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Biomedical subjects

J Furui

Publications and source records attributed to J Furui.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Herniation of the small bowel through the port site following removal of drains during laparoscopic surgery.

BACKGROUND/AIMS: Generally, the port site is used as the delivery route for drainage after laparoscopic abdominal surgery. We report this case because of the rarity of the complication related to laparoscopic procedures. METHODS: A 75-year-old woman underwent a laparoscopic-assisted sigmoid colectomy for early stage cancer. RESULTS: After the operation, her postoperative course was uneventful. However, just after removing the drains, the small bowel was found to have herniated through the port site used as the insertion route for the drains. An emergency relaparotomy was done and a segment of the necrotic small bowel had to be resected. CONCLUSION: To prevent this complication, we suggest that, first of all, in elderly and thin patients smaller trocar insertion sites (<10 mm) should be utilized as insertion routes for the drains and, secondly, the fascial defect should be closed just after removing the drains whenever the defect measures 10 mm or more in size.

Aged↗
PubMed1999

Tetanus after a resection for a gangrenous perforated small intestine: report of a case.

We report herein the case of a 75-year-old man who developed severe tetanus 24 h after the resection of a gangrenous perforated small intestine. It seemed that the tetanus was caused by a spillage of the intestinal contents harboring Clostridium tetani; however, this was not identified by a culture. The diagnosis of tetanus was made only when opisthotonus in this patient became evident and normal tetanus treatment proved to be successful.

Aged↗
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

Detection of the pancreas-specific gene in the peripheral blood of patients with pancreatic carcinoma.

The prognosis of patients with pancreatic carcinoma remains very poor. To improve the therapeutic results, the early detection of this cancer is needed. The present study was performed to detect the pancreas-specific gene, chymotrypsinogen, in the peripheral blood from patients with pancreatic carcinoma by using reverse transcription polymerase chain reaction (RT-PCR) in order to evaluate the clinical significance of this gene. Ten patients with pancreatic carcinoma, two with acute pancreatitis, three with chronic pancreatitis and ten control subjects were examined for the presence of chymotrypsinogen using RT-PCR techniques in the peripheral blood. To confirm that the chymotrypsinogen gene was expressed in a pancreas-specific manner, the expression of chymotrypsinogen in various types of human adult tissue was evaluated by RT-PCR. The specific band of the chymotrypsinogen gene was detected in the pancreas. Serial dilution studies demonstrated the chymotrypsinogen gene to be detected at a concentration of one pancreatic cell per 10(6) peripheral blood cells. Seven out of the ten (70%) patients with pancreatic carcinoma were found to be positive based on the RT-PCR findings. In contrast, no pancreas-specific gene was detected in the peripheral blood of any patients with acute pancreatitis, chronic pancreatitis or the control subjects. Our observations show that the detection of the pancreatic specific gene, chymotrypsinogen, is therefore useful as a genetic diagnostic marker in pancreatic carcinoma.

Adult↗
PubMed1999

Progression of congenital heart disease in the prenatal period.

BACKGROUND: Prenatal echocardiography has shown evidence of prenatal development of congenital heart disease. Prenatal cardiac anatomy, chamber size and function change during gestation, so that the appearance of cardiac structure in abnormal hearts may be different from that which is usually seen postnatally. METHODS: Published prenatal echocardiographic studies were reviewed and in utero development of congenital heart disease from midtrimester to the early postnatal period is discussed. RESULTS: The growth of the great vessels and ventricles is reduced in fetuses with ventricular outflow obstruction. Valve regurgitation may progress. The foramen ovale and ductus arteriosus have been reported to become restrictive in utero in several settings. Pulmonary vascular obstructive changes may progress prenatally. Fetal arrhythmia (both bradycardia and tachycardia) may develop in utero. Development of congestive heart failure is a very important issue during follow up of fetuses with significant cardiac or extracardiac problems. Some may progress to fetal hydrops and prognosis of the affected fetuses is usually very poor. CONCLUSIONS: Correct knowledge of possible development is important for accurate prenatal diagnosis. Information on prenatal progression of the cardiac anomaly is also important to make plans for follow up and perinatal management, to predict outcomes and to counsel family. Furthermore, the benefits of prenatal treatment instead of postnatal treatment should be assessed by the accurate prediction of the progression of the cardiac problem in utero. Further extensive studies using a large number of cases is required to predict progression accurately. In addition, further studies for elucidating the mechanisms of progression is important to provide better outcomes for fetuses with various congenital heart diseases.

Arrhythmias, Cardiac↗
PubMed1999

Utility of technetium-99m-labeled-galactosyl human serum albumin scintigraphy for estimating the hepatic functional reserve.

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-GSA) is a receptor binding agent, specific for asialoglycoprotein receptor, that resides exclusively on the plasma membrane of mammalian hepatocytes. The usefulness of Tc-GSA for estimating the hepatic functional reserve was retrospectively evaluated in patients undergoing a hepatic resection. Tc-GSA scintigraphy was performed in 35 patients before hepatectomy, and the hepatic uptake ratio (LHL15) was calculated. The LHL15 was then compared with the findings of conventional liver function tests, the indocyanine green retention rate in 15 minutes (ICG R15), and histologic activity index (HAI) score. Significant correlations were observed between the LHL15 and values of ICG R15, prothrombin time activity, serum levels of total bilirubin, hyaluronic acid, and values of HAI score. Ratios of LHL15 to preoperative liver volume (LHL-V) correlated well with the regenerative rates of the residual liver after major hepatectomy. In addition, patients with more than 0.76 of LHL-V value had no complications in postoperative course, whereas those with less than 0.73 had several complications due to hepatic dysfunction. Tc-GSA scintigraphy thus appears to be a useful diagnostic tool for evaluating functioning mass of the liver and the values of LHL-V seems to be able to demonstrate regenerative activity in the residual liver after hepatectomy.

Adult↗
PubMed1999

In vivo microdialysis assessment of nerve-stimulated contractions associated with increased acetylcholine release in the dog intestine.

Intestinal contractility and release of endogenous acetylcholine (ACh) were measured simultaneously in vivo in the small intestine of the anesthetized dog. Electrical stimulation of nerves in the intestinal seromuscular layers caused contractions and increased concentrations of ACh in the dialysate, which were abolished by infusion of tetrodotoxin into the intestinal marginal artery at 75 nmol/ml. Intraarterial administration of atropine at 150 nmol/ml abolished the stimulated contractions, without significant effects on increases in concentrations of dialysate ACh. Thus, the nerve-stimulated contractions were found in vivo to be associated with a local increase in ACh release from the intestinal cholinergic neurons.

Acetylcholine↗
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↗
PubMed1998

Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family.

BACKGROUND: The transcription of interferon (IFN) and IFN-inducible genes is mainly regulated by the interferon regulatory factor (IRF) family of proteins, which recognize a unique AAGTGA hexamer repeat motif in the regulatory region of IFN genes. A DNA-binding domain of approximately 100 amino acids has been commonly found in the IRF family of proteins, but it has no sequence homology to known DNA-binding motifs. Elucidation of the structures of members of the IRF family is therefore useful to the understanding of the regulation and evolution of the immune system at the structural level. RESULTS: The solution structure of the DNA-binding domain of interferon regulatory factor-2 (IRF-2) has been determined by NMR spectroscopy. It is composed of a four-stranded antiparallel beta sheet and three alpha helices, and its global fold is similar to those of the winged helix-turn-helix (wHTH) family of proteins. A long loop (Pro37-Asp51) is found immediately before the HTH motif, which is not found in other wHTH proteins. The NMR signals of residues in this long loop, as well as the second helix of the HTH motif, are strongly affected upon the addition of the hexamer repeat DNA, suggesting that these structural elements participate in DNA recognition and binding. CONCLUSIONS: The structural similarity of the DNA-binding domain of IRF-2 with those of proteins in the wHTH family shows that the IRF proteins belong to the wHTH family, even though there is no apparent sequence homology among proteins of the two families. The sequential structure alignment program (SSAP) shows that IRF-2 has a slightly different structure from typical wHTH proteins, mainly in the orientation of helix 2. The IRF family of proteins should therefore be categorized into a subfamily of the wHTH family. The evidence here implies that the evolutional pathway of the IRF family is distinct from that of the other wHTH proteins, in other words, the immune system diverged from an evolutional stem at an early stage.

Amino Acid Sequence↗
PubMed1998

Successful surgical treatment of gastric cancer with a tumor thrombus in the portal and splenic veins: report of a case.

We report herein the case of a 70-year-old woman with histologically confirmed gastric Borrmann type 3 cancer in the posterior wall of the fundus in whom computed tomography demonstrated a dilated portal trunk and splenic vein containing a low-density mass, but no evidence of liver metastases. The venous phase of a superior mesenteric arteriogram subsequently showed occlusion of the main portal vein with venous collaterals. At surgery, a tumor thrombus was noted to extend from the short gastric vein to the portal vein via the splenic vein. Thus, an extensive gastric resection together with removal of the tumor thrombus from the veins was performed, and successful results were achieved.

Aged↗
PubMed1998

Detection of carcinoembryonic antigen mRNA in the mesenteric vein of patients with resectable colorectal cancer.

The detection of tumor cells in the drainage venous blood of patients with colorectal cancer was made feasible by demonstrating carcinoembryonic antigen (CEA) mRNA in the mononuclear cell component of the blood, using a nested reverse transcription-polymerase chain reaction. CEA mRNA was detected in the drainage venous blood from 11 (42%) of 26 patients, and the rate of detection increased according to the grade of vessel invasion. CEA mRNA was detected in all patients with synchronous liver metastases, even though there was no significant correlation between the presence of CEA mRNA in the drainage venous blood and the clinicopathological findings. As the presence of CEA mRNA in the drainage venous blood is an indicator of the spread of tumor cells in patients with colorectal cancer, this assay can be used to assess the possible outcome of patients with colorectal cancer, providing one more tool for the physician-oncologist to use in designing appropriate treatments.

Aged↗