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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 19 recordsLinked to original sources
PubMed2007

Concurrent chemoradiation for patients with squamous cell carcinoma of the cervical esophagus.

Little is known concerning the role of concurrent chemoradiation (CCRT) in the management of carcinoma of the cervical esophagus. We retrospectively evaluated our treatment approach for patients with cervical esophageal cancer with special emphasis on CCRT with or without surgery. Medical records of 21 consecutive patients with cervical esophageal carcinoma treated mainly with CCRT (1997-2004) were reviewed, and factors that influenced patient survival were analyzed retrospectively. Nineteen received CCRT with cisplatin/5-fluorouracil and five underwent curative surgery. Two patients who were deemed unfit for CCRT received radiation therapy alone. All had three-dimensional treatment planning (median total dose, 40 Gy with surgery, 64 Gy without surgery). Of the 19 patients who received CCRT, 11 patients including five who underwent curative surgery achieved initial local control. Neither of the two patients who received radiation therapy alone achieved local control. Among 19 patients who underwent CCRT, 9/11 with T1-3 grade tumors achieved initial local control, but only 2/8 patients with T4 tumors (P = 0.011, chi(2) test) achieved initial local control. No patient without initial local control survived > 20 months compared with 2-year and 5-year survival rates of 60% and 40% in those who achieved initial local control (P = 0.038). No patient with T4 tumors survived > 18 months, whereas 2- and 5-year survival rates were 62% and 41%, respectively, in those with T1-3 tumors (P = 0.006). The significant effect of T-classification on survival was maintained when analyzed among 19 patients who received CCRT. CCRT shows promise for cervical esophageal carcinoma. T-classification and initial local control had significant impact on survival.

Aged↗
PubMed2006

Efficacy of computer-assisted pedicle screw insertion for cervical instability in RA patients.

We evaluated the efficacy of the computer-assisted cervical pedicle screw insertion, compared with those inserted without the help of the system on the cervix of rheumatoid arthritis (RA) patients. Eighty-six cervical pedicle screws were inserted without the help of the system. Of the 86, 59 screws were in non-RA patients with degenerative spine, and 27 were in RA patients. The accuracy of the screw insertions was evaluated by a CT-based method. Then, 25 screws were inserted with the system into the cervical spines between C2 and C6 in RA patients (Navigation group). The efficacy of the system was assessed by the CT-based method, compared with 27 screws inserted without the system (Conventional group). The screws in RA patients tended to be more deviated than those in non-RA patients. In Conventional group, four screws (15%) were placed far laterally, and two (7%), far medially. In contrast, no screw was placed far laterally or medially in Navigation group (P < 0.05).

Adult↗
PubMed2006

Clinicopathologic investigation of a family with expanded SCA8 CTA/CTG repeats.

We investigated a family manifesting progressive ataxia, with expanded SCA8 CTA/CTG repeats. Neuropathologically, degeneration of Purkinje, inferior olivary, and nigral neurons and periaqueductal gliosis were evident. The sites of Purkinje cell loss were occupied by fibrillary accumulations. The remaining Purkinje cells showed somatic sprouts, and intracytoplasmic 1C2-positive granular structures were recognizable. This characteristic distribution of neurodegeneration and Purkinje cell cytopathology were distinct from those of other hereditary spinocerebellar ataxias previously reported.

Adult↗
PubMed2006

Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats.

PURPOSE: The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity. METHODS: Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON. RESULTS: Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters. CONCLUSIONS: These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.

Analysis of Variance↗
PubMed2006

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress.

We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein. We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5'untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis.

Cell Line, Tumor↗
PubMed2006

Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy.

DNA repair enzymes repair DNA damaged by platinum agents and ionising radiation. Single nucleotide polymorphisms (SNPs) in DNA repair genes modulate the repair capacity and might affect response and prognosis following platinum-based chemoradiotherapy (CRT). We investigated associations between the functional SNPs in DNA repair genes and response and survival in muscle-invasive bladder cancer patients treated with CRT to determine the predictive value of the SNPs in patient selection for bladder conservation therapy. The study group comprised 78 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms in xeroderma pigmentosum complementation groups C (Lys939Gln, A/C), D (XPD; Lys751Gln, A/C), and G (Asp1104His, G/C), and X-ray repair cross-complementing groups 1 (XRCC1; Arg399Gln, G/A) and 3 (Thr241Met, T/C) genes were genotyped. Combined genotypes with at least one variant allele in XPD or XRCC1 were significantly associated with improved cancer-specific survival compared with remaining groups (P=0.009). In multivariate analysis, only the combined XPD and XRCC1 genotypes were independently associated with cancer-specific survival (P=0.04). The association was stronger in stage T3/T4 patients (P=0.0008). These results suggest that combined XPD and XRCC1 genotypes might be prognostic factors in muscle-invasive bladder cancer patients treated with CRT.

Aged↗
PubMed2006

Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection.

BACKGROUND: Some, but not all studies have provided evidence that the CagA status of Helicobacter pylori strains is a predictive factor for the outcome of eradication therapy. AIM: To clarify the association between CagA status and eradication outcome. METHODS: We included studies reporting the numbers of successful and failed cases in H. pylori-eradication therapy according to the CagA status. Fourteen studies (1529 patients) were included of 325 articles identified in the search. The pooled risk ratio for H. pylori-eradication failure in CagA-negative relative to CagA-positive strains and the pooled risk difference in eradication success between the two groups were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: The summary risk ratio for eradication failure in CagA-negative relative to CagA-positive was 2.0 (95% CI: 1.6-2.4, P < 0.001), corresponding with the summary risk difference for eradication success between the groups of 11% (95% CI: 3-19%, P = 0.011). Meta-regression analysis demonstrated that usage of polymerase chain reaction examination for CagA status and a high proportion of non-ulcer dyspepsia patients were factors for heterogeneity among studies. CONCLUSIONS: Our meta-analysis confirmed the importance of the presence of CagA as a predictor for successful eradication of H. pylori.

Antigens, Bacterial↗
PubMed2006

Influence of smoking and CYP2C19 genotypes on H. pylori eradication success.

CYP2C19 polymorphisms and smoking influence the efficacy of H. pylori eradication therapy, but interaction between the two have hitherto not been examined. A total of 142 H. pylori-positive patients who received triple drug therapy with lansoprazole, amoxicillin and clarithromycin were categorized into three groups with regard to diplotypes of CYP2C19: homozygous extensive metabolizer (homEM), heterozygous EM (hetEM), and poor metabolizer (PM). The overall success rate was 61.3%. Smoking was an independent risk factor of eradication failure (OR 2.81, 95% CI 1.14-6.91), whereas CYP2C19 polymorphisms were less influential. Among non-smokers, the homEM and hetEM groups showed worse eradication rates (58.5 and 67.3%) relative to PM (76.2%) as expected; however, an opposite trend was observed among smokers (homEM 50.0%, hetEM 46.7%, PM 20.0%), indicating possible interactions with CYP2C19 polymorphisms. Smoking has a greater influence on H. pylori eradication than the CYP2C19 genotype. Interaction between smoking and CYP2C19 should be examined in the future.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2006

Surface-emitted terahertz-wave generation by ridged periodically poled lithium niobate and enhancement by mixing of two terahertz waves.

Surface-emitted terahertz- (THz-) wave generation by difference-frequency mixing with ridge-shaped periodically poled lithium niobate (PPLN) was demonstrated. The PPLN had a ridge height of 300 microm, a thickness of 20 microm, and an interaction length of 35 mm. The ridge behaves as a slab waveguide for optical pump beams. The PPLN gives rise to THz waves in opposite directions, perpendicular to the pump-beam direction. Reflecting the THz wave on one side and overlapping it with the THz wave on the other side increased the total THz-wave intensity approximately 2.7 times compared with that without reflection and mixing.

Journal Article↗
PubMed2006

Intercellular adhesion molecule-1 mediates the inhibitory effects of hyaluronan on interleukin-1beta-induced matrix metalloproteinase production in rheumatoid synovial fibroblasts via down-regulation of NF-kappaB and p38.

OBJECTIVE: In rheumatoid arthritis (RA), it is well known that rheumatoid synovial fibroblasts (RSF) produce matrix metalloproteinases (MMPs) when stimulated with proinflammatory cytokines such as interleukin-1beta (IL-1beta), which causes joint destruction. We have previously shown that hyaluronan (HA) inhibits IL-1beta actions in RSF via CD44, the principal HA receptor. However, CD44 mediates HA effects only partially, and intracellular events after the HA binding to its receptors remain unclear. We investigated the role of intercellular adhesion molecule-1 (ICAM-1), another cell surface receptor for HA, and the intracellular signalling pathways in the actions of HA. METHODS: RSF were isolated from rheumatoid synovial tissues by enzymatic digestion and cultured in monolayers. The confluent cells were incubated for 48 h with IL-1beta, IL-1beta in the presence of HA, or IL-1beta in the presence of HA with pretreatment with anti-ICAM-1 antibody. Secretion of MMP-1 and MMP-3 was analysed by immunoblotting and immunofluorescence cytochemistry. Immunofluorescence cytochemistry was also performed to evaluate binding of HA to ICAM-1. The phosphorylation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was analysed by immunoblotting. RESULTS: Production of MMP-1 and MMP-3 by RSF was stimulated by IL-1beta. HA at > or =2 mg/ml significantly inhibited MMP production induced by IL-1beta in a dose-dependent manner. Moreover, pretreatment with anti-ICAM-1 antibody at 50 mug/ml significantly blocked the effects of HA on the actions of IL-1beta on RSF, as shown by immunoblotting and immunofluorescence cytochemistry. Another immunofluorescence cytochemistry study demonstrated that HA bound RSF via ICAM-1. Inhibition studies revealed the requirement of NF-kappaB, p38 and c-jun NH2-terminal kinase (JNK) for IL-1beta-induced MMP production. IL-1beta activated all three pathways, whereas HA down-regulated their phosphorylation. Pretreatment with anti-ICAM-1 antibody reversed the inhibitory effects of HA on the activation of NF-kappaB and p38 without affecting JNK. CONCLUSION: HA suppresses IL-1beta-enhanced MMP-1 and MMP-3 synthesis in RSF via ICAM-1 through down-regulation of NF-kappaB and p38. Intra-articular injection of HA of high molecular weight may work through such a mechanism in RA joints.

Arthritis, Rheumatoid↗
PubMed2006

BRAF mutations and phosphorylation status of mitogen-activated protein kinases in the development of flat and depressed-type colorectal neoplasias.

Although some molecular differences between flat-depressed neoplasias (FDNs) and protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF mutations or the status of phosphorylated mitogen-activated protein kinase (p-MAPK) are different between theses two groups. We evaluated the incidence of BRAF and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the immunohistochemical status of p-MAPK in the nonserrated neoplasias (46 FDNs and 57 PNs). BRAF mutations were detected in four FDNs (9%) and none of PNs (P=0.0369 by Fisher's exact test). KRAS mutations were observed in none of FDNs and in 14 PNs (25%; P=0.0002 by Fisher's exact test). MSI-H was detected in seven out of 44 FDNs (16%) and in one out of 52 of PNs (2%) (P=0.022 by Fisher's exact test). Type B and C immunostaining for p-MAPK was observed in 34 out of 46 FDNs (72%), compared with 24 out of 55 PNs (44%; P=0.0022 by chi(2) test). There was no significant difference in the type B and C immunostaining of p-MAPK between FDNs with and without BRAF mutations. BRAF and KRAS mutations are mutually exclusive in the morphological characteristics of colorectal nonserrated neoplasia. Abnormal accumulation of p-MAPK protein is more likely to be implicated in the tumorigenesis of FDNs than of PNs. However, this abnormality in FDNs might occur via the genetic alteration other than BRAF or KRAS mutation.

Adenocarcinoma↗
PubMed2006

Combination study of myocardial perfusion and left ventricular filling provides an excellent prediction of clinical outcomes in patients with reperfused myocardial infarction.

The no reflow phenomenon and left ventricular (LV) diastolic dysfunction are surrogate markers of poor outcomes in patients with myocardial infarction (MI). We studied the relationship between contrast perfusion defects and restrictive filling patterns for predicting prognosis after MI. Mitral inflow velocity and myocardial contrast perfusion were studied 2 weeks after reperfusion in 226 consecutive patients with acute MI. The cohort was divided into two groups according to the number of perfusion defect segments (PD); large-PD and small-PD. Mitral inflow was classified into two categories according to deceleration time; non-restrictive and restrictive. The patients were divided into 4 groups (small-PD/non-restrictive, n = 124; small-PD/restrictive, n = 29; large-PD/non-restrictive, n = 50; large-PD/restrictive, n = 23). LV end-diastolic volume index was the greatest and cardiac event rate was the highest in large-PD/restrictive, followed by large- PD/non-restrictive, small-PD/restrictive, and by small- PD/non-restrictive (81 +/- 19 vs. 74 +/- 17 vs. 66 +/- 19 vs. 59 +/- 15 ml/m2, events: 61 % vs. 16% vs. 14% vs. 8 %). Multivariate analysis revealed the large-PD is the most powerful predictive factor related to cardiac events (odds ratio = 5.5, P = 0.004) followed by the restrictive filing pattern (4.3, P = 0.005). Co-existence of large-PD and restrictive filling is a strong predictor of adverse outcomes in the patients with MI.

Aged↗
PubMed2006

A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases affecting the C-terminus of the transporter.

Cystinuria is caused by the inherited defect of apical membrane transport systems for cystine and dibasic amino acids in renal proximal tubules. Mutations in either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene have been identified mainly from Italian, Libyan Jewish, North American, and Spanish patients. In the present study, we have analyzed cystinuria cases from oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1 genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine in COS-7 cells was measured to determine the functional properties of mutants. The protein expression and localization were examined by Western blot and confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to possess mutations in SLC7A9. The most frequent one was a novel missense mutation P482L that affects a residue near the C-terminus end of the protein and causes severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein was expressed and sorted to the plasma membrane as well as wild type. The alteration of Pro482 with amino acids with bulky side chains reduced the transport function of b(0,+)AT/BAT1. Interestingly, the mutations of SLC7A9 for Japanese cystinuria patients are different from those reported for European and American population. The results of the present study contribute toward understanding the distribution and frequency of cystinuria-related mutations of SLC7A9.

Amino Acid Substitution↗
PubMed2006

Intra-operative monitoring of vagal nerve activity with wire electrodes.

A monitoring system for tracking the electromyogram (EMG) of the vocal cords with wire electrodes embedded in an endotracheal tube was designed to identify the recurrent laryngeal nerve during thyroidectomy. Our recent experience in two cases suggests that vagal nerve activity can be correctly detected by recording of the EMG of the vocal cords using a special endotracheal tube embedded with wire electrodes.

Adult↗
PubMed2006

Hyper-reactive mononuclear cells and neutrophils in chronic periodontitis.

OBJECTIVES: Stimulated mono- and polymorphonuclear cells from patients with periodontitis have shown increased release of interleukin-1beta (IL-1beta) and oxygen radicals, respectively. The aim was to study whether this hyper-reactivity could be found both in mono- and polymorphonuclear cells from the same patient, and whether there was a relation to the gene coding for IL-1beta (IL-1beta(+3953)). MATERIAL AND METHODS: Peripheral mononuclear cells from 14 non-smoking and well-treated patients and pair-matched controls were incubated with opsonized Staphylococcus aureus and lipopolysaccharide (LPS). Released IL-1beta and tumour necrosis factor (TNF)-alpha were determined with ELISA. Generation of oxygen radicals from the Fcgamma-receptor-stimulated neutrophils was measured with chemiluminescence and the polymorphism at IL-1beta(+3953) was measured with polymerase chainreaction. RESULTS: The mononuclear cells from the patients released more IL-1beta after incubation with LPS (p<0.001) and with bacteria (p<0.05). The release of TNF-alpha tended to be higher in the patient group. The peripheral neutrophils from the patients generated more oxygen radicals (p<0.06). We found no differences between the study groups regarding the IL-1beta(+3953) polymorphism. CONCLUSION: The similarity in systemic inflammation between patients and controls suggests that the increased release/generation of IL-1beta and oxygen radicals from peripheral leukocytes in periodontitis patients is of a constitutional nature and of pathogenic relevance.

Alleles↗