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Biomedical subjects

Ichiro Yokota

Publications and source records attributed to Ichiro Yokota.

11 recordsLinked to original sources
PubMed2005

Past 10-year status of insulin therapy for preschool-age Japanese children with type 1 diabetes.

The aim of this study was to evaluate the past 10-year status of insulin therapy for preschool-age children with type 1 diabetes in Japan. One-hundred and forty-two patients who had been diagnosed at less than 5 years of age within the past 10 years (1993-2002) at 36 hospitals were registered in this study on April 2003. The methods of daily insulin therapy and episodes of severe hypoglycemia during the preschool period were investigated. Eighty-six (60.6%) children were treated with a pen-type device and 56 (39.4%) were treated with a syringe-type device. The once-a-day insulin regimen was used for 2, a twice-a-day regimen for 104, a three-times-a-day for 28 and a four-times-a-day for 8. Episodes of severe hypoglycemia were recorded in nearly half of the subjects, and one-fourth of the subjects had repeated episodes. One hundred and eleven of their parents were questioned regarding the degree of psychosocial stress experienced during the care of their children. Most parents worried about the glycosylated hemoglobin value at each hospital visit. They were next very afraid of nocturnal severe hypoglycemia, independent of any actual experience. These results suggest that although insulin therapy can involve various methods, the important point is to simultaneously provide good glycemic control and prevent severe hypoglycemia, especially during this age.

Child, Preschool↗
PubMed2005

Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation.

The octanoylation of Ser3 is essential for the biological function of ghrelin. We examined the concentrations of the n-octanoylated active-form ghrelin in cord and neonatal blood using an RIA system that specifically recognized n-octanoylated ghrelin, as well as a system that measured the total ghrelin concentration. Plasma levels of active ghrelin in cord blood ranged from 7.7 to 38.4 pmol/l and correlated excellently with those of total ghrelin (r = 0.81, p<0.0001). The active ghrelin/total ghrelin (A/T) ratio ranged from 0.038 to 0.12 (median 0.072). The active ghrelin concentrations negatively correlated with birth body weight (r = -0.34, p = 0.01) and IGF-1 concentrations (r = -0.40, p = 0.003), but did not correlate with growth hormone (GH) concentrations. A considerable level of active ghrelin was detected in premature newborns. Venous cord blood samples showed a significantly higher active ghrelin concentration (p = 0.03) and A/T ratio (p = 0.01) than those in the artery. In neonatal blood, active ghrelin concentrations ranged from 4.6 to 22.6 pmol/l and the A/T ratio ranged from 0.02 to 0.081. These results demonstrate the existence of active-form ghrelin in fetal and neonatal circulation and may suggest the energy supply-dependent regulation of ghrelin expression/secretion in utero.

Birth Weight↗
PubMed2004

Genetic background markedly influences vulnerability of the hippocampal neuronal organization in the "twitcher" mouse model of globoid cell leukodystrophy.

The twitcher mouse is well known as a naturally occurring authentic mouse model of human globoid cell leukodystrophy (GLD; Krabbe disease) due to genetic deficiency of lysosomal galactosylceramidase. The twitcher mice used most commonly are on the C57BL/6J background. We generated twitcher mice that were on the mixed background of C57BL/6J and 129SvEv, the standard strain for production of targeted mutations. Twitcher mice on the mixed background were smaller and had a shorter lifespan than were those on the C57BL/6J background. Many twitcher mice on the mixed background developed generalized seizures around 30 days that were never seen in twitcher mice on the C57BL/6J background. Neuropathologically, although the degree of the typical demyelination with infiltration of macrophages was similar in the central and peripheral nervous systems, in both strains, marked neuronal cell death was observed only in twitcher mice on the mixed background. In the hippocampus, the neuronal cell death occurred prominently in the CA3 region in contrast to the relatively well-preserved CA1 and CA2 areas. This neuropathology has never been seen in twitcher mice on the C57BL/6J background. Biochemically, the brain of twitcher mice on the mixed background showed much greater accumulation of lactosylceramide. Genetic background must be carefully taken into consideration when phenotype of mutant mice is evaluated, particularly because most targeted mutants are initially on a mixed genetic background and gradually moved to a pure background. These findings also suggest an intriguing possibility of important function of some sphingolipids in the hippocampal neuronal organization and maintenance.

Animals↗
PubMed2004

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight.

OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.

Adiponectin↗
PubMed2004

[Case of methylmalonic acidemia presenting clinically Leigh encephalopathy].

A 1-year-old boy with methylmalonic acidemia had symmetrical lesions of the bilateral basal ganglia, which suggested Leigh encephalopathy. The findings on brain magnetic resonance imaging (MRI) and his physical condition greatly improved by the intravenous administration of vitamin B1. We hypothesized that in this case, clinical Leigh encephalopathy was caused by a impairment of the activity of pyruvate carboxylase induced by the accumulation of methylmalonyl CoA and an impairment of energy production due to a lack of vitamin B1, especially impairment of the activity of pyruvate dehydrogenase complex during an acute worsening of methylmalonic acidemia. Thus, in the treatment of methylmalonic acidemia, attention should be paid to vitamin B1 deficiency. During an acute worsening, vitamin B1 should be administered by intravenous drip injection.

Brain↗
PubMed2003

Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance.

To investigate the relationship between ghrelin and both fetal and neonatal growth parameters and energy balance, we measured plasma ghrelin concentrations in 54 cord blood samples (male, n = 34; female, n = 20; gestational age, 37.0-41.6 wk; birth weight, 2206-4326 g) and 47 neonatal blood samples (male, n = 27; female, n = 20; postnatal d 3-8). The plasma ghrelin concentrations in cord blood ranged from 110.6-446.1 pmol/liter (median, 206.7 pmol/liter), which were equal to or higher than those in normal weight adults. These values were inversely correlated with birth weight (r = -0.40; P = 0.002), birth length (r = -0.36; P = 0.007), placental weight (r = -0.35; P = 0.01), and IGF-I concentration (r = -0.49; P = 0.0002), but were not significantly correlated with the GH concentration (r = 0.22; P = 0.12). The ghrelin concentrations in small for gestational age newborn were significantly higher than those in appropriate for gestational age newborns (P = 0.0008). The ghrelin concentrations in the vein were significantly higher than those in the artery in 8 cord blood samples (P = 0.01), which suggests that the placenta is an important source of fetal ghrelin. In neonates, the ghrelin concentrations ranged from 133.0-481.7 pmol/liter (median, 268.3 pmol/liter), which were significantly higher than those in cord blood (P < 0.0001). These results suggest that ghrelin may contribute to fetal and neonatal growth.

Birth Weight↗
PubMed2002

Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region.

The human pyruvate dehydrogenase complex (PDHC) catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment is very effective for some patients with PDHC deficiency. Among these patients, five mutations of the pyruvate dehydrogenase (E1)alpha subunit have been reported previously: H44R, R88S, G89S, R263G, and V389fs. All five mutations are in a region outside the thiamine pyrophosphate (TPP)-binding region of the E1alpha subunit. We report the biochemical and molecular analysis of two patients with clinically thiamine-responsive lactic acidemia. The PDHC activity was assayed using two different concentrations of TPP. These two patients displayed very low PDHC activity in the presence of a low (1 x 10(-4) mM) TPP concentration, but their PDHC activity significantly increased at a high (0.4 mM) TPP concentration. Therefore, the PDHC deficiency in these two patients was due to a decreased affinity of PDHC for TPP. Treatment of both patients with thiamine resulted in a reduction in the serum lactate concentration and clinical improvement, suggesting that these two patients have a thiamine-responsive PDHC deficiency. The DNA sequence of these two male patients' X-linked E1alpha subunit revealed a point mutation (F205L and L216F) within the TPP-binding region in exon 7.

Binding Sites↗
PubMed2002

Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency.

Pyruvate dehydrogenase complex (PDHC) deficiency is a major cause of congenital lactic acidemia in children. PDHC catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment was effective for some patients with PDHC deficiency. We reexamined 30 patients with congenital lactic acidemia of unknown origin who had normal PDHC activity in their cultured fibroblasts using a routine assay with a high (0.4 mM) thiamine pyrophosphate (TPP) concentration. We measured the activity of PDHC in the presence of a low (1x10(-4) mM) TPP concentration, and analyzed for mutations in the E1alpha subunit gene. Three males had low PDHC activity in the presence of 1x10(-4) mM TPP. The DNA sequence of these three patients' X-linked E1alpha subunit revealed a substitution of alanine for valine at position 71 (V71A) in exon 3, phenylalanine for cysteine at position 101 (C101F) in exon 4, and glycine for arginine at position 263 (R263G) in exon 8, respectively. Thiamine treatment was effective in these three patients. Therefore, they had a thiamine-responsive PDHC deficiency due to a point mutation in the E1alpha subunit gene. PDHC activity should be measured at a low TPP concentration to detect thiamine-responsive PDHC deficiency so that thiamine treatment can be initiated as soon as possible.

Acidosis, Lactic↗
PubMed2002

Three novel SURF-1 mutations in Japanese patients with Leigh syndrome.

Leigh syndrome, a severe neurodegenerative disorder, commonly is associated with cytochrome c oxidase deficiency. Recent studies in white patients indicate that SURF-1 gene mutations can cause Leigh syndrome associated with cytochrome c oxidase deficiency. When we measured cytochrome c oxidase activity in cultured lymphoblastoid cells from our Japanese patients with typical Leigh syndrome, three patients demonstrated cytochrome c oxidase deficiency. Three novel mutations of the SURF-1 gene were identified in two of these three patients with cytochrome c oxidase deficiency. All mutations predicted loss of function of the SURF-1 protein; in both patients' cells, cytochrome c oxidase activity was decreased to less than 20% of the control mean. These results indicate that cultured lymphoblastoid cells are useful for elucidating the etiology of Leigh syndrome, and that loss of function of the SURF-1 gene product can be responsible for Leigh syndrome associated with severe cytochrome c oxidase deficiency in Japanese patients.

Amino Acid Sequence↗