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Biomedical subjects

M Yokota

Publications and source records attributed to M Yokota.

At least 55 records · Page 3Linked to original sources

Ion heating and high-energy-particle production by ion-cyclotron heating in the large helical device

Ion-cyclotron heating was applied to the Large Helical Device. When the proton-cyclotron resonance was near the saddle point of the magnetic field-strength plane, strong ion-cyclotron damping occurred. Under these conditions efficient plasma heating was achieved for more than one minute. A high-energy ion tail was observed, and the effective tail temperature was determined by a balance between the wave acceleration and the electron-drag relaxation. There was no apparent sign of particle orbit loss effect in the investigated density range of 0.8-1.3x10(19) m(-3).

Journal Article↗

Effect of combined leukotriene D(4) and thromboxane A(2) receptor antagonist on mediator-controlled resistance in guinea pigs.

The effects of YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl )propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene D(4) and thromboxane A(2) receptors, on antigen-induced increases in airway resistance were investigated in mediator-controlled novel asthmatic models using actively sensitized guinea pigs. While the predominant mediator was thromboxane A(2), complete inhibition of cyclooxygenase induced mediation by cysteinyl-leukotrienes. About 1-mg/kg indomethacin induced a state where both mediators participated equally. YM158 inhibited increases in resistance whether only one or both mediators were involved. When leukotriene D(4) and thromboxane A(2) equally participated, ED(50) values for 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzo pyran hemihydrate (pranlukast; 3.9 mg/kg) and 7-(3,5,6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid (seratrodast; 2.1 mg/kg) were similar to that for YM158 (8.3 mg/kg), although those effects on the corresponding mediator-induced reaction were 10 times stronger than those of YM158. Additionally, the maximum inhibition of YM158 was stronger than those of either single receptor antagonist. In conclusion, YM158 has a potentially greater efficacy in wider types of experimental asthmatic models than single receptor antagonists.

Administration, Oral↗

Association of a T29-->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is an important regulator of vascular remodeling and is involved in the pathogenesis of atherosclerosis. A T-->C transition at nucleotide 29 of the TGF-beta1 gene results in a Leu-->Pro substitution at amino acid 10 of the signal peptide. We have now examined a possible association of TGF-beta1 genotype with myocardial infarction (MI) in a Japanese population. METHODS AND RESULTS: TGF-beta1 genotype was determined in 315 Japanese patients (234 men and 81 women) with MI and 591 control subjects (289 men and 302 women). We found that age, body mass index, and incidence of habitual smoking, hypertension, diabetes mellitus, and hypercholesterolemia did not differ between the 2 groups for either men or women. Multivariable logistic regression analysis, however, demonstrated the frequency of the T allele to be significantly higher in male subjects with MI than in controls (TT + TC versus CC; P<0.0001, odds ratio 3.5, 95% CI 2.0 to 6.3). In contrast, the T allele was not associated with the prevalence of MI in women. In both male MI patients and controls, the serum concentration of TGF-beta1 was significantly higher in individuals with the CC genotype than in subjects with the TT or TC genotype. CONCLUSIONS: Findings suggest that the T allele at nucleotide 29 in the TGF-beta1 gene is a risk factor for genetic susceptibility to MI, at least in middle-aged Japanese men.

Aged↗

Correlations between plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and PAF-AH genotype, age, and atherosclerosis in a Japanese population.

Platelet-activating factor acetylhydrolase (PAF-AH), a plasma enzyme that hydrolyzes PAF and oxidized phospholipids, is thought to be involved in protecting cells against oxidative stress. A G(994) (M allele)-->T (m allele) mutation in the plasma PAF-AH gene, which results in a Val(279)-->Phe substitution in the mature protein, leads to a loss of catalytic activity. To elucidate the relationships among PAF-AH enzyme activity, genotype, age, and atherosclerosis, we assayed these parameters in a large Japanese population (n=3932) that consisted of three groups; a control group (healthy individuals; n=1684), a risk-factor group (individuals having at least one conventional risk factor for atherosclerosis; n=1398), and a diseased group (patients who had suffered a myocardial infarction or stroke; n=850). We observed a significantly increased frequency of the m allele in the diseased group as compared with the control or risk-factor groups. Plasma PAF-AH activity increased significantly with age in women in the control group with the MM and Mm genotypes, and in men in the control group with the MM genotype, but not in men with the Mm genotype. In both the risk-factor and diseased groups, however, no correlation was observed between plasma PAF-AH activity and age in subjects with either genotype. These results suggest that in individuals with the MM genotype, plasma PAF-AH activity may be increased in response to stresses induced by PAF and/or oxidized phospholipids that might accumulate with age, but that this response is not evident or reduced in healthy individuals with the m allele, or in subjects with atherosclerotic disease, or having risk factors. Together with our previous findings, the G(994)-->T mutation in the PAF-AH gene may be one of the genetic determinants for atherosclerotic disease in the Japanese population.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Severe ectopic calcification of the intestinal wall in a patient on long-term continuous ambulatory peritoneal dialysis therapy.

We report autopsy findings of a 69-year-old man on long-term CAPD therapy for 13 years who showed linear peritoneal calcification. Continuous ambulatory peritoneal dialysis (CAPD) was started in 1982. He has been administered excessive amounts of vitamin D(3) derivatives (VitD) (2.0 to 2.5 microg daily) and calcium carbonate (4 g daily) for secondary hyperparathyroidism since initiation of CAPD. In May 1995, his intact parathyroid hormone (PTH) level increased over 1,000 pg/mL. Immediately after VitD was changed from pill to liquid, the dose was increased to 5 microg daily. Although the serum calcium level remained between 4.5 and 4.9 mEq/L, and serum phosphate level was 5.0 to 7.2 mg/dL, plain abdominal radiography and computed tomography showed continuous calcification along the intestinal wall in October 1995. In spite of the continuation of CAPD therapy, he remained asymptomatic until he died of congestive heart failure in January 1997. He experienced eight episodes of peritonitis during his clinical course. Autopsy showed that numerous calcified plaques were present on the submucosal portion between the thickened serosa and the longitudinal layer of the muscularis externa. The remainder of the subserosa was fibrotic, and the small arteries had markedly thickened intima and severely narrowed lumina.

Abdominal Muscles↗

Splenectomy may improve the glomerulopathy of type II mixed cryoglobulinemia.

Many patients with type II mixed cryoglobulinemia have been shown to be infected with hapatitis C virus (HCV). Therefore, interferon-alfa has become the first choice of treatment for patients with HCV-associated cryoglobulinemia. However, the disease often relapses after the discontinuation of interferon therapy. The long-term effect of interferon therapy is controversial. Therefore, a more effective therapy needs to be developed. A 62-year-old Japanese woman was admitted to our hospital for the examination of abnormal liver function tests, severe edema, and purpura in her lower extremities. Glomerulopathy secondary to HCV-related cryoglobulinemia was suspected. Her serum creatinine was increased to 2.1 mg/dL. Interferon therapy was considered initially. However, because of pancytopenia caused by liver cirrhosis and splenomegaly, splenectomy was performed in February 1997, before the start of interferon therapy. Renal biopsy specimen taken at the time of the splenectomy showed typical cryoglobulinemic glomerulonephritis. Gradually, after surgery, the patient's thrombocytopenia and anemia improved, her proteinuria and hematuria were decreased, her cryocrit dropped from 15% to 5%, the Ccr increased from 21.1 mL/min to 48.8 mL/min, and the purpura in her lower extremities disappeared. A repeat renal biopsy performed in May 1998 showed marked histological improvement. Splenectomy is not widely accepted as a treatment for cryoglobulinemia. Our case suggests the possibility that the monoclonal-IgM component of the type II cryoglobulin may be formed in the spleen. In conclusion, splenectomy may be an effective therapy for cryoglobulinemia in patients with HCV-positive liver cirrhosis and pancytopenia secondary to splenomegaly.

Anemia↗

A case of DNA analysis of ABO blood group variant allele A2.

The ABO phenotype of a bloodstain (B) on a knife that was used as a weapon in an attempted murder case was found to be different from that of the Peruvian victim's blood (AB). Serological analysis showed that the A-antigenicity was much weaker than B antigenicity, suggesting that the victim's phenotype was A(2)B or A(3)B. So, the ABO genotypes of the knife bloodstain and the victim's blood were determined by DNA analysis. The 261st G deletion, specific to the O(1) allele, was not detected in the specimens by restriction fragment length polymorphism analysis. Also, the 871st A, specific to the A(3) allele, was not found by the allele-specific amplification method. Amplified product length polymorphism and direct sequencing methods finally demonstrated that the typical B sequence was found in one allele and a single C deletion in the 1,059th-1,061st C stretch in the other allele, indicating that the ABO phenotype of the bloodstain and victim's blood were A(2)B.

Journal Article↗

Declining of memory functions of normal elderly persons.

Two studies examined the declining of memory functions in normal elderly persons using the Yokota memory test (YMT), which includes 15 items concerning verbal and non-verbal memory functions. In the first study, 552 subjects over 40 years of age in five age groups were examined. Factor analysis revealed that YMT consisted of two factors pertaining to short-term/working memory, and two factors pertaining to long-term memory. It is suggested that the former was more affected than the latter, with aging. In the second study, YMT was examined in relation to the revised version of Hasegawa dementia scale (HDS-R), which was the most popular intelligence scale for the elderly in Japan. As a result, memory functions differentially declined with the decreasing score of HDS-R, which suggests that memory functions differentially declined with progressive risk of dementia.

Adult↗

Different beta-adrenergic regulation of myocardial contraction and relaxation between apical and nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The impaired adrenergic control of both inotropic and lusitropic reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM) but not in those with apical HCM (APH). OBJECTIVES: We examined the influence of increases in heart rate and adrenergic stimulation on inotropic and lusitropic reserves in HCM and APH with normal resting left ventricular (LV) systolic function. METHODS: We evaluated LV isovolumic contraction and relaxation during atrial pacing and during supine leg exercise in 7 patients with APH and in 8 patients with HCM. RESULTS: Heart rate was significantly correlated with LV isovolumic contraction and relaxation during pacing and exercise in all patients. In all patients with APH, the increase in LV isovolumic contraction was greater during exercise (101%) than pacing alone (27%) for similar increase in heart rate. In 5 patients with HCM, the increase in LV isovolumic contraction was greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with HCM the increase in LV isovolumic contraction was similar between during exercise (25%) and during pacing alone (22%). In all patients with APH, relaxation was shorter during exercise (39%) than pacing alone (16%). Conversely, in patients with HCM relaxation was similarly shortened between during pacing alone (20%) and during exercise (19%). CONCLUSIONS: The force-frequency and the relaxation-frequency relations were well-preserved in all patients. In patients with HCM, the adrenergic enhancement of force-frequency relation and/or relaxation-frequency relation was impaired. In patients with APH, however, adrenergic control of both force-frequency and relaxation-frequency relations was well-preserved, which may indicate a preserved beta-adrenergic signaling pathway.

Adult↗

Sudden-onset tinnitus associated with arterial dissection of the vertebrobasilar system.

Magnetic resonance (MR) images of 62 patients with tinnitus were reviewed. These included T1-weighted and T2-weighted axial images and three-dimensional spoiled gradient-recalled acquisition in steady-state (3D-SPGR) imaging with gadopentetate dimeglumine. In 49 cases with tinnitus occurring gradually, the MR images of 2 cases (4.1%) suggested arterial dissection of the vertebrobasilar system. One of these patients underwent vertebral angiography (VAG) and no dissection was confirmed. In 13 cases of sudden-onset tinnitus, MR images of 3 cases (23.1%) suggested arterial dissection. Of these three cases, VAG was performed in two, resulting in arterial dissections being confirmed in two cases. It was concluded that the arterial dissection of the vertebrobasilar system was one of the causes of sudden-onset tinnitus. Abnormalities in neurotological examinations in cases with tinnitus caused by the arterial dissection of vertebrobasilar system implied that the tinnitus was caused by inner ear dysfunction.

Acute Disease↗

Successful pregnancy following blastocyst vitrification: case report.

A 32 year old woman and her 32 year old spouse were referred to our IVF programme. Following recovery of 12 mature oocytes, nine were fertilized following conventional IVF. Three fresh embryos were transferred to the uterus, but all failed to result in pregnancy. Six supernumerary embryos were cultured in vitro until day 5 in order to create blastocysts. Two grew to the blastocyst stage and were vitrified using a modification of a previous method. Two blastocysts survived the freeze-thaw process and were transferred to the patient's uterus during a natural cycle, 3 months after the previous retrieval cycle. Implantation resulted in a healthy pregnancy; delivery is expected in June 2000. This report documents the first successful pregnancy in Japan, achieved via blastocyst vitrification.

Blastocyst↗

Influence of movement arousal on circadian rhythm of blood pressure in obstructive sleep apnea syndrome.

OBJECTIVE: To investigate the hypothesis that repeated arousals at the termination of apnea/hypopnea in obstructive sleep apnea syndrome (OSAS) are related to abnormal circadian rhythm of blood pressure (BP). DESIGN AND METHODS: We performed polysomnography (PSG) with pulse oximetry in 26 middle-aged patients with OSAS aged 42-58 years (mean age 51.8 years). The intensity of arousal on PSG was graded into two levels: grade 1 (EEG arousal, EA), an abrupt shift in EEG frequency, and grade 2 (movement arousal, MA), EEG arousal with an increase in electromyogram activity lasting at least 3 s. The number of apnea/hypopneas per hour (apnea/hypopnea index, AHI), and length of time during which nocturnal oxygen saturation decreased below 90% (oxygen desaturation time, ODT) were also evaluated. Percentage EA and %MA were assessed by the ratio of the number of apneas and hypopneas with EA or MA to the number of apneas and hypopneas in total. The 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively. Multiple regression analysis was performed among AHI, ODT, %EA and %MA or among age, body mass index and %MA. RESULTS: The %MA was the most significant factor contributing to the elevated 24 h SBP (r= 0.46, P< 0.05); oxygen desaturation (r= 0.44, P< 0.05) was the next most important contributing factor. The level and pattern of 24 h BP differed significantly between the patients with %MA 85% and %MA < 85% (mean 24 h SBP: 147 +/- 16.8 versus 125 +/- 19.6 mmHg, P< 0.01; mean 24 h DBP: 97.5 +/- 14.3 versus 85.6 +/- 14.6 mmHg, P< 0.01), and also differed between those with severe OSAS, i.e. ODT > or = 130 min, and mild to moderate OSAS, i.e. ODT < 130 min, (mean 24 h SBP: 149 +/- 15.8 versus 132 +/- 20.6 mmHg, P < 0.01; mean 24 h DBP: 100 +/- 14.1 versus 87.4 +/- 14.0 mmHg, P < 0.01). CONCLUSION: Our findings suggest that MA and oxygen desaturation in OSAS make an important contribution to abnormal circadian rhythm of BP. We conclude that repeated end-apneic arousal and/or hypoxic asphyxia and the subsequent sleep fragmentation may contibute to nocturnal and diurnal elevation of BP.

Adult↗

Acute effects of a single low oral dose of pimobendan on left ventricular systolic and diastolic function in patients with congestive heart failure.

A recent long-term multicenter trial has shown that pimobendan is more effective when administered in low doses. However, no data are available concerning the effect of a low dose of pimobendan on the systolic and diastolic pressure-volume relations in patients with heart failure. Therefore we examined the effects of a single low dose of oral pimobendan, a calcium sensitizer, on systolic and diastolic hemodynamics in patients with cardiomyopathy and congestive heart failure. We measured the left ventricular (LV) pressure-volume relations using a conductance catheter with a micromanometer tip in 10 patients with chronic congestive heart failure resulting from idiopathic cardiomyopathy before and 45 and 90 min after administration of a single oral dose of 2.5 mg of pimobendan. End-systolic elastance was used as an index of LV contractility and was measured during transient occlusion of the inferior vena cava. End-systolic elastance increased significantly by 25% at 45 min (p < 0.05) and by 55% at 90 min (p < 0.01) without an increase in myocardial oxygen consumption. The inotropic effect was accompanied by improved ventriculoarterial coupling. This effect was attenuated in patients with severely impaired myocardial contractility. LV relaxation, assessed by the time constant of isovolumic pressure decay (T(1/2)), was significantly shortened at 90 min (from 47.7 +/- 1.9 to 41.2 +/- 1.7 ms; p < 0.01), although it remained unchanged at 45 min. The diastolic pressure-volume relation showed a leftward and downward shift in all patients. These results indicate that low-dose oral pimobendan had favorable short-term inotropic and lusitropic effects in patients with congestive heart failure caused by idiopathic dilated cardiomyopathy, and may thus be a useful alternative to traditional agents. Further study in a large-scale trial is merited.

Administration, Oral↗

Phenotypic variation of familial hypertrophic cardiomyopathy caused by the Phe(110)-->Ile mutation in cardiac troponin T.

Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familial hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals, including 6 with HCM, was subjected to genetic and clinical assessment. Five exons of the cTnT gene were sequenced in all family members. A heterozygous or homozygous T(340)-->A (Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was detected in 11 subjects. Morphological and functional evaluation of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderate cardiac hypertrophy. Cardiac hypertrophy and other clinical features in the 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM. Thus, the clinical features of HCM due to the Phe(110)-->Ile mutation in the cTnT gene appear to be modified by a gene dosage effect.

Adolescent↗

Effects of lithium on the pharmacokinetics of valproate in rats.

Combined treatment with lithium and valproate has been used for bipolar disorder. However, the studied interaction between these two drugs has not been fully investigated. We therefore examined the effects of lithium on the pharmacokinetics (plasma disappearance, metabolism and urinary excretion) of valproate in rats. Lithium (2 mEq kg(-1)) was administered intraperitoneally twice a day for ten days. Plasma disappearance curves of valproate (50 mg kg(-1), i.v.), valproate-metabolizing activities of UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) in liver microsomes and urinary excretion of free valproate and valproate-glucuronide were examined. The metabolizing activity of UGT and CYP were determined by enzyme assays and a fluorescence polarization immunoassay system. Urinary valproate-glucuronide was obtained using this system by subtracting the free level from total level, which was determined after deconjugating the sample with heat and NaOH. The half-life of plasma disappearance of valproate was 25% reduced by lithium pretreatment (0.428 +/- 0.031 h with repeated lithium pretreatment vs 0.578 +/- 0.062 h for controls). The valproate-metabolizing activity of UGT and CYP were not altered by lithium although lithium increased the urinary excretion of valproate-glucuronide. In conclusion, lithium pretreatment causes a decrease in plasma valproate levels and an increase in urinary excretion of valproate-glucuronide in rats.

Animals↗

Antitumor promoting effect of an active component of Polyporus, ergosterol and related compounds on rat urinary bladder carcinogenesis in a short-term test with concanavalin A.

The effect of fractions from a water extract of Polyporus on bladder tumor promotion was examined using 5% sodium saccharin (SS) in a short-term test with concanavalin A (Con A) in Wistar rats. Rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) in drinking water for one week, and then promoter alone or test samples (given orally) plus promoter was administered for 3 weeks. Treatment with the BuOH fraction isolated from the water extract showed a strong inhibitory effect against the promoter. It was found that the inhibitory effect of the BuOH fraction is due to the effect of ergosterol contained in the fraction. Treatment with ergosterol showed a strong inhibitory effect against 5% SS, 0.01% BHBN, 3% DL-tryptophan (Trp) or 2% butylated hydroxyanisole (BHA); ID50 was 1.4 microg/kg/d, 2.9 microg/kg/d, 11.6 microg/kg/d, and 11.7 microg/kg/d against SS, BHBN, Trp and BHA, respectively. We also examined the effect of steroids and related compounds. Squalene and vitamin D2 showed strong inhibitory effect against 5% SS-induced bladder tumor promotion. These results strongly suggest that ergosterol could provide significant protection against the promotion of bladder tumor induced by many types of promoters in the environment.

Agglutination Tests↗