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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 433 records · Page 24Linked to original sources

[Histological findings of specimens obtained by directional coronary atherectomy from patients with acute myocardial infarction].

The histological characteristics of acute myocardial infarction were examined in specimens obtained from infarct-related coronary artery lesions (20 left anterior descending artery, 2 left circumflex artery, 8 right coronary artery) in 30 patients with initial acute myocardial infarction who underwent directional coronary atherectomy following intracoronary thrombolysis within 6 hours after the onset of chest pain. Resected tissues were fixed in 10% buffered formalin and embedded in paraffin, and the 4 microns-thick paraffin sections were stained with hematoxylin-eosin and examined by light microscopy. Thrombus and/ or intramural hemorrhage were present in all samples. There were high incidences of cholesterol cleft in 19 (63%), foam cell in 21 (70%), calcium deposit in 19 (63%) and intimal proliferation in 16 (53%). These data suggest that thrombus and/or intramural hemorrhage are important in the onset of acute myocardial infarction.

Aged↗

[Evaluation of changes in hepatic energy metabolism during exercise by ketone body ratio in humans].

Changes in the redox state of liver mitochondria were investigated by measuring the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate: AKBR) in nine healthy volunteers (eight males and one female, mean age 38.4 +/- 5.0 years) during exercise. The correlation between the changes in AKBR and levels of various hormones controlling energy metabolism was also investigated. Subjects participated in symptom-limited exercise test using the ramping bicycle ergometer with expired gas analysis, blood pressure and 12 lead electrocardiogram monitoring. Anaerobic threshold by gas exchange parameters (ATge) was determined from the expired gas data with the v-slope method. AKBR, glucose, non-esterified fatty acid (NEFA) and lactate were measured in arterial plasma samples. Catecholamines (epinephrine, norepinephrine, dopamine), insulin, glucagon, antidiuretic hormone (ADH), growth hormone (GH), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), human-atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were measured in venous plasma samples. AKBR was gradually decreased by exercise from the resting value of 1.82 +/- 0.20. AKBR reduction was potentiated after ATge to 0.93 +/- 0.18 (p < 0.01 vs rest) at peak exercise. AKBR was further decreased during recovery to the minimum value of 0.70 +/- 0.06 (p < 0.01) at 6 min in the recovery phase. AKBR then began to increase and reached 0.95 +/- 0.07 30 min after peak exercise. Epinephrine increased from 45.9 +/- 11.0 to 210 +/- 75 pg/ml (p < 0.01), norepinephrine increased from 348 +/- 52 to 1,277 +/- 111 pg/ml (p < 0.01), and dopamine increased from 13.0 +/- 1.9 to 25.0 +/- 2.5 pg/ml (p < 0.01) between rest and peak exercise, respectively. Insulin decreased from 22.0 +/- 3.5 to 14.2 +/- 2.1 pg/ml (p < 0.05). No significant change was observed in glucagon, ADH, GH, TSH, T3, T4, hANP or BNP. Glucose decreased from 124 +/- 9 to 84 +/- 8 mg/dl (p < 0.05), whereas NEFA increased from 94 +/- 10 to 190 +/- 66 mg/dl (p < 0.05). A negative correlation was observed between AKBR and lactate (r = -0.41, p < 0.001). These results indicate that hepatic adenosine triphosphate production is promoted as energy demand increases by exercise, and maximizes early in the recovery phase when hepatic energy demand is maximum due to active gluconeogenesis. The levels of catecholamines, insulin and lactate contribute to the control of liver energy metabolism.

Adult↗

[Multidrug resistance of cancer cells mediated by ABC superfamily transporters].

ATP-binding cassette(ABC) superfamily transporters, including P-glycoprotein and MRP, actively transport various structurally dissimilar chemotherapeutic compounds out of cancer cells and confer multidrug resistance. Members of ABC superfamily which may extrude anti-cancer drugs are still expanding, thus the importance of these proteins are further increasing for cancer chemotherapy. Multidrug resistance will be acquired either by the induction of expression of ABC superfamily transporters or by mutations of ABC superfamily genes which cause amino acids substitutions. We recently found that amino acid substitutions in the first predicted transmembrane domain of P-glycoprotein increase the ability to confer resistance to important anti-cancer drugs adriamycin and VP-16. The mechanisms for drug recognition and transport of human P-glycoprotein and MRP are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Enantioselective local disposition of semotiadil (R-enantiomer) and levosemotiadil (S-enantiomer) in perfused rat liver.

The enantioselective local disposition of semotiadil (R-enantiomer) and levosemotiadil (S-enantiomer) in rat liver was investigated in the single-pass perfusion system containing 1% bovine serum albumin (BSA). After an instantaneous injection of semotiadil, levosemotiadil, or Evans Blue (a marker of BSA), each outflow time profile from the liver was analyzed by a two-compartment dispersion model. The recovery ratio, FH (1.88 +/- 0.28%), of semotiadil was significantly smaller than that (8.99 +/- 1.40%) of levosemotiadil. The mean transit time, fH (0.146 +/- 0.014 min) of semotiadil was significantly smaller than that (0.191 +/- 0.012 min) of levosemotiadil. The biliary excretion kinetics of these enantiomers was also evaluated by moment analysis. The parent compound (semotiadil or levosemotiadil) was not detected in bile, but four metabolites generated from each parent enantiomer were found in the bile. A portion (16.5 +/- 1.2%) of the drug eliminated by the liver was recovered as R-metabolites in the bile within 1 hr after an injection of semotiadil, whereas 11.2 +/- 1.6% was recovered as S-metabolites in the bile within 1 hr after an injection of levosemotiadil. This excreted percentage into the bile was significantly different between R- and S-metabolites. The mean biliary excretion time MRTe (19.1 +/- 2.2 min) of total R-metabolites was significantly larger than that (14.8 +/- 1.1 min) of total S-metabolites. In conclusion, stereo-selectivity was suggested both at the hepatic elimination of the parent compound and at the biliary excretion of the metabolites.

Animals↗

Detection of heterogeneity of 18S rRNA inter-genes and mutation arising during PCR amplification.

Direct sequencing revealed sequence heterogeneity among ribosomal RNA gene (rDNA) operons, consisting of 8 base heterogeneous sites on the 18S rDNA of Galactomyces citri-aurantii IFO 10822, and 6 base heterogeneous sites in the same region on the 18S rDNA of G. citri-aurantii IFO 10821. Sequence analysis of the cloned 18S rRNA genes of 14 species (19 strains) of ascomycetous yeast-like fungi detected a total of 32 substitutions between two cloned sequences from each of 10 strains. Eight substitutions came from heterogeneity of G. citri-aurantii IFO 10822, and 24 substitutions were predicted to be due to misincorporation by the Taq DNA polymerase. A low frequency of random substitution, estimated to occur in PCR at approximately 1 in 2690 nucleotides, was detected; and transitions occurred 7 times more frequently than transversions.

DNA, Ribosomal↗

Nuclear proteins binding to the recombination hotspot region of the retinoic acid receptor alpha gene.

Acute promyelocytic leukemia (APL) has been characterized by 15;17 chromosomal translocation, which involves the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. An extremely restricted region (ERR) of 50 bps within the second intron of the RARA gene was identified as the cluster region of breakpoints by sequencing analyses. ERR was tested by in vitro transfection-recombination assay, and was shown to be the recombination hot spot. In this study, presence of DNA binding proteins to the 148 bps DNA fragment which contains ERR was confirmed by gel-mobility shift analysis in the nuclear extract of NIH3T3 cells and human leukemia cell lines. Furthermore, in vitro study with the mouse sarcoma cell lines using the recombination reporter plasmid containing ERR showed that ERR might be involved in the homologous recombination in addition to the illegitimate recombination. The DNA binding proteins specific to ERR might play an important role in chromosome translocation.

3T3 Cells↗

[Serratia marcescens prosthetic mitral valve endocarditis associated with hemolytic anemia].

A 57-year-old female who had been performed mitral valve replacement (MVR) using 31 mm prosthetic valve 32 months before entered the hospital for the evaluation of long standing severe hemolytic anemia without infectious sign. Transesophageal echocardiogram revealed a moderate sized vegetation on the atrial site of the prosthetic valve. The size and number of the vegetation were increased after deterioration of infectious illness. Blood culture grew serratia marcessans and alpha-hemolytic Streptococcus. Re-MVR was carried out with the diagnosis of prosthetic valve endocarditis (PVE). As the symptom of PVE, hemolytic anemia without infectious sign is a rare condition. TEE is an useful method to make diagnosis of PVE by detecting the vegetations and evaluating their change of size and methods and to evaluate the effectiveness of the treatment.

Anemia, Hemolytic↗

[Anti-HCV antibody and hemolytic complement activity in sera from alcoholic patients].

We examined the association of complement activation at a low temperature in vitro with hepatitis C virus infection in alcoholic patients. The incidence of cold activation among these patients was 4.1%, which was higher than the reported incidence of 1.7% among general patients consulting a hospital, and that of 0.5% among donors for blood transfusion. In any population, most cases that showed cold activation were HCV antibody positive. The difference between the incidence of cold activation among HCV antibody positive cases in alcohol high consumers (6/21) and that in control patients (42/103) was regarded as nonsignificant. The higher incidence of cold activation among alcoholic patients may not directly associate with high alcohol consumption and may associate with higher incidence of HCV infection among the group.

Alcoholism↗

Favorable response to heparin in a pregnant woman with possible glomerular thrombosis as a complication of systemic lupus erythematosus and anti-phospholipid antibody syndrome.

A rare case of possible glomerular thrombosis during pregnancy is reported in a patient with active systemic lupus erythematosus and the presence of anti-phospholipid antibodies. Acute renal impairment was restored by administering infusions of heparin. Cesarean section was performed due to fetal distress, and resulted the live birth of a healthy infant.

Adult↗

A case of an interstitial tandem direct duplication of long arm of chromosome 4: 46, XY, dup (4) (q25q31.3) de novo.

We report a 4 2/12-year-old Japanese boy with a de novo direct tandem dup (4) (q25q31.3). The major clinical picture includes postnatal growth and psychomotor retardation, thick eye-lashes, a cleft lip, and large and prominent helix and antitragus. He did not have any hearing deficit. His eyegrounds were normal. There was no organ malformations including brain, kidney, liver, pancreas, gallbladder, urinary bladder, stomach, and heart. Routine hematological tests, blood chemistry including thyroid hormones, and urinalysis including urinary screening tests for congenital metabolic disorders showed normal results. He showed an electroencephalographic abnormality which could have resulted from mild aseptic meningitis at 2 months. Our case supports the idea that the association of thumb and renal deformities in duplication 4q syndrome is related to the region 4q22-q23 as many researchers have already pointed out.

Child↗

[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↗

[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↗