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M Iida

Publications and source records attributed to M Iida.

At least 19 recordsLinked to original sources
PubMed2006

The atypical antipsychotic clozapine impairs insulin secretion by inhibiting glucose metabolism and distal steps in rat pancreatic islets.

AIMS/HYPOTHESIS: Diabetogenic effects of some atypical antipsychotic drugs have been reported, although the mechanisms are not fully understood. We investigated the long-term effects of culturing isolated rat pancreatic islets with atypical antipsychotic clozapine. METHODS: Glucose- and non-glucose-stimulated insulin secretion, glucose metabolism and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in islets cultured with or without clozapine. RESULTS: Although acute incubation or 3-day culture with clozapine did not affect glucose-stimulated insulin secretion, clozapine suppressed glucose-stimulated insulin secretion by 53.2% at 1.0 micromol/l (therapeutic concentration) after 7 days of culture. Islet glucose oxidation and [Ca(2+)](i) elevation by high glucose were not affected after 3 days of culture, but clozapine significantly inhibited islet glucose oxidation, ATP production, and [Ca(2+)](i) elevation by high glucose after 7 days of culture. Moreover, 7 days of culture with clozapine inhibited insulin secretion stimulated by: (1) membrane depolarisation induced by high K(+); (2) protein kinase C activation; and (3) mastoparan at 16.7 mmol/l glucose under stringent Ca(2+)-free conditions. Elevation of [Ca(2+)](i) by high K(+)-induced membrane depolarisation was similar in control and clozapine-treated islets. Clozapine, a muscarinic blocker, acutely inhibited carbachol-induced insulin secretion, as did atropine, whereas after 7 days of culture atropine did not have the inhibitory effect shown by clozapine after 7 days. The impairment of glucose-stimulated insulin secretion recovered 3 days after the removal of clozapine treatment. CONCLUSIONS/INTERPRETATION: The present study demonstrated that the atypical antipsychotic drug clozapine directly impaired insulin secretion via multiple sites including glucose metabolism and the distal step in insulin exocytosis in a long-term culture condition. These mechanisms may be involved in the form of diabetes mellitus associated with atypical antipsychotic drugs.

Adenosine Triphosphate↗
PubMed2006

Persistent hyperparathyroidism in renal allograft recipients: vitamin D receptor, calcium-sensing receptor, and apoptosis.

The phenotypic changes in parathyroid cells after successful renal transplantation remain to be elucidated. We compared 10 diffuse and 11 nodular hyperplastic parathyroid glands from five renal allograft recipients with persistent hyperparathyroidism, with five diffuse and 13 nodular hyperplasia from seven uremic patients on hemodialysis, and 13 normal glands. Comparisons included expressions of both vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), proliferative activity (Ki67), and apoptosis (TUNEL). Immunoreactivity was assessed semiquantitatively and expressed as labeling index. The area/cell was also measured to assess cellular hypertrophy. The labeling indexes of VDR (587+/-71; mean+/-s.e.m.) and CaSR (45.0+/-2.8) in recipients' diffuse hyperplasia were significantly higher than those in uremic diffuse hyperplasia (224+/-44, 29.3+/-2.3, respectively) (P<0.01, each). However, these expressions remained low in recipients' nodular hyperplasia (42+/-8, 11.8+/-1.4, respectively). Ki67 labeling index in recipients' nodular hyperplasia (7+/-1) was significantly smaller than in uremic patients (24+/-6, P<0.01). TUNEL labeling index in recipients' diffuse hyperplasia (30+/-5) was the highest among the groups. The cell volume tended to be smaller in both patterns of hyperplasia in allograft recipients compared with uremic patients. Our results suggest that the phenotypic change in parathyroid cells after renal transplantation depends on the pattern of hyperplasia, where it is normalized only in diffuse hyperplastic glands in which the number of cells also regresses with significant induction of apoptosis.

Apoptosis↗
PubMed2006

Decreasing incidence of lacunar vs other types of cerebral infarction in a Japanese population.

BACKGROUND: There is scant information on secular trends in the incidence and survival of ischemic stroke subtypes. METHODS: The authors established three cohorts of Hisayama residents age > or =40 years in 1961 (1,618 subjects), 1974 (2,038 subjects), and 1988 (2,637 subjects). They followed up with each cohort for 12 years, comparing the incidence and survival rate of ischemic stroke subtypes. Morphologic examinations by autopsy or brain imaging was performed on most of the ischemic stroke cases in all cohorts. RESULTS: The age-standardized incidence of lacunar infarction significantly declined by 59% for men and by 28% for women from the first to the second cohort. It continued to decline by 41% for men, but the decline decelerated for women between the second and third cohort. The age-standardized incidence of atherothrombotic infarction tended to decline from the first to the second cohort, whereas it was sustained between the second and third cohort for both sexes. The age-standardized incidence of cardioembolic infarction was unchanged throughout the cohorts. In these cohorts, mean blood pressure levels among hypertensive subjects and the prevalence of current smoker decreased with time, though the prevalence of hypertension remained stable. The 5-year survival rate after lacunar infarction significantly improved among the cohorts, but those of atherothrombotic and cardioembolic infarction did not. CONCLUSIONS: These data suggest that, in the Japanese population, the incidence of lacunar infarction steadily declined for the last 40 years. The improvement of hypertension control and decreasing prevalence of smoking might be responsible for this trend.

Adult↗
PubMed2006

Loss of SOCS3 in the liver promotes fibrosis by enhancing STAT3-mediated TGF-beta1 production.

Recently, DNA methylation and reduced expression of the suppressor of the cytokine signaling-3 (SOCS3) gene in human hepatocellular carcinoma (HCC) patients have been reported. However, the roles of SOCS3 in HCC development in vivo have not been clarified. Using RT-PCR analysis and Western blotting, we confirmed that SOCS3 expression was reduced in HCC patients. However, reduced expression of SOCS3 occurred not only in HCC but also in nontumor regions, and this reduction was stronger as the fibrosis grade increased. Furthermore, SOCS3 levels were inversely correlated with signal transducers and activators of transcription-3 (STAT3) activation as well as transforming growth factor (TGF)-beta1 levels in the non-HCC region. To define the molecular consequences of SOCS3 silencing/STAT3 hyperactivation and liver fibrosis, we examined liver-specific SOCS3-deficient mice. We demonstrated that SOCS3 deletion in the liver resulted in hyperactivation of STAT3 and promoted ConA- and chemical-induced liver fibrosis. The expression of TGF-beta1, a mediator of fibrosis, was enhanced by SOCS3 gene deletion, but suppressed by the overexpression of a dominant-negative STAT3 or SOCS3 both in vivo and in vitro. These data suggest that TGF-beta1 is a target gene of STAT3 and could be one of the mechanisms for enhanced fibrosis in SOCS3-deficient mice. Thus, our present study provides a novel role of SOCS3 and STAT3 in HCC development: in addition to the previously characterized oncogenic potentials, STAT3 enhances hepatic fibrosis through the upregulation of TGF-beta1 expression, and SOCS3 prevents this process.

Animals↗
PubMed2006

A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis.

BACKGROUND AND AIMS: Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis (UC), while the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies. METHODS: Patients with refractory active UC were randomly assigned to a high trough concentration (10-15 ng/ml) group (HT group) (n = 21), low trough concentration (5-10 ng/ml) group (LT group) (n = 22), or placebo group (n = 20). Patients received an initial oral dose of 0.025 [DOSAGE ERROR CORRECTED] mg/kg tacrolimus or placebo twice daily. Efficacy was evaluated in 60 patients based on a disease activity index (DAI) score. Fifty eight patients had additional treatment with tacrolimus and were evaluated for efficacy in a 10 week open label extension. RESULTS: An improvement in DAI score (>or=4 points, all categories improved) was observed for 68.4% of cases in the HT group compared with 10.0% in the placebo group (p<0.001). In the HT group, 20.0% of patients had clinical remission and 78.9% had mucosal healing. In the open label extension, 55.2% of all patients had an improved DAI score at week 10. Mean dose of prednisolone was reduced from 19.7 mg/day at study entry to 7.8 mg/day at week 10. The incidence of side effects in the HT group was significantly higher than that of the placebo group (p = 0.043). The most common event was mild finger tremor. CONCLUSIONS: Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC. The optimal target range appears to be 10-15 ng/ml in terms of efficacy with two week therapy.

Administration, Oral↗
PubMed2006

Parathyroid growth and regression in experimental uremia.

Early 1,25-dihydroxyvitamin D(3) (VD(3)) therapy during the course of renal failure prevents the downregulation of VD(3) receptor (VDR), calcium-sensing receptor (CaSR) or p21, and the parathyroid (PT) growth. We hypothesized that VD(3) could restore the decreased expressions of VDR and CaSR, and cause regression in enlarged PT glands. 5/6 nephrectomized rats fed high-phosphorus diet were killed at 1, 3, 5, or 7 days and at 2, 3, 4, 8, or 12 weeks. VD(3)-treated rats were given VD(3) intraperitoneally for 1, 2, 3, or 4 weeks, starting 8 weeks after 5/6 nephrectomy. PT glands were weighed and subjected to immunohistochemical analyses for VDR, CaSR, p21, Ki67, and Tdt-mediated dUTP nick end-labeling (TUNEL) assay. The area per cell was measured as the parameter of cell size. The expression of VDR and p21 began to decrease at day 1, and Ki67 increased at day 3, but decreased thereafter. There was a significant increase in PT gland weight to week 12 with the increase of cell size. VD(3) treatment significantly increased both VDR and CaSR expressions 2 weeks after the start of injection, and reduced the PT gland weight at week 3 with significant increase of TUNEL-positive cells and decrease of cell size. Our results suggest that PT growth in uremic rats involves both PT cell proliferation and hypertrophy, in association with the reduction of VDR, CaSR, and p21 expressions. In addition, VD(3) treatment could reverse PT hyperplasia and hypertrophy via restoration of these proteins.

Animals↗
PubMed2006

Elevated cerebrospinal fluid lactate levels and the pathomechanism of calcification in Fahr's disease.

In this study, we report the case of a 68-year-old man complaining of involuntary movement of his left shoulder and lower jaw plus dyspnea. On cranial computed tomography and magnetic resonance imaging, marked and symmetrical calcification at the basal ganglia and dentate nuclei was documented. An elevated cerebrospinal fluid (CSF) lactate level was confirmed by spinal tap examination and magnetic resonance spectroscopy. The raised CSF lactate level, clinical characteristics such as diabetes, bilateral hearing loss and symmetrical cerebral calcification strongly suggested some kinds of mitochondrial disease. However, gene analysis of peripheral blood leukocytes revealed no typical or known mutations. Under the diagnosis of Fahr's disease, we treated him with haloperidol, which completely abolished his symptoms. In Ellsworth-Howard test, he showed markedly decreased phosphaturic response to parathyroid hormone with same pattern as type 2 pseudohypoparathyroidism. This abnormal response in our patient, probably due to respiratory alkalosis reflecting chronic hyperventilation, might in part explain similar mechanism of ectopic calcification underlying these two diseases.

Aged↗
PubMed2006

Candida glabrata fungemia in a diabetic patient with neurogenic bladder: successful treatment with micafungin.

A 69-year-old man was transferred to our hospital because of fever and acute renal failure. 5 weeks prior to admission, he was admitted to another hospital and treated with several antibiotics including vancomycin, but fever did not subside and renal dysfunction showed rapid progression. On admission, laboratory findings revealed pyuria, inflammatory changes, acute renal failure, and disseminated intravascular coagulation (DIC). Computed tomography showed left ureteral stone and hydronephrosis. Gallium scintigraphy showed avid uptake in the left kidney. Serum concentration of vancomycin was 57.4 micro/ml. Candida glabrata was isolated from blood, sputum and urine. Under the diagnosis of fungemia and left pyelonephritis, he was treated with micafungin (150 mg/day), gabexate mesilate and insertion of a double-ended pigtail catheter. The above treatment produced regression of systemic inflammation, DIC and acute renal failure. At the last follow-up 3 weeks after discharge, ureteroscopy showed that the ureter stone had already passed but a soft white-yellowish bezoar was detected in the ureter. In this case, neurogenic bladder, poorly controlled diabetes, and long-term antibiotic treatment probably enhanced the development of C. glabrata infection. Antifungal treatment with micafungin is useful in patients with non-albicans Candida infection.

Aged↗
PubMed2005

Two Japanese brothers with hereditary gamma-glutamyl transpeptidase deficiency.

We report on two Japanese brothers with hereditary deficiency in gamma-glutamyl transpeptidase. The propositus was 48 years old when he first visited our medical center and had a 51-year-old brother. The brothers were both tall and slender and had long limbs; the younger was diagnosed as having Marfan syndrome. Both patients both showed a tendency to retarded mental development. gamma-Glutamyltranspeptidase activity was below the detection limit of 1 IU/L in both patients. Glutathionaemia and glutathionuria were evident in both brothers. The analyses of sulphydryl compounds in the plasma (and serum for certain test items) and urine indicated high concentrations of glutathione, gamma-glutamylcysteine, cysteine and cysteinylglycine. Urine amino acid analysis on an automatic analyser showed a slightly increased excretion of cystine and a large peak in the citrulline position due, at least in part, to thio-compounds.

Amino Acid Metabolism, Inborn Errors↗
PubMed2005

Selective induction of DeltaFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of DeltaFosB and galectin-1 in neuroprotection and neurogenesis.

Transient forebrain ischemia causes selective induction of DeltaFosB, an AP-1 (activator protein-1) subunit, in cells within the ventricle wall or those in the dentate gyrus in the rat brain prior to neurogenesis, followed by induction of nestin, a marker for neuronal precursor cells, or galectin-1, a beta-galactoside sugar-binding lectin. The adenovirus-mediated expression of FosB or DeltaFosB induced expression of nestin, glial fibrillary acidic protein and galectin-1 in rat embryonic cortical cells. DeltaFosB-expressing cells exhibited a significantly higher survival and proliferation after the withdrawal of B27 supplement than the control or FosB-expressing cells. The decline in the DeltaFosB expression in the survivors enhanced the MAP2 expression. The expression of DeltaFosB in cells within the ventricle wall of the rat brain also resulted in an elevated expression of nestin. We therefore conclude that DeltaFosB can promote the proliferation of quiescent neuronal precursor cells, thus enhancing neurogenesis after transient forebrain ischemia.

Adenoviridae↗
PubMed2005

Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia.

Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n=7) or a control vector encoding beta-galactosidase (Adbetagal, n=7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant differences in cerebral blood flow 1 h after ischemia between AdMK and Adbetagal groups. Infarct volume of AdMK group was 51+/-27 mm3, which was significantly smaller than that of Adbetagal group (86+/-27 mm3, P<0.05). TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adbetagal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action. Thus, gene transfer of midkine to the ischemic brain may be effective in the treatment of brain ischemia.

Adenoviridae↗
PubMed2005

Comparison of capsule endoscopy and enteroscopy with the double-balloon method in patients with obscure bleeding and polyposis.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy and double-balloon enteroscopy (DBE) are novel methods of enteroscopy. The aim of this investigation was to compare the value of CE and DBE in the diagnosis of small-intestinal pathology. PATIENTS AND METHODS: Thirteen patients with gastrointestinal bleeding of obscure origin and nine patients with known gastrointestinal polyposis were examined using antegrade or retrograde DBE, and the most distal or proximal site in the explored small intestine was marked by submucosal injection of sterilized ink. The patients were then evaluated by CE. Video images obtained by CE were reviewed by an observer who was blinded to the DBE findings. RESULTS: DBE identified positive findings in 12 patients (54.5 %). CE identified positive findings in the area explored by DBE in eight patients (36.4 %), and in the unexplored area in 11 patients (50.0 %). The overall diagnostic yield in the area explored by DBE did not differ between the two procedures. The enteroscopic findings in the area explored by DBE were concordant in 12 of 13 patients with gastrointestinal bleeding of obscure origin. In patients with polyposis, the diagnoses were discordant in three patients, in whom CE failed to detect any polyp. In two of three polyposis patients with concordant positive findings, DBE detected a larger number of polyps than CE did. CONCLUSIONS: DBE appears to be superior to CE in the diagnosis of small-intestinal polyps, whereas the value for diagnosing gastrointestinal bleeding of obscure origin is similar in the two procedures.

Adult↗
PubMed2005

Mucosal proinflammatory cytokine and chemokine expression of gastroduodenal lesions in Crohn's disease.

BACKGROUND: The stomach and the duodenum are frequent sites of involvement by diminutive lesions in Crohn's disease (CD). AIM: To assess mucosal proinflammatory cytokines and chemokines in gastroduodenal lesions of CD. METHODS: 13C-Urea breath test and upper endoscopy were performed in 29 CD patients and seven control subjects, and biopsy specimens were obtained from the gastric cardia and the duodenum. Histology and mucosal levels of IL-1beta, IL-8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients, these procedures were repeatedly performed after administration of famotidine. RESULTS: H. pylori was less frequently positive in CD patients than in controls (10% vs. 71%, P = 0.003). Prevalence of cardial and duodenal lesion was significantly higher in CD than in controls (59% vs. 0%, P = 0.008 for gastric lesion; 45% vs. 0%, P = 0.034 for duodenal lesion). There were no differences in IL-1beta, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1beta and IL-8 were significantly higher in positive duodenal lesion than in negative duodenal lesion. However, there were no such differences with respect to cardial lesions. Endoscopic findings remained unchanged after administration of famotidine, while there was a trend towards decreases in IL-1beta and IL-8 in the gastric cardia. CONCLUSIONS: The pathogenesis of diminutive lesions of CD may be different between the stomach and the duodenum. Famotidine may not have a therapeutic effect on duodenal lesion in CD.

Adolescent↗
PubMed2005

Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats.

AIMS: Increased oxidative stress may contribute to the development of diabetic nephropathy. Conversely, it has been proposed that enhanced glomerular production of prostaglandin E(2) (PGE(2)) may be the cause of glomerular hyperfiltration in streptozotocin (STZ)-induced diabetic rats. As the role of superoxide anion (O(2-)) production in early diabetic nephropathy is not fully understood, we investigated the effect of vitamin C and desferrioxamine treatment on glomerular O(2-) and PGE(2) production in diabetic rats. METHODS: STZ-induced diabetic rats were given drinking water containing 1 g/l of vitamin C and desferrioxamine for 10 days, and glomerular O(2-) production, glomerular PGE(2) synthesis and creatinine clearance were examined. RESULTS: Glomerular O(2-) production increased in untreated diabetic rats compared to non-diabetic controls (142.2 +/- 12.4 vs. 65.4 +/- 3.6 counts/mg protein/min). Treatment with vitamin C and desferrioxamine significantly decreased glomerular O(2-) production (93.7 +/- 6.7 counts/mg protein/min). Glomerular PGE(2) synthesis and creatinine clearance were significantly increased in untreated diabetic rats compared to controls and PGE(2) synthesis was reduced and creatinine clearance tended to decrease by the treatment. CONCLUSIONS: Our results demonstrated that vitamin C and desferrioxamine suppressed the enhanced glomerular O(2-) production with subsequent decrease in PGE(2) production. Antioxidant therapy may be beneficial in preventing the development of diabetic nephropathy.

Animals↗
PubMed2005

Relationship between obesity, glucose tolerance, and periodontal disease in Japanese women: the Hisayama study.

BACKGROUND: Recent studies have reported a relationship between obesity and periodontal disease. Obesity is the strongest risk factor for type 2 diabetes, which is, in turn, a risk factor for periodontal disease. An oral glucose tolerance test is necessary to diagnose diabetes; however, no study has examined the relationship between obesity and periodontal disease by taking oral glucose tolerance test results into consideration. METHODS: In all, 584 Japanese women aged between 40 and 79 years old, with at least 10 teeth, underwent health examinations. Body mass index, waist-hip ratio, body fat, and oral glucose tolerance test results were used as independent variables with known risk factors for periodontal disease. Mean probing pocket depth and mean attachment loss were used as the dependent variables. RESULTS: In all of the analyses, body mass index, body fat, and waist--hip ratio were significantly associated with the highest quintile of mean probing pocket depth, even when adjusted for oral glucose tolerance test results. In the multivariate analysis, the subjects with the highest quartile of body mass index had a significantly higher odds ratio (OR) for the highest quintile of mean probing pocket depth [OR, 4.3; 95% confidence interval (CI), 2.1--8.9; p<0.001], whereas neither impaired glucose tolerance nor diabetes were significantly associated with deep pockets. The relationships between the obesity indexes and mean attachment loss did not reach statistical significance. CONCLUSION: Obesity was associated with deep pockets in Japanese women, even after adjusting for oral glucose tolerance test.

Adult↗