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Biomedical subjects

Y Fujimura

Publications and source records attributed to Y Fujimura.

At least 199 records · Page 11Linked to original sources

Efficacy of benidipine hydrochloride on myocardial ischemia and reperfusion.

The efficacy of benidipine hydrochloride in preventing myocardial ischemia and reperfusion injury was evaluated in isolated rabbit hearts (n = 28). Isovolumic left ventricular function, coronary flow, creatine phosphokinase (CPK) release, and myocardial water content were measured after ischemia during both normothermia (37 degrees C; Group I) and hypothermia (23 degrees C; Group II). After baseline measurements, hearts were induced to arrest by chilled cardioplegic solution. Each group was divided into two subgroups, depending upon whether benidipine hydrochloride (10(-9) mole/liter) was added in the cardioplegia (A, without benidipine; B, with benidipine). After 30 min of ischemia for Group I and 180 min for Group II (which added another cardioplegia every 30 min), hearts were reperfused. Measurements the same as those at baseline were carried out every 15 or 30 min for up to 60 min. Benidipine-treated hearts started beating in a shorter time than did control hearts (Group I-B, 38.7 +/- 3.7 sec vs Group I-A, 59.9 +/- 5.6; Group II-B, 36.7 +/- 2.0 vs Group II-A, 47.8 +/- 3.3). The percentage of recovery of left ventricular developed pressure after 60 min of reperfusion was significantly better in benidipine groups (P < 0.05). With respect to changes in coronary flow and CPK release after reperfusion, benidipine groups were preserved extremely well. We conclude that the addition of benidipine hydrochloride to cardioplegic solution significantly improves ventricular function after myocardial ischemia and reperfusion.

Animals↗

Macroamylasemia associated with ulcerative colitis.

We describe a very rare case in which macroamylasemia was associated with ulcerative colitis of total colitis type. The patient's serum amylase isozyme pattern by electrophoresis showed a broad abnormal peak toward the side of the positive pole compared with regular salivary and pancreatic fractions. Sephadex G-200 column chromatography showed a sedimentation coefficient of 6.6 S. Amylase activity was bound to IgG. Double diffusion experiments demonstrated that amylase activity could be precipitated in gel by an antibody to the lambda chain. Although inflammatory bowel disease is occasionally associated with hyperamylasemia due to pancreatitis, we emphasize that, when hyperamylasemia is recognized in patients with inflammatory bowel disease, macroamylasemia also should be considered.

Adult↗

Shear stress-induced platelet aggregation in various types of von Willebrand disease.

We here examined the shear stress-induced platelet aggregation (SIPA) in various types of von Willebrand Disease (vWD), using a novel cone-and-plate viscometer recently developed by Ikeda et al. [1]. Under experimental conditions of high shear stress (90-108 dyne/cm2) known to induce von Willebrand factor (vWF)-dependent platelet aggregation in normal individuals, a variety of SIPA patterns, from a normal to total defect, were observed in 6 patients with type I vWD, while SIPA was totally absent in all 7 type IIA patients examined. One patient with Normandy type vWD exhibited a normal SIPA pattern under these experimental conditions. These findings, together with the vWF parameters of each patient, suggested that the presence of higher molecular weight multimers of plasma vWF, as well as an appropriate level of vWF antigen, is essential for SIPA to occur under high shear stress. Interestingly, vWF-dependent SIPA in 3 patients with type IIB vWD was found to be initiated by a low shear stress force, which did not induce such platelet aggregation in normal individuals. This might explain the intravessel platelet clumping that occurs, resulting in the intermittent thrombocytopenia observed in this type of the disease.

Adolescent↗

Prognosis of neurological deficits associated with upper cervical spine injuries.

We investigated the type of injury and neurological prognosis in 82 patients with an upper cervical spine injury with neurological deficits, from a total of 247 such patients that we treated, from which 11 patients who were dead on arrival had been excluded. The incidence of neurological deficits in upper cervical spine injury was 33%. They were classified into three signs; cord, upper cervical nerve root, and cranial nerve signs. The types of injury accompanied by neurological deficits were burst fracture of the atlas, type II dens fracture, body fracture of the axis, type II traumatic spondylolisthesis of the axis, atlanto-occipital dislocation, and atlanto-axial dislocation. Most were unstable vertebral injuries. The four patients who died after arrival at hospital had complete tetraplegia with respiratory distress. The neurological deficit was one of paresis in the 78 patients who survived; in many, the paresis was mild with a resulting good neurological prognosis.

Adolescent↗

Fibronectin and 130-kDa molecule complex mimics snake venom botrocetin-like structure potentially modulating association between von Willebrand factor and vascular vessel wall.

We established seven hybridomas secreting monoclonal antibodies (MoAbs) against the venom from Bothrops jararaca. Six of them were demonstrated to specifically recognize botrocetin, a venom protein which binds with von Willebrand factor (vWf) and induces platelet agglutination. Two of them, BCT4-3 and BCT115-2 MoAbs, could significantly inhibit botrocetin binding with plasma vWf. BCT4-3 could react slightly with a monolayer of human endothelial cells (ECs), and BCT4-3 binding to ECs was drastically enhanced by the coexistence of human plasma in a dose-dependent manner, indicating that a biological modulator structurally resembling botrocetin is created initially on the EC surface complexed with some plasma proteins. Botrocetin-like components could be immuno-purified only by immobilized BCT4-3, but not by the other immobilized MoAbs, from umbilical vein extracts. Interestingly, the immunoisolated materials were identified to consist essentially of fibronectin (Fn) and a 130 kDa molecule, and this complex bound to vWf in the extracts. Depletion of Fn from plasma decreased BCT4-3 binding to ECs. The epitope of BCT4-3 expressed on the endothelial surface, comprising plasma Fn and the coisolated 130 kDa molecule, is proposed to be a physiological modulator structurally mimicking botrocetin, and essentially supporting vWf-binding to injured endothelium and subsequently to circulating platelets.

Antibodies, Monoclonal↗

Acquired von Willebrand disease associated with multiple myeloma; characterization of an inhibitor to von Willebrand factor.

Acquired von Willebrand disease (vWD) has been described in a few patients with multiple myeloma. The present study characterizes an inhibitor of von Willebrand factor (vWF) isolated from a patient with multiple myeloma (IgG-kappa). Multimeric analysis of vWF from this patient's plasma showed a reduction in multimers of all sizes. The inhibitor (IgG) detected only the vWF subunit from plasma of normal individuals. It reacted with intact vWF subunit and a 39/34kDa dispase-digested fragment of vWF (residues; Leu480/Val481-Gly718), but did not react with platelet membrane glycoproteins (GPs) or adhesive proteins. The binding of vWF to GPIb mediated by ristocetin and by botrocetin was inhibited by the patient's IgG with an IC50s of 0.3 mg/ml and 0.48 mg/ml, respectively. The platelet aggregation induced by ristocetin or botrocetin was also inhibited by the IgG. These results indicate that this inhibitor may recognize the binding region of vWF to GPIb. Therefore, the antibody to vWF appears to represent the likely pathophysiological mechanism responsible for the acquired vWD in this patient.

Autoantibodies↗

Impaired high-shear-stress-induced platelet aggregation in patients with chronic renal failure undergoing haemodialysis.

We investigated shear-induced platelet aggregation (SIPA) in 30 patients with chronic renal failure (CRF) undergoing haemodialysis. 26 patients showed a significant decrease in SIPA at high shear stress but no change in SIPA at low shear stress. The former reaction reflects the interaction between plasma von Willebrand factor (vWF) and its platelet receptors, glycoprotein (GP) Ib-IX and IIb/IIIa complex, whereas the latter is assumed to involve the binding of plasma fibrinogen to GP IIb/IIIa complex. These SIPA profiles in CRF patients after haemodialysis showed almost no change compared to those before haemodialysis. The ratio of ristocetin cofactor/vWF antigen in plasma was slightly lower in CRF patients than in controls (P < 0.01). However, the level of GPIb antigen in the platelets of these patients was significantly reduced (42.1 +/- 20.3% of normal platelets), with partial destruction of GPIb antigen. The number of vWF receptors on the GPIb molecule was quantitated using the GPIb-binding protein alboaggregin-B (AL-B), purified from the snake venom of Trimeresurus albolabris. AL-B bound to GPIb at a total of 48,760 +/- 9944 molecules per normal platelet and a Kd of 85.44 +/- 15.70 nM at saturation. In contrast, binding in CRF platelets was 22,980 +/- 6395 molecules per platelet and Kd was 50.08 +/- 13.83 nM. Taking these results together, we conclude that the impaired SIPA found in CRF patients is due to both abnormalities in plasma vWF and in its platelet GPIb receptor.

Adult↗

ABO blood group genotype and plasma von Willebrand factor in normal individuals.

von Willebrand factor (vWF) is a multimeric plasma protein with ABO (H) blood group sugar chains. We investigated a total of 330 plasmas from normal individuals having various ABO genotypes, with special reference to vWF antigen and its platelet glycoprotein-Ib-related biological activities, termed ristocetin cofactor (RCof) and botrocetin cofactor (BCof). RCof reflects the biological activity of higher vWF multimers, while BCof reflects that of vWF of multimers of all sizes. Plasmas from normal individuals carrying one O gene (genotypes AO and BO) had slightly, but proportionally lower levels of vWF antigen, RCof, and BCof than those carrying no O gene (genotypes AA, AB, and BB). Normal plasmas from individuals carrying two O genes (genotype OO) showed much lower values for these parameters than the other plasmas, as previously reported. However, multimeric analysis of plasma vWF antigen revealed no differences among the different genotypes.

ABO Blood-Group System↗

Recombinational rescue of the stalled DNA replication fork: a model based on analysis of an Escherichia coli strain with a chromosome region difficult to replicate.

To examine the physiological effects of DNA replication arrest at the terminus (Ter), we constructed a replication-blocked Escherichia coli strain so that both bidirectional replication forks would be impeded at two flanking Ter sites, one artificial and the other natural. While the blocked strain grew slightly more slowly than a control strain, it had abnormal phenotypes similar to those of E. coli dam mutants, i.e., hyper-Rec phenotype, recA(+)- and recB+ (C+)-dependent growth, and constitutive SOS induction. The observation that these two apparently unrelated mutants cause similar phenotypes led us to design a model. We propose that the following sequential events may occur in both strains. A double-strand (ds) break occurs at the blocked replication fork in the blocked strain and at the ongoing fork in the dam mutant, through which RecBCD enzyme enters and degrades the ds DNA molecule, and the degradation product serves as the signal molecule for SOS induction. When RecBCD enzyme meets an appropriately oriented Chi sequence, its DNase activity is converted to recombinase enzyme, which is able to repair the ds end, recombinationally. this model (i) explains the puzzling phenotype of recA and recB (C) mutants and the SOS-inducing phenotype of polA, lig, and dna mutants under restrictive conditions, (ii) provides an interpretation for the role of the Chi sequence, and (iii) suggests a possible key role for homologous recombination with regard to cell survival following the arrest of DNA replication.

Chromosomes, Bacterial↗

[An enzyme-linked immunosorbent assay determining anti-principal neutralizing determinant antibodies using synthetic peptides deduced from cDNA sequences of HIV-1 V3 loop domain].

The V3 domain, one of the hypervariable regions of gp 120 in HIV-1 possesses principal type-specific neutralizing determinant (PND). The V3 domain has the epitopes for class I major histocompatibility antigens of cytotoxic-T lymphocyte and helper-T-lymphocyte recognition sites, and also has major determinants for cell tropism towards macrophage, microglia, and human brain-derived fibroblast. Therefore, establishment for the assay of anti-PND antibodies in patients with HIV-1 infection appears to be important for the estimation on developing AIDS in these patients. We here describe a simple enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-PND antibodies found in Japanese hemophiliacs. ELISA was performed using synthetic peptides, each 15 amino acid residues deduced from cDNA sequences of seven HIV-1 V3 domain mutants, which include 5 North-American and European strains (IIIB, MN, RF, SC, and WMJ-2) and 2 African strains (Af1. Con and Af2, Con). The specific antibody binding to each peptide was determined after subtraction of the non-specific binding from the total. In 49 control sera from healthy individuals with HIV-1 antibody negative, the absorbance (M +/- 1SD) at 405 nm was -0.002 +/- 0.064. Then, the cut off value was determined to be M + 4SD. In 48 hemophiliac sera with HIV-1 antibody negative, the absorbance was uniformly less than the cut off value. However, among 44 hemophiliac sera with HIV-1 antibody positive, the anti-PND antibodies were detected in the following frequencies; 2 for IIIB, 20 for MN, 1 for RF, 1 for Af1. Con, and 5 for Af2. Con.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

[Clinical evaluation of patients with cardiopulmonary bypass by plasma granulocyte elastase].

To evaluate the role of granulocyte elastase (GEL) at cardiopulmonary bypass (CPB), the plasma GEL level was measured in 24 patients who underwent elective cardiac surgery and 47 patients who underwent elective gastroenterological surgery. The cardiac surgical patients were divided into two groups: 5 patients with CPB less than 120 minutes (HL group), and 19 patients with CPB more than 120 minutes (HH group). The patients with gastro-enterological surgery were also divided into two groups: 15 patients with postoperative complications (GC group), and 32 patients without postoperative complications (GU group). All the patients of GU, HL and HH groups were alive. Two patients of GC group died because of multiple organ failure (MOF). The serum levels of GEL in both the HH group and the GC group remained higher than in the GU group at 6 postoperative day (POD). The high serum level of IL-8 gave rise to high serum level of GEL in the HH group, even after cardiac surgery. We assumed that anti-cytokine therapy and aggressive administration of Ulinastatin are useful against postoperative complications and that careful management is need after long CPB.

Cardiac Surgical Procedures↗

[Clinical analysis of the surgical therapy of DeBakey type I acute aortic dissection].

We investigated relation of operative mortality with factors such as during from onset to operation, cardiac tamponade, age (more than 70 years old), aortic regurgitation, and shock. Fourteen patients underwent emergent surgery for DeBakey type I acute aortic dissection. These patients were the basis for this reports. Operative mortality was 43% (6/14). Although not statistically significant, there was a trend toward preoperative cardiac tamponade, namely the patients with preoperative tamponade had a poor prognosis. Causes of death were as follows, two patients related to the residual false lumen, two patients to surgical procedure, one patients to ischemic heart and one to mis-swallowing after operation. Among two patients who related to the residual false lumen, one died of rupture of the descending aorta that the clamping was performed during operation and the other occlusion of superior mesenteric artery 43 days after operation. Causes of deaths in patients in relation with surgical procedure were brain death and postoperative bleeding in 1 each. We concluded that the residual false lumen is a risk factor in the peri-operative stage.

Adult↗

[Changes in intraoperative and postoperative colloid oncotic pressure after open heart surgery especially in relation to non-blood priming or blood priming].

In order to evaluate the colloid oncotic pressure (COP) is useful index of hemodynamics and respiratory recovery after open heart surgery, cardiac index (CI), pulmonary capillary wedge pressure (PCWP), (A-a) Do2 and COP were measured in 34 patients during 48 hours after the cardiopulmonary bypass (CPB). The patients were divided into non-blood priming group: 11 patients and blood priming group (23 patients). In addition, blood priming group divided into two groups, one with dopamine (more than 15 micrograms/kg/min), epinephrine or intraaortic balloon pumping (severe blood subgroup, n = 6) and the other without these treatments after open heart surgery (slight blood subgroup n = 17). The COP levels in the non-blood priming group were significantly higher than those in the blood priming group from aortic cross-clamp to 10 minutes after aortic declamping (p < 0.01). From 1 to 48 hours after CPB, COP in the non-blood priming group and slight blood subgroups was significantly higher than severe blood subgroups (p < 0.05). CI and COP-PCWP levels were significantly higher in the non-blood priming group and slight blood subgroups than those in the severe blood group (p < 0.05). It is concluded that COP is useful index of hemodynamics and respiratory recovery after open heart surgery and our priming system without blood is effective in order to eliminate the blood transfusion.

Aged↗

Isolation and characterization of jararaca GPIb-BP, a snake venom antagonist specific to platelet glycoprotein Ib.

A platelet glycoprotein Ib-binding protein (GPIb-BP) was isolated from the snake venom of Bothrops jararaca. Jararaca GPIb-BP showed a single band with M(r) of 30,000, and two distinct bands with M(r) of 17,000/13,000 under non-reducing and reducing conditions, respectively, on SDS-polyacrylamide gel electrophoresis. Jararaca GPIb-BP itself induced neither platelet aggregation nor serotonin release from platelets, but specifically bound to GPIb (40,629 +/- 2,521 molecules per normal platelet, with Kd 39.1 +/- 2.4 nM at saturation). The purified venom protein completely inhibited ristocetin- or botrocetin-induced von Willebrand factor (vWF) binding, and blocked the bovine vWF binding to GPIb, with IC50 values ranging from 28 to 42 nM, without affecting the platelet aggregation induced by ADP or alpha-thrombin. 125I-jararaca GPIb-BP binding to GPIb was not altered by the presence of human alpha-thrombin. Jararaca GPIb-BP at a final concentration of 104 nM totally abolished vWF-dependent shear-induced platelet aggregation (SIPA) at a high shear stress, but had no effect on SIPA at a low shear stress. Reduced and S-carboxyamido-methylated jararaca GPIb-BP lost its inhibitory activity on SIPA. The NH2-terminal amino acid sequences of the subunits revealed a high degree of homology with those of several Ca(2+)-dependent lectins, especially to those of two functionally opposite venom proteins, botrocetin (a vWF-modulator) and alboaggregin-B (a GPIb-modulator).

Amino Acid Sequence↗

[Shear-induced platelet aggregation (SIPA) monitoring of hemostatic effect during platelet transfusion in a patient with Glanzmann's thrombasthenia: a comparison between SIPA and conventional platelet aggregation].

Shear-induced platelet aggregation (SIPA) in a patient with Glanzmann's thrombasthenia was examined during platelet infusion therapy. Prior to platelet infusion, SIPA measured with the modified cone-and-plate type viscometer, as well as ADP-and collagen-induced platelet aggregation measured with the conventional platelet aggregometer, were absent. The patient's SIPA after multiple infusions of platelet, in parallel with the bleeding time and the clinical hemostatic effect, improved to the normal level, while ADP-and collagen-induced platelet aggregation remained abnormal. These observations imply that SIPA is physiologically more relevant than the conventional agonist-induced platelet aggregometry in this type of the disease.

Adenosine Diphosphate↗

Realignment of postoperative cervical kyphosis in children by vertebral remodeling.

STUDY DESIGN: This study analyzed radiographically change in the sagittal curvature of the cervical spine after atlantoaxial (C1-C2) posterior fusion in children. OBJECTIVES: This study clarified the process of spinal remodeling after postoperative cervical deformation in children. SUMMARY OF BACKGROUND DATA: Postoperative spinal deformations in children are observed frequently. However, there have been only a few reports on postoperative changes in the sagittal curvature of the cervical spine and spinal remodeling after those changes. METHODS: Between 1979 and 1991, there was a total of 12 children who underwent C1-C2 posterior fusions. The average age at the time of surgery was 9.8 years. The alignment of the cervical spine was classified into four groups (lordosis, straight, kyphosis, and swan-neck deformity). Radiographic findings suggestive of the remodeling were as follows: 1) new bone formation on the anterior vertebral cortex, and 2) increase in body/canal ratio (BCR). The follow-up period averaged 6.2 years. RESULTS: Postoperative cervical malalignment (kyphosis or swan-neck deformity) occurred in four patients. In all four patients, new bone formation and increase in BCR at the apex of kyphosis were observed. Therefore, there was gradual improvement of the malalignment by vertebral remodeling. This phenomenon was not observed in eight patients with normal alignment. CONCLUSION: Realignment of postoperative cervical kyphosis by vertebral remodeling was observed in children. The results of this study suggested that remodeling occurred even in the spine, which was similar to the remodeling in long bones.

Atlanto-Axial Joint↗