Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal perfusion methods with a nonabsorbable marker allow an exact quantitative determination of intestinal absorption and secretion provided that methodological pitfalls are avoided. A modified technique is applied to the simultaneous measurement of biliary and pancreatic secretion during and depending on emptying of a mixed test meal. A duodenal segment was perfused with an isotonic polyethyleneglycol solution (PEG). Reinjection of duodenal aspirates maintained a normal enterohepatic circulation of bile acids (interruption less than 10%). The perfusion was performed in healthy volonteers over a period of 12 to 24 hours, with three mixed formula meals containing 51CrCl3 as a marker ingested at conventional feeding hours. Influence of meal size was studied by means of a high caloric (40 Kcal/b. wt. per day) test meal. Patients with cholesterol gallstones and cirrhosis of the liver only received one formula test meal of 300 Kcal. Instead of concentrations output of trypsin, lipase, bile acids and cholesterol (the latter corrected for duodenal absorption) was calculated from the dilution of PEG in the duodenal juice and gastric emptying was determined by following quantitatively the flow of 51CrCl3. Gastric emptying can be expressed by a single exponential function over most of the time. Only the last 60-100 Kcals were expelled by the stomach at a faster rate. The daily biliary and pancreatic secretion depend indirectly on the amount of food ingested. But during the day light hours (with continuous meal flow), secretion was similar in high and low caloric subjects, while a significant difference became obvious during night hours corresponding to differences in gastric emptying time. Mean hourly output of bile acid, biliary cholesterol, trypsin and lipase is independent from meal size and secretion of pancreatic enzymes reaches the values close to those after maximal stimulation by i.v. CCK-PZ. Output of pancreatic enzymes does not differ in health and gallstone disease or cirrhosis of the liver respectively. Since during digestion in normals approximately one forth of the bile acid pool is secreted hourly into the gut, the number of daily enterohepatic cycles of bile acids can be calculated by 4-6. Patients with cholesterol gallstones maintain normal bile acid output by enhanced cycling of the small pool: An average of 50% of the pool passed the duodenum per hour. A decreased bile acid pool is also present in cases of advanced cirrhosis of the liver. However, hourly output of bile acids in these patients is significantly less than in mild cirrhosis (with normal bile acid pool) or normal controls. Therefore the hourly fraction of the pool secreted is similar to healthy subjects. These findings provide an important information to explain abnormalities in bile acid metabolism in cirrhosis.
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PMID:[Simultaneous determination of gastric emptying and bile and pancreatic enzyme secretion]. 106 80

Basal plasma cholecystokinin levels were measured by a bioassay using dispersed rat pancreatic acini in various digestive diseases and compared with corresponding values by CCK-8 specific radioimmunoassay. The mean basal level in healthy volunteers was 0.40 +/- 0.06 pM. The basal level in liver cirrhosis was significantly elevated to 0.92 +/- 0.14 pM. The patients with cholestasis, that is, primary biliary cirrhosis and obstructive jaundice due to choledocholithiasis, bile duct cancer or lymph node metastasis , had markedly increased basal plasma CCK-8 like bioactivities from 1.88 pM to more than 25 pM. These CCK bioactivities were not correlative with CCK immunoreactivities. It was concluded not only that basal plasma CCK in patients with bile flow disturbance were truly increased, but also that interfering substances of the bioassay might appear in the plasma of these patients.
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PMID:[Basal plasma cholecystokinin levels in digestive diseases--comparison between CCK-8 like bioactivity by bioassay and CCK immunoreactivity by radioimmunoassay]. 260 Nov 19

In anesthetized rats, a marked decrease in CCK-OP activity and, to a far lesser extent, in the pancreatic secretory effect of CCK-33 were found after portal administration, compared to the femoral route. Changes in the biological activity of CCK-OP were further investigated after 30 min incubation with different subcellular liver fractions (1000 X g, 12,000 X g, microsomal fraction with or without NADPH). All the subcellular liver fractions caused an approximately 70% decrease in the CCK-effect, as calculated from dose-response relationships. The inactivation of CCK-OP after incubation with microsomal fractions of thioacetamide (TAA)-induced cirrhotic liver did not differ from that of control rats. The CCK-OP dose-response curves were similar in cirrhotic and control rats, but the pancreatic secretion was sustained to a greater extent and the inhibitory effect of supramaximal stimulation was delayed in cirrhotic rats. It was concluded that CCK-OP can be inactivated by liver proteins present in microsomal fractions, by a NADPH-independent mechanism. This inactivation did not diminish in liver cirrhosis. There were no changes in CCK-OP elimination in cirrhotic rats in vivo, thus pancreatic hypertrophy in experimental cirrhosis must be explained by other mechanisms.
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PMID:Inactivation of cholecystokinin octapeptide by normal and cirrhotic liver in rats. 368 Oct 28

Cholecystokinin-8 like immunoreactivity (CCK-8 IR) was measured in different brain regions of rats with experimental liver cirrhosis. A statistically significant reduction of CCK-8 content was observed in the hypothalamus of cirrhotic rats. No significant modification of brain CCK fractionation pattern was observed in treated animals as compared to controls. The decrease of CCK-8 IR parallels the recently reported hypothalamic depletion of beta endorphin in cirrhotic rats confirming that central neuropeptides are affected by chronic liver failure.
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PMID:Brain cholecystokinin-8 immunoreactivity in rats with experimental liver cirrhosis. 630 71

We have studied the volume, protein concentration, total protein, and chymotrypsin and trypsin outputs in pure pancreatic juice (PPJ) following endoscopic cannulation of the pancreatic duct in 11 male and 2 female patients with advanced alcoholic cirrhosis (AC). Results were compared to those obtained from 21 nonalcoholic volunteers (NAV) and 26 chronic alcoholic (CA) patients without cirrhosis. Intravenous stimulation with secretin followed 10 min later by intravenous cholecystokinin-pancreozymin (CCK-PZ) resulted in highly significant increases in volumes during both phases of pancreatic stimulation in AC compared to NAV and CA. Protein concentration and total output during secretin stimulation was not different among the three groups. During CCK-PZ stimulation, CA exhibited a significant elevation in protein concentration and total output compared to NAV and AC. Although total chymotrypsin output was lower in secretin-stimulated CA than other groups, no other differences between the groups were observed in either of the hormone-stimulation phases. Marked elevations in trypsin output were observed in secretin-stimulated AC and in CCK-PZ-stimulated AC and CA. The high PPJ volume and the relatively low protein concentration observed in AC may effect a washout phenomenon resulting in a decreased tendency for ductal protein precipitation in these patients.
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PMID:Pancreatic secretion after secretin and cholecystokinin stimulation in chronic alcoholics with and without cirrhosis. 665 99

Size of gallbladder after overnight fasting and the kinetics of gallbladder contraction following i.v. injection of 1 I. U. of CCK was investigated in patients with chronic liver disease (liver cirrhosis: n = 26; chronic hepatitis: = 12; fatty liver: n = 5). The results were compared with those obtained in an age and sex matched control group of subjects without symptoms of diseases of the liver or gastrointestinal tract (n = 15). Ultrasound was used for continuous monitoring of gallbladder emptying. In the cirrhotics the cartographically determined initial area of the gallbladder was significantly greater than in the controls (p less than 0,01). The kinetic of gallbladder emptying following CCK-pancreozymin stimulation was similar in the groups of patients with liver diseases to that of the control subjects. However, the residual area of the gallbladder following maximal contraction was again significantly greater in the cirrhotics when compared to the control group (p less than 0.05). The area of the gallbladder in patients with chronic hepatitis exhibited similar changes of the values in the fasting state and after maximal contraction as seen in the patients with liver cirrhosis, although the differences when compared to the control group were not significant. The results show that in spite of distinct signs of a hypotonic state of the unstimulated gallbladder in patients with chronic liver disease the kinetic of contraction following an exogenous stimulus with CCK remains normal.
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PMID:[Ultrasound measurement of gallbladder response to cholecystokinin in patients with chronic liver disease (author's transl)]. 731 56

Stathmin is a microtubule-destabilizing protein ubiquitously expressed in vertebrates and overexpressed in a variety of human malignancies. Down-regulation of its expression will contribute to optimize therapeutic outcomes in the treatment of these malignancies. This research aimed to demonstrate effects of stathmin expression silencing on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, cell adhesion and motility behavior in vitro and further reveal significance of stathmin expression in tissues associated with hepatocarcinogenesis. The expression of stathmin in normal liver, hepatitis, cirrhosis and HCC tissues was detected by immunohistochemistry analysis (IHC), stathmin expression was inhibited in an HCC cell line-HCCLM3 with high metastatic potential by small interfering RNAs (siRNAs). After transfection with siRNAs, HCCLM3 cells proliferation was detected by CCK-8 (cell count kit), cell apoptosis was analyzed by FACS, cell adhesion was investigated by cell adhesion assay and motility ability was demonstrated by in vitro migration and invasion assays. Stathmin expression was up-regulated in HCC tissues, especially in metastatic HCC tissues, compared with normal liver, hepatitis and hepatic cirrhosis tissues. Expression of stathmin in HCCLM3 cells was efficiently inhibited by specific siRNAs. Silencing of stathmin expression obviously suppressed HCCLM3 cell proliferation and markedly induced cell apoptosis. Moreover, defect of stathmin expression in HCCLM3 cell inhibited cell adhesion, restrained cell migration and repressed invasion. Stathmin expression correlates with hepatocarcinogenesis and tumor progression. This molecule may be a promising therapeutic target in patients with hepatocellular carcinoma.
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PMID:Up-regulated expression of stathmin may be associated with hepatocarcinogenesis. 2020 89

Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal sorting complex required for transport (ESCRT)-III complex, plays an important part in cytokinetic membrane abscission and the late stage of mitotic cell division. In this study, we explored the prognostic significance of CHMP4B in human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was significantly upregulated in HCC tissues, compared with adjacent non-tumorous tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B expression was correlated with multiple clinicopathological variables, including AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that CHMP4B served as an independent prognostic factor for survival of HCC patients. Using HCC cell cultures, we found that the expression of CHMP4B was progressively upregulated after the release from serum starvation. To verify whether CHMP4B could regulate the proliferation of HCC cells, CHMP4B was knocked down through the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays indicated that interference of CHMP4B led to cell cycle arrest and proliferative impairment of HCC cells. Additionally, depletion of CHMP4B expression could increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together, our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC.
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PMID:High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma. 2587 85

Exonuclease 1 (EXO1), a member of the RAD2 nuclease family, was first described as possessing 5' to 3' nuclease activity and 5' structure-specific endonuclease activity. Here, we show that EXO1 is significantly upregulated in HCC tumor tissues and that high EXO1 expression is significantly correlated with liver cirrhosis. We further demonstrate that EXO1 knockdown decreases proliferation and colony forming abilities of HCC cells in vitro and tumorigenicity in vivo, as well as decreases migration and invasive capabilities of HCC cells. Alternatively, EXO1 overexpression significantly increases the proliferation, colony forming ability, and migration and invasive capabilities of HCC cells in vitro. Additionally, we truncated a region upstream of the transcription start site (TSS) of EXO1 and used the region with the strongest transcriptional activity to predict that the transcription factor FOXP3 can bind to the EXO1 promoter. Bioinformatics analysis found that FOXP3 was positively correlated with EXO1 and luciferase reporter assays and RT-PCR confirmed that FOXP3 could enhance the transcriptional activity of EXO1. CCK-8 assays showed that depletion of FOXP3 further reduces cell proliferation ability after knocking down of EXO1 in vitro. Taken together, our findings indicate that EXO1 acts as an oncogene in HCC and its expression level is related to FOXP3 activity.
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PMID:EXO1 Plays a Carcinogenic Role in Hepatocellular Carcinoma and is related to the regulation of FOXP3. 3262 39