Biomedical subjects
Publications and source records attributed to H Ohshiro.
An 8-year-old Japanese girl with a portosystemic shunt had shown hyperammonaemia since she was 3 years of age. MRI of her brain showed bilateral hyperintense globus pallidus. A portosystemic shunt was evident on US and angiography. She underwent surgical banding of the shunt, after which the lesion and clinical symptoms disappeared.
A case of extrahepatic biliary atresia (EBA) associated with trisomy 18 is presented. A 1-month-old boy was suspected to have Alagille syndrome with obstructive jaundice, a systolic heart murmur, growth retardation, and a small, pointed chin. However, surgery and chromosomal analysis revealed EBA associated with trisomy 18. Chromosomal examination must be performed in patients with jaundice and congenital anomalies. It is possible that EBA in trisomy 18 syndrome is due to a chromosomal disorder.
Explore the source record for details and available documents.
BACKGROUND/PURPOSE: The authors surgically treated seven of eight patients with congenital portosystemic shunt and hyperammonemia. This entity is uncommon in children. METHODS: The patients included five boys and three girls with a mean age of 8 years (range, 7 months to 24 years). Preoperative symptoms included hyperammonemia. Hepatic encephalopathy was evident in five patients. Diagnosis and assessment were made by ultrasound scan, magnetic resonance imaging (MRI), angiography, and 123 I-iodoamphetamine per-rectal portal scintigraphy. Surgical banding was done for five patients and transvenous coil embolization for two. One patient was not a surgical candidate because there were no intrahepatic portal veins. RESULTS: In four of the five patients treated using surgical banding, and in both patients who underwent coil embolizations, hyperammonemia and clinical symptoms improved soon after surgery. However, in the remaining patient, hyperammonemia worsened after surgery, and reoperation was needed because of a severe portal hypertension, possibly caused by malconformation of hepatic veins. CONCLUSIONS: For patients with congenital portosystemic shunt, early diagnosis and surgery are needed to prevent damage to central nerves caused by persistent hyperammonemia. Maldevelopment of the intrahepatic portal veins is a surgical option, if the patient has a normal liver architecture, but malconformation of hepatic veins or severe anomalies such as cardiac defects would rule out surgical intervention.
Two patients who had aortopulmonary fistula of postoperative origin with hemoptysis underwent successful repair by means of an endovascular stent graft procedure. One patient had undergone repeated thoracotomies two times, and the other one time to repair anastomotic aneurysms of the descending aorta after surgery for Takayasu's arteritis. A self-expanding stainless steel stent covered with a Dacron graft was inserted into the lesion through the external iliac or femoral artery. The patients recovered well, with no signs of infection or recurrent hemoptysis 8 months after the procedure. Endovascular stent grafting may be a therapeutic option for treating patients with aortopulmonary fistula.
A survey of all fractures in patients > or =35 years of age for hip, distal radius, and proximal humerus was performed in Tottori Prefecture, Japan. Hip fracture survey was done for the years 1986-1988, and also 1992-1994. A distal radius and proximal humerus fracture survey was done for the years 1986-1988, 1992, and 1995. The age- and gender-specific incidence rates of these three types of fracture among Japanese were substantially lower than those of whites living in North America or northern Europe. The age-adjusted incidence rates of hip fracture (per 100,000 person-years) were 40.7 and 114.1 in 1986 and 57.1 and 145.2 in 1994 for men and women, respectively, showing a significant increase with time for women. Upon examination of individual fracture types, there was no significant increase in cervical fractures, whereas a significant increase was observed in trochanteric fractures for women. The age-adjusted incidence rates of distal radius fractures for women were 164.9 in 1986 and 211.4 in 1995, showing a significant increase with time; however, no increase was observed among men. Incidence of proximal humerus fractures was 10.3 and 42.0 in 1986 and 17.1 and 47.9 in 1995 for men and women, respectively, and these increases were significant for both genders.
The therapeutic effects of an intravenously injected carboxamide derivative (IS-741) on lung injury were studied in rats with cerulein-induced pancreatitis complicated by endotoxemia. Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hr intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 hr following the first cerulein injection as a challenge of endotoxemia. Rats were divided into four groups: group I, pancreatitis with LPS; group II, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.03 mg/kg/hr); group III, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 0.3 mg/kg/hr); and group IV, pancreatitis with LPS treated with a continuous intravenous injection of IS-741 at 3 mg/kg/hr). IS-741 was administered 30 min before the endotoxemia challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats with LPS (group I), but hemorrhage was not seen in group IV rats receiving a continuous injection of IS-741 shortly before the induction of endotoxemia. The IS-741-treated rats (groups II, III, and IV) had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). The number of neutrophils infiltrating the lung in groups II, III, and IV was significantly lower than that of group I. Conversely, CINC production by bronchoalveolar macrophages in vitro were stimulated by LPS but were reduced by the presence of IS-741. The carboxamide derivative IS-741 effectively prevented pancreatitis-associated lung injury following the challenge of endotoxemia.
We report the presence of a patent ductus venosus in three brothers who underwent surgical correction. Patent ductus venosus was demonstrated by ultrasonography. Portosystemic venous shunt ratios as evaluated by [123I]iodoamphetamine per rectal portal scintigraphy were 67%, 50%, and 77%, respectively. Histologic examination of liver biopsy specimens revealed fatty degeneration in all cases. Portal vein pressure before and after temporarily occluding the patent ductus venosus was estimated by an Anthron P-U catheter introduced into the portal vein via the ligament teres hepatis. Portal venous pressure increased from 10 to 17 cm H2O, 16 to 23 cm H2O, and 14 to 27 cm H2O, respectively. Therefore, banding of the ductus venosus with Teflon tape was attempted to prevent portal hypertension following complete ligation. As a result, portal venous pressures after stricture of the ductus venosus were 12, 21, and 20 cm H2), respectively. Bile acid and liver enzymes decreased and returned to normal within 14 days after surgery. Interestingly, serum concentrations of hepatocyte growth factor (HGF) increased significantly after restoration of the portal blood flow and then gradually decreased, but remained persistently elevated for at least two weeks in two cases measured after surgical correction. One month after correction, liver function returned to normal as assessed by serological and histological parameters in all cases. These results suggest that it is important to determine whether stricture or complete ligation is indicated for a patent ductus venosus during surgical correction, based on the portal venous pressure after temporal test occlusion of the duct. In addition, HGF may be a useful marker for normalization of hepatic microcirculation after surgery.
Activated factor X (FXa) is a trypsinlike serine protease involved in the cascade of blood coagulation. The monocyte chemoattractant protein-1 (MCP-1) may be important in the pathophysiology of liver ischemia-reperfusion injury. We investigated the effects of a selective FXa inhibitor, DX-9065a, on MCP-1 expression after ischemia-reperfusion in the rat liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. DX-9065a was injected intravenously 5 min before vascular clamping. Serum concentrations of MCP-1 were measured by enzyme-linked immunosorbent assay. The levels of MCP-1 mRNA in the liver after reperfusion were determined by northern blot analysis. In vitro MCP-1 production by peritoneal macrophages in response to alpha-thrombin was examined. Serum concentrations of MCP-1 increased and peaked at 6 hr after reperfusion. However, pretreatment of animals with DX-9065a resulted in significantly smaller increases in the serum concentration of MCP-1 after reperfusion in a dose-dependent manner. Pretreatment with DX-9065a significantly reduced MCP-1 mRNA levels in the liver after ischemia-reperfusion. In vitro MCP-1 production by peritoneal macrophages was enhanced by alpha-thrombin. In addition, DX-9065a significantly reduced tissue factor mRNA levels in peripheral monocytes after ischemia-reperfusion, compared to untreated animals. In conclusion, a selective inhibitor of FXa, DX-9065a, limited MCP-1 production after ischemia-reperfusion of the rat liver.
We investigated the role of platelet-activating factor (PAF) as a priming signal for cytokine-induced neutrophil chemoattractant (CINC) expression by bronchoalveolar macrophages in acute pancreatitis. Pancreatitis was induced by four intramuscular injections of cerulein (50 micrograms/kg at 1-h intervals) in Wistar rats. The animals were injected intraperitoneally with 10 micrograms/kg of lipopolysaccharide (LPS) as a septic challenge. Pancreatitis rats were treated with a bolus intravenous injection of TCV-309 (3 or 30 micrograms/kg) 30 min before the septic challenge. Intense mononuclear cell infiltration and lung hemorrhage occurred in pancreatitis rats complicated with sepsis but were not seen in pancreatitis rats receiving a bolus TCV-309. Pancreatitis rats treated with TCV-309 had lower serum concentrations of CINC after septic challenge and lower levels of CINC messenger RNA (mRNA) in the lung, as well as fewer pulmonary infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). In vitro CINC production in response to LPS by bronchoalveolar macrophages obtained from pancreatitis rats 6 h after the first cerulein injection, immediately before septic challenge, was enhanced but was significantly reduced in a TCV-309-sensitive manner. LPS-stimulated in vitro CINC production by naive bronchoalveolar macrophages was significantly enhanced by pretreatment with PAF. TMB-8 (an inhibitor of calcium release from endoplasmic reticulum) or W7 (calmodulin antagonist) completely abrogated the chemoattractant production by bronchoalveolar macrophages pretreated with PAF after LPS stimulation. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of bronchoalveolar macrophages to release CINC after triggering with LPS during acute cerulein-induced pancreatitis. The PAF antagonist TCV-309 effectively prevented hyperactivity of bronchoalveolar macrophages and pancreatitis-associated lung injury after the septic challenge.
BACKGROUND/AIMS: The priming mechanism of macrophages to secrete cytokines in acute pancreatitis is important for remote organ failure following septic complication. The effects of novel carboxamide derivative, IS-741, on neutrophil chemoattractant production by bronchoalveolar macrophages were studied in rats with cerulein-induced pancreatitis complicated by sepsis. METHODS: Pancreatitis was induced by four intramuscular injections of cerulein (50 microg/kg at 1-hour intervals). Pancreatitis rats were injected intraperitoneally with 10 mg/kg of lipopolysaccharide (LPS) 6 h following the first cerulein injection as a septic challenge. Pancreatitis rats received a continuous intravenous injection of IS-741 (3 mg/kg/h) 30 min before the septic challenge. RESULTS: Intense mononuclear cell infiltration and lung hemorrhage occurred in untreated pancreatitis rats complicated with sepsis, but hemorrhage was not seen in septic pancreatitis rats receiving a continuous intravenous injection of IS-741 shortly before sepsis induction. The IS-741-treated rats had lower serum concentrations of cytokine-induced neutrophil chemoattractant (CINC), as well as fewer the pulmonary neutrophils and infiltrates immunoreactive for CINC or Mac-1 (CD11b/CD18). CONCLUSION: The novel carboxamide derivative IS-741 reduced CINC production by bronchoalveolar macrophages and effectively prevented pancreatitis-associated lung injury following the septic challenge.
BACKGROUND: Intrathymic events undergoing allograft rejection remain undefined. The present study investigated the role of tumor necrosis factor-beta on acute thymic involution in rat hepatic allograft recipients during rejection. METHODS: Apoptosis and cellular phenotypic changes in the thymus were studied after hepatic transplantation. RESULTS: Thymocytes in both the medulla and cortex were sparse during acute rejection. Phenotypically, CD4+CD8+ T cells decreased significantly, whereas there were relative increases in CD4-CD8-, CD4+CD8-, and CD4-CD8+ T cells in untreated allograft recipients. Additionally, thymic apoptosis was found by in situ DNA end labeling and electron microscopy. Apoptotic cells were predominantly distributed in the cortex. Biologic lymphotoxin (tumor necrosis factor-beta)/tumor necrosis factor-alpha cytotoxic activity in the serum was significantly increased in untreated hepatic allograft recipients. Tumor necrosis factor-beta mRNA was detected in untreated allograft livers, and intraperitoneal administration of recombinant human tumor necrosis factor-beta induced extensive apoptosis of thymocytes in vivo. In contrast, no significant thymic involution was observed in donor-specific blood transfusion-treated allograft and isograft recipients. Intraperitoneal administration of rabbit anti-human tumor necrosis factor-beta polyclonal antibody or recombinant human interleukin-10 inhibited thymic apoptosis in untreated hepatic allograft recipients. CONCLUSIONS: Allograft rejection, but not donor-specific transfusion-induced immunologic unresponsiveness, is associated with thymic involution, a process that may be mediated by tumor necrosis factor-beta.
BACKGROUND: Elastase released from activated neutrophils is an important mediator of inflammatory tissue damage. We investigated the effect of human neutrophil elastase (NE) inhibitor (ONO-5046) on reperfusion injury after pancreaticoduodenal transplantation in rats by measuring the expression of intercellular adhesion molecule-1 (ICAM-1). Additional in vitro experiments were conducted to investigate the effect of NE on ICAM-1 mRNA transcription in a rat endothelial cell line (WK-5) and human umbilical vein endothelial cells (HUVEC). METHODS: In an in vivo experiment, male Wistar rats were transplanted with syngeneic pancreaticoduodenal grafts. An NE inhibitor, ONO-5046, was injected intravenously 5 min before vascular clamping and immediately after reperfusion at a dose of 10 mg/kg. ICAM-1 expression was determined by immunostaining and Northern analysis. In in vitro experiments, the effects of NE and chemical agents on ICAM-1 mRNA transcripts were determined in WK-5 cells and HUVEC. RESULTS: Pretreatment with ONO-5046 decreased ICAM-1 immunostaining in the pancreatic graft and inhibited the increase in ICAM-1 mRNA levels in grafts after reperfusion. ICAM-1 mRNA levels in WK-5 cells and HUVEC showed stimulation by NE, while ONO-5046 inhibited this increase. Calcium ionophore (A23187) augmented NE stimulation of ICAM-1 mRNA levels in these cells. In contrast, a phospholipase C inhibitor (U73122) blunted NE induction of ICAM-1 mRNA, and either calcium chelator (TMB-8) or a nuclear factor-kappa B inhibitor (pyrrolidine dithiocarbamate) completely inhibited induction. CONCLUSION: These results indicate that NE stimulates ICAM-1 expression in pancreatic grafts via intracellular Ca2+ influx and a phospholipase C signal transduction.
BACKGROUND: A single intravenous injection of donor-specific blood (DST) 7 days before transplantation significantly prolongs survival of hepatic allografts from fully allogeneic ACI(RT1a)-->LEW(RT1(1)) rats. The aim of this study was to investigate the kinetics of nitric oxide synthesis by macrophages in rat hepatic allografts treated with DST. METHODS: We investigated macrophages expressing inducible nitric oxide synthase in animal group I (receiving isografts), group II (hepatic allografts), and group III (hepatic allografts after donor-specific blood). RESULTS: Serum nitrite/nitrate, interferon-gamma, and tumor necrosis factor-alpha concentrations increased significantly in group II for 7 days after transplantation but were significantly much lower in groups I and III. Numbers of macrophages immunostained with an anti-macrophage nitric oxide synthase monoclonal antibody and inducible nitric oxide synthase mRNA levels in liver specimens also were much lower in groups I and III than in group II. In addition, Northern blot analysis demonstrated abundant interleukin-10 mRNA transcripts in the DST-treated hepatic allografts compared to untreated allografts. Double immunostaining revealed anti-macrophage synthase-containing cells, including both ED1+ and ED2+ cells, in liver and spleen as more numerous in group II. CONCLUSIONS: Inducible nitric oxide synthase is suppressed in immunologic unresponsiveness to grafts after donor-specific blood transfusion.
Intercellular adhesion molecule-1 (ICAM-1) is important in neutrophil-dependent injury. We investigated the effects of monocyte chemoattractant protein-1 (MCP-1) produced by Kupffer cells on ICAM-1 expression after ischemia-reperfusion in rat liver by occluding the portal vein for 30 minutes. Serum concentrations of MCP-1 increased persistently. By Northern analysis, MCP-1 mRNA increased early and persisted. Kupffer cells harvested 6 hours after reperfusion also expressed this transcript. The transcript and protein also were produced by Kupffer cells from naive controls in response to reactive oxygen species. ICAM-1 mRNA transcripts increased, peaked 3 hours after reperfusion, and decreased gradually thereafter. The level of ICAM-1 mRNA transcripts in the WK-5 rat endothelial cell line were markedly enhanced by MCP-1. These results suggest that MCP-1 released by Kupffer cells early after ischemia-reperfusion modulates neutrophil-dependent tissue injury via ICAM-1.
It has previously been shown that a single intravenous injection of freshly heparinized donor-specific blood transfusion (DST) before transplantation significantly prolongs the survival of fully allogeneic ACI (RT1a)-to-LEW(RT1(1)) rat hepatic allografts. Additionally, we have shown that pretreatment of LEW rats with PVG.r1 blood, which shares only the RT1.A major histocompatibility complex (MHC) region with ACI, significantly prolongs the survival of ACI hepatic allografts. In this study, we report the cellular identity of hepatic allograft leukocyte infiltrates following transplantation. Fluorescence-activated cell sorting (FACS) analysis revealed that CD4+ T cells infiltrating liver allografts could be divided into two subsets, CD45RC- CD4+ and CD45RC+ CD4+ T cells, and that the ratio of CD45RC- CD4+/CD45RC+ CD4+ T cells was significantly higher in hepatic allografts of recipients pretreated with DST or PVG.r1 blood as compared to untreated allografts. Further, CD8+ T cells that accumulated in the liver grafts could be similarly divided into two subsets, and the ratio of CD45RC- CD8+/CD45RC+ CD8+ T cells was also significantly higher in hepatic allografts of recipients pretreated with DST or PVG.r1 blood. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that CD45RC- CD4+ T cells harvested from hepatic allografts pretreated with PVG.r1 blood expressed interleukin-4 (IL-4) and interleukin-10 (IL-10), but not interleukin-2 (IL-2) or interferon-gamma (IFN-gamma). In contrast, CD45RC- CD8+ T cells from hepatic allografts pretreated with PVG.r1 blood expressed IL-4, IL-10, and IFN-lambda, but not IL-2. These results indicate that the CD45RC leukocyte common antigen could be used to differentiate CD4+ and CD8+ T cells following pretreatment with DST or PVG.r1 blood. Persistent infiltration of CD45RC- CD4+ and CD45RC- CD8+ T cells, capable of secreting Th2-type cytokines may prevent allograft rejection by causing immunologic unresponsiveness.
We investigated the effects of the xanthine oxidase inhibitor, BOF-4272, on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF-4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF-4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF-4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF-4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF-4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF-4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.
In 3 (9 %) of 34 children with biliary atresia, US revealed gallbladder contraction following an oral feed, given on admission, but not with subsequent feeds. Surgery revealed a Kasai type IIIa biliary atresia with a patent communication between the gallbladder and duodenum. We propose that the bile ducts may initially have been patent, but then gradually became obliterated secondary to inflammation. These cases may explain the development of one type of biliary atresia.