[Endothelium-dependent relaxation of collateral microvessels following intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia].
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Biomedical subjects
Publications and source records attributed to M Ochiai.
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The purpose of this article is to propose an "aggressive strategy" in the treatment of patients with acute coronary syndrome (ACS), especially unstable angina. The indication and timing of emergent coronary angiography in patients with ACS remains to be validated. The results of TIMI III B trial, a randomized, controlled trial about this issue, show that an early invasive strategy reduced the average length of initial hospitalization and the incidence of rehospitalization within 6 weeks. However, the same kind of clinical trial named VANQWISH reported that no benefit was obtained from such an aggressive strategy. It is of paramount importance to note that these 2 studies were performed in the era of plain old balloon angioplasty. Now we can use many kinds of coronary stent which impart both excellent radial strength and flexibility. Recent studies have demonstrated that culprit lesions of ACS can be treated at the same success rate as those of stable effort angina. In our hospital, use of coronary stents in patients with ACS dramatically reduced the recurrence of ACS and the incidence of angiographic restenosis with the same initial procedure success rate. Since the mid-nineties, the radial artery has been used as a vascular access site of coronary intervention. The major advantage of this technique is lesser access site-related complications and increased patient comfort, which reduced hospital stay and cost. Recently it was demonstrated that ad-hoc transradial intervention can be applied in patients with unstable angina or even those with acute myocardial infarction by trained angioplasters. Thus, we would like to conclude that the best strategy in the management of ACS is to perform emergent coronary angiography from the radial artery as soon as possible after admission, and to do ad-hoc intervention using coronary stents suitable for the lesion anatomy.
An unusual case of paraganglioma of posterior mediastinum occurred in a young adult with local recurrence and multiple distant metastasis. Because of its rarity, the determinants of prognosis factor between benign and malignant paraganglioma are uncertain. In this case, we investigated abnormalities of the p53 gene and ras gene mutations in tissues of primary and metastatic lesions. Neither abnormalities of p53 gene nor ras gene mutations were detected. The molecular approach is recommended as a means of clarifying the trend towards the malignancy of paraganglioma.
Proton magnetic resonance spectroscopy (1H-NMS) was used to examine the ratio of choline-containing compound (Cho) to creatine (Cr) in the basal ganglia. Subjects comprised 10 bipolar I affective disorder patients and 10 healthy control subjects. No significant difference was found in the Cho/Cr, N-acetyl-aspartate (NAA)/Cr, or NAA/Cho ratios between bipolar patients and control subjects. Within the bipolar group, negative correlations emerged between the NAA/Cr ratio in the right lenticular nuclei and both age at onset and age at the time of study. The results suggest that a late onset of illness and older age are associated with neuronal cell loss in the right lenticular nuclei in bipolar patients.
Recently, individuals with the short form of the serotonin transporter were found to be associated with neurotic characteristics. An association study on this polymorphism was performed in anxiety disorder patients and control subjects. The short form allele frequency in patients tended to be higher than that in control subjects (81.7 vs. 74.5%). Although it is difficult to ascribe significance to these 'tendencies', these data may suggest that variation of this functional polymorphism makes some contribution to anxiety disorders.
BACKGROUND: Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. METHODS AND RESULTS: Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 microg of a plasmid encoding VEGF or ss-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 microm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6+/-17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1+/-8.4% in VEGF-treated animals (P<0.05). CONCLUSIONS: These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.
Several studies have shown that the morbidity risk for anxiety disorders is increased among the relatives of patients with obsessive-compulsive disorder (OCD). Recently, it was reported that a polymorphism of the catechol-O-methyltransferase (COMT) gene is significantly associated with OCD. The purpose of this study was to determine the association, if any, between the COMT polymorphism and anxiety disorders. We undertook an association study of the COMT polymorphism in 108 patients who met DSM-IV criteria for anxiety disorders and 135 healthy controls. All subjects were unrelated Japanese. The subdiagnostic groups did not differ significantly from the control group in either the genotypic or allelic frequencies. There were no statistically significant differences between the genotype and males, females, or a family history. The mean age of onset did not significantly differ among the genotypes. Our results suggest this functional COMT polymorphism does not make an important contribution to anxiety disorders in the Japanese population.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant mutagenic heterocyclic amine (HCA) present in cooked foods. PhIP induces colon cancer in male Fischer 344 (F344) rats, and its role in human colon carcinogenesis has been suspected. To study the ecogenetics in PhIP colon carcinogenesis, rat system using aberrant crypt focus (ACF) formation as a phenotypic marker was applied. Among Buffalo (BUF), Brown Norway (BN), F344 and ACI/N (ACI) strains of rats, F344 rats produced a lower level of PhIP-DNA adducts than other three strains, and the number of ACFs/rat was highest in BUF, intermediate in BN and F344 and lowest in ACI. Thus there was no correlation between adduct levels and number of ACF induced by PhIP. F1 progenies of BUF and ACI developed ACF at a similar level to that of F344, and F1 progenies of F344 and ACI developed ACF at a similar level to that of F344. Thus it was indicated that susceptibility of F344 to the ACF induction was autosomally dominant over ACI rats. The results also suggest that BUF rats have at least two genes, one is autosomally recessive against ACI rats and one is autosomally dominant similar to that F344 has. A total of 170 progeny of ACI backcross of F344/ACI F1 were examined for number of ACFs and 65 progeny were phenotyped as F344 and 60 were ACI. Using these 125 rats, chromosomal mapping is being performed using markers of simple sequence length polymorphism (SSLP) and representational difference analysis (RDA). By mapping the gene, we will be able to identify humans who might belong to high risk group in general population, and cancer can be prevented more efficiently by attaining early diagnosis.
The carcinogenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) was examined in Big Blue female mice with the genetic background of C57BL/6N. With the administration of 300 ppm of MeIQ in their diet for 92 weeks, the Big Blue female mice developed intestinal tumors and hepatocellular carcinomas. The incidences of adenocarcinomas were 42% (8/19) in the colon and 68% (13/19) in the cecum. The incidence of hepatocellular carcinomas was 84% (16/19). No carcinomas of the intestine or the liver were induced in the control group. As we previously reported, administration of 300 ppm of MeIQ in a diet for 12 weeks induced lacI mutants at the highest frequency in colonocytes, and at only less than one-tenth of the colon in cells of the liver, forestomach and bone marrow, indicating no direct correlation between the lacI mutant frequency (MF) and cancer incidence (CI). The fate of cells with lacI mutation in each organ should be taken into consideration to validate MF as an indicator of carcinogenic potency of a chemical in different organs.
We classified 33 patients with a first anterior infarction and single-vessel disease who had undergone successful primary angioplasty and had a patent infarct-related artery into groups based on the development of late potentials. Left ventricular function improved between 1 and 3 months after angioplasty only in patients without late potentials; the development of late potentials after acute anterior infarction was associated with prolonged left ventricular dysfunction despite successful revascularization with primary angioplasty.
We designed a novel guide catheter specifically for interventions to the left coronary artery via a right upper limb approach. The catheter has a novel first loop design which utilizes the angle between the right subclavian and innominate arteries for support. The first loop introduces the catheter into the correct position and generates powerful and coaxial back-up power. We report successful implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter.
OBJECTIVE: Platelet aggregation has been implicated in the pathogenesis of acute coronary syndromes. Small aggregates consisting of < or = 100 platelets cannot be quantified with a conventional aggregometer employing optical density. Using a recently developed aggregometer based on laser light scattering, we studied platelet aggregability in patients with acute coronary syndromes. METHODS: Peripheral blood samples were obtained from 39 patients with acute myocardial infarction or unstable angina who had received no prior antiplatelet or anticoagulant therapy, to be assayed immediately using a PA-100 platelet aggregometer. Blood samples from 14 healthy volunteers were used as controls. RESULTS: Spontaneous formation of platelet aggregates was observed only in patients with acute coronary syndromes. The size of these aggregates was small, consisting of < or = 100 platelets (primary aggregation). Agonist-induced aggregation consisted of two phases. In the first few minutes, the number of small aggregates increased markedly (primary aggregation), followed by an increase in larger aggregates (secondary aggregation). The EC50 of epinephrine for primary aggregation was nearly 50 times lower in acute coronary patients than in controls (P < 0.001), while the EC50 for secondary aggregation was only 2 times lower (P < 0.001). CONCLUSIONS: Aggregometry using light scattering suggests that platelet hyperaggregability and hypersensitivity in acute coronary syndromes may occur in primary but not secondary aggregation.
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In previous experiments we analyzed the mutant frequency (MF) and mutational types in various organs of lacI transgenic mice which were fed a diet containing 300 p.p.m. 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a food-borne mutagen/carcinogen. To clarify the relationships between mutational type and adduct molecular species and between adduct level and MF we analyzed adducts in the same DNA samples. The DNA adduct in the liver, heart, colon, forestomach and bone marrow was determined by the modified intensification method of 32P-post-labeling at time points 1, 4 and 12 weeks. Only a single spot corresponding to N2-(deoxyguanosin-8-yl)MeIQ 5'-monophosphate was detected in DNA from all organs at all time points examined, with a recovery of 48%. The difference in mutation type between bone marrow and other organs detected in the previous experiment was not explained by adduct molecular species. At 4 and 12 weeks administration the adduct levels were highest in the liver and then heart, colon, forestomach and bone marrow in decreasing order, with values of 28.3, 8.4, 3.3, 1.3 and 0.4 molecule/10(7) nucleotides at 12 weeks. Based on our previously reported data, lacI MF was highest in the colon and those in the liver, bone marrow and forestomach were 10-60% of that of the colon; no increase in MF was detected in the heart, where no DNA replication is expected except for vascular endothelial cells. There was no direct relationship between MF and adduct level. The MF may be the product of adduct level and cell proliferation rate.
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