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Biomedical subjects

S Eguchi

Publications and source records attributed to S Eguchi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Experimental application of microwave tissue coagulation to ventricular myocardium.

BACKGROUND: It is difficult to create transmural lesions in a beating, normothermic perfused heart. The aim of this study was to evaluate the effect of microwave tissue coagulation on a beating heart. METHOD: We used a microwave tissue coagulator that emits microwaves of 2,450 MHz. Studies were conducted on 30 mongrel dogs weighing between 9 and 13 kg, and microwave tissue coagulation was performed at the free wall of the left ventricle in a beating heart without cardiopulmonary bypass. RESULTS: Microwave tissue coagulation created transmural degenerated lesions in the left ventricle without risk of ventricular rupture. The lesion width of microwave ablation increased from 10 to 60 seconds. Histologic examinations revealed well-demarcated areas of heat degeneration consisting of coagulation necrosis and contraction band necrosis of the myocardium. The lesion healed to hard scar tissue, which was sharply demarcated from the normal myocardium. No animals had inducible ventricular tachycardia through programmed ventricular stimulation. CONCLUSIONS: Microwave ablation with a monopolar antenna created transmural lesions with only a few proarrhythmic events occurring during ablation.

Animals↗
PubMed1999

Biocompatibility of a silicone-coated polypropylene hollow fiber oxygenator in an in vitro model.

BACKGROUND: A silicone-coated microporous hollow-fiber membrane oxygenator has been developed to prevent plasma leakage during long-term use. The objective of this study was to evaluate the biocompatibility of the oxygenator. METHODS: A silicone-coated oxygenator was compared with an uncoated oxygenator in an in vitro model of cardiopulmonary bypass. Simulated circulation was maintained for 6 h at 37 degrees C. RESULTS: Platelet counts decreased significantly (p < 0.05) and leukocyte counts tended to decline; however, the differences between groups were not significant. Concentrations of C3a increased significantly in both groups (p < 0.05), but levels were significantly less in the silicone-coated oxygenator (p = 0.008). In contrast, concentrations of C4a, beta-thromboglobulin, and granulocyte elastase increased significantly (p < 0.05), but the differences between groups were not significant. CONCLUSIONS: Silicone coating over a microporous hollow-fiber membrane may improve biocompatibility by reducing C3a activation.

Coated Materials, Biocompatible↗
PubMed1999

Creating cataract in a pig eye.

The purpose of this study was to create a uniform, reproducible hardened lens nucleus and an anterior capsule in a pig eye that approximate those in the human eye for use in cataract surgery training. The lens nuclei was hardened and anterior capsule elasticity was reduced in pig eyes by injecting the lens with mixtures of formalin and alcohol (ethanol, 2-propanol, or both). A 30 gauge needle was used to pierce the lens 3.0 mm from the limbus. Then, 0.2 mL of the formalin and alcohol mixture was injected. The most effective mixture was formalin, ethanol, and 2-propanol in the ratio 4:3:3. Fifteen minutes after this mixture was injected, the pig eye had nuclear cataract with grade III hardness and an anterior capsule that approximated the capsule in a human cataractous eye. The cataract created by this method will be useful in teaching continuous curvilinear capsulorhexis, divide and conquer and phaco chop phacoemulsification, and nuclear hydrodelineation and rotation.

2-Propanol↗
PubMed1999

A role for transcriptional repressors in targeting the yeast Swi/Snf complex.

Genetic and biochemical studies indicate that the evolutionarily conserved Swi/Snf complex acts at a subset of genes to help transcriptional activators function on chromatin templates. The mechanism by which this complex is targeted to specific chromosomal loci remains unknown. We show that Swi/Snf is required for expression of the yeast histone HTA1-HTB1 locus because of the role of Hir1p and Hir2p corepressors in negatively regulating transcription. Snf5p, Snf2p/Swi2p, and Swi3p, three components of the yeast Swi/Snf complex, coimmunoprecipitate with each Hir protein, and Snf5p is maximally associated with the HTA1-HTB1 promoter when the Hir-based repression system is intact and the Swi/Snf complex is functional. The data support a role for the Hir repressors in the gene-specific targeting of Swi/Snf.

Adenosine Triphosphatases↗
PubMed1999

A comparison of methods for estimating individual pharmacokinetic parameters.

Characteristics of the methods for estimating individual pharmacokinetic parameters are compared both theoretically and numerically. The methods examined represent the range of most of modern methods and include the ordinary least squares, iteratively reweighted least squares, extended least squares, generalized least squares, maximum quasi-likelihood and its extended scheme, and minimum relative entropy methods. When the function representing the mean itself is used as a variance function, which may be then related to a Poisson distribution, the iteratively reweighted least squares estimator and maximum quasi-likelihood estimator are both identical to that of the minimum relative entropy method. These methods work by minimizing a kind of relative entropy between observed data and corresponding theoretical values. Furthermore, these methods guarantee agreement between the sum of the observed values and the estimate of the sum. This relation does not hold in general for the other estimators. The sum can, in a sense, be viewed as an approximation of the area under the curve. In addition, it is shown by numerical study that these methods are robust against the misspecification of the variance model and work as effectively as such sophisticated methods as the extended least squares, generalized least squares, and maximum extended quasi-likelihood methods. These sophisticated methods require complicated numerical optimization techniques and should be used only in cases where the estimation of the variance function is demanded. In the other cases, the method of minimum relative entropy or its equivalent is sufficient or even preferable for estimating individual pharmacokinetic parameters.

Computer Simulation↗
PubMed1999

Changes in liver regenerative factors in a case of living-related liver transplantation.

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living-related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16-yr-old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patient's mother. In the recipient, the pre-transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post-transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c-met on the membrane of the hepatocytes were positive. TGF-beta was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c-met was clearly detected on the cell membrane of the hepatocytes. Neither TGF-beta nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non-parenchymal cells and c-met was positive in the cytoplasm of the hepatocytes. TGF-beta was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF-beta. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c-met system is thought to be involved in the mechanism of regeneration. Intrahepatic apoptosis was detected in the graft on the 3rd post-transplant day probably due to transient ischemia in the liver, which was not related to the Fas/Fas-ligand system.

Adolescent↗
PubMed1999

Angiotensin receptors: molecular biology and signalling.

1. The active peptide hormone angiotensin II (AngII) is formed from its prohormone angiotensinogen by way of inactive angiotensin I. The highly specific protease, renin, responsible for the initiation of this system was elusive and considered unstable. We isolated it in a pure and stable form from the kidney of the pig, human, rat, and land submandibular glands of the mouse. It was shown that there is only one type of renin with highly stringent substrate specificity, except certain strains of the mouse which have two gene products. 2. The well-known diversity of action of AngII can be attributed to the presence of more than two subtypes, AT1 and AT2, as well as multiple signalling pathways for both of them. 3. The first subtype AT1 was shown to mediate most of the traditionally recognized AngII functions such as vasoconstriction, electrolyte homeostasis etc. 4. Although the identification of the signalling modes of the second subtype AT2 still remains elusive, we and others have shown evidence that its action is generally antagonistic to that of AT1. AT2 inhibits AT1 (growth factor-stimulated cell growth), AT2 attenuates the vasoconstriction induced by AT1. Since AT2 seems to mediate nitric oxide formation in the renal cells, it may initiate a natriuretic pathway in contrast to the sodium-retaining action of AT1-mediated AngII action. 5. Newer mechanisms and functions of these and other receptors will be clarified by the combination of molecular, cellular and integrated physiological studies.

Amino Acid Sequence↗
PubMed1999

Quantitative analysis of regular and irregular astigmatism induced by pterygium.

PURPOSE: To quantitatively evaluate the influence of pterygium and its removal surgery on both regular and irregular corneal astigmatism. METHODS: In 19 eyes of 19 patients undergoing pterygium surgery, videokeratographic measurements were taken before and 1 month after surgery. Using Fourier harmonic analysis, dioptric data on mire rings were decomposed into spherical, regular astigmatism, and irregular astigmatism (decentration and higher order irregularity) components. The distance between the line of sight and the advancing edge of pterygium was measured, and the eyes were classified into two groups: large pterygium group (the distance <2.0 mm, n = 7) and small pterygium group (> or =2.0 mm, n = 12). Fifteen eyes of 15 subjects served as age-matched normal control eyes. RESULTS: Before surgery, the magnitudes of regular astigmatism and higher order irregular astigmatism showed significant correlation with the size of pterygium. Regular astigmatism, asymmetry, and higher order irregularity in the large pterygium group were significantly greater than those of normal control eyes. The pterygium removal surgery significantly improved these changes, but regular astigmatism and higher order irregularity in the large pterygium group still remained significantly greater than those in the normal control eyes. CONCLUSION: Pterygium induces a significant amount of regular and irregular astigmatism in proportion to its size. The removal surgery can improve these changes, but corneal distortion does not normalize completely in eyes with advanced pterygium.

Aged↗
PubMed1999

Pancreatic beta-cell replication in streptozotocin-diabetic rats: the effect of liver compensatory growth on intraportally engrafted islets.

Early studies showed that compensatory liver growth after anterior portal branch ligation (aPBL) may restore normoglycemia in streptozotocin (STZ)-diabetic rats, in which a subtherapeutic islet mass was previously transplanted into the liver. We hypothesized that this effect could be related to islet regeneration at the graft site. This study was designed to characterize the proliferative response of the intraportally transplanted islets, shortly after aPBL. Male Wistar-Furth rats were used as syngeneic islet donors and/or recipients. STZ-diabetic rats were divided in four groups: groups 1 and 2 underwent selective 250-islet transplantation (Tx) into the posterior liver lobes, followed by aPBL 10 days later; rats were killed 24 h (n = 9) and 48 h (n = 10) after aPBL, respectively; groups 3 and 4 underwent selective 250-islet Tx into the posterior liver lobes, followed by sham aPBL 10 days later; rats were killed 24 h (n = 3) and 48 h (n = 3) after aPBL, respectively. Two hours before killing, all animals were injected with 5'-bromo-2'-deoxyuridine (BrdU; 50 mg/kg, i.v.). Liver sections were immunostained for insulin and BrdU, and both hepatocyte and islet cell labeling index (LI) were calculated. Islet cell LI was 2.30+/-1.18% in group 1, 2.23+/-1.00% in group 2, 0.43+/-0.29% in group 3, and 0.39+/-0.21% in group 4 (group 1 vs. group 3: p<0.02; group 2 vs. group 4: p<0.01). Hepatocyte LI was 2.50+/-2.14% in group 1, 15.0+/-7.6% in group 2, 0.12 +/-0.04 in group 3, and 0.11+/-0.03% in group 4, respectively (group 1 vs. group 2: p<0.02; group 1 vs. group 3: p<0.001; group 2 vs. group 4: p<0.001). Our study showed that intraportally transplanted islets undergo a concurrent proliferative response after aPBL, although with a lower extent and a different timing when compared with the liver-cell response.

Animals↗
PubMed1999

Involvement of PYK2 in angiotensin II signaling of vascular smooth muscle cells.

-PYK2, a recently identified Ca2+-sensitive tyrosine kinase, has been implicated in extracellular signal-regulated kinase (ERK) activation via several G protein-coupled receptors. We have reported that angiotensin II (Ang II) induces Ca2+-dependent transactivation of the epidermal growth factor receptor (EGFR) which serves as a scaffold for preactivated c-Src and downstream adaptors (Shc/Grb2), leading to ERK activation in cultured rat vascular smooth muscle cells (VSMC). Herein we demonstrate the involvement of PYK2 in this cascade. Ang II rapidly induced tyrosine phosphorylation of PYK2, whose effect was completely inhibited by an AT1 receptor antagonist and an intracellular Ca2+ chelator. A Ca2+ ionophore also induced PYK2 tyrosine phosphorylation to a level comparable with that by Ang II, whereas phorbol ester-induced phosphorylation was less than that by Ang II. Moreover, PYK2 formed a complex coprecipitable with catalytically active c-Src after Ang II stimulation. Although a selective EGFR kinase inhibitor completely abolished Ang II-induced recruitment of Grb2 to EGFR and markedly attenuated Ang II-induced ERK activation, it had no effect on Ang II-induced PYK2 tyrosine phosphorylation or its association with c-Src and Grb2. These data suggest that the AT1 receptor uses Ca2+-dependent PYK2 to activate c-Src, thereby leading to EGFR transactivation, which preponderantly recruits Grb2 in rat VSMC.

Angiotensin II↗
PubMed1999

Endothelin-mediated vascular growth requires p42/p44 mitogen-activated protein kinase and p70 S6 kinase cascades via transactivation of epidermal growth factor receptor.

Endothelin-1 (ET-1), a potent endothelium-derived vasoconstrictor peptide, exerts a growth-promoting effect on vascular smooth muscle cells, implicating its pathogenic role in vascular remodeling. To gain insight into the cellular and molecular mechanism whereby ET-1 induces vascular growth, we studied whether transactivation of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor, are required for activation of p42/p44 mitogen-activated protein (MAP) kinase and p70 S6 kinase (p70S6K), and subsequent growth-promotion by ET-1 in cultured rat vascular smooth muscle cells. Immunoblotting with antiphosphotyrosine antibody revealed that ET-1 rapidly (within 2 min) and transiently induced tyrosine phosphorylation of several proteins, among which 180-kDa protein was shown to be EGFR. ET-1 rapidly increased association of EGFR and Shc with glutathione-S-transferase-Grb2 fusion protein. The ET-1-induced activation of MAP kinase was reduced by an EGFR kinase inhibitor (AG1478) but not by a platelet-derived growth factor receptor kinase inhibitor (AG1296). AG1478 dose-dependently decreased ET-1-stimulated MAP kinase activity as well as [3H]leucine and [3H]thymidine uptake. The ET-1-induced tyrosine phosphorylation of EGFR, as well as MAP kinase activation, was inhibited by an ETA receptor antagonist and intracellular Ca2+ antagonists but not by an ETB receptor antagonist, pertussis toxin, or protein kinase C inhibitors. In addition, dominant negative mutant of H-Ras and a MAP kinase kinase (MEK-1) inhibitor (PD98059) completely blocked ET-1-induced MAP kinase activation as well as [3H]leucine and [3H]thymidine uptake. Both AG1478 and PD98059 inhibited ET-1-induced phosphorylation and activation of p70S6K. Furthermore, rapamycin, a selective inhibitor of mammalian target of rapamycin, completely blocked ET-1-stimulated [3H]leucine and [3H]thymidine uptake. These results suggest that ETA receptor-mediated vascular growth by ET-1 requires both MAP kinase and p70S6K cascades mediated partly via Ca2+-dependent EGFR transactivation.

Animals↗
PubMed1999

Intracellular signaling in rat cultured vascular smooth muscle cells: roles of nuclear factor-kappaB and p38 mitogen-activated protein kinase on tumor necrosis factor-alpha production.

Lipopolysaccharide (LPS) is responsible for initiating host responses leading to septic shock, and tumor necrosis factor-alpha (TNF alpha) is thought to be its primary mediator. In addition, TNF alpha is one of the major components of the pathogenesis of insulin resistance in various conditions. It has been shown that LPS induced TNF alpha production in rat vascular smooth muscle cells (VSMC). However, little is known about the signaling pathway by which VSMC in culture produce TNF alpha. We investigated the possible signaling components involved in this pathway. LPS elicited phosphorylation of p42/44 mitogen-activated protein kinase (MAPK) and p38 MAPK, degradation of inhibitor of kappaB (IkappaB), and an increase in nuclear binding activity of activating protein-1 and nuclear factor-kappaB (NF-kappaB). Different types of NF-kappaB inhibitors, pyrrolidine dithiocarbamate and MG132, which specifically abolished IkappaB degradation and subsequent NF-kappaB activation by LPS, suppressed TNF alpha secretion from VSMC. Although PD98059, a specific MAPK kinase inhibitor and SB203580, a specific p38 MAPK inhibitor, had no effect on NF-kappaB activity, SB203580 suppressed TNF alpha secretion; however, PD98059 did not. A cotransfection assay showed that transfection of dominant negative IkappaB or pretreatment with SB203580 suppressed the TNF alpha gene promotor-dependent transcription. TNF alpha messenger RNA expression induced by LPS was inhibited by pyrrolidine dithiocarbamate, MG132, and SB203580, but not by PD98059. These observations indicate that TNF alpha production in VSMC is stimulated by LPS, and its transcription and translation are dependent on NF-kappaB activation through proteasome-mediated IkappaB degradation. It is likely that p38 MAPK may play a critical role in regulating transcription of the TNF alpha gene in VSMC, unlike in other cell lines.

Animals↗
PubMed1999

Selective suppression of cerebellar GABAergic transmission by an autoantibody to glutamic acid decarboxylase.

Humoral immune response to glutamic acid decarboxylase (GAD) has been implicated in the pathogenesis of stiff-man syndrome and cerebellar ataxia, but the underlying pathomechanism is unclear. Using a whole-cell patch-clamp technique with rat cerebellar slices, we found that immunoglobulins present in the cerebrospinal fluid of an ataxic patient acted presynaptically to cause a selective suppression of GABAergic transmission. This synaptic depression was most likely elicited by an autoantibody to GAD.

Aged↗
PubMed1999

Effects of anticoagulants on porcine hepatocytes in vitro: implications in the porcine hepatocyte-based bioartificial liver.

For the clinical treatment with porcine hepatocyte-based bioartificial liver (BAL), the use of an anticoagulant in the extracorporeal system is essential. In this experiment, we studied the effect of various anticoagulants on cultured porcine hepatocytes. Porcine hepatocytes were isolated and seeded at a density of 2 x 10(5) cells on a collagen-coated plate in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal calf serum (FCS). Twenty-four hours later, the medium was changed to DMEM with various anticoagulants such as nafamostat mesilate (NM), sodium heparin (SH) and sodium citrate (SC) at concentration used clinically. As a control, the hepatocytes were cultured in only DMEM. After culturing for 6 hours, the viability of the porcine hepatocytes, lactate dehydrogenase (LDH) release, lidocaine clearance (cytochrome p450 function) and albumin synthesis were investigated. SC did not affect either the viability or the p450 function of the hepatocytes. In the NM group, the viability of porcine hepatocytes and lidocaine clearance were decreased significantly more than in the other groups. SH did not affect the viability of porcine hepatocytes, however, it seemed to reduce the p450 function. In conclusion, SC may therefore be the optimal anticoagulant available for hepatocyte-based BAL circuit in terms of its cell toxicity.

Albumins↗
PubMed1999

Efficacy of Nafamostat Mesilate for improving the performance of a bioartificial liver using porcine hepatocytes.

Our bioartificial liver (BAL) consists of porcine hepatocytes attached to beads and plasma perfused through the system. The function of our BAL lasts for approximately 7 hours. The objective of the present study was to investigate the efficacy of Nafamostat Mesilate (NM), a protease inhibitor and potent complement inhibitor, for improving the performance of the BAL. The experimental groups were divided as follows; the NM group (n=7) where the BAL had porcine hepatocytes with 3.8x10(-4) M, of NM, and the control group where the BAL had no NM. Plasma obtained from patients suffering from hepatic failure was perfused through the BAL for 10 hours. The viability of the porcine hepatocytes and the levels of alanine aminotransferase (ALT) in the human plasma were measured during perfusion. After the 10-hour perfusion, another human hepatic failure plasma was perfused for an additional 1 hour and then the function of the BAL was evaluated. After the 10-hour perfusion, the viability of the hepatocytes in the NM group was 51 +/- 7%, whereas that in the control group was rapidly reduced by 35 +/- 5%. Although the levels of ALT in the human plasma in both groups increased with the perfusion time, those in the NM group were significantly lower than those in the control group (p < 0.05). These results suggest that NM prevented damage to the porcine hepatocytes in human hepatic failure plasma as compared to the control group. In the human hepatic failure plasma before perfusion, the partial thrombin time (PT) and the plasma ammonia (NH3) levels were 19.8 +/- 12% and 288 +/- 102 microg/dl, respectively. Fischer's ratios were 0.98 +/- 0.39. Even after the 10-hour perfusion, the BAL in the NM group significantly improved the levels of PT (38 +/- 10%; p < 0.05), NH3 (214 +/- 34 microg/dl; p < 0.05) and Fischer's ratios (1.4 +/- 0.3; p < 0.05). On the other hand, the BAL in the control group did not show any improvement in those parameters. In conclusion, NM was found to help in maintaining the viability of porcine hepatocytes in human hepatic failure plasma, thereby allowing the porcine hepatocyte-based BAL to function much better.

Alanine Transaminase↗
PubMed1999

Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases.

In addition to its well known involvement in Gq/11-mediated vasoconstriction and its key roles in the homeostasis of electrolyte balances, the angiotensin II type 1 (AT1) receptor activates mitogen-activated protein kinase (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellular signal-regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells. The mechanism for Gq-mediated activation of the tyrosine kinase pathways has not been clear. It was found that the initial release of intracellular Ca2+ results in the activation of the epidermal growth factor receptor (EGF-R), without autocrine release of epidermal growth factor. EGF-R provides a scaffold needed for the activation of p21-Ras, which leads to the activation of MAPK. MAPK plays pivotal roles in the activation of complex growth-promoting pathways. The pathway from the EGF-R involves protein tyrosine phosphorylation initiated by AT1 receptors. On the other hand, the angiotensin II type 2 (AT2) receptor counteracts the AT1 receptor-mediated tyrosine kinase activation by activating several tyrosine phosphatases and serine/threonine phosphatases, and it suppresses the cell growth process stimulated by various growth factors. The relative importance of AT1 and AT2 receptor actions depends on the levels of AT1 and AT2 receptor expression.

Animals↗