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Biomedical subjects

S Eguchi

Publications and source records attributed to S Eguchi.

At least 19 recordsLinked to original sources
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

Adiponectin versus angiotensin II: Key pathological role of their misbalance.

Kurata et al. report that an angiotensin II type-1 receptor blocker (ARB) inhibits obesity-induced hypoadiponectinemia in rats through inhibition of reactive oxygen species generation. Taken together with the recently reported functional interplay between adiponectin and angiotensin II, this suggests that adiponectin probably mediates tissue-protective effects of ARBs in obesity and metabolic syndrome.

Adiponectin↗
PubMed2004

Search for low-mass exoplanets by gravitational microlensing at high magnification.

Observations of the gravitational microlensing event MOA 2003-BLG-32/OGLE 2003-BLG-219 are presented, for which the peak magnification was over 500, the highest yet reported. Continuous observations around the peak enabled a sensitive search for planets orbiting the lens star. No planets were detected. Planets 1.3 times heavier than Earth were excluded from more than 50% of the projected annular region from approximately 2.3 to 3.6 astronomical units surrounding the lens star, Uranus-mass planets were excluded from 0.9 to 8.7 astronomical units, and planets 1.3 times heavier than Saturn were excluded from 0.2 to 60 astronomical units. These are the largest regions of sensitivity yet achieved in searches for extrasolar planets orbiting any star.

Journal Article↗
PubMed2004

Genotyping of single nucleotide polymorphism using model-based clustering.

MOTIVATION: Single nucleotide polymorphisms have been investigated as biological markers and the representative high-throughput genotyping method is a combination of the Invader assay and a statistical clustering method. A typical statistical clustering method is the k-means method, but it often fails because of the lack of flexibility. An alternative fast and reliable method is therefore desirable. RESULTS: This paper proposes a model-based clustering method using a normal mixture model and a well-conceived penalized likelihood. The proposed method can judge unclear genotypings to be re-examined and also work well even when the number of clusters is unknown. Some results are illustrated and then satisfactory genotypings are shown. Even when the conventional maximum likelihood method and the typical k-means clustering method failed, the proposed method succeeded.

Algorithms↗
PubMed2004

Influence of serum from rats with fulminant hepatic failure on hepatocytes in a bioartificial liver system.

Fulminant hepatic failure (FHF) is a life-threatening condition marked by many excessively increased unmetabolized toxins and growth factors. Recently developed bioartificial liver (BAL) systems containing hepatocytes can be used to treat patients with FHF However, the behavior of these hepatocytes on exposure to FHF serum in vitro remains unclear. In the present study, we used FHF rat models and the sera from these rats (i.e., FHF serum) contained elevated inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), HGF, and TGF-beta1. In addition, 1x10(8) hepatocytes were harvested from the livers of inbred rats and incubated with microcarrier beads. Four hours later, the hepatocyte-coated beads were inoculated into a hollow-fiber module (=BAL system). FHF serum or normal control serum circulated for 6 hours through the BAL system. Expressions of mRNA for albumin, GST A1, CYP 1A2, OTC and c-fos were investigated by RT-PCR, and PCNA staining was performed before and after perfusion. The expressions of albumin, GST A1, and CYP 1A2 mRNAs were markedly decreased, whereas those of OTC and c-fos were modestly decreased. PCNA positive cells were low and showed no difference between FHF and normal serum-exposed hepatocytes. In conclusion, the exposure of hepatocytes to hypercytokinemia, including inflammatory cytokines and positive and negative growth factors, caused a loss in liver specific functions. This environment also failed to facilitate hepatocyte regeneration.

Animals↗
PubMed2003

Metalloprotease-dependent ErbB ligand shedding in mediating EGFR transactivation and vascular remodelling.

AngII (angiotensin II) and its G-protein-coupled AT(1) receptor play critical roles in mediating cardiovascular diseases such as hypertension, atherosclerosis and restenosis after vascular injury. It is widely believed that AngII promotes these diseases by inducing vascular remodelling that involves hypertrophy, hyperplasia and migration of VSMCs (vascular smooth muscle cells). We have shown that transactivation of an ErbB family receptor, EGFR (epidermal growth factor receptor; ErbB1), is essential for VSMC hypertrophy and migration induced by AngII. However, the precise signal transduction mechanism by which AngII transactivates EGFR/ErbB1 and whether other ErbBs are also required for AngII function remains unclear. Recent studies suggest an involvement of a metalloprotease-dependent ErbB family ligand production in the transactivation. Here, we will discuss the roles and mechanisms of AngII/AT(1) receptor in promoting ErbB receptors transactivation in VSMCs. Further elucidation of this ErbB activation machinery not only will give us a better understanding of the critical molecular mechanism underlying vascular remodelling stimulated by AngII, but will also contribute to development of novel treatment strategies for cardiovascular diseases.

Animals↗
PubMed2001

Unique regulation of c-Jun N-terminal kinase by PYK2/CAK-beta in angiotensin II-stimulated vascular smooth muscle cells.

Activation of tyrosine kinases is believed to play a central role in angiotensin II (AngII) signaling. Here, we have investigated whether a tyrosine kinase, PYK2, is functionally involved in AngII-induced c-Jun N-terminal kinase (JNK) activation in vascular smooth muscle cells (VSMCs). Adenovirus expressing PYK2 kinase-inactive mutant K457A or a tyrosine phosphorylation site mutant Y402F was transfected in VSMCs. AngII-induced JNK phosphorylation was markedly enhanced by K457A, whereas it was suppressed by Y402F. Protein synthesis induced by AngII was also enhanced by K457A and inhibited by Y402F. In this regard, K457A suppressed PYK2 kinase activation by AngII, whereas it enhanced AngII-induced PYK2 Tyr(402) phosphorylation. By contrast, Y402F inhibited PYK2 Tyr(402) phosphorylation, whereas it markedly enhanced AngII-induced PYK2 kinase activation. Thus, we conclude that PYK2 kinase activity negatively regulates JNK activation and protein synthesis, whereas Tyr(402) phosphorylation positively regulates these events in AngII-stimulated VSMCs, suggesting a unique role of PYK2 in mediating vascular remodeling.

Adenoviridae↗
PubMed2001

N-acetylcysteine inhibits angiotensin ii-mediated activation of extracellular signal-regulated kinase and epidermal growth factor receptor.

Angiotensin II (Ang II) is known to stimulate reactive oxygen species (ROS) generation and epidermal growth factor (EGF) receptor transactivation to mediate growth-promoting signals such as extracellular signal-regulated kinase (ERK) in vascular smooth muscle cells (VSMCs). However, how ROS and EGF receptor interact to orchestrate these signals in VSMCs remains unclear. Here we found that an antioxidant, N-acetylcysteine, inhibited ERK activation and EGF receptor tyrosine phosphorylation induced by Ang II. Moreover, H(2)O(2) stimulates EGF receptor tyrosine phosphorylation and EGF receptor inhibitors attenuated H(2)O(2)-induced ERK activation. These data indicate that ROS mediate Ang II-induced EGF receptor transactivation, a critical mechanism for ERK-dependent growth in VSMCs.

Acetylcysteine↗
PubMed2001

Attenuated familial adenomatous polyposis associated with advanced rectal cancer in a 16-year-old boy: report of a case.

We herein present a case of attenuated familial adenomatous polyposis (AFAP) with advanced rectal cancer in a 16-year-old boy. His mother and younger brother both had subcutaneous soft tissue tumors in the back and sparse-type colorectal polyposis. His mother also had dental anomalies and gastric fundic gland polyposis. The patient was admitted to our hospital for investigation of bloody stools. Barium enema and colonofiberscopy revealed advanced rectal cancer and sparse (<50) colorectal polyps. He also had dental anomalies, a subcutaneous soft tissue tumor in the back, and gastric fundic gland polyposis as extracolonic manifestations. A total proctocolectomy and ileoanal anastomosis were performed, and histological examination of the resected specimens confirmed moderately differentiated adenocarcinomas of the rectum with metastases to the regional lymph nodes. The other colorectal polyps were tubular adenomas with no evidence of malignancy. Germline mutations in the APC gene were observed in codons 486, 545, 1493, and 1556. This case serves to demonstrate that a total proctocolectomy with ileoanal anastomosis should be the procedure of choice for young patients found to have advanced rectal cancer associated with FAP.

Adenocarcinoma↗
PubMed2001

Piggyback foldable intraocular lens implantation in patients with microphthalmos.

PURPOSE: To evaluate the clinical results of phacoemulsification and implantation of 2 foldable acrylic intraocular lenses (IOLs) in microphthalmic eyes. SETTING: University of Tokyo School of Medicine, Tokyo, Eguchi Eye Hospital, Hakodate, and Osaka Rosai Hospital, Osaka, Japan. METHODS: This study comprised 5 eyes of 3 patients whose manifest spherical equivalent was +10.5 to +18.0 diopters (D) and axial length was 15.79 to 16.82 mm. After phacoemulsification, 2 foldable acrylic IOLs with a mean power of +43.0 D +/- 9.5 (SD) (range +32.0 to +55.0 D) were implanted in the capsular bag. RESULTS: There were no significant intraoperative complications, and there was significant improvement in uncorrected and best corrected visual acuities after surgery. The spherical equivalent decreased significantly; however, the postoperative refraction was considerably more hyperopic than predicted in all eyes. Except for posterior synechias in 2 eyes and slight interlenticular opacification in 2 eyes, no major postoperative complications occurred during the mean follow-up of 14.8 months. CONCLUSIONS: Implanting 2 piggyback IOLs was beneficial in eyes with an extremely short axial length. However, the current system of lens power calculation markedly underestimates the required lens power, resulting in a hyperopic refractive error after surgery. The benefits of in-the-bag placement of 2 foldable lenses are questionable.

Acrylic Resins↗
PubMed2001

[Long-term results of valve-retaining homograft and xenograft patch for transannular reconstruction of the right ventricular outflow tract in tetralogy of Fallot].

Thirteen patients with tetralogy of Fallot underwent reconstruction for hypoplastic right ventricular outflow tract using a preserved homograft or xenograft patch with single or double cusps. Homografts and xenografts preserved in 70% ethanol were implanted in 10 patients, and xenografts treated with glutaraldehyde were used in 3 patients. All the patients are doing well in their profession without one who died 18 years after operation. Valve-retaining homograft and xenograft patches provided excellent early hemodynamic function, but did not prevent pulmonary insufficiency late after the operation. Both homograft and xenograft cusps tended to degenerate several years after implantation, but cusp failure was not accompanied by outflow stenosis.

Adolescent↗
PubMed2001

Protein kinase C inhibits insulin-induced Akt activation in vascular smooth muscle cells.

Protein kinase C (PKC) activation, enhanced by hyperglycemia, is associated with many tissue abnormalities observed in diabetes. Akt is a serine/threonine kinase that mediates various biological responses induced by insulin. We hypothesized that the negative regulation of Akt in the vasculature by PKC could contribute to insulin resistant states and, may therefore play a role in the pathogenesis of cardiovascular disease. In this study, we specifically looked at the ability of PKC to inhibit Akt activation induced by insulin in cultured rat aortic vascular smooth muscle cells (VSMCs). Activation of Akt was determined by immunoblotting with a phospho-Akt antibody that selectively recognizes Ser473 phosphorylated Akt. A PKC activator, phorbol 12-myristate 13-acetate (PMA), inhibited insulin-dependent Akt phosphorylation. However, PMA did not inhibit platelet-derived growth factor (PDGF)-induced activation of Akt. We further showed that the PKC inhibitor, G06983, blocked the PMA-induced inhibition of Akt phosphorylation by insulin. In addition, we demonstrated that PMA inhibited the insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). From these data, we conclude that PKC is a potent negative regulator of the insulin signal in the vasculature, which indicate an important role of PKC in the development of insulin resistance in cardiovascular disease.

Animals↗
PubMed2000

Activation of MAPKs by angiotensin II in vascular smooth muscle cells. Metalloprotease-dependent EGF receptor activation is required for activation of ERK and p38 MAPK but not for JNK.

In cultured vascular smooth muscle cells (VSMC), the vasculotrophic factor, angiotensin II (AngII) activates three major MAPKs via the G(q)-coupled AT1 receptor. Extracellular signal-regulated kinase (ERK) activation by AngII requires Ca(2+)-dependent "transactivation" of the EGF receptor that may involve a metalloprotease to stimulate processing of an EGF receptor ligand from its precursor. Whether EGF receptor transactivation also contributes to activation of other members of MAPKs such as p38MAPK and c-Jun N-terminal kinase (JNK) by AngII remains unclear. In the present study, we have examined the effects of a synthetic metalloprotease inhibitor BB2116, and the EGF receptor kinase inhibitor AG1478 on AngII-induced activation of MAPKs in cultured VSMC. BB2116 markedly inhibited ERK activation induced by AngII or the Ca(2+) ionophore without affecting the activation by EGF or PDGF. BB2116 as well as HB-EGF neutralizing antibody inhibited the EGF receptor transactivation by AngII, suggesting a critical role of HB-EGF in the metalloprotease-dependent EGF receptor transactivation. In addition to the ERK activation, activation of p38MAPK and JNK by AngII was inhibited by an AT1 receptor antagonist, RNH6270. and EGF markedly activate p38MAPK, whereas but not EGF markedly activates JNK, indicating the possible contribution of the EGF receptor transactivation to the p38MAPK activation. The findings that both BB2116 and AG1478 specifically inhibited activation of p38MAPK but not JNK by AngII support this hypothesis. From these data, we conclude that ERK and p38MAPK activation by AngII requires the metalloprotease-dependent EGF receptor transactivation, whereas the JNK activation is regulated without involvement of EGF receptor transactivation.

Angiotensin II↗
PubMed2000

Signal transduction of angiotensin II type 1 receptor through receptor tyrosine kinase.

In cultured vascular smooth muscle cells, the angiotensin II (AngII) type-1 (AT(1)) receptor generates growth-promoting signals via the epidermal growth factor (EGF) receptor system. This 'transactivation' mechanism now appears to be utilized by a variety of G-protein-coupled receptors in many cells. The AngII-induced EGF receptor transactivation leads to activation of downstream signaling molecules including Ras, ERK, c-fos, Akt/protein kinase B, and p70 S6 kinase. We propose three possible mechanisms may be involved in the transactivation, (i) an upstream tyrosine kinase, (ii) reactive oxygen species, and (iii) a juxtacrine activation of the EGF receptor ligand. Whether the EGF receptor signal transduction induced by AngII plays an essential role in cardiovascular remodeling remains to be investigated.

Animals↗
PubMed2000

Synergistic effect of anti-T cell receptor monoclonal antibody and 15-deoxyspergualin on cardiac xenograft survival in a mouse-to-rat model.

BACKGROUND: Successful xenograft transplantation faces several obstacles including the presence of xenoantibodies, natural killer cell- and macrophage-mediated rejection, and T lymphocyte activation. METHODS: A mouse-to-rat cardiac xenograft model was used to examine the synergistic effect of anti-T cell receptor (TCR) monoclonal antibodies (mAb) and 15-deoxyspergualin (DSG) on graft survival. RESULTS: Pretransplantation injections (days -5, -3, and -1) of anti-TCR mAb (500 microg/kg/day) combined with continuous i.p. infusion of DSG (5 mg/kg/day) from day -7 to 28 significantly prolonged graft survival compared to untreated controls (3.3+/-0.5 vs. 44.2+/-5.6 days, P<0.001). Postoperative splenectomy combined with discontinuation of all other treatment on day 28 enhanced graft survival in rats treated with anti-TCR mAb and DSG to 71.0+/-2.5 days. Histological examination of grafts showed characteristic signs of vascular rejection: interstitial edema and hemorrhage, and polymorphonuclear cell infiltration. Antimouse antibody titers in recipients were increased upon rejection in each group that received a xenograft. Flow cytometry analysis showed a markedly decreased T cell population and a relatively increased mature B cell population (IgM(bright)/IgD(dull)) in spleens of rats treated with anti-TCR mAb and DSG on day 28. CONCLUSIONS: The mechanism of prolonged xenograft survival in this model may include inhibition of antibody production by arrest of B-cell maturation during development from IgM(dull)/IgD(bright) mature B cells to antibody producing cells, and inhibition of T cell activation. The rejection seen in our model may be caused by xenoreactive antibodies and may be associated with T cells, natural killer cells, and macrophages.

Animals↗
PubMed2000

PYK2/CAKbeta represents a redox-sensitive tyrosine kinase in vascular smooth muscle cells.

In vascular smooth muscle cells (VSMCs), the focal adhesion kinase-related tyrosine kinase PYK2/CAKbeta is activated by vascular mitogens. Because reactive oxygen species (ROS) are assumed to mediate mitogenic signals by these agonists, we examined the possible link between ROS and PYK2 in cultured rat VSMCs. Here we present several lines of evidence showing that PYK2 is activated by ROS in VSMCs. The inhibitory effect of an antioxidant, N-acetyl-cysteine, on PYK2 activation by its specific agonists further suggests the pivotal role of PYK2 in vascular remodeling associated with enhanced ROS production.

Animals↗
PubMed2000

MRI facilitated a diagnosis of endometriosis of the rectum.

A 51-year-old pre-menopausal Japanese woman suffering from chronic lower abdominal pain was referred to our hospital. A barium enema showed a stenotic lesion in the recto-sigmoid region, and a pelvic computed axial tomography (CAT) scan revealed a thickened rectal wall. A colonoscopic examination showed the rectum to be constrictive, but the mucosa appeared to be intact. Magnetic resonance imaging (MRI) with T1 high-intensity revealed a cystic lesion in the thickened wall of the rectum, which led us to suspect possible bowel endometriosis. Part of the biopsy specimen showed endometrial epithelium within the interstitial layer of histologically normal mucosa; finally, endometriosis of the rectum was diagnosed. The patient became asymptomatic after the initiation of hormonal treatment and later experienced spontaneous menopause. MRI was effective for diagnosis and the patient did not undergo unnecessary laparotomy. Although bowel endometriosis is generally diagnosed by means of resected specimens, in our patient, diagnosis was made using MRI and biopsy, and hormonal therapy had an effective role as a bridge to menopause.

Biopsy↗