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Biomedical subjects

H Yamazaki

Publications and source records attributed to H Yamazaki.

At least 199 records · Page 11Linked to original sources
PubMed1999

Contingent negative variation in children with anorexia nervosa.

BACKGROUND: Central catecholamines, particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN. METHODS: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press. RESULTS: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Cz than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV. CONCLUSION: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

Adolescent↗
PubMed1999

Ratio of eosinophil cationic protein/eosinophil count as a new marker in children with acute asthma.

BACKGROUND: It is a matter of concern whether serum eosinophil cationic protein (ECP) can be considered as a disease marker in children with acute asthma being treated without corticosteroids. METHODS: Fourteen children (nine male, five female, aged 6-12 years) with acute asthmatic exacerbation, administered the appropriate drugs, with the exception of systemic or inhaled corticosteroids, were examined. They were all free from apparent asthmatic attacks during a follow-up period of 1 month. Serum ECP, eosinophil count and forced expiratory volume in 1 s (FEV1) were measured at referral, on the day of discharge, 1 week and 4 weeks after discharge, respectively. RESULTS: The ratio of ECP/eosinophil count (ECP:Eo ratio), expressed as micrograms of ECP (microgram/L)/the number of eosinophil (/microL) x 1000, was also evaluated as a marker of eosinophil activation. Compared with the value at referral, FEV1 (% predicted) significantly increased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). However, serum ECP concentrations showed no significant changes during the follow-up period. Eosinophil count showed no significant changes on the day of discharge or 1 week after discharge, but significantly increased 4 weeks after discharge (P < 0.05). In contrast, the ECP:Eo ratio significantly decreased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). CONCLUSION: These data suggest that serum ECP is a poor disease marker in asthmatic children with acute exacerbation who receive no corticosteroid therapy, probably due to marked changes in the eosinophil count. However, the ECP:Eo ratio might be a better marker than serum ECP in such patients.

Adrenal Cortex Hormones↗
PubMed1999

Isoform selective inhibition and inactivation of human cytochrome P450s by methylenedioxyphenyl compounds.

1. A series of methylenedioxyphenyl compounds were evaluated for their inhibitory and inactivation effects on nine human cytochrome P450 (CYP) activities using microsomes from human B-lymphoblast cells expressing specific human CYP isoforms. 2. Methylenedioxyphenyl compounds which possess a bulky structure such as 1,4-benzothiazine showed substantial inhibition of S-warfarin 7-hydroxylation catalysed by CYP2C9, S-mephenytoin 4'-hydroxylation by CYP2C19, bufuralol 1'-hydroxylation by CYP2D6, and testosterone 6beta-hydroxylation by CYP3A4. Regarding ethoxyresorufin O-deethylation catalysed by CYP1A1 and benzyloxyresorufin O-dealkylation by CYP2B6, the subtle change of a substitution of the 1,4-benzothiazine structure affected the inhibition selectivity. Ethoxyresorufin O-deethylation by CYP1A2, coumarin 7-hydroxylation by CYP2A6, and chlorzoxazone 6-hydroxylation by CYP2E1 were not inhibited by almost any of the methylenedioxyphenyl compounds. The inhibitory effects of methylenedioxyphenyl compounds that possess a short chain amino group on the human CYP isoforms were not significant. 3. The methylenedioxyphenyl compounds inactivated CYP1A1 (k(inact) = 0.034 min(-1) and K(i) = 0.81 microM), CYP2C9 (k(inact) = 0.041 and 0.042 min(-1) and K(i) = 0.56 and 0.15 microM), CYP2D6 (k(inact) = 0.044-0.339 min(-1) and K(i) = 0.21-19.88 microM), and CYP3A4 (k(inact) = 0.076-0.251 min(-1) and K(i) = 0.25-0.69 microM). These results suggested that the methylenedioxyphenyl compounds investigated in this study would be potent mechanism-based inactivators of these human CYP isoforms. In contrast, CYP2B6 and CYP2C19 were not inactivated. 4. The present study suggested that the selectivity of inhibition or inactivation of human CYP isoforms by methylenedioxyphenyl compounds may vary according to the structure of the side chain.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by human cytochrome P450 enzymes.

1. Effects of arachidonic acid, prostaglandins, retinol, retinoic acid and cholecalciferol on xenobiotic oxidations catalysed by 12 recombinant human cytochrome P450 (P450 or CYP) enzymes and by human liver microsomes have been investigated. 2. Arachidonic acid (50 microM) significantly inhibited CYP1A1- and 1A2-dependent 7-ethoxycoumarin O-deethylations, CYP2C8-dependent taxol 6alpha-hydroxylation and CYP2C19-dependent R-warfarin 7-hydroxylation. This chemical also inhibited slightly the xenobiotic oxidations catalysed by CYP1B1, 2B6, 2C9, 2D6, 2E1 and 3A4 in recombinant enzyme systems. 3. Retinol, retinoic acid and cholecalciferol were strong inhibitors for xenobiotic oxidations catalysed by recombinant CYP1A1, 2C8 and 2C19. 4. Dixon plots of inhibitions of CYP1A1-, 1A2-, 2C8- and 2C19-dependent xenobiotic oxidations by arachidonic acid, of CYP1A1-, 2B6- and 2C19-dependent activities by retinol, and of CYP1A1- and 2C19-dependent activities by cholecalciferol indicated that these chemicals inhibit P450 activities mainly through a competitive mechanism. 5. In human liver microsomes, arachidonic acid inhibited CYP1A2-dependent theophylline hydroxylation, CYP2C8-dependent taxol 6alpha-hydroxylation and CYP2C19-dependent omeprazole 5-hydroxylation. Taxol 6alpha-hydroxylation was also inhibited by retinol and retinoic acid, and omeprazole 5-hydroxylation was inhibited by retinol in human liver microsomes. 6. These results suggest that xenobiotic oxidations by P450 enzymes are affected by endobiotic chemicals and that the endobiotic-xenobiotic interactions as well as drug-drug interactions may be of great importance when understanding the basis for pharmacological and toxicological actions of a number of xenobiotic chemicals.

Arachidonic Acid↗
PubMed1999

Role of human N-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in Salmonella typhimurium NM6001 and NM6002.

Human NAT1 and NAT2 genes were subcloned into pACYC184 vector and the plasmids thus obtained were introduced into Salmonella typhimurium O-acetyltransferase-deficient strain NM6000 (TA1538/1, 8-DNP/pSK1002), establishing new strains NM6001 and NM6002, respectively. We compared the sensitivities of these two strains with those of NM6000 towards carcinogenic nitroarenes and aromatic amines in the SOS/umu response. The induction of umuC gene expression by these chemicals in the presence and absence of the S9 fraction was assayed by measuring the cellular beta-galactosidase activity expressed by the umuC"lacZ fusion gene in the tester strains. 2-Nitrofluorene and 2-aminofluorene induced umuC gene expression more strongly in the NM6001 strain than in the NM6002 strain. In contrast, induction of umuC gene expression by 1, 8-dinitropyrene, 6-aminochrysene and 2-amino-3,5-dimethylimidazo[4, 5-f]quinoline was weaker in the NM6001 strain than in the NM6002 strain. 1-Nitropyrene, 2-amino-6-methyl-dipyrido[1,2-a:3', 2'-d]imidazole, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methyl-9H-pyrido[2,3-b]indole were found to induce umuC gene expression at similar extents in both strains. These results suggest that the newly developed strains can be employed for the studies on mechanisms of genotoxicity of a variety of nitroarenes and aromatic amines, along with the assessment of cancer risk to humans.

Arylamine N-Acetyltransferase↗
PubMed1999

Characterization of an alg2 mutant of the zygomycete fungus Rhizomucor pusillus.

The zygomycete fungus Rhizomucor pusillus secretes an aspartic proteinase (MPP) that contains asparagine ( N )-linked oligosaccharides at two sites. Mutant strain 1116 defective in N -glycosylation secretes MPP with truncated oligo-saccharide chains. Lipid-linked oligosaccharides in mutant 1116 were labeled with [6-(3)H]glucosamine and [2-(3)H]mannose, prepared by cycles of solvent extraction, and analyzed by gel filtration chromatography on a Bio-Gel P-4 column after mild acid-hydrolysis. Mutant 1116 accumulated an intermediate, Man(1)GlcNAc(2)-dolichol pyrophosphate (PP-Dol), whereas wild-type strain F27 synthesized the fully assembled oligosaccharide precursor Glc(3)Man(9)GlcNAc(2)-PP-Dol. Consistent with this, alg2 encoding a mannosyltransferase in the lipid-linked oligosaccharide biosynthetic pathway in mutant 1116 had a 5 bp insertion that generated a stop codon in the middle of the coding sequence. Transformation of mutant 1116 with the intact alg2 gene on a pUC19-derived plasmid generated transformants that contained multicopies of alg2 at the alg2 locus. Glycosylation of the total proteins in the transformants was recovered to the same level as in strain F27, as determined with peroxidase-concanavalin A. These transformants produced MPP mainly with the same N -linked oligosaccharides as that produced by strain F27, but still with truncated oligosaccharides in small amounts. All of these data show that Alg2 is an alpha-1,3 or alpha-1,6 mannosyltransferase that elongates Man(1)GlcNAc(2)-PP-Dol to Man(2)GlcNAc(2)-PP-Dol. The slower growth of mutant 1116 was significantly recovered on introduction of alg2. The viability of the alg2 mutants of the zygomycete R.pusillus makes a contrast with the lethal effect of ALG2 mutations in the yeast Saccharomyces cerevisiae.

Amino Acid Sequence↗
PubMed1999

Function of the propeptide region in recombinant expression of active procathepsin L in Escherichia coli.

In order to determine the functional role of the procathepsin L propeptide region for the preparation of active recombinant rat cathepsin L (CL), cDNAs encoding two short-length propeptides (C-terminal 2 and 27 residues) and the full-length (96 residues) one plus the entire CL were expressed as two soluble fusion proteins with a fragment of maltose-binding protein and an insoluble fusion protein with glutathione-S-transferase in Escherichia coli, respectively. After refolding of the insoluble fusion protein, each gene product was purified to homogeneity by amylose or glutathione-Sepharose-4B affinity column, and digestion with factor Xa and alpha-thrombin under alkaline conditions (pH approximately 8.0) led to the elution of two pure short-length procathepsin Ls (PCLs) and a full-length one, respectively. The enzymatic activity, estimated by hydrolytic assaying of benzoxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide under acidic conditions (pH 5.5), indicated that the two short-length PCLs exhibited in a great loss of the activity, as compared with the full-length PCL. The CD spectra of the short-length PCLs were different from that of the full-length one. The present results clearly show that the full-length propeptide is essential for construction of the active tertiary structure of CL at the stage of recombinant protein expression, although the expression of CL itself in E. coli does not require the propeptide. Based on the tertiary structure of PCL, the propeptide region necessary for the construction of the CL active structure has been discussed.

Animals↗
PubMed1999

Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.

Adolescent↗
PubMed1999

Effectiveness of radiation therapy in nephrotic syndrome associated with advanced lung cancer.

Paraneoplastic nephrotic syndrome is rare, bur occurs mostly in lung cancer. The glomerular lesion usually exhibits membranous nephropathy. Although surgical therapy has been shown to be effective, the treatment of a paraneoplastic nephrotic syndrome has always been a challenge. Currently no standard therapy has been established, if the paraneoplastic nephrotic syndrome is associated with advanced cancer with unresectable lesions. We present 2 cases having paraneoplastic nephrotic syndrome associated with advanced squamous cell carcinoma of the lung. Radiation therapy of the primary tumor effectively caused regression of the paraneoplastic nephrotic syndrome without affecting the renal function. Our results suggest that irradiation can be the first choice in the treatment of nephrotic syndrome, if the primary tumor is unresectable.

Aged↗
PubMed1999

[Adhesive and sealing effects of TO-193 on tissues and organs in various experimental models].

We studied the adhesive and sealing effects of sheet style fibrin adhesive, TO-193 (TachoComb), on some tissues and organs, comparing them with those of sheet style collagen agent, collagen sponge, Novacol, and Avitene and liquid fibrin adhesive agent, Beriplast P. TO-193 showed more a potent adhesive effect on liver than the sheet style collagen agents and was more potent on bone and skin than the liquid fibrin adhesive agent. Furthermore, TO-193 had a potent sealing effect at the site of incomplete suture immediately after application on a motile organ such as lung and stomach. These effects may be partly attributable to rapid expression of the effect due to the presence of a high concentration of fibrinogen on coverage. Enhancement of fibrin penetrability to the tissues by compression and inhibition of cleavage of coverage by the collagen sponge also may be participating in the effects of TO-193. These results suggest that TO-193 will be a valuable adhesive and sealing agent.

Animals↗
PubMed1999

Malignant intravascular lymphomatosis associated with venous stenosis. Case report.

This 55-year-old man presented with malignant intravascular lymphomatosis, a rare vascular disorder of the central nervous system characterized by proliferation of malignant lymphoma cells. The clinical manifestations were focal neurological signs and progressive dementia. Angiography demonstrated stenoses of the cortical veins. Postmortem examination revealed infiltration of tumor cells into the lumen and vascular wall, although the stenoses were caused primarily by fibrin thrombi. To the authors' knowledge this is the first case of malignant intravascular lymphomatosis associated with venous stenosis.

Angiography, Digital Subtraction↗
PubMed1999

Stromal expression of thrombospondin-1 is correlated with growth and metastasis of human gallbladder carcinoma.

Thrombospondin-1 (TSP1) is one of the extracellular matrix glycoproteins that affect cell adhesion, motility and growth. Based on its effects on tumors, TSP1 is thought to be a potential regulator of tumor growth and metastasis. In this study, we examined TSP1 expression in human gallbladder adenocarcinoma and its clinicopathological significance. TSP1 immunoreactivity was detected mainly in the cancer stroma and was observed infrequently in cancer cells. According to the TNM classification, 74.5% (29/39) of the T2 and T3 gallbladder cancers were TSP1-positive, while none (0/14) of the T1 cancers showed TSP1 expression (p<0.001). Lymph node metastasis and venous involvement were frequently found in the TSP1-positive cases (90.0% and 87.1%, respectively) of gallbladder adenocarcinoma (p<0.001). These observations suggested that TSP1 expression plays an important role in cancer cell growth and metastasis of human gallbladder adenocarcinomas, and that stromal TSP1 immunoreactivity is a good predictor of vascular involvement and lymph node metastasis.

Adenocarcinoma↗
PubMed1999

Expression of angiostatic factors in colorectal cancer.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. We examined expression of genes encoding various angiostatic factors: thrombospondin 1 (TSP1), thrombospondin 2 (TSP2), brain-specific angiogenesis inhibitor 1 (BAI1) and angiopoietin 2 (AGP2) in 62 colorectal cancers and 40 samples of extraneoplastic colon mucosa. The expression of the angiostatic factors TSP2 and AGP2 were significantly increased in the cancerous mucosa as compared to these in extraneoplastic mucosa (o2 test; p<0. 0001, and Fisher's exact test; p<0.0001), while the increase in TSP1 expression was not significant. BAI1 expression was slightly decreased in the cancer tissue. These results suggested that specific types of angiostatic factors might have protective roles against cancer cell proliferation via dormancy due to hyponutrition caused by decreased vascularity.

Angiogenesis Inhibitors↗
PubMed1999

[Digital rectal examination, transrectal ultrasonography and prostate specific antigen for diagnosis of prostate cancer in clinical urological practice-detection of impalpable cancer].

OBJECTIVE: The clinical usefulness of multimodality detection for prostate cancer by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and serum PSA determination (PSA) was evaluated in this retrospective study. PATIENTS AND METHODS: A total of 1344 symptomatic male patients who underwent DRE, TRUS and PSA in our outpatient clinic were studied. Prostate biopsies were performed when at least one diagnostic test was positive. RESULTS: Of 1344 patients, 436 (32.4%) had positive test results. Among 403 patients who underwent biopsy, 121 patients (30.0%) were found to have prostate cancer. The overall cancer detection rate was 9.0%. Among the 121 cancer patients, if examination had been carried out using only one or two tests, cancer would have not been detected in 22 patients (18.2%) by DRE alone, 27 patients (22.3%) by TRUS alone, 18 patients (14.9%) by PSA alone, 12 patients (9.9%) by a combination of DRE and TRUS, and 6 patients (5.0%) by a combination of DRE and PSA. Among the 121 patients with cancer, 22 (18.2%) had impalpable cancer. Impalpable cancer was more likely to be localized (77.3%) than palpable cancer (28.3%, p < 0.001) and more likely to be well or moderately differentiated (72.7%) than palpable cancer (41.4%, p = 0.008). CONCLUSION: This study confirmed the need for multimodality detection using DRE, TRUS and PSA as complementary methods in order to minimize decrease in cancer detection. In particular, impalbable cancers not detectable by DRE were detected and were revealed to be more likely to be localized and amenable to curative therapy. These results therefore underscore the importance of multimodality detection for early diagnosis of prostate cancer in urological practice.

Adult↗
PubMed1999

Tissue response of a small saccular aneurysm after incomplete occlusion with a Guglielmi detachable coil.

A 49-year-old woman had a small saccular aneurysm that was incompletely occluded with a Guglielmi detachable coil (GDC). She died from rupture of another aneurysm 42 days after the treatment. Autopsy for the embolized aneurysm revealed no neoendothelium at the aneurysmal neck, but an organized thrombus was observed limited to the periphery of the aneurysmal lumen. Although isolation of the aneurysm was not apparent, loose embolization with this method may help to reinforce the aneurysmal wall.

Aneurysm, Ruptured↗
PubMed1999

Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be metabolized mainly to desmethylazelastine and 6-hydroxyazelastine in mammals. In the present study, the inhibitory effects of azelastine and its two metabolites on human cytochrome P-450 (CYP) isoform-dependent reactions were investigated to predict the drug interactions of azelastine using microsomes from human B-lymphoblast cells expressing CYP. The specific activities for human CYP isoforms included: 7-ethoxyresorufin O-deethylation (CYP1A1), phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), 7-benzyloxyresorufin O-dealkylation (CYP2B6), S-warfarin 7-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and testosterone 6beta-hydroxylation (CYP3A4). In almost all the activities, desmethylazelastine exhibited stronger inhibition than azelastine and 6-hydroxyazelastine. Desmethylazelastine, but not azelastine and 6-hydroxyazelastine, uncompetitively inhibited CYP2B6 activity (Ki = 32.6 +/- 4.8 microM). Azelastine, desmethylazelastine, and 6-hydroxyazelastine competitively inhibited CYP2C9 activity (Ki = 13. 9 +/- 1.8, 15.0 +/- 3.1, and 17.0 +/- 4.1 microM, respectively), CYP2C19 activity (Ki = 21.9 +/- 2.2, 7.3 +/- 1.6, and 9.3 +/- 1.6 microM, respectively), and CYP2D6 activity (Ki = 1.2 +/- 0.1, 1.5 +/- 0.2, and 3.0 +/- 0.5 microM, respectively). Azelastine and desmethylazelastine competitively inhibited CYP3A4 activity (Ki = 23. 7 +/- 4.6 and 13.2 +/- 2.3 microM). 6-Hydroxyazelastine interfered with the determination of testosterone 6beta-hydroxylation by HPLC. CYP1A2, CYP2A6, and CYP2E1 activities were not significantly inhibited by azelastine and the two metabolites. Among the human CYPs tested, the inhibitory effects of azelastine and its two metabolites were the most potent on human CYP2D6. In consideration of the Ki values and the concentration of azelastine and desmethylazelastine in human livers after chronic oral administration of azelastine, the possibility of in vivo drug interaction of azelastine and other drugs that are mainly metabolized by CYP2D6 was suggested although it might not cause critical side effects. The inhibition of CYP2C9, CYP2C19, and CYP3A4 activity by azelastine and its two metabolites might be clinically insignificant.

Anti-Allergic Agents↗