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Biomedical subjects

M Yokota

Publications and source records attributed to M Yokota.

At least 127 records · Page 7Linked to original sources

Lack of association between variants of the angiotensinogen gene and the risk of coronary artery disease in middle-aged Japanese men.

The renin-angiotensin system is important in cardiovascular remodeling. Although a variant of the angiotensinogen gene is associated with an increased generation of angiotensinogen, it is unclear how this genetic variant might influence the activity of the renin-angiotensin system and thereby contribute to the predisposition to coronary artery disease (CAD). The relation between genetic polymorphisms in the gene-encoding angiotensinogen and the risk of CAD in middle-aged Japanese men was investigated. Two polymorphisms in exon 2 of the angiotensinogen gene, M235T and T174M, were analyzed in 327 patients with CAD and 352 matched control subjects. The genotype distribution of both polymorphisms did not differ between patients with CAD and control subjects. No combination of genotypes of the two polymorphisms was associated with CAD. Results indicate that the M235T and T174M variants of the angiotensinogen gene are not associated with CAD in Japanese men.

Angiotensinogen↗

Analysis of heart rate variability demonstrates effects of development on vagal modulation of heart rate in healthy children.

OBJECTIVES: Analysis of heart rate variability (HRV) has been found to be a useful method of assessing cardiovascular autonomic control, but normal values for standard HRV measures in children have not been established. We analyzed HRV in 60 healthy children aged 3 to 15 years to determine normal values and to assess the effects of development on cardiac autonomic control with the use of ambulatory electrocardiographic monitoring. RESULTS: The high-frequency (HF) component, an index of cardiac autonomic tone, increased significantly with age from 3 to 6 years (p < 0.01) and decreased with age from 6 to 15 years (p < 0.01), and the magnitude of HF correlated significantly with the R-R intervals. Thus the changes in cardiac autonomic tone could be described as a simple equation using age and heart rate. CONCLUSIONS: We present normal values and changes in the cardiac autonomic system during childhood after HRV analysis, which could lead to a better understanding and treatment of cardiac disease in children.

Adolescent↗

Effects of protein kinase C activation and inhibition on endothelin-1 release from human aortic and pulmonary artery endothelial cells: comparison with effects on bovine endothelin-1 and human prostaglandin I2 release.

Protein kinase C (PKC) has been implicated in the regulation of endothelin-1 production by bovine and porcine endothelial cells. The role of PKC in the synthesis and release of endothelin-1 has not been demonstrated previously in human arterial endothelial cells. The effects of activators and an inhibitor of PKC on endothelin-1 release from cultured human arterial endothelial cells have now been examined. Endothelial monolayers were incubated with the PKC activators phorbol 12-myristate 13-acetate (PMA) or 1-oleoyl 2-acetyl glycerol (OAG) for 30 min to 8 h and the amount of endothelin-1 released into the medium was determined. PMA (0.1 micromol/L) and OAG (0.1 mmol/L) stimulated endothelin-1 release, with maximal increases of 85% and 90%, respectively, apparent at 30 min in aortic endothelial cells, and of 81% and 75%, respectively, apparent at 1 h in pulmonary artery endothelial cells. Endothelin-1 release had returned to control values by 4 h and was approximately one-third to one-half of control values after 8 h of continuous exposure of both cell types to PMA or OAG. Long-term exposure of both types of cells to the PKC inhibitor staurosporine (0.1 micromol/L) reduced both basal endothelin-1 release and the enhancement of release by PMA or OAG. The PKC agonists also stimulated endothelin-1 release by bovine aortic endothelial cells. The maximal effects of PMA and OAG in these cells were apparent at 4 h, at which time endothelin-1 release was increased by 154% and 125%, respectively; after 4 h, endothelin-1 release had decreased, but was still 132% and 120%, respectively, of the control value at 8 h. The PKC activators markedly stimulated prostaglandin I2 (PGI2) release by human pulmonary artery endothelial cells. The enhancement of PGI2 release continued for up to 8 h, at which time 109-fold and threefold increases in PGI2 release were apparent with PMA and OAG, respectively. Therefore, activation of PKC results in a rapid increase in endothelin-1 release by human arterial endothelial cells. The subsequent decrease in endothelin-1 release in the presence of PMA or OAG is presumably attributable to activator-induced downregulation of PKC, which was apparent earlier in human than in nonhuman endothelial cells. The downregulation of endothelin-1 release also occurred much earlier than that of PGI2 release in human pulmonary artery endothelial cells.

Animals↗

Lack of association of polymorphisms of the angiotensin converting enzyme and angiotensinogen genes with nonfamilial hypertrophic or dilated cardiomyopathy.

Although several genes or genetic loci that are either responsible for or confer susceptibility to familial hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) have been identified, genetic defects that underlie nonfamilial HCM or DCM remain to be characterized. An allelic association study for the angiotensin converting enzyme (ACE) and angiotensinogen genes has now been performed with 71 patients with nonfamilial HCM, 88 patients with nonfamilial DCM, and 122 healthy control subjects in the Japanese population. The distribution of ACE genotypes for an insertion/deletion (I/D) polymorphism in intron 16 did not differ significantly among control subjects and patients with HCM or DCM. Similarly, the distributions of angiotensinogen genotypes for methionine-235-threonine (M235T) and threonine-174-methionine (T174M) polymorphisms did not differ significantly among the three groups. Echocardiographic parameters that are indicators of the severity or progression of disease did not differ significantly among ACE I/D or angiotensinogen M235T and T174M genotypes in the two patient groups. Finally, no additive or synergistic effect of any combined genotypes or haplotypes of the ACE and angiotensinogen polymorphisms on the association with HCM or DCM was detected. Results indicate that the ACE I/D and angiotensinogen M235T and T174M polymorphisms are not related to HCM or DCM in the Japanese population, and that variants of these polymorphisms do not contribute to the genesis or progression of these cardiomyopathies.

Angiotensinogen↗

Lack of association of angiotensin converting enzyme gene polymorphism or serum enzyme activity with coronary artery disease in Japanese subjects.

The association of an insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene or the serum activity of ACE with coronary artery disease (CAD) was investigated in Japanese men and women. The ACE genotype of 947 CAD subjects who underwent coronary angiography and of 893 control subjects was determined by polymerase chain reaction analysis. No association of the DD genotype or the D allele with CAD was observed in men or women. In a low risk group (defined by a body mass index below the median value and the absence of a history of hypertension, diabetes mellitus, and hypercholesterolemia), there was also no association between the ACE gene polymorphism and CAD. No significant difference in serum ACE activity was detected between CAD subjects and controls of all genotypes or of the same genotype, whereas a significant association was apparent between serum ACE activity and ACE genotype for both CAD subjects and controls among both men and women. These results indicate that the ACE I/D polymorphism and genotype associated variation in serum ACE activity are not risk factors for CAD in Japanese men or women.

Adult↗

Aberrant glycosylation based on the neo-expression of poly-N-acetyllactosamine structures in squamous cell carcinomas of the head and neck.

An immuno- and lectin-histochemical study was performed to investigate the aberrant expression of blood group-related antigens and poly-N-acetyllactosamine structures in squamous cell carcinomas of the maxillary sinus, the larynx, the apipharynx, the hypopharynx, the oral cavity, the parotid gland and the tonsil from 52 patients using monoclonal antibodies against A, B and H antigens, and six lectins, UEA-I, PNA, VVA-B4, PWM, LEA and DSA. In addition, GSA-II staining following endo-beta-galactosidase digestion procedure was also applied. A, B and H antigens were expressed in most normal epithelial cells of head and neck organs, and depended on the patient blood type. However, in squamous cell carcinoma, A antigen was not detected in eight out of 25 individuals of blood groups A and AB, although B antigen was consistently expressed in carcinoma cells from all the B and AB individuals. On the other hand, H antigen was expressed in carcinoma cells not only from all blood group O individuals, but from 32 out of 35 individuals of blood groups A, B and AB. T and Tn antigens, which are recognized by PNA and VVA-B4, were strongly expressed in carcinoma cells from 40 and 42 out of 52 individuals respectively. Reactivity with GSA-II staining following endo-beta-galactosidase digestion, which recognizes linear poly-N-acetyllactosamine structures, was found in a few malignant cells from 21 individuals. Staining with anti-A, -B and -H monoclonal antibodies and UEA-I lectin was diminished after endo-beta-galactosidase digestion in some cases. Lectins specific for poly-N-acetyllactosamine, such as PWM, LEA and DSA, exhibited reactivity in some malignant cells from 30, 22 and 32 out of 52 individuals respectively. These results suggested that the expression of the blood group-related antigens is suppressed and immature carbohydrate chains, that is H, T and Tn antigens, are accumulated in squamous cell carcinomas of the head and neck. The results further suggested that poly-N-acetyllactosamine structures are simultaneously synthesized along with the deletion of A antigen and the accumulation of precursors.

ABO Blood-Group System↗

Periodontal parameters of osseointegrated dental implants. A 4-year controlled follow-up study.

The aim of this study was to evaluate the periodontal parameters of osseointegrated dental implants. The condition of the peri-implant mucosa was assessed using periodontal parameters, i.e., of plaque index, bleeding on probing, probing pocket depth, probing attachment level and Periotest scores as well as a radiographic parameter, over a 4-year follow-up period. 32 non-submerged ITI dental implants, all placed in the mandible, were studied in 12 patients who had good oral hygiene. All patients were regularly recalled at 6-month intervals. The overall implant success rate was 100%. None of the implants showed any signs of inflammation, radiographic bone loss or any detectable mobility during the follow-up period. Methods similar to those used to evaluate the natural dentition were effectively employed to assess the clinical status of the dental implants. The diagnostic value of these parameters could not, however, be determined from this study due to the absence of any peri-implant tissue complications. The results indicated that some periodontal parameters of healthy peri-implant mucosa might be slightly different from healthy periodontal tissue.

Alveolar Process↗

Suppressed cardiac and electroencephalographic arousal on apnea/hypopnea termination in elderly patients with cerebral infarction.

The goal of the present investigation is to show the clinical significance of arousal response at termination of apnea/hypopnea in patients with sleep apnea syndrome (SAS) after cerebral infarction. We polygraphically assessed "cardiac arousal," which is defined as an abrupt increase in heart rate at a termination of sleep apnea/hypopnea, and electroencephalographic (EEG) arousal. There were six elderly subjects, bedridden after cerebral infarction, with SAS aged 71-87 years (mean 72.3 years) and 11 age-matched patients with SAS aged 61-78 years (mean 62.3 years) as controls. The following sleep parameters were measured: number of apneas per hour (apnea index [AI]), number of hypopneas per hour (hypopnea index [HI]), summation of the two (apnea/hypopnea index [AHI]), and duration in which nocturnal oxygen saturation was decreased below 90% (duration of SaO2 < 90%). We calculated the ratio of apnea/hypopnea per hour with cardiac arousal to total apnea/hypopneas (XI) (% cardiac arousal [XI/AHI x 100]) and the ratio of that with EEG arousal (YI) (% EEG arousal [YI/AHI x 100]). Between the two groups, we found no significant difference in body mass index, the ratio of central apnea to total apnea/hypopnea, AHI, duration of apnea/hypopnea, lowest SaO2, and duration of SaO2 < 90%. Compared with controls, % cardiac and % EEG arousals were significantly lower in patients with cerebral infarction. In contrast, the ratio of HI to AHI was significantly higher in patients with cerebral infarction than in control subjects. Our findings indicate that cardiac and EEG arousals at termination of apnea/hypopnea are significantly suppressed in elderly patients with SAS after cerebral infarction, which may provide useful information on the pathophysiology of SAS in patients with cerebrovascular disease.

Aged↗

Effect of dobutamine and OPC-18790 on diastolic chamber stiffness in patients with idiopathic dilated cardiomyopathy.

We investigated the acute effects of the positive inotropic agents (dobutamine and a novel phosphodiesterase inhibitor OPC-18790) on left ventricular diastolic chamber stiffness in patients with idiopathic dilated cardiomyopathy (DCM). We obtained pressure-volume (PV) data before and after drug administration in 17 patients with DCM by using a conductance catheter with a micromanometer tip. Patients were randomly assigned to receive intravenous infusions of dobutamine (2.5-7.5 micrograms/kg body weight per min, n = 8) or OPC-18790 (5-10 micrograms/kg body weight per min, n = 9). The dynamic diastolic chamber stiffness constant was calculated from a steady-state beat. The passive diastolic chamber stiffness constant was determined from the end-diastolic PV relation determined during transient inferior vena caval occlusion. Dobutamine and OPC-18790 similarly improved left ventricular end-systolic elastance (Ees) and left ventricular isovolumic relaxation time constants. The dynamic diastolic chamber stiffness constant decreased significantly in both the dobutamine (0.0934 +/- 0.0271 to 0.0685 +/- 0.0248; p < 0.01) and OPC-18790 (0.0843 +/- 0.0477 to 0.0569 +/- 0.0246; p < 0.05) groups. The passive diastolic chamber stiffness constant decreased significantly in the OPC-18790-treated group (0.0211 +/- 0.0114 to 0.0144 +/- 0.0117; p < 0.005) but not in the dobutamine-treated group (0.0197 +/- 0.0130 to 0.010186 +/- 0.0102; p > 0.05). Thus both dobutamine and OPC-18790 reduced the dynamic diastolic chamber stiffness constant, but only OPC-18790 reduced the passive diastolic chamber stiffness constant. OPC-18790 had a favorable effect on diastolic function in patients with DCM, compared with that of dobutamine. The passive diastolic chamber stiffness obtained from the end-diastolic PV relations represents more likely passive chamber properties than the dynamic diastolic chamber stiffness obtained from traditional single-beat analysis.

Adult↗

Protective activity of Borrelia duttonii-specific immunoglobulin subclasses in mice.

To analyse the immune response of mice to Borrelia duttonii infection, BALB/c mice were inoculated intraperitoneally with B. duttonii strain 406K, and the titres of B. duttonii-specific immunoglobulins - IgM, IgG1, IgG2a, IgG2b and IgG3 - were determined by ELISA. IgM antibodies appeared first, followed by IgG2a and IgG3, and then IgG1 and IgG2b. The protective activity of individual classes and subclasses of B. duttonii-specific immunoglobulins was then determined by passive immunisation of BALB/c mice with immunoglobulin preparations purified by affinity chromatography. The mice were then challenged by intraperitoneal inoculation of B. duttonii. The study demonstrated that B. duttonii-specific IgM and IgG3 protected against the development of spirochaetaemia and death after borrelial infection, whereas B. duttonii-specific IgG1, IgG2a and IgG2b had low protective activities.

Animals↗

Enhanced motility of the vagotomized canine stomach by electrical stimulation.

Functional impairment of the vagotomized stomach used as a substitute oesophagus seriously deteriorates the quality of life of patients following oesophageal cancer surgery. We speculated that if the enteric neurons of the reconstructed gastric tube survived functionally, the motility of the gastric tube could be facilitated and the recovery process after operation would improve as a consequence. In the present study we investigated whether direct electrical stimulation was effective for facilitating the motility of the canine vagotomized stomach. Dogs underwent truncal vagotomy by transabdominal approach and, in some cases, arteries to the upper stomach and the oesophagus were also ligated and resected to resemble the blood supply and surgical invasion of the reconstructed gastric tube. Electrical stimulation, a few minutes of positive rectangular current pulses, amplitude 20 V (or 15 mA), duration 0.5 ms and frequency between 0.2 and 7 Hz, was delivered on the greater curvature of the mid corpus. Changes in mechanical contractions were recorded using strain gauge force transducers. Electrical stimulation successfully enhanced the mechanical force of the phasic ring contractions of the vagotomized stomach in a frequency dependent manner. Aboral propagation and periodicity of the contractions, impaired by surgical procedures, were restored during stimulation. These excitatory effects were inhibited by atropine, hexamethonium and tetrodotoxin, suggesting that electrical stimulation acts on intramural cholinergic nerves that have survived functionally. These results suggest that electrical stimulation could be an effective method for improving the motility of the vagotomized stomach.

Animals↗

Recording of electroencephalograms and electrocardiograms during daytime sleep in trained canines: preparation of the sleeping dogs.

Although respiration in trained canines is well investigated, the process of preparing dogs has not been described in any great detail. Moreover, their daytime patterns of sleep and wakefulness during 1 or 2 h of electroencephalogram (EEG) and electrocardiogram (ECG) recordings are not clear. Therefore, we describe the process of selecting and training dogs, in which we recorded EEG and ECG in the laboratory. First, 14 of 1242 dogs dealt with over a 1 year period were chosen. They were trained for 2 h to lie quietly and to sleep in the laboratory; this training procedure was repeated 152 times. Three dogs were then selected and a permanent tracheostomy was performed in one. Finally, EEG and ECG were recorded with the bipolar fine needle electrodes; respiration was recorded simultaneously through a tube inserted to a tracheostomy in one dog. Wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep (REMS) were identified according to the EEG pattern and on the basis of the behavioral criteria. Recordings were performed 12 or 13 times in each dog. Complete sleep cycles, including wakefulness, SWS and REMS in this sequence, were observed 3.9-4.1 times. The mean duration of SWS was 2.2-4.4 min and that of REMS was 3.5-4.6 min. The REMS latency was 33.9-41.8 min. Fluctuation of heart rate with respiration, termed respiratory sinus arrhythmia, was noted in the ECG. Heart beat increased with inspiration and decreased with expiration. The present study demonstrates how to select and train sleeping dogs and shows their undisturbed daytime sleep and wakefulness patterns.

Animals↗

[Social support of chronically-ill children and healthy children].

The purpose of this study was to describe characteristics of social support of chronically-ill children and to compare social support of chronically-ill children with those of healthy children. Subjects consisted of 204 chronically-ill children aged between 9 and 18 years old and 544 healthy children aged between 10 and 17 years old. Results of this study were as follows: 1. In both chronically-ill children and healthy children, parents' support score and teachers' support score were significantly higher in elementary school children than high school students. In both groups, friends' support score was significantly higher in girls than boys. 2. Chronically-ill children reported significantly higher scores of parents' support, friends' support and teachers' support than those of healthy children. 3. Parents' support score was significantly lower in children with diabetes than those with asthma and cancer. 4. The total score of social support and teachers' support score were significantly lower in children with employed mothers than those with unemployed mothers. 5. The total social support score of children who participated in non-sports extracurricular activities was significantly higher than those of children who did not participate in non-sports activities.

Adolescent↗

[Evaluation of electrocardiographic left ventricular hypertrophy with both QRS voltage and ST-T change using echocardiography].

The purpose of the present study is to determine whether electrocardiographic QRS voltage criteria with ST-T change is useful in the diagnosis of left ventricular hypertrophy (LVH) using echocardiography. One hundred men including 59 with hypertension (HT), 9 with hypertrophic cardiomyopathy (HCM), and 32 without any cardiovascular disease were enrolled in this study. All of them had the electrocardiographic evidence of LVH by Sokolow-Lyon voltage criteria (RV5 or RV6 > 2.6 mV, SV1+RV5 or SV1+RV6 > or = 3.5 mV). They were classified into three groups based on ST-T pattern as follows: Normal ST-T (group N): normal ST-T in twelve leads; Early strain ST-T (group ES): ST depression, flat T (T/R < 1/10), diphasic T or T wave inversion < 0.1 mV in V5 or V6; and Strain ST-T (group S): inverted T wave in V5 and V6. Echocardiographic LVH was determined when either interventricular septal thickness (IVST) or left ventricular posterior wall thickness (LVPWT) > or = 12 mm was present. According to this echocardiographic evidence, 31.7%(20/63) of group N, 75.0% (12/16) of group ES, and 100% (21/21) of group S were diagnosed. There were significant correlations between QRS voltage indices (RV5, RV6, SV1+RV5 and SV1+RV6) and IVST, (IVST+LVPWT)/2, and LV mass in group S(r = 0.650 to 0.858, p < 0.05) but not in group N. Values for IVST and LV mass were significantly greater in group S than in group ES or N. The electrocardiographic diagnosis of LVH with both QRS voltage and ST-T change thus appeared to be more useful than that with QRS voltage criteria alone.

Adult↗

[Mitral valve prolapse and autonomic activity in normal women].

We examined relationships between mitral valve prolapse (MVP) and circadian rhythm of autonomic activity using spectral analysis of heart rate variability and echocardiography in 31 normal women. The heart rate variability was calculated from 24-hour ambulatory electrocardiogram by Fourier transformation. The power spectra were quantified at 0.04-0.15 Hz (low frequency power (LF) 1n (ms2)) and 0.15-0.40 Hz (high frequency power (HF) 1n (ms2)). The HF component and the ratio of LF/HF were used as indices of parasympathetic and sympathetic activity, respectively. MVP was present in 22.6%. There were no significant differences in left ventricular dimension between subjects with MVP (group MVP (+)) and subjects without MVP (group MVP(-)). Number of ventricular premature contractions in group MVP(+) tend to be higher compared with that in group MVP(-). The level of high frequency power at 0-5 am in group MVP(+) was significantly higher than that in group MVP(-), which parasympathetic activity during sleep in MVP(+) group was higher compared with that in group MVP(-). The evaluation of autonomic activity using spectral analysis of heart rate variability for 24-hour ambulatory electrocardiogram might provide useful information about the pathology of MVP.

Adult↗

Function of FK506 binding protein (FKBP) in chick embryonic cardiac development.

FK506 binding protein (BP) 12, an immunophilin of FK506-binding proteins, is involved in intra-cellular signal transduction through the calcineurin-nuclear factor pathway. FKBP12 is reported to be associated with the ryanodine-receptor and IP3 Ca2+ channels, and to regulate cell proliferation via binding transforming growth factor (TGF)-beta receptor and cyclin dependent kinase (CDK). To elucidate the function of FKBP12 in cardiac development, we analyzed the temporal profile and regulation of FKBP12 expression in chick heart and in cultured cardiomyocytes. FKBP12 is expressed in embryos as early as day 4 and is predominantly associated with cardiomyocytes and osteo-chondrocytes. Tissue FKBP level in the heart increases with development. Immunohistochemically, the distribution and levels of FKBP12 appear to be related to sarco-endoplasmic reticulum Ca-ATPase 2 (SERCA2) but not to sarcomeric proteins. In proliferating cells, FKBP12 expression correlates with cellular mitosis, but not with DNA synthesis. In earlier embryos (< day 8), suppressing the activity of FKBP by FK506 administration is lethal, and induces cardiomegaly at later stages. In cultured cardiomyocytes, FK506 reduces the level of contractile proteins and inhibits cell proliferation. These results show that FKBP12 is enriched in cell types involved in dynamic Ca handling, and is likely an important molecule for cardiac development. FKBP12 most likely functions by affecting cellular Ca handling, since its effects are modified by modulators of Ca handling by sarcoplasmic reticulum.

Animals↗

Depressed mechanoenergetics and compensatory responses in idiopathic dilated cardiomyopathy.

The aim of this study was to clarify that the depressed mechanoenergetics in patients with idiopathic dilated cardiomyopathy (DCM) resulted from compensation for the decreased contractility. The study population consisted of eight control subjects, with normal left ventricular size and ejection fraction and 31 patients with DCM. Left ventricular end-systolic elastance (Ees), effective arterial elastance (Ea), external work (EW), and the pressure-volume area (PVA) were measured, using a dual-field volume conductance catheter equipped with a micromanometer-tipped catheter. Ea/Ees was evaluated as ventriculoarterial coupling. Normal hearts worked at almost optimal condition (defined as Ea/Ees = 1/2), while ventriculoarterial coupling was far from the optimum (Ea > Ees) in patients with DCM. Ees in patients with DCM was less than that in control subjects; however, Ea was similar in the two groups. The mismatch of Ea/Ees observed in DCM leads to depressed mechanoenergetics as a result of the compensatory response to maintain adequate blood pressure. Volume enlargement plays an important role in maintaining adequate blood pressure and cardiac output in the course of chronic deterioration of contractility.

Blood Pressure↗