Spotted and rippled reticulate hypermelanosis: a possible variant of Dowling-Degos disease.
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Child, Preschool↗
Biomedical subjects
T Ota
Publications and source records attributed to T Ota.
Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with type 2 diabetes.
AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND METHODS: We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT. RESULTS: Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1. CONCLUSIONS/INTERPRETATION: Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.
Aged↗
Albumin induces endoplasmic reticulum stress and apoptosis in renal proximal tubular cells.
Chronic proteinuria appears to be a key factor in tubulointerstitial damage. Recent studies have emphasized a pathogenic role of endoplasmic reticulum (ER) stress which is induced by the accumulation of misfolded proteins in ER, extracellular stress, etc. In the present study, we investigated ER stress and ER stress-induced apoptosis in proximal tubular cells (PTCs). Immortalized rat PTCs (IRPTCs) were cultured with bovine serum albumin (BSA). The viability of IRPTCs decreased proportionately with BSA overload in a time-dependent manner. Quantitative real-time polymerase chain reaction analysis revealed that 40 mg/ml BSA increases mRNA of ER stress markers by 7.7- and 4.6-fold (glucose-regulated protein 78 (GRP78) and oxygen-regulated protein 150 (ORP150), respectively) as compared to control. The increased expression of ORP150 and GRP78 in IRPTCs with albumin overload was detected by Western blot and immunofluorescence study. These in vitro observations were supported by in vivo studies, which demonstrated that ER stress proteins were upregulated at PTCs in experimental proteinuric rats. Furthermore, increased ER stress-induced apoptosis and activation of caspase-12 were observed in IRPTCs with albumin overload and kidneys of experimental proteinuric rats. We confirmed that apoptotic cell death was attenuated by co-incubation with caspase-3 inhibitor or calpain inhibitors. These results indicate that the ER stress-induced apoptosis pathway contributed to the insult of tubular cells by proteinuria. In conclusion, renal tubular cells exposed to high protein load suffer from ER stress. ER stress may subsequently lead to tubular damage by activation of caspase-12.
Acrylates↗
Brain acetylcholinesterase activity in FTDP-17 studied by PET.
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Acetylcholinesterase↗
Few-electron molecular states and their transitions in a single InAs quantum dot molecule.
We study electronic configurations in a single pair of vertically coupled self-assembled InAs quantum dots, holding just a few electrons. By comparing the experimental data of nonlinear single-electron transport spectra in a magnetic field with many-body calculations, we identify the spin and orbital configurations to confirm the formation of molecular states by filling both the quantum mechanically coupled symmetric and antisymmetric states. Filling of the antisymmetric states is less favored with increasing magnetic field, and this leads to various magnetic field induced transitions in the molecular states.
Journal Article↗
Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in gastrointestinal tumour.
The human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumour-suppressor gene inactivated by methylation in several cancers. In this study, we analysed the methylation and expression status of hDAB2IP in gastrointestinal tumours. The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines. The gene expression was semiquantified by real-time RT-PCR, and the results indicated that the m2b promoter region might be an authentic methylation-mediated key regulator of the gene expression. Based on the sequence data, we developed a methylation-specific PCR (MSP) for the m2a and m2b regions and applied it to the samples. Methylation-specific PCR revealed aberrant methylation in the m2a region in eight of 12 gastric cancer cell lines (67%), 16 of 35 gastric cancer tissues (46%) and 29 of 60 colorectal cancer tissues (48%), and in the m2b region in eight of 12 cell lines (67%), 15 of 35 gastric cancer tissues (43%) and 28 of 60 colorectal cancer tissues (47%). On the other hand, seven (12%) and 11 (19%) of 59 gastrointestinal nonmalignant mucosal specimens showed methylation in the m2a and m2b regions, respectively, suggesting that hDAB2IP methylation might play a causative role in carcinogenesis. The 5-aza-2'-deoxycytidine treatment restored the gene expression in the m2b-methylated cell lines, confirming that the methylation caused gene downregulation. We also examined the relationship between hDAB2IP methylation and the clinicopathological features in patients with primary tumours, and determined that methylation in the m2b region was associated with location of the tumour in the stomach. In summary, our results demonstrated that hDAB2IP methylation is frequently present in gastrointestinal tumours and that the resulting gene silencing plays an important role in gastrointestinal carcinogenesis.
Azacitidine↗
Multiple organ failure caused by end-stage liver disease successfully treated with living donor liver transplantation using perioperative percutaneous cardiopulmonary support: a case report.
A 54-year-old female diagnosed with primary biliary cirrhosis (PBC) 10 years earlier was referred for a living donor liver transplant (LDLT). During her workup, she developed pulmonary edema and respiratory failure due to aspiration pneumonia, which required artificial ventilation. The PaO2/FiO2 (P/F) ratio at that time was 60. Although continuous hemodiafiltration (CHDF) and plasma exchange (PE) were initiated, improvement in the P/F ratio was limited to 133. As transplantation was the only approach to save this patient, we performed LDLT using a right lobe graft aided by percutaneous cardiopulmonary support (PCPS). The graft weight was 650 g and the graft weight/recipient weight ratio was 1.6%. During LDLT, the patient's cardiopulmonary function was stable with PCPS, and the surgical procedure was completed without complications. Following the surgery, she continued to have high-end inspiratory pressure and progressed to the chronic phase of adult respiratory distress syndrome (ARDS). We treated her with low-dose steroid therapy and she improved gradually. The patient was weaned off mechanical ventilation and was discharged approximately 25 weeks after LDLT. In the condition of cardiac or respiratory failure, cadaveric liver transplantation using plasmapheresis is contraindicated because of the associated high mortality rate. Our case suggests that if infections are controlled, a patient with multiple organ failure (MOF) due to end-stage liver disease might be successfully treated with LDLT aided by plasmapheresis and PCPS.
Cardiopulmonary Resuscitation↗
Electron-spin and electron-orbital dependence of the tunnel coupling in laterally coupled double vertical dots.
We employ a new laterally coupled, vertical double dot with a tunable tunnel-coupling gate in a parallel configuration to study the electron spin and orbital dependence of quantum mechanical tunnel coupling on the size of the honeycomb vertices in the small electron numbers regime. We find a transition from the weak coupling regime, where fluctuations in tunnel coupling due to varying electron configuration dominate the anticrossings, to a regime where the two dots coalesce. We apply a magnetic field to ascertain the orbital angular momenta of the Fermi surface eigenstates, which correlate with anticrossing size, and we identify spin pairs with congruent behavior.
Journal Article↗
Single-dot spectroscopy via elastic single-electron tunneling through a pair of coupled quantum dots.
We study the electronic structure of a single self-assembled InAs quantum dot by probing elastic single-electron tunneling through a single pair of weakly coupled dots. In the region below pinch-off voltage, the nonlinear threshold voltage behavior provides electronic addition energies exactly as the linear, Coulomb blockade oscillation does. By analyzing it, we identify the s and the p shell addition spectrum for up to six electrons in the single InAs dot, i.e., one of the coupled dots. The evolution of the shell addition spectrum with magnetic field provides Fock-Darwin spectra of the s and p shells.
Journal Article↗
Genes for systemic vascular complications are differentially expressed in the livers of type 2 diabetic patients.
AIMS/HYPOTHESIS: Type 2 diabetes is characterised by excessive hepatic glucose production and frequently leads to systemic vascular complications. We therefore analysed the relationship between the gene expression profile in the liver and the pathophysiology of Type 2 diabetes. METHODS: Liver biopsy samples were obtained from twelve patients with Type 2 diabetes and from nine non-diabetic patients. To assay gene expression globally in the livers of both groups, we made complementary DNA (cDNA) microarrays consisting of 1080 human cDNAs. Relative expression ratios of individual genes were obtained by comparing cyanine 5-labelled cDNA from the patients with cyanine 3-labelled cDNA from reference RNA from the liver of a non-diabetic patient. RESULTS: On assessing the similarities of differentially expressed genes, the gene expression profiles of the twelve diabetic patients formed a separate cluster from those of the non-diabetic patients. Of the 1080 genes assayed, 105 (9.7%) were up-regulated and 134 (12%) were down-regulated in the diabetic livers (p<0.005). The genes up-regulated in the diabetic patients included those encoding angiogenic factors such as vascular endothelial growth factor, endothelin and platelet-derived growth factor. They also included TGF superfamily genes such as TGFA and TGFB1 as well as bone morphogenetic proteins. Among the down-regulated genes in the diabetic patients were molecules defending against stress, e.g. flavin-containing monooxygenase and superoxide dismutase. CONCLUSIONS/INTERPRETATION: These findings suggest that livers of patients with Type 2 diabetes have gene expression profiles indicative of an increased risk of systemic vascular complications.
Adult↗
A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice.
BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3(-/-) mice to Rag2(-/-) immunodeficient mice that expressed Dsg3. OBJECTIVES: We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3(-/-) mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. METHODS: We adoptively transferred naive Dsg3(-/-) splenocytes into Rag2(-/-) mice and compared their PV phenoytpe with those mice receiving immunized Dsg3(-/-) splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. RESULTS: Mice that received naive Dsg3(-/-) splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3(-/-) mice were essential for the production of anti-Dsg3 IgG antibodies. CONCLUSIONS: Dsg3-specific naive lymphocytes in Dsg3(-/-) mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets.
Adoptive Transfer↗
Modulating effects of olanzapine on the development of diabetic ketoacidosis.
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Adult↗
Helicobacter pylori infection modifies gastric and plasma ghrelin dynamics in Mongolian gerbils.
BACKGROUND: and aim: Although ghrelin, a novel growth hormone releasing peptide localised mainly in the gastric fundus, is reported not only to accelerate food passage and gastrointestinal motility but also to affect appetite and weight control, regulation of gastric ghrelin secretion under the conditions of gastric Helicobacter pylori infection is unknown. The present study was designed to investigate plasma and gastric ghrelin levels in Mongolian gerbils with H pylori colonisation of the gastric mucosa. METHODS: Gerbils orally inoculated with H pylori were examined after inoculation. To examine preproghrelin mRNA expression in the gastric mucosa, cDNA encoding the gerbil preproghrelin and glyceraldehyde-3-phosphate dehydrogenase homologue was isolated and a quantitative reverse transcription-polymerase chain reaction system was established. RESULTS: In gerbils showing H pylori colonisation (H pylori group), expression of preproghrelin mRNA and total ghrelin levels were significantly decreased 17 and 23 weeks later (p<0.01). Although the number of ghrelin immunoreactive cells decreased as the stomach weight increased, the gastric contents of total and active ghrelin in this group were the same as those in controls. Gastric myeloperoxidase activity showed a positive correlation with plasma ghrelin levels. On the other hand, at 17 weeks, plasma ghrelin levels were significantly increased in the H pylori group (p<0.05), suggesting a compensatory increase in secretion of the peptide at this time point. CONCLUSION: The present experimental study demonstrated that gastric and plasma ghrelin dynamics are altered in response to H pylori infection.
Amino Acid Sequence↗
Intrapancreatic accessory spleen: diagnosis using contrast enhanced ultrasound.
Intrapancreatic accessory spleen (IPAS) is a mass that can mimick a neoplastic mass in the pancreas. As it poses no clinical problem no treatment is required. Unfortunately almost all the reported cases of IPAS have been misdiagnosed and unnecessary surgery performed. We performed contrast-enhanced ultrasound (CEUS) in a patient with IPAS for a research purpose, and confirmed that CEUS is useful for diagnosing this entity.
Adult↗
Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model.
AIMS/HYPOTHESIS: We investigated the effect of cerivastatin, a statin, on the development of diabetic nephropathy in spontaneously hypertensive rats (SHR) with streptozotocin-induced diabetes. METHODS: Diabetic SHR were given standard chow or chow containing cerivastatin at a dose of 0.1 mg/kg or 1.0 mg/kg for 12 weeks. Effects of cerivastatin on urinary albumin excretion, mesangial expansion, glomerular macrophage infiltration, and the number of anionic sites on the glomerular basement membrane (GBM) were assessed. RESULTS: Cerivastatin did not affect the blood glucose concentration, blood pressure or serum cholesterol concentration in diabetic SHR. However, cerivastatin treatment caused a dose-dependent decrease of albuminuria and hyperfiltration. At 1.0 mg/kg, cerivastatin inhibited the diabetes-induced expansion of mesangial and tuft areas on histological examination of the kidneys, as well as the loss of anionic sites from the GBM evaluated with polyetyleneimine and the intraglomerular infiltration of ED1-positive macrophages evaluated by immunohistochemistry. Whole-kidney expression of mRNA for MCP-1 and TGF-beta, estimated by the real-time quantitative RT-PCR, was increased (both 2.6-fold) in untreated diabetic SHR at 12 weeks. Cerivastatin treatment (1.0 mg/kg) inhibited the up-regulated expression of MCP-1 and TGF-beta mRNA (decreased to 48% and 34%, respectively) in diabetic SHR. CONCLUSION/INTERPRETATION: In this hypertensive model of diabetic nephropathy, cerivastatin decreased albuminuria through suppression of glomerular hyperfiltration, mesangial expansion, and the loss of charge barrier independently of a cholesterol-lowering effect. These preventive effects could be at least partly due to inhibition of macrophage recruitment and activation, and inhibition of TGF-beta overexpression.
Animals↗
Marked improvement of glycaemic control with pioglitazone in a Type 2 diabetic patient associated with Charcot-Marie-Tooth disease.
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Body Weight↗
The amygdala and Alzheimer's disease: positron emission tomographic study of the cholinergic system.
The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P <0.0001 in the two-tailed t test), 14% in the hippocampus (P <0.001), and 33% in the amygdala (P <0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P <0.001) and the amygdala (P <0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.
Aged↗
The mature form of adrenomedullin correlates with brain natriuretic peptide in plasma of chronic hemodialysis patients.
AIM: Adrenomedullin (AM), a hypotensive and natriuretic peptide, consists of an amidated mature form (mAM) and an intermediate form in human plasma, of which only mAM exerts biological activity. Like atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), plasma levels of mAM are reported to be significantly elevated in hemodialysis (HD) patients, suggesting that mAM may be stimulated partly by increased body fluid volume in a manner similar to the natriuretic peptides. Here, we examined the relationship between mAM levels and ANP or BNP levels and the effect of HD on plasma mAM in HD patients. PATIENTS AND METHODS: We measured plasma levels of mAM, total AM (tAM), ANP and BNP before and after HD in patients on long-term HD (n = 22, mean age 56.3 +/- 3.2 years) using radioimmunoassay. RESULTS: Baseline mAM (2.7 +/- 0.3 fmol/ml) and tAM (23.6 +/- 2.0 fmol/ml) were significantly higher in HD patients than in healthy subjects (1.1 +/- 0.2 fmol/ml, 9.0 +/- 2.1 fmol/ml, respectively). HD significantly reduced the levels to 1.2 +/- 0.2 fmol/ml and 13.8 +/- 1.4 fmol/ml, respectively, although tAM levels were still elevated compared to healthy subjects. Similar plasma ANP and BNP levels were obtained in HD patients. There were significant correlations between mAM and tAM levels before and after HD and between HD-induced changes in mAM and tAM levels. In the pre-HD state, levels of both mAM and tAM correlated significantly with BNP levels, but the correlation of BNP with mAM was closer than that with tAM. In contrast, no correlations were observed between the 2 forms of AM and ANP. Changes in mAM levels during HD also correlated significantly with BNP but not ANP levels, although the changes in tAM did not correlate with those of the 2 natriuretic peptides. CONCLUSION: Our results suggest that the secretion/metabolism of mAM may be regulated in a manner similar to that of BNP in HD patients.
Adrenomedullin↗