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Biomedical subjects

T Konno

Publications and source records attributed to T Konno.

At least 145 records · Page 8Linked to original sources

Functional and molecular characteristics of acute lymphoblastic leukemia cells with a mature T-cell phenotype from a patient with ataxia telangiectasia.

A 12-year-old male patient with ataxia telangiectasia developed an acute lymphoblastic leukemia of T-cell phenotype. The lymphoblasts showed uniform surface expression of CD3, CD7, CD8, and T-cell receptor (TCR) alpha/beta chains, positive immunofluorescent staining of terminal deoxynucleotidyl transferase, complex cytogenetic aberrations including t(14;14) (q11;q32) and unique rearrangements of TCR beta and gamma chain genes, indicating the clonal expansion of leukemic cells. CD25 expression could be readily induced on the leukemic cells by mitogenic stimulation, followed by CD71 expression, but interleukin-2 production and subsequent proliferation in response to mitogens were subnormal.

Antigens, CD↗

[Clinical study of eel calcitonin for relief of pain from metastatic bone lesions].

Thirty patients with bone metastasis were treated with eel calcitonin (CT) to relieve severe pain from metastatic bone lesions. Patients were two males and twenty-eight females with a mean age of 52.8. CT was administered intramuscularly in twenty-seven patients and intravenously in three. CT was effective on 55.6% of patients to reduce severe bone pain but did not decrease the amount of analgesics in most patients. Serum Ca and P were not changed markedly. As side-effects, two patients complained of nausea and vomiting after administration of CT but they weren't severe. These results indicate that CT is quite useful drug for relief of severe bone pain from metastatic lesions in patients with breast or digestive tract carcinomas.

Adult↗

Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle.

The isolation and characterization of five clones carrying sequences of the alpha-, beta-, gamma-, delta- and epsilon-subunit precursors of the rat muscle acetylcholine receptor (AChR) are described. The deduced amino acid sequences indicate that these polypeptides contain 457-519 amino acids and reveal the structural characteristics common to subunits of ligand-gated ion channels. The pattern of subunit-specific mRNA levels in rat muscle shows characteristic changes during development and following denervation, suggesting that innervation of muscle reduces the expression of the alpha-, beta- and delta-subunit mRNAs, suppresses the expression of the gamma-subunit mRNA, and induces expression of epsilon-subunit mRNA. Subunit-specific cRNAs generated in vitro were injected into Xenopus laevis oocytes, resulting in the assembly of two functionally different AChR channel subtypes. The AChR gamma, composed of the alpha-, beta-, gamma- and delta-subunits, has functional properties similar to those of the native AChRs in fetal muscle. The AChR epsilon, composed of alpha-, beta-, delta- and epsilon-subunits, corresponds to the end-plate channel of the adult muscle. Thus in rat skeletal muscle the motor nerve regulates the expression of two functionally different AChR subtypes with different molecular composition by the differential expression of subunit-specific mRNAs.

Amino Acid Sequence↗

Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium.

Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors.

Aclarubicin↗

Unusual expression of IgG Fc receptors on peripheral granulocytes from patients with leukocyte adhesion deficiency (CD11/CD18 deficiency).

Leukocyte adhesion deficiency (LAD) is a hereditary disease characterized by defective expression of leukocyte adhesion glycoproteins; lymphocyte function-associated Ag-1 (CD11a/CD18), CR3 (CD11b/CD18) and p150,95 (CD11c/CD18). Granulocytes, monocytes, and lymphocytes of patients with LAD show profoundly defective in vivo and in vitro adherence-dependent immune functions. We investigated the expression of FcR for IgG on polymorphonuclear cells (PMN) and monocytes from patients with LAD, and their luminol- and lucigenin-enhanced chemiluminescence production in response to SRBC sensitized with murine (m) IgG2a and IgG2b. Unstimulated patient PMN showed an enhanced chemiluminescence in response to mIgG2a-SRBC and an increased phagocytosis of mIgG2a-SRBC. The up-regulated functions were inhibited by monomeric human IgG in a dose-dependent manner, which was attributed to an increase in expression of FcRI on patient PMN, as shown by flow cytometry using monoclonal antibody, 32.2, specific for human FcRI. In contrast, neither the expression of FcR on the monocytes of LAD patients nor their FcR-mediated functions were different from those of controls.

Antibodies, Monoclonal↗

Determination of aromatization of 19-oxygenated 16 alpha-hydroxyandrostenedione with human placental microsomes by high-performance liquid chromatography coupled with coulometric detection.

A sensitive assay of aromatization of 16 alpha-hydroxylated androgens, 16 alpha-hydroxyandrostenedione (16 alpha-OHA), 16 alpha,19-dihydroxyandrostenedione [16 alpha,19-(OH)2A], and 16 alpha-hydroxy-19-oxo androstenedione (16 alpha-OH-19-oxo A), was developed using reversed phase high-performance liquid chromatography with a coulometric detector. The estrogens, estriol and 16 alpha-hydroxyestrone, were simultaneously detected in quantities as low as 300 pg of the estrogens formed in an assay by an internal standard method. Apparent Km and Vmax of the microsomal aromatase for 16 alpha-OHA, 16 alpha,19-(OH)2A or 16 alpha-OH-19-oxo A were 1.06, 4.00 or 571 microM and 0.014, 0.087 or 1.67 pmol/min/micrograms protein, respectively. The results show that the 19-oxo steroid has extremely low affinity for aromatase relative to the other substrates.

Androstenedione↗

Spontaneous and agonist-induced openings of an acetylcholine receptor channel composed of bovine muscle alpha-, beta- and delta-subunits.

During the development of mammalian muscle the gamma-subunit of the nicotinic acetylcholine receptor (AChR) is replaced by the epsilon-subunit to produce well-defined alterations in the conductance and gating of the channel. To gain a better understanding of the functional role of the gamma- and epsilon-subunits, we have studied the properties of an AChR channel lacking these subunits. The AChR expressed in Xenopus oocytes injected with the bovine alpha-, beta- and delta-subunit-specific mRNAs (referred to as alpha beta delta-AChR) is unusual in that its channel opens spontaneously at a high frequency in the absence of agonist. From a comparison of the alpha beta delta-AChR with complete receptors containing either the gamma- or epsilon-subunit, we conclude that the gamma- and epsilon-subunits influence most channel properties, including agonist binding, and are especially important for stabilizing the closed state of the unliganded receptor channel. The alpha beta delta-AChR can form when a complete set of four subunit-specific mRNAs is injected. The ease with which it is assembled raises the possibility that the alpha beta delta-AChR contributes to some of the variations in receptor properties that occur during development.

Animals↗

Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. III. Determination of vapor pressure of solid drugs by steam distillation.

The vapor pressures of solid drugs were determined by the steam distillation method. Experiments using a series of benzoic acid derivatives indicated that this method offered consistent and satisfactory values for vapor pressure at about 100 degrees C. The vapor pressures of two nonsteroidal antiinflammatory drugs, flufenamic acid (FFA) and mefenamic acid (MFA), were found to be 3.8 x 10(-3) and 1.8 x 10(-4) mmHg, respectively. These values explain the difference in the rate of change to the amorphous state between mixtures of each with magnesium aluminum silicate (MAS) when they were stored under reduced pressure. It was concluded that the vapor pressures of solid drugs at about 100 degrees C, as determined by steam distillation, may be suitable indices for predicting whether or not these drugs have an inherent propensity to become amorphous readily in mixtures with an adsorbent.

Benzoates↗

Physical and chemical changes of medicinals in mixtures with adsorbents in the solid state. IV. Study on reduced-pressure mixing for practical use of amorphous mixtures of flufenamic acid.

Flufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) at a reduced pressure of about 10 to 50 mmHg employing a commercial mixer for pharmaceutical production. An amorphous state of FFA in the mixture was efficiently achieved with this equipment, and the dissolution of FFA was enhanced in comparison with that of the physical mixture. Effects of the conditions of mixing, such as pressure, temperature and rotating speed, on dissolution of FFA were determined. Through stability tests at 40 degrees C under both dry and humid conditions, no change in dissolution profiles was recognized in a 5% FFA mixture stored under any conditions. On the other hand, decreases in dissolution behavior were observed in 10% and 20% FFA mixtures when they were stored under humid conditions. These results suggested that humidity should be avoided during the storage of amorphous mixtures of FFA with MAS for production purposes.

Adsorption↗

Synthesis of 16 alpha-hydroxyandrost-4-ene-3,17,19-trione and 3 beta, 16 alpha-dihydroxyandrost-5-ene-17,19-dione; potential intermediates of estriol biosynthesis.

16 alpha-Hydroxyandrost-4-ene-3,17,19-trione (10) was synthesized from the 16 alpha-hydroxy-6 beta,19-epoxy-17-one 3 via protection of the 16 alpha-hydroxy function as its tert-butyldimethylsilyl ether or acetate. Reductive cleavage of the epoxy ring of the silyl ether 4 or the acetate 5 with zinc dust gave the 19-alcohol 6 or 7, which was treated with pyridinium dichromate or Jones reagent, respectively, and then hydrolyzed with diluted sulfuric acid, yielding the desired steroid 10. 3 beta,16 alpha-Dihydroxyandrost-5-ene-17,19-dione (14) was also synthesized from 5 alpha-bromo-3 beta,16 alpha-diacetoxy-6 beta, 19-epoxyandrostan-17-one (11) through the intermediates 12 and 13 with the 3 beta- and 16 alpha-hydroxy functions protected as their acetates in a reaction sequence similar to that above.

Androstenediols↗

Laterality of cerebral controls on somatic and autonomic functions.

The mode of cerebral representation for each half of the body is various according to the functions that are represented; contralateral, ipsilateral and bilateral. We reviewed, and discussed the meaning of, such different patterns of cerebral representation for somatic and autonomic functions.

Autonomic Nervous System↗

Enzymatic removal of bilirubin toxicity by bilirubin oxidase in vitro and excretion of degradation products in vivo.

The toxic effects of the degradation products of bilirubin that were formed by reaction with bilirubin oxidase were investigated with the C 1300 mouse neuroblastoma cell line by examining the following parameters: growth inhibition, morphologic characteristics, membrane transport, DNA synthesis, and protein synthesis. The addition of bilirubin to the cells resulted in definite cytotoxic effects on all of these parameters in a dose-dependent fashion; the addition of bilirubin oxidase reversed the toxic effects on the C 1300 cells in vitro. Furthermore, we found that most of these enzymatic degradation products of bilirubin were excreted by the kidney into the urine in a few hours after intravenous injection of the degradation products; in contrast, no intact bilirubin was excreted. Thus, these findings suggest that hyperbilirubinemia in newborn infants (kernicterus) may be prevented by administering polyethylene glycol-conjugated bilirubin oxidase, with a longer plasma half-life which has been reported previously to oxidize bilirubin to its nontoxic components in the bloodstream.

Animals↗

[Treatment of carcinomatous effusion with oily anticancer agents dissolved in lipiodol].

The oily anticancer agents dissolved in lipiodol used for arterial administration against various solid tumors in our department were found to be applicable to treat for pleural or peritoneal carcinomatosis experimentally and clinically. The pharmacokinetic study with rat model showed oily anticancer agents were retained in a high concentration in the peritoneal cavity compared to water-soluble anticancer agents. In our pilot clinical study all patients with pleural or peritoneal carcinomatosis showed improvement cytologically and physically.

Adult↗

[Serum bilirubin subfractionation by high-performance liquid chromatography in patients with fulminant hepatic failure].

Serum bilirubin subfractionation, using high-performance liquid chromatography (HPLC), was carried out and clinically evaluated in 9 patients with fulminant hepatic failure (FHF). Serum unconjugated bilirubin (UCB), C-8 bilirubin mono-conjugate (MBC), C-12BMC and bilirubin di-conjugate (BDC) were quantified by the alkaline methanolysis-HPLC method described by Blanckaert. Similar studies were performed in 10 patients with acute hepatitis (AH) and 6 patients with obstructive jaundice and the results were compared. In patients with rising serum bilirubin, the serum C-12BMC/C-8BMC ratio was calculated to be as follows: 2.10 +/- 0.21 for FHF, 1.05 +/- 0.34 for AH and 0.81 +/- 0.08 for obstructive jaundice, respectively. A significant differences were observed between FHF and AH (P less than 0.01). As there was almost no overlapping, it was considered that this determination is useful for the differential diagnosis of jaundiced patients, especially, in those patients with AH whose sera show a prolonged prothrombin time lower than 40%, and there is a concern that they may develop FHF. The calculation of C-12BMC/C-8BMC allows us to make a differential diagnosis between AH and FHF at an early period in the development of the disease, and it was proved that serum C-12BMC/C-8BMC ratio can reflect the magnitude of hepatocyte damage as well as bilirubin metabolism disturbance.

Acute Disease↗

[New techniques of immunochemical analysis: clinical application of time-resolved fluoroimmunoassay to CA 50 determination].

New techniques in immunochemical analysis were reviewed briefly. Introduction of these new techniques into routine tests has made test results more precise and informative than before. By using one of these techniques, time-resolved fluoroimmunoassay, serum concentrations of CA 50 were quantitated in various malignancies. Clinical usefulness of its quantitation was proved especially in the diagnosis of pancreatic cancer.

Adolescent↗

Comparison of human, simian, and bovine rotaviruses for requirement of sialic acid in hemagglutination and cell adsorption.

Human rotaviruses (Wa, KUN, MO) showed hemagglutination (HA) only with fixed 1-day-old chicken erythrocytes, and their HA activities were completely destroyed by trypsin activation of virions. Simian SA-11 and bovine NCDV had HA activities not only against fixed erythrocytes but also against fresh erythrocytes from various species. Their HA activities against fixed erythrocytes were also inhibited by trypsin activation, but those against fresh erythrocytes were not. Neuraminidase treatment of fixed erythrocytes did not inhibit HA by trypsin-untreated rotaviruses. In contrast, HA of fresh human erythrocytes by SA-11 and NCDV was completely inhibited by neuraminidase treatment of erythrocytes or glycophorin A, the major erythrocyte sialoglycoprotein. Adsorption and infection of SA-11 and NCDV to monkey kidney MA104 cells were also inhibited by neuraminidase treatment of cells. Adsorption and infection of human rotaviruses were not, however, affected by treatment of cells with neuraminidase from Vibrio cholerae or Arthrobacter ureafaciens or with potassium periodate. Therefore, HA of fixed chicken erythrocytes by trypsin-untreated human and animal rotaviruses may be independent of sialic acids, whereas that of fresh erythrocytes by SA-11 and NCDV is sialic acid dependent and probably mediated by glycophorin A. Sialic acids also constitute an essential part of the cellular receptors for SA-11 and NCDV, whereas those for human rotaviruses were quite resistant to treatments known to destroy major types of sialic acids.

Animals↗

Monoclonal antibody directed to human T-cell malignancy antigen.

A murine monoclonal antibody (B2D) against a cultured pre-T acute lymphoblastic leukemia (ALL) cell line THP-6 has been produced. The antibody reacted with seven out of eight cultured T-ALL cell lines and with leukemic cells from three out of four T-ALL/lymphoma patients. The antibody did not react with normal T and B lymphocytes, monocytes, granulocytes, platelets, erythrocytes, bone marrow lymphoid-like precursor cells, thymocytes and other acute and chronic leukemic cells of non-T cell origin. Furthermore, B2D did not react with phytohemagglutinin-activated T cells nor with concanavalin A-activated T cells. The molecules immunoprecipitated with B2D had molecular weights of 50-55 kD. Thus, B2D seems to be highly specific for T-cell malignancies. These results show that B2D defines one of human leukemia antigens which are expressed on the cell surface of T-ALL cells. Monoclonal antibody B2D may be useful for the subclassification of T-ALL cells and has therapeutic potential for a certain type of T-ALL.

Antibodies, Monoclonal↗