Both angiotensinogen M235T and alpha-adducin G460W polymorphisms are associated with hypertension in the Japanese population.
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Alleles↗
Biomedical subjects
T Miki
Publications and source records attributed to T Miki.
Changes in cholinergic function in the frontal cortex and hippocampus of rat exposed to ethanol and acetaldehyde.
Our previous microdialysis study demonstrated that both ethanol (EtOH) and acetaldehyde (ACe) decrease in vivo acetylcholine (ACh) release in the medial frontal cortex of freely moving rats. To better understand the mechanisms of EtOH and ACe's effects on the cholinergic system in the brain, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) expression was examined at 40 and 240 min after a dose of EtOH (1 g/kg) in the rat frontal cortex and hippocampus. The control group was treated with 0.9% saline, and other groups received EtOH or cyanamide (CY, 50 mg/kg, a potent aldehyde dehydrogenase inhibitor) and 60 min later by EtOH intraperitoneally. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed that ChAT mRNA levels were decreased by 72.8% and 71.6% in the EtOH and CY+EtOH groups, respectively, at 40 min after EtOH injection compared with saline in the frontal cortex. The hippocampal ChAT levels were reduced by 76.5% and 53.0% in the EtOH and CY+EtOH groups, respectively, at this time. CY+EtOH-induced depletion in ChAT mRNA levels was markedly higher than EtOH in the hippocampus. A similar decrease pattern of ChAT was observed at protein levels as determined by Western blot, but the reduced ChAT levels were significantly higher in the CY+EtOH group as compared with the EtOH group both in the frontal cortex and hippocampus. At 240 min after EtOH injection, the EtOH group had no effect on ChAT at mRNA levels, as compared with saline, whereas CY+EtOH group induced a significant decrease in ChAT mRNA expression to 62.0% and 65.5% in the frontal cortex and hippocampus, respectively. These data were consistent with the results of the Western blot analysis. AChE expression at mRNA levels was not changed at either 40 or 240 min after EtOH dosing in either of these groups in the frontal cortex and hippocampus. Within 40 and 240 min, a statistically significant difference in ChAT expression at mRNA and protein levels was found in the EtOH and CY+EtOH groups both in the frontal cortex and hippocampus. The data obtained from this study demonstrate that EtOH and ACe concentrations decreased ChAT expression at 40 and 240 min after EtOH administration in the frontal cortex and hippocampus, and this result suggests that reduced ChAT expression is strongly related to a decrease in ACh release in the rat brain.
Acetaldehyde↗
Cerebral glucose transporters expression and spatial learning in the K-ATP Kir6.2(-/-) knockout mice.
K-ATP channels formed of the Sur and Kir subunits are widely distributed in the brain. Sur1-Kir6.2 is the most common combination of K-ATP channel subunits in the brain and Kir6.2 plays an important role in glucose metabolism through pancreatic insulin secretion or hypothalamic glucose sensing. K-ATP channels have also been reported to play a role in memory processing. Therefore, the aim of the present experiment is to assess the gene and protein expression of GLUT1, GLUT3 and GLUT4 in various brain regions of Kir6.2(-/-) K-ATP knockout mice and to test their working memory performance. GLUT4 was measured using two antibodies, one recognizing an intracellular epitope and the other, an extracellular epitope. Relative to their corresponding wild type, semi-quantitative immunohistochemistry showed that GLUT4 protein expression as measured by a GLUT4 antibody recognizing an extracellular epitope was increased in the Kir6.2(-/-) K-ATP mice. However, there was only a small increase in GLUT4 labeling using the GLUT4 antibody recognizing the intracellular epitope. These results suggest a compensatory higher GLUT4 inclusion at the cellular neuronal membrane in the cerebral cortex, hippocampus and cerebellum of the Kir6.2(-/-) K-ATP knockout mice. However, there was no change in GLUT4 gene expression assessed by TaqMan PCR except for a decrease in the cerebellum of these mice. Working memory performance of the Kir6.2(-/-) K-ATP mice was disrupted at age of 12 weeks but not at 5 weeks. The mild glucose intolerance that is observed in the Kir6.2 knockout mice is unlikely to have created the memory deficits observed. Rather, in light of the effects of K-ATP channel modulators on memory, the memory deficits in the Kir6.2(-/-) K-ATP mice are more likely due to the absence of the Kir6.2 and possible disruption of the GLUT4 activity in the brain.
Age Factors↗
Body fat mass and lean mass as predictors of survival in hemodialysis patients.
A higher body mass index (BMI) is a predictor of better survival in hemodialysis patients, although the relative importance of body fat and lean mass has not been examined in the dialysis population. We performed an observational cohort study in 808 patients with end-stage renal disease on maintenance hemodialysis. At baseline, fat mass was measured by dual-energy X-ray absorptiometry and expressed as fat mass index (FMI; kg/m2). Lean mass index (LMI) was defined as BMI minus FMI. During the mean follow-up period of 53 months, 147 deaths, including 62 cardiovascular (CV) and 85 non-CV fatal events, were recorded. In univariate analysis, LMI was not significantly associated with CV or non-CV death, whereas a higher FMI was predictive of lower risk for non-CV death. Analyses with multivariate Cox models, which took other confounding variables as covariates, indicated the independent associations between a higher LMI and a lower risk of CV death, as well as between a higher FMI and a lower risk of non-CV death. These results indicate that increased fat mass and lean mass were both conditions associated with better outcomes in the dialysis population.
Absorptiometry, Photon↗
Behavioral phenotyping of mice lacking the K ATP channel subunit Kir6.2.
ATP-sensitive potassium (K(ATP)) channels are expressed in various tissues and cell-types where they act as so-called metabolic sensors that couple metabolic state to cellular excitability. The pore of most K(ATP) channel types is built by Kir6.2 subunits. Analysis of a general Kir6.2 knockout (KO) mouse has identified a variety of different functional roles for central and peripheral K(ATP) channels in situations of metabolic demand. However, the widespread distribution of these channels suggests that they might influence cellular physiology and animal behavior under metabolic control conditions. As a comprehensive behavioral description of Kir6.2 KO mice under physiological control conditions has not yet been carried out, we subjected Kir6.2 KO and corresponding wild-type (WT) mice to a test battery to assess emotional behavior, motor activity and coordination, species-typical behaviors and cognition. The results indicated that in these test situations Kir6.2 KO mice were less active, had impaired motor coordination, and appeared to differ from controls in their emotional reactivity. Differences between KO and WT mice were generally attenuated in test situations that resembled the home cage environment. Moreover, in their home cages KO mice were more active than WT mice. Thus, our results suggest that loss of Kir6.2-containing K(ATP) channels does affect animal behavior under metabolic control conditions, especially in novel situations. These findings assign novel functional roles to K(ATP) channels beyond those previously described. However, according to the widespread expression of K(ATP) channels, these effects are complex, being dependent on details of test apparatus, procedure and prior experience.
Analysis of Variance↗
Phosphorylation of the cytokinesis regulator ECT2 at G2/M phase stimulates association of the mitotic kinase Plk1 and accumulation of GTP-bound RhoA.
The epithelial cell transforming gene 2 (ECT2) protooncogene encodes a Rho exchange factor, and regulates cytokinesis. ECT2 is phosphorylated in G2/M phases, but its role in the biological function is not known. Here we show that two mitotic kinases, Cdk1 and polo-like kinase 1 (Plk1), phosphorylate ECT2 in vitro. We identified an in vitro Cdk1 phosphorylation site (T412) in ECT2, which comprises a consensus phosphospecific-binding module for the Plk1 polo-box domain (PBD). Endogenous ECT2 in mitotic cells strongly associated with Plk1 PBD, and this binding was inhibited by phosphatase treatment. A phosphorylation-deficient mutant form of ECT2, T412A, did not exhibit strong association with Plk1 PBD compared with wild-type (WT) ECT2. Moreover, ECT2 T412A, but not phosphomimic T412D, displayed a diminished accumulation of GTP-bound RhoA compared with WT ECT2, suggesting that phosphorylation of Thr-412 is critical for the catalytic activity of ECT2. Moreover, while overexpression of WT ECT2 or the T412D mutant caused cortical hyperactivity in U2OS cells during cell division, this activity was not observed in cells expressing ECT2 T412A. These results suggest that ECT2 is regulated by Cdk1 and Plk1 in concert.
Binding Sites↗
Do motorcyclists have erectile dysfunction? A preliminary study.
The aim of the present study was to evaluate the relationship between motorcycling and erectile dysfunction (ED). We investigated the relationship between motorcycling and erectile function using the 5-items version of the International Index of Erectile Function (IIEF5) in 234 motorcyclists (response rate 75%) and 752 healthy controls (response rate 66%). In all, 161 (69%) of 234 motorcyclists were diagnosed as ED based on IIEF5. The prevalence of ED in the motorcycle group increased by age as: 58, 63, 76 and 93%, for motorcyclists in 20-29, 30-39, 40-49 and 50-59 years, respectively. There was a significant difference in the prevalence of ED between the motorcycle group and the control group in all age groups. On stepwise logistic regression analysis, motorcycling was the strongest risk factor for ED. Although the severity of ED in motorcyclists was not so severe, motorcycling may be one of risk factors for ED.
Adult↗
Cytokinesis regulator ECT2 changes its conformation through phosphorylation at Thr-341 in G2/M phase.
The Rho activator ECT2 functions as a key regulator in cytokinesis. ECT2 is phosphorylated during G2/M phase, but the physiological significance of this event is not well known. In this study, we show that phosphorylation of ECT2 at threonine-341 (T341) affects the autoregulatory mechanism of ECT2. In G2/M phase, ECT2 was phosphorylated at T341 most likely by Cyclin B/Cyclin-dependent kinase 1 (Cdk1), and then dephosphorylated before cytokinesis. Depletion of ECT2 by RNA interference (RNAi) efficiently induced multinucleate cells. Expression of the phospho-deficient mutant of ECT2 at T341 suppressed the multinucleation induced by RNAi to ECT2, indicating that ECT2 is biologically active even when it is not phosphorylated at T341. However, the phospho-mimic mutation at T341 weakly stimulates the catalytic activity of ECT2 as detected by serum response element reporter gene assays. As T341 is located at the hinge region of the N-terminal regulatory domain and C-terminal catalytic domain, phosphorylation of T341 may help accessing downstream signaling molecules to further activate ECT2. We found that the phospho-mimic mutation T341D increases binding with itself or the N-terminal half of ECT2. These results suggest a conformational change of ECT2 upon phosphorylation at T341. Therefore, ECT2 activity might be regulated by the phosphorylation status of T341. We propose that T341 phosphorylation by Cyclin B/Cdk1 could be a trigger for further activation of ECT2.
Amino Acid Sequence↗
Management of intracranial germ cell tumors presenting with rapid deterioration of consciousness.
OBJECTIVES: The value of surgical intervention in the management of intracranial germ cell tumors remains controversial. PATIENTS: We report three patients who presented with rapid deterioration of consciousness but resulted in complete remission of the tumor after emergency surgery for both diagnostic (biopsy) and therapeutic (for hydrocephalus) purposes followed by prompt initiation of radiochemotherapy. CONCLUSION: For management of these rapidly deteriorating patients, immediate histological verification and avoidance of delay in the induction of radiochemotherapy are essential. Thus, emergency surgery with a less invasive procedure is the first choice of treatment, i. e., endoscopic surgery for pineal region tumor and CT-guided biopsy for basal ganglia tumor.
Adult↗
Restless legs syndrome in hemodialysis patients: health-related quality of life and laboratory data analysis.
AIMS: To compare clinical data, sleep quality and health-related quality of life (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The international RLS study group diagnosis questionnaire was completed by 228 HD patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and age at the initiation of HD were significantly younger in the RLS group. Serum calcium concentration (Ca) was significantly higher in the RLS group. Sleep quality evaluated by PSQI was significantly lower in the RLS group. In SF-36 domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role functioning emotional, mental health and mental component score were significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF, symptoms/problems, burden of kidney disease, cognitive function, quality of social interaction, sleep and patient satisfaction were significantly lower in the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology of RLS which impaired sleep quality as well as HRQOL including mental health and many kidney disease related scales.
Adult↗
[Usefulness of ultrasonically activated scalpel for pulmonary resection in video-assisted thoracoscopic surgery].
We evaluated the reliability and efficacy of the ultrasonically activated scalpel (Harmonic Scalpel) for pulmonary resection in video-assisted thoracoscopic surgery (VATS). Fifty-six cases of primary or metastatic lung cancer with history of lobectomy or segmentectomy from July 2003 to June 2006 were investigated. The ultrasonically activated scalpel was used to separate aborted lobulation and segment in the surgery. The outcome of the operation using the ultrasonically activated scalpel revealed the mean operation time of 224.5 minutes and mean blood loss volume of 116.7 ml. The chest drainage catheter was removed at the postoperative day 3.4 and hospitalization lasted 10.4 days on average. By means of statistical analysis, no significant differences were noted when compared with the cases using surgical stapler to separate the lobules or segments of the lungs. Histopathological results showed destruction of alveolar structures and denaturation of cells at the cut surface of the resected lung through the use of the ultrasonically activated scalpel. This method resulted in good lung expansion and preservation of the residual lung volume. Furthermore, it prevented postoperative air leakage by appropriate treatment to the cut surfaces of the residual lung. Indeed, the method appears to be useful in the separation of lung tissues in severe aborted lobulation and segmentectomy by VATS.
Aged↗
Treadmill running causes significant fiber damage in skeletal muscle of KATP channel-deficient mice.
Although it has been suggested that the ATP-sensitive K(+) (K(ATP)) channel protects muscle against function impairment, most studies have so far given little evidence for significant perturbation in the integrity and function of skeletal muscle fibers from inactive mice that lack K(ATP) channel activity in their cell membrane. The objective was, therefore, to test the hypothesis that K(ATP) channel-deficient skeletal muscle fibers become damaged when mice are subjected to stress. Wild-type and K(ATP) channel-deficient mice (Kir6.2(-/-) mice) were subjected to 4-5 wk of treadmill running at either 20 m/min with 0 degrees inclination or at 24 m/min with 20 degrees uphill inclination. Muscles of all wild-type mice and of nonexercised Kir6.2(-/-) mice had very few fibers with internal nuclei. After 4-5 wk of treadmill running, there was little evidence for connective tissues and mononucleated cells in Kir6.2(-/-) hindlimb muscles, whereas the number of fibers with internal nuclei, which appear when damaged fibers are regenerated by satellite cells, was significantly higher in Kir6.2(-/-) than wild-type mice. Between 5% and 25% of the total number of fibers in Kir6.2(-/-) extensor digitum longus, plantaris, and tibialis muscles had internal nuclei, and most of such fibers were type IIB fibers. Contrary to hindlimb muscles, diaphragms of Kir6.2(-/-) mice that had run at 24 m/min had few fibers with internal nuclei, but mild to severe fiber damage was observed. In conclusion, the study provides for the first time evidence 1) that the K(ATP) channels of skeletal muscle are essential to prevent fiber damage, and thus muscle dysfunction; and 2) that the extent of fiber damage is greater and the capacity of fiber regeneration is less in Kir6.2(-/-) diaphragm muscles compared with hindlimb muscles.
Animals↗
p38 MAP kinase plays a role in G2 checkpoint activation and inhibits apoptosis of human B cell lymphoma cells treated with etoposide.
p38 MAPK is mainly activated by stress stimuli and mediates signals that regulate various cellular responses, including cell-cycle progression and apoptosis, depending on cell types and stimuli. Here we examine the role of p38 in regulation of apoptosis and cell cycle checkpoint in Daudi B-cell lymphoma cells treated with the topoisomerase II inhibitor etoposide. Etoposide activated p38, inhibited the G2/M transition with the persistent inhibitory phosphorylation of Cdc2 on Tyr15, and caused apoptosis of Daudi cells. Inducible expression of a dominant negative p38alpha mutant in Daudi cells reduced the inhibition of Cdc2 as well as G2/M arrest and augmented apoptosis induced by etoposide. SB203580, a specific inhibitor of p38alpha and p38beta, similarly reduced the inhibitory phosphorylation of Cdc2 as well as G2/M arrest and augmented apoptosis of Daudi cells treated with etoposide. These results suggest that p38 plays a role in G2/M checkpoint activation through induction of the persistent inhibitory phosphorylation of Cdc2 and, thereby, inhibits apoptosis of Daudi cells treated with etoposide. The present study, thus, raises the possibility that p38 may represent a new target for sensitization of lymphoma cells to DNA-damaging chemotherapeutic agents.
CDC2 Protein Kinase↗
Glucose transporter plasticity during memory processing.
Various types of learning, including operant conditioning, induce an increase in cellular activation concomitant with an increase in local cerebral glucose utilization (LCGU). This increase is mediated by increased cerebral blood flow or changes in brain capillary density and diameter. Because glucose transporters are ultimately responsible for glucose uptake, we examined their plastic expression in response to cellular activation. In vitro and in vivo studies have demonstrated that cerebral glucose transporter 1 (GLUT1) expression consistently parallels changes in LCGU. The present study is the first to investigate the effect of memory processing on glucose transporters expression. Changes in GLUT expression produced by training in an operant conditioning task were measured in the brain of CD1 mice. Using semi-quantitative immunohistochemistry, Western blot and real time RT-PCR the cerebral GLUT1 and GLUT3 expression was quantified immediately, 220 min and 24 h following training. Relative to sham-trained and naive controls, operant conditioning training induced an immediate increase in GLUT1 immunoreactivity level in the hippocampus CA1 pyramidal cells as well as in the sensorimotor cortex. At longer post-learning delays, GLUT1 immunoreactivity decreased in the sensorimotor cortex and putamen. Parallel to the changes in protein levels, hippocampus GLUT1 mRNA level also increased immediately following learning. No effect of learning was found on hippocampal GLUT3 protein or mRNA expression. Measures of changes in glucose transporters expression present a link between cellular activation and glucose metabolism. The learning-induced localized increases in GLUT1 protein as well as mRNA levels observed in the present study confirm the previous findings that GLUT1 expression is plastic and respond to changes in cellular metabolic demands.
Animals↗
Indications for neuroendoscopic aqueductoplasty without stenting for obstructive hydrocephalus due to aqueductal stenosis.
OBJECTIVE: Neuroendoscopic aqueductoplasty (EAP) is a curative and radical procedure for obstructive hydrocephalus due to aqueductal stenosis that re-establishes the physiological circulation of cerebrospinal fluid (CSF). We assessed the indications for safe neuroendoscopic aqueductoplasty without stenting to treat aqueductal stenosis. METHODS: In the past 5 years, 6 (5.5 %) of the 110 patients with obstructive hydrocephalus due to aqueductal stenosis were judged to be suitable for EAP on the basis of the MRI features of the aqueduct and intraoperative neuroendoscopic findings from the third ventricle for the aqueductal stenosis. The remaining 104 patients were treated by neuroendoscopic third ventriculostomy. Indications for safe EAP were determined retrospectively based on the clinical features, preoperative MRI, intraoperative neuroendoscopic findings and outcome of the 6 patients who underwent EAP. RESULTS: There were no deaths due to EAP. All of the patients showed improvement or resolution of their preoperative symptoms. In 5 patients, dilatation of the third ventricle and lateral ventricles diminished, and prestenotic dilatation of the aqueduct also disappeared. After an average follow-up period of 39.5 months, recurrence of aqueductal stenosis has not been observed. In one patient, there was a complication of oculomotor nerve paresis after EAP. CONCLUSIONS: EAP can be considered the best surgical procedure for restoring physiological circulation of CSF in patients with obstructive hydrocephalus caused by aqueductal stenosis. However, EAP candidates must be selected very carefully using the following indications: 1) obstructive triventricular hydrocephalus with increased intracranial pressure, 2) translucent membranous stenosis or aqueduct obstruction, and 3) prestenotic dilatation of the aqueduct.
Adolescent↗
Can we develop biomarkers that predict response of cancer patients to immunotherapy?
PRIMARY OBJECTIVE: The primary objective is to delineate the potential utility of cancer biomarkers that correlate and predict response to immunotherapy in cancer patients who are refractory to conventional therapeutics. Unlike significant development of biomarkers that predict response to chemotherapy, very few biomarkers have been developed to predict the response to immunotherapy. MAIN OUTCOMES AND RESULTS: This article describes briefly the importance of characterizing and validating biomarkers for immunotherapy. A few examples have been provided, such as the transcription factor NF-kappaB, the transcription repressor Yin-Yang 1 (YY1), the pro-apoptotic gene product (Smac/DIABLO) and the circulating Fas and Fas ligand. These biomarkers have been determined to be of prognostic significance in different cancers. CONCLUSIONS: Immunotherapy is considered as an alternative therapy in the treatment of cancer patients who are refractory to chemotherapy/radiation/hormonal therapies. Cross-resistance to apoptosis develops between cancer cells that are resistant to conventional therapeutics and immunotherapy. Therefore, it is important to develop biomarkers that will determine patient response to immunotherapy.
Animals↗
Spontaneous healing of chyle leakage after lymphangiography.
We report a 34-year-old man with the complication of chylous ascites after retroperitoneal lymphadenectomy that was refractory to various conservative therapies. Because surgical treatment for chylous ascites was considered, lymphangiography was performed to identify the area of leakage of chyle, after which the chylous ascites spontaneously healed.
Adult↗
Multidetector-row CT findings of colonic perforation: direct visualization of ruptured colonic wall.
BACKGROUND: We examined the findings of contrast-enhanced multidetector-row computed tomography (MD-CT) in patients with colonic perforation. METHODS: Abdominal contrast-enhanced MD-CT findings in six patients with colonic perforation were reviewed retrospectively. Patients (three men and three women) were 74 to 88 years old (mean age = 78 years). Colonic perforation was confirmed by surgery. CT findings were correlated with surgical and pathologic findings. RESULT: The site of colonic perforation was suggested by the following combination of CT findings: free air, dirty mass, dirty fat sign, extraluminal fluid collection, bowel wall thickening, and interruption of colonic wall. The ruptured colonic wall was directly visualized in four cases (67%). CONCLUSION: Abdominal contrast-enhanced MD-CT may improve the accuracy of diagnosis and localization of colonic perforation.
Aged↗