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Biomedical subjects

Y Mizuno

Publications and source records attributed to Y Mizuno.

At least 289 records · Page 16Linked to original sources
PubMed1997

Relation of electrocardiographic left ventricular hypertrophy with and without T-wave changes to systemic blood pressure, body mass, and serum lipids and blood glucose levels in Japanese men.

Left ventricular (LV) hypertrophy, especially combined with an abnormal ST-T, is considered 1 of many coronary risk factors. Seven hundred forty-nine Japanese men were selected according to their electrocardiographic findings, i.e., normal electrocardiogram, LV hypertrophy without an abnormal ST-T segment, LV hypertrophy with a flat T wave, and LV hypertrophy with a negative T wave. Coronary risk factors were compared among these 4 age-matched groups. Groups with LV hypertrophy with negative or flat T waves had larger body mass index (24.9 vs 22.9 kg/m2), higher mean systemic blood pressure (111 vs 95 mm Hg), larger LV mass (265 vs 157 g), higher blood glucose (110 vs 100 mg/dl), higher serum triglyceride (148 vs 122 mg/dl), higher total cholesterol (206 vs 198 mg/dl), and lower high-density lipoprotein cholesterol (47 vs 54 mg/dl) than the normal group or the group with LV hypertrophy without T-wave change. Among these risk factors, blood pressure and glucose remained higher even after the adjustment by body mass index or by body mass index and blood pressure. Electrocardiographic LV hypertrophy with a changed T wave signified higher risk of coronary artery disease in Japanese men.

Blood Glucose↗
PubMed1997

Postischemic accumulation of lipid peroxidation products in the rat brain: immunohistochemical detection of 4-hydroxy-2-nonenal modified proteins.

We report an immunohistochemical study on the distribution and alterations of 4-hydroxy-2-nonenal (HNE)-modified proteins, an indicator of lipid peroxidation, in the rat brain after 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion. HNE immunoreactivity was not observed in intact neurons, but it appeared in some shrunken neurons within the infarcted zone at 3 h after reperfusion. The number of HNE-positive neurons increased with the spread of the infarcted area. The pyramidal neurons in the third layer of the frontoparietal cortex were HNE-positive and the intensity of their HNE immunoreactivity was highest at 24 h after reperfusion. At 48 h, HNE-positive neurons were observed in the medial part of the striatum, the lateral side of the frontoparietal cortex, and at the boundary between the infarcted and noninfarcted zones. In addition, strong HNE immunoreactivity was seen in microglia (identified by OX-42 immunostaining). This method seems to be useful to follow the progress of lipid peroxidation at the cellular level after ischemic injury.

Animals↗
PubMed1997

Oral bacteria inhibit Helicobacter pylori growth.

Various oral bacterial species were found to inhibit the growth of Helicobacter pylori strains. The growth inhibitory activities of most of these oral bacteria were adversely affected by heating at 80 degrees C for 60 min or by protease treatment, indicating that these bacteria produce bacteriocin-like inhibitory proteins against H. pylori strains. The antagonistic effects of oral bacteria against H. pylori may restrain colonization by this organism in the oral cavity.

Adult↗
PubMed1997

Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death in Parkinson's disease.

The oxidative stress theory, the mitochondrial (mt) hypothesis, and the apoptosis hypothesis are proposed as the cause of neuronal cell death in Parkinson's disease (PD). However, the direct link between them has remained unknown. Recently, the mt control of nuclear apoptosis is documented that collapse of mt transmembrane potential due to energy crisis leads to release of apoptotic protease activating-factors into cytosol and subsequently nuclear DNA fragmentation. However, an endogenous factor responsible for the energy crisis under physiological conditions is missing. Here we report the missing factor as that mtDNA in the striatum of a parkinsonian patient fragments into 134 types of deleted pieces, being detected by the total detection system for mtDNA deletion. The system has documented that the mtDNA is extremely susceptible to hydroxyl radical damage, hence to oxidative stress, enough to cause the cellular energy crisis. The extensive fragility of mtDNA in brain stem could link the oxidative stress up with the apoptotic neuronal cell-death of PD.

Adolescent↗
PubMed1997

Genetic association between susceptibility to Parkinson's disease and alpha1-antichymotrypsin polymorphism.

The apolipoprotein E (ApoE*) gene is a major risk factor of developing Alzheimer's disease (AD) and the alpha1-antichymotrypsin (ACT) polymorphism is likely to modify susceptibility of the ApoE* gene for AD. Because pathogenesis of AD is partly similar to that in idiopathic Parkinson's disease (PD), we investigated the distribution of genotypes of the ApoE and the ACT in patients with PD. The number of individuals with two copies of the ACT-A allele (ACT-AA genotype) in patients with PD increased significantly compared to that in healthy controls (19.9% versus 8.3%, P < 0.02), and the ACT-A allele frequency in patients with PD was significantly higher than that in healthy controls (chi2 = 5.96, df = 1, P < 0.015). The odds ratio for developing PD in individuals with the ACT-AA genotype was 3.36 compared to individuals with two copies of another allele, the ACT-T allele (ACT-TT genotype). There was no association between ApoE genotypes and susceptibility to PD. These data suggest that the etiological basis of PD might be partly similar to that of AD and the ACT gene might be one of the susceptibility factors for PD.

Adult↗
PubMed1997

An immunohistochemical study on manganese superoxide dismutase in Parkinson's disease.

We report an immunohistochemical study on manganese superoxide dismutase (Mn SOD) in Parkinson's disease (PD) patients and age-matched control subjects. Overall appearance of immunostaining intensity of nigral neurons did not differ significantly between the PD patients and the control subjects. However, when the immunostaining intensity of each neuron was semiquantitatively analyzed, both very intensely stained (more than normal) neurons as well as neurons stained only weakly were more frequently detected in the lateral part than in the medial and the central parts of the substantia nigra in PD patients. As a result, the proportion of normally stained neurons was significantly smaller in the lateral part of the substantia nigra in PD patients; however, the overall distribution of the neurons among the three rating grades for immunostaining did not differ significantly. The immunostaining intensity of the neuropils in the medial and the central part of the substantia nigra tended to be more intense in PD patients than in the control subjects. Our results suggest up-regulation of Mn SOD mainly in the dendritic processes of the less involved nigral neurons.

Aged↗
PubMed1997

Neurotoxic effects of papaverine, tetrahydropapaverine and dimethoxyphenylethylamine on dopaminergic neurons in ventral mesencephalic-striatal co-culture.

We report neurotoxic effects of papaverine, tetrahydropapaverine, dimethoxyphenylethylamine (DMPEA), and 1-methyl-4-phenylpyridinium ion (MPP+) on dopaminergic neurons in ventral mesencephalic-striatal co-culture. These compounds have been reported as mitochondrial toxins which may be implicated in the etiology and pathogenesis of Parkinson's disease. Tyrosine hydroxylase (TH)-positive neurons were decreased in dose-dependent manner by these compounds. Papaverine and MPP+ were most toxic to TH-positive neurons among the compounds tested. The order of the toxicity on TH-positive neurons was papaverine, MPP+, tetrahydropapaverine and then DMPEA. This order of toxicity was approximately the same as that reported on the inhibitory effect of these compounds on NADH-linked mitochondrial respiration and complex I activity. These findings indicate that the presence of dimethoxy residues in the catechol ring augments toxicity to dopaminergic neurons in culture.

1-Methyl-4-phenylpyridinium↗
PubMed1997

The interconversion of protein phosphatase 2A between PP2A1 and PP2A0 during retinoic acid-induced granulocytic differentiation and a modification on the catalytic subunit in S phase of HL-60 cells.

Alterations in protein phosphatase 2A (PP2A) during retinoic acid-induced differentiation of HL-60 cells have been investigated. PP2A activity of HL-60 cells for phosphorylated myelin basic protein showed a sharp and transient increase after 18-h treatment with 1 microM retinoic acid, which corresponded to G1/S boundary of the cell cycle. This PP2A of the 18-h treated cells was eluted from a DEAE-Sepharose column with 0.13 M NaCl, while PP2A from control cells was eluted with 0.23 M NaCl. The phosphorylase phosphatase activity of PP2A in the 0.13 M eluate was greatly enhanced in the presence of protamine compared with that of the later eluting PP2A. Immunoblot analyses with antisera against B' and B alpha subunits showed that the PP2A in the 0.13 M NaCl eluate from 18-h retinoic acid-treated cells was PP2A0 (AC-B'), whereas the PP2A eluted with 0.23 M NaCl from 24-h retinoic acid-treated cells and 0-, 18-, and 24-h control cells was PP2A1 (AC-B alpha). These results strongly suggest that PP2A undergoes a transient and reversible interconversion of holoenzyme forms during the initial stage of retinoic acid-induced granulocytic differentiation. PP2A activity assayed after dissociation of the catalytic subunit, for phosphorylase as substrate, showed a sharp and transient decrease in S phase of HL-60 cells irrespective of the presence or absence of retinoic acid. Immunoblot analyses with antisera against C-terminus and N-terminus of the catalytic subunit of PP2A suggested that a modification at the C-terminus is responsible for the decrease in PP2A activity. Immunoreactivity to the C-terminal antibody was restored after treatments of the S-phase extract with alkali or ethanol, the conditions which remove the methyl group from the C-terminus. These results suggest that the C-terminus of PP2A catalytic subunit is transiently methylated in S phase of HL-60 cells.

Blotting, Western↗
PubMed1997

Pulse-spray thrombolysis in acutely obstructed coronary artery in critical situations.

Pulse-spray thrombolysis (PST) was performed to treat large coronary thrombus in 3 patients in critical situations. The originally developed pump system and a custom infusion catheter (SciMed/Boston Scientific, Maple Grove, MN) were used in combination. Case 1, a 48-yr-old male with extensive anterior myocardial infarction, failed to be recanalized by systemic thrombolysis. He underwent emergent coronary angiography, which revealed proximal occlusion of a large left anterior descending artery (LAD). TIMI 3 flow was achieved after 20 min with 200,000 units of urokinese by PST, followed by balloon angioplasty. In case 2, a 57-yr-old male, subacute stent thrombosis occurred 4 days after two and a half Palmatz-Schatz stents were implanted in mid-LAD. TIMI 3 flow was recovered at 20 min with 240,000 units of urokinese and an additional 72,000 units of rt-PA, followed by redilatation with a quarter-size larger balloon than that used in stent deployment. In case 3, a 70-yr-old male, during ultrasound study for unstable angina, a massive thrombotic complication occurred which occluded the left main trunk. PST was immediately performed under cardiac resuscitation, and the patient recovered from shock after 15 min. TIMI 3 flow was restored after 25 min. Two Palmatz-Schatz stents were implanted after thrombus completely disappeared. There were no complications, including distal embolization, intimal dissection, or bleeding. There was also no recurrence of the ischemic event. PST may be considered a potential treatment modality for coronary artery disease where large thrombus plays a major role.

Aged↗
PubMed1997

Apoptosis in neurodegenerative disorders.

Although the exact mechanism of nigral cell death in Parkinson's disease (PD) is not known, increasing evidence suggests the presence of apoptotic cell death in PD. When we applied the TUNEL method to detect DNA fragmentation, four out of seven late onset sporadic patients with PD showed TUNEL-positive neurons. The percentages of those neurons among the remaining melanin containing neurons were 0.6 to 4.8% (average 2.1%). But TUNEL-positive neurons could not be detected in control subjects as well as four patients with young onset (under 40 years of the age) PD. Numbers of nigral toxins such as MPTP, complex I inhibitors, and mitochondrial respiratory inhibitors have been reported to induced apoptotic cell death. These findings suggest that apoptosis is involved in nigral cell cleath in PD at least in part and warrant further studies on apoptosis-related substances in PD.

1-Methyl-4-phenylpyridinium↗
PubMed1997

Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease.

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.

Aged↗
PubMed1997

Catechol-O-methyltransferase genotype and susceptibility to Parkinson's disease in Japan. Short communication.

We report -108Met/Val polymorphism of the COMT gene in Japanese patients with Parkinson's disease (PD). The allele frequency for -108Val was higher in PD patients compared with controls, although the differences did not reach the statistical significance. However, the frequency of -108Val homozygotes was significantly higher in PD patients (56.8%) than in control subjects (44.2%), and heterozygotes of -108Met/Val were less in PD. COMT gene polymorphism may constitute a genetic risk factor for PD among Japanese.

Aged↗
PubMed1997

Multiple ulcers of the ileum due to Cytomegalovirus infection in a patient who showed no evidence of an immunocompromised state.

68-year-old woman presented with abdominal pain and vomiting. After initial conservative therapy, laparotomy showed multiple ulcers of the ileum, one of which had perforated and adhered to the uterus. The affected segment of the ileum was resected. Numerous cytomegalic cells, corresponding to endothelia and macrophages, with intranuclear inclusion bodies, were found in microscopic sections of the ulcerated lesions. These findings were consistent with cytomegalic vasculitis and enteritis. Cytomegalovirus infections of the alimentary tract have been reported mainly in severely immunocompromised patients or those with predisposing disorders such as ulcerative colitis; their prognosis is usually poor. In our patient, there was no obvious immunocompromised state or other gastrointestinal disorders. The postoperative course has been uneventful for 2 years after surgery. The prognosis of Cytomegalovirus-associated lesions in the alimentary tract may be quite good in the immunocompetent patient.

Aged↗
PubMed1997

Linkage map of Syrian hamster with restriction landmark genomic scanning.

We have constructed the linkage map with precise genetic analysis of the Syrian hamster, Mesocricetus auratus, according to the restriction landmark genomic scanning (RLGS) spot mapping method. Although only 3.2-6.6% of the total RLGS spots between the two strains, ACN and BIO 14.6, showed genetic variance, 572 loci were found to be polymorphic. Out of 569 RLGS loci and 3 other loci, 531 were mapped with the backcross (ACN x BIO 14.6) F1 x BIO 14.6. The cumulative map was 1111.6 cM, indicating that the spots/loci are located throughout the genome at 1.94 cM intervals on average. Thus, RLGS provides us with a rapid tool to construct the genetic map of any species, even if it has less genetic variation.

Animals↗
PubMed1997

A tactile sensor for laparoscopic cholecystectomy.

During laparoscopic surgery, surgeons observe the three-dimensional abdominal cavity on a two-dimensional TV monitor, which is a limitation. Another limitation is that surgeons are unable to estimate the softness of organs or tissues during laparoscopic surgery as they are only allowed to use instruments which touch objects and direct palpation is not permitted during the procedure. The tactile sensor which we used displays the object softness immediately as a digital score, which can then be superimposed on a TV monitor as a graph. With the tactile sensor, we were able to ascertain the presence of a gallstone in the gallbladder or cholecystic duct during laparoscopic cholecystectomy and also able to discriminate between a stone and an air bubble during intraoperative cholangiography. We were convinced that the tactile sensor would be useful in laparoscopic surgery, which does not permit surgeons to palpate objects with human fingers.

Cholangiography↗
PubMed1997

Increased plasma tissue factor levels in acute myocardial infarction.

BACKGROUND: Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis. METHODS AND RESULTS: We examined plasma TF levels in 31 consecutive patients with acute myocardial infarction (AMI) (within 6 hours after the onset of symptoms), 27 patients with stable exertional angina, and 27 control subjects. Ten patients with AMI had a history of unstable angina before infarction, and 21 had a sudden onset of infarction. The plasma TF level was higher in the AMI group than in the stable exertional angina and control groups (240 +/- 112 vs 184 +/- 46 pg/ml [p < 0.05] vs 177 +/- 37 pg/ml, p < 0.01, respectively). TF levels were decreased in the chronic phase (2 weeks after admission) compared with the acute phase of infarction (from 240 +/- 112 pg/ml to 222 +/- 97 pg/ml, p < 0.05). In addition, plasma TF levels were higher in patients with AMI with prodromal unstable angina than in patients with a sudden onset of infarction (300 +/- 169 pg/ml vs 212 +/- 57 pg/ml, p < 0.05). TF levels were similar in the acute and chronic phases in the patients with AMI with prodromal unstable angina (300 +/- 169 pg/ml vs 290 +/- 136 pg/ml, p = not significant) but were decreased in the chronic phase in the patients with AMI with sudden onset (from 212 +/- 57 pg/ml to 190 +/- 49 pg/ml, p < 0.05). CONCLUSION: Increased plasma TF levels in patients with AMI may reflect enhanced intravascular procoagulant activity. The higher TF levels in patients with AMI with prodramol unstable angina may be associated with repeated episodes of myocardial ischemia and reperfusion.

Aged↗
PubMed1997

The effects of the angiotensin-converting enzyme inhibitor imidapril on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction.

This study sought to determine whether early treatment with angiotensin-converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI) is useful for the improvement of fibrinolytic function, as well as left ventricular function. This study was designed to examine the levels of plasma plasminogen activator inhibitor (PAI) activity and serum ACE activity during the course of 2 weeks in 40 patients with AMI within 12 hours after the onset of the symptom and who randomly received early treatment with either the ACE inhibitor imidapril or a placebo (20 patients in the imidapril group and 20 in the placebo group). The levels of serum ACE activity in the imidapril group decreased significantly (p < 0.01) 8 hours after the administration of imidapril, and the levels 24 hours after administration were significantly lower than those in the placebo group (3.6 +/- 0.6 IU/L vs 7.4 +/- 0.8 IU/L; p < 0.001). The plasma PAI activity increased gradually to peak levels 16 hours after the administration of imidapril and placebo. The levels in the placebo group decreased gradually but remained high during the study period. On the other hand, the levels of PAI activity in the imidapril group decreased rapidly and those 48 hours after administration were significantly lower than those in the placebo group (7.9 +/- 1.9 IU/ml vs 18.4 +/- 3.5 IU/ml; p < 0.01). The levels of left ventricular ejection fraction about 2 weeks after admission were significantly higher in the imidapril group than in the placebo group (65.9% +/- 2.5% vs 49.1% +/- 4.4%; p < 0.01). This study showed that imidapril, an ACE inhibitor, might be useful for the improvement of fibrinolytic function and left ventricular function in the acute phase of myocardial infarction.

Aged↗