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Biomedical subjects

Hiroyuki Yamamoto

Publications and source records attributed to Hiroyuki Yamamoto.

At least 91 records · Page 5Linked to original sources
PubMed2003

Expression of ets-related transcriptional factor E1AF is associated with tumor progression and over-expression of matrilysin in human gastric cancer.

Expression of E1AF/PEA3 (ETV4), an ets family transcriptional factor, has been implicated in tumor progression through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human gastric cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we analyzed 100 gastric cancer tissues for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analyzed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 64% of the 100 gastric cancer tissues, but was undetectable or only faintly detected in adjacent non-tumor tissues. E1AF expression was significantly correlated with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumor-node-metastasis stage and recurrence. Patients with E1AF-positive tumors had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumors (P < 0.0001 and P < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (P = 0.0082 and P = 0.0096, respectively). Among the MMPs analyzed, expression of matrilysin (MMP-7) was significantly correlated with E1AF expression. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of matrilysin was often co-localized. Antisense E1AF-transfected MKN45 gastric cancer cells expressed reduced levels of matrilysin and were less invasive in vitro than mock-transfected MKN45 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of matrilysin, plays a key role in the progression of gastric cancer.

Adenovirus E1A Proteins↗
PubMed2003

Genetic blockade of the insulin-like growth factor-I receptor: a promising strategy for human pancreatic cancer.

Pancreatic cancer is one of the most lethal malignant tumors. Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for maintenance of growth and tumorigenicity of many tumors, but this pathway has not been well studied in pancreatic cancer. We have shown previously successful therapy in colorectal and lung cancer xenograft models using recombinant adenoviruses expressing dominant negative IGF-I receptors. In this study, we sought to better dissect the mechanism of action of this virus and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human pancreatic cancer cells. Truncated IGF-I receptors (IGF-Ir/dn; 482 and 950 amino acids long, respectively, IGF-Ir/482st and IGF-Ir/950st) that function as dominant negative inhibitor were cloned into recombinant adenoviruses and used to treat human pancreatic cancer cells. We assessed the effect of IGF-Ir/dn on signaling blockade, growth, stress response, chemotherapy, radiation-induced apoptosis, and in vivo therapeutic efficacy in xenografts. IGF-Ir/dn expression suppressed tumorigenicity both in vitro and in vivo and up-regulated stressor-induced apoptosis. It effectively blocked both IGF-I and IGF-II-induced activation of Akt-1. IGF-Ir/dn expression increased radiation and chemotherapy-induced apoptosis, and the combination therapy of IGF-Ir/dn with chemotherapy was very effective against tumors in mice. In an i.p. model, IGF-Ir/dn therapy reduced dissemination and prolonged survival times. Moreover, IGF-Ir/482st was more effective than IGF-Ir/950st because of its bystander effect. The antitumor activity of IGF-Ir/dn is mediated through inhibition of Akt-1 and enhances the efficacy of chemotherapy. Adenovirus-IGF-Ir/482st may be a useful anticancer therapeutic for pancreatic cancer.

Adenoviruses, Human↗
PubMed2003

Association of trypsin expression with tumour progression and matrilysin expression in human colorectal cancer.

Overexpression of the matrix serine protease (MSP) trypsin has been implicated in tumour growth, invasion, and metastasis. The objective of this study was to clarify the clinicopathological and prognostic significance of trypsin expression in colorectal cancer. This study analysed the association between immunohistochemically detected trypsin expression in colorectal cancer and clinicopathological characteristics, and investigated whether trypsin is a predictor of recurrence and/or survival. Trypsin immunoreactivity was more intense at the invasive front than in the superficial part of the tumour. Sections with immunostaining signals in more than 30% of carcinoma cells at the invasive front, which were observed in 48 cases (48%), were judged to be positive for trypsin. Trypsin positivity was significantly correlated with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advanced pathological tumour-node-metastasis (TNM) stage, and recurrence. Patients with trypsin-positive carcinoma had significantly shorter overall and disease-free survival periods than did those with trypsin-negative carcinoma. Trypsin retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors. It is well known that trypsin activates matrilysin (matrix metalloproteinase-7), which plays an important role in colorectal cancer progression. Patients with concordant overexpression of trypsin and matrilysin at the invasive front, in which they were often co-localized, had the worst prognosis. Trypsinogen-1-transfected HCT116 colon cancer cells showed not only trypsin activity, but also active matrilysin activity and were more invasive in vitro than mock-transfected HCT116 cells. These results suggest that trypsin plays a key role in the progression of colorectal cancer. Detection of trypsin expression as well as matrilysin is useful for the prediction of recurrence in and poor prognosis of colorectal cancer patients.

Aged↗
PubMed2003

Association of ets-related transcriptional factor E1AF expression with tumour progression and overexpression of MMP-1 and matrilysin in human colorectal cancer.

Expression of E1AF/PEA3 (ETV4), an ets family transcription factor, has been implicated in the invasive potential of several cancer cell lines through induction of matrix metalloproteinase (MMP) expression. The aim of this study was to examine E1AF mRNA expression and to determine whether it is correlated with progression of, and/or MMP expression in, human colorectal cancer. Using the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), 100 colorectal cancer tissues were analysed for E1AF mRNA expression. Expression of ER81 (ETV1) and ERM (ETV5), the other two members of the PEA3 subfamily, and Ets-1 and Ets-2 was also analysed. The results were correlated with clinicopathological characteristics and MMP expression. Immunohistochemical analysis and an in vitro invasion assay were also performed. E1AF mRNA expression was detected in 62% of the 100 colorectal cancer tissues, but was undetectable or only faintly detected in adjacent non-tumour tissues. E1AF mRNA was detected in all of the ten liver metastases from colorectal cancers. E1AF expression correlated significantly with depth of invasion, lymphatic and venous invasion, lymph node and distant metastasis, advance in pathological tumour-node-metastasis stage, and recurrence. Patients with E1AF-positive tumours had significantly shorter overall and disease-free survival periods than did those with E1AF-negative tumours (p < 0.0001 and p < 0.0001, respectively). E1AF expression retained its significant predictive value for overall and disease-free survival in multivariate analysis that included conventional clinicopathological factors (p = 0.0066 and p = 0.0109, respectively). Among the MMPs analysed, expression of MMP-1 and matrilysin correlated significantly with E1AF expression. In contrast, expression of ER81 and ERM did not correlate with clinicopathological characteristics or the expression of these MMPs. Immunohistochemical expression of E1AF was predominantly observed at the invasive front, where the expression of MMP-1 and matrilysin and nuclear beta-catenin expression were often co-localized. Antisense E1AF-transfected HT-29 colon cancer cells expressed reduced levels of MMP-1 and matrilysin and were less invasive in vitro than neo-transfected HT-29 cells. The results of this study suggest that E1AF, the expression of which is closely correlated with the expression of MMP-1 and matrilysin, plays a key role in the progression of colorectal cancer.

Adenocarcinoma↗
PubMed2003

The expression of matrix metalloproteinase matrilysin indicates the degree of inflammation in ulcerative colitis.

BACKGROUND: Any alteration in the synthesis and breakdown of the extracellular matrix is important in tissue remodeling during inflammation and wound healing. The degradation of the extracellular matrix components is regulated by a cascade of matrix metalloproteinases (MMPs). The present study attempted to assess the relationship between MMPs and the degree of inflammation in ulcerative colitis. METHODS: The expression of MMPs, including MMP-1, -2, -3, -7 (matrilysin), and -9, and that of their inhibitors (tissue inhibitor of metalloproteinases [TIMP]-1 and -2) were analyzed immunohistochemically by using 52 formalin-fixed and paraffin-embedded specimens from patients with ulcerative colitis who had undergone a biopsy or surgery. RESULTS: It was observed that MMP-1, -2, and -9, and the TIMPs were expressed in stromal cells, MMP-3 was expressed in both the epithelial cells and stromal components, and matrilysin was expressed only in the epithelial cells on the edge of ulcers. The expression of the MMPs was increased compared with that of the TIMPs. The frequency of matrilysin expression was increased corresponding to the severity of the inflammation. Matrilysin was also expressed in epithelial cells with dysplasia and cancer. CONCLUSIONS: Matrilysin expression could be an important marker of activity and could be used for the prediction of subsequent transformation in patients with ulcerative colitis.

Adolescent↗
PubMed2003

A novel RDH5 gene mutation in a patient with fundus albipunctatus presenting with macular atrophy and fading white dots.

PURPOSE: To report a novel homozygous RDH5 gene mutation in a 76-year-old fundus albipunctatus who developed macular atrophy with the disappearance of white dots. DESIGN: Observational case report. METHODS: Direct genomic sequencing for RDH5 mutations was done after complete ophthalmic examination. RESULTS: Fundoscopy revealed only macular atrophy with notable absence of white dots. A homozygous G490T (Val164Phe) missense RDH5 gene mutation was detected. CONCLUSIONS: This is the first reported long-term case of fundus albipunctatus demonstrating macular atrophy with fading of the typical white dots. Gene studies may be the only method for distinguishing fundus albipunctatus from other types of macular atrophy in the elderly.

Aged↗
PubMed2003

Serial measurement of serum S-100B protein as a marker of cerebral damage after cardiac surgery.

BACKGROUND: We used serial measurements of serum S-100B protein to evaluate the time course of serum S-100B protein concentration after cardiovascular surgery and to determine the clinical relevance of its concentration and cerebral damage. METHODS: We assessed neurologic function in 149 patients undergoing cardiovascular surgery with cardiopulmonary bypass. The patients were classified into three groups according to their early postoperative outcome: those without complications (group A), those having unconsciousness or convulsion or both but no hemiplegia (group B), and those having unconsciousness and hemiplegia either with or without convulsion (group C). Serum S-100B protein concentrations were measured with a commercially available immunoluminometric assay, Sangtec 100 LIA, at seven time-points: before cardiopulmonary bypass, at the end of cardiopulmonary bypass, and at 5, 12, 24, 48, and 72 hours after cardiopulmonary bypass. RESULTS: At 5 hours after cardiopulmonary bypass, the S-100B values in groups B and C were significantly higher than the value in group A. Although the S-100B level decreased in group C during the first 5 hours after cardiopulmonary bypass, it increased thereafter (12 through 24 hours) and continued at a high level until the final measurement at 72 hours. At 12 hours after cardiopulmonary bypass, S-100B was significantly higher in group C than in group B. This late increase in S-100B was associated with radiologically detected abnormalities and cerebral damage. CONCLUSIONS: Serial measurement of serum S-100B protein in the initial 12 hours after cardiopulmonary bypass can be used to predict early postoperative brain injury.

Aged↗
PubMed2003

Solid-state 13C and 1H spin diffusion NMR analyses of the microfibril structure for bacterial cellulose.

To obtain further information about the cause for the rather large splitting of the C4 resonance line into the downfield (C4D) and upfield (C4U) lines in CP/MAS 13C NMR spectra for native cellulose, 13C and 1H spin diffusion measurements have been conducted by using different types of bacterial cellulose samples. In 13C spin diffusion measurements, the C4D resonance line is selectively inverted by the Dante pi pulse sequence and the 13C spin diffusion is allowed to proceed from the C4D carbons to other carbons including the C4U carbons with use of the 13C4-enriched bacterial cellulose sample. The analysis based on the simple spin diffusion theory for the process experimentally observed reveals that the C4U carbons may be located at distances less than about 1 nm from the C4D carbons. In 1H spin diffusion measurements, poly(vinyl alcohol) (PVA) films in which ribbon assemblies of bacterial cellulose are dispersed are employed and the 1H spin diffusion process is examined from the water-swollen PVA continuous phase to the dispersed ribbon assemblies by the 13C detection through the 1H-13C CP technique. As a result, it is found that the C4D and C4U carbons are almost equally subjected to the 1H spin diffusion from the PVA phase, indicating that the C4U carbons are not localized in some limited area, e.g. in the surfacial region, but are distributed in the whole area in the microfibrils. These experimental results suggest that the C4U carbons may exist as structural defects probably due to conformational irregularity associated with disordered hydrogen bonding of the CH(2)OH groups in the microfibrils.

Acetobacter↗
PubMed2003

Green mussel Perna viridis L.: attachment behaviour and preparation of antifouling surfaces.

The green mussel Perna viridis LINNE can be kept in simulated seawater for more than 6 months in good condition. The mussel forms many threads by secreting an adhesive protein from the foot, and attaches with more than 50 byssal threads, which makes most mussels clump together. In order to investigate the preparation of the antifouling surfaces toward green mussels, the attachment of mussels was tested using glass surfaces modified with silane coupling agents, together with non-treated material surfaces such as glass and silicone. The correlation between the attachment percentage and the mean number of the secreted byssus was highly significant, indicating that the mussel selects a favorable surface prior to the secretion of byssus. The relationships between the mussel attachment and the surface chemical parameters (surface free energy (sfe) and its dispersion and polar components) were examined based on a working hypothesis, which we have previously reported. The result of statistical regression test indicated that a certain correlation was found between the dispersion component and the mussel attachment, while the polar component did not correlate to the mussel attachment. The present surface chemical approach provided an additional clue for the preparation of ecologically clean antifouling materials that takes into account the combination of the wettability of both the marine adhesive proteins (MAP) and the modified surfaces.

Animals↗
PubMed2003

Characterization of a hydroperoxide lyase gene and effect of C6-volatiles on expression of genes of the oxylipin metabolism in Citrus.

A number of C6-volatile products of the lipoxygenase (LOX) pathway was examined for their antifungal activity and a potential role as a signal molecule in citrus. trans-2-Hexenal induced the rough lemon lipoxygenase gene (RlemLOX), hydroperoxide lyase gene (RlemHPL) and AOS gene, but hexanal, and hexanol suppressed them. cis-3-Hexenol and trans-2-hexenol increased expression of the AOS gene but not RlemLOX and RlemHPL. Transcripts of the RlemHPL and AOS gene were detected constitutively in leaves by northern blot, but wounding or inoculation with nonpathogenic Alternaria alternata rapidly increased the transcript accumulation. Transcripts of the RlemHPL and AOS genes were also induced with pathogenic A. alternata, which produces the host-selective ACR-toxin, but the signal declined rapidly after inoculation. An increase in enzymatic activity of HPL after wounding or inoculation with nonpathogen was suppressed in leaves infected with the pathogen. Interestingly, vapor treatment with trans-2-hexenol delayed necrotic spot formation in the leaves inoculated with the pathogenic A. alternata. Since trans-2-hexenol has no antifungal activity to A. alternata and also did not inhibit necrosis formation by ACR-toxin alone, the delay of symptoms may be caused by activation of AOS in the LOX pathway to produce oxylipin derivatives such as methyl jasmonate for activation of defense related genes with antifungal activity.

Aldehyde-Lyases↗
PubMed2003

[Serotypes and antibody levels of group B streptococci in pregnant women].

Group B streptococcus were isolated from 1404 pregnant out-patient women in the Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, from June 1, 1992 to May 31, 2001. Serotype of 187 (13.3%) fresh isolates of GBS was determined by using hemolytic streptococcus-typing immune sera (Denka Seiken, Tokyo, Japan). With these strains there were 59 (31.6%), 46 (26.6%), 19 (10.2%), 16 (8.6%), 16 (8.6%), 12 (6.4%) and 3 (1.6%) indicating that their types were VIII, VI, III, Ia, V, Ib and II respectively. Also, bacterial agglutination reaction was employed for detection of titer to GBS in pregnant women serum. Positive reaction showed in 31 (57.4%) samples but 23 (42.6%) samples were not seen in this essay. It is assumed that the high antibody levels in pregnant women serum plays an important role as an in vivo defence factor in neonatal infection by GBS.

Antibodies, Bacterial↗
PubMed2003

Metabolism and disposition of novel des-fluoro quinolone garenoxacin in experimental animals and an interspecies scaling of pharmacokinetic parameters.

Garenoxacin is a novel quinolone that does not have a fluorine substituent at the C-6 position in the quinoline ring. Garenoxacin or 14C-garenoxacin was intravenously or orally administered to rats, dogs, and monkeys. Metabolic profiles and pharmacokinetic parameters were investigated focusing on the species differences and the allometric scaling of pharmacokinetic parameters. Garenoxacin was well absorbed following oral administration then underwent phase II metabolism in all species tested. Major metabolites of garenoxacin were the sulfate of garenoxacin (M1) and glucuronide (M6). Oxidative metabolites were present in very minor concentrations in all species tested. Another minor route of metabolism was the formation of the carbamoyl glucuronide. Garenoxacin is characterized across species by the observation that it circulates systemically, is excreted renally as unchanged drug, and is metabolized to M1 and M6, which are excreted specifically into the bile. The total clearances (CL) were 12.1, 2.43, and 3.39 ml/min/kg for rats, dogs, and monkeys, respectively. The distribution volume values of garenoxacin (Vss) were 0.88, 1.29, and 0.96 l/kg for rats, dogs, and monkeys, respectively. In all animals tested, the extrarenal clearance was larger than the renal clearance, and neither of the clearances was limited by blood flow. Despite these conditions, garenoxacin showed a good correlation for CL and Vss for allometric interspecies scaling.

Animals↗
PubMed2003

[A case of pseudoscleroderma as paraneoplastic syndrome due to carcinoma of cervical uteri].

A 65-year-old female began experiencing arthralgia, morning stiffness and psychroesthesia in April 2000. She visited a rheumatologist and was suspected of having early-stage rheumatoid arthritis. She was referred to our hospital, and was admitted in December 2000. At that time, sclerosis of the skin was advanced, and Raynaud's phenomenon was confirmed. The patient also exhibited nailfold bleeding, and was diagnosed as having systemic scleroderma. She visited a gynecologist for screening and cervical uteri carcinoma was confirmed. She underwent surgery in March 2001, and subsequently, sclerosis in her skin was almost stopped. We believe that these clinical symptoms were related to paraneoplastic syndrome. We therefore immunochemically investigated the pathogenesis of paraneoplastic syndrome and found that connective tissue growth factor (CTGF) might be involved and transforming growth factor-beta (TGF-beta) might not be involved in this case.

Aged↗
PubMed2003

[Usefulness of CT-perfusion in acute cerebral infarction].

CT-perfusion (CTP) examination was performed in 30 cases of acute cerebral infarction (ACI) caused by middle cerebral artery (MCA) occlusion. Data were analyzed using cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). The results of the affected side were compared with those of the other side in terms of relative value and difference. A high correlation in relative value was found between CBF and CBV (r=0.81) and in both the relative (r=0.76) and difference (r=0.77) value between CBF and MTT. No correlation was seen between CBV and MTT. The time-density curve, along with CBF, CBV, and MTT, was classified into three patterns of ischemic brain damage: collateral, delayed, and flat patterns. In conclusion, CT-perfusion examination is useful for determining a treatment plan in ACI.

Acute Disease↗