Biomedical subjects

T Aoyama

Publications and source records attributed to T Aoyama.

At least 91 records · Page 5Linked to original sources

PubMed1999

Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene.

We have reported the cDNA cloning of a modified low-density-lipoprotein (LDL) receptor, designated lectin-like oxidized LDL receptor-1 (LOX-1), which is postulated to be involved in endothelial dysfunction and the pathogenesis of atherosclerosis. Here, we determined the organization of the human LOX-1 gene, including the 5'-regulatory region. The 5'-regulatory region contained several potential cis-regulatory elements, such as GATA-2 binding element, c-ets-1 binding element, 12-O-tetradecanoylphorbol 13-acetate-responsive element and shear-stress-responsive elements, which may mediate the endothelium-specific and inducible expression of LOX-1. The major transcription-initiation site was found to be located 29 nucleotides downstream of the TATA box and 61 nucleotides upstream from the translation-initiation codon. The minor initiation site was found to be 5 bp downstream from the major site. Most of the promoter activity of the LOX-1 gene was ascribed to the region (-150 to -90) containing the GC and CAAT boxes. The coding sequence was divided into 6 exons by 5 introns. The first 3 exons corresponded to the different functional domains of the protein (cytoplasmic, transmembrane and neck domains), and the residual 3 exons encoded the carbohydrate-recognition domain similar to the case of other C-type lectin genes. The LOX-1 gene was a single-copy gene and assigned to the p12.3-p13.2 region of chromosome 12. Since the locus for a familial hypertension has been mapped to the overlapping region, LOX-1 might be the gene responsible for the hypertension.

Base Sequence↗

PubMed1999

Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.

Human HADHA and HADHB genes encode the subunits of an enzyme complex, the trifunctional protein, involved in mitochondrial beta-oxidation of fatty acids. Both genes are located in the same region of chromosome 2p23. We isolated genomic clones, including 5' flanking regions, for HADHA and HADHB. Sequencing revealed that both of these genes are linked in a head-to-head arrangement on opposite strands and have in common a 350-bp 5' flanking region. The 5' flanking region has bidirectional promoter activity within this region; two cis elements proved critical for the activity. Transcription factor Sp1 functions as an activator for the bidirectional promoter by binding to both elements. Therefore, expression of trifunctional protein subunits are probably coordinately regulated by a common promoter and by Sp1.

Base Sequence↗

PubMed1999

Tissue factor pathway inhibitor-2 is a novel mitogen for vascular smooth muscle cells.

A mitogen for growth-arrested cultured bovine aortic smooth muscle cells was purified to homogeneity from the supernatant of cultured human umbilical vein endothelial cells by heparin affinity chromatography and reverse-phase high performance liquid chromatography. This mitogen was revealed to be tissue factor pathway inhibitor-2 (TFPI-2), which is a Kunitz-type serine protease inhibitor. TFPI-2 was expressed in baby hamster kidney cells using a mammalian expression vector. Recombinant TFPI-2 (rTFPI-2) stimulated DNA synthesis and cell proliferation in a dose-dependent manner (1-500 nM). rTFPI-2 activated mitogen-activated protein kinase (MAPK) activity and stimulated early proto-oncogene c-fos mRNA expression in smooth muscle cells. MAPK, c-fos expression and the mitogenic activity were inhibited by a specific inhibitor of MAPK kinase, PD098059. Thus, the mitogenic function of rTFPI-2 is considered to be mediated through MAPK pathway. TFPI has been reported to exhibit antiproliferative action after vascular smooth muscle injury in addition to the ability to inhibit activation of the extrinsic coagulation cascade. However, structurally similar TFPI-2 was found to have a mitogenic activity for the smooth muscle cell.

Animals↗

PubMed1999

Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells.

A functional change in the endothelium induced by oxidized low density lipoprotein (OxLDL) and its lipid-constituent, lysophosphatidylcholine (LPC), has been implicated in atherogenesis. Recently, we have cloned lectin-like OxLDL receptor (LOX-1) from bovine aortic endothelial cells (BAE). It is the major binding protein for OxLDL on the surface of BAE and is expressed in atheromatous intima of the human carotid artery as well as in intima of normal bovine aorta. In the present study, we found that OxLDL induced the expression of LOX-1 in BAE. OxLDL upregulated the level of mRNA and protein for LOX-1 in a dose- and time-dependent manner. This induction was blocked by anti-LOX-1 antibody. OxLDL also increased the activity for taking up OxLDL in BAE. Similarly, a major constituent of OxLDL, lysophosphatidylcholine (LPC), induced expression of LOX-1 in mRNA, protein and activity level, suggesting the OxLDL induced expression of LOX-1, at least in part, mediated by LPC. Since LPC did not significantly change the half-life of LOX-1 mRNA, the upregulation seemed to occur at the transcriptional level. These results suggest that LOX-1 is upregulated by the uptake of OxLDL through LOX-1 in atheromatous tissues in vivo, which would further enhance the uptake and endothelial activation and dysfunction.

Animals↗

PubMed1999

Sesamin, a sesame lignan, is a potent inducer of hepatic fatty acid oxidation in the rat.

The effects of sesamin, one of the most abundant lignans in sesame seed, on hepatic fatty acid oxidation were examined in rats that were fed experimental diets containing various amounts (0%, 0.1%, 0.2%, and 0.5%) of sesamin (a 1:1 mixture of sesamin and episesamin) for 15 days. Dietary sesamin dose-dependently increased both mitochondrial and peroxisomal palmitoyl-coenzyme A (CoA) oxidation rates. Mitochondrial activity almost doubled in rats on the 0.5% sesamin diet. Peroxisomal activity increased more than 10-fold in rats fed a 0.5% sesamin diet in relation to rats on the sesamin-free diet. Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase. Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently. Examination of hepatic mRNA levels using specific cDNA probes showed a sesamin-induced increase in the gene expression of mitochondrial and peroxisomal fatty acid oxidation enzymes. Among these various enzymes, peroxisomal acyl-CoA oxidase and bifunctional enzyme gene expression were affected most by dietary sesamin (15- and 50-fold increase by the 0.5% dietary level). Sesamin-induced alterations in the activity and gene expression of carnitine palmitoyltransferase I and acyl-CoA oxidase were in parallel with changes in the mitochondrial and peroxisomal palmitoyl-CoA oxidation rate, respectively. In contrast, dietary sesamin decreased the hepatic activity and mRNA abundance of fatty acid synthase and pyruvate kinase, the lipogenic enzymes. However, this lignan increased the activity and gene expression of malic enzyme, another lipogenic enzyme. An alteration in hepatic fatty acid metabolism may therefore account for the serum lipid-lowering effect of sesamin in the rat.

Administration, Oral↗

PubMed1999

Biochemical markers of bone turnover in breast cancer patients with bone metastases: a preliminary report.

BACKGROUND: Some biochemical markers of bone turnover are expected to reflect the disease activity of metastatic bone tumor. In the present study six biochemical markers were evaluated to determine appropriate markers for the detection of metastatic bone tumors from breast cancer (BC). METHODS: A panel of bone turnover markers was assessed in 11 normocalcemic patients with bone metastases from BC and in 19 BC patients without clinical evidence of bone metastases. Bone formation was investigated by measuring serum bone isoenzyme of alkaline phosphatase (BALP), osteocalcin (OC) and carboxy-terminal propeptide of type I procollagen (PICP): Bone resorption was investigated by measuring serum carboxy-terminal telopeptide of type I collagen (ICTP), fasting urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr). RESULTS: PICP was influenced by age and menopausal status. Significant correlations were observed between each of bone turnover markers except between BALP and OC. The mean levels of the six bone turnover markers were higher in patients with bone metastases than in those without them and significance was observed except for OC. The best diagnostic efficiency by receiver-operating characteristic (ROC) analysis was provided by ICTP followed by Pyr or D-Pyr, BALP, PICP and OC and significance was observed between ICTP and OC. Multiple logistic regression analysis adjusted by age revealed that the only significant marker related to bone metastases was ICTP. CONCLUSIONS: Serum ICTP appears to be the leading marker of bone metastases from BC. However, to reveal the clinical usefulness of these markers, further examination will be needed to account for the ease and cost-effectiveness of the measurements.

Adult↗

PubMed1999

Predictive performance of equations to estimate creatinine clearance from serum creatinine in Japanese patients with congestive heart failure.

Seven methods using patient's age, weight, gender, and serum creatinine concentration were evaluated for mathematical and clinical predictive performance in estimating the creatinine clearance of Japanese patients. We compared the measured and estimated creatinine clearance in 179 hospitalized heart failure patients. The Gates equation was the most biased (mean prediction error, 17.9 mL/min), and the Yukawa equation was the most precise (mean absolute prediction error, 10.4 mL/min), followed by the Jelliffe, Bjornsson, Cockcroft and Gault, and Mawer equations. For all methods, precision was less when serum creatinine concentrations of <0.6 mg/dL were rounded than when serum creatinine concentrations of >/=0.6 mg/dL were rounded. We conclude that in clinical practice where the renal function can vary widely, any of the published formulas can give satisfactory results. The Yukawa formula is concise and gives better results in Japanese patients.

Adolescent↗

PubMed1999

Prevalence of autoantibodies in patients with recurrent miscarriages.

PROBLEM: It is well known that the prevalence of several autoantibodies is higher in patients with recurrent miscarriages than in normal women. However, links between individual autoantibodies are unclear. The present study focuses on the possible association between beta 2-glycoprotein I (beta 2-GPI)-dependent anticardiolipin antibody (aCL), lupus anticoagulant (LA), and antinuclear antibody (ANA) in patients with recurrent miscarriages. METHOD OF STUDY: Three hundred and one patients, with a history of two or more unexplained miscarriages, were studied. The titers of beta 2-GPI-dependent aCL and LA were then compared between single-antibody-positive and three-antibody-positive groups. RESULTS: The prevalences of beta 2-GPI-dependent aCL, LA, and ANA were 3.3, 10.0, and 25.2%, respectively. Four of the 301 patients had all three antibodies. The LA titers in patients with positive values for three antibodies was significantly higher than in cases with only LA. CONCLUSION: beta 2-GPI-dependent aCL, LA, and ANA define three distinct, but partly related populations in patients with recurrent miscarriage. We should test at least two kinds of autoantibodies in recurrent aborters, because it has been found that, e.g., beta 2-GPI-dependent aCL and LA are predictors for miscarriages.

Abortion, Habitual↗

PubMed1999

The role of volume-weighted mean nuclear volume in predicting disease outcome in patients with stage M1 prostate cancer.

BACKGROUND: Various factors have been reported to be of value in predicting the prognosis of prostate cancer. Gleason score (GS) and prostate-specific antigen (PSA) are the two most powerful prognosticators among them. We previously reported that estimation of volume-weighted mean nuclear volume (MNV) was a more useful prognosticator for prostate cancer than subjective histologic grading. In this study, we compared estimates of MNV with PSA and GS for predicting the prognosis of stage M1 prostate cancer. EXPERIMENTAL DESIGN: A retrospective prognostic study of 66 patients with stage M1 prostate cancer diagnosed between January 1989 and December 1996 at Shizuoka City Hospital and Shizuoka Prefectural Hospital was performed. The prognostic value of unbiased estimates of MNV were compared with PSA and histologic grading according to GS. RESULTS: Univariate analysis revealed that estimates of MNV (p=0.0136) and post-treatment nadir PSA level (p<0.0001) correlated significantly with the prognosis of stage M1 prostate cancer, whilst GS (p=0.9377), pre-treatment PSA level (p=0.7377) and rate of decrease in PSA level within 1 month after the beginning of therapy (p=0.8999) had no prognostic value. Multivariate analysis revealed that post-treatment PSA level and estimates of MNV were the two most powerful prognosticators. CONCLUSIONS: This study indicates that estimation of MNV is an important prognosticator, in conjunction with post-treatment nadir PSA level, in stage M1 prostate cancer.

Aged↗

PubMed1999

[Effect of antibiotics and antibody on phagocytic bactericidal activity of polymorphonuclear neutrophils of Bordetella pertussis].

The phagocytic bactericidal activity of the polymononucler neutrophils (PMNs) that were collected from healthy volunteer with and without antibody against Bordetella pertussis was investigated. Furthermore, these activity against B. pertussis under observing penicillins or macrolides antibiotics was investigated. Although no efficacy to B. pertussis strain by the PMNs in serum without antibody, but the viable cells of B. pertussis decreased to 1/1,000 1 hr after incubation and was not detected after 4 hrs. In particular, the viable cells of B. pertussis by the PMNs in serum with antibody was markedly reduced when azithromycin was present. These results suggests that the synergistic action of macrolide antibiotics and antibody-mediated phagocytic bactericidal activity on B. pertussis may have clinical relevance.

Anti-Bacterial Agents↗

PubMed1999

Shade avoidance responses are mediated by the ATHB-2 HD-zip protein, a negative regulator of gene expression.

The ATHB-2 gene encoding an homeodomain-leucine zipper protein is rapidly and strongly induced by changes in the ratio of red to far-red light which naturally occur during the daytime under the canopy and induce in many plants the shade avoidance response. Here, we show that elevated ATHB-2 levels inhibit cotyledon expansion by restricting cell elongation in the cotyledon-length and -width direction. We also show that elevated ATHB-2 levels enhance longitudinal cell expansion in the hypocotyl. Interestingly, we found that ATHB-2-induced, as well as shade-induced, elongation of the hypocotyl is dependent on the auxin transport system. In the root and hypocotyl, elevated ATHB-2 levels also inhibit specific cell proliferation such as secondary growth of the vascular system and lateral root formation. Consistent with the key role of auxin in these processes, we found that auxin is able to rescue the ATHB-2 lateral root phenotype. We also show that reduced levels of ATHB-2 result in reciprocal phenotypes. Moreover, we demonstrate that ATHB-2 functions as a negative regulator of gene expression in a transient assay. Remarkably, the expression in transgenic plants of a derivative of ATHB-2 with the same DNA binding specificity but opposite regulatory properties results in a shift in the orientation of hypocotyl cell expansion toward radial expansion, and in an increase in hypocotyl secondary cell proliferation. A model of ATHB-2 function in the regulation of shade-induced growth responses is proposed.

Arabidopsis↗

PubMed1999

[Quantitative analysis of factors to influence the environment of the clean room and clean bench during preparation of intravenous hyperalimentation (IVH) admixtures].

We quantitatively studied factors influencing the environment cleanliness for intravenous hyperalimentation (IVH) admixing. The environment cleanliness was evaluated by measuring the counts of particles (> 0.5 micron) and bacteria floating in 1 ft3 of the air inside the clean room (23.6 m3) and in the clean bench built in the department of pharmacy, The University of Tokyo Hospital in 1998. The number of particles at the center of the clean room during IVH admixing by 4 pharmacists was higher than that at the medicine passing area (150 +/- 50/ft3 vs. 260 +/- 60/ft3; mean +/- S.D., n = 12). The cleanliness inside the clean room was improved as the measurement point became higher from the floor (600 +/- 180/ft3, 150 +/- 50/ft3, and 35 +/- 15/ft3 at 50, 100, and 150 cm height, respectively) and the number of persons working inside the room decreased. The changes in the counts of floating bacteria were similar to that of floating particles under the same conditions. In addition the effect of disinfection on the counts of bacteria was clearly observed. When the cleanliness of the room became lower by turning off the air conditioning, the particle counts inside the clean bench became lower along with the distance from the front glass becoming deeper (i.e., 1400 +/- 550/ft3, 140 +/- 70/ft3, and 40 +/- 30/ft3 at 0, 5, and 15 cm, respectively). From these lines of evidence, the following items were suggested in order to maintain the environment cleanliness for IVH admixing. First, the number of persons residing in the clean room should be kept to be minimum. Second, the clean bench should be set up in the center of the clean room. Finally IVH admixing operation should be performed at more than 15 cm depth inside the front glass surface of the clean bench. Moreover, the effect of mopping-up of the clean room with 0.1% benzethonium chloride clearly demonstrated the importance of disinfection on a routine basis.

Air Conditioning↗

PubMed1999

[Preparation of ketamine tablets for treatment of patients with neuropathic pain].

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.

Adult↗

PubMed1999

[Effects of the rational use of corticosteroids eye drops for the prevention of ocular toxicity in high-dose cytosine arabinoside therapy].

Although the use of corticosteroid (CS) eye drops of the use of eye washing by artificial tears was effective for the prevention of ocular toxicity such as keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy, the toxicity was not prevented perfectly. We studied the effects of the rational use of CS eye drops, and the combined use of CS eye drops and eye washing by physiological saline in order to prevent the ocular toxicity. Before the study, the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was carried out at 4-6 times per day during the high-dose Ara-C therapy, and continued for several days after the high-dose Ara-C therapy. However, the rational use of "eyelid closure" and "naso-lacrimal occlusion" after the instillation was not performed Consequently, the ocular toxicity was observed in 3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4 times per day was carried out rationally according to the consultation of pharmacist during the high-dose Ara-C therapy and for additional 10 days after the therapy, no ocular toxicity was observed in all cases (0 of 6 cases). Furthermore, the combined use of eye washing by physiological saline and instillation of BM eye drops was effective for the decrease of the risk of ocular toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy (0 of 34 cases). Our procedure in this study would be effective for the prevention of ocular toxicity in the high-dose Ara-C therapy.

Adolescent↗

PubMed1999

Residual cardiomyocytes and scintigraphic findings in advanced coronary artery disease: correlation with technetium-99m-tetrofosmin and thallium-201 single photon emission computed tomography.

A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (99mTc)-tetrofosmin and thallium-201 (201Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution 201Tl, reinjection 201Tl and rest 99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the 201Tl redistribution images, r=0.913 for the 201Tl reinjection images and r=0.917 for the rest 99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD.

Aged↗

PubMed1999

Physiological effects of water-soluble soybean fiber in rats.

Four-week-old rats were fed on diets containing either no dietary fiber (DF) or a DF source (WSSF, ISF or cellulose) for 4 weeks. The DF level was adjusted to 5%. The WSSF diet contained 3% and 2%, respectively, of WSSF and cellulose. No rat in any group experienced diarrhea, and none of the experimental diets suppressed the growth of rats, the apparent absorption of major nutrients being almost 100%. However, the rate of degradation of DF during the digestive process was significantly different (p < 0.05, cellulose, 23.6%; WSSF with cellulose, 64.5% (WSSF degradation only was 91.8%); and ISF, 77.6%). The plasma and liver lipid levels were within normal ranges, although the liver cholesterol level in those rats fed on WSSF and ISF was significantly lower (p < 0.05) than in those fed on cellulose. The cecal organic acid contents were in the order of WSSF > ISF > cellulose > DF-free. Furthermore, WSSF was effective in shortening the gastrointestinal transit time. The results indicate that WSSF seems to have favorable effects on the intestinal functions.

Animals↗

PubMed1999

Cancer mortality among radiological technologists in Japan: updated analysis of follow-up data from 1969 to 1993.

A retrospective cohort study was conducted for 12,195 male radiological technologists who received the occupational exposure to low dose radiation over a long term. A total of 1,097 deaths including 435 from cancer were ascertained by Koseki and death certificates from 1969 to 1993. Cancer mortality among the study population was basically compared with that of whole Japanese men. The significant low SMRs were obtained for all cancers, stomach and lung cancer partly due to Healthy Worker Effect, unlike the results of the early reports with some inappropriateness in the methods. Apparent high risks of lymphatic and hematopoietic cancers were observed, although none of site-specific cancers revealed the statistically significant increase. For these cancers, the SMRs among old sub-cohort were somewhat higher than those of young sub-cohort, whereas similar SMRs for solid cancer were obtained between the two sub-cohorts. The SMR for leukemia reached statistically significant level of 1.75 (95% CI: 1.07-2.71) when using whole professional and technical workers as a standard population. The study results might suggest that the chronic exposure to low-dose radiation enhanced the risk of lymphatic and hematopoietic cancers.

Adult↗

PubMed1999

[Long-term results of ureteral replacement using ileum: report of four cases].

A total of four patients underwent ureteral replacement using ileum without the antireflux mechanism for extensive ureteral loss from 1985 to 1995. The indications included surgical trauma, retroperitoneal fibrosis, ureteral obstruction due to abscess, and ureteritis. One case had bilateral reconstruction. The followup interval ranged from 3 to 14 years. Urinary infections were noted in 2 cases. One patient, who had urinary infections and neurogenic bladder, had symptoms, but, in all cases, serum creatinine was unchanged or decreased and the pyelogram was normal or showed mild hydronephrosis. Thus, the procedure was considered successful in all cases. This procedure provides excellent long-term results for reconstruction of ureter when the normal ureter cannot be used. Creation of the antireflux mechanism may not be necessary in patients with normal renal function.

Adult↗