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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 73 records · Page 4Linked to original sources

[Severe thrombocytopenia induced by radiographic non-ionic contrast medium].

A 70-year-old man was admitted to our hospital because of right hemiparesis. He had no allergies or previous exposure to radiographic contrast medium, and the platelet count on admission was within the normal range. On day 8 of hospitalization, he underwent computed tomography of the brain with 100 ml of iopamidol administered intravenously. Three hours later, his platelet count fell to 5,000/microliter, and he developed purpura. Because drug-induced thrombocytopenia was suspected, platelet transfusion was undertaken and corticosteroids were administered. The platelet count returned gradually to normal in 2 days. At the time, we were unable to ascertain the cause of the thrombocytopenia. To clarify whether the contrast medium had been responsible, iopamidol was added to the patient's heparinized whole blood. Subsequent platelet aggregation was observed microscopically and the platelet count decreased, suggesting that the thrombocytopenia had been due to contrast medium-induced platelet aggregation. Although thrombocytopenia after injection of contrast medium is extremely rare, such cases should be evaluated carefully because the condition can be life-threatening if severe.

Aged↗

[Destructed knee in patient with systemic lupus erythematosus treated with total knee arthroplasty: a case report].

We reported a case of a 61-year-old female with arthritis of right knee associated with systemic lupus erythematosus (SLE). She suffered from SLE at age 31 and felt pain around her right knee at age 60. It gradually increased despite intraarticular injections of steroid and arthroscopic synovectomy. On admission, the range of motion of her right knee was 20 to 135 degrees and remarkable gait disturbance were noted due to the pain. Radiographs of the right knee showed joint space narrowing and bone erosion. YMCK total knee arthroplasty was performed. Operation findings showed smooth and thick synovium and cartilage defect. Histological examination revealed fibrin on surface, proliferad connective tissue and newly development of vasculature. Synovium eroded both cartilage and bone. In SLE, soft tissue contructure was reported to be a main cause of joint dislocation, but there were only a few report of progressive joint destruction due to SLE. In this case, the main cause of joint destruction may be invasion synovium into cartilage and bone.

Arthritis↗

Adenine excisional repair function of MYH protein on the adenine:8-hydroxyguanine base pair in double-stranded DNA.

Adenine paired with 8-hydroxyguanine (oh(8)G), a major component of oxidative DNA damage, is excised by MYH base excision repair protein in human cells. Since repair activity of MYH protein on an A:G mismatch has also been reported, we compared the repair activity of His(6)-tagged MYH proteins, expressed in Spodoptera frugiperda Sf21 cells, on A:oh(8)G and A:G mismatches by DNA cleavage assay and gel mobility shift assay. We also compared the repair ability of type 1 mitochondrial protein with type 2 nuclear protein, as well as of polymorphic type 1-Q(324) and 2-Q(310) proteins with type 1-H(324) and 2-H(310) proteins by DNA cleavage assay and complementation assay of an Escherichia coli mutM mutY strain. In a reaction buffer with a low salt (0-50 mM) concentration, adenine DNA glycosylase activity of type 2 protein was detected on both A:oh(8)G and A:G substrates. However, in a reaction buffer with a 150 mM salt concentration, similar to physiological conditions, the glycosylase activity on A:G, but not on A:oh(8)G, was extremely reduced and the binding activity of type 2 protein for A:G, but not for A:oh(8)G, was proportionally reduced. The glycosylase activity on A:oh(8)G and the ability to suppress spontaneous mutagenesis were greater for type 2 than type 1 enzyme. There was apparently no difference in the repair activities between the two types of polymorphic MYH proteins. These results indicate that human MYH protein specifically catalyzes the glycosylase reaction on A:oh(8)G under physiological salt concentrations.

Adenine↗

Isolation of Xenopus frizzled-10A and frizzled-10B genomic clones and their expression in adult tissues and embryos.

Frizzled genes, encoding WNT receptors, play key roles in cell fate determination. Here, we isolated two Xenopus frizzled genes (Xfz10A and Xfz10B), probably reflecting pseudotetraploidy in Xenopus. Xfz10A (586 amino acids) and Xfz10B (580 amino acids) both encoded by a single exon, consisted of the N-terminal cysteine-rich domain, seven transmembrane domains, and the C-terminal Ser/Thr-X-Val motif. Xfz10A and Xfz10B were 97.0% identical at the amino acid level, and Xfz10B was 100% identical to previously reported Xfz9, yet Xfz10A was 85.3% and 62.4% identical to FZD10 and FZD9, respectively. Xfz10 mRNA appeared as 3.4 kb in adult tissues and embryos. RT-PCR analyses revealed the expression of more Xfz10A mRNA in stomach, kidney, eye, skeletal muscle, and skin, and more Xfz10B mRNA in heart and ovary, but in embryos, two mRNAs were equally expressed from the blastula stage with their peak expression at the late gastrula stage. The main site of Xfz10 mRNA expression was neural fold at the neurula stage and the dorsal region of midbrain, hindbrain, and spinal cord at the tadpole stage. These results suggest that Xfz10 has important roles in neural tissue formation.

Amino Acid Sequence↗

Alternative splicing of the WNT-2B/WNT-13 gene.

Secreted glycoprotein WNTs play important roles in carcinogenesis and development. We have previously reported molecular cloning of WNT-2B/WNT-13. Here, we have isolated a novel WNT-2B isoform (WNT-2B2), in addition to the original WNT-2B isoform (WNT-2B1). WNT-2B1 and WNT-2B2 are completely different in the 5'-UTR and in the N-terminal part of the coding region. The N-terminal hydrophobic domain is contained in WNT-2B1, but not in WNT-2B2. WNT-2B1 and WNT-2B2 share the WNT-core domain, and show 87.0% amino-acid identity. We have determined the structure of the WNT-2B gene. The WNT-2B1 mRNA consists of exons 1, 2, and 4-7, while the WNT-2B2 mRNA consists of exons 3-7. WNT-2B2 was expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis, glioblastoma cell lines A172, SW1783, gastric cancer cell lines MKN28, MKN74, and cervical cancer cell line HeLa S3. WNT-2B1 expression level was relatively higher in fetal brain and fetal lung than in other tissues or cell lines expressing WNT-2B2. These results indicate that the WNT-2B1 and WNT-2B2 mRNAs are transcribed due to alternative splicing with distinct expression profile. This is the first report on the WNT isoforms derived from the same gene due to alternative splicing.

5' Untranslated Regions↗

Molecular cloning and characterization of human FGF-20 on chromosome 8p21.3-p22.

The fibroblast growth factors (FGFs) play important roles in morphogenesis, angiogenesis, tissue remodeling, and carcinogenesis. Human FGF-20 has been cloned and characterized in this study. FGF-20 encodes a 211-amino-acid polypeptide with the FGF-core domain. A strong hydrophobic region was found in the FGF-core domain of FGF-20; however, no typical N-terminal signal sequence was found in FGF-20, just as in FGF-9 and FGF-16. Total amino acid identities are as follows: FGF-20 vs FGF-9, 71.6%; FGF-20 vs FGF-16, 66.2%; FGF-9 vs FGF-16, 72.4%. Phylogenic analysis indicated that FGF-20, FGF-9, and FGF-16 constitute a subfamily among the FGF family. FGF-20 mRNA of 2.4 kb in size was detected in colon cancer cell line SW480 by Northern blot analysis. Lower levels of FGF-20 mRNA were detected in human fetal tissues and primary cancers by cDNA-PCR. The nucleotide sequence of FGF-20 cDNA is split into three parts in the human genome sequence of the chromosome 8p21.3-p22 region (Accession No. AB020858). These results indicate that the FGF-20 gene, located on human chromosome 8p21.3-p22, consists of three exons. Compared with the nucleotide sequence of FGF-20 cDNA determined in this study, one nucleotide deletion and one nucleotide substitution in the putative coding region were identified in human genome sequence AB020858.

Alternative Splicing↗

Micelle-mediated extraction for concentrating hydrophobic organic compounds.

An extraction method based on polymer-induced phase separation of aqueous micellar solutions of octyl-beta-D-thioglucoside (OTG) was assessed for concentrating hydrophobic analytes. Various hydrophobic compounds such as polycyclicaromatic hydrocarbons, alkylbenzenes, alkylphenols, chlorobenzenes, chlorophenols, phthalic esters, pesticides, and steroid hormones could be efficiently concentrated into a small volume of surfactant-rich phase, while hydrophilic matrix components remained in the bulk aqueous phase. The surfactant-rich phase containing concentrated OTG could be directly introduced into the hygro-organic mobile phase of high-performance liquid chromatography with ultra-violet photometric detection. The application of this method greatly enhanced the signal intensity in the chromatogram while reducing the interference of matrix components.

Chromatography, High Pressure Liquid↗

Molecular cloning and genomic structure of human frizzled-3 at chromosome 8p21.

WNT receptors encoded by the Frizzled genes are implicated in carcinogenesis as well as in embryonic development. Human Frizzled-3 (FZD3) gene, encoding seven-transmembrane receptor with the N-terminal cysteine-rich domain, has been cloned and characterized. Expression of the FZD3 mRNAs was investigated by using three FZD3 specific probes: HF3S1, corresponding to the 5'-UTR and a part of the coding region; HF3S2, corresponding to a part of the coding region; HF3S3, corresponding to the 3'-UTR. HF3S1 and HF3S2 hybridized to the 14.0-, 9.0-, 4.0- and 1.8-kb FZD3 mRNA, while HF3S3 hybridized to the 14.0-, 9.0-, and 4.0-kb FZD3 mRNA. The 14. 0-kb FZD3 mRNA was the major transcript in fetal brain and adult cerebellum, while the 1.8-kb FZD3 mRNA was the major transcript in adult pancreas, and many cancer cell lines examined. The 1.8-kb FZD3 mRNA, alternatively polyadenylated by the internal AATAAA signal in the coding region, is predicted to encode the truncated FZD3 protein lacking the region through the second extracellular loop to the C-terminal tail, and might function as the transmembrane-type antagonist for WNTs. The FZD3 gene consists of 8 exons, and has been mapped to human chromosome 8p21.

Adenosine Monophosphate↗

Clinical significance of increased plasma concentration of macrophage colony-stimulating factor in patients with angina pectoris.

OBJECTIVES: To determine the effect of macrophage colony-stimulating factor (MCSF) on atherogenesis in patients with coronary artery disease (CAD), we assessed the relation between the plasma concentration of MCSF and the incidence of acute coronary events in patients with CAD. BACKGROUND: Cytokines such as MCSF play a central role in inflammatory and proliferative responses in patients with acute coronary syndromes. However, the effect of MCSF on the clinical course in patients with CAD is still not known. METHODS: We measured the plasma MCSF concentration in 142 patients with documented CAD (62 +/- 9 years) and followed up for a mean period of 14 +/- 6 months. The study included 97 patients with stable angina (SA), 45 patients with unstable angina (UA) and 22 age-matched control subjects. The predictors of coronary events were analyzed by using a Cox proportional hazards model. RESULTS: The mean plasma MCSF concentration in patients with UA was significantly higher than that in patients with SA and in control subjects (981 +/- 277 vs. 693 +/- 223 vs. 680 +/- 158 pg/ml, p < 0.001). The mean plasma MCSF concentration in the 20 patients with coronary events was significantly higher than that in patients without coronary events (1,192 +/- 232 vs. 690 +/- 213 pg/ml, p < 0.001). The predictors of unfavorable outcome were an increased MCSF concentration, the presence of CAD and a low ejection fraction. CONCLUSIONS: These findings suggest that an increased circulating MCSF concentration reflects atherosclerotic progression in patients with CAD and predicts future cardiac events.

Adult↗

63Cu NQR evidence of dimensional crossover to anisotropic 2D regime in S = 1 / 2 three-Leg ladder Sr2Cu3O5

We probed spin-spin correlations up to 725 K with 63Cu nuclear quadrupole resonance in the S = 1 / 2 three-leg ladder Sr2Cu3O5. We present experimental evidence that below 300 K weak interladder coupling causes dimensional crossover of the spin-spin correlation length xi from the quasi-1D (xi approximately 1 / T) to the anisotropic 2D regime ( xi approximately exp2pirho(s) / T, where 2pirho(s) = 290+/-30 K is the effective spin stiffness).

Journal Article↗

Age-related changes in myelopoietic response to lipopolysaccharide in senescence-accelerated (SAM) mice.

The effects of in vivo lipopolysaccharide (LPS) administration on myelopoiesis were examined in senescence-accelerated (SAM) mice. Young mice injected with LPS exhibited: (a) increased femoral proliferative pool size; (b) transient reduction in femoral non-proliferative pool size and number of femoral colony forming unit-granulocyte macrophages (CFU-GMs); (c) marked increase in splenic CFU-GMs; and (d) transient increase in S-phase of femoral CFU-GMs. The responses of old mice after LPS administration differed from those of young mice in the following points: (a) no recovery of the femoral non-proliferative pool or femoral CFU-GMs, (b) less significant augmentation of the femoral proliferative pool and splenic CFU-GMs, and (c) prolonged reduction in S-phase of femoral CFU-GM. Injection of LPS into mice resulted in a hyperproduction of colony-stimulating activity (CSA) in bone followed by production of colony-inhibitory activity (CIA) in young mice and in contrast, an excessive CIA secretion from bone without an increase in CSA levels in old mice. These imbalances in the regulatory factors derived from non-hemopoietic cells in the bones may lead to an inappropriate response of myelopoiesis in aged SAM mice after LPS administration, which may play a key role in infections.

Aging↗

Multiple myeloma presenting high fever and high serum levels of lactic dehydrogenase, CRP, and interleukin-6.

Two myeloma patients presented high fever with no signs or data indicating infection at diagnosis or relapse. Both patients had plasmablastic myeloma, and serum levels of lactic dehydrogenase (LDH) and CRP were extremely high. Plasmablastic morphology, high LDH, and CRP were recognized as poor prognostic factors, indicating a fulminant phase of multiple myeloma. Interleukin-6 (IL-6) was only high in measured cytokines. We proposed that IL-6 caused high fever and induced the fulminant phase in these 2 cases.

C-Reactive Protein↗

Difference in human cardiovascular response between upright and supine recovery from upright cycle exercise.

Cardiovascular responses were examined in seven healthy male subjects during 10 min of recovery in the upright or supine position following 5 min of upright cycle exercise at 80% peak oxygen uptake. An initial rapid decrease in heart rate (fc) during the early phase of recovery followed by much slower decrease was observed for both the upright and supine positions. The average fc at the 10th min of recovery was significantly lower (P < 0.05) in the supine position than in the upright position, while they were both significantly greater than the corresponding pre-exercise levels (each P < 0.05). Accordingly, the amplitude of the high frequency (HF) component of R-R interval variability (by spectrum analysis) in both positions was reduced with a decrease in mean R-R interval, the relationship being expressed by a regression line--mean R-R interval = 0.006 x HF amplitude + 0.570 (r = 0.905, n = 28, P < 0.001). These results would suggest that the slower reduction in fc following the initial rapid reduction in both positions is partly attributable to a retardation in the restoration of the activity of the cardiac parasympathetic nervous system. Post-exercise upright stroke volume (SV, by impedance cardiography) decreased gradually to just below the pre-exercise level, whereas post-exercise supine SV increased markedly to a level similar to that at rest before exercise. The resultant cardiac output (Qc) and the total peripheral vascular resistance (TPR) in the upright and supine positions returned gradually to their respective pre-exercise levels in the corresponding positions. At the 10th min of recovery, both average SV and Qc were significantly greater (each P < 0.005) in the supine than in the upright position, while average TPR was significantly lower (P < 0.05) in the supine than in the upright position. In contrast, immediately after exercise, mean blood pressure dropped markedly in both the supine and upright positions, and their levels at the 10th min of recovery were similar. Therefore we concluded that arterial blood pressure is maintained relatively constant through various compensatory mechanisms associated with fc, SV, Qc, and TPR during rest and recovery in different body positions.

Adult↗

Evidence for the involvement of bone morphogenetic protein-2 in phenytoin-stimulated osteocalcin secretion in human bone cells.

Recent work has shown that the actions of phenytoin on bone cell proliferation and differentiation are, in part, mediated through the upregulation of transforming growth factor-beta1 (TGF-beta(1)). The present study was undertaken to examine the effect of phenytoin on bone morphogenetic proteins (BMP)-2 and -4, which are well-recognized osteoinductive proteins of the TGF-beta superfamily, in osteoblastic cells. Treatment with 5-50 microM of phenytoin increased the amount of mRNA for BMP-2 after a 0.5-24 h incubation in normal human mandible-derived bone cells (HOB-M cells), but failed to affect the mRNA for BMP-4. Phenytoin treatment for 48 h significantly increased the secretion of BMP-2 by approx. four-fold, at an optimal concentration of 10 microM. While TGF-beta(1) inhibited osteocalcin secretion from HOB-M cells, both phenytoin and BMP-2 significantly stimulated it. Importantly, the stimulatory effects of phenytoin on osteocalcin release were completely blocked by the neutralizing antihuman BMP-2 monoclonal antibody. These results indicate that the stimulatory action of phenytoin on osteocalcin secretion in normal human bone cells is mediated, at least partly, through the upregulation of BMP-2, rather than that of TGF-beta(1).

Analysis of Variance↗

Long-lasting binding of IT-066 to human histamine H2 receptor.

Based on animal models, IT-066, a histamine H2-receptor antagonist, is reported to possess potent and long-lasting antagonisms on histamine H2 receptor (H2R) -mediated effects. However, no reports have been published concerning its interaction with the human H2R. The aim of this study is to characterize its interaction with human H2R. Chinese hamster ovary cell lines stably expressing human H2Rs were obtained. The effects of IT-066, famotidine, and ranitidine on tiotidine binding and histamine-stimulated cAMP production were analyzed. IT-066 inhibited [3H]tiotidine binding and histamine-stimulated cAMP production more potently than famotidine or ranitidine. In addition, preincubation with 10(-5) M IT-066, but not with 10(-5) M famotidine or 10(-4) M ranitidine, had marked inhibitory effects long after extensive washing. Paraformaldehyde fixation of the cells blunted inhibition of [3H]tiotidine binding induced by preincubation with IT-066, but not that by preincubation with famotidine or ranitidine. IT-066 has potent and long-lasting antagonisms on human H2R. At least one of the IT-066 binding sites is not shared by famotidine, ranitidine, or tiotidine and is affected by paraformaldehyde fixation.

Animals↗

Improvement of extrathymic T cell type of large granular lymphocyte (LGL) leukemia by cyclosporin A: the serum level of Fas ligand is a marker of LGL leukemia activity.

We report a case of gammadelta T-cell-type large granular lymphocyte (LGL) leukemia (CD3 +,CD8 +, CD57 +,TCR gammadelta+), which was accompanied by pure red cell aplasia, neutropenia and thrombocytosis. Southern blotting analysis of the T-cell receptor beta gene showed the germline configuration, but clonal TCR J gamma rearrangements were identified. These granular lymphocytes demonstrated non-major histocompatibility complex-restricted cytotoxicitity. The serum-soluble FasL (sFasL) concentration of this patient was very high, whereas the serum levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), interleukin-1 beta (IL-1beta), interleukin-2 (IL-2) and thrombopoietin were normal. After treatment with cyclosporin A, anemia and thrombocytosis were improved, and LGL and the elevated sFasL concentration decreased. These observations suggested that FasL may have played a role in the establishment of the clinical symptoms of this patient and could be useful as an indicator of disease activity.

CD3 Complex↗

The impact of acute phase response on the plasma clearance of antipyrine, theophylline, phenytoin and nifedipine in rabbits.

The impact of acute phase response (APR) on the plasma clearances of antipyrine, theophylline, phenytoin and nifedipine was studied using 50 female rabbits. APR was induced by a bolus intramuscular injection of Escherichia coli lipopolysaccharide (LPS, 50 microg/kg). No abnormal findings, other than an increase in rectal body temperature and the plasma concentration of interleukin-6 (IL-6), were observed in the LPS-treated animals. Twenty-four hours after LPS injection, the pharmacokinetic parameters of the four drugs were obtained following intravenous administrations of antipyrine (7 mg/kg), theophylline (5 mg/kg), phenytoin (10 mg/kg) and nifedipine (1 mg/kg). Total body clearances of antipyrine, theophylline, phenytoin and nifedipine in LPS-treated rabbits decreased, and terminal elimination half-life and the mean residence time of these drugs increased compared with those in the control rabbits. The apparent volume of distribution for phenytoin and nifedipine increased after the LPS injection, although the binding percentage of the drugs with plasma protein did not change. These results suggested that APR appears to decrease the plasma clearances of these drugs in rabbits, which may be due to the suppression of the activity of cytochrome P450 enzymes.

Acute-Phase Reaction↗