Search PubMed⌕ Search

Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 541 records · Page 30Linked to original sources

A novel fucosylated glycosphingolipid from the millipede, Parafontaria laminata armigera.

A novel fucosylated glycosphingolipid (GL-3a) was isolated and purified from whole tissues of the millipede, Parafontaria laminata armigera. Its chemical structure was characterized as Man beta 1-4(Fuc alpha 1-3)Glc beta 1-ceramide (I3 alpha Fuc,MlOse2Cer) by gas-liquid chromatography, permethylation study, partial acid hydrolysis, exoglycosidase degradation, TLC/enzyme-immunostaining, negative fast atom bombardment-mass spectrometry and proton nuclear magnetic resonance spectroscopy. This compound was unique in containing a fucose branch linked to the glucose residue of the disaccharide, mannosylglucose. The ceramide moiety was mainly composed of d17:1 (64.3%) and d18:1 (20.0%) sphingoids, and 22:0 (41.8%), 23:0 (16.4%) and 24:0 (15.8%) fatty acids.

Animals↗

E1A repression of IL-6-induced gene activation by blocking the assembly of IL-6 response element binding complexes.

Some viral products interfere with host antiviral defense mechanisms. Adenovirus E1A represses IFN signal transduction pathways which induces gene activation and an antiviral state. Both IFN and IL-6 activate Jak/Tyk protein tyrosine kinases and the STAT (signal transducer and activator of transcription) family proteins. We showed that 12S E1A repressed IL-6 signals activating the junB promoter and the two IL-6 response elements (REs), JRE-IL6 and type II IL-6 RE (also called acute phase response element), required for IL-6-induced activation of the junB promoter and the type II acute phase reactant genes, respectively, in hepatocytes. Conserved region 1 of the 12S E1A was responsible for the repression. Target molecules of the repression by E1A appeared to be IL-6-inducible DNA-binding proteins acting on the IL-6 REs. In a rat 3Y1 cell line stably expressing E1A, the levels of IL-6-induced IL-6 RE binding proteins were severely reduced compared with those in a parental 3Y1 cell line. Moreover, we found that the levels of the STAT family proteins including Stat1-alpha (p91), Stat1-beta (p84), Stat2 (p113), and Stat3 were decreased by the stable expression of adenovirus E1A. The E1A-induced reduction in the amount of DNA-binding proteins seemed to be partly responsible for the decreased transcriptional activity of the IL-6 RE-driven gene expression in response to IL-6. This repression mechanism may be applicable to the E1A repression of IFN-gamma-induced gene activation.

Adenovirus E1A Proteins↗

Organization and expression of the mouse spot35/calbindin-D28k gene: identification of the vitamin D-responsive promoter region.

Spot35/calbindin-D28k is transcriptionally induced by 1,25-dihydroxyvitamin D3 in the intestine and kidney but not the brain. The structural organization of the mouse calbindin-D28k gene has now been determined and its transcriptional activation examined. Two direct repeat motifs homologous to other vitamin D-responsive elements were identified at positions -2295 to -2281 and -1160 to -1146. Undirectional deletion analyses of the 5' flanking region indicated that the sequence between -1339 and -1038 conferred vitamin D sensitivity on a reporter construct. Furthermore, the proximal (AGGTGAtgaAAGTCA), but not the distal (AGGTGAacaGGTTCA), direct repeat enhanced 1,25(OH)2D3-stimulated transcription in an orientation-dependent manner when placed upstream of the heterologous SV40 promoter. In conclusion, the proximal direct repeat plays a critical role in mediating the vitamin D-induced expression of calbindin-D28k in the kidney.

Animals↗

Transcriptional activation of the IL-6 response element in the junB promoter is mediated by multiple Stat family proteins.

IL-6 signals activate an IL-6 response element in the junB promoter, JRE-IL6, in a Ras-independent manner. IL-6 rapidly induced a DNA-binding activity to the Ets binding site of JRE-IL6 (JEBS), one of necessary DNA motifs of the IL-6 response element. The IL-6-induced JEBS-binding activity was indistinguishable from those to acute phase response element (APRE) in both kinetics of induction and its DNA-binding specificity. Purified APRE binding factors (APRFs) from IL-6-stimulated rat liver were found to be composed of multiple Stat3-related proteins and Stat1. Moreover the purified APRFs specifically made a complex with JRE-IL6 with the same mobility as that observed in the crude extracts. These results indicate that an immediate early signal of IL-6 leading to activation of JRE-IL6 is mediated by STAT family transcription factors.

Animals↗

Synthetic studies on an oligosaccharide of a glycolipid from the spermatozoa of bivalves. IX. Synthesis of lipids I, II, and IV.

Glycosphingolipids isolated from the spermatozoa of the freshwater bivalve, Hyriopsis schlegelii, have a unique structure containing one or two mannosyl residues and novel linkages, including an internal fucopyranosyl residue, as well as terminal xylosyl and 4-O-methyl-D-glucopyranosyluronic acid groups. The octasaccharide of lipid IV was synthesized as follows. Condensation of methyl (2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-methyl-alpha-D-galactopyranosyl )- (1-->3)-[methyl(2,3-di-O-acetyl-4-O-methyl-beta-D-glucopyranosyluronate) - (1-->4)]-2-O-benzyl-1-thio-alpha,beta-L-fucopyranoside (18) with (3-O-acetyl-6-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-- >2)- (3,4,6-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-[(2,3,4-tri-O-acetyl -beta - D-xylopyranosyl)-(1-->2)]-(4,6-di-O-acetyl-beta-D-mannopyranosyl)-(1-->4 )- 2,3-di-O-acetyl-1,6-anhydro-beta-D-glucopyranose (14), in the presence of dimethyl (methylthio) sulfonium triflate (DMTST), gave the corresponding octasaccharide (19). Removal of the protecting groups gave 2-acetamido-2-deoxy-3-O-methyl-alpha-D-galactopyranosyl-(1-->3)-[4-O- methyl-beta-D-glucopyranosyl uronic acid-(1-->4)]-alpha-L-fucopyranosyl-(1-->4)-2-acetamido-2-deoxy-beta-D- glucopyranosyl-(1-->2)-alpha-D-mannopyranosyl-(1-->3)- beta-D-xylopyranosyl- (1-->2)]-beta-D-mannopyranosyl-(1-->4)-1,6-anhydro-beta-D-glucopyranose (22). The other two oligosaccharides that constitute the partial structure of lipid IV, called lipid I and II, were also synthesized.

Animals↗

pct1+, which encodes a new DNA-binding partner of p85cdc10, is required for meiosis in the fission yeast Schizosaccharomyces pombe.

The transcriptional activation of genes at late G1 is an important regulatory step in the commitment to a new cell division cycle. In Schizosaccharomyces pombe, this regulation is mediated by MCB elements that serve as binding sites for the MBF/DSC-1 complex. The cdc10(+)-encoded protein is a component of this complex. We report the cloning of a new gene, pct1+, encoding a 73-kD protein that interacts with p85cdc10 to form an MCB-binding heteromer. Pct1+ is related to, but distinct from, the res1+/sct1+ gene that also encodes a p85cdc10 partner. p73pct1 has centrally located ankyrin repeats and a putative amino-terminal DNA-binding domain that has extensive sequence similarity to the DNA-binding domains of the Saccharomyces cerevisiae SWI4 and MBP1 proteins. The p73pct1/p85cdc10 complex binds both in vitro and in vivo to MCB but not SCB or E2F sites. Overexpression of pct1+ is sufficient to rescue the growth of the cdc10-129 temperature-sensitive mutant at the restrictive temperature, although it is unable to rescue a cdc10 null mutation. A deletion of pct1+ is not lethal but does result in a severe meiotic defect. Our results indicate that there are two cdc10-containing heteromeric complexes that bind to MCB elements and play differential roles in mitotic division and meiosis.

Amino Acid Sequence↗

Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats.

To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.

Animals↗

Synthesis of a glycopeptide with phytoalexin elicitor activity. I. Synthesis of a triglycosyl L-serine and a triglycosyl L-seryl-L-proline dipeptide.

A stereocontrolled synthesis of the model compound for the phytoalexin elicitor-active glycoprotein is described. Glycosylation of the disaccharide, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl-(1-->6)-2,3,4-tri-O-acetyl- alpha- D-mannopyranosyl trichloroacetimidate, with N-(carbobenzoxy)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-L- serine methyl ester or N-(carbobenzoxy)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-L- seryl-L- proline methyl ester by use of AgOTf gave the desired trisaccharide-serine or trisaccharide-seryl-proline derivatives, which were transformed into beta-D-glucopyranosyl-(1-->6)-alpha-D-mannopyranosyl-(1-->6)-alpha-D- mannopyranosyl-(1-->3)-L-serine and triglycosyl-(1-->3)-L-seryl-L-proline via removal of the N-carbobenzoxy group, followed by deacylation.

Carbohydrate Conformation↗

Protein alterations in age-related cataract associated with a persistent hyaloid vascular system in senescence-accelerated mouse (SAM).

The occurrence of age-related cataract associated with a persistent hyaloid vascular system is the most prominent feature in SAMP9, an inbred strain of Senescence-accelerated Mouse. To examine the cataractogenesis, we analysed protein changes in the process of cataract formation in the lens. The cataractous lenses showed a striking decrease in water-soluble protein content, in contrast to increases in the amount of water insoluble protein. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blots of water-soluble protein in the cataractous lenses showed additional high molecular weight beta-crystallin proteins of about 43 kDa, concomitant with decreased amounts of 29-kDa and 31-kDa beta-crystallins and 21-kDa gamma-crystallin, as compared with findings in normal lenses. Although there was no apparent difference between the patterns of SDS-PAGE of urea-soluble and urea-insoluble proteins isolated from cataractous and normal lenses, slightly increased reactivity of bands around 43 kDa against anti-beta-crystallin antibody was observed in cataractous lenses. The calcium content was elevated and activity of transglutaminase was increased in the cataractous lenses. While the molecular weight of beta-crystallin polymers cross-linked in vitro by exogenous transglutaminase was not completely compatible with those of high molecular weight beta-crystallins observed in the cataractous lenses, these findings do suggest the contribution of this enzyme to production of high molecular weight beta-crystallins and to insolubilization of these proteins in the cataractous lenses in SAMP9.

Aging↗

Molecular analysis of the dhp1+ gene of Schizosaccharomyces pombe: an essential gene that has homology to the DST2 and RAT1 genes of Saccharomyces cerevisiae.

The DST2 gene of Saccharomyces cerevisiae encodes a DNA strand exchange protein, STP beta, which is required for homologous recombination in both mitotic or meiotic cells. We have cloned a DST2-related gene from the fission yeast Schizosaccharomyces pombe and designated it dhp1+. The nucleotide sequence of dhp1+ revealed an open reading frame encoding a protein composed of 991 amino acids. The predicted amino acid sequence was significantly homologous to the S. cerevisiae STP beta, but lacked the carboxy-terminal sequence present in STP beta. Furthermore, dhp1+ shows greater homology to RAT1/HKE1, a gene which is involved in RNA trafficking and processing. Genetic experiments showed that dhp1+ on an S. cerevisiae expression vector could rescue both the defects of the S. cerevisiae DST2 disruptant, slow growth rate and a sporulation defect, and the lethality of the S. cerevisiae rat1ts mutation. This implies the functional similarity of dhp1+ to both DST2 and RAT1. However unlike DST2, dhp1+ is an essential gene for cell growth in S. pombe, suggesting that dhp1+ is not the true homologue of DST2 but rather of RAT1 in S. pombe. The possible roles of dhp1+ in recombination and cell growth in S. pombe are discussed.

Amino Acid Sequence↗

Outcomes of 116 patients with hepatocellular carcinoma.

We studied the outcomes of 116 patients with hepatocellular carcinoma (HCC) diagnosed in our hospital between January 1980 and August 1992. The patients were divided into groups according to the principal treatment procedure. The 3-year survival rates in the patients treated by percutaneous ultrasonically guided ethanol injection (PEI), operation (hepatic resection), and transcatheter hepatic arterial embolization (TAE) were 90.9%, 53.6%, and 29.0%, respectively. None of the patients treated by one-shot injection of an anticancer agent into the hepatic artery and chemotherapy survived for more than 2 years. The outcomes of the patients treated by PEI and hepatic resection were significantly better than those of the patients treated by the other procedures. There was no significant difference when the patients were stratified according to the year of detection. The 3-year survival rate was 57.3% for 19 patients in whom HCCs were detected during clinical follow-up for chronic liver disease and 17.3% for the other 97 patients. We concluded that hepatic resection in patients with good liver function and PEI for early HCC yielded significantly better survival rates than the other procedures. Moreover, for early detection and treatment of HCC, we recommend clinical follow-up of patients with chronic liver disease.

Adult↗

Pancreatic resection for periampullary carcinoma in the elderly.

The effect of pancreatic resection for periampullary carcinoma in the elderly was studied by comparing the pre- and perioperative factors affecting survival in 102 patients less than 70 years of age (group A) with those in 28 patients 70 years and older (group B). Concomitant cardiac and pulmonary diseases were significantly more frequent in group B (P < 0.05), but the difference in routine laboratory data was not significant. The overall operative mortality was 7% (7/102) in group A and 18% (5/28) in group B, while the actuarial 5-year survival rates were 31% in group A and 23% in group B, these differences not being significant. A multivariate analysis using a logistic model showed that blood loss was the greatest risk factor for early postoperative death in the elderly patients, whereas anastomotic dehiscence and postoperative bleeding were significant factors in the younger patients. Thus, we conclude that age is not a contraindication to pancreaticoduodenectomy which offers the only hope for long-term survival in patients with periampullary carcinoma; however, meticulous dissection to minimize blood loss is especially important in elderly patients.

Actuarial Analysis↗

Use of immobilized histidine in assay for endotoxin in patients with liver disease.

The Limulus amebocyte lysate (LAL) test has the disadvantage of being influenced by various inhibitors and activators. We have developed a method for the LAL reaction that involves the specific adsorption and isolation of endotoxin using a membrane filter unit and immobilized histidine; in this present study we used the method to measure endotoxin in the plasma of patients with acute or chronic liver disease. The adsorbed endotoxins are separated from LAL-inhibitors or -activators by the membrane filter unit, and their activity is directly assayed with the LAL reagent in a filter cup without any inhibition or activation. The study population consisted of 23 subjects, 3 with fulminant hepatitis and 20 with cirrhosis (9 with esophageal varices and 11 without). All 3 (100%) of the samples of plasma from patients with fulminant hepatitis were positive for endotoxin, as were the samples of 7 (78%) of the 9 patients with cirrhosis and esophageal varices, and 2 (18%) of the 11 patients with cirrhosis but without such varices. The results suggested that this method appears to be useful for assaying the concentration of endotoxin in patients with fulminant hepatitis or cirrhosis of the liver.

Acute Disease↗

Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women, evaluated by dual-energy X-ray absorptiometry.

To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirrhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P < 0.001) and in those with cirrhosis of the liver (P < 0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone.

Absorptiometry, Photon↗