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Biomedical subjects

G Takada

Publications and source records attributed to G Takada.

At least 73 records · Page 4Linked to original sources
PubMed1998

In situ morphometric analysis of the coronary arterial growth in perinatal rats.

The perinatal changes in the diameters of left and right coronary arteries in rats were studied using the rapid whole body freezing technique. The main portion of the left coronary artery and left anterior descending and circumflex branches rapidly increased in diameter after birth as well as ascending aorta. The ratios of the diameters of the left coronary artery and anterior descending branch to the diameter of ascending aorta increased significantly after 4 days of age. In contrast, there were no significant changes in the diameter of the right coronary artery from the fetus to the 8-day-old pups and the ratio of the right coronary artery to the ascending aorta significantly decreased after birth. We report here that the left coronary artery in rats increases in diameter more rapidly than the right coronary artery in the early newborn period.

Animals↗
PubMed1998

Abnormal left ventricular diastolic filling patterns in small-for-gestational-age infants.

Doppler transmitral flow velocity patterns in assessing left ventricular diastolic function in small-for-gestational-age infants have been poorly understood. The purpose of this study is to examine Doppler filling patterns in small-for-gestational-age infants (n = 13) and to compare them with those in age-matched appropriate-for-gestational-age infants (n = 29). We measured peak flow velocities of early diastole (peak E wave) and atrial contraction (peak A wave), ratio of peak E wave to peak A wave (peak E/A wave), velocity time integrals of E wave (VTIE wave) and A wave (VTIA wave), ratio of VTIE wave to VTIA wave (VTIE/A wave), first third filling fraction, peak filling rate normalized to stroke volume, and deceleration time. Mean gestational age and heart rate did not show a significant difference between the appropriate- and the small-for-gestational-age infants. The mean birth weight in the small-for-gestational-age infants was significantly lower than that in the appropriate-for-gestational-age infants (802+/-220 vs. 1184+/-260 g, P<0.01). In the small-for-gestational-age infants, the peak E wave, peak A wave, peak E/A wave,VTIE wave, first third filling fraction, and peak filling rate normalized to stroke volume were significantly lower than those in the age-matched appropriate-for-gestational-age infants (21.9+/-6.7 vs. 32.2+/-6.9 cm/s, 26.5+/-6.2 vs. 34.5+/-6.2 cm/s, 0.82+/-0.15 vs. 0.93+/-0.14, 1.88+/-0.45 vs. 2.39+/-0.51 cm, 0.36+/-0.04 vs. 0.41+/-0.04, 5.86+/-0.75 vs. 7.11+/-0.63/s, P<0.05, respectively). In the small and appropriate for gestational age infants, peak E wave, VTIE wave, and peak E/A increased significantly with increasing body weight. In the small-for-gestational-age infants, the slopes of regression lines between body weights and peak E wave and VTIE wave were significantly lower than those in the appropriate for gestational age infants, suggesting a significant reduction in E wave even when considering a difference in their body weight. This study suggests that the significant decreases in the early diastolic filling in the small-for-gestational-age infants may be related to the reduced left ventricular diastolic function.

Blood Flow Velocity↗
PubMed1998

Maturational changes in left ventricular contractile state.

It has been suggested from animal and human studies that age-related alterations in left ventricular contractility occur. However, there is little information about growth-related changes in left ventricular performance from preterm infants to older children. In 22 preterm infants, 23 fullterm infants, and 35 children, left ventricular contractility was evaluated by two-dimensional and M-mode echocardiography. The rate-corrected mean velocity of fiber shortening (mVcfc)-end-systolic wall stress (ESS) relation was used as an index of contractility. There were significant inverse linear correlations between ESS and mVcfc in the three groups (all P<0.01). The slopes and y-intercepts of the regression lines of mVcfc-ESS relation were both significantly greater in the premature infants (mVcfc=-0.0133 ESS+1.62) and neonates (mVcfc=-0.0107 ESS+1.55) than those in the children (mVcfc=-0.0047+1.29). However, there were no significant differences between the premature and fullterm infants. Thus, these findings suggest that the contractility and afterload sensitivity of the left ventricle in the premature infants may be similar to those in the fullterm infants. In addition, our serial study in the premature infants showed that the ESS increased significantly with growth while the mVcfc did not change, suggesting that the left ventricular performance in the premature infants during early life was preserved in the setting of a lower afterload.

Analysis of Variance↗
PubMed1998

Changes in superior vena cava velocity patterns in normal neonates.

We demonstrated serial changes in the flow velocity patterns of both the superior vena cava and the tricuspid flow velocity patterns during the first day of life. These changes in waveforms may be related to alterations in loading conditions induced by the closing process of the ductus arteriosus.

Blood Flow Velocity↗
PubMed1998

Role of left ventricular mass/volume ratio on transmitral flow velocity patterns from infancy to childhood.

Age-related changes in left ventricular diastolic filling have been reported to occur in normal children in studies using Doppler echocardiographic methods. However, little information currently exists on the relationships between transmitral flow velocity patterns and the left ventricular mass. We measured left ventricular end-diastolic volume, left ventricular mass, mass/volume ratio, and transmitral flow velocity patterns by M-mode and Doppler echocardiography in 165 normal children aged 5 days to 195 months. Subjects were divided into 6 age groups: <1; 1 to <3; 3 to <5; 5 to <7; 7 to <9; and > or = 9 years old. The left ventricular end-diastolic volume and mass increased progressively with increasing age. However, the mass/volume ratio in infants <1 year was significantly higher than that in infants 1 to <3 years (1.32+/-0.25 vs. 1.14+/-0.16, p<0.01) without any changes of the ratio thereafter. The peak E wave in infants <1 year was significantly lower than that in 1 to <3 years (71+/-18 vs. 92+/-13 cm/s, p<0.01) without changes thereafter. As the flow velocity time integral of E wave increased and that of A wave remained constant, the flow velocity time integral of E/A wave increased with increasing age. The early diastolic tilling fraction in infants <1 year was lower than that in infants 1 to 3 years. (0.61+/-0.07 vs. 0.70+/-0.06, p<0.01). The atrial filling fraction in infants <1 year was higher than that in infants 1 to <3 years (0.40+/-0.08 vs. 0.30+/-0.06, p<0.01) with a little decrease thereafter. The peak E wave, early diastolic tilling fraction, and the atrial filling fraction correlated with the logarithm of age (p<0.01). Age-related changes in these Doppler echocardiographic findings suggest reduced left ventricular early diastolic filling patterns. The mass/volume ratio correlated linearly with peak E wave, early diastolic filling fraction, and atrial filling fraction (r=-0.38, -0.33, and 0.26, p<0.01). No significant relationships between mass/volume ratio and the other Doppler indices were found. Thus, the age-related reduction in the mass/volume ratio may be one of the mechanisms underlying age-related changes in the early diastolic ventricular filling as assessed by Doppler echocardiography.

Aging↗
PubMed1998

An infant with hypereosinophilic syndrome and heart failure markedly responded to prednisolone: serial changes of left ventricular wall thickening and left ventricular diastolic dysfunction observed by echocardiography.

We encountered an infant with congestive heart failure due to idiopathic hypereosinophilic syndrome. The patient showed marked thickening of the left ventricular wall and left ventricular diastolic dysfunction, both of which, shortly after prednisolone therapy, markedly improved together with improvement of the congestive heart failure and hypereosinophilia. Observation of pulmonary venous flow patterns detected by pulsed Doppler echocardiography may be useful for evaluation of left ventricular diastolic function.

Echocardiography, Doppler, Pulsed↗
PubMed1998

Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family.

Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.

Adolescent↗
PubMed1998

Morphological maturation of left ventricle in fetal rats: changes in left ventricular volume, mass, wall thickness, and mitral valvular size.

Morphological changes in the left ventricles of fetal rats from 17 to 21 days of gestation were studied using the rapid whole-body freezing technique. Wistar rats (pregnant period, 21.5 days) were used. Left ventricular volume, mass, wall thickness, and area of mitral valvular orifice increased rapidly and linearly during the observation period. The ratio of the mass to volume of the left ventricle gradually decreased as the fetuses grew older, and by 21st day of gestation it was 52% that of 17 days of gestation. The ratio of the area of mitral valvular orifice to left ventricular volume also decreased by 29% during the same period. Thus we see that the left ventricle of fetal rat was in the condition of physiological hypertrophy and had the large mitral valvular orifice in early gestational age. We suggest that the decrease of the ratio of mass to volume of the left ventricle with the progression of gestational age indicates the morphological maturation of the left ventricle to adapt to the rapid increase of volume overload during the perinatal period.

Animals↗
PubMed1998

Effect of carnitine on valproic acid concentrations in serum, brain, and liver.

This study investigates the influence of L-carnitine supplementation on valproic acid concentrations in rat serum, brain, and liver. Carnitine supplementation increased carnitine concentrations significantly in serum and liver but not in the brain. Free valproic acid concentrations in the brain were significantly increased by carnitine supplementation without any change of carnitine concentrations in the brain. The increase of serum-free valproic acid concentrations by carnitine supplementation apparently caused brain-free valproic acid concentrations to increase. This study suggests that L-carnitine supplementation to valproic acid therapy may potentiate valproic acid effects in the brain, even when the clinical dosage in humans is used.

Animals↗
PubMed1998

Changes in patterns of left ventricular diastolic filling revealed by Doppler echocardiography in infants with ventricular septal defect.

To evaluate left ventricular diastolic filling in infants with ventricular septal defect, which has yet to be documented, we measured various Doppler echocardiographic indexes from transmitral flow in the following groups: 10 infants with ventricular septal defect without pulmonary hypertension; 10 infants with ventricular septal defect with pulmonary hypertension; and 9 normal infants to serve as controls. The peak A, total velocity time integral, E area, and A area in patients without pulmonary hypertension were all significantly larger than those in controls. The peak ratio E/A, and 1/3 filling fraction, in patients without pulmonary hypertension were significantly lower than in controls. The peak A, A area, and deceleration time in patients with pulmonary hypertension were significantly larger than in patients without pulmonary hypertension and controls. The peak E/A, area E/A, and 1/3 filling fraction in patients with pulmonary hypertension were significantly lower than in those without pulmonary hypertension and controls. The index of left ventricular mass, as well as the index of end-diastolic left ventricular wall thickness, correlated strongly with peak A, A area, and deceleration time. The ratio between the systolic pulmonary and systemic pressures correlated strongly with peak A, A area, peak E/A, area E/A, and 1/3 filling fraction. These results demonstrated that the patterns of left ventricular filling in infants with ventricular septal defect were different from those in normal infants, and suggested that the abnormal patterns may indicate the insufficiency of adaptation of left ventricle (increase of left ventricular compliance) for volume overload in the presence of a ventricular septal defect.

Cardiac Catheterization↗
PubMed1998

Mutational analyses in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1.

We analysed the gene of the human alpha-subunit of liver phosphorylase kinase (PHKA2) in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1 by RT-PCR followed by PCR-single-strand conformation polymorphism and direct DNA sequencing. In this study, two novel mutations (Y116D and 2675A-->G) and one mutation previously reported (P1205L) were identified, revealing molecular heterogeneity in Japanese patients. Considering the dissimilarity in phenotype among our patients even with an identical mutation in the PHKA2 gene, it seems that each genetic deficiency in this gene may not be the only factor to determine the clinical heterogeneity in this disease.

Base Sequence↗
PubMed1998

Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and steatosis.

Idiopathic neonatal hepatitis (INH) is a heterogeneous disease of undetermined cause. We report a retrospective histologic reevaluation of INH. Sixty patients with INH were reviewed along with 32 biliary atresia (BA) patients. Histologic findings, iron and fat deposits, giant cell transformation, portal fibrosis, and bile duct proliferation were semiquantitatively graded from 0 to 4+. Significant histologic findings were defined as > or =2+. Frequencies of patients with significant histologic findings in the INH group were compared with those of the BA group. Among the patients with significant histologic findings, those in the INH group had significantly less iron deposits (P < 0.01), portal fibrosis (P < 0.01), and bile duct proliferation (P < 0.01) than those of the BA group. A combination of significant hepatic macrovesicular steatosis and siderosis was observed in 10 INH patients but not in any BA patient (10/60 vs 0/32, P < 0.05). Without extensive treatment, the 10 INH patients all recovered, and hepatic abnormalities normalized by the age of 12 months. In conclusion, the present study showed that the recognition of hepatic siderosis is helpful to distinguish BA from INH and that in a subset of INH patients hepatic macrovesicular steatosis and siderosis occurs.

Biliary Atresia↗
PubMed1998

Effect of N-methyl-D-aspartate and potassium on striatal monoamine metabolism in immature rat: an in vivo microdialysis study.

Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1-3 mM) and potassium (200-800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Evidence for linkage of human primary systemic carnitine deficiency with D5S436: a novel gene locus on chromosome 5q.

Primary systemic carnitine deficiency (SCD) is a rare hereditary disorder transmitted by an autosomal recessive mode of inheritance. The disorder includes cardiomyopathy, muscle weakness, hypoketotic coma with hypoglycemia, and hyperammonemia. In this study, we conducted a linkage analysis of a Japanese SCD family with a proband-a 9-year-old girl-and 26 members. The serum and urinary carnitine levels were determined for all members. The entire genome was searched for linkage to the gene locus for SCD, by use of a total of approximately 300 polymorphic markers located approximately 15-20 cM apart. In the family, there were two significantly different phenotypes, in terms of serum free-carnitine levels: low serum free-carnitine level (29.5+/-5.0 microM; n=14) and normal serum free-carnitine level (46.8+/-6.2 microM; n=12). There was no correlation of urinary free-carnitine levels with the low serum-level phenotype (putative heterozygote), but in normal phenotypes (wild type) urinary levels decreased as the serum levels decreased; renal resorption of free carnitine appeared to be complete in wild-type individuals, when the serum free-carnitine level was <36 microM. Linkage analysis using an autosomal dominant mode of inheritance of heterozygosity revealed a tight linkage between the disease allele and D5S436 on chromosome 5q, with a two-point LOD score of 4.98 and a multipoint LOD score of 5.52. The haplotype analysis revealed that the responsible genetic locus lies between D5S658 and D5S434, which we named the "SCD" locus. This region was syntenic with the jvs locus, which is responsible for murine SCD. Phylogenic conversion of the SCD locus strongly suggests involvement of a single gene, in human SCD.

Carnitine↗
PubMed1998

Neonatal intrahepatic cholestasis with hepatic siderosis and steatosis.

Neonatal intrahepatic cholestasis is a heterogeneous disease of undetermined cause. There is an unreported subset of idiopathic neonatal intrahepatic cholestasis with an unusual histological combination of hepatic siderosis and macrovesicular steatosis. The patients were a 34-day-old female and a 39-day-old male with normal birth weights. Their mothers had received oral iron supplement 4-6 weeks before delivery. The patients had obstructive jaundice noticed at the well-baby clinic at 1 month of life. They had high levels of serum galactose and tyrosine, hyperferritinemia. Urinary organic acid and bile acid analyses were negative, and galactose-1-phosphate uridyltransferase activity in red cells was normal. Liver biopsies showed diffuse iron deposits and macrovesicular fat. By substituting formula milk with lactose-free milk, the patients responded, and had normal biochemical tests within 5 months of life. Follow-up biopsies, at the age of 12 months, showed mild residual fibrosis without iron or fat deposits. They are both well at 3 and 6 years of age, respectively, without biochemical liver dysfunction and neurologic impairment. Prenatal iron-overload might contribute to the pathogenesis of the disease, but further studies are needed to confirm the assumption.

Cholestasis, Intrahepatic↗
PubMed1998

Expression of Aspergillus aculeatus No. F-50 cellobiohydrolase I (cbhI) and beta-glucosidase 1 (bgl1) genes by Saccharomyces cerevisiae.

A cellobiohydrolase I (cbhI) and a beta-glucosidase 1 (bgl1) gene of Aspergillus aculeatus were expressed in Saccharomyces cerevisiae. The transformed cells secreted the enzymes efficiently in an active form. The recombinant CBHI gave two bands of different molecular mass (110 and 90 kDa) and the recombinant BGL1 gave one band (180 kDa) by SDS-PAGE. The recombinant CBHI and BGL1 had the same enzymatical properties as the native enzyme except for the specific activity toward cellulosic substrates. By the combination of three different types of cellulases, FI-CMCase, CBHI, and BGL1, we could hydrolyze Avicel up to 59% under our experimental conditions.

Aspergillus↗