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Biomedical subjects

K Miyazawa

Publications and source records attributed to K Miyazawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Re-evaluation of refractory anemia with excess blasts in transformation.

The category 'refractory anemia with excess blasts in transformation (RAEBt)' consists of two sub-sets; one group is categorized based on the percentage of blasts in the marrow (> or =20%) and other is based on the percentage of blasts in the peripheral blood (> or =5%). We separated RAEBt patients based on these two criteria and compared hematologic and clinical relevance to assess the reasonable basis for the new classification. All RAEBt patients showing peripheral blood (PB) blasts of > or =5% were re-classified as RAEB by the WHO classification. This subset of RAEBt patients had lower percentages of bone marrow (BM) blasts, and notably they showed frequent complex cytogenetic abnormalities, including -5/5q- and/or -7/7q-. Moreover, the RAEBt patients of this group had shorter survivals compared to RAEBt patients with BM blasts between 20 and 30%. We next assessed hematologic and clinical relevance between refractory anemia with excess blasts (RAEB) and RAEBt patients with PB blasts of > or =5%. Except for the percentage of blasts in the PB (P=0.0037) and BM (P=0.0073), there was no significant difference in hematologic or clinical features between RAEB patients with BM blasts of > or =11% and RAEBt patients with PB blasts of > or =5%. When MDS patients with PB blasts of > or =5% (RAEBt by the FAB classification) were included as RAEB-II based on the "MDS 2000 classification', there was a high frequency of patients with complex chromosome changes, involving 5q and 7q, with significant poorer outcome compared to those with RAEB-I. Although it is still controversial whether MDS patients with BM blasts 20% or more should be considered as acute leukemia, the utilization of the 'MDS 2000 classification' might be useful to designate MDS patients diagnosed based on the percentage of blasts in the peripheral blood.

Adult↗
PubMed2001

Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells: dichotomous nature of vitamin K2 in leukemia cells.

We originally reported that vitamin K2 (VK2) analogs, including menaquinone 4 (MK4) but not vitamin K1, effectively induce apoptosis in various types of primary cultured leukemia cells and leukemia cell lines in vitro. It has also been reported by others that VK2 showed the differentiation-inducing activity in leukemia cell lines. To investigate the discrepancy between apoptosis- and differentiation-inductions of leukemia cells by VK2 treatment, we used bcl-2 gene transfected HL-60 cells (HL-60-bcl-2) which resulted in five-fold over-expression of BCL-2 protein, and then compared the effects of MK4 to the control HL-60-neo cells. Seventy-two hours of exposure to various concentrations of MK4 resulted in growth inhibition of these cells in a dose-dependent manner (0.1-50 microM), however, HL-60-bcl-2 was less sensitive against MK4. MK4 potently induced apoptosis of HL-60-neo cells along with the depolarization of mitochondrial membrane potential and caspase-3 activation. Notably, HL-60-bcl-2 was almost completely resistant to apoptosis induction in response to MK4, although cell growth inhibition was still observed. In spite of the abrogation of apoptosis induction, about 90% of HL-60-bcl-2 cells were arrested in the G0/G1 phase within 48 h of exposure to 10 microM of MK4 accompanied by up-modulation of p27KIP1 expression. Concomitantly, HL-60-bcl-2 cells underwent monocytic differentiation. These data suggest that VK2 also shows the differentiation inducing effects on leukemia cells which are resistant against VK2-inducing apoptosis. The dichotomous nature of VK2 against leukemia cells appears to have clinical benefits for the treatment of patients with leukemias and myelodysplastic syndromes.

Apoptosis↗
PubMed2001

Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T-cell receptor gene rearrangements.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report four patients with MDS with erythroid hypoplasia who received immunosuppressive therapy. All were elderly, had severe transfusion-dependent anaemia, morphological evidence of myelodysplasia and a low percentage (3.2-13.6%) of erythroid precursors. Administration of cyclosporin A (CsA) improved their anaemia; all transfusion-dependent patients achieved transfusion-independence. An inverted CD4/8 ratio was seen in three patients who also demonstrated T-cell receptor (TCR)-beta and -gamma gene rearrangements by Southern blotting and clonality by polymerase chain reaction. Treatment with CsA can be an attractive alternative treatment for patients with MDS with erythroid hypoplasia, which may be associated with a clonal abnormality in T cells.

Aged↗
PubMed2001

Usefulness of Dennis Colorectal Tube in endoscopic decompression of acute, malignant colonic obstruction.

BACKGROUND: Colonoscopic decompression has been attempted in patients with acute colonic obstruction caused by colon cancer to avoid emergency surgery and multiple subsequent operations but has usually been unsuccessful. This is an evaluation of the usefulness of a new device for endoscopic decompression in these patients. METHODS: Nine consecutive patients (6 men, 3 women; 65 to 89 years of age) with acute colonic obstruction resulting from colon cancer underwent endoscopic decompression with a Dennis Colorectal Tube. RESULTS: In all 9 patients (1 with carcinoma of the sigmoid colon, 3 with carcinoma of descending colon, 2 with carcinoma of the transverse colon, 2 with carcinoma of the ascending colon, and 1 with carcinoma of the cecum), endoscopic decompression was successful. After decompressing and cleansing the colon for several days, a one-stage operation was possible in all patients. CONCLUSION: Dennis Colorectal Tube is an excellent device for endoscopic decompression of acute, malignant colonic obstruction.

Acute Disease↗
PubMed2001

A resin veneer for enamel protection during orthodontic treatment.

The aims of this study were to test the tensile bond strength of a recently developed veneer. Sound premolar teeth (120) extracted for orthodontic purposes were divided into two experimental and two control groups. In one experimental group (V1) 4-META/MMA-TBB resin (4META) was used on the surface veneer prepared with micro particle filled resin (MFR) as an adhesive for bracketing and in the second group (V2) 4META was applied on the surface veneer with the trial resin. For the controls, in group R 4META was used on the enamel surface without veneer and in group G light-cured glass ionomer cement was applied. The 30 samples in each group were divided into three groups of 10 samples and thermal cycled (TC) at 3000, 10,000 or left uncycled. Tensile testing was carried out using an Instron machine. After tensile testing the bond failures in the experimental groups were recorded using a stereomicroscope. Statistical analysis was performed using ANOVA. In group V2 the resin veneer was able to maintain sufficient bond force to enamel during clinical use. The bond strength of group V1 was significantly higher than that of groups R (P < 0.05) and G (P < 0.01) at TC 0, but for both TC 3000 and 10,000, the bond strength of group V1 was lower than groups R and G, respectively. There were significant differences between groups V1 and R (P < 0.01) for TC 3000, and between groups V1 and R and G (P < 0.01) at TC 10,000. The bond strength of group V2 was almost equal to that of group R at TC 0. At TC 3000, group V2 showed significantly lower bond strength than group R (P < 0.05), but no significant difference was found compared with group G. At TC 10,000, there were no significant differences between groups V2, R or G. When comparing groups V1 and V2, the bond strength of group V1 was significantly higher than that of group V2 (P < 0.01) at TC 0, but the bond strength of group V1 was significantly lower than that of group V2 for both TC 3000 (P < 0.05) and TC 10,000 (P < 0.01). Comparison between groups R and G, showed that the bond strength of group R was significantly higher than that of group G for both TC 0 (P < 0.01) and TC 3000 (P < 0.01), but no significant difference was found for TC 10,000. In group V2, nine samples showed adhesive failure between the veneer surface and bracket adhesive before thermal cycling. There were significant differences between the MFR and both trial resin and glass ionomer cement (P < 0.01) when examining thermal expansion. No significant difference was found between the trial resin and glass ionomer cement. It is suggested that application of a resin veneer prior to bracket bonding is suitable for clinical application to protect the teeth and to prevent decalcification and caries.

Acrylic Resins↗
PubMed2001

Deletion of mitochondrial ATPase inhibitor in the yeast Saccharomyces cerevisiae decreased cellular and mitochondrial ATP levels under non-nutritional conditions and induced a respiration-deficient cell-type.

T(1), a mutant yeast lacking three regulatory proteins of F(1)F(o)ATPase, namely ATPase inhibitor, 9K protein and 15K protein, grew on non-fermentable carbon source at the same rate as normal cells but was less viable when incubated in water. During the incubation, the cellular ATP content decreased rapidly in the T(1) cells but not in normal cells, and respiration-deficient cells appeared among the T(1) cells. The same mutation was also induced in D26 cells lacking only the ATPase inhibitor. Overexpression of the ATPase inhibitor in YC63 cells, which were derived from the D26 strain harboring an expression vector containing the gene of the ATPase inhibitor, prevented the decrease of cellular ATP level and the mutation. Isolated T(1) mitochondria exhibited ATP hydrolysis for maintenance of membrane potential when antimycin A was added to the mitochondrial suspension, while normal and YC63 mitochondria continued to show low hydrolytic activity and low membrane potential. Thus, it is likely that deletion of the ATPase inhibitor induces ATPase activity of F(1)F(o)ATPase to create a dispensable membrane potential under the non-nutritional conditions and that this depletes mitochondrial and cellular ATP. The depletion of mitochondrial ATP in turn leads to occurrence of aberrant DNA in mitochondria.

Adenosine Triphosphate↗
PubMed2001

Myelodysplastic syndrome accompanied by Addison's disease and multiple autoimmune phenomena: steroid therapy resolved cytopenias and all immune disorders.

We report here a patient with myelodysplastic syndromes (MDS), which was complicated with several autoimmune disorders and asymptomatic immunologic abnormalities. An 82-year-old woman with refractory anemia (RA) rapidly developed thrombocytopenia with the appearance of symptoms such as purpura, fatigue, anorexia, and weight loss. Furthermore, clinical examinations revealed that she also had Addison's disease, rheumatoid arthritis, and autoimmune hematological diseases such as thrombocytopenia and hemolytic anemia. However, the cytopenia and all autoimmune disorders were remarkably improved after she received steroid therapy.

Addison Disease↗
PubMed2001

MALT lymphoma originating in breast and uvula.

A case of marginal zone B cell lymphoma of MALT type arising in the uvula and breast is reported. The patient, a 30-year-old woman who delivered a child and lactated in 1997, was suffering from Sjögren syndrome (SS). She was diagnosed with MALT lymphoma after a biopsy of the right breast and uvula. To investigate the relationship of the delivery, lactation and MALT lymphoma, we examined the immunohistochemical analysis of hormone receptors. As a result, lymphoid cells of the breast were stained with anti-progesterone receptor antibodies in the cytoplasm. Consequently, the MALT lymphoma of the uvula appeared to be associated with SS. Moreover, hormones such as progesterone may have influenced the breast involvement of MALT lymphoma in our case.

Adult↗
PubMed2000

Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment.

Hepatocyte growth factor activator (HGFA) is responsible for proteolytic activation of the precursor form of hepatocyte growth factor in injured tissues. To date, two specific inhibitors of HGFA have been identified, namely HGFA inhibitor type 1 (HAI-1) and type 2 (HAI-2)/placental bikunin (PB). Both inhibitors are first synthesized as integral membrane proteins having two Kunitz domains and a transmembrane domain, and are subsequently released from cell surface by shedding. Here we show that an active form of HGFA is specifically complexed with membrane-form HAI-1, but not with HAI-2/PB, on the surface of epithelial cells expressing both inhibitors. This binding required the enzyme activity of HGFA. The selective binding of HGFA to the cell surface HAI-1 was further confirmed in an engineered system using Chinese hamster ovary cells, in which only the cells expressing HAI-1 retained exogenous HGFA. The binding of HGFA to HAI-1 was reversible, and no irreversible modifications affecting the enzyme activity occurred during the binding. Importantly, HAI-1 and the HGFA.HAI-1 complex were quickly released from the cell surface by treatment with phorbol 12-myristate 13-acetate or interleukin 1beta accompanying the generation of 58-kDa fragments of HAI-1, which are less potent against HGFA, as well as significant recovery of HGFA activity in the culture supernatant. This regulated shedding was completely inhibited by BB3103, a synthetic zinc-metalloproteinase inhibitor. We conclude that HAI-1 is not only an inhibitor but also a specific acceptor of active HGFA, acting as a reservoir of this enzyme on the cell surface. The latter property appears to ensure the concentrated pericellular HGFA activity in certain cellular conditions, such as tissue injury and inflammation, via the up-regulated shedding of HGFA.HAI-1 complex. These findings shed light on a novel function of the integral membrane Kunitz-type inhibitor in the regulation of pericellular proteinase activity.

Animals↗
PubMed2000

A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP.

Hrs-binding protein (Hbp) is a Src homology 3 (SH3) domain-containing protein that tightly associates with Hrs. Hbp together with Hrs is thought to play a regulatory role in endocytic trafficking of growth factor-receptor complexes through early endosomes. Association of Hbp with a binding partner(s) via the SH3 domain seems to be essential for Hbp to exert its function. In this study, we searched for Hbp-binding proteins by a far Western screening and isolated a mouse cDNA clone encoding a deubiquitinating enzyme mUBPY as an Hbp SH3-binding protein. mUBPY has two Hbp-SH3 domain binding sites. Mutagenic analysis identified a consensus sequence PX(V/I)(D/N)RXXKP as the Hbp-SH3 domain binding motif. It is a novel SH3-binding motif and does not contain the canonical proline-rich consensus binding motif, PXXP. Ubiquitination of growth factor receptors is thought to regulate their intracellular degradation. Thus, UBPY may play a regulatory role in the degradation by interaction with the SH3 domain of Hbp via the novel SH3-binding motif.

3T3 Cells↗
PubMed2000

A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation.

During development, control of proliferation of neuronal precursor cells plays a crucial role in determining the number of neurons. Proliferation is driven by mitogens, but how it is terminated remains a mystery. In this study, we examined the role of cyclin-dependent kinase inhibitors in the control of proliferation of cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell lineage in the developing and adult cerebellum. In developing cerebella, p27 was expressed in the external germinal layer (the deeper regions), the molecular layer, and the granule layer. In adult cerebella, p27 was expressed in the cells of the granule layer. We isolated and purified GCPs from cerebella of developing mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at various times. We found that there was an inverse correlation between BrdU uptake and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog, a potent mitogen, the cells eventually stopped dividing and differentiated, expressing p27 strongly. We also examined mice in which one or both copies of the p27 gene have been inactivated by targeted gene disruption and found that their cerebella were larger than those of wild-type mice. In cell cultures, GCPs prepared from p27-deficient mice showed enhanced proliferation compared with GCPs from wild-type mice. Taken together, these results suggest that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism.

Age Factors↗
PubMed2000

Mouse hepatocyte growth factor activator gene: its expression not only in the liver but also in the gastrointestinal tract.

A cDNA encoding mouse hepatocyte growth factor activator (HGFA) has been cloned by RT-PCR, based on the screening result from the database of expressed sequence tags. Subsequently, its gene was cloned from a mouse genomic bacterial artificial chromosome library using the cDNA as a probe. Sequencing analysis revealed that mouse HGFA protein deduced from the cDNA, similar to its human and rat counterparts, has two epidermal growth factor-like domains, type 1 and 2 fibronectin homology domains, a single kringle domain and a catalytic domain of serine proteinase, and the gene consists of 14 exon spanning approximately 7.5 kb. Interestingly, mouse HGFA mRNA was detected not only in the liver but also in the gastrointestinal tract by RNA blot analysis. Since hepatocyte growth factor (HGF) is up-regulated in the damaged gastrointestinal mucosa, our present data suggest that HGFA might activate proHGF directly in the gastrointestinal mucosa and play an important role in wound repair throughout the gastrointestinal tract.

Amino Acid Sequence↗
PubMed2000

Primary structures of two hemagglutinins from the marine red alga, Hypnea japonica.

As the first examples among marine algal hemagglutinins, the primary structures of two hemagglutinins, named hypnin A-1 and A-2, from the red alga Hypnea japonica, were determined by Edman degradation. Both hemagglutinins were single-chain polypeptides composed of 90 amino acid residues including four half-cystines, all of which were involved in two intrachain disulfide bonds, Cys(5)-Cys(62) and Cys(12)-Cys(89). Hypnin A-1 and A-2 had calculated molecular masses of 9146.7 and 9109.7 Da which coincided with determined values, 9148 and 9109 Da, by electrospray ionization-mass spectrometry, respectively. Both hemagglutinins only differed from each other at three positions; Pro(19), Arg(31) and Phe(52) of hypnin A-1 as compared with Leu(19), Ser(31), and Tyr(52) of hypnin A-2. Approximately 43% of total residual numbers consisted of three kinds of amino acids: serine, glycine and proline. The hemagglutination activities were lost by reduction and alkylation of the disulfide bonds. The nature of the small-sized polypeptides, including disulfide bonds, may contribute to the extreme thermostability of the hemagglutinins. Sequence having overall similarity to hypnin A-1 or A-2 was not detected in databases. Unexpectedly, however, hypnins contained a motif similar to the alignment of the C-terminal conserved amino acids within carbohydrate-recognition domains of C-type animal lectins. Furthermore, interestingly, the hemagglutination activities were inhibited by a protein, phospholipase A-2 besides some glycoproteins, suggesting that hypnins may possess both a protein-recognition site(s) and a carbohydrate-recognition site(s).

Amino Acid Sequence↗
PubMed2000

Predimerization of recombinant platelet-derived growth factor receptor extracellular domains increases antagonistic potency.

Platelet-derived growth factor (PDGF) is a dimeric growth factor acting through tyrosine kinase alpha- and beta-receptors. In both receptors, the extracellular parts are composed of five Ig-like domains. Functional mapping of the extracellular part of the receptors have shown that ligand-binding occurs to Ig-like domains 2 and 3 and that Ig-like domain 4 is involved in receptor-receptor interactions. Recombinant GST-fusion proteins of PDGF alpha-receptor Ig-like domains 1-4 and beta-receptor Ig-like domains 1-3 (alphaRD1-4-GST and betaRD1-3-GST) were generated and compared with their cleaved counterparts (alphaRD1-4 and betaRD1-3) with regard to their ability to block PDGF binding to cell surface receptors. In the case of both the alpha- and the beta-receptors, 100-1000-fold lower concentrations of the GST-fusion proteins were required, as compared to the cleaved forms, for inhibition of PDGF binding to cell surface receptors. alphaRD1-4-GST and betaRD1-3-GST, in contrast to alphaRD1-4 and betaRD1-3, were shown to occur as ligand independent dimers. Covalently cross-linked alphaRD1-4 dimers displayed a 50-fold increased potency as compared to alphaRD1-4. We thus conclude that the dimeric nature of alphaRD1-4-GST and betaRD1-3-GST is responsible for the high antagonistic potency of the fusion proteins.

Animals↗