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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 397 records · Page 22Linked to original sources
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↗
PubMed1997

Ultrastructure of the lesions of psoriasis vulgaris transplanted into the subcutaneous tissue of nude mice by the skin fenestrating transplantation method.

We have developed a new skin transplantation method, called the skin fenestrating transplantation method, in which the nude mouse skin covering the lesion was removed one week after the transplant was embedded. One week later, transplanted psoriatic skin was biopsied and specimens were examined by electron microscopy. The basal cells and the nuclei of transplanted psoriatic epidermis were long and slender. Projections of basal cells extended to the dermis. Erythrocytes and lymphocytes were seen in the intercellular space. In the spinous cell layer, the cytoplasm and the nuclei were round. In the cytoplasm, mitochondria and endoplasmic reticuli were abundant, and tonofibrillar formation was poor. In the upper part of the epidermis, the cells were horizontally elliptic and, in the cytoplasm, short tonofibril bundles were formed. In the uppermost layers, in the cytoplasm of flat cells, degenerated flat nuclei, low dense lipid droplets and clumps of ribosomes were observed. These findings resembled the findings of intact psoriasis lesions more closely than those obtained by the skin embedding transplantation method.

Animals↗
PubMed1997

Breast milk is not a significant source for early Epstein-Barr virus or human herpesvirus 6 infection in infants: a seroepidemiologic study in 2 endemic areas of human T-cell lymphotropic virus type I in Japan.

In order to evaluate the possibility of Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) transmission via breast milk, a total of 331 serum specimens collected from bottle-fed and breast-fed children and their mothers, in 2 endemic areas of human T-cell lymphotropic virus type I (HTLV-I) in Japan, were assayed for antibodies to EBV and HHV-6. The seroprevalences of EBV and HHV-6 were over 95% both in the mothers of bottle-fed children and in those of breast-fed children. The seroprevalence of EBV at 12-23 months of age was 54.5% (36/66) and 55.8% (24/43) in breast-fed children and bottle-fed children, respectively. The seroprevalence of HHV-6 at 12-23 months of age was 90.9% (60/66) and 93.0% (40/43) in breast-fed children and bottle-fed children, respectively. No difference was observed between the seroprevalences of EBV and HHV-6 in breast-fed and bottle-fed children at 12-23 months of age. Our seroepidemiologic data indicate that breast milk is not a significant source of early EBV or HHV-6 infection in infancy.

Antibodies, Viral↗
PubMed1997

Blood pressure measurement in preschool children: the Hisayama Study.

OBJECTIVE: To establish the blood pressure (BP) measurement protocol for Japanese preschool children, systolic BP (K1) and diastolic BP (K4, K5) were measured along with anthropometric values. METHODOLOGY: Commercially available mercury sphygmomanometers were used. In the first group of children (group A), BP was measured in 79 boys and 85 girls using a cuff 9 cm wide and 23 cm long. In the second group (group B), the length and circumference of the upper right arm of 147 boys and 139 girls were measured to select cuffs appropriate for their sizes. Blood pressure measurements were performed twice on the right arm of the children in the seated position at a mean interval of 5 min. RESULTS: There were no significant differences in the anthropometric values (height, bodyweight, body mass index [BMI], length and circumference of the upper arm) between groups A and B. The BP values at K1, K4 and K5 in the first measurement of group B were 91 +/- 9, 54 +/- 8, and 48 +/- 10 mmHg (boys) and 90 +/- 9, 54 +/- 8, and 48 +/- 12 mmHg (girls), respectively. There were no significant differences between the first and second measurements in both groups, however, there were significant differences in the first and second measurements of K4 between groups A and B. Multiple regression analysis by the stepwise method revealed a strong correlation between K1 and the length of the upper arm in the boys and the bodyweight in the girls: between K4 and the bodyweight in the boys and the BMI in the girls, and between K5 and the height in the boys and the upper arm circumference in the girls. CONCLUSIONS: From these results it would appear that a single measurement is sufficient under appropriate measurement conditions such as rest before measurement and the choice of the cuff size according to the upper arm circumference, and that BP is closely correlated with the anthropometric values in preschool children.

Anthropometry↗