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Biomedical subjects

M Kondo

Publications and source records attributed to M Kondo.

At least 577 records · Page 32Linked to original sources
PubMed1995

A novel cancer therapy based on oxygen radicals.

The antitumor effect of oxygen radicals produced by hypoxanthine and xanthine oxidase reaction was studied in an experimental rabbit model. VX2 carcinomas were transplanted into rabbit hind legs. Hypoxanthine was administered continuously through the ear vein, while xanthine oxidase was administered simultaneously through the femoral artery. As a result, hypoxanthine and xanthine oxidase reacted only in the hind leg, and superoxide was produced in that area. The volume of the VX2 carcinoma was measured immediately prior to treatment and 7 days later. As an index of lipid peroxidation, thiobarbituric acid-reactive substances in the tumor tissue were measured 60 min following infusion of hypoxanthine and xanthine oxidase. Tumor growth was suppressed significantly by the hypoxanthine-xanthine oxidase reaction, and thiobarbituric acid-reactive substances in the tumor tissue infused with hypoxanthine and xanthine oxidase were significantly increased. In addition, the antitumor effect of the hypoxanthine and xanthine oxidase reaction was significantly inhibited by the administration of superoxide dismutase and catalase. Pathological examination showed that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction were selectively more destructive for VX2 carcinoma tissue than muscle tissue surrounding the tumor region. These results suggest that oxygen radicals produced by hypoxanthine and xanthine oxidase reaction produce an anticancer effect and that the VX2 carcinoma used in this study was more sensitive to oxygen radicals than normal muscle tissue.

Animals↗
PubMed1995

Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers.

Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.

Adult↗
PubMed1995

Involvement of the interleukin-2 receptor gamma subunit in interleukin-4-dependent activation of mouse hematopoietic cells and splenic B cells.

Interleukin-4 (IL-4) has various activities on B cells and on hematopoietic cells. We previously reported that TUGm2, a monoclonal antibody to the gamma subunit of the IL-2 receptor (IL-2R gamma), inhibited IL-4-dependent proliferation of CTLL2, a cytotoxic T cell line. We proposed that IL-2R gamma is required for the functional IL-4 receptor (IL-4R) in T cells. In the present work, we further examined whether or not IL-2R gamma is involved in IL-4R function in mouse myeloid cell lines and splenic B cells. TUGm2 suppressed the IL-4-induced proliferation of BA/F3 or IC2 cells, as well as of purified splenic B cells. TUGm2 partially suppressed proliferation of B cells induced by the combination of IL-4 and anti-immunoglobulin M (IgM) antibody. In contrast, TUGm2 had no effect on proliferation of B cells induced by anti-IgM antibody alone or lipopolysaccharide (LPS). TUGm2 also inhibited IgE production induced by IL-4 of LPS-stimulated B cells. The induction of major histocompatibility complex class II molecules or CD23 by IL-4 was virtually unaffected by TUGm2 antibody. These results indicate that IL-2R gamma is differentially involved in various IL-4-dependent reactions.

Animals↗
PubMed1995

Differences in the interleukin-2 (IL-2) receptor system in human and mouse: alpha chain is required for formation of the functional mouse IL-2 receptor.

Reconstitution with mouse interleukin-2 (IL-2) receptor subunits demonstrated that the mouse IL-2 receptor complex was different from the human complex in the alpha chain requirement for the functional mouse receptor complex. The heterotrimeric complex of the mouse exogenous alpha and beta chains and the endogenous gamma chain on mouse lymphoid BW5147 cells showed the ability to bind IL-2 with high affinity, resulting in IL-2-induced tyrosine phosphorylation of a cytosolic tyrosine kinase, JAK3, which is involved in IL-2-dependent signals. Exogenous introduction of the beta chain with the endogenous gamma chain, however, could neither confer appreciable IL-2 binding nor IL-2-induced signal transduction on BW5147 cells, unlike the human beta gamma heterodimer. Mouse spleen CD8+ cells, not having the alpha chain initially, showed IL-2-dependent cell proliferation only when expression of the alpha chain was induced. Collectively, these results illustrate that the functional mouse IL-2 receptor complex necessarily includes the alpha chain, and that the regulation of CD8+ T cell growth during immune reaction depends upon alpha chain expression.

Animals↗
PubMed1995

Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury.

The objectives of this study were to determine the roles of neutrophil-endothelial cell interactions and oxygen-derived free radicals in the pathogenesis of aspirin-induced gastric mucosal injury in rats. Oral administration of acidified aspirin (200 mg/kg) resulted in linear hemorrhagic erosions and an increase in myeloperoxidase activity, an index of neutrophil infiltration, in the gastric mucosa. Aspirin-induced gastric damage and the increase in myeloperoxidase activity were significantly inhibited by the injection of anti-CD11a, anti-CD11b, anti-intercellular adhesion molecule-1 monoclonal antibodies, and the combination of superoxide dismutase and catalase, which are scavengers of active oxygen species. These results suggest that neutrophil-endothelial adhesive interactions, which occur via CD11a/ CD18- and CD11b/CD18-dependent interactions with intercellular adhesion molecule-1, and oxygen-derived free radicals produced by neutrophils are implicated in the production of aspirin-induced gastric mucosal injury.

Animals↗
PubMed1995

Effects of free radical scavengers on indomethacin-induced aggravation of gastric ulcer in rats.

Effects of treatment with free radical scavengers in the healing process of acetic acid-induced gastric ulcer on the ulcer aggravation induced by indomethacin were investigated. Gastric ulcers were produced on the anterior wall of the stomach of male Sprague-Dawley rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcer were treated with scavengers for six weeks and then treated with indomethacin (1 mg/kg/day). While superoxide dismutase (10,000 units/kg/day) did not affect the ulcer area after indomethacin treatment, allopurinol (50 mg/kg/day) slightly inhibited the increase in ulcer area. Dimethyl sulfoxide (1% solution, ad libitum) produced a significant decrease in size of the ulcer after indomethacin treatment. Increased lipid peroxides in the gastric mucosa after indomethacin treatment decreased significantly in the rats of the dimethyl sulfoxide and allopurinol groups. These results indicate that lipid peroxidation mediated by oxygen radicals plays an important role in the mechanism of ulcer aggravation induced by indomethacin.

Acetates↗
PubMed1995

Poly A-linked non-isotopic microtiter plate reverse transcriptase assay for sensitive detection of clinical human immunodeficiency virus isolates.

A colorimetric reverse transcriptase assay (cRT assay) was developed for quantitative detection of HIV-1. In this format, reverse transcriptase incorporates biotin-labeled dUTP onto oligo-dT primers hybridized to poly A templates. The templates are covalently bound to the surface of microtiter wells. The amount of incorporated biotin-labeled dUTP is measured by binding horseradish peroxidase conjugated streptavidin, washing away unbound peroxidase, adding colorimetric substrate and then reading with a standard colorimetric reader. The sensitivity of the assay is very good. As little as 3 x 10(5) molecules of recombinant HIV-RT can be detected after 20 h of reaction time. Direct comparison using 3 cultured clinical isolates indicates that this level of detection is equivalent to the commercially available p24 antigen capture assay and the HIV-RNA assay based on branched DNA signal amplification. Other retroviruses, such as HIV-2 and feline immunodeficiency virus (FIV), can also be detected in this format. This non-isotopic assay is easy to perform and could provide a convenient and quantitative method for HIV study by monitoring reverse transcriptase, an essential activity in the infection process.

Animals↗
PubMed1995

Hydroxyl radical scavenging by rebamipide and related compounds: electron paramagnetic resonance study.

We studied the scavenging activity of rebamipide, a novel antipeptic ulcer agent, and seven related compounds against hydroxyl radicals using the electron paramagnetic resonance (EPR) spin trapping technique. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was used as a spin trapping agent. We estimated the second order rate constant for the reaction between the agents tested and hydroxyl radical at pH 7.8 by kinetic competition studies. All compounds tested scavenged the hydroxyl radicals with a certain relationship between concentration and scavenging efficacy. A structure-scavenging activity relationship was derived from the kinetic evidence available on the formation and inhibition of the DMPO spin adduct EPR signal of hydroxyl radicals (DMPO-OH). Important determinants for scavenging hydroxyl radicals were the 3,4-double bond of the quinolinone ring in conjunction with a 2-oxo function and the carbonyl portion of the amido group in conjunction with a para-chlorobenzoyl function.

Alanine↗
PubMed1995

Relationship between morphological classification of the degree of maturation and the ploidy of micromegakaryocytes in myelodysplastic syndrome patients.

To clarify the biological behavior of micromegakaryocytes in myelodysplastic syndrome (MDS), the relationship between the morphological classification and the ploidy of megakaryocytes was studied in bone marrow aspirates obtained from patients with MDS and from normal controls. The morphology was determined according to Feinendegen's classification, which is considered to reflect megakaryocytic maturation, and the ploidy was determined by microcytofluorometry, using 4',6-diamidino-2-phenylindole (DAPI) staining after the removal of Wright-Giemsa stain. Most micromegakaryocytes (i.e., megakaryocytes < 20 microns in diameter) in MDS were morphologically mature, as were those in the normal controls. The peak micromegakaryocytic ploidy was 4N or 8N, whereas that of the megakaryocytes in normal controls was 16N. These findings indicated that the micromegakaryocytes in MDS were morphologically mature but had impaired polyploidization.

Adult↗
PubMed1995

Probucol prevents the progression of fatty liver in MSG obese mice.

We investigated the effect of Probucol in preventing fatty liver in monosodium-L-glutamate (MSG) treated obese mice and control mice fed a high fat diet. MSG mice became significantly obese 9 weeks after birth with higher levels of serum blood glucose, total cholesterol, HDL-cholesterol, GPT, and cholinesterase, and had greater triglyceride contents in their livers relative to control mice. Morphologically, MSG obese mice also had a marked fatty liver. Administration of Probucol mixed with the high fat diet for 2 weeks significantly decreased the serum levels of total cholesterol and HDL-cholesterol, and liver triglyceride contents in both MSG and control mice. Morphologically, the livers were less fatty after Probucol treatment. These results suggest that Probucol prevents the development of fatty liver, and in addition reduces hypercholesterolemia.

Animals↗
PubMed1995

Liver transplantation: late complications of the biliary tract and their management.

Even though the incidence of biliary complications has decreased over the years, the biliary tract is still a source of significant morbidity and graft failure in patients after liver transplantation. Biliary strictures and the secondary effects of obstruction make up the majority of complications that are identified at a time beyond the initial posttransplant hospitalization. Management of these complications has moved from a purely surgical realm to one involving invasive radiologic and endoscopic techniques. Expertise in procedural methodology has grown dramatically over the last 10 years. Prompt recognition of biliary complications and effective use of a combination of management techniques has resulted in improved palliation, greater graft salvage, and reduced patient mortality. Research into the pathogenesis and prevention of bile duct injury is needed.

Bile↗
PubMed1995

Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex.

The third subunit, the so-called common gamma (gamma c) chain, of the IL-2 receptor is shared among the receptors for IL-2, IL-4, IL-7 and IL-15, and dysfunction of the gamma c chain is thought to cause X-linked severe combined immunodeficiency (XSCID) ascribed to impairment of early T cell development. However, cytokines linked to XSCID are as yet unidentified. A mAb specific for the gamma c chain, TUGm2, profoundly inhibited cell proliferation in response to IL-9. Another mAb, TUGm3, immunoprecipitated [125I]IL-9 cross-linked with either the IL-9 receptor or the gamma c chain. These results demonstrate that the gamma c chain is included in the functional receptor complex for IL-9, which was initially characterized as a T cell growth factor and is essential for IL-9-dependent growth signal transduction.

Animals↗
PubMed1995

Dimeric chemotactic peptides discriminate between chemotaxis and superoxide production of human neutrophils.

A series of dimeric fMLPs were synthesized by cross-linking with hydrophilic linkers, mono-, di-, tri-, and tetraethylene glycols. All of the dimers showed higher activities than monomeric fMLP in chemotaxis assays for human neutrophils. The magnitude of the activity enhancement was dependent on the linker length. On the other hand, production of superoxide anion was not as enhanced as chemotaxis. The experimental results indicate that these dimers, especially the triethylene glycol-bridged fMLP dimer, D-fMLP-G3, are selective agonists for chemotaxis. In order to distinguish between biological activities and intracellular signaling, rapid mobilization of the intracellular calcium was also measured. D-fMLP-G3 strongly enhanced the calcium mobilization. These results suggest that chemotaxis was correlated with the increase of the intracellular calcium concentration, whereas NADPH oxidase was not activated to generate superoxide by this elevation of cytoplasmic calcium caused by the dimeric ligand, D-fMLP-G3. The dimeric fMLPs might act as useful ligands for studying the intracellular signaling mechanisms of human neutrophils.

Amino Acid Sequence↗
PubMed1995

Acquired hypochromic and microcytic sideroblastic anaemia responsive to pyridoxine with low value of free erythrocyte protoporphyrin: a possible subgroup of idiopathic acquired sideroblastic anaemia (IASA).

Patients with idiopathic acquired sideroblastic anaemia (IASA) usually show macrocytic or normocytic anaemia and increased free erythrocyte protoporphyrin (FEP). The mean cell haemoglobin concentration is normal or slightly low. Here we report a pyridoxine-responsive IASA patient with microcytic and hypochromic anaemia and low FEL level; these features are usually seen in cases of hereditary sideroblastic anaemia. Microcytosis increased during therapy. There may be a subgroup of IASA with microcytic and hypochromic anaemia, low normal FEP and some response to pyridoxine like hereditary sideroblastic anaemia.

Adult↗