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Biomedical subjects

Y Tanaka

Publications and source records attributed to Y Tanaka.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of carbonic anhydrase isozyme VI (CA-VI) in bovine sera, saliva, milk and tissues.

Concentrations of bovine carbonic anhydrase isozyme VI (CA-IV) in bovine serum, saliva, normal milk, colostrum, submandibular gland, liver, and mammary gland were determined. CA-VI was purified from bovine saliva and an antibody to CA-VI was generated. The concentrations of CA-VI in the saliva (7.8 +/- 7.9 microg/ml), serum (2.1+/- 5.7 ng/ml), milk (7.9 +/- 12.1 ng/ml), submandibular gland (284.7 microg/g protein), liver (921.0 +/- 180.7 ng/g protein) and mammary gland (399.6 +/- 191.2 ng/g protein) were determined by ELISA. No seasonal change in CA-VI levels was observed in normal milk. The concentration of CA-VI in colostrum (day 1 post partum) was 119 ng/ml and decreased rapidly by 1 month following birth. Mammary gland contained much smaller amounts than the submandibular gland. CA-VI mRNA was detected in the liver and mammary gland of cow by RT-PCR. The ELISA used in this study proved to be a precise and sensitive method for determining CA-VI concentrations in saliva, serum, milk and tissue specimens from cows. The ELISA may enable the study of changes in CA-VI associated with hereditary or metabolic disorders of the salivary gland, mammary gland and liver using small samples of saliva, serum or milk.

Animals↗
PubMed2006

Identification of EGFR mutations in esophageal cancer.

BACKGROUND: It is well known that the prognosis for esophageal cancer is worse than for other digestive cancers in spite of multimodality treatment, and there is an urgent need to improve this situation. The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, was approved in Japan to treat advanced non-small cell lung cancer patients and several papers have since reported that the successfully treated patients had genetic mutations in EGFR. PURPOSE: The aim of this study was to investigate the existence of EGFR mutations in esophageal cancer cell lines and primary lesions, and also to explore the possibility of treating esophageal cancer using gefitinib. MATERIALS AND METHODS: Nineteen esophageal cancer cell lines were cultured and DNA was extracted using an ultracentrifugation method. Fifty cases of primary cancer and corresponding normal tissue samples were obtained and DNA was extracted using the same protocol. Nested PCR and DNA sequencing targeting exons 18, 19, 20 and 21 of EGFR were performed to investigate the presence of mutations in esophageal cancer cell lines and primary tumors. RESULTS: Three of the 19 cell lines had the same silent mutation at nucleotide 2607, a G-to-A substitution in exon 20. One of the 50 patients had an EGFR mutation in codon 719, resulting in an amino acid substitution from glycine to aspartic acid. CONCLUSION: EGFR mutations in esophageal carcinoma are rare but do exist, and thus gefitinib could be included in esophageal cancer treatment regimens by selecting those patients who possess such mutations.

Biomarkers, Tumor↗
PubMed2006

Calcium phosphate formation on titanium by low-voltage electrolytic treatments.

Electrochemical treatments are expected to be effective for the coating of calcium phosphate ceramics to a titanium substrate. In the present study, two types of chronoamperometry with a step potential and a cyclic wave potential at low voltage (up to 2.0 V) and low current density were performed in Hanks' solution to modify the surface characteristics of titanium. Titanium oxide film formed by self-passivation, that formed as reconstructed film during electrochemical treatments, and a calcium phosphate layer precipitated through treatments were characterised by X-ray photoelectron spectroscopy. The thickness and compositions of the surface films and layers were quantified from the XPS results. Calcium phosphate formation during immersion in Hanks' solution for 1.0 Ms was evaluated by scanning electron microscopy with energy-dispersive X-ray spectrometry. The results confirmed that the electrolytic treatments in this study were effective to accelerate calcium phosphate formation on titanium in Hanks' solution in spite of their lower voltage than conventional methods. The results also suggested that the hydroxyl group in the surface oxide film might contribute to the formation of calcium phosphate. This technique is a promising process for the treatment of thin titanium materials.

Calcium Phosphates↗
PubMed2006

Endoanal ultrasonography in the diagnosis and operative management of perianal endometriosis: report of two cases.

We report two cases of perianal endometriosis in which we were greatly assisted by endoanal ultrasonography. Patient 1 was a 43-year-old woman with perianal pain. Endosonography showed a hypoechoic mass in the anterior perianal region without involvement of the anal sphincter. Local excision was performed under spinal anesthesia without damage to the anal sphincter. Patient 2 was a 30-year-old woman with perianal pain coinciding with her menstrual period. Endosonography showed a heterogeneous mass containing cystic anechoic areas in the right anterior perianal region and involving the external anal sphincter. Wide excision, including the episiotomy scar and part of the external anal sphincter, and primary sphincteroplasty were performed under spinal anesthesia. According to our experience, preoperative endosonography is a reliable technique for visualizing perianal endometriosis and for diagnosing anal sphincter involvement. Operative management should be determined on the basis of preoperative and intraoperative ultrasonographic assessment.

Adult↗
PubMed2006

Difference of hepatitis B virus genotype distribution in two groups of mexican patients with different risk factors. High prevalence of genotype H and G.

BACKGROUND: Hepatitis B virus (HBV) has been classified in eight genotypes, from A to H (HBV/A to HBV/H). HBV genotypes were determined in two groups with different risk factors. METHODS: Group I consisted of 42 patients with chronic and acute hepatitis and group II with 25 men who have sex with men (MSM). HBV genotypes were determined by DNA sequencing of the S-gene. RESULTS: Both groups differed with respect to genotype distribution (p < 0.001). In group I, there were 31 (74%), 9 (21%) and 2 patients (5%) with HBV/H, HBV/D and HBV/A; respectively. In group II, HBV/H, HBV/A, and HBV/G were found in 13 (52%), 8 (32%) and 4 (16%) cases, respectively. By using an HBV/G-specific PCR, 3 more cases of HBV/G were identified in group II, rising to a total 28%. All HBV/G strains were present in coinfection with other HBV genotypes, 86% with HBV/H, and 14% with HBV/A. CONCLUSIONS: HBV/H predominated in both groups. A high frequency of HBV/G was found in MSM, which was always coinfected with HBV/H or HBV/A. Significant differences in HBV genotype distribution were also found, since HBV/D was present only in patients with liver disease, whereas HBV/G was present only in MSM.

DNA, Viral↗
PubMed2006

Amelioration of glucose tolerance by hepatic inhibition of nuclear factor kappaB in db/db mice.

AIMS/HYPOTHESIS: Recent studies have identified the involvement of inhibitor IkappaB kinase (IKK) in the pathogenesis of insulin resistance. To investigate the mechanism involved, we examined the role of nuclear factor kappaB (NF-kappaB), the distal target of IKK, in hepatic glucose metabolism. METHODS: To inhibit NF-kappaB activity, db/db mice were infected with adenovirus expressing the IkappaBalpha super-repressor. RESULTS: The IkappaBalpha super-repressor adenovirus infection caused a moderate reduction of NF-kappaB activity in liver. The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin-stimulated phosphorylation of Akt. On the other hand, quantification of mRNA in the liver revealed marked reduction of expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, concurrent with reduced expression of gene encoding peroxisome proliferator-activated receptor gamma coactivator-1alpha (PPARGC1A, also known as PGC-1alpha). Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection. CONCLUSIONS/INTERPRETATION: Our results indicate that moderate inhibition of NF-kappaB improved glucose tolerance through decreased gluconeogenesis associated with reduced PGC-1alpha gene expression in db/db mice, and suggest that inhibition of NF-kappaB activity in liver is a potentially suitable strategy for the normalisation of blood glucose concentration in type 2 diabetes.

AMP-Activated Protein Kinases↗
PubMed2006

Effect of the vortices on the nuclear spin relaxation rate in the unconventional pairing states of the organic superconductor (TMTSF)2PF6.

This Letter theoretically discusses quasiparticle states and nuclear spin relaxation rates T1-1 in the quasi-one-dimensional superconductor (TMTSF)2PF6 under a magnetic field applied parallel to the conduction chains. We study the effects of Josephson-type vortices on T1(-1) by solving the Bogoliubov-de Gennes equation for p-, d- or f-wave pairing interactions. In the presence of line nodes in pairing functions, T1(-1) is proportional to T in sufficiently low temperatures because quasiparticles induced by vortices at the Fermi energy relax spins. We also try to identify the pairing symmetry of (TMTSF)2PF6.

Journal Article↗
PubMed2006

Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis.

OBJECTIVES: Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC. METHODS: We analysed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScan. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation was observed by microscopy. RESULTS: Among many epithelial-expressed factors, macrophage colony-stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed in RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAECs were inhibited by M-CSF neutralizing antibody. CONCLUSIONS: M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.

Arthritis, Rheumatoid↗
PubMed2006

Clinicopathological features of pyothorax-associated lymphoma; a retrospective survey involving 98 patients.

To investigate clinicopathological features of pyothorax-associated lymphoma (PAL), we examined medical records of 98 patients (88 males and 10 females) with PAL at a median age of 70 years (range 51-86). Seventy-nine patients had a history of artificial pneumothorax. Median interval between diagnosis and artificial pneumothorax was 43 years (range 19-64). At diagnosis, performance status (PS) was 0-1 (n=56) and 2-4 (n=42). Clinical stages were I (n=42), II (n=26), III (n=8) and IV (n=22). Pathological diagnosis comprised diffuse large-B-cell (n=78) and peripheral T-cell lymphoma (n=1). Seventeen were treated supportively. The other 81 received aggressive treatments; chemotherapy (n=52), radiotherapy (n=7), surgery (n=4) and combination (n=18). Five-year overall survival (OS) was 0.35 (95% confidence interval, 24% to 45%). Causes of deaths were PAL (n=39), respiratory failure (n=13) and others (n=12). Multivariate analysis identified prognostic factors for OS; lactate dehydrogenase levels [hazard ratio (HR)=2.36; P=0.013], sex (female versus male) (HR=0.15; P=0.01), PS (2-4 versus 0-1) (HR=2.20; P=0.02), clinical stages (III/IV versus I/II) (HR=1.95; P=0.037) and chemotherapy (HR=0.31; P=0.01). Most patients with PAL are elderly and have comorbidities, while some of them achieve durable remission with appropriate treatments. These findings prompt us to establish an optimal treatment strategy on the basis of risk stratification of individual patients.

Aged↗
PubMed2006

ELMO1 increases expression of extracellular matrix proteins and inhibits cell adhesion to ECMs.

We have previously identified the engulfment and cell motility 1 (ELMO1) as a susceptibility gene for diabetic nephropathy. To elucidate the role of ELMO1 in the pathogenesis of chronic renal injury, we examined the expression of Elmo1 in the kidney of a rat model for chronic glomerulonephritis (uninephrectomy plus anti-Thy1.1 antibody [E30] injection). We found that the expression of the Elmo1 was significantly increased in the renal cortex and glomeruli of uninephrectomized rats injected with E30 compared to controls. By in situ hybridization, the expression of Elmo1 was shown to be elevated in the diseased kidney, especially in glomerular epithelial cells. In COS cells, the overexpression of ELMO1 resulted in a substantial increase in fibronectin expression, whereas the depletion of the ELMO1 by small interfering RNA (siRNA) targeting ELMO1 significantly suppressed the fibronectin expression in ELMO1 overexpressing and control cells. We also found that the expression of integrin-linked kinase (ILK) was significantly increased in ELMO1 overexpressing cells, and the ELMO1-induced increase in fibronectin was partially, but significantly, inhibited by siRNA targeting ILK. Furthermore, we identified that the cell adhesion to ECMs was considerably inhibited in cells overexpressing ELMO1. These results suggest that the ELMO1 contributes to the development and progression of chronic glomerular injury through the dysregulation of ECM metabolism and the reduction in cell adhesive properties to ECMs.

Animals↗
PubMed2006

Absence of tyrosine kinase mutations in Japanese colorectal cancer patients.

Tyrosine kinases, which are important regulators of intracellular signal-transduction pathways, have mutated forms that are often associated with oncogenesis and are attractive targets for therapeutic intervention. Recently, systematic mutational analyses of tyrosine kinases revealed that a minimum of 30% of colorectal cancer contain at least one mutation in the tyrosine kinases. To further explore these mutations, we examined all reported mutations of NTRK3, FES, KDR, EPHA3, NTRK2, JAK1, PDGFRA, EPHA7, EPHA8, ERBB4, FGFR1, MLK4 and GUCY2F genes in the 24 colorectal cancer cell lines. Unexpectedly, among 24 colorectal cancer cell lines, only two cell lines (LoVo and CaR1) harbored mutation C1408T (R470C) in MLK4 gene. The mutation rate was extremely low compared to that previously reported. Therefore, we analyzed mutations in 46 colorectal cancer samples resected from the same number of Japanese patients. Surprisingly, none of the 46 samples contained any of the mutations reported. Based on our study, we advise that a more comprehensive tyrosine kinase gene mutation assay is necessary in the future.

Aged↗
PubMed2006

Risk factors for de novo acute cardiac events in patients initiating hemodialysis with no previous cardiac symptom.

An initial major adverse cardiac event (MACE) is an important predictor of future cardiovascular events in patients with chronic kidney disease (CKD). We sought to identify factors influencing occurrence of initial MACE in new maintenance hemodialysis patients without previous cardiac symptoms during the predialysis phase of CKD. Among 112 participating patients with no predialysis cardiac history, 57 underwent coronary angiography, whereas the other 55 underwent stress thallium-201 single-photon emission computed tomography within 1 month of beginning hemodialysis to detect asymptomatic coronary artery disease (CAD). In subsequent follow-up for a median of 24 months, subjects experiencing an initial MACE were compared with those who did not have such an event based on several clinical parameters at the end of predialysis phase. Asymptomatic CAD was present in 47 patients (42%), who had a higher cumulative MACE rate, than subjects without CAD (49 vs 3%, P<0.001). Multivariate Cox's regression analysis showed that three variables independently predicted initial MACE: asymptomatic CAD (hazard ratio or HR, 611.31; 95% confidence interval or CI, 14.07-26549.23; P<0.001), diabetes (HR, 20.41; 95% CI, 2.07-200.00; P=0.010), and each 1 mg/l increment in C-reactive protein (CRP) (HR, 1.94; 95% CI, 1.27-2.94; P=0.002). In conclusion, detection of asymptomatic CAD, presence of diabetes, or elevated CRP at the end of the predialysis phase were significantly associated with occurrence of an initial MACE in CKD patients starting hemodialysis who had no CAD symptoms.

Aged↗
PubMed2006

Absence of PIK3CA hotspot mutations in hepatocellular carcinoma in Japanese patients.

A recent study revealed that the p110alpha (PIK3CA), catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is somatically mutated in many types of cancer. For example, PIK3CA is mutated in an estimated 35.6% of hepatocellular carcinoma (HCC) cases. To measure the frequency of PIK3CA hotspot mutations in Japanese HCC patients, exons 9 and 20 of the PIK3CA gene were sequenced in 47 clinical HCC samples. Contrary to expectations, no hotspot mutations were found any of the HCC samples. In addition, we found abnormally migrating waves near the end of exon 9 in the PCR chromatograms from 13 of the 47 samples. PCR amplification and subsequent cloning and sequencing revealed that these chromatograms contained two distinct sequences, the wild-type p110alpha sequence and a different sequence found on human chromosome 22q11.2, the Cat Eye Syndrome region, which contains a putative pseudogene of PIK3CA. These abnormally migrating waves were also found in noncancerous liver tissue, indicating that this was not a result of HCC-associated mutations. Therefore, it is likely that the percentage of hotspot mutations in the PIK3CA gene of Japanese HCC patients is lower than was previously reported.

Adult↗
PubMed2006

X-ray diffractometer combining synchrotron radiation and pulsed magnetic fields up to 40 T.

A synchrotron X-ray diffractometer incorporating a pulsed field magnet for high fields up to 40 T has been developed and a detailed description of this instrument is reported. The pulsed field magnet is composed of two coaxial coils with a gap of 3 mm at the mid-plane for passage of the X-rays. The pixel detector PILATUS 100K is used to store the diffracted X-rays. As a test of this instrument, X-ray diffraction by a powder sample of the antiferromagnet CoO is measured below the Néel temperature. A field-dependent lattice distortion of CoO due to magnetostriction is observed up to 38 T.

Journal Article↗
PubMed2006

Hormonal regulation of renal multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4) in mice.

Multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4) are expressed at much higher levels in female than male kidney. Sex steroids and sex-specific growth hormone (GH) secretion patterns often mediate gender-predominant gene expression. Thus, three models were used to investigate potential endocrine regulation of Mrp3 and Mrp4: (1) gonadectomized (GNX) mice with 17beta-estradiol (E2) or 5alpha-dihydroxytestosterone (DHT) replacement; (2) hypophysectomized (HPX) mice receiving E2, DHT, or simulated male-pattern (MP) or female-pattern (FP) GH secretion; (3) lit/lit mice, which have a spontaneous mutation in the growth-hormone releasing-hormone (GHRH) receptor, with simulated MP- or FP-GH secretion. GNX and HPX decreased Mrp3 mRNA levels compared with intact females. In both respective models E2 administration increased Mrp3 expression in GNX and HPX mice. DHT markedly repressed Mrp3 from GNX+placebo levels, however, this was not observed in the HPX model. In lit/lit mice, Mrp3 expression was lower than in wild-type controls, and MP-GH and FP-GH simulation slightly increased Mrp3 expression. Whereas GNX increased Mrp4 in males to female levels, HPX actually increased Mrp4 expression in both genders +375% and +66%, respectively. In both models DHT markedly repressed Mrp4. Furthermore, Mrp4 was higher in lit/lit than wild-type male mice, and simulation of MP-GH secretion suppressed female-predominant Mrp4 expression. In conclusion, these data indicate that E2 contributes to higher Mrp3 mRNA expression in females, yet a role for androgens in Mrp3 repression cannot be discounted. In contrast, Mrp4 mRNA is higher in females due to repression by both DHT and MP-GH secretion in males.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Uniform mixing of high-Tc superconductivity and antiferromagnetism on a single CuO2 plane of a Hg-based five-layered cuprate.

We report a site selective Cu-NMR study on underdoped Hg-based five-layered high-Tc cuprate HgBa2Ca4CU5O(12+delta) with a Tc = 72 K. Antiferromagnetism (AFM) has been found to take place at T(N) = 290 K, exhibiting a large antiferromagnetic moment of 0.67-0.69 microB at three inner planes (IP). This value is comparable to the values reported for nondoped cuprates, suggesting that the IP may be in a nearly nondoped regime. Most surprisingly, the AFM order is also detected with M(AFM)(OP) = 0.1 microB even at two outer planes (OP) that are responsible for the onset of superconductivity (SC). The high-Tc SC at Tc = 72 K can uniformly coexist on a microscopic level with the AFM at OP's. This is the first microscopic evidence for the uniform mixed phase of AFM and SC on a single CuO2 plane in a simple environment without any vortex lattice and/or stripe order.

Journal Article↗
PubMed2006

Spindle checkpoint protein Bub1 corrects mitotic aberrancy induced by human T-cell leukemia virus type I Tax.

Bub1 is a component of the mitotic spindle checkpoint apparatus. Abnormality of this apparatus is known to cause multinuclei formation, a hallmark of chromosomal instability (CIN). A549, aneuploid cell line, aberrantly passed through the mitotic phase and became multinuclei morphology in the presence of nocodazole. Time-lapse videomicroscopy showed unreported bizarre morphology, which we named 'mitotic lobulation' in A549 cells just before the exit from mitosis and multinuclei formation. External expression of wild-type Bub1-EGFP clearly suppressed the multinuclei formation by retaining A549 cells at the mitotic phase during 48 h of time-lapse observation. This suppressive effect on mitotic aberrancy should not be mere restoration of normal Bub1 function, because A549 cells express proper amount of Bub1, which distributed cytoplasm during interphase and concentrated at kinetochore in metaphase. Furthermore, external expression of wild-type Bub1-EGFP suppressed multinuclei formation induced by Tax both in A549 and HeLa cells. Tax is known to induce mitotic abnormality by binding and inactivating Mad1. These observations, therefore, suggest functional redundancy between Bub1 and other mitotic checkpoint protein(s) and a possibility of correction of mitotic aberrancy by external Bub1 expression.

Cell Cycle Proteins↗