Serum levels of amino acids in candidates for living-related liver transplantation.
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Amino Acids↗
Biomedical subjects
S Eguchi
Publications and source records attributed to S Eguchi.
Mechanisms of immunosuppressive effects of FK 506 in light of apoptosis of hepatocytes and infiltrating lymphocytes in rat allografted livers.
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Alanine Transaminase↗
Effect of bioartificial liver in pigs with total ischemic liver failure.
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Ammonia↗
PCDDs/DFs emissions from crematories in Japan.
Concentrations of PCDDs and PCDFs in emission gases from 10 crematories were measured. The relationship between PCDDs/DFs and several factors such as structure, equipment and operational state of the crematory is discussed. Furthermore, emission of PCDDs/DFs from all crematories in Japan is estimated. The following results are obtained: (1) total concentration of PCDDs/DFs was 2.2-290 ng/N m3, whose TEQ concentration was 0.0099-6.5 ng TEQ/N m3; (2) total concentration of PCDFs was higher than that of PCDDs; (3) T4CDFs was the highest in the homologue pattern and 2,3,7,8-T4CDF was the highest in the isomer pattern; (4) emission of PCDDs/DFs was the largest in the first 20 min of cremation; (5) concentration of PCDDs/DFs was related to the existence of a secondary combustion chamber and a dust collector, and the ratio of the numbers of main and secondary combustion chambers; (6) total emission of PCDDs/DFs from crematories in Japan was estimated to be 8.9 g TEQ/yr.
Age Factors↗
Analysis of liquid accumulated in the distended capsular bag in early postoperative capsular block syndrome.
PURPOSE: To analyze the transparent liquid between the posterior lens capsule and the posterior chamber intraocular lens (PC IOL) in early postoperative capsular block syndrome and discuss the mechanism of posterior capsule distention. SETTING: Department of Ophthalmology, Tokyo University School of Medicine, and Tokyo Research Institute, Seikagaku Corporation, Tokyo, Japan. METHODS: This study evaluated 3 cases of capsular block syndrome presenting with transparent liquid in the distended capsular bag 1 day after cataract surgery. The transparent liquid material between the posterior capsule and PC IOL was aspirated and analyzed using high-performance liquid chromatography (HPLC). Also, sodium hyaluronate was diluted using a dialyzer to determine whether the aqueous humor was drawn into the capsular bag by an osmotic gradient across the capsule. RESULTS: The elution time of the samples was almost the same as that of sodium hyaluronate 1.0% (Healon) The concentration of the samples ranged from 3.29 to 9. 01 mg/mL by HPLC analysis. The sodium hyaluronate absorbed the physiological salt solutions through the dialyzer and expanded to 1. 9 times its original volume. CONCLUSIONS: These results indicate that the main ingredient of the transparent liquid in capsular bags is sodium hyaluronate and that the distention is caused by aqueous humor being drawn into the capsular bag by an osmotic gradient across the capsule when the capsulorhexis diameter is smaller than that of the PC IOL and by viscoelastic material retained and trapped in the bag intraoperatively.
Aged↗
Comparative study of bioartificial liver support and plasma exchange for treatment of pigs with fulminant hepatic failure.
Recently, bioartificial liver (BAL) treatment was reported to provide beneficial effects for patients with fulminant hepatic failure (FHF). Some success in experimental or clinical trials has been reported; however, the evaluation of BAL efficacy remains unclear, especially in comparison with other treatments for FHF. The purpose of this study was to compare the efficacy between BAL and plasma exchange (PE) in experimentally induced FHF in pigs. Pigs undergoing hepatic devascularization (HD) were placed into the following groups: no treatment (control; n = 6), BAL treatment (BAL; n = 5), and plasma exchange (PE; n = 5). Each treatment was initiated 6 h after HD and lasted for 4 h. BAL treatment significantly improved liver functions in FHF pigs. The decrease in cerebral perfusion pressure was also significantly suppressed in the pigs with BAL, and their survival time was prolonged compared with the results in pigs with PE. The effects of BAL outperform those of PE in the treatment of experimental FHF model.
Analysis of Variance↗
Safe and efficient gene transfer into porcine hepatocytes using Sendai virus-cationic liposomes for bioartificial liver support.
Establishment of a bioartificial liver support system using genetically modified hepatocytes is a potential approach to improve the treatment of severe liver failure. We describe the development of an efficient ex vivo method of gene transfer into a large number of porcine hepatocytes using hemagglutinating virus of Japan (HVJ)-liposome. The transfection efficiency of HVJ-liposome into isolated porcine hepatocytes attached to microcarrier beads was evaluated by beta-galactosidase (beta-gal) staining, fluorescence activated cell sorting analysis for beta-gal and luciferase assay, respectively. To examine the function and cellular damage of transduced hepatocytes, we used enzyme-linked immunosorbent assay for porcine albumin synthesis, lidocaine clearance test (P-450 activity), aspartate aminotransferase, and lactic dehydrogenase release assays. The optimal conditions for gene transfer into the beads-attached hepatocytes using HVJ-liposome included 4 microg of deoxyribonucleic acid with 200 microg of lipid/2 x 105 cells and exposure duration of 90 min. Under these conditions, beta-gal and luciferase genes were transduced to 2.5 x 108 isolated porcine hepatocytes following attachment to the beads. Positive beta-gal staining was observed in more than 30% of the beads-attached hepatocytes. The gene transfer activity of HVJ-liposome method determined by luciferase activities was about 100-fold of that of the lipofection method. Transfected porcine hepatocytes remained functional without any significant cell damage. Our results demonstrated that HVJ-liposome mediated gene transfer into microcarrier-attached porcine hepatocytes is an efficient and nontoxic method suitable for a bioartificial liver support sytem.
Animals↗
Effects of scleral buckling and encircling procedures on human optic nerve head and retinochoroidal circulation.
AIMS: To study the effects of segmental scleral buckling and encircling procedures on tissue circulation in the human optic nerve head (ONH) and choroid and retina. METHODS: Using the laser speckle method, the normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 seconds and averaged over three pulses in the optic nerve head (NB(ONH)) and choroid and retina (NB(ch-ret)) in 10 patients with unilateral rhegmatogenous retinal detachment (mean age 52 (SD 17)). NB(ONH), NB(ch-ret), and intraocular pressure (IOP) in both eyes, and blood pressure (BP) were measured before, and 1, 4, and 12 weeks after the scleral buckling and encircling procedure. RESULTS: NB(ch-ret) on the buckled side was significantly reduced after surgery and smaller than that in the unoperated contralateral eye throughout the study period (ANOVA, p<0.0001). NB(ch-ret) on the unbuckled side, in the foveal area, NB(ONH), IOP, and BP showed no significant change. CONCLUSIONS: It was indicated that the segmental scleral buckling procedure with encircling elements decreased tissue blood velocity in the choroid and retina on the buckled side but caused no significant change on tissue circulation in other areas of the fundus or ONH.
Adult↗
Comparative study of intraoperative mitomycin C and beta irradiation in pterygium surgery.
AIMS: To compare the rate of recurrence and complication after surgery for primary pterygium performed by one surgeon using either intraoperative mitomycin C or beta irradiation. METHODS: A retrospective study was performed of 164 eyes in 164 patients who had undergone primary pterygium surgery. After the pterygium was excised, the bare sclera was covered by sliding adjacent superior conjunctiva. 103 eyes received intraoperative mitomycin C (0.04%, 150 seconds) and 61 eyes beta irradiation (total dose 21.6 Gy). The mean follow up period was 20.2 (SD 17.9) months (range 1-66 months). Recurrence was defined as the postoperative regrowth of fibrovascular tissue crossing the corneoscleral limbus. RESULTS: The recurrence rate after mitomycin C and beta irradiation was 8.74% and 23.0% of eyes, respectively, after mean follow up of 17.9 and 31.2 months, respectively. The Kaplan-Meier survival analysis revealed a significantly better outcome for those who had intraoperative mitomycin C (Mantel-Cox log rank analysis, p=0.031). The mean interval to recurrence was not significantly different between the two groups. During the follow up, none of the patients showed side effects or reactions related to mitomycin C or beta irradiation. CONCLUSIONS: The intraoperative administration of 0.04% mitomycin C is more effective than beta irradiation as an adjunctive treatment for pterygium surgery in the patient population examined in this study.
Adult↗
Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor.
We have studied whether activation of epidermal growth factor receptor (EGFR) is involved in stretch-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation and protein synthesis in cultured rat vascular smooth muscle cells (VSMC). Cyclic stretch (1 Hz) induced a rapid (within 5 min) phosphorylation of ERK1/2, an effect that was time and strength dependent and inhibited by an EGFR kinase inhibitor (AG-1478) but not by a platelet-derived growth factor receptor kinase inhibitor (AG-1296). The stretch rapidly (within 2 min) induced tyrosine phosphorylation of several proteins, among which 180-kDa protein was shown to be EGFR as revealed by blockade with AG-1478 as well as immunoprecipitation with anti-EGFR antibody coupled with immunoblotting with anti-phosphotyrosine antibody. The stretch rapidly (within 2 min) induced association of tyrosine-phosphorylated EGFR with adaptor proteins (Shc/Grb2) as revealed by coprecipitation with glutathione-S-transferase-Grb2 fusion protein coupled with immunoblotting with anti-phosphotyrosine, anti-EGFR, and anti-Shc antibodies. Transfection of a dominant-negative mutant of H-Ras also inhibited stretch-induced ERK1/2 activation. Treatment with a stretch-activated ion channel blocker (Gd(3+)) and an intracellular Ca(2+) antagonist (TMB-8) inhibited stretch-induced phosphorylation of EGFR and ERK1/2. Treatment with AG-1478 and a mitogen-activated protein kinase kinase inhibitor (PD-98059), but not AG-1296, blocked [(3)H]leucine uptake stimulated by a high level of stretch. These data suggest that ERK1/2 activation by mechanical stretch requires Ca(2+)-sensitive EGFR activation mainly via stretch-activated ion channels, thereby leading to VSMC growth.
Adaptor Proteins, Signal Transducing↗
Involvement of reactive oxygen species in the activation of tyrosine kinase and extracellular signal-regulated kinase by angiotensin II.
Reactive oxygen species (ROS) have been proposed to mediate vascular hypertrophy induced by angiotensin II (Ang II). Recently, we and others have shown that growth-promoting signals by Ang II involve protein tyrosine kinase (PTK) and extracellular signal-regulated kinase (ERK). However, whether ROS contribute to the Ang II-induced PTK and/or ERK activation in vascular smooth muscle cells (VSMCs) remains largely unclear. Here, we have investigated the possible involvement of ROS in Ang II-induced PTK and ERK activation. In the presence of a NADH/NADPH oxidase inhibitor, diphenyleneiodonium (DPI) or an antioxidant, alpha-tocopherol, Ang II-induced protein tyrosine phosphorylation of two major proteins (p120, p70) and ERK activation were markedly reduced, whereas ERK activation by epidermal growth factor was unaffected. DPI also inhibited Ang II-induced H2O2 production and PTK activation. In this regard, H2O2 and a membrane permeable thiol-oxidizing agent, diamide, stimulated protein tyrosine phosphorylation of p120 and p70, and ERK activation in VSMCs. H2O2 also enhanced PTK activity. From these data, we conclude that ROS play a critical role in the Ang II-induced PTK and ERK activation in VSMCs, thereby contributing to vascular growth associated with enhanced Ang II activity.
Angiotensin II↗
Angiotensin II-mediated vascular smooth muscle cell growth signaling.
The mechanism by which Ang II stimulates the growth of vascular smooth muscle cells was investigated by measuring the phosphorylation of mitogen-activated protein kinases ERK 1 and ERK 2. Ca2+ ionophore was found to have effects practically analogous to Ang II. We found that the signaling pathway involves the activation of epidermal growth factor receptor (EGFR) kinase, activation of the adaptor proteins Shc and Grb2, and the small G-protein Ras. Although the mechanism of AT1- (or Ca2+)-induced activation of EGFR is not yet clear, we have found that calcium-dependent protein kinase CAKss/PYK2 and c-Src are involved in this process. These studies indicate a transactivation mechanism that utilizes EGFR as a bridge between a Gq-coupled receptor and activation of phosphotyrosine generation.
Angiotensin II↗
Intracellular signaling of angiotensin II-induced p70 S6 kinase phosphorylation at Ser(411) in vascular smooth muscle cells. Possible requirement of epidermal growth factor receptor, Ras, extracellular signal-regulated kinase, and Akt.
Activation of p70 S6 kinase (p70(S6K)) by growth factors requires multiple signal inputs involving phosphoinositide 3-kinase (PI3K), its effector Akt, and an unidentified kinase that phosphorylates Ser/Thr residues (Ser(411), Ser(418), Ser(424), and Thr(421)) clustered at its autoinhibitory domain. However, the mechanism by which G protein-coupled receptors activate p70(S6K) remains largely uncertain. By using vascular smooth muscle cells in which we have demonstrated Ras/extracellular signal-regulated kinase (ERK) activation through Ca(2+)-dependent, epidermal growth factor (EGF) receptor transactivation by G(q)-coupled angiotensin II (Ang II) receptor, we present a unique cross-talk required for Ser(411) phosphorylation of p70(S6K) by Ang II. Both p70(S6K) Ser(411) and Akt Ser(473) phosphorylation by Ang II appear to involve EGF receptor transactivation and were inhibited by dominant-negative Ras, whereas the phosphorylation of p70(S6K) and ERK but not Akt was sensitive to the MEK inhibitor. By contrast, the phosphorylation of p70(S6K) and Akt but not ERK was sensitive to PI3K inhibitors. Similar inhibitory pattern on these phosphorylation sites by EGF but not insulin was observed. Taken together with the inhibition of Ang II-induced p70(S6K) activation by dominant-negative Ras and the MEK inhibitor, we conclude that Ang II-initiated activation of p70(S6K) requires both ERK cascade and PI3K/Akt cascade that bifurcate at the point of EGF receptor-dependent Ras activation.
Angiotensin II↗
Mechanotransduction of rat aortic vascular smooth muscle cells requires RhoA and intact actin filaments.
The growth-promoting effect of mechanical stress on vascular smooth muscle cells (VSMCs) has been implicated in the progress of vascular disease in hypertension. Extracellular signal-regulated kinases (ERKs) have been implicated in cellular responses, such as vascular remodeling, induced by mechanical stretch. However, it remains to be determined how mechanical stretch activates ERKs. The cytoskeleton seems the most likely candidate for force transmission into the interior of the cell. Therefore, we examined (1) whether the cytoskeleton involves mechanical stretch-induced signaling, (2) whether Rho is activated by stretch, and (3) whether Rho mediates the stretch-induced signaling in rat cultured VSMCs. Mechanical stretch activated ERKs, with a peak response observed at 20 minutes, followed by a significant increase in DNA synthesis. Treatment with the ERK kinase-1 inhibitor, PD98059, inhibited the stretch-induced increase in DNA synthesis. Cytochalasin D, which selectively disrupts the network of actin filaments, markedly inhibited stretch-induced ERK activation. In the control state, RhoA was observed predominantly in the cytosolic fraction, but it was translocated in part to the particulate fraction in response to mechanical stretch. Botulinum C3 exoenzyme, which inactivates Rho p21 (known to participate in the reorganization of the actin cytoskeleton), attenuated stretch-induced ERK activation. Inhibition of Rho kinase (p160ROCK) also suppressed stretch-induced ERK activation dose dependently. Our results suggest that mechanotransduction in VSMCs is dependent on intact actin filaments, that Rho is activated by stretch, and that Rho/p160ROCK mediates stretch-induced ERK activation and vascular hyperplasia.
ADP Ribose Transferases↗
Epidermal growth factor receptor is indispensable for c-Fos expression and protein synthesis by angiotensin II.
We have reported that angiotensin II induces the epidermal growth factor (EGF) receptor transactivation leading to extracellular signal-regulated kinase (ERK) activation in rat vascular smooth muscle cells. Here, we report that the EGF receptor kinase inhibitor AG1478 and the ERK kinase inhibitor PD98059 markedly inhibited angiotensin II-induced c-Fos expression and protein synthesis but not c-Jun expression in these cells. These data suggest that the EGF receptor transactivation and subsequent ERK activation are indispensable for angiotensin II-mediated growth promotion of vascular smooth muscle cells providing a new mechanistic insight whereby angiotensin II contributes abnormal vascular remodeling.
Animals↗
Regression of hepatocellular carcinoma in vitro and in vivo by radiosensitizing suicide gene therapy under the inducible and spatial control of radiation.
To improve the efficacy and selectivity of gene therapy for hepatocellular carcinoma (HCC), we designed a strategy for suicide gene therapy in conjunction with radiation therapy using an HVJ-liposome vector system. The radio-inducible suicide gene was constructed by insertion of the early growth response gene 1 (Egr-1) promoter upstream of the HSV-tk gene (EGF-tk). First, to test the tumor specificity of Egr-1, RT-PCR and immunohistochemistry were performed. The Egr-1 gene was highly expressed in HCC compared with normal liver, where expression was barely detectable. Next, radiation-inducible activity of the Egr-1 promoter was examined in primary cultured normal hepatocytes and human hepatoma cell lines Huh7, HepG2, and PLC/PRF/5 by luciferase assay as a reporter gene system. Egr-1 promoter activity was markedly increased in hepatoma cell lines in a radiation dose-dependent manner, with maximum activation (15- to 28-fold) 12 hr after irradiation. In contrast, only a twofold increase in activation was noted in normal hepatocytes. An in vitro gene therapy experiment showed that EGR-tk-transduced hepatoma cells became highly sensitive to ganciclovir (GCV) after irradiation, but not without irradiation. GCV with or without irradiation did not show any cytotoxic effects against control gene-transfected cells. In addition, a "radiosensitization effect" was also demonstrated by combination therapy with the HSV-tk/GCV system and irradiation. To examine the efficacy of this EGR-tk/GCV gene therapy in vivo, xenografted liver tumors in nude mice were targeted using the HVJ-liposome vector system. EGR-tk-transfected tumors regressed significantly after a combination therapy of irradiation and GCV in all mice (n = 8), and almost disappeared in 3 weeks without any side effects. In comparison, tumors continued to grow in all mice (n = 8 in each group) treated by transfer of EGR-tk followed by either irradiation without GCV or GCV without irradiation. Our data indicate that HSV-tk gene therapy under the control of a radioinducible promoter is effective, and might be selective for hepatoma cells because of its inducible and radiosensitive capacity after radiation exposure as well as its tumor-specific activation.
Aged↗
Bioartificial liver treatment in rats with fulminant hepatic failure: effect on DNA-binding activity of liver-enriched and growth-associated transcription factors.
BACKGROUND: We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobe necrosis. In FHF rats, lack of regeneration of the residual liver was associated with delayed expression of HGF and HGF receptor c-met and elevated blood HGF and TGF-beta1 levels. We then found that intrasplenic hepatocyte transplantation prolonged survival in FHF rats and triggered hepatocyte proliferation in the native liver. The latter effect was associated with accelerated expression of HGF and c-met mRNA in the liver and lowering of blood HGF and TGF-beta1 levels. In the present study we show that in FHF rats, treatment with a bioartificial liver (BAL) had similar effects. MATERIALS AND METHODS: FHF was induced in inbred Lewis rats and after 4 h, Group 1 rats were subjected to a 4-h whole blood perfusion through the BAL loaded with 3 x 10(8) microcarrier-attached syngeneic hepatocytes, whereas Group 2 control rats were treated with the BAL containing microcarriers only. RESULTS: Compared to sham-BAL-treated rats, the test rats lived longer (28 +/- 5 vs 17 +/- 2 h; P = 0.0005), had better coagulation parameters, maintained higher body core temperature, and showed decreased plasma TGF-beta1 levels. In addition, their liver remnants were HGF positive and showed increased DNA binding of transcription factors engaged in the modulation of hepatocyte proliferation (e.g., STAT3) and liver-specific gene expression (e.g., HNF1, HNF4, C/EBP). CONCLUSIONS: This study demonstrates that hepatocyte-based extracorporeal support not only can provide metabolic support by increasing the available functional liver mass but also is capable of modifying humoral and molecular mechanisms which are responsible for proliferation and organ-specific functions of residual hepatocytes.
Animals↗
Open reduction for congenital dislocation of the hip: comparison of the long-term results of the wide exposure method and Ludloff's method.
We compared the long-term clinical and radiographic results of two methods of open reduction for congenital dislocation of the hip; a wide exposure method (360-degree circumferential capsulotomy) versus Ludloff's method (limited capsulotomy via the medial approach). Thirty-one hips in 24 patients assigned to group A received the wide exposure method and 32 hips in 27 patients assigned to group B had the Ludloff reduction. All patients were surgically reduced at less than 3 years of age. The follow-up averaged 16 years. None of the hips in group A required additional operations; however, 34.4% of the hips in group B did. At the latest review, 26 (83.9%) of the hips in group A were rated as Severin class I or II. Except for one patient, none had pain or a limp. Of the hips in group B, 18 (56.3%) were rated as Severin class I or II. Three patients had pain or Trendelenburg gait. Avascular necrosis occurred in 3.2% of hips in group A and in 21.9% of hips in group B. The wide exposure method is capable of completely releasing the posterosuperior tightness resulting from capsular adhesion to the ilium and the contracted short external rotators. Releasing the posterosuperior tightness from these structures seemed to provide a better chance of achieving an anatomically and functionally satisfactory hip.
Acetabulum↗