Biomedical subjects

S Tanaka

Publications and source records attributed to S Tanaka.

At least 55 records · Page 3Linked to original sources

PubMed2005

Coronary arterial calcification is associated with albuminuria in type 2 diabetic patient.

AIM: Although microalbuminuria has been suggested as an independent risk factor for ischemic heart disease, the relationship between diabetic nephropathy and macroangiopathy remains unclear. Previously, we reported that coronary artery calcification detected by electron beam computed tomography (EBCT) could indicate the degree of coronary atherosclerosis in type 2 diabetic patients. In this study, we examine the association between coronary arterial calcification and microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two hundred and fifty-six patients, including 177 type 2 diabetic patients (106 patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic patients were evaluated by assessing the urinary albumin excretion rate and using EBCT to determine a coronary calcification score (CCS) and an aortic calcification score (ACS). RESULTS: No differences were observed regarding age, smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p < 0.05). In contrast, no difference was observed in ACS among three groups. Multiple regression analysis showed that CCS is significantly associated with urinary albumin excretion rate as well as age, duration of diabetes and serum creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking, serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is associated with coronary arterial calcification in diabetic patients.

Age Factors↗

PubMed2005

Double heterozygosity for a novel missense mutation of Ile304 to Asn in addition to the missense mutation His280 to Pro in the integrin beta3 gene as a cause of the absence of platelet alphaIIbbeta3 in Glanzmann's thrombasthenia.

BACKGROUND: Glanzmann's thrombasthenia (GT) is a hereditary bleeding disorder characterized by a defect in the expression or the function of alphaIIbbeta3. OBJECTIVES: The purpose of the present study was to identify genetic defects in a GT patient. METHODS: The expression of alphaIIbbeta3 was determined by flow cytometric analysis and Western blotting. We analyzed the cDNA sequences of both alphaIIb and beta3, and performed transfection experiments using COS7 cells to confirm that a specific mutation was responsible for the GT case. RESULTS: Flow cytometric analysis and Western blotting showed remarkably reduced expression of alphaIIbbeta3. Sequence analysis of the patient's cDNA indicated a new missense mutation that led to the amino acid substitution of Ile304 (ATC) with Asn (AAC) in exon 6 of the beta3 gene. This was in addition to the missense mutation of His280 (CAT) to Pro (CCT) in exon 5, which had been previously reported. The missense mutation of Ile304 (ATC) to Asn (AAC) in beta3 was found to be responsible for this GT case. This was because transfection experiments using COS7 cells indicated that alphaIIbbeta3 possessing Asn304 in beta3 was not expressed on the surface of the transfected cells. In addition, immunoprecipitation analysis demonstrated that alphaIIbbeta3 was absent inside the transfected COS7 cells possessing Asn304 in beta(3). CONCLUSION: In this study, we describe a new missense mutation (ATC to AAC) at position 1009 in exon 6 that leads to an amino acid substitution (Ile304 to Asn) in beta3, which is responsible for this GT case.

Adult↗

PubMed2005

Insertion of a C in the exon 28 of integrin alphaIIb gene leading to a frameshift mutation is responsible for Glanzmann thrombasthenia in a Japanese case.

BACKGROUND: Glanzmann thrombasthenia (GT) is a hereditary bleeding disorder caused by a qualitative or quantitative defect in the integrin alphaIIbbeta3. OBJECTIVE: Our objective is to identify the gene mutation that resulted in GT. PATIENTS AND METHODS: The patient was a 66-year-old male with a history of frequent bleeding. The expression levels of the integrin proteins in the platelets were determined by flow cytometry and Western blot analysis. The sequences of genomic DNA and mRNA encoding for alphaIIb and beta3 were analyzed by the dye-terminator cycle sequencing method. For transfection experiments, expression vectors encoding for wild-type alphaIIb, mutated alphaIIb, beta3, green fluorescent protein (GFP) fusion wild-type alphaIIb, GFP fusion mutated alphaIIb and DsRed fusion beta3 were constructed. These vectors were transfected to COS-7 cells, and the expression levels were determined. RESULTS: The alphaIIb protein was remarkably reduced in the patient's platelets, and gene analysis showed that the patient possessed compound heterozygous mutations in the alphaIIb gene. One was a C --> G substitution at the splice acceptor site (- 3) of exon 26 (CAG -->GAG) and the other was the insertion of an additional C at the region including six C bases between 2911 and 2916 in exon 28 (InsC). Transfection experiments using COS-7 cells showed that alphaIIb containing InsC had expressed and formed a complex with beta3, but had not been transported to the Golgi apparatus. CONCLUSIONS: In the present study the novel mutation InsC, leading to a frameshift that affects the transmembrane domain and the cytoplasmic tail, was found to be responsible for GT.

Aged↗

PubMed2005

The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development.

The docking protein FRS2alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2alpha is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2alpha also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos. These experiments underscore the critical role of FRS2alpha in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis.

Animals↗

PubMed2005

Loss of heterozygosity on chromosome 10p14-p15 in colorectal carcinoma.

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14-p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14-p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.

Aged↗

PubMed2005

Elastic moduli of thyroid tissues under compression.

The aim of this study was to evaluate the elastic moduli of thyroid tissues under uniaxial compression and to establish the biomechanical fundamentals for accurate interpretation of thyroid elastograms. A total of 67 thyroid samples (24 samples of normal thyroid tissue, 2 samples of thyroid tissue with chronic thyroiditis, 12 samples of adenomatous goiter lesions and 7 samples of follicular adenoma, 19 samples of papillary adenocarcinoma (PAC) and 3 samples of follicular adenocarcinoma (FAC)) obtained from 36 patients who had received thyroid surgery were subjected to biomechanical testing within three hours after surgical resection at precompression strains of 5%, 10% and 20% and applied strains of 1%, 2%, 5% and 10% of sample height. As a result, the mean values of elastic moduli for benign thyroid lesions at all examined precompression levels were significantly higher than those for normal thyroid tissue measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, benign thyroid nodule samples were 1.7 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 2.4 times. Stiffness of PAC samples was significantly higher than those for normal thyroid tissue and benign thyroid tumors measured at the same load (p<0.01). At low precompression (5%) and compression (1-2%) levels, PAC samples were 5.0 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 17.7 times. In contrast, samples of FAC were much softer than PAC (p<0.05) and were comparable in stiffness to normal thyroid tissues. The significant differences in the stiffness between normal thyroid tissue and thyroid tumors may provide useful information for accurate interpretation of thyroid elastograms.

Adult↗

PubMed2005

Immunocytochemical and phylogenetic distribution of aquaporins in the frog ventral skin and urinary bladder.

We recently cloned three cDNAs encoding frog aquaporin (AQP-h1, BAC07470; AQP-h2, BAC82379; and AQP-h3, BAC07471) from the ventral pelvic skin of the tree frog, Hyla japonica. The present study demonstrated that Hyla AQP-h2 was translocated from cytoplasmic pools to the apical plasma membranes of the granular cells in the bladder after antidiuretic hormone stimulation and that Hyla AQP-h2 and AQP-h3 behaved similarly in the ventral pelvic skin. Further, we found that terrestrial and tree frogs, but not aquatic and semiterrestrial-adapted frogs, absorbed water from their ventral pelvic skin by AQP-h3-like protein in concert with AQP-h2-like protein.

Animals↗

PubMed2005

Inflammatory cytokine gene expression in different types of granulomatous lesions during asymptomatic stages of bovine paratuberculosis.

The granulomatous lesions in bovine paratuberculosis have been classified into two types, i.e., the lepromatous type and the tuberculoid type. To clarify the immunopathologic mechanisms at the site of infection, we compared inflammatory cytokine gene expression between the two types of lesions. Samples were obtained from noninfected control cows (n = 5) and naturally infected cows (n = 7) that were diagnosed by enzyme-linked immunosorbent assay (ELISA) and fecal culture test. Although none of the infected cows showed clinical signs, tuberculoid lesions were observed in five cows (tuberculoid group) and lepromatous lesions in two cows (lepromatous group). Among the cytokines examined by reverse transcription-polymerase chain reaction (RT-PCR), Th2-type cytokines interleukin-4 (IL-4) and IL-10, and Th1-type cytokine IL-2 were expressed more significantly in the lepromatous group than in the tuberculoid (P < 0.01) and noninfected groups (P < 0.05). No statistical differences were observed in the expression of interferon-gamma, IL-1 beta, TNF-alpha, and GM-CSF among lepromatous, tuberculoid, and noninfected groups. Expression of proinflammatory cytokine IL-12 mRNA, however, did not differ among the three groups; IL-18 was expressed at lower levels in the lepromatous group than in the tuberculoid group and the noninfected group (P < 0.0001). Moreover, the number of cells in which IL-18 mRNAs were detected by in situ hybridization was markedly decreased in the lepromatous group. These results indicate that the formation of lepromatous-type lesions or tuberculoid-type lesions may be influenced by alterations in Th1/Th2-type cytokine production and that IL-18 may play an important role in a Th1-to-Th2 switch in paratuberculosis.

Animals↗

PubMed2005

[Off-pump versus conventional coronary artery bypass grafting in octogenarians].

Coronary artery bypass grafting (CABG) in elderly patients is becoming increasingly common. From January 1996 to February 2002, 836 patients underwent CABG in our hospital, of whom 33 patients (3.9%) were aged 80 years or older. We evaluated the clinical and short-term results of 7 cases of off-pump CABG (OPCAB) and 26 cases of conventional CABG (C-CABG). Mean patient age and preoperative risk factors were similar in both groups. The OPCAB group had significantly decreased operation time (218 versus 281 minutes, p<0.05), and the number of distal anastomoses was significantly fewer in the OPCAB group than in the C-CABG group (1.9 versus 3.8, p<0.05). The frequency of complete revascularization in C-CABG was significantly higher than that of the OPCAB group (84.6% versus 42.9%, p<0.05), and there were no differences in the incidence of major postoperative complications between the groups. There was no hospital death in either group. Cumulative cardiac event free rates were 75% at 1 year and 75% at 3 years in the OPCAB group and 100% at 1 year and 84.6% at 3 years in the C-CABG group (p<0.05). In conclusion, CABG is safe and effective for myocardial revascularization in octogenarians. Except for high-risk cases, complete revascularization with OPCAB or C-CABG should be performed, because favorable outcomes can be expected even in the elderly patients.

Aged↗

PubMed2005

[Autologous fibrin sealant preparing system in coronary artery bypass grafting].

Autologous fibrin sealant (AFS) which is not based on the conventional method of co-administering fibrinogen, thrombin and aprotinin was prepared by Vivostat system, and was used in coronary artery bypass grafting (CABG). The purpose of this study was to investigate the safety and efficacy of the AFS prepared by the Vivostat system. In 6 of 68 cases of CABG, normal AFS was not prepared due to device failures. AFS was prepared and sprayed in 62 cases. There were the total of 230 anastomosis sprayed AFS and the bleeding could not seen in 225 anastomosis. Surgical hemostatic procedures (4 cases) were or other sealant usage (1 case) was performed 5 bleeding anastomosis sites. The rate of hemostasis at the anastomosis using AFS was 97.8%. This study was conducted in patients undergoing CABG. In this group of patients, a number of commercial available fibrin sealant products are routinely used. The usefulness of Vivostat as medical device to prepare and administer AFS was confirmed in this study.

Adult↗

PubMed2005

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress.

Our previous data indicate that ischemia and amyloid beta peptide (A beta) cause an oxidative damage to macromolecules. In the present study we investigated the role of p53 protein in cell survival and death after administration of A beta. The experiments were carried out on pheochromocytoma cells (PC-12) and cortical primary neurons in culture. The cortical neurons were exposed (48 h, 10 microM) to the action of a short A beta 25-35 neurotoxic fragment and the involvement of p53 was evaluated after addition of the p53 inhibitor pifithrin-alpha. Changes in cell morphology were evaluated by 4', 6-diamidino-2-phenylindole staining and the concentration-dependent effect of pifithrin-alpha on cells viability was determined. Additionally, we studied the effect of pifithrin-alpha on neuronal survival in vivo after a 5-min global brain ischemia followed by 7 days' reperfusion in gerbils. We found that A beta enhanced apoptotic cell death in cortical primary neurons. Pifithrin-alpha, at a 10 microM final concentration, protected the neuronal cells from the apoptotic death. However, at concentrations of 0.1 and 1 mM, the p53 inhibitor decreased PC-12 cells' viability in a dose-dependent manner. In in vivo experiments we did not observe any neuroprotection by pifithrin-alpha in the CA1 hippocampal layer, which suggests that its effects strongly depend on the duration and type of an ischemic insult. Our data indicate that pifithrin-alpha affects neuronal cells in a dual manner. It has a protective effect at a low concentration, but becomes neurotoxic at higher concentrations.

Amyloid beta-Peptides↗

PubMed2004

Induction of canine pyometra by inoculation of Escherichia coli into the uterus and its relationship to reproductive features.

To characterize oestrus-related factors affecting the induction of and recovery from pyometra in bitches, 60 clinically healthy beagle bitches were used for induction of pyometra by inoculation of Escherichia coli into the uterus during oestrous and metoestrous stages. The animals were classified into the following six groups according to inoculation time: Days 1-10, 11-20, 21-30, 31-40, 41-50 and 51-60 after LH surge. The incidence of pyometra during the periods Days 11-20 and 21-30 after LH surge was 90.9% and 78.9% respectively, while that during Days 1-10 and 51-60 after LH surge was less than 20%, and the patterns of the incidence of pyometra and the serum progesterone levels were similar. There was no difference in the incidence of pyometra induced in bitches less than 5 years old compared to bitches over 6 years old. Oestrus in all of the bitches with pyometra induced by E. coli returned with or without PGF 2alpha treatment, unlike in bitches with spontaneous pyometra. The duration of the oestrous cycle in the non-treated and PGF 2alpha-treated groups was 231.4+/-55.2 days and 162.1+/-40.6 days (P < 0.001), respectively, and there was no difference in the rate of return of oestrus between the two groups. The conception rate in all of the bitches in which oestrus had returned was 81.8%. The above findings indicate that the period during which severe pyometra could be induced was limited to the early stage in metoestrus.

Animals↗

PubMed2004

An antibody to VacA of Helicobacter pylori in the CSF of patients with Miller-Fisher syndrome.

The authors examined antibodies against native vacuolating cytotoxin (VacA) of Helicobacter pylori in CSF from 12 patients with Miller-Fisher syndrome (MFS). The VacA protein was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis was carried out. Eight of 12 MFS patients had a specific immunoglobulin G antibody against VacA in the CSF. There is sequence homology between VacA and some membrane ion transport proteins, raising the possibility that A-VacA-Ab involves the ion channels in the node of Ranvier in some patients with MFS.

Adult↗

PubMed2004

Chronic gastritis with expression of inducible nitric oxide synthase is associated with high expression of interleukin-6 and hypergastrinaemia.

BACKGROUND AND AIMS: High levels of inducible nitric oxide synthase and nitrotyrosine in Helicobacter pylori-infected gastric mucosa may contribute to development of gastric cancer. We investigated the relation between expression of inducible nitric oxide synthase and proinflammatory cytokines in gastric mucosa and serum markers of gastritis. METHODS: The study included 103 patients with H. pylori infection. We examined levels of interleukin-1beta, interleukin-6 and interleukin-8 by enzyme-linked immunosorbent assay and evaluated expression of inducible nitric oxide synthase and nitrotyrosine by immunohistochemical staining. Furthermore, we assessed serum levels of pepsinogens, gastrin, anti-parietal cell antibody, nitrite and nitrate, as markers of gastritis. RESULTS: Thirty-seven of 103 (35.6%) gastric mucosa specimens showed simultaneous expression of inducible nitric oxide synthase and nitrotyrosine. In these patients (inducible nitric oxide synthase-positive group), the serum level of gastrin was significantly higher than that of the inducible nitric oxide synthase-negative group (509.5 +/- 141.5 pg/mL vs. 210.0 +/- 227.2 pg/mL; P < 0.01), whereas there were no significant differences in serum levels of pepsinogen, anti-parietal cell antibody, and nitrate and nitrite or in scores of histological gastritis. Interleukin-6 levels were significantly higher in the inducible nitric oxide synthase-positive group than in the inducible nitric oxide synthase-negative group (25.9 +/- 7.0 pg/mg protein vs. 10.6 +/- 4.9 pg/mg protein; P < 0.05). CONCLUSIONS: Inducible nitric oxide synthase-producing gastritis was correlated with high levels of interleukin-6. Patients with hypergastrinaemia should be carefully followed on a long-term basis to ensure that the development of any malignancy is detected early.

Adult↗

PubMed2004

Spatial and temporal expression of the ventral pelvic skin aquaporins during metamorphosis of the tree frog, Hyla japonica.

Most adult anurans absorb water through their ventral skin to maintain the proper water balance. We examined spatial and temporal expression of frog (Hyla japonica) aquaporins, Hyla AQP-h2 and AQP-h3 proteins, in the ventral pelvic skin by using specific antibodies. Immunofluorescence indicates that AQP-h2 and AQP-h3 first appear in the granular cells of the pelvic skin of the tadpoles at Gosner stage 42, and such labeling is seen in later stages as well. These findings were confirmed by Western blot analysis. In addition, Northern blot analysis demonstrated that V2-type vasotocin (AVT)-receptor mRNA is first expressed at the same stage as are the AQP proteins, which suggests a functional relationship between expression of AQP proteins and AVT receptor. Also, AQP expression in the ventral pelvic skin is consistent with the morphological changes that occur in the skin for adaptation from life in water to that on land.

Animals↗

PubMed2004

Transferrin microheterogeneity in fetal blood.

OBJECTIVES: To investigate the distribution of microheterogeneous subfractions of transferrin in fetal blood and the influence of highly sialylated transferrins on fetal growth. STUDY METHOD: Serum transferrin concentrations were determined by a standard turbidimetric assay. Microheterogeneous transferrin subfractions were assessed by crossed immunoisoelectric focusing. RESULTS: In normal term infants, total serum transferrin concentrations and percent distribution of highly sialylated transferrins (> or = 5-sialo-transferrins) were markedly lower; the percent distributions of hyposialylated transferrins (0- and 1-sialo-transferrins) were apparently higher than those in non-pregnant and pregnant women. There was no significant positive correlation between the serum concentrations of total transferrin or highly sialylated transferrins in infants' blood and birth weights (r = 0.187, p = 0.582; r = 0.374, p = 0.257, respectively). CONCLUSION: The transferrin microheterogeneity pattern shifted towards reduced glycosylation and sialylation in addition to a decrease in total transferrin concentration in fetal blood compared to that of non-pregnant and pregnant women. The concentrations of serum total transferrin and the highly sialylated transferrins in fetal blood, if higher than a certain level, did not seem to have any influence on normal fetal growth.

Female↗

PubMed2004

An extremely rare inversion of the preduodenal portal vein and common bile duct associated with multiple malformations. Report of an adult cadaver case with a brief review of the literature.

A preduodenal position of the portal vein (PDPV) is a very rare congenital anomaly; even rarer is its association with a preduodenal position of the common bile duct (PDCBD). To the seven cases of PDCBD mentioned in the literature, we add this particularly rare case which is associated with multiple abnormalities such as situs inversus totalis, intestinal malrotation, short pancreas, bilobed spleen, accessory spleen, and abnormal ramification of the celiac axis, superior mesenteric artery and renal arteries. Besides describing and illustrating this case, we also discuss the anatomy and embryology of these structures and briefly review the patterns of previously reported cases that we found. We performed an immunohistochemical examination of the pancreas to demonstrate the ventro-dorsal pancreas in our case. For the explanation of the embryology of the PDCBD, the ventro-dorsal pancreas and PDPV malformation, we emphasized the reverse rotation of the ventral pancreas and duodenum.

Abnormalities, Multiple↗

PubMed2004

Crystallization of a globular protein in lipid cubic phase.

We studied the crystallization of a globular protein, lysozyme, in the cubic phase of the lipid mono-olein. The solubility of lysozyme in salt solution decreased by a factor of approximately 4 when confined in cubic phase. Monte Carlo simulations and calculations show that this can be explained by the confinement of lysozyme molecules to the narrow water cells in the cubic phase.

Crystallization↗