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Biomedical subjects

Y Moriyama

Publications and source records attributed to Y Moriyama.

At least 19 recordsLinked to original sources

Circulating levels of secretory type II phospholipase A(2) predict coronary events in patients with coronary artery disease.

Background-The circulating levels of secretory nonpancreatic type II phospholipase A(2) (sPLA(2)) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA(2) may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA(2) may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA(2) were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA(2) levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA(2) (>246 ng/dL; 75th percentile of sPLA(2) distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA(2) were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA(2) is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA(2) levels with inflammatory activity in atherosclerotic arteries.

Aged

Association of plasma levels of activated protein C with recanalization of the infarct-related coronary artery after thrombolytic therapy in acute myocardial infarction.

Protein C is one of the most important antithrombotic components. After activation by the thrombin-thrombomodulin complex on endothelial cells, activated protein C (APC) inactivates factors Va and VIIIa, which leads to the inhibition of thrombin formation. We examined the association of plasma levels of APC with the responsiveness to coronary thrombolytic therapy of the infarct-related coronary artery in patients with acute myocardial infarction (AMI). Plasma levels of APC, thrombin-antithrombin III complex (TAT), and plasminogen activator inhibitor (PAI) activity were measured in 32 consecutive AMI patients who underwent coronary angiography followed by thrombolytic therapy, and compared to the measurements in 23 control subjects. On admission, APC levels (ng/mL) were significantly elevated in patients with AMI, as compared with controls (2.5+/-0.4 vs. 1.2+/-0.2, 1.3+/-0.2, respectively, p<0.01). At discharge, plasma levels in AMI patients decline to values not significantly different from those in controls. (1.2+/-0.2, 1.3+/-0.2, respectively). TAT levels (ng/mL) were different among the groups in a fashion similar to that of APC (14.1+/-3.1 on admission vs. 3.3+/-0.4 at discharge, 1.8+/-0.1 in the control subjects, respectively, p<0.01). PAI activity levels (IU/mL) were higher on admission than at discharge and higher than the control subjects (19.7+/-1.8 vs. 10.5+/-1.0, 5.4 +/- 0.7, respectively, p<0.01). Thirty-two patients with AMI were classified into two groups according to the results of thrombolysis: the success group (24 patients) and the failure group (eight patients). APC levels were higher in the failure group than in the success group (5.1+/-0.7 vs. 1.6+/-0.2, p<0.01). TAT levels were also higher in the failure group than in the success group (30.8+/-9.6 vs. 8.6+/-1.7, p<0.01). PAI activity levels (IU/mL) were lower in the failure group than in the success group (13.5+/-3.1 vs. 21.7+/-2.1, p<0.05). There were correlations between APC and TAT levels both on admission (r=0.75, p<0.0001) and at discharge (r=0.71, p<0.0001). Elevated APC was thought to correlate with increased thrombin generation in patients with AMI. This study demonstrated that there was a significant relation between plasma APC level and the responsiveness to thrombolytic therapy of the infarct artery. This study may also indicate that increased thrombin generation is a cause of the resistance to thrombolytic therapy.

Acute Disease

D-aspartate is present in human retinoblastoma Y79 cells.

In mammals, D-aspartate is present in various neuroendocrine cells, being especially abundant in pinealocytes. Although D-aspartate is suggested to be involved in some neuroendocrine function, little is known about its origins as well as its physiological roles. In the present study, we found that an appreciable amount of D-aspartate (50.8 pmol/1 x 10(6) cells) is present in clonal human retinoblastoma Y79 cells. The amount of D-aspartate corresponds to 28% of that in rat pinealocytes. The D-aspartate concentration did not change with the culture duration or passage, suggesting de novo biosynthesis of it. Thus, Y79 cells may constitute a suitable experimental system for studies on the biogenesis and signal transduction of D-aspartate in mammalian cells.

Animals

Functional expression of metabotropic glutamate receptor type 5 in rat pinealocytes.

Mammalian pinealocytes, endocrine cells for melatonin, express class II metabotropic glutamate receptors (mGluRs), which are involved in negative regulation of melatonin synthesis through an inhibitory cAMP cascade. We investigated whether mGluRs other than class II receptors are expressed in rat pinealocytes. RT-PCR analysis and Northern blotting indicated that the mRNA of mGluR5, a class I receptor, was present in pineal glands. Quisqualate and 1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), class I receptor agonists, increased the intracellular [Ca2+] of fura-2 loaded cultured pinealocytes in the absence of extracellular Ca2+ which is blocked by methylcarboxyphenylglycine, a class I receptor antagonist. These results suggest that mGluR5 is functionally expressed in pinealocytes and triggers Ca2+ efflux from intracellular stores.

Animals

Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus.

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.

Base Sequence

Application of a manifold system for temporary reperfusion during proximal anastomoses in conventional coronary bypass surgery.

We report the application of a manifold system which is attached to saphenous vein grafts after the completion of distal coronary anastomosis. This technique permits not only the direct delivery of cardioplegic solution into the distal coronary artery, but also the reperfusion of revascularized coronary arteries via saphenous vein grafts by changing the connection to the arterial circuit during proximal anastomosis under a partial occlusion of the aorta in conventional coronary artery bypass surgery.

Cardioplegic Solutions

Repair of an acute type A dissection: fate of the remnant false lumen and preserved aortic valve.

From January 1992 through March 1997, 75 patients (DeBakey type I/II = 56/19) underwent a surgical repair of a type A acute dissection. The patients included 37 men and 38 women ranging in age from 23 to 83 years with a mean of 65 years. All patients were admitted to our hospital with a mean interval of 2.2 days from the episode of onset. The overall hospital mortality rate was 25% (19/75). There were three late deaths among the 56 patients discharged from the hospital. The actuarial survival rate for the patients surviving the operation was 87% at 5 years after repair. A subsequent aortic operation was necessary in 6 patients, while 3 other patients who had late aortic complications were put on medical therapy alone. As a result, the aortic event-free survival rate was 54% at 5 years. For a type I dissection the false lumen was completely thrombosed after repair in 34%. The descending thoracic aorta with a patent false lumen was markedly enlarged in proportion to the follow-up time. After a conservative approach to the aortic valve, all but one patient demonstrated an adequate valve function throughout this study period. This experience with a midterm follow-up showed an acceptable durability of the preserved aortic valve and a progressive enlargement of the persistent false lumen with a high rate of aortic complications. Hence, all patients with a type A dissection need a close follow-up to assess the aorta for complications of either recurrent or residual aneurysms and dissections.

Acute Disease

Myxoma of mitral valve associated with infective endocarditis.

A 20-year-old man was hospitalized for persistent fever, embolism, and syncopal attack. Echocardiography demonstrated a tumor on the mitral posterior leaflet. It was removed under extracorporeal circulation following extirpation of thrombus in the right common like artery. The tumor consisted of myxoma and vegetation with bacterial colony. Myxoma and/or vegetation had destroyed the mitral posterior leaflet. Accordingly, it was necessary to perform mitral valve replacement. The postoperative course was uneventful. This is the 14th surgical case of mitral valve myxoma, and the first case of that associated with infective endocarditis.

Adult

Coronary artery aneurysm after stent implantation.

A coronary artery aneurysm that developed 6 months after coronary stent implantation in the left anterior descending artery, was treated by double coronary artery bypass grafting due to restenosis of the affected vessel and progression of right coronary artery stenosis. Although the poststenting aneurysm initially remained postoperative angiography showed that it had disappeared. In addition to thrombotic occlusion, another mechanism behind its disappearance may be that geometric changes of the implanted stent caused by heart retraction during surgery closed the entrance to the aneurysm.

Adult

Is direct closure dangerous for treatment of doubly committed subarterial ventricular septal defect?

BACKGROUND: We performed direct closure of doubly committed subarterial ventricular septal defects with aortic cusp prolapse. Postoperative echocardiographic studies showed that this method improved coaptation of the prolapsing aortic cusp, especially in patients with mild aortic regurgitation (AR). METHODS: Twenty-one patients (mean age, 7.8+/-4.3 years; range, 2 to 18 years) with doubly committed subarterial ventricular septal defect underwent direct closure alone. Aortic valve prolapse was observed in all 21 patients, with mild AR found in 13 patients but not in the remaining 8. The site of the prolapsed aortic valve was in the right coronary cusp in all patients. We inserted an interrupted 4-0 or 5-0 polypropylene suture with a pledget from the lower margin of the ventricular septal defect to the pulmonary ring to increase protrusion of the prolapsed cusp by pushing it back and to improve coaptation of the aortic cusp. RESULTS: The interval between surgical treatment and the last postoperative evaluation ranged from 3 to 24 months (median, 11 months). No residual ventricular septal defect was detected in any patient. In the 8 patients who had aortic valve prolapse without AR preoperatively, no AR was found at follow-up. Of the 13 patients who had mild AR associated with aortic valve prolapse preoperatively, AR diminished in 7 and did not progress in the remaining 6. Furthermore, no anatomic changes in either the aortic or pulmonary annulus were found on follow-up echocardiography. In the group of 13 patients with mild preoperative AR, AR significantly persisted in patients who were more than 10 years old at operation (p<0.05). CONCLUSIONS: Our findings suggest that direct closure for this type of ventricular septal defect is safe and reliable in improving mild AR and that direct closure is more effective for younger patients in whom the prolapsing aortic cusp is mobile enough to be protruded. However, further long-term follow-up studies will be needed to ascertain the adequacy and usefulness of the method.

Adolescent

Rubber-like elasticity and volume changes in the isolated spasmoneme of giant Zoothamnium sp. under Ca2+-induced contraction.

Using glycerinated spasmoneme of giant Zoothamnium sp., the physical properties of spasmoneme before and after Ca2+-induced contraction (pCa 4.5) were investigated. The volume change of spasmoneme contraction was measured under zero tension. The length and diameter decreased by about 50% of their initial value as a result of contraction, which means that contraction is nearly isotropic. Thus the volume of spasmoneme decreased drastically by 86% of its original value. The swollen ratio of extended and contracted spasmoneme were 0.07 and 0.37, respectively. Tension-extension relationships of extended and contracted spasmonemes were measured. By applying the theory of rubber elasticity, the number of segments of a chain in originally extended spasmoneme was only 3.3, i.e., the chain was almost a straight one. On the other hand, the number of segments of a chain in contracted spasmoneme was more than 100, i.e., the chain was essentially a random one. Furthermore, the total number of chains in single spasmoneme was the same in extended and contracted spasmoneme. This means that the interchain cross-links of chains were not influenced by addition or removal of Ca2+. Moreover, the molecular weight of a chain is estimated to be at most about 50 kd. By considering all these results, it is concluded that the contractile mechanism of spasmoneme originates in the intramolecular folding and unfolding induced by Ca2+ binding and detaching.

Animals

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.

OBJECTIVES: This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels. BACKGROUND: Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis. METHODS: Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients). RESULTS: Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.4% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05). CONCLUSIONS: Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction, in patients with high remnants levels.

Adult

Inactivation of both alleles of the DPC4/SMAD4 gene in advanced colorectal cancers: identification of seven novel somatic mutations in tumors from Japanese patients.

Loss of heterozygosity (LOH) of loci on chromosome 18q occurs in a majority of colorectal cancers. The DPC4/SMAD4 gene, lying in close proximity to the DCC gene at 18q21.1, was recently identified as a candidate tumor suppressor for the genesis of pancreatic cancer as well as a predisposing gene for Juvenile Polyposis Syndrome (JPS). The gene product functions as a cytoplasmic mediator in the signaling pathway of transforming growth factor beta (TGF-beta). To investigate the potential role of DPC4/SMAD4 gene in colorectal cancers, we examined 73 tumors of clinical stages II or III from Japanese patients, for LOH at 18q21 and also for subtle mutations anywhere within the coding region of DPC4/SMAD4. LOH was identified in 50 (78%) of the 64 tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in seven of those tumors: two frameshift mutations, a 1-bp deletion (326 del T) in exon 8 and a 1-bp insertion (50-51 ins A) in exon 1; two nonsense mutations, Arg445Ter in exon 10 and Glu538Ter in exon 11; and three missense mutations, Asn129Lys in exon 2, Tyr95Asn in exon 2, and Asp355Glu in exon 8. Three of the seven mutations were observed in the mad homology 1 (MH1) domain encoded by exons 1 and 2. In all of the tumors carrying intragenic mutations of one allele, LOH analysis had shown that the other allele was missing. The results demonstrated that inactivation of both alleles of the DPC4/SMAD4 gene occurs in a substantial proportion of advanced colorectal cancers, and that the DPC4/SMAD4 gene probably exerts a tumor-suppressor effect for colorectal carcinogenesis that fulfills the criterion of the two-hit concept proposed by Knudson [A.G. Knudson, Hereditary cancer, oncogenes, and anti-oncogenes, Cancer Res. 45 (1985) 1437-1443.].

Alleles