Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipopolysaccharide (LPS) Binding Protein (LBP) is an acute phase protein with the ability to recognize bacterial LPS and transport it to the CD14 molecule or into HDL particles. It is synthesized in hepatocytes and secreted into the blood stream. LBP levels significantly rise during the acute phase response and levels of LBP may be important for an appropriate host reaction to bacterial challenge and for developing the sepsis syndrome. In order to elucidate the mechanisms of LBP regulation we investigated its transcription pattern and performed promoter studies under experimental conditions mimicking an acute phase scenario. In human hepatoma cell lines stimulation with IL-1 beta, IL-6, TNF-alpha and dexamethasone leads to strong transcriptional activation of the LBP gene in a dose- and time-dependent manner. IL-6 alone induces LBP significantly, whereas IL-1 beta mainly increases the IL-6 effect when applied in combination. Our results furthermore show that AP-1 and C/EBP beta are transcription factors involved in the activation of the LBP gene, as revealed by Luciferase reporter gene analysis and electromobility shift assays. Elucidating the mechanism of transcriptional activation of LBP potentially may help in understanding host-pathogen response patterns and mechanisms involved in the acute phase reaction and in the pathophysiology of sepsis.
 ...
PMID:The transcriptional activation pattern of lipopolysaccharide binding protein (LBP) involving transcription factors AP-1 and C/EBP beta. 944 84

Nineteen patients with hepatocellular carcinoma associated with hepatolithiasis were retrospectively analyzed. Eleven of the 19 patients presented with hepatolithiasis-related biliary infection. Diagnosis was erroneously assumed to be hepatolithiasis alone, liver abscess, or cholangiocarcinoma in five of 11 patients before surgery was attempted. Middle-age, male sex, liver cirrhosis, hepatitis B or C infection, abnormal alpha-fetoprotein, and negative carcinoembryonic antigen raised the suspicion of associated hepatocellular carcinoma rather than cholangiocarcinoma in patients with hepatolithiasis. Antibiotics and nonoperative methods to resolve biliary infection first, followed by hepatectomy, in selected cases, to eradicate hepatocellular carcinoma and hepatolithiasis simultaneously provides the best chance for long-term survival. Otherwise, patients often died of hepatolithiasis-related biliary sepsis rather than hepatocellular carcinoma per se in the long run.
 ...
PMID:Hepatocellular carcinoma complicated with coexisting hepatolithiasis: pitfalls in diagnosis and management. 982 39

Recent studies suggest that release of cytokines during inflammatory states such as septic shock leads to hypocholesterolemia. To examine whether tumor necrosis factor alpha (TNF), which is the major cytokine in inflammatory disease, causes hypocholesterolemia, we measured serum levels of total (bioactive and receptor-bound) TNF, cholesterol, Apo B, and Apo A1 in seven patients with septic shock over a period of 8 days. Since elevated serum TNF levels are accompanied by the release of soluble TNF receptors, levels of TNF receptors p55 and p75 were also measured. Patients with septic shock had significantly higher serum TNF and TNF receptor levels compared with healthy controls. Increased cytokine levels were accompanied by a significant decline in total serum cholesterol apolipoprotein A1 and B. In vitro studies with cultured human skin fibroblasts, human umbilical vein endothelial cells, and HepG2 hepatoma cells showed that TNF increased the degradation of 125I-labeled low-density lipoprotein in all the cell lines tested. Recombinant soluble TNF receptors inhibited the TNF-induced stimulation of low-density lipoprotein receptor in a concentration-dependent manner. However, the calculated ratio of TNF receptors to total TNF measured in serum of these patients was not able to counteract the stimulatory effect of TNF, possibly due to the higher molar excess of TNF receptors required to achieve this effect in vitro. Our data strengthen the hypothesis that serum values of total TNF determine the extent of hypocholesterolemia during sepsis and septic shock despite the presence of a high concentration of TNF receptors. Studies with recombinant TNF also confirm the role of TNF in hypocholesterolemia in inflammation.
 ...
PMID:Association of serum tumor necrosis factor levels with decrease of cholesterol during septic shock. 984 Jun 52

Vibrio vulnificus causes severe wound infections and sepsis, mostly in persons with chronic liver diseases. Survival of this organism in the whole blood collected from healthy volunteers and patients with chronic hepatitis, liver cirrhosis, and hepatoma was analyzed as an indication of susceptibility. The bacterial numbers in the blood after 5 h of incubation tended to increase with the severity of the liver disease and differed significantly between hepatoma patients and healthy volunteers (P<.05). Survival of V. vulnificus in the whole blood correlated positively with serum ferritin concentration (r=.266; P<.05) and percentage of transferrin iron saturation (r=. 200; P<.05) and correlated negatively with serum C4 concentration (r=-.198; P<.05) and phagocytosis by neutrophils (r=-.204; P<.05). Among these parameters, low phagocytosis activity (P<.01) and high ferritin level (P<.01) in the blood were the independent predictors.
 ...
PMID:Survival of Vibrio vulnificus in whole blood from patients with chronic liver diseases: association with phagocytosis by neutrophils and serum ferritin levels. 984 54

Fibrolamellar hepatoma has a clinical course distinct from that of typical histologic hepatocellular carcinoma. The clinical behavior and prognostic features of nonresectable metastatic fibrolamellar hepatoma have not previously been fully addressed and are the focus of this report. Retrospective chart review of all patients (n = 17) with nonresectable metastatic fibrolamellar hepatoma referred to the Johns Hopkins Oncology Center from 1985 through 1990 was carried out. All patients had hepatic parenchymal involvement and regional node metastases at the time of referral. Metastases were limited to regional nodes in four patients. The remaining patients had lung metastases (n = 4), peritoneal metastases (n = 5), or both (n = 4). To assess the impact of the fibrolamellar variant, characteristic-matched control patients with typical histologic hepatocellular carcinoma were obtained from the Radiation Therapy Oncology Group database. Actuarial median survival from treatment was 14 months in the patients with fibrolamellar hepatoma and 7.7 months in the patients with hepatocellular carcinoma (p < 0.001). Karnofsky performance status and hepatic tumor volume at time of referral were important prognostic features. Multimodality treatment included radiation therapy and radiolabelled antibody, cisplatin-based chemotherapy, or both; results are discussed. Thirteen patients died, nine of liver failure, three of metastatic disease, and one of sepsis. Fibrolamellar histologic type, liver function tests, tumor volume, and patient performance status were significant predictors of survival. The cause of death in fibrolamellar hepatoma differs considerably from that observed in typical histologic hepatocellular carcinoma in the United States. The techniques of treatment of this uncommon disease were modeled after advances in the multimodality treatment of hepatocellular carcinoma and are discussed. Median survival was 14 months in patients with metastatic nonresectable fibrolamellar hepatoma.
 ...
PMID:Metastatic nonresectable fibrolamellar hepatoma: prognostic features and natural history. 1002 74

TNF alpha and IL-1 alpha are thought to contribute to impaired anabolism in a variety of clinical states, including sepsis, cancer cachexia and the AIDS wasting syndrome. We asked whether cytokines exert direct effects on hepatic production of IGFBP-1, an important modulator of IGF bioavailability. C57BL/6 mice were treated with 100 micrograms/kg of recombinant IL-1 alpha or TNF alpha by intraperitoneal injection. Western ligand blotting and immunoprecipitation with specific antisera revealed that serum levels of IGFBP-1 (but not IGFBP-2, -3, -4, -5 or -6) are increased approximately 4 fold 2 h after treatment and then decline. Northern blotting confirms that hepatic IGFBP-1 mRNA abundance also is increased acutely in both IL-1 alpha- and TNF alpha-treated animals. Similar results obtained in adrenalectomized mice indicate that adrenal activation is not required for this effect. Cell culture studies show that cytokines exert direct effects on the production of IGFBP-1 by HepG2 hepatoma cells, increasing IGFBP-1 levels in conditioned medium and the abundance of IGFBP-1 mRNA approximately 3-fold. In contrast, transient transfection studies with IGFBP-1 promoter/luciferase reporter gene constructs show that IGFBP-1 promoter activity is reduced after 18 hr cytokine treatment. We conclude that IL-1 alpha and TNF alpha increase circulating levels of IGFBP-1, reflecting direct effects on hepatic IGFBP-1 mRNA abundance. Stimulation of hepatic IGFBP-1 production may contribute to alterations in IGF bioactivity and impaired anabolism in clinical conditions where cytokine production is high. Additional studies are required to identify specific mechanisms mediating effects of cytokines on hepatic production of IGFBP-1.
 ...
PMID:Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) regulate insulin-like growth factor binding protein-1 (IGFBP-1) levels and mRNA abundance in vivo and in vitro. 1022 4

Hilar tumors are extremely difficult to manage with a considerably lower resection rate. We performed endoscopic biliary drainage for 288 patients with hilar tumors (Klatskin tumor 184, gallbladder carcinoma 23, HCC 47 and other metastases 34) in the past 3 years. 162 patients underwent endoscopic nasobiliary drainage, 80 plastic biliary stenting, and 46 expandable metal stent implantation. 4 patients were given double stents insertion simultaneously, 43.1% of patients received good drainage with the total effective rate of 67.0%, but postprocedure cholangitis took place in 13.8% of patients within one month and 3 died of cholangitis and sepsis. In the long-term follow-up patients without surgical treatment, the median sruvival was 5.3 months. The outcome was closely related to Bismuth types, and jaundice could be relieved if more than about 40% of the liver was drained. The double stents for the left and right intrahepatic duct in the meantime could enlarge drainage area and improve the theraputic effectiveness. To get highest benefit, the 3 endoscopic biliary drainage methods should be choosen properly and exchanged flexibly. We conclude that endoscopic biliary drainage is a safe and useful management for the hilar tumor and should be the treatment of choice for palliating jaundice in the inoperable patients.
 ...
PMID:[The evaluation of endoscopic biliary drainage for 288 patients with malignant hilar obstruction]. 1037 80

The purpose of this Phase II study was to determine the response rate, the toxicity, and the effect on survival of the combination of cisplatin, doxorubicin, 5-fluorouracil, and alpha-IFN (PIAF) in advanced unresectable hepatocellular carcinoma. Fifty patients with either unresectable or metastatic disease were treated with PIAF: cisplatin (20 mg/m2 i.v., days 1-4), doxorubicin (40 mg/m2 i.v., day 1), 5-fluorouracil (400 mg/m2 i.v., days 1-4), and alpha-IFN (5 MU/m2 s.c., days 1-4). Treatment was repeated every 3 weeks to a maximum of six cycles. All patients were evaluable for response, toxicity, and survival. As assessed by conventional imaging criteria, there were no complete responses, but 13 patients (26%) had a partial response. Among the 36 patients who had an initially high alpha-fetoprotein level (>500 ng/ml), 15 (42%) had a >50% fall after therapy. Nine patients underwent surgical resection after achieving partial response and, in 4 of these patients, histological examination of the resected specimens revealed no viable tumor cells. All these nine patients are alive, and eight patients remain in complete remission at between 7.6 and 25.8 months at the time of analysis. The overall median survival was 8.9 months. Toxicity was mainly myelosuppression and mucositis. There were two treatment-related deaths due to neutropenic sepsis. PIAF is active in hepatocellular carcinoma despite considerable hematological toxicity. Complete pathological remission is possible with this systemic combination. Apparently, persistent radiological lesions may still represent complete pathological resolution of active disease.
 ...
PMID:Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. 1043 68

Sepsis and liver abscess are serious complications following transarterial embolization (TAE) for hepatocellular carcinoma (HCC). However, the exact incidence and the necessity of antibiotic prophylaxis remain undetermined. Between November 1996 and November 1997, we prospectively studied bacterial infections in 231 HCC patients who underwent 287 angiographic procedures without antibiotic prophylaxis, including 176 TAEs and 111 hepatic arteriographies (HAs). Four of the 111 HAs were complicated by transient asymptomatic bacteremia. Of the 176 TAEs, 2 were associated with asymptomatic bacteremia, and 7 (4%) were associated with symptomatic bacterial infection, including 3 cases of sepsis, 2 of liver abscess, and 2 of infected biloma. For patients with HCC, TAE was associated with a higher risk of developing symptomatic bacterial infections than was HA (4% vs. 0, respectively; P = .03). Previous gastrectomy was the only possible risk factor for liver abscess. Finally, early diagnosis and treatment of these infectious complications usually result in successful outcome.
 ...
PMID:Bacterial infections associated with hepatic arteriography and transarterial embolization for hepatocellular carcinoma: a prospective study. 1043 80

Thirty patients with primary hepatocellular carcinoma or liver metastases were entered into a program of chemoembolization with cisplatin, lipiodol, and escalating doses of thiotepa. Doses of cisplatin were 100/m2, and thiotepa doses ranged from 9 mg/m2 to 24 mg/m2. Two of three patients with ocular melanoma had partial responses in the liver metastases for 3+ and 16 months. In patients with either hepatocellular carcinoma (15 patients) or primary cholangiocarcinoma of the liver (three patients), there were two partial responses, for 22 and 33 months. Five patients had minor responses: four with a 40% reduction in tumor and one with a mixed response. There were four early deaths, which involved sepsis in two patients, respiratory failure in one, and acute myocardial infarction in one. Otherwise, toxicity was tolerable and reversible and included abdominal pain and transient elevation of serum creatinine, bilirubin, and transaminases. Less common toxicities included ototoxicity and peripheral neuropathy. Chemoembolization of the liver with cisplatin, thiotepa, and lipiodol can produce responses, but toxicity can be significant. The recommended starting phase II dose for future studies is thiotepa 24 mg/m2 and cisplatin 100 mg/m2.
 ...
PMID:A phase I study of chemoembolization with cisplatin, thiotepa, and lipiodol for primary and metastatic liver cancer. 1044 Jan 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>