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Biomedical subjects

S Eguchi

Publications and source records attributed to S Eguchi.

At least 73 records · Page 4Linked to original sources

The Influence Function of Principal Component Analysis by Self-Organizing Rule.

This article is concerned with a neural network approach to principal component analysis (PCA). An algorithm for PCA by the self-organizing rule has been proposed and its robustness observed through the simulation study by Xu and Yuille (1995). In this article, the robustness of the algorithm against outliers is investigated by using the theory of influence function. The influence function of the principal component vector is given in an explicit form. Through this expression, the method is shown to be robust against any directions orthogonal to the principal component vector. In addition, a statistic generated by the self-organizing rule is proposed to assess the influence of data in PCA.

Journal Article↗

Down-regulation of adenylate cyclase coupled to adrenomedullin receptor in vascular smooth muscle cells.

Adrenomedullin activates receptor-mediated adenylate cyclase to cause vasorelaxation. To elucidate whether desensitization of adenylate cyclase coupled to vascular adrenomedullin receptors occurs, we studied the adenylate cyclase activity after treatment with rat adrenomedullin in cultured rat aortic vascular smooth muscle cells. Cyclic AMP (cAMP) generation induced by adrenomedullin was markedly decreased by pretreatment with adrenomedullin: a maximal reduction (approximately 80%) was induced after 2 h and persisted during 24 h. Desensitization was independent of protein kinase A, protein kinase C, protein tyrosine kinase or receptor sequestration, because pretreatment with either isoproterenol, forskolin, tetradecanoylphorbol acetate, cytochalasin D, or colchicine did not affect the adrenomedullin-stimulated cAMP response. Furthermore, preincubation with inhibitors for these protein kinases prior to pretreatment with adrenomedullin failed to affect the adrenomedullin-induced decrease in cAMP response following the second stimulation with adrenomedullin. The present results provide the evidence for the existence of desensitization of adenylate cyclase coupled to vascular adrenomedullin receptors.

Adenylyl Cyclases↗

Calcium-dependent epidermal growth factor receptor transactivation mediates the angiotensin II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells.

We have recently reported that angiotensin II (Ang II)-induced mitogen-activated protein kinase (MAPK) activation is mainly mediated by Ca2+-dependent activation of a protein tyrosine kinase through Gq-coupled Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMC). In the present study, we found Ang II rapidly induced the tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and its association with Shc and Grb2. These reactions were inhibited by the EGF receptor kinase inhibitor, AG1478. The Ang II-induced phosphorylation of the EGF receptor was mimicked by a Ca2+ ionophore and completely inhibited by an intracellular Ca2+ chelator. Thus, AG1478 abolished the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. Moreover, Ang II induced association of EGF receptor with catalytically active c-Src. This reaction was not affected by AG1478. These data indicate that Ang II induces Ca2+-dependent transactivation of the EGF receptor which serves as a scaffold for pre-activated c-Src and for downstream adaptors, leading to MAPK activation in VSMC.

Adaptor Proteins, Signal Transducing↗

The long-term survival rates of patients after repair of abdominal aortic aneurysms.

This study was undertaken to examine the long-term survival rates of patients following abdominal aortic aneurysm (AAA) repair in comparison with an age-matched normal population, and to determine by multivariate analysis the factors influencing long-term survival. Of 125 patients who underwent AAA repair prior to July 1986, 13 died during hospitalization. Of these 13 patients, 6 who suffered aneurysmal rupture all died within 30 days. The survival rate of patients with ruptured aortic aneurysms was significantly lower than that of those with nonruptured aneurysms. Of the 112 patients surviving hospitalization, 85 died within 0.48 to 24 years after their operation. The long-term survival rate of patients who had suffered a preoperative cardiovascular event was significantly lower than that of those who had not suffered a preoperative cardiovascular event. The actual survival rate was significantly lower than the expected survival rate. According to a multivariate analysis, the significant predictors of late survival were age, aneurysmal rupture, and chronic renal failure in all the patients, and age, chronic renal failure, and pre- and postoperative cardiovascular events in patients who did not die in hospital. These findings indicate the importance of improving immediate perioperative management of ruptured AAA and that cardiovascular events should be prevented, or treated during long-term follow-up.

Adult↗

Successful surgery for an acute type A aortic dissection following repair of a descending thoracic aortic aneurysm.

Acute type A aortic dissection in the presence of a previously repaired atherosclerotic descending thoracic aortic aneurysm is rarely reported. We experienced a patient who underwent an ascending aortic replacement with reconstruction of the aortic arch 16 months after repair of a descending thoracic aortic aneurysm. We succeeded in the redo operation with comprehensive techniques involving selective cerebral perfusion, deep hypothermia, early antegrade systemic circulation for cerebral protection, and femoro-femoral bypass with occlusion of the descending aorta for lower systemic perfusion as well as renal perfusion. The patient recovered and is doing well one year after the redo operation.

Acute Disease↗

Successful removal of massive cardiac neurilemoma with cardiopulmonary bypass.

A 46-year-old woman was referred to our hospital because of cardiac enlargement seen on a chest radiograph. Imaging studies showed a massive intrapericardial tumor with a size of 12x8x7 cm. Tumor dissection included inspection of the inner aspect of the superior vena cava with use of cardiopulmonary bypass, because the mass was tightly adherent to both superior vena cava and right atrium. The pathologic diagnosis was neurilemoma.

Cardiopulmonary Bypass↗

Surgery for giant popliteal artery aneurysm with a modified Sims' position.

A 73-year-old man with a giant popliteal artery aneurysm extending from the mid-thigh to the popliteal fossa underwent exclusion, bypass, and obliterative endoaneurysmorrhaphy while in a modified Sims' position. The use of this position allowed for exposure of the saphenous vein and the entire popliteal artery in the same operative field. No muscle division was required. Moreover, this position provided easy access to the superficial femoral and distal below-knee popliteal arteries.

Aged↗

Mediation between the shamanistic model and the psychiatric model in a shamanistic climate: a viewpoint of medical anthropology.

It is suggested that any clinician working on the Miyako islands, Okinawa, Japan, be a mediator or a negotiator between two worlds, namely the shamanistic and the modern psychiatric ones. On these islands, to subscribe to either is possible only by ignoring conflicting clinical realities. The main point is to summarize the complementary practices of these two medical systems on these islands. Psychiatric illness attributed to kamidaari is introduced. The initiatory illness for seeing a shaman is called kamidaari or kamburi. From the viewpoint of medical anthropology, aspects of the treatment of such patients in a shamanistic 'climate' (which is called fudo in Japanese), will be reported. In the shamanistic fudo, it must be recognized that, at a critical moment, shamanistic epistemology and psychiatric epistemology penetrate each other, and they exist together in a clinical 'mesh'. Two epistemologies must join in a coalition to access, and build continuity into, psychiatric and shamanistic medical care. It is demonstrated that these two worlds almost merge in dialogue but do not fuse, and that clinical relations occur on the boundary between these two epistemologies. 'Climatic' specific therapeutic stances are introduced and are clinically illustrated.

Adult↗

Total blood exchange suppresses the early stage of liver regeneration following partial hepatectomy in rats.

Despite its obscure and short effect, plasma exchange (PE) remains a mainstay in the treatment of liver disease. However, the question still remains as to whether or not PE suppresses the regeneration of the liver because PE deprives patients of hepatotrophic factors. The effect of PE, which could be a total blood exchange (TBE) in a syngeneic setting, on liver regeneration following a 68% partial hepatectomy (PH) was investigated in rats. In Group 1, 20 ml of blood from normal rats was infused while native blood was removed at 6 and 12 h after PH. In Group 2, 20 ml of blood obtained from PH rats at the same time points was infused. The regeneration rate, labeling index of proliferating cell nuclear antigen (PCNA), and plasma hepatocyte growth factor (HGF) level were determined, and standard liver function tests performed at 24, 48, and 72 h. Although all liver function tests improved in Group 1 at 24 and 48 h, the regeneration rate was significantly impaired. Similarly, the PCNA labeling index was significantly lower in Group 1 than that in Group 2. The plasma HGF level was significantly reduced in Group 1 (6 h blood out versus blood in: 1.1+/-0.5 vs. 0.1+/-0.1 ng/ml, p < 0.05). TBE with normal blood following PH suppressed the early stage of liver regeneration, in part, because of the reduction of HGF even though the blood was purified.

Alanine Transaminase↗

Complete intercostal artery reimplantation using a method of aneurysmoplasty.

We report the case of a 58-year-old woman who underwent repair of a chronic dissecting thoracoabdominal aortic aneurysm. Using a method of aneurysmoplasty under normothermic cardiopulmonary bypass, all intercostal arteries were quickly reperfused, and the spinal cord ischemic time was minimized. No neurological deficits developed in our patient using this method.

Aortic Dissection↗

Endothelin-1 stimulates DNA synthesis of vascular smooth-muscle cells through transactivation of epidermal growth factor receptor.

To elucidate the molecular mechanism of the mitogenic effect of endothelin-1 (ET-1) on vascular smooth-muscle cells (VSMCs), we studied the effect of AG1478, a novel epidermal growth factor receptor (EGFR) kinase inhibitor, on p42/44 mitogen-activated protein (MAP) kinase activation, c-Fos expression, and DNA synthesis stimulated by ET-1. AG1478 dose-dependently (2.5 x 10(-8) M-2.5 x 10(-7) M) inhibited ET-1-induced MAP kinase activation. The ET-1-induced c-Fos protein expression was inhibited by AG1478 (2.5 x 10(-7) M). AG1478 also dose-dependently inhibited ET-1-stimulated [3H]thymidine incorporation. These data suggest that ET-1 induces MAP kinase activation, c-Fos expression, and promotes proliferation of VSMCs via transactivation of EGFR.

Animals↗

Lysophosphatidylcholine stimulates MAP kinase activity in rat vascular smooth muscle cells.

Lysophosphatidylcholine (lyso-PC) has been implicated in atherogenesis and the inflammatory process. Although lyso-PC has been reported to contribute to the mitogenic effect of oxidized LDL on rat cultured vascular smooth muscle cells (VSMCs), the signaling mechanisms by which lyso-PC promotes its proliferation are poorly characterized. Mitogen-activated protein (MAP) kinases are important mediators involved in the intracellular network of interacting proteins that transduces extracellular cues to intracellular responses. We therefore examined the effect of lyso-PC on MAP kinase activation, proto-oncogene expression, and AP-1 binding activity using cultured rat VSMC. Marked activation of MAP kinase occurred within 10 minutes of lyso-PC treatment, whereupon rapid inactivation ensued. MAP kinase activation by lyso-PC was concentration-dependent (6.25 to 25 micromol/L). Pertussis toxin treatment did not affect lyso-PC-induced MAP kinase phosphorylation. Lyso-PC (25 micromol/L) also increased the mRNA expression of c-fos and c-jun genes. An electrophoretic mobility shift assay showed that AP-1 binding activity was enhanced by lyso-PC. To examine the upstream signaling of MAP kinase, we used several inhibitors on MAP kinase activation induced by lyso-PC. Although lyso-PC induced sustained increase in intracellular Ca2+ concentration, EGTA had no effect on MAP kinase activation induced by lyso-PC. However, protein kinase C inhibitor GF109203X and downregulation of protein kinase C activity by prolonged treatment with phorbol ester inhibited lyso-PC-induced MAP kinase activation. These data suggest that lyso-PC transmits its mitogenic activity through a MAP kinase-AP-1 pathway, which exists downstream of its protein kinase C activation in VSMCs.

Animals↗

Adrenomedullin as a novel growth-promoting factor for cultured vascular smooth muscle cells: role of tyrosine kinase-mediated mitogen-activated protein kinase activation.

To examine whether adrenomedullin (AM), a novel vasodilator peptide, acts as a growth modulator in the vasculature, the effects of AM on protein tyrosine phosphorylation, mitogen-activated protein kinase (MAPK) activation, protooncogene expression, DNA synthesis, and cell proliferation were studied in cultured rat vascular smooth muscle cells (VSMC). AM and calcitonin gene-related peptide (CGRP), although weaker than AM, stimulated DNA synthesis and cell proliferation of quiescent VSMC, whose effects were inhibited by a CGRP receptor antagonist, CGRP-(8-37). AM induced a rapid increase in MAPK activity, followed by the expression of the immediate early protooncogene c-fos. AM-induced MAPK activation and cell proliferation were completely blocked by protein tyrosine kinase inhibitors (genistein and ST638). Moreover, AM rapidly induced tyrosine phosphorylation of several proteins (approximately 120, approximately 90, and approximately 50 kDa) and transiently increased association of a tyrosine-phosphorylated protein (approximately 120 kDa) and Shc with the glutathione-S-transferase-Grb2 fusion protein. A MAPK kinase inhibitor (PD98059) also reduced the AM-induced MAPK activation, c-fos messenger RNA expression, and cell proliferation. Although AM has been shown to induce vasodilation through cAMP production in VSMC, a cAMP antagonist (Rp-cAMP-thionate) and a protein kinase A inhibitor (KT5720) failed to block AM-induced MAPK activation and DNA synthesis. Moreover, 8-bromo-cAMP and forskolin did not affect the MAPK activity. AM had no effect on either the intracellular Ca2+ concentration or inositol 1,4,5-trisphosphate formation. In addition, a protein kinase C inhibitor (GF109203X) did not inhibit the AM-induced MAPK activation. These data suggest that in addition to its vasodilatory effect through the cAMP-dependent pathway, AM exerts its mitogenic activity via protein tyrosine kinase-mediated MAPK activation in quiescent rat VSMC.

Adrenomedullin↗

[Treatment of cytomegalovirus retinitis in AIDS with an intraocular sustained-release ganciclovir implant].

Active cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) was treated with an intraocular sustained-release ganciclovir implant. A total number of 19 implants were performed in 15 eyes of 9 AIDS patients. The intraocular sustained-release ganciclovir was effective in preventing reactivation of CMV retinitis in 15 of the 19 implants, ineffective in 3, and undetermined in 1. All ineffective cases had been resistant to ganciclovir therapy before the implants. Vision after the therapy was maintained at better than 0.5 except for one eye. There were no serious ocular complications caused by the therapy. Among 5 patients with unilateral CMV retinitis, 2 unaffected eyes developed CMV retinitis during this therapy. In addition, another patient developed presumed CMV infection in other systemic organs. Based on these data, the intraocular sustained-release ganciclovir implant was considered to be useful for the treatment of CMV retinitis in AIDS.

AIDS-Related Opportunistic Infections↗

Treatment of severe liver failure with a bioartificial liver.

Orthotopic liver transplantation (OLT) is the definitive therapy for severe liver failure. However, many patients die before an organ becomes available, mostly from cerebral edema. To provide temporary liver support, we developed a bioartificial liver (BAL) based on porcine hepatocytes and a charcoal column. Fifty-four consecutive BAL treatments were carried out in three groups of patients: Group I (n = 15) patients presented with FHF were listed for emergent OLT, Group II (n = 3) patients with primary non-function (PNF) of their liver grafts required urgent re-transplantation and Group III (n = 10) patients with acute exacerbation of chronic liver disease were not candidates for OLT. Patients were managed in a critical care unit receiving maximal standard support. Each BAL treatment was conducted for 6 hours. In Group I, all patients showed significant neurologic improvement, intracranial pressure (ICP) decreased and cerebral perfusion pressure (CPP) increased; other significant improvements, included lowered plasma ammonia and liver enzymes and increased glucose. One patient recovered spontaneously without OLT, all other patients were "bridged" to OLT, and recovered. Group II: PNF patients showed similar benefits. Group III: Chronic liver patients demonstrated transient beneficial effects after BAL treatment(s), however, most (n = 8) eventually succumbed to sepsis and multiple organ failure as they were not candidates for OLT; two patients, recovered, later were successfully transplanted and survived. Our clinical experience demonstrates that the BAL can serve as a bridge to OLT in patients with acute liver failure.

Adult↗

Fetal rat hepatocytes: isolation, characterization, and transplantation in the Nagase analbuminemic rats.

BACKGROUND: In contrast to adult hepatocytes, fetal hepatocytes (FH) are thought to be highly proliferative, less immunogenic, and resistant to cryopreservation and ischemic injury. These qualities could enhance FH engraftment, proliferation, and gene transfer requiring active DNA synthesis. METHODS: Rat FH were obtained using the nonperfusion collagenase/DNase digestion method. Free and cultured cells were studied using electron microscopy, fluorescence-activated cell sorting, and Northern analysis using alpha-fetoprotein and albumin as markers of hepatocyte lineage. DNA synthetic activity was measured in quiescent and mitogen-stimulated fetal and adult hepatocytes by [3H]thymidine incorporation. Susceptibility of cultured FH to retrovirally mediated gene transfer was studied using an amphotropic retroviral vector carrying the Escherichia coli lac-Z gene. Nagase analbuminemic rats were used as recipients to study the effects of intraportal FH transplantation. Analysis of serum albumin was carried out by enzyme-linked immunosorbent assay. RESULTS: In fetal liver, 87+/-2% of the cells showed morphological and molecular features of hepatocytes. DNA synthetic activity in nonstimulated cultured FH was 10 times greater than the maximal hepatocyte growth factor-driven response in adult rat hepatocytes. A total of 5-15% FH stained positive for X-gal; results of transduction in adult hepatocyte cultures were negative. In Nagase analbuminemic rat recipients, FH produced significant amounts of albumin only when a hepatic regenerative stimulus was applied. Immunohistochemistry confirmed presence of albumin-positive hepatocytes. CONCLUSIONS: Fetal rat liver from the late gestation period is highly enriched with hepatocyte progenitors. They are highly proliferative and susceptible to retroviral transduction and can engraft and function in the adult rat liver if transplanted under a hepatic regenerative stimulus.

Acetylglucosaminidase↗