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Biomedical subjects

S Tagawa

Publications and source records attributed to S Tagawa.

At least 55 records · Page 3Linked to original sources

Long-term survival in a case of high-risk type IgD myeloma; a possibility of effectiveness of interferon-alpha and erythropoietin.

The prognosis of patients with IgD myeloma is poorest among all types of multiple myeloma. We report a case of a patient with IgD myeloma who survived for an extraordinarily long period post-diagnosis (65 months). According to the new risk grouping of IgD myeloma (Shimamoto Y. et al., Eur. J. Haematol. 47, 262 (1991), he was classified as being in the high-risk group, with a zero percent expected 5-yr survival. Nevertheless, he survived for 65 months. We discuss the usefulness of interferon-alpha and erythropoietin for the treatment of IgD myeloma.

Antineoplastic Agents↗

Polymorphonuclear neutrophils in saliva and blood: a comparative study of morphology, function and phenotype.

The morphology, phagocytic activity, production of hydrogen peroxide (H2O2) and expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), complement receptor type 3 (CR3; CD11b/CD18), p150,95 (CD11c/CD18), and platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) by oral polymorphonuclear neutrophils (PMN) are assessed and the results compared with those of blood PMN. There were no differences in the morphology and phagocytic activity between oral and blood PMN. H2O2 production was measured following stimulation with phorbol myristate acetate (PMA) and N-formyl-L-leucyl-L-phenylalanine (FMLP) as indicators of bactericidal activity. There was a significant difference in the H2O2 production by the two groups when stimulated with FMLP; the level of H2O2 production by oral PMN was significantly higher than that by blood PMN. However, there was no significant difference in H2O2 production between oral and blood PMN when stimulated with PMA. The percentage of CD11a- and CD11c-positive concentrated oral PMN was significantly lower than that seen in blood PMN, as was the percentage of CD31-positive cells. Higher H2O2 production by oral PMN following stimulation with FMLP may result in enhanced bactericidal activity. Low expression of CD31 may lead to the accumulation of PMN in the mouth by blocking their return to the bloodstream. These phenomena may be necessary for oral PMN to protect periodontal tissues from bacteria in the mouth.

Cell Adhesion Molecules↗

VLA-5 in the plasma cell line, FR4ds, acts as a common regulator of VLA-4 and VLA-6 in spreading induced by fibronectin and laminin.

VLA-5 recognizes the GRGDSP sequence of fibronectin (FN) in the extracellular matrix (ECM). We examined the role of beta1 integrin in the spreading of the human plasma cell line, FR4ds, induced by FN and laminin (LN). We first examined the role of VLA-5 in the spreading induced by FN. Anti-alpha4 antibody induced 46.4% inhibition, whereas anti-alpha5 had no effect. A combination of anti-alpha4 and anti-alpha5 enhanced the inhibition of spreading significantly. Complementary inhibition was also demonstrated using the GRGDSP peptide plus anti-alpha4 and the GRGDNP peptide of LN plus anti-alpha4. The results suggested that VLA-5 is a regulator of VLA-4 and that it is involved in the recognition of GRGDNP. We then examined the role of VLA-5 in the spreading induced by LN. Anti-alpha6 induced 53.1% inhibition. Anti-alpha5 alone had no effect. A combination of alpha5 and anti-alpha6, however, significantly enhanced the inhibition of spreading. The combination of GRGDSP plus anti-alpha6 and GRGDNP plus anti-alpha6 resulted in complete inhibition. These results suggested that VLA-5 participates in the recognition of LN cooperatively with VLA-6 and that VLA-5 is a common regulator of VLA-4 and the LN receptor, VLA-6.

Cell Movement↗

Infection with GB virus C (GBV-C) in patients with fulminant hepatitis.

BACKGROUND/METHODS: There appear to be hepatitis viruses other than hepatitis A, B, C, D and E. One of these has been proposed with a designation of GB virus C. Sera from 44 patients with fulminant hepatitis were tested for RNA of GB virus C by reverse-transcription polymerase chain reaction with nested primers deduced from the putative non-structural 3 (helicase) region. RESULTS: RNA of GB virus C was detected in three (20%) of 15 patients with hepatitis B virus infection and three (12%) of 25 patients without markers of hepatitis A-E virus infection. Overall, GB virus C RNA was detected in six (14%) of the 44 patients with fulminant hepatitis, at a frequency significantly higher (p < 0.001) than that in three (0.9%) of 326 blood donors matched for age with the patients. CONCLUSIONS: These results indicate a role of GB virus C in inducing fulminant hepatitis either by itself or in concert with the other hepatitis viruses.

Acute Disease↗

Adenomatoid serous hyperplasia of sublingual gland: a case report.

We present an example of adenomatoid serous lobular hyperplasia of the sublingual gland. Pathologic examination revealed the lesion was composed of multiple aggregates of normal-appearing serous and mucous acini that varied in size. The ratio of serous gland to mucous glands was 7 to 1. We cannot identify the cause of this condition, however, calcium channel blocking agents prescribed for the treatment of this patient's essential hypertension cannot be ruled out as a pathogenetic factor in the development of the lesion.

Adenomatoid Tumor↗

Fas ligand in human serum.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.

Animals↗

Interleukin-6 inhibits the chemotaxis of human malignant plasma cell lines.

The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory roles of the bone marrow microenvironment. Five human malignant plasma cell lines, FR4ds, OPM-1ds, U266/B1, RPMI-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM-1ds and U266/B1 cells showed chemotaxis promoted by FN (ChFN) and LN (ChLN). ARH-77 cells showed ChFN but not ChLN. RPMI-8226 cells did not show either ChFN or ChLN. The supernatant from KM-101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by FN or LN. Among the cytokines produced by KM-101 cells, it was postulated that IL-6 mediated this inhibitory effect because anti-IL-6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantly reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a similar inhibitory effect. Because anti-gp130 MoAb significantly reversed the chemotaxis inhibitory effect of rIL-6, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130. The chemotaxis-regulatory effect is another previously unrecognized function of this pleiotropic cytokine, IL-6. High levels of IL-6 in the bone marrow microenvironment of patients with multiple myeloma appears to be favourable for the localization of myeloma cells there.

Antigens, CD↗

[Effects of retinal intrinsic dopamine on the in in vivo electroretinogram of rabbits].

The effects of intravitreal injection of nomifensine, a potent dopamine uptake blocker, on the electroretinogram (ERG) were investigated in rabbit. Nomifensine enhanced the amplitude of the oscillatory potentials at 100 microM (intravitreal concentration) and 300 microM (p < 0.05), but it attenuated the oscillatory potentials at 1,000 microM (p < 0.01). Nomifensine attenuated the amplitude of the scotopic b-wave at 100 microM and 1,000 microM (p < 0.05), leaving the peak latency of the scotopic b-wave unaltered at all concentrations tested (30, 100, 300, 500 and 1,000 microM). Neither the amplitude nor the peak latency of the dark-adapted a- and b-waves elicited by bright stimuli was altered at any nomifensine concentration tested. 1 microM dopamine and 30 microM nomifensine together, each of which is insufficient to alter either of the scotopic b-wave or the oscillatory potentials when applied alone, reduced the scotopic b-wave and enhanced the oscillatory potentials. These results suggest that intrinsic dopamine release in the retina is large enough to alter the ERG.

Animals↗

[D1 receptor mediates dopamine-induced enhancement of electroretinographic oscillatory potentials].

The inhibitory action of SCH 23390 (SCH, D1-antagonist) or sulpiride (SUL, D2-antagonist) on the dopamine-induced enhancement of the electroretinographic oscillatory potentials was examined in anesthetized albino rabbits. Enhancement of the oscillatory potentials by intravitreal dopamine (50 microM intravitreal concentration) injection was blocked by a simultaneous intravitreal injection of SCH (20 microM) but not by SUL (50 microM, 100 microM). These results suggest that D1-receptor is mainly responsible for the dopamine-induced enhancement of the oscillatory potentials.

Action Potentials↗

[Large granular lymphocyte leukemia].

Large granular lymphocyte leukemia (LGLL) is defined as clonal proliferation of LGLs in peripheral blood. The following studies were conducted to address some issues in chronic LGLL. (1) Chronic LGLL is characterized by the indolent course, and the diagnosis of leukemia is difficult in such patients as those without distinct organomegaly and/or any evidence of monoclonality. We performed immunohistological studies in a patient with persistent NK lymphocytosis. No organomegaly had been seen in the patient during a three-year-observation, who died from cerebrovascular accident. The autopsy findings revealed multi-organ infiltration including spleen, liver, bone marrow, lymph nodes and lung. These findings suggest that the cells of chronic LGLL have infiltrative capacity characteristic of malignant cells. (2) Lymphocytosis in chronic LGLL is usually stable for a long period. We found that both T- and NK-LGLL cells strongly expressed CD95, an apoptosis related protein. Anit-CD95 did not induce apoptosis, but suppressed proliferation induced by IL-2 or anti-CD3. These results suggest that CD95-CD95 ligand system is involved in the slow cell growth characteristic of chronic LGLL. (3) CD4+CD8+ double positive (DP) cases are rarely seen in LGLL, and the physiologic counterpart of the leukemic cells has not been determined yet. We found that the DP-LGLL had alpha alpha type in the CD8 subunit and did not express RAG-1, these findings being characteristic of peripheral T cells. We also found that they expressed IL-4 mRNA and secreted IL-4 on activation. These results strongly suggest that DP-T-LGLL represents an expansion of a rare subset of peripheral DP-T cells, possibly derived from IL-4 activated CD4 single positive T cells.

Aged↗

[LGL lymphoma].

We reported in this article two patients with large granular lymphocytic lymphoma (abbreviated as LGL lymphoma). One was the patient with LGL leukemia/lymphoma (patient 1) and other was the patient with NK-LGL lymphoma (patient 2). Because the gene of TCR delta was rearranged in the patient 1, the clonality of the LGL leukemia/lymphoma was confirmed. However, it is not determined yet whether the lineage of tumor cells is T cells or NK cells. The cytochemical features of the lymphoma cells of the patient 2 were studied. It was found that NK cell-derived lymphoma cells of the patient were positively stained with these two monoclonal antibodies that are reactive with T cell; one is anti-CD45RO (UCHL-1) and other is anti-CD3. Judging from the result, malignant NK-LGL cells in some patients are cytoplasmic CD3+ and UCHl-1+. It is emphasized that May-Grünwald-Giemsa stain of biopsied specimen of the lymphoma is required for making the diagnosis of LGL lymphoma.

Adult↗

Constitutive expression of the thrombopoietin gene in a human hepatoma cell line.

The gene of thrombopoietin (TPO) has been cloned and identified to be identical to gene of the c-mpl ligand. It is known that the mRNA of TPO is expressed in liver and kidney. However, it is not clarified which cells in the liver produce TPO. Using a human hepatoma cell line, HepG2, we demonstrated that the TPO mRNA was expressed by liver parenchymal cells without any stimulation. To clarify the regulation of the expression of the TPO mRNA in HepG2 cells by cytokines, we assessed the effects of 5 cytokines, transforming growth factor-beta 1, activin A, platelet-derived growth factor, hepatocyte growth factor, and interleukin-6. These cytokines have no significant regulative effect on the expression of the TPO mRNA in HepG2 cells. Our results suggest that liver parenchymal cells may be the TPO producing cells and also suggest that some hepatoma cells may produce TPO constitutively.

Base Sequence↗

A direct demonstration of the catalytic action of monodehydroascorbate reductase by pulse radiolysis.

To elucidate the catalytic mechanism of monodehydroascorbate (MDA) reductase from cucumber, its interaction with MDA radical was investigated by the use of pulse radiolysis. When approximately equimolar MDA radical to the fully reduced MDA reductase was generated, the fully reduced enzyme reacted first with MDA radical to form the red semiquinone, and the semiquinone further reacted with MDA radical to form the oxidized enzyme. At a low ratio (< 20) of MDA radical to enzyme concentration, the fully reduced enzyme reacted quantitatively with MDA radical to form the semiquinone with a second-order rate constant of 2.6 x 10(8) M-1 s-1 at pH 7.4. At excess MDA radical to enzyme concentration, a similar rate constant was obtained from the decay of MDA radical. These results suggest that the reaction of the semiquinone with MDA radical occurs at the same rate or rate-limiting step of the oxidation of the fully reduced enzyme by MDA radical. The rate constants decreased with an increase in NaCl concentration, suggesting that the localization of cationic groups of amino acid residue near the active site may provide electrostatic guidance to the anionic substrate of MDA radical.

Catalysis↗

Interaction of NADPH-adrenodoxin reductase with NADP+ as studied by pulse radiolysis.

The reduction of flavin in NADH--adrenodoxin reductase by the hydrated electron (eaq-) was investigated by pulse radiolysis. The eaq- reduced directly the flavin of the reductase to form a blue semiquinone of the enzyme. Subsequently, the semiquinone decayed by dismutation to form the oxidized and fully reduced forms of the enzyme with a second-order rate constant of 4.4 x 10(4) M-1 s-1. In the presence of equimolar NADP+, the decay of eaq- accompanied an absorption increase at 400 nm, the spectrum of which, formed transiently, is identical to that of NADP radical (NADP.). Subsequently, the transient species decayed concomitantly with the formation of the semiquinone. The rate constant in the formation of the semiquinone was independent of the concentration of the enzyme (6.1 x 10(4) s-1 at pH 7.5). From these results, it is concluded that eaq- reacts with NADP+ bound to the enzyme to form NADP. initially, and subsequently, an electron flows from the NADP. to the flavin by an intracomplex electron transfer. A similar result was obtained in the reaction of CO2- or N-methylnicotinamide radical with the NADP(+)-adrenodoxin reductase complex. These results suggest that the nicotinamide moiety of NADP+ bound to the enzyme is accessible to the solvent and masks the flavin completely.

Animals↗