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T Uchino

Publications and source records attributed to T Uchino.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan.

In Japan, urea cycle disorders (UCDs) are one of the most frequent inborn errors of metabolism, estimated to have a prevalence of 1 per 50,000 live births. In an attempt to develop more effective treatment and enhance the quality of life, we investigated the clinical manifestations and prognosis of 216 patients with UCDs diagnosed and treated between 1978 and 1995. These included 92 cases of neonatal-onset UCD and 116 of late-onset UCD. Two cases of ornithine transcarbamylase (OTC) deficiency in males and 2 cases of argininosuccinase (AL) deficiency were diagnosed prospectively. By far the most common disorder was OTC deficiency, accounting for 2/3 of all cases. At the end of 1995, the 5-year survival rate was 22% for the neonatal-onset type and 41% for the late-onset type. Among the 20 long-term survivors with neonatal-onset UCD, 18 (90%) had moderate to severe neurodevelopmental deficits; this contrasts with 13 of 47 (28%) survivors with the late-onset type. In analysing 108 UCD cases, peak blood ammonia level during the first hyperammonaemic attack was correlated with neurodevelopmental outcome. When the concentration of blood ammonia was less than 180 mumol/L (5 times normal), there was no severe neurological damage. When the concentration of blood ammonia exceeded 350 mumol/L (10 times normal) at the first hyperammonaemic attack, the patients died or had severe neurological deficits. Our data point to the importance of early diagnosis and aggressive treatment.

Age of Onset↗
PubMed1998

[Arginase deficiency].

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Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Low-Frequency Raman Scattering and the Fast Relaxation Process in Glycerol

Ab initio molecular orbital calculations were used to determine the structure and vibrational frequencies of the cyclic glycerol trimer, which represents the region of medium-range ordering in liquid and supercooled glycerol. The calculations reproduced the experimentally observed low-frequency Raman scattering peak (or the "boson peak") at approximately50 per centimeter, which suggests that the peak results from the localized collective motions of the cooperatively hydrogen-bonded hydroxyl groups. The calculations also suggest that the fast relaxation process may result from the translational motion of each glycerol molecule in the cyclic structure. On the basis of these results, a model of the glass transition was developed.

Journal Article↗
PubMed1996

Apoptosis in the aged dog brain.

Apoptosis similar to that seen in Alzheimer's disease patients was found in the brain of aged dogs by the TUNEL method of detecting in situ DNA fragmentation. Apoptosis was observed in both neurons and glial cells, and was morphologically characterized by round and swollen cytoplasm and aggregated nuclear chromatin, although these changes were slight. Neurons and astrocytes in the gray matter and oligodendrocytes in the white matter were affected. The number of ApopTag-positive brain cells increased slightly with age, but was not correlated to the number of senile plaques. A good correlation between the number of ApopTag-positive cells and the dementia index was clearly found. The present study indicates that brain cell apoptosis could account for dementia in aged dogs and suggested that aged dogs may be useful as a simplified animal model for Alzheimer's disease in man.

Aging↗
PubMed1996

Three brothers with progressive hepatic dysfunction and severe hepatic steatosis due to a patent ductus venosus.

Three Japanese brothers with progressive deterioration of hepatic function and fatty degeneration of the liver eventually leading to hepatic encephalopathy were recently encountered. Each of them had a congenital intrahepatic portosystemic venous shunt due to a patent ductus venosus. Liver dysfunction and hepatic steatosis reverted to normal with surgical correction of the ductus venosus. Our observations suggest that impairment of liver function occurs first in the presence of malnutrition related to a reduction of blood in the portal vein. Hepatic steatosis is a consequence of a depleted metabolism of hepatocytes. Congenital portosystemic venous shunt due to a patent ductus venosus in this family has a genetic background.

Angiography↗
PubMed1995

Molecular basis of phenotypic variation in patients with argininemia.

Argininemia is an autosomal recessive disorder caused by a deficiency in the liver-type arginase enzyme. Clinical manifestations include progressive spastic diplegia and mental retardation. While the quality of life can severely deteriorate in most such patients, some do show remarkable improvement in neurological symptoms while on controlled diets. We examined the thesis that differences in clinical responses to dietary treatment are based on molecular heterogeneity in mutant arginase alleles. Genomic DNAs from 11 patients with argininemia were examined using the polymerase chain reaction, cloning, and sequencing. Nine mutations representing 21/22 mutant alleles were identified in 11 patients with argininemia, and four of these mutations were expressed in vitro to determine the severity of enzymatic defects. We found that these mutations accounted for 64% of the mutant alleles in our patients. Based on findings in vitro expression tests, the mutations can be considered either severe or moderate. Patients with at least one moderate mutant allele responded well to dietary treatment; concentrations of plasma arginine were controlled within 300 microM. In contrast, patients with two severely mutated alleles did not respond to dietary treatment and plasma arginine was over 400 microM. Argininemia is heterogeneous at the molecular level. The degree of clinical improvement during dietary treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment is reflected in the concentration of arginine in plasma, as a measure of metabolic control. Plasma arginine levels during treatment correlated with types of molecular defects in the arginase genes.

Alleles↗
PubMed1994

[Estimation of myocardial damage after cardiac surgery by myosin light chain I and troponin T].

The purpose of the study was to test cardiac myosin light chain I (MLCI) and troponin T (TNT) as markers of myocardial damage after heart surgery. Forty-three patients undergoing cardiac surgery were arbitrarily divided into three groups according to the creatine kinase MB isoenzyme (CK-MB) levels and postoperative electrocardiogram (ECG) changes. Group 1: CK MB > 100 micrograms/l and Infarction pattern changes in ECG (Infarction): Group 2: CK-MB < 100 micrograms/l and no ECG changes (minimal myocardial damage). Group 3: CK-MB > 100 micrograms/l or non specific ECG changes (myocardial injury). MLCI levels showed strong correlations with TNT levels after the operation. The peak MLCI and TNT levels in group 1 were significantly higher than in group 2. The peak MLCI in group 1 was significantly higher than in group 3. TNT showed different patterns in the Infarction and Injury groups. The study showed that MLCI and TNT estimation could evaluate myocardial damage over several postoperative days. TNT estimation could identify myocardial damage earlier than MLCI, however MLCI could discriminate perioperative infarction better than TNT.

Aged↗
PubMed1994

Measurement of myosin light chain I and troponin T as markers of myocardial damage after cardiac surgery.

The purpose of the study was to test cardiac myosin light chain I (CMLCI) and troponin T (TNT) as markers on myocardial damage after heart surgery. Forty-three patients undergoing cardiac surgery were arbitrarily divided into two groups according to creatine kinase MB isoenzyme (CK-MB) levels and postoperative electrocardiogram (ECG) changes. Group 1: CK-MB > 100 micrograms/L or ECG changes (extensive myocardial damage, 42%); Group 2: CK-MB < 100 micrograms/L and no ECG changes (minimal myocardial damage, 58%). Group 1 was divided into 2 groups (Infarction and Injury groups). CMLCI levels showed strong correlations with TNT levels after the operation. The peak CMLCI and TNT levels in group 1 were significantly higher than in group 2. The peak CMLCI in the Infarction group was significantly higher than in the Injury group. TNT showed different patterns in the Infarction and Injury groups. This study showed that CMLCI and TNT estimation could evaluate myocardial damage over several postoperative days. TNT estimation could identify myocardial damage earlier than CMLCI, however CMLCI could discriminate perioperative infarction better than TNT.

Aged↗
PubMed1993

Isolation and characterization of a novel serine proteinase complexed with alpha 2-macroglobulin from porcine gastric mucosa.

Porcine stomach mucosa was found to contain a 740-kDa protein having endopeptidase activity toward peptide 4-methylcoumaryl-7-amide substrates and low molecular mass peptides. This protein was purified to an apparent homogeneity by a series of chromatographic steps on DEAE-cellulose, Sepharose CL-4B, hydroxylapatite, and fast protein liquid chromatography Mono Q columns. The protein was shown to be a complex of the plasma proteinase inhibitor alpha 2-macroglobulin and a 25-kDa endopeptidase. The enzyme activity was completely inhibited by diisopropyl fluorophosphate, p-amidinophenylmethanesulfonyl fluoride, leupeptin, antipain, bovine pancreatic trypsin inhibitor, soybean trypsin inhibitor, and ovomucoid, indicating that the entrapped enzyme is a serine proteinase. The proteinase could be released from alpha 2-macroglobulin by mild acid treatment and the released enzyme showed activity toward protein substrates. Substrate specificity studies using synthetic and peptide substrates indicated that the enzyme preferentially hydrolyzes Arg-X bonds and, to a much lesser extent, Lys-X bonds, and is apparently distinct from thrombin, kallikrein, plasmin, and other trypsin-like proteinases so far reported including tryptase. Thus, the present enzyme is thought to be a novel type of serine proteinase. The proteinase associated with alpha 2-macroglobulin was also found in porcine intestinal mucosa, but not in plasma.

Amino Acid Sequence↗
PubMed1993

Pharmacokinetic properties of recombinant feline interferon and its stimulatory effect on 2',5'-oligoadenylate synthetase activity in the cat.

The pharmacokinetic behavior of recombinant feline interferon produced in silkworm infected with recombinant baculovirus harboring cDNA coding for feline interferon was studied in vivo in cats. The decreasing profile of the serum interferon level after intravenous administration was fitted to a two-compartment model. The half-times of the first phase (distribution phase) and second phase (metabolic phase) were 5.0 +/- 0.5 min and 31 +/- 5 min, respectively. In the whole body autoradiogram, at 15 min after the administration, the highest radioactivity was observed in urine in the bladder, and predominant radioactivity in the kidneys, liver, thyroid gland and spleen. Almost no radioactivity was detected in the brain or fat. Three hr after administration, the highest radioactivity was recorded in the thyroid gland, urine in the bladder, intestinal contents, and gastric mucous membrane. The data obtained in this study suggest that recombinant feline interferon has similar pharmacokinetic properties to human interferons and that it is distributed primarily in the liver and kidneys, is catabolized rapidly mainly in the kidneys, and is excreted in the urine without residual accumulation in the body. It was confirmed that 2',5'-oligoadenylate synthetase activity was increased by the interferon in vivo for 3 days after an intravenous bolus injection in cats.

2',5'-Oligoadenylate Synthetase↗
PubMed1993

The influence of heparin-coated and uncoated extracorporeal circuits on blood rheology during cardiac surgery.

The effect of heparin-coated perfusion circuits on blood trauma during clinical cardiopulmonary bypass (CPB) was studied in order to find out if traumatic changes in the blood could be minimized. Twenty-four patients undergoing coronary artery bypass surgery were randomized prospectively to CPB with heparin-coated circuits (HCC) or non-coated circuits (NCC). The trauma to blood was assessed by measuring damage to blood cells by estimating red and white cell rheology changes. These were measured as red cell filtration rate (RFR) and white cell filtration rate (WFR) using standard microfiltration methods. Furthermore, changes in plasma hemoglobin (P-Hb), whole blood and plasma viscosity were simultaneously assessed. The RFR was significantly reduced in both groups during CPB by 10% in the HCC and 32% in the NCC groups (p less than 0.01). When comparing the HCC and NCC groups, a significant difference was first seen after 30 minutes of bypass (p less than 0.05) and increased at the end of CPB (p less than 0.01). Similar results were seen regarding WFR (15% and 36%, p less than 0.01). After 30 minutes of bypass, a significant difference was seen between HCC and NCC groups (p less than 0.05). Furthermore, a significant increase in P-Hb levels were seen during CPB in both patient groups. At the end of CPB, there was a significant difference in P-Hb levels (HCC 305+/-90 mg/L; NCC 455+/-78 mg/L, p less than 0.01) when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Detection of perioperative myocardial structural damage by the estimation of cardiac myosin light chain I.

The accurate estimation of myocardial damage is desirable for the assessment of myocardial protection and surgical treatments. The purpose of the study was to estimate myocardial damage by measuring cardiac myosin light chain I (CMLCI). Forty-nine patients undergoing cardiac surgery (for angina or valvular disease) were arbitrarily divided into four groups according to the maximum CMLCI level. Group 1: max CMLCI < 10 micrograms/L (37%); Group 2: max CMLCI 10-20 micrograms/L (39%); Group 3: max CMLCI 20-30 micrograms/L (16%); Group 4: max CMLCI > 30 micrograms/L (8%). Electrocardiogram (ECG) and serum creatine kinase MB isoenzyme (CK-MB) were conventionally used as standards of myocardial damage, and compared with CMLCI. Perioperative myocardial infarction, injury and minimum damage were determined by combinations of ECG pattern changes and CK-MB levels. The max CMLCI level was usually seen on the third postoperative day. None of the patients in group 1 had any ECG changes. The number of patients with ECG changes was much higher as the max CMLCI level increased, and evidently increased when the max CMLCI was over 20 micrograms/L. The number of patients with high CK-MB > 100 micrograms/L followed the same pattern. Furthermore, perioperative infarction was only seen when the max CMLCI was > 30 micrograms/L. The peak CMLCI level was significantly higher in the infarction group than injury and minimum damage groups. This study showed that CMLCI was able to estimate the actual extent and severity of the myocardial damage and enhanced the diagnosis of perioperative infarction.

Aged↗
PubMed1993

[Molecular basis of urea cycle disorders].

Five different enzymes, carbamyl phosphate synthetase I (CPS I), ornithine transcarbamylase (OTC) argininosuccinate synthetase (AS), argininosuccinate lyase (AL) and arginase (AR) play a role in urea synthesis from ammonium. The structures of cDNA of all these enzymes and those of genome DNA of some enzymes (OTC, AL, AR) have been already clarified, and using of the information, the alleles of each enzyme deficiency have been identified. Alleles are extremely heterogeneous in all enzyme deficiencies, in sharp difference from other inborn errors of metabolism, such as cystic fibrosis and hemoglobinopathies.

Alleles↗
PubMed1992

Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia.

Argininemia is caused by a hereditary deficiency of liver-type arginase (E.C.3.5.3.1) and is characterized by psychomotor retardation and spastic tetraplegia. We examined findings in three Japanese patients with argininemia, by using the PCR, cloning, and sequencing procedures. We found three different mutations--G-to-A-365 in exon 4, G-to-C-703 in exon 7, and C-del-842 in exon 8--thereby leading to mutant arginase proteins of W122X, G235R, and L282FS, respectively. Patient 1 was a compound heterozygote, inheriting the allele with G-to-A-365 from his mother and the allele with G-to-C-703 from his father. Patients 2 and 3 were homozygotes of the allele with G-to-C-703 and of the allele with C-del-842, respectively. Expression tests of these mutant arginases in Escherichia coli indicated that the mutant arginase of W122X did not remain a stable product. The other two mutant arginases--G235R and L282FS--were detected by immunoblot analyses. There was no evidence of activity of the three mutant arginases expressed in E. coli. We tentatively conclude that argininemia is heterogeneous, at the molecular level.

Amino Acid Sequence↗
PubMed1992

Effects of warfarin at beginning doses on patients with valve replacement.

Warfarin administered to patients with valve replacement at a dose of 0.1 mg/kg for 2 days after surgery, and blood levels of warfarin, TT, PT, HPT, total vitamin K and vitamin K1-epoxide were determined at various time intervals after the administration of the drug. The measurements were obtained from 15 patients: 8 patients with AVR, 6 patients with MVR, and 1 patient with DVR. The blood levels of warfarin reached a peak of 462 +/- 160 ng/ml 6 hours after the administration, TT, PT and HPT were 40% of the initial values 24 hours after the administration, and vitamin K1-epoxide was 1.28 +/- 0.30 ng/ml 24 hours after the administration. It is clear from the results that warfarin exhibits sufficient anticoagulant effects at a beginning dose of 0.1 mg/kg after surgery to prevent a sudden decrease in blood coagulation.

Blood Coagulation Factors↗
PubMed1992

[A successful case of thoracic aortic aneurysm with mixed cryoglobulinemia].

Cold-reactive proteins, such as cold agglutinins, cryoglobulins, and cryofibrinogens, are reversibly precipitates, or gel, upon exposure to cold temperatures. Cryoglobulins are usually not of importance, but under special conditions, such as surgical hypothermia, hyperviscosity and damage in microcirculation may occur in patients with high plasma concentration of cryoglobulins. Several groups have reported their efforts to reduce further the risks of surgical hypothermia in patients with cold agglutinins, but rarely in patients with cryoglobulins. A 57-year-old woman with thoracic aneurysm, requiring replacement of the ascending aorta and the aortic arch, had mixed cryoglobulinemia (cryocrit 29%) associated with rheumatoid arthritis. Steroids therapy and preoperative plasmapheresis were performed, and cryocrit levels were decreased until 0% before operation. Systemic hypothermia (25 degrees C), hemodilution techniques during cardiopulmonary bypass, and cold crystalloid cardioplegia were successfully employed, and no clinical evidence of microcirculation damage was posed after operation.

Aorta, Thoracic↗
PubMed1991

Cloning and sequence of a cDNA encoding human carbamyl phosphate synthetase I: molecular analysis of hyperammonemia.

Carbamyl phosphate synthetase I (CPSI) is the first enzyme involved in urea synthesis. CPSI deficiency is an autosomal recessive disorder characterized by hyperammonemic coma in the neonatal period. To analyze the enzyme and gene structures, and to elucidate the nature of mutations in CPSI deficiency, we isolated cDNA clones encoding human liver CPSI. Oligo(dT)-primed and random primer human liver cDNA libraries in lambda gt11 were screened using 5', middle, and 3' fragments of the rat CPSI cDNA as probes. Seven positive clones covered the full-length cDNA sequence with an open reading frame encoding a precursor polypeptide of 1500 amino acids (aa) (deduced Mr, 164,828) with a putative N-terminal presequence of 38 or 39 aa, a 5'-untranslated sequence of 118 bp and a 3'-untranslated sequence of 597 bp. Comparison with the rat CPSI cDNA showed that the deduced aa sequence of the human liver CPSI precursor is 94.4% identical to the rat enzyme precursor. A molecular analysis was made of the genomic DNA from three patients with CPSI deficiency. Heterogeneity of hybridized fragments that may or may not be the cause of the deficiency was apparent on the DNA blots from tissues from one patient.

Amino Acid Metabolism, Inborn Errors↗