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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 451 records · Page 25Linked to original sources
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

High-Spatial-Resolution Medical-Imaging System Using a HARPICON Camera Coupled with a Fluorescent Screen.

A high-sensitivity HARPICON camera was developed for medical X-ray imaging using a fluorescent screen. It is an avalanche-multiplication-type image pick-up tube and is 32 times more sensitive than conventional tubes. The camera also has a wider dynamic range than conventional medical-imaging cameras because a maximum output signal current of 2.3 muA is obtained and, in high-illumination-intensity regions, photocurrent is not proportional to illumination intensity. The fluorescent screen is an intensifying screen of the type used for radiographic screen-film combinations in medical examination. An X-ray image on the screen is focused on the photoconductive layer of the pick-up tube using a coupling lens with f/0.65. Experiments were performed using monochromated X-rays at the Photon Factory. An image of a spatial resolution test chart was taken in a 525 scanning-line mode of the camera. The chart pattern of 5 line-pairs mm(-1 )(spatial resolution of 100 mum) was observed at an X-ray input field of 50 x 50 mm. Real-time digital images of the heart of a 12 kg dog were obtained at a frame rate of 60 images s(-1) after injection of a contrast medium into an artery. The images were stored in digital format at 512 x 480 pixels with 12 bits pixel(-1). High-spatial-resolution and high-contrast images of coronary arteries were obtained in aortography using X-rays with energy above that of the iodine K edge; the image quality was comparable with that of conventional selective coronary angiography.

Journal Article↗
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↗