Biomedical subjects

S Motoyama

Publications and source records attributed to S Motoyama.

At least 19 recordsLinked to original sources

PubMed2001

Localization of a novel susceptibility gene for familial ovarian cancer to chromosome 3p22-p25.

We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was >50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.

Adult↗

PubMed2001

Cancer of the gastric tube reconstructed through the posterior mediastinal route after radical surgery for esophageal cancer.

Among 750 patients diagnosed with esophageal carcinoma in our department between 1972 and 1997, we reviewed our 10 cases in which cancer occurred within gastric tubes reconstructed through the posterior mediastinal route after radical surgery for esophageal cancer. The interval between esophagectomy and cancer onset in the reconstructed gastric tube was relatively long (mean interval: 72 months). Five of our 10 subjects had gastric tube cancer detected at follow-up endoscopy. Four underwent total or partial gastric tube resection with open thoracotomy using colonic or jejunal reconstruction; 3 underwent endoscopic resection. To the best of our knowledge, this is the first report on patients undergoing total resection of gastric tubes reconstructed through the posterior mediastinal route after esophagectomy and rereconstruction using the pedicled colon for the gastric tube cancer.

Aged↗

PubMed2001

Relationship between thrombolytic therapy and perfusion defect detected by Gd-DTPA-enhanced fast magnetic resonance imaging in acute myocardial infarction.

To study whether thrombolytic therapy affects Gd-DTPA-enhanced pattern and whether its pattern indicates myocardial viability, Gd-DTPA-enhanced magnetic resonance imaging (MRI) was performed in 43 patients with reperfused acute myocardial infarction 14.8+/-5.0 days after onset with breathhold scanning on a 1.5-T whole body system. The hypoenhanced area at 90 sec after contrast injection was defined as a perfusion defect (PD). Patients were divided into PD(+) and PD(-) groups. The PD was detected in 77.8% of patients treated with direct percutaneous transluminal coronary angioplasty (PTCA) and in 28.6% of patients treated by thrombolytic therapy with or without PTCA in the thrombolysis in myocardial infarction grade 3 group (p < 0.05). The myocardial wall was divided into seven segments based on the American Heart Association committee report. Wall motion of each segment was classified by one of six patterns (wall motion score [WMS]: dyskinesis, -1; akinesis, 0; severe hypokinesis, 1; hypokinesis, 2; slight hypokinesis, 3; normal, 4). By echocardiography, the average WMS and ejection fraction were similar between the PD(+) group and the PD(-) group on admission. Those parameters were significantly worse in the PD(+) group than in PD(-) group 1 month after onset. The change in WMS was significantly lower in the PD(+) group than in the PD(-) group. The number of patients and segments with more than two grades of improvement of WMS in the PD(+) group was significantly lower than that in the PD(-) group. Angiographically, left ventricular ejection fraction and WMS of the PD(+) group were significantly lower than those of the PD(-) group 3 months later. PDs were detected significantly less frequently in patients treated with thrombolytic therapy, suggesting that microvascular embolization related to formation of the no-reflow phenomenon.

Aged↗

PubMed2001

Super high-dose intraarterial cisplatin infusion under percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma: I. Analysis for pharmacokinetics, tumor response, and toxicity of platinum.

The present study was designed to elucidate the clinical feasibility of a new intraarterial infusion system with an extracorporeal charcoal chemofiltration circuit, which is expected to achieve a super high-dose cisplatin pelvic perfusion with a limited systemic exposure to platinum. After inferior vena cava isolation was percutaneously achieved by balloon catheter technique, cisplatin (140-240 mg/m2) was administered by selective intrauterine arterial infusion, with inferior and superior gluteal arterial embolization. The platinum-containing blood was pumped through an extracorporeal charcoal chemofiltration circuit. Pharmacokinetics, tumor response, and toxicity of platinum under this system were studied in 14 patients with locally advanced uterine cervical carcinoma. Extracorporeal charcoal filters significantly (p < 0.05) reduced the prefilter area under concentration-time curve of plasma-free platinum by 86.7 +/- 5.2% at postfilter site and 76.3 +/- 6.6% at peripheral circulation, respectively. Although all adverse effects were mild under this system, tumor response and tissue platinum concentrations were augmented dose dependently with the administration of cisplatin. The extracorporeal chemofiltration system achieved a super high-dose cisplatin pelvic perfusion with the minimal adverse effects, allowing further cisplatin dose escalation with further augmented tumor response. This will contribute to the reduction in the extent of disease of locally advanced uterine cervical carcinoma.

Adenocarcinoma↗

PubMed2001

Super high-dose intraarterial cisplatin infusion under percutaneous pelvic perfusion with extracorporeal chemofiltration for advanced uterine cervical carcinoma: II. Its impact on clinical response and subsequent surgery.

The present pilot study was conducted to investigate the clinical efficacy of super high-dose intraarterial cisplatin infusion with percutaneous pelvic perfusion under extracorporeal chemofiltration (PPPEC) for locally advanced uterine cervical carcinoma. Cisplatin (140-240 mg/m2) was infused in uterine arteries in a neoadjuvant setting in 20 patients under the PPPEC system twice during a 2-week interval. Fourteen of 17 patients in whom reduction of the disease (tumor downstaging) was confirmed underwent radical surgery. Despite the tumor downstaging, the remaining three patients had poor PS and the other three showed insufficient stage regression. Clinical responses, histologic responses, and surgical review were studied. The rate of overall tumor response (complete response plus partial response), tumor downstaging, overall histologic response, and radical surgery performance after the second course of PPPEC were 95.0%, 85.0%, 95.0%, and 70.0%, respectively. Curative surgery, defined as negative carcinoma cells in surgical margins, was achieved in 85.7% of the cases, whereas the rate of complete surgery defined as negative carcinoma cells both in surgical margins and regional lymph nodes was 42.9%. With 42 months of median follow-up time, 3 of the 14 surgical patients died of the original disease, and the remaining 9 patients are in recurrence-free survival, whereas 2 patients are alive with disease. PPPEC achieved a high frequency of rapid tumor downstaging of locally advanced uterine cervical carcinoma without severe adverse effects and resulted in the favorable performance of the subsequent radical surgery and prognosis.

Adenocarcinoma↗

PubMed2001

Abundant expression of platelet-derived growth factor in spiral arteries in decidua associated with pregnancy-induced hypertension and its relevance to atherosis.

OBJECTIVE: To elucidate the role of platelet-derived growth factor (PDGF) in the pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral arteries of the decidua demonstrate the atherosclerotic change. DESIGN AND METHODS: We determined serum levels of PDGF and PDGF expression in the decidua as well as serum levels of 17 beta-estradiol (E2) and progesterone (P4) both in normotensive cases and in PIH cases. Furthermore, we investigated whether sex steroid hormones could interact with PDGF in cultured vascular smooth muscle cells (SMC) by immunohistochemical staining for proliferating cell nuclear antigen. RESULTS: Serum PDGF levels were higher (P<0.01) but serum E2 levels were lower (P<0.01) in PIH cases compared with normotensive cases. There was no statistically significant difference between serum P4 levels in PIH cases and those in normotensive cases. Immunohistochemical staining for PDGF in SMC of spiral arteries was more prominent in PIH cases than in normotensive cases. The proliferative potential of cultured SMC was stimulated by PDGF, but inhibited by concomitant treatment with PDGF and E2. CONCLUSIONS: PDGF is suggested to play an important role in the pathophysiology of PIH through its stimulatory effect on vascular SMC proliferation which may elicit the atherosclerotic change in the spiral arteries of the placenta.

Adult↗

PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗

PubMed2000

A clinical study of surgical treatment of patients with carcinoma of the cervical esophagus extending to the thoracic esophagus.

OBJECTIVE: We studied optimum surgery for carcinoma of the cervical esophagus extending to the thoracic esophagus (Ce-Ut carcinoma). METHODS: Subjects were 13 patients diagnosed with Ce-Ut carcinoma treated at our institute from January 1989 to December 1998. Clinicopathologic information such as surgical procedures, pathologic findings, and postoperative complications were analyzed. RESULTS: In 10, laryngoesophagectomy was conducted due to tracheal invasion by the tumor. In 7, mediastinal tracheostomy was done because of the extended resection of the proximal trachea. In 3, the larynx was preserved and, in 2, cricopharyngeal myotomy was added. Lymph node metastasis was found only in the neck and the upper mediastinum at surgery and recurrences were all lung metastasis. The incidence of postoperative complications was very high (76.9%), and 1 patient died due to widespread tracheal necrosis. The cumulative 5-year survival rate for the group was 33.3% and that for the 9 curative cases was 50%, but most of the cases who underwent noncurative resection and/or who received preoperative therapy for widespread invasion to surrounding organs died within a year. CONCLUSION: The prognosis of patients who undergoing curative extended resection of the proximal trachea and suitable lymph node dissection in the neck and upper mediastinum may improve, and larynx-preserving surgery is recommended for patients without tracheal invasion. Despite preoperative chemoradiotherapy, the prognosis of patients with widespread invasion to surrounding organs was very poor, and clinical studies on new therapeutic strategies for these advanced cases are needed to improve the prognosis of Ce-Ut carcinoma patients.

Adult↗

PubMed2000

Does central venous pressure reflect the circulating blood volume for the decrement of compliance just after esophagectomy?

This study investigates whether the pressure parameters obtained from the Swan-Ganz catheter (SGC) accurately reflect the circulating blood volume just after en bloc resection of the thoracic esophagus with regional lymph node dissection. It is well known that this operation induces severe hemodynamic changes and although the pressure parameters obtained from the SGC are an accepted means of monitoring circulating blood volume, we have often experienced a discrepancy between the SGC data and the clinical state. We examined the pressure parameters and diameter of the inferior vena cava (IVC) and left ventricle (LV), and the central venous compliance using SGC and echocardiography in ten patients who underwent esophagectomy for esophageal cancer. The central venous pressure, pulmonary arterial mean pressure, and pulmonary artery wedged pressure were significantly increased just after the operation compared with the preoperative levels, while the diameters of the IVC and LV decreased just after the operation. The compliances of the IVC decreased significantly just after the operation. The hemodynamic shift to the third space after esophagectomy induces decrement of the compliances of IVC. As the CVP does not always reflect the circulating blood volume, measuring the diameter of the IVC using echocardiography is extremely useful for monitoring circulating blood volume just after esophagectomy.

Blood Volume↗

PubMed2000

Red blood cells attenuate sinusoidal endothelial cell injury by scavenging xanthine oxidase-dependent hydrogen peroxide in hyperoxic perfused rat liver.

AIMS/BACKGROUND: Rat liver perfused with an oxygenated buffered solution alone results in degenerative changes even when the perfusion flow is accelerated to give a sufficient oxygen supply. On the other hand, perfusion media supplemented with red blood cells (RBCs) preserve the viability of the liver. The present study was conducted to clarify how RBCs protect the isolated perfused liver. METHODS: The liver was perfused with and without RBCs in a perfusate equilibrated with supra-physiological oxygen tension at regulated inflow pressures, and controlled hepatic oxygen consumption. We examined alanine aminotransferase and purine nucleoside phosphorylase activity in the perfusate as specific markers of liver cells injury. Hydrogen peroxide (H2O2) production and morphological changes were determined using cerium electron microscopy. Apoptosis was detected by measuring CPP 32 protease activity and using TdT-mediated dUTP-digoxigenin nick end-labeling. RESULTS: When the liver was perfused with RBC-free buffer, H2O2 production and consequent injury progressing to apoptosis were initiated in the sinusoidal endothelial cells (SECs). After SECs were injured, H2O2 appeared in the hepatocytes. H2O2 production and associated degenerative changes were attenuated both morphologically and enzymatically by the addition of RBCs, a specific xanthine oxidase (XOD) inhibitor and the H2O2 radical scavenger, catalase. CONCLUSIONS: In the liver perfused with RBC-free buffer, H2O2 production and consequent injury were initiated in SECs. RBCs attenuate liver injury by scavenging XOD-dependent H2O2.

Alanine Transaminase↗

PubMed2000

Effects of new polymer-coated extracorporeal circuits on biocompatibility during cardiopulmonary bypass.

An inflammatory response due to bioincompatibility of extracorporeal circuits is a major clinical issue during cardiopulmonary bypass (CPB). By using a swine model, we determined whether new polymer-coated circuits, the blood-contacting surfaces of which are coated with poly(2-methoxyethylacrylate) (PMEA), would reduce the inflammatory response during CPB. Plasma bradykinin levels and the percentages of CD35-positive monocytes in PMEA-coated circuits were significantly lower than those in uncoated circuits during CPB. The amount of proteins adsorbed on the PMEA-coated circuits was significantly lower than that on the uncoated circuits (0.30 microg/cm2 versus 3.42 microg/ cm2). Almost no IgG, IgM, or C3c/d was detected in proteins adsorbed on the PMEA-coated circuits although these proteins were clearly detected in proteins adsorbed on the uncoated circuits. We concluded that PMEA coating could reduce complement activation during CPB by suppressing the adsorption of IgG and IgM, which activate C3 via the classical pathway, on the surface of the circuits.

Acrylates↗

PubMed2000

Hydrogen peroxide induces midzonal heat shock protein 72 and apoptosis in sinusoidal endothelial cells of hypoxic rat liver.

OBJECTIVE: To investigate the heat shock protein (HSP) 72 expression and apoptosis induced by hydrogen peroxide in hypoxic rat liver. DESIGN: Prospective control study using the isolated rat liver. SETTING: Animal research facility. SUBJECTS: Fasted, pathogen-free specific, male Sprague-Dawley rats. INTERVENTIONS: A low-flow hypoxia model was made by reducing an afferent pressure from 10 to 2.5 cm H2O, and by perfusing the isolated rat liver for 2 hrs. MEASUREMENT AND MAIN RESULTS: We investigated the hydrogen peroxide production by using the 2'-7' dichlorofluorescein image, the induction of HSP 72 by using immunohistochemistry, and apoptosis by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling method in the low flow hypoxic rat liver. In low-flow hypoxia, hydrogen peroxide production, HSP 72 expression, and apoptosis were induced in the midzone of rat liver. Prevalence of HSP 72 expression was higher in the sinusoidal endothelial cells (SEC) than in the hepatocytes. All apoptotic cells were SEC with expression of HSP 72. Hydrogen peroxide was derived from hepatocytes. Pretreatment with the specific xanthine oxidase inhibitor, sodium(-)-8-(3-methoxy-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate significantly attenuated hydrogen peroxide production, HSP 72 expression, and apoptosis of SEC in the midzone. CONCLUSION: Xanthine oxidase-dependent hydrogen peroxide induces midzonal and SEC-dominant HSP 72 expression and apoptosis in hypoxic rat liver.

Animals↗

PubMed1999

The effective removal of proinflammatory cytokines by continuous hemofiltration with a polymethylmethacrylate membrane following severe burn injury: report of three cases.

The serum levels of proinflammatory cytokines were investigated in three patients with severe burn injuries complicated by sepsis and pulmonary edema, who were treated with continuous hemofiltration (CHF) using a polymethylmethacrylate (PMMA) membrane. All patients had suffered burn injuries to more than 30% of their total body surface area (TBSA) and had burn indexes of 20 or more. Both interleukin (IL)-6 and tumor necrosis factor-alpha were detectable in one patient, while the serum IL-6 levels were elevated in the remaining two patients. The serum cytokines decreased 24 h after the initiation of CHF. Determinations of IL-6 in inflow and outflow blood samples as well as in the filtration fluid revealed that IL-6 was ultrafiltrated and/or adsorbed by the filter. Two of the three patients did not survive. Nevertheless, the results of this study indicate that since burn injuries are frequently associated with hypercytokinemia, the removal of cytokines by CHF with a PMMA membrane may be effective in the management of severe burn injuries.

Adult↗

PubMed1999

Severe aspiration pneumonia after surgery for reconstructed gastric tube cancer treated with extracorporeal life support.

A 68-year-old man who had received resection for thoracic esophageal cancer 8 years ago, was operated on for the cancer of the reconstructed gastric tube. On the day of the operation, he accidentally swallowed gastric juice due to an obstruction in the reconstructed gastric tube. He suffered from acute hypoxic respiratory failure which could not be controlled with conventional therapy on postoperative day 1. Therefore, extracorporeal life support was employed at 3.0 L/min. extracorporeal flow for 11 days. Before extracorporeal life support data: PO2/FiO2 = 45, A-aDO2 = 600. During extracorporeal life support, the ventilator setting was pressure control (16 cmH2O) ventilation with a positive end expiratory pressure of 8 cmH2O, respiratory rate of 5 breaths/min., and FiO2 of 0.4. The patient was successfully weaned from extracorporeal life support and extubated on postoperative day 12. After extracorporeal life support data: PO2/FiO2 = 225, A-aDO2 = 465. We report on a successful weaning case from extracorporeal life support and discuss the efficacy these of regarding this patient.

Aged↗

PubMed1998

Bcl-2 is located predominantly in the inner membrane and crista of mitochondria in rat liver.

Bcl-2 is now recognized as a potent inhibitor of apoptotic cell death. It has been reported that Bcl-2 is located in the mitochondria, endoplasmic reticulum, and nuclear membrane in some cell lines, and it is not expressed in normal human and rat liver. An earlier study showed that Bcl-2 is an inner mitochondrial membrane protein. On the contrary, the following investigations using immunoelectron microscopy demonstrated that Bcl-2 resides predominantly in the mitochondrial outer membrane. In this study, using a cryo-sectioning immunogold labeling technique and immunoblotting, we carefully determined the subcellular localization of Bcl-2. Here we report that Bcl-2 is expressed in normal rat liver, and it is located predominantly in the inner membrane and crista rather than in the outer membrane of mitochondria.

Animals↗

PubMed1998

[An analysis of the mechanism of postoperative hyperbilirubinemia following resection of thoracic esophageal cancer in terms of hepatic venous oxygen saturation and excessive systemic reactions].

Hepatic venous oxygen saturation (ShvO2), parameters of systemic circulation and cytokine (Interleukin 6) (IL-6)) level were measured in 21 patients with thoracic esophageal cancer in order to analyze the mechanism of occurrence of postoperative hyperbilirubinemia (PHB). ShvO2 fell during operation, especially during intrathoracic procedures, and a significant correlation was noted between the total time during which ShvO2 was below 60% and the postoperative peak serum bilirubin level (peak-Bil) (r = 0.595, p = 0.0037). Patients with PHB (group H) had worse systemic circulation and a lower oxygen supply postoperatively than patients without PHB (group N). Body weight and water balance recovered earlier in group N. Postoperatively, numbers of peripheral lymphocytes and platelets changed lower in group H, while CRP and IL-6 changed higher in group H. Furthermore, a significant correlation was noted between the IL-6 level just after operation and peak-Bil (r = 0.669, p = 0.0006). These results suggests PHB results from intraoperative liver hypoxia and poor postoperative systemic circulation. Individual severeness of reactions to the operative stress, excessive or adequate, plays a role in the occurrence of PHB as well.

Aged↗

PubMed1998

Hydrogen peroxide derived from hepatocytes induces sinusoidal endothelial cell apoptosis in perfused hypoxic rat liver.

BACKGROUND & AIMS: Evidence is accumulating that hypoxic liver injury involves not only necrosis but also apoptosis. Reactive oxygen species can cause apoptosis. This study examined the hypothesis that H2O2 induces apoptosis in hypoxic rat liver. METHODS: Blood-perfused rat livers were made hypoxic by reducing the perfusion flow. H2O2 was detected by both 2',7'-dichlorofluorescein fluoroimaging and cerium electron-microscopic methods. To evaluate the apoptosis, the liver was stained with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method. To further investigate the involvement of H2O2 in hypoxia-induced liver cell apoptosis, small pieces of liver in the cultured media were exposed to 0.5 mmol/L of reagent H2O2 and stained with the TUNEL method. RESULTS: In the hypoxic liver, H2O2 was produced predominantly by hepatocytes, and the number of apoptotic nonparenchymal cells was significantly increased, particularly in the midzone. All the apoptotic cells were positively stained with monoclonal antibody against the hepatic sinusoidal endothelial cells (SECs). In incubated liver pieces, reagent H2O2 induced apoptosis selectively in SECs. CONCLUSIONS: Low-flow hypoxia induces H2O2 production in hepatocytes, and this H2O2 induces apoptosis selectively in SECs in the rat liver.

Animals↗

PubMed1998

Serum antibodies to human herpesvirus 7, human herpesvirus 6 and cytomegalovirus in patients with idiopathic facial nerve palsy or sudden deafness.

The aetiology of idiopathic facial nerve palsy (Bell's palsy) and sudden deafness are not known, although viruses have been suspected as a cause of them. We investigated the relationship between Bell's palsy or sudden deafness, and reactivation of cytomegalovirus, human herpesvirus 6 (HHV-6) and 7 (HHV-7). Paired sera were collected from 22 patients with Bell's palsy and 24 patients with sudden deafness. IgG antibody titres to HHV-7 were increased in one patient with Bell's palsy. IgG antibody titres to HHV-6 were increased in one patient with Bell's palsy and two with sudden deafness. IgG antibody titres to cytomegalovirus were increased in one patient with sudden deafness. Titres of the three viral antibodies were not increased simultaneously in any patients. These viruses may contribute to the development of Bell's palsy or sudden deafness in some cases. It is, however, unlikely that these viruses are the main cause of Bell's palsy and sudden deafness in the majority of patients.

Adolescent↗