Activation of the coagulation system in women with mitral stenosis and sinus rhythm.
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Adult↗
Biomedical subjects
T Ozawa
Publications and source records attributed to T Ozawa.
A missense mutation of L-gulono-gamma-lactone oxidase causes the inability of scurvy-prone osteogenic disorder rats to synthesize L-ascorbic acid.
The osteogenic disorder Shionogi (ODS) rat is a mutant Wistar rat that is subject to scurvy, because it lacks L-gulono-gamma-lactone oxidase, a key enzyme in L-ascorbic acid biosynthesis. Sequencing of polymerase chain reaction-amplified cDNAs for mutant and normal rat L-gulono-gamma-lactone oxidases demonstrated that the mutant cDNA has a single base mutation from G to A at nucleotide 182, which mutation alters the 61st amino acid residue from Cys to Tyr. To test the effect of this mutation on the expression of L-gulono-gamma-lactone oxidase, we inserted a region of the cDNAs coding for normal and mutant L-gulono-gamma-lactone oxidases into an expression vector, pSVL, and transfected COS-1 cells with such vectors. The result indicated that the defined amino acid substitution does decrease both the amount of immunologically detectable protein and the level of enzyme activity to about one-tenth of their normal values, while it does not affect the amount of the mRNA produced in the transfected cells. This situation is similar to our previous observation that L-gulono-gamma-lactone oxidase is expressed in the liver of the ODS rat at a very low level irrespective of the presence of a normal amount of L-gulono-gamma-lactone oxidase-specific mRNA of a normal size (Nishikimi, M., Koshizaka, T., Kondo, K., and Yagi, K. (1989) Experientia (Basel) 45, 126-129). Thus it became clear that the Cys-->Tyr substitution is responsible for the L-gulono-gamma-lactone oxidase deficiency in the ODS rat.
Animals↗
Ultrastructural and ultracytochemical differences between megakaryoblastic leukemia in children and adults. Analysis of 49 patients.
BACKGROUND: Acute megakaryoblastic leukemia (AMKL) has two peaks in distribution of incidence (in adults and children 1 to 2 years of age) and is frequently seen in children with Down syndrome. The current study was undertaken to disclose whether there were any differences between these groups. METHODS: Electron microscopic and ultrastructural cytochemical features of 49 children and adults with a AMKL or chronic myelogenous leukemia (CML) in megakaryoblastic crisis were compared. RESULTS: Blast cells from children with AMKL, including those with and without Down syndrome, had immature features lacking typical alpha granules and a demarcation membrane system (DMS). However, blast cells from patients with AMKL with Down syndrome had more theta, electron-lucent, and basophil-like granules, suggesting that the blast cells had more potential to differentiate into other cell lines than megakaryocytes. The AMKL blast cells of adult patients showed a higher percentage of platelet peroxidase (PPO) positivity than other subgroups, and they occasionally contained typical alpha granules and DMS. This indicated that the blast cells of adults with AMKL were more mature than those of children and CML in megakaryoblastic crisis. CONCLUSIONS: By electron microscopic analysis, leukemic megakaryoblasts differed between children with AMKL with and without Down syndrome, adults with AMKL, and patients with CML in megakaryoblastic crisis.
Acid Phosphatase↗
LMW heparin (anti-Xa) assays for clinical monitoring and pharmacokinetic studies on the automated coagulation laboratory (ACL).
Chromogenic anti-Xa activity procedures were developed for monitoring LMW heparins on the Automated Coagulation Laboratory 300 Plus (ACL, Instrumentation Laboratory) system. For daily monitoring, a "Routine" procedure was devised which allows accurate measurements between plasma levels of 0.1 and 1.0 u/ml LMW heparin. For lower levels a "Routine-Low" method was developed which assesses activities between 0.05 and 0.4 u/ml. Due to variabilities in dODs of individual baseline plasmas, levels below 0.05 u/ml might be inaccurate when pooled normal plasma is used to establish the reference curve. While levels less than 0.05 u/ml should rarely be encountered when monitoring LMW heparins for routine clinical use, pharmacokinetic studies require accurate measurements below that level. For this reason a "Research-High" and a "Research-Low" procedure was designed. For these procedures a study subject's own baseline plasma was used to establish the reference curve. The "Research-High" measures activities between 0.4 and 2.0 u/ml, the "Research-Low" between zero and 0.4 u/ml. The procedures have excellent within-run and inter-run coefficients of variation (less than 5%) and high levels of accuracies. Even inter-instrumental reproducibilities are less than 10%. Different manufacturers' LMW heparins can be analyzed by these assays. The procedures offer full automation, great cost-effectiveness due to lower reagent volumes, rapid turn-around time and great accuracy and reproducibility.
Antithrombin III↗
Inhibition by cyclosporine of the production of superoxide radicals.
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Cells, Cultured↗
Significant existence of deleted mitochondrial DNA in cirrhotic liver surrounding hepatic tumor.
To understand the role of mitochondria in carcinogenesis, we compared the amount of deleted mtDNAs between human hepatic tumors and surrounding cirrhotic portion of the liver of ten patients by using polymerase chain reaction (PCR). Multiple mtDNA deletions were detected in cirrhotic portion, but no deletions were detected in the tumor portion. Direct sequencing of the fragments revealed a 7,079-bp deletion (nucleotide position 8,992-16,072) involving no direct repeated sequences and a 7,436-bp deletion (position 8,649-16,084) involving a 12-bp directly repeated sequence of 5'-CATCAACAACCG-3' exists in both the ATP6 gene and the D-loop region. These mtDNA mutations could be one of the endogenous factors that induce somatic mutations in nuclear genome and etiologically contribute to human carcinogenesis.
Adenoma, Bile Duct↗
Development of a diagnostic and therapeutic simulation system based on patient data and specialist's knowledge. I. Simulation of diagnostic process.
A new simulation system of diagnostic and therapeutic processes is developed. The aim is to train medical students for the practical use of their knowledge, utilizing patient data in a total hospital information system. The knowledge in the system is presented by the specialists for every case. In medical school there are many specialists in various fields. With their cooperation the system can grow up to a comprehensive CAI system for clinical education. The system is designed to work on the mainframe for easiness of development, maintenance and extensions of the system. The present framework has been applied to the simulation of diagnostic process. The usefulness of the present system has been confirmed by specialists and students.
Computer-Assisted Instruction↗
The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats.
This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.
Adenine Nucleotides↗
Mechanism and prevention of chronic colonic inflammation with trinitrobenzene sulfonic acid in rats.
1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined. 2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6-keto-prostaglandin (PG) F1 alpha, PGF2 alpha, PGE2, PGD2 and thromboxane B2. 3. In TNBS-induced experimental colitis, all prostanoid concentrations except PGD2 increased, although the time courses differed from each other. 4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS-induced colitis. However, indomethacin did not show any effect on damage scores. 5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations. 6. Prostanoids might be produced secondarily in the genesis of TNBS-induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic inflammation.
Animals↗
Increased mitochondrial DNA deletions in the skeletal muscle of myotonic dystrophy.
Mitochondrial abnormality in the skeletal muscles of 13 patients with myotonic dystrophy was analyzed by both histochemical and molecular biologic methods. Nine of 13 patients had ragged-red fibers (50 +/- 116 per 10,000 muscle fibers, mean +/- SD), and 10 patients had cytochrome c oxidase-negative fibers (41 +/- 90 per 10,000 muscle fibers). Southern blot analysis detected no mitochondrial DNA deletions, while PCR revealed multiple mitochondrial DNA deletions in all the specimens. Direct sequencing of one of the deleted mitochondrial DNAs disclosed that the junctional sequence of a 3,460-bp deletion involved a 6-bp directly repeated sequence (5'-TAGAAG-3') flanked by C-rich regions located on the CO3 gene and the ND5 gene. Quantitative analysis of PCR amplified deleted mitochondrial DNAs revealed that the amount of deleted mitochondrial DNAs had positive correlation both with the frequencies of ragged-red fibers and cytochrome c oxidase-negative fibers. Although deleted mitochondrial DNAs were observed even in controls above age 30, the mean amount of deleted mitochondrial DNAs in patients with myotonic dystrophy was significantly higher than in controls. Moreover, the increase of deleted mitochondrial DNAs with aging was more marked in myotonic dystrophy than in controls. These results suggest that increased mitochondrial DNA deletions and consequent impairment of mitochondrial function contribute to the pathophysiology of myotonic dystrophy.
Adolescent↗
Implication of oxygen radicals on airway hyperresponsiveness after ovalbumin challenge in guinea pigs.
We elucidated the implication of oxygen radicals on airway hyperresponsiveness after ovalbumin (OA) challenge in guinea pigs. Ten days OA exposure increased airway responsiveness, i.e., a significant decrease in log [acetylcholine (Ach) PC200] (2.445 +/- 0.227) was observed compared with the control group (3.398 +/- 0.269). After OA exposure, the number of beta-adrenoceptors decreased by 38%, and adenylate cyclase activity decreased by 36% (isoproterenol stimulated) and 28% (basal). Significant increases in xanthine oxidase activities in lung tissue, bronchoalveolar lavage fluid (BALF), and serum were observed after the tenth OA exposure (49.1 +/- 11.7 mU/g tissue, 12.6 +/- 3.16 mU/ml, and 11.5 +/- 2.66 mU/ml, respectively) compared with those in the control group (7.35 +/- 6.48 mU/g tissue, 2.85 +/- 1.17 mU/ml, and 3.51 +/- 1.15 mU/ml, respectively). Administration of long-acting superoxide dismutase (SOD) (5,000 U/kg twice a day intraperitoneally) or gamma-glutamylcysteine ethyl ester (gamma-GCE) (10 mg/kg, twice a day, intraperitoneally), a prodrug of glutathione, maintained log [Ach PC200] (3.248 +/- 0.415 and 3.298 +/- 0.246, respectively) in spite of 10 days OA exposure. Decreases in the number of beta-adrenoceptors and adenylate cyclase activity were prevented by long-acting SOD or gamma-GCE. In contrast, long-acting SOD or gamma-GCE inhibited significantly, but not completely, the elevation of xanthine oxidase activities. These results support suggestions that oxygen radicals might be involved in the underlying mechanism of airway hyperresponsiveness after OA challenge in guinea pigs.
Adenylyl Cyclases↗
[Mechanism responsible for age-related deterioration of cardiac performance--aging of mitochondrial DNA].
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Adolescent↗
[Survey of the antibody to HCV in National Leprosarium Suruga].
Blood specimens from 210 leprosy patients (average age 67.4 years old) and 84 staff members (average age 43.5 years old) in National Leprosarium Suruga were tested for anti-HCV antibody using Ortho's Ab ELISA system. Among the patients, 17 patients had chronic hepatic dysfunction as well as leprosy. Twenty of the 210 patients (9.5%) had anti-HCV antibody in their blood. Eleven of the 17 patients (65%) with chronic hepatic dysfunction were positive for anti-HCV antibody. Only one of the staff member was anti-HCV antibody positive. This high positive ratio of anti-HCV antibody in the leprosy patients is similar to the results of another research reported from National Leprosarium Oku Komyo-En. We, therefore, conclude that the prevalence of anti-HCV antibody in leprosy patients is higher than that of the general population and that anti-HCV antibody is related closely to chronic hepatic dysfunction. Some investigators have recently reported that there was an increased incidence of hepatocellular carcinoma in leprosy patients. And so, it is speculated that this is due to the high prevalence of the hepatitis C virus. However, the reason for this high prevalence of anti-HCV antibody in the sample is obscure.
Adult↗
[Therapeutic consideration of patients with mental diseases].
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Hospitals, Psychiatric↗
[Hemodynamic difference accounted for the orientation of a Björk-Shiley mitral prosthesis: a color Doppler echocardiographic study].
To determine whether the orientation of the major orifice of a mitral tilting disc prosthesis affects hemodynamics, intracavitary blood flow patterns were studied in 45 patients with well-functioning Björk-Shiley mitral prosthesis using color Doppler flow imaging. The major orifice was oriented towards the septum in 23 patients (12 men, 11 women, age 58 +/- 11 years; group S), and towards the posterior wall in 22 patients (8 men, 14 women, age 55 +/- 9 years; group P). 1) The left ventricular end-diastolic dimensions (S: 4.8 +/- 0.9 cm, P: 5.2 +/- 1.0 cm), end-systolic dimensions (S: 3.6 +/- 0.9 cm, P: 3.8 +/- 1.2 cm), and left atrial dimensions (S: 5.0 +/- 1.0 cm, P: 4.7 +/- 0.9 cm) did not differ significantly between the 2 groups. 2) The peak mitral flow velocities (S: 1.43 +/- 0.38 m/sec, P: 1.43 +/- 0.27 m/sec), pressure gradients (S: 8.5 +/- 4.0 mmHg, P: 8.4 +/- 3.1 mmHg), and pressure half-times (S: 94.0 +/- 19.0 msec, P: 86.5 +/- 21.7 msec) did not differ significantly between the 2 groups. 3) Although mitral regurgitation was detected in 8 patients (35%) in the S group and in 2 patients (9%) in the P group, hemodynamically significant regurgitation was detected in only 4 patients in the S group (3 mild, one moderate). 4) The patients in the S group had reversed intracavitary blood flow; mitral flow was first directed towards the left ventricular outflow tract during diastole, while the outflow pattern was displaced into the left ventricular inflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Assessment of prognosis of old myocardial infarction].
In an attempt to predict high risk myocardial infarction, we studied 201 patients with Q wave infarction with dipyridamole-loading thallium-201 myocardial perfusion scintigraphy (D-MPS), left ventriculography, coronary angiography and treadmill exercise testing. The results of these tests were related to the use of initial PTCA or CABG, and the occurrence of cardiac deaths and nonfatal cardiac events during a mean follow-up period of 39 months. Three high risk parameters were identified by D-MPS; partial redistribution, diffuse slow washout, and extensive fixed defects. The patients were categorized into 3 groups according to the numbers of high risk parameters: group A (n = 50), patients with 2 or more high risk parameters; group B (n = 95), patients with one high risk parameter; group C (n = 56), patients without a high risk parameter. The prevalence of 3-, 2-, and one- or insignificant vessel disease was 72, 20 and 8% in group A, 15, 16, and 69% in group B, and 5, 13 and 82% in group C, respectively. Initial PTCA or CABG was performed in 42% of the patients in group A, 5% of the patients in group B, and 2% of the patients in group C. Among medically-treated patients, cardiac deaths occurred in 31% in group A, 4% in group B, and in none in group C. Nonfatal cardiac events occurred in 24, 12, and 4%, respectively. Coronary angiography revealed 3-vessel disease in 53 patients, 2-vessel disease in 32, and one-vessel disease or insignificant lesions in 116 patients. Initial PTCA or CABG was performed in 45% of the patients with 3-vessel disease, 6% of those with 2-vessel disease and 1% of those with one-vessel disease. Among medically-treated patients, cardiac deaths occurred in 31% with 3-vessel disease, 7% with 2-vessel disease, and in 2% with one-vessel disease. Nonfatal cardiac events occurred in 17, 10, and 3%, respectively.
Adult↗
Reactions of copper(II)-N-polycarboxylate complexes with hydrogen peroxide in the presence of biological reductants: ESR evidence for the formation of hydroxyl radical.
The formation of hydroxyl radicals (.OH) by the reaction of CuII(edta) (edta: ethylenediaminetetraacetic acid) with hydrogen peroxide (H2O2) in the presence of biological reductants, such as L-ascorbic acid and L-cysteine, has been demonstrated for the first time by ESR spectroscopy using water-soluble spin-traps, 5,5-dimethyl-1-pyrroline N-oxide (DMPO, 1), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN, 2) and 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS, 3). Ethylenediaminetetraacetic acid (edta) is one of the polyamine-N-polycarboxylate chelating agents and it is commonly used by chemists and biochemists. Edta can chelate several metal ions. It is known that the CuII(edta) complex is usually less active than free copper ions in radical reactions, whereas complexes of edta with Fe(II) or Fe(III) still react with hydrogen peroxide (H2O2) or superoxide ion (O2-) (1). In our previous papers (2-4), we also have shown that copper(II) complexes with polyamine-N-polycarboxylates, such as edta and dtpa (diethylenetriaminepentaacetic acid), do not react with H2O2, whereas CuII(en)2 (en: ethylenediamine) can easily do so to give hydroxyl radical (.OH) as a reactive intermediate. Further, we assumed that the change of redox potential of Cu(II) ions as a result of ligation with different ligands causes the difference in reactivity of Cu(II) complexes towards H2O2. To verify this assumption, the reactions of CuII(edta), which was chosen as a Cu(II)-polyamine-N-polycarboxylate complex, with H2O2 were investigated in the presence of some biological reductants, using an ESR-spin trapping method.(ABSTRACT TRUNCATED AT 250 WORDS)
Ascorbic Acid↗
Diurnal blood pressure variations and silent cerebrovascular damage in elderly patients with hypertension.
OBJECTIVE: To examine the effect of diurnal blood pressure changes upon cerebrovascular damage in elderly patients with hypertension. DESIGN: Fifty-four asymptomatic hypertensive and 34 normotensive elderly subjects underwent both 24-h non-invasive ambulatory blood pressure monitoring and brain magnetic resonance imaging. METHODS. Diurnal variation was defined as a difference of greater than or equal to 10 mmHg between mean awake and asleep systolic blood pressure. Hypertensives were thus classified as dippers or non-dippers. Low intense foci (lacunae) and advanced periventricular hyperintensity were identified as silent cerebrovascular damage. RESULTS: In the hypertensive group, lacunae were correlated more closely with mean asleep systolic blood pressure than with mean awake systolic blood pressure. Age, awake blood pressure, predicted whole blood viscosity, lipid profiles or quantity of sleep did not differ between the hypertensive dippers or non-dippers. The non-dippers, however, showed significantly higher grades of cerebrovascular damage as well as cardiac hypertrophy by electrocardiography than the dippers, whose results were similar to those of normotensives in this regard. CONCLUSIONS: An absent or lower nocturnal blood pressure fall in elderly hypertensives is associated with silent cerebrovascular damage. In contrast, the presence of a nocturnal fall could prevent the development of hypertensive vascular damage.
Aged↗