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Y Kazama

Publications and source records attributed to Y Kazama.

At least 19 recordsLinked to original sources
PubMed2001

Genomic structure and promoter activity of the human tissue factor pathway inhibitor-2 gene.

Human type-2 tissue factor pathway inhibitor (TFPI-2), also known as placental protein 5, is a 32 kDa serine proteinase inhibitor consisting of three tandemly arranged Kunitz-type inhibitor domains homologous to tissue factor pathway inhibitor. TFPI-2 strongly inhibits a wide variety of serine proteinases including trypsin, chymotrypsin, plasmin, kallikrein and blood coagulation factor XIa. In this study, we have isolated and characterized a genomic clone from an artificial chromosome genomic library that encodes the entire human TFPI-2 gene. The human TFPI-2 gene spans approximately 7 kb and consists of five exons and four introns. Each Kunitz-type domain is encoded by a single exon, similar to that observed for murine TFPI-2 and other Kunitz-type proteinase inhibitors. A total of 535 bp of the 3'-flanking region contain two probable polyadenylation sites (AATAAA) at +4297 and +4314. A single transcription initiation site was identified by oligo-capping and reverse transcription-PCR analysis. Transient transfection of reporter plasmids containing segments of the 5'-flanking region into human transformed bone marrow endothelial cells and glioblastoma cells identified an 85 bp region (-224 to -139) sufficient for transcription of the human TFPI-2 gene.

Amino Acid Sequence↗
PubMed2001

Myelodysplastic syndrome progresses rapidly into erythroleukemia associated with synchronous double cancers of the stomach and the papilla of Vater.

Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of developing cancers. However, it is extremely rare that synchronous double cancers develop in an MDS patient. We report a case of MDS that progressed rapidly into erythroleukemia (M6 by French-American-British classification) complicated by gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with refractory anemia with excess of blasts in transformation [RAEB-T]) was made by bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric cancer was also diagnosed by endoscopic examination. The peripheral blasts gradually proliferated and the disease progressed to M6. A chromosome abnormality 46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen was started as a remission-induction therapy. However, obstructive jaundice developed and a marked dilatation of bile ducts was observed by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was detected by endoscopy. As remission was achieved and the pancytopenia improved, the patient subsequently underwent a surgical jejuno-choledochostomy to manage the jaundice. However, the leukemia relapsed thereafter and additional chromosome abnormalities including der(5)t(5;10)(p15:q11) were observed.

Aclarubicin↗
PubMed2001

Brain metastases of malignant melanoma showing unbalanced whole arm chromosomal translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10) in a Japanese patient.

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).

Aged↗
PubMed2001

[Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus in a patient with sarcoidosis].

Occurrence of autoimmune diseases with sarcoidosis is well known. However, a case in which more than one of these diseases coexist with sarcoidosis is rare. We present a young man with suspected sarcoidosis, complicated by idiopathic thrombocytopenic purpura (ITP) and type 1 A diabetes mellitus (DM). A 21-year-old man was admitted to our hospital because of thrombocytopenia, hyperglycemia, and bilateral hilar lymphadenopathy (BHL). Although a histological proof could not be obtained, the patient was considered to have sarcoidosis because 67-gallium scintigraphy disclosed "Lambda" and "Panda" signs which are highly specific for sarcoidosis. Type 1 A DM was also diagnosed as the patient had antiglutamic acid decarboxylase antibodies. The patient disclosed no hepatosplenomegaly or no lymphadenopathy and diagnosis of ITP was confirmed by bone marrow examination. High dose steroid was started as the thrombocytopenia progressed. The platelet number increased satisfactorily and shrinkage of BHL was also observed with the therapy.

Adult↗
PubMed2000

Nucleotide sequence of the gene encoding murine tissue factor pathway inhibitor-2.

Tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein 5, is a 32 kDa extracellular matrix-associated serine proteinase inhibitor consisting of three tandemly-arranged Kunitz-type domains. Two overlapping genomic clones containing sequences encoding murine TFPI-2 were isolated from a lambda FIXII 129 SVJ mouse genomic library, and the complete nucleotide sequence of the gene was determined. The murine TFPI-2 gene spans approximately 9.3 kilobases and consists of five exons and four introns. The nucleotide sequences surrounding all the exon-intron boundaries are highly conserved and obey the GT-AG rule. Each Kunitz-type domain is encoded by a single exon, similar to that observed for other Kunitz-type proteinase inhibitors. A total of 1,577 bp of the 3'-flanking region contains a probable polyadenylation site (ATTAAA) at +5,759 and an apparent cleavage or termination site (CATTG) at +6,170. The 5'-flanking region of the murine TFPI-2 gene contains a prototypical TATA box, a GC box and two CAAT boxes. In addition, several candidate transcription factor binding sites responsible for placenta-, endothelial cell-, and smooth muscle cell-specific expression of the TFPI-2 gene were also identified.

Amino Acid Sequence↗
PubMed1998

Relationship between MLR blocking antibodies and the outcome of the third pregnancy in patients with two consecutive spontaneous abortions.

To determine the relationship between mixed lymphocyte culture reaction (MLR) blocking antibodies (BAbs), immunological humoral factors, which generated in pregnant women and the outcome of pregnancy, the natural outcome of the third pregnancy in fifty-five patients with primary twice consecutive abortion was evaluated, and MLR-BAbs in sera were examined during their third pregnancy. The third pregnancy in 39 of 55 patients (70.9%) continued successfully, and remaining 16 patients (29.1%) experienced repeated abortion at the first trimester. Out of these 55 patients, MLR-BAbs were examined in 27 (17 with successful outcome and 10 with repeated abortion). The positive rate of MLR-BAbs was 82.4% in patients with successful outcome (15 of 17 cases), and that in patients with repeated abortion was 10% (one of 10 cases). The positive rate of MLR-BAbs was significantly higher in the successful pregnancy group compared with that in the repeated abortion group (p < 0.001). The blocking effect on MLR significantly increased along with the prenatal course in patients with successful outcome. Thus, MLR-BAbs are strongly associated with the outcome of pregnancy in patients with primary twice consecutive spontaneous abortions.

Abortion, Habitual↗
PubMed1997

The importance of the binding of factor Xa to phospholipids in the inhibitory mechanism of tissue factor pathway inhibitor: the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory action of tissue factor pathway inhibitor.

To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhibited by TFPI-factor Xa complex in the presence of phospholipids, but was not in the absence of phospholipids. In addition, TFPI did not inhibit factor VIIa-TF1-219 activity in the presence of gamma-carboxyglutamic acid-domainless factor Xa. The ability of TFPI-factor Xa complex to inhibit factor VIIa-TF1-219 activity was totally dependent on the presence of phospholipids and was neutralized by prothrombin fragment 1 in a dose-dependent manner. These results indicate that the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory mechanism of TFPI and confirm that the binding of factor Xa to phospholipids through its gamma-carboxyglutamic acid domain is essential for this reaction.

Anticoagulants↗
PubMed1995

Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation.

Previous studies have shown that hepsin is a putative membrane-associated serine protease that is required for cell growth (Torres-Rosado, A., O'Shea, K. S., Tsuji, A., Chou, S.-H., and Kurachi, K. (1993) Proc. Natl. Acad. Sci. U.S. A. 90, 7181 7185). In the present study, we have transfected baby hamster kidney (BHK) cells with a plasmid containing the cDNA for human hepsin and examined these cells for their ability to activate several blood coagulation factors including factors X, IX, VII, prothrombin, and protein C. Little, if any, proteolytic activation of factors X, IX, prothrombin, or protein C was observed when these clotting factors were incubated with hepsin-transfected cells. On the other hand, hepsin-transfected cells proteolytically activated significant concentrations of human factor VII in a time- and calcium-dependent manner, whereas essentially no activation of factor VII was observed in BHK cells transfected with plasmid lacking the cDNA for hepsin. The factor VII activating activity in the hepsin-transfected BHK cell line was confined exclusively to the total membrane fraction and was inhibited > 95% by antibody raised against a fusion protein consisting of maltose-binding protein and the extracellular domain of human hepsin. An active site factor VII mutant, S344A factor VII, was cleaved as readily as plasma-derived factor VII by hepsin-transfected cells, indicating that factor VII was not converted to factor VIIa autocatalytically on the cell surface. In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. In the copresence of factor VII and factor X, hepsin-transfected BHK cells supported the formation of factor Xa. In addition, in the copresence of factor VII, factor X, and prothrombin, hepsin-transfected BHK cells supported the formation of thrombin. These results strongly suggest that membrane-associated hepsin converts zymogen factor VII to factor VIIa, which in turn, is capable of initiating a coagulation pathway on the cell surface that ultimately leads to thrombin formation.

Animals↗
PubMed1993

Isolation and characterization of proteolytic fragments of human factor VIIa which inhibit the tissue factor-enhanced amidolytic activity of factor VIIa.

The interaction of circulating factor VII/VIIa with tissue factor presented by cells in extravascular tissues represents the initial event in the extrinsic pathway of blood coagulation. To determine the tissue factor binding domains in human factor VIIa, we have subjected recombinant human factor VIIa to tryptic digestion and isolated two proteolytic fragments (molecular mass = 32 and 20 kDa) by a combination of immunoaffinity chromatography and reversed phase high performance liquid chromatography (HPLC) which strongly inhibits the tissue factor-enhanced amidolytic activity of factor VIIa and inhibits the activation of factor X by factor VIIa in the presence of tissue factor. The 32-kDa factor VIIa fragment consisted of residues 1-137/143 from the light chain of factor VIIa connected by a disulfide bond to residues 153-277 from the heavy chain. The 20-kDa factor VIIa fragment consisted of residues 1-137 of the light chain of factor VIIa in disulfide linkage with residues 248-266 of the heavy chain. The 32- and 20-kDa factor VIIa fragments inhibited the tissue factor apoprotein-enhanced factor VIIa amidolytic activity with Ki values of 35 and 65 nM, respectively. The Ki values for the inhibition of relipidated tissue factor apoprotein-enhanced factor VIIa amidolytic activity by the 32- and 20-kDa factor VIIa fragments were 70 and 610 nM, respectively. Factor X activation by factor VIIa-relipidated tissue factor was inhibited half-maximally by the 32- and 20-kDa factor VIIa fragments at 65 and 680 nM concentrations, respectively. Equilibrium binding studies indicated that the 32- and 20-kDa factor VIIa fragments interacted with cell surface tissue factor expressed on J82 cells in a specific and saturable manner with Kd values of 30 and 64 nM, respectively. In addition, a peptide consisting of residues 1-109 from the light chain of factor VIIa obtained by reduction and HPLC of the 20-kDa factor VIIa fragment retained inhibitory activity, but the selective removal of the gamma-carboxyglutamic acid domain from the 20-kDa factor VIIa fragment by cathepsin G cleavage resulted in the complete loss of inhibitory activity in this fragment. Our data strongly suggest that the epidermal growth factor-like domains covalently linked to the gamma-carboxyglutamic acid domain in factor VIIa constitute the high affinity tissue factor binding domain in this molecule.

Amino Acid Sequence↗
PubMed1993

Tissue factor pathway inhibitor and protease nexin-1 are major factor Xa binding proteins on the HepG2 cell surface.

Previous studies indicated that human factor Xa bound to a human hepatocellular carcinoma cell line (HepG2) that constitutively synthesizes a factor V/Va molecule. Factor Xa binding to this cell line was not measurably affected by pretreatment of the cells with anti-factor V IgG and to a large extent (approximately 70%) was calcium-independent, suggesting the presence of cell-surface binding proteins specific for factor Xa other than factor V/Va. In the present study, we have further characterized the interaction of factor Xa with the HepG2 cell and performed chemical cross-linking and immunoprecipitation studies to determine the identity of the HepG2 surface protein(s) interacting with factor Xa. Initial studies demonstrated that HepG2-bound 125I-factor Xa was not significantly displaced by unlabeled factor Xa blocked at the active site with dansyl-L-glutamyl-glycyl-L-arginine (DEGR)-chloromethyl ketone (DEGR-Xa), whereas DEGR-Xa effectively inhibited prothrombinase activity of cell-bound factor Xa (Ki = 5 nmol/L). Essentially no 125I-DEGR-Xa binding to the HepG2 cells was observed, suggesting that an intact factor Xa active site was a prerequisite for binding. 125I-factor Xa binding to HepG2 cells was inhibited approximately 70% by pretreatment of the cells with anti-tissue factor pathway inhibitor (TFPI) IgG in the presence or absence of calcium ions, but was without effect on the expression of prothrombinase activity. Immunoprecipitation of 125I-factor Xa chemically cross-linked to its cell-surface binding protein with anti-factor X IgG followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a complex with an apparent molecular weight of 96,000. An identical molecular weight complex was observed following immunoprecipitation of this radiolabeled complex with anti-TFPI IgG. In addition to TFPI, approximately 30% of cell-bound factor Xa appears to form a covalent complex with HepG2 cell-surface protease nexin-1 (PN-1) as shown by pretreatment of the HepG2 cell with murine anti-PN-1 IgG. These results suggest that approximately 1% to 2% of the factor Xa interacts with HepG2 cell-surface factor V/Va to form a productive prothrombinase complex, while the remaining factor Xa forms a non-productive complex with either TFPI or PN-1.

Amyloid beta-Protein Precursor↗
PubMed1993

Ultrasonographic detection of a live fetus in recurrent spontaneous abortion during the first trimester.

To examine whether recurrent spontaneous abortion (RSA) can be distinguished from repeated sporadic spontaneous abortion, the clinical course of 38 cases with three or more consecutive and unexplained first trimester RSAs were retrospectively investigated in this study. For comparison with controls, the clinical course was examined of 38 fertile females, who had had sporadic abortions. In 19 (50%) RSAs and 6 (16%) controls, fetal cardiac activity was demonstrated by ultrasound during the course of pregnancy. The rate of detection of live fetus during pregnancy or at 8 weeks +/- 7 days gestation, was significantly greater in the RSA group compared to the control. The rate of vaginal bleeding before spontaneous abortion was significantly less in the RSA group than in the control group. There was no difference between the two groups in age or gestational age at spontaneous abortion. The patients with RSA were all examined for antiphospholipid antibodies in their sera and these were detected in eight of them. However, there was no difference in the rate of positive fetal cardiac activity between the RSA patients who tested positive or negative for antibody. These results reveal that the clinical course of RSA is very different from the course of sporadic abortion. Although sporadic abortion is a common complication of pregnancy, RSA is not a random repeated abortion, but rather a separate disease from sporadic abortion in normal fertile females.

Abortion, Habitual↗
PubMed1993

Is an additional vaccination necessary for a successful second pregnancy in unexplained recurrent aborters who were successfully immunized with their husband's lymphocytes before the first pregnancy?

PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy? METHODS: The successive pregnancy outcome was analyzed in 22 patients out of 29 unexplained recurrent aborters who had undergone immunotherapy with their husband's lymphocytes according to our previously reported protocol (Takakuwa et al., Am J Reprod Immunol Microbiol. 10:1-9, 1986; Takakuwa et al., Am J Reprod Immunol. 23:37-41, 1990) and had obtained successful outcome between January 1983 and December 1989. In addition, the alteration of blocking antibodies (BAbs), which was evaluated by a one-way mixed lymphocyte culture reaction (MLR) blocking assay between the spouses, was analyzed in 26 patients out of 29. RESULTS: None of the 22 patients underwent further immunotherapy because a significantly high titer of MLR-BAbs had been detected before the new pregnancy. In 19 out of the 21 patients (90.5%), pregnancy was successful. CONCLUSION: Additional immunotherapy is not necessary for patients who have obtained successful results after the initial immunotherapy and are positive for MLR-BAbs after their first delivery.

Abortion, Habitual↗