[Diagnosis and treatment of thoracic myelopathy].
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Humans↗
Biomedical subjects
Y Fujimura
Publications and source records attributed to Y Fujimura.
Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on ischemic brain damage induced by four-vessel occlusion in rats.
The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was evaluated in a rat four-vessel occlusion model and compared to the effect of another NMDA antagonist (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intravenously immediately following occlusion. At 72 h after the ischemia, latency in the passive avoidance test was significantly shorter in ischemic control rats in comparison with sham-operated rats. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly lengthened the latency. At 2 weeks after ischemia, ischemic control rats showed no differences in latency compared to sham-operated rats. The number of survived neurons of control rats was significantly less than that of sham-operated rats at 72 h and 2 weeks after ischemia. CGP 40116 at the doses of 3 and 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly increased the number of survived neurons. Adenosine triphosphate (ATP) level in striatum of control rats was significantly lower than that of sham-operated rats at 24 h after ischemia when an acquisition trial was performed in the passive avoidance test. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg ameliorated the decrease. These results suggest that CGP 40116 might have an ameliorative effect on the memory deficits in the passive avoidance test after ischemic injuries through the suppression of changes in brain energy metabolism.
2-Amino-5-phosphonovalerate↗
Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 4th communication: improvement of heart failure of rats with myocardial infarction by valasartan.
The hemodynamic effects of valsartan ((S)-N-valeryl-N-¿[2'-(1H-tetrazol-5-yl)bipheneoyl-4-yl]meth yl¿valine, CAS 137862-53-4, CGP 48933), a new angiotensin II type 1 receptor antagonist, on rats with myocardial infarction induced by coronary artery ligation was examined. Four weeks after ligation, mean blood pressure, left ventricular pressure and cardiac output decreased, while left ventricular end-diastolic pressure increased in control rats. Left ventricular end-diastolic pressure significantly decreased in rats treated with valsartan at 30 mg/kg/d p.o. for 4 weeks. Total systemic resistance remarkably decreased in those with enalapril 3 mg/kg/d p.o. and valsartan 30 mg/kg/d p.o. Valsartan and enalaprilat did not affect cardiac functions of isolated intact rat hearts before and after ischemia in Langendorff apparatus. In addition to hemodynamic effects observed in vivo, valsartan at 30 mg/kg p.o. significantly inhibited left ventricular hypertrophy. Valsartan would thus appear to be clinically useful for treating heart failure following myocardial infarction.
Angiotensin Receptor Antagonists↗
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↗
Dorsal shift and expansion of the spinal cord after expansive open-door laminoplasty.
We investigated dorsal shift and anteroposterior spinal cord diameter after expansive open-door laminoplasty, comparing pre- and postoperative computed tomographic myelographic images to clarify the relationships between surgical outcome and these changes. Dorsal shift occurred at the midcervical spine in cervical spondylotic myelopathy (CSM) but was less extensive in ossification of the posterior longitudinal ligament (OPLL). Spinal cord anteroposterior diameter expanded for OPLL but did not for CSM. Correlation of outcome and dorsal shift was not significant for OPLL or CSM. Correlation of outcome and expansion was significant for OPLL, but not for CSM.
Adult↗
[Information on von Willebrand disease].
The revised classification of von Willebrand disease (VWD) was approved by the International Society of Thrombosis and Haemostasis (ISTH)/SSC in 1993. It consists of three major categories : quantitative defect in type 1, qualitative defect in type 2, and complete deficiency in type 3. Type 2 has four subtypes : decreased GPIb binding with deficient larger multimer of VWF in type 2A, excessive GPIb binding in type 2B, defective GPIb binding with larger multimer in type 2M, and defective FVIII binding in type 2N. Subsequently, criteria for diagnosis of VWD is being reconsidered by the association. Therefore, we introduced the guidelines for diagnosis of VWD type 1 and type 2N in our department.
Autoantigens↗
[Influence of cardiopulmonary bypass on lymphocyte function].
It is known that lymphocyte function is impaired after cardiopulmonary bypass (CPB). In this study, the lymphocyte stimulation test (LST) with PHA was used before and after CPB in 28 adult patients, and compared with the surgical parameters and serum cytokine (IL-6, IL-8) levels. LST was impaired after CPB in all patients. Although this value usually recovered by the third postoperative day (POD); (normal group, n = 16), some patients showed prolonged duration of the impaired LST (delayed group, n = 12). Therefore, the parameters of surgery, white blood cell (WBC) count, lymphocytes and subsets, and serum cytokine levels were compared between the normal and the delayed groups. There was no significant difference in the number of WBCs or lymphocytes between these two groups. OKT4-positive cells were reduced on the first POD in both groups, and in the normal group, the number of OKT4-positive cells recovered more quickly than in the delayed group. Serum IL-6 and IL-8 levels in the delayed group were elevated after CPB, and were significantly higher in the delayed group than in the normal group. In conclusion, patients who showed prolonged impairment of lymphocyte function may be partly due to prolonged CPB.
Adult↗
Role and initiation mechanism of the interaction of glycoprotein Ib with surface-immobilized von Willebrand factor in a solid-phase platelet cohesion process.
To know the role and initiation mechanism of the interaction of glycoprotein (GP) Ib with surface-immobilized von Willebrand factor (vWF), we examined the effect of shear stress levels on platelet binding to vWF-coated plates using a cone-and-plate type viscometer capable of loading various levels of shear stress. The extent of platelet binding to immobilized vWF reached a plateau at the shortest period tested (20 seconds) under high shear stress (90 dyne/cm2), whereas 9 to 12 minutes was necessary for saturable platelet binding under static conditions. This shear effect, which was found to be dependent on the vWF-GP Ib interaction, was observed even under the lowest shear stress (1.5 dyne/cm2) examined. In contrast with the high shear effect previously reported to initiate the interaction of GP Ib with soluble vWF, these results indicate that relatively low levels of shear stress can promote the interaction of GP Ib with surface-immobilized vWF. This effect of shear stress was observed regardless of the manner in which vWF was immobilized, suggesting that immobilization itself and not, as previously hypothesized, a conformational change in vWF induced by direct adsorption to the surface is responsible for the enhanced GPIb binding. Thus, the present findings suggest that the vWF-GP Ib interaction contributes optimally to rapid platelet cohesion on a thrombogenic surface when vWF is in a static state and when platelets are moved by an appropriate rheological force such as low shear stress.
Humans↗
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↗
A simple micro-method for determining urea cycle intermediates in blood: ornithine, arginine and argininosuccinic acid.
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Adult↗
Purification and characterization of bitiscetin, a novel von Willebrand factor modulator protein from Bitis arietans snake venom.
We have screened 20 snake venoms and purified a novel snake venom protein, named bitiscetin, from Bitis arietans venom that specifically binds to human von Willebrand factor (vWF) and induces platelet agglutination. Bitiscetin showed a heterodimeric structure composed of disulfide-linked alpha (16kDa) and beta (13kDa) subunits on SDS-PAGE and showed a basic nature with pI value of 9.1, in contrast to botrocetin (pI 4.6), a vWF modulator isolated from another snake (Bothrops jararaca) venom. Bitiscetin-induced platelet agglutination was dependent on vWF and platelet membrane glycoprotein (GP) Ib, but not on Ca2+ and GPIIb/IIIa. vWF bound to bitiscetin but not to botrocetin electroblotted to a PVDF membrane after SDS-PAGE and this binding was diminished after reduction of disulfide bonds of bitiscetin. Bitiscetin did not cross-react to anti-botrocetin monoclonal antibodies. These results suggest that bitiscetin directly interacts with vWF and requires the protein conformation for its interaction as well as botrocetin, but its interaction manner with vWF appears to be different from that of botrocetin.
Amino Acid Sequence↗
Atlantoaxial instability in os odontoideum with myelopathy.
STUDY DESIGN: This study analyzed the correlation between the atlantoaxial instability (especially sagittal plane rotatory instability) and myelopathy. Thirty-four patients with os odontoideum were reviewed in clinical symptoms and radiographs. OBJECTIVES: The results were correlated to provide a rationale for the genesis of myelopathy. SUMMARY OF BACKGROUND DATA: Instability of the atlantoaxial joint has been evaluated with atlantodental interval, space available for the spinal cord, instability index, and others. These are excellent indices for anteroposterior instability. However, they are insufficient for the evaluation of the multidirectional instability in os odontoideum. METHODS: Thirty-four patients were analyzed in three parameters on the lateral radiographs: the minimum distance from the posterior border of the C2 body to the posterior arch of atlas, the difference of the atlanto-axial angle between the flexion and extension position (sagittal plane rotation angle), and the change of space available for the spinal cord from flexion to extension (Instability Index). RESULTS: The correlation between the sagittal plane rotation angle and the instability index was low (r = 0.561). In patients with more than 20 degrees of the sagittal plane rotation angle, myelopathy was shown at a high rate (86%). Myelopathy was also shown at a high rate (90%) in the patients with more than 40% of the instability index. CONCLUSIONS: It is important to check the sagittal plane rotation angle and the instability index to evaluate the instability in os odontoideum. If the patient has either a sagittal plane rotation angle of more than 20 degrees or an instability index of more than 40%, he or she is likely to have the cord signs.
Adolescent↗
Complete amino acid sequence and identification of the platelet glycoprotein Ib-binding site of jararaca GPIb-BP, a snake venom protein isolated from Bothrops jararaca.
Jararaca GPIb-BP, a snake venom protein composed of alpha and beta subunits purified from Bothrops jararaca, binds to platelet glycoprotein (GP)Ib and functions as a receptor blocker for von Willebrand factor binding to GPIb (Fujimura, Y., Ikeda, Y., Miura, S., Yoshida, E., Shima, H., Nishida, S., Suzuki, M., Titani, K., Taniuchi, Y., and Kawasaki, T. (1995) Thromb. Haemostasis 74, 743-750). We present here the entire 142- and 123-residue amino acid sequence of the respective alpha and beta subunits and also demonstrate that the platelet GPIb-binding site resides on the beta and not on the alpha subunit based on an enzyme-linked immunosorbent assay using biotin-labeled jararaca GPIb-BP and competing ligands. Sequences of the alpha and beta subunits were determined by analysis of the intact S-pyridylethylated proteins and their peptides generated by digestion with Achromobacter protease I, Staphyloccocus aureus V8 protease, pepsin, endoproteinase Asp-N, or L-1-tosylamino-2-phenylethyl chloromethyl ketone-trypsin. A 38-39% identity of amino acid sequence between the alpha and beta subunits of jararaca GPIb-BP was observed, as well as a high degree of sequence identities (38-64%) with the respective subunits of botrocetin (Usami, Y., Fujimura, Y., Suzuki, M., Ozeki, Y., Nishio, K., Fukui, H., and Titani, K (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 928-932) and the beta-chain of echicetin (Peng, M., Holt, J. C., and Niewiarowski, S. (1994) Biochem. Biophys. Res. Commun. 205, 68-72).
Amino Acid Sequence↗
Inhibition assay for the binding of biotinylated von Willebrand factor to platelet-bound microtiter wells in the presence of ristocetin or botrocetin.
We developed a solid-phase inhibition assay for the binding of biotinylated von Willebrand factor (vWF) to platelet glycoprotein (GP)Ib based on an enzyme-linked immunosorbent assay (ELISA) with platelet-bound microtiter wells. Washed platelets were immobilized onto the microplates via the anti-GPIIb/IIIa monoclonal antibody (mAb) VNR-5. In the presence of an antibiotic ristocetin (1 mg/ml, final) or the snake venom botrocetin (2 micrograms/ml, final), biotinylated vWF bound to the affixed platelets with half-maximal binding occurring at a vWF concentration of approximately 2 micrograms/ml. Several specific inhibitors of the binding of vWF to GPIb abolished the interaction of biotinylated vWF with GPIb in a dose-dependent fashion, with comparable protein concentrations to those seen in the liquid-phase inhibition assay using 125I-vWF. These inhibitors included mAb against vWF (NMC-4), mAb against GPIb (AP-1), and two vWF fragments containing vWF's putative GPIb-binding domain, namely a 39/34-kDa dispase-digested vWF fragment and a recombinant vWF fragment. Thus, this new assay is a convenient alternative to the conventional inhibition assay using 125I-vWF.
Anti-Bacterial Agents↗
Primary structure of alboaggregin-B purified from the venom of Trimeresurus albolabris.
The complete amino acid sequences of alpha and beta subunits of alboaggregin-beta are presented. The alpha and beta subunits were separated by reversed-phase HPLC after reduction and S-pyridylethylation, and their sequences were determined by analysis of peptides generated by enzymatic or chemical digestion. The alpha and beta subunits consist of 133 and 123 amino acid residues, respectively. The sequences are highly homologous to each other (41.4% identity) and also to those of the alpha and beta subunits of botrocetin (a von Willebrand factor modulator) and the A and B chains of factor IX/X binding protein from other snake venoms. It is also homologous to C-type lectins with a homodimeric structure, but it shows no lectin-like activity.
Amino Acid Sequence↗
The EWS-ATF-1 gene involved in malignant melanoma of soft parts with t(12;22) chromosome translocation, encodes a constitutive transcriptional activator.
Molecular characterization of malignant melanoma of soft parts or soft tissue clear cell sarcoma which shares t(12;22) chromosome translocation revealed fusion of EWS with a transcriptional factor gene ATF-1. The EWS gene, which encodes an RNA binding protein, was also shown to be involved in Ewing sarcoma, related primitive neuroectodermal tumors and desmoplastic small round cell tumors. In order to understand the functional role of EWS-ATF-1 chimeric protein in human solid tumors, we have cloned the aberrant human ATF-1 (EWS-ATF-1) cDNA and studied its DNA binding, transcriptional activation properties and compared with normal ATF-1 protein. Our results demonstrate that EWS-ATF-1 binds weakly to DNA in vitro but functions as an efficient constitutive transcriptional activator unlike the normal ATF-1 which needs to be induced with cAMP. Deletion analysis revealed that EWS-fusion domain functions as a regulatory domain for the transcriptional activation properties of EWS-ATF-1 chimeric protein. Deletion of leucine zipper domain results in a loss of transcriptional activation of EWS-ATF-1 chimeric protein suggesting that protein-protein interaction play a role in the transcriptional activation properties of EWS-ATF-1. We demonstrate that EWS-fusion domain negatively regulates the DNA binding activity of EWS-ATF-1 chimeric protein. Therefore replacement of part of the amino-terminal kinase regulatory domain of ATF-1 protein with EWS regulatory domain results in an altered DNA binding, protein-protein interactions and transcriptional activation properties of EWS-ATF-1 causing deregulated gene expression which may be responsible for the genesis of t(12;22) chromosome translocation-bearing human solid tumors. Targeting the transcriptional cofactors (CBP, etc) by EWS-fusion proteins could be one of the mechanisms of activation of EWS-fusion proteins in human neoplasia.
Activating Transcription Factor 1↗
Atrophy of the nuchal muscle and change in cervical curvature after expansive open-door laminoplasty.
We analyzed computed tomography (CT) images and plain X-ray films of 53 patients who had undergone expansive open-door laminoplasty, in a 3-year study. The relationship between the postoperative changes in the nuchal muscles and those in the cervical curvature was investigated. On postoperative CT images, the cross-sectional area of all nuchal muscles was reduced to approximately 80% of its preoperative size. This atrophic change was especially intense in the multifidus muscle and the semispinalis cervicis muscle. Postoperative cross-sectional area of the deep nuchal muscles was reduced approximately 30% from its preoperative size. No significant correlation was found between the all cross-sectional area of the nuchal muscles and the cervical curvature. However, a weak correlation was found between the deep nuchal muscles area and the curve index (correlation coefficient 0.29).
Adult↗
The results of surgery on primary malignant tumors of the spine.
The results of surgery on primary malignant tumors of the spine in 18 patients treated in our hospital between 1976 and 1993 were reviewed. Curettage was less effective in controlling primary malignant lesions than wide excision, and the condition of the resected margin was closely related to the prognosis of the disease. Some patients in the hematopoietic tumor group receiving combined adjuvant therapy survived for a long time. The role of surgery is important in tumors such as chordoma and chondrosarcoma that have low sensitivity to adjuvant therapy, and it is essential to secure tumor-free resected margins.
Adolescent↗