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Biomedical subjects

Yuji Nimura

Publications and source records attributed to Yuji Nimura.

At least 55 records · Page 3Linked to original sources
PubMed2005

Unsuspected gallbladder carcinoma after laparoscopic cholecystectomy.

BACKGROUND/PURPOSE: Many cases have been reported of disastrous port-site recurrence after laparoscopic cholecystectomy (LC) revealed unsuspected gallbladder carcinoma (GBC). Some investigators have reported that the prognosis of patients after LC showed unsuspected GBC is not worsened by laparoscopic procedures. We retrospectively reviewed our cases and the literature to reconfirm the intrinsic risks of LC for unsuspected GBC. METHODS: Of 1663 patients who underwent LC from January 1991 to December 2003 in a single institution, 9 (0.54%) with unsuspected GBC were reviewed. RESULTS: These 9 patients consisted of 5 men and 4 women, whose ages ranged from 58 to 87 years, with a median age of 73 years. Two patients with a pT1a tumor (limited to mucosa) and 2 patients with a pT1b tumor (muscle layer) underwent no further operation. The remaining 5 patients with a pT2 tumor (subserosa) underwent further operations with lymph node dissection. Five patients (2 patients with pT1b and 3 patients with pT2) developed recurrence and all of them died within a median period of 19 months (range 14-37 months) after LC. The causes of death were bone metastases in 1 patient (pT2), local recurrence in 2 patients (pT1b and pT2), and peritoneal metastasis in 2 patients (one elderly patient with pT1b who underwent laparoscopic common bile duct exploration, and one patient with pT2 in whom the cystic duct was damaged during surgery). Four patients (2 with pT1 and 2 with pT2) have been doing well with a median follow-up of 39.5 months (range 12-99 months) after LC. CONCLUSIONS: Surgeons should always prevent bile spillage during LC and when removing the resected gallbladder. When laparoscopic common bile duct exploration is planned, especially for elderly women, surgeons should also bear in mind the increasing possibility of unsuspected GBC.

Adenocarcinoma↗
PubMed2005

Current understanding of gender dimorphism in hepatic pathophysiology.

Studies have shown gender dimorphic response of the liver for various hepatic stresses including ischemia/reperfusion, hemorrhagic shock-resuscitation, hepatectomy, liver cirrhosis, endotoxemia, and chronic alcoholic consumption. The mechanisms responsible for the gender dimorphic response include differences in pro-inflammatory cytokine release, production of reactive oxygen species, and alteration in hepatic vasoregulatory action. These effects were shown to be modulated by circulating sex steroid levels. In this regard, modulation of sex steroid levels by agents/drugs has been proposed as a therapeutic option for preventing hepatic damage in various hepatic stress models. Further elucidation of precise mechanisms responsible for the gender-related differences in the hepatic pathophysiology is essential for the potential clinical application of sex hormone modulation therapy. In this article, current progress in our understanding the gender difference in the hepatic pathophysiology under the condition of hepatic stress is reviewed and discussed.

Estrogens↗
PubMed2005

Surgical treatment for colorectal liver metastases involving the paracaval portion of the caudate lobe.

BACKGROUND: Hepatic neoplasms in the paracaval portion of the caudate lobe (S1r) are usually difficult to treat surgically because such neoplasms often invade the hepatic veins and/or inferior vena cava (IVC). We reevaluated resected cases of colorectal liver metastases involving S1r to confirm the significance of aggressive surgical treatments. METHODS: Between July 1977 and December 2002, 95 consecutive patients with colorectal liver metastases underwent hepatic resection. Seven patients with liver metastases involving the S1r underwent resection. RESULTS: The surgical procedures for liver metastases comprised 3 isolated caudate lobectomies, 2 right hepatectomies, and 2 right hepatic trisectionectomies with caudate lobectomy. Combined resections included partial resection of the hepatic vein in 2 patients, wedge resection of the IVC in 3, and segmental resection of the IVC in 1. Six of the 7 patients with S1r metastasis had recurrent disease in liver and/or lung. A second hepatectomy was carried out in 4 patients and a partial lung resection in 2 patients. Four of the 7 patients survived more than 5 years, but 2 of them died of recurrent disease at 61 and 95 months after initial hepatectomy. The remaining 2 patients are alive 72 and 118 months without any sign of recurrence. The median survival time of the 7 patients was 60 months. CONCLUSION: Liver metastases involving the S1r could be resected radically with en bloc resection of the major hepatic veins and/or the inferior vena cava. An aggressive surgical approach with combined resection of the adjacent major vessels may offer a better chance of long-term survival in selected patients with caudate lobe metastasis from colorectal cancer.

Aged↗
PubMed2005

One hundred consecutive hepatobiliary resections for biliary hilar malignancy: preoperative blood donation, blood loss, transfusion, and outcome.

BACKGROUND: Many reports on blood loss and transfusion requirements during hepatectomy for metastatic liver cancer or hepatocellular carcinoma have been published; however, there are no reports on these issues in hepatectomy for biliary hilar malignancy. The aim of this study was to review our experience with blood loss and perioperative blood requirements in 100 consecutive hepatectomies for biliary hilar malignancy. METHODS: One hundred consecutive hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for hilar malignancies were performed, including 81 perihilar cholangiocarcinomas and 19 advanced gallbladder carcinomas involving the hepatic hilus. Fifty-eight hilar resections were combined with other organ and/or vascular resection. Data on preoperative blood donation, intraoperative blood loss, and perioperative transfusion were collected and analyzed. RESULTS: Preoperative autologous blood donation was possible in 73 patients (3.4 +/- 1.2 U). Intraoperative blood loss was 1850 +/- 1000 mL (range, 677-5900 mL), and it was < 2000 mL in 62 patients. Intraoperatively, only 7 of the 73 patients (10%) who donated blood received transfusion of unheated, homologous blood products (packed red blood cells or fresh frozen plasma), whereas 18 the 23 patients (67%) without donation received homologous transfusions. Only 16 patients received transfusion postoperatively, and overall, 35 patients received unheated homologous blood products. Total serum bilirubin concentrations after hepatectomy in patients receiving autologous blood transfusion only was similar to those in patients who did not receive transfusion. The incidence of postoperative complications was higher in the 35 patients who received perioperative homologous transfusion than in 65 patients who did not (94% vs 52%; P <.0001). The mortality rate (including all deaths) was 3% (myocardial infarction, intra-abdominal bleeding, and liver failure, 1 patient each). CONCLUSIONS: Despite the technical difficulties arising from hepatectomy for biliary hilar malignancy, approximately two thirds of hepatectomies can be performed in an experienced center without perioperative homologous blood transfusion using preoperative blood donation.

Adult↗
PubMed2005

Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1.

Transforming growth factor-beta1 (TGF-beta1) is involved in tumor progression by promoting angiogenesis or suppressing the immune system; yet TGF-beta1 also has a growth-inhibitory effect on epithelial cells including carcinoma cells. Several mechanisms of impaired TGF-beta1 responsiveness of carcinoma cells have been reported. In this study, we examined how TGF-beta1 participates in the development and progression of intrahepatic cholangiocarcinoma (ICC) associated with hepatolithiasis, and how ICC cells escape from growth inhibitory effect of TGF-beta1. A total of 40 cases of hepatolithiasis were studied, including 16 cases of ICC, and in vitro studies were conducted with cultured murine non-neoplastic biliary epithelial cells (MBEC) and three ICC cell lines. Immunohistochemically, TGF-beta1 was expressed in mononuclear cells and mesenchymal cells around the stone-containing bile ducts and invasive ICC, and also in biliary epithelial cells (hyperplastic and precursor lesions, and ICC). TGF-beta type II receptor (TbetaR-II) was constantly expressed on biliary epithelial cells irrespective of biliary lesions. In cell culture studies, TGF-beta1 significantly inhibited proliferation of MBEC via downregulation of cyclin D1, cdk4, and cdk6, while TGF-beta1 did not influence the proliferation of ICC cells. After suppression of cyclin D1 expression in one ICC cell line using cyclin D1 small interfering RNA, TGF-beta1 significantly inhibited the proliferation of ICC cells. In conclusion, high levels of TGF-beta1 around ICC or its precursors may be involved in development and progression of ICC in hepatolithiasis. ICC cells could escape the growth inhibitory effect of TGF-beta1 by overexpression of cyclin D1.

Cell Division↗
PubMed2005

Intense PET signal in the degenerative necrosis superimposed on chronic pancreatitis.

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.

Aged↗
PubMed2005

Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement.

Biliary lining epithelia of the bile ducts in biliary diseases are known to have intraepithelial atypical/proliferative lesions related to the development of cholangiocarcinoma. The purpose of the present study was to determine the histological criteria for these lesions based on interobserver agreement. Digital images of 30 intraepithelial atypical/proliferative lesions in the stone-containing intrahepatic bile ducts of hepatolithiasis (30 cases) were sent to 10 pathologists. At first, 10 pathologists made a diagnosis (either of reactive/regenerative change, low-grade or high-grade biliary intraepithelial neoplasia (BilIN-1 and BilIN-2), or in situ carcinoma (BilIN-3)) based on their own criteria. The histological criteria for these four lesions were then determined, and the digital images of the same lesions with proposed criteria were re-distributed. Interobserver agreement on these four lesions was slightly improved (kappa = 0.44, first diagnosis; 0.49, second diagnosis) and intraobserver agreement was 'almost perfect' (kappa = 0.82 at both first and second diagnosis). Interobserver agreement between BilIN-1 and BilIN-2 and that between BilIN-2 and BilIN-3 were 'moderate', although the agreement between regenerative/reactive change and BilIN-1 was 'fair'. In this report, we propose histological criteria for reactive/regenerative change, BilIN-1, BilIN-2 and BilIN-3. Improvement of interobserver agreement suggests their applicability in diagnostic and research fields.

Bile Duct Neoplasms↗
PubMed2005

Aberrant expression of pyloric gland-type mucin in mucin-producing bile duct carcinomas: a clear difference between the core peptide and the carbohydrate moiety.

The authors have recently defined the clinopathological entity of a mucin-producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: 'columnar-type' and 'cuboidal-type' MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal-type tumors than in columnar-type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin-producing bile duct carcinomas (MPBC; cuboidal-type, n = 15; columnar-type, n = 23), using immunohistochemistry. The staining rate was graded as follows: -, <5% of neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, > or =50%. In cuboidal-type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (-, 15/15; P < 0.0001). In columnar-type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +, 1/23; -, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; -, 11/23; not significant). Our results clearly demonstrate that cuboidal-type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083-. This unique profile may be related to different outcomes of patients with MPBC.

Adenocarcinoma, Mucinous↗
PubMed2005

Acid and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction.

OBJECTIVE: Patients who undergo esophagectomy with gastric tube reconstruction incur increased risk for acid reflux and duodenogastroesophageal reflux. Few postesophagectomy studies of gastroesophageal reflux disease have included simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with gastric tube reconstruction. METHODS: Reflux symptom evaluation, endoscopy, and simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic esophagogastrostomy, and digital dilation of the pyloric ring as treatment for esophageal cancer. RESULTS: Reflux symptoms were severe, mild, and absent in 2, 7, and 16 patients, respectively. Reflux esophagitis and Barrett's esophagus was observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7 patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11 patients (44%). Reflux profile analysis identified three patterns: 4 subjects (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%) with only elevated acid reflux; and 7 (28%) with only elevated duodenogastroesophageal reflux. Of 7 patients with only elevated duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux symptoms did not correlate with endoscopic esophagitis, a significant correlation was observed between endoscopic esophagitis and acid reflux and/or duodenogastroesophageal reflux. CONCLUSIONS: Reflux symptoms represented a poor indication of esophagitis in patients with esophagectomy and gastric tube reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in identifying patients at high risk for reflux esophagitis, as well as indicating the cause of esophagitis.

Aged↗
PubMed2004

Mechanotransduction by integrin is essential for IL-6 secretion from endothelial cells in response to uniaxial continuous stretch.

We previously reported that uniaxial continuous stretch in human umbilical vein endothelial cells (HUVECs) induced interleukin-6 (IL-6) secretion via IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) activation. The aim of the present study was to clarify the upstream signaling mechanism responsible for this phenomenon. Stretch-induced IKK activation and IL-6 secretion were inhibited by application of alpha(5)beta(1) integrin-inhibitory peptide (GRGDNP), phosphatidylinositol 3-kinase inhibitor (LY-294002), phospholipase C-gamma inhibitor (U-73122), or protein kinase C inhibitor (H7). Although depletion of intra- or extracellular Ca(2+) pool using thapsigargin (TG) or EGTA, respectively, showed little effect, a TG-EGTA mixture significantly inhibited stretch-induced IKK activation and IL-6 secretion. An increase in the intracellular Ca(2+) concentration ([Ca(2+)](i)) upon continuous stretch was observed even in the presence of TG, EGTA, or GRGDNP, but not in a solution containing the TG-EGTA mixture, indicating that both integrin activation and [Ca(2+)](i) rise are crucial factors for stretch-induced IKK activation and after IL-6 secretion in HUVECs. Furthermore, while PKC activity was inhibited by the TG-EGTA mixture, GRGDNP, LY-294002, or U-73122, PLC-gamma activity was retarded by GRGDNP or LY-294002. These results indicate that continuous stretch-induced IL-6 secretion in HUVECs depends on outside-in signaling via integrins followed by a PI3-K-PLC-gamma-PKC-IKK-NF-kappaB signaling cascade. Another crucial factor, [Ca(2+)](i) increase, may at least be required to activate PKC needed for NF-kappaB activation.

Calcium↗
PubMed2004

Changes in splenic volume during liver regeneration.

Little is known about the relation between liver regeneration and splenic size. We monitored serial changes in liver and spleen volumes using computed tomography in 24 patients with biliary cancer who underwent right hepatectomy or more extensive liver resection following portal vein embolization (PVE). Nonembolized hepatic segments increased in volume from 316 +/- 97 cm3 (34% +/- 8% of total liver volume) before PVE to 410 +/- 115 cm3 (44% +/- 8%) after PVE. The volume of nonembolized hepatic segments (i.e., remnant liver) increased to 617 +/- 111 cm3 (59% +/- 10% of total liver volume before PVE) 14 days after hepatectomy and then increased slowly to reach 795 +/- 231 cm3 (76% +/- 16%) 1 year after hepatectomy. Splenic volume increased from 87 +/- 29 cm3 before PVE to 104 +/- 38 cm3 (119% +/- 17% of original volume) after PVE. Splenic volume increased to 137 +/- 65 cm3 (155% +/- 40%) by 14 days after hepatectomy and to 155 +/- 67 cm3 (179% +/- 41%) by 28 days after hepatectomy, with no further change at 1 year after hepatectomy (153 +/- 92 cm3; 174% +/- 79%). The rate of increase in splenic volume within the first 14 days after hepatectomy was 2.7 +/- 3.6 cm3/day, correlating well with increases in remnant liver volume ( r = 0.64, p = 0.0006). These data indicate that the spleen is enlarged during liver regeneration, suggesting that the liver and spleen share certain common growth regulatory mechanisms.

Aged↗
PubMed2004

Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival.

In this study, we report for the first time reduced expression of the let-7 microRNA in human lung cancers. Interestingly, 143 lung cancer cases that had undergone potentially curative resection could be classified into two major groups according to let-7 expression in unsupervised hierarchical analysis, showing significantly shorter survival after potentially curative resection in cases with reduced let-7 expression (P = 0.0003). Multivariate COX regression analysis showed this prognostic impact to be independent of disease stage (hazard ratio = 2.17; P = 0.009). In addition, overexpression of let-7 in A549 lung adenocarcinoma cell line inhibited lung cancer cell growth in vitro. This study represents the first report of reduced expression of let-7 and the potential clinical and biological effects of such a microRNA alteration.

Adult↗
PubMed2004

Survival after surgical treatment of early gastric cancer, surgical techniques, and long-term survival.

Early gastric cancer (EGC) is well accepted as having a favorable prognosis after surgical treatment. Difference in treatment strategies for EGC between Japan and western countries indicates a need for current information to be evaluated with regard to long-term survival rates of EGC patients throughout the world. To analyze survival rates and recurrence after resection of EGC, we investigated 51 reports in English that each included more than 50 cases of EGC treated by gastrectomy and had been published during the past 12 years (1992-2003). Prevalence of EGC among all gastric cancers was 45%-51% in Japan, but only 7%-28% in western countries. Mean age at diagnosis was less than 60 years in Japan and Korea, but was more than 60 in most of the Western countries. Actuarial and disease-specific 5-year survival rates for EGC were 72%-95.8% and 88%-98.3%, respectively. Those for EGC that were invading the submucosal layer were 71.6%-94.1% and 82%-96.6%, respectively. Those for EGC with lymph node metastasis were 57%-89.1% and 72%-93.5%, respectively. Prevalence of recurrence ranged from 1.0% to 13.8%. Larger clinical series with more EGC cases showed a lower prevalence of recurrence (P=0.531, P=0.0026). Liver and blood-borne distant metastasis represented the predominant pattern of relapse, accounting for over half (54%). Local recurrence and peritoneal dissemination represented 20% and 18% of all recurrences, respectively. Clinicopathological studies have shown lymph node metastasis to be closely related to depth of invasion, size of lesion, histological type, presence of ulcer or ulcer scar, and vessel involvement. Information on these factors is the key to successful treatment of EGC. When sufficient information has been assessed preoperatively, surgeons can select patients for whom less-invasive surgery should not increase the risk of recurrence.

Aged↗
PubMed2004

Expression of CD109 in human cancer.

It was recently reported that the human CD109 gene encodes a glycosyl-phosphatidylinositol-anchored glycoprotein that is a member of the alpha(2)-macroglobulin/C3, C4, C5 family of thioester-containing proteins. In this study, we found that the expression of mouse CD109 gene was upregulated in NIH3T3 cells expressing RET tyrosine kinase with a multiple endocrine neoplasia 2B mutation. Northern blot analysis showed a high level of expression of the CD109 gene only in the testis in normal human and mouse tissues. In addition, its expression was high in some human tumor cell lines, which included squamous cell carcinoma and glioblastoma cell lines, whereas it was undetectable in neuroblastoma and small-cell lung carcinoma cell lines. When CD109 expression was examined in 33 cases of human lung cell carcinomas by quantitative RT-PCR, a significant high expression of CD109 was detected in about half of squamous cell carcinomas examined, but not in adenocarcinoma, large-cell carcinoma and small-cell carcinoma. Similarly, upregulation of CD109 was observed in nine out of 17 esophageal squamous cell carcinomas. Thus, these results suggested that CD109 might be a useful molecular target for the development of new therapeutics for malignant tumors, such as squamous cell carcinoma.

Amino Acid Sequence↗
PubMed2004

Prognostic significance of the location of intramural metastasis in patients with esophageal squamous cell carcinoma.

BACKGROUND: Although the presence of an intramural metastasis (IM) from esophageal cancer is associated with a poor prognosis, some patients with IM have a relatively favorable course. METHODS: Clinicopathological factors including number, location, and size of IM and the distance between the primary tumor and IM were assessed in 212 patients with esophageal squamous cell carcinoma who underwent esophagectomy. RESULTS: Twenty-three patients (10.8%) had IM. IM size ranged from 2 to 100 mm (18+/-26), and the distance between primary lesion and IM ranged from 5 to 70 mm (27+/-18). Survival of ten patients with an IM less than 20 mm from the primary tumor was significantly longer than that of 13 patients with a more distant IM ( P=0.0184); median survival time were 2.3 and 0.7 years, respectively. CONCLUSION: A subgroup of patients with an IM less than 20 mm from the primary esophageal cancer may have a relatively favorable prognosis. When an IM is found preoperatively or in a resected specimen, measurement of the distance between the primary tumor and the IM might be useful in determination of treatment strategy and evaluation of prognosis.

Adult↗
PubMed2004

Susceptibility of murine periportal hepatocytes to hypoxia-reoxygenation: role for NO and Kupffer cell-derived oxidants.

Ischemia/reperfusion (I/R) is an important problem in liver resection and transplantation that is associated with hepatocellular dysfunction and injury. This study was designed to investigate whether a difference in hepatocyte susceptibility occurs in the periportal (PP) and/or perivenous (PV) zones in response to hypoxia/reoxygenation (H/R), and to delineate the mechanisms underlying this susceptibility. H/R was induced in an in situ perfused mouse liver model with deoxygenated Krebs-Henseleit buffer followed by oxygenated buffer. Selective destruction of PP or PV sites was achieved by digitonin perfusion into the portal or inferior vena cava, and was confirmed by histological evaluations and zone-specific enzymes. Hepatocellular injury was assessed by alanine aminotransferase (ALT) release. In whole liver, H/R significantly increased perfusate ALT. H/R of PP-enriched zones caused ALT release that was similar to that of whole liver (80 + 10 vs. 70 + 12 U/mg protein), consistent with significant PP hepatocyte injury. Minimal ALT release occurred in PV zones (10 + 5 U/mg protein). Administration of N-acetyl L-cysteine or a chimeric superoxide dismutase (SOD)-SOD2/3, a genetically engineered SOD-abrogated ALT release in H/R-perfused PP zones, implicating a role for superoxide (O(2) (-)). This elevated ALT release was attenuated by gadolinium chloride pretreatment, indicating that Kupffer cells are the O(2) (-) source. Enzymatic inhibition of cellular nitric oxide synthase (NOS) or genetic depletion of endothelial nitric oxide synthase (eNOS) aggravated hypoxia injury while exogenous NO and inducible nitric oxide synthase (iNOS) deficiency abolished reoxygenation injury. In conclusion, PP hepatocytes are more vulnerable to H/R; this injury is mediated directly or indirectly by Kupffer cell derived O(2) (-) and is limited by eNOS-derived NO.

Animals↗
PubMed2004

Kupffer cell-derived interleukin 10 is responsible for impaired bacterial clearance in bile duct-ligated mice.

Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and-most importantly-postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 10(7) colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon gamma production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti-IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL-lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fas-mediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells.

Animals↗