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T Saitoh

Publications and source records attributed to T Saitoh.

At least 55 records · Page 3Linked to original sources

Bis(tetrahydrofuran-kappa O)(meso-5,10,15,20-tetraisopropylporphyrinato-kappa(4)N)iron(III) perchlorate.

The title complex, [Fe(C(32)H(36)N(4))(C(4)H(8)O)(2)]ClO(4), shows an S(4)-ruffled porphyrin ring, where the maximum deviation of the meso-carbon from the least-squares plane of the [Fe(C(20)N(4))] core is as high as 0.675 (9) A. This is the highest class of deviation among S(4)-ruffled iron(III) porphyrin complexes. The average Fe-N(p) bond distance is 1.967 (12) A (N(p) denotes an N atom of the equatorial ligand).

Crystallography, X-Ray↗

Potent and long-lasting action of lafutidine on the human histamine H(2) receptor.

BACKGROUND/AIM: Based on animal models, lafutidine, a novel histamine H(2) receptor (H(2)R) antagonist, is reported to show potent and long-lasting antagonisms of histamine H(2)R-mediated effects. However, no reports have been published concerning its direct interaction with the human H(2)R. This study aims at characterizing its interaction with human H(2)R. METHODS: Chinese hamster ovary cell lines stably expressing human H(2)Rs were obtained. The dose-dependent effects of lafutidine and famotidine on [(3)H]tiotidine binding and histamine-stimulated cAMP production were analyzed. The effects of preincubation with 2.78 x 10(-7) M of lafutidine or famotidine for 30 min on histamine-dependent cAMP production and [(3)H]tiotidine binding were also examined after 0, 1, 2, 4, and 12 h. This concentration is below the C(max) of lafutidine (10 mg p.o.) and above the C(max) of famotidine (20 mg p.o.). RESULTS: Lafutidine inhibited [(3)H]tiotidine binding and histamine-stimulated cAMP production as or more potently than famotidine. At higher concentrations lafutidine was more potent than famotidine. In addition, preincubation with 2.78 x 10(-7) M lafutidine, but not with 10(-5) M famotidine, had marked inhibitory effects which persisted as long as after extensive washing. CONCLUSION: Lafutidine shows a potent and long-lasting antagonism on the human H(2)R.

Acetamides↗

Intramolecular capture of pummerer reaction intermediates by an aromatic nucleophile: selective construction of 1,4-benzothiazine and indole ring systems.

The simple alkyl sulfoxide 6 carrying two aromatic nucleophiles, when treated with trifluoroacetic anhydride at room temperature (Pummerer reaction conditions), underwent an intramolecular aromatic sulfenylation of the 6-exo-tet process in an exclusive manner to yield two regioisomeric 1,4-benzothiazine derivatives, 8 and 9. On the other hand, a similar reaction of the alpha-acyl sulfoxide 7, possessing identical aromatic nucleophiles, caused an intramolecular aromatic alkylation of the 5-exo-trig process to produce the 3-oxo-indole derivative 14 in a quantitative yield. These results demonstrate that the construction of 1,4-benzothiazine and indole ring systems can be achieved in a selective manner by proper choice of the sulfoxide side chain.

Acetic Anhydrides↗

A synthesis of 3-phenyl-1,2,3,4-tetrahydroisoquinoline and 2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine via Pummerer-type cyclization: enhancing effect of boron trifluoride diethyl etherate on the cyclization.

A synthesis of 6,7-dimethoxy-3-phenyl-1,2,3,4-tetrahydroisoquinoline (14a) and 7,8-dimethoxy-2-phenyl-1,2,4,5-tetrahydro-3H-3-benzazepine (14b) was achieved via the cyclization of N-(3,4-dimethoxyphenyl)methyl-1-phenyl-2-(phenylsulfinyl)ethylformamide (6a) and N-2-(3,4-dimethoxyphenyl)ethyl-1-phenyl-2-(phenylsulfinyl)-ethylformamide (6b) using the Pummerer reaction as a key step, respectively. The Pummerer reaction of 6a,b under usual conditions using trifluoroacetic anhydride yielded the vinyl sulfides (8a, b), non-cyclized products, as a major product. The cyclization proceeded when boron trifluoride diethyl etherate was used as an additive reagent, thus giving rise to the corresponding cyclized products (7a) and (7b) in moderate yields. We propose that the enhancing effect of the Lewis acid on the cyclization may be attributable to the involvement of a dicationic intermediate, sulfonium-carbenium dication (23).

Benzazepines↗

[Micelle-mediated extraction for concentrating conjugated bilirubin in urine].

An extraction method based on the phase separation of aqueous micellar solutions of n-octyl-beta-D-thioglucoside (OTG) was applied to the concentrating conjugated bilirubin in urine. The analyte in sample solutions could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components including urinary protein, ascorbic acid, and saccharide remained in the aqueous phase. The concentrated OTG negligibly affected the diazo reaction and the subsequent spectrophotometric detection. Conjugated bilirubin was successfully determined in the concentration range from 0.05 microgram/ml to 5 micrograms/ml with a 96-well microplate reader absorption spectrophotometer.

Bilirubin↗

Celiac artery aneurysm: a case evaluated preoperatively with three-dimensional computed tomographic angiography.

In a 63-year-old woman computed tomography (CT) incidentally detected a celiac artery aneurysm approximately 3 cm in diameter. While conventional angiography suggested that the splenic artery and common hepatic artery arose from the celiac artery aneurysm, three-dimensional CT angiography indicated that the aneurysm involved only the mid portion of the celiac artery. Considering the risk of eventual aneurysm rupture, surgery was performed. Aneurysmectomy and devascularization of hepatic, splenic, and celiac arteries were carried out following complete cross-clamping of the celiac artery. The distal segment of the celiac artery was directly anastomosed to the proximal segment in an end-to-end fashion. Histologically, the aneurysm wall showed atheromatous changes. Contrast-enhanced abdominal CT confirmed complete removal of the celiac artery aneurysm, and postoperative angiography confirmed good arterial flow. The patient recovered uneventfully after surgery, with normalization of transiently abnormal hepatic function parameters. In this case of celiac artery aneurysm, three-dimensional CT angiography was found to be valuable in determining the relationships of the aneurysms to important arterial branches.

Aneurysm↗

[Brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura].

The increased susceptibility to infection following splenectomy has been well documented. We report here, a case of brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura (ITP). A 65-year-old woman was admitted to our hospital because of fever, mental disorientation, and weakness in August, 1999. She had been followed with diagnoses of essential hypertension and type 2 diabetes mellitus (DM) since 1988. The patient was diagnosed as having ITP in 1992, and then underwent splenectomy in 1994. Monoclonal gammopathy of undetermined significance (MGUS) of IgG, lambda type was found in February 1999. Though high grade fever persisted after admission, blood cultures were negative. Antibiotics were given without a satisfactory effect. Right hemiparesis and worsening of consciousness developed subsequently. Contrast enhanced cranial computed tomography (CT) disclosed a ringed enhanced low density mass in the left parieto-occipital lobe compatible with a diagnosis of brain abscess. Surgical drainage was performed and 20 ml of pus was obtained. No primary infectious focus of the brain abscess was detected with intensive examinations.

Aged↗

Genotype Arg/Arg, but not Trp/Arg, of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample.

OBJECTIVE: Despite a large number of studies, no association of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor gene with obesity and type 2 diabetes has yet to be clearly elucidated. We examined the associations in a large population-based sample. RESEARCH DESIGN AND METHODS: A total of 1,685 subjects (935 women and 750 men, aged 58.7 +/- 12.4 years) from a cohort population (n = 3,706) of the Funagata Diabetes Study were divided into three groups according to genotypes: Trp/Trp (n = 1,155), Trp/Arg (n = 486), and Arg/Arg (n = 44). Glucose tolerance was diagnosed according to the 1985 World Health Organization criteria. Subjects who had a BMI > or =30 kg/m(2) were considered obese. Associations with the traits related to obesity, diabetes, hypertension, and dyslipidemia were also examined. The chi(2) test and analysis of variance were used for the association studies and to assess the differences in the traits' values, respectively. RESULTS: More subjects with genotype Arg/Arg were obese and had diabetes (13.6% for each) than those with genotype Trp/Trp (3.29%, P < 0.001; and 4.16%, P = 0.007, respectively) or genotype Trp/Arg (2.06%, P < 0.001; and 5.97%, P = 0.051, respectively). No significant differences in the frequencies of occurrence of these conditions were observed between genotypes Trp/Arg and Trp/Trp. Traits related to obesity, such as percent body fat (28.82 +/- 7.95 vs. 25.93 +/- 7.21, P = 0.038) and BMI (25.07 +/- 3.84 vs. 23.63 +/- 3.18, P = 0.018), were higher in the genotype Arg/Arg than in the genotype Trp/Trp groups. CONCLUSIONS: Genotype Arg/Arg, but not Trp/Arg, of the beta(3)-adrenergic receptor was associated with both obesity and type 2 diabetes in a large Japanese sample.

Aged↗

Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2.

Mouse Frizzled-8, encoding a WNT receptor, is a potent cancer-associated gene to activate the beta-catenin-TCF pathway. However, these is a possibility that mouse Frizzled-8 might be a pseudogene, because structure and expression profile of mouse Frizzled-8 mRNA are still unclear. We have cloned and characterized the human Frizzled-8 (FZD8) gene, a human homologue of mouse Frizzled-8. Comparison between FZD8 genome clones and FZD8 cDNA clones isolated in this study revealed no intron within the FZD8 gene. FZD8 was found to encode a 694 amino-acid polypeptide with the frizzled-like cysteine-rich domain, seven transmembrane domains, and the C-terminal Ser/Thr-X-Val motif. Among human FZD family, FZD8 was most homologous to FZD5 (total amino-acid identity 69.1%). The 4.0-kb FZD8 mRNA was detected in fetal kidney and brain, and also in adult kidney, heart, pancreas, and skeletal muscle. These results indicate that human FZD8 is not a pseudogene. The FZD8 gene was mapped to human chromosome 10p11.2 by fluorescence in situ hybridization. Among human cancer cell lines, FZD8 was relatively highly expressed in HeLa S3 (cervical uterus cancer) and A549 (lung cancer). Up-regulation of FZD8 might play key roles in several types of human cancer through activation of the beta-catenin-TCF pathway.

Amino Acid Sequence↗

Molecular cloning and characterization of human Frizzled-5 gene on chromosome 2q33.3-q34 region.

Hfz5 is a potent cancer associated gene, encoding WNT receptor with the potential to activate beta-catenin - TCF signaling pathway. Here, human Frizzled-5 (FZD5) gene and cDNAs were cloned and characterized. FZD5 was almost identical to Hfz5, except for six amino-acid substitutions at codon 88, 262, 263, 345, 357, and 402. HF5S1 probe (nucleotide position 2036-2535 of FZD5 cDNA) hybridized to 7.5- and 3.5-kb FZD5 mRNAs, and HF5S2 probe (nucleotide position 5572-6194 of FZD5 cDNA) hybridized only to 7.5-kb FZD5 mRNA. FZD5 cDNA was polyadenylated at the nucleotide position 6534, while several FZD5 ESTs were polyadenylated at the nucleotide position 2561. The 7.5- and 3.5-kb FZD5 mRNAs were transcribed probably due to alternative splicing. FZD5 was highly expressed in fetal liver and adult pancreas, and moderately expressed in fetal lung, kidney and adult liver. Among human cancer cell lines, FZD5 was highly expressed in K-562 cells derived from chronic myelogenous leukemia. FZD5 gene, consisting of two exons, was mapped to human chromosome 2q33.3-q34 region, near the FZD7 gene and the FRA2I fragile site. These results suggest that FZD5 up-regulation might play key roles in chronic myelogenous leukemia through activation of the WNT - beta-catenin - TCF signaling pathway.

Amino Acid Sequence↗

FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated in gastric cancer.

FRAT1 and FRAT2 are cancer-associated genes encoding GSK-3beta-binding proteins. Over-expression of FRAT1 or FRAT2 lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway. We have previously cloned and characterized FRAT2. Here, we found that FRAT1 and FRAT2 genes were clustered in the human chromosome 10q24.1 region. Blast search revealed that FRAT1 and FRAT2 genes, consisting of a single exon, were located together on human genome draft sequences AC006098.1 and AL355490.7, corresponding to the human chromosome 10q24.1 region. FRAT1 and FRAT2 genes were clustered in a tail to tail manner with an interval of about 10.7 kb. The 2.7-kb FRAT1 mRNA was relatively highly expressed in fetal brain, adult spleen, pancreas, HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). FRAT1 and FRAT2 were co-expressed in 7 gastric cancer cell lines and 10 cases of primary gastric cancer, and were up-regulated together in gastric cancer cell line TMK1 and 2 cases of primary gastric cancer. These results indicated that FRAT1 and FRAT2 genes were up-regulated together in several cases of human gastric cancer. Up-regulation of FRAT1 and FRAT2 in gastric cancer might lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway.

Adaptor Proteins, Signal Transducing↗

Molecular cloning and characterization of human WNT5B on chromosome 12p13.3 region.

WNT signaling pathway plays a key role in carcinogenesis and embryogenesis. We have cloned and characterized the human WNT5B. Overlapping WNT5B cDNAs, containing 1080-bp ORF, were isolated. WNT5B encoded a 359-amino-acid polypeptide with the N-terminal signal peptide, four N-linked glycosylation sites, and consensus amino-acid residues conserved among the WNT family. WNT5B showed 80.5% total-amino-acid identity with WNT5A. Comparison between nucleotide sequence of WNT5B cDNA and human genome draft sequences revealed that the WNT5B gene, consisting of 4 exons, was located on human chromosome 12p13.3 region. Northern blot analyses with W5B2 probe detected the 2.8- and 2.4-kb WNT5B mRNAs. WNT5B was moderately expressed in adult prostate and fetal brain, and weakly expressed in fetal lung, kidney, adult liver, ovary, and small intestine. Among human cancer cell lines, WNT5B was expressed in gastric cancer cell lines MKN7, MKN45, KATO-III, and a teratocarcinoma cell line NT2. WNT5B might be implicated in human carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway, just like Wnt5a.

Amino Acid Sequence↗

Proto-oncogene WNT10B is up-regulated by tumor necrosis factor alpha in human gastric cancer cell line MKN45.

WNT10A and WNT10B genes are human orthologues of mouse proto-oncogene Wnt-10b. We have previously cloned and characterized WNT10A, and demonstrated up-regulation of WNT10A by tumor necrosis factor alpha (TNFalpha) in gastric cancer. Here, we cloned and characterized human WNT10B, which showed Gly60Asp amino-acid substitution compared with human WNT10B previously reported by another group. Gly60 WNT10B allele was identified in 2 human genome draft sequences and 7 human ESTs, while Asp60 WNT10B allele was not identified in any human genome draft sequences or ESTs. The Gly60-type WNT10B cDNA isolated in this study might be derived from more common WNT10B allele. WNT10B was most homologous to WNT10A (64.5% total amino-acid identity) among human WNTs. Variable region in the WNT core domain of WNT10B and WNT10A were longer than that of other WNTs, such as WNT2B1, WNT2B2, WNT3, WNT3A, WNT5B, WNT7B, WNT8A, WNT11, WNT14, and WNT14B/WNT15. We next investigated expression of WNT10B in human gastric cancer. WNT10B was moderately expressed in MKN45 and MKN74 cells, and weakly expressed in Okajima, TMK1, MKN7, MKN28, and KATO-III cells. Because interferon gamma (IFNgamma) and TNFalpha were frequently elevated in gastric mucosa with Helicobacter pylori infection, effects of IFNgamma and TNFalpha on WNT10B expression in MKN45 cells were investigated. TNFalpha induced transient up-regulation of WNT10B mRNA in MKN45 cells. Up-regulation of WNT10B in human gastric mucosa might lead to gastric carcinogenesis through activation of the beta-catenin - TCF signaling pathway, just like up-regulation of Wnt-10b in mouse mammary gland leads to mammary carcinogenesis.

Amino Acid Sequence↗

Expression profiles of betaTRCP1 and betaTRCP2, and mutation analysis of betaTRCP2 in gastric cancer.

betaTRCP1 and betaTRCP2, components of the beta-catenin-ubiquitin ligase complex, are negative regulators of the WNT signaling pathway. We have previously isolated the betaTRCP2 gene, and detected betaTRCP2 in all gastric cancer cell lines examined. Here, expression profiles of betaTRCP1 and betaTRCP2 in various normal tissues and in primary gastric cancer were investigated. betaTRCP1 was predominant in small intestine, while betaTRCP2 was predominant in stomach. betaTRCP1 was expressed in gastric cancer cell lines MKN28, MKN45, MKN74, and KATO-III, but not in any cases of primary gastric cancer. betaTRCP2 was expressed in most cases of primary gastric cancer at almost the equal level in tumor and in non-cancerous portion of gastric mucosa. As betaTRCP2 was found to be the major betaTRCP expressed in gastric cancer, genetic alterations of betaTRCP2 in 7 gastric cancer cell lines and 12 cases of primary gastric cancer were investigated. A nucleotide substitution (Tright curved arrow C) at the nucleotide position 1486 of betaTRCP2 was identified in OKAJIMA cells, which lead to F462S amino acid substitution in the seventh WD-repeat domain. F462 was conserved among betaTRCPs derived from human, mouse, Xenopus laevis, and Drosophila melanogaster. As WD-repeats of betaTRCPs are the substrate-recognition motif of the beta-catenin-ubiquitin ligase, F462S amino-acid substitution might lead to beta-catenin stabilization, and might be implicated in carcinogenesis through activation of the WNT signaling pathway. This is the first report on comprehensive expression analyses of betaTRCP1 and betaTRCP2, and also on mutation analysis of betaTRCP2.

Blotting, Northern↗

Molecular cloning and characterization of human WNT8A.

WNT - beta-catenin - TCF pathway is involved in carcinogenesis and fetal development. Xenopus wnt-8 is one of the most potent Wnts with the capacity to activate beta-catenin - TCF pathway in the Xenopus axis duplication assay. Here, we have cloned and characterized WNT8A, a novel human homologue of Xenopus wnt-8. The WNT8A gene, consisting of at least 6 exons, was found to encode a 351-amino-acid polypeptide with the N-terminal signal peptide, three N-linked glycosylation sites, and conserved amino-acid residues of the WNT family. WNT8A showed 63.2% total-amino-acid identity to WNT8B. C-terminal region of WNT8A, WNT8B, WNT2, WNT2B1 and WNT2B2 were longer than that of other WNTs. Among various normal human tissues and 34 human cancer cells lines, the 3.5-kb WNT8A mRNA was detected only in a human teratocarcinoma cell line NT2. These results strongly suggest that WNT8A might be implicated in development of early embryos as well as germ cell tumors through activation of the WNT - beta-catenin - TCF pathway.

Amino Acid Sequence↗

[The feasibility of a limited operation for primary lung cancer].

We reviewed 33 patients who underwent a limited operation for primary lung cancer between 1980 and 1998. These cases were divided into three groups; a poor risk group consisting of 18 patients who had a high risk such as pulmonary or cardiac dysfunction and who underwent partial resection of a lung, a reduction group consisting of 9 patients who had advanced lung cancer or uncontrolled cancer of an organ other than the lung and who underwent partial resection, and an active limited operation group consisting of 6 patients who underwent segmentectomy with lymphoadenectomy for the treatment of early lung cancer. The 1 and 3-year survival rates in the poor risk group, reduction group and active limited operation group were 73.9, 60.0, 100%, and 63.4, 0.0, 100%, respectively. The results of limited operations performed for poor risk cases were satisfactory in terms of both functional state and prognosis. Limited operations performed to reduce tumor in advanced lung cancer cases did not improve the prognosis. Although an active limited operation for a case of early lung cancer remains controversial with respect to indication, it is thought that this operation is not inferior to a standard radical operation (lobotomy with mediastinal lymphoadenectomy) in selective cases in which the maximum tumor diameter is 2 cm or less. The indication for a limited operation must be further examined from aspects of tumor size, tumor histology and the other factors of the tumor.

Adenocarcinoma↗