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Biomedical subjects

Y Fujimura

Publications and source records attributed to Y Fujimura.

At least 19 recordsLinked to original sources
PubMed2006

Preoperative portal vein embolization with a mixture of gelatin sponge and iodized oil: efficacy and safety.

PURPOSE: To evaluate whether portal vein embolization (PVE) using a mixture of gelatin sponge (GS) pieces and iodized oil is safe and effective in inducing hypertrophy of the future liver remnants (FLR). MATERIAL AND METHODS: PVE was performed in 14 patients (eight male and six female, mean age 65 years, range 35-81 years) diagnosed with malignant liver tumor before surgery, whose FLR volumes were judged too small to allow for safe resection. Liver volume change, biochemical data change, complications related to PVE, and postoperative complications were retrospectively evaluated. RESULTS: PVE was successful in all patients, and there were no procedural complications. Absolute FLR volume and FLR/total liver volume (TLV) ratio increased by 102 cm3 and 8% (mean values), respectively. Planned hepatectomies were cancelled in three patients due to extrahepatic metastasis or bile duct infection. Five of the 11 patients (45%) who underwent hepatectomies had major postoperative complications. However, complications due to hepatic failure were not seen. In 10 patients, except one whose outcome was fatal outcome, the mean hospitalization days with and without major complications were 73 and 33 days, respectively. CONCLUSION: PVE using a mixture of GS and iodized oil seems to be effective and safe in inducing hypertrophy of the FLR.

Adult↗
PubMed2005

Platelets treated with ticlopidine are less reactive to unusually large von Willebrand factor multimers than are those treated with aspirin under high shear stress.

Much attention has recently been focused on the interaction between unusually large von Willebrand factor multimers (UL-VWFM) and platelets under high shear stress in pathological thrombus formation. The antiplatelet drugs acetylsalicylic acid (aspirin) and a thienopyridine derivative (ticlopidine) are commonly used to treat cerebral ischemia but exert different effects on high-shear-stress-induced platelet aggregation (H-SIPA) in the plasma. To examine the effects of these drugs in the absence of plasma factors, we studied H-SIPA using washed platelets (WPs) and purified UL-VWFM. WPs were prepared from the blood of 9 aspirin-treated and 11 ticlopidine-treated patients with cerebral ischemia, and H-SIPA in the presence of UL-VWFM was measured using a cone plate aggregometer. Plasma levels of VWF antigen with its multimer analysis, ristocetin cofactor and VWF-cleaving protease (ADAMTS13) activity were also measured. Forty-six healthy volunteers from 2 age groups, 20-40 years (n=20) and 41-60 years old (n=26), were also tested as controls. H-SIPA was significantly inhibited for ticlopidine-treated platelets, but it was observed to a lesser extent for aspirin-treated platelets. For both groups, no difference in the plasma levels of VWF antigen, ristocetin cofactor and ADAMTS13 activity was noted. All patients possessed UL-VWFM, and it was detected in healthy volunteers with increasing frequency with increasing age. Under plasma-free conditions, platelets from aspirin-treated patients exhibit marginal but significant inhibition of H-SIPA. Furthermore, the presence of UL-VWFM in the plasma of patients and normal volunteers is directly related to their age rather than being a consequence of underlying disease.

ADAM Proteins↗
PubMed2005

Thrombotic thrombocytopenic purpura associated with polyarteritis nodosa.

We present a case of classical polyarteritis nodosa (PN) overlapping thrombotic thrombocytopenic purpura (TTP). A 70-year-old woman was transferred to our hospital because of general fatigue and fever. On admission, laboratory findings revealed leukocytosis, normochromic normocytic anemia and renal dysfunction. About one week later, she developed disturbance of consciousness, and laboratory findings revealed rapidly progressive thrombocytopenia and renal dysfunction. We suspected the presence of microscopic polyangiitis (MPA), based on mild elevation of myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA). On post-admission Day 11, renal biopsy was performed but the diagnosis of MPA could not be confirmed because of the absence of glomerular crescent formation or vasculitis. However, the biopsy specimen showed many collapsed glomeruli and interstitial inflammation, indicating the presence of occlusive lesions, such as vasculitis in larger arteries. We instituted methylprednisolone pulse therapy, cyclophosphamide and plasma exchange, because the clinical symptoms also satisfied the criteria of TTP. Despite the intensive treatment, the patient died on 43rd day of hospitalization due to thalamic hemorrhage. Autopsy showed typical findings of classical PN including disruption of arterial walls and fibrinoid necrosis in the medium-sized arteries of the kidneys and colon. We detected reduced activity of von Willebrand factor-cleaving protease (VWF-CP) and the presence of plasma inhibitory IgG against VWF-CP. A better understanding of the mechanisms would be useful.

Aged↗
PubMed2004

Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor.

Inhibitory antibody to von Willebrand factor (vWF)-cleaving protease (ADAMTS13) was detected in a patient with intravascular lymphomatosis. The increased serum level of the antibody paralleled an increase in the expression of uncleaved vWF, which might cause microvascular thrombosis and platelet consumption. Malignant cell proliferations with superimposed thrombosis within the lumina throughout the entire vasculature account for diffuse neurodeficits observed in the patient.

ADAM Proteins↗
PubMed2003

Changes of cervical spinal cord and cervical spinal canal with age in asymptomatic subjects.

STUDY DESIGN: Prospective study on magnetic resonance imaging (MRI) and radiographic findings of the cervical spine. OBJECTIVE: To elucidate the age-related changes of the cervical spinal cord and the cervical spinal canal and the relationship between the spinal cord and the spinal canal in asymptomatic subjects using MRI and radiography. SETTING: Tokyo, Japan. METHODS: The transverse area of the cervical spinal cord and the ratio of the anteroposterior diameter to the transverse diameter (RAPT) were investigated, using MRI in 229 asymptomatic subjects. The sagittal spinal canal diameter and anteroposterior diameter of the cervical vertebral body were also measured on plain lateral radiographs. The canal body ratio (CBR), which was defined as the diameter of the spinal canal divided by that of the vertebral body, was calculated. RESULTS: The transverse spinal cord area correlated negatively with age. RAPT did not correlate with age. The CBR correlated negatively with age. The correlation between spinal cord area and CBR was significant but weak and the correlation between RAPT and CBR was not significant. CONCLUSION: The transverse area of the cervical spinal cord measured by MRI decreased with age, while RAPT remained unchanged. The bony spinal canal became narrower with age. The spinal cord area and the shapes of the spinal cord were independent from the spinal canal diameter in asymptomatic subjects. These facts should be considered when evaluating radiological findings in patients with cervical spinal disorders.

Adolescent↗
PubMed2003

Clinical features associated with recurrence of tumours of the spinal cord and cauda equina.

STUDY DESIGN: Retrospective review of consecutive cases of recurrent spinal cord and cauda equina tumours. OBJECTIVES: We sought to identify factors and conditions resulting in re-operation to treat recurrences of spinal cord and cauda equina tumours. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: Re-operation was performed in 39 patients with spinal cord and cauda equina tumours. Times of operation, interval between operations, affected spinal level, tumour site on cross section, configurations among dumb-bell tumours, and pathologic diagnoses were analysed. Recurrence rates were defined in terms of the number of cases with re-operation due to tumour recurrence relative to the total number of surgical cases for the same period at our institution. RESULTS: Recurrence rates were relatively high for intradural, extramedullary tumours and for tumours located anteriorly rather than laterally. Of patients with intradural, extramedullary plus extradural tumours who underwent initial surgery at our hospital, 75% (9/12) recurred; all tumours had dumb-bell-type configurations. The overall rate of re-operation due to tumour recurrence in 249 cases was 7.2% at our institution. By tumour types, 40% of malignant schwannomas recurred (2/5), as did 35.7% of neurofibromas (5/14), and 33.3% of ependymomas (6/18). CONCLUSION: Risk factors for tumour recurrence were anterior location, an intradural, extramedullary plus extradural site, extensive dumb-bell tumours, and pathologic diagnoses of neurofibroma, ependymoma, or malignant schwannoma.

Adolescent↗
PubMed2002

Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication after stem cell transplantation (SCT), characterized by thrombus formation in hepatic venules leading to a symptom triad of hyperbilirubinemia, hepatomegaly, and ascites. Multifactorial defects in the hemostatic system may contribute to its pathogenesis, but its remains to be investigated. Unusually large VWF multimers (UL-VWFMs), produced in and released from vascular endothelial cells, are most biologically active in the interaction with platelets under a high shear stress. UL-VWFMs are cleaved and degraded into smaller VWFMs by a specific liver producing plasma protease, termed VWF-cleaving protease (VWF-CPase), which has recently been identified as a metalloprotease solely produced in liver, termed ADAMTS13. Herein, we studied the correlation between plasma VWF-CPase activity and UL-VWFMs in 21 patients who received SCT, seven patients with VOD and 14 patients without VOD. In non-VOD patients, activities (mean +/- 1s.d.) of VWF-CPase were 78 +/- 17% of the control before the conditioning regimen, 76 +/- 18% on day 0, 64 +/- 19% on day 7, 57 +/- 23% on day 14, 68 +/- 13% on day 21 and 79 +/- 19% on day 28 after SCT. The respective values in VOD patients were 32 +/- 19%, 27 +/- 15%, 18 +/- 11%, 22 +/- 18%, 26 +/- 22% and 12 +/- 4%. Thus, VWF-CPase activity was significantly reduced in VOD patients, even before the conditioning regimen, and such a difference was not found in other laboratory tests. However, despite such a clear difference, UL-VWFMs were present in plasmas of both patient groups, together with the increase of VWF antigen and ristocetin cofactor activity. These results indicate that the measurement of this enzyme activity is extremely useful in predicting the occurrence of VOD prior to a demonstration of its direct involvement in its pathogenesis.

ADAM Proteins↗
PubMed2001

EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function.

The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans-activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.

Blotting, Western↗
PubMed2001

Increase of oligodendrocyte progenitor cells after spinal cord injury.

The reaction of oligodendrocyte progenitor cells (OPCs) after spinal cord injury (SCI) is poorly understood. In this study, we examined oligodendroglial reactions after contusion SCI in adult rats by immunohistochemistry. OPCs were identified by staining with monoclonal antibodies (mAbs) A2B5 and O4. Each of the A2B5-, O4-positive OPCs and galactocerebroside-positive oligodendrocytes dramatically increased in the lesion of the dorsal posterior funiculus. Bromodeoxyuridine (BrdU) incorporation studies showed that most O4-positive cells in the lesion were labeled with BrdU, suggesting that these OPCs were proliferative. In contrast, the expression of myelin basic protein was decreased in the lesion compared with controls that received laminectomy only. From the injured cord, OPCs were isolated by immunopanning with mAb A2B5. We observed an increased number of OPCs from the injured spinal cords compared with those isolated from controls and unoperated animals. After several days in culture, the OPCs from the lesion expressed galactocerebroside. These results suggest that OPCs are induced and can differentiate following SCI in the adult rat.

Animals↗
PubMed2001

Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations.

STUDY DESIGN: A retrospective follow-up study of conservatively treated patients with mild cervical myelopathy caused by cervical soft disc herniation. OBJECTIVE: To investigate the outcome of conservative treatment for patients with mild myelopathy caused by cervical soft disc herniation and to evaluate usefulness of magnetic resonance findings in the prediction of the outcomes. SUMMARY OF BACKGROUND DATA: Recent studies on conservative treatment for cervical soft disc herniation have focused mainly on radiculopathy, and not on myelopathy. METHODS: Twenty-seven patients with mild cervical myelopathy secondary to cervical soft disc herniation were treated conservatively for more than 6 months by cervical bracing and restriction of daily activities. Of the 27 patients, 17 patients (Group A) underwent conservative treatment only and it was associated with improvement in their neurologic deficits, while the other 10 patients (Group B) ultimately underwent decompression surgery because of neurologic deterioration. Comparisons between the two groups were made in regard to JOA scores, patient satisfaction, and magnetic resonance findings, including location of the disc herniation (focal or diffuse in the sagittal plane, median or paramedian in the axial plane). RESULTS: The JOA scores were 13.6 +/- 1.6 in Group A and 14.1 +/- 1.6 in Group B before treatment, 14.9 +/- 1.0 and 12.9 +/- 2.1, respectively, at 3 months, and 16.2 +/- 0.8 and 16.0 +/- 1.2, respectively, at the final follow-up. The JOA scores at 3 months were significantly lower in Group B than in Group A. Satisfaction with the results of treatment at the final follow-up was reported by 77% of the patients in Group A and 90% in Group B. Focal-type herniation was present in 47% of the patients in Group A and 70% in Group B, while median-type herniation was diagnosed in 77% in Group A and 30% in Group B. Follow-up magnetic resonance imaging of the patients in Group A showed spontaneous regression of a herniated mass in 10 patients (59%). Diffuse-type herniations were more likely to regress spontaneously than focal-type herniations (78% vs. 37%). CONCLUSIONS: Conservative treatment is an effective treatment option for mild cervical myelopathy caused by cervical soft disc herniation. A good outcome can be expected in patients with a median-type and/or diffuse-type herniation on magnetic resonance imaging.

Adult↗
PubMed2001

Complete amino acid sequence of kaouthiagin, a novel cobra venom metalloproteinase with two disintegrin-like sequences.

The primary structure of kaouthiagin, a metalloproteinase from the venom of the cobra snake Naja kaouthia which specifically cleaves human von Willebrand factor (VWF), was determined by amino acid sequencing. Kaouthiagin is composed of 401 amino acid residues and one Asn-linked sugar chain. The sequence is highly similar to those of high-molecular mass snake venom metalloproteinases from viperid and crotalid venoms comprised of metalloproteinase, disintegrin-like, and Cys-rich domains. The metalloproteinase domain had a zinc-binding motif (HEXXHXXGXXH), which is highly conserved in the metzincin family. Kaouthiagin had an HDCD sequence in the disintegrin-like domain and uniquely had an RGD sequence in the Cys-rich domain. Metalloproteinase-inactivated kaouthiagin had no effect on VWF-induced platelet aggregation but still had an inhibitory effect on the collagen-induced platelet aggregation with an IC(50) of 0.2 microM, suggesting the presence of disintegrin-like activity in kaouthiagin. To examine the effects of these HDCD and RGD sequences, we prepared synthetic peptides cyclized by an S-S linkage. Both the synthetic cyclized peptides from the disintegrin-like domain and from the Cys-rich domain) had an inhibitory effect on collagen-induced platelet aggregation with IC(50) values of approximately 90 and approximately 4.5 microM, respectively. The linear peptide (RAAKHDCDLPELC) and the cyclized peptide had little effect on collagen-induced platelet aggregation. These results suggest that kaouthiagin not only inhibits VWF-induced platelet aggregation by cleaving VWF but also disturbs the agonist-induced platelet aggregation by both the disintegrin-like domain and the RGD sequence in the Cys-rich domain. Furthermore, our results imply that the corresponding part of the Cys-rich domain in other snake venom metalloproteinases also has a synergistic disturbing effect on platelet aggregation, serving as a second disintegrin-like domain. This is the first report of an elapid venom metalloproteinase with two disintegrin-like sequences.

Amino Acid Motifs↗
PubMed2001

Molecular characterization of L-amino acid oxidase from Agkistrodon halys blomhoffii with special reference to platelet aggregation.

L-Amino acid oxidase (LAO, EC 1.4.3.2) is widely distributed in snake venom, and induces apoptosis in vascular endothelial cells, causing prolonged bleeding from vessel walls at bite sites. The effect of snake venom LAOs on platelet function is controversial. Further, we have little information on their structural characterization. We purified M (mamushi)-LAO, a single-chain glycoprotein with a molecular mass of 60 kDa and a pI of 4.9, from Agkistrodon halys blomhoffii (Japanese mamushi) venom, and determined the N-terminal and several internal amino acid sequences of this enzyme. Molecular cloning based on these data was conducted to elucidate its full-length cDNA structure (2192 nucleotides), which includes a putative 18 amino acid residue signal peptide and a 504 residue mature subunit. The predicted M-LAO translation product shares 87.3% identity with that of Crotalus adamanteus (Southeastern diamondback rattlesnake) LAO. M-LAO, up to a final concentration of 2.6 microM, inhibited both agonist- and shear stress-induced platelet aggregation (SIPA) dose-dependently. In agonist-induced platelet aggregation, M-LAO predominantly inhibited the second aggregation, but with a marginal inhibition of the first. In SIPA, the inhibition was more dramatic under low-shear stress than high-shear stress, and was enhanced by the presence of L-leucine, a substrate of this enzyme. Catalase, a H2O2 scavenger, totally quenched such enhancement. These results suggest that M-LAO inhibits the interaction between activated platelet integrin alphaIIb/beta3 and fibrinogen through the continuous generation of H2O2, and may contribute to prolonged bleeding from the vessels at snake bite sites.

Agkistrodon↗
PubMed2001

Enhanced low shear stress induced platelet aggregation by Shiga-like toxin 1 purified from Escherichia coli O157.

The effect of Shiga-like toxin 1 (Stx1) produced by Escherichia coli O157 on platelets was studied with an argon laser light-assisted shear-induced platelet aggregometer and with binding assays. Stx1 markedly enhanced the platelet aggregation under low shear stress but did not affect it under high shear stress. Minimal concentration of Stx1 required for the enhancement was 0.25 ng/ml, and almost maximal enhancement was observed at a final concentration of > or =2.5 ng/ml. This enhanced platelet aggregation disappeared after leukocyte depletion from normal platelet-rich plasma with a specific filter. In contrast, a standard platelet aggregometer was unable to detect this enhanced platelet aggregation in either the presence or the absence of ADP. 125I-labeled purified Stx1 did not specifically bind to normal washed platelets depleted of leukocytes, and thin-layer chromatographic analysis of glycolipids extracted from normal platelet lysates also confirmed that leukocyte-depleted normal platelets lack Stx1-specific receptor globotriaosylceramide (Gb3). Supernatant from the monocyte suspension stimulated with Stx1 exhibited the enhanced low shear stress induced platelet aggregation, but that from the polymorphonuclear cell suspension did not. Several cytokines produced from monocytes reproduced this event in vitro. Further, plasmas from six out of seven patients with hemolytic uremic syndrome (HUS) had activity similar to the purified Stx1. This activity was almost totally impaired after treatment of HUS plasmas with Gb3 in accord with reduction of plasma Stx1 levels. Taken together, these results indicate that platelets lack Gb3, and Stx1 appears to modulate platelet aggregation in an indirect fashion, presumably by the release of cytokines or chemical compounds from the target tissues.

Bacterial Toxins↗
PubMed2001

Ticlopidine-Associated thrombotic thrombocytopenic purpura with an IgG-type inhibitor to von Willebrand factor-cleaving protease activity.

A 41-year-old Japanese man complained of a left-sided visual disturbance. Imaging by magnetic resonance angiography revealed a narrowing of the left internal cervical artery. Thus, ticlopidine (Tc) administration was started at a daily dose of 300 mg. However, 2 weeks later, severe thrombocytopenia, fever, nausea, and psychiatric symptoms developed; Tc was therefore discontinued. Based on the diagnostic hallmark of 5 clinical signs, the patient's disease was diagnosed as thrombotic thrombocytopenic purpura (TTP). Daily plasmapheresis was performed for the first 4 days, and the patient's clinical signs gradually improved. Von Willebrand factor-cleaving protease (vWF-CPase) activity in his plasma was less than 3% of that of the control sample at diagnosis, but that value recovered steadily following plasmapheresis. In addition, immunoglobulin G purified from the patient plasma inhibited vWF-CPase activity in normal plasma with a specific activity of 0.8 Bethesda units/mg. No sign of TTP relapse has been noted following cessation of Tc. Thus, it was concluded that the patient developed TTP by producing an inhibitory autoantibody against vWF-CPase activity that was presumably triggered by Tc administration.

ADAM Proteins↗
PubMed2001

Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic thrombocytopenic purpura.

Upshaw-Schulman syndrome (USS) is a congenital bleeding disorder characterized by repeated episodes of thrombocytopenia and microangiopathic hemolytic anemia that respond to infusions of fresh frozen plasma. Inheritance of USS has been thought to be autosomal recessive, because 2 siblings in the same family are often affected but their parents are asymptomatic. Recently, chronic relapsing thrombotic thrombocytopenic purpura (CR-TTP), reported almost exclusively in adults, was shown to be caused by inherited or acquired deficiency in the activity of a plasma von Willebrand factor-cleaving protease (vWF-CPase). The pathogenesis of USS is unknown, and a relationship between CR-YEP and USS has not been reported. We studied 3 unrelated USS patients (ST, SY, and KI) who presented with severe indirect neonatal hyperbilirubinemia. All 3 patients had undetectable vWF-CPase activity, and the inhibitors to vWF-CPase were all negative. In their parents with no clinical symptoms, vWF-CPase activities as a percentage of control samples (mother/father) were 17/20 for ST, 60/45 for SY, and 36/5.6 for KI. Thus, USS and vWF-CPase activity appear to be coinherited as autosomal recessive traits. Transfusion of fresh frozen plasma in 2 patients (ST and SY) resulted in the expected maximal increment of approximately 7% to 8% in vWF-CPase activity at 1 to 4 hours, but the levels became less than 3% within 2 days. After this decrease, platelet counts increased, plateaued in the normal range at 10 to 12 days, and declined thereafter. Thus, the 2 to 3 weeks of therapeutic benefit from plasma infusions will be discussed in relation to the intravascular lifetime of vWF-CPase.

ADAM Proteins↗