Microparticles and coronary artery disease.
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Biomarkers↗
Biomedical subjects
H Kagawa
Publications and source records attributed to H Kagawa.
Doppler blood flow velocity waveforms of the umbilical artery during variable decelerations in labor.
OBJECTIVE: To investigate the changes in resistance indices of blood flow velocity waveforms of the umbilical artery (UmA-RIs) during variable decelerations (VDs) vs. early decelerations (EDs). METHODS: UmA-RIs were measured before and during uterine contractions in 30 cases with VDs, nine cases with EDs and 20 cases without decelerations. In 12 out of 30 cases with VDs, UmA-RI was determined at the following five stages of a VD; before the deceleration, downward, bottom, upward and resumption stages. RESULTS: UmA-RIs during VDs were significantly higher compared with those at preceding periods. UmA-RIs at downward and bottom stages of VDs were significantly higher than those at the upward stage, although no differences in heart rate were found between downward and upward stages. UmA-RIs during EDs or uterine contractions without decelerations did not differ from those preceding them. CONCLUSION: UmA-RIs increased during VDs, particularly at downward and bottom stages during which the cord seemed to be actually compressed.
Blood Flow Velocity↗
Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins.
An approach to mapping antigenic B cell epitopes within alpha-helical coiled coil proteins has been developed and applied to two proteins: Streptococcal M protein and C. elegans paramyosin protein UNC-15. Overlapping peptides derived from an alpha-helical coiled coil conformational epitope were embedded between helical flanking peptides derived from the completely unrelated GCN4 leucine zipper peptide. The resulting chimeric peptides exhibited helical propensity. Chimeric peptides were tested for antigenicity (recognition by antibody) or immunogenicity (production of appropriate antibody response). A conformational epitope within the Streptococcal M protein recognised by three mAbs spanned 12 residues. Analysis of chimeric peptides based on C. elegans UNC-15 has enabled fine mapping of the minimal B cell epitope recognised by monoclonal antibody NE1-6B2 to seven non-contiguous residues (spanning 15 residues); the footprint of contact residues involved in antibody recognition being restricted to the hydrophilic face of the helix and covering five helical turns. This chimeric peptide epitope when coupled to diphtheria toxoid was highly immunogenic in mice and antisera recognised the conformationally dependent native peptide epitope. This approach has the potential to map conformational epitopes and design minimal epitopes for use as vaccine candidates.
Amino Acid Sequence↗
Developmental sequence of human fetal body movements in the second half of pregnancy.
To describe fetal body movements precisely and to clarify their developmental sequence in the second half of pregnancy, fetal body movements were observed in 31 normal fetuses between 20 and 41 weeks of pregnancy by using multiple ultrasonic machines. All movements of the whole trunk were able to be classified into six fundamental movements: flexion, stretch, rolling, startle, stepping, and writhing. Startle was always observed as a single movement, but others were more frequently observed as a part of combination rather than as a single movements. The incidence of flexion and stretch peaked at 28-31 weeks, whereas the incidence of startle and stepping lowered at the period. The incidence of rolling and upper half trunk movements increased at 40-41 weeks. Limb movements were frequent and did not exhibit characteristic change in the incidence. In conclusion, we classified fetal body movements into several fundamental movements instead of using the expression of "general movements" by focusing principally on movements of the trunk. In particular, some of the fundamental movements seem to appear in characteristic ways as related to gestational age. In view of that fetal behaviors are closely related to the neural activity, the present findings may contribute to an understanding of the developmental process of the central nervous system.
Abdomen↗
Mutations and expressions of the tropomyosin gene and the troponin C gene of Caenorhabditis elegans.
How does muscle gene mutation affect the muscle structure and function of an animal? Mutant animals of the tropomyosin and troponin C genes of Caenorhabditis elegans show Pat (paralyzed, arrested elongation at twofold) phenotypes together with abnormal muscle filament assembly. We present evidence that the mutation sites of lev-11 gene was in the tropomyosin gene, tmy-1 and that of pat-10 was in the troponin C gene, tnc-1, of the worm, respectively. The lev-11 (st557) mutation occurred at the splice donor site of exon 1 and results in translation termination. Although the gene product from heterozygous (+/st557) animal was not detected, our result could be the reason for the Pat phenotype of this mutation. The lev-11(x12) mutation, isolated as an allele of levamisole resistance, occurred in exon 7 and results in amino acid substitution at 234 from Glu to Lys. This substitution give a charge change from - to + at this point which is common in three isoforms. There may be functional importance of this region for molecular interaction of the tropomyosin. Mutation site of pat-10(st575) was Asp64 to Asn and Trp153 to termination in the troponin C. The first mutation site was in the second calcium binding site and the second mutation raised the deletion of H helix in the troponin C. Both might affect the calcium binding or the retaining of the conformation for its function. Results presented here will be useful to understand the interaction site between the tropomyosin and troponin complex.
Animals↗
Aplastic anemia complicating Sjögren's syndrome.
A 47-year-old woman was referred to our hospital because of severe anemia and polyclonal gammopathy. She developed sicca syndrome after admission. Laboratory data revealed pancytopenia (white blood cells, 2,800/microliter; hemoglobin, 6.4 g/dl; platelets, 6.1 x 10(4)/microliter) and hyper gamma globulinemia (5.2 g/dl), and bone marrow was hypoplastic. Histology of the salivary gland showed infiltration of lymphocytes. We report a good response to immunosuppressive therapy in a rare case of aplastic anemia complicating Sjögren's syndrome.
Anemia, Aplastic↗
Polyangiitis overlap syndrome.
A 33-year-old man was admitted to our hospital because of intermittent claudication and finger tip ulceration with a skin rash on the upper and lower extremities. He later developed a massive melena. Angiography revealed arterial occlusion in the hand and foot, skin biopsy showed vasculitis with eosinophilic infiltration, and biopsy of the colon showed mucosal vasculitis with thrombosis. A diagnosis of polyangiitis overlap syndrome was made, and all these symptoms improved after corticosteroid therapy.
Adult↗
Effect of a new monoclonal anti-glycoprotein IX antibody, KMP-9, on high shear-induced platelet aggregation.
Human platelet glycoprotein Ib/IX complex acts as a receptor for von Willebrand factor. It is widely accepted that glycoprotein Ib is the essential receptor component, but the role of glycoprotein IX is still unclear. We produced a new monoclonal anti-glycoprotein IX antibody (KMP-9) by the hybridoma technique using platelets from a patient with Glanzmann's thrombasthenia. The epitope of KMP-9 was localized to the C-terminal 8 kD fragment of glycoprotein IX using ELISA analysis of polyethylene-pin-synthesized peptides, as well as Western blot analysis of platelets after digestion with N-glycosidase and Staphylococcus aureus V8 protease. KMP-9 partially inhibited high shear stress-induced platelet aggregation, but had no effect on aggregation induced by ristocetin or low shear stress. Its inhibitory effect on high shear stress-induced aggregation was weaker than that of anti-glycoprotein Ib or anti-glycoprotein IIb/IIIa monoclonal antibodies. A 21-mer synthetic peptide (glycoprotein IX L110-G130) inhibited the binding of KMP-9 to platelets. It also competively inhibited the suppression of high shear stress-induced platelet aggregation by KMP-9, but had no direct effect on this aggregation. KMP-9 may be useful to clarify the physiological role of GPIX.
Amino Acid Sequence↗
High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles.
Previous studies have demonstrated that a high level of shear stress can produce platelet aggregation without the addition of any agonist. We investigated whether high shear stress could cause both platelet aggregation and shedding of microparticles from the platelet plasma membrane. A coneplate viscometer was used to apply shear stress and microparticle formation was measured by flow cytometry. It was found that microparticle formation increased as the duration of shear stress increased. Both microparticles and the remnant platelets showed the exposure of procoagulant activity on their surfaces. Investigation of the mechanisms involved in shear-dependent microparticle generation showed that binding of von Willebrand factor (vWF) to platelet glycoprotein lb, influx of extracellular calcium, and activation of platelet calpain were required to generate microparticles under high shear stress conditions. Activation of protein kinase C (PKC) promoted shear-dependent microparticle formation. Epinephrine did not influence microparticle formation, although it enhanced platelet aggregation by high shear stress. These findings suggest the possibility that local generation of microparticles in atherosclerotic arteries, the site that pathologically high shear stress could occur, may contribute to arterial thrombosis by providing and expanding a catalytic surface for the coagulation cascade.
Blood Platelets↗
The effect of non-activated prothrombin complex concentrate (Proplex ST) on intraperitoneal hematoma in a hemophilia A patient with a factor VIII inhibitor.
A 28-year-old severe hemophiliac with a factor VIII inhibitor was admitted to our hospital with a massive and serious intraperitoneal hematoma. He was a high-responder patient showing maximal serum inhibitor levels as high as 255 Bethesda Units/ml (BU/ml). He was successfully treated with "bypass therapy" using a prothrombin complex concentrate (PCC).
Adult↗
HLA typing of a family with systemic lupus erythematosus.
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Adult↗
Expression of prothrombinase activity and CD9 antigen on the surface of small vesicles from stimulated human endothelial cells.
We employed flow cytometry and monoclonal antibodies (MoAb) to study the surface membrane protein of shed particles (small vesicles, SV) that were released from vascular endothelial cells (EC) by agonists such as a Ca ionophore (A23187) and thrombin. After stimulation of EC by A23187, CD9 antigens disappeared entirely from the EC surface in a time- and concentration-dependent manner; they subsequently moved onto the SV surface. Von Willebrand factor (vWF) and P-selectin from Weibel-Palade (W-P) bodies were expressed rapidly on the EC surface after thrombin stimulation, but not on the SV surface. P-selectin may have some effect on maintenance of hemostasis on the EC surface. We demonstrated that the surfaces of SV and EC significantly supported prothrombinase activity and confirmed that A23187-induced SV from EC express binding sites for factors IXa and Xa. These results suggest that the SV are an important factor in a novel controlling mechanism of the coagulation system on the EC surface.
Antibodies, Monoclonal↗
Genome structure, mapping and expression of the tropomyosin gene tmy-1 of Caenorhabditis elegans.
The complete tropomyosin gene, designated tmy-1, of Caenorhabditis elegans was recovered by genome walking from a fragment that was obtained by exon-expression cloning using specific cloning using specific anti-tropomyosin antiserum as a probe. The genome structure of the tmy-1 gene has been determined by combining the DNA sequences of cDNA clones with those of the genomic fragments. The single-copy gene spans approximately 13 kb and include 14 exons. Comparison of cDNA and genomic sequences demonstrates that three isoforms are encoded by the gene tmy-1. Homology of the 27 C-terminal amino acid residues to those of Drosophila and vertebrates suggest that these may be the body wall, pharyngeal and non-muscle types. Tissue-specific expression of the tmy-1 gene was determined by microinjection of a promoter/lacZ fusion gene and with immunohistochemistry by using affinity-purified tissue-specific anti-tropomyosins. The 5' end promoter common to CeTMI and CeTMII is expressed in the body wall muscles, vulva, anus muscles and male tail muscles. Control sequences of the 5' end promoter are located 660 to 800 bp upstream of the initial methionine codon. The third isoform, CeTMIII, encoding 256 amino acids residues was expressed in the pharyngeal muscles by the promoter in the third intron. The mRNA of CeTMIII was trans-spliced with SL1 and SL2. These results allow is to solve the question of what is common from this worm to vertebrates, and also what are the cross-species complexities and the tissue-specific differences of tropomyosins. The tmy-1 gene is located on the C. elegans genomic YAC grid near the right end of chromosome I, in the region on the lev-11 gene.
Alternative Splicing↗
Immunocytochemical localization of IGF-I in the ovary of the red seabream, Pagrus major.
There are many biochemical and molecular biological data indicating that IGF-I is present in teleost fish. The present study examines red seabream for the presence and cellular distribution of IGF-I in the ovarian follicles during oocyte growth and final maturation of oocytes by immunocytochemistry. Immunoreactivity appeared in the granulosa cells at the lipid stage. Immunoreactivity became strong at the primary yolk globule stage and diminished in intensity during development of maturational competence (responsiveness to maturation-inducing steroid) and final maturation of oocytes. Intense immunoreactivity was also localized in the outer layer of the zona radiata and the peripheral region of the ooplasm at the primary yolk globule stage. Postovulatory follicles had low immunoreactivity in the early phase of degeneration. These immunocytochemical observations show that the granulosa cell layer is the main site of IGF-I production. IGF-I may be involved in granulosa cell proliferation and differentiation.
Animals↗
Relationship of microparticles with beta 2-glycoprotein I and P-selectin positivity to anticardiolipin antibodies in immune thrombocytopenic purpura.
We investigated the association of beta 2-glycoprotein I and P-selectin with platelet-derived microparticles in 48 patients with immune thrombocytopenic purpura and 20 normal controls using two-color flow cytometric analysis. In addition, anticardiolipin antibodies were detected by an enzyme-linked immunosorbent assay. Platelet microparticles from the patients showed a higher positivity for beta 2-glycoprotein I than those from the normal controls (23.1 +/- 15.4% vs. 5.3 +/- 3.1%, p < 0.01), but this positivity was not related to the presence of platelet-associated IgG or to the severity of thrombocytopenia. In the 18 patients with more than 20% P-selectin-positive microparticles, beta 2-glycoprotein I positivity was significantly higher than in the 30 patients with less than 20% P-selectin-positive microparticles (37.1 +/- 20.5% vs. 21.5 +/- 17.3%, p < 0.01). In addition, anticardiolipin antibodies were detected in eight patients, and they had a significantly higher level of beta 2-glycoprotein I-positive microparticles than the patients without such antibodies (42.0 +/- 22.9% vs. 22.6 +/- 18.9%, p < 0.05). Our results suggest that anticardiolipin antibodies activate platelets in immune thrombocytopenic purpura and cause the generation of microparticles rich in beta 2-glycoprotein I and P-selectin. These microparticles may then act to regulate coagulation abnormalities in patients with anticardiolipin antibodies.
Adolescent↗
Platelet-derived microparticles may influence the development of atherosclerosis in diabetes mellitus.
We investigated the association between low-density lipoprotein (LDL), triglycerides, and platelet activation in 18 patients with hypertension age 41-64 years and 18 with diabetes mellitus aged 43-70 years. Platelet P-selectin positivity and the microparticle level (indicators of activation) were both significantly higher in the diabetics than in healthy controls (P-selectin: 28.0% +/- 7.5% vs. 7.3% +/- 4.2%, P < 0.001; microparticles: 1900 +/- 966 vs. 526 +/- 158/10(4) platelets, P < 0.01). In contrast, there was no significant increase of either parameter in the patients with hypertension. Plasma microparticle levels were also significantly greater in the diabetics with high LDL levels than in those with low LDL levels (2375 +/- 949 vs. 1519 +/- 796/10(4) platelets, P < 0.05), and in those with high rather than low triglyceride levels (2188 +/- 845 vs. 1492 +/- 783/10(4) platelets, P < 0.05). However, platelet positivity for P-selectin was not significantly different between these two subgroups. Microparticle and P-selectin levels both showed no significant difference between the hypertensive patients with high and low LDL or triglyceride levels. These results suggest that platelet-derived microparticles may participate in the development or progression of atherosclerosis in patients with diabetes mellitus.
Adult↗
Significance of cytokines and CD68-positive microparticles in immune thrombocytopenic purpura.
We investigated the significance of cytokines (soluble interleukin-2 receptor, granulocyte-macrophage colony-stimulating factor, interleukin-6, and interferon-gamma) and CD68-positive microparticles in immune thrombocytopenic purpura. Cytokines were measured by enzyme-linked immunosorbent assay and microparticles were detected by flow cytometry. CD68 expression by histiocytic U937 cells incubated with lipopolysaccharide or cytokines was also assessed in a control study. The level of CD68-positive microparticles was significantly higher in the patients with thrombocytopenia than in normal controls (p < 0.01). The soluble interleukin-2 receptor level was also significantly higher in patients than in controls (p < 0.01), but the other cytokines did not show a significant difference. However, patients with severe thrombocytopenia (platelet count > 20,000/microliters) had significantly higher levels of granulocyte-macrophage colony-stimulating factor and interleukin-6 than the controls (p < 0.05). When opsonized platelets were incubated with activated U937 cells, lipopolysaccharide and granulocyte-macrophage colony-stimulating factor caused an increase of CD68-positive microparticles in the supernatant. These results suggest that granulocyte-macrophage colony-stimulating factor is released by activated T cells in immune thrombocytopenic purpura and activates monocyte/macrophage phagocytosis, resulting in an increase of circulating CD68-positive microparticles and enhanced platelet destruction.
Adolescent↗
[Detection of soluble interleukin-2 receptor in idiopathic thrombocytopenic purpura].
We measured soluble interleukin-2 receptor (sIL-2 R) in serum samples from 57 patients with idiopathic thrombocytopenic purpura (ITP). The sIL-2 R level was significantly increased in the ITP patients (481.3 +/- 378.5 U/ml) compared with controls (176.2 +/- 66.9 U/ml) (p < 0.001), and was significantly higher in 8 patients positive for hepatitis C virus (HCV) antibody positive (1,140.7 +/- 194.3 U/ml) than in 49 HCV-antibody negative patients (378.9 +/- 278.6 U/ml) (p < 0.0001). There was also a significant difference between the HCV-antibody negative ITP patients and the controls (p < 0.01). Elevated sIL-2 R levels correlated with the CD 4/8 ratio (p < 0.05), but not with the platelet count or the level of platelet-associated IgG. The increase of sIL-2 R in ITP may be related to the immunological abnormalities underlying this disease.
Adult↗