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K Imai

Publications and source records attributed to K Imai.

At least 19 recordsLinked to original sources
PubMed2007

Significance of human beta-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infections.

Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa.

Aged↗
PubMed2006

Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma- reaction at E gamma = 1.5-2.4 GeV.

Differential cross sections and photon-beam asymmetries have been measured for the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using liquid deuterium and hydrogen targets with incident linearly polarized photon beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin 1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large positive asymmetries are observed, indicating the dominance of K* exchange. The large difference between the asymmetries for the K+ Sigma- and K+ Sigma0 reactions cannot be explained by simple theoretical considerations based on Regge model calculations.

Journal Article↗
PubMed2006

Characterization of H9N2 influenza A viruses isolated from chicken products imported into Japan from China.

We characterized eleven H9N2 influenza A viruses isolated from chicken products imported from China. Genetically they were classified into six distinct genotypes, including five already known genotypes and one novel genotype. This suggested that such multiple genotypes of the H9N2 virus have possibly already become widespread and endemic in China. Two isolates have amino-acid substitutions that confer resistance to amantadine in the M2 region, and this supported the evidence that this mutation might be a result of the wide application of amantadine for avian influenza treatment in China. These findings emphasize the importance of surveillance for avian influenza virus in this region, and of quarantining imported chicken products as potential sources for the introduction of influenza virus.

Animals↗
PubMed2006

High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.

The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.

DNA Mutational Analysis↗
PubMed2006

Epigenetic inactivation of TCF2 in ovarian cancer and various cancer cell lines.

Transcription factor 2 gene (TCF2) encodes hepatocyte nuclear factor 1beta (HNF1beta), a transcription factor associated with development and metabolism. Mutation of TCF2 has been observed in renal cell cancer, and by screening aberrantly methylated genes, we have now identified TCF2 as a target for epigenetic inactivation in ovarian cancer. TCF2 was methylated in 53% of ovarian cancer cell lines and 26% of primary ovarian cancers, resulting in loss of the gene's expression. TCF2 expression was restored by treating cells with a methyltransferase inhibitor, 5-aza-2'deoxycitidine (5-aza-dC). In addition, chromatin immunoprecipitation showed deacetylation of histone H3 in methylated cells and, when combined with 5-aza-dC, the histone deacetylase inhibitor trichostatin A synergistically induced TCF2 expression. Epigenetic inactivation of TCF2 was also seen in colorectal, gastric and pancreatic cell lines, suggesting general involvement of epigenetic inactivation of TCF2 in tumorigenesis. Restoration of TCF2 expression induced expression of HNF4alpha, a transcriptional target of HNF1beta, indicating that epigenetic silencing of TCF2 leads to alteration of the hepatocyte nuclear factor network in tumours. These results suggest that TCF2 is involved in the development of ovarian cancers and may represent a useful target for their detection and treatment.

Base Sequence↗
PubMed2006

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells.

Signal transducers and activators of transcription (STATs) are latent transcription factors that mediate cytokine- and growth factor-induced transcription. Constitutive activation of STAT3 has been shown in human cancers and transformed cell lines. We report that STAT3, but not STAT1 and STAT5, becomes phosphorylated in response to epidermal growth factor (EGF) and achieves maximal induction of collagenase-1 (MMP-1) transcription by interacting with c-JUN. Phosphorylation of STAT3 protein is biphasic: the first peak within 30 min and the second peak between 4 and 8 h. Association of STAT3 with c-JUN is detected and its constituting STAT3 is increasingly phosphorylated. The STAT and AP-1 elements are necessary for effective induction of MMP-1 promoter by EGF. Mutation of AP-1 element closely located at the STAT site abolishes the binding not only of c-JUN but also of STAT3 to MMP-1 promoter, resulting in the loss of the responsiveness to EGF. By blocking STAT3 activity with the dominant-negative form, we show the requirement of STAT3 for EGF induction of MMP-1 and MMP-10 (stromelysin-2). Furthermore, expression of the dominant-negative STAT3 is sufficient to inhibit the constitutive and EGF-inducible cell migration and invasion and the tumor formation in nude mice. These results demonstrate that STAT3 phosphorylation and its possible interaction with c-JUN are required for the strong responsiveness of MMP-1 to EGF, and STAT3 activation is crucial for exhibition of malignant characteristics in T24 bladder cancer cells.

Animals↗
PubMed2006

Therapeutic implications of the specific inhibition of causative matrix metalloproteinases in experimental colitis induced by dextran sulphate sodium.

Extracellular matrix dynamics, crucial for tissue remodelling, are highly regulated by a cascade of matrix metalloproteinases (MMPs) during inflammation and wound healing processes in inflammatory bowel disease (IBD). Contrary to expectations, there are limited reports to date that MMP inhibitors have some beneficial therapeutic effects in experimental colitis models. Furthermore, clinical trials of MMP inhibitors against certain tumours have failed to show any therapeutic benefit. One major reason for this lack of success may be the apparent uncertainty about the precise spectrum of inhibitory activity required. Since tumour necrosis factor alpha (TNFalpha), a key mediator in colonic inflammation, promotes MMP production in a dose-dependent manner, the therapeutic success of anti-TNFalpha agents against IBD motivated us to re-evaluate the therapeutic potential of MMP inhibition. First, using a quantitative polymerase chain reaction (PCR), western blotting, and zymography, we determined which MMPs were relevant to experimental colitis induced in mice by dextran sulphate sodium. Next, we examined a distinct role for MAPK and NFkappaB signalling pathways in the regulation of the expression of these MMP genes. Finally, we examined whether transcriptional regulation of these MMPs, either indirectly using inhibitors of MAPK and/or NFkappaB signalling pathways or directly using siRNA directed against these MMPs, contributes to the prevention of colitis. Changes in the expression level of colonic MMP-3 and MMP-10 preceded the clinical course of colitis. Colitis improved in mice that received these signal inhibitors, together with suppression of MMP expression. Moreover, siRNA that targeted MMP-3 and MMP-10 effectively reduced both the transcription of these MMPs and the severity of colitis. We conclude that MMP-3 and MMP-10 play a causal role in excess tissue destruction in colitis. Specific inhibition of these MMPs should provide novel therapeutics against IBD.

Animals↗
PubMed2006

Hematopoietic stem cell transplantation for 30 patients with primary immunodeficiency diseases: 20 years experience of a single team.

We retrospectively analyzed our results of 30 patients with three distinctive primary immunodeficiency diseases (PIDs)--severe combined immunodeficiency (SCID, n = 11), Wiskott-Aldrich syndrome (WAS, n = 11) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n = 8)--who underwent hematopoietic SCT (HSCT) during the past 20 years. Until 1995, all donors were HLA-haploidentical relatives with T-cell depletion (TCD) (n = 8). Since 1996, the donors have been HLA-matched related donors (MRD) (n = 8), unrelated BM (UR-BM) (n = 7) and unrelated cord blood (UR-CB) (n = 7). Twenty-seven of 30 patients had various pre-existing infections with or without organ damages before HSCT. Conditioning regimen and GVHD prophylaxis were determined according to disease, donor and pretransplant status. Although one of eight patients transplanted with TCD is alive with full engraftment, the other seven died. On the other hand, 18 of 22 patients transplanted without TCD are alive and well, including six of eight transplanted from MRD, seven of seven from UR-BM and five of seven from UR-CB. All 19 survivors did not require Ig supplementation after HSCT. These results indicate that UR-CBT as well as UR-BMT provides good results for PID comparable to MRD-SCT, and that early diagnosis, HSCT at early stage, careful supportive therapy and monitoring for various pathogens are important for the successful HSCT.

Adolescent↗
PubMed2006

Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis.

Histone deacetylase (HDAC) inhibitors modify transcription of selected genes and eventually induce apoptosis. However, molecular mechanisms for their proapoptotic activity remain unclear. We here demonstrate that HDAC inhibitors FK228 and CBHA preferentially upregulated the BH3-only protein Bmf in a broad range of cancer cells. In contrast, HDAC1 overexpression distinctly reduced Bmf expression. FK228 induced histones H3 and H4 acetylation at Bmf promoter region, but not at its 3' region, suggesting that histone hyperacetylation causes Bmf transcriptional activation. Knockdown of Bmf transcripts rescued cells from FK228 or CBHA-induced cell death, disruption of mitochondrial membrane potential (DeltaPsim) and DNA fragmentation. Taken together, FK228 and CBHA activate Bmf transcription by histone hyperacetylation at its promoter region, and inhibition of this action decreased their proapoptotic activity, thereby highlighting a central role of Bmf in HDAC inhibitor-mediated apoptosis.

Acetylation↗
PubMed2006

Unpleasant sweet taste: a symptom of SIADH caused by lung cancer.

A 56 year old woman with large cell lung carcinoma complained of an unpleasant sweet taste (dysgeusia). She developed hyponatraemia caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Dysgeusia disappeared when serum sodium normalised and recurred when hyponatraemia relapsed. Dysgeusia was the initial and only symptom of SIADH in this case.

Carcinoma, Large Cell↗
PubMed2006

Pathology of fatal highly pathogenic H5N1 avian influenza virus infection in large-billed crows (Corvus macrorhynchos) during the 2004 outbreak in Japan.

Highly pathogenic H5N1 avian influenza viruses were isolated in 9 large-billed crows that died in Kyoto and Osaka prefectures in Japan from March to April in 2004. We studied 3 of the 9 crows using standard histologic methods, immunohistochemistry, and virus isolation. The most prominent lesions were gross patchy areas of reddish discoloration in the pancreas. The consistent histologic lesions included severe multifocal necrotizing pancreatitis, focal degeneration and necrosis of neuron and glial cells in the central nervous system, and focal degeneration of cardiac myocytes. All of these tissues contained immunohistochemically positive influenza viral antigens. The virus was isolated from the brain, lung, heart, liver, spleen, and kidney of the crows examined. Thus we concluded that highly pathogenic avian influenza virus was associated with clinical disease, severe pathologic changes, and death in the 3 crows.

Animals↗
PubMed2006

[Pericardioperitoneal fenestration for chronic exudative pericarditis using a subxiphoidal approach; report of a case].

A 77-year-old woman with a previous history of median sternotomy and collagen disease, presented with chief complaints of resting dyspnea as a result of recurrent pericardial effusions or restrictive ventilatory impairment. She experienced significant symptom amelioration after undergoing pericardioperitoneal fenestration. We weighed the positive against the negative of various pericardial effusion drainage methods in this study. This operative procedure is not innovative, but favorable because it can be carried out conveniently and safely, enabling early rehabilitation without appreciable postoperative complications.

Aged↗
PubMed2006

[Aortic valve replacement for calcified aortic valve and annulus with ultrasonic decalcification].

UNLABELLED: We conducted ultrasonic decalcification on calcified annulus in patients with aortic stenosis (AS) using an ultrasonic operator, Sonopet (UST 2001) prior to aortic valve replacement (AVR). We studied the reliability of this method. SUBJECT AND METHOD: From January 2002 to August 2005, AVR was conducted for AS using the Sonopet in 45 patients, comprising of 18 male and 27 female subjects. The mean age was 73.3 +/- 9.7. RESULT: Artificial valves were successfully inserted at the intra-annular level in 37 patients and at the supra-annular level in 8 patients without conducting annular enlargement. In the patients with narrow annuli of less than 19 mm (23 patients), the preoperative mean annular diameter was 18.2 +/- 1.0 mm, but significantly larger artificial valves with an average diameter of 19.3 +/- 1.5 mm (p=0.003) were successfully inserted. CONCLUSION: AVR was proved to be safe and easy by previous ultrasonic decalcification of the annuls using the Sonopet. This method was very useful because it required no enlargement of aortic annulus.

Aged↗
PubMed2006

[Off-pump coronary artery bypass in high-risk patients].

In this study, 110 consecutive patients who had undergone off-pump coronary artery bypass (OPCAB) in the past 2 years were evaluated for early results of OPCAB. Patients were classified as a high-risk group (H group: 68 patients consisting of 46 men and 22 women) and a low-risk group (L group: 42 patients consisting of 31 men and 11 women), respectively, and were evaluated for the early operative results. No differences were noted between the H and L groups in the mean number of bypass grafts (2.9 +/- 0.9 in the H group, 2.9 +/- 0.9 in the L group), the rates of complete revascularization (85% in the H group, 93% in the L group), those of various graft materials bypassed, or those of sequential bypass. In all patients, we were able to undergo coronary revascularization by the aortic no-touch technique using arterial grafts exclusively. In the H group, 1 patient (1.5%) died in hospital, but no patients developed cerebral infarction postoperatively, and the frequency of complications was similar to that in the L group. The results of OPCAB for high-risk patients were good, and it was suggested that OPCAB using in situ arterial grafts was very useful particularly in patients with cerebrovascular diseases.

Aged↗
PubMed2006

Clot removal therapy by aspiration and extraction for acute embolic carotid occlusion.

BACKGROUND AND PURPOSE: The purpose of our retrospective study was to investigate the feasibility, safety, and efficacy of clot removal therapy by aspiration and extraction for patients with acute stroke with embolic internal carotid artery (ICA) occlusion. METHODS: Of 814 consecutive patients with acute ischemic stroke admitted to our institution from March 2003 to April 2005, clot removal therapy was performed for 14. Inclusion criteria were patients (1) presenting within 6 hours of onset of cardioembolic stroke, (2) with serious neurologic symptoms defined by a National Institutes of Health Stroke Scale (NIHSS) score of at least 11, (3) without extensive high signal intensity on diffusion-weighted MR images but with decreased ipsilateral hemispheric cerebral blood flow on perfusion-weighted images (perfusion/diffusion mismatch), and (4) with total ICA occlusion on angiograms. We removed clots by aspiration and extraction with a microsnare through either a guiding or balloon guide catheter. Radiographic results, 7-day NIHSS, 3-month modified Rankin Scale, and procedure-related complications were evaluated. RESULTS: Of 10 patients treated with the balloon guide catheter to temporarily interrupt proximal flow, 7 obtained complete or partial recanalization. The 4 patients treated with the guiding catheter had no recanalization. Of the 7 patients with recanalization, 6 had favorable 7-day neurologic and 3-month functional outcome; all showed anatomic crossflow via the anterior communicating artery. A procedure-related complication, distal embolization into the ipsilateral anterior cerebral artery, occurred in 1 patient. CONCLUSION: Balloon guide catheter-assisted clot removal therapy for embolic ICA occlusion may provide a high recanalization rate and good clinical outcome in patients with anatomic crossflow.

Adult↗
PubMed2005

Near-threshold diffractive psi-meson photoproduction from the proton.

Photoproduction of a phi meson on protons was studied by means of linearly polarized photons at forward angles in the low-energy region from threshold to Egamma = 2.37 GeV. The differential cross sections at t = -|t|min do not increase smoothly as Egamma increases but show a local maximum at around 2.0 GeV. The angular distributions demonstrate that phi mesons are photoproduced predominantly by helicity-conserving processes, and the local maximum is not likely due to unnatural-parity processes.

Journal Article↗
PubMed2005

Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis.

BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and non-inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t-test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real-time ploymerase chain reaction. RESULTS: We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non-inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.

Acrosome↗