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Biomedical subjects

K Furihata

Publications and source records attributed to K Furihata.

At least 145 records · Page 8Linked to original sources

Structure of the toxin isolated from carp (Cyprinus carpio) bile.

Attempts were made to elucidate the structure of the toxin isolated from the bile of carp Cyprinus carpio, which is possibly responsible for carp poisoning. By fast atom bombardment (FAB) mass spectrometry, along with 1H- and 13C-NMR, a molecular formula of C27H48O8S containing a sulfate ester group was deduced. Those and other analytical data allowed us to conclude the structure of carp toxin to be 5 alpha-cholestane-3 alpha, 7 alpha, 12 alpha, 26, 27-pentol 26-sulfate, which agreed essentially with that of 5 alpha-cyprinol, an alcohol specific to carp bile, in which the sulfate ester at the C-26 position is lacking.

Animals↗

Structural studies on new depsipeptide antibiotics, variapeptin and citropeptin.

Variapeptin and citropeptin were found as novel hexadepsipeptide antibiotics produced by Streptomyces variabilis and Streptomyces flavidovirens, respectively. Their structures were elucidated by NMR spectral analysis including a variety of 2D techniques. Variapeptin and citropeptin are structurally realted to azinothricin and A83586C, respectively.

Anti-Bacterial Agents↗

A human monoclonal autoantibody specific for human platelet glycoprotein IIb (integrin alpha IIb) heavy chain.

Splenocytes from a patient with chronic, immune-mediated thrombocytopenic purpura (ITP) were transformed with Epstein-Barr virus. A stable lymphoblastoid cell line (LCL) derived from this transformation (2A3) produces IgM antibody reactive with platelet glycoprotein IIb. 2A3 was fused to the 6-thioguanine-resistant ouabain-resistant, murine-human heteromyeloma cell line, F6. The resultant heterohybridomas were selected by growth in medium containing hypoxanthine/aminopterin/thymidine and ouabain. One hybridoma line, 2E7, produces high levels of IgM antibody (2 to 4 micrograms IgM/ml/24 hr/10(5) cells) reactive with glycoprotein IIb. 2E7 has been repeatedly subcloned by limiting dilution and has been maintained in continuous culture for 26 months. 2E7 binds to human platelets but not endothelial cells, as determined by flow cytometry, and does not react with platelets of patients with Glanzmann's thrombasthenia that lack IIb-IIIa. The epitope recognized by 2E7 is likely to be a contiguous peptide sequence since the antibody binds to the IIb heavy chain in immunoblot assays of denatured, reduced platelet protein. Treatment of intact platelets or purified IIb-IIIa with papain or chymotrypsin, but not SV8 protease, destroys the epitope. Thus, the 2E7 epitope may be at or very close to a site on IIb that is cleaved by these proteases. The expression of the 2E7 epitope is significantly affected by the presence of divalent cations. Treatment of intact platelets with EDTA at 37 degrees C results in a three-to four-fold increase in the number of 2E7 molecules bound per platelet and an eight-fold increase in the affinity of the antibody. The binding of 2E7 to normal platelets does not inhibit any of the functions attributed to IIb-IIIa, such as fibrinogen-dependent platelet aggregation or clot retraction. 2E7 represents the first human monoclonal antibody reported to recognize an epitope on platelet glycoprotein IIb. The epitope is unique to IIb and not shared by other integrin alpha subunits.

Adolescent↗

[Granular lymphocyte leukemia of natural killer cell type; association with 47 XY, +8 by interleukin 2 (IL-2)-stimulated chromosomal analysis].

A 28-year-old male was admitted to our hospital because of hepatosplenomegaly and granular lymphocytosis. His peripheral leukocyte count was 3,000/microliters with 43% of granular lymphocytes (GL). These GLs were immunologically phenotyped as CD2+CD3-CD4-CD8-CD16+CD56+HLA-DR+ and were found that TcR genes coding beta and gamma chains were not rearranged. Chromosomal analysis of his GLs stimulated with IL-2 showed 47 XY, +8. This patient was diagnosed as a granular lymphocyte leukemia of natural killer cell type. Blood chemistry showed elevation of serum GOT, GPT and LDH values. The fever persisted until administration of prednisolone was initiated. But 40 days after, high fever appeared again and the liver and spleen were extremely enlarged. Combined chemotherapy was then started but resulted in no effects. He died of hepatic failure on the 77th day from admission. 47 XY, +8, that has been reported in acute non-lymphocytic leukemia and myelodysplastic syndrome, may be related to the pathogenesis in some cases of granular lymphocyte leukemia.

Adult↗

Studies on new phosphate ester antifungal antibiotics phoslactomycins. II. Structure elucidation of phoslactomycins A to F.

Phoslactomycins A to F are new antifungal antibiotics produced by Streptomyces nigrescens SC-273. On the basis of physico-chemical properties and NMR studies, their structures have been determined as shown in Fig. 6. They are characterized by possessing alpha, beta-unsaturated delta-lactone, phosphate ester, conjugated diene and cyclohexane ring moieties. The structural difference between them is ascribed to a substituent bound to the cyclohexane ring.

Antifungal Agents↗

Posttransfusion purpura associated with alloantibody specific for the platelet antigen, Pen(a).

Posttransfusion purpura (PTP) and severe thrombocytopenia occurred 9 days after transfusion of red blood cells to a 48-year-old, multiparous Navajo woman. The platelet count rose to hemostatic levels after treatment with prednisone and three plasma exchange transfusions. Serologic studies showed that the patient's serum contained the potent antibody reactive with platelets from nearly all normal subjects, but nonreactive with autologous platelets obtained after recovery. This antibody was found to be specific for a high-frequency, platelet-specific antigen, designated Pen(a),implicated previously as an immunogen in neonatal alloimmune thrombocytopenic purpura. An exchange of serum showed that Pena is identical with an alloantigen designated Yuk(b) by Japanese workers. We conclude that PTP can occur in association with alloimmunization against Pen(a) (Yuk(b).

Antibody Specificity↗

Human anti-PlE1 antibody recognizes epitopes associated with the alpha subunit of platelet glycoprotein Ib.

Together, a platelet-reactive antibody in the serum of a polytransfused patient (proband) and a platelet-reactive antibody in the serum of a mother of an infant with neonatal thrombocytopenia have served to establish the diallelic, platelet-specific alloantigen system, PlE. We now provide evidence that the platelet-specific antibody in the serum of the proband, anti-PlE1, recognizes epitopes associated with the alpha subunit of glycoprotein (GP) Ib. By 51Cr release, platelets from two of three patients with the Bernard-Soulier syndrome (BSS) responded sub-normally to anti-PlE1, and the apparently normal response of platelets from the last BSS patient was attributable to anti-HLA-A2 antibodies in the proband serum. These results suggested that the PlE1 antigen is associated with the GPIb complex (glycoproteins Ib kX) known to be absent from BSS platelets. This possibility was confirmed by ELISA using the purified GPIb complex or glycocalicin, the N-terminal fragment of GPIb alpha produced by proteolysis with endogenous platelet calpain, as solid-phase antigen. Anti-PlE1 antibody bound specifically to both the GPIb complex and glycocalicin. 3H-labelled platelet membrane glycoproteins with apparent molecular weights of 130k, 25k, and 21k (under reduced conditions) corresponding to GPIb alpha, GPIb beta, and GPIX were immunoprecipitated by anti-PlE1 plasma. Finally, at a titre of 1:16, anti-PlEl completely inhibited ristocetin-induced platelet agglutination, a property of platelets mediated by GPIb.

Antigens, Human Platelet↗