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Biomedical subjects

S Matsui

Publications and source records attributed to S Matsui.

At least 127 records · Page 7Linked to original sources

Deletion of Epstein-Barr virus latent membrane protein 1 gene in Japanese and Brazilian gastric carcinomas, metastatic lesions, and reactive lymphocytes.

A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Information on this deletion in EBV-associated gastric carcinoma (EBVaGC) is limited. The association of gastric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) in situ hybridization in 510 patients from Japan and 80 patients from Brazil. We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the corresponding EBER1-positive metastatic lesions in lymph nodes (10 cases) and EBV-infected reactive lymphocytes from dissected nonmetastatic lymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction products obtained after amplification with primers flanking the site of the deletion. We also performed EBV typing and LMP1 protein immunohistochemistry. EBV DNA was amplified by polymerase chain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV-associated GC cases with EBER1-positive lymphocytes. The 30-bp LMP1 gene deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japan and two of four (50%) cases of Brazilian EBVaGC as compared with EBER1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases and 9 of 12 (75%) cases of non-EBV-associated GC. The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the same among reactive lymphocytes, primary and secondary lesions of EBVaGC in all cases for which all three tissue types were studied (six of six). There was no correlation between the presence of the 30-bp deletion with depth of cancer invasion or presence of metastasis. Type A was detected in all available EBV-positive cases. The similar high incidence of 30-bp deletion in LMP1 gene in both carcinoma cells and reactive lymphocytes in EBVaGC cases suggests that this deletion may not be relevant to the pathogenesis of EBVaGC.

Adult↗

[Objective assessment of subjective symptom in chronic heart failure].

Objective assessment of subjective symptoms in patients with chronic heart disease (CHF) is useful not only in determining severity and prognosis, but also in evaluating the effects of therapy. Recently anaerobic threshold (AT) was introduced as an objective index for functional capacity. We began by evaluating the AT for assessing functional capacity in patients with CHF, using the cardiopulmonary exercise test. In this study, patients with CHF tended to show low values of VO2 at AT. Furthermore, VO2 at AT was decreased in accordance with the increasing severity of the NYHA classification. These results indicate that VO2 at AT can be used as an objective and reliable index for evaluating the functional capacity in patients with CHF. Decreased functional capacity is a major clinical problem in patients with CHF and is associated with skeletal muscle fatigue and/or dyspnea. Secondly, we observed the oxygenation of both working skeletal and respiratory muscles during exercise, using near-infrared spectroscopy to study the factors contributing to exercise limitation of CHF. In this study, the oxygenation profile of exercising skeletal muscle was similar to that of respiratory muscle, but the former showed anaerobic metabolism at an earlier stage of exercise than the latter. In patients with CHF this phenomenon was more prominent than that in normal subjects. These results indicate that near-infrared spectroscopy might be useful in objective assessment of subjective symptoms, namely skeletal muscle fatigue and dyspnea, in patients with CHF.

Anaerobic Threshold↗

Cardioprotective effects of beraprost sodium against experimental ischemia and reperfusion as compared with propranolol and diltiazem.

We compared the cardioprotective effects during experimental ischemia and reperfusion of beraprost sodium (beraprost), a prostacyclin analog, with those of propranolol and diltiazem. Coronary perfused guinea-pig right ventricular free wall preparations were subjected to 30 min no-flow ischemia with or without drugs, followed by 60 min reperfusion without drugs. In control preparations, decrease in contractile force and increase in resting tension were observed during the no-flow period. On reperfusion, contractile force returned to less than 50% of preischemic values. Beraprost, at 0.1 microM, showed no inotropic effect under normoxic condition and during the no-flow period, but significantly enhanced the recovery of contractile force after reperfusion to about 80% of control values. Propranolol (30 microM) or diltiazem (10 microM) produced similar enhancement of recovery of contractile force after reperfusion, but these two drugs decreased the contractile force under normoxic conditions to less than 20% of control values. Thus, the cardioprotective effect of beraprost was different from those of propranolol and diltiazem in that it was not accompanied by cardiosuppressive effects.

Animals↗

[Analysis of 18 breast cancer patients with hypercalcemia].

A total of 91 breast cancer patients died of advanced and recurrent breast cancer at the Osaka Teishin Hospital from 1986 to 1996. There were 18 cases (19.8%) among them showing hypercalcemia (serum corrected Ca > or = 11.0 mg/dl). These 18 cases were analyzed to determine the incidence of hypercalcemia and to find a more effective treatment. All these patients had multiple bone metastases during their clinical course, and six patients (33.3%) had pathologic bone fracture just before the occurrence of hypercalcemia. Their common symptoms were general fatigue, gastrointestinal symptoms, renal dysfunction or neurological symptoms. There was no definitive correlation between clinical signs and serum calcium values. Among various therapies, the use of pamidronate disodium (Aredia) in combination with hydration, steroid and calcitonin was found to be the most effective treatment for hypercalcemia. The survival time from the diagnosis of hypercalcemia in the patients undergoing treatment with Aredia was significantly better than without it (p < 0.01). This suggests that Aredia should be effective and useful for advanced breast cancer patients with hypercalcemia.

Adult↗

[Chronic necrotizing pulmonary aspergillosis resistant to antimycotic drugs and treated by partial pulmonary resection].

A 46-year-old man with a history of left upper lobectomy for pulmonary tuberculosis was admitted to our hospital because of dilated cardiomyopathy. During hospitalization, fever and weight loss developed. The cause was suspected to be a round mass inside a cavity and a neighboring infiltrative shadow in the left upper lung field as seen on chest radiography. A percutaneous needle biopsy was done, and examination of the specimen showed an aggregate of Aspergillus fumigatus hyphae. Fluconazole (FCZ) was injected through an intracavitary catheter every day, and was then given by mouth. Treatment with FCZ was effective temporarily. However, he was again admitted to our hospital because of lower extension of the cavity and deteriorated inflammatory findings. From the clinical course, chronic necrotizing pulmonary aspergillosis was diagnosed. Treatment with all available antifungal agents did not improve his condition. Although he had decreased cardiac function due to dilated cardiomyopathy, partial pulmonary resection was done. The cavity with the fungus ball was resected completely. As of the time of this writing, he remains free of aspergillosis.

Antifungal Agents↗

Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain.

BACKGROUND: Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. To examine whether cardiac glycosides also modulate cytokine production, we evaluated the effects of ouabain on the production of cytokines in vitro and in vivo. METHODS AND RESULTS: Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers. PBMC were cultured with or without ouabain in the presence or absence of lipopolysaccharide (LPS). Ouabain induced the production of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in PBMC and induced mRNA of these cytokines, an induction apparently at the transcriptional level. Amiloride, staurosporin, and genistein inhibited cytokine production, and protein kinase C and tyrosine kinase appeared to be involved in the modulation of cytokine production induced by ouabain. However, when PBMC were stimulated with LPS, ouabain suppressed the production of IL-6 and TNF-alpha. To investigate whether ouabain modulates cytokine production in vivo, we evaluated the effects of ouabain in LPS-treated mice. Ouabain was found to protect against LPS-induced lethal toxicity in mice and decreased circulating IL-6 and TNF-alpha levels in vivo. CONCLUSIONS: These previously unrecognized immunomodulating effects of a cardiac glycoside may explain either the beneficial or the detrimental effects of these drugs in heart failure patients.

Animals↗

Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production.

BACKGROUND: Although calcium channel blockers have not been shown to be beneficial for the treatment of patients with heart failure, a recent clinical trial demonstrated a favorable effect of amlodipine on the survival of patients with heart failure resulting from nonischemic dilated cardiomyopathy. We investigated the effects of amlodipine on a murine model of congestive heart failure induced by the M variant of encephalomyocarditis virus (EMCV). METHODS AND RESULTS: Four-week-old male DBA/2 mice were inoculated with EMCV and administered amlodipine, diltiazem, or vehicle PO for 2 weeks. The heart weight-to-body weight ratio and the histopathological grades of myocardial lesions were significantly lower and survival was significantly increased in the amlodipine-treated group (P < .01, P < .05, and P < .05, respectively) than in the control group. In vitro, amlodipine added to murine J774A.1 macrophages concomitant with EMCV inhibited nitrite formation in a concentration-dependent manner, but diltiazem did not. Furthermore, NG-monomethyl-L-arginine, an inhibitor of NO synthesis, decreased myocardial lesions significantly in this murine model. Immunohistochemistry revealed that the number of cells stained with antibody against an inducible NO synthase decreased significantly in the amlodipine-treated group compared with that in the control group (P < .01). CONCLUSIONS: Amlodipine appears to have a protective effect against myocardial injury in this animal model of congestive heart failure. The therapeutic effect of amlodipine may be in part resulting from inhibition of overproduction of NO.

Amlodipine↗

Prolongation of murine cardiac allograft survival with vesnarinone.

Vesnarinone is a non-glycoside positive inotropic drug that has immunomodulating actions. In the present study, the effects of vesnarinone on both cardiac allografts and lymphocytes were investigated. First, in a mouse model of primary vascularized heterotopic cardiac transplantation, the oral vesnarinone treatment at a dose of 50 mg/kg/day prolonged median graft survival time significantly as compared with the vehicle-treated control. Histopathological examination revealed that cellular infiltration and interstitial edema were less prominent in the vesnarinone-treated than in the vehicle-treated allografts. The plasma concentrations of vesnarinone in mice treated with a single dose of 50 mg/kg were within the range of clinical relevance. To clarify the mechanism of action, in vitro studies were performed. The generation of specific cytotoxic T lymphocytes in mixed lymphocyte culture was significantly suppressed by the treatment with vesnarinone, especially at 3 and 10 microg/ml. The production of interferon-gamma in the co-culture was also suppressed by 10 microg/ml vesnarinone. However, the level of cyclic adenosine monophosphate was not significantly affected by vesnarinone at 10 microg/ml. The results suggest that vesnarinone acts beneficially on rejecting cardiac allografts through its lymphocyte-suppressive property, although this property may not be closely associated with the inhibiting action of the drug on the cyclic adenosine monophosphate-phosphodiesterase enzyme.

Adjuvants, Immunologic↗

Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits.

An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of either beta-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n = 10), a group immunized with the peptide corresponding to the beta-adrenoceptor (beta 1 group) (n = 10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n = 10). If the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in the beta 1 group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to the beta 1 group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the sex control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy, induces morphological changes in the heart similar to those found in the human disease.

Amino Acid Sequence↗

Effects of extracellular ATP on cytosolic Ca2+ concentration and secretory responses in rat parotid acinar cells.

At concentrations >50 microM, extracellular ATP dose-dependently increased cytosolic Ca2+ concentration ([Ca2+]i) via activation of P(2Z) purinoceptors in rat parotid acinar cells. This increase in [Ca2+]i is primarily due to entry of Ca2+ from the extracellular medium. Inositol trisphosphate formation and Ca2+ release from intracellular Ca2+ stores were slightly stimulated by ATP. These responses seem to result from the activation of a P2 purinoceptor subtype different from P(2Z) because the maximum responses were induced by much lower concentrations ( <0.25 mM) of ATP than those (> 1 mM) required to produce the maximum activation of Ca2+ entry. ATP did not stimulate amylase release, supporting the view that an increase in [Ca2+]i is not a sufficient stimulus. In addition, ATP evoked a marked K+ release in the presence and absence of extracellular Ca2+, while in carbachol-stimulated cells. only a transient release of K+ was observed in the absence of extracellular Ca2+. The ATP-induced K+ release may be mediated by a mechanism independent of the opening of the Ca(2+)-sensitive K+ channels.

Adenosine Triphosphate↗

Evaluation of prognostic factors following expansive laminoplasty for cervical spinal stenotic myelopathy.

BACKGROUND: Expansive laminoplasty of several types has been proposed for patients with cervical multisegmental stenotic myelopathy to reduce postlaminectomy complications. Its effectiveness has not been fully explored by evaluating long-term results and magnetic resonance imaging (MRI) findings before and after surgery. METHODS: We conducted a 5-year follow-up study of 22 patients with cervical spondylotic myelopathy and/or ossification of the posterior longitudinal ligament surgically treated with expansive laminoplasty. The operative results were examined using the Japanese Orthopedic Association (JOA) disability scale, with reference to the findings of MRI, computed tomography, and radiography. RESULTS: Postoperative improvement was observed in 18 (81.8%) of the 22 patients. In 11 patients the percentage recovery of the JOA score was higher than 50% (average: 83.1%), while in the remaining 11 patients it was lower than 50% (average: 20.1%). Factors contributing to incomplete recovery appear to be related mainly to cord degeneration with atrophy (depicted as a T2-high intensity area) and to specific factors such as long symptom duration, age higher than 70 years, deterioration due to trauma, severe cord compression, radiculopathy, and kyphotic cervical curvature. CONCLUSIONS: In cervical myelopathy, patients with multisegmental stenosis, expansive laminoplasty can be expected to provide a favorable outcome by providing sufficient cord decompression and stabilization of the cervical spine, when the stenotic cervical canal is enlarged to the normal range (over 12 mm residual anteroposterior diameter and 200 mm2 residual canal area). The efficacy can be restricted by various factors, especially irreparable cord degeneration.

Aged↗

Expression, localization and alternative splicing pattern of fibronectin messenger RNA in fibrotic human liver and hepatocellular carcinoma.

BACKGROUND/AIMS: Fibronectin is a multifunctional glycoprotein and plays important roles in cell-to-cell or cell-to-matrix interaction. The molecular and functional diversity of fibronectin arises from alternative splicing of pre-mRNA at three variable regions, termed ED-A, ED-B and IIICS. Cellular fibronectin with ED-A and ED-B regions has different biological activities from plasma fibronectin lacking these regions. This study was aimed at investigating the type-specific expression of fibronectin in human liver diseases. METHODS: Immunohistochemistry with anti-total and anti-cellular fibronectin monoclonal antibodies, in situ hybridization with cDNA probes detecting common and ED-A regions and RT-PCR to amplify each variable region were performed in 35 specimens, including 4 control, 16 chronic hepatitis, 7 liver cirrhosis and 8 hepatocelular carcinoma. RESULTS: In control liver, there were slight deposits of cellular fibronectin [ED-A(+)fibronectin] in portal areas. In chronic hepatitis, it was strongly deposited at the margin of the fibrously enlarged portal areas where new collagen fibers were formed. Cellular fibronectin was evenly and abundantly accumulated in fibrotic septa in liver cirrhosis, and in fibrotic septa and capsules of tumor nodules in hepatocellular carcinoma. In control liver, cellular fibronectin mRNA was localized in a few hepatocytes and non-parenchymal cells around central veins, and was increased in the same cell populations near fibrously enlarged portal areas as hepatic fibrosis progressed. In hepatocellular carcinoma, it was expressed in most hepatoma cells. Fibronectin mRNA with three variable regions was detectable by RT-PCR in control liver as well as in each disease group. CONCLUSIONS: The expression of cellular fibronectin was increased in fibrotic human liver and hepatocellular carcinoma. In human liver, both non-parenchymal cells and hepatocytes participated together in cellular fibronectin production. In hepatocellular carcinoma, hepatoma cells were the main producer. Our results indicate that, in human liver, cellular fibronectin may participate in the hepatic fibrogenesis and in the malignant phenotypes of hepatocellular carcinoma.

Alternative Splicing↗

Fast imaging of the second moment using magic echo trains.

Approaches are discussed to imaging of the second moment of proton NMR dipolar spectra. Two methods are proposed using the peak shapes of the magic echo trains for evaluation of the second moment. One is a quasi-multidimensional FT approach where the peak shapes of the magic echoes are spatially resolved, and the other is the fast version of the former approach, collecting the same data in a much shorter measurement time. Preliminary results of spatially 2D, as well as 1D, experiments are reported.

Fourier Analysis↗

A unique response to staphylococcal enterotoxin B by intrahepatic lymphocytes and its relevance to the induction of tolerance in the liver.

It has been reported that the intrahepatic lymphocyte (IHL) population is somewhat differently constituted from lymphocytes in other lymphoid tissues. Staphylococcal enterotoxin B (SEB) is a superantigen which can induce T-cell tolerance in mice. The authors investigated the in vitro and in vivo responses of mouse IHL to SEB. An intravenous injection of SEB did not result in the augmentation of the proliferative response of IHL, while mesenteric and splenic lymphocytes (mLNC and SPC, respectively) had augmented responses. Interleukin-2 (IL-2) mRNA was clearly detected in mLNC and SPC by reverse transcriptase-polymerase chain reaction (RT-PCR) shortly after the administration of SEB, but it was scarcely expressed in IHL. The expression of CD25 (IL-2 receptor) was also augmented in mLNC and SPC in the early period, while it was not changed in IHL. These findings suggested that the time required for tolerance induction is different locally and that the loss of augmentation of IL-2 and IL-2 receptor production by IHL may be relevant to the rapid induction of T-cell tolerance in the liver.

Animals↗

Appraisal of combination treatment for hepatocellular carcinoma: long-term follow-up and lipiodol-percutaneous ethanol injection therapy.

Since 1988, 124 patients with hepatocellular carcinoma were treated in our departments. Among them, 31 cases treated by surgical resection and 30 cases administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte, France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-, and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy group. The follow-up results at less than 4 years after the procedures revealed that the survival rate with the combination therapy was slightly better than that with the surgical treatment. However, in the subsequent 4 years, the survival rate of the combination therapy group decreased rapidly. The reasons for this deterioration were local recurrence and/or new primary lesions of hepatocellular carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the ethanol so that the location of the injected ethanol could be easily confirmed. The effectiveness of L-PEIT was thus confirmed by computed tomography, performed on the following day. Defective Lipiodol accumulation in the tumor and/ or neighboring tissues was able to be corrected by additional ethanol injections. With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore, a better prognosis is expected.

Antibiotics, Antineoplastic↗

Augmentation of natural killer cell activity induced by cytomegalovirus infection in mice treated with FK506.

Comparable rates of patient and graft survival after FK506 and cyclosporine treatments have been reported in the prevention of liver allograft rejection. On this basis, we examined the effect of FK506 on pathogenesis of cytomegalovirus (CMV) infection in mice. FK506 induced apparent immunosuppression in mice which could be monitored by the level of antibody production. The effective dose of trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) for 50% reduction in antibody production was 0.9 mg/kg. Even in such an immunosuppressed status at this or higher dose of FK506, CMV infection was relatively alleviated, which was observed by the frequency of virus isolation and the mean virus titer of the lungs of mice treated with 0.1-1 mg/kg FK506 in comparison to untreated mice. The dose of FK506 attaining 50% frequency of lung infection was 1.5 mg/kg. The activity of natural killer (NK) cells was enhanced in infected mice. This enhancement was stronger in infected mice treated with FK506 at 0.32 mg/kg and 10 mg/kg than in untreated infected mice on day 3 post infection (p.i.). Thus, an immunosuppressant FK506 augmented inducible NK cell activity and alleviated MCMV infection even under immunosuppression.

Animals↗

[A case of pulmonary arteriovenous fistula presenting as multiple brain abscesses after a sustained period without treatment].

A 64-year-old man was admitted to our hospital with multiple brain abscesses accompanied by pulmonary arteriovenous fistula (PAVF). He had been diagnosed with PAVF eight years previously, but had refused any treatment despite a developing exertional dyspnea. Rendu-Osler-Weber disease was diagnosed as well because the patient exhibited teleangiectasis of the nasopharyngeal mucosa and persistent gastro-intestinal bleeding. Despite administration of antibiotics and corticosteroids the abscesses perforated into the lateral ventricle. The natural history of this rare disease is still incompletely understood. Thus, the time at which treatment should be commenced remains unclear. However the natural course of PAVF is unsatisfactory, and it appears that treatment by surgery and/or embolization should be considered in all cases.

Arteriovenous Fistula↗