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Biomedical subjects

S Tamura

Publications and source records attributed to S Tamura.

At least 19 recordsLinked to original sources
PubMed2007

Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: Type 1A diabetes results from autoimmune destruction of pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as well as of T cells, macrophages and dendritic cells, in the destruction of beta cells in patients with recent-onset type 1 diabetes. MATERIALS AND METHODS: We obtained pancreatic biopsy specimens from six patients with recent-onset type 1 diabetes and analysed these by immunohistochemistry. RESULTS: T cell infiltration was less common in islets without beta cells (12.5 [0-33.3]%) than in those with beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a similar extent of infiltration into islets both with or without beta cells. TNF-alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of dendritic cells infiltrating the islets in samples from each patient, but not at all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each patient (all values median [range]). CONCLUSIONS/INTERPRETATION: Macrophages and dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF-alpha and IL-1beta) during the development of type 1A diabetes.

Adolescent↗
PubMed2006

Hemophagocytic syndrome after adult-to-adult living donor liver transplantation.

Hemophagocytic syndrome is a fatal complication after liver transplantation that is rarely reported. Among 260 adult patients who underwent living donor liver transplantation at our hospital, three cases (1%) were complicated with hemophagocytic syndrome. Intensive investigation revealed Aspergillus, cytomegalovirus, and hepatitis C virus as the most likely causative organisms in each patient. Despite the immediate initiation of anti-infectious treatment and supportive care, all patients died. When pancytopenia with possible underlying infectious disease is observed in liver transplant recipients, hemophagocytic syndrome should be suspected and bone marrow biopsy considered. The prognosis of hemophagocytic syndrome remains poor and further investigations are required to establish effective therapeutic options.

Adult↗
PubMed2006

Renal impairment after living donor liver transplantation.

BACKGROUND: There are few reports of postoperative renal impairment after living donor liver transplantation (LDLT). METHODS: We reviewed 246 LDLT recipients to examine the effects of postoperative renal impairment on the results of LDLT. RESULTS: The incidence of renal impairment and the requirements for postoperative renal replacement therapy were 29% and 9%, respectively. Intraoperative blood loss (P<.0001) and preoperative serum creatinine (P=.0002) were significant independent risk factors for the development of early renal dysfunction. Patients who required renal replacement therapy had a lower survival rate (P=.01). CONCLUSIONS: We identified the risk factors for postoperative renal impairment, providing useful metrics to establish a treatment strategy for high risk liver transplant patients.

Adult↗
PubMed2006

Impact of celiac axis stenosis on living donor hepatectomy.

BACKGROUND: Celiac axis stenosis was once cited as a reason for exclusion from living donor liver transplantation. Donor hepatectomy, however, leaves the pancreaticoduodenal artery arcade untouched, and theoretically, celiac axis stenosis has no impact on otherwise possible donors. METHODS: Among 350 consecutive adult living donors of liver transplantation at Tokyo University Hospital, we experienced 11 (3%) donors with celiac axis stenosis or occlusion due to the median arcuate ligament. RESULTS: Harvesting of the right liver was the most common procedure (n = 8), followed by harvesting of segments II and III (n = 2), and left liver (n = 1). The postoperative course was uneventful in all of the donors. CONCLUSIONS: Our results indicate that donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis.

Adult↗
PubMed2006

New-onset diabetes mellitus after living donor liver transplantation: possible association with hepatitis C.

BACKGROUND: The relationship between hepatitis C virus (HCV) infection and new-onset diabetes mellitus (NODM) after liver transplantation is a controversial issue. METHODS: A total of 223 adult living donor liver transplantation (LDLT) recipients followed for more than 6 months were analyzed for the prevalence of NODM. The prevalence was compared between 62 HCV-positive and 161 HCV-negative patients. All the HCV-positive patients underwent preemptive antiviral treatment with interferon alpha2b and ribavirin. RESULTS: Preoperative diabetes mellitus was more frequently observed in HCV-positive patients (18% vs 4%, P = .001). NODM occurred more frequently in HCV-positive patients (41% vs 22%, P = .003). Multivariate analysis, however, revealed that HCV was not a predictor for NODM. A comparison of 14 HCV-positive patients with persistent NODM and 48 patients without persistent NODM indicated that there was no significant difference in the frequency of the viral response to antiviral therapy nor in HCV-RNA levels. Impaired glucose tolerance did not impact postoperative survival after LDLT. CONCLUSIONS: HCV was not associated with the prevalence of NODM after LDLT. NODM did not influence patient survival.

Adult↗
PubMed2005

Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action.

Insulin-stimulated glucose disposal in skeletal muscle proceeds predominantly through a nonoxidative pathway with glycogen synthase as a rate-limiting enzyme, yet the mechanisms for insulin activation of glycogen synthase are not understood despite years of investigation. Isolation of putative insulin second messengers from beef liver yielded a pseudo-disaccharide consisting of pinitol (3-O-methyl-d-chiro-inositol) beta-1,4 linked to galactosamine chelated with Mn(2+) (called INS2). Here we show that chemically synthesized INS2 has biological activity that significantly enhances insulin reduction of hyperglycemia in streptozotocin diabetic rats. We used computer modeling to dock INS2 onto the known three-dimensional crystal structure of protein phosphatase 2C (PP2C). Modeling and FlexX/CScore energy minimization predicted a unique favorable site on PP2C for INS2 in a surface cleft adjacent to the catalytic center. Binding of INS2 is predicted to involve formation of multiple H-bonds, including one with residue Asp163. Wild-type PP2C activity assayed with a phosphopeptide substrate was potently stimulated in a dose-dependent manner by INS2. In contrast, the D163A mutant of PP2C was not activated by INS2. The D163A mutant and wild-type PP2C in the absence of INS2 had the same Mn(2+)-dependent phosphatase activity with p-nitrophenyl phosphate as a substrate, showing that this mutation did not disrupt the catalytic site. We propose that INS2 allosterically activates PP2C, fulfilling the role of a putative mediator mimetic of insulin signaling to promote protein dephosphorylation and metabolic responses.

Amino Acid Substitution↗
PubMed2005

Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment.

AIMS/HYPOTHESIS: We have previously reported that fulminant type 1 diabetes is characterised by an absence of diabetes-related antibodies and a remarkably abrupt onset. However, little is known about the mechanism of beta cell destruction in this diabetes subtype, and to obtain insights into the aetiology of the disease, we investigated residual endocrine cells and the expression of Fas and Fas ligand in fulminant type 1 diabetes. METHODS: Residual beta and alpha cells were morphologically assessed in pancreatic tissue obtained by biopsy from five patients with recent-onset fulminant type 1 diabetes and five patients with recent-onset typical autoimmune type 1 diabetes. In addition, the expression of Fas and Fas ligand was evaluated by immunohistochemistry. RESULTS: In fulminant type 1 diabetes, beta and alpha cell areas were decreased significantly, compared with autoimmune type 1 diabetes and control subjects. In contrast, the alpha cell area was not decreased significantly in autoimmune type 1 diabetes, compared with that in control subjects. No Fas expression in islets and Fas ligand expression in CD3(+) cells in the exocrine pancreas were found in the fulminant type 1 diabetic patients who underwent this evaluation. CONCLUSIONS/INTERPRETATION: Our study showed that beta and alpha cells are damaged in fulminant type 1 diabetes. In addition to the lack of Fas and Fas ligand expression, the results suggest that the mechanism of beta cell destruction in fulminant type 1 diabetes is different from that in autoimmune type 1 diabetes.

Acidosis↗
PubMed2005

Wavelet-crosscorrelation analysis: Non-stationary analysis of neurophysiological signals.

OBJECTIVE: Wavelet-crosscorrelation analysis is a new application of wavelet analysis used to show the propagation of epileptiform discharges and to localize the corresponding lesions. We have shown previously that this analysis can help predict brain conditions statistically (Mizuno-Matsumoto et al. 2002). Our objective was to assess whether wavelet-crosscorrelation analysis reveals the initiation and propagation of epileptiform activity in human patients. METHODS: The data obtained from three patients with simple partial seizures (SPS) using whole-head magnetoencephalography (MEG) were analyzed by the wavelet-crosscorrelation method. Wavelet-crosscorrelation coefficients (WCC), the coherent structure of each possible pair of signals from 64 MEG channels forvarious periods, and the time lag (TL) in two related signals, were ascertained. RESULTS: We clearly demonstrated both localization of the irritative zone and propagation of the epileptiform discharges. CONCLUSIONS: Wavelet-crosscorrelation analysis can help reveal and visualize the dynamic changes of brain conditions. The method of this analysis can compensate for other existing methods for the analysis of MEG, electroencephalography (EEG) or Elecotrocorticography (ECoG). SIGNIFICANCE: Our proposed method suggests that revealing and visualizing the dynamic changes of brain conditions can help clinicians and even patients themselves better understand such conditions.

Adult↗
PubMed2005

TRPV2, a capsaicin receptor homologue, is expressed predominantly in the neurotrophin-3-dependent subpopulation of primary sensory neurons.

TRPV2, a member of transient receptor potential ion channels, responds to high-threshold noxious heat, but neither to capsaicin nor to proton. Although TRPV2 is expressed in medium- to large-sized dorsal root ganglion (DRG) neurons with myelinated fibers in adult rodents, little is known about the neurotrophin dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. In the present study, using immunohistochemistry, we found that TRPV2 was first expressed in DRG neurons at embryonic day (E) 11.5, when neither TRPV1 nor TRPM8 was detected yet. Double-immunofluorescence staining revealed that tyrosine kinase receptor C (TrkC) was expressed in most of TRPV2-positive DRG neurons at E11.5 and E13.5. In addition, the percentage of TRPV2-positive neurons in the total DRG neurons at E13.5 reached the same as that of adulthood. In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively. These results suggest that TRPV2 is expressed predominantly in the NT-3-dependent subpopulation of DRG neurons throughout development and in adult mice.

Age Factors↗
PubMed2005

Up-regulated phosphorylation of signal transducer and activator of transcription 3 and cyclic AMP-responsive element binding protein by peripheral inflammation in primary afferent neurons possibly through oncostatin M receptor.

Oncostatin M (OSM), a member of interleukin-6 family cytokines, contributes to the development of nociceptive sensory neurons. However, little is known about the role of OSM in dorsal root ganglia (DRGs) of adult mice after peripheral inflammation. In the present study, we showed that OSM mRNA was highly expressed in the inflamed skin during acute inflammation induced by complete Freund's adjuvant (CFA), while the expression of oncostatin M receptor (OSMR) did not change in the ipsilateral DRG. Although peripheral inflammation induced significant increases in the number of neurons with phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated p38 mitogen-activated protein kinase (p-p38) in ipsilateral DRGs, OSMR-positive neurons exhibited neither p-ERK nor p-p38. In addition, we found significant increases in the number of neurons with phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and phosphorylated cAMP-responsive element binding protein (p-CREB) in the ipsilateral DRGs. Interestingly, OSMR-positive neurons with p-STAT3 and p-CREB were significantly increased after peripheral inflammation. Thus, our results suggest that acute inflammation induce the phosphorylations of several signal molecules, including ERK, p38, cAMP-responsive element binding protein, and STAT3. Among them, the up-regulation of p-STAT3 and p-CREB may be induced possibly through OSMR.

Animals↗
PubMed2005

Expression of mKirre, a mammalian homolog of Drosophila kirre, in the developing and adult mouse brain.

mKirre, a mammalian homolog of the Drosophila kirre, is expressed in bone marrow stromal cells and the brain. Although mKirre has been shown to support the hematopoietic stem cells, little is known about the function of mKirre in the brain. In the present study, to gain insights into the function of mKirre, we investigated the expression pattern of mKirre gene in the developing and adult mouse brain using in situ hybridization. In the adult brain, mKirre mRNA was highly expressed in the olfactory bulb, the piriform cortex, the cochlear nucleus, and the cerebellum. At embryonic day (E) 11.5, we could observe mKirre mRNA in the differentiating zones of various regions, such as the caudate-putamen, the geniculate body, the thalamus, the amygdala, and the brainstem. Its gene expression in these regions at E11.5 also persisted to the adult, in which its expression levels were much less prominent. After birth, we could first observe high expression of mKirre mRNA in the glomerular and mitral layers of the olfactory bulb, the cortical plate of the neocortex, the cochlear nucleus, and the molecular and granule cell layers of the cerebellum. In the hippocampus, its gene expression was first observed in the dentate gyrus at postnatal day 7. The spatiotemporal expression pattern of mKirre mRNA suggests important roles of mKirre in later developmental processes, especially the synapse formation.

Age Factors↗
PubMed2005

Long-term survival and causes of late graft loss after adult-to-adult living donor liver transplantation.

The vast amount of experience with deceased donor liver transplantation allows for the evaluation of the causes underlying late graft loss and the adoption of strategies for its prevention. In contrast, the long-term results or causes of late graft loss after adult-to-adult living donor liver transplantation have not been fully examined. Thus, we analyzed 176 adult recipients who survived at least 1 year after living donor liver transplantation. The median follow-up period was 33 months. Of the 176 recipients, eight died and three others underwent retransplantation. The most common cause of graft loss in our series was cholangitis (n = 4), which might be due partly to technical problems. The 3-year and 5-year patient survival rates of the subjects were 95% and 90%, respectively. Long-term survival after living donor liver transplantation was satisfactory in our series. Further improvement of surgical techniques for biliary reconstruction may reduce late graft loss.

Adult↗
PubMed2005

Enhanced expression of suppressor of cytokine signalling-1 in the liver of chronic hepatitis C: possible involvement in resistance to interferon therapy.

Interferon-alpha (IFN-alpha) is widely used in the treatment of chronic hepatitis C (CHC). The suppressor of cytokine signalling (SOCS) family has been implicated in the regulation of JAK-STAT signalling, including IFN signalling. The negative effect of SOCS expression on the response of CHC to IFN-alpha is demonstrated here. The transcriptional levels of SOCS-1 and -3 in the livers of 21 patients with CHC and eight controls were investigated by quantitative reverse transcription-polymerase chain reaction. We established stable transfectants of SOCS-1 in a human hepatoma cell line, PLC/PRF/5 and analysed the effects of SOCS-1 on the phosphorylation of IFN-alpha-induced STAT-1 tyrosine by immunoblotting and the expression of antiviral genes by Northern blot. A prospective cohort study on SOCS-1 expression and clinical outcome was carried out in 77 patients with CHC who received IFN therapy. SOCS-1, but not SOCS-3, transcripts in the livers of CHC were significantly higher than controls (P < 0.005). IFN-alpha-induced STAT-1 phosphorylation and the expression of antiviral genes were inhibited in SOCS-1-transfected cells. Patients showing high SOCS-1 expression in the liver had a significantly lower rate of sustained virological response (SVR) to IFN therapy than those with low SOCS-1 expression (P = 0.0014). A multivariate analysis performed with host factors revealed that SOCS-1 staining in the liver can serve as a significant predictor for IFN SVR (P = 0.004). SOCS-1 expression is enhanced in the livers of CHC patients and might be involved in resistance to IFN therapy.

Adult↗
PubMed2005

Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease.

BACKGROUND AND AIMS: A characteristic feature of Crohn's disease (CD) is mesenteric adipose tissue hypertrophy. Mesenteric adipocytes or specific proteins secreted by them may play a role in the pathogenesis of CD. We recently identified adiponectin as an adipocyte specific protein with anti-inflammatory properties. Here we report on expression of adiponectin in mesenteric adipose tissue of CD patients. METHODS AND RESULTS: Mesenteric adipose tissue specimens were obtained from patients with CD (n = 22), ulcerative colitis (UC) (n = 8) and, for controls, colon carcinoma patients (n = 28) who underwent intestinal resection. Adiponectin concentrations were determined by enzyme linked immunosorbent assay, and adiponectin mRNA levels were determined by real time quantitative reverse transcription-polymerase chain reaction. Tissue concentrations and release of adiponectin were significantly increased in hypertrophied mesenteric adipose tissue of CD patients compared with normal mesenteric adipose tissue of CD patients (p = 0.002, p = 0.040, respectively), UC patients (p = 0.002, p = 0.003), and controls (p<0.0001, p<0.0001). Adiponectin mRNA levels were significantly higher in hypertrophied mesenteric adipose tissue of CD patients than in paired normal mesenteric adipose tissue from the same subjects (p = 0.024). Adiponectin concentrations in hypertrophied mesenteric adipose tissue of CD patients with an internal fistula were significantly lower than those of CD patients without an internal fistula (p = 0.003). CONCLUSIONS: Our results suggest that adipocytes in hypertrophied mesenteric adipose tissue produce and secrete significant amounts of adiponectin, which could be involved in the regulation of intestinal inflammation associated with CD.

Adipocytes↗
PubMed2004

In vitro release of Tacrolimus from Tacrolimus ointment and its speculated mechanism.

The in vitro release profiles and the bleeding phenomenon of Tacrolimus and propylene carbonate (PC) as a dispersing solvent for Tacrolimus drug substance in Tacrolimus ointment were investigated when changing concentrations of Tacrolimus and PC in the ointment were used, respectively. The bleeding test result indicated that Tacrolimus was in equilibrium between inside and outside of PC droplets in intact ointment base. A cumulative release amount of Tacrolimus from ointment, plotted against the square root of time, showed a straight line initially with a slope of q1 followed to change a slope to be q2 at a certain time, where the relation of these slopes being q1<q2. The q1 values increased with the concentration of Tacrolimus but decreased with PC concentration in Tacrolimus ointment. And the q2 values increased with Tacrolimus concentration but were independent of PC concentration. These profiles indicated that there were two phases for Tacrolimus release from ointment, namely, first phase was related with the period during PC release and the second phase was related with the state of ointment after PC release. When the PC release was applied to the Higuchi's release equation, the above slope q1 was found to be correlated to the parameter of A/phi(0), where A was a parameter of release rate of PC and phi(0) was an initial volume fraction of PC droplets. It should be indicated that more rapid release rate of PC rather than that of Tacrolimus resulted in the generation of amorphous phase of Tacrolimus outside of remaining PC droplets. During PC release, the slope q1 could be influenced by the thermodynamic activity of Tacrolimus dissolved in PC droplets. After PC release, it would be reasonable to speculate that the amorphous cluster of Tacrolimus with a constant thermodynamic activity would give constant q2 values regardless of PC contents in Tacrolimus ointment.

Chemistry, Pharmaceutical↗