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Biomedical subjects

S Ueda

Publications and source records attributed to S Ueda.

At least 19 recordsLinked to original sources

Streptozotocin-induced partial beta cell depletion in nude mice without hyperglycaemia induces pancreatic morphogenesis in transplanted embryonic stem cells.

AIMS/HYPOTHESIS: It appears that the adult pancreas has limited regenerative ability following beta cell destruction by streptozotocin (STZ). However, it is not clear if this limitation is due to an inability to respond to, rather than an absence of, regenerative stimuli. In this study we aimed to uncouple the regenerative signal from the regenerative response by using an exogenous stem cell source to detect regenerative stimuli produced by the STZ-injured pancreas at physiological blood glucose levels. METHOD: Adult nude mice received 150 mg/kg STZ and 1x10(6) J1 mouse embryonic stem (ES) cells by i.p. injection. Permanent beta cell depletion of 50% was estimated from the ratio of beta:alpha cells in pancreata from STZ-treated mice compared with control animals after 24 days. RESULTS: Transplanted ES cells homed to the STZ-injured pancreas and formed tumours. Immunocytochemical analysis of pancreas-associated ES tumours revealed foci containing insulin/PDX-1 double-positive and glucagon-positive/PDX-1-negative cell clusters associated with PDX-1-positive columnar lumenal epithelium and extensive alpha-amylase-positive pancreatic acini comprising approximately 0.1% of ES tumour volume. CONCLUSIONS/INTERPRETATION: These data indicate that (1) the adult pancreas produces a milieu of regenerative stimuli following beta cell destruction, and (2) this is not dependent on hyperglycaemic conditions; (3) these regenerative stimuli appear to recapitulate the signalling pathways of embryonic development, since both exocrine and endocrine lineages are produced from PDX-1-positive precursor epithelium. This model will be useful for characterising the regenerative mechanisms in the adult pancreas.

Animals↗

Polyamines in renal failure.

The levels of polyamines (putrescine, spermidine and spermine) and polyamine oxidase in plasma of patients with chronic renal failure were determined. The level of putrescine was increased but the level of spermine was decreased in the plasma of these patients. The patients also had increased plasma polyamine oxidase activity leading to increased degradation of spermine. As acrolein was a major toxic compound produced from spermine by polyamine oxidase, the levels of free and protein-conjugated acrolein in plasma were also measured. Acrolein levels were enhanced in plasma of patients with chronic renal failure. The accumulated acrolein found as protein conjugates was equivalent to 170 microM, which was about 5-fold higher than in plasma of normal subjects. It was found that acrolein is mainly produced by spermine oxidase in plasma. An increase in putrescine, spermine oxidase and acrolein in plasma was observed in all cases such as diabetic nephropathy, chronic glomerulonephritis and nephrosclerosis. After patients with chronic renal failure had undergone hemodialysis, their levels of plasma polyamines, spermine oxidase and acrolein returned towards normal. It is likely that acrolein produced from spermine accumulates in the blood due to decreased excretion into urine and may function as a uremic "toxin".

Acrolein↗

Roles of aquaporin-3 water channels in volume-regulatory water flow in a human epithelial cell line.

Membrane water transport is an essential event not only in the osmotic cell volume change but also in the subsequent cell volume regulation. Here we investigated the route of water transport involved in the regulatory volume decrease (RVD) that occurs after osmotic swelling in human epithelial Intestine 407 cells. The diffusion water permeability coefficient (Pd) measured by NMR under isotonic conditions was much smaller than the osmotic water permeability coefficient (Pf) measured under an osmotic gradient. Temperature dependence of Pf showed the Arrhenius activation energy (Ea) of a low value (1.6 kcal/mol). These results indicate an involvement of a facilitated diffusion mechanism in osmotic water transport. A mercurial water channel blocker (HgCl(2)) diminished the Pf value. A non-mercurial sulfhydryl reagent (MMTS) was also effective. These blockers of water channels suppressed the RVD. RT-PCR and immunocytochemistry demonstrated predominant expression of AQP3 water channel in this cell line. Downregulation of AQP3 expression induced by treatment with antisense oligodeoxynucleotides was found to suppress the RVD response. Thus, it is concluded that AQP3 water channels serve as an essential pathway for volume-regulatory water transport in, human epithelial cells.

Aquaporin 3↗

Effect of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis in adult rat hippocampus and spatial learning.

The dentate gyrus of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating to neurogenesis have been identified in the adult dentate gyrus. For example, exposure to an enriched environment enhances neurogenesis in the dentate gyrus and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the dentate gyrus. However, there was no improvement of the spatial learning test in adult rats in standard and in environmental enrichment housings. Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine, on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine-labeled new cells in the dentate gyrus. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of bromodeoxyuridine-labeled cells in the dentate gyrus of 5,7-dihydroxytryptamine-injected rats did not differ between 1 day and 4 weeks after bromodeoxyuridine injection. These data suggest that survival of newly generated dentate gyrus cells remains relatively constant under long-lasting serotonin depletion.

5,7-Dihydroxytryptamine↗

The thioredoxin system in retroviral infection and apoptosis.

Human thioredoxin (TRX) was first identified in human T-cell leukemia virus type I (HTLV-I)-positive T-cell lines and is associated with the pathophysiology of retroviral infections. TRX is a vital component of the thiol-reducing system and regulates various cellular function (redox regulation). Members of the TRX system regulate apoptosis through a wide variety of mechanisms. A family of thioredoxin-dependent peroxidases (peroxiredoxins) protects against apoptosis by scavenging hydrogen peroxide. Thioredoxin 2 is a critical regulator of cytochrome c release and mitochondrial apoptosis; transmembrane thioredoxin-related molecule (TMX) has a protective role in endoplasmic reticulum (ER) stress-induced apoptosis. TRX interacts with apoptosis signal-regulating kinase 1 (ASK1) and is a sensor of oxidative stress. Thioredoxin binding protein-2/vitamin D(3) upregulated protein 1 is a growth suppressor and its expression is suppressed in HTLV-I-transformed cells. Studies of these molecules of the TRX system provide novel insights into the apoptosis associated with retroviral diseases.

Animals↗

Dichotomy of all-trans retinoic acid inducing signals for adult T-cell leukemia.

We previously reported that all-trans retinoic acid (ATRA) inhibits growth in human T-cell leukemia virus type 1 (HTLV-1)-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. However, the mechanism of this inhibition is not clear. In the present study, we observed that NF-kappaB transcriptional activity as well as cell growth decreased significantly in HTLV-1-positive T-cell lines in the presence of ATRA. Furthermore, we observed that ATRA reduced HTLV-1 proviral DNA, HTLV-1 genes (gag, tax, or pol mRNA) using the real-time quantitative polymerase chain reaction. SIL-2R was reduced by ATRA in both protein level (culture supernantant) and mRNA level in HTLV-1-positive T-cell lines. Interestingly, ATRA significantly inhibited RT activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. Moreover, AZT inhibited proviral DNA but not NF-kappaB transcriptional activity, and sIL-2R on HTLV-1; however, ATRA inhibited of NF-kappaB, proviral DNA and sIL-2R on HTLV-1. These results suggested that the decrease in sIL-2R induced by ATRA may be caused by the actions of a NF-kappaB inhibitor acting on the NF-kappaB/sIL-2R signal pathway. These results suggested that ATRA could have two roles, as a NF-kappaB inhibitor and as an RT inhibitor.

Adult↗

[Pulmonary thromboembolism after thoracoscopic pulmonary wedge resection; report of a case].

We encountered a case of acute pulmonary embolism after lung cancer surgery. The case was a 64-year-old female. She was admitted to our hospital with an abnormal shadow on chest X-ray. There was a past history of hypopituitarism medicated with steroids. Chest computed tomography (CT) demonstrated ground glass attenuation shadow measuring 10 mm in the left upper lobe. She underwent left thoracoscopic pulmonary wedge resection due to bronchioloalveolar cell carcinoma. Postoperatively, the patient suddenly complained of chest pain and dyspnea the day after surgery. Chest CT showed left and right pulmonary arterial thromboembolism. Thrombolytic and anticoagulation therapy with urokinase and heparin sodium were immediately started. Venography demonstrated thrombus located in the vein of the bilateral lower leg region. We inserted an inferior vena cava filter to prevent aggravation of pulmonary embolism. After 11 days, CT showed completed thrombolysis in the bilateral pulmonary artery. The patient was discharged on the 25th postoperative day, and has been followed with anticoagulation therapy.

Acute Disease↗

Otsuka Long-Evans Tokushima fatty (OLETF) rat is not a suitable animal model for the study of angiopathic diabetic retinopathy.

We have previously shown that the peak latency of oscillatory potential (OP), the earliest electroretinographic manifestation of diabetic retina, was prolonged in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of non-insulin-dependent diabetes. These observations suggest that retinal neuronal dysfunction revealed by the OP abnormality in the electroretinogram takes place prior to the angiopathic diabetic changes in this animal model. However whether acellular capillaries and pericyte ghosts, one of the histopathological hallmarks of early diabetic retinopathy in humans, could occur in OLETF rat remains to be elucidated. In the present study, we first prepared the retinal trypsin digests of OLETF and control Long-Evans Tokushima Otsuka (LETO) rats at 45 weeks old and then compared the number of acellular capillaries and pericyte ghosts in the retinas of OLETF rats with that in LETO rats. Blood glucose levels were higher in the OLETF rats than those in LETO rats. Retinal capillaries of OLETF rats were found to remain morphologically normal and pericyte ghosts were barely detectable. There was no difference in the number of acellular capillaries in the retinas between OLETF and LETO rats. The present study indicates that acellular capillaries and pericyte ghosts, the characteristic morphological changes in early diabetic retinopathy, are not accelerated in OLETF rats. Our data suggest that OLETF rat is not a suitable animal model for the study of angiopathic diabetic retinopathy.

Animals↗

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗

Limits on the neutrino magnetic moment using 1496 days of Super-Kamiokande-I solar neutrino data.

A search for a nonzero neutrino magnetic moment has been conducted using 1496 live days of solar neutrino data from Super-Kamiokande-I. Specifically, we searched for distortions to the energy spectrum of recoil electrons arising from magnetic scattering due to a nonzero neutrino magnetic moment. In the absence of a clear signal, we found micro(nu)</=(3.6x10(-10))micro(B) at 90% C.L. by fitting to the Super-Kamiokande day-night spectra. The fitting took into account the effect of neutrino oscillation on the shapes of energy spectra. With additional information from other solar neutrino and KamLAND experiments constraining the oscillation region, a limit of micro(nu)</=(1.1x10(-10))micro(B) at 90% C.L. was obtained.

Journal Article↗

In vivo transfer of a neuronal nitric oxide synthase expression vector into the rat bladder by electroporation.

OBJECTIVE: To investigate the possibility of in vivo gene transfer by attempting to transfer the neuronal nitric oxide synthase (nNOS) gene into rat bladder using electroporation. MATERIALS AND METHODS: The bladder was exposed through an abdominal midline incision in 8-week-old male rats. Plasmid DNA of the marker genes green fluorescent protein (GFP) and luciferase, and the nNOS gene, was then injected into the subserosal space of the bladder and electroporation applied. At 72 h after gene transfer, GFP and luciferase were assayed in the isolated bladder and immunohistochemical staining used to detect nNOS; NO(x) released from isolated bladder strips was also assessed using microdialysis and high-performance liquid chromatography. RESULTS: From the luciferase assay, 45 V, 1 Hz, 50 ms and eight pulses were selected as the optimum conditions for electroporation. Bladder specimens with GFP genes injected by electroporation showed bright and numerous sites of GFP expression in the smooth muscle layer. In rats with the nNOS gene injected by electroporation there was marked nNOS immunoreactivity, and NO(x) released from bladder strips was significantly greater than in the control groups. CONCLUSIONS: These results suggest that electroporation is a useful technique for in vivo gene transfer into rat bladder smooth muscles, and that the nNOS gene transferred by this procedure functionally expresses and contributes to NO production.

Animals↗

A single dose of nateglinide improves post-challenge glucose metabolism and endothelial dysfunction in Type 2 diabetic patients.

AIMS: This randomized crossover placebo-controlled study aimed to assess the efficacy of nateglinide, a phenylalanine-derived insulin secretagogue, on forearm endothelial function in diabetic subjects before and after an oral glucose load. METHODS: Forearm blood flow (FBF) was measured using strain-gauge plethysmography during reactive hyperaemia before and after an oral glucose load (75 g) with a prior use of placebo or nateglinide (90 mg) in 15 diet-treated Type 2 diabetic patients or age-matched controls with normal glucose tolerance. RESULTS: The peak FBF response and total reactive hyperaemic flow (flow debt repayment: FDR), indices of resistance artery endothelial function, were decreased after an oral glucose load in diabetic patients, but unchanged in controls. Nateglinide administered to diabetic patients accelerated insulin secretion and reduced post-challenge plasma glucose, and also abolished the post-challenge impairment of endothelial function. The peak FBF and FDR were well correlated with 120-min glucose levels and 30-min insulinogenic index. CONCLUSIONS: A single challenge of glucose was shown to impair endothelial function in diabetic patients, and the post-challenge endothelial dysfunction was improved by a prior use of nateglinide. Long-term effects of nateglinide on endothelial function in Type 2 diabetic patients need to be clarified in future studies.

Administration, Oral↗

Advances in the treatment of pediatric brain tumors.

Brain tumors are a heterogeneous group of neoplasms with different origins, pathobiologies, treatments and prognoses. The collective contributions from the fields of neuro-oncology, neurosurgery, radiation oncology, neurology, neuropathology, neuroradiology and molecular biology have all led to significant advances in the treatment of certain brain tumors. Ideas from these fields, under the cooperative umbrella of clinical cancer trial consortia, have been tested in large-scale studies. As a result, patient survivals have increased markedly for these tumor types. Unfortunately, there are certain brain tumors in childhood, such as the diffuse intrinsic pontine glioma and atypical teratoid rhabdoid tumor, for which survival advantages have not been found. This review will discuss the current and possible future therapies of the most common pediatric brain tumors and highlight some of the novel imaging modalities that are used pre- and intraoperatively.

Astrocytoma↗

Pulmonary angiomyolipoma recurring 26 years after nephrectomy for angiomyolipoma: benign clinical course.

Angiomyolipoma (AML), a benign renal tumor, has various clinical forms, and the nature of AML is not sufficiently understood because of few reports of long-term observation. We report a 57-year-old female without tuberous sclerosis who developed multiple pulmonary AML 26 years after a right nephrectomy for renal AML. A computed tomogram demonstrated multifocal round lesions with lipid-like density throughout both lung fields. An open lung biopsy revealed a histological diagnosis of pulmonary AML. An abdominal computed tomogram was also compatible with splenic AML. She has been in good health for 12 years since the lung biopsy over the 38 years since the nephrectomy. This case suggests that multicentric AML can recur at distant organs even after long-term silence in a patient who has a past history of renal AML.

Angiomyolipoma↗

[Preoperative evaluation for lung resection using right ventricular hemodynamic functions by unilateral pulmonary arterial occlusion test].

We performed a unilateral pulmonary arterial occlusion (UPAO) test for the preoperative evaluation of right ventricular functions as a loading test in patients undergoing a lung resection without cardiac complications preoperatively. We investigated the relationship between changes in right ventricular hemodynamic functions and postoperative cardiac complications, namely right heart failure or arrhythmia. To evaluate the right ventricular hemodynamic function test, we measured the mean pulmonary arterial pressure, cardiac index, right ventricular ejection fraction end-diastolic volume, and stroke volume before and during the UPAO test using the thermodilution method, and calculated the total pulmonary vascular resistance and right ventricular stroke work indexes. The incidence of postoperative cardiac complications was not related to the changes in the total pulmonary vascular resistance index. However, the postoperative cardiac complications were common in patients whose right ventricular end-diastolic volume index was increased by more than 20% during the UPAO test. These results suggest that the changes in the right ventricular end-diastolic volume index during the UPAO test can predict postoperative cardiac complications in patients undergoing a pulmonary resection.

Arrhythmias, Cardiac↗