism in NAFLD causes a selective loss of intrahepatic CD4(+) but not CD8(+) T lymphocytes, leading to accelerated hepatocarcinogenesis. We also demonstrate that CD4(+) T lymphocytes have greater mitochondrial mass than CD8(+) T lymphocytes and generate higher levels of mitochondrially derived reactive oxygen species (ROS). Disruption of mitochondrial function by linoleic acid, a fatty acid accumulated in NAFLD, causes more oxidative damage than other free fatty acids such as palmitic acid, and mediates selective loss of intrahepatic CD4(+) T lymphocytes. In vivo blockade of ROS reversed NAFLD-induced hepatic CD4(+) T lymphocyte decrease and delayed NAFLD-promoted HCC. Our results provide an unexpected link between lipid dysregulation and impaired anti-tumour surveillance.
    Type of Publication: Journal article published
    PubMed ID: 26934227
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  • 9
    ISSN: 0167-4889
    Keywords: (Erythrocyte) ; (Human) ; ADP-ribose transport ; ADP-ribose uptake ; Ectoenzyme ; NAD glycohydrolase
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0925-4005
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Type of Medium: Electronic Resource
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