Distribution in nitric oxide neurons after rat small intestinal transplantation.
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Animals↗
Biomedical subjects
K Yanai
Publications and source records attributed to K Yanai.
Comparison of jejunal and ileal grafts from the aspects of cold preservation and immunologic reaction.
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Adenosine↗
Efficacy of cytologic examination of luminal exudate in monitoring acute rejection of rat intestinal allografts.
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Acute Disease↗
Behavioural characterization and amounts of brain monoamines and their metabolites in mice lacking histamine H1 receptors.
Behavioural assessments were made of mutant mice lacking histamine H1 receptors to reveal the function of H1 receptors in the behaviour of mice. Exploratory behaviour of mice in a new environment was examined to discover whether the absence of H1 receptors in mice affects actions relating to their emotions. The H1 receptor-deficient mice showed a significant decrease in ambulation in an open field and on an activity wheel. Cognitive functions and anxiety were examined using passive avoidance response test and the elevated plus-maze test, respectively. The passive avoidance test did not show any change in latency. The elevated plus-maze test revealed that the transfer latency of the mutant mice was significantly prolonged, indicating that H1 receptors are partly associated with the control of anxiety. Aggressive behaviour was examined by a resident-intruder aggression test. When confronted with an intruder, the mutant mice attacked the intruder significantly slower and less frequently than did wild-type mice after a six-month isolation period. A formalin test and a forced swimming test were used to evaluate the nociceptive response and depressive or despairing state, respectively, of both groups. The mutant mice showed a significant decrease of nociceptive response in the late phase without affecting the early phase. There was no significant difference in the forced swimming test between the two groups. The brain content of monoamines and their metabolites was measured in the H1 receptor null and wild-type mice. The turnover rate of 5-hydroxytryptamine defined by the ratio of 5-hydroxyindoleacetic acid and 5-hydroxytryptamine was significantly increased in the cerebral cortex and hippocampus of H1 receptor null mice. These results support the previous pharmacological findings that histamine modulates various neurophysiological functions such as locomotor activity, emotion, memory and learning, nociception and aggressive behaviour through H1 receptors.
Aggression↗
Longterm outcomes and quality of life after Z-shaped anastomosis for Hirschsprung's disease.
BACKGROUND: Z-shaped anastomosis is one of the modifications of Duhamel's procedure that was designed to eliminate the blind rectal pouch and to achieve complete resection of the colorectal septum. It has been the most widely performed operation in Japan for many years. The longterm postoperative function of evacuation and quality of life of the patients are considered important to evaluate this procedure. METHODS: At Kyushu University Hospital, from 1963 to 1997, 127 patients with Hirschsprung's disease underwent Z-shaped anastomosis. As a result, 122 out of 127 patients (96%) survived. The present status and symptoms, and anorectal functions, including a manometric study and barium enema, were evaluated during the clinical followup. RESULTS: A total of 99 of the 122 surviving patients (81%) were available for this study, and the mean postoperative period was 16 years. Evacuation scores in all patients were as follows; excellent, 62.2%; good, 28.6%; fair, 8.2%; and poor, 1.0%. The percentage of the patients who showed severe symptoms was 4.1% for diarrhea, 3.1% for constipation, 5.1% for incontinence, and 7.1% for soiling. The evacuation score improved chronologically and tended to reach a plateau at 10 to 15 years after operation, at which time 73% of the patients showed excellent outcomes and 95% were satisfactory (good or excellent). The appearance of a sense of defecation and an increase in the pressure difference between the anal canal and the rectum substantially contributed to the improvement in the defecation score. The appearance of the rectosphincteric reflex, including the atypical one, was seen in 40.5% of patients, but the appearance of a reflex did not seem to be related to the clinical status of defecation. Twenty-two of 30 patients older than 20 years were married, and 8 patients had children. CONCLUSIONS: The evacuation scores of in-patients undergoing Z-shaped anastomosis improved with age and were satisfactory (good or excellent) in most patients at least 10 years after operation. Most of the patients adapted to a normal social life.
Adolescent↗
Estimation of organ cumulated activities and absorbed doses on intakes of several 11C labelled radiopharmaceuticals from external measurement with thermoluminescent dosimeters.
We have developed a method for obtaining the cumulated activities in organs from radionuclides, which are injected into the patient in nuclear medicine procedures, by external exposure measurement with thermoluminescent dosimeters (TLDs) which are attached to the patient's body surface close to source organs to obtain information on body-surface doses. As the surface dose is connected to the cumulated activities in source organs through radiation transmission in the human body which can be estimated with the aid of a mathematical phantom, the organ cumulated activities can be obtained by the inverse transform method. The accuracy of this method was investigated by using a water phantom in which several gamma-ray volume sources of known activity were placed to simulate source organs. We then estimated by external measurements the organ cumulated activities and absorbed doses in subjects to whom the radiopharmaceuticals 11C-labelled Doxepin, 11C-labelled YM09151-2 and 11C-labelled Benzotropin were administered in clinical nuclear medicine procedures. The cumulated activities in the brain obtained with TLDs for Doxepin and YM09151-2 are 63.6 +/- 6.2 and 32.1 +/- 12.0 kBq h MBq-1 respectively, which are compared with the respective values of 33.3 +/- 9.9 and 23.9 +/- 6.2 kBq h MBq-1 with direct PET (positron emission tomography) measurements. The agreement between the two methods is within a factor of two. The effective doses of Doxepin, YM09151-2 and Benzotropin are determined as 6.92 x 10(-3), 7.08 x 10(-3) and 7.65 x 10(-3) mSv MBq-1 respectively with the TLD method. This method has great advantages, in that cumulated activities in several organs can be obtained easily with a single procedure, and the measurements of body surface doses are performed simultaneously with the nuclear medicine procedure, as TLDs are too small to interfere with other medical measurements.
Asian People↗
[Functional neuropharmacology in the human brain using positron emission tomography: PET imaging of impaired cognitive performance induced by sedative antihistamines].
Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistamines is of central importance because of their widespread use in current medical practice. Positron emission tomography (PET) was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [11C]-doxepin after the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human cortex caused by antihistamines is significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is well proportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced "sleepiness and impaired cognition", the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H2(15)O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain.
Animals↗
Histamine-induced calcium mobilization in single cultured cells expressing histamine H1 receptors: a relationship between its sensitivity and the density of H1 receptors.
Stimulation of histamine H1 receptors initiates the hydrolysis of phosphatidylinositides and results in the production of inositol (1, 4,5)-triphosphate and intracellular Ca2+ mobilization. Although the mechanism for signal transduction via the H1 recptor has been extensively investigated, little is known about the correlation between the sensitivity of histamine-induced Ca2+ mobilization and the density of H1 receptors in cultured cells. Cytosolic free Ca2+ concentration ([Ca2+]i) after stimulation by histamine was monitored in single CHO and rat C6-glioma cells stably expressed with H1 receptors and astrocytoma 1321N1 cells using the Ca2+-sensitive dye Indo-1 and dynamic single cell imaging techniques (ACAS 570 laser cytometer). Both of the H1 receptor-expressed CHO cells and C6-glioma cells were over 10 times more sensitive to histamine than astrocytoma 1321N1 cells in which H1 receptors were naturally present. The density of H1 receptors in the transfected cells was also more than 10-fold that of 1321N1 cells. In addition, inhibition of intracellular Ca2+-ATPase by thapsigargin elicited an increase in [Ca2+]i in H1 receptor-overexpessed cells and astrocytoma 1321N1 cells with similar sensitivity. These data suggest that the sensitivity of Ca2+ mobilization by histamine in these cells was correlatively augmented with the increase in the density of H1 receptors.
Animals↗
Effects of long-term treatment with eicosapentaenoic acid on the heart subjected to ischemia/reperfusion and hypoxia/reoxygenation in rats.
The effects of eicosapentaenoic acid (EPA) and long-term treatment with EPA-ethylester (EPA-E) were examined in perfused rat hearts subjected to ischemia/reperfusion and adult rat cardiomyocytes subjected to hypoxia/reoxygenation. EPA (0.1 microM) improved postischemic contractile dysfunction of the ischemic/reperfused heart. EPA (10 microM) attenuated hypoxia/reoxygenation-induced morphological deterioration of cardiomyocytes. The results suggest the presence of direct cardioprotective effects of EPA. Rats were orally treated for 4 weeks with 1 g/kg/day of EPA-E to elucidate ex vivo effects of EPA, and the fatty acid composition of cardiac phospholipids was determined. The percent ratio of EPA in total fatty acids of cardiac phospholipids increased whereas that of arachidonic acid decreased. The percent ratio of n-3/n-6 fatty acid did not increase. Treatment with EPA-E did not improve the post-ischemic contractile function, but attenuated the ischemia/reperfusion-induced release of prostaglandins during reperfusion. Treatment with EPA-E preserved a better morphological appearance of the cardiomyocytes subjected to hypoxia/reoxygenation. The results suggest that the mechanisms responsible for cytoprotective effects of hypoxic/reoxygenated cardiomyocytes or inhibition of metabolic alterations of the ischemic/reperfused heart by long-term EPA-E treatment did not contribute substantially to recovery of post-ischemic contractile dysfunction. The direct in vitro effects of EPA may play a role in the protection of the heart from ischemia/reperfusion or hypoxia/reoxygenation injury.
Animals↗
Molecular variation of the human angiotensinogen core promoter element located between the TATA box and transcription initiation site affects its transcriptional activity.
Recent genetic studies indicate that several molecular variants discovered in angiotensinogen (AG), the precursor of vasoactive octapeptide angiotensin II, could potentially be responsible for inherited predisposition to human blood pressure variation. We have previously shown that a ubiquitously expressed nuclear factor, AGCF1, bound to AGCE1 (AG core promoter element 1 including the core nucleotides, CTCGTG, CTC-type) located between the TATA box and transcription initiation site (positions -25 to -1) is an authentic regulator of human AG transcription. In the present study, we showed that AGCF1 has biologically and immunologically similar properties to those of a helix-loop-helix nuclear factor USF1 and examined the effects of two other naturally occurring molecular variants (ATCGTG, ATC-type and ATTGTG, ATT-type) found in the AGCE1 position on the human AG transcriptional activity. Competitive gel-shift and transfection experiments demonstrated that the transcriptional activity for the CTC- and ATC-type promoters was 2.5 times higher than that for the ATT-type through the alteration of AGCF1-binding affinity. These results suggest the possible involvement of USF1 as a component in AGCF1 formation and the potential importance of AGCE1 variation in blood pressure regulation through human AG expression.
Angiotensinogen↗
Excitotoxic lesions of histaminergic neurons by excitatory amino acid agonists in the rat brain.
Excitotoxic lesions of histaminergic (HA) neurons in the rat hypothalamus were observed by the injection of ibotenate and N-methyl-D-aspartate (NMDA) while kainate, quisqualate and quinolinate had no significant effects on HA neurons. An NMDA selective antagonist, 2-amino-5-phosphonopentanoic acid, was able to block the toxic effects of both NMDA and ibotenate almost completely, but kynurenate was a weaker inhibitor of ibotenate or NMDA-induced neurotoxicity. These results suggest that there exists an ibotenate-sensitive and quinolinate-insensitive NMDA receptor subtype on HA neurons.
Animals↗
ATF-like element contributes to hepatic activation of human angiotensinogen promoter.
Angiotensinogen is the precursor protein of angiotensin II that is involved in regulating blood pressure and electrolyte homeostasis, and it is mainly synthesized in the liver. In the present study, we analyzed the human angiotensinogen proximal promoter region by means of Chloramphenicol acetyltransferase assays, and suggested that the region from -106 to +44 is sufficient for hepatoma cell line (HepG2)-specific expression. Electrophoretic mobility shift assays using ALE (ATF-like element, -102 to -87) fragment identified CREB/ATF family nuclear factors and novel ones, ALF (ALE-binding factor). The deletion and in vivo competition of ALE decreased the human angiotensinogen promoter activity. Furthermore, the heterologous promoter analysis demonstrated that ALE acts as a HepG2-dependent activating element. These results indicate that ALE plays an important role in hepatic expression of human angiotensinogen gene.
Activating Transcription Factors↗
Differential action of AGCF2 upon cell type-dependent expression of human angiotensinogen gene.
To investigate the regulatory mechanisms of human angiotensinogen (ANG) gene expression in the brain, we analyzed the 1.3-kb promoter by transfection studies and gel shift assays. The region from -106 to +44 was sufficient for promoter activity in glioblastoma cells, and multiple nuclear factors including AGCF2 (human ANG core promoter binding factor 2) bound within this 150-bp region. The mutations within AGCF2-binding elements decreased the transcriptional activity in glioblastoma cells but rather increased it in hepatoma cells. These results indicate that AGCF2 has a differential function between these cells and contributes to the glia-dependent angiotensinogen promoter activity.
Angiotensinogen↗
Total colonic aganglionosis with or without small bowel involvement: a changing profile.
BACKGROUND/PURPOSE: To identify recent trends in the diagnosis and treatment of total colonic aganglionosis with or without small bowel involvement (TCSA), the authors analyzed the findings in 107 patients who had TCSA seen between 1988 and 1992 at 147 medical institutions throughout Japan and compared the results with those of a previous survey conducted between 1978 and 1982. RESULTS: The estimated incidence of total colonic aganglionosis was 1 in 58,084 live births, the male to female ratio was 1.5:1, and the incidence of associated anomalies was 15%. These findings were all very similar to those of the previous survey. Ten years ago, 83.6% of all patients underwent Martin's procedure. In the recent survey, this rate had fallen to 52.1%, and a right colon patch method has also been developed as a new procedure. A marked decrease in the overall mortality rate from 40.9% to 21.5% was observed. However, a high mortality rate persists in those cases with small bowel involvement (33.3%); most such cases are complicated with enterocolitis. CONCLUSIONS: Although the general features of TCSA were similar to those in the previous survey, a substantial improvement in the treatment results for TCSA has occurred. However, further efforts are still required both to prevent and more effectively to treat enterocolitis, especially in cases involving any aganglionosis extending into small bowel.
Enterocolitis↗
Energy metabolism during cold ischemia and reperfusion in rat small intestinal transplantation: comparison of jejunal and ileal grafts.
BACKGROUND/PURPOSE: In segmental small intestinal transplantation, the question as to whether the jejunum or ileum is the better graft remains unclear. The authors investigated this question regarding nutrition, blood chemistry, and adaptation. METHODS: The authors compared the jejunum and ileum as the proper portion of segmental graft in rat small intestinal transplantation, regarding energy metabolism both during cold preservation and after reperfusion using high-performance liquid chromatography, as well as histological examination. RESULTS: In a cold preservation study, the concentrations of adenosine triphosphate (ATP) in the jejunum versus ileum at 0, 6, 12, 24, and 48 hours of cold preservation were 1.98 +/- 0.93 versus 1.83 +/- 0.84, 0.79 +/- 0.51 versus 0.55 +/- 0.41, 0.60 +/- 0.41 versus 0.58 +/- 0.45, 0.38 +/- 0.28 versus 0.47 +/- 0.39, and 0.44 +/- 0.26 versus 0.55 +/- 0.29 (micromol/g dry weight), respectively. There were no significant differences between the jejunum and ileum at any times of preservation. Adenosine monophosphate (AMP), adenosine diphosphate (ADP), total adenine nucleotides (TAN), and energy charge (EC) also showed no significant differences between the jejunum and ileum at any times of preservation. In the reperfusion study, the concentrations of ATP in jejunum versus ileum 30 minutes after reperfusion after 6, 12, and 24 hours of cold preservation were 0.68 +/- 0.19 versus 0.50 +/- 0.17, 0.71 +/- 0.51 versus 0.42 +/- 0.14, and 0.93 +/- 0.29 versus 0.75 +/- 0.47 (micromol/g dry weight), respectively. Each value was slightly higher in the jejunum than that in the ileum; however, there were no statistically significant differences. TAN showed the same changes as ATP. No significant differences were found between the jejunum and ileum in either AMP, ADP, or EC. The histological findings both just before and 30 minutes after reperfusion were also compared. However, no evident differences were found between the jejunum and ileum. CONCLUSION: These results thus suggest that no significant differences exist between the jejunum and ileum regarding energy metabolism either during cold preservation or after reperfusion in small intestinal transplantation.
Animals↗
Effects of haloperidol and cocaine pretreatments on brain distribution and kinetics of [11C]methamphetamine in methamphetamine sensitized dog: application of PET to drug pharmacokinetic study.
Repeated administration of methamphetamine (MAP) causes behavioral sensitization in animals. We previously reported that the maximum accumulation level of [11C]MAP in the MAP-sensitized dog brain was 1.4 times higher than that in the control. In behavioral studies, haloperidol (a dopamine D2 receptor antagonist) prevents MAP-induced behavioral sensitization, and cocaine (a dopamine reuptake blocker) has the cross-behavioral sensitization with MAP. In the present study, to elucidate the relation between the MAP-induced behavioral sensitization and the pharmacokinetics of MAP, we investigated the effects of haloperidol and cocaine pretreatments on brain regional distribution and kinetics of [11C]MAP using positron emission tomography (PET). A significant increase of [11C]MAP uptake into the sensitized dog brain was prevented by haloperidol and cocaine pretreatments. These pharmacokinetic changes were not due to the changes in the rate of MAP metabolism. These results suggest haloperidol and cocaine can change the cerebral pharmacokinetic profile of MAP in the behavioral-sensitized dog. The variations of MAP-accumulation may affect the development or expression of MAP-induced behavioral sensitization.
Animals↗
[Neurotransmission in human brains measured by positron emission tomography (PET)].
Various techniques have been developed to image human brain function in the past decade. X-ray computerized tomography and magnetic resonance imaging (MR) are used to evaluate brain structure. Recently, positron emission tomography (PET) and MR are often utilized to perform human brain mapping such as attention, cognition, language comprehension, and so on. PET also makes it possible to evaluate the states of various types of neurotransmission. These techniques cannot only be used to map "brain neurochemistry" in normal human brains, but they will also increase our knowledge by demonstrating neurochemical abnormalities in a wide range of neurological and psychiatric disorders or those that occur during normal aging. The PET techniques are applicable to the development of new drugs in the pharmaceutical industry. Using PET techniques of imaging neurotransmission, it is feasible to measure the release of neurotransmitter after activation of the CNS by various methods (ligand activation study). We have developed the methodology of using 11C-labeled antagonists for mapping functional histamine H1-receptors in human brain directly and noninvasively by PET. The present review article provides an outline of the conceptual and methodological progress over the past several years that has made it possible to visualize neurotransmission in human brains by PET.
Animals↗
The effect of haloperidol on the histaminergic neuron system in the rat brain.
In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.
Animals↗