[Adaptation of English-written health-related quality of life measure for children].
Explore the source record for details and available documents.
Child↗
Biomedical subjects
A Nakai
Publications and source records attributed to A Nakai.
The effects of the 5-HT3 antagonist, alosetron, on brain serotonin synthesis in patients with irritable bowel syndrome.
Serotonin (5-HT) plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Using alpha-[(11)C]methyl-L-tryptophan-positron emission tomography (PET), it was demonstrated that brain 5-HT synthesis is increased in patients with IBS, in a gender-specific manner. The aims of the study were to evaluate the effects of alosetron on brain 5-HT synthesis in patients with IBS. Six male and five female non-constipation-predominant IBS patients were enrolled. The subjects received alosetron or a placebo for 14 days, separated by a 2-week washout period. On day 14, rectal distensions commenced just prior to the PET scan (which was performed for 80 min), and continued for 20-min periods. The functional images were analysed with SPM99. Alosetron vs placebo treatments, in a randomized, double-blinded, crossover manner, were studied. 5-HT synthesis was greater in several regions in the males than in the females during the alosetron treatment, whereas there was no region in which the females had greater synthesis. There were significant gender-treatment interactions of synthesis in the cingulate gyrus, caudate nucleus, globus pallidus, and cerebellum. The gender differences in the effect of alosetron on brain 5-HT synthesis may be related to the gender differences in the efficacy of alosetron.
Brain↗
Treatment with low-dose angiotensin-converting enzyme inhibitor (ACEI) plus angiotensin II receptor blocker (ARB) in pediatric patients with IgA nephropathy.
AIM: IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria. PATIENTS: We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids. RESULTS: With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-beta-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy. CONCLUSION: These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.
Angiotensin II Type 1 Receptor Blockers↗
Alpha-[11C] methyl-L-tryptophan and glucose metabolism in patients with temporal lobe epilepsy.
OBJECTIVE: To determine whether metabolism in the brain serotonergic system, including the kynurenine pathway, is involved in temporal lobe epilepsy (TLE). METHODS: The authors studied 14 patients with intractable TLE by PET using alpha-[11C] methyl-L-tryptophan (alpha-MTrp) and 2-[18F]-fluoro-deoxy-glucose (FDG) and compared results with 21 healthy control subjects who had alpha-MTrp PET studies. Seven patients had unilateral hippocampal atrophy (HA), and seven had normal hippocampal volumes (NV). The regional uptake constant (K*) for alpha-MTrp and regional FDG uptake were calculated in regions with high serotonergic innervation, including the hippocampus, amygdala, lateral temporal lobe, frontal lobe, thalamus, lenticular nucleus, and cingulate cortex. RESULTS: A significant increase of alpha-MTrp uptake was observed in the hippocampus ipsilateral to the seizure focus in seven TLE patients with NV compared to seven patients with HA as well as to healthy controls. In patients with TLE, glucose utilization in the lateral temporal lobe ipsilateral to the seizure focus was correlated negatively with K* for alpha-MTrp in the ipsilateral hippocampus and positively with K* in the ipsilateral lenticular nucleus and cingulate cortex. Glucose utilization in the frontal lobe ipsilateral to the seizure shows a reduction in the glucose utilization which relates to the increase in the alpha-MTrp uptake in the ipsilateral lateral temporal lobe. CONCLUSION: This study demonstrates dysfunction of the serotonergic system, which could include metabolism through the kynurenine pathway in TLE patients with normal hippocampal volumes. alpha-MTrp PET studies might be useful for lateralizing the epileptic focus in TLE patients with normal hippocampal volumes.
Adolescent↗
Assessment of the hepatic arterial and portal venous blood flows during pregnancy with Doppler ultrasonography.
PURPOSE: The aim of this study was to evaluate whether the dual hepatic blood supply is altered in healthy pregnant women compared with that in nonpregnant women. MATERIALS AND METHODS: Flow wave-forms in common hepatic artery and portal vein were obtained in 67 healthy pregnant women at 10-40 weeks gestation and 22 nonpregnant women by using Doppler ultrasonography. RESULTS: In the nonpregnant group, the mean (SD) hepatic arterial blood flow, portal venous blood flow, and total liver blood flow were 0.57 (0.31) L/min, 1.25 (0.46) L/min, and 1.82 (0.63) L/min, respectively. In the healthy pregnant group, the portal venous blood flow and total liver blood flow significantly increased after 28 weeks gestation. However, the hepatic arterial blood flow remained unchanged during pregnancy. There was no relationship between the hepatic arterial blood flow and the portal venous blood flow. CONCLUSION: The results demonstrated that the hepatic perfusion increased during third trimester compared to nonpregnant level. Because the hepatic arterial blood flow remained unchanged during pregnancy, major determinant of the increase in the hepatic perfusion was the portal venous return. The data suggest that the hepatic arterial and portal venous vascular territories have regulatory mechanisms that allow for independent changes during pregnancy.
Adult↗
Reproducibility of pulsed Doppler measurements of the maternal renal circulation in normal pregnancies and those with pregnancy-induced hypertension.
OBJECTIVE: To assess the inter- and intraobserver reproducibilities of pulsed Doppler measurements of the maternal renal circulation in normal pregnancies and those affected by pregnancy-induced hypertension. MATERIALS AND METHODS: Color and pulsed Doppler ultrasound was used to measure acceleration time and resistance index in the renal segmental and interlobar arteries. For the investigation of interobserver reproducibility, two sonographers performed measurements blindly in six normal pregnant women and 14 women with pregnancy-induced hypertension between 28 and 36 weeks' gestation. A second group of 10 patients between 30 and 35 weeks' gestation were examined by one sonographer to assess the level of intraobserver reproducibility of measurements. For each patient in this group, the flow waveform was measured three times in succession. Calculations of the intraclass correlation coefficient Ri were used to determine the level of reproducibility. RESULTS: The interobserver Ri and intraobserver Ri for acceleration time in the segmental artery were 0.95 and 0.96 and for the interlobar artery they were 0.97 and 0.98, respectively. For the resistance index, these values were 0.01 and 0.01 in the segmental artery and 0.52 and 0.29 in the interlobar artery. CONCLUSION: Both the inter- and intraobserver reproducibility of acceleration time measurements in the renal segmental and interlobar arteries were clinically acceptable but the equivalent reproducibilities of resistance index measurements were poor.
Adult↗
Changes of endothelin in streptozotocin-induced diabetic rats: effects of an angiotensin converting enzyme inhibitor, enalapril maleate.
Endothelin-1 (ET-1) concentrations are increased in patients with diabetes mellitus, particularly those with diabetic retinopathy, or essential hypertension. We hypothesized that ET-1 might participate in the development and progression of diabetic microangiopathy. In this study, the effects of the angiotensin converting enzyme (ACE) inhibitor, enalapril maleate, on diabetic angiopathy were examined in streptozotocin (STZ)-induced diabetic (STZ-DM) rats by monitoring variations in renal function and ET-1 concentrations in blood and organ tissues. Significant increases in kidney weight and in concentrations of urinary albumin, N-acetyl-fl-d-glucosamidase (NAG) and serum ET-1 were observed in the STZ-DM rats as compared with the non-diabetic rats, and the concentration of ET-1 in the kidneys tended to be increased. Microscopic and electron microscopic analyses showed increased mesangial cell proliferation, matrix expansion and enlarged mesangial area in the kidney of the diabetic rats. After administration of the ACE inhibitor, increased concentrations of urinary albumin and NAG in the STZ-DM rats were reduced to the control values with a slight improvement in the electron microscopic changes. These data suggest that ET-1 may be involved in the development and progression of diabetic nephropathy and may explain, in part, why diabetes is liable to complicate hypertension. ACE inhibitor may help to restore diabetic nephropathy in the STZ-induced diabetic rats.
Acetylglucosaminidase↗
Localizing value of alpha-methyl-L-tryptophan PET in intractable epilepsy of neocortical origin.
BACKGROUND: [(11)C] alpha-methyl-L-tryptophan (alpha-MTrp) has been developed as a tracer for the study of the synthesis of serotonin in the brain with PET. However, it has been shown that in pathologic conditions the tracer may reflect the activation of kynurenine metabolism. Increased levels of serotonin and quinolinic acid have been described in resected epileptogenic cortex, raising the possibility that alpha-MTrp can localize seizure foci in patients with intractable partial epilepsy. The authors assessed the uptake of alpha-MTrp in 18 patients (11 men, mean +/- SD age 27.1 +/- 10.1 years, range 13 to 54) with intractable partial epilepsy to correlate the PET findings with the epileptogenic area defined by electroclinical and neuroimaging data. METHOD: Seven patients with cortical dysplasia (CD) and 11 with partial epilepsy in which conventional MRI and fluorine-18-deoxyglucose ((18)FDG)-PET studies failed to detect any abnormality were studied. All underwent scalp EEG monitoring during the PET scan to exclude ictal events and estimate the interictal epileptic activity. RESULTS: In seven patients (39%; CD four and cryptogenic partial epilepsy three), PET showed focal increased uptake of alpha-MTrp corresponding to the epileptogenic area. alpha-MTrp uptake in the epileptic focus correlated with the frequency of interictal spikes (r = 0.7, p < 0.05). CONCLUSIONS: alpha-MTrp-PET may be of value in the localization of the epileptogenic area not only in patients with visible dysplastic lesions, but also in those with cryptogenic partial epilepsy.
Adolescent↗
Cell cycle transition under stress conditions controlled by vertebrate heat shock factors.
The roles of heat shock transcription factors (HSFs) under physiological conditions have recently become the focus of intense study. We generated avian cells lacking two heat-inducible HSFs, HSF1 and HSF3. In addition to complete loss of activation of heat shock genes under stress conditions, these cells exhibited a marked reduction in Hsp90alpha expression under normal growth conditions. Reduction in Hsp90alpha expression caused instability of a cyclin-dependent kinase, Cdc2, and cell cycle progression was blocked mainly at the G2 phase, but also at G1 phase even at mild heat shock temperatures. Restoration of Hsp90alpha expression rescued the temperature sensitivity without induction of HSPS: We demonstrated for the first time a molecular target affected by heat shock in vivo that causes cell cycle arrest in vertebrates and a novel mechanism of stress resistance controlled by vertebrate HSFS:
Animals↗
Influence of mild hypothermia on delayed mitochondrial dysfunction after transient intrauterine ischemia in the immature rat brain.
The aim of this study was to determine the effect of different maternal thermal conditions during transient intrauterine ischemia on the mitochondrial respiratory activities in the immature rat brain. On 17 days of gestation, transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion under hypothermic (33.5-34.5 degrees C, n=6), normothermic (36.5-37.5 degrees C, n=6), and hyperthermic conditions (39.5-40.5 degrees C, n=6). All of the pups were delivered by cesarean section at 21 days of gestation and cerebral neocortical tissue was sampled 1 h after delivery. The mitochondrial respiration was measured polarographically in homogenates. In the ischemic uterine horn, ADP-stimulated respiration of the normothermia and the hyperthermia groups decreased significantly to 73 and 74% of the non-ischemic controls, respectively. Since non-stimulated respiration remained unchanged, the respiratory control ratio (RCR) of the normothermia and the hyperthermia groups decreased significantly to 59 and 54% of the non-ischemic levels, respectively. In contrast, the mitochondrial respiratory activities of the hypothermia group showed no differences between the non-ischemic and the ischemic uterine horns. The results demonstrate that mild maternal hypothermia ameliorates the cerebral mitochondrial dysfunction in neonatal rats after intrauterine ischemia due to transient uterine artery occlusion and suggest that maternal thermal conditions, particularly during uteroplacental insufficiency, have important implications for the neuropathological outcome of the newborn.
Animals↗
Effect of the immunosuppressant drug FK506 on neonatal cerebral mitochondrial function and energy metabolism after transient intrauterine ischemia in rats.
Mitochondrial respiratory activities and energy metabolism were measured in neonatal rat brains to evaluate the influence of transient intrauterine ischemia on the near-term fetus and to assess the effect of the immunosuppressant drug FK506 treatment. Transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion at 17 days of gestation in Wistar rats. The vehicle or 1.0 mg/kg of FK506 was administered after 1 h of recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and samples of cerebral cortical tissue were obtained from pups at 1 h after birth. The mitochondrial respiration was measured polarographically in homogenates. For the analysis of ATP, ADP, and AMP, neonatal brains were frozen in situ and fluorometric enzymatic techniques were used. In the neonatal cortical tissue exposed to ischemia, mitochondrial respiratory activities and ATP concentrations decreased significantly to approximately 59 and 67% of those in normoxic controls, respectively. The deterioration of both mitochondrial respiratory activities and high-energy phosphates was prevented by FK506, given 1 h after the start of recirculation. The present results indicate that transient intrauterine ischemia is accompanied by mitochondrial dysfunction and cellular bioenergetic failure in the neonatal rat brain and suggest that treatment with FK506 prevents the deterioration, even when administered after the ischemic periods.
Animals↗
Doppler velocimetry of maternal renal circulation in pregnancy-induced hypertension.
PURPOSE: The purpose of this study was to evaluate whether the Doppler waveforms of the maternal main renal, segmental, and interlobar arteries are altered in women with pregnancy-induced hypertension (PIH) compared with healthy pregnant women. METHODS: Flow waveforms of the maternal main renal, segmental, and interlobar arteries were obtained from 42 healthy pregnant women between 24 and 41 weeks of gestation and 21 women with PIH between 28 and 40 weeks of gestation using pulsed Doppler sonography. We used spectral analysis to measure the peak systolic and end-diastolic velocities and the acceleration time. The presence or absence of the normal early systolic compliance peak-reflective-wave complex (ESP) was assessed in only the main renal artery. RESULTS: The acceleration times of the segmental and interlobar arteries were significantly prolonged in the PIH group compared with those in the healthy pregnant women. Of the 21 women with PIH, 3 showed loss of the ESP in the renal artery, but these changes were not significant. CONCLUSIONS: Decreased systolic acceleration and the absence of ESP, the hemodynamic indicators for significant proximal stenosis, suggest that severe stenosis or continuous vasospasm in the proximal arteries, such as the main renal or segmental artery, may be implicated in the pathogenesis of PIH.
Adult↗
Anatomy and physiology of the female pelvis: MR imaging revisited.
This article reviews the normal anatomy of the female pelvis and focuses on uterine physiology, presenting the kinematics of the uterus that can be identified on ultra-fast MR imaging. It also discusses the many facets of the junctional zone on MR imaging. Ultra-fast MR imaging seems to be a powerful tool for evaluating normal anatomy, physiology, and pathology of the uterus. J. Magn. Reson. Imaging 2001;13:842-849.
Female↗
Maternal treatment with NMDA receptor antagonist (MK-801) attenuates delayed mitochondrial dysfunction after transient intrauterine ischemia in the neonatal rat brain.
PURPOSE: Mitochondrial respiratory activities were measured in neonatal rat brains to evaluate the influence of transient intrauterine ischemia on the near-term fetus and to assess the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. METHODS: Transient intrauterine ischemia was induced by 30 min of right uterine artery occlusion at 17 days of gestation in Wistar rats. Vehicle (saline) or 0.5 mg/kg of MK-801 was administered after 1 h of recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and samples of cerebral cortical tissue were obtained from pups at 1 h after birth. Adenosine diphosphate (ADP)-stimulated, nonstimulated, and uncoupled respirations were measured polarographically in homogenates. The respiratory control ratio was defined as ADP-stimulated divided by non-stimulated respiration. RESULTS: In the vehicle-treated group the neonatal cortical tissue exposed to ischemia showed a significant decrease in ADP-stimulated respiration and respiratory control ratio compared with these findings in normoxic control animals. The delayed mitochondrial respiratory dysfunction was prevented by MK-801, given 1 h after the start of recirculation (P < 0.05). CONCLUSION: The present results indicate that transient intrauterine ischemia in the near-term rat fetus is associated with delayed mitochondrial dysfunction in the neonatal brain; the results suggest that maternal treatment with MK-801 attenuates the deterioration, even when administered 1 h after the start of recirculation.
Journal Article↗
The therapeutic effect of lipo PGE1 on diabetic neuropathy-changes in endothelin and various angiopathic factors.
A high blood concentration of endothelin (ET)-1 may participate in the onset and progress of diabetic microangiopathy, resulting in neuropathy. We examined the therapeutic effects of prostaglandin E1 (PGE1), which possesses both a peripheral vasodilating action and inhibition of platelet aggregation, on diabetic microangiopathy. Increases in both skin temperature and peripheral never conduction velocity in diabetic patients were recorded four weeks after Lipo PGE1 administration. A quantitative decrease in urinary albumin concentration was also observed, suggesting its efficacy of action was on diabetic nephropathy. Lipo PGE1 administration reduced the elevated circulating plasma ET-1 levels in the diabetic patients. As an increase in ET-1 concentrations is thought to correlate with the onset and progress of diabetic microangiopathy, the reduction of plasma ET-1 concentration by Lipo PGE1 administration may be one reason for the improvement in diabetic neuropathy and nephropathy.
Adult↗
Polymorphisms of the insulin gene among Japanese subjects.
We have sequenced the insulin gene in 72 unrelated Japanese subjects (52 with type 2 diabetes mellitus and 20 with normal glucose tolerance). We identified 6 mutations and all were found at a low frequency (1% to 4%). Three mutations were new. These included a C-to-G substitution in the promoter region, a G-to-A substitution in codon-2 resulting in an Ala-to-Thr replacement in amino acid -2 of the signal peptide, and a G-to-A substitution in intron 2. We have no evidence that any of the mutations that we found are the cause of diabetes. Thus, mutations in the insulin gene do not appear to be an important genetic factor contributing to the development of diabetes in this population.
Adult↗
Developmental changes in tolerance to transient intrauterine ischemia in rat cerebral mitochondria.
OBJECTIVE: Mitochondfial respiratory activities were measured in neonatal rat brain to compare the influence of transient intrauterine ischemia in the preterm fetus with that in the term fetus and to evaluate the effect of alpha-phenyl-N -tert-butyl-nitrone treatment. STUDY DESIGN: Intrauterine ischemia was induced by a 30-minute occlusion of the right uterine artery. The control group consisted of term fetuses (20 days old) exposed to normoxia (n = 8) and ischemia (n = 8). For the investigation into maturity effect, preterm fetuses (14 days old) were exposed to normoxia (n = 8) or ischemia (n = 8), and for the alpha-phenyl-N -tert-butyl-nitrone treatment investigation, term fetuses were exposed to ischemia with alpha-phenyl-N -tert-butyl-nitrone (n = 8). All subjects underwent cesarean delivery at 21 days of gestation, and the mitochondrial respiration was measured polarographically 1 hour after delivery. RESULTS: In the control group the neonatal cortical tissue exposed to ischemia showed a significant decrease in mitochondrial activities compared with those in normoxic control animals. In the preterm group the mitochondrial activities of ischemic fetuses were maintained close to normoxic levels. The neonatal mitochondrial deterioration caused by term ischemia was prevented by alpha-phenyl-N -tert-butyl-nitrone. CONCLUSION: The results indicate that preterm fetuses are more capable than term fetuses of maintaining mitochondrial function under conditions of transient intrauterine ischemia and suggest that oxygen derived free radicals may play a crucial role in the development of neonatal neurologic deficit.
Adenosine Diphosphate↗
Alteration of endothelin-1 concentration in STZ-induced diabetic rat nephropathy. Effects of a PGI(2) derivative.
BACKGROUND: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. METHODS: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I(2) derivative to investigate the effect of PGI(2) in diabetic vascular disturbance. RESULTS: Renal weight, urinary albumin, urinary N-acetyl-beta,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI(2) derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI(2) derivative is effective in diabetic nephropathy. As the PGI(2) derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. CONCLUSION: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI(2) derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI(2) derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.
Albuminuria↗