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Biomedical subjects

M Ishibashi

Publications and source records attributed to M Ishibashi.

At least 19 recordsLinked to original sources

Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK II phosphorylation in rats.

Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.

Animals↗

Elevated cerebrospinal fluid lactate levels and the pathomechanism of calcification in Fahr's disease.

In this study, we report the case of a 68-year-old man complaining of involuntary movement of his left shoulder and lower jaw plus dyspnea. On cranial computed tomography and magnetic resonance imaging, marked and symmetrical calcification at the basal ganglia and dentate nuclei was documented. An elevated cerebrospinal fluid (CSF) lactate level was confirmed by spinal tap examination and magnetic resonance spectroscopy. The raised CSF lactate level, clinical characteristics such as diabetes, bilateral hearing loss and symmetrical cerebral calcification strongly suggested some kinds of mitochondrial disease. However, gene analysis of peripheral blood leukocytes revealed no typical or known mutations. Under the diagnosis of Fahr's disease, we treated him with haloperidol, which completely abolished his symptoms. In Ellsworth-Howard test, he showed markedly decreased phosphaturic response to parathyroid hormone with same pattern as type 2 pseudohypoparathyroidism. This abnormal response in our patient, probably due to respiratory alkalosis reflecting chronic hyperventilation, might in part explain similar mechanism of ectopic calcification underlying these two diseases.

Aged↗

Relationship between intraoperative transoesophageal echocardiography findings and perfusion lung scintigraphy results on first postoperative day.

BACKGROUND: Although intraoperative transoesophageal echocardiography (TOE) has been used to detect the occurrence of echogenic macro- and/or microembolic phenomena during total hip arthroplasty (THA), no direct correlation between macroembolism and the formation of pulmonary embolism (PE) has been conclusively determined in early postoperative periods after THA. METHODS: Sixty-two patients scheduled for primary THA were enrolled in this study. Intraoperative TOE images were continuously recorded on videotape and the echogenic events were evaluated throughout surgery. Perfusion lung scintigraphy was performed on the first postoperative day (POD1). RESULTS: Perfusion lung scintigraphy revealed the existence of PE in nine (15%) of the 62 patients who underwent THA: five (25%) of 20 patients with cemented THA and four (10%) of 42 patients with non-cemented THA. The grading score of intraoperative TOE findings, including the amount of echogenic particles in right atrium, the longest time of echogenesis and the diameter of the largest echogenic particles, did not differ between the groups with and without PE. The sensitivity, specificity, and positive and negative predictive values for the detection of echogenic macroemboli for the prediction of the development of PE on POD1 were 0.78, 0.60, 0.25 and 0.94, respectively. CONCLUSION: Intraoperative TOE monitoring did not predict the occurrence of PE on POD1.

Adult↗

Morphological imaging in the localization of neuroendocrine gastroenteropancreatic tumors found by somatostatin receptor scintigraphy.

PURPOSE: To evaluate the necessity of morphological images (MI) in reading somatostatin receptor scintigraphy (SRS) in patients with suspected neuroendocrine gastroenteropancreatic (GEP) tumors. MATERIAL AND METHODS: A Japanese multicenter clinical trial of SRS was conducted in 40 patients with suspected GEP tumors. Three experienced radiologists interpreted the images in three separate sessions in a blinded manner (1: SRS images alone, 2: MI alone, 3: SRS and MI analyzed simultaneously), and the reading results of each session were compared. In addition, the diagnostic abilities of SRS, MI and SRS alone and simultaneous SRS and MI readings were compared for patients where final diagnosis was obtained. RESULTS: SRS detected more suspected lesions (positive or inconclusive uptake) than morphological images did (51 vs 27 lesions), but included many physiological uptakes detected as positive or inconclusive uptakes. Combined reading of SRS and morphological images helped to correctly recognize these physiological uptakes, and also helped in determining the anatomical localization of the abnormal uptakes. Combined reading of SRS and morphological images gave the highest diagnostic impact. CONCLUSION: The sensitivity of SRS with regard to GEP is high. However the specificity is very low. Morphologic imaging is necessary for the exclusion of physiological uptake and correct anatomic location of an abnormal tracer uptake. The combined reading of SRS and morphologic imaging studies gives the highest diagnostic impact.

Adenocarcinoma↗

Pancreas-kidney transplantation in Japan: impact of cyclosporine on the development of immunosuppressive therapy.

The number of pancreas transplants reached 16,043 worldwide in October 2001, with 1800 performed in 2000. Since the introduction of cyclosporine (CyA) in 1979, a regimen consisting of CyA, azathioprine, and steroids has been shown to improve long-term survival of clinical transplants. In Japan, the first simultaneous pancreas-kidney transplantation was performed in 1984, using organs from a brain-dead donor. This procedure was followed by 14 pancreas transplantations from cardiac arrest donors. All cases utilized a CyA-based regimen with antilymphocyte globulin or OKT3 induction. Six of the 15 recipients required less insulin postoperatively. Under a new transplant law enforced in 1997, 10 pancreas/pancreas-kidney transplantations were performed in patients diagnosed with end-stage renal failure due to diabetes mellitus type 1. In 1 patient, the graft failed due to venous thrombosis, but the other 9 recipients achieved an increased quality of life without the need for insulin or for dialysis. Pancreas transplantation represents an effective treatment worldwide and in Japan, due to the availability of CyA or tacrolimus in combination with other agents such as antilymphocyte globulin, OKT3, or mycophenolate mofetil. This investigation presents the results of pancreas-kidney transplantation in Japan, in comparison with those worldwide, and describes a recent case in Japan.

Adult↗

Characteristics of pancreas transplantation currently performed in japan.

The Pancreas Transplantation (tx) Program under the Japanese Organ Transplant Act was started in 2000. PTx is indicated for type 1 diabetic patients on hemodialysis therapy. As of April 2003 93 patients are listed as candidates. Ten cases of PTx with enteric or bladder-drained technique were performed during the last 3 years as well as nine SPK and one PAK. Of 10 cases, nine recipients are insulin-free with HbA1c values ranging from 4.4% to 5.7%, although exogenous insulin was required in six cases temporarily, namely for a median 63 days (12 to 225 days). One case was lost due to pancreatic graft thrombosis. All 10 kidney grafts are functioning. Based on the experiences with 14 cases of pancreas tx using non-heart-beating (NHB) donors, we defined the criteria of NHB donor as: age younger than 40 years and cessation of respiratory support. One case of SPK with graft of NHB donor was done, and the recipient is off insulin. Pancreas and kidney are allocated for SPK if the recipient shares at least one HLA-DR antigen. Marginal donors were defined as higher mean donor age, median 37 (range 18 to 58 years); mean 38 +/- 12 years), and no death cause of by trauma. The revascularization of gastroduodenal artery to the pancreatic graft was performed in eight cases to minimize the risk of ischemic injury to the pancreatic graft and technical failure in cases of marginal donor.

Adult↗

Inhibition of neointimal hyperplasia after balloon injury by cis-element 'decoy' of early growth response gene-1 in hypercholesterolemic rabbits.

Early growth response factor-1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury and thus might contribute to vascular proliferation and inflammation. We hypothesized that Egr-1 might therefore be a therapeutic target against restenosis. Hypercholesterolemic rabbits were intraluminally administered synthetic DNA as a 'decoy' against Egr-1 immediately after carotid artery balloon injury. Efficient transfection was confirmed by the delivery of a fluorescence-labeled decoy. Gel mobility-shift assay showed increased Egr-1 activity after balloon injury and its prevention by Egr-1 decoy transfection in vivo. Egr-1 decoy transfection attenuated early inflammation and proliferation and later neointimal hyperplasia. In addition, Egr-1 decoy transfection reduced gene expression and protein production of Egr-1-dependent genes such as platelet-derived growth factor-B, transforming growth factor-beta1, and monocyte chemoattractant protein-1. The Egr-1 pathway has an essential role in the pathogenesis of neointimal hyperplasia after balloon injury in hypercholesterolemic rabbits. This decoy strategy is a potential practical form of therapy for human restenosis.

Angioplasty, Balloon↗

The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation.

AIM: Choroidal neovascularisation (CNV) is a major cause of blindness in adults. The aim of this study was to investigate the role of infiltrating cells in the development of experimental CNV. METHODS: CNV was induced in C57BL/6 (B6) mice by laser photocoagulation (PC). After PC, the numbers of each subset of infiltrated cells were analysed by flow cytometry at multiple time points. Each subset (except for macrophages) was depleted by the specific antibodies in vivo. Thereafter, the area of CNV was compared between the control B6 mice and the specific antibody treated mice 7 days after PC. The CNV formation in neutrophil depleted CC chemokine receptor-2 (CCR2) knockout mice was also examined to minimise the effects of macrophages. RESULTS: In the early phase of CNV formation, a large number of neutrophils and macrophages infiltrated to the eyes. Natural killer (NK) cells and T lymphocytes were barely detected while no B lymphocytes were detected. The CNV areas did not significantly change compared between the control B6 mice and the specific antibody treated mice. However, the neutrophil depleted CCR2KO mice resulted in a reduction of CNV. CONCLUSION: Although lymphocytes and NK cells had little effect on CNV formation, neutrophils partially contributed to CNV in the absence of macrophages.

Animals↗

A polymorphism of DRD2 gene and brain atrophy in methamphetamine psychosis.

Our group, Ujike et al., recently reported that the A1 allele of TaqI A polymorphism of the dopamine receptor D2 (DRD2) gene, associated with transient psychosis, significantly differs from that of patients with prolonged psychosis in methamphetamine psychosis. Therefore, we examined the association between the TaqI A polymorphism of the DRD2 gene and the brain MRI view for patients with methamphetamine psychosis. The subjects underwent brain MRI scans using the FLAIR method. Genotyping was performed by PCR-RFLP methods using genomic DNA extracted from peripheral blood by the phenol method. Ten subjects had the A1/A2 genotype, eleven subjects had the A2/A2 genotype, and no subject had the A1/A1 genotype. The domain size, including the thalamus and basal ganglia that were inside each side of the putamens, did not differ between the three groups (the A1/A2-group, the A2/A2-group, and the young healthy person group). In the comparison based on this domain, the temporal lobe tended to narrow in the A2/A2-group compared to the A1/A2-group (P = .06). The other domain (cerebrum, corpus callosum, etc.) showed no difference between the A1/A2-group and the A2/A2-group. It is suggested that in methamphetamine psychosis the TaqI A polymorphism not only regulates prolongation of psychosis symptoms but also influences the form of the temporal lobe.

Adult↗

Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric analysis of opiates and metabolites in rat urine after inhalation of opium.

To examine the urinary excretion of opiates and their metabolites following inhalation exposure of rats to opium, analytical procedures for the simultaneous determination of the compounds in opium, the vapor derived by the volatilization of opium and the urine of rats exposed to the opium vapor were developed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). Seven compounds were determined in the opium, namely morphine, codeine, thebaine, noscapine, papaverine, meconic acid and meconin. All seven were extracted with 2.5% acetic acid solution and subjected to LC-APCI-MS analysis. The separation was performed on an ODS column in acetonitrile-50 mM ammonium formate buffer (pH 3.0) using a linear gradient program and quantitative analysis was carried out in the selected ion monitoring mode ([M+H](+)). For the analysis of the volatilization of opium, the opium (1 g) was added to a glass pipe, which was then heated at 300 degrees C for 20 min. Negative pressure (air flow-rate; 300 ml/min) was used to draw the vapor through a series of glass wool and methanol traps. The total amount of each compound in the vapor was estimated by measurement of the compounds trapped in the glass wool and methanol. Wister rats (n=3) were exposed to the vapor derived from the volatilization system and the urinary amounts (0-72 h) of the six opiates and metabolites including morphine-3-grucronide (M3G) and morphine-6-grucronide (M6G) were measured after solid-phase extraction. The calibration curves for those compounds in the rat urine were linear over the concentration range 10-500 ng/ml. The recoveries for each analyte from the rat urine sample spiked with standard solution were generally greater than 80%, and the relative standard deviation for the analytical procedure was less than 8% with the exception of meconin. After inhalation exposure of rats to opium, M3G (5.45-14.38 micro g), morphine (2.27-4.65 micro g), meconin (0.54-1.85 micro g), codeine (0.54-1.85 micro g), noscapine (0.34-0.40 micro g) and papaverine (0.01-0.04 micro g) were detected in the urine over 72 h. However, only trace levels of thebaine were observed despite it being one of the major alkaloids found in the opium. On the other hand, a relatively large amount of meconin was detected in the vapor and the urine as compared with the opium. It is suggested that the presence of meconin in biological fluids could be indicative of opium ingestion by inhalation.

Administration, Inhalation↗

Percentage of the positive area of bone metastasis is an independent predictor of disease death in advanced prostate cancer.

We addressed in this study whether quantifying the extent of disease on bone scans can predict the disease death of patients with advanced prostate cancer using computer-assisted image analysis. Pretreatment radionuclide bone scans were reviewed in 56 patients with bone metastases from prostate cancer, and the percentage of the positive area on a bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program for estimation of the accurate extent of metastatic bone lesions on a bone scan. The significance of the %PABS as well as the other known prognostic factors was evaluated using univariate and multivariate Cox proportional hazards analysis. In univariate regression analysis, the %PABS (P=0.0155), serum alkaline phosphatase (P=0.0272), the tumour grade based on biopsy (P=0.044) and the number of bone lesions on bone scans (P=0.0388) were well associated with disease-specific survival. In multivariate analysis, the %PABS (P=0.0155, relative risk ratio 2.603), but not the other factors, was the independent predictor of the disease death. These results suggest that the %PABS is a novel parameter for predicting the prognosis of patients with advanced prostatic cancer.

Adenocarcinoma↗

Prevalence and serodiversity of the pandemic clone among the clinical strains of Vibrio parahaemolyticus isolated in southern Thailand.

We collected diarrhoea specimens in two hospitals in southern Thailand in 1999 to examine whether infection by the Vibrio parahaemolyticus pandemic clone is prevalent. V. parahaemolyticus was isolated from 317 specimens. Seventy-six per cent of the isolated strains had the pandemic clone-specific characteristics (tdh+, trh-, and an unique toxRS sequence detectable by GS-PCR) and an associated characteristic (the ORF8 sequence of f237 phage). These strains belonged to the three pandemic servovars with the O3:K6 strains being dominant and three other serovars (O1:K25, O1:K41 and O4:K12). We also found O1:K25 and O1:K41 strains with the pandemic clone-specific characteristics among the strains isolated from the international travellers who left Thailand and three other Asian countries between 1998 and 1999, verifying pandemic potential of these strains. The results demonstrate prevalence of infection by the pandemic clone in southern Thailand and suggest emergence of various serovariants in this area and their implication in international spread.

Bacterial Typing Techniques↗

Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

Adolescent↗

NaCl-activated nucleoside diphosphate kinase from extremely halophilic archaeon, Halobacterium salinarum, maintains native conformation without salt.

Enzymes from extremely halophilic archaea are readily denatured in the absence of a high salt concentration. However, we have observed here that a nucleoside diphosphate kinase prepared from Halobacterium salinarum was active and stable in the absence of salt, though it has the amino acid composition characteristic of halophilic enzymes. Recombinant nucleoside diphosphate kinase expressed in Escherichia coli requires salt for activation in vitro, but once it acquires the proper folding, it no longer requires the presence of salts for its activity and stability.

Amino Acid Sequence↗