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Biomedical subjects

T Sakai

Publications and source records attributed to T Sakai.

At least 73 records · Page 4Linked to original sources
PubMed2002

Comparison of insulinotrophic actions of nateglinide with glibenclamide dissociated from absorption in conscious dogs.

Nateglinide is more rapidly absorbed than glibenclamide. Therefore, the different absorption kinetics of both drugs were eliminated by intraportal administration in conscious fasted dogs. The plasma insulin profiles were compared under similar kinetic changes in plasma drug concentrations. After a priming dose of nateglinide (1 mg/kg. 5 min) or glibenclamide (40 microg/kg. 5 min), plasma drug concentrations reached a peak at 4 minutes (nateglinide, 80 +/- 5 micromol/L, n = 6 and glibenclamide, 263 +/- 60 nmol/L, n = 6) followed by a sustained level at approximately 30% of the peak concentration at 30 minutes. Nateglinide led to a rapid and constant reduction in arterial glucose of approximately 30% basal, while glibenclamide promoted a gradual decrease to approximately 50% basal at 120 minutes. An increase in plasma insulin level by nateglinide of 4 times basal (218 +/- 58 pmol/L v 47 +/- 3 pmol/L, P <.05, n = 6) occurred at 6 to 10 minutes followed by sustained release of 1.4 times basal (67 +/- 15 pmol/L, n = 6). The insulin surge was more than doubled (484 +/- 209 pmol/L, n = 6) under a euglycemic clamp. Insulin release by glibenclamide increased gradually reaching 10-fold basal (449 +/- 166 pmol/L, n = 6) at 60 minutes. This was not enhanced during a euglycemic clamp. Lowering the primed doses of nateglinide resulted in a diminished peak plasma insulin concentration. In contrast, glibenclamide caused only a slower increase, but eventually reaching a similar peak. By increasing the continuous infusion of nateglinide, the sustained insulin release was not altered. Glibenclamide, but not nateglinide, evoked prompt and sustained insulin release in the continuing presence of the other. These results are consistent with the concept that nateglinide produces a quick, but very short-lived, interaction with sulfonylurea (SU)-receptors on plasma membrane by free access of the drug from the cell exterior. In contrast, glibenclamide promotes a slow and longer interaction with the receptor by distribution of the drug into the cell inferior. We conclude, therefore, that not only the different kinetics of gastrointestinal (GI) absorption, but also the inherent difference in the interaction with beta cells is attributed to the different insulin release characteristics between nateglinide and glibenclamide in vivo.

ATP-Binding Cassette Transporters↗
PubMed2002

Functional and locomotive characteristics of stroke survivors in Japanese community-based rehabilitation.

OBJECTIVE: The purposes of this study were as follows: (1) to compare the characteristics of functional fitness of Japanese stroke survivors with those of control subjects of a similar age; and (2) to relate these characteristics to the extent of physical impairment and the period after stroke onset to better design community-based rehabilitation programs for stroke survivors. DESIGN: One hundred fifty-three stroke survivors who participated in community-based rehabilitation and 119 control subjects were measured. Twelve performance test items were designed to assess functional fitness. RESULTS: The average functional fitness score for the stroke survivors was significantly lower than that of the control group. However, some survivors had higher performance scores than the control group. Significant correlations were shown between some functional fitness items and Brunnstrom recovery stage in the stroke survivors. CONCLUSION: The large variability in functional fitness scores for stroke survivors indicates a need to design variable rehabilitation programs so that survivors can be grouped according to their specific levels of functional fitness.

Activities of Daily Living↗
PubMed2002

Cystic meningioma in a dog.

There have been few reports of the occurrence of, and treatment methods for, cystic meningioma in the dog. This report describes a case in a Maltese which presented with a three-month history of seizures. Cystic meningioma was diagnosed by magnetic resonance imaging using contrast medium (gadoteridol) enhanced images. Attempted surgical removal of the mass was successful, and the outcome following surgery was good.

Animals↗
PubMed2002

Alterations of quantitative EEG and mini-mental state examination in interferon-alpha-treated hepatitis C.

We have recently observed a diffuse slowing of brain waves using serial quantitative electroencephalographic (qEEG) examinations in interferon (IFN)-alpha-treated chronic hepatitis C patients. However, it remains unclear how this alteration could be assessed. We evaluated the correlation between the qEEG changes and three tests of mental status, including the Mini-Mental State Examination (MMSE), in such patients. This is the first study to undertake a clinical evaluation of the adverse effects on brain function due to IFN. We undertook blind, prospective and serial qEEG examinations on 56 chronic hepatitis C patients at three independent hospitals. IFN-alpha was administered intramuscularly at a dose of 9 x 10(6) IU daily for the first 4 weeks and then 3 times/week for the next 20 weeks. Serial EEGs were obtained before, at 2 and 4 weeks of treatment, and after the IFN-alpha treatment. The absolute power values of each frequency band in each patient at different stages of treatment were recorded by qEEG. Each patient was assessed by the MMSE, Hamilton Rating Scale for Depression (HSD), and Hamilton Rating Scale for Anxiety (HSA). We statistically evaluated the correlations between the changes in power values and alterations of scores on the mental status tests during IFN-alpha treatment. The decreased scores observed on the MMSE ranged from 2 to 5 points at both 2 and 4 weeks of IFN-alpha treatment. There were no significant differences in age distribution for each decreased score on the MMSE. As the alteration in MMSE score during IFN treatment increased, the alteration in absolute power values for the slow waves during IFN treatment increased significantly, while that for the alpha 2 and fast waves during treatment decreased significantly. However, the changes in the HDS and HSA revealed no significant correlations. The alteration of the qEEG was reversible after the treatment. MMSE scores represent one screening method for the clinical assessment of IFN-alpha-induced alterations of brain function.

Adult↗
PubMed2002

Postnatal changes in ghrelin mRNA expression and in ghrelin-producing cells in the rat stomach.

Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. Although it is well known that a large amount of ghrelin is produced in the gastrointestinal tract, developmental changes in ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin-ip) and mRNA-expressing (ghrelin-ex) cells in the stomach have not been elucidated. In this study, we therefore investigated the changes in ghrelin mRNA expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs of 1- to 8-week-old male and female rats by Northern blot analysis, immunohistochemistry and in situ hybridization. Northern blot analysis showed that the level of weak ghrelin mRNA expression was low in the postnatal period but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were found in female rats than in male rats, and this finding was confirmed by Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular base of the fundic gland and then they were found in the glandular base and the glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin cells is extended from the glandular base to the glandular neck during the postneonatal development period. This is the first report on detailed changes in postneonatal ghrelin expression level and in the number of ghrelin cells in the rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell differentiation suggest that ghrelin plays an important physiological role in the stomach.

Animals↗
PubMed2002

Acute renal failure and hearing loss due to sodium bromate poisoning: a case report and review of the literature.

Acute renal failure with hearing loss due to sodium bromate intoxication is described. A 48-year-old woman who ingested permanent wave neutralizer in a suicide attempt and developed anuria was admitted to our hospital for hemodialysis. Bromate intoxication was suspected and hemodialysis was carried out; she required maintenance dialysis 3 times a week. Irreversible severe sensorineural hearing loss continued and peripheral polyneuropathy developed in the lower limbs. We measured the concentration of bromine in the serum before and after the first hemodialysis and found its removal rate to be 61.3%. This is the first report that proved the utility of hemodialysis for bromate intoxication in a clinical setting.

Acute Kidney Injury↗
PubMed2002

[An adult case of Bochdalek hernia without an obvious cause; report of a case].

A 72-year-old female was transported by ambulance to our department to undergo transthoracic surgery. She had previously undergone transabdominal surgery under a diagnosis of adult Bochdalek hernia, but the restoration was believed to have been incomplete. During the transthoracic procedure, a dorsolateral defect of the diaphragm was detected and reinforcement with a Gore-Tex patch was performed. The patient's postoperative course was uneventful. Adult Bochdalek hernia is rare, but it requires immediate surgical intervention. Although transabdominal surgery is generally considered the first line treatment approach to restore Bochdalek hernia, restoration of the diaphragm is occasionally difficult. On the other hand, a transthoracic approach is thought to be effective as it allows for observation of the lung and diaphragm, and easy closure of the diaphragmatic defect. As complete restoration through early surgical intervention is important, a transthoracic approach in conjunction with transabdominal surgery should be considered whenever necessary.

Aged↗
PubMed2001

Characteristics of velocity-controlled knee movement in patients with cervical compression myelopathy: what is the optimal rehabilitation exercise for spastic gait?

STUDY DESIGN: The isokinetic strength of knee extensors and flexors was measured at various controlled velocities in patients with spastic paraparesis caused by cervical compression myelopathy. OBJECTIVE: To evaluate leg function objectively in patients with myelopathy. SUMMARY OF BACKGROUND DATA: Cervical compression myelopathy causes varying degrees of spastic paresis in the legs and affects the activities of patients. However, the leg function characteristics of the patients have not been fully elucidated. METHODS: Velocity-controlled voluntary knee movements were studied in 39 patients (25 men and 14 women) with compression myelopathy. Their mean age was 60.2 years (range, 44-77 years). The patients were divided into Group A (ambulation without aid, n = 22) and Group AA (ambulation with aid, n = 17). Isometric peak torque values were measured in knee flexor and extensor muscles at 60 degrees of knee flexion, and isokinetic peak torque values were determined in maximal voluntary concentric movements of these muscles at constant angle velocities of 40 degrees, 80 degrees, 120 degrees, 160 degrees, and 180 degrees per second. The relative strength (percentage of isometric peak torque value) of the isokinetic motion was calculated at each velocity. RESULTS: In both groups, the relative strength decreased as the velocity increased, and the degree of reduced strength in the flexors at the high velocities of 160 degrees and 180 degrees per second was significantly greater in Group AA than in Group A (P < 0.05), whereas no significant difference was found in the extensors between the groups. CONCLUSIONS: The results indicate that isokinetic strength at a high velocity may reflect the severity of spastic paresis in the legs resulting from compression myelopathy.

Aged↗
PubMed2001

Promoter structure and transcription initiation sites of the human death receptor 5/TRAIL-R2 gene.

The death receptor 5 (DR5) is a receptor for tumor necrosis factor-related apoptosis-inducing ligand and is able to induce apoptosis in various tumor cells. The expression of DR5 is up-regulated at the transcriptional level by p53, genotoxic stress and so on. To investigate the structure of the DR5 gene promoter, we screened and sequenced a genomic clone containing the 5'-flanking region of the DR5 gene. RNase protection assays showed two major transcription start sites around -122 and -137 upstream of the translation initiation codon ATG. Transient transfections with serial 5'-deletion mutants identified the minimal promoter element spanning -198 to -116. Site-directed mutagenesis demonstrated that the DR5 gene promoter has no typical TATA-box, but has two Sp1 sites responsible for the basal transcription activity of the DR5 gene promoter.

5' Flanking Region↗
PubMed2001

Immunohistochemical analyses of thyroid-specific enhancer-binding protein in the fetal and adult rat hypothalami and pituitary glands.

Thyroid-specific enhancer-binding protein (T/EBP), also known as NKX2.1 or TTF-1, regulates the expression of thyroid- and lung-specific genes. The t/ebp/Nkx2.1-null mutant mouse was stillborn but lacked the thyroid gland, pituitary gland, ventral region of the forebrain and normal lungs. These data demonstrated that T/EBP/NKX2.1 plays an important role not only in tissue-specific gene expressions in adults but also in genesis of these organs during development. Although the expression of t/ebp/Nkx2.1 in the brain has been reported, its function in the brain remains unknown. The present study was designed to determine the localization of T/EBP/NKX2.1 in the hypothalamus and pituitary gland of fetal and adult rats by immunohistochemistry as the first step toward understanding the function of T/EBP/NKX2.1 in the rat brain. In the fetal rat hypothalamus, T/EBP/NKX2.1 was localized widely in the ventral hypothalamic areas. In the adult rat brain, T/EBP/NKX2.1 was localized in the ventromedial hypothalamic nucleus, medial tuberal nucleus, arcuate nucleus and mammillary body. No T/EBP/NKX2.1 immunoreactivity was observed in the anterior or intermediate lobe of the pituitary gland in either fetal or adult rats. On the other hand, immunoreactive T/EBP/NKX2.1 was found in the posterior lobe of the pituitary gland. This paper presents results of detailed analyses of the distributions of T/EBP/NKX2.1 protein in the fetal and adult rat hypothalami and pituitary glands, and these results should provide important information for understanding the function of T/EBP/NKX2.1 in the brain.

Age Factors↗
PubMed2001

YCu3Al2, an example of an AB5 structure type.

Yttrium tricopper dialuminium, YCu(3)Al(2), is isostructural with hexagonal CaCu(5), in which each Cu atom at the 3g((1/2),0,(1/2)) position in space group P6/mmm (No. 191) is partially replaced by an Al atom. The hydrogen-uptake properties are usually enhanced in other AB(5) structures by aluminium substitution. YCu(5) does not show any hydrogen absorption, and the goal of the present work is to investigate whether aluminium substitution could expand the metal-atom lattice enough to provide better interstitial positions for hydrogen storage. However, no enthalpy change was observed up to 773 K under 3 MPa static H(2) pressure by differential thermal analysis (DTA) for the title compound. The compound does not show any significant hydrogen absorption/desorption in the pressure-composition isotherms (P-C-T diagrams) in the temperature range 298-673 K under 3.3 MPa H(2) pressure.

Journal Article↗
PubMed2001

Circadian rhythms of female mating activity governed by clock genes in Drosophila.

The physiological and behavioral activities of many animals are restricted to specific times of the day. The daily fluctuation in the mating activity of some insects is controlled by an endogenous clock, but the genetic mechanism that controls it remains unknown. Here we demonstrate that wild-type Drosophila melanogaster display a robust circadian rhythm in the mating activity, and that these rhythms are abolished in period- or timeless-null mutant flies (per(01) and tim(01)). Circadian rhythms were lost when rhythm mutant females were paired with wild-type males, demonstrating that female mating activity is governed by clock genes. Furthermore, we detected an antiphasic relationship in the circadian rhythms of mating activity between D. melanogaster and its sibling species Drosophila simulans. Female- and species-specific circadian rhythms in the mating activity of Drosophila seem to cause reproductive isolation.

Animals↗
PubMed2001

Brainstem activates paroxysmal discharge in human generalized epilepsy.

In nine patients with generalized epilepsy of convulsive seizures, the excitability change of the brainstem was evaluated over the course of the interictal paroxysmal discharge (poly spike-and-wave complex, poly SWC). The evaluation was carried out by a sequential analysis of brainstem auditory evoked potentials (BAEPs) before and during one sequence of poly SWC. The characteristics of BAEPs, i.e. far-field evoked potentials, allowed the evaluation of the excitability change in the brainstem, which was not influenced by the cortical activity. The excitability in the ventral brainstem, measured with the parameters of wave-III, showed a biphasic fluctuation (deceleration--acceleration) before the onset of poly SWC (minima at -0.7+/-0.4 s). On the other hand, the excitability in the dorsal brainstem, measured with the parameters of wave-V, showed no significant difference over the course of poly SWC. The results suggest that the biphasic excitability change in the ventral brainstem is conveyed to the cortex through the ascending activating system. The excitability acceleration preceded by deceleration in the ventral brainstem probably synchronizes the cortical activity profoundly enough to produce poly SWC through the activation of intralaminar thalamic neurons.

Adolescent↗