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T Koike

Publications and source records attributed to T Koike.

At least 145 records · Page 8Linked to original sources
PubMed2000

beta(2)-glycoprotein I deficiency: prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis.

beta(2)-glycoprotein I (beta(2)-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum beta(2)-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete beta(2)-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the beta(2)-GPI cDNA was deleted in every beta(2)-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6. 3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum beta(2)-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of beta(2)-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.

Adult↗
PubMed2000

Selective recognition of consecutive G sequence in double-stranded DNA by a zinc(II)-macrocyclic tetraamine complex appended with an anthraquinone.

A zinc (II) complex with a macrocyclic tetraamine appended with an anthraquinone ((9,10-anthraquinon-2-yl)methyl-1,4,7,10-tetraazacyclododecane, ZnL, anthraquinonyl-cyclen) selectively recognizes consecutive G sequence in double-stranded DNA. The affinity of the Zn2+-anthraquinonyl-cyclen to consecutive dG groups in DNA was disclosed by comparison of K(app) values (=[DNA-bound ZnL]/[uncomplexed ZnL][uncomplexed nucleobase in DNA]) determined by the UV spectrophotometric titrations at pH 8, I=0.1 (NaNO3), and 25 degrees C for poly(dG) x poly(dC) (K(app) = 1.5 x 10(5) M(-1)), poly(dG-dC)2 (2.8 x 10(4) M(-1)), poly(dA-dT)2 (4.3 x 10(4) M(-1)), and calf thymus DNA (2.8 x 10(4) M(-1)). The corresponding K(app) values with the Zn2+-free ligand were 5.3 x 10(3) M(-1), 7.4 x 10(3) M(-1), 7.4 x 10(3) M(-1), and 5.9 x 10(3) M(-1), respectively. The selective recognition of consecutive G sequence was concluded from the DNase I footprinting of SV40 early promotor DNA fraction (197 bp) containing a TATA box and six GC boxes. The present finding is in remarkable contrast to the previous selective T-recognition by Zn2+-cyclen complexes appended with acridine, quinoline(s), and naphthalene(s) [J. Am. Chem. Soc. 121 (1999) 5426]. While the Zn2+-acridinyl-cyclen inhibited TATA binding protein from interacting with a TATA box consensus DNA [J. Inorg. Biochem. 79 (2000) 253], the present Zn2+-anthraquinonyl-cyclen inhibited the Sp1 transcriptional factor protein from interacting with a GC box-consensus DNA.

Anthraquinones↗
PubMed2000

Controlling gene expression by zinc(II)-macrocyclic tetraamine complexes.

The zinc(II) complexes of 12-membered macrocyclic tetraamines (1,4,7,10-tetraazacyclododecane, cyclen) appended with one or two aryl-methyl group(s) (quinolyl-methyl, naphthyl-methyl, and acridinyl-methyl) selectively bind to thymines in a TATA box of the SV40 early promoter region and thus inhibit the binding of a transcriptional factor, TATA binding protein. These Zn2+-cyclen derivatives also act as inhibitors of DNA-targeted enzymes, type I and type II topoisomerases. They also exhibited strong antimicrobial activities for the gram-positive bacterial strain. These biochemical and biological properties were compared with those of conventionally established AT-recognizing drugs, distamycin A and DAPI. The Zn2+-cyclen complexes are a new type of small molecular, genetic transcriptional regulation factor.

Base Sequence↗
PubMed2000

Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY.

We have used the 7AAD/PY method to analyze the cell cycle status of normal human bone marrow hematopoiesis, and found that the cell kinetics differed. There were cells with relatively low levels of RNA in the S-phase (Type I) and a high level in the S-phase (Type 11). T-cells, B-cells, nucleated red cells and CD34+/CD19+ early B-cells in bone marrow were Type I, whereas myelomonocytic subset and CD34+/CD33-dim+ common myeloid cells were Type II. AC133+/CD38-dim cells, which were thought to be lineage-marker negative hematopoietic stem cells, had intermediate amounts of RNA in the S-phase between Type I and II (Type 0). Seventy-four cases of acute leukemia were also analyzed. Most of the T- and B-ALL cases were found to be Type I, most of the ANLL cases were Type II, and there were 10 cases that were Type 0. These findings yielded fundamental information about normal hematopoiesis and acute leukemia.

Adult↗
PubMed2000

Thrombopoietin activates the growth of megakaryoblasts in patients with chronic myeloproliferative disorders and myelodysplastic syndrome.

The effects of thrombopoietin (TPO) on cell proliferation and differentiation, and the relation between these effects and the expression of c-mpl on leukemia cells were studied in seven acute myelogeneous leukemia cell lines and seven myelogeneous blast cell preparations from patients with chronic myeloproliferative disorders (CMPDs) and myelodysplastic syndrome (MDS). Among the leukemia cells, five preparations of megakaryoblastic leukemia cells from patients and one megakaryoblastic cell line, CMK 11.5, proliferated in response to TPO in vitro. CMK 11.5 and the blastic cells from one patient diagnosed with MDS with myelofibrosis differentiated with increasing expression of CD41a in response to TPO. However, TPO had no effect on the cells lacking megakaryocytic characteristics. Some patients with CMPD and MDS develop acute transformation with blasts demonstrating megakaryocytic features, and some of these cells show growth in response to TPO. Therefore, in vivo administration of TPO should be considered carefully for patients with CMPD or MDS, since TPO may induce leukemic cell proliferation.

Cell Differentiation↗
PubMed2000

Effective high-dose chemotherapy combined with CD34+-selected autologous peripheral blood stem cell transplantation in a patient with cutaneous CD30-negative large T cell lymphoma.

Generalized multiple cutaneous tumors developed in a 60-year-old Japanese man. Skin biopsy revealed atypical large T lymphocytes infiltrating the dermis. CD30 staining was negative in the tumor cells. The diagnosis of CD30-negative cutaneous large T cell lymphoma was made. Axial and inguinal lymphadenopathy was present, but there was no evidence of bone marrow involvement. Seven cycles of chemotherapy and local electron beam irradiation were administered and complete remission (CR) was attained. As CD30-negative cutaneous large T cell lymphoma has a poor prognosis despite intensive chemotherapy, high-dose chemotherapy followed by CD34+-selected autologous peripheral blood stem cell transplantation (CD34+-APBSCT) was prescribed. The clinical course after CD34+-selected APBSCT was complicated with CMV infection occurring twice but administration of ganciclovir resolved the symptoms. He has remained in CR for 16 months after CD34+-APBSCT. This appears to be the first case report of CD34+-APBSCT in a patient with CD30-negative cutaneous large T cell lymphoma. Bone Marrow Transplantation (2000) 25, 1315-1317.

Antigens, CD34↗
PubMed2000

Large scale purification of human blood CD34+ cells from cryopreserved peripheral blood stem cells, using a nylon-fiber syringe system and immunomagnetic microspheres.

Isolation of large numbers of human peripheral blood CD34+ cells could lead to therapeutic applications, including purging of malignant cells from blood cell transplantations, purging of T cells from allogeneic bone marrow, and even blood cell transplantation. This procedure has limitations if there are not sufficient numbers of progenitor cells in the leukapheresis concentrates available for selection after detection of tumor cells in apheresis products. Use of frozen/thawed peripheral blood mononuclear cell (PBMC) samples would make feasible pooling of two or even more stem cell harvests collected at different time points and the total number of CD34+ progenitor cells available would increase. We established an efficient method for purification of CD34+ cells from cryopreserved apheresis products, using a nylon-fiber syringe system and immunomagnetic microspheres. We compared purity, recovery rate and clonogenicity of CD34+ cells purified from fresh (n = 22) and cryopreserved apheresis products (n = 14), using a nylon-fiber syringe system and immunomagnetic microspheres. The purity of CD34+ cells from cryopreserved products was less than that from fresh products (85.9 +/- 14.4% vs 94.6 +/- 10.0%), but the recovery rate of CD34+ cells and colony-forming cells was comparable between fresh and cryopreserved products. One patient underwent grafting with peripheral blood CD34+ cells selected after freezing, with good success. Therefore, these cells are capable of rapidly reconstituting hematopoiesis after high-dose chemotherapy. Bone Marrow Transplantation (2000) 26, 787-793.

Antigens, CD34↗
PubMed2000

Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation.

Some cytokines are believed to play a role in the development of acute and chronic GVHD after allo-hematopoietic stem cell transplantation. It has been reported that TNF-alpha and IL-10 gene polymorphisms are associated with the production of those cytokines and the development of graft failure after organ transplantation and systemic lupus erythematosus. We examined whether TNF-alpha and IL-10 gene polymorphisms affect the severity of acute GVHD (aGVHD) and chronic GVHD (cGVHD). Sixty-two and 54 patients were available for the analysis of aGVHD and cGVHD, respectively. We analyzed the gene polymorphisms derived from pre- and post-transplant blood cells. Donor-derived TNF2 allele (A) was more frequently detected in patients with aGVHD III/IV than those aGVHD 0-II (2/6 vs 2/56) (P = 0.04). The donors of the patients with cGVHD more frequently possessed a greater number of alleles (allele 13 or more which contain 26 or more CA repeats) in IL-10.G than those without (13/26 vs 5/28) (P = 0.02), and the patients with cGVHD had more CA repeats in donor-derived IL-10.G than those without (mean = 25.2 vs 23.4) (P = 0.01). Donor-derived TNF-308 and IL-10.G alleles may contribute to severe aGVHD and cGVHD, respectively, and will help us distinguish those patients at high risk for GVHD.

Acute Disease↗
PubMed2000

Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins on neurite outgrowth-promoting activities of nerve growth factor.

Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G(1) phase in vitro and to suppress tumor growth in vivo. However, their effects on neurons are unclear. Here, we report that some cyclopentenone PGs function as neurite outgrowth-promoting factors. They promoted neurite outgrowth from PC12 cells and from dorsal root ganglion explants but only in the presence of nerve growth factor (NGF). We refer to these PGs as neurite outgrowth-promoting PGs (NEPPs). Through study of the structure-function relationship of NEPP1-10 and related compounds, we found that the cross-conjugated dienone moiety of NEPPs was essential for promoting neurite outgrowth, and NEPP10 was concluded to be the best candidate for drug development. We also investigated the intracellular mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin heavy chain binding protein/glucose-regulated protein 78 (BiP/GRP78) plays a role in the promotion, based on the following observations: Antisense nucleotides for BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein level increased in response to NEPPs; and overexpression of BiP/GRP78 protein by adenoviral gene transfer promoted the neurite outgrowth by NGF.

Adenoviridae↗
PubMed2000

Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies on extrinsic fibrinolysis.

Antiphospholipid antibodies (aPLs) are associated with an increased incidence of thrombosis, but the mechanisms responsible for thrombosis are unclear. The present study investigated the effect of both beta2-glycoprotein I (beta2-GPI) and aPLs on the activity of extrinsic fibrinolysis. The remaining tissue-plasminogen activator (t-PA) of the sample consisting of beta2-GPI, two-chain recombinant t-PA, plasminogen activator inhibitor (PAI) -1 was measured by a chromogenic assay using synthetic substrate S-2251, Glu-plasminogen, and soluble fibrin monomer. Without PAI-1, beta2-GPI did not affect t-PA activity. When 14.3 ng/ml PAI-1 was added to 3.6 U/ml t-PA, the remaining t-PA activity was increased from 48.9% to 60.4% by the addition of beta2-GPI (190 microg/ml). The effect of beta2-GPI did not require phospholipids. The beta2-GPI seems to protect t-PA activity from the inhibition by PAI-1. When monoclonal anticardiolipin antibodies (aCLs), EY1C8, and EY2C9, which were established from a patient with antiphospholipid syndrome, were further added to the mixture with a diluted phospholipid (Platelin) to investigate the influence of aPL, the remaining t-PA activity decreased to 50.1 and 80.7%. Monoclonal aCLs appeared to inhibit the effect of beta2-GPI, that is, these monoclonals inhibited the fibrinolytic activity by an elevation in PAI-1 activity. These results suggest the possibility that the impairment of fibrinolytic activity by aCLs is one of reasons for the increased incidence in thrombosis in patients with aCLs.

Antibodies, Anticardiolipin↗
PubMed2000

Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection.

BACKGROUND: Persistent infection with hepatitis C virus (HCV) leads to liver cirrhosis (LC) and often to liver cancer. Little is known about host factors that determine the variable natural history. Mannose-binding lectin (MBL) is an important constituent of the innate immune system. In white patients there is an association between codon 52 mutation of the MBL gene and persistent hepatitis B virus (HBV) infection. To determine whether MBL gene polymorphisms affect the course of HCV infection, we investigated the association between MBL gene polymorphisms and HCV infection in Japanese subjects. METHODS: Fifty-two HCV-infected Japanese patients (8 with chronic inactive hepatitis (CIH), 31 with chronic active hepatitis (CAH), 13 with LC) and 50 normal controls were studied. MBL gene mutations were determined by means of polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: Codon 52 and codon 57 mutations were absent in all subjects. Homozygous mutation in codon 54 was present in one (0.9%) patient. Heterozygous codon 54 mutation was present in 17 (32%) of the 52 patients and in 21 (41%) of the controls. No significant difference in the frequency of codon 54 mutation was observed between patient and control groups. However, although no significant relationship was observed between MBL polymorphisms and the levels of HCV RNA, all patients with heterozygous or homozygous codon 54 mutations had CAH or LC. In contrast, 8 of the 34 patients without codon 54 mutation remained at CIH. (P = 0.0405). CONCLUSION: MBL may be one of the factors that influence the course of HCV infection.

Aged↗
PubMed2000

Generation of dendritic cells from adherent cells of cord blood by culture with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha.

Although dendritic cells (DC) can be cultured from cord blood (CB) CD34+ progenitor cells, the generation of DC from CB monocytes has not been reported. In this paper, we explored the generation of DC from CB monocytes to establish the simplest way to obtain a substantial number of DC from CB. We isolated monocytes from CB mononuclear cells (CB-MNC) by the plastic adherence method. These adherent cells (monocyte-rich cells) were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) or in serum-free X-VIVO 15 medium (SFM) for 7 days, both of which contained 100 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF) and 10 ng/ml interleukin-4 (IL-4) with or without 10 ng/ml tumor necrosis factor-alpha (TNF-alpha) (added at day 5). In the presence of GM-CSF and IL-4, CB-adherent cells became nonadherent, acquired DC morphology, and showed increased expression of CD1a, CD80, CD86, and HLA-DR; they lost membrane CD14 and some cells with the expression of CD83 and CMRF-44 were generated. With the addition of TNF-alpha to these cultures and culturing for further 2 days, the proportion of CD83+ cells was elevated in both the FBS and SFM culture systems, compared with the culture without TNF-alpha. In the culture with TNF-alpha, cells expressing CD1a, CD80, CD86, HLA-DR, and HLA-DQ were markedly increased. TNF-alpha-treated cells were demonstrated to be stronger stimulators for proliferation of both allogeneic CB lymphocytes and PB lymphocytes than were cells not treated with TNF-alpha. The yield of CD83+ DC at day 7 of cultures was 4.9 +/- 1.1 x 10(5) or 3.0 +/- 0.5 x 10(5) per 1.2 x 10(7) CB-MNC plated initially when cultured in FBS or SFM, respectively. These results have shown that a substantial number of mature DC could be generated from CB-adherent cells even by serum-free culture. We then compared these CB-adherent cell-derived DC (CB-DC) with peripheral blood (PB)-adherent cell-derived DC (PB-DC) in cell-surface phenotype and function. We found day 7 CB-DC have lower expression of CD80, CD1a, CD83, and CMRF-44 than day 7 PB-DC, but CB-DC have a similar capacity to stimulate the proliferation of both allo-CB lymphocytes and PB lymphocytes, compared with PB-DC. CB-DC cultured with GM-CSF and IL-4 have almost identical capacity of phagocytosis to take up fluorescein isothiocyanate (FITC)-dextran and Lucifer yellow (LY), compared with PB-DC. In summary, our findings suggest CB adherent cells, when cultured with GM-CSF, IL-4, and TNF-alpha, are a potent source of functional DC. Thus, CB-DC as well as PB-DC may become valuable tools for immunotherapy.

Cell Adhesion↗
PubMed2000

A knowledge model for analysis and simulation of regulatory networks.

MOTIVATION: In order to aid in hypothesis-driven experimental gene discovery, we are designing a computer application for the automatic retrieval of signal transduction data from electronic versions of scientific publications using natural language processing (NLP) techniques, as well as for visualizing and editing representations of regulatory systems. These systems describe both signal transduction and biochemical pathways within complex multicellular organisms, yeast, and bacteria. This computer application in turn requires the development of a domain-specific ontology, or knowledge model. RESULTS: We introduce an ontological model for the representation of biological knowledge related to regulatory networks in vertebrates. We outline a taxonomy of the concepts, define their 'whole-to-part' relationships, describe the properties of major concepts, and outline a set of the most important axioms. The ontology is partially realized in a computer system designed to aid researchers in biology and medicine in visualizing and editing a representation of a signal transduction system.

Animals↗
PubMed2000

Clinical efficacy of peritoneovenous shunting for the treatment of severe ovarian hyperstimulation syndrome.

We investigated prospectively the clinical efficacy of a newly developed continuous autotransfusion system of ascites (CATSA) without protein supplement in patients with severe ovarian hyperstimulation syndrome (OHSS). Peritoneovenous shunting was used to recirculate ascites. The CATSA was performed for 5 h at a rate of 100-200 ml/h once a day. Eighteen patients were treated with the CATSA (CATSA group) and 36 were treated with an intravenous 37.5 g/day of albumin supplement (albumin group). Hospital stay was significantly shorter in the CATSA group than in the albumin group (10.0 +/- 5.7 versus 13.9 +/- 6.2 days, P < 0.01). Haematocrit value reached <40% significantly earlier in the CATSA group (on hospital days 3.9 +/- 3.2 versus 5.9 +/- 2.5, P < 0.01). Using a single procedure, haemoconcentration, urinary output and pulse pressure were markedly improved in the CATSA group compared with the albumin group. Discomfort due to massive ascites diminished promptly and did not recur in nine of 18 CATSA group patients, whereas it persisted in all 36 patients in the albumin group. The serum concentration of protein was maintained in the CATSA group, whereas it did not increase in the albumin group despite daily supplementation with 37. 5 g of albumin. Apparent adverse effects of each procedure were not observed in either group. The mean values of several parameters in the serum pertinent to the coagulation-fibrinolysis system did not change significantly in either group after the procedure. It was concluded that the CATSA procedure expanded circulating plasma volume without exogenous albumin and appeared to lead to a prompt recovery from severe conditions of OHSS.

Adult↗
PubMed2000

Proteolytic cleavage of beta(2)-glycoprotein I: reduction of antigenicity and the structural relationship.

Binding of beta(2)-glycoprotein I (beta(2)-GPI)-dependent anticardiolipin antibodies (aCL) derived from antiphospholipid syndrome (APS) is significantly reduced in aCL ELISA due to loss of the phospholipid (PL) binding property of beta(2)-GPI by plasmin treatment. In the present study, the treatment generated a nicked form of beta(2)-GPI and resulted in loss of antigenicity for the autoantibodies detected in ELISA, using an beta(2)-GPI directly adsorbed polyoxygenated carboxylated plate, the assay system of which was not related to PL binding. The nicked form bound to neither Cu(2+)-oxidized low-density lipoprotein (oxLDL) nor to beta(2)-GPI-specific lipid ligands isolated from oxLDL, the result being a complete loss of subsequent binding of anti-beta(2)-GPI autoantibodies. The conformational change in the nicked domain V was predicted from its intact structure determined by an X-ray analysis (implemented in Protein Data Bank: 1C1Z), molecular modeling and epitope mapping of a monoclonal anti-beta(2)-GPI antibody, i.e. Cof-18, which recognizes the related structure. The analysis revealed that novel hydrophobic and electrostatic interactions appeared in domain V after the cleavage, thereby affecting the PL binding of beta(2)-GPI. Such a conformational change may have important implications for exposure of cryptic epitopes located in the domains such as domain IV.

Amino Acid Sequence↗
PubMed2000

Neurotoxicity of advanced glycation end-products for cultured cortical neurons.

The Maillard reaction that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients and in aging. AGEs are believed also to contribute to the pathology of Alzheimer disease (AD) and other neurodegenerative processes. Incubation of cortical neurons with 5 immunochemically distinct AGEs, designated AGEs-1 to -5, produced a dose-dependent increase in neuronal cell-death, as assessed by MTT assay, Trypan blue and Hoechst 33258 staining. The structural epitope designated AGE-2 was found to have the greatest cytopathic effect and the neurotoxicity of AGE-2 was neutralized by the addition of an anti-AGE-2-specific antibody, but not by other types of anti-AGE antibodies. Distinct classes of AGE structures also have been established to circulate in the blood of individuals with diabetes mellitus and end-stage renal disease treated by hemodialysis (DM-HD). We fractionated serum from normal control and DM-HD patients by gel filtration and identified 2 fractions that contained AGE epitopes-1 to -5 and as well as the defined AGE structure carboxymethyllysine (CML). The addition of these 2 fractions led to the death of cultured neuronal cells and this cytotoxic effect was completely prevented by the addition of the anti-AGE-2-specific antibody. We propose that the structural epitope AGE-2 is an important toxic moiety for neuronal cells.

Animals↗