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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 379 records · Page 21Linked to original sources
PubMed1997

Mechanism for reduction of serum folate by antiepileptic drugs during prolonged therapy.

To determine whether the induction of liver enzymes by antiepileptic drugs play a major role in folate depletion, serum concentrations of folate were measured in age-matched control subjects without anemia and in epileptic outpatients who were being treated with a single antiepileptic drug. Two of the four drugs being administered were enzyme inducers. A protein binding radioassay was used to measure folate levels. Compared with serum folate levels in controls (5.14 +/- 1.88 ng/ml: n = 74), mean serum folate levels were reduced significantly in patients treated with phenobarbitone (3.91 +/- 1.73 ng/ml, p < 0.01: n = 33) and carbamazepine (3.85 +/- 1.02 ng/ml, p < 0.01: n = 36): both of which are enzyme-inducing agents. In contrast, patients treated with the non-enzyme-inducer valproate (5.39 +/- 1.71 ng/ml: n = 41) or zonisamide (5.59 +/- 2.60 ng/ml: n = 25) exhibited serum folate levels that did not differ significantly from values in controls. Findings showed that a reduction in serum folate is associated with the induction of enzymes by antiepileptic drugs. Thus, the induction of microsomal liver enzymes may be critical to the depletion of folate by antiepileptic drugs.

Adolescent↗
PubMed1997

Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants.

Plasma total homocysteine (tHcy) and serum folate (FA) concentrations were measured in 130 epileptic patients taking anticonvulsant drugs. A significant inverse correlation was found between FA and tHcy. This was greater in the older group (> or = 15 years) than in the younger group (1 to 14 years). There were four FA-deficient patients (FA concentration < 3 ng/mL regardless of symptoms), including three patients in the older group and one in the younger group. All FA-deficient patients had received long-term treatment (> 7 years) with multiple anticonvulsants. Their tHcy levels were higher than the 90th percentile of those in control subjects. Two patients showed extremely high levels of tHcy (57.9 and 29.1 mumol/L) and subnormal plasma methionine levels. After FA therapy, their tHcy decreased to levels the same as or less than those of control subjects and FA increased to above the normal range. Based on these findings, we conclude that measuring FA and tHcy concentrations may be useful for preventing thrombosis due to hyperhomocysteinemia in epileptic patients taking anticonvulsants, particularly those who receive long-term treatment with multiple agents.

Adolescent↗
PubMed1997

Serum concentrations of cortisone and cortisol in premature infants.

To determine the relationship between biological active cortisol and its inert metabolite cortisone accurately in premature infants, serum cortisone and cortisol concentrations were measured by reversed-phase high-performance liquid chromatography (HPLC) in a group of 232 premature infants and in a control group of 127 children and 88 adults. In the control group, serum cortisone concentrations were greater than serum cortisol levels during the first 2 months after birth; cortisol levels were higher than cortisone levels after 2 months of age. However, in premature infants, serum cortisone concentrations were greater than serum cortisol levels even after the first 2 months, and total concentrations of cortisone and cortisol were equal to those in controls. Results were then analyzed according to the equivalent gestational age of premature infants. Cortisone was predominant in premature infants older than 32 weeks of equivalent gestational age, but cortisol was higher than cortisone from equivalent gestational age 24 to 31 weeks. These findings suggest that the ability of premature infants to secrete glucocorticoids resembled that of normal controls. Also, the fetal zone of the cortex, which is associated with a predominance of cortisone, remained functional in premature infants for a longer time than in control infants. Our findings that in premature infants cortisone was predominant compared with cortisol and the sum of cortisone and cortisol was equal to that in the controls indicate that cortisone cannot be disregarded whenever the cortisol level is estimated, although cortisone itself is recognized to be biologically inactive. Simultaneous measurement of serum cortisone and cortisol concentrations is important when adrenocortical function is being determined, especially in premature infants.

Adolescent↗
PubMed1997

Prevalence of the Trp64Arg missense mutation of the beta3-adrenergic receptor gene in Japanese subjects.

Prompted by the recent findings that a tryptophan to arginine (Trp64Arg) mutation in the beta3-adrenergic receptor gene was associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal obesity and insulin resistance in Finns, and with an increased capacity to gain weight in French whites, we studied the prevalence of this mutation in 231 diabetic and 95 nondiabetic Japanese subjects and assessed its contribution to the development of obesity and NIDDM. The allelic frequencies of the mutation were 0.18 in diabetic and 0.23 in nondiabetic subjects, showing no significant difference between the two groups (P = .067). In nondiabetic subjects, body mass index (BMI) did not differ between those with and without the mutation (22.2 +/- 3.5 v 21.4 +/- 3.2 kg/m2, P = .252). In NIDDM subjects, BMI at the time of study and maximal BMI before the start of treatment did not differ between those with and without the mutation (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m2, P = .678, and 24.7 +/- 2.6 v 24.9 +/- 3.1 kg/m2, P = .277). Homozygotes for the mutation did not have trends to have increased BMI in either diabetic or nondiabetic subjects. The age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/- 9.9 v 47.8 +/- 12.5 years, P = .796). Fasting serum cholesterol and triglyceride levels and systolic and diastolic blood pressure before the start of treatment did not differ between NIDDM subjects with and without the mutation. In conclusion, although the Trp64Arg mutation is not uncommon in Japanese, it does not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or dyslipidemia. Our results suggest that the mutation has minor effects, if any, on the development of obesity and NIDDM in Japanese.

Adult↗
PubMed1997

Intrapulmonary Mycobacterium avium infection as the first manifestation of chronic granulomatous disease.

A 10-month-old Japanese male infant, with no history of being prone to infections, contracted an intrapulmonary mycobacterial infection. After 2 months of intermittent fever, radiological examinations revealed mass lesions in the lung and mediastinum. Biopsy specimens showed granulomas with caseous necrosis, from which Mycobacterium avium was isolated. There was no history of mycobacteriosis or immunodeficiency diseases among his relatives. Analyses of the O2- release and expression of NADPH oxidase components verified that he suffered from gp91-phox- chronic granulomatous disease (CGD), and that his mother was a carrier of the disease. This is a rare clinical presentation for the onset of CGD, suggesting that the invasive mycobacteriosis might result from defective intracellular killing of CGD-phagocytes.

Granulomatous Disease, Chronic↗
PubMed1997

Cleavage of viral RNA and inhibition of viral translation by hepatitis C virus RNA-specific hammerhead ribozyme in vitro.

BACKGROUND/AIMS: A hammerhead ribozyme has been used as a new way to suppress specific gene expression. We designed hammerhead ribozymes directed against hepatitis C virus RNA, and investigated their cleavage efficiency and inhibitory effect on viral translation in vitro. METHODS: Three hammerhead ribozymes bearing different cleavage sites in the core region of hepatitis C virus RNA (genotype 1b) were designed in this study. Ribozymes and the target hepatitis C virus RNA were synthesized by in vitro transcription. The cleavage efficiency was evaluated by the ribozyme cleavage assay. The inhibitory effect of the ribozyme on viral translation was further studied by the viral translation inhibition assay. RESULTS: All ribozymes specifically cleaved the target RNA of 1217 bases at a physiological temperature in a dose-dependent manner, with the specific cleavage increasing with a longer incubation period. The target RNA was cleaved most efficiently by the ribozyme with the cleavage site located nearest to the initiation codon. In the viral translation inhibition assay, all ribozymes showed a significant inhibitory effect on viral translation. The ribozyme with the cleavage site located farthest from the initiation codon blocked viral translation most efficiently, and demonstrated almost 70 to 80% inhibition. For ribozymes with the T7 transcription terminator sequence, both the target RNA cleavage and the inhibition of viral translation tended to be achieved less efficiently by ribozymes with T7 terminator than by those without it. CONCLUSIONS: These findings suggest that ribozyme-mediated hepatitis C virus RNA cleavage may serve as a new strategy in the treatment of hepatitis C virus infection.

Hepacivirus↗
PubMed1997

Twenty-three-year follow-up study of rubella antibodies after immunization in a closed population, and serological response to revaccination.

Twenty-six institutionalized children immunized with a Japanese rubella vaccine, Matsuba strain, have been observed for 23 years and the persistence of vaccine-induced rubella immunity documented. All vaccinees were shown to have seroconverted to rubella virus in a haemagglutination inhibition (HI) test, and the geometric mean titre (GMT) of rubella HI antibody rose to 2 5-8 months after vaccination (Ueda et al., Acta Paediatrica Japonica, Overseas Edition 1978, 20, 8-14). The GMT then declined gradually to 2 23 years after inoculation, except in four cases (15.4%) which had reverted to negative. However, three of the four maintained a rubella HI antibody titre of 1:4. Twelve of the 26 vaccinees were revaccinated 24 years after primary vaccination, and all ten cases having initial titres of < or = 1:16 demonstrated secondary responses. Rubella immunity induced by vaccination had persisted, so routine booster immunization did not seem necessary. However, a second immunization programme should be considered to achieve high antibody-positive rates and to protect against primary vaccine failure.

Adolescent↗
PubMed1997

Enantioselective protein binding of semotiadil and levosemotiadil determined by high-performance frontal analysis.

An on-line frontal analysis HPLC system was developed for the determination of the unbound concentrations of semotiadil, a new calcium antagonist with non-dihydropyridine structure, and its antipode (Levosemotiadil), and was applied to the enantioselective investigation of their plasma protein binding properties. This system consists of a high-performance frontal analysis (HPFA) column, an extraction column, and an analytical column, which are connected via two switching valves. After the direct injection of the sample solution into the HPFA column, the drug was eluted as a zonal peak with a plateau region. The unbound drug concentration was determined as the drug concentration in the plateau. As low as 1.04 nM of the unbound drug was determined with good reproducibility. Semotiadil (R-isomer) and levosemotiadil (S-isomer) are bound strongly and enantioselectively to human serum albumin (HSA) and human alpha 1-acid glycoprotein (AGP), and the enantioselectivity was reversed between these plasma proteins. While HSA binds S-isomer more strongly than the antipode, human AGP binds R-isomer more strongly. In human plasma, the unbound drug fraction was less than 1%, and the enantioselectivity was similar to that observed in AGP solution.

Blood Proteins↗
PubMed1997

Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis.

OBJECTIVES: This study was undertaken to assess how prodromal angina affects long-term prognosis after acute myocardial infarction. BACKGROUND: Although it has been reported that prodromal angina occurring shortly before the onset of acute myocardial infarction has protective effects against ischemia, its implication for long-term prognosis remains unclear. METHODS: We studied consecutive 350 patients with anterior myocardial infarction who underwent coronary angiography within 24 h after the onset of chest pain. Follow-up was achieved for 340 patients (97%). RESULTS: Eighty-nine patients had one or more episodes of angina within 24 h before infarction. On initial angiography, patients with prodromal angina in the 24 h before infarction had a patent infarct-related artery more frequently than did those without prodromal angina (34% vs. 22%, p = 0.03). Among 213 patients who underwent thrombolytic therapy for an occluded infarct-related artery, reperfusion was more frequently achieved in patients with prodromal angina in the 24 h before infarction (76% vs. 56%, p = 0.01). Prodromal angina in the 24 h before infarction was associated with a lower in-hospital mortality rate (6% vs. 14%, p = 0.02) and better 5-year survival (p = 0.009). There was no significant difference in survival between patients with previous angina at any time (n = 202) and those without. Multivariate analysis showed that prodromal angina in the 24 h before infarction was an independent factor related to 5-year survival after acute myocardial infarction (odds ratio 0.49, p = 0.04). CONCLUSIONS: Prodromal angina occurring shortly before the onset of infarction, but not previous angina itself, has a beneficial effect on long-term prognosis after infarction, suggesting a relation to ischemic preconditioning.

Aged↗
PubMed1997

Treatment outcome of AT-B88 regimen for B-cell non-Hodgkin's lymphoma and surface immunoglobulin-positive acute lymphoblastic leukemia in children.

We conducted a multicenter study to improve the treatment of B-cell non-Hodgkin's lymphoma and acute lymphoblastic leukemia (NHL/ALL) in Japanese children. The subjects were a total of 57 untreated patients with the B-cell type of either NHL (27 Burkitt's and 9 diffuse large) or ALL between 2 and 15 years old (median: 8 years) seen between 1988 and 1994. All patients received the same cytoreductive therapy (half doses of vincristine and prednisolone) and the same first and second induction courses (vincristine, prednisolone, high-dose methotrexate, repetitive high-dose cyclophosphamide, and adriamycin). Three cycles of consolidation blocks A and B (consisting of reduced doses of similar agents used in the second induction course) followed for patients with stage III or IV NHL or B-ALL, while only one cycle was given for stage I or II disease. Fifty-three patients (93.0%) achieved complete remission. Eight patients had relapse all occurring within 1 year. Another patient had secondary myelodysplastic syndrome. The median follow-up period was 48 months (range: 24-94 months). The overall survival and event-free survival (EFS) rates for all patients were, respectively, 75.9% (S.E.: 5.9) and 70.1 (S.E.: 6.1). The relapse-free interval rate of the 53 patients who achieved CR was 83.5% (S.E.: 5.3). EFS was 75.0% (S.E.: 21.7) in stage I, 84.6% (S.E.: 10.0) in stage II, 78.63% (S.E.: 11.0) in stage III, 80.0% (S.E.: 17.9) in stage IV, and 52.4% (S.E.: 10.9) in ALL. Among the stage IV NHL and ALL patients, EFS was significantly worse in patients with initial CNS involvement than in those without it (14.3% (S.E.: 13.2) vs. 73.7% (S.E.: 10.1); P = 0.0025). In conclusion, our regimen (AT-B88) produced a more than 70% cure-rate for children with any stage of B-cell NHL/ALL without initial CNS involvement. However, a new regimen is needed for patients with initial CNS involvement.

Adolescent↗
PubMed1997

Two-dimensional aortographic coronary arteriography with above-K-edge monochromatic synchrotron radiation.

RATIONALE AND OBJECTIVES: The diagnostic potential of two-dimensional aortographic coronary arteriography with synchrotron radiation was examined in dogs. METHODS: The experiment was performed at a wiggler beam line by using a silicon monocrystal, fluorescent plate, and avalanche-type camera. The x-ray energy was adjusted to just above the iodine K-edge to obtain the highest contrast. Quantitative densitometry was used to compare intravenous coronary arteriography with aortographic coronary arteriography. RESULTS: Aortographic coronary arteriography clearly depicted the branches of the coronary arteries such as the left anterior descending coronary artery, circumferential coronary artery, and right coronary artery to sizes of less than 0.2 mm without major overlap of coronary arteries. Intravenous coronary arteriography depicted only the branches of the left anterior descending coronary artery and right coronary artery with poor image quality. The ratio of contrast material dilution was about 2.4 to 3.4 in aortographic procedures, whereas in intravenous procedures it ranged widely from 7.7 to 15.6. CONCLUSION: These preliminary investigations indicate that two-dimensional aortographic coronary arteriography with synchrotron radiation promises to be a minimally invasive and easily repeatable method of clearly imaging the coronary arteries.

Animals↗
PubMed1997

Severe lactic acidosis and neonatal death in Pearson syndrome.

Pearson marrow-pancreas syndrome, a fatal disease associated with mitochondrial DNA rearrangements, is characterized by refractory sideroblastic anaemia during infancy. Only a few neonates with Pearson syndrome have been reported with metabolic acidosis. A female neonate who exhibited severe metabolic acidosis and anaemia at birth is described here. Her condition progressively worsened, with pancytopenia and uncontrollable metabolic acidosis resulting in death at the age of 14 days. A 4988-base pair deletion of mtDNA was detected in the patient's leukocytes, liver and muscle. When a neonate exhibits severe metabolic acidosis of unknown cause, the possibility of Pearson syndrome should be considered.

Acidosis, Lactic↗
PubMed1997

The association between haematological manifestation and mtDNA deletions in Pearson syndrome.

We studied the proportion of deleted mitochondrial DNA in blood cells from patients with Pearson syndrome. Patient 1 is a 17-year-old female with Kearns-Sayre syndrome who survived Pearson syndrome. Patient 2 is a 5-year-old boy with Pearson syndrome who recovered from refractory anaemia but continues to have thrombocytopenia and neutropenia. Patient 3 is a female neonate who died with severe acidosis and pancytopenia at 14 days of age. Southern blot analysis was performed with total DNA from three patients' blood cells and two samples of bone marrow cells from one patient. In peripheral blood, patients with a higher proportion of deleted mitochondrial DNA had lower blood cell counts. In patient 2, the percentage of mutant mitochondrial DNA in bone marrow cells decreased as anaemia improved. This indicates that the proportion of deleted mitochondrial DNA in peripheral blood and in bone marrow has a tendency to correlate to the severity of haematological manifestation.

Adolescent↗
PubMed1997

Further investigation of the light chain shifting phenomenon: light chain replacement through secondary rearrangement induced by lectin stimulation in the hybridoma cell line HB4C5.

We found that when the hybridoma cell line HB4C5 was stimulated with wheat germ agglutinin (WGA), loss of production of the original lambda light chain occurred, followed by production of new light chain, which mirrored the reaction when stimulated with concanavalin A (ConA). We previously reported that the RAG genes are expressed not only in HB4C5 and its ConA-treated variant subclones, but also in the in the parental Namalwa cells, which are known to be in the plasma state. However, the new lambda light chains were expressed only in the HB4C5 cells and not in the parental Namalwa cells. Here we found that the RAG genes are expressed in HB4C5 cells after continuous stimulation with WGA. To further investigate the mechanism of this loss of original lambda light chain production by stimulation with lectins in HB4C5 cells, which leads to a sIg-negative subpopulation, we analyzed the differences between HB4C5 and Namalwa cells. In this present study, we found that a 70 kDa phosphorylated protein in HB4C5 cells became undetectable after stimulation with lectins (WGA and ConA), and was not detected in Namalwa cells before or after lectin stimulation. It has been believed that the RAG genes and loss of original lambda light chain production are required to induce expression of a new lambda light chain in the HB4C5 cells. We suggested that the phosphorylated 70 kDa protein in HB4C5 cells play important roles in regulating the production of new lambda light chains which is induced by lectins.

Amino Acid Sequence↗
PubMed1997

Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy.

We assessed the therapeutic significance of systematic aortic and pelvic lymphadenectomy followed by adjuvant therapy in node-positive endometrial carcinoma. Among 173 stage I-III patients, 30 (17%) had positive nodes: ten in the pelvic region alone (group P) and 20 in the aortic region alone or in both regions (group A). The adjuvant therapy was administered as follows: subjects in group P received 50 Gy pelvic radiation, including three post-surgical T3 (pT3) patients who received either one or three cycles of cisplatin-based chemotherapy before radiation. Subjects in group A were given three cycles of chemotherapy followed by 50 Gy pelvic and 50 Gy extended field periaortic radiation using a four-field or conformational technique. Five-year survival was 95% for 143 patients with negative nodes and 84% for 30 patients with positive nodes (100% for group P and 75% for group A). In group A, 5-year survival was 38% for eight patients with both pT3 and histology other than endometrioid type G1, and 91% for the remaining 12 patients. Either way, both group P and group A patients had a better prognosis than previously reported. In summary, aortic and pelvic lymphadenectomy and subsequent chemotherapy and radiation therapy based on node status seem to improve the survival of endometrial cancer patients with positive nodes.

Adenocarcinoma, Clear Cell↗
PubMed1997

Prolonged resolution of hemophagocytic lymphohistiocytosis following myeloablative chemotherapy and subsequent autologous peripheral blood stem cell transplantation.

A 30-month-old boy with hemophagocytic lymphohistiocytosis (HLH) received an autologous peripheral blood stem cell transplant (PBSCT) following high-dose chemotherapy. He presented with hemophagocytic syndrome (HPS) at 6 months of age, but relapsed despite the repeated administration of prednisolone, VP-16, cyclosporin A (CsA), and other cytotoxic agents. PBSC were obtained using combination chemotherapy with etoposide (VP16, 450 mg/m2), doxorubicin (70 mg/m2), vincristine (2 mg/m2) and cyclophosphamide (CY, 1200 mg/m2). 2.7 x 10(5)/kg CFU-GM PBSC were transplanted after similar high-dose VP16 preconditioning used for allogeneic BMT for HLH. The boy continues to remain in complete remission 30 months after PBSCT while receiving low-dose PSL/CsA therapy. High-dose chemotherapy followed by PBSCT may be an optional therapeutic approach for patients with HLH.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals.

Amyloid beta protein (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brain, is known to exert toxic effects on cultured neurons. The role of the voltage-sensitive Ca2+ channel (VSCC) in beta (25-35) neurotoxicity was examined using rat cultured cortical and hippocampal neurons. When L-type VSCCs were blocked by application of nimodipine, beta (25-35) neurotoxicity was attenuated, whereas application of omega-conotoxin GVIA (omega-CgTX-GVIA) or omega-agatoxin IVA (omega-Aga-IVA), the blocker for N- or P/Q-type VSCCs, had no effects. Whole-cell patch-clamp studies indicated that the Ca2+ current density of beta (25-35)-treated neurons is about twofold higher than that of control neurons. Also, beta (25-35) increased Ca2+ uptake, which was sensitive to nimodipine. The 2', 7'-dichlorofluorescin diacetate assay showed the ability of beta (25-35) to produce reactive oxygen species. Nimodipine had no effect on the level of free radicals. In contrast, vitamin E, a radical scavenger, reduced the level of free radicals, neurotoxicity, and Ca2+ uptake. These results suggest that beta (25-35) generates free radicals, which in turn, increase Ca2+ influx via the L-type VSCC, thereby inducing neurotoxicity.

Amyloid beta-Peptides↗