Biomedical subjects

Akira Tamura

Publications and source records attributed to Akira Tamura.

At least 19 recordsLinked to original sources

PubMed2004

Endoplasmic reticulum stress and N-glycosylation modulate expression of WFS1 protein.

Mutations of the WFS1 gene are responsible for two hereditary diseases, Wolfram syndrome and low frequency sensorineural hearing loss. The WFS1 protein is a glycoprotein located in the endoplasmic reticulum (ER) membrane but its function is poorly understood. Herein we show WFS1 mRNA and protein levels in pancreatic islets to be increased with ER-stress inducers, thapsigargin and dithiothreitol. Another ER-stress inducer, the N-glycosylation inhibitor tunicamycin, also raised WFS1 mRNA but not protein levels. Site-directed mutagenesis showed both Asn-663 and Asn-748 to be N-glycosylated in mouse WFS1 protein. The glycosylation-defective WFS1 protein, in which Asn-663 and Asn-748 had been substituted with aspartate, exhibited an increased protein turnover rate. Consistent with this, the WFS1 protein was more rapidly degraded in the presence of tunicamycin. These data indicate that ER-stress and N-glycosylation play important roles in WFS1 expression and stability, and also suggest regulatory roles for this protein in ER-stress induced cell death.

Animals↗

PubMed2004

Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy.

Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.

Aged↗

PubMed2004

In vivo influence of ceramide accumulation induced by treatment with a glucosylceramide synthase inhibitor on ischemic neuronal cell death.

It has been shown that exogenous ceramide induces delayed neuronal death (DND) of cultured hippocampal neurons. To evaluate the role of endogenous ceramide in ischemic DND, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to generate ceramide in gerbil hippocampi in vivo. The trimethylsilylated derivatives of ceramide were analyzed directly by gas chromatography mass spectrometry, after separation with high-performance thin-layer chromatography. The ceramide compositions in vehicle hippocampus consisted mainly of C18:0 fatty acyl sphingosine (87.9%), with C16:0 and C20:0 ceramides being minor components (7.1% and 5.1%, respectively). Ceramide level in the hippocampi from gerbils subjected to D-PDMP treatment was 1.5-fold higher than those from vehicle-treated gerbils. In spite of the accumulation of ceramide observed in the D-PDMP group, the histological studies did not reveal any ischemic neuronal death in hippocampal CA1 neurons with the gerbils that had been subjected to a sham operation (2-min sublethal ischemia). These results suggest that the ceramide accumulation induced by blocking the de novo synthesis of glucosylceramide with D-PDMP may be independent of the metabolic pathway underlying ischemic DND.

Animals↗

PubMed2004

Association of peripheral mononuclear cells containing Chlamydia pneumoniae DNA with acute coronary syndrome and stable coronary artery disease in Japanese subjects.

To clarify the association of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells (PBMCs) with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) in Japanese adults, touchdown-nested polymerase chain reaction was used to detect the presence of C. pneumoniae DNA. The prevalence of C. pneumoniae DNA in PBMCs was similar in a comparison of 88 patients (52.3%) with ACS, 164 patients (50.0%) with stable CAD, and 88 control subjects (50.0%). Temporal changes in the prevalence of C. pneumoniae DNA in PBMCs were also assessed every 3 months during a 1-year period (n=59). The prevalence was significantly higher in the first 3-month period (January through March) than in any of the other 3-month periods. In conclusion, the prevalence of C. pneumoniae DNA in PBMCs in patients with ACS or stable CAD was comparable to that in control populations. Furthermore, the presence of circulating C. pneumoniae was strongly associated with seasonal variability.

Aged↗

PubMed2004

The leaf extract of Ginkgo Biloba L. suppresses oxidized LDL-stimulated fibronectin production through an antioxidant action in rat mesangial cells.

1 The leaf extract of Ginkgo Biloba L. exhibits a variety of pharmacological effects through an antioxidant action. We examined the effects of the leaf extract (Ginkgolon-24) on the production of fibronectin induced by oxidized low-density lipoprotein (oxLDL) in rat mesangial cells. 2 Stimulation with oxLDL accelerated the production of fibronectin with the preceding generation of reactive oxygen species (ROS). Pretreatment with Ginkgolon-24 inhibited the oxLDL-induced fibronectin production as well as ROS generation. 3 oxLDL also elicited the activation of SP-1, nuclear factor-kappaB, and cAMP response element-binding protein, which are transcription factors involved in the fibronectin production. Among these activated transcription factors, Ginkgolon-24 inhibited the activation of SP-1 only. 4 Furthermore, 7-ketocholesterol, an oxidized lipid in oxLDL particles, induced the production of fibronectin and the activation of SP-1, which were also suppressed by Ginkgolon-24. 5 These results suggest that the leaf extract of Ginkgo Biloba L. inhibits the oxLDL-induced production of fibronectin probably through inhibitory effects on ROS generation and SP-1 activation in rat mesangial cells.

Animals↗

PubMed2004

Blood pressure management in acute intracerebral hemorrhage: relationship between elevated blood pressure and hematoma enlargement.

BACKGROUND AND PURPOSE: The association between elevated blood pressure (BP) and hematoma enlargement in acute intracerebral hemorrhage (ICH) has not been clarified. We investigated the association between maximum systolic BP (SBP) and hematoma enlargement, measuring SBP between a baseline and a second CT scan in patients with hypertensive ICH. METHODS: We assessed 76 consecutive patients with hypertensive ICH retrospectively. We usually attempted to lower SBP below targets of 140, 150, or 160 mm Hg. Recordings of serial BP from admission until the second CT scan were assessed. A neuroradiologist, who was not informed of the aim of this study, reviewed CT films. Hematoma enlargement was defined as an increase in volume of > or =140% or 12.5 cm3. RESULTS: Hematoma enlargement occurred in 16 patients. Maximum SBP was significantly associated with hematoma enlargement (P=0.0074). A logistic regression model for predicting hematoma enlargement was constructed with the use of maximum SBP, hematoma volume, and Glasgow Coma Scale score at admission. After adjustment for these factors, maximum SBP was independently associated with hematoma enlargement (odds ratio per mm Hg, 1.04; 95% CI, 1.01 to 1.07). Target SBPs of > or =160 mm Hg were significantly associated with hematoma enlargement compared with those of < or =150 mm Hg (P=0.025). CONCLUSIONS: Our findings suggest that elevated BP increases the risk of hematoma enlargement. Efforts to lower SBP below 150 mm Hg may prevent this risk.

Acute Disease↗

PubMed2004

Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion.

Wolfram syndrome, an autosomal recessive disorder characterized by juvenile-onset diabetes mellitus and optic atrophy, is caused by mutations in the WFS1 gene. In order to gain insight into the pathophysiology of this disease, we disrupted the wfs1 gene in mice. The mutant mice developed glucose intolerance or overt diabetes due to insufficient insulin secretion in vivo. Islets isolated from mutant mice exhibited a decrease in insulin secretion in response to glucose. The defective insulin secretion was accompanied by reduced cellular calcium responses to the secretagogue. Immunohistochemical analyses with morphometry and measurement of whole-pancreas insulin content demonstrated progressive beta-cell loss in mutant mice, while the alpha-cell, which barely expresses WFS1 protein, was preserved. Furthermore, isolated islets from mutant mice exhibited increased apoptosis, as assessed by DNA fragment formation, at high concentration of glucose or with exposure to endoplasmic reticulum-stress inducers. These results strongly suggest that WFS1 protein plays an important role in both stimulus-secretion coupling for insulin exocytosis and maintenance of beta-cell mass, deterioration of which leads to impaired glucose homeostasis. These WFS1 mutant mice provide a valuable tool for understanding better the pathophysiology of Wolfram syndrome as well as WFS1 function.

Adenoviridae↗

PubMed2004

Hepatic resection using stapling devices.

BACKGROUND: The progress and development of stapling devices has been remarkable. They have become indispensable for gastrointestinal diseases and are increasingly utilized in laparoscopic operations. Liver surgery applications for this technique are continuing to emerge, and in this study, we introduced the use of stapling devices to hepatic surgery. METHODS: We examined the operative procedure and efficacy of hepatic resections using stapling devices as follows: transection of Glisson's pedicle and the hepatic vein using endolineal stapling devices in right and left lobectomies; bisegmentectomy II and III en masse using a stapling device; and application of endolineal stapling devices to vessel transections and dissections of the hepatic parenchyma in laparoscopic hepatectomies. RESULTS: It was considered useful to tactfully apply stapling devices to vessel transections and dissections of the hepatic parenchyma in order to simplify the operative procedures of right or left lobectomies and lateral segmentectomies. Furthermore, the use of endoscopic stapling devices was an acceptable alternative to vessel transactions and dissections of the hepatic parenchyma in laparoscopic hepatectomies. CONCLUSIONS: We believe that stapling devices will become utilized in liver surgery hereafter.

Hepatectomy↗

PubMed2004

Cerebrospinal fluid cytokines in Salmonella urbana encephalopathy.

We present a case report of encephalopathy associated with Salmonella urbana infection in a child. A 5-year-old boy was admitted to our clinic with convulsions and coma. Cerebrospinal fluid (CSF) interleukin-6 (IL-6) and IL-8 were elevated at onset and were decreased within normal limit on the fifth day. Residual neurological deficits included severe mental deficits and spastic tetraplegia. High levels of CSF proinflammatory cytokines might be related to central nervous system (CNS) disease activity. Although encephalopathy is a rare complication of non-typhi Salmonella infection, it should be borne in mind as an occasionally serious and potentially lethal disease.

Brain↗

PubMed2003

DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes.

To elucidate the role of intraepithelial lymphocytes (IEL) and enterocytes in the defense mechanism of the small intestine, we designed experiments to stimulate the IEL by anti-CD3epsilon, anti-TCRalphabeta, or anti-TCRgammadelta monoclonal antibodies (mAbs), and to examine the subsequent changes to the enterocytes. The enterocytes of the duodenum and jejunum, but not of the ileum, showed massive DNA fragmentation 30 min after intraperitoneal injection of anti-CD3 mAb. These responses were also induced by anti-TCRgammadelta mAb, but not by anti-TCRalphabeta mAb, and were completely inhibited by cyclosporin A. Nearly half of the enterocytes of the villi in the duodenum and jejunum were exfoliated into the lumen 4 h after the injection of the mAb. Administration of anti-CD3 mAb also induced DNA fragmentation in Fas-deficient MRL/lpr mice, indicating that the Fas-Fas ligand system was not involved in these events. The anti-CD3 mAb treatment also induced massive DNA fragmentation in the intestinal epithelium of the duodenum and jejunum in TNF-receptor-1-deficient mice, whereas TNF-alpha induced only the detachment of intestinal epithelium of wild-type mice, implying the dissociation of two independent factors and/or mechanisms for DNA fragmentation and the subsequent epithelial cell detachment in the murine duodenum and jejunum. The mAb failed to exfoliate the epithelium in TNF-R1-deficient mice. Thus, TCRgammadelta(+) IEL, when treated with anti-CD3 or anti-TCRgammadelta mAbs, induced rapid DNA fragmentation and subsequent detachment of the duodenal and jejunal epithelia, but not in the ileum ("the silent ileum"), partly because of the paucity of TCRgammadelta(+) IELs in the ileum.

Animals↗

PubMed2003

Distribution of two types of lymphocytes (intraepithelial and lamina-propria-associated) in the murine small intestine.

The intestine, which is exposed to nutrition and to food-derived antigens and microbes including viruses and bacteria, might be an important site for the immune response. Crucial structural and functional differences exist between the small and large intestine, regional differences even having been demonstrated within the small intestine. Accordingly, intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) might be heterogeneous among the different intestinal regions. The aim of this study has been to describe, as accurately as possible, the numbers and T-cell receptor (TCR) phenotypes of IELs and LPLs present in distinct regions of the murine small intestine under physiological conditions. Using an immunohistological technique to differentiate IELs from LPLs, the differential enumeration of IELs and LPLs in distinct regions of the murine small intestine, based upon their definition originally determined by their location, has been performed for the first time and has demonstrated that (1) there are more IELs than LPLs in the duodenum and jejunum, but more LPLs than IELs in the ileum, (2) in the duodenum and jejunum, TCRgammadelta IELs account for 70%-75% of the total CD3(+) IELs, a much greater percentage than previously reported, (3) the ratio of TCRgammadelta to TCRalphabeta IELs is inverted in the ileum, with more than 75% IELs being TCRalphabeta-positive, (4) the lamina propria forms one functional unit throughout the small intestine in terms of the TCR subset components (TCRalphabeta:TCRgammadelta=3:1), and (5) the ileum is entirely different from other regions of the small intestine. To deepen our understanding of the functional significance of the small intestine as an immunologically competent organ, the precise distributions of IELs and LPLs, the ratio of their various subsets, and the strict distinction of IELs and LPLs, as described in this study, is indispensable.

Animals↗

PubMed2003

Phylogenetic characterization of Orientia tsutsugamushi isolated in Taiwan according to the sequence homologies of 56-kDa type-specific antigen genes.

Fourteen strains of Orientia tsutsugamushi isolated in Taiwan were characterized by sequencing 56-kDa type-specific antigen genes and patterns of restriction fragment length polymorphism (RFLP) predicted by a computer program. The strains showed high varieties in sequence homologies and were classified to 10 types by predicted patterns of RFLP. Furthermore, all Taiwan strains were not identical in typing with strains analyzed previously. These results suggest that there are various types of O. tsutsugamushi in Taiwan that are different from those distributed in other countries.

Antigens, Bacterial↗

PubMed2003

Effect of mild hypothermia on focal cerebral ischemia. Review of experimental studies.

The purposes of this review are to clarify the effect of hypothermia therapy on focal cerebral ischemia in rats, and to consider the relevancy of its application to human focal cerebral ischemia. Since 1990, 26 reports confirming the brain-protecting effect of hypothermia in rat focal cerebral ischemia models have been published. Seventy-four experimental groups in these 26 reports were classified as having transient middle cerebral arterial occlusion (MCAO) with mild hypothermia (group A; 43 groups), permanent MCAO with mild hypothermia (group B; 14 groups), permanent MCAO with deep hypothermia (group C; 8 groups) and transient or permanent MCAO with mild hyperthermia (group D; 9 groups). The results were evaluated as the % infarct volume change caused by hypothermia or hyperthermia compared with the infarct volume in normothermic animals. The effectiveness was confirmed in 36 (83%) of the 43 groups in group A, 10 (71%) of the 14 in group B, and six (75%) of the eight in group C. The infarct volume of eight of the nine groups in group D was markedly aggravated. The percent infarct volume change was 55.3% +/- 27.1% in group A, 57.6% +/- 24.7% in group B, 60.8% +/- 45.5% in group C, and 189.7% +/- 89.4% in group D. For effective reduction of the infarct volume, hypothermia should be started during ischemia or within 1 h, at latest, after the beginning of reperfusion in the rat transient MCAO model. However, it is not clear whether this neuroprotective effect of hypothermia can also be observed in the chronic stage, such as several months later. Keeping the body temperature normothermic in order to avoid mild hyperthermia seems to be rather important for not aggravating cerebral infarction. Clinical randomized studies on the efficacy of mild hypothermia for focal cerebral ischemia and sophisticated mild hypothermia therapy techniques are mandatory.

Animals↗

PubMed2003

Relationship between heart rate variability and left ventricular remodeling after reperfused first anterior wall acute myocardial infarction.

The aim of the present study was to test the hypothesis that inadequate improvement in heart rate variability (HRV) in the healing stage of acute myocardial infarction (AMI) is associated with left ventricular (LV) remodeling. The study group comprised 20 patients (14 men, 6 women; mean age, 61+/-12 years) with a reperfused first anterior AMI (</=24 h). The standard deviation of normal RR intervals (SDNN) was calculated from the 24-h ambulatory electrocardiogram recorded on day 3 of admission and at predischarge from the hospital. Left ventriculography was performed immediately after primary angioplasty and at predischarge. The change in SDNN (deltaSDNN) was compared with the change in the LV end-systolic volume index (deltaLVESVI), a parameter of LV remodeling. SDNN increased from 73+/-19 ms on day 3 to 109+/-35 ms at predischarge (p=0.0003). SDNN at predicharge and deltaSDNN correlated negatively with deltaLVESVI (r=-0.52, p=0.02, and r=-0.61, p=0.004, respectively), whereas SDNN on day 3 did not correlate with deltaLVESVI. Multiple regression analysis selected deltaLVESVI (p=0.02) as an independent factor of deltaSDNN. This study indicates that deltaSDNN and SDNN at predicharge are associated with deltaLVESVI in patients with a reperfused first anterior wall AMI, indicating that persistently reduced HRV is associated with postinfarction LV remodeling.

Aged↗

PubMed2003

Osteopontin is released from the heart into the coronary circulation in patients with a previous anterior wall myocardial infarction.

The present study was designed to clarify whether osteopontin, an extracellular matrix protein, is released from the heart into the coronary circulation in patients with a previous (>3 months) anterior wall myocardial infarction (MI). Using a commercially available enzyme immunoassay kit, plasma concentrations of osteopontin were measured in 30 patients (26 men, 4 women; mean age, 61+/-12 years). Blood samples were obtained from the aortic root and coronary sinus. The difference in the plasma concentrations of osteopontin in the aortic root and coronary sinus, which reflects the cardiac production of osteopontin released into the coronary circulation, was compared with the left ventricular ejection fraction (LVEF) and volumes obtained from contrast left ventriculography. Plasma osteopontin concentrations were significantly higher in the coronary sinus than in the aortic root (672+/-446 vs 610+/-398 ng/ml, p=0.02). The transcardiac gradient of plasma osteopontin concentration correlated negatively with LVEF (r=-0.55, p=0.0005) and positively with left ventricular (LV) end-diastolic (r=0.63, p=0.0001) and end-systolic volume indexes (r=0.79, p<0.0001). This is the first study to show that in patients with a previous anterior wall MI osteopontin is released from the heart into the coronary circulation in proportion to the LV systolic function and volumes, suggesting that this extramatrix protein is associated with post-MI LV remodeling.

Aged↗

PubMed2003

Effects of atorvastatin and pravastatin on malondialdehyde-modified LDL in hypercholesterolemic patients.

The aim of the present study was to compare the effects of atorvastatin and pravastatin on lipid parameters and the concentration of malondialdehyde-modified low-density lipoprotein (MDA-LDL) in hypercholesterolemic patients. A total of 17 patients (10 men, 7 women; mean age, 68+/-9 years) who were indicated for drug therapy based on the National Cholesterol Education Program II underwent an 8-week regimen of atorvastatin (10 mg/day) or pravastatin (10 mg/day) with a 4-week washout period between drugs. After an overnight fast, lipid parameters and MDA-LDL concentration were measured before and after the 8-week treatment with each drug. Both atorvastatin and pravastatin produced significant reductions in low-density lipoprotein (LDL) cholesterol and MDA-LDL concentrations, with a significant increase in high-density lipoprotein cholesterol concentration. The percent reductions in LDL cholesterol and MDA-LDL concentration were significantly greater with atorvastatin than pravastatin (46 +/-6% vs 24+/-10%, p<0.0001, and 44+/-10% vs 14+/-13%, p<0.0001, respectively). The ratios of percent reductions in MDA-LDL concentrations and percent reductions in LDL cholesterol concentrations were significantly greater for atorvastatin than pravastatin (0.96+/-0.19 vs 0.59+/-0.55, p<0.0001). In conclusion, atorvastatin reduced serum concentrations of LDL cholesterol and MDA-LDL to a greater degree than pravastatin, indicating that atorvastatin not only has stronger lipid-lowering effects, but also stronger antioxidative effects than pravastatin.

Aged↗

PubMed2003

Natural hypothermia immediately after transient global cerebral ischemia induced by spontaneous subarachnoid hemorrhage.

OBJECT: Spontaneous subarachnoid hemorrhage (SAH) has an aspect of graded transient global cerebral ischemia. The purpose of the present study was the documentation of sequential changes in body temperature immediately after SAH-induced transient global cerebral ischemia in humans. METHODS: Patients admitted within 12 hours after the initial onset of SAH were examined retrospectively (426 patients). Patients with unruptured cerebral aneurysms served as a control group (73 patients). Body temperature measured at the axilla on admission was analyzed. The grade of SAH was established according to the Glasgow Coma Scale (GCS): Grade I, GCS Score 15; Grade II, GCS Score 11 to 14; Grade III, GCS Score 8 to 10; Grade IV, GCS Score 4 to 7; and Grade V, GCS Score 3. The mean body temperature of patients in the control group was 36.49 +/- 0.45 degrees C (mean +/- standard deviation). The mean body temperature of patients in the SAH group who had been admitted within 4 hours of onset for Grades I to V were significantly different (p < 0.001, analysis of variance [ANOVA]): 36.26 +/- 0.7 degrees C, 59 patients; 35.98 +/-0.85 degrees C, 73 patients; 35.52 +/- 0.79 degrees C, 25 patients; 35.9 +/- 1.09 degrees C, 108 patients; and 35.56 +/- 1.14 degrees C, 73 patients, respectively. These values were significantly lower than those in control volunteers, except for patients with Grade I SAH. The reduction in body temperature was unrelated to the location of the cerebral aneurysm and was not the product of circadian rhythm. The temperatures of patients in the SAH group who were admitted beyond 4 hours after onset for each grade were significantly different (p < 0.01, ANOVA): 36.8 +/- 0.91 degrees C, 36 patients; 36.74 +/- 0.68 degrees C, 31 patients; 36.73 +/- 0.38 degrees C, three patients; 37.41 +/- 1.37 degrees C, 17 patients; and 38.9 degrees C, one patient, respectively. These values were significantly higher than those in patients admitted within 4 hours of SAH onset for all grades except Grade V, and significantly higher than control values in patients with Grades I and IV SAH. CONCLUSIONS: These results indicate that body temperature falls and then rises immediately after the SAH-induced transient global cerebral ischemia without cardiac arrest in humans. The reduction in temperature may be a natural cerebral protection mechanism that is activated shortly after ischemic insult.

Adult↗

PubMed2003

In vitro reactivation of human immunodeficiency virus-1 upon stimulation with scrub typhus rickettsial infection.

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and beta-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.

Cytokines↗