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N Suzuki

Publications and source records attributed to N Suzuki.

At least 19 recordsLinked to original sources
PubMed2007

Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells.

We have found previously that Txk, a member of the Tec family tyrosine kinases, is involved importantly in T helper 1 (Th1) cytokine production. However, how Txk regulates interferon (IFN)-gamma gene transcription in human T lymphocytes was not fully elucidated. In this study, we identified poly(ADP-ribose) polymerase 1 (PARP1) and elongation factor 1alpha (EF-1alpha) as Txk-associated molecules that bound to the Txk responsive element of the IFN-gamma gene promoter. Txk phosphorylated EF-1alpha and PARP1 formed a complex with them, and bound to the IFN-gamma gene promoter in vitro. In particular, the N terminal region containing the DNA binding domain of PARP1 was important for the trimolecular complex formation involving Txk, EF-1alpha and PARP1. Several mutant Txk which lacked kinase activity were unable to form the trimolecular complex. A PARP1 inhibitor, PJ34, suppressed IFN-gamma but not interleukin (IL)-4 production by normal peripheral blood lymphocytes (PBL). Multi-colour confocal analysis revealed that Txk and EF-1alpha located in the cytoplasm in the resting condition. Upon activation, a complex involving Txk, EF-1alpha and PARP1 was formed and was located in the nucleus. Collectively, Txk in combination with EF-1alpha and PARP1 bound to the IFN-gamma gene promoter, and exerted transcriptional activity on the IFN-gamma gene.

Cell Nucleus↗
PubMed2006

Cooperation of oncogenic K-ras and p53 deficiency in pleomorphic rhabdomyosarcoma development in adult mice.

Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53. To investigate their possible involvement in the tumorigenesis, we generated a knock-in mouse line with oncogenic K-ras, conditionally expressed by Cre/LoxP system on a background of p53 alteration. Electroporation of Cre expression vector in skeletal muscle tissues resulted in the generation of tumor in adults with tumor incidences of 100% at 10 weeks and 40% at 15 weeks, in p53(-/-) and p53(-/+) backgrounds, respectively. The tumor histology was pleomorphic RMS with characteristic bizarre giant cells, positive for desmin and alpha-sarcomeric actin and exhibiting remarkable increase in total and phosphorylated extracellular signal-regulated protein kinase (ERK)1 and ERK2. Loss of the wild-type p53 was detected in K-rasG12V-expressed tumors of p53(-/+) mice. Early lesions 3 weeks after electroporation consisted of proliferating populations of myogenic progenitors, including stem cells positive for ScaI antigen, immature cells positive for desmin and neural cell adhesion molecule-positive myotubes. Thus, cooperation of oncogenic K-ras and p53 deficiency resulted in the development of pleomorphic RMS in adult mice, providing a useful mouse model for further detailed studies.

Animals↗
PubMed2006

Pns4 of rice dwarf virus is a phosphoprotein, is localized around the viroplasm matrix, and forms minitubules.

Rice dwarf virus (RDV), a member of the family Reoviridae, has a 12-segmented dsRNA genome. Seven segments, designated S1, S2, S3, S5, S7, S8, and S9, encode structural proteins, while the remainder encode nonstructural proteins. One of the nonstructural proteins, Pns4, which is encoded by S4, was characterized. Pns4 was a phosphorylatable substrate in a phosphorylation assay in vivo; it associated with large cytoplasmic fibrils and formed novel minitubules in infected cultured cells of its leafhopper insect vector, as revealed by immunofluorescence and immunoelectron microscopy. Early in infection, Pns4 was detected at the periphery of the viroplasm, and it was then observed on amorphous or fibrillar inclusions, which were identified as bundles of minitubules, at later stages of infection. Since viroplasms are believed to be the site of RDV replication, the intracellular location of Pns4 suggests that this protein might be involved in the process of assembly of the RDV virion.

Animals↗
PubMed2006

Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53.

We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it.

Apoptosis↗
PubMed2006

Development of a video assessment scoring method to determine the accuracy of endoscopist performance at screening flexible sigmoidoscopy.

BACKGROUND AND AIMS: Variation in the adenoma detection rate (ADR) at flexible sigmoidoscopy screening has been shown to be due to variation in endoscopist performance. There are no objective methods for scoring an endoscopist's performance reliably, and the aim of this study was to develop a valid and reliable objective scoring method using video footage of screening flexible sigmoidoscopies. METHODS: In a series of five experiments, experienced endoscopists (the scorers) independently scored a sample (n = 43) of the 40 000 flexible sigmoidoscopy extubations recorded as part of the United Kingdom Flexible Sigmoidoscopy Screening Trial (UK FSST). The scoring system, the parameters scored, and their definitions evolved over the course of the five experiments. The initial visual analogue score (range 0-100) used in the first two experiments evolved into a five-point score that ranged from 1 (E, poor) to 5 (A, excellent) in the last three experiments. The final parameters scored were: time spent viewing the mucosa, re-examination of poorly viewed areas, suctioning of fluid pools, distension of the lumen, lower rectal examination, and overall quality of the examination. The first four experiments scored one individual case per endoscopist; in experiment 5, an overall score was awarded for five cases performed by each endoscopist being assessed. RESULTS: Scoring five cases examined by an individual endoscopist using the A-E grading system was the most reliable method (interclass correlation coefficient 0.89). Cluster analysis demonstrated that the endoscopists in the high-scoring ADR group (ADR 14.7-15.9 %) could be differentiated from those in the intermediate- and low-scoring ADR groups (ADR 8.6-12.6 %). CONCLUSIONS: An objective scoring system for assessing the accuracy of performance at screening flexible sigmoidoscopy, based on video footage, is described. Endoscopists who might benefit from further training can be identified using this method.

Adenoma↗
PubMed2006

Judgement of the quality of bowel preparation at screening flexible sigmoidoscopy is associated with variability in adenoma detection rates.

BACKGROUND AND STUDY AIMS: Adenoma detection rates (ADRs) at screening flexible sigmoidoscopy are known to vary between endoscopists. Variability in the technique used and in the quality of bowel preparation may explain this. The aim of this study was to establish whether there is a relationship between the grading of bowel preparation and the ADR. MATERIALS AND METHODS: The relationship between the ADR and assessment of bowel preparation was examined using the full United Kingdom Flexible Sigmoidoscopy Screening Trial data set (n = 38 601). The consistency of the bowel preparation classification was then investigated by six experienced endoscopists (video scorers), who examined 260 flexible sigmoidoscopy cases - 20 from each of the 13 trial endoscopists. RESULTS: Overall, the ADR was significantly higher in flexible sigmoidoscopy examinations with excellent or good bowel preparation ( P = 0.02). However, endoscopists with a higher ADR coded a smaller proportion of their examinations as having excellent/good preparation ( P = 0.002). Video scorers agreed with the trial endoscopists' definition of bowel preparation in 48.9 % of the readings, but they scored the quality of preparation as poorer than the trial endoscopists in 36.4 % and 40.6 %, respectively, in the intermediate-performance group (10 % < ADR < 14 %) and lower-performance group (ADR </= 10 %) in comparison with only 12.9 % in the high-performance group (ADR > or =14 %). There was a significant linear trend between the proportion scored as having poor bowel preparation and the ADR ( P < 0.001), varying from 2.7 % in the higher-performance ADR group to 13.4 % in the lower-performance group. CONCLUSIONS: Endoscopists with a higher ADR are more likely to be critical of the quality of bowel preparation. Training in judgement processes such as non-acceptance of suboptimal bowel preparation is required in order to ensure universally high standards in screening procedures.

Adenoma↗
PubMed2006

Volumetric coronary angiography using the 256-detector row computed tomography scanner: comparison in vivo and in vitro with porcine models.

PURPOSE: To investigate the feasibility of volumetric cine imaging in human cardiac studies by comparing in vivo and in vitro coronary angiography using a 256-detector row computed tomography (CT) without ECG gating. MATERIAL AND METHODS: The left and right coronary arteries of two domestic pigs were scanned in vivo and in vitro in cine mode using the 256-detector row CT. The device scanned approximately 100 mm in the cranio-caudal direction with one rotation, with a slice thickness of 0.5 mm. RESULTS: The coronary arteries could be observed to the third-degree branches in vitro, but could be visualized clearly only to the proximal portion (first-degree or second-degree branches) in vivo. CONCLUSION: Application of cardiac volumetric cine imaging with 256-detector row CT may be a promising means of obtaining diagnostic information and has potential for adoption to human studies.

Animals↗
PubMed2006

Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7.

Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha, prostaglandin E(2) (PGE(2)), macrophage inflammatory protein (MIP)-1alpha and MIP-1alpha, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet's disease and Crohn's disease. In addition, the nicotinic acetylcholine receptor-alpha7 (alpha7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the alpha7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes. Fluorescein isothiocyanate (FITC)-labelled alpha-bungarotoxin demonstrated the cell surface expression of the alpha7nAchR subunit. Pretreatment with low-dose nicotine caused inhibition of TNF-alpha, PGE(2), MIP-1alpha and MIP-1alpha production, and mRNA expression of TNF-alpha, MIP-1alpha and MIP-1alpha and COX-2 in lipopolysaccharide (LPS)-activated monocytes. These suppressive effects of nicotine were caused at the transcriptional level and were mediated through alpha7nAChR. Nicotine suppressed the phosphorylation of I-kappaB, and then inhibited the transcriptional activity of nuclear factor-kappaB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.

Cells, Cultured↗
PubMed2006

Effect of mineral trioxide aggregate on proliferation of cultured human dental pulp cells.

AIM: To investigate the effect of mineral trioxide aggregate (MTA) on the proliferation of human dental pulp (HDP) cells ex-vivo. METHODOLOGY: Human dental pulp cells were cultured with MTA or calcium hydroxide-containing cement (Dycal) using culture plate inserts. Control cells were cultured with culture plate inserts only. Cell proliferation was measured for up to 14 days using a Cell Counting kit, and the concentration of calcium ions released from the tested materials was assessed using a Calcium E-test kit. To confirm that the effect of MTA was attributable to released calcium ions, cell proliferation was measured in the presence of exogenous calcium chloride as a source of calcium ions while in the absence of MTA. RESULTS: Mineral trioxide aggregate significantly stimulated cell proliferation after 12 days, whereas Dycal had no such effect. The number of calcium ions released from MTA was significantly higher than that released from Dycal. Following the addition of calcium chloride, cell proliferation increased in a dose-dependent manner after 12 days. Moreover, cell proliferation showed a similar pattern whether a given concentration of calcium ions was produced by calcium chloride or by release from MTA. CONCLUSIONS: In this ex-vivo study, the elution components such as calcium ions from MTA had higher proliferation ability of HDP cells than control and Dycal.

Adult↗
PubMed2006

Characterizing the specific coaggregation between Actinobacillus actinomycetemcomitans serotype c strains and Porphyromonas gingivalis ATCC 33277.

A visual coaggregation study showed specific interspecies coaggregation between an Actinobacillus actinomycetemcomitans serotype c strain and Porphyromonas gingivalis strains ATCC 33277 and 381. We mutagenized A. actinomycetemcomitans SUNYaB 67 (serotype c) with transposon IS903phikan and isolated three transposon insertion mutants that had a reduced ability to aggregate with P. gingivalis ATCC 33277. The three transposon insertions in the mutant strains mapped to the genes at ORF12, ORF13 and ORF16 of the gene cluster responsible for producing serotype c-specific polysaccharide antigen (SPA). Western blot analysis with serotype c-specific antibody showed that these strains did not produce the high-molecular-mass smear of SPA. Furthermore, two SPA-deficient mutants and an SPA-producing mutant were constructed. The two SPA-deficient mutants were deficient for ORF12 and ORF14, which are necessary for the synthesis of serotype c-SPA, and the SPA-producing mutant was deficient for ORF17, which is not related to SPA synthesis. The ORF12- and ORF14-deficient mutants showed reduced ability to aggregate with P. gingivalis ATCC 33277, while the ORF17-deficient mutant aggregated with ATCC 33277 to the same extent as wild-type SUNYaB 67. Our findings suggest that serotype c-SPA of A. actinomycetemcomitans mediates coaggregation with P. gingivalis ATCC 33277.

Aggregatibacter actinomycetemcomitans↗
PubMed2006

Implication of augmented vasogenic leakage in the mechanism of persistent aura in sporadic hemiplegic migraine.

The aim of this study is to report a possible implication of augmented vasogenic leakage in the mechanism of prolonged aura in sporadic hemiplegic migraine. A 35-year-old woman with sporadic hemiplegic migraine presented with headache followed by right arm weakness, right visual field defect, aphasia and confusion that persisted for 1 week. During the acute stage, focal hyperaemia was seen in the left cerebral hemisphere corresponding to persistent aura symptoms. Augmented vasogenic leakage was demonstrated on delayed enhanced fluid-attenuated inversion recovery image. Magnetic resonance angiography showed dilation of the left middle cerebral artery. During the convalescent stage, such abnormal findings were not seen. Based on these results, we speculate that augmented vasogenic leakage from the leptomeningeal vessels, probably associated with activation of the trigeminovascular system, may delay the recovery of hemiplegic migraine aura.

Adrenal Cortex Hormones↗
PubMed2006

Narrow band imaging with magnification for dysplasia detection and pit pattern assessment in ulcerative colitis surveillance: a case with multiple dysplasia associated lesions or masses.

A 62 year old man with longstanding ulcerative colitis and previous endoscopic excision of two dysplasia associated lesions or masses (DALMs) was admitted to our endoscopy unit for evaluation and resection of other possible DALMs. He had previously been offered and refused colectomy because of comorbidity from Parkinson's disease. He had multiple polypoid and sessile lesions which were assessed using a third generation prototype narrow band imaging (NBI) colonoscope with magnification. Selected lesions were either biopsied or resected with a combination of endoscopic submucosal dissection and endoscopic mucosal resection techniques. We correlated the pit pattern and vascular pattern intensity seen with magnification NBI with histology of both inflammatory and dysplastic lesions. Dysplastic areas showed Kudo pit patterns II, IIIL, and IV and high vascular pattern intensity. Non-dysplastic and dysplastic areas of recurrence immediately adjacent to the scar from a previous endoscopic mucosal resection site were also assessed. This is the first case report where NBI has been shown to help in DALM detection and to distinguish dysplastic from non-dysplastic mucosa in ulcerative colitis.

Colitis, Ulcerative↗
PubMed2006

Effect of fructose-rich high-fat diet on glucose sensitivity and atherosclerosis in nonhuman primate.

The present study examined a new model of impaired glucose tolerance (IGT) in a nonhuman primate fed with a high-fructose and high-fat (HFF) diet that contained 15% lard, 31% fructose, and 1% cholesterol. Female cynomolgus monkeys (age, 3-4 years) were divided into two groups: 1) those fed with normal control diet (N = 5) and 2) those fed with HFF diet (N = 5). In the HFF diet group, total cholesterol and low-density lipoprotein cholesterol in blood were significantly increased four- to fivefold when compared with the normal control diet group. No difference in the blood glucose, insulin, hemoglobin A1c, and triglyceride levels was detected between the two groups. Plasma levels of adiponectin, but not of resistin, were significantly higher in HFF diet at 20 weeks after HFF diet feeding. Oral glucose tolerance test was performed before HFF diet feeding and at 12 and 24 weeks after HFF diet feeding, but no significant changes in glucose sensitivity were observed even 24 weeks after HFF diet feeding. Twenty-four weeks after HFF diet feeding, accumulated foam cells and infiltrated macrophages were histologically detected in the thoracic aorta, in addition to a fatty liver. Interestingly, the pancreatic beta cells appeared normal in the HFF diet group. These results show that a chronic HFF diet does not induce IGT but can cause atherosclerotic lesions in conjunction with the generation of a fatty liver phenotype in cynomolgus monkey; however, the present results are very preliminary and they need to be validated in larger-scale studies in the future.

Adiponectin↗
PubMed2005

Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

14-3-3 Proteins↗
PubMed2005

Isolation and characterization of a novel polychlorinated biphenyl-degrading bacterium, Paenibacillus sp. KBC101.

The biphenyl-utilizing bacterial strain KBC101 has been newly isolated from soil. Biphenyl-grown cells of KBC101 efficiently degraded di- to nonachlorobiphenyls. The isolate was identified as Paenibacillus sp. with respect to its 16S rDNA sequence and fatty acid profiles, as well as various biological and physiological characteristics. In the case of highly chlorinated biphenyl (polychlorinated biphenyl; PCB) congeners, the degradation activities of this strain were superior to those of the previously reported strong PCB degrader, Rhodococcus sp. RHA1. Recalcitrant coplanar PCBs, such as 3,4,3',4'-CB, were also efficiently degraded by strain KBC101 cells. This is the first report of a representative of the genus Paenibacillus capable of degrading PCBs. In addition to growth on biphenyl, strain KBC101 could grow on dibenzofuran, xanthene, benzophenone, anthrone, phenanthrene, naphthalene, fluorene, fluoranthene, and chrysene as sole sources of carbon and energy. Paenibacillus sp. strain KBC101 presented heterogeneous degradation profiles toward various aromatic compounds.

Bacillaceae↗
PubMed2005

Type IX collagen is crucial for normal hearing.

cDNA microarray analysis indicated that COL9A1 and COL9A3 are highly expressed in the human inner ear, suggesting that type IX collagen has a crucial functional role in the inner ear. This study further confirmed, by means of real-time PCR, the presence of collagen type IX genes in the mouse inner ear. Immunocytochemical analysis also revealed that type IX collagen is distributed in the tectorial membrane, where it co-localizes with type II collagen, indicating that type IX collagen may contribute to the three-dimensional integrated structure of type II collagen molecules. Mice with targeted disruption of the col9a1 gene were shown through assessment by auditory brain stem response to have hearing loss, suggesting an important role of type IX collagen in maintaining normal hearing. At the light microscopic level, the tectorial membrane of knock-out mice was found to be abnormal in shape, and electron microscopy confirmed disturbance of organization of the collagen fibrils. An antibody against type II collagen failed to detect type II collagen in the tectorial membrane of type IX collagen knock-out mice, suggesting that a lack of type IX collagen may affect the three-dimensional structure of type II collagen molecules. These findings indicate that genes encoding each chain of type IX collagen may fulfill an important function associated with the tectorial membrane in the auditory system.

Animals↗
PubMed2005

Possible involvement of urokinase-type plasminogen activator release from human peripheral blood lymphocytes in the pathophysiology of chronic allograft nephropathy.

BACKGROUND: Little is known of the fibrinolytic host immune mechanisms responsible for induction of chronic allograft nephropathy (CAN), defined as a loss in glomerular filtration rate (GFR) caused by tubular atrophy and interstitial fibrosis, often with fibrous intimal thickening in the small arteries. However, chronic rejection has been reported to be associated with decreased activity of the fibrinolytic system. In our previous study, [Deamino-Cys1, D-Arg8]-vasopressin (dDAVP) induced urokinase-type plasminogen activator (uPA) release from human peripheral T lymphocytes via arginine vasopressin (AVP) V2-receptor-mediated reaction enhanced by an AVP V1-receptor antagonist. Therefore, we examined the level of uPA released from peripheral T lymphocytes by AVP in transplant patients with CAN in comparison with control groups. PATIENTS AND METHODS: In this study, we evaluated in vitro uPA releasing activity of lymphocytes obtained from renal allograft patients with well-functioning grafts (n = 9), CAN (n = 5), or acute rejection episodes (n = 5) compared with lymphocytes from healthy volunteers with normal renal function (n = 12) or patients with renal insufficiency (n = 5). RESULTS: Lymphocytes prepared from patients with chronic allograft nephropathy showed a significantly lower increase in uPA release induced by the combination of the V1-receptor antagonist and dDAVP compared with those from the other groups. CONCLUSION: This finding suggested that a decrease in uPA release from human peripheral blood lymphocytes by AVP-related peptides may be potentially involved in the pathophysiology of CAN.

Adult↗