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Biomedical subjects

H Kodama

Publications and source records attributed to H Kodama.

At least 217 records · Page 12Linked to original sources

Stress increases plasma enzyme activity in rats: differential effects of adrenergic and cholinergic blockades.

Plasma creatine phosphokinase, lactic dehydrogenase, glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities significantly increased in rats immersed in 23 degrees C water for 6 hr after restraint (water immersion stress). The stress-induced rises in the four enzymes were significantly prevented by the intraperitoneal injection of 6-hydroxydopamine (80 mg/kg), propranolol (1 and 10 mg/kg) or timolol (1 and 10 mg/kg) but not by phentolamine (0.1-10 mg/kg) and atropine (0.1-10 mg/kg). The stress also significantly increased plasma urea nitrogen and glucose levels; however, neither propranolol (0.1-10 mg/kg) nor timolol (0.1-10 mg/kg) did affect these levels. On the other hand, 6-hydroxydopamine (80 mg/kg) and phentolamine (10 mg/kg) slightly but significantly prevented the increase in plasma urea nitrogen level, and the stress-induced hyperglycemia was significantly prevented by either phentolamine (10 mg/kg) or atropine (1 and 10 mg/kg). Plasma norepinephrine and epinephrine levels were also increased significantly by the stress, and the norepinephrine response was suppressed significantly by 6-hydroxydopamine. In conclusion, excessive peripheral sympathetic activity possibly plays an important role in the water immersion stress-induced increases in the plasma enzymes activity primarily via beta-adrenoceptors, whereas alpha-adrenoceptors and the cholinergic nerves might be involved in the stress-induced increases in plasma urea nitrogen and glucose levels.

Adrenergic Antagonists↗

Development of erythroid cells from mouse embryonic stem cells in culture: potential use for erythroid transcription factor study.

We developed an efficient differentiation induction system from mouse embryonic stem (ES) cells into blood cells by coculture on a novel stromal cell line named OP9, in order to analyze molecular mechanisms of hematopoietic cell development and differentiation. ES cells could give rise to adult type definitive erythrocytes, myeloid and B lineage cells via multipotential hematopoietic precursor cells, when the cells were simply cocultured with the OP9 stromal cells. The temporal pattern of the appearance of erythroid lineage cells during the differentiation induction was very similar to that detected in mouse ontogeny. This differentiation induction method should facilitate to dissect the function of erythroid transcription factors during erythroid lineage cell development.

Animals↗

[An anaphylactic shock case after hepatic arterial infusion of zinostatin stimalamer suspension improved by anti-histaminics].

A 47-year-old man with hepatocellular carcinoma (HCC) at anterior and medical segment in the liver was treated with hepatic arterial infusion of Zinostatin Stimalamer-lipiodol suspension (SMANCS). After the 2nd infusion of SMANCS, the accumulation of lipiodol in the tumor was not good (Grade II), so additional administration was undertaken at five-weeks intervals. His systolic blood pressure immediately decreased from 120 to 60 mmHg, and he had numbness of hands, shaking chills, sweating, chest pain and numerous urticaria-like red exanthema. In spite of treatment by anti-shock agents such as steroid and catecholamines, these symptoms did not disappear, but antihistaminics greatly improved them without any serious side effects. Because of the remarkable effects of the antihistaminics and possibility of antibody production (IgE) after repeated infusions of high molecular SMANCS, this patient may have suffered anaphylactic shock caused by massive histamine release from mast cells.

Anaphylaxis↗

[A case of amyopathic dermatomyositis associated with interstitial pneumonitis].

A patient (47-year old female) who had erythema similar to Gottron's sign on bilateral finger joints since two years ago, started to have polyarthralgia on bilateral knee and shoulder on the spring of 1993. Polyarthralgia was extended to both wrist and hand joints on Oct. of 1995. On the middle of Dec. 1995, she began to have exertional dyspnea and was referred and admitted in our hospital on 18th, Dec., 1995. Chest X-ray and CT scan showed the shadow for active interstitial pneumonitis on bilateral lower lung fields. Blood gas analysis indicated hypoxia (PaO2: 62.8 mmHg) and low % DLCO (64.7%). Skin eruption of face (heliotrope-like erythema) and hands (Gottron's sign) and skin biopsy (right hand) findings were compatible with that in dermatomyositis. The analysis in blood biochemistry showed no elevation for muscle enzymes. The diagnosis for amyopathic dermatomyositis (ADM) was made according to the criteria proposed by Euwer & Sontheimer (1993). The steroid pulse therapy and 50 mg per day of cyclophosphamide were immediately administered. The dyspnea and dermatitis were improved within two weeks after therapy. She is presently in remission until Jan. 1997 with the maintenance dosis of 10 mg per day of oral prednisolone.

Anti-Inflammatory Agents↗

Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine induce the tyrosyl phosphorylation of 45 kDa protein in parallel with its stimulation of superoxide generation in human neutrophils.

Human peripheral blood polymorphonuclear leukocytes were preincubated with lanthionine, S-(2-aminoethyl)-L-cysteine, and some of their derivatives found in normal human urine and bovine brain. Among these compounds, lanthionine ketimine and to a lesser extent S-(2-aminoethyl)- L-cysteine ketimine enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation. These ketimines induced tyrosyl phosphorylation of 45 kDa protein of cells. The tyrosyl phosphorylation was markedly increased with time, and the phosphorylation process was dependent on the concentration of both ketimines. However, lanthionine, 1,4-thiomorpholine-3,5-dicarboxylic acid, S-(2-aminoethyl)-L-cysteine and 1,4-thiomorpholine-3-carboxylic acid were without effect both on superoxide generation and on tyrosyl phosphorylation of 45 kDa protein. Lanthionine ketimine and S-(2-aminoethyl)-L-cysteine ketimine also enhanced superoxide generation induced by opsonized zymosan but not the one induced by arachidonic acid and phorbol 12-myristate 13-acetate. Ketimine-primed superoxide generation and tyrosyl phoshorylation of 45 kDa protein were inhibited by genistein, an inhibitor of protein tyrosine kinase, but not by 1-(5-isoquinoline sulfonyl)-2- methylpiperazine, an inhibitor of protein kinase C.

Amino Acids, Sulfur↗

Preferential proliferation of murine colony-forming units in culture in a chemically defined condition with a macrophage colony-stimulating factor-negative stromal cell clone.

The establishment of culture conditions that selectively support hematopoietic stem cells is an important goal of hematology. In this study, we investigated the possibility of using for this purpose a defined medium, mSFO2, which was developed for stromal cell-dependent bone marrow cultures. We found that a combination of epidermal growth factor (EGF), the OP9 stromal cell line, which lacks macrophage colony-stimulating factor, recombinant stem cell factor, and the chemically defined medium mSFO2 provides a microenvironment where c-Kit+ Thy-1+/lo Mac-1+/lo B220- TER119- common beta + IL-2R gamma + gp130+ cells are selectively propagated from normal, unfractionated bone marrow cells. This cell population produced an in vitro colony at a very high efficiency (50%), whereas it has only limited proliferative ability in the irradiated recipient. Thus, the cells selected in this culture condition might represent colony-forming units in culture (CFU-c) with short-term reconstituting ability. Transferring this cell population into medium containing differentiation signals resulted in the rapid production of mature myelomonocytic and B cell lineages in vitro and in vivo. The fact that a similar culture condition was created by erb-B2-transduced OP9 in the absence of EGF indicated that EGF exerts its effect by acting on OP9 rather than directly on CFU-c. These results suggested that the balance between self-renewal and differentiation of CFU-c can be regulated by extra-cellular signals.

Animals↗

Structural organization and tissue-specific expression of the gene encoding rat cysteine dioxygenase.

Cysteine dioxygenase (CDO) is a key enzyme involved in the metabolism of L-cysteine. Genomic clones containing the 5'-flanking sequence of the rat CDO gene were isolated and characterized. The CDO gene spanned about 15 kb, and comprised 5 exons. All boundaries between the exons and introns matched the GT/AG rule. The major transcription start point (tsp) was A at 213 bp upstream from the ATG codon. The 5'-flanking region contained a TATA-box-like sequence and putative cis-acting regulatory elements. The 3' end of CDO was polyadenylated at several sites. Northern blots of RNA from rat tissues revealed the highest CDO mRNA level in the liver. Significant levels were observed in the kidney, lung and brain, implying tissue-specific differences in CDO promoter function.

Animals↗

Effect of cystathionine and cystathionine metabolites on the phosphorylation of tyrosine residues in human neutrophils.

The effect of cystathionine and cystathionine metabolites found in the urine of patients with cystathioninuria on the phosphorylation of tyrosine residues was studied with human peripheral blood polymorphonuclear leukocytes. Among the cystathionine metabolites, cystathionine ketimine markedly increased phosphorylation of a 45 kDa protein with time and the phosphorylation depended on the concentration of cystathionine ketimine, while cystathionine and the reduced form of cystathionine ketimine (cyclothionine) did not increase the phosphorylation of the 45 kDa protein. The phosphorylation of the 45 kDa protein induced by cystathionine ketimine was inhibited by genistein and herbimycin A, inhibitors of tyrosine kinase, but was not inhibited by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and staurosporine, inhibitors of protein kinase C.

Benzoquinones↗

Functional coupling of adenosine A2a receptor to inhibition of the mitogen-activated protein kinase cascade in Chinese hamster ovary cells.

Activation of Gs-coupled receptors enhances the increase in cyclic AMP mediated by adenylate cyclases. As it has been shown that cyclic AMP inhibits the epidermal growth factor-activated mitogen-activated protein kinase (MAPK) signalling pathway, stimulation of Gs-coupled receptors may lead to the inhibition of MAPK activation. To investigate the effect of a Gs-coupled receptor on the MAPK cascade, we cloned the adenosine (Ado) A2a receptor from a guinea-pig leucocyte cDNA library, and established Chinese hamster ovary (CHO) cells stably expressing the receptor (CHOAdoA2R). The [3H]5'-N-ethylcarbamoyladenosine (NECA) binding characteristics (Kd = 91.0 +/- 5.4 nM, Bmax = 707 +/- 11 fmol/mg of protein, n = 3) and NECA-induced cyclic AMP production indicate that the cloned Ado A2a receptor was functionally expressed in the cells. In CHO cells, thrombin induced intracellular Ca2+ increase and MAPK activation through the intrinsic G-coupled receptor. In CHOAdoA2R cells, NECA partially inhibited thrombin-elicited MAPK activation. When combining NECA-treatment with 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester (BAPTA-AM) loading, a nearly complete inhibition of the MAPK activation occurred. Forskolin also partially inhibited the MAPK activation and synergized with BAPTA-AM, suggesting that partial inhibition of MAPK activation by NECA results from cyclic AMP production via Ado A2a receptor activation. The same synergism of MAPK inhibition between wortmannin and BAPTA-AM was observed, but not between wortmannin and NECA. These results suggest that cyclic AMP production through Ado A2a receptor inhibits thrombin-elicited MAPK activation by a Ca(2+)-independent/wortmannin-sensitive pathway in CHO cells.

Adenosine↗

In vitro development of primitive and definitive erythrocytes from different precursors.

During mouse embryogenesis the production of "primitive" erythrocytes (EryP) precedes the production of "definitive" erythrocytes (EryD) in parallel with the transition of the hematopoietic site from the yolk sac to the fetal liver. On a macrophage colony-stimulating factor-deficient stromal cell line OP9, mouse embryonic stem cells were shown to give rise to EryP and EryD sequentially with a time course similar to that seen in murine ontogeny. Studies of the different growth factor requirements and limiting dilution analysis of precursor frequencies indicate that most EryP and EryD probably developed from different precursors by way of distinct differentiation pathways.

Animals↗

Effect of cystathionine ketimine on the stimulus coupled responses of neutrophils and their modulation by various protein kinase inhibitors.

Human peripheral blood polymorphonuclear leukocytes were perincubated with cystathionine and cystathionine metabolites found in the urine of the patients with cystathioninuria. Among the cystathionine metabolites, cystathionine ketimine significantly enhanced the N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation, but cystathionine and cyclothionine did not enhance the superoxide generation. Cystathionine ketimine also enhanced superoxide generation induced by opsonized zymosan but not those induced by arachidonic acid and phorbol myristate acetate. Superoxide generation induced by cystathionine ketimine was inhibited by genistein, an inhibitor of tyrosine kinase, and was enhanced by 1-(5-isoquinoline-sulfonyl)-2-methyl-piperazine, an inhibitor of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Characteristic interaction of Ca2+ ions with elastin coacervate: ion transport study across coacervate layers of alpha-elastin and elastin model polypeptide, (Val-Pro-Gly-Val-Gly)n.

Ion transport characteristics across a macrocoacervate layer membrane composed of aqueous elastin model polypeptides with a specific repeating pentapeptide sequence, H-(Val-Pro-Gly-Val-Gly)n-Val-OMe (n > or = 40), were investigated. Transmembrane potential responses for NaCl. MgCl2, and CaCl2 concentration-cell systems were measured and examined systematically by comparing with those across a coacervate membrane composed of bovine neck ligamental alpha-elastin. In the case of the NaCl and MgCl2 systems, potential responses across these protein liquid membranes were different noticeably from each other depending upon the molecular structure with and without charged peptide side chains, whereas in the CaCl2 systems the transmembrane potential responses across the noncharged polypentapeptide coacervate membrane were comparable with those across the alpha-elastin coacervate membrane carrying both the positively and negatively charged amino acid residues as an amphoteric ion-exchange membrane. These results indicated that mechanisms of major Ca2+ ion transport are based on the specific and selective interactions with electrically neutral sites of elastin, such as the polypentapeptide backbone chain.

Amino Acid Sequence↗

Induction of IL-6 production by bone marrow stromal cells on the adhesion of IL-6-dependent hematopoietic cells.

Cellular interactions between hematopoietic cells and stromal cells play crucial roles in the proliferation and differentiation of the hematopoietic cells. Interleukin-6 (IL-6)-dependent 7TD1 cells markedly proliferated without IL-6 when they were co-cultured with hematopoietic-supportive bone marrow stromal cells, HESS-5 cells and HESS-1 CL.3 cells, which can support long-term hematopoiesis in vitro with but not without direct cell contact, cell contact being prevented with a microporous membrane. The production of IL-6 and the amount of IL-6 mRNA in hematopoietic-supportive stromal cells but not 7TD1 cells significantly increased only when the stromal cells were co-cultured in direct contact with 7TD1 cells. Furthermore, the amount of IL-6 mRNA increased according to the number of 7TD1 cells co-cultured. These inductions were not observed on co-culture with a murine myeloid cell line, M1 cells, or on the addition of the co-culture supernatant. These results suggest that 7TD1 cells transmit the signal to stromal cells that enhances IL-6 production by stromal cells via direct cell contact. A certain specific molecule for transduction of the signals may exist on the surface membrane of stromal cells and hematopoietic cells.

Animals↗

Modification of fatty acid composition by over- and antisense-expression of a microsomal omega-3 fatty acid desaturase gene in transgenic tobacco.

omega-3 fatty acid desaturases, which catalyse the conversion of linoleic acid (18:2) to linolenic acid (18:3) in lipids, are located in the microsomes and plastid membranes. Transgenic tobacco plants were produced that express the transcripts of a tobacco microsomal omega-3 fatty acid desaturase gene (NtFad3) in antisense and sense orientations under the control of the cauliflower mosaic virus 35S promoter. The antisense construct has the 0.5-kb fragment of the NtFad3 cDNA containing a 3'-flanking region and a part of the coding region in antisense orientation. The antisense-transformant lines showed decreases of the steady-state NtFad3 mRNA level to 30% of the control plants. In these lines, the 18:3 content decreased to about 80% in root tissues and to about 70-80% in leaf tissues when compared with the control plants. The sense construct has the 1.4-kb full-length cDNA of NtFad3. In one of the sense-transformant lines, the NtFad3 mRNA level increased 8 times when compared with that of the control plants. In this line, the 18:3 content increased by about 1.5-fold in root tissues and by about 1.1-fold in leaf tissues. These results indicate that the up- and down-regulation of the transcript level in the microsomal omega-3 fatty acid desaturase gene is useful to modify the 18:3 content in the vegetative tissues of higher plants.

Antisense Elements (Genetics)↗

Sperm immobilization antibodies in infertile male sera decrease the acrosome reaction: a possible mechanism for immunologic infertility.

OBJECTIVE: To study the effect of sperm-immobilizing antibodies from male sera on spontaneous and A23187-induced acrosome reactions (AR). DESIGN: Swim-up spermatozoa obtained from three fertile donors were incubated with 13 sera with sperm-immobilizing antibodies obtained from infertile men and three control sera obtained from healthy fertile males. Sperm acrosomes were examined by staining with pisum sativum agglutinin labeled with fluorescein isothiocyanate (30 micrograms/ml; Sigma Chemical Co., St. Louis. MO) as spontaneous and A23187 (used at a final concentration of 10 microM; Sigma Chemical Co.) induced. RESULTS: The incidence of spontaneous AR of spermatozoa incubated with antisperm antibody positive male sera (6.2 +/- 0.7) was significantly (P < 0.001) lower than that of spermatozoa incubated with control sera (10.7 +/- 0.5). And the incidence of A23187-induced and -inducible (incidence of induced minus spontaneous) ARs of spermatozoa incubated with sperm antibody-positive male sera (12.4 +/- 1.9 and 6.2 +/- 1.9) was significantly lower (P < 0.001) than that of spermatozoa incubated with control sera (31.0 +/- 0.5 and 20.3 +/- 0.9). Sperm-immobilizing antibody-positive sera decreased spontaneous, A23187-induced, and inducible ARs. CONCLUSIONS: Sperm-immobilizing antibodies from male sera interfere with fertilization by inhibiting the AR.

Acrosome↗

Inhibition of cytotoxic activity of carp lymphocytes (Cyprinus carpio) by anti-thymocyte monoclonal antibodies.

A series of monoclonal antibodies (mAbs) were developed against carp thymocytes and carp immunoglobulin (IgM). Anti-thymocyte mAbs reacted with thymocytes, head kidney lymphocytes (HKL) as well as peripheral blood lymphocytes (PBL) at various proportions. Anti-IgM antibody reacted with HKL and PBL but not with thymocytes. PBL from carp immunized with xenogeneic mouse myeloma cells exhibited cytotoxic activity against target cells but PBL from unimmunized fish showed weak cytotoxicity. Treatment of PBL with anti-thymocyte mAbs and guinea pig complement suppressed the cytotoxic activity dose dependently; however, anti-IgM mAb did not. These results indicate the cytotoxic cells in PBL possess cell surface antigens common to thymocytes.

Animals↗

Spontaneous immunoglobulin production by adenoidal and tonsillar lymphocytes in relation to age and otitis media with effusion.

Spontaneous immunoglobulin (Ig) production by autologous adenoidal and tonsillar lymphocytes cultured without any mitogen was measured by an enzyme-linked immunosorbent assay (ELISA) in 18 children with or without otitis media with effusion (OME). Both IgG and IgA levels synthesized by adenoidal or tonsillar lymphocytes significantly increased with age. The average concentrations of IgG and IgA produced by adenoidal lymphocytes from children with OME were significantly lower than those from children without OME. Adenoidal lymphocytes produced IgG and IgM at significantly lower levels than autologous tonsillar lymphocytes did in children with OME. In contrast, no significant difference between adenoidal and tonsillar lymphocytes was seen on Ig production for any isotypes in children without OME. These results may indicate immunological impairment of the adenoids associated with OME.

Adenoids↗