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E Tsuda

Publications and source records attributed to E Tsuda.

At least 55 records · Page 3Linked to original sources
PubMed1998

Natural hepatocyte growth factor (HGF) from human serum and a bound form of recombinant HGF with heparan sulfate are indistinguishable in their physicochemical properties.

Natural hepatocyte growth factor (nHGF) purified from human serum showed a difference in molecular mass (Mr) between SDS PAGE (76-90 kDa) and gel filtration chromatography on a Sephadex G-200 column (> 200 kDa), whereas nHGF or recombinant HGF (rHGF) from cell culture medium did almost the same Mr (74-100 kDa). A bound form of rHGF with heparan sulfate (or heparin), and an aggregate form of rHGF itself showed a homogeneous band with a Mr of 76-90 kDa on SDS PAGE, but showed a Mr larger than 200 kDa on a Sephadex G-200 column. Both nHGFs, rHGF and the bound form were basic, but the aggregate form was acidic in ionic nature. No significant difference was found in affinity for heparin among these HGF preparations. The bound form treated by the procedures for purification of nHGF from human serum still showed a larger molecular form. The bound form mimicked physicochemical properties of nHGF purified from human serum. These results suggest that a possible form of nHGF in human serum may be a bound form with heparin-like molecules such as heparan sulfate, which are found in the circulation and on cell surface, and purified as the bound form.

Animals↗
PubMed1998

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy.

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 +/- 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 +/- 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.

Animals↗
PubMed1998

Asymptomatic familial cerebral aneurysms.

PURPOSE: We evaluated the prevalence and features of cerebral aneurysms in the family members of people with asymptomatic aneurysms among 8680 participants undergoing magnetic resonance angiography. METHODS: Of the 8680 participants, 380 had family histories of aneurysms and 8300 did not. The prevalence and features of asymptomatic aneurysms were compared in these two subgroups. In addition, the prevalence in all living first- or second-degree relatives was evaluated in 20 families. RESULTS: The prevalence of asymptomatic aneurysms was 7.0% (606 of 8680 participants) overall and 10.5% (40 of 380 participants) and 6.8% (566 of 8300 participants) in the subgroups with and without family histories of aneurysms, respectively. The prevalence in the female participants with family histories of aneurysms (12.3%, 28 of 228 participants) was higher than that in the male participants with family histories of aneurysms (7.9%, 12 of 152 participants) (P < 0.0001). Compared with the entire group, this subgroup more commonly showed aneurysms situated at the junction of the internal carotid and posterior communicating arteries (P < 0.0005) and at the middle cerebral artery (P < 0.0001). The prevalence of aneurysms in 115 members of the 20 families was 33.9%. Although the members of 14 families with aneurysmal subarachnoid hemorrhage showed higher prevalence of ruptured and asymptomatic aneurysms (42.1%) than did the members of 6 families with only asymptomatic aneurysms (17.9%), the former had very low prevalence of asymptomatic aneurysms. CONCLUSION: The prevalence of aneurysms is significantly elevated in family members of people with asymptomatic aneurysms. It is suggested that familial asymptomatic aneurysms are more likely to rupture in families having members with aneurysmal subarachnoid hemorrhage than in those without.

Adolescent↗
PubMed1998

Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro.

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.

Amino Acid Sequence↗
PubMed1998

Hypocalcemic effect of osteoclastogenesis inhibitory factor/osteoprotegerin in the thyroparathyroidectomized rat.

Osteoclastogenesis inhibitory factor (OCIF), also termed as osteoprotegerin (OPG), is a soluble member of the tumor necrosis factor receptor family. Although OCIF/OPG is shown to inhibit osteoclast formation in vitro and prevent ovariectomy-induced bone loss in vivo, its effect on serum calcium level remains to be determined. In this study we examined the acute effect of OCIF on thyroparathyroidectomized rats whose serum calcium concentrations were raised either by exogenous PTH or 1,25-(OH)2D3. When OCIF was administered at the start of PTH infusion, it attenuated the initial rise in serum calcium. When OCIF was administered into rats with established hypercalcemia, it decreased serum calcium rapidly (within 2 hr) and dramatically. OCIF did not increase urinary calcium excretion. These findings, especially the rapid onset of its hypocalcemic effect, suggest that OCIF not only inhibits the formation of osteoclasts but also affects the function and/or survival of mature osteoclasts at doses used in this study.

Animals↗
PubMed1998

[Osteoclastogenesis inhibitory factor (OCIF)/OPG].

A novel cytokine termed osteoclastogenesis inhibitory factor (OCIF) was purified to homogeneity from conditioned medium of human embryonic lung fibroblasts. OCIF is a heparin-binding basic glycoprotein with Mr of 60 kDa for a monomer and 120 kDa for a homodimer. OCIF specifically inhibits osteoclastogenesis in vitro and increases bone mineral density and bone volume in normal rats. The cloning of OCIF cDNA revealed that OCIF is a soluble member of the tumor necrosis factor receptor (TNFR) superfamily consisting of four cystein-rich domains, two death domain homologous regions (DDHs), and C-terminal basic domain. Mutational analysis of OCIF revealed that N-terminal portion of OCIF consisting of four cystein-rich domains is sufficient to inhibit osteoclastogenesis. OCIF inhibits osteoclastogenesis by binding to the sites expressed on osteoblastic cells and interrupting cell-to-cell signaling between osteoblastic cells and osteoclast progenitors.

Animals↗
PubMed1997

Another critical region for deletion of 22q11: a study of 100 patients.

Deletions at 22q11.1-q11.2 present with variable manifestations usually referred to as DiGeorge or velo-cardio-facial syndrome. We previously reported that deletions observed in patients with the syndrome can be subgrouped into three types (common large deletion, proximal deletion, and distal deletion) and demonstrated the presence of a second critical region for the syndrome. In order to characterize further the second critical region, a 22q11 deletion map was constructed from the data of 100 patients, using 12 DNA markers scattered in the common large deletion, and then a phenotype-genotype correlation was analyzed. The second critical region was found to correspond to the distal deletion encompassing the HCF2, cHKAD26, and D22S935 loci, and the proximal and distal deletions do not overlap each other. Although it seems that this condition is a contiguous gene syndrome, the phenotype of patients with these two types of deletion was indistinguishable from that of patients with the common large deletion. Thus, it is plausible that several genes located in the two segments corresponding to the two deleted regions are involved in the same developmental pathway or in an extremely long-range position effect.

Chromosome Deletion↗
PubMed1997

Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.

A factor which inhibits osteoclast-like cell formation was found in the conditioned medium of human embryonic lung fibroblasts, IMR-90. The factor, termed osteoclastogenesis inhibitory factor, OCIF, was purified to homogeneity. OCIF is a heparin-binding basic glycoprotein and has been isolated as a monomer with an apparent molecular weight (Mr) of 60,000 and a homodimer with a Mr of 120,000. The N-terminus of OCIF is blocked and the determination of internal amino acid sequences revealed that OCIF has no homology to known proteins. OCIF inhibited in a dose-dependent manner osteoclastogenesis elicited through three distinct signaling pathways stimulated by 1 alpha,25-dihydroxy vitamin D3, parathyroid hormone, and interleukin-11, respectively, in a dose range of 1 to 40 ng/ml (IC50 = 4 to 6 ng/ml). OCIF neither inhibits bone resorption by mature osteoclasts nor exerts any other biological activities. These data strongly suggest that OCIF is a novel cytokine which specifically inhibits osteoclastogenesis.

Acid Phosphatase↗
PubMed1997

[Efficacy of MR angiographic original images on surgery for posterior communicating artery aneurysms].

This study evaluated the usefulness of axial source images of magnetic resonance angiography (MRA) on preoperative depiction of surgical topography around posterior communicating artery aneurysms. Twenty patients with posterior communicating artery aneurysms, two ruptured and eighteen unruptured, underwent conventional angiography as well as axial source and projection images obtained by three-dimensional time-of-flight MRA techniques. By comparing the topography based on these angiograms to that confirmed during surgery, we evaluated useful information specific to the source images of MRA. Source images of MRA visualized the posterior communicating artery and the anterior choroidal artery in eighteen cases (90%) and five cases (25%), respectively. The posterior communicating artery was recognized at a higher rate by source images of MRA than by conventional angiography (65%), while the anterior choroidal artery was recognized at a lower rate than by combined angiography (75%). We realized some specific information to the source images of MRA including the topographical relations between the aneurysmal neck and the orifice of the posterior communicating artery, the relations between the aneurysmal dome and the oculomotor nerve and the aneurysmal dome buried into the temporal lobe. The information suggested a satisfactory direction of safe aneurysmal clipping so as not to occlude the posterior communicating artery. It was concluded that the source images of MRA provided additional useful information on surgical topography in 60% of the cases involving posterior communicating artery aneurysms. Although not essential in every case, the information would be beneficial in cases with the aneurysmal dome suspected to be in the temporal lobe or when the surrounding topography can not be clearly understood by angiography.

Adult↗
PubMed1996

Biological and physicochemical characterization of recombinant human erythropoietins fractionated by Mono Q column chromatography and their modification with sialyltransferase.

Ten erythropoietin (EPO) fractions differing in sialic acid content, ranging from 9.5 to 13.8 mol mol-1 of EPO, were obtained from baby hamster kidney cell-derived recombinant human EPO by Mono Q column chromatography. The mean pI values of the EPO fractions determined by IEF-gel electrophoresis systematically shifted from 4.11 to 3.31, coinciding with the sialic acid content, without a change in the constitution of asialo N-linked oligosaccharides of each fraction. Although a linear relationship between the in vivo bioactivity and the sialic acid content of the fractionated samples was observed until 12.1 mol mol-1 of EPO, there was no further increase in their activity over 12.4 mol mol-1 of EPO. On the other hand, an inverse relationship between the in vitro bioactivity and sialic acid content of EPO was observed. Also, we showed that the in vivo bioactivity of some fractions with low sialic acid contents was increased after treatment with alpha 2,6-sialyltransferase, but the in vivo bioactivity of the other fractions with high sialic acid contents was either decreased or not affected.

Animals↗
PubMed1996

Surgical results and the related topographic anatomy in paraclinoid internal carotid artery aneurysms.

Paraclinoid internal carotid artery aneurysms arising between the roof of the cavernous sinus and the origin of the posterior communicating artery are of considerable interest with regard to their anatomical variations and technical surgical challenges. Twenty-seven patients with 30 paraclinoid aneurysms were treated surgically through pterional intradural approach. Neck clipping was performed in 22 (73%) of the 30 aneurysms, coating in seven, and trapping in one. The surgical outcome was excellent in 24 patients (24/27, 89%), with two patients showing ipsilateral partial visual field defect (2/27, 7%). There was one death (4%) due to infarction after unintended carotid artery trapping. The characteristic topographic anatomical features which we considered to pose technical difficulties and to be responsible for the complications or failure in neck clipping were aneurysmal dome extending into the anterior clinoid process, atheroma at the neck, multiple paraclinoid aneurysms, ophthalmic artery originating at the neck, and marked supero-medial shift of the C2 segment of the carotid artery. pre-operative depiction of the topographical anatomy around the paraclinoid aneurysm is essential but not always possible on the basis of conventional angiography. Magnetic resonance or three-dimensional computerized tomographic angiography, and their axial source imaging, were useful in delineating the topography with unusual aneurysmal growth, overlap of aneurysm with the parent artery, and uncommon variations of the surrounding structures.

Adult↗
PubMed1994

Hepatocyte growth factor and its variant with a deletion of five amino acids are distinguishable in their biological activity and tertiary structure.

A naturally occurring splice variant of hepatocyte growth factor (HGF) lacks a 5-amino acid sequence in the first kringle domain. Comparison of HGF and the deletion variant (dHGF) revealed that the deletion significantly altered the biological activities, solubility, and immunological property of HGF. HGF was respectively about 20-, 10-, and 2-fold more potent than dHGF in the stimulation of DNA synthesis in human umbilical vein endothelial cells, human aorta smooth muscle cells, and NSF-60 (murine myeloblastic cells). Conversely, dHGF was respectively about 3-, 2-, and 2-fold more potent than HGF in the stimulation of DNA synthesis in LLC-PK1 (pig kidney epithelial cells), OK (American opossum kidney epithelial cells), and rat hepatocytes. Moreover, HGF was over 70-fold more soluble than dHGF in PBS. Several monoclonal antibodies raised against dHGF recognized only dHGF and neither HGF nor reduced dHGF, demonstrating that the deletion caused a tertiary structural change. The structural change in HGF may be responsible for its altered biological activities and solubility.

Animals↗
PubMed1992

Late death after arterial switch operation for transposition of the great arteries.

Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.

Abnormalities, Multiple↗
PubMed1992

[Cardiac performance in total anomalous pulmonary venous connection].

Cardiac performance in 54 patients with total anomalous pulmonary venous connection was investigated by cardiac catheterization before and after surgery. 51 patients underwent intracardiac repair, and 17 of them died during or immediately after operation. According to the preoperative study, the left ventricular ejection fraction (LVEF) of surviving patients was significantly higher than that of patients who died, and the pulmonary arterial mean pressure of surviving patients was significantly lower than that of patients who died. However, there was no significant difference between the left ventricular end-diastolic volume (LVEDV), right ventricular ejection fraction (RVEF), and right ventricular end-diastolic volume (RVEDV) in surviving patients and those who died. Post-operative catheterization studies showed significant increases of LVEF and LVEDV compared to pre-operative figures. RVEF and RVEDV and pulmonary arterial mean pressure decreased significantly after surgery. It was concluded that preoperative cardiac performance of surviving patients was better than that of those who died, and post-operative cardiac performance of surviving patients was basically normal.

Blood Pressure↗
PubMed1992

[Thallium-201 myocardial imaging in cases involving transposition of the great arteries after arterial switch operation].

Forty patients, including 39 with complete transposition of the great arteries and one with double outlet right ventricle, after arterial switch operation were studied with thallium myocardial imaging (TMI). In patients who had post-operative cardiac catheterization, the TMI findings were compared to those of catheterization studies. The right ventricular to left ventricular up-take ratio (RV/LV ratio) shown by TMI correlated well with the right-to-left ventricular systolic pressure ratio. Supravalvular pulmonic stenosis with significant pressure gradient was found in 14 patients, and all of them were noted to have an elevated RV/LV ratio. This ratio was noted to increase progressively on serial TMI studies in most patients who had significant pulmonic stenosis on first postoperative catheterization. Three patients had significant perfusion defects indicating the presence of myocardial damage. Two of them had occlusion of the coronary artery, but the other one had no coronary abnormalities able to be found by coronary arteriography. Air embolism or some other intra-operative transient insults to the myocardium were most likely to have been responsible for the perfusion defects. Thus, TMI was valuable as one of the noninvasive tools for follow-up of patients after arterial switching, particularly for those with late complications such as supravalvular pulmonic stenosis and coronary problems.

Cardiac Surgical Procedures↗
PubMed1991

Tumor cytotoxic factor/hepatocyte growth factor from human fibroblasts: cloning of its cDNA, purification and characterization of recombinant protein.

Two different forms of cDNA for F-TCF were isolated from cDNA library prepared with mRNA from human embryonic lung fibroblast, IMR-90 cells. One of them was completely identical to the cDNA for placenta type hepatocyte growth factor (HGF) and the other one was a variant cDNA for the HGF with a deletion of 15 base pairs in the coding region. The cDNAs were expressed in CHO cells and recombinant proteins were purified and characterized. The deleted form of recombinant F-TCF (rF-TCF) was slightly lower in heparin affinity than the intact form. Both rF-TCFs showed almost same dose-response curves for cytotoxicity on Sarcoma 180 or Meth A sarcoma cells. Dose-response curves for the stimulation of DNA synthesis in rat hepatocytes were also almost same before reaching maximal activity at 12.5 ng/ml but significantly different at higher concentrations. The deleted form of rF-TCF maintained maximal activity in the dose range of 12.5 to 100 ng/ml, although the intact form decreased the activity dose-dependently at more than 25 ng/ml. This suggests that the deletion of five amino acids results in a conformational change which alters heparin binding and hepatocyte growth stimulating activities.

Amino Acid Sequence↗
PubMed1991

[Pharmacokinetics and the time course of pharmacodynamics of recombinant human erythropoietin (SNB-5001)].

Pharmacokinetics and the time course of pharmacodynamics of recombinant erythropoietin (SNB-5001) were investigated. The plasma concentration of SNB-5001 reached Cmax at 6-7 hr after the subcutaneous injection and gradually decreased. Most of the SNB-5001 in plasma disappeared at 48 hr. Serum erythropoietin activity changed similarly to plasma SNB-5001 concentration. It was indicated that SNB-5001 moves into the plasma and organs having intact bio-activity after its injection. The decrease in serum iron and increase in unsaturated iron binding capacity (UIBC) began at 8 hr after the injection. Both the trough point of serum iron decrease and the peak point of UIBC increase were 24 hr after the injection. Each value recovered to the initial level at 72 hr. Total iron binding capacity did not change. Increase in reticulocytes began at 24 hr and reached the peak at 72-96 hr after the injection of SNB-5001. Reticulocytes count recovered to the initial level at 120 hr. The pharmacodynamics time course after the subcutaneous injection of SNB-5001 was the same as that after the intravenous injection. It was indicated that SNB-5001 reached an effective plasma level at the earlier absorption phase after the subcutaneous injection.

Animals↗