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Biomedical subjects

M Okuma

Publications and source records attributed to M Okuma.

At least 181 records · Page 10Linked to original sources
PubMed1992

Accelerated declining tendency of human T-cell leukemia virus type I carrier rates among younger blood donors in Kumamoto, Japan.

The annual age- and sex-specific human T-cell leukemia virus type I carrier rate of blood donors in Kumamoto, Kyushu, Japan from 1986 to 1990 revealed that the carrier rates of all the age groups below 50 years declined linearly in both sexes (P less than 0.005). Furthermore, the annual declining rates relative to the carrier rates of 16-19-year-old and 20-29-year-old males were higher than those of all of the older males (P less than 0.02), and all female age groups below 50 years had higher relative declining rates than 50-64-year-old females (P less than 0.05). Although several factors, such as a notification program at obstetric clinics, methodological and technical improvement of the assays, wider knowledge of human T-cell leukemia virus type I infection in the latter years, and immigration of individuals from a nonendemic area, might cause an absolute decline of the carrier rate of the blood donors, these factors could not explain the acceleration of the relative declining rate among younger donors. Therefore, this acceleration represents the tendency of the general population.

Adolescent↗
PubMed1992

Analysis of the defective signal transduction mechanism through the platelet thromboxane A2 receptor in a patient with polycythemia vera.

We previously reported a patient with polycythemia vera whose platelets showed subnormal responses to thromboxane A2 (TXA2) (Thromb Haemostas 1987; 57: 158-64). The patient's platelets showed normal binding activity to TXA2 analogues but the generation of second messengers was defective. We further studied the mechanism of this dysfunction in this work. The coupling of TXA2 receptor with its relevant GTP binding protein was examined using STA2(a synthetic TXA2 mimetic)-induced augmentation of GTPase activity as its measure. Only subnormal increase in the GTPase activity of the patient's platelet membrane was found after STA2 stimulation. Down regulation of TXA2 receptor of the patient's platelet also showed abnormal behavior. These results suggested that the defective coupling of TXA2 receptor with GTP binding protein could be included as a cause of defective signal transduction in this patient's platelets. This defect might be due to the abnormality of TXA2 receptor itself if the receptor was down regulated by its phosphorylation through agonist-induced conformational change.

Blood Platelets↗
PubMed1992

Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen-induced platelet aggregation.

Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen-induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B2 in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca2+]i) in fura2-loaded platelets. In contrast, thrombin caused TXB2 formation and an increase of [Ca2+]i in his platelets. These results suggest defective interaction between the platelets and collagen. The IgG from the ITP-patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPIa/IIa and thrombospondin were normally present. These results indicate that impaired collagen-induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.

Adenosine Triphosphate↗
PubMed1992

Bone marrow stromal cells attenuate mitoxantrone cytotoxicity against HL-60 leukemic cells.

We evaluated the effect of cultured human bone marrow (BM) stromal cells on the cytotoxicity of mitoxantrone (MIT) against the HL-60 leukemic cell line. BM-derived fibroblastoid cells (BMFC) suppressed colony formation of HL-60 cells in the absence of MIT. BMFC increased the survival of HL-60 colony-forming cells in the presence of 50 ng/ml MIT. A significant decrease in the drug concentration was not detected on BMFC. Our results suggest that BM stromal cells can modulate the antileukemic effect of an anticancer drug.

Cell Adhesion↗
PubMed1992

Myelodysplastic syndrome (MDS)-associated inhibitory activity on haematopoietic progenitor cells: contribution of monocyte-derived lipid containing macrophages (MDLM).

We studied myelodysplastic syndrome-associated inhibitory activity (MDS-IA), which inhibited colony formation in vitro of normal granulocyte-macrophage progenitors (CFU-GM). When adherent marrow cells were incubated with fetal calf serum for 21-24 d, monocyte-derived lipid containing huge macrophages (MDLM) developed. MDLM from MDS marrow (MDS-MDLMs) and their conditioned medium (MDLM-CM) consistently suppressed the growth of normal CFU-GM colony formation. MDS-IA was active on CFU-GM during the S-phase and relatively resistant to heating. Monoclonal antibody against H subunit (acidic) ferritin and polyclonal antibody against placental ferritin neutralized the inhibitory activity of MDS-MDLMs. In addition, cell lysates of MDS-MDLMs reacted to both monoclonal anti-H subunit ferritin and polyclonal anti-placental ferritin in Western blotting analysis, indicating that the inhibitory activity was predominantly acidic isoferritin. On the other hand, MDLMs obtained from normal bone marrow had a CFU-GM enhancing activity. These results suggest that MDS-MDLMs may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors, notably H subunit isoferritin.

Adolescent↗
PubMed1992

Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin-activated platelets.

The effect of thrombin-activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura-2. [Ca2+]i of PMNs was transiently elevated by thrombin-activated platelets. The supernatant of thrombin-activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 mumol/l adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin-activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin-sensitive factor(s).

Adenosine Triphosphate↗
PubMed1992

Gene analyses of abnormal fibrinogens with a mutation in the gamma chain.

In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp-330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations.

DNA Mutational Analysis↗
PubMed1992

[Coexistence of myeloma and primary myelodysplastic syndrome (MDS)].

Coexistence of myeloma and MDS was noted in a patient without history of exposure to cytotoxic drugs. A 73-year-old man was admitted because of fever and dyspnea on exertion. A complete blood count revealed macrocytic anemia with hemoglobin 7.1 g/dl, RBC 191 x 10(4)/microliters and MCV 111.2 fl. WBC was 6,000/microliters, with normal differentials. Bone marrow showed erythroid hyperplasia with M/E ratio of 1.36. There were marked tri-lineage cellular abnormalities, which included megaloblastic changes, multinucleated erythroblasts, hypersegmentation of neutrophils, giant neutrophils, and giant platelets. Ringed-sideroblasts were demonstrated in 20% of the erythroblasts. These findings were compatible with MDS. Although plasma cells accounted for only 9.7% of the nucleated marrow cells, there were many immature plasma cells with inclusion bodies, and the patient showed lambda-light chain type monoclonal gammopathy with corresponding Bence Jones protein. Immuno-histochemical staining of the bone marrow biopsy specimen revealed monoclonal growth of lambda-positive plasma cells. A punched-out lesion of the skull eventually developed. These findings suggest existence of myeloma. There have been some reports of coexistence of MDS and myeloma; supporting the idea of pluripotent stem cell origin of the disease. This is the first documentation of such a case in Japan.

Aged↗
PubMed1992

[Sequential changes of specific IgE, IgG4 antibodies and the development of allergic diseases in the first year of life].

Thirty infants who had siblings with major allergy were prospectively followed up to 12 months. Among 15 infants, in whom egg and milk were eliminated by the mother during third trimester and 12 months after birth, three infants developed food allergy. But, among 15 infants without any elimination either by the mother or the infant, 7 infants developed food allergy though this was not statistically significant. Among ten cases with food allergy, eight developed the symptoms during first six months. There were no correlations between allergic symptoms and Total IgE. Also, specific IgG4 did not show significant correlation with specific IgE and allergic symptoms except in several cases. Even though there was no significant decrease of food allergy by elimination of egg and milk during third trimester and 12 months after birth, elimination of egg and milk during that period give some benefit to the infant with strongly positive family history of major allergy under the close observation for growth and development of the infant.

Humans↗
PubMed1992

Phorbol esters up-regulate p55 and down-regulate p75 expression of interleukin-2 receptors in human T cells.

We examined the effects of phorbol esters on the expression of interleukin 2 receptors (IL-2R) in T cell clones. By flow cytometric analysis, we found that phorbol esters up-regulated IL-2R p55 expression, while they down-regulated p75 expression. The expression of IL-2R p55 in T cell clones treated with phorbol esters showed an initial transient and marginal decrease, which was followed by a progressive increase after 6 h of incubation. On the other hand, the expression of IL-2R p75 progressively decreased to a minimum plateau level. Down-regulation of p75 was also revealed in cells treated with diacylglycerols instead of phorbol esters, but there was no up-regulation of p55 in these cells. Moreover, in the presence of cycloheximide, phorbol esters down-regulated p75 expression but did not up-regulate p55 expression. Therefore, it seems that a transient activation of protein kinase C (PKC) is sufficient to down-regulate p75, but not to up-regulate p55, and that a novel protein synthesis is required to increase p55 expression.

Down-Regulation↗
PubMed1991

Interleukin-3-induced downregulation of the expression of interleukin-2 receptor beta chain in human T cells.

We examined the effect of interleukin-3 (IL-3) on human CD4+ cloned T cells, P607 and 1C2. By flow cytometric analysis, we found that IL-3 downregulated the surface expression of IL-2 receptor (R) beta chain in a dose-dependent manner but had little effect on that of IL-2R alpha chain. A simultaneous 125I-labeled IL-2 binding assay showed a decrease in the number of high-affinity, but not of low-affinity, IL-2Rs by IL-3. The downregulation of the IL-2R beta chain began 3 hours after culture initiation, increased further thereafter, and was completely inhibited by anti-IL-3 antibodies. Expression of mRNA for either alpha or beta chain was not reduced by IL-3, and this suggests that the reduction of surface beta chain expression was not caused by the reduction of beta chain mRNA. IL-3-accelerating internalization of IL-2R beta chain appeared to be one of the mechanisms for IL-3-induced downregulation of surface IL-2R beta chain expression. IL-3 alone increased the proliferation of T-cell clones but decreased the existing increment of their proliferation by IL-2. Accordingly, IL-3 may be one of the factors acting as a liaison between the hematopoietic and immune systems.

Blotting, Northern↗
PubMed1991

The IL-2 receptor alpha-chain alters the binding of IL-2 to the beta-chain.

The binding of IL-2 to its high affinity receptor results in the formation of the ternary complex consisting of IL-2, alpha-chain (p55, Tac) and beta-chain (p75). We studied the role of alpha-chain in IL-2 binding to the high affinity receptor using IL-2 analog Lys20 which was made by the substitution of Lys for Asp20 of wild-type rIL-2. Lys20 bound to MT-1 cells solely expressing alpha-chain at low affinity, but did not bind to YT-2C2 cells which solely expressed beta-chain. However, direct binding of radiolabeled Lys20 to ED515-D cells, an HTLV-I-infected and IL-2-dependent T cell line, revealed both high affinity and low affinity binding although the Kd value of high affinity binding was 50 to 100 times higher than that of the high affinity binding of wild-type rIL-2. High affinity binding of Lys20 was completely blocked by 2R-B mAb recognizing IL-2R beta-chain. Anti-Tac mAb recognizing IL-2R alpha-chain abolished all of the specific Lys20 bindings. In contrast to the replacement of cell bound 2R-B mAb with wild-type rIL-2 at 37 degrees C, the addition of an excess of Lys20 did not cause the detachment of cell-bound radiolabeled or FITC-labeled 2R-B mAb. Consistent with the results of binding studies, Lys20 induced the proliferation of ED515-D cells, but not large granular lymphocyte leukemic cells. The growth of ED-515D cells was completely suppressed by either anti-Tac mAb or 2R-B mAb. These results strongly suggest that coexpression of the IL-2R alpha- and beta-chains alters the binding affinity of Lys20 and that the interaction between IL-2 and the alpha-chain is a key event in the formation of the IL-2/IL-2R ternary complex.

Antibodies, Monoclonal↗
PubMed1991

Centrally administered NPY stimulated gastric acid and pepsin secretion by a vagally mediated mechanism.

We investigated the possible roles of centrally administered neuropeptide Y (NPY) on gastric secretion, serum gastrin levels and gastric mucosal blood flow in anesthetized rats. Centrally administered NPY dose-dependently stimulated gastric acid and pepsin secretion. The stimulatory effect of intracerebroventricular administration of NPY was more potent than that of intracisternal administration. Centrally administered NPY also increased gastric secretion in the central noradrenaline depleted rats. In contrast, intravenously administered NPY had no influence on gastric secretion. These stimulatory effects were abolished by vagotomy or atropine pretreatment. The serum gastrin levels did not change after central NPY injection. Although intravenously administered NPY slightly increased gastric mucosal blood flow, centrally administered NPY slightly diminished gastric mucosal blood flow. These results indicate that centrally administered NPY markedly influences gastric functions in the rat.

Animals↗
PubMed1991

Fibrinogen Kyoto II, a new congenitally abnormal molecule, characterized by the replacement of A alpha proline-18 by leucine.

A new case of heterozygous dysfibrinogenemia characterized by an amino acid replacement in the NH2-terminal region of the fibrin alpha-chain was found in a 27-year-old woman with a bleeding problem. Her one-stage prothrombin time and activated partial thromboplastin time were slightly prolonged, and the purified fibrinogen from this patient had a markedly prolonged thrombin or reptilase time. Release of fibrinopeptides A and B was normal, but the polymerization of fibrin monomers was impaired. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified fibrinogen under the reduced condition showed no abnormalities in the apparent molecular weights of its three chains. Reverse-phase high performance liquid chromatography (HPLC) of the lysylendopeptidase-cleaved purified A alpha-chains showed a decrease in one peptide compared with the normal amount and the appearance of an abnormal peptide peak. These peptides were treated with thrombin and further separated on HPLC. Amino acid sequence analysis of the abnormal peptide indicated that A alpha proline-18, the second residue from the NH2-terminus of the fibrin alpha-chain, was replaced by leucine. The synthetic peptide Gly-Pro-Arg-Pro inhibited both thrombin- and reptilase-induced fibrin aggregation, but Gly-Leu-Arg-Pro showed little or no inhibition under the same conditions. The discovery of this abnormal fibrinogen supports the findings that A alpha proline-18 is important as part of the polymerization site in the NH2-terminus of the fibrin alpha-chain. The propositus' mother had the same abnormal fibrinogen. This unique inherited abnormal fibrinogen was designated as fibrinogen Kyoto II.

Adult↗