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Biomedical subjects

E Naito

Publications and source records attributed to E Naito.

At least 37 records · Page 2Linked to original sources

Fast reaction to different sensory modalities activates common fields in the motor areas, but the anterior cingulate cortex is involved in the speed of reaction.

We examined which motor areas would participate in the coding of a simple opposition of the thumb triggered by auditory, somatosensory and visual signals. We tested which motor areas might be active in response to all three modalities, which motor structures would be activated specifically in response to each modality, and which neural populations would be involved in the speed of the reaction. The subjects were required to press a button with their right thumb as soon as they detected a change in the sensory signal. The regional cerebral blood flow (rCBF) was measured quantitatively with (15)O-butanol and positron emission tomography (PET) in nine normal male subjects. Cytoarchitectural areas were delimited in 10 post mortem brains by objective and quantitative methods. The images of the post mortem brains subsequently were transformed into standard anatomic format. One PET scanning for each of the sensory modalities was done. The control condition was rest with the subjects having their eyes closed. The rCBF images were anatomically standardized, and clusters of significant changes in rCBF were identified. These were localized to motor areas delimited on a preliminary basis, such as supplementary motor area (SMA), dorsal premotor zone (PMD), rostral cingulate motor area (CMAr), and within areas delimited by using microstructural i.e., cytoarchitectonic criteria, such as areas 4a, 4p, 3a, 3b, and 1. Fields of activation observed as a main effect for all three modalities were located bilaterally in the SMA, CMAr, contralateral PMD, primary motor (M1), and primary somatosensory cortex (SI). The activation in M1 engaged areas 4a and 4p and expanded into area 6. The activation in SI engaged areas 3b, 1, and extended into somatosensory association areas and the supramarginal gyrus posteriorly. We identified significant activations that were specific for each modality in the respective sensory association cortices, though no modality specific regions were found in the motor areas. Fields in the anterior cingulate cortex, rostral to the CMAr, consistently showed significant negative correlation with mean reaction time (RT) in all three tasks. These results show that simple reaction time tasks activate many subdivisions of the motor cortices. The information from different sensory modalities converge onto the common structures: the contralateral areas 4a, 4p, 3b, 1, the PMD, and bilaterally on the SMA and the CMAr. The anterior cingulate cortex might be a key structure which determine the speed of reaction in simple RT tasks.

Acoustic Stimulation↗

Concomitant administration of sodium dichloroacetate and thiamine in west syndrome caused by thiamine-responsive pyruvate dehydrogenase complex deficiency.

We treated a female patient with West syndrome caused by thiamine-responsive pyruvate dehydrogenase complex (PDHC) deficiency. Infantile spasms occurred in association with elevated blood and CSF lactate concentrations; these symptoms disappeared when lactate concentrations had been lowered by treatment with concomitant sodium dichloroacetate (DCA) and high dose thiamine. Sequencing the patient's PDHC E(1)alpha subunit revealed a substitution of serine for glycine at position 89 in exon 3 (G89S). This mutation must be a de novo mutation because it was not found in either parents' genome DNA. To our knowledge, five previously described patients with PDHC deficiency have displayed the West syndrome. All six known patients, including our own, were female, even though an approximately equal number of males and females have been identified with PDHC deficiency and overall West syndrome occurs somewhat more frequently in males. These results indicated that West syndrome occurred more frequently in female patients with PDHC deficiency. It is suggested that lactate concentration should be measured in patients with West syndrome for potential PDHC deficiency, especially in females.

Amino Acid Substitution↗

Illusory arm movements activate cortical motor areas: a positron emission tomography study.

Vibration at approximately 70 Hz on the biceps tendon elicits a vivid illusory arm extension. Nobody has examined which areas in the brain are activated when subjects perceive this kinesthetic illusion. The illusion was hypothesized to originate from activations of somatosensory areas normally engaged in kinesthesia. The locations of the microstructurally defined cytoarchitectonic areas of the primary motor (4a and 4p) and primary somatosensory cortex (3a, 3b, and 1) were obtained from population maps of these areas in standard anatomical format. The regional cerebral blood flow (rCBF) was measured with (15)O-butanol and positron emission tomography in nine subjects. The left biceps tendon was vibrated at 10 Hz (LOW), at 70 or 80 Hz (ILLUSION), or at 220 or 240 Hz (HIGH). A REST condition with eyes closed was included in addition. Only the 70 and 80 Hz vibrations elicited strong illusory arm extensions in all subjects without any electromyographic activity in the arm muscles. When the rCBF of the ILLUSION condition was contrasted to the LOW and HIGH conditions, we found two clusters of activations, one in the supplementary motor area (SMA) extending into the caudal cingulate motor area (CMAc) and the other in area 4a extending into the dorsal premotor cortex (PMd) and area 4p. When LOW, HIGH, and ILLUSION were contrasted to REST, giving the main effect of vibration, areas 4p, 3b, and 1, the frontal and parietal operculum, and the insular cortex were activated. Thus, with the exception of area 4p, the effects of vibration and illusion were associated with disparate cortical areas. This indicates that the SMA, CMAc, PMd, and area 4a were activated associated with the kinesthetic illusion. Thus, against our expectations, motor areas rather than somatosensory areas seem to convey the illusion of limb movement.

Adult↗

Dynamic changes in serum leptin concentrations during the fetal and neonatal periods.

We investigated the dynamics of the leptin concentration throughout the perinatal period. Serum leptin concentrations in venous cord blood at different gestational ages were measured in 20 preterm and 139 term newborns, as well as in 143 pregnant women and 24 term newborns at approximately 6 d of life. Leptin concentrations in preterm newborns (mean 4.6+/-6.9 ng/mL) were lower than those in term newborns (mean 19.6+/-14.3 ng/mL) and tended to increase according to gestational age and birth weight, especially from the late stage of gestation. Leptin concentrations in pregnant women increased from the first trimester and then remained higher than those in non-pregnant women throughout the remainder of pregnancy even after controlling for body mass index. The leptin concentrations of newborns declined rapidly and were extremely low by approximately 6 d of life (mean 1.9+/-1.1 ng/mL). These results suggest that fetuses might produce a part of circulating leptin in their own adipocytes and that the relatively high leptin concentrations at birth and their rapid decline in the early neonatal period might reflect the dramatic changes of the hormonal and nutritional state during the perinatal period.

Body Mass Index↗

Comparative studies on iodine levels in gallstones and bile of Japanese and Thais (Chiang Mai and Bangkok).

We measured the iodine content of gallstones and bile from patients in three areas (Kawasaki in Japan, and Chiang Mai and Bangkok in Thailand) by means of neutron activation analysis. The mean values for iodine content in three types of gallstones (cholesterol, pigment and rare stones) and bile from patients living in Chiang Mai were clearly smaller than those from patients living in Kawasaki and Bangkok. The low iodine intake by Chiang Mai patients continued from the start of gallstone formation until the time when the stones were excised, and the iodine intake was low when bile was collected. The PBI levels in the sera of Chiang Mai residents with low iodine intake over a long period were clearly lower than those of Bangkok patients with normal intake, and the levels in goiter patients were similar to those in healthy people and patients with gallstones among Chiang Mai residents.

Bile↗

Molecular genetic analysis of pyridoxine-nonresponsive homocystinuric siblings with different blood methionine levels during the neonatal period.

Two mutations in the cystathionine beta-synthase (CBS) gene were found in two Japanese siblings with pyridoxine non-responsive homocystinuria who had different methionine levels in their blood during the neonatal period. Both patients were compound heterozygotes of two mutant alleles: one had an A-to-G transition at nucleotide 194 (A194 G) that caused a histidine-to-arginine substitution at position 65 of the protein (H65R), while the other had a G-to-A transition at nucleotide 346 (G346A) which resulted in a glycine-to-arginine substitution at position 116 of the protein (G116R). The two mutant proteins were separately expressed in Escherichia coli, and they completely lacked catalytic activity. Despite their identical genotypes and almost equal protein intake, these siblings showed different levels of blood methionine during the neonatal period, suggesting that the level of methionine in blood is determined not only by the defect in the CBS gene and protein intake, but also by the activity of other enzymes involved in methionine and homocysteine metabolism, especially during the neonatal period. Therefore, high-risk newborns who have siblings with homocystinuria, even if the level of methionine in their blood is normal in a neonatal mass screening, should be followed up and diagnosed by an assay of enzyme activity or a gene analysis so that treatment can be begun as soon as possible to prevent the development of clinical symptoms. In addition, a new, more sensitive method for the mass screening of CBS deficiency in neonates should be developed.

Adolescent↗

Effect of growth hormone on the translocation of GLUT4 and its relation to insulin-like and anti-insulin action.

To elucidate the effect of growth hormone (GH) on the insulin signal transduction pathway leading to the translocation of glucose transporter-4 (GLUT4), we constructed Chinese hamster ovary cells that overexpressed GH receptor and GLUT4. Treatment with GH triggered GLUT4 translocation, and this translocation was completely inhibited by wortmannin. GH-induced GLUT4 translocation reached a maximum level after 30 min, and then gradually decreased and returned to the basal level after 2 h. Tyrosine phosphorylation of JAK2 also became maximal after 30 min and then gradually decreased. In contrast, GLUT4 translocation remained unchanged for 2 h after insulin treatment, and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) also remained constant for up to 2 h. Chronic GH treatment had almost no effect on insulin-stimulated Akt kinase activation and GLUT4 translocation. These results suggest that GH and insulin translocate GLUT4 in a similar manner, at least in part, and the difference in translocation depends on the difference in the tyrosine phosphorylation of JAK2 and IRS-1. The anti-insulin action of GH after chronic GH treatment does not appear to be mainly due to the inhibition of GLUT4 translocation.

Androstadienes↗

Thiamine-responsive lactic acidaemia: role of pyruvate dehydrogenase complex.

UNLABELLED: Lactic acidaemia is sometimes associated with a defect of the pyruvate dehydrogenase complex (PDHC), catalysing the thiamine-dependent decarboxylation of pyruvate. The activity of PDHC for different thiamine pyrophosphate (TPP) concentrations was determined in 13 patients with lactic acidaemia, clinically responsive to thiamine treatment in order to assess the role of PDHC in the aetiology of thiamine-responsive lactic acidaemia. Culture of lymphoblastoid cells and skin fibroblasts and muscle biopsies were performed in these 13 patients. The activity of PDHC to sodium dichloroacetate (DCA), known as the activator of PDHC, was also examined. Three groups were identified according to PDHC activity. Group 1 (two patients) displayed very low PDHC activity, which was not increased by DCA. This PDHC activity increased at high TPP concentrations. Group 2 (five patients) displayed below normal PDHC activity at low TPP concentrations, increased by DCA. This PDHC activity became normal at high TPP concentrations. PDHC deficiency in these patients of groups 1 and 2 was due to a decreased affinity of PDHC for TPP. Group 3 included six patients with normal PDHC activity at low as well as high TPP concentrations. This PDHC activity was increased by DCA. CONCLUSION: High concentrations of TPP may be required for maximal activity of PDHC in some patients with lactic acidaemia. The assay of PDHC activity, performed at a low concentration of TPP (1 x 10(-4)mM) allows selection of patients with thiamine-responsive lactic acidaemia.

Acidosis, Lactic↗

Regional cerebral blood flow changes in human brain related to ipsilateral and contralateral complex hand movements--a PET study.

The purpose of this study was to investigate the cortical motor areas activated in relation to unilateral complex hand movements of either hand, and the motor area related to motor skill learning. Regional cerebral blood flow (rCBF) was measured in eight right-handed healthy male volunteers using positron emission tomography during a two-ball-rotation task using the right hand, the same task using the left hand and two control tasks. In the two-ball-rotation tasks, subjects were required to rotate the same two iron balls either with the right or left hand. In the control task, they were required to hold two balls in each hand without movement. The primary motor area, premotor area and cerebellum were activated bilaterally with each unilateral hand movement. In contrast, the supplementary motor area proper was activated only by contralateral hand movements. In addition, we found a positive correlation between the rCBF to the premotor area and the degree of improvement in skill during motor task training. The results indicate that complex hand movements are organized bilaterally in the primary motor areas, premotor areas and cerebellum, that functional asymmetry in the motor cortices is not evident during complex finger movements, and that the premotor area may play an important role in motor skill learning.

Adult↗

Comparison of GAD and ICA512/IA-2 antibodies at and after the onset of IDDM.

OBJECTIVE: Longitudinal changes in GAD antibody (Ab) and ICA512/IA-2 (ICA512) Ab were examined in relation to age at the onset of diabetes and autoimmunity against the thyroid gland. RESEARCH DESIGN AND METHODS: GADAb, ICA512Ab, and antithyroid autoantibody were examined at onset in 40 juvenile-onset IDDM patients (17 males, 23 females, age at onset 9.4 +/- 4.1 years, range 1.7-20). To assess the changes in antibody levels, 29 patients were followed up with sequential serum samples for up to 5 years. RESULTS: At onset, GADAb, ICA512Ab, and antithyroid autoantibody (thyroglobulinAb or thyroid peroxidaseAb) were found in 70, 58, and 25% of the 40 patients, respectively. Prepubertal patients (n = 21) had a significantly higher prevalence and index of ICA512Ab compared with pubertal patients (n = 19) (76 vs. 37%, P = 0.012, and 2.43 +/- 2.36 vs. 0.66 +/- 1.23, P = 0.011), while GADAb was more prevalent in pubertal patients (57 vs. 84%, P = 0.09). A longitudinal analysis of GADAb and ICA512Ab showed that GADAb levels declined more slowly than those of ICA512Ab (P = 0.008). Patients with continuous extremely high levels of GADAb also had high levels of antithyroid autoantibody. CONCLUSIONS: The measurement of ICA512Ab is useful in prepubertal patients, who often show rapid progression of the disease. The presence of autoimmunity against thyroid gland seems to influence the GADAb level but not the ICA512Ab level.

Adolescent↗

[Vitamin B1 dependency].

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3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency.

We report molecular analysis of thiamin-responsive pyruvate dehydrogenase complex (PDHC) deficiency in a patient with an X-linked form of Leigh syndrome. PDHC activity in cultured lymphoblastoid cells of this patient and his asymptomatic mother were normal in the presence of a high thiamin pyrophosphate (TPP) concentration (0.4 mmol/L). However, in the presence of a low concentration (1 x 10(-4) mmol/L) of TPP, the activity was significantly decreased, indicating that PDHC deficiency in this patient was due to decreased affinity of PDHC for TPP. The patient's older brother also was diagnosed as PDHC deficiency with Leigh syndrome, suggesting that PDHC deficiency in these two brothers was not a de novo mutation. Sequencing of the X-linked PDHC E1 alpha subunit revealed a C-->G point mutation at nucleotide 787, resulting in a substitution of glycine for arginine 263. Restriction enzyme analysis of the E1 alpha gene revealed that the mother was a heterozygote, indicating that thiamin-responsive PDHC deficiency associated with Leigh syndrome due to this mutation is transmitted by X-linked inheritance.

DNA↗