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T Kaneko

Publications and source records attributed to T Kaneko.

At least 91 records · Page 5Linked to original sources

Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction.

Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignancy associated with a poor outcome. Despite the relatively high incidence of MDS in the elderly, differentiation of MDS from de novo acute myeloid leukemia (AML) still remains problematic. Identification of genes expressed in an MDS-specific manner would allow the molecular diagnosis of MDS. Toward this goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like fractions have been collected from a variety of leukemias in a large-scale and long-term genomics project, referred to as "Blast Bank," and transcriptome of these purified blasts from the patients with MDS were then compared with those from AML through the use of oligonucleotide microarrays. A number of genes were shown to be expressed in a disease-specific manner either to MDS or AML. Among the former found was the gene encoding the protein Delta-like (Dlk) that is distantly related to the Delta-Notch family of signaling proteins. Because overexpression of Dlk may play a role in the pathogenesis of MDS, the disease specificity of Dlk expression was tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS. Dlk could be the first candidate molecule to differentiate MDS from AML. The proposal is made that microarray analysis with the Blast Bank samples is an efficient approach to extract transcriptome data of clinical relevance for a wide range of hematologic disorders.

DNA↗

Immunocytochemical localization of candidates for vesicular glutamate transporters in the rat cerebral cortex.

Brain-specific Na(+)-dependent inorganic phosphate cotransporter (BNPI) was recently reported to serve as a vesicular glutamate transporter (VGluT), and was renamed VGluT1 (Bellocchio et al. [ 2000] Science 289:957-960; Takamori et al. [2000] Nature 407:189-194). Ahead of these reports, cDNA encoding another brain-specific inorganic phosphate transporter, which showed 82% amino acid identity to VGluT1, was cloned and designated differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI; Aihara et al. [2000] J Neurochem 74:2622-2625). In the present study, we produced a specific antibody against a C-terminal portion of DNPI, and studied the immunohistochemical localization of DNPI in the rat cerebral cortex in comparison with that of VGluT1. DNPI immunoreactivity was enriched in neuropil of layers I and IV and to a lesser extent in the upper portion of layer VI of the cerebral neocortex, whereas VGluT1 immunoreactivity was distributed more evenly in neuropil of the neocortex. Electron microscopic observation revealed that both DNPI and VGluT1 immunoreactivities were mainly located on synaptic vesicles in nerve terminals which made asymmetrical contacts in the neocortex. Furthermore, neither DNPI nor VGluT1 immunoreactivity in the neocortex was colocalized with gamma aminobutyric acid (GABA)ergic axon terminal markers, immunoreactivity for glutamic acid decarboxylase or vesicular GABA transporter. Neuronal depletion in the ventrobasal thalamic nuclei produced by the kainic acid injection resulted in a clear reduction of DNPI immunoreactivity in layers I, IV, and VI of the somatosensory cortex. These results indicate that DNPI is located on the membrane of synaptic vesicles in thalamocortical axon terminals, and that it may be a candidate for VGluT of thalamocortical glutamatergic neurons.

ATP-Binding Cassette Transporters↗

Delay of the diagnostic lumbar puncture and intrathecal chemotherapy in children with acute lymphoblastic leukemia who undergo routine corticosteroid testing: Tokyo Children's Cancer Study Group study L89-12.

PURPOSE: To determine the effects of eliminating initial lumbar punctures in 418 consecutively treated children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Patients were enrolled onto a trial conducted in central Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinduction therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection of chemotherapy, was performed after 1 week of prednisolone sensitivity testing (day 8). End points included response to prednisolone, CNS status at the time of the day 8 lumbar puncture, subsequent adverse events in CNS and bone marrow, and event-free survival (EFS). RESULTS: The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their diagnostic lumbar puncture and first instillation of intrathecal chemotherapy on day 0. Overall, 84.5% of the patients had good responses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive value of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional strategies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. CONCLUSION: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controlled evaluations are needed to establish the validity of this conclusion.

Adolescent↗

Angiotensin-converting enzyme inhibition attenuates hypofibrinolysis and reduces cardiac perivascular fibrosis in genetically obese diabetic mice.

BACKGROUND: Obesity and insulin resistance are associated with accelerated macrovascular and microvascular coronary disease, cardiomyopathic phenomena, and increased concentrations and activity in blood of plasminogen activator inhibitor type 1 (PAI-1), the primary physiological inhibitor of fibrinolysis. METHODS AND RESULTS: To determine whether hypofibrinolysis in blood and tissues and its potential sequelae could be attenuated pharmacologically, we studied genetically modified obese mice. By 10 weeks of age, obese mice exhibited increases in left ventricular weight and glucose and immunoreactive insulin in blood. PAI-1 activity in blood measured spectrophotometrically was significantly elevated as well. The difference compared with values in lean controls widened by 20 weeks of age. Perivascular fibrosis in coronary arterioles and small coronary arteries was evident in obese mice 10 and 20 weeks of age, paralleling increases in PAI-1 and tissue factor expression evident by immunohistochemical image analysis, in situ hybridization, and reverse transcription-polymerase chain reaction. Inhibition of ACE activity initiated in obese mice 10 weeks of age and continued for 20 weeks arrested the increase in PAI-1 activity in blood and in cardiac PAI-1 and tissue factor mRNA as well as coronary perivascular fibrosis. CONCLUSIONS: Thus, inhibition of proteo(fibrino)lysis and augmented tissue factor expression in the heart precede and may contribute to the coronary perivascular fibrosis seen with obesity and insulin resistance. Furthermore, inhibition of ACE activity can attenuate all 3 phenomena.

Angiotensin-Converting Enzyme Inhibitors↗

Morphological features and electrophysiological properties of serotonergic and non-serotonergic projection neurons in the dorsal raphe nucleus. An intracellular recording and labeling study in rat brain slices.

The morphology and electrophysiological properties of serotonergic and non-serotonergic projection neurons in the dorsal raphe nucleus (DRN) of the rat were examined in frontal brain slices. Biocytin was injected intracellularly into the intracellularly recorded neurons. Then the morphology of the recorded neurons was observed after histochemical visualization of biocytin. The recorded neurons extending their main axons outside the DRN were considered as projection neurons. Subsequently, serotonergic nature of the neurons was examined by serotonin (5-HT) immunohistochemistry. The general form of the dendritic trees is radiant and poorly branching in both 5-HT- and non-5-HT neurons. However, the dendrites of the 5-HT neurons were spiny, whereas those of the non-5-HT neurons were aspiny. The main axons of both 5-HT- and non-5-HT neurons were observed to send richly branching axon collaterals to the DRN, ventrolateral part of the periaqueductal gray and the midbrain tegmentum. In response to weak, long depolarizing current pulses, the 5-HT neurons displayed a slow and regular firing activity. The non-5-HT neurons fired at higher frequencies even when stronger current was injected. Some other differences in electrophysiological properties were also observed between the 5-HT-immunoreactive spiny projection neurons and the 5-HT-immunonegative aspiny projection neurons.

Action Potentials↗

Age-related changes in oxidative damage to lipids and DNA in rat skin.

Skin is a tissue exposed most frequently to oxidative stress from the environment in daily life. Age-related changes of oxidative damage and antioxidant enzyme activity in the skin were examined in male Fischer 344 rats aged 6 to 30 months. The contents of phosphatidylcholine hydroperoxide (PCOOH) and thiobarbituric acid-reacting substances (TBARS) increased linearly with age. The content of cholesterol hydroperoxide increased until 24 months of age and then decreased. The content of 8-oxo-2'-deoxyguanosine (8-oxodG) increased gradually with age, and was significantly higher at 30 months of age than at 6 months of age. Superoxide dismutase activity tended to decrease with age. The activities of catalase and glutathione peroxidase showed no changes with age. We examined the effect of dietary restriction on the accumulation of oxidative damage in rat skin. The increase in PCOOH content in the skin of dietary-restricted rats was suppressed until 30 months of age. The TBARS and cholesterol hydroperoxide contents in the skin of dietary-restricted rats were significantly lower than in the skin of ad libitum-fed rats, while the 8-oxodG content was somewhat lower in the dietary-restricted rats than the ad libitum-fed rats. These results indicate that oxidative damage to the lipids and DNA in rat skin increases with age and that dietary restriction delays the accumulation of oxidative damage in skin.

8-Hydroxy-2'-Deoxyguanosine↗

Cell migration from the corticostriatal angle to the basal telencephalon in rat embryos.

Lateral cortical stream (LCS) has been described as a flow of cell migration found in the lateral cortex of the embryonic telencephalon of mammals. The destinations of the cell migration were reported as the ventrolateral neocortex, the pyriform cortex, endopyriform nucleus and the claustrum. At the same time, however, other destinations of LCS have been suggested in the ventral telencephalon. Therefore, we investigated the additional destinations of the LCS using a combination of several molecular biological techniques. Using an expression vector of modified green fluorescent protein (GFP) introduced into the ventricular zone (VZ) around the corticostriatal angle, both tangential and radial cell migration was revealed in the LCS. The radial cell migration in the LCS supplied cells to the ventro-lateral neocortex, pyriform cortex and to the level of the lateral olfactory tract. In the second experiment, we injected COS-1 cells transfected with a Sema3A expression vector into one side of the neocortex. The cell supply to the destination of the LCS ceased due to the formation of a large necrosis in the LCS, which was triggered by the Sema3A-COS cell injection, and the dense cell layer in the olfactory tubercle shrunk on the side where COS cells were injected. These data indicated that the majority of neurons in the dense cell layer of the olfactory tubercle reached this point through the LCS. One of the origins of the cells in the LCS would be in the corticostriatal angle.

Animals↗

Collateral projections of nucleus raphe dorsalis neurones to the caudate-putamen and region around the nucleus raphe magnus and nucleus reticularis gigantocellularis pars alpha in the rat.

It was examined whether or not the nucleus raphe dorsalis (RD) neurons projecting to the caudate-putamen (CPu) might also project to the motor-controlling region around the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis pars alpha (Gia) in the rat. Single RD neurons projecting to the CPu and NRM/Gia by way of axon collaterals were identified by the retrograde double-labeling method with fluorescent dyes, Fast Blue and Diamidino Yellow, which were injected respectively into the CPu and NRM/Gia. Then, serotonin (5-HT)-like immunoreactivity of the double-labeled RD neurons was examined immunohistochemically; approximately 60% of the double-labeled RD neurons showed 5-HT-like immunoreactivity. The results indicated that some of serotonergic and non-serotonergic RD neurons might control motor functions simultaneously at the levels of the CPu and NRM/Gia by way of axon collaterals.

Amidines↗

Activation of autoreactive T cells that help nucleobindin-injected mice produce anti-DNA antibodies.

Nucleobindin (Nuc) is a DNA- and calcium-binding protein that was originally identified as an anti-DNA antibody-enhancing factor in MRL/MpJ-lpr/lpr (MRL/lpr) mice. In MRL/lpr mice, both expression of Nuc mRNA in enlarged lymph nodes and serum concentration of Nuc protein are shown to increase as disease progresses. Administration of recombinant (r) Nuc to young MRL/MpJ-+/+ and normal BALB/c mice leads to augmentation or induction of IgG anti-double-stranded (ds) DNA autoantibodies. In this study, spleen cells prepared from MRL/lpr mice were found to show a proliferative response to rNuc, indicating existence of T cells that are specific to this autoantigen in peripheral lymphoid tissues. Furthermore, CD4+ T cell lines were generated from a BALB/c mouse that had been producing anti-dsDNA antibodies as a result of repeated injections of rNuc. These T cell lines were confirmed to be autoreactive, because they proliferated in culture with syngeneic but not with allogeneic spleen cells without addition of any exogenous antigens. Their proliferation was enhanced by rNuc, and inhibited by an anti-MHC class II monoclonal antibody. Upon in vivo inoculation, these T cells provided help for rNuc-injected BALB/c mice to produce anti-DNA antibodies. These results suggest that Nuc is able to activate autoreactive peripheral T cells through an MHC-class II pathway leading to acceleration or induction of anti-DNA antibody production when it is excessively produced in lupus-prone mice or experimentally administered into normal mice.

Animals↗

Evaluation of urinary rapid test for Helicobacter pylori in general practice.

There is increasing interest in noninvasive tests for the diagnosis of Helicobacter pylori (H. pylori) infection. One such test, a urine-based rapid test kit (RAPIRUN H. pylori Antibody, Otsuka Pharmaceutical Co., Ltd.) for detection of antibody to H. pylori, has been developed and is considered ideal. In addition to its noninvasiveness and safe handling-due to use of urine as a sample-the assay procedure used for the urinary rapid test is very simple. Only 10-20 minutes are required to complete an assay, and no instruments are needed. The aim of this study was to examine the clinical usefulness of this urine-based rapid test. A total of 189 patients, including 76 patients with gastroduodenal disease, were recruited. A pair of random single-void urine and serum samples was collected from each of the 189 patients, and antibody to H. pylori in the urine and serum samples was measured using the urine-based rapid test kit and three commercially available serum-based ELISA kits. For the patients with gastroduodenal disease, invasive diagnostic methods using endoscopic biopsy specimens such as culture, histology, and rapid urease test were also performed. The sensitivity, specificity, and accuracy of the urinary rapid test were evaluated on the basis of the three serum ELISA results or the invasive diagnostic results. In addition, various urinalyses were performed, and the effects of substances existing in urine on the urinary rapid test results were examined. Of the 189 patients, the urinary rapid test was positive for 110 (58.2%), negative for 78 (41.3%), and invalid for only one patient (0.5%). Based on the three serum-based ELISA results, the sensitivity, specificity, and accuracy of the urinary rapid test were 93.7, 88.9, and 92.2%, respectively. On the basis of the biopsy-based test results, the sensitivity of the urinary rapid test was 100% and its accuracy (95.2%) was equivalent or superior to that of each serum-based ELISA. In addition, no significant differences were observed between groups positive and negative on urinary rapid testing in any urinalysis parameter examined. The novel urinary rapid test kit evaluated in this study enables simple, rapid, and accurate diagnosis of H. pylori infection, and is an ideal test method for point-of-care testing.

Adult↗

Inhibition of azoxymethane-induced aberrant crypt foci formation in rat colorectum by whole leaf Aloe arborescens Miller var. natalensis Berger.

We examined the modifying effect of whole-leaf Aloe arborescens Miller var. natalensis Berger (designated as 'ALOE') on azoxymethane (AOM)-induced aberrant crypt foci (ACF), putative preneoplastic lesions, in the rat colorectum. Male F344 rats (4 weeks old) were fed the basal diet, or experimental diets containing 1% or 5% ALOE for 5 weeks. One week later, all rats except those in the vehicle-treated groups were injected s.c. with AOM (15 mg/kg, once weekly for 3 weeks). At 9 weeks of age, all the rats were killed, and the colorectum and liver were evaluated for ACF and cytosolic quinone reductase (QR; a phase 2 enzyme), respectively. In rats given AOM and ALOE (1% or 5% in diet) the numbers of ACF/colorectum, aberrant crypts/colorectum, aberrant crypts/focus and large ACF/colorectum were significantly decreased compared with those of rats given AOM alone (all p < 0.01). No ACF were found in rats treated without AOM. In addition, ALOE significantly increased cytosolic QR activity in the liver (p < 0.01). These results indicated that ALOE inhibited the development of AOM-induced ACF in the rat colorectum, with increased QR activity in the liver, and therefore suggested that ALOE might have a chemopreventive effect against colon carcinogenesis at least in the initiation stage.

Aloe↗

Ammonia chemical ionization tandem mass spectrometry in structural determination of alkaloids. II. Tetraponerines from pseudomyrmecine ants.

Chemical ionization tandem mass spectrometry (CI-MS/MS) of alkaloids with ammonia reagent gas and collision-activated dissociation as well as EI-MS/MS were applied to the tetraponerine alkaloids in extracts from six pseudomyrmecine ants of the genus Tetraponera. The MS/MS techniques along with gas chromatography Fourier transform infrared (GC/FTIR) spectra allowed identification in two extracts of seven of the eight known tetraponerines. The EI-MS/MS fragmentations proved diagnostic for the ring system and the CI-MS/MS patterns for the C-8 or C-9 substitution, while the Bohlmann bands in FTIR spectra were diagnostic for the C-8 or C-9 configurations. An Indian ant (T. allaborans) had T-2, T-4 and T-8, while a Chinese ant (T. binghami) had T-5, T-6, T-7 and T-8. Four other ants, T. rufonigra (India), T. penzigi (Africa), T. clypeata (Africa) and T. sp. cf. emeryi (Africa), had no tetraponerines.

Alkaloids↗

Transgene expression of thioredoxin (TRX/ADF) protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hematotoxicity.

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a variety of toxic effects on a number of organs, including the hematopoietic system. The importance of TCDD-induced oxidative stress has been evaluated in several target organs. However, its role in hematotoxicity remains poorly understood, although bone marrow is known to produce reactive oxygen species. The aim of this study is to evaluate not only the contribution of oxidative stress to TCDD-induced hematotoxicity but also the protective function of TRX/ADF, a known anti-oxidative stress agent, on the hematotoxicity of TCDD in ADF wild-type (WT) and transgenic (Tg) mice. WT and Tg mice received a single intraperitoneal injection of 20 microg TCDD/kg. One day after the treatment, blood and bone marrow cellularity was measured and bone marrow levels of granulotyce/macrophage colony-forming units were determined in the in vitro colony assay. The expression of human TRX transgene by their bone marrow cells was analyzed by Western blot electrophoresis. Our results showed that overexpression of TRX/ADF protects against TCDD-induced hematotoxicity, indicating that induction of oxidative stress that results in disruption of redox regulation may be an important mechanism in TCDD-induced bone marrow toxicity. Moreover, we detected a significant decrease of AhR mRNA levels in bone marrow cells of Tg mice following TCDD treatment, suggesting a biological role of TRX/ADF in the AhR-mediated pathway through which TCDD induces oxidative stress.

Animals↗

Extra-strong graduated compression stocking reduces usage of vasopressor agents during spinal anesthesia for cesarean section.

Because a standard type of graduated compression stocking is not effective for the prevention of spinal anesthesia hypothension during cesarean section, we have used an extra-strong type of graduated compression stocking. This study examined whether the extra-strong stocking reduces usage of vasopressor agents. Forty-eight and 47 full term parturients were fitted with the standard stocking and the extra-strong stocking, respectively. Spinal anesthesia was performed by injecting 2.0 ml 0.3% dibucaine hyperbaric solution. When systolic blood pressure decreased to 90-100 mmHg or to less than 70% of the pre-anesthesia value, ephedrine was injected. There was no significant difference in systolic blood pressure or heart rate during spinal anesthesia between the groups. The mean dose of ephedrine injected during anesthesia was 12.2 and 4.3 mg, and the incidence of ephedrine injected was 85 and 49%, in the standard and extra-strong stocking groups, respectively. The extra-strong stocking group showed significantly lower values. Fitting the extra-strong stocking on both legs for cesarean sections undergoing spinal anesthesia reduced usage of vasopressor agents, suggesting a promising use of this stocking for non-invasive prophylaxis.

Adolescent↗

Reversal of portal flow after acute rejection in living-donor liver transplantation.

Portal hepatofugal flow is rare after liver transplantation. We experienced a case in which hepatofugal portal flow was observed in acute rejection. A 6-year-old boy with glycogen storage disease type Ia underwent living-donor liver transplantation. On postoperative day 7, portal venous peak velocity was markedly decreased without portal thrombosis and obstruction of the hepatic vein, and hepatic arterial peak velocity increased reciprocally. Based on a diagnosis of acute rejection, made on postoperative day 8, we initiated steroid pulse therapy. Despite the employment of this therapy, continuous hepatofugal portal flow was observed in the entire liver on postoperative day 8. On day 12, as the liver disorder progressed, the Doppler waveform in the portal vein changed from continuous to pulsatile hepatofugal flow. The patient died of liver failure on day 14. The histological findings of a biopsy specimen on day 9 showed centrilobular necrosis, while total hepatocellular necrosis was seen at autopsy. Hepatofugal flow after liver transplantation is considered to be an ominous sign caused by several factors, and its appearance indicates a fatal condition.

Child↗

Delayed rupture of a pseudoaneurysm following pancreatoduodenectomy: report of a case.

We report herein the case of a 63-year-old man in whom delayed rupture of a pseudoaneurysm occurred 120 days following pancreatoduodenectomy. Color Doppler examination indicated a pseudoaneurysm originating from the ligated gastroduodenal artery. Transcatheter arterial embolization was done at the common hepatic artery, proximal and distal to the pseudoaneurysm, with microcoils. The patient had a minor elevation of liver enzymes, which subsequently returned to normal. Due to the absence of any postoperative complications such as pancreatic anastomotic leakage, we assumed that the pseudoaneurysm formation had been caused by a weakness in the arterial wall according to skeletonization resulting from lymphadenectomy and intraoperative radiation therapy. To our knowledge, this case represents the longest interval between pancreatoduodenectomy and rupture of a pseudoaneurysm ever to be reported in the literature.

Aneurysm, False↗