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Biomedical subjects

K Miyazawa

Publications and source records attributed to K Miyazawa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion.

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.

Adenocarcinoma↗
PubMed2000

Paralytic toxins in a ribbon worm Cephalothrix species (Nemertean) adherent to cultured oysters in Hiroshima Bay, Hiroshima Prefecture, Japan.

In 1998, during the surveillance of the toxicity of various marine fouling organisms in Hiroshima Bay, Hiroshima Prefecture, Japan, specimens of the ribbon worm, "himomushi" Cephalothrix sp. (Nemertean) adherent to the shells of cultured oysters hanging onto floating culture rafts were found to contain toxins which showed strong paralytic action in mice throughout the survey period, February to May. The maximum toxicity (as tetrodotoxin, TTX) was 14,734 MU/g whole body. Attempts were made to identify the paralytic toxins in this worm. The "himomushi" toxin (HMT) was extracted from the worm with 80% methanol acidified with acetic acid and the extract defatted with dichloromethane. The aqueous layer was chromatographed on activated charcoal and the unbound and bound toxic fractions were analyzed by high-performance liquid chromatography and gas chromatography-mass spectrometry. It was rather unexpectedly revealed from these results that HMT was comprised of TTX, 4-epiTTX, anhydroTTX and three unidentified toxins. To our knowledge, this is the first report of the occurrence of toxic organisms, containing a high concentration of TTX, adherent to cultured bivalves such as oysters.

Animals↗
PubMed2000

Refractory anemia with ringed sideroblasts with a low IPSS score progressed rapidly with de novo appearance of multiple karyotypic abnormalities and into acute erythroleukemia (AML-M6A).

We report here a case of refractory anemia with ringed sideroblasts (RARS) with a low risk group by the International Prognostic Scoring System (IPSS) at the time of diagnosis but had a rapid disease progression. Although the patient showed a normal male karyotype at the time of RARS diagnosis, his marrow cells had del(5)(q14) and add(17)(p12) abnormalities 2 months after the diagnosis, and later the marrow cells had multiple abnormalities and the patient expired 6 months after the initial diagnosis of RARS. The patient was diagnosed as having RARS with a low risk group by the IPSS classification, however, one should keep in mind that some patients with myelodysplastic syndromes with low risks by either the French-American-British (FAB) classification or the IPSS classification may have progressive disease and subsequential cytogenetic analysis could predict the disease progression.

Acute Disease↗
PubMed2000

Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia.

Refractory anemia (RA) in myelodysplastic syndrome (MDS) without prominent dysplasia closely resemble the mild type of aplastic anemia (AA) in their hematological features. This sometimes makes it difficult to distinguish clearly between the two diseases. Using the multi-color flow cytometric technique, we compared cell surface antigen expression patterns on bone marrow hematopoietic progenitor cells which were isolated as a CD34 positive- CD45 dull positive with low side scatter intensity (CD34(+)CD45(dull+)SSC(low)) population in flow cytogram between RA (n=12) and AA (n=11). The antigens analyzed in CD34(+)CD45(dull+)SSC(low) mononuclear cells were: CD38 and CD71 for cell growth-related antigens, CD 33 and CD13 for myeloid and monocytoid lineage-associated antigens, CD7 and CD19 for lymphoid lineage, and CD14 for a monocytic lineage specific antigen. The percentages of CD34(+)CD45(dull+)SSC(low) cells in bone marrow non-erythroid mononuclear cells, and the expression frequencies of CD38, CD71, CD33 and CD13 antigens in CD34(+)CD45(dull+)SSC(low) progenitors were all significantly decreased in AA compared to normal bone marrows (n=7) (P<0.005). In contrast, in RA bone marrows the percentages of CD34(+)CD45(dull+)SSC(low) cells showed wide distribution and the cell surface antigen expression patterns varied among each case: some cases showed low frequencies of CD38 and CD71 expression as well as AA, whereas the others showed high expression frequency of specific antigen(s) which may reflect the clonal expansion of an abnormal clone in bone marrow. An MDS patient who had progressed from RA to RAEB showed further projecting pattern of expression of CD38 and CD33 in CD34(+)CD45(dull+)SSC(low) population in accordance with the disease progression. These data suggest that analysis of cell surface antigen expression patterns of CD34(+)CD45(dull+)SSC(low) progenitor cells by multi-color flow cytometry appears to be a useful method for qualitative and quantitative assessment of marrow progenitor states in AA and RA, therefore this method could be helpful for early detection of clonal evolution in MDS.

ADP-ribosyl Cyclase↗
PubMed2000

Purification and characterization of a fibrinolytic enzyme and identification of fibrinogen clotting enzyme in a marine green alga, Codium divaricatum.

A fibrinolytic enzyme was isolated from a marine green alga, Codium divaricatum, and designated C. divaricatum protease (CDP). This protease effectively hydrolyzed fibrinogen A alpha chain, while it had very low hydrolyzing efficiency for B beta and gamma chains. This property was similar to that of alpha-fibrinogenase isolated from snake venom. Protease activity peaked at pH 9, and was completely inhibited by diisopropyl fluorophosphate (DFP) and phenylmethylsulfonyl fluoride (PMSF), identifying it as a serine protease. Its molecular form was single polypeptide structure and molecular weight was estimated as 31,000 by SDS-PAGE. Fibrinogen clotting enzyme was also identified in a fraction by ion-exchange chromatography. Analysis of clots formed by the enzyme and by thrombin by SDS-PAGE showed that the fibrinogen clotting enzyme would act like thrombin and have high substrate specificity.

Blood Coagulation↗
PubMed2000

Purification and characterization of a novel lectin from a freshwater cyanobacterium, Oscillatoria agardhii.

In the survey of 14 species of laboratory-cultured cyanobacteria for hemagglutinins, we newly detected the activity in two species, Oscillatoria agardhii, strain NIES-204, and Phormidium foveolarum, strain NIES-503. From the extract of O. agardhii, which showed the highest activity with trypsin-treated erythrocytes of rabbit, a lectin was purified to homogeneity by the combination of precipitation with (NH4)2SO4, gel filtration, hydrophobic chromatography and reverse phase chromatography. The purified lectin, designated OAA, was a monomeric protein with an apparent molecular weight of 13,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 16,000 on gel filtration. The amino acid composition was rich in glycine and acidic amino acids. The hemagglutination activity was inhibited by glycoproteins such as yeast mannan, but not by any of the monosaccharides tested. The activity was stable over a wide range of pH (4-11) and at a high temperature of 80 degrees C, and independent on the presence of divalent cations. The features of OAA resembled those of many of lectins from marine macroalgae. The sequence of amino-terminal residues of OAA was determined as ALYNVENQWGGSSAPWNEGG, which was highly homologous to those of lectins from macroalgae of the genus Eucheuma and that of a myxobacterium Myxococcus xanthus hemagglutinin.

Amino Acid Motifs↗
PubMed2000

Hepatitis G virus coinfection influences the liver histology of patients with chronic hepatitis C.

AIMS/BACKGROUND: The present investigation compared the histological features of the liver of chronic hepatitis C patients who are or are not coinfected with hepatitis G virus (HGV) to determine the histological and clinical characteristics of HGV infection. SUBJECTS AND METHODS: This study included 194 patients with chronic hepatitis C who visited our institution between 1993 and 1995. Detection of serum HGV RNA was performed by nested reverse transcription-polymerase chain reaction. Scores were assigned to indicate the severity of each of the following features on the liver biopsy of a patient: inflammatory cell infiltration in the periportal, parenchymal, and portal area; fibrous stage; lymphoid aggregates in the portal area; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; bile duct damage; bridging necrosis; and irregular regeneration of hepatocytes (IR). RESULTS: HGV RNA was detected in the sera of 18 (9.3%) of the 194 patients. The histological features of the HGV RNA-positive patients show significantly more severe bile duct damage, perivenular fibrosis, pericellular fibrosis and IR than the liver of the HGV RNA-negative patients. The biochemical results in the two groups did not significantly differ. CONCLUSION: Our data suggest that chronic HGV coinfection worsens the histological features of liver disease.

Bile Ducts↗
PubMed2000

Spontaneous reduction of leukemic lymphoma cells possibly by anti-tumor antibody-mediated phagocytosis; a kappa lambda-dual-positive B cell lymphoma.

We have investigated the possible role of anti-tumor antibody detected in a case of follicular lymphoma which demonstrated the spontaneous reduction of leukemic tumor cells. The tumor cells genotypically had monoclonal rearrangements of the immunoglobulin J H and C kappa genes, but phenotypically exhibited surface IgG, A, kappa and lambda (kappa lambda dual positivity). The culture study revealed that IgGlambda, at least, was derived from the serum, and IgAkappa was expressed intrinsically. Furthermore, the positive correlation between the densities of both surface light chains on two-color flow cytometry, the rosette formation study and its inhibition test by the Fcgamma fragment suggested that the serum IgGlambda combined with some antigens on the tumor-cell surface via its Fab portion and with the Fcgamma receptor of macrophages via its Fc portion. From these findings, we regarded the present case as an anti-tumor antibody-coated lymphoma. In addition, the phagocytic study disclosed that the serum-derived IgGlambda, at least, might have induced the phagocytosis of circulating lymphoma cells by macrophages. In conclusion, the existence of the anti-tumor antibody-coated lymphoma may be helpful in clarifying the immunological mechanism of the spontaneous regression occasionally seen in lymphomas.

Adult↗
PubMed2000

In vitro antitumor activity, intracellular accumulation, and DNA adduct formation of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II) suspended in lipiodol.

SM-11355, cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)] platinum (II), is a lipophilic platinum complex under clinical development that targets primary hepatocellular carcinoma using Lipiodol as a carrier. SM-11355 was compared with cisplatin (CDDP) using an in vitro evaluation system capable of examining the release characteristics and the cytotoxicity of drugs suspended in Lipiodol. SM-11355 suspended in Lipiodol (SM-11355/Lipiodol) and CDDP suspended in Lipiodol (CDDP/Lipiodol) showed cytotoxic activity against rat ascites hepatoma AH-109A cells in a dose-dependent manner. Their IC50 values following 7-day exposure were 22.3 and 0.40 microg/ml, respectively. Following the subsequent 7-day exposure, from day 7 to day 14 after preparation of the suspension, SM-11355/Lipiodol showed an almost equivalent activity, but CDDP/Lipiodol did not show any activity at all. SM-11355/Lipiodol showed a sustained release into the culture medium over the course of a 14-day exposure. Following the exposure to CDDP/Lipiodol, the platinum concentration in the medium was at its maximum on the first day and remained constant thereafter. Intracellular platinum uptake and formation of platinum-DNA adducts were dependent on the release characteristics of each drug suspension. For SM-11355/Lipiodol, the drug release, intracellular drug uptake, and formation of platinum-DNA adducts over the course of the subsequent 7-day exposure were similar to those observed during the first 7 days. DPC, one of the compounds released from SM-11355/Lipiodol, was taken up by cells and showed formation of platinum-DNA adducts. Thus, this study suggests that SM-11355/Lipiodol may release active platinum compound(s) that bind to nuclear DNA and mediate the cytotoxic activity of SM-11355/Lipiodol.

Animals↗
PubMed2000

Cytotoxicity of cis-[((1R,2R)-1,2-cyclohexanediamine-N,N')bis(myristato)]-platinum (II) suspended in Lipiodol in a newly established cisplatin-resistant rat hepatoma cell line.

The cytotoxic activity of cis-[((1R,2R)-1,2-cyclohexanediamine-N, N')bis(myristato)]platinum (II) (SM-11355) was evaluated in a cisplatin (CDDP)-resistant tumor cell line, and compared with that of CDDP. H4-II-E / CDDP with acquired resistance to CDDP was established by continuous exposure of a rat hepatic tumor line, H4-II-E, to increasing concentrations of CDDP over 12 months. Compared with the parental cell line, this cell line exhibited an 8.8-fold increase in resistance to CDDP and was not cross-resistant to 1,2-diaminocyclohexane platinum (II) dichloride (DPC). There were no differences in sensitivity to six non-platinum antitumor drugs between H4-II-E and H4-II-E / CDDP, which suggests that H4-II-E / CDDP is not multidrug-resistant. Intracellular platinum accumulation and the formation of a platinum-DNA adduct following CDDP exposure were significantly reduced in H4-II-E / CDDP compared to the parental cell line. The acquired CDDP resistance in H4-II-E / CDDP appeared to be predominantly due to reduced CDDP uptake. H4-II-E / CDDP was also resistant to CDDP suspended in Lipiodol (CDDP / Lipiodol), but was not cross-resistant to SM-11355 suspended in Lipiodol (SM-11355 / Lipiodol). Also, there were no differences in intracellular platinum accumulation or the formation of platinum-DNA adducts after SM-11355 / Lipiodol exposure between H4-II-E and H4-II-E / CDDP. These results suggest that acquired CDDP resistance in H4-II-E / CDDP does not influence the cytotoxic activity of SM-11355 / Lipiodol.

Animals↗
PubMed2000

IgA-lambda/IgG-kappa biclonal myeloma in which two clones proliferated in individual sites.

A 72-year-old man was admitted to our hospital because of lumbago and numbness of legs. Tumor invasion at the fourth lumbar vertebra was revealed. Immunohistochemistry using specific antibodies against each heavy and light chain of immunoglobulin revealed that the myeloma cells in bone marrow were all IgA-lambda type whereas they were all positive for IgG-kappa type in a tumor of the fourth lumbar vertebra. These data indicate that the patient had IgG-kappa/IgA-lambda biclonal myeloma. Different phenotypes of M-proteins and distinct proliferating sites for two clones suggest that they may have resulted from two independent transforming events.

Aged↗
PubMed2000

Combination of granulocyte colony-stimulating factor and low-dose cytosine arabinoside further enhances myeloid differentiation in leukemia cells in vitro.

We examined the differentiation-inducing effect on freshly isolated myeloid leukemia cells in liquid suspension culture by combined treatment with granulocyte colony-stimulating factor (G-CSF) plus low-dose cytosine arabinoside (Ara-C; 5-10 ng/ml) in 25 patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in leukemic transformation. Culture with G-CSF alone showed leukemic cell growth stimulation in 15 out of the 25 cases (60%) and induction of cell differentiation in 19 out of the 25 cases (76%), respectively. In 23 cases (92%), either growth stimulation and/or differentiation induction of leukemia cells was observed in response to G-CSF. This suggests that most myeloid leukemia cells are able to respond to G-CSF stimulation. In addition, treatment of cells with low-dose Ara-C alone resulted in the enhancement of myeloid specific antigens expression in 16 cases (64%). Treatment of leukemia cells with higher concentrations of Ara-C (over 50 ng/ml) alone resulted in cytocidal effects but not in the induction of differentiation. Furthermore, 15 cases (60%) showed pronounced myeloid differentiation of leukemia cells after combined exposure to G-CSF plus low-dose Ara-C as compared with cells treated with either G-CSF or Ara-C alone. The enhanced effect of differentiation induction by combining G-CSF plus low-dose Ara-C was also observed in a murine myeloid leukemia cell line WEHI-3B in vitro. These data suggest that treatment with G-CSF plus low-dose Ara-C is capable of inducing differentiation of leukemic cells in vitro, and also appears to be useful for the differentiation-based therapy of patients with AML and MDS.

Adult↗
PubMed2000

[Chromophobe cell renal carcinoma: a case report].

Chromophobe cell renal carcinoma is an uncommon subtype of renal cell carcinoma and the number of cases studied is still limited in Japan. We here report a case of chromophobe cell renal carcinoma in a 41-year-old Mexican male. He visited our branch hospital with the symptom of upper abdominal pain. Ultrasound examination showed a left renal mass. He was admitted to our hospital for treatment of a left renal mass. Radiological examinations revealed a hypervascular tumor in the left kidney. Under the clinical diagnosis of possible renal cell carcinoma, left radical nephrectomy was performed. This tumor was diagnosed as chromophobe cell renal carcinoma with a microscopic examination of H & E stained specimens, histochemical staining using Hale's colloidal iron and an ultrastructural study.

Adult↗
PubMed2000

[Diffuse large B-cell lymphoma showing CNS invasion by CD30-positive multinuclear giant cells mimicking the clinical features of progressive multifocal leukoencephalopathy].

We report a 55-year-old woman with diffuse large B-cell lymphoma showing central nervous system (CNS) infiltration by CD30-positive lymphoma cells. The patient was admitted with pleural effusion, ascites and a large mass in the abdominal cavity. Southern blot analysis of DNA extracted from the ascites revealed IgJH rearrangement, and therefore she was initially diagnosed as B-cell neoplasia. She received combined chemotherapy (DICE and CHOP regimens), and achieved a transient clinical response. Three months later, she developed various neurological abnormalities, and brain magnetic resonance imaging revealed diffuse infiltration of the cerebral white matter. We considered the possibility of CNS involvement by the lymphoma or progressive multifocal leukoencephalopathy (PML), and began a course of anti-virus therapy and radiation therapy. Because multiple lumbar punctures demonstrated large multinuclear lymphoma cells in the cerebrospinal fluid, a diagnosis of metastatic CNS lymphoma was made. Immunohistochemistry revealed that these lymphoma cells were reactive with anti-CD30 antibody. Although the radiation therapy was temporarily effective against the CNS involvement, the patient died of systemic invasion of the lymphoma cells. The final diagnosis was diffuse large B-cell lymphoma on the basis of pathologic findings, immunohistochemistry, and Southern blot analysis using a mesenteric lymph node obtained at autopsy. Cytospin preparations and immunohistochemistry of specimens obtained from frequent lumbar punctures were useful for differentiating CNS lymphoma from PML.

Brain Neoplasms↗
PubMed2000

[Rapidly progressive fibrosis and increased CD68-positive cells in the bone marrow at the terminal stage of adult T-cell leukemia accompanied by polycythemia vera].

We report a case of adult T-cell leukemia (ATL) accompanied by polycythemia vera (PV) in which rapid development of myelofibrosis and clinical features of hemophagocytic syndrome (HPS) were observed at the terminal stage. The patient, a 53-year-old man who was born in Oita Prefecture, Japan, was diagnosed as having PV in 1996. He had undergone venesection but had not received any chemotherapy. In June 1997, he showed systemic lymphadenopathy with positivity for serum HTLV-1 antibody (x 10,240). Pathological findings and Southern blotting analysis for detection of monoclonal integration of HTLV-1 provirus DNA in a lymph node biopsy sample revealed that he also had acute-type ATL. Although several courses of chemotherapy were transiently effective, high fever, pancytopenia, increased serum LDH, hypoproteinemia and hyperferritinemia appeared, all of which were compatible with the clinical features of HPS. In addition, cytomegalovirus infection became evident. He died of multiple organ failure with rapid progression of myelofibrosis in May 1998. Detection of both increased CD68-positive histiocytes by immunohistochemistry and iron-stained phagocytic cells in marrow biopsy specimens appeared to be helpful for diagnosis of HPS in this patient, whose marrow showed myelofibrosis with hypocellularity.

Antigens, CD↗
PubMed1999

Large-Scale Mapping Observations of the C i (3P1-3P0) and CO (J = 3-2) Lines toward the Orion A Molecular Cloud.

Large-scale mapping observations of the 3P1-3P0 fine-structure transition of atomic carbon (C i, 492 GHz) and the J=3-2 transition of CO (346 GHz) toward the Orion A molecular cloud have been carried out with the Mount Fuji submillimeter-wave telescope. The observations cover 9 deg2 and include the Orion Nebula M42 and the L1641 dark cloud complex. The C i emission extends over almost the entire region of the Orion A cloud and is surprisingly similar to that of 13CO (J=1-0). The CO (J=3-2) emission shows a more featureless and extended distribution than C i. The C i/CO (J=3-2) integrated intensity ratio shows a spatial gradient running from the north (0.10) to the south (1.2) of the Orion A cloud, which we interpret as a consequence of the temperature gradient. On the other hand, the C i/13CO (J=1-0) intensity ratio shows no systematic gradient. We have found a good correlation between the C i and 13CO (J=1-0) intensities over the Orion A cloud. This result is discussed on the basis of photodissociation region models.

Journal Article↗
PubMed1999

p38 mitogen-activated protein kinase regulates human T cell IL-5 synthesis.

Involvement of p38 mitogen-activated protein (MAP) kinase in human T cell cytokine synthesis was investigated. p38 MAP kinase was clearly induced in human Th cells activated through the TCR. SB203580, a highly selective inhibitor of p38 MAP kinase, inhibited the induction of p38 MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4, IL-5, and IFN-gamma, were produced by Der f 2-specific Th clones upon stimulation through the TCR. IL-5 synthesis alone was significantly inhibited by SB203580 in a dose-dependent manner, whereas the production of IL-2, IL-4, and IFN-gamma was not affected. The proliferation of activated T cells was not affected. IL-5 synthesis of human Th clones induced upon stimulation with rIL-2, phorbol ester plus anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble anti-CD28 mAb was also suppressed by SB203580 in the same concentration response relationship. The results clearly indicated that IL-5 synthesis by human Th cells is dependent on p38 MAP kinase activity, and is regulated distinctly from IL-2, IL-4, and IFN-gamma synthesis. Selective control of IL-5 synthesis will provide a novel treatment devoid of generalized immune suppression for bronchial asthma and atopic dermatitis that are characterized by eosinophilic inflammation.

Clone Cells↗