Biomedical subjects
Publications and source records attributed to K Kaneko.
The phonon dispersion curves of the superconductor PuCoGa(5) were studied by inelastic x-ray scattering at room temperature. The experimental data agree well with ab initio lattice dynamics calculations. An accurate description of the phonon spectrum is obtained only when a local Coulomb repulsion U approximately equal 3 eV among 5f electrons is taken into account.
BACKGROUND: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. AIMS AND METHODS: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. RESULTS: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. CONCLUSION: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.
Although some molecular differences between flat-depressed neoplasias (FDNs) and protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF mutations or the status of phosphorylated mitogen-activated protein kinase (p-MAPK) are different between theses two groups. We evaluated the incidence of BRAF and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the immunohistochemical status of p-MAPK in the nonserrated neoplasias (46 FDNs and 57 PNs). BRAF mutations were detected in four FDNs (9%) and none of PNs (P=0.0369 by Fisher's exact test). KRAS mutations were observed in none of FDNs and in 14 PNs (25%; P=0.0002 by Fisher's exact test). MSI-H was detected in seven out of 44 FDNs (16%) and in one out of 52 of PNs (2%) (P=0.022 by Fisher's exact test). Type B and C immunostaining for p-MAPK was observed in 34 out of 46 FDNs (72%), compared with 24 out of 55 PNs (44%; P=0.0022 by chi(2) test). There was no significant difference in the type B and C immunostaining of p-MAPK between FDNs with and without BRAF mutations. BRAF and KRAS mutations are mutually exclusive in the morphological characteristics of colorectal nonserrated neoplasia. Abnormal accumulation of p-MAPK protein is more likely to be implicated in the tumorigenesis of FDNs than of PNs. However, this abnormality in FDNs might occur via the genetic alteration other than BRAF or KRAS mutation.
The toxic effects and changes in biochemical markers related to kidney and bone in depleted uranium (DU)-injected rats were examined in order to clarify the relation between clinical biochemical markers and the degree of damage in these organs. Male Wistar rats received a single injection in the femoral muscles of 0.2, 1.0 or 2.0 mg kg(-1) of DU which was dissolved in nitric acid solution adjusted to pH 3.2, for comparison with the group injected with nitric acid solution, and the control group. Urine and faeces were collected periodically over a 24 h period. Thereafter, the rats were killed at 28 d after DU injection. The body weights of the DU-injected groups decreased dose-dependently for the first 3-7 d, and then began to increase. The DU concentrations in the urine and faeces decreased rapidly within 3-7 d after DU injection. Urinary N-acetyl-beta-D-glucosaminidase (NAG)/creatinine peaked at the third day after DU injection, with a high correlation to the injected DU doses. There were high correlations among the injected DU doses, DU concentrations in the kidney and urinary NAG/creatinine values that were obtained at 28 d, respectively. The blood urea nitrogen (BUN) and creatinine in the serum also showed a high correlation with the DU-injected doses. The results indicated that urinary NAG/creatinine, BUN and creatinine in serum were useful indicators to diagnose the renal damage by DU, as well as to estimate the DU intake and concentration in the kidney when the intake is >2 mg kg(-1) DU. The total bone mineral density of the proximal metaphysis of the tibia decreased in the 2 mg kg(-1) DU group. In addition, alterations of the trabecular bone structure by inhibiting bone formation and promoting bone resorption were observed by bone histomorphometery. The bone biochemical markers osteocalcin, tartrate-resistance acid phosphatase, pyridinoline and rat-parathyroid hormone increased in all the DU injected groups, indicating that these markers were useful as sensitive indicators for diagnosing bone damage, even if the DU dose injected is low.
PURPOSE: To evaluate O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) uptake in mouse malignant thymoma (EL4), and its biodistribution in mice and humans. MATERIAL AND METHODS: First, 18F-FET uptake in EL4 cells was examined in an in vitro study. Second, the kinetics of 18F-FET uptake and its biodistribution were examined in mice after subcutaneous injection of EL4 cells and complete Freund's adjuvant. Finally, the kinetics of 18F-FET uptake and its biodistribution in healthy human volunteers were examined. RESULTS: In an in vitro study, 18F-FET was extensively incorporated in EL4 cells. In an animal study, 18F-FET accumulation in normal organs peaked within 30 min postinjection. The mean ratios of 18F-FET uptake in tumors and in inflammatory lesions to that in muscle tissue at 60 min postadministration were 2.18 (range 2.00-2.29) and 1.04 (range 0.95-1.14), respectively. In a human study, static images were taken 60 min after 18F-FET administration. Mean standardized uptake values (SUVs) of the liver (1.52, range 1.38-1.71) and kidneys (1.90, range 1.74-2.24) were nearly equal or slightly higher than that of muscle tissue (1.19, range 0.99-1.33). CONCLUSION: This study demonstrates that 18F-FET accumulation in thymoma is significantly higher than in normal organs. 18F-FET could be a useful tracer for tumor imaging.
Aceruloplasminemia (ACP) is an inherited disorder of iron metabolism caused by the lack of ceruloplasmin activity; the neuropathological hallmarks are excessive iron deposition, neuronal loss, bizarrely deformed astrocytes, and numerous 'grumose or foamy spheroid bodies (GFSBs)'. We histopathologically examined two autopsied ACP brains, and observed for the first time that GFSBs form in clusters at the ends of perivascular astrocytic foot processes. Both the deformed astrocytes and the GFSBs contained ferric iron and were intensely immunolabelled with antibodies against the antioxidant proteins ferritin and manganese superoxide dismutase (Mn SOD). Ceruloplasmin is largely produced by perivascular astrocytes in the central nervous system and exhibits a ferroxidase activity that inhibits iron-associated lipid peroxidation and hydroxyl radical formation; therefore, the lack of ceruloplasmin causes direct oxidative stress on astrocytes. The intense immunolabelling of ferritin and Mn SOD most likely reflects a defensive response to iron-mediated oxidative stress. This study suggests that astrocytes play key roles in iron trafficking and the detoxification of iron-mediated free radicals at the blood-brain barrier and in the parenchyma in ACP brain. The antioxidative ability of astrocytes is one of their essential neuroprotective effects, and the decompensation of this ability may lead to secondary neuronal cell death in ACP.
BACKGROUND AND PURPOSE: In Moyamoya disease, the relationship between cerebral hemodynamics and angiographic findings has not been fully evaluated. The purpose of this study is to evaluate hemodynamics in Moyamoya disease with perfusion-weighted MR imaging (PWI) and cerebral angiography. METHODS: Twenty patients with Moyamoya disease were the subjects. Mean transit time (MTT) derived from PWI was calculated in the medial frontal lobes, the posterior frontal lobes, the occipital lobes, and the basal ganglia. From the angiographies, we classified the degrees of internal carotid artery (ICA) and posterior cerebral artery (PCA) stenoses as well as the degrees of Moyamoya vessels and leptomeningeal anastomosis (LMA). MTT in each region was compared with the angiographic findings. RESULTS: MTT positively correlated with the degree of ICA stenosis in the medial frontal (P < .01), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of PCA stenosis in the medial frontal (P < .001), posterior frontal (P < .001), and occipital (P < .001) lobes, as well as in the basal ganglia (P < .001). MTT correlated with the degree of Moyamoya vessels in the medial frontal (P < .05) and posterior frontal (P < .01) lobes. A multivariate analysis revealed that ICA and PCA stenoses and Moyamoya vessels were independent factors that prolonged MTT. CONCLUSION: Both ICA and PCA stenoses may influence overall cerebral perfusion in Moyamoya disease. The development of Moyamoya vessels may indicate hemodynamic impairment.
Magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have shown that restricted fetal growth, i.e. intrauterine growth retardation (IUGR), is associated with an increased risk of insulin resistance in adult life. We previously postulated that the intracellular magnesium of cord blood platelets is lower in the small for gestational age group than in the appropriate for gestational age group, suggesting that intrauterine magnesium deficiency may result in IUGR. Taken together, intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. We hypothesize that intrauterine magnesium deficiency may induce a metabolic syndrome in later life. Prospective studies will further clarify whether infants with IUGR induced by magnesium deficiency are at higher risk for metabolic syndromes in childhood or adulthood.
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We report inelastic neutron scattering experiments performed to investigate the low energy magnetic excitations on single crystals of the heavy-fermion superconductor PrOs(4)Sb(12). The observed excitation clearly softens at a wave vector Q=(1,0,0), which is the same as the modulation vector of the field-induced antiferro-quadrupolar ordering, and its intensity at Q=(1,0,0) is smaller than that around the zone center. This result directly evidences that this excitonic behavior is derived mainly from nonmagnetic quadrupolar interactions. Furthermore, the narrowing of the linewidths of the excitations below the superconducting transition temperature indicates the close connection between the superconductivity and the excitons.
Recent studies have demonstrated that astrocytes express a variety of ion channels and neurotransmitter receptors and can modulate the activity of neurons. Since a single astrocyte makes tight contacts with many neighboring neuronal cells, they can provide efficient and wide modulation of neuronal networks. Here, we provide direct evidence for mutual interactions between perineuronal astrocytes and interneurons in the stratum radiatum of the rat hippocampus. Direct depolarization of a perineuronal astrocyte suppressed the excitatory postsynaptic currents in an adjacent interneuron and increased the paired-pulse ratio, indicating that perineuronal astrocytes have a suppressive effect on presynaptic elements. Moreover, perineuronal astrocyte activation modulated the directly induced firing pattern of the interneuron, with initial facilitation and subsequent suppression. Conversely, direct firing of the interneuron depolarized the membrane potential and reduced the input resistance of the perineuronal astrocyte. These results directly demonstrate the existence of bidirectional interactions between neurons and perineuronal astrocytes.
The dose calculation system IMAGINE is being developed keeping in mind remotely supporting external radiation therapy using photon beams. The system is expected to provide an accurate picture of the dose distribution in a patient body, using a Monte Carlo calculation that employs precise models of the patient body and irradiation head. The dose calculation will be performed utilising super-parallel computing at the dose calculation centre, which is equipped with the ITBL computer, and the calculated results will be transferred through a network. The system is intended to support the quality assurance of current, widely carried out radiotherapy and, further, to promote the prevalence of advanced radiotherapy. Prototypes of the modules constituting the system have already been constructed and used to obtain basic data that are necessary in order to decide on the concrete design of the system. The final system will be completed in 2007.
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In this paper, we investigate the effect of the solid surface on the fluid-fluid intermolecular potential energy. This modified fluid-fluid interaction energy due to the inducement of a solid surface is used in the grand canonical Monte Carlo (GCMC) simulation of various noble gases, nitrogen, and methane on graphitized thermal carbon black. This effect is such that the effective interaction potential energy between two particles close to surface is less than the potential energy if the solid substrate is not present. With this modification the GCMC simulation results agree extremely well with the experimental data over a wide range of pressures while the simulation results with the unmodified potential energy give rise to a shoulder near the neighborhood of monolayer coverage and the significant overprediction of the second and higher layer coverages. In particular the unmodified GCMC results exhibit very sharp change in those higher layers while the experimental data have a much gradual change in the uptake. We will illustrate this theory with adsorption data of argon, xenon, neon, nitrogen, and methane on graphitized thermal carbon black.
We sought to clarify pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth. Colorectal carcinomas resected at Showa University Hospital in Tokyo included 86 with characteristics of polypoid growth (PG) and 21 with those of nonpolypoid growth (NPG). Mutations of APC, Ki-ras, and p53 genes, as well as microsatellite instability (MSI), were analysed using fluorescence-based polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). Carcinomas with an NPG pattern were smaller than PG tumours (P<0.0001). Carcinomas with a PG pattern were more likely to harbour Ki-ras mutations (36%) than NPG tumours (0%; P<0.0001). Mutation types in the APC gene differed significantly between PG and NPG carcinomas (P=0.0189), including frameshift mutations in 66% of PG carcinomas but no NPG carcinomas. Presence of a p53 mutation at a 'hot spot' also was more likely in PG carcinomas (37%) than in NPG carcinomas (0%; P=0.0124). No significant difference in presence of MSI was evident between carcinomas with PG and NPG patterns. In conclusion, significant genetic differences were evident between carcinomas with PG and NPG patterns. Genetic changes in NPG carcinomas differed from those of the conventional adenoma-carcinoma sequence. Assuming that some nonpolypoid growth lesions transform rapidly into advanced carcinomas, 20% of all colorectal carcinomas may progress in this manner.
We propose a new methodology projected for the estimation of the adsorption energy distribution from the monolayer part of a single nitrogen adsorption isotherm determined at 77 K based on the lattice density functional theory (DFT) via the Aranovich-Donohue formalism. At first sight, the presented approach is computationally more difficult than a classical one. However, it is more flexible and comprehensible. Next, we developed a numerical program and used it for the estimation of the adsorption energy distribution from the experimental data on carbon black samples. The main nitrogen molecule-carbon black surface interaction energy can be estimated as approximately 7-8 kJ/mol, but the heterogeneity of the investigated materials differs significantly. Furthermore, we compare the results obtained from the lattice DFT via the Aranovich-Donohue formalism with the solution of the integral equation with the kernel represented by the classical monolayer localized Fowler-Guggenheim isotherm equation. The similarity between these two independent approaches is observed. The proposed methodology can be used for the investigation of the energetic heterogeneity of not only the carbonaceous materials but also the other "flat-surfaced" solids.
AIM: Few studies have looked at the cytokine profile in gastric mucosa in children with Helicobacter pylori infection. This study investigated cytokines and their effects on histological abnormalities in the gastric mucosa of children with H. pylori infection. METHODS: The levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-8 proteins were measured in biopsy specimens from the gastric antrum and corpus of children with H. pylori infection, and related to inflammatory cell infiltrations. RESULTS: The antral and corporal mucosal levels of IFN-gamma and IL-8 proteins were significantly higher in children with H. pylori infection than in uninfected children, but there was no such difference in the levels of IL-4 protein. The antral mucosal level of IL-8 protein was significantly higher than the corporal mucosal level of IL-8 protein in the infected children. Inflammatory cell infiltration was significantly higher in the infected children than in the uninfected children, but there were no significant correlations between mucosal cytokine levels and inflammatory cell infiltrations. CONCLUSION: The results suggest that the predominant Th1 cytokine response and enhanced IL-8 production in the mucosa may be involved in the gastric inflammation seen in children infected with H. pylori, as well as in adult patients.
The liquid chromatography-mass spectrometry (LC-MS) following on from the two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique was applied for the analysis of proteins in a renal stone found in a hyperuricemic patient. This technique was sensitive enough to detect small quantities of proteins even in a renal stone.