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Biomedical subjects

Toru Inoue

Publications and source records attributed to Toru Inoue.

18 recordsLinked to original sources
PubMed2006

Generation of carbamoyl- and thiocarbamoyllithium synthons having a hydrogen(s) or an aryl group on the nitrogen and their trapping with carbonyl electrophiles.

Dimetalated amides 1 (Y = O) were generated as the synthons of carbamoyllithiums 2 (Y = O) by the reaction of isocyanates with iBu2AlTenBu and a subsequent tellurium-lithium exchange reaction. A series of amide derivatives 3 (Y = O) were obtained by the trapping of dianion 1 with electrophiles. This transformation can be successfully applied to the generation and trapping of thiocarbamoyllithium synthons 1 (Y = S) as well as to the nucleophilic introduction of the parent carbamoyl moiety H2NC(O).

Journal Article↗
PubMed2006

The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer.

BACKGROUND & AIMS: The CpG island methylator phenotype (CIMP) is one of the mechanisms involved in colorectal carcinogenesis (CRC). Although CIMP is probably the cause of high-frequency microsatellite instability (MSI-H) sporadic CRCs, its role in microsatellite stable (MSS) tumors is debated. The majority of MSS CRCs demonstrate chromosomal instability (CIN) with frequent loss of heterozygosity (LOH) at key tumor suppressor genes. We hypothesized that the majority of sporadic CRCs without CIN would be associated with CIMP. METHODS: We tested 126 sporadic CRCs for MSI and LOH and categorized tumors into MSI, LOH, or MSI-/LOH- subgroups. Methylation status was evaluated using 6 CIMP-related markers (MINT1, MINT2, MINT31, p16(INK4alpha), p14(ARF), and hMLH1) and 6 tumor suppressor genes (PTEN, TIMP3, RUNX3, HIC1, APC, and RARbeta2). BRAF V600E mutation analysis was performed using allele-specific polymerase chain reaction and DNA sequencing. RESULTS: We observed frequent methylation at all 12 loci in all CRCs. BRAF V600E mutations correlated with the MSI (P < .0001) and MSI-/LOH- (P = .03) subgroups. MSI and MSI-/LOH- tumors exhibited more promoter methylation than CRCs with LOH (P < .0001). We also found an inverse correlation between the frequencies of methylation and LOH (rho = -0.36; P < .0001). CONCLUSIONS: The associations between methylation frequencies at CIMP-related markers and MSI or MSI-/LOH- sporadic CRCs suggest that the majority of these tumors evolve through CIMP. These findings suggest that CIN and CIMP represent 2 independent and inversely related mechanisms of genetic and epigenetic instability in sporadic CRCs and confirm that MSI cancers arise as a consequence of CIMP.

Adult↗
PubMed2006

Electron conductive three-dimensional polymer of cuboidal C60.

Single crystals of three-dimensional (3D) C60 polymer were prepared by the topotactic conversion of two-dimensional (2D) C60 polymer single crystals at a pressure of 15 GPa at 600 degrees C. The x-ray single crystal study revealed that the 3D C60 polymer crystallized in a body centered orthorhombic space group Immm, and spherical C60 monomer units were substantially deformed to rectangular parallelepiped (cuboidal) shapes, each unit being bonded to eight cuboidal C60 neighbors via [3 + 3] cycloaddition. The 3D C60 polymer was electron conductive, in contrast with the nonconductive behavior of 2D polymers.

Journal Article↗
PubMed2006

Synchronous adenocarcinomas of the ileum and transverse colon detected by capsule endoscopy: report of a case.

A 77-year-old woman was admitted to our hospital with anemia and anorexia. Neither gastrointestinal endoscopy nor computed tomography showed by abnormal findings; however, a capsule endoscopy, performed to detect obscure gastrointestinal bleeding, revealed a tumor in the ileum. When we tried to take biopsies of the ileal tumor by push enteroscopy via the anus, we found another tumor in the transverse colon. On exploration, tumors were identified in the ileum and the transverse colon. Thus, we resected the ileum and transverse colon with regional lymph node dissection. Histologic sections from both the ileum and colon revealed moderately differentiated adenocarcinomas with no lymph node metastasis.

Adenocarcinoma↗
PubMed2006

Development and evaluation of an indirect enzyme-linked immunosorbent assay for detection of foot-and-mouth disease virus nonstructural protein antibody using a chemically synthesized 2B peptide as antigen.

Forty peptides were synthesized corresponding to hydrophilic clusters of amino acids within the sequences of foot-and-mouth disease virus (FMDV) nonstructural proteins (NSP). Six peptides were studied in more detail and the most promising, a 2B peptide, was evaluated in enzyme-linked immunosorbent assay (ELISA) using sera from naive, vaccinated, and vaccinated-and-challenged cattle as well as bovine sera from field outbreaks. The performance of the new NSP peptide ELISA was compared to that of 4 commercial NSP ELISA kits. Antibody to 2B was detectable from the end of the first week to the second week after infection in most of the nonvaccinated animals and by the second to third week in vaccinated-and-challenged animals. The sensitivity of the 2B peptide ELISA was comparable to the 3ABC Ceditest (Ceditest FMDV-NS, Cedi Diagnostics B.V.; Chung et al., 2002). With some modification and further validation, this 2B test could be useful as a screening or conformational NSP test in postvaccination surveillance for FMD.

Amino Acid Sequence↗
PubMed2005

Importance of arginine 20 of the swine vesicular disease virus 2A protease for activity and virulence.

A major virulence determinant of swine vesicular disease virus (SVDV), an Enterovirus that causes an acute vesicular disease, has been mapped to residue 20 of the 2A protease. The SVDV 2A protease cleaves the 1D-2A junction in the viral polyprotein, induces cleavage of translation initiation factor eIF4GI, and stimulates the activity of enterovirus internal ribosome entry sites (IRESs). The 2A protease from an attenuated strain of SVDV (Ile at residue 20) is significantly defective at inducing cleavage of eIF4GI and the activation of IRES-dependent translation compared to the 2A protease from a pathogenic strain (J1/73, Arg at residue 20), but the two proteases have similar 1D-2A cleavage activities (Y. Sakoda, N. Ross-Smith, T. Inoue, and G. J. Belsham, J. Virol. 75:10643-10650, 2001). Residue 20 has now been modified to every possible amino acid, and the activities of each mutant 2A protease has been analyzed. Selected mutants were reconstructed into full-length SVDV cDNA, and viruses were rescued. The rate of virus growth in cultured swine kidney cells reflected the efficiency of 2A protease activity. In experimentally infected pigs, all four of the mutant viruses tested displayed much-reduced virulence compared to the J1/73 virus but a significant, albeit reduced, level of viral replication and excretion was detected. Direct sequencing of cDNA derived from samples taken early and late in infection indicated that a gradual selection-reversion to a more efficient protease occurred. The data indicated that extensive sequence change and selection may introduce a severe bottleneck in virus replication, leading to a decreased viral load and reduced or no clinical disease.

Amino Acid Sequence↗
PubMed2004

Evaluation of microsatellite instability, hMLH1 expression and hMLH1 promoter hypermethylation in defining the MSI phenotype of colorectal cancer.

INTRODUCTION: About 15% of all colorectal cancers (CRCs) demonstrate high levels of microsatellite instability (MSI-H) and are currently best identified by molecular analysis of microsatellite markers. Most sporadic CRCs with MSI-H are known to be associated with the methylation of the hMLH1 promoter. Promoter methylation coincided with lack of hMLH1 expression. We aimed to investigate the association between MSI status, hMLH1 protein expression and methylation status of the hMLH1 promoter, and to determine the usefulness of each method in defining the MSI phenotype in sporadic CRCs. MATERIALS AND METHODS: CRCs from 173 patients from the Cancer and Leukemia Group B (CALGB) were assessed for their MSI status. An additional cohort of 18 MSI-H tumors from the University of California San Diego (UCSD) was included in the analysis of the MSI-H subgroup. MSI testing was performed by PCR using five standard MSI markers. hMLH1 promoter analysis was investigated by methylation specific PCR (MSP), and expression of the MMR genes hMLH1 and hMSH2 was examined by immunohistochemistry (IHC). RESULTS: Of the 173 CALGB tumors, 111 (64%) were MSS, 35 (20%) were MSI-L and 27 (16%) MSI-H, respectively. Data on hMLH1 protein expression, hMSH2 protein expression and hMLH1 methylation are available on 128, 173 and 81 of these tumors, respectively. Presence of hMLH1 and hMSH2 protein expression was significantly associated with MSI status. Four of 45 (8.9%) MSI-H tumors and 0 of 146 (0%) MSS/MSI-L tumors did not express hMSH2 (p = 0.0028). hMLH1 protein expression was present in 107 of 108 (99%) MSS and MSI-L tumors versus 11 of 20 (55%) MSI-H tumors (p < 0.0001). Of 61 MSS and MSI-L cancers studied for methylation, 11 (18%) were methylated at the hMLH1 promoter whereas 14 of 20 (70%) MSI-H cancers were methylated (p = 0.0001). In 27 MSI-H tumors studied for hMLH1 protein expression and methylation, 93% of tumors with loss of expression (93%) were also methylated while 42% (5/12) with positive immunostaining for hMLH1 were methylated at the hMLH1 promoter (p = 0.009). CONCLUSIONS: Promoter methylation and hMLH1 expression are significantly associated with the MSI-H phenotype in CRC. Promoter methylation analysis provides a useful means to screen for MSI-H tumors. Our data further suggests that hMLH1 promoter methylation analysis alone cannot replace MSI testing, as a significant number of MSI-H tumors could be potentially overseen by such an approach. We suggest that phenotypic evaluation of CRC is performed most reliably with MSI testing, although expression analysis and investigation of the promoter methylation status may complement the screening process.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Dialyzability of the antiepileptic drug zonisamide in patients undergoing hemodialysis.

PURPOSE: The influence of hemodialysis on plasma zonisamide (ZNS) concentration has not been clarified. In this study, the dialyzability of ZNS during hemodialysis was investigated in four ZNS-treated women with systemic lupus erythematosus complicated by seizures. METHODS: The total and unbound plasma concentrations of ZNS were measured before and after hemodialysis. The concentration of ZNS in the spent dialysate also was determined. RESULTS: The reduction in plasma ZNS concentration after a 4.5-h hemodialysis was 52.0 +/- 7.6%, and the dialyzer (BLF-16GW) clearance of ZNS was 55.1 +/- 7.0 ml/min. Dosage was gradually increased up to 200 to 500 mg/day, and the seizures were controlled satisfactorily. CONCLUSIONS: The plasma concentration of ZNS was reduced by approximately 50% during one session of dialysis. For patients undergoing daytime hemodialysis sessions every 2 or 3 days, the usual dosage of ZNS (4-8 mg/kg/day) may be prescribed once a day in the evening. If seizures occur after hemodialysis, a supplemental daily dose may be prescribed in the morning.

Adult↗
PubMed2004

Prevalence of Helicobacter pylori antibodies in long-term dialysis patients.

BACKGROUND: Helicobacter pylori has been reported to play an important role in the development of gastritis and gastric ulcer. METHODS: This study included 168 patients with end-stage renal disease (ESRD; 30 non-dialysis patients, 138 patients receiving dialysis; mean duration of dialysis: 57.3 +/- 61.7 months) and 138 control volunteers. We investigated the prevalence of H. pylori infection by measuring H. pylori antibody (IgG) levels. RESULTS: The prevalence of H. pylori infection was 62.3% in the control group, 53.3% in the non-dialysis patients, and 36.9% in the dialysis patients. The percentage decreased with a reduction of renal function. In addition, the proportion of H. pylori-positive patients decreased with the duration of dialysis, and the antibody titre was also significantly decreased. There was no association between long-term oral administration of H2RA (H2 receptor antagonist) and the incidence of H. pylori infection. CONCLUSION: Among dialysis patients, the proportion of H. pylori-positive patients was low. An aetiological factor other than H2RA agents was suggested. Renal failure or dialysis treatment may influence H. pylori infection.

Adult↗
PubMed2003

A nitric oxide-generating beta-blocking agent prevents renal injury in the rat remnant kidney model. Comparative study of two beta-blocking drugs, nipradilol and propranolol.

BACKGROUND: The L-arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether beta-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. METHODS: Nipradilol, a beta-blocker with an ONO(2) group (5, 10 or 15 mg/kg/day) and propranolol, a beta-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-L-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U(NOx)) and cyclic GMP (U(cGMP)). RESULTS: Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U(NOx) in comparison with the sham-operated rats. Nipradilol increased U(NOx) and U(cGMP) significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U(NOx). The addition of nipradilol increased U(NOx) and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. CONCLUSION: These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The beta-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.

Adrenergic beta-Antagonists↗
PubMed2002

Unique characteristics of a picornavirus internal ribosome entry site from the porcine teschovirus-1 talfan.

The teschoviruses constitute a recently defined picornavirus genus. Most of the genome sequence of the porcine teschovirus-1 (PTV) Talfan and several other strains is known. We now demonstrate that initiation of protein synthesis occurs at nucleotide (nt) 412 on the PTV Talfan RNA and that nt 1 to 405 contains an internal ribosome entry site (IRES) that functions efficiently in vitro and within mammalian cells. In comparison with other picornavirus IRES elements, the PTV IRES is relatively short and lacks a significant polypyrimidine tract near the 3' end. Expression of an enterovirus 2A protease, which induces cleavage of eIF4G within the translation initiation complex eIF4F, has little effect on the PTV IRES activity within BHK cells. The PTV IRES has a unique set of properties and represents a new class of picornavirus IRES element.

5' Untranslated Regions↗
PubMed2002

Carbamylated hemoglobin as a therapeutic marker in hemodialysis.

Carbamylation requires isocyanic acid derived from urea. Carbamylation of hemoglobin (Hb) produces carbamylated Hb (carbHb), which could serve as a marker of posttranslational protein modification possibly associated with such uremic complications as atherosclerosis. Since relative carbHb levels are determined by mean urea concentration and duration of exposure, they could be used to assess the adequacy of a patient's hemodialysis (HD) regimen. We therefore determined the relationship between carbHb and urea kinetics in patients with chronic renal failure (CRF) undergoing maintenance HD. In pre-HD determinations as well as in nondialyzed subjects including healthy subjects and CRF patients without dialysis, carbHb correlated well with blood urea nitrogen (BUN) concentrations, especially with BUN averaged for the preceding 1-3 months. In HD patients, carbHb correlated significantly with urea kinetics (time-averaged concentration of urea, or TAC(urea), K(t)/V and urea reduction rate). The estimated mean urea concentration in HD patients calculated from the relationship between carbHb and averaged BUN over 3 months in the nondialyzed groups was lower than TAC(urea), suggesting that TAC(urea) may be an overestimate. Pre-HD BUN is not a good nutritional index since detrimental decreases in urea elimination from the body can elevate pre-HD BUN independently of nutrition. We therefore devised a new nutritional index, BUN/carbHb, which correlated significantly with serum albumin as well as the normalized protein catabolic rate. These results demonstrate that carbHb accurately reflects uremic control and the BUN/carbHb ratio could serve as an index of nutritional state in HD patients.

Biomarkers↗
PubMed2002

A rare combination of sites of involvement by Mycobacterium intracellulare in a hemodialysis patient: multifocal synovitis, spondylitis, and multiple skin lesions.

PURPOSE: Atypical mycobacterial infection is a rare but serious hazard in immunocompromised patients including those undergoing maintenance hemodialysis and immunosuppressive therapy. Recognition of unusual involvement patterns is important. METHODS: We describe an extremely rare combination of complications caused by such an organism in a patient with end-stage renal disease: spinal osteolysis and multiple skin lesions associated with synovitis. RESULTS: The patient had received a renal allograft 18 years previously but developed infection with Mycobacterium avium-M. intracellulare complex including dermatologic manifestations, spondylitis, and synovitis involving the wrist and lateral malleolus after initiation of hemodialysis when the transplanted kidney failed. An empirical antibiotic regimen failed to alleviate skin lesions or fevers, or to lower an elevated C-reactive protein concentration, until the patient's dose of methylprednisolone was increased to treat mild adrenal insufficiency. The increase resulted in rapid resolution of skin lesions. A compression fracture 6 months later was attributed to spondylitis caused by the same organism. CONCLUSIONS: We suspect that spondylitis represented the primary focus of M. intracellulare infection.

Female↗
PubMed2002

Impairment of vascular responses to reactive hyperemia and nitric oxide in chronic renal failure.

BACKGROUND: Cardiovascular events are the leading cause of morbidity and mortality in patients with end-stage renal disease. The role of endothelial dysfunction, an early marker of arteriosclerosis, in patients with chronic renal failure (CRF) before the initiation of maintenance hemodialysis (HD), and the factors affecting endothelial dysfunction in the setting of chronic renal failure remain poorly understood. METHODS: We evaluated endothelial function by measuring flow-mediated vasodilation (%FMD) during reactive hyperemia in healthy individuals (HCS) and patients with chronic renal failure with (HD) or without (ND) hemodialysis. Nonspecific endothelium-independent vasodilation (%NTG) was measured after the administration of sublingual glyceryl trinitrate spray (0.3 mg). Factors affecting %FMD and %NTG were also tested. RESULTS: In ND and HD, plasma homocysteine, cysteine and stable NO metabolite (NO(-)(3)) concentrations were significantly elevated. In ND and HD, reactive hyperemia as well as %NTG and %FMD were attenuated to a similar degree. On multivariate regression analysis, NO(-)(3) concentration was directly correlated with both %FMD and %NTG, while the glutathione (GSH) concentration correlated with only %NTG. CONCLUSIONS: Our findings indicate that chronic renal failure before the initiation of maintenance hemodialysis impairs endothelial function and/or the response to NO, which is accompanied by the attenuated reactive hyperemia. Furthermore, the impairment might be related to the decreased synthesis or the dissipation of NO.

Blood Pressure↗
PubMed2002

Cushing's syndrome with a large pituitary adenoma producing both corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH).

A 57-year-old man showed high serum cortisol, plasma adrenocorticotropin (ACTH) and corticotropin-releasing hormone (CRH) levels with a large pituitary tumor and a prostatic cancer. High dose dexamethasone did not suppress cortisol secretion and CRH administration did not stimulate cortisol secretion. After surgical removal of the pituitary tumor, plasma CRH, ACTH and serum cortisol levels were normalized. Histological examinations showed pituitary adenoma and prostatic adenocarcinoma, and pituitary adenoma was stained with both anti-CRH and anti-ACTH antibodies, but prostatic cancer was not stained. A CRH-producing pituitary adenoma is a new type of Cushing's syndrome.

Adenocarcinoma↗
PubMed1999

Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis.

BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer.METHODS: One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system.

Journal Article↗
PubMedDate not supplied

Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus 5-FU-leucovorin in colorectal cancer.

BACKGROUND: 5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In addition, activation of 5-FU to form various nucleotides via three pathways requires phosphorylation by orotate phosphoribosyltransferase, thymidine phosphorylase and uridine phosphorylase, respectively. The aim of this study was to assess the predictive value of the expression of these genes in patients receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer. PATIENTS AND METHODS: Twenty-seven patients with metastatic, or recurrent colorectal cancer were studied. Enzyme gene expression was measured in primary tumors by the real-time reverse transcription PCR method. RESULTS: The TS mRNA level was significantly higher in the responders than in the non-responders (p=0.0409). CONCLUSION: The effect of IFL therapy may be determined by the extent of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for predicting the effect of intravenous regimens such as FOLFIRI.

Adult↗