PubMed Health⌕ Search

Biomedical subjects

M Horiuchi

Publications and source records attributed to M Horiuchi.

At least 109 records · Page 6Linked to original sources
PubMed1998

Characterization of differentially expressed genes in the bovine T lymphoma cell line.

A differential display (D.D.) analysis was made to detect differentially expressed genes in a bovine T lymphoma cell line, BTL-26, derived from the calf type of sporadic bovine lymphosarcoma. A D.D. analysis comparing BTL-26 with the bovine epithelial cell line CKT-1 and healthy bovine thymocytes yielded 24 cDNA clones. The DNA sequencing analysis followed by a homology search showed that 20 of the 24 cDNA clones had no significant homology to any sequences in DNA data base. The remaining four genes were homologous to known sequences. Northern blot hybridization among BTL-26, CKT-1 and healthy bovine thymocytes showed that a cDNA clone, BC8, was differentially expressed in BTL-26. The cloning of full-length cDNA for the BC8 clone and its DNA sequences showed that the BC8 clone is a bovine nuclear domain protein homologous to the human NDP52 gene. Northern blot analysis showed that the BC8 clone bovine NDP52 was predominantly expressed in tumor cell line BTL-26, compared with the transcripts from several bovine tissues.

Amino Acid Sequence↗
PubMed1998

Effects of SA6541, a leukotriene A4 hydrolase inhibitor, and indomethacin on carrageenan-induced murine dermatitis.

We investigated the effects of S-(4-dimethylaminobenzyl)-N-[(2S)-3-mercapto-2-methylpropionyl]-L- cysteine (SA6541), a potent leukotriene A4 hydrolase inhibitor. on early phase of carrageenan-induced dermatitis model. Carrageenan injection induced edema and neutrophil influx in the mouse ear. SA6541 inhibited edema formation and neutrophil influx. SA6541 also inhibited leukotriene B4 production but not prostaglandin E2 production in the mouse ear. On the other hand, indomethacin inhibited edema formation but not neutrophil influx. Indomethacin also inhibited prostaglandin E2 production but not leukotriene B4 production. Combination therapy with SA6541 and indomethacin strongly inhibited edema formation in comparison with treatment with either agent alone. These results suggest that leukotriene B4 may be important in the pathogenesis of dermatitis.

Aniline Compounds↗
PubMed1998

Characterization of the sheep apolipoprotein E (ApoE) gene and allelic variations of the ApoE gene in scrapie Suffolk sheep.

Apolipoprotein E (ApoE) plays a central role in lipid transport and is suggested to be involved in neuronal repair. Human ApoE epsilon 4 allele is known as a risk factor for Alzheimer's disease, and an association of the human ApoE genotype with the human prion disease, Creutzfeldt-Jakob disease, is suggested, albeit controversial. We analyzed the sheep ApoE gene to determine whether any association between the sheep ApoE genotype and the sheep prion disease, scrapie, existed. The sheep ApoE cDNA contained an open reading frame (ORF) consisting of 948 base pairs (bp) that encoded 316 amino acids (aa). The sheep ApoE gene was composed of four exons separated by three introns, and the ORF was encoded by three exons, designated exons 2, 3, and 4. Nucleotide sequence analysis also showed the presence of one G/T nucleotide polymorphism in the ORF that resulted in an Ala/Ser amino-acid substitution at codon 258. PCR-restriction fragment length polymorphism analysis of genomic DNA showed the presence of three sheep ApoE genotypes that were the result of the homologous and heterologous combinations of the two alleles. We analyzed the sheep ApoE genotypic and the allelic frequencies in scrapie and control Suffolk sheep, but they did not significantly differ from those in the control sheep, even though PrP genotype-matched populations were compared. The ApoE genotype appeared not to be associated with the progression of the disease when looking at the age at death. These results indicated that in Suffolk sheep, none of the ApoE genotypes was associated with scrapie.

Alleles↗
PubMed1998

Role of AP-1 complex in angiotensin II-mediated transforming growth factor-beta expression and growth of smooth muscle cells: using decoy approach against AP-1 binding site.

The cis element double-stranded oligodeoxynucleotides (ODN) ("decoy") approach has enabled us to clarify the responsible elements. Using this approach, we transfected AP-1 decoy ODN into VSMC cultured from WKY rats (WKY Adu) which produce latent TGF-beta, but not active TGF-beta, and Sprague-Dawley rats (CNC) which produce active and latent TGF-beta under Ang II-stimulation. AP-1, but not mismatched, decoy ODN abolished Ang II-stimulated TGF-beta gene expression and production in both Adu and CNC. However, AP-1 decoy did not alter DNA, RNA, and protein synthesis in Adu. In contrast, cell number was increased under Ang II stimulation by AP-1 decoy ODN in CNC without significant change in RNA and protein synthesis. These results showed that Ang II stimulated TGF-beta production through the AP-1 complex. In VSMC that produce active TGF-beta (CNC), the AP-1 complex stimulated by Ang II may inhibit cell growth through active TGF-beta production. Overall, this study demonstrates the utility of the decoy approach to study the specific function of cis elements in endogenous gene regulation such as Ang II-induced TGF-beta expression.

Angiotensin II↗
PubMed1998

Involvement of leukotriene B4 in murine dermatitis models.

Leukotriene B4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid (AA) metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. To investigate the role of LTB4 in dermatitis, we used S-(4-dimethylaminobenzyl)-N-[(2S)-3-mercapto-2-methylpropionyl]-L- cysteine (SA6541), a potent leukotriene A4 (LTA4) hydrolase inhibitor. SA6541 inhibited LTB4 production with an IC50 value of 270 nM in vitro. 5-Hydroperoxyeicosatetraenoic acid (5-HPETE) or AA injection induced LTB4 production and neutrophil influx in mouse ear. SA6541 inhibited 5-HPETE- and AA-induced LTB4 production and neutrophil influx in mouse ear when administered orally at a dose of 50 mg/kg. SA6541 also inhibited 5-HPETE-induced prostaglandin E2 (PGE2) production, probably by an indirect effect through the inhibition of LTB4 production. These results suggest that LTB4 may be important in the pathogenesis of dermatitides such as psoriasis.

Aniline Compounds↗
PubMed1998

Cardiac-specific overexpression of angiotensin II AT2 receptor causes attenuated response to AT1 receptor-mediated pressor and chronotropic effects.

Angiotensin (Ang) II has two major receptor isoforms, AT1 and AT2. Currently, AT1 antagonists are undergoing clinical trials in patients with cardiovascular diseases. Treatment with AT1 antagonists causes elevation of plasma Ang II which selectively binds to AT2 and exerts as yet undefined effects. Cardiac AT2 level is low in adult hearts, whereas its distribution ratio is increased during cardiac remodeling and its action is enhanced by application of AT1 antagonists. Although in AT2 knock-out mice sensitivity to the pressor action of Ang II was increased, underlying mechanisms remain undefined. Here, we report the unexpected finding that cardiac-specific overexpression of the AT2 gene using alpha-myosin heavy chain promoter resulted in decreased sensitivity to AT1-mediated pressor and chronotropic actions. AT2 protein undetectable in the hearts of wild-type mice was overexpressed in atria and ventricles of the AT2 transgenic (TG) mice and the proportions of AT2 relative to AT1 were 41% in atria and 45% in ventricles. No obvious morphological change was observed in the myocardium and there was no significant difference in cardiac development or heart to body weight ratio between wild-type and TG mice. Infusion of Ang II to AT2 TG mice caused a significantly attenuated increase in blood pressure response and the change was completely blocked by pretreatment with AT2 antagonist. This decreased sensitivity to Ang II-induced pressor action was mainly due to the AT2-mediated strong negative chronotropic effect and exerted by circulating Ang II in a physiological range that did not stimulate catecholamine release. Isolated hearts of AT2 transgenic mice perfused using a Langendorff apparatus also showed decreased chronotropic responses to Ang II with no effects on left ventricular dp/dt max values, and Ang II-induced activity of mitogen-activated protein kinase was inhibited in left ventricles in the transgenic mice. Although transient outward K+ current recorded in cardiomyocytes from AT2 TG mice was not influenced by AT2 activation, this study suggested that overexpression of AT2 decreases the sensitivity of pacemaker cells to Ang II. Our results demonstrate that stimulation of cardia AT2 exerts a novel antipressor action by inhibiting AT1-mediated chronotropic effects, and that application of AT1 antagonists to patients with cardiovascular diseases has beneficial pharmacotherapeutic effects of stimulating cardiac AT2.

Angiotensin II↗
PubMed1998

Four cases of Warthin's tumor of the parotid gland detected with FDG PET.

In the cancer screening with FDG PET for 1,872 medical health club members, high FDG accumulation in the parotid gland was found in four males (age, 57-70 years). Warthin's tumor was confirmed by surgical pathology. The exact mechanism of high FDG accumulation in Warthin's tumor is not yet known. This tumor may be found incidentally during FDG PET studies. When high FDG accumulation is found in the parotid gland, integrated consideration of the results of the physical examination, medical history and 99mTc-pertechnetate scintigraphy makes it possible to differentiate Warthin's tumor from other lesions.

Adenolymphoma↗
PubMed1998

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis and antagonizes angiotensin II type 1 receptor action: an in vitro gene transfer study.

Angiotensin II type 2 (AT2) receptor is expressed abundantly in the fetal vasculature with rapid decline after birth and re-expressed in the adult vasculature after injury, whereas angiotensin II type 1 (AT1) receptor is expressed. We studied their effects on apoptosis in cultured rat vascular smooth muscle cells (VSMC). Serum starvation induced VSMC DNA fragmentation and the stimulation of AT1 receptor inhibited this apoptotic change. We transfected rat AT2 receptor cDNA, since cultured adult VSMCs show very low level of endogenous AT2 receptor. In AT2 receptor transfected VSMC, selective stimulation of AT2 receptor facilitated serum-deprivation-induced apoptosis and AT1 receptor stimulation inhibited it. Moreover we observed that AT1 receptor stimulation activated extracellular signal-regulated kinase (ERK), whereas the AT2 receptor stimulation inhibited the activation of ERK. Taken together, our results suggest that AT1 and AT2 receptors exert counteracting effects on ERK activation and consequently VSMC apoptosis and differential expression of these receptors may participate in vascular development and vascular remodeling.

Animals↗
PubMed1998

Genomic structure of the bovine PrP gene and complete nucleotide sequence of bovine PrP cDNA.

The present authors previously reported the nucleotide sequence of the 5' half of a cDNA encoding bovine prion protein (PrP) and the genomic structure of the bovine PrP gene encoding the 5' -untranslated region. Here they report the extent of intron 2 of the bovine PrP gene and the nucleotide sequence of the 3' half of bovine PrP cDNA that had not been determined before. This newly sequenced 3' half of the bovine PrP cDNA consisted of 2149 bp. The entire 3'-untranslated region (3'-UTR) was found to be encoded by a single exon, exon 3. One nucleotide polymorphism was found in the 3'-UTR. The length of intron 2 was estimated to be about 14 kbp. The structure of bovine PrP gene can be defined by combining the present results and previous reports on the bovine PrP gene.

Animals↗
PubMed1998

Study of the pharmacokinetics of cefpirome sulphate in the elderly.

OBJECTIVE: To determine the appropriate method of administration of the cephem antibiotic cefpirome sulphate in elderly patients. METHOD: We studied cefpirome's pharmacokinetics in patients with urinary tract infections. Patients received cefpirome sulphate 0.5 g by intravenous drip infusion over 30 mins. RESULTS: Patients with a creatinine clearance rate (Ccr) of 80 ml/min had an AUC of 96.7 microg.h/ml and a T1/2 of 2.36 h, whereas those with Ccr of 40-80 ml/min had an AUC of 172.0 microg.h/ml and a T1/2 of 3.45 h and those with Ccr of < 40 ml/min had an AUC of 152 microg.h/ ml and a T1/2 of 4.86 h. CONCLUSION: These results indicate that decreased kidney function can cause increases in the AUC and T1/2 of cefpirome. Thus in elderly patients and perhaps also in other patients with decreased kidney function, cefpirome should be administered at an initial dose of 0.5 g.

Aged↗
PubMed1998

Chronic thyroiditis: diffuse uptake of FDG at PET.

PURPOSE: To determine the frequency and clinical importance of diffuse 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in the thyroid gland. MATERIALS AND METHODS: A total of 1,102 healthy subjects underwent whole-body positron emission tomography (PET). PET images were evaluated for increased diffuse FDG uptake in the thyroid gland. Serum free thyroxine and thyrotropin levels were measured in 36 subjects with increased uptake and in 36 matched control subjects without uptake. Antithyroid antibodies were also measured. Morphologic abnormalities were examined by using ultrasonography (US). RESULTS: Diffuse FDG uptake was found in three men and 33 women; the prevalence was significantly higher in women (P < .01). Thirty-five subjects were euthyroid; one had hypothyroidism. Antithyroid antibodies were positive in 27 subjects. In most subjects, US findings facilitated the diagnosis of chronic thyroiditis. In control subjects, the positive rates for antithyroid antibodies and US abnormalities were significantly lower than those of the study group (P < .01). CONCLUSION: Diffuse thyroidal FDG uptake may be an indicator of chronic thyroiditis. The actual prevalence of the disorder was not low in this series, and such lesions may be found incidentally at FDG PET.

Adult↗
PubMed1998

An oligonucleotide decoy for transcription factor E2F inhibits mesangial cell proliferation in vitro.

The transcription factor E2F controls expression of several genes involved in cell proliferation including c-myc, c-myb, proliferating cell nuclear antigen (PCNA), and cdk2 kinase. Having established that both PCNA and cdk2 kinase are induced in rat mesangial cells (MC) by serum stimulation, we attempted to inhibit MC proliferation in vitro by transfecting these cells with cationic liposomes containing a synthetic double-stranded oligodeoxynucleotide (ODN) with high affinity for E2F. Using a gel mobility shift assay, we detected increased specific binding of E2F in MC following serum stimulation. This binding was completely inhibited by preincubation of MC nuclear extracts with the double-stranded ODN with high affinity for E2F but not by preincubation with a missense ODN containing two point mutations. MC were also transfected with a luciferase reporter gene construct containing three E2F binding sites. Luciferase activity was enhanced by serum stimulation of MC, and this effect was specifically abolished by cotransfection of MC with E2F decoy ODN. Furthermore, RT-PCR analysis revealed that serum-induced upregulation of PCNA and cdk2 kinase gene expression was inhibited by E2F decoy ODN transfection but not by transfection of missense ODN. These changes in gene expression were paralleled by a reduction in PCNA and cdk2 kinase protein expression in E2F decoy ODN transfected cells. MC number increased following serum stimulation. This effect was blunted by transfection with E2F decoy ODN but not by transfection of missense ODN. These data suggest that the transcription factor E2F plays a crucial role in the regulation of MC proliferation and that this factor can be successfully targeted to inhibit MC cell cycle progression.

Animals↗
PubMed1998

Virus inactivation in superoxide dismutase preparations by ultraviolet light irradiation.

Viral inactivation in superoxide dismutase (SOD) derived from human red cells was carried out by ultraviolet light C (UVC) irradiation. With 400 J/m2 UVC irradiation, the titer of canine parvovirus (CPV, a nonenveloped virus), M13 bacteriophage (M13, a nonenveloped phage) and vesicular stomatitis virus (VSV, an enveloped virus), which were spiked into SOD solution, were reduced by > 4.6 log10 (detection limit), 7.0 log10 and 6.2 log10, respectively. The SOD activity was maintained and the band pattern of SOD on an electrophoresis gel was not changed even by 1000 J/m2 UVC irradiation. These results indicate that UVC irradiation is a promising method for the inactivation of both enveloped and nonenveloped viruses in SOD preparations while maintaining its activity.

Animals↗
PubMed1998

Chicken monoclonal antibodies against synthetic bovine prion protein peptide.

Chicken monoclonal antibodies (mAbs) were developed against bovine prion protein (PrP) peptide. Chickens immunized with bovine PrP peptide B204 (amino acid residues 204-220) coupled to keyhole limpet hemocyanin produced specific antibodies to the peptide as determined by an enzyme-linked immunosorbent assay (ELISA) using the B204 peptide coupled to ovalbumin as target antigen. From a fusion experiment using the chicken fusion partner cell line MuH1 and immune spleen cells, 19 mAbs reactive with B204 were generated. These mAbs were subdivided into five groups based on competitive ELISA using B204 and four 10-amino acid peptides. These five groups included all combinations expected based on comparison of amino acid sequences among the five species, bovine, mouse, human, sheep and hamster, examined. These results indicate that the chicken mAb system is a suitable technique for immunological analysis of PrP in mammals.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetics of danaparoid sodium, dalteparin sodium and heparin determined by inhibitory effect on the activated coagulation factor X activity after single intravenous administration in rabbits.

The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with that of dalteparin sodium (DLS, CAS 9041-08-1) and heparin (CAS 9005-49-6) after single intravenous administration at a dose of 640 anti-Xa U/kg to male rabbits. The elimination of half-life of DAS was 9.90 h and was 6.0 times longer than that of DLS and 16.5 times longer than that of heparin. The area under the plasma concentration-time curve (AUC) of DAS was 47.13 +/- 14.55 anti-Xa U.h/ml and was 2.4 times larger than that of DLS and 2.9 times larger than that of heparin. The urinary cumulative excretion of anti-Xa activity of DAS and DLS was 42.6 +/- 6.4% and 16.4 +/- 0.8% of dose, respectively, in 24 h after dosing, respectively. But the anti-Xa activity in urine was not detected at any sampling points after administration of heparin. DAS has a longer elimination half-life and a higher renal excretion of anti-Xa activity than that of DLS and heparin. Therefore, in comparison to DLS and heparin, it seems that the anticoagulant activity of DAS has a long duration.

Animals↗