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Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 127 records · Page 7Linked to original sources
PubMed1998

Determinants of ventricular arrhythmias in hemodialysis patients. Evaluation of the effect of arrhythmogenic substrate and autonomic imbalance.

BACKGROUND/AIMS: In chronic hemodialysis patients, we evaluated determinants of repetitive ventricular tachyarrhythmias which included late potentials and heart rate variability. METHODS: We compared the presence of late potentials and heart rate variability obtained by ambulatory electrocardiogram (ECG), findings of echocardiography, and laboratory data between patients with and those without ventricular arrhythmias of Lown class 4A or 4B. Ambulatory ECG was recorded for 24 h from the beginning of hemodialysis. Heart rate variability was evaluated by the standard deviation of the normal RR interval (SDNN). RESULTS: Thirty patients (17%) had ventricular arrhythmias of Lown class 4A or 4B. They were older than patients without such arrhythmias (p=0.0021). Left-ventricular wall motion score (2.0+/-3.9 and 0.3+/-1.2, respectively, p < 0.0001) and left-ventricular mass index (167 +/-59 and 140+/-44 g/m2, respectively, p=0.0053) were larger in patients with ventricular arrhythmias of Lown class 4A or 4B than in those without. Stepwise logistic regression analysis was performed to select variables related to ventricular arrhythmias of Lown class 4A or 4B from the following 8 candidate variables; age, sex, presence of ischemic heart disease, diabetic nephropathy as the primary renal disease, presence of late potentials, SDNN, left-ventricular wall motion score and left-ventricular mass index. Higher left-ventricular wall motion score (p < 0.0001), older age (p=0.0022) and male sex (p=0.0235) were the variables associated with ventricular arrhythmias of Lown class 4A or 4B. CONCLUSION: In patients receiving hemodialysis, predominantly with chronic glomerulonephritis, ventricular arrhythmias of Lown class 4A or 4B were not associated with arrhythmogenic substrate revealed by late potentials or autonomic dysfunction assessed by heart rate variability. Left-ventricular wall motion abnormalities, age and sex were significant factors.

Autonomic Nervous System Diseases↗
PubMed1998

Comparison between cilnidipine and nisoldipine with respect to effects on blood pressure and heart rate in hypertensive patients.

Cilnidipine is a new and unique 1,4-dihydropyridine calcium antagonist that has both L-type and N-type voltage-dependent calcium channel blocking actions. We compared the effects of cilnidipine and another once-daily dihydropyridine calcium antagonist, nisoldipine, on 24-h blood pressure and heart rate in patients with essential hypertension. We enrolled 10 hypertensive outpatients [9 men and 1 woman; age, 55+/-3 yr (means+/-SEM)] in this study. Their ambulatory blood pressure and heart rate were monitored for 24 h at intervals of 30 min with a portable recorder (TM-2425) after 8 wk of treatment with cilnidipine (5 to 20 mg once daily) and after 8 wk of treatment with nisoldipine (5 to 20 mg once daily). The order of the two treatments was randomized. Blood pressure and heart rate measurements for a 24-h period were analyzed for four segments of the day: morning (06:00 to 11:30), afternoon (12:00 to 17:30), nighttime (18:00 to 23:30), and sleeping time (0:00 to 5:30). Blood pressure levels were similar during the two treatment periods for each 6-h segment of the day. Heart rate was significantly higher during treatment with nisoldipine than during treatment with cilnidipine in the morning segment [by 4.1+/-1.3 beats/min (p < 0.05)] and the afternoon segment [by 6.4+/-3.6 beats/min (p< 0.05)]. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and causes reflex tachycardia less than does nisoldipine.

Antihypertensive Agents↗
PubMed1998

A novel epitope (pentapeptide) in the human hemoglobin beta chain.

We have cloned 16 monoclonal antibodies by immunizing mice with human hemoglobin for the purpose of analyzing epitopes in human hemoglobin. By using one, SU-115, which is specific for the beta chain, an epitope in the beta chain reacting with this monoclonal antibody was investigated, and a pentapeptide was identified as a novel epitope. After digestion of the beta chain by lysylendopeptidase, the antigenicity of degradation products was examined. An antigenic fragment against SU-115 was found to be a peptide corresponding to residues 96-120 of the beta chain by amino acid analysis of its N-terminal region. Several peptides involved in the region of beta96-120 were synthesized to be examined for their reactivity to SU-115 using dot-blot analysis and a resonant mirror detection method, and a pentapeptide (N108VLVC) was determined as a major sequence of an epitope. By injecting this pentapeptide into a mouse, an antibody reacting human hemoglobin (alpha2beta2) in the same order of strength as SU-115, was obtained. The pentapeptide described in this paper seems to be the minimum size as a major sequence of the actual epitope in human hemoglobin so far reported, and in the primary structure of this region (108-112) there is a difference of three amino acids between human and mouse hemoglobin.

Amino Acid Sequence↗
PubMed1998

[Usefulness of telomerase activity in the diagnosis of small hepatocellular carcinoma].

The diagnosis of small hepatocellular carcinoma (HCC) is sometimes difficult because of the similarity of the histological appearance with adjacent liver tissue. Recent advancement of the quantitative telomerase assay can diagnose small HCC effectively, and the positive rate surpasses those of alpha-fetoprotein and PIVKA-II. The application to a clinical field is, however, limited because the small nodules with the possibility of malignant phenotype tend to be treated easily with ethanol injection therapy without an additional biopsy for this assay only. Further analysis of telomerase related proteins might make it possible to visualize the activity in the tissue sections and expand the usefulness of telomerase as a diagnostic tool in routine clinical use.

Biomarkers, Tumor↗
PubMed1998

FDG uptake, GLUT-1 glucose transporter and cellularity in human pancreatic tumors.

UNLABELLED: We previously reported that grading of GLUT-1 glucose transporter expression was related closely to FDG accumulation in FDG PET in human cancers. But in this strong GLUT-1 expression group, there was an enormous range of standardized uptake values (SUVs) within them. METHODS: To evaluate other factors determining the FDG PET uptake, FDG PET was performed in 36 preoperative patients (mean age 62.0 yr) suspected of having pancreatic tumors, including 33 malignant and 3 benign neoplastic tumors. FDG uptake at 50 min after injection of 185 MBq 18F-FDG with > 5 hr fasting condition was semiquantitatively analyzed as SUVs. The GLUT-1 expression was studied by immunohistochemistry of paraffin sections from these tumors after the operation using the antiGLUT-1 antibody. The number of tumor cells within a 5- x 5-mm square was counted manually using x200 magnification photographs and was graded immunohistochemically as strong, weak or negative. RESULTS: In all 36 cases there were 3 cases of GLUT-1 negative, 8 of GLUT-1 weak positive and 25 of GLUT-1 strong positive. In all cases, the total number of tumor cells had no significant value for SUVs. Among 33 GLUT-1 positive cases, the number of GLUT-1 positive tumor cells correlated significantly with SUVs (p < 0.01). Only in 25 strong grade cases, the number of GLUT-1 strong positive tumor cells had a more significant value for SUVs (p < 0.005). Computational multivariate analysis using multiple regression for SUVs was performed evaluating the five variables as follows: tumor size, GLUT-1 immunohistochemical grading, number of total tumor cells, number of total GLUT-1 positive tumor cells and number of GLUT-1 strong positive cells. This analysis revealed that only the variable, the number of GLUT-1 strong positive cells, had a significant regression coefficient for SUVs (standard regression coefficient = 0.855, p < 0.0001). CONCLUSION: These data indicate that GLUT-1 expression plays an essential role in higher FDG accumulation in pancreatic tumor FDG PET, and the cellularity has a significant influence on SUVs only in the condition of GLUT-1 strong positive expression.

Adenocarcinoma↗
PubMed1997

[Computer-aided occupational health education for post-graduates].

Nowadays, it's inevitable that occupational physicians enhance the activities in the field of occupational health through the use of the computer. Moreover, computer-aided self-education programs are one of the most useful tools for occupational physicians because they must learn a large volume of multidiscipline expertise for occupational health. Thus, we tried to apply a practical training program using the software of our own making in the post-graduate training course of fundamental occupational health. One is a self-education software for the study of electrocardiograms, and the other is a simple system to manage the serial data of a medical checkup and the reports of an inspection tour in the workplace. By this system one is also able to receive information such as a chest X-ray via the internet. Twenty-three students appraised our programs as for the contents (easily understandable, adequate volume); teacher's attitudes (enthusiastic approach to the training, enough time for questions, attention to the reaction of the class) and free comments. Because 4.3 points (at most 5.0) on an average was obtained, we are encouraged to make multimedia instructional materials on occupational health.

Computer Communication Networks↗
PubMed1997

[Report on occupational health and safety practice, level 4].

Recently, because international standardization systems have been set up in many fields, it is necessary for Japanese companies to employ persons who have specific knowledge and techniques in regards to occupational health and safety. In this paper, therefore, we discuss Occupational Health and Safety Practice, Level 4, and try to compare it with Japanese licences. The standard was developed by the Occupational Health and Safety Lead Body (OHSLB) in England. This standard is intended for occupational health and safety practitioners working in general health and safety. We conclude that the training system for occupational health and safety practitioners in Japan must be developed more fully.

Health Knowledge, Attitudes, Practice↗
PubMed1997

Cloning and sequencing for the largest subunit of Chinese hamster RNA polymerase II gene: identification of a mutation related to abnormal induction of sister chromatid exchanges.

In order to analyze the mutation sites related to abnormal induction of sister chromatid exchanges (SCEs) in the RNA polymerase II largest subunit (RpII LS) gene of the Chinese hamster CHO-KI cell mutant, we have completely sequenced the whole region of the RpII LS cDNAs obtained from normal and mutant cells. By comparing both sequences, a mutation that results in an amino acid (aa) change in the RpII LS gene was found. This aa change was Pro (CCC) to Ser (TCC) at position 1006. Multiple alignment for aa sequences of RpII LS from various species revealed that this Pro residue was highly conserved throughout the eukaryotes. Considering the differences in physico-chemical properties between Pro and Ser residues, the Pro-->Ser substitution may alter the RpII LS structure.

Amino Acid Sequence↗
PubMed1997

Hydroxyl radical mediates N epsilon-(carboxymethyl)lysine formation from Amadori product.

Recent studies demonstrated N epsilon-(carboxymethyl)lysine (CML) in several tissue proteins. Incubation of proteins with glucose leads through a Schiff base to Amadori products. Oxidative cleavage of Amadori products is considered as a major route to CML formation in vivo, whereas it is not known which reactive oxygen species (ROS) is involved. The present study is undertaken to identify such a ROS. We prepared heavily glycated human serum albumin (HSA) which contained a high level of Amadori products, but an undetectable level of CML. Incubation of glycated HSA with FeCl2, but not with H2O2, led to CML formation which was enhanced by H2O2, but inhibited by catalase or mannitol, whereas superoxide dismutase had no effect. Similar data were obtained by experiments using Boc-fructose-lysine as a model Amadori compound. These data indicate that hydroxyl radical generated by the reaction of Fe2+ with H2O2 mediates CML formation from Amadori compounds.

Catalase↗
PubMed1997

A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Animals↗
PubMed1997

Comprehensive cloning of Schizosaccharomyces pombe genes encoding translation elongation factors.

In the course of the Schizosaccharomyces pombe cDNA project, we succeeded in cloning all the genes encoding translation elongation factors EF-1alpha, EF-1beta, EF-1gamma, EF-2 and EF-3. With the exception of the EF-1gamma gene, the nucleotide (nt) sequence of S. pombe elongation factors has not been previously reported. For EF-1alpha, we found three genes whose amino acid (aa) sequences are quite homologous each other (99.5%), but whose 3' untranslated regions (UTRs) are completely different. Southern blot indicated that those three EF-1alpha genes are located at different loci. Northern analysis indicated that one of three EF-1alpha genes was inducible with UV-irradiation, while the level of expression for another of three EF-1alpha genes was repressed by UV and heat-shock (HS) treatments. The aa sequence predicted from the nt sequence of the S. pombe EF-1beta cDNA clone covered almost all the coding sequence (CDS) of EF-1beta except the first methionine which has 55.4% identity with that of S. cerevisiae. We also identified two copies of S. pombe EF-2 genes. Their aa sequences deduced from nt sequences are identical (100%), but they have different 3' UTRs. The location of these two EF-2 genes in different loci was proved by Southern analysis. The S. pombe EF-3 cDNA clone encoded only a third of the CDS from the C-terminal and its deduced aa sequence has a 76% identity with those of other yeasts and fungi.

Amino Acid Sequence↗
PubMed1997

Cellular immuno-competence of infected root canal contents in pathogenesis of periapical lesions.

The soluble fractions of infected root canal contents (IRCC) were collected from about 300 human extracted teeth and examined for the presence of mononuclear cell (MNC) chemotaxis and cellular immunocompetence. IRCC showed remarkable chemotactic activity for polymorphonuclear leukocytes but a weak activity for MNC. However, generation of intrinsic MNC chemotaxis and induction of cellular immunity were confirmed in rats given repeated injections of IRCC.

Animals↗
PubMed1997

Specificity of polyclonal antibodies raised against a novel 24,25-dihydroxyvitamin D3-bovine serum albumin conjugant linked through the C-11alpha or C-3 position.

Novel hapten-carrier conjugants were prepared by coupling 11 alpha-hemiglutaryloxy-(24R)-24,25-dihydroxyvitamin D3 or (24R)-24,25-dihydroxyvitamin D3 [24,25(OH)2D3] 3-hemiglutarate with bovine serum albumin (BSA), to obtain an antibody with high specificity and affinity for use in 24,25(OH)2D3 immunoassay. The polyclonal antibodies showing high titre were each elicited in three or four rabbits against these two conjugants; the antibodies obtained from the former and the latter conjugants were expressed as Ab11 and Ab3, respectively. These had a much higher affinity for 24,25(OH)2D3 than that of the vitamin D binding protein (DBP). Specificity of the antibodies was investigated by crossreactivities with 11 related compounds in a radioimmunoassay (RIA) system. The Abll well discriminated the 1 alpha-hydroxylated metabolites such as 1,24,25(OH)3D3 (< or = 0.69%) and 1,25(OH)2D3 (< or = 0.25%), but significantly crossreacted with some side chain modified compounds such as (24S)-24,25-dihydroxyvitamin D3 [24S,25(OH)2D3] (> or = 67%), 25(OH)D3 (> or = 14%) and 25,26(OH)2D3 (> or = 23%). On the other hand, the Ab3 showed only negligible crossreactivities with the compounds having a different side chain structure such as 24S,25(OH)2D3 (< or = 3.0%), 25(OH)D3 (< 0.3%) and 25,26(OH)2D3 (< or = 0.53%). A significant crossreaction was found only with 1,24,25(OH)3D3 (> or = 68%). These results demonstrated that the Ab3 are promising for developing an immunoassay system which is much more specific and sensitive than conventional competitive protein binding assays based on DBP.

24,25-Dihydroxyvitamin D 3↗
PubMed1997

Pharmacological characterization of endothelin-induced rat pulmonary arterial dilatation.

1. The aim of study was to characterize endothelin (ET)-induced vasodilation in isolated extrapulmonary rat arteries (EPA) and in intrapulmonary arteries (IPA) preconstricted with 1 microM phenylephrine. 2. The ET-3 (1 nM-100 nM)- and ET-1 (10 nM-100 nM)-induced transient vasodilatations in EPA were more potent than those in IPA. The vasodilatation induced by ET-3 (100 nM) was larger than that induced by ET-1 (100 nM). 3. Both the ETB antagonist, BQ788 (3 microM) and or endothelium denudation, but not the ETA antagonist, BQ123 (3 microM), abolished the vasodilation induced by ET-1 or ET-3 (100 nM each) in EPA and in IPA. The ATP-sensitive K + channel blocker, glibenclamide (20 microM) and the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA, 1 mM) suppressed the ET-induced vasodilatation in EPA and in IPA. 4. We conclude that the vasodilatation induced by endothelins is markedly reduced in rat isolated IPA, and suggest that the endothelial ETB-mediated vasodilatation varies depending on rat pulmonary arterial regions. Furthermore, ETB-mediated vasodilatation involves activation of ATP-sensitive K+ channels and of nitric oxide synthase in rat isolated EPA and IPA.

Animals↗
PubMed1997

Pharmacological heterogeneity of constrictions mediated by endothelin receptors in rat pulmonary arteries.

The endothelin (ET) receptors mediating rat pulmonary arterial constrictions were investigated. ET-1 and ET-3 constricted both isolated intrapulmonary artery (IPA) and extrapulmonary artery (EPA), with ET-1 having a potency approximately 10 times that of ET-3. The ET(B) selective agonist IRL-1620 produced constriction of only IPA. The ET(B) selective antagonist BQ-788 suppressed the ET-1-induced constriction of IPA only. The ET(A) selective antagonist BQ-123 more effectively antagonized the ET-1-induced constriction of EPA than that of IPA. The combination of BQ-123 and BQ-788 increased the antagonistic response to ET-1 in IPA but not in EPA. Then, large constriction remained in IPA and EPA. The receptor nonselective antagonist PD-145065 almost completely inhibited the ET-1-induced constriction of IPA and EPA. BQ-123 completely inhibited the ET-3-induced constriction of EPA; however, it partially suppressed that of IPA. The combination of BQ-123 and BQ-788 completely inhibited the ET-3-induced constriction of IPA. These results demonstrate that the ET-1-induced constrictions are mediated by both ET(A) and ET(B) in IPA and by ET(A) in EPA. Because of differences in sensitivity to ET receptor antagonists for ET-1- and ET-3-induced constrictions, pharmacological heterogeneity of ET(A) is suggested. Additionally, endothelial denudation affected the ET-3-induced constriction of EPA, but not of IPA, and it didn't affect the response to ET-1. This suggests that the vasodilatory effect of endothelium on ET-3-induced vasoconstrictions varies depending on pulmonary vascular regions.

Animals↗
PubMed1997

Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma.

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

Acute Kidney Injury↗
PubMed1997

Relationship between Asbestos Exposures and 8-Hydroxydeoxyguanosine Levels in Leukocytic DNA of Workers at a Chinese Asbestos-material Plant.

The objective of the study was to evaluate the level of 8-hydroxydeoxyguanosine (8-OHdG) in DNA of peripheral-blood leukocytes as a biological marker of asbestos exposure and/or its fibrotic effects in an occupational population exposed to asbestos. The setting was a large-scale asbestos plant in China producing brake linings, asbestos rubber, and textile using chrysotile. From a base population of active and retired workers with various levels of cumulative exposure to asbestos and grades of asbestosis, 39 study subjects were randomly selected to reflect incremental grades of asbestosis based on Chinese diagnostic standards. They consisted of 19 "normal" (control) and ten "suspected" and ten "definite" asbestosis-grade subjects, group-matched for age and sex. Leukocytic DNA was extracted from 5-mL samples of peripheral blood and 8-OHdG level measured by high-pressure liquid chromatography. A cumulative asbestos exposure index (CEI) was calculated for each subject as the summed product of duration and level of asbestos exposure per job, incorporating a job-exposure matrix. Geometric mean 8-OHdG levels showed a positive gradient in relation to increasing grades of asbestosis (control: 1.78, suspected: 2.21, definite: 2.58), with a significant difference between the control and definite-asbestosis subgroups (p < 0.05). The 8-OHdG level of the two subgroups combined as one "asbestosis" group was significantly higher than that of the control group (control: 1.78, asbestosis: 2.39, p = 0.01). Further, 8-OHdG levels were moderately correlated with CEIs for all subjects (r = 0.35, p < 0.05) and with grades of asbestosis for all (r = 0.47, p < 0.01) and for male subjects (r = 0.43, p < 0.05). In multiple regression analyses, grade of asbestosis explained 27% of the total variation in 8-OHdG and was a better predictor than CEI or duration of exposure. Thus, the 8-OHdG level in leukocytic DNA is related to grade of asbestosis and to individual cumulative exposure and may serve as a biologic marker reflecting the status of oxidative DNA damage by asbestos.

Journal Article↗