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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 163 records · Page 9Linked to original sources
PubMed1997

[Alterations of the p53 gene and clinical features in childhood acute lymphoblastic leukemia].

Correlations between alterations of the p53 gene and clinical features were examined in childhood acute lymphoblastic leukemia (ALL). We analyzed 147 patients and 38 cell lines for p53 mutations within exons 5 to 9 (2 to 11 in some of them) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. p53 gene mutations were found in 3 of 62 (5%) patients at diagnosis, 1 of 14 (7%) patients at relapse, and 13 of 20 (65%) cell lines in T-ALL, 2 of 20 (10%) patients at diagnosis, 4 of 4 (100%) patients at relapse, and 4 of 5 (80%) cell lines in t(1;19)-ALL, 1 of 23 (4%) patients at diagnosis, 2 of 22 (9%) patients at relapse, and 5 of 12 (42%) cell lines in common ALL other than t(1;19) or t(9;22)-ALL and 3 of 3 (100%) patients at diagnosis in B-ALL. In t(1;19)-ALL, p53 gene alterations were associated with a poor prognosis. The patients with p53 mutations had a trend towards poor prognosis in childhood ALL without B-ALL. p53 gene mutation is not always associated with the current prognostic factors. This alteration may become one of the important prognostic factors, if the detection of a small number of the leukemic cells with the p53 gene mutation would be possible.

Adolescent↗
PubMed1997

[Structures and functions of xenobiotic efflux pump P-glycoprotein and MRP--important molecular targets for cancer chemotherapy].

This paper deals with the basic features of the xenobiotic efflux pump (P-glycoprotein and MRP) and the clinical significance of the search for specific modulators of these proteins. P-glycoprotein and MRP function as ATP-dependent efflux pumps that extrude cytotoxic drugs from the cells before the drugs reach their intracellular targets, thus conferring resistance to many structurally dissimilar anti-cancer drugs. These proteins are responsible for multidrug resistance of tumor cells, a major obstacle to cancer chemotherapy. To develop well-designed modulators, structural information regarding the specific drug binding sites is important. We recently found that mutations in the putative transmembrane domain (TM) 1 of human P-glycoprotein alter the drug resistance pattern. Some amino acid residues in TM1 together with TM5-6 and TM11-12 may help to govern substrate specificity. The features common to substrates for P-glycoprotein and MRP are also discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Clinical significance of cortisone and cortisone/cortisol ratio in evaluating children with adrenal diseases.

Cortisone is derived from the peripheral metabolism of cortisol and lacks biological activity. The rapid interconversion between cortisol and cortisone has been well established. The altered equilibrium between these steroids may regulate glucocorticoid activity in various tissues. We evaluated the serum levels of cortisol and cortisone, and the cortisone/cortisol ratio in ten children with adrenal diseases using reversed-phase high performance liquid chromatography. Children with hypoadrenalism exhibited a greater decrease in cortisol as compared with cortisone. Cortisone levels were higher than cortisol levels, and the cortisone/ cortisol ratio exceeded 1.0. Children with adrenal cancer exhibited normal or high values of cortisol, whereas cortisone levels were decreased and the cortisone/cortisol ratio was decreased to nearly zero. The ratio returned to normal after the excision of adrenal tumors. The simultaneous evaluation of cortisol, cortisone, and cortisone/cortisol ratio provides a clinical clue of adrenal diseases.

Adolescent↗
PubMed1996

Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P-glycoproteins.

The human MDR1 gene encodes the multidrug transporter P-glycoprotein (Pgp). Although the MDR2/Pgp shares about 80% identity at the amino acid level with the MDR1/Pgp, the MDR2/Pgp cannot act as a multidrug transporter. We examined the drug sensitivity of Saccharomyces cerevisiae expressing either the human MDR1/Pgp or MDR2/ Pgp. The human MDR1/Pgp conferred about 4-fold resistance to aureobasidin A, a cyclic depsipeptide antifungal antibiotic, on the drug-sensitive yeast strains. Interestingly the human MDR2/Pgp also conferred about 2.5-fold resistance to aureobasidin A. The resistance to aureobasidin A conferred by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine, verapamil, and cyclosporin A, depending on their concentrations, but not by colchicine. Aureobasidin A probably interacts directly with Pgps, because it overcame multidrug resistance of human cells and inhibited azidopine photoaffinity labeling of MDR1/Pgp in human cell membranes. These results suggest the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for drug recognition.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

Hammerhead ribozyme-mediated inhibition of telomerase activity in extracts of human hepatocellular carcinoma cells.

Telomerase, a ribonucleoprotein that directs the synthesis of telomeric DNA repeats and compensates for the telomeric losses that occur with cell division, is absent from most mortal cells but is present in immortal cells. Telomerase activity is thought to be essential for continuous cell division as seen in malignant tumor cells, and its inhibition could be a strategy for anti-cancer therapy. We prepared a hammerhead ribozyme (teloRZ) directed against the RNA component of human telomerase and tried to find if it could serve as an inhibitor of telomerase. TeloRZ showed a specific cleavage activity against a synthesized portion of the telomerase RNA component used as the substrate. Furthermore, when added to cell extracts from HepG2 or Huh-7, human hepatocellular carcinoma derived lines, teloRZ inhibited the telomerase activity in both. These findings support the potential application of ribozymes capable of telomerase inhibition as new therapeutic agents directed against immortalized cancer cells.

Base Sequence↗
PubMed1996

S phase specific formation of the human Rad51 protein nuclear foci in lymphocytes.

The Rad51 protein, which is a homologue of the bacterial RecA protein, is involved in mitotic and meiotic recombination and in repair of double-strand breaks of DNA in yeast. The Rad51 homologue is conserved from yeast to human. In this study, the Rad51 protein was shown to be induced in peripheral blood lymphocytes (PBLs) 36 h after phytohemagglutinin (PHA) stimulation. Immunofluorescence study revealed that the distribution of the Rad51 protein in the nucleus was not uniform and focus-like staining was observed. Formation of the Rad51 foci was induced at 36 h after treatment of the cells with PHA. Twenty five percent of the cells had the foci at this time and the number of cells with foci declined thereafter. Cell cycle study using laser microscope by double staining method suggested that the appearance of the Rad51 nuclear foci was S phase specific. Furthermore, double staining study for the Rad51 protein and incorporated BrdU confirmed S phase specific appearance of the Rad51 nuclear foci. Formation of the Rad51 nuclear foci in PHA-stimulated lymphocytes might be involved in DNA recombination or DNA repair in S phase. The roles of RAD51 foci in S-phase will be discussed.

Cell Nucleus↗
PubMed1996

Activation of N-myc2 gene expression by cis-acting elements of oncogenic hepadnaviral genomes: key role of enhancer II.

Woodchuck hepatitis virus (WHV) is strongly oncogenic in its native host, producing hepatocellular carcinomas in the majority of chronically infected animals. An important step in this oncogenic process is the activation of N-myc transcription in the liver as a result of integration of viral sequences in cis to the N-myc2 locus. We have examined the viral sequences involved in the up-regulation of N-myc2 using transient transfection assays of permissive HepG2 cells in culture. WHV sequences corresponding to enhancer I of human hepatitis B virus are nearly inactive in N-myc2 activation when tested alone and are not significantly activated by WHV X gene coexpression. By contrast, sequences corresponding to enhancer II strongly activate expression in a position and orientation-independent manner and are only modestly further up-regulated by WHx expression. Qualitatively similar results were observed with sequences of the ground squirrel hepatitis virus (GSHV), which produces hepatomas in woodchucks without insertional activation of N-myc2, but the GSHV EnII element is fourfold less active in N-myc2 up-regulation than its WHV counterpart.

Cloning, Molecular↗
PubMed1996

The aerial mycelium-defective phenotype of Streptomyces griseus resulting from A-factor deficiency is suppressed by a Ser/Thr kinase of S. coelicolor A3(2).

A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is essential for aerial mycelium formation and streptomycin (Sm) production in Streptomyces griseus. A protein Ser/Thr kinase (AfsK), the product of the Streptomyces coelicolor A3(2) afsK gene, controlling secondary metabolism in this strain, reversed the aerial mycelium-negative phenotype of an A-factor-deficient mutant strain, S. griseus HH1, and induced sporulation without affecting A-factor productivity or Sm production. A mutant AfsK protein lacking kinase activity failed to induce aerial mycelium formation which indicates the importance of the kinase activity for suppression in S. griseus. These data suggest that a Ser/Thr kinase functionally similar to S. coelicolor A3(2) AfsK plays a regulatory role in aerial mycelium formation in S. griseus, either as a member in the A-factor regulatory network or independently of this network.

4-Butyrolactone↗
PubMed1996

Measurement of endogenous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay.

Endogenous plasma granulocyte colony-stimulating factor (G-CSF) concentrations were serially measured in 68 patients with acquired aplastic anemia (AA). A very sensitive chemiluminescent immunoassay (CLEIA) was used to measure the plasma G-CSF concentration. The minimum detection limit of this assay (0.5 pg/mL) was sufficient for the determination of G-CSF concentrations in patients and normal subjects. The plasma G-CSF concentrations were significantly higher in 51 AA patients without signs of infection as compared with healthy control subjects. In AA patients with signs of infection, the G-CSF concentrations appeared to increase during the acute phase. There was a significant negative correlation between plasma G-CSF concentrations and absolute neutrophil counts (ANC) in AA patients without signs of infection. Although a decrease in the plasma G-CSF concentration was observed in all patients who achieved self-sustaining hematopoiesis following bone marrow transplantation (BMT) or immunosuppressive (IS) therapy, it was lower in patients undergoing BMT as compared with those receiving IS therapy for any given degree of neutropenia. Plasma G-CSF concentrations were higher in patients responding to IS therapy than in nonresponders. This study demonstrated the negative feedback regulation of G-CSF that plasma G-CSF concentrations may be useful in predicting the clinical response to IS therapy.

Adolescent↗
PubMed1996

Protein kinase inhibitor attenuates apoptotic cell death induced by amyloid beta protein in culture of the rat cerebral cortex.

Amyloid beta protein (A beta) is deposited characteristically in the brain of patients with Alzheimer's disease. Effects of protein kinase inhibitors (H-89, H-7, KN-62) on A beta-induced neuronal cell death were examined in primary culture of dissociated cerebral cortical cells. beta(25-35), the active fragment of A beta, induced neuronal cell death with apoptotic features including chromatin condensation and DNA fragmentation. The cell death was attenuated by cycloheximide or by H-89, a specific protein kinase A (PKA) inhibitor, but not by H-7 or KN-62. These data suggest that beta(25-35) induces apoptotic cell death through the PKA-mediated pathway.

Alzheimer Disease↗
PubMed1996

Erythropoietin in mouse avascular yolk sacs is increased by retinoic acid.

Erythropoiesis begins first in the visceral yolk sac (VYS) of the embryo; however, the involvement of erythropoietin (EPO) in yolk-sac erythropoiesis has not been studied adequately. This study reports the expression of EPO in normal and hypoxic VYSs and alterations in yolk sac components induced by retinoic acid (RA) in mice. Gravid mice (plug day = day 0 of gestation) were given one oral dose of 60 mg/kg of RA in olive oil on days 6, 6.5, 7, 7.5, or 8 of gestation and were sacrificed 2.5, 3, or 3.5 days later. Control mice received olive oil without RA. None of the dams developed anemia, but more than 80% of the embryos of the dams that received RA on day 6, 6.5, or 7 of gestation had avascular yolk sacs (AVYs) and anemia. In these AVYs, the adenosine triphosphate (ATP) level was as low as 18-59% of that in the control VYSs. Reverse transcription-polymerase chain reaction and Southern analysis of products demonstrated that mRNA for EPO receptor (EPR) was expressed in both VYSs and AVYs on days 9-11 of gestation, and EPO mRNA was present in VYSs and AVYs on days 9 and 10 of gestation and in vehicle-exposed VYSs on day 11 of gestation. Furthermore, enzyme immunoassay of EPO indicated that AVYs contained more EPO protein than control VYSs. Light microscopy revealed that, in AVYs, in addition to the defective hemopoietic cells, the endodermal layer was exclusively altered: The presence of focal proliferated regions and the separation from the mesenchyme led to a single layer from which some immature cells seemed to be migrating. Immunolocalization of EPO showed its presence in all components of VYSs with a characteristic distribution pattern: In the endodermal layer, cells with positive EPO staining decreased as gestation advanced, and erythroid precursor cells showed positive staining. In AVYs, the proliferated endodermal cells had EPO in abundance; in the separated regions, the distinction between positive and negative EPO staining became clearer than that in the control VYSs, and the immature cells in the lumens also had EPO. EPR was seen on the cell surface of the corresponding cells that reacted to EPO. These findings suggest that VYSs not only produce EPO temporarily but also respond to the oxygen content in situ. EPO and EPR appear to be synthesized in the endodermal cells of the VYSs that are likely to respond to the circumstances induced by RA.

Adenosine Triphosphate↗
PubMed1996

The effect of hydration upon the conformation and dynamics of neocarrabiose, a repeat unit of beta-carrageenan.

Molecular mechanics calculations have been performed for the disaccharide neocarrabiose, one of the repeat units of beta-carrageenan, as a general model for the (1-->3)-linkage in the carrageenans. An adiabatic conformational energy map for this molecule has been prepared by constrained energy minimization and compared to previously reported relaxed maps. Neither the experimentally determined crystal structure of neocarrabiose nor the fiber diffraction conformation of iota-carrageenan is a low energy conformation on the relaxed Ramachandran map. Molecular dynamics simulations in vacuum produced trajectories consistent with this relaxed vacuum surface. However, a simulation with explicitly included solvent water molecules produced a trajectory that remained in the region of the two experimental structures. This dramatic solvation effect is apparently the result of the breaking of an interring hydrogen bond between the O2 hydroxyl groups of neocarrabiose as both groups hydrogen bond to solvent.

Carbohydrate Conformation↗
PubMed1996

Secondary contour reconstruction of maxillectomy defects with a bone graft vascularized by flowthrough from radial vascular system.

We describe post-total maxillectomy secondary facial contour reconstruction using an osteocutaneous scapular flap nourished by flow-through vascularization from the radial vascular system. Scar contracture caused by either total or partial maxillectomy for maxillary cancer was completely released with exposure of the edge of the zygomatic arch, orbital floor, and nasal bone. The scapular skin flap was placed into the mucosal defect, and the orbital floor and zygomatic prominence were reconstructed with the scapular bone. The flap nutrient vessels were anastomosed to radial vessels and cephalic vein grafts. Two representative cases are illustrated to demonstrate the application and advantage of this operative method.

Anastomosis, Surgical↗
PubMed1996

Comparison of end-to-end and end-to-side venous anastomosis in free-tissue transfer following resection of head and neck tumors.

A comparative study was conducted of the results of venous end-to-end and end-to-side anastomosis in 948 clinical cases of microvascular free-tissue transfers for head and neck reconstruction following tumor resection. End-to-side anastomosis to the internal jugular vein was achieved uneventfully in the present series, while a variety of recipient veins was used for end-to-end anastomosis. The incidence of thrombosis was 1.8% (15/835) in the end-to-end anastomosis group and 2.7% (3/113) in end-to-side venous anastomosis. No statistical difference was observed between the two groups. One may hesitate to perform end-to-side anastomosis because of unfamiliarity, concern over technical difficulty, and unreliability. As a result of our statistical analysis, we are convinced that end-to-side anastomosis directly to the internal jugular vein, whenever available, is the preferred procedure in microvascular free-tissue transfers for reconstruction of the head and neck following tumor resection.

Adolescent↗
PubMed1996

Experience of a new surgical procedure for the treatment of unilateral obstructive lymphedema of the lower extremity: adipo-lymphatico venous transfer.

We report five cases of adipo-lymphatico venous transfer (ALVT) performed to treat unilateral obstructive lymphedema of the lower extremity. ALVT is a surgical procedure that utilizes the long saphenous vein and its surrounding lymphatic tissue from the unaffected limb for the treatment of lymphedema. Since ALVT does not necessitate anastomoses of lymphatic vessels, it can be performed regardless of the severity and duration of lymphedema, and stable long-term results can be obtained when the transferred lymphatic tissue shows viability.

Adipose Tissue↗
PubMed1996

Magnetoencephalographic analysis of rolandic discharges in benign childhood epilepsy.

We report the detailed analysis of the generator and propagation of rolandic discharges in benign childhood epilepsy with centrotemporal spikes by means of 37-channel magnetoencephalography with neuromagnetic three-dimensional dipole localization. Equivalent current dipoles of prominent negative sharp waves of rolandic discharges appeared as tangential dipoles in the rolandic region, positive poles being situated anteriorly. These equivalent current dipoles showed a relatively limited localization and regular directions compared with other components. Equivalent current dipoles of preceding small positive waves, positive waves following negative sharp waves, and negative slow waves appeared in the vicinity of negative sharp waves. Equivalent current dipoles of rolandic discharges were located around the generator of somatosensory evoked magnetic fields stimulated at the lower lip. These findings suggest that rolandic discharges are generated through basically a mechanism similar to that for the middle-latency components of somatosensory evoked responses.

Child↗