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Sample records for quantitative liver function

  1. Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging

    PubMed Central

    Xiang, Canhong; Chen, Yingmao; Shao, Mingzhe; Li, Can; Huang, Xin; Gong, Lei; Li, Ang; Duan, Weidong; Zhang, Aiqun; Dong, Jiahong

    2016-01-01

    Abstract To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T− group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ± 0.13 vs 0.68 ± 0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ± 0.21 vs 0.58 ± 0.12, P = 0.002) but not in Group N (0.60 ± 0.19 vs 0.55 ± 0.13, P = 0.294). FLD was 0.45 ± 0.17 in the T+ group and 0.60 ± 0.08 in the T− group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression. PMID:26945357

  2. Three-Dimensional Quantitative Evaluation of the Segmental Functional Reserve in the Cirrhotic Liver Using Multi-Modality Imaging.

    PubMed

    Xiang, Canhong; Chen, Yingmao; Shao, Mingzhe; Li, Can; Huang, Xin; Gong, Lei; Li, Ang; Duan, Weidong; Zhang, Aiqun; Dong, Jiahong

    2016-03-01

    To quantitatively evaluate the regional functional reserve in the cirrhotic liver and to seek related index that reflects diminished segmental liver function. A 3D system for quantitative evaluation of the liver was used to fuse technetium-99m galactosyl human serum albumin single-photon emission computed tomography and computed tomography images from 20 patients with cirrhotic liver and hepatocellular carcinoma. A set of parameters reflecting liver function including morphological liver volume, functional liver volume, functional liver density (FLD), and the drug absorption rate constant for hepatic cells (GSA-K) was calculated. Differences in FLD and GSA-K in intrahepatic segments were compared in patients with a tumor embolus (Group Y) and those without such an embolus (Group N) in the right portal vein. Differences in FLD and GSA-K in tumor-bearing (T+ group) and tumor-free (T- group) segments in patients with no tumor embolus (Group N) were also compared. Eleven living donor liver transplantation donor served as the control group. The FLD of the liver as a whole was significantly lower in patients with cirrhosis than in the control group (0.53 ± 0.13 vs 0.68 ± 0.10, P = 0.010). The FLD in segments of the right hemiliver was significantly lower than that in segments of the left hemiliver in Group Y (0.31 ± 0.21 vs 0.58 ± 0.12, P = 0.002) but not in Group N (0.60 ± 0.19 vs 0.55 ± 0.13, P = 0.294). FLD was 0.45 ± 0.17 in the T+ group and 0.60 ± 0.08 in the T- group (P = 0.008). Differences in GSA-K in intrahepatic segments were not significant. In the control group, differences in FLD and GSA-K in intrahepatic segments were not significant. The segmental liver functional reserve can be quantitatively calculated. FLD, but not GSA-K, is an index that reflects diminished regional liver function caused by portal flow obstruction or tumor compression. PMID:26945357

  3. Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study.

    PubMed

    Beyeler, C; Reichen, J; Thomann, S R; Lauterburg, B H; Gerber, N J

    1997-03-01

    The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1-8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at

  4. Liver Function Tests

    MedlinePlus

    ... herbal supplements you are taking. What are normal ranges for liver function tests? Normal ranges for liver function tests can vary by age, ... other factors. Laboratory test results usually provide normal ranges for each liver function test with your results. ...

  5. Liver Function Tests

    MedlinePlus

    ... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

  6. Evaluation of abnormal liver function tests.

    PubMed

    Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

    2016-04-01

    Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID:26842972

  7. [Nuclear medicine for evaluation of liver functions].

    PubMed

    Yamamoto, K

    1994-05-01

    The clinical usefulness of colloid liver scintigraphy to detect space occupying lesions in the liver has been reduced by X-ray CT and ultrasonography. However, scintigraphic examinations have potentials for characteristic diagnosis of liver tumors, such as 99mTc RBC SPECT for hepatic hemangioma, 99mTc PMT for positive imaging of hepatocellular carcinoma and its extrahepatic metastasis, and radioimmunoscintigraphy for metastatic tumors. Moreover, prediction of the prognosis and monitoring therapeutic effect to liver cancer can be made by the use of nuclear medicine techniques. Recently, 99mTc galactosyl serum albumin (GSA), a newly developed radiotracer to evaluate hepatocyte function, has become commercially available. Quantitative parameters of liver functions can be obtained by analysis of time-activity curve in blood and liver after 99mTc-GSA administration. In several cases, 99mTc-GSA study showed intrahepatic unevenness of function, which could not be depicted by other imaging examinations. Positron emission tomography (PET) with 18F-fluoro-2-deoxy glucose (FDG) is useful to detect malignant tumors in the liver. Since PET can provide absolutely quantitative data in better resolution, it is expected that regional true metabolic functions in the liver may be able to be quantitatively evaluated with PET in near future. PMID:8028225

  8. Monitoring of Total and Regional Liver Function after SIRT

    PubMed Central

    Bennink, Roelof J.; Cieslak, Kasia P.; van Delden, Otto M.; van Lienden, Krijn P.; Klümpen, Heinz-Josef; Jansen, Peter L.; van Gulik, Thomas M.

    2014-01-01

    Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications. PMID:24982851

  9. Quantitative Liver Function Tests Improve the Prediction of Clinical Outcomes in Chronic Hepatitis C: Results from the HALT-C Trial

    PubMed Central

    Everson, Gregory T.; Shiffman, Mitchell L.; Hoefs, John C.; Morgan, Timothy R.; Sterling, Richard K.; Wagner, David A.; Lauriski, Shannon; Curto, Teresa M.; Stoddard, Anne; Wright, Elizabeth C.

    2011-01-01

    Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C. We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred twenty seven participants in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (k), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, and perfused hepatic mass (PHM) and liver and spleen volumes (SPECT) were measured. Baseline QLFTs were significantly worse (p=0.0017 to <0.0001) and spleen volumes larger (p<0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95%CI 1.29–3.78) for GEC to 6.52 (95%CI 3.63–11.71) for CA Cloral. QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with “high risk” results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome. Conclusion QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance noninvasive monitoring, counseling, and management of patients with chronic hepatitis C. PMID:22030902

  10. Hepatic (Liver) Function Panel

    MedlinePlus

    ... AST). This enzyme, which plays a role in processing proteins, is found in the liver, heart, muscles, ... doctor. © 1995- The Nemours Foundation. All rights reserved. Images provided by The Nemours Foundation, iStock, Getty Images, ...

  11. Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis

    PubMed Central

    Blomqvist, L; Douglas, L; Nordell, A; Janczewska, I; Näslund, E; Jonas, E

    2013-01-01

    Objective: The aims of this study were to use dynamic hepatocyte-specific contrast-enhanced MRI to evaluate liver volume and function in liver cirrhosis, correlate the results with standard scoring models and explore the inhomogeneous distribution of liver function in cirrhotic livers. Methods: 10 patients with liver cirrhosis and 20 healthy volunteers, serving as controls, were included. Hepatic extraction fraction (HEF), input relative blood flow and mean transit time were calculated on a voxel-by-voxel basis using deconvolutional analysis. Segmental and total liver volumes as well as segmental and total hepatic extraction capacity, expressed in HEFml, were calculated. An incongruence score (IS) was constructed to reflect the uneven distribution of liver function. The Mann–Whitney U-test was used for group comparison of the quantitative liver function parameters, liver volumes and ISs. Correlations between liver function parameters and clinical scores were assessed using Spearman rank correlation. Results: Patients had larger parenchymal liver volume, lower hepatocyte function and more inhomogeneous distribution of function compared with healthy controls. Conclusion: The study demonstrates the non-homogeneous nature of liver cirrhosis and underlines the necessity of a liver function test able to compensate for the heterogeneous distribution of liver function in patients with diseased liver parenchyma. Advances in knowledge: The study describes a new way to quantitatively assess the hepatic uptake of gadoxetate or gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid in the liver as a whole as well as on a segmental level. PMID:23403453

  12. Non-Invasive Assessment of Liver Function

    PubMed Central

    Helmke, Steve; Colmenero, Jordi; Everson, Gregory T.

    2015-01-01

    Purpose of review It is our opinion that there is an unmet need in Hepatology for a minimally- or noninvasive test of liver function and physiology. Quantitative liver function tests (QLFTs) define the severity and prognosis of liver disease by measuring the clearance of substrates whose uptake or metabolism is dependent upon liver perfusion or hepatocyte function. Substrates with high affinity hepatic transporters exhibit high “first-pass” hepatic extraction and their clearance measures hepatic perfusion. In contrast, substrates metabolized by the liver have low first-pass extraction and their clearance measures specific drug metabolizing pathways. Recent Findings We highlight one QLFT, the dual cholate test, and introduce the concept of a disease severity index (DSI) linked to clinical outcome that quantifies the simultaneous processes of hepatocyte uptake, clearance from the systemic circulation, clearance from the portal circulation, and portal-systemic shunting. Summary It is our opinion that dual cholate is a relevant test for defining disease severity, monitoring the natural course of disease progression, and quantifying the response to therapy. PMID:25714706

  13. Electrical and optical spectroscopy for quantitative screening of hepatic steatosis in donor livers

    NASA Astrophysics Data System (ADS)

    McLaughlin, B. L.; Wells, A. C.; Virtue, S.; Vidal-Puig, A.; Wilkinson, T. D.; Watson, C. J. E.; Robertson, P. A.

    2010-11-01

    Macro-steatosis in deceased donor livers is increasingly prevalent and is associated with poor or non-function of the liver upon reperfusion. Current assessment of the extent of steatosis depends upon the macroscopic assessment of the liver by the surgeon and histological examination, if available. In this paper we demonstrate electrical and optical spectroscopy techniques which quantitatively characterize fatty infiltration in liver tissue. Optical spectroscopy showed a correlation coefficient of 0.85 in humans when referenced to clinical hematoxylin and eosin (H&E) sections in 20 human samples. With further development, an optical probe may provide a comprehensive measure of steatosis across the liver at the time of procurement.

  14. [Liver cirrhosis: pulmonary function].

    PubMed

    Marichal, I; Dublet, P; Medrano, G; Hinestrosa, H; Tálamo, C; Korchoff, W; Alvarado, R; Quirós, E

    1991-01-01

    We performed a functional respiratory examination which consisted of arterial gasometry, spirometry, diffusion capacity to CO2, alveolo-arterial gradient of O2 and pulmonary volumes to 8 patients with cirrhosis diagnosed by clinical history, laboratory exams, abdominal ultrasound and histology. Our results showed a slight obstructive pattern of peripheric airways (FMM: 88.87 +/- 8.7%) in the spirometry, no difference in arterial gases at upright and recumbent position was observed, with low values of apO2 (75.51 +/- 1.16 upright and 75.87 +/- 2.16 mmHg recumbent) without statistic significance. The gradient G(Aa) O2 increased to (30.89 +/- 1.06 mmHg). Besides there was a diffusion abnormality with a DLCO2/VA of (71.87 +/- 6.05%). Breathing 100% O2, did not change the gradient which allows us to postulate the existence of an abnormality of gaseous interchange due to shunts. We found no relationship between albumin levels and DLCO2/VO neither with pO2 in upright position; there was a relationship at recumbent position between the hepatic disorder and the arterial desaturation. We concluded that there is no significant hypoxia even with position changes, there is increase of G (Aa) O2 by shunt type disorders and that this is probably related with albumin levels. PMID:1843958

  15. Abnormality on Liver Function Test

    PubMed Central

    2013-01-01

    Children with abnormal liver function can often be seen in outpatient clinics or inpatients wards. Most of them have respiratory disease, or gastroenteritis by virus infection, accompanying fever. Occasionally, hepatitis by the viruses causing systemic infection may occur, and screening tests are required. In patients with jaundice, the tests for differential diagnosis and appropriate treatment are important. In the case of a child with hepatitis B virus infection vertically from a hepatitis B surface antigen positive mother, the importance of the recognition of immune clearance can't be overstressed, for the decision of time to begin treatment. Early diagnosis changes the fate of a child with Wilson disease. So, screening test for the disease should not be omitted. Non-alcoholic fatty liver disease, which is mainly discovered in obese children, is a new strong candidate triggering abnormal liver function. Muscular dystrophy is a representative disease mimicking liver dysfunction. Although muscular dystrophy is a progressive disorder, and early diagnosis can't change the fate of patients, it will be better to avoid parent's blame for delayed diagnosis. PMID:24511518

  16. Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy

    PubMed Central

    Zou, Si-Juan; Chen, Dong; Li, Yan-Zhao; Du, Dun-Feng; Chen, Zhi-Shui; Zhu, Xiao-Hua

    2015-01-01

    Abstract The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients. In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic 99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed. Quantitative 99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters. Quantitative 99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters

  17. Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy.

    PubMed

    Zou, Si-Juan; Chen, Dong; Li, Yan-Zhao; Du, Dun-Feng; Chen, Zhi-Shui; Zhu, Xiao-Hua

    2015-11-01

    The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic Tc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (Tmax), and time for peak activity to decrease by 50% (T1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of Tmax for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative Tc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of Tmax for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, Tmax) were statistically significantly associated with the conventional liver function parameters.Quantitative Tc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and Tmax values obtained from dynamic HBS show good correlation with conventional liver function parameters. PMID:26559297

  18. In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy

    SciTech Connect

    Zhuo, Shuangmu E-mail: hanry-yu@nuhs.edu.sg; Yan, Jie; Kang, Yuzhan; Peng, Qiwen; and others

    2014-07-14

    Various structural features on the liver surface reflect functional changes in the liver. The visualization of these surface features with molecular specificity is of particular relevance to understanding the physiology and diseases of the liver. Using multi-photon microscopy (MPM), we have developed a label-free, three-dimensional quantitative and sensitive method to visualize various structural features of liver surface in living rat. MPM could quantitatively image the microstructural features of liver surface with respect to the sinuosity of collagen fiber, the elastic fiber structure, the ratio between elastin and collagen, collagen content, and the metabolic state of the hepatocytes that are correlative with the pathophysiologically induced changes in the regions of interest. This study highlights the potential of this technique as a useful tool for pathophysiological studies and possible diagnosis of the liver diseases with further development.

  19. In vivo, label-free, three-dimensional quantitative imaging of liver surface using multi-photon microscopy

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Yan, Jie; Kang, Yuzhan; Xu, Shuoyu; Peng, Qiwen; So, Peter T. C.; Yu, Hanry

    2014-07-01

    Various structural features on the liver surface reflect functional changes in the liver. The visualization of these surface features with molecular specificity is of particular relevance to understanding the physiology and diseases of the liver. Using multi-photon microscopy (MPM), we have developed a label-free, three-dimensional quantitative and sensitive method to visualize various structural features of liver surface in living rat. MPM could quantitatively image the microstructural features of liver surface with respect to the sinuosity of collagen fiber, the elastic fiber structure, the ratio between elastin and collagen, collagen content, and the metabolic state of the hepatocytes that are correlative with the pathophysiologically induced changes in the regions of interest. This study highlights the potential of this technique as a useful tool for pathophysiological studies and possible diagnosis of the liver diseases with further development.

  20. Loss of brain function - liver disease

    MedlinePlus

    ... may be made by the body, such as ammonia. Or they may be substances that you take ... MRI EEG Liver function tests Prothrombin time Serum ammonia level Sodium level in the blood Potassium level ...

  1. Shear wave elastography results correlate with liver fibrosis histology and liver function reserve

    PubMed Central

    Feng, Yan-Hong; Hu, Xiang-Dong; Zhai, Lin; Liu, Ji-Bin; Qiu, Lan-Yan; Zu, Yuan; Liang, Si; Gui, Yu; Qian, Lin-Xue

    2016-01-01

    AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures

  2. Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

    NASA Astrophysics Data System (ADS)

    Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

    1997-04-01

    There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

  3. Quantitative ultrasound assessment of thermal damage in excised liver

    NASA Astrophysics Data System (ADS)

    Kemmerer, Jeremy P.; Ghoshal, Goutam; Oelze, Michael L.

    2012-10-01

    Quantitative ultrasound (QUS) is a novel approach for characterizing tissue microstructure and changes in tissue microstructure due to therapy. In this report, we discuss changes in QUS parameters in liver tissues after being exposed to thermal insult. Effective scatterer diameter (ESD) and effective acoustic concentration (EAC) from the normalized backscattered power spectrum were examined in rat liver specimens heated in a degassed saline bath. Individual liver samples were bisected, with half of each sample heated to a therapeutic temperature of 60°C for 10 minutes and the other half held at 37°C. The ultrasonic backscatter and attenuation coefficient were then estimated at 37°C from both halves. ESD was observed to decrease by an average of 34% in exposed compared to unexposed sample sections, EAC increased by 18 dB, and the attenuation coefficient increased by 70%. Histological slides from these samples indicate cell size and/or concentration may be affected by heating. This work was supported by NIH R01-EB008992.

  4. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  5. Quantitative proteomic survey of endoplasmic reticulum in mouse liver.

    PubMed

    Song, Yanping; Jiang, Ying; Ying, Wantao; Gong, Yan; Yan, Yujuan; Yang, Dong; Ma, Jie; Xue, Xiaofang; Zhong, Fan; Wu, Songfeng; Hao, Yunwei; Sun, Aihua; Li, Tao; Sun, Wei; Wei, Handong; Zhu, Yunping; Qian, Xiaohong; He, Fuchu

    2010-03-01

    To gain a better understanding of the critical function of the endoplasmic reticulum (ER) in liver, we carried out a proteomic survey of mouse liver ER. The ER proteome was profiled with a new three-dimensional, gel-based strategy. From 6152 and 6935 MS spectra, 903 and 1042 proteins were identified with at least two peptides matches at 95% confidence in the rough (r) and smooth (s) ER, respectively. Comparison of the rER and sER proteomes showed that calcium-binding proteins are significantly enriched in the sER suggesting that the ion-binding function of the ER is compartmentalized. Comparison of the rat and mouse ER proteomes showed that 662 proteins were common to both, comprising 53.5% and 49.3% of those proteomes, respectively. We proposed that these proteins were stably expressed proteins that were essential for the maintenance of ER function. GO annotation with a hypergeometric model proved this hypothesis. Unexpectedly, 210 unknown proteins and some proteins previously reported to occur in the cytosol were highly enriched in the ER. This study provides a reference map for the ER proteome of liver. Identification of new ER proteins will enhance our current understanding of the ER and also suggest new functions for this organelle. PMID:20073521

  6. Quantitative aspects of chemical carcinogenesis and tumor promotion in liver.

    PubMed Central

    Kunz, H W; Tennekes, H A; Port, R E; Schwartz, M; Lorke, D; Schaude, G

    1983-01-01

    Chronic exposure of rodents to high dose levels of drugs, food additives and environmental chemicals frequently results in liver enlargement. Several of these compounds have been found to enhance the incidence of liver tumors in animals briefly exposed previously to hepatocarcinogens. Accordingly, it has been advanced that these agents act as tumor promoters. This contention has remained subject of controversy following reports that these substances may also cause liver tumors in noncarcinogen-treated rodents, particularly in those characterized by a relatively high incidence of "spontaneous" liver tumors. Since many of these chemicals are in common use, a crucial question would seem to be whether such effects are due to facilitation of the expression of pre-existing oncogenic potential, i.e., to tumor promotion, or to the synergistic action of weakly carcinogenic agents. As a result of mechanistic differences tumor promotion and syn-carcinogenesis must exhibit different dose-time-response characteristics, and, accordingly, it should be possible, in principle, to discriminate between these phenomena. However, since tumor manifestation periods in low-dose groups frequently exceed the animals average lifespan, this approach may not always yield conclusive data, unless a sensitive early marker of carcinogenic activity can be employed. There is evidence that enzyme-deficient preneoplastic areas in liver can be used for this purpose. A strong quantitative correlation between carcinogen dose, the extent of ATPase deficient areas, and the subsequent appearance of tumors has now been established for a number of hepatocarcinogens. Experimental data are consistent with the concept that two critical events (hits) are required for induction of ATPase deficiency in hepatocytes. The first hit is carcinogen-dependent, whereas the second hit would seem to be due to time-dependent event(s). Tumor-promoters, such as phenobarbital, were found to accelerate and increase formation of

  7. Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

    PubMed

    Badawi, A M; Derbala, A S; Youssef, A M

    1999-08-01

    Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history

  8. Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI

    PubMed Central

    Nilsson, Henrik; Blomqvist, Lennart; Douglas, Lena; Nordell, Anders; Jonas, Eduard

    2010-01-01

    Objectives Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified. Methods Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (Cmax, Tmax and T1/2), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM). Results Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child–Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child–Pugh scores. Conclusions Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels. PMID:20887325

  9. A novel RNA oligonucleotide improves liver function and inhibits liver carcinogenesis in vivo

    PubMed Central

    Reebye, V.; Sætrom, P.; Mintz, P.J.; Huang, K.W.; Swiderski, P.; Peng, L.; Liu, C.; Liu, X.X.; Jensen, S.; Zacharoulis, D.; Kostomitsopoulos, N.; Kasahara, N.; Nicholls, J.P.; Jiao, L.R.; Pai, M.; Mizandari, M.; Chikovani, T.; Emara, M.M.; Haoudi, A.; Tomalia, D.A.; Rossi, J.J.; Habib, N.A.; Spalding, D.R.

    2015-01-01

    Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here, we show an innovative RNA-based targeted approach to enhance endogenous albumin production whilst reducing liver tumour burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBPα (CCAAT/enhancer-binding protein-α), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBPα and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBPα-saRNA transfected HepG2 cells. Intravenous injection of C/EBPα-saRNA in a cirrhotic rat model with multifocal liver tumours increased circulating serum albumin by over 30% showing evidence of improved liver function. Tumour burden decreased by 80% (p = 0.003) with a 40% reduction in a marker of pre-neoplastic transformation. Since C/EBPα has known anti-proliferative activities via retinoblastoma, p21 and cyclins; we used mRNA expression liver cancer specific microarray in C/EBPα-saRNA transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis and metastasis. Up-regulated genes were enriched for tumour suppressors and positive regulators of cell differentiation. A quantitative PCR and Western-blot analysis of C/EBPα-saRNA transfected cells suggested that in addition to the known anti-proliferative targets of C/EBPα, we also observed suppression of IL6R, c-Myc and reduced STAT3 phosphorylation. Conclusion We demonstrate for the first time that a novel injectable saRNA-oligonucleotide that enhances C/EBPα expression successfully reduces tumour burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model. PMID:23929703

  10. Immunological functions of liver sinusoidal endothelial cells.

    PubMed

    Knolle, Percy A; Wohlleber, Dirk

    2016-05-01

    Liver sinusoidal endothelial cells (LSECs) line the liver sinusoids and separate passenger leukocytes in the sinusoidal lumen from hepatocytes. LSECs further act as a platform for adhesion of various liver-resident immune cell populations such as Kupffer cells, innate lymphoid cells or liver dendritic cells. In addition to having an extraordinary scavenger function, LSECs possess potent immune functions, serving as sentinel cells to detect microbial infection through pattern recognition receptor activation and as antigen (cross)-presenting cells. LSECs cross-prime naive CD8 T cells, causing their rapid differentiation into memory T cells that relocate to secondary lymphoid tissues and provide protection when they re-encounter the antigen during microbial infection. Cross-presentation of viral antigens by LSECs derived from infected hepatocytes triggers local activation of effector CD8 T cells and thereby assures hepatic immune surveillance. The immune function of LSECs complements conventional immune-activating mechanisms to accommodate optimal immune surveillance against infectious microorganisms while preserving the integrity of the liver as a metabolic organ. PMID:27041636

  11. The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function

    PubMed Central

    Nilsson, Henrik; Karlgren, Silja; Blomqvist, Lennart; Jonas, Eduard

    2015-01-01

    Background Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. Methods In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. Results Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median −3.5% (−9.3–3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (−0.7–2.5%)]. Discussion The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved. PMID:25297934

  12. A comparative analysis of liver transcriptome suggests divergent liver function among human, mouse and rat.

    PubMed

    Yu, Yao; Ping, Jie; Chen, Hui; Jiao, Longxian; Zheng, Siyuan; Han, Ze-Guang; Hao, Pei; Huang, Jian

    2010-11-01

    The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function, we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. Our results show that 17396 genes are expressed in the human liver. 238 genes were identified as liver enrichment genes, involved in the functions of immune response and metabolic processes, from the MPSS and EST datasets. A comparative analysis of liver transcriptomes was performed in humans, mice and rats with microarray datasets shows that the expression profile of homologous genes remains significantly different between mouse/rat and human, suggesting a functional variance and regulation bias of genes expressed in the livers. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease. PMID:20800674

  13. Circadian Clock Control of Liver Metabolic Functions.

    PubMed

    Reinke, Hans; Asher, Gad

    2016-03-01

    The circadian clock is an endogenous biological timekeeping system that synchronizes physiology and behavior to day/night cycles. A wide variety of processes throughout the entire gastrointestinal tract and notably the liver appear to be under circadian control. These include various metabolic functions such as nutrient uptake, processing, and detoxification, which align organ function to cycle with nutrient supply and demand. Remarkably, genetic or environmental disruption of the circadian clock can cause metabolic diseases or exacerbate pathological states. In addition, modern lifestyles force more and more people worldwide into asynchrony between the external time and their circadian clock, resulting in a constant state of social jetlag. Recent evidence indicates that interactions between altered energy metabolism and disruptions in the circadian clock create a downward spiral that can lead to diabetes and other metabolic diseases. In this review, we provide an overview of rhythmic processes in the liver and highlight the functions of circadian clock genes under physiological and pathological conditions; we focus on their roles in regulation of hepatic glucose as well as lipid and bile acid metabolism and detoxification and their potential effects on the development of fatty liver and nonalcoholic steatohepatitis. PMID:26657326

  14. Loss of brain function - liver disease

    MedlinePlus

    ... of chronic liver damage. Common causes of chronic liver disease in the United States are: Chronic hepatitis B ... hepatitis Bile duct disorders Some medicines Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) Once you have ...

  15. Systems proteomics of liver mitochondria function.

    PubMed

    Williams, Evan G; Wu, Yibo; Jha, Pooja; Dubuis, Sébastien; Blattmann, Peter; Argmann, Carmen A; Houten, Sander M; Amariuta, Tiffany; Wolski, Witold; Zamboni, Nicola; Aebersold, Ruedi; Auwerx, Johan

    2016-06-10

    Recent improvements in quantitative proteomics approaches, including Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS), permit reproducible large-scale protein measurements across diverse cohorts. Together with genomics, transcriptomics, and other technologies, transomic data sets can be generated that permit detailed analyses across broad molecular interaction networks. Here, we examine mitochondrial links to liver metabolism through the genome, transcriptome, proteome, and metabolome of 386 individuals in the BXD mouse reference population. Several links were validated between genetic variants toward transcripts, proteins, metabolites, and phenotypes. Among these, sequence variants in Cox7a2l alter its protein's activity, which in turn leads to downstream differences in mitochondrial supercomplex formation. This data set demonstrates that the proteome can now be quantified comprehensively, serving as a key complement to transcriptomics, genomics, and metabolomics--a combination moving us forward in complex trait analysis. PMID:27284200

  16. Astaxanthin as a Potential Protector of Liver Function: A Review

    PubMed Central

    Chen, Jui-Tung; Kotani, Kazuhiko

    2016-01-01

    Protecting against liver damage, such as non-alcoholic fatty liver disease, is currently considered to be important for the prevention of adverse conditions, such as cardiovascular and cancerous diseases. Liver damage often occurs in relation to oxidative stress with metabolic disorders, including cellular lipid accumulation. Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′dione), a xanthophyll carotenoid, is a candidate for liver protection. Here, we briefly review astaxanthin as a potential protector against liver damage. In particular, studies have reported antioxidative effects of astaxanthin in liver tissues. Astaxanthin treatment is also reported to improve hyperlipidemia, which indirectly induces the antioxidative effects of astaxanthin on liver pathologies. Furthermore, astaxanthin may alleviate liver damage independent of its antioxidative effects. Of note, there are still insufficient human data to observe the effect of astaxanthin treatment on liver function in clinical conditions. More studies investigating the relevance of astaxanthin on liver protection are necessary.

  17. Integrative Quantitative Proteomics Unveils Proteostasis Imbalance in Human Hepatocellular Carcinoma Developed on Nonfibrotic Livers*

    PubMed Central

    Negroni, Luc; Taouji, Said; Arma, Daniela; Pallares-Lupon, Nestor; Leong, Kristen; Beausang, Lee Anne; Latterich, Martin; Bossé, Roger; Balabaud, Charles; Schmitter, Jean-Marie; Bioulac-Sage, Paulette; Zucman-Rossi, Jessica; Rosenbaum, Jean; Chevet, Eric

    2014-01-01

    Proteomics-based clinical studies represent promising resources for the discovery of novel biomarkers or for unraveling molecular mechanisms underlying particular diseases. Here, we present a discovery study of hepatocellular carcinoma developed on nonfibrotic liver (nfHCC) that combines complementary quantitative iTRAQ-based proteomics and phosphoproteomics approaches. Using both approaches, we compared a set of 24 samples (18 nfHCC versus six nontumor liver tissue). We identified 43 proteins (67 peptides) differentially expressed and 32 peptides differentially phosphorylated between the experimental groups. The functional analysis of the two data sets pointed toward the deregulation of a protein homeostasis (proteostasis) network including the up-regulation of the Endoplasmic Reticulum (ER) resident HSPA5, HSP90B1, PDIA6, and P4HB and of the cytosolic HSPA1B, HSP90AA1, HSPA9, UBC, CNDP2, TXN, and VCP as well as the increased phosphorylation of the ER resident calnexin at Ser583. Antibody-based validation approaches (immunohistochemistry, immunoblot, Alphascreen®, and AMMP®) on independent nfHCC tumor sets (up to 77 samples) confirmed these observations, thereby indicating a common mechanism occurring in nfHCC tumors. Based on these results we propose that adaptation to proteostasis imbalance in nfHCC tumors might confer selective advantages to those tumors. As such, this model could provide an additional therapeutic opportunity for those tumors arising on normal liver by targeting the tumor proteostasis network. Data are available via ProteomeXchange with identifier PXD001253. PMID:25225353

  18. Photoacoustic molecular imaging for in vivo liver iron quantitation

    NASA Astrophysics Data System (ADS)

    Maccarinelli, Federica; Carmona, Fernando; Regoni, Maria; Arosio, Paolo

    2016-05-01

    A recent study showed that ferritin is a suitable endogenous contrast agent for photoacoustic molecular imaging in cultured mammalian cells. We have therefore tested whether this imaging technique can be used for in vivo quantification of iron in mouse livers. To verify this hypothesis, we used multispectral optoacoustic tomography (MSOT) to image albino CD1 mice before and after experimental iron loading. Postmortem assays showed that the iron treatment caused a 15-fold increase in liver iron and a 40-fold increase in liver ferritin levels, while in vivo longitudinal analysis using MSOT revealed just a 1.6-fold increase in the ferritin/iron photoacoustic signal in the same animals. We conclude that MSOT can monitor changes in ferritin/iron levels in vivo, but its sensitivity is much lower than that of ex vivo iron assays.

  19. Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

    PubMed Central

    De Gasperi, Andrea; Mazza, Ernestina; Prosperi, Manlio

    2016-01-01

    Indocyanine green (ICG) kinetics (PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors (pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests. PMID:26981173

  20. Quantitative analysis of real-time tissue elastography for evaluation of liver fibrosis

    PubMed Central

    Shi, Ying; Wang, Xing-Hua; Zhang, Huan-Hu; Zhang, Hai-Qing; Tu, Ji-Zheng; Wei, Kun; Li, Juan; Liu, Xiao-Li

    2014-01-01

    The present study aimed to investigate the feasibility of quantitative analysis of liver fibrosis using real-time tissue elastography (RTE) and its pathological and molecule biological basis. Methods: Fifty-four New Zealand rabbits were subcutaneously injected with thioacetamide (TAA) to induce liver fibrosis as the model group, and another eight New Zealand rabbits served as the normal control group. Four rabbits were randomly taken every two weeks for real-time tissue elastography (RTE) and quantitative analysis of tissue diffusion. The obtained twelve characteristic quantities included relative mean value (MEAN), standard deviation (SD), blue area % (% AREA), complexity (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT), entropy (ENT), inverse different moment (IDM), angular secon moment (ASM), correlation (CORR) and liver fibrosis index (LF Index). Rabbits were executed and liver tissues were taken for pathological staging of liver fibrosis (grouped by pathological stage into S0 group, S1 group, S2 group, S3 group and S4 group). In addition, the collagen I (Col I) and collagen III (Col III) expression levels in liver tissue were detected by Western blot. Results: Except for KURT, there were significant differences among the other eleven characteristic quantities (P < 0.05). LF Index, Col I and Col III expression levels showed a rising trend with increased pathological staging of liver fibrosis, presenting a positive correlation with the pathological staging of liver fibrosis (r = 0.718, r = 0.693, r = 0.611, P < 0.05). Conclusion: RTE quantitative analysis is expected for noninvasive evaluation of the pathological staging of liver fibrosis. PMID:24955175

  1. Comprehensive and quantitative analysis of lysophospholipid molecular species present in obese mouse liver by shotgun lipidomics

    PubMed Central

    Wang, Chunyan; Wang, Miao; Han, Xianlin

    2015-01-01

    Shotgun lipidomics exploits the unique chemical and physical properties of lipid classes and individual molecular species to facilitate the high-throughput analysis of a cellular lipidome on a large scale directly from the extracts of biological samples. A platform for comprehensive analysis of lysophospholipid (LPL) species based on shotgun lipidomics has not been established. Herein, after extensive characterization of the fragmentation pattern of individual LPL class and optimization of all experimental conditions including developing new methods for optimization of collision energy, and recovery and enrichment of LPL classes from the aqueous phase after solvent extraction, a new method for comprehensive and quantitative analysis of LPL species was developed. This newly developed method was applied for comprehensive analysis of LPL species present in mouse liver samples. Remarkably, the study revealed significant accumulation of LPL species in the liver of ob/ob mice. Taken together, by exploiting the principles of shotgun lipidomics in combination with a novel strategy of sample preparation, LPL species present in biological samples can be determined by the established method. We believe that this development is significant and useful for understanding the pathways of phospholipid metabolism and for elucidating the role of LPL species in signal transduction and other biological functions. PMID:25860968

  2. [Function of zinc in liver disease].

    PubMed

    Katayama, Kazuhiro

    2016-07-01

    Zinc deficiency is highly prevalent in cirrhotic patients, and contributes to several clinical symptoms such as hepatic encephalopathy and liver fibrosis. Ammonia is detoxified in liver to urea through urea cycle, and is also detoxified in extrahepatic tissue to glutamine through glutamine synthetase. The reduced ability of ammonia detoxification in liver cirrhosis is ascribed to zinc deficiency, because a member of urea cycle, ornithine transcarbamylase is a zinc enzyme. In this condition, glutamine synthesis is enhanced, which enables the body, at least temporarily, to suppress the increase of ammonia. However, the glutamine is metabolized predominantly in enterocyte to ammomia and glutamate, indicating that a vicious cycle in glutamine synthesis and glutamine breakdown occurs in liver cirrhosis. Attention should be given to the clinical significance of zinc in liver diseases. PMID:27455801

  3. Quantitative proteomics analysis of the liver reveals immune regulation and lipid metabolism dysregulation in a mouse model of depression.

    PubMed

    Wu, You; Tang, Jianyong; Zhou, Chanjuan; Zhao, Libo; Chen, Jin; Zeng, Li; Rao, Chenglong; Shi, Haiyang; Liao, Li; Liang, Zihong; Yang, Yongtao; Zhou, Jian; Xie, Peng

    2016-09-15

    Major depressive disorder (MDD) is a highly prevalent and debilitating mental illness with substantial impairments in quality of life and functioning. However, the pathophysiology of major depression remains poorly understood. Combining the brain and body should provide a comprehensive understanding of the etiology of MDD. As the largest internal organ of the human body, the liver has an important function, yet no proteomic study has assessed liver protein expression in a preclinical model of depression. Using the chronic unpredictable mild stress (CUMS) mouse model of depression, differential protein expression between CUMS and control (CON) mice was examined in the liver proteome using isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry. More than 4000 proteins were identified and 66 most significantly differentiated proteins were used for further bioinformatic analysis. According to the ingenuity pathway analysis (IPA), we found that proteins related to the inflammation response, immune regulation, lipid metabolism and NFκB signaling network were altered by CUMS. Moreover, four proteins closely associated with these processes, hemopexin, haptoglobin, cytochrome P450 2A4 (CYP2A4) and bile salt sulfotransferase 1 (SULT2A1), were validated by western blotting. In conclusion, we report, for the first time, the liver protein expression profile in the CUMS mouse model of depression. Our findings provide novel insight (liver-brain axis) into the multifaceted mechanisms of major depressive disorder. PMID:27247144

  4. Quantitative evaluation of noise reduction and vesselness filters for liver vessel segmentation on abdominal CTA images

    NASA Astrophysics Data System (ADS)

    Luu, Ha Manh; Klink, Camiel; Moelker, Adriaan; Niessen, Wiro; van Walsum, Theo

    2015-05-01

    Liver vessel segmentation in CTA images is a challenging task, especially in the case of noisy images. This paper investigates whether pre-filtering improves liver vessel segmentation in 3D CTA images. We introduce a quantitative evaluation of several well-known filters based on a proposed liver vessel segmentation method on CTA images. We compare the effect of different diffusion techniques i.e. Regularized Perona-Malik, Hybrid Diffusion with Continuous Switch and Vessel Enhancing Diffusion as well as the vesselness approaches proposed by Sato, Frangi and Erdt. Liver vessel segmentation of the pre-processed images is performed using a histogram-based region grown with local maxima as seed points. Quantitative measurements (sensitivity, specificity and accuracy) are determined based on manual landmarks inside and outside the vessels, followed by T-tests for statistic comparisons on 51 clinical CTA images. The evaluation demonstrates that all the filters make liver vessel segmentation have a significantly higher accuracy than without using a filter (p  <  0.05) Hybrid Diffusion with Continuous Switch achieves the best performance. Compared to the diffusion filters, vesselness filters have a greater sensitivity but less specificity. In addition, the proposed liver vessel segmentation method with pre-filtering is shown to perform robustly on a clinical dataset having a low contrast-to-noise of up to 3 (dB). The results indicate that the pre-filtering step significantly improves liver vessel segmentation on 3D CTA images.

  5. Quantitative Liver-Specific Protein Fingerprint in Blood: A Signature for Hepatotoxicity

    PubMed Central

    Hu, Zhiyuan; Lausted, Christopher; Yoo, Hyuntae; Yan, Xiaowei; Brightman, Amy; Chen, Jiankui; Wang, Weizhi; Bu, Xiangli; Hood, Leroy

    2014-01-01

    We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane-bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks. PMID:24465277

  6. FT-IR imaging for quantitative determination of liver fat content in non-alcoholic fatty liver.

    PubMed

    Kochan, K; Maslak, E; Chlopicki, S; Baranska, M

    2015-08-01

    In this work we apply FT-IR imaging of large areas of liver tissue cross-section samples (∼5 cm × 5 cm) for quantitative assessment of steatosis in murine model of Non-Alcoholic Fatty Liver (NAFLD). We quantified the area of liver tissue occupied by lipid droplets (LDs) by FT-IR imaging and Oil Red O (ORO) staining for comparison. Two alternative FT-IR based approaches are presented. The first, straightforward method, was based on average spectra from tissues and provided values of the fat content by using a PLS regression model and the reference method. The second one – the chemometric-based method – enabled us to determine the values of the fat content, independently of the reference method by means of k-means cluster (KMC) analysis. In summary, FT-IR images of large size liver sections may prove to be useful for quantifying liver steatosis without the need of tissue staining. PMID:26051164

  7. Rapid Quantitative Determination of Squalene in Shark Liver Oils by Raman and IR Spectroscopy.

    PubMed

    Hall, David W; Marshall, Susan N; Gordon, Keith C; Killeen, Daniel P

    2016-01-01

    Squalene is sourced predominantly from shark liver oils and to a lesser extent from plants such as olives. It is used for the production of surfactants, dyes, sunscreen, and cosmetics. The economic value of shark liver oil is directly related to the squalene content, which in turn is highly variable and species-dependent. Presented here is a validated gas chromatography-mass spectrometry analysis method for the quantitation of squalene in shark liver oils, with an accuracy of 99.0 %, precision of 0.23 % (standard deviation), and linearity of >0.999. The method has been used to measure the squalene concentration of 16 commercial shark liver oils. These reference squalene concentrations were related to infrared (IR) and Raman spectra of the same oils using partial least squares regression. The resultant models were suitable for the rapid quantitation of squalene in shark liver oils, with cross-validation r (2) values of >0.98 and root mean square errors of validation of ≤4.3 % w/w. Independent test set validation of these models found mean absolute deviations of the 4.9 and 1.0 % w/w for the IR and Raman models, respectively. Both techniques were more accurate than results obtained by an industrial refractive index analysis method, which is used for rapid, cheap quantitation of squalene in shark liver oils. In particular, the Raman partial least squares regression was suited to quantitative squalene analysis. The intense and highly characteristic Raman bands of squalene made quantitative analysis possible irrespective of the lipid matrix. PMID:26620374

  8. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    PubMed Central

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  9. Quantitative characterization of fatty liver disease using x-ray scattering

    NASA Astrophysics Data System (ADS)

    Elsharkawy, Wafaa B.; Elshemey, Wael M.

    2013-11-01

    Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

  10. Mesenchymal Stem Cell-Derived Hepatocytes for Functional Liver Replacement

    PubMed Central

    Christ, Bruno; Stock, Peggy

    2012-01-01

    Mesenchymal stem cells represent an alternate cell source to substitute for primary hepatocytes in hepatocyte transplantation because of their multiple differentiation potential and nearly unlimited availability. They may differentiate into hepatocyte-like cells in vitro and maintain specific hepatocyte functions also after transplantation into the regenerating livers of mice or rats both under injury and non-injury conditions. Depending on the underlying liver disease their mode of action is either to replace the diseased liver tissue or to support liver regeneration through their anti-inflammatory and anti-apoptotic as well as their pro-proliferative action. PMID:22737154

  11. Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver

    PubMed Central

    Sabidó, Eduard; Bosch, Elena

    2016-01-01

    Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients. PMID:26582562

  12. Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver.

    PubMed

    Engelken, Johannes; Espadas, Guadalupe; Mancuso, Francesco M; Bonet, Nuria; Scherr, Anna-Lena; Jímenez-Álvarez, Victoria; Codina-Solà, Marta; Medina-Stacey, Daniel; Spataro, Nino; Stoneking, Mark; Calafell, Francesc; Sabidó, Eduard; Bosch, Elena

    2016-03-01

    Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients. PMID:26582562

  13. Optimizing global liver function in radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Wu, Victor W.; Epelman, Marina A.; Wang, Hesheng; Romeijn, H. Edwin; Feng, Mary; Cao, Yue; Ten Haken, Randall K.; Matuszak, Martha M.

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose (\\ell \\text{EUD} ) (conventional ‘\\ell \\text{EUD} model’), the so-called perfusion-weighted \\ell \\text{EUD} (\\text{fEUD} ) (proposed ‘fEUD model’), and post-treatment global liver function (GLF) (proposed ‘GLF model’), predicted by a new liver-perfusion-based dose-response model. The resulting \\ell \\text{EUD} , fEUD, and GLF plans delivering the same target \\ell \\text{EUD} are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to 4.6 % ≤ft(7.5 % \\right) more liver function than the fEUD (\\ell \\text{EUD} ) plan does in 2D cases, and up to 4.5 % ≤ft(5.6 % \\right) in 3D cases. The GLF and fEUD plans worsen in \\ell \\text{EUD} of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and

  14. Optimizing global liver function in radiation therapy treatment planning.

    PubMed

    Wu, Victor W; Epelman, Marina A; Wang, Hesheng; Edwin Romeijn, H; Feng, Mary; Cao, Yue; Ten Haken, Randall K; Matuszak, Martha M

    2016-09-01

    Liver stereotactic body radiation therapy (SBRT) patients differ in both pre-treatment liver function (e.g. due to degree of cirrhosis and/or prior treatment) and radiosensitivity, leading to high variability in potential liver toxicity with similar doses. This work investigates three treatment planning optimization models that minimize risk of toxicity: two consider both voxel-based pre-treatment liver function and local-function-based radiosensitivity with dose; one considers only dose. Each model optimizes different objective functions (varying in complexity of capturing the influence of dose on liver function) subject to the same dose constraints and are tested on 2D synthesized and 3D clinical cases. The normal-liver-based objective functions are the linearized equivalent uniform dose ([Formula: see text]) (conventional '[Formula: see text] model'), the so-called perfusion-weighted [Formula: see text] ([Formula: see text]) (proposed 'fEUD model'), and post-treatment global liver function (GLF) (proposed 'GLF model'), predicted by a new liver-perfusion-based dose-response model. The resulting [Formula: see text], fEUD, and GLF plans delivering the same target [Formula: see text] are compared with respect to their post-treatment function and various dose-based metrics. Voxel-based portal venous liver perfusion, used as a measure of local function, is computed using DCE-MRI. In cases used in our experiments, the GLF plan preserves up to [Formula: see text] more liver function than the fEUD ([Formula: see text]) plan does in 2D cases, and up to [Formula: see text] in 3D cases. The GLF and fEUD plans worsen in [Formula: see text] of functional liver on average by 1.0 Gy and 0.5 Gy in 2D and 3D cases, respectively. Liver perfusion information can be used during treatment planning to minimize the risk of toxicity by improving expected GLF; the degree of benefit varies with perfusion pattern. Although fEUD model optimization is computationally inexpensive and often

  15. The Proteome of Human Liver Peroxisomes: Identification of Five New Peroxisomal Constituents by a Label-Free Quantitative Proteomics Survey

    PubMed Central

    Ofman, Rob; Bunse, Christian; Pawlas, Magdalena; Hayen, Heiko; Eisenacher, Martin; Stephan, Christian; Meyer, Helmut E.; Waterham, Hans R.; Erdmann, Ralf; Wanders, Ronald J.; Warscheid, Bettina

    2013-01-01

    The peroxisome is a key organelle of low abundance that fulfils various functions essential for human cell metabolism. Severe genetic diseases in humans are caused by defects in peroxisome biogenesis or deficiencies in the function of single peroxisomal proteins. To improve our knowledge of this important cellular structure, we studied for the first time human liver peroxisomes by quantitative proteomics. Peroxisomes were isolated by differential and Nycodenz density gradient centrifugation. A label-free quantitative study of 314 proteins across the density gradient was accomplished using high resolution mass spectrometry. By pairing statistical data evaluation, cDNA cloning and in vivo colocalization studies, we report the association of five new proteins with human liver peroxisomes. Among these, isochorismatase domain containing 1 protein points to the existence of a new metabolic pathway and hydroxysteroid dehydrogenase like 2 protein is likely involved in the transport or β-oxidation of fatty acids in human peroxisomes. The detection of alcohol dehydrogenase 1A suggests the presence of an alternative alcohol-oxidizing system in hepatic peroxisomes. In addition, lactate dehydrogenase A and malate dehydrogenase 1 partially associate with human liver peroxisomes and enzyme activity profiles support the idea that NAD+ becomes regenerated during fatty acid β-oxidation by alternative shuttling processes in human peroxisomes involving lactate dehydrogenase and/or malate dehydrogenase. Taken together, our data represent a valuable resource for future studies of peroxisome biochemistry that will advance research of human peroxisomes in health and disease. PMID:23460848

  16. Assessment of Liver Function Using 99mTc-Mebrofenin Hepatobiliary Scintigraphy in ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy)

    PubMed Central

    Cieslak, Kasia P.; Olthof, Pim B.; van Lienden, Krijn P.; Besselink, Marc G.; Busch, Olivier R.C.; van Gulik, Thomas M.; Bennink, Roelof J.

    2015-01-01

    ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) is a new surgical technique for patients in whom conventional treatment is not feasible due to insufficient future remnant liver (FRL). During the first stage of ALPPS, accelerated hypertrophy of the FRL is induced by ligation of the portal vein and in situ split of the liver. In the second stage, the deportalized liver is removed when the FRL volume has reached ≥25% of total liver volume. However, FRL volume does not necessarily reflect FRL function. 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) with SPECT-CT is a quantitative test enabling regional assessment of parenchymal uptake function using a validated cut-off value for the prediction of postoperative liver failure (2.7%/min/m2). This paper describes the changes in FRL function and FRL volume in a 79-year-old patient diagnosed with metachronous colonic liver metastases who underwent ALPPS. We have observed a substantial difference between the increase in FRL volume and FRL function suggesting that HBS with SPECT-CT enables monitoring of the FRL function and could be a useful tool in the timing of resection in the second stage of the ALPPS procedure. PMID:26675783

  17. Correlation analysis between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis

    PubMed Central

    TANG, NING; ZHANG, YAPING; LIU, ZEYU; FU, TAO; LIANG, QINGHONG; AI, XUEMEI

    2016-01-01

    The aim of the present study was to investigate the correlation between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis. A total of 30 infants with cholestasis and 20 healthy infants were included in the study. Biochemical assays based on the initial rate method and colorimetric assays were conducted to determine the levels of liver function markers in the serum [such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), γ-glutamyl transferase (γ-GT), cholinesterase (CHE) and total bile acids (TBA)] and four serum biomarkers of liver fibrosis were measured using radioimmunoassays [hyaluronic acid (HA), procollagen type III (PCIII), laminin (LN) and collagen type IV (cIV)]. The serum levels of ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01); the serum levels of CHE in the infants with cholestasis were significantly lower compared to the healthy infants (P<0.01). The serum levels of HA, PCIII, and cIV in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01). Correlation analyses between liver function and the four biomarkers of liver fibrosis showed that HA was positively correlated with AST and γ-GT (P<0.05) and negatively correlated with ALT, CHE and TBA (P<0.05). cIV was positively correlated with γ-GT (P<0.05) and negatively correlated with CHE (P<0.05). In conclusion, statistically significant differences were identified for the liver function markers (ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA) and the biomarkers HA, PCIII and cIV of liver fibrosis between infants with cholestasis and healthy infants. Thus, the serum levels of HA, cIV, γ-GT and CHE are sensitive markers for cholestatic liver fibrosis in infants. PMID:27347413

  18. Function of GATA Factors in the Adult Mouse Liver

    PubMed Central

    Zheng, Rena; Rebolledo-Jaramillo, Boris; Zong, Yiwei; Wang, Liqing; Russo, Pierre; Hancock, Wayne; Stanger, Ben Z.; Hardison, Ross C.; Blobel, Gerd A.

    2013-01-01

    GATA transcription factors and their Friend of Gata (FOG) cofactors control the development of diverse tissues. GATA4 and GATA6 are essential for the expansion of the embryonic liver bud, but their expression patterns and functions in the adult liver are unclear. We characterized the expression of GATA and FOG factors in whole mouse liver and purified hepatocytes. GATA4, GATA6, and FOG1 are the most prominently expressed family members in whole liver and hepatocytes. GATA4 chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) identified 4409 occupied sites, associated with genes enriched in ontologies related to liver function, including lipid and glucose metabolism. However, hepatocyte-specific excision of Gata4 had little impact on gross liver architecture and function, even under conditions of regenerative stress, and, despite the large number of GATA4 occupied genes, resulted in relatively few changes in gene expression. To address possible redundancy between GATA4 and GATA6, both factors were conditionally excised. Surprisingly, combined Gata4,6 loss did not exacerbate the phenotype resulting from Gata4 loss alone. This points to the presence of an unusually robust transcriptional network in adult hepatocytes that ensures the maintenance of liver function. PMID:24367609

  19. Hepatic encephalopathy: effects of liver failure on brain function.

    PubMed

    Felipo, Vicente

    2013-12-01

    Liver failure affects brain function, leading to neurological and psychiatric alterations; such alterations are referred to as hepatic encephalopathy (HE). Early diagnosis of minimal HE reveals an unexpectedly high incidence of mild cognitive impairment and psychomotor slowing in patients with liver cirrhosis - conditions that have serious health, social and economic consequences. The mechanisms responsible for the neurological alterations in HE are beginning to emerge. New therapeutic strategies acting on specific targets in the brain (phosphodiesterase 5, type A GABA receptors, cyclooxygenase and mitogen-activated protein kinase p38) have been shown to restore cognitive and motor function in animal models of chronic HE, and NMDA receptor antagonists have been shown to increase survival in acute liver failure. This article reviews the latest studies aimed at understanding how liver failure affects brain function and potential ways to ameliorate these effects. PMID:24149188

  20. Liver morphology and function in visceral leishmaniasis (Kala-azar).

    PubMed Central

    el Hag, I A; Hashim, F A; el Toum, I A; Homeida, M; el Kalifa, M; el Hassan, A M

    1994-01-01

    AIM--To study the morphology and function of the liver in visceral leishmaniasis (Kala-azar). METHODS--Percutaneous liver biopsy specimens from 18 patients with confirmed visceral leishmaniasis were examined under light and electron microscopy before and after treatment with pentovalent antimony. The tissue was also examined for hepatitis B surface and core antigens using immunoperoxidase staining. Liver function was investigated in nine patients before and after treatment. RESULTS--Specimens before treatment showed Kupffer cells and macrophages colonised by leishmania parasites in 40% of cases. A chronic mononuclear cell infiltrate had affected the portal tracts and lobules. Ballooning degeneration of the hepatocytes, fibrosis of the terminal hepatic venules, and pericellular fibrosis were common findings. The fibrosis was related to Ito cells transforming to fibroblast-like cells. None of the patients had hepatitis B infection. All patients had biochemical evidence of liver dysfunction before treatment. Liver function improved after treatment. CONCLUSION--Visceral leishmaniasis causes morphological and functional disturbance in the liver. Focal fibrosis rather than cirrhosis occurs. The exact aetiology of hepatic damage is unclear but may have an immunological basis. Images PMID:8063939

  1. Functions of autophagy in normal and diseased liver

    PubMed Central

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  2. Quantitative Estimation of the Amount of Fibrosis in the Rat Liver Using Fractal Dimension of the Shape of Power Spectrum

    NASA Astrophysics Data System (ADS)

    Kikuchi, Tsuneo; Nakazawa, Toshihiro; Furukawa, Tetsuo; Higuchi, Toshiyuki; Maruyama, Yukio; Sato, Sojun

    1995-05-01

    This paper describes the quantitative measurement of the amount of fibrosis in the rat liver using the fractal dimension of the shape of power spectrum. The shape of the power spectrum of the scattered echo from biotissues is strongly affected by its internal structure. The fractal dimension, which is one of the important parameters of the fractal theory, is useful to express the complexity of shape of figures such as the power spectrum. From in vitro experiments using rat liver, it was found that this method can be used to quantitatively measure the amount of fibrosis in the liver, and has the possibility for use in the diagnosis of human liver cirrhosis.

  3. Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

    PubMed Central

    Hong, Yun Soo; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Juhee; Kang, Danbee; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure (ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis (type A), cirrhosis (type B) and cirrhosis with previous decompensation (type C). RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in types B and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate (85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate (55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different (85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02). CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF. PMID:27076763

  4. Sarcopenia, obesity and sarcopenic obesity: effects on liver function and volume in patients scheduled for major liver resection

    PubMed Central

    Lodewick, Toine M; Roeth, Anjali AJ; Olde Damink, Steven WM; Alizai, Patrick H; van Dam, Ronald M; Gassler, Nikolaus; Schneider, Mark; Dello, Simon AWG; Schmeding, Maximilian; Dejong, Cornelis HC; Neumann, Ulf P

    2015-01-01

    Background Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic-obese patients might be reduced, possibly leading to more post-operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection. Methods In 2011 and 2012, all consecutive patients undergoing the methacetin breath liver function test were included. Liver volumetry and muscle mass analysis were performed using preoperative CT scans and Osirix® software. Muscle mass and body-fat% were calculated. Predefined cut-off values for sarcopenia and the top two body-fat% quintiles were used to identify sarcopenia and obesity, respectively. Histologic assessment of the resected liver gave insight in background liver disease. Results A total number of 80 patients were included. Liver function and volume were comparable in sarcopenic(-obese) and non-sarcopenic(-obese) patients. Obese patients showed significantly reduced liver function [295 (95–508) vs. 358 (96–684) µg/kg/h, P = 0.018] and a trend towards larger liver size [1694 (1116–2685) vs. 1533 (869–2852) mL, P = 0.079] compared with non-obese patients. Weight (r = −0.40), body surface area (r = −0.32), estimated body-fat% (r = −0.43) and body mass index (r = −0.47) showed a weak but significant negative (all P < 0.05) correlation with liver function. Moreover, body-fat% was identified as an independent factor negatively affecting the liver function. Conclusion Sarcopenia and sarcopenic obesity did not seem to influence liver size and function negatively. However, obese patients had larger, although less functional, livers, indicating dissociation of liver function and volume in these patients. PMID:26136191

  5. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools.

    PubMed

    Wang, Yan; Hou, Jin-Lin

    2016-05-01

    Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine. PMID:26742762

  6. Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.

    PubMed

    Cullen, S; Donohoe, A; McGoldrick, A; McCaffrey, N; Davenport, C; Byrne, B; Donaghy, C; Tormey, W; Smith, D; Warrington, G

    2015-11-01

    The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond. PMID:26212243

  7. Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of Rifampicin in Liver Tissues.

    PubMed

    Chumbley, Chad W; Reyzer, Michelle L; Allen, Jamie L; Marriner, Gwendolyn A; Via, Laura E; Barry, Clifton E; Caprioli, Richard M

    2016-02-16

    Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) elucidates molecular distributions in thin tissue sections. Absolute pixel-to-pixel quantitation has remained a challenge, primarily lacking validation of the appropriate analytical methods. In the present work, isotopically labeled internal standards are applied to tissue sections to maximize quantitative reproducibility and yield accurate quantitative results. We have developed a tissue model for rifampicin (RIF), an antibiotic used to treat tuberculosis, and have tested different methods of applying an isotopically labeled internal standard for MALDI IMS analysis. The application of the standard and subsequently the matrix onto tissue sections resulted in quantitation that was not statistically significantly different from results obtained using HPLC-MS/MS of tissue extracts. Quantitative IMS experiments were performed on liver tissue from an animal dosed in vivo. Each microspot in the quantitative images measures the local concentration of RIF in the thin tissue section. Lower concentrations were detected from the blood vessels and around the portal tracts. The quantitative values obtained from these measurements were comparable (>90% similarity) to HPLC-MS/MS results obtained from extracts of the same tissue. PMID:26814665

  8. Functional and histopathologic changes in the liver during sepsis.

    PubMed

    Caruana, J A; Montes, M; Camara, D S; Ummer, A; Potmesil, S H; Gage, A A

    1982-05-01

    Although liver failure from sepsis is a frequent occurrence in serious ill, hospitalized patients, little information is available on the histologic changes of the liver. We examined the histopathology of the liver of 19 patients who died of clinical sepsis and attempted to relate certain features of the illness or treatment to the observed histopathologic changes. The most striking finding was midzonal and peripheral necrosis of a moderate to marked degree in 11 of 19 patients. Other important changes were acute inflammation and cholestasis. The severity of hepatocellular necrosis did not appear to be influenced by the premortem circulating pathogen, by the nutritional support administered or by the arterial blood pressure. It is suggested that hepatocellular necrosis is characteristic of sepsis and may be caused by loss of specific factors which normally maintain liver function and structure. PMID:6803371

  9. Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

    2014-03-01

    To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

  10. Quantitative Functional Morphology by Imaging Flow Cytometry.

    PubMed

    Vorobjev, Ivan A; Barteneva, Natasha S

    2016-01-01

    This chapter describes advantages and limitations of imaging flow cytometry (IFC) based on Imagestream instrumentation using a hybrid approach of morphometric measurement and quantitation of multiparametric fluorescent intensities' distribution in cells and particles. Brief comparison is given of IFC with conventional flow cytometry and fluorescent microscopy. Some future directions of the IFC technology are described and discussed. PMID:27460234

  11. Clinical value of real-time elastography quantitative parameters in evaluating the stage of liver fibrosis and cirrhosis

    PubMed Central

    GE, LAN; SHI, BAOMIN; SONG, YE; LI, YUAN; WANG, SHUO; WANG, XIUYAN

    2015-01-01

    The aim of the present study was to assess the value of real-time elastography (RTE) quantitative parameters, namely the liver fibrosis (LF) index and the ratio of blue area (%AREA), in evaluating the stage of liver fibrosis. RTE quantitative analysis software was used to examine 120 patients with chronic hepatitis in order to obtain the values for 12 quantitative parameters from the elastic images. The diagnostic performance of two such parameters, the LF index and %AREA, were assessed with a receiver operating characteristic (ROC) curve to determine the optimal diagnostic cut-off values for liver cirrhosis and fibrosis. A good correlation was observed between the LF index and %AREA with the fibrosis stage. The areas under the ROC curve for the LF index were 0.985 for the diagnosis of liver cirrhosis and 0.790 for liver fibrosis. With regard to %AREA, the areas under the ROC curve for the diagnosis of liver cirrhosis and fibrosis were 0.963 and 0.770, respectively. An LF index of >3.25 and a %AREA of >28.83 for the diagnosis of cirrhosis stage resulted in sensitivity values of 100 and 100%, specificity values of 88.9 and 85.9% and accuracy values of 90.8 and 88.3%, respectively. The LF index and %AREA parameters exhibited higher reliability in the diagnosis of liver cirrhosis compared with the diagnosis of the liver fibrosis stage. However, the two parameters possessed a similar efficacy in the diagnosis of liver cirrhosis and the stage of liver fibrosis. Therefore, the quantitative RTE parameters of the LF index and %AREA may be clinically applicable as reliable indices for the early diagnosis of liver cirrhosis, without the requirement of an invasive procedure. PMID:26622426

  12. Glycation of Liver Cystatin: Implication on its Structure and Function.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2016-09-01

    The increased level of reducing sugars and their derivatives in a diabetic condition has been the main cause of protein related complications. The changes in native state of proteins upon glycation induce loss in the function and structure of proteins. This further leads to cell damage and accumulation of immune system inducing AGE formation. Here in the present study cystatin was purified from liver (BLC) through affinity chromatography and was incubated with glucose, fructose and ribose. Changes were observed in the intensity of Trp absorption at 280 nm as well as AGE's specific fluorescence at 435 nm upon excitation at 370 nm to monitor the formation of BLC-sugar adducts. Protein intrinsic fluorescence showed marked conformational changes when BLC was incubated with D-ribose, glucose and fructose. Glycation with D-ribose induces BLC to misfold rapidly into an intermediate state retaining a low percentage of α-helical content compared to fructose and glucose as revealed by far-UV CD data. Furthermore, a caseinolytic assay of papain in presence of glycated liver cystatin showed decreased activity in the protein induced by these reducing sugars. Ribose had more effect on the structure as well as the function of liver cystatin followed by fructose and least for glucose. Absorption spectroscopy shows change in BLC and formation of AGE's. These results shows that liver cystatin-cathepsin imbalance is compromised in diabetic state which may lead to improper balance of proteinases leading to cirrhosis or liver damage. PMID:27351669

  13. Homogeneous distribution of phosphofructokinase in the rat liver acinus: a quantitative histochemical study.

    PubMed

    Frederiks, W M; Marx, F; van Noorden, C J

    1991-10-01

    A quantitative histochemical method was developed for the demonstration in rat liver of the activity of phosphofructokinase, one of the enzymes assumed to be rate-limiting for glycolysis. The procedure was based on the reduction of a tetrazolium salt as final electron acceptor and a multistep reaction using the exogenous or endogenous auxiliary enzymes aldolase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase. The highest activity was found in unfixed cryostat sections of rat liver when the incubation medium contained 17% (wt/vol) polyvinyl alcohol, 100 mmol/L Tris-maleate buffer (pH 8.4), 20 mmol/L fructose-6-phosphate, 2 mmol/L ATP, 2 mmol/L MgCl2, 5.9 mmol/L NAD+, 0.47 mmol/L 1-methoxyphenazine methosulfate, 5 mmol/L sodium azide and 5 mmol/L Nitro BT. The addition of auxiliary enzymes was not necessary to demonstrate maximum activity in rat liver. The specificity of the reaction was proven by the absence of any specific (test minus control) reaction when the incubation was performed in the presence of 25 mmol/L phosphoenolpyruvate, a competitive inhibitor of phosphofructokinase. Cytophotometric analysis revealed that linear relationships exist between the amount of specific reaction product formed and incubation time and the section thickness. The Km values for fructose-6-phosphate and the Vmax values were not significantly different in periportal and pericentral areas of livers from either normally fed or 24-hr-fasted rats. The homogeneous distribution of phosphofructokinase activity in the liver acinus is in line with biochemical findings using hepatocytes isolated from the two different areas showing that these cells contained similar amounts of enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1833303

  14. Liver Function Tests Following Irreversible Electroporation of Liver Tumors: Experience in 174 Procedures.

    PubMed

    Froud, Tatiana; Venkat, Shree R; Barbery, Katuzka J; Gunjan, Arora; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) is a relatively new ablation modality that uses electric currents to cause cell death. It is commonly used to treat primary and secondary liver tumors in patients with normal liver function and preexisting cirrhosis. Retrospective analysis of 205 procedures sought to evaluate changes in liver function after IRE. Liver function tests (LFTs) results before and after IRE were evaluated from 174 procedures in 124 patients. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (ALKP), and total bilirubin levels were analyzed. The study was Health Insurance Portability and Accountability Act compliant and institutional review board approved. Informed consent was waived. Changes in LFT results after IRE were compared with baseline and were followed up over time to see if they resolved. Changes were compared with volume of ablation. The greatest perturbations were in transaminase levels. The levels increased sharply within 24 hours after IRE in 129 (74.1%) procedures to extreme levels (more than 20 times the upper limit of normal in one-third of cases). Resolution occurred in 95% and was demonstrated to have occurred by a mean of approximately 10 weeks, many documented as early as 7 days after procedure. ALKP levels elevated in 10% procedures, was slower to increase, and was less likely to resolve. Total bilirubin level demonstrated 2 different patterns of elevation--early and late--and similar to ALKP, it was more likely to remain elevated. There was no increased risk in patients with cirrhosis or cholangiocarcinoma. There was no correlation of levels with volume of ablation. IRE results in significant abnormalities in LFT results, but in most of the cases, these are self-limiting, do not preclude treatment, and are similar to the changes seen after radiofrequency and cryoablation in the liver. PMID:26365543

  15. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues

    NASA Astrophysics Data System (ADS)

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health. Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper, we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameters can provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis.

  16. Mueller matrix microscope: a quantitative tool to facilitate detections and fibrosis scorings of liver cirrhosis and cancer tissues.

    PubMed

    Wang, Ye; He, Honghui; Chang, Jintao; He, Chao; Liu, Shaoxiong; Li, Migao; Zeng, Nan; Wu, Jian; Ma, Hui

    2016-07-01

    Today the increasing cancer incidence rate is becoming one of the biggest threats to human health.Among all types of cancers, liver cancer ranks in the top five in both frequency and mortality rate all over the world. During the development of liver cancer, fibrosis often evolves as part of a healing process in response to liver damage, resulting in cirrhosis of liver tissues. In a previous study, we applied the Mueller matrix microscope to pathological liver tissue samples and found that both the Mueller matrix polar decomposition (MMPD) and Mueller matrix transformation (MMT) parameters are closely related to the fibrous microstructures. In this paper,we take this one step further to quantitatively facilitate the fibrosis detections and scorings of pathological liver tissue samples in different stages from cirrhosis to cancer using the Mueller matrix microscope. The experimental results of MMPD and MMT parameters for the fibrotic liver tissue samples in different stages are measured and analyzed. We also conduct Monte Carlo simulations based on the sphere birefringence model to examine in detail the influence of structural changes in different fibrosis stages on the imaging parameters. Both the experimental and simulated results indicate that the polarized light microscope and transformed Mueller matrix parameter scan provide additional quantitative information helpful for fibrosis detections and scorings of liver cirrhosis and cancers. Therefore, the polarized light microscope and transformed Mueller matrix parameters have a good application prospect in liver cancer diagnosis. PMID:27087003

  17. Bioreactor Technologies to Support Liver Function In Vitro

    PubMed Central

    Ebrahimkhani, Mohammad R; Neiman, Jaclyn A Shepard; Raredon, Micah Sam B; Hughes, David J; Griffith, Linda G

    2014-01-01

    Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drive efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models. PMID:24607703

  18. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    PubMed

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  19. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

    PubMed Central

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    Background Schistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. Methodology/Principal Findings Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. Conclusion/Significance This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID:26267788

  20. Bilirubin binding with liver cystatin induced structural and functional changes.

    PubMed

    Mustafa, Mir Faisal; Bano, Bilqees

    2014-05-01

    Cysteine proteinases and their inhibitors play a significant role in the proteolytic environment of the cells. Inhibitors of cysteine proteinases regulate the activity of these enzymes helping in checking the degdration activity of cathepsins. The bilirubin secreated by liver cells can bind to cystatin present in the liver resulting in its functional inactivation, which may further lead to the increase in cathepsins level causing liver cirrhosis. In case of some pathophysiological conditions excess bilirubin gets accumulated e.g. in presence of Fasciola hepatica (liver fluke) in mammals and humans, leading to liver cirrhosis and possibly jaundice or normal blockade of bile duct causing increased level of bilirubin in blood. Protease-cystatin imbalance causes disease progression. In the present study, Bilirubin (BR) and liver cystatin interaction was studied to explore the cystatin inactivation and structural alteration. The binding interaction was studied by UV-absorption, FT-IR and fluorescence spectroscopy. The quenching of protein fluorescence confirmed the binding of BR with buffalo liver cystatin (BLC). Stern-Volmer analysis of BR-BLC system indicates the presence of static component in the quenching mechanism and the number of binding sites to be close to 1. The fluorescence data proved that the fluorescence quenching of liver cystatin by BR was the result of BR-cystatin complex formation. FTIR analysis of BR-Cystatin complex revealed change in the secondary structure due to perturbation in the microenvironment further confirmed by the decreased caseinolytic activity of BLC against papain. Fluorescence measurements also revealed quenching of fluorescence and shift in peak at different time intervals and at varying pH values. Photo-illumination of BR-cystatin complex causes change in the surrounding environment of liver cystatin as indicated by red-shift. The binding constant for BR-BLC complex was found to be 9.279 × 10(4) M(-1). The cystatin binding with

  1. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

    Summary Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases. PMID:26116792

  2. Quantitation of rat liver xanthine oxidase by radioimmunoassay. A mechanism for sex-specific differences

    SciTech Connect

    Decker, D.E.; Levinson, D.J.

    1982-03-01

    To further delineate the mechanism responsible for the differences in xanthine oxidase activity in male and female Sprague-Dawley rats, a sensitive and specific radioimmunoassay (RIA) was developed for the measurement of hepatic xanthine oxidase. The RIA could detect as little as 5 mg of liver enzyme. Specificity of the RIA was confirmed by 1) Ouchterlony double immuno-diffusion in which a single precipitin band exhibited xanthine oxidase activity, when crude liver homogenate and an enzyme-specific stain were used; 2) parallelism between purified 125I-labeled xanthine oxidase and serial dilutions of crude liver homogenate; 3) a linear correlation between xanthine oxidase activity and the level of enzyme protein; and 4) a single protein band coincident with purified xanthine oxidase, when an immunoprecipitate prepared from antisera and crude liver homogenate was analyzed on sodium dodecyl sulfate (SDS) polyacrylamide gels. Whether xanthine oxidase activity was assayed in the absence of nicotinamide adenine dinucleotide (NAD+) (oxidase form) or in the presence of NAD+ (dehydrogenase), male values were consistently higher, and both forms of the enzyme correlated significantly with each other. When purified to homogeneity, neither form of the enzyme was appreciably affected by 17 beta-estradiol or testosterone propionate. When the RIA was employed, levels of hepatic xanthine oxidase were significantly greater in male than in female rats. We concluded from these data that increased xanthine oxidase activity in the male corresponds to a greater quantitative complement of xanthine oxidase protein. Furthermore, lower xanthine oxidase activity in the female cannot be explained by immunologically cross-reactive material without enzyme activity nor by a direct sex-steroid enzyme interaction.

  3. Quantitative assessment of protein function prediction programs.

    PubMed

    Rodrigues, B N; Steffens, M B R; Raittz, R T; Santos-Weiss, I C R; Marchaukoski, J N

    2015-01-01

    Fast prediction of protein function is essential for high-throughput sequencing analysis. Bioinformatic resources provide cheaper and faster techniques for function prediction and have helped to accelerate the process of protein sequence characterization. In this study, we assessed protein function prediction programs that accept amino acid sequences as input. We analyzed the classification, equality, and similarity between programs, and, additionally, compared program performance. The following programs were selected for our assessment: Blast2GO, InterProScan, PANTHER, Pfam, and ScanProsite. This selection was based on the high number of citations (over 500), fully automatic analysis, and the possibility of returning a single best classification per sequence. We tested these programs using 12 gold standard datasets from four different sources. The gold standard classification of the databases was based on expert analysis, the Protein Data Bank, or the Structure-Function Linkage Database. We found that the miss rate among the programs is globally over 50%. Furthermore, we observed little overlap in the correct predictions from each program. Therefore, a combination of multiple types of sources and methods, including experimental data, protein-protein interaction, and data mining, may be the best way to generate more reliable predictions and decrease the miss rate. PMID:26782400

  4. Quantitation of renal function using radioisotopic techniques.

    PubMed

    O'Malley, J P; Ziessman, H A

    1993-03-01

    Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF. PMID:8462269

  5. Quantitative analysis of ultrasonic images of fibrotic liver using co-occurrence matrix based on multi-Rayleigh model

    NASA Astrophysics Data System (ADS)

    Isono, Hiroshi; Hirata, Shinnosuke; Hachiya, Hiroyuki

    2015-07-01

    In medical ultrasonic images of liver disease, a texture with a speckle pattern indicates a microscopic structure such as nodules surrounded by fibrous tissues in hepatitis or cirrhosis. We have been applying texture analysis based on a co-occurrence matrix to ultrasonic images of fibrotic liver for quantitative tissue characterization. A co-occurrence matrix consists of the probability distribution of brightness of pixel pairs specified with spatial parameters and gives new information on liver disease. Ultrasonic images of different types of fibrotic liver were simulated and the texture-feature contrast was calculated to quantify the co-occurrence matrices generated from the images. The results show that the contrast converges with a value that can be theoretically estimated using a multi-Rayleigh model of echo signal amplitude distribution. We also found that the contrast value increases as liver fibrosis progresses and fluctuates depending on the size of fibrotic structure.

  6. Redox Control of Liver Function in Health and Disease

    PubMed Central

    Marí, Montserrat; Colell, Anna; Morales, Albert; von Montfort, Claudia; Garcia-Ruiz, Carmen

    2010-01-01

    Abstract Reactive oxygen species (ROS), a heterogeneous population of biologically active intermediates, are generated as by-products of the aerobic metabolism and exhibit a dual role in biology. When produced in controlled conditions and in limited quantities, ROS may function as signaling intermediates, contributing to critical cellular functions such as proliferation, differentiation, and cell survival. However, ROS overgeneration and, particularly, the formation of specific reactive species, inflicts cell death and tissue damage by targeting vital cellular components such as DNA, lipids, and proteins, thus arising as key players in disease pathogenesis. Given the predominant role of hepatocytes in biotransformation and metabolism of xenobiotics, ROS production constitutes an important burden in liver physiology and pathophysiology and hence in the progression of liver diseases. Despite the recognized role of ROS in disease pathogenesis, the efficacy of antioxidants as therapeutics has been limited. A better understanding of the mechanisms, nature, and location of ROS generation, as well as the optimization of cellular defense strategies, may pave the way for a brighter future for antioxidants and ROS scavengers in the therapy of liver diseases. Antioxid. Redox Signal. 12, 1295—1331. PMID:19803748

  7. A model for provoking ischemic necrosis in rat liver parenchyma and its quantitative analysis.

    PubMed

    Frederiks, W M; James, J; Bosch, K S; Schröder, M J; Schuyt, H C

    1982-01-01

    Ischemia in the left lateral and median lobe of the rat liver was provoked by means of a small clip, as applied in human microvascular surgery. After various periods of ischemia (30, 40, 50, 60 and 90 min) the blood flow to these lobes was restored. Twenty-four hours after restoration, the extent of necrosis was estimated quantitatively via morphometric measurements of the relative surfaces of necrotic tissue in photomicrographs of gallocyanin-stained serial sections. After periods of ischemia longer than 40 min, the percentage of necrotic tissue increased linearly with the period of clamping. After 40 min of total ischemia the changes in hepatocytes are for the greater part reversible, whereas after 90 min the majority of the cells have passed the "point of no return" and will no more be able to maintain their integrity. PMID:7160451

  8. Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

    PubMed

    Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. PMID:27288631

  9. Basic investigation on acoustic velocity change imaging method for quantitative assessment of fat content in human liver

    NASA Astrophysics Data System (ADS)

    Mano, Kazune; Tanigawa, Shohei; Hori, Makoto; Yokota, Daiki; Wada, Kenji; Matsunaka, Toshiyuki; Morikawa, Hiroyasu; Horinaka, Hiromichi

    2016-07-01

    Fatty liver is a disease caused by the excess accumulation of fat in the human liver. The early diagnosis of fatty liver is very important, because fatty liver is the major marker linked to metabolic syndrome. We already proposed the ultrasonic velocity change imaging method to diagnose fatty liver by using the fact that the temperature dependence of ultrasonic velocity is different in water and in fat. For the diagonosis of a fatty liver stage, we attempted a feasibility study of the quantitative assessment of the fat content in the human liver using our ultrasonic velocity change imaging method. Experimental results showed that the fat content in the tissue mimic phantom containing lard was determined by its ultrasonic velocity change in the flat temperature region formed by a circular warming ultrasonic transducer with an acoustic lens having an appropriate focal length. By considering the results of our simulation using a thermal diffusion equation, we determined whether this method could be applied to fatty liver assessment under the condition that the tissue had the thermal relaxation effect caused by blood flow.

  10. Quantitation of human MAO A and B in liver, intestine and placenta: Reassessment of activity

    SciTech Connect

    Riley, L.A.

    1989-01-01

    Monoamine oxidases (MAO) oxidize a variety of exogenous and endogenous amines including neurotransmitters such as serotonin, dopamine and norepinephrine as well as the potent dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The two forms of MAO (A and B) differ in molecular weight and inhibitor selectivity, and are differentially expressed in the nervous system and many other tissues. Although some substrates are preferentially oxidized by one form of MAO, substrates that can be oxidized by only one MAO form have not been reported. How well each MAO oxidizes various substrates has not been thoroughly characterized because of difficulties in separating and quantitating MAO A and B active sites. By immunoblotting SDS-polyacrylamide gels of mitochondrial extracts with monoclonal antibodies specific for each form of MAO, MAO B protein was detected in intestine and placenta, tissues that have been reported to contain MAO A activity. An improved procedure was developed for quantitating the ratio and amounts of MAO A and B active sites, using the ligand ({sup 3}H)-pargyline to label MAO and specific monoclonal antibodies to separate MAO A from B. Data from liver, placenta and platelets were used to re-evaluate the molecular activity of both MAO A and B for six commonly studied substrates.

  11. Warmer ambient temperatures depress liver function in a mammalian herbivore

    PubMed Central

    Kurnath, Patrice; Dearing, M. Denise

    2013-01-01

    Diet selection in mammalian herbivores is thought to be mainly influenced by intrinsic factors such as nutrients and plant secondary compounds, yet extrinsic factors like ambient temperature may also play a role. In particular, warmer ambient temperatures could enhance the toxicity of plant defence compounds through decreased liver metabolism of herbivores. Temperature-dependent toxicity has been documented in pharmacology and agriculture science but not in wild mammalian herbivores. Here, we investigated how ambient temperature affects liver metabolism in the desert woodrat, Neotoma lepida. Woodrats (n = 21) were acclimated for 30 days to two ambient temperatures (cool = 21°C, warm = 29°C). In a second experiment, the temperature exposure was reduced to 3.5 h. After temperature treatments, animals were given a hypnotic agent and clearance time of the agent was estimated from the duration of the hypnotic state. The average clearance time of the agent in the long acclimation experiment was 45% longer for animals acclimated to 29°C compared with 21°C. Similarly, after the short exposure experiment, woodrats at 29°C had clearance times 26% longer compared with 21°C. Our results are consistent with the hypothesis that liver function is reduced at warmer environmental temperatures and may provide a physiological mechanism through which climate change affects herbivorous mammals. PMID:24046878

  12. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.

    PubMed

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-02-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  13. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

    PubMed Central

    Shi, Xiao-Lei; Gao, Yimeng; Yan, Yupeng; Ma, Hucheng; Sun, Lulu; Huang, Pengyu; Ni, Xuan; Zhang, Ludi; Zhao, Xin; Ren, Haozhen; Hu, Dan; Zhou, Yan; Tian, Feng; Ji, Yuan; Cheng, Xin; Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian

    2016-01-01

    Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and α-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system. PMID:26768767

  14. Liver reserve function assessment by acoustic radiation force impulse imaging

    PubMed Central

    Sun, Xiao-Lan; Liang, Li-Wei; Cao, Hui; Men, Qiong; Hou, Ke-Zhu; Chen, Zhen; Zhao, Ya-E

    2015-01-01

    AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse (ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin (ALB), total bilirubin (T-Bil), and other indicators were observed. Liver stiffness (LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green (ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh (CP) scores were carried out based on patient’s preoperative biochemical tests and physical condition. Correlations among CP scores, ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. Kruskal-Wallis test was used to compare LS values of CP scores, and the receiver-operator characteristic (ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B (1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C (1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15 (r = 0.617, P < 0.01) and CP score (r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K (r = -0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively

  15. Controlled therapy by imaging of functional structures of intact liver

    NASA Astrophysics Data System (ADS)

    Wang, W.; Zhuang, Feng Y.; Ruan, G.; Kakihana, Yasuyuki; Krug, A.; Kessler, Manfred D.

    2000-04-01

    Ligustrazine, a Chinese herb medicine has been used to treat the diseases of cardiovascular and cerebral vascular diseases in China by Chinese traditional physicians or many years. Recently, results showed that ligustrazine is a powerful hepatic vasodilator. It can greatly change the blood supply of the tissues. Due to micro-optical tissue sensor developed recently it became possible to image functional structures of tissue on the level of intact blood capillaries. In our experiment we used the Oxyscan in order to study the effect of Ligustrazine on the oxygen supply of rat liver.

  16. Function of Autophagy in Nonalcoholic Fatty Liver Disease.

    PubMed

    Czaja, Mark J

    2016-05-01

    Autophagy is a lysosomal degradative pathway that functions to promote cell survival by supplying energy in times of stress or by removing damaged organelles and proteins after injury. The involvement of autophagy in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) was first suggested by the finding that this pathway mediates the breakdown of intracellular lipids in hepatocytes and therefore may regulate the development of hepatic steatosis. Subsequent studies have demonstrated additional critical functions for autophagy in hepatocytes and other hepatic cell types such as macrophages and stellate cells that regulate insulin sensitivity, hepatocellular injury, innate immunity, fibrosis, and carcinogenesis. These findings suggest a number of possible mechanistic roles for autophagy in the development of NAFLD and progression to NASH and its complications. The functions of autophagy in the liver, together with findings of decreased hepatic autophagy in association with conditions that predispose to NAFLD such as obesity and aging, suggest that autophagy may be a novel therapeutic target in this disease. PMID:26725058

  17. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    PubMed Central

    Eun, Chai Ryoung; Ahn, Jae Hee; Seo, Ji A

    2014-01-01

    Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication. PMID:24741459

  18. Delayed Liver Function Impairment Secondary to Interferon β-1a Use in Multiple Sclerosis

    PubMed Central

    Liao, Ming-Feng; Yen, Su-Chen; Chun-Yen, Lin; Rong-Kuo, Lyu

    2013-01-01

    Interferon β-1a is a widely used immunomodulation treatment for multiple sclerosis. Liver function impairment is a common side effect and usually develops in the first 6 months after interferon use. Here, we describe 2 multiple sclerosis patients who developed delayed liver function impairment 5 years after receiving interferon β-1a treatment. Their liver function recovered after discontinuing interferon use, and further detailed hepatological evaluations excluded other etiologies of liver function impairment. Our case reports illustrate that liver function impairment induced by interferon β-1a can be delayed for 5 years after starting treatment and, probably, this is an idiosyncratic reaction. Regular liver function monitoring in multiple sclerosis patients who receive interferon β is necessary even after the first 6 months of treatment, especially in those patients with concomitant use of other liver-toxic medications. PMID:23904853

  19. Quantitative reactivity profiling predicts functional cysteines in proteomes

    PubMed Central

    Weerapana, Eranthie; Wang, Chu; Simon, Gabriel M.; Richter, Florian; Khare, Sagar; Dillon, Myles B.D.; Bachovchin, Daniel A.; Mowen, Kerri; Baker, David; Cravatt, Benjamin F.

    2010-01-01

    Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here, we describe a proteomics method to quantitatively profile the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyperreactivity was a rare feature among cysteines and found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyperreactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and involved in iron-sulfur protein biogenesis. Finally, we demonstrate that quantitative reactivity profiling can also form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs. PMID:21085121

  20. Quantitative reactivity profiling predicts functional cysteines in proteomes.

    PubMed

    Weerapana, Eranthie; Wang, Chu; Simon, Gabriel M; Richter, Florian; Khare, Sagar; Dillon, Myles B D; Bachovchin, Daniel A; Mowen, Kerri; Baker, David; Cravatt, Benjamin F

    2010-12-01

    Cysteine is the most intrinsically nucleophilic amino acid in proteins, where its reactivity is tuned to perform diverse biochemical functions. The absence of a consensus sequence that defines functional cysteines in proteins has hindered their discovery and characterization. Here we describe a proteomics method to profile quantitatively the intrinsic reactivity of cysteine residues en masse directly in native biological systems. Hyper-reactivity was a rare feature among cysteines and it was found to specify a wide range of activities, including nucleophilic and reductive catalysis and sites of oxidative modification. Hyper-reactive cysteines were identified in several proteins of uncharacterized function, including a residue conserved across eukaryotic phylogeny that we show is required for yeast viability and is involved in iron-sulphur protein biogenesis. We also demonstrate that quantitative reactivity profiling can form the basis for screening and functional assignment of cysteines in computationally designed proteins, where it discriminated catalytically active from inactive cysteine hydrolase designs. PMID:21085121

  1. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease.

    PubMed

    Bell, Catherine C; Hendriks, Delilah F G; Moro, Sabrina M L; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C A; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L; Jenkins, Rosalind E; Nordling, Åsa; Mkrtchian, Souren; Park, B Kevin; Kitteringham, Neil R; Goldring, Christopher E P; Lauschke, Volker M; Ingelman-Sundberg, Magnus

    2016-01-01

    Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI. PMID:27143246

  2. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease

    PubMed Central

    Bell, Catherine C.; Hendriks, Delilah F. G.; Moro, Sabrina M. L.; Ellis, Ewa; Walsh, Joanne; Renblom, Anna; Fredriksson Puigvert, Lisa; Dankers, Anita C. A.; Jacobs, Frank; Snoeys, Jan; Sison-Young, Rowena L.; Jenkins, Rosalind E.; Nordling, Åsa; Mkrtchian, Souren; Park, B. Kevin; Kitteringham, Neil R.; Goldring, Christopher E. P.; Lauschke, Volker M.; Ingelman-Sundberg, Magnus

    2016-01-01

    Liver biology and function, drug-induced liver injury (DILI) and liver diseases are difficult to study using current in vitro models such as primary human hepatocyte (PHH) monolayer cultures, as their rapid de-differentiation restricts their usefulness substantially. Thus, we have developed and extensively characterized an easily scalable 3D PHH spheroid system in chemically-defined, serum-free conditions. Using whole proteome analyses, we found that PHH spheroids cultured this way were similar to the liver in vivo and even retained their inter-individual variability. Furthermore, PHH spheroids remained phenotypically stable and retained morphology, viability, and hepatocyte-specific functions for culture periods of at least 5 weeks. We show that under chronic exposure, the sensitivity of the hepatocytes drastically increased and toxicity of a set of hepatotoxins was detected at clinically relevant concentrations. An interesting example was the chronic toxicity of fialuridine for which hepatotoxicity was mimicked after repeated-dosing in the PHH spheroid model, not possible to detect using previous in vitro systems. Additionally, we provide proof-of-principle that PHH spheroids can reflect liver pathologies such as cholestasis, steatosis and viral hepatitis. Combined, our results demonstrate that the PHH spheroid system presented here constitutes a versatile and promising in vitro system to study liver function, liver diseases, drug targets and long-term DILI. PMID:27143246

  3. Quantitative Shear-Wave Elastography of the Liver in Preterm Neonates with Intra-Uterine Growth Restriction

    PubMed Central

    Alison, Marianne; Biran, Valérie; Tanase, Anca; Bendavid, Matthieu; Blouet, Marie; Demené, Charlie; Tanter, Mickael; Baud, Olivier

    2015-01-01

    The feasibility and reproducibility of liver stiffness measurements using Supersonic Shear-wave Imaging (SSI) in preterm neonate have not been reported. Our aim was to determine if liver stiffness differs between intra-uterine growth restriction (IUGR) and appropriate for gestational age (AGA) preterm infants with/without cholestasis. We measured liver stiffness (in kPa) in 45 AGA and 18 IUGR preterm infants, and assessed reproducibility in 26 preterms using Intraclass Correlation Coefficients (ICC) and Bland-Altman tests. Liver stiffness values were compared between AGA and IUGR with and without cholestasis and correlated with birth weight. Measurements showed high reproducibility (ICC = 0.94–0.98 for intra-operator, 0.86 for inter-operator) with good agreement (95% limits: -1.24 to 1.24 kPa). During the first postnatal week, liver stiffness was higher in IUGR (7.50 ±1.53 kPa) than in AGA infants (5.11 ±0.80 kPa, p<0.001). After day 8, liver stiffness remained unchanged in AGA but increased progressively in IUGR infants (15.57 ±6.49 kPa after day 21). Liver stiffness was higher in IUGR neonates with cholestasis (19.35 ± 9.80 kPa) than without cholestasis (7.72 ± 1.27 kPa, p<0.001). In conclusion, quantitative liver SSI in preterms is feasible and reproducible. IUGR preterms who will develop cholestasis present high liver stiffness even at birth, before biological cholestasis occurs. PMID:26580807

  4. [Problems and prospects of creation of extracorporal systems for support of functional livers status].

    PubMed

    Ryabinin, V E

    2015-01-01

    The review considers features of efferent therapy employing extracorporeal systems, the devices known as "artificial liver" and "bioartificial liver" in the treatment of liver insufficiency. Analysis of literature data shows the need for further development of these biomedical studies and the search for optimal solutions in the selection of the source of hepatocytes, the development of bioreactors and biomaterials forming the basis of devices like "bioartificial liver". Taking into consideration certain advantages and disadvantages typical for various methods of extracorporeal support of the functional state of the liver one can evaluate prior experience in the treatment of liver diseases and approaches to the development of new, more effective medical technologies. PMID:26539863

  5. SU-E-J-260: Quantitative Image Feature Analysis of Multiphase Liver CT for Hepatocellular Carcinoma (HCC) in Radiation Therapy

    SciTech Connect

    Choi, W; Wang, J; Lu, W; Kang, M

    2015-06-15

    Purpose: To identify the effective quantitative image features (radiomics features) for prediction of response, survival, recurrence and metastasis of hepatocellular carcinoma (HCC) in radiotherapy. Methods: Multiphase contrast enhanced liver CT images were acquired in 16 patients with HCC on pre and post radiation therapy (RT). In this study, arterial phase CT images were selected to analyze the effectiveness of image features for the prediction of treatment outcome of HCC to RT. Response evaluated by RECIST criteria, survival, local recurrence (LR), distant metastasis (DM) and liver metastasis (LM) were examined. A radiation oncologist manually delineated the tumor and normal liver on pre and post CT scans, respectively. Quantitative image features were extracted to characterize the intensity distribution (n=8), spatial patterns (texture, n=36), and shape (n=16) of the tumor and liver, respectively. Moreover, differences between pre and post image features were calculated (n=120). A total of 360 features were extracted and then analyzed by unpaired student’s t-test to rank the effectiveness of features for the prediction of response. Results: The five most effective features were selected for prediction of each outcome. Significant predictors for tumor response and survival are changes in tumor shape (Second Major Axes Length, p= 0.002; Eccentricity, p=0.0002), for LR, liver texture (Standard Deviation (SD) of High Grey Level Run Emphasis and SD of Entropy, both p=0.005) on pre and post CT images, for DM, tumor texture (SD of Entropy, p=0.01) on pre CT image and for LM, liver (Mean of Cluster Shade, p=0.004) and tumor texture (SD of Entropy, p=0.006) on pre CT image. Intensity distribution features were not significant (p>0.09). Conclusion: Quantitative CT image features were found to be potential predictors of the five endpoints of HCC in RT. This work was supported in part by the National Cancer Institute Grant R01CA172638.

  6. Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods

    PubMed Central

    Zhang, Dong; Song, Xiao-jing; Li, Shun-yue; Wang, Shu-you; Chen, Bing-jun; Bai, Xiao-Dong; Tang, Li-mei

    2016-01-01

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy. PMID:27443832

  7. Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods.

    PubMed

    Zhang, Dong; Song, Xiao-Jing; Li, Shun-Yue; Wang, Shu-You; Chen, Bing-Jun; Bai, Xiao-Dong; Tang, Li-Mei

    2016-01-01

    Imaging methods to evaluate hepatic microcirculation (HM) and liver function (LF) by directly monitoring overall liver tissue remain lacking. This study establish imaging methods for LF that combines Laser speckle perfusion imaging (LSPI) and in vivo optical imaging (IVOI) technologies to investigate changes of hepatic microcirculation and reserve function in the animals gavaged with 50% ethanol (15 ml/kg·bw) for a model of acute alcoholic liver injury (ALI), and for evaluation of electroacupuncture (EA) effect. The liver blood perfusion and indocyanine green (ICG) distribution were observe by LSPI and IVOI separately. After EA, the livers were collected to measure the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), thromboxane A (TXA2), prostacyclin (PGI2) and endothelin (ET). The acquisitions of newly established LSPI of liver and ICG in vivo fluorescence imaging (ICG-IVFI), combining the results of other indexes showed: hepatic microcirculation perfusion (HMP) significantly reduced, ICG metabolism reduced, and ALT/AST increased in animal model with acute ALI. EA can reverse these changes. The use of LSPI of liver and ICG-IVFI, which was novel imaging methods for LF established in this study, could display the LF characteristics of ALI and the EA efficacy. PMID:27443832

  8. Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

    PubMed Central

    Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

    2011-01-01

    Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

  9. Structure and function of sinusoidal lining cells in the liver.

    PubMed

    Wisse, E; Braet, F; Luo, D; De Zanger, R; Jans, D; Crabbé, E; Vermoesen, A

    1996-01-01

    The hepatic sinusoid harbors 4 different cells: endothelial cells (100, 101), Kupffer cells (96, 102, 103), fat-storing cells (34, 51, 93), and pit cells (14, 107, 108). Each cell type has its own specific morphology and functions, and no transitional stages exist between the cells. These cells have the potential to proliferate locally, either in normal or in special conditions, that is, experiments or disease. Sinusoidal cells from a functional unit together with the parenchymal cells. Isolation protocols exist for all sinusoidal cells. Endothelial cells filter the fluids, exchanged between the sinusoid and the space of Disse through fenestrae (100), which measure 175 nm in diameter and are grouped in sieve plates. Fenestrae occupy 6-8% of the surface (106). No intact basal lamina is present under these cells (100). Various factors change the number and diameter of fenestrae [pressure, alcohol, serotonin, and nicotin; for a review, see Fraser et al (32)]. These changes mainly affect the passage of lipoproteins, which contain cholesterol and vitamin A among other components. Fat-storing cells are pericytes, located in the space of Disse, with long, contractile processes, which probably influence liver (sinusoidal) blood flow. Fat-storing cells possess characteristic fat droplets, which contain a large part of the body's depot of vitamin A (91, 93). These cells play a major role in the synthesis of extracellular matrix (ECM) (34, 39-41). Strongly reduced levels of vitamin A occur in alcoholic livers developing fibrosis (56). Vitamin A deficiency transforms fat-storing cells into myofibroblast-like cells with enhanced ECM production (38). Kupffer cells accumulate in periportal areas. They specifically endocytose endotoxin (70), which activates these macrophages. Lipopolysaccharide, together with interferon gamma, belongs to the most potent activators of Kupffer cells (28). As a result of activation, these cells secrete oxygen radicals, tumor necrosis factor

  10. Breath-hold black blood quantitative T1rho imaging of liver using single shot fast spin echo acquisition

    PubMed Central

    Chan, Queenie; Wáng, Yì-Xiáng J.

    2016-01-01

    Background Liver fibrosis is a key feature in most chronic liver diseases. T1rho magnetic resonance imaging is a potentially important technique for noninvasive diagnosis, severity grading, and therapy monitoring of liver fibrosis. However, it remains challenging to perform robust T1rho quantification of liver on human subjects. One major reason is that the presence of rich blood signal in liver can cause artificially high T1rho measurement and makes T1rho quantification susceptible to motion. Methods A pulse sequence based on single shot fast/turbo spin echo (SSFSE/SSTSE) acquisition, with theoretical analysis and simulation based on the extended phase graph (EPG) algorithm, was presented for breath-hold single slice quantitative T1rho imaging of liver with suppression of blood signal. The pulse sequence was evaluated in human subjects at 3.0 T with 500 Hz spinlock frequency and time-of-spinlock (TSL) 0, 10, 30 and 50 ms. Results Human scan demonstrated that the entire T1rho data sets with four spinlock time can be acquired within a single breath-hold of 10 seconds with black blood effect. T1rho quantification with suppression of blood signal results in significantly reduced T1rho value of liver compared to the results without blood suppression. Conclusions A signal-to-noise ratio (SNR) efficient pulse sequence was reported for T1rho quantification of liver. The black blood effect, together with a short breath-hold, mitigates the risk of quantification errors as would occur in the conventional methods. PMID:27190769

  11. Quantitative functional MRI in a clinical orthotopic model of pancreatic cancer in immunocompetent Lewis rats

    PubMed Central

    Zhang, Zhuoli; Zheng, Linfeng; Li, Weiguo; Gordon, Andrew C; Huan, Yi; Shangguan, Junjie; Procissi, Daniel; Bentrem, David J; Larson, Andrew C

    2015-01-01

    primary tumors and that in metastases. Similarly, quantitative ADC measurements were similar for both primary tumor and liver metastases (1.13 ± 0.3 × 10-3 and 1.24 ± 0.4 × 10-3 mm2/s, respectively). Histologic fibrosis and MVD measurements were similar in primary tumors and metastases. Conclusions: Anatomic and quantitative functional MRI measurements are feasible in orthotropic DSL rat model and will permit non-invasive monitoring of tumor responses during longitudinal studies intended to develop new interventional therapies for primary and metastatic disease. PMID:26550449

  12. Quantitative criteria for estimation of natural and artificial ecosystems functioning

    NASA Astrophysics Data System (ADS)

    Pechurkin, N. S.

    It's necessary to have quantitative criteria to elaborate efficient artificial ecosystems (AES). As usual, these criteria are connected with exact objectives of AES designed. For example, if AES is considered for use in space, it's to be efficient in its use of mass, power, volume (size) and human labor and to be reliable. Another task arises: how to determine, to find out the quantitative criteria for natural ecosystems functioning. To solve the problem, it's fruitful to use a hierarchical approach suitable for both individual links and ecosystem as a whole. Energy fluxes criteria (principles) were developed to estimate the functional activities of biosystems at populations, communities and ecosystems levels. Major feature of ecosystem as a whole is a biotic turnover of matter the rate of which is restricted by the lack of limiting substances. Obviously, the most generalized criterion is to take into account: energy fluxes used by the biosystem and quantity of limiting substance included into its turnover. The use (utilization) of energy fluxes by ecosystem can be easily measured as a net primary production of photosynthesis (NPP). So, the ratio of NPP to the total mass of limiting substrate can serve as a main universal criterion (MUC). This MUC characterizes the specific cycling rate of limiting chemical elements in the system and effectiveness of every ecosystem functioning, including Biosphere. Comparative analysis and elaboration of quantitative criteria for estimation of natural and artificial ecosystems activities is of high importance both for theoretical considerations and for real applications.

  13. Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy.

    PubMed

    Yang, S; Tan, T M C; Wee, A; Leow, C K

    2004-01-01

    For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration. PMID:14745500

  14. Effects of exercise and ethanol on liver mitochondrial function

    SciTech Connect

    Ardies, C.M.; Morris, G.S.; Erickson, C.K.; Farrar, R.P.

    1987-03-16

    Rates of ADP stimulated respiration for various substrates were determined in mitochondria isolated from the livers of female Sprague-Dawley rats following 8 weeks of treatment with daily swimming, ethanol consumption, or both. All rats were fed an American Institute of Nutrition (AIN) type liquid diet with the ethanol treated rats receiving 35% of the calories as ethanol. Chronic exposure to ethanol depressed both state 3 respiration with glutamate as a substrate and cytochrome oxidase activity. Respiratory control ratios and P:O ratios, however, were unaffected by the ethanol exposure. Exercise alone had no effect on hepatic mitochondrial function. There were also no significant alterations in oxidative function of hepatic mitochondria from rats which were endurance-trained by swimming while receiving the ethanol diet. This lack of alteration in mitochondrial function was in spite of the fact that these rats consumed an identical amount of ethanol as those which incurred mitochondrial dysfunction. These results indicate that regular exercise has the potential to attenuate the ethanol induced decline in hepatic mitochondria. 32 references, 2 figures, 1 table.

  15. LIVER FUNCTION AFTER IRRADIATION BASED UPON CT PORTAL VEIN PERFUSION IMAGING

    PubMed Central

    Cao, Yue; Pan, Charlie; Balter, James M.; Platt, Joel F.; Francis, Isaac R.; Knol, James A.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.

    2009-01-01

    Purpose The role of radiation in the treatment of intrahepatic cancer is limited by the development of radiation-induced liver disease (RILD), which occurs weeks after the course of radiation is completed. We hypothesized that, as the pathophysiology of RILD is veno-occlusive disease, we could assess individual and regional liver sensitivity to radiation by measuring liver perfusion during a course of treatment using dynamic contrast enhanced CT (DCE-CT) scanning. Materials and Methods Patients with intrahepatic cancer undergoing conformal radiotherapy underwent DCE-CT (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) prior to, during, and one month after treatment. We wished to determine if the residual functioning liver (i.e. those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. Results Radiation doses from 45 to 84 Gy resulted in undectable regional portal vein perfusion one month after treatment. The volume of each liver with undectable portal vein perfusion ranged from 0% to 39% and depended both on the patient’s sensitivity and dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (P < .001). Conclusion This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function, and has the potential to be a tool for individualizing therapy. PMID:17855011

  16. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers.

    PubMed

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J

    2016-07-01

    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD. PMID:26946466

  17. Learning Quantitative Sequence-Function Relationships from Massively Parallel Experiments

    NASA Astrophysics Data System (ADS)

    Atwal, Gurinder S.; Kinney, Justin B.

    2016-03-01

    A fundamental aspect of biological information processing is the ubiquity of sequence-function relationships—functions that map the sequence of DNA, RNA, or protein to a biochemically relevant activity. Most sequence-function relationships in biology are quantitative, but only recently have experimental techniques for effectively measuring these relationships been developed. The advent of such "massively parallel" experiments presents an exciting opportunity for the concepts and methods of statistical physics to inform the study of biological systems. After reviewing these recent experimental advances, we focus on the problem of how to infer parametric models of sequence-function relationships from the data produced by these experiments. Specifically, we retrace and extend recent theoretical work showing that inference based on mutual information, not the standard likelihood-based approach, is often necessary for accurately learning the parameters of these models. Closely connected with this result is the emergence of "diffeomorphic modes"—directions in parameter space that are far less constrained by data than likelihood-based inference would suggest. Analogous to Goldstone modes in physics, diffeomorphic modes arise from an arbitrarily broken symmetry of the inference problem. An analytically tractable model of a massively parallel experiment is then described, providing an explicit demonstration of these fundamental aspects of statistical inference. This paper concludes with an outlook on the theoretical and computational challenges currently facing studies of quantitative sequence-function relationships.

  18. SILAM for quantitative proteomics of liver Akt1/PKBα after burn injury

    PubMed Central

    LU, X.-M.; TOMPKINS, R.G.; FISCHMAN, A.J.

    2012-01-01

    Akt1/protein kinase Bα (Akt1/PKBα) is a downstream mediator of the insulin signaling system. In this study we explored mechanism(s) for its role in burn injury. Akt1/PKBα in liver extracts from mice with burn injury fed with (2H7)-L-Leu was immunoprecipitated and isolated with SDS-PAGE. Two tryptic peptides, one in the kinase loop and a control peptide just outside of the loop were sequenced via nano-LC interfaced with quadruple time-of-flight tandem mass spectrometry (Q-TOF tandem MS). Their relative isotopologue abundances were determined by stable isotope labeling by amino acids in mammalians (SILAM). Relative quantifications based on paired heavy/light peptides were obtained in 3 steps. The first step included homogenization of mixtures of equal amounts of tissue from burned and sham-treated animals (i.e., isotope dilution) and acquisition of uncorrected data based on parent monoisotopic MS ion ratios. The second step included determination of isotopic enrichment of the kinase from burned mice on Day 7 and the third step enrichment correction of partially labeled heavy and light monoisotopic MS ion ratios for relative quantification of bioactivity (loop peptide) and expression level (control peptide). Protein synthesis and enrichment after injury were found to be dependent on tissue and turnover of individual proteins. Three heavy and light monoisotopic ion ratios for albumin peptides from burned mice indicated ~55% enrichment and ~16.7-fold downregulation. In contract, serum amyloid P had ~66% enrichment and was significantly upregulated. Akt1/PKBα had ~56% enrichment and kinase level in response to the burn injury was upregulated compared with the control peptide. However, kinase bioactivity, represented by the Cys296 peptide, was significantly reduced. Overall, we demonstrated that i) quantitative proteomics can be performed without completely labeled mice; ii) measurement of enrichment of acyl-tRNAs is unnecessary and iii) Cys296 plays an important role

  19. Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers.

    PubMed

    Banan, Babak; Watson, Rao; Xu, Min; Lin, Yiing; Chapman, William

    2016-07-01

    Donor organ shortages have led to an increased interest in finding new approaches to recover organs from extended criteria donors (ECD). Normothermic extracorporeal liver perfusion (NELP) has been proposed as a superior preservation method to reduce ischemia/reperfusion injury (IRI), precondition suboptimal grafts, and treat ECD livers so that they can be successfully used for transplantation. The aim of this study was to investigate the beneficial effects of a modified NELP circuit on discarded human livers. Seven human livers that were rejected for transplantation were placed on a modified NELP circuit for 8 hours. Perfusate samples and needle core biopsies were obtained at hourly intervals. A defatting solution that contained exendin-4 (50 nM) and L-carnitine (10 mM) was added to the perfusate for 2 steatotic livers. NELP provided normal temperature, electrolytes, and pH and glucose levels in the perfusate along with physiological vascular flows and pressures. Functional, biochemical, and microscopic evaluation revealed no additional injuries to the grafts during NELP with an improved oxygen extraction ratio (>0.5) and stabilized markers of hepatic injury. All livers synthesized adequate amounts of bile and coagulation factors. We also demonstrated a mild reduction (10%) of macroglobular steatosis with the use of the defatting solution. Histology demonstrated normal parenchymal architecture and a minimal to complete lack of IRI at the end of NELP. In conclusion, a modified NELP circuit preserved hepatocyte architecture, recovered synthetic functions, and hepatobiliary parameters of ECD livers without additional injuries to the grafts. This approach has the potential to increase the donor pool for clinical transplantation. Liver Transplantation 22 979-993 2016 AASLD. PMID:27027254

  20. Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in Culture.

    PubMed

    Chinnici, Cinzia Maria; Timoneri, Francesca; Amico, Giandomenico; Pietrosi, Giada; Vizzini, Giovanni; Spada, Marco; Pagano, Duilio; Gridelli, Bruno; Conaldi, Pier Giulio

    2015-01-01

    This study was designed to assess liver-specific functions of human fetal liver cells proposed as a potential source for hepatocyte transplantation. Fetal liver cells were isolated from livers of different gestational ages (16-22 weeks), and the functions of cell preparations were evaluated by establishing primary cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures contained a predominance of cells with hepatocytic traits that did not divide in vitro but were functionally competent. Fetal hepatocytes performed liver-specific functions at levels comparable to those of their adult counterpart. Moreover, exposure to dexamethasone in combination with oncostatin M promptly induced further maturation of the cells through the acquisition of additional functions (i.e., ability to store glycogen and uptake of indocyanine green). In some cases, particularly in cultures obtained from fetuses of earlier gestational ages (16-18 weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and the primary cultures were mainly populated by clusters of proliferating cells. Consequently, the values of liver-specific functions detected in these cultures were low. We observed that a low cell density culture system rapidly prompted loss of the mature hepatocytic phenotype with downregulations of all the liver-specific functions. We found that human fetal liver cells can be cryopreserved without significant loss of viability and function and evaluated up to 1 year in storage in liquid nitrogen. They might, therefore, be suitable for cell banking and allow for the transplantation of large numbers of cells, thus improving clinical outcomes. Overall, our results indicate that fetal hepatocytes could be used as a cell source for hepatocyte transplantation. Fetal liver cells have been used so far to treat end-stage liver disease. Additional studies are needed to include these cells in cell-based therapies aimed to treat liver failure and inborn

  1. Functional linear models for association analysis of quantitative traits.

    PubMed

    Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

    2013-11-01

    Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. PMID:24130119

  2. Quantitative analysis of gene function in the Drosophila embryo.

    PubMed Central

    Tracey, W D; Ning, X; Klingler, M; Kramer, S G; Gergen, J P

    2000-01-01

    The specific functions of gene products frequently depend on the developmental context in which they are expressed. Thus, studies on gene function will benefit from systems that allow for manipulation of gene expression within model systems where the developmental context is well defined. Here we describe a system that allows for genetically controlled overexpression of any gene of interest under normal physiological conditions in the early Drosophila embryo. This regulated expression is achieved through the use of Drosophila lines that express a maternal mRNA for the yeast transcription factor GAL4. Embryos derived from females that express GAL4 maternally activate GAL4-dependent UAS transgenes at uniform levels throughout the embryo during the blastoderm stage of embryogenesis. The expression levels can be quantitatively manipulated through the use of lines that have different levels of maternal GAL4 activity. Specific phenotypes are produced by expression of a number of different developmental regulators with this system, including genes that normally do not function during Drosophila embryogenesis. Analysis of the response to overexpression of runt provides evidence that this pair-rule segmentation gene has a direct role in repressing transcription of the segment-polarity gene engrailed. The maternal GAL4 system will have applications both for the measurement of gene activity in reverse genetic experiments as well as for the identification of genetic factors that have quantitative effects on gene function in vivo. PMID:10628987

  3. Liver.

    PubMed

    Kim, W R; Lake, J R; Smith, J M; Skeans, M A; Schladt, D P; Edwards, E B; Harper, A M; Wainright, J L; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    The median waiting time for patients with MELD ≥ 35 decreased from 18 days in 2012 to 9 days in 2014, after implementation of the Share 35 policy in June 2013. Similarly, mortality among candidates listed with MELD ≥ 35 decreased from 366 per 100 waitlist years in 2012 to 315 in 2014. The number of new active candidates added to the pediatric liver transplant waiting list in 2014 was 655, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) continued to decline, 401 active and 173 inactive. The number of deceased donor pediatric liver transplants peaked at 542 in 2008 and was 478 in 2014. The number of living donor liver pediatric transplants was 52 in 2014; most were from donors closely related to the recipients. Graft survival continued to improve among pediatric recipients of deceased donor and living donor livers. PMID:26755264

  4. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.**

    EPA Science Inventory

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  5. Quantitative changes in endogenous DNA adducts correlate with conazole mutagenicity and tumorigenicity in mouse liver.

    EPA Science Inventory

    We have previously shown that the conazole fungicides triadimefon and propiconazole, which are tumorigenic in mouse liver, are in vivo mouse liver mutagens in the Big Blue" transgenic mutation assay when administered in feed at tumorigenic doses. The nontumorigenic conazole myclo...

  6. TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

    SciTech Connect

    Wu, V; Epelman, M; Feng, M; Cao, Y; Wang, H; Romeijn, E; Matuszak, M

    2014-06-15

    Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUD (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD

  7. Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation?

    PubMed Central

    Vondran, Florian Wolfgang Rudolf; Schumacher, Carsten; Johanning, Kai; Hartleben, Björn; Knitsch, Wolfgang; Wiesner, Olaf; Jaeckel, Elmar; Manns, Michael Peter; Klempnauer, Juergen; Bektas, Hueseyin; Lehner, Frank

    2016-01-01

    Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient. PMID:27274881

  8. A study on the quantitative evaluation of skin barrier function

    NASA Astrophysics Data System (ADS)

    Maruyama, Tomomi; Kabetani, Yasuhiro; Kido, Michiko; Yamada, Kenji; Oikaze, Hirotoshi; Takechi, Yohei; Furuta, Tomotaka; Ishii, Shoichi; Katayama, Haruna; Jeong, Hieyong; Ohno, Yuko

    2015-03-01

    We propose a quantitative evaluation method of skin barrier function using Optical Coherence Microscopy system (OCM system) with coherency of near-infrared light. There are a lot of skin problems such as itching, irritation and so on. It has been recognized skin problems are caused by impairment of skin barrier function, which prevents damage from various external stimuli and loss of water. To evaluate skin barrier function, it is a common strategy that they observe skin surface and ask patients about their skin condition. The methods are subjective judgements and they are influenced by difference of experience of persons. Furthermore, microscopy has been used to observe inner structure of the skin in detail, and in vitro measurements like microscopy requires tissue sampling. On the other hand, it is necessary to assess objectively skin barrier function by quantitative evaluation method. In addition, non-invasive and nondestructive measuring method and examination changes over time are needed. Therefore, in vivo measurements are crucial for evaluating skin barrier function. In this study, we evaluate changes of stratum corneum structure which is important for evaluating skin barrier function by comparing water-penetrated skin with normal skin using a system with coherency of near-infrared light. Proposed method can obtain in vivo 3D images of inner structure of body tissue, which is non-invasive and non-destructive measuring method. We formulate changes of skin ultrastructure after water penetration. Finally, we evaluate the limit of performance of the OCM system in this work in order to discuss how to improve the OCM system.

  9. Quantitative criteria for estimation of natural and artificial ecosystems functioning

    NASA Astrophysics Data System (ADS)

    Pechurkin, N. S.

    Using biotic turnover of substances in trophic chains, natural and artificial ecosystems are similar in functioning, but different in structure. It is necessary to have quantitative criteria to evaluate the efficiency of artificial ecosystems (AES). These criteria are dependent on the specific objectives for which the AES are designed. For example, if AES is considered for use in space, important criteria are efficiency in use of mass, power, volume (size) and human labor and reliability. Another task involves the determination of quantitative criteria for the functioning of natural ecosystems. To solve the problem, it is fruitful to use a hierarchical approach suitable for both individual links and the ecosystem as a whole. Energy flux criteria (principles) were developed to estimate the functional activities of biosystems at the population, community and ecosystem levels. A major feature of ecosystems as a whole is their biotic turnover of matter the rate of which is restricted by the lack of limiting substances. Obviously, the most generalized criterion is to take into account the energy flux used by the biosystem and the quantity of limiting substance included in its turnover. The use of energy flux by ecosystem, EUSED - is determined from the photoassimilation of CO 2 by plants (per time unit). It can be approximately estimated as the net primary production of photosynthesis (NPP). So, the ratio of CO 2 photoassimilation rate (sometimes, measured as NPP) to the total mass of limiting substrate can serve as a main universal criterion (MUC). This MUC characterizes the specific cycling rate of limiting chemical elements in the system and effectiveness of every ecosystem including the global Biosphere. Comparative analysis and elaboration of quantitative criteria for estimation of natural and artificial ecosystems activities is of high importance both for theoretical considerations and for real applications.

  10. Quantitative objective assessment of peripheral nociceptive C fibre function.

    PubMed Central

    Parkhouse, N; Le Quesne, P M

    1988-01-01

    A technique is described for the quantitative assessment of peripheral nociceptive C fibre function by measurement of the axon reflex flare. Acetylcholine, introduced by electrophoresis, is used to stimulate a ring of nociceptive C fibre endings at the centre of which the increase in blood flow is measured with a laser Doppler flowmeter. This flare (neurogenic vasodilatation) has been compared with mechanically or chemically stimulated non-neurogenic cutaneous vasodilation. The flare is abolished by local anaesthetic and is absent in denervated skin. The flare has been measured on the sole of the foot of 96 healthy subjects; its size decreases with age in males, but not in females. Images PMID:3351528

  11. Synthesis and application of lactosylated, 99mTc chelating albumin for measurement of liver function.

    PubMed

    Chaumet-Riffaud, Philippe; Martinez-Duncker, Ivan; Marty, Anne-Laure; Richard, Cyrille; Prigent, Alain; Moati, Frederic; Sarda-Mantel, Laure; Scherman, Daniel; Bessodes, Michel; Mignet, Nathalie

    2010-04-21

    Neogalactosylated and neolactosylated albumins are currently used as radiopharmaceutical agents for imaging the liver asialoglycoprotein receptors, which allows the quantification of hepatic liver function in various diseases and also in healthy liver transplant donors. We developed an original process for synthesizing a chelating neolactosylated human albumin using maleimidopropyl-lactose and maleimidopropyl-diethylene triamine pentaacetic acid (DTPA) derivatives. The lactosylated protein (LACTAL) conjugate showed excellent liver uptake compared to nonlactosylated protein and a very high signal-to-noise ratio, based on functional assessment of biodistribution in mice using (99m)Tc-scintigraphy. PMID:20201600

  12. Clinical Implications of Non-Steatotic Hepatic Fat Fractions on Quantitative Diffusion-Weighted Imaging of the Liver

    PubMed Central

    Dijkstra, Hildebrand; Handayani, Astri; Kappert, Peter; Oudkerk, Matthijs; Sijens, Paul E.

    2014-01-01

    Diffusion-weighted imaging (DWI) is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF) are higher than 5.5% (steatosis). However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0) were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM) model. Four circular regions (ø22.3 mm) were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF≤2.75%), group 2 (2.75< HFF ≤5.5%) and group 3 (HFF>5.5%). DWI parameters and T2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49 ×10−3 mm2/s) and T2* (32.2, 27.2 and 21.0 ms) differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%). Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = −0.514, p<0.001) and T2* (−0.714, p<0.001). Similar results were obtained for the majority of individual liver segments. It was concluded that fat significantly decreases molecular diffusion in the liver, also in absence of steatosis (HFF≤5.5%). Also, it was confirmed that fat influences T2*. Determination of HFF prior to quantitative DWI is therefore crucial. PMID:24505333

  13. Stable isotope dimethyl labeling combined with LTQ mass spectrometric detection, a quantitative proteomics technology used in liver cancer research

    PubMed Central

    TANG, BO; LI, YANG; ZHAO, LIANG; YUAN, SHENGGUANG; WANG, ZHENRAN; LI, BO; CHEN, QIAN

    2013-01-01

    Liver cancer is a common malignant disease, with high incidence and mortality rates. The study on the proteomics of liver cancer has attracted particular attention. The quantitative study method of proteomics depends predominantly on two-dimensional (2D) gel electrophoresis. In the present study we reported a rapid and accurate proteomics quantitative study method of high repeatability that includes the use of stable isotope labeling for the extraction of proteins and peptides via enzymolysis to achieve new type 2D capillary liquid chromatography-mass spectrometry separation using the separation mode of cation-exchange chromatography in conjunction with reversed-phase chromatography. LTQ OrbiTrap mass spectrometry detection was also performed. A total of 188 differential proteins were analyzed, including 122 upregulating [deuterium/hydrogen ratio (D/H) >1.5)] and 66 downregulating proteins (D/H<0.67). These proteins may play an important role in the occurrence, drug resistance, metastasis and recurrence of cancer or other pathological processes. Such a proteomics technology may provide biological data as well as a new methodological basis for liver cancer research. PMID:24648984

  14. Effects of simulated heliox diving at high altitudes on blood cells, liver functions and renal functions.

    PubMed

    Hu, Hui-Jun; Fan, Dan-Feng; Lv, Yan; Zhang, Yu; Yang, Chen; Zhao, Ling; Zhao, Ru-Gang; Pan, Xiao-Wen

    2013-01-01

    The aim of the present study was to examine the effects of simulated heliox diving at high altitudes on divers' blood cells, liver functions and renal functions. In this experiment, four divers lived for nine consecutive days in a dual-function high-low pressure chamber, which simulated air pressure at an altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and 30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in depth. Total time underwater was 60 minutes. The subjects breathed heliox (with oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero altitude to 30 meters and while remaining underwater; they breathed air while ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and helium at 73.3%) in the simulated dive from zero altitude to 50 meters underwater, in remaining underwater and in ascending from 50 meters to 29; air while ascending from 29 meters to 18. Pure oxygen was breathed while ascending from 18 meters to the surface; then air. Results indicated: (1) the correlating indices of routine blood, liver and renal functions, and urine routine were all within normal reference ranges; and (2) the indices tested at other periods of time were not significantly different (p > 0.05) from the results at zero-meter level and 3,000-meter level. The study suggests that the heliox diving processes at different high altitudes simulated in this experiment have no significant impact upon divers' blood routine, liver functions and renal functions. PMID:23957203

  15. Quantitative detection of liver-relevant biomarkers by SERS-immunolabeled gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Payne, William Mark

    Lab-on-a-chip technology has the potential to rapidly change the way experiments are conducted in a variety of fields ranging from medicine to environmental science. Specifically, sensors, detectors, and monitoring devices are increasingly being miniaturized to perform many experiments or measurements on a single chip. In this research, we develop an immunolabeled gold nanoparticle complex capable of detecting liver organoid biomarkers intended for use in a microfluidic device. Human Serum Albumin (HSA) and alpha-Glutathione S-Transferase (alpha-GST) are liver biomarkers that indicate liver health and damage respectively. Herein we demonstrate detection of the liver organoid biomarkers at nanomolar concentrations. Through plasmonic coupling induced by aggregation in the presence of analyte, the SERS signal obtained from the nanoparticles is dramatically increased. Furthermore, detection is demonstrated in a simple fluidic device to show the feasibility of implementing an optimized SERS-immunolabeled nanoparticle for translational application.

  16. Systems genetics of liver fibrosis: identification of fibrogenic and expression quantitative trait loci in the BXD murine reference population.

    PubMed

    Hall, Rabea A; Liebe, Roman; Hochrath, Katrin; Kazakov, Andrey; Alberts, Rudi; Laufs, Ulrich; Böhm, Michael; Fischer, Hans-Peter; Williams, Robert W; Schughart, Klaus; Weber, Susanne N; Lammert, Frank

    2014-01-01

    The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine 'genetic reference panel' of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL) analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs) with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury. PMID:24586654

  17. Systems Genetics of Liver Fibrosis: Identification of Fibrogenic and Expression Quantitative Trait Loci in the BXD Murine Reference Population

    PubMed Central

    Hall, Rabea A.; Liebe, Roman; Hochrath, Katrin; Kazakov, Andrey; Alberts, Rudi; Laufs, Ulrich; Böhm, Michael; Fischer, Hans-Peter; Williams, Robert W.; Schughart, Klaus

    2014-01-01

    The progression of liver fibrosis in response to chronic injury varies considerably among individual patients. The underlying genetics is highly complex due to large numbers of potential genes, environmental factors and cell types involved. Here, we provide the first toxicogenomic analysis of liver fibrosis induced by carbon tetrachloride in the murine ‘genetic reference panel’ of recombinant inbred BXD lines. Our aim was to define the core of risk genes and gene interaction networks that control fibrosis progression. Liver fibrosis phenotypes and gene expression profiles were determined in 35 BXD lines. Quantitative trait locus (QTL) analysis identified seven genomic loci influencing fibrosis phenotypes (pQTLs) with genome-wide significance on chromosomes 4, 5, 7, 12, and 17. Stepwise refinement was based on expression QTL mapping with stringent selection criteria, reducing the number of 1,351 candidate genes located in the pQTLs to a final list of 11 cis-regulated genes. Our findings demonstrate that the BXD reference population represents a powerful experimental resource for shortlisting the genes within a regulatory network that determine the liver's vulnerability to chronic injury. PMID:24586654

  18. Focal Lesions in Fatty Liver: If Quantitative Analysis Facilitates the Differentiation of Atypical Benign from Malignant Lesions

    PubMed Central

    Shan, Quan-Yuan; Chen, Li-Da; Zhou, Lu-Yao; Wang, Zhu; Liu, Guang-Jian; Huang, Yang; Li, Wei; Liu, Jin-ya; Xie, Xiao-yan; Lu, Ming-de; Liu, Jie; Wang, Wei

    2016-01-01

    To evaluate the diagnostic performance of quantitative analysis as an adjunctive diagnostic tool to contrast-enhanced ultrasound (US) for the differentiation of atypical benign focal liver lesions (FLLs) from malignancies in fatty liver. Twenty-seven benign FLLs and fifty-six malignant FLLs that appeared hyper-enhanced during the arterial phase with washout in the portal or late phase in fatty liver were analyzed. Chi-square tests and logistic regression were applied to identify the specific features. Three sets of criteria were assigned: 1) all FLLs subjected to routine contrast-enhanced US; 2) all FLLs subjected to quantification analysis and contrast-enhanced US; and 3) parts of FLLs that could not be diagnosed using contrast-enhanced US (n = 66, 75.9%) but instead were diagnosed using parametric features. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) of the three sets of criteria were analyzed. The AUCs of the criterion set 2 were significantly higher than those of criterion set 1 (0.904 versus 0.792, P = 0.008). Criterion set 3 showed a relatively high sensitivity (90.2%) with a relatively high AUC (0.845). The quantification analysis offers improved diagnostic performance for the differential identification of atypical benign FLLs from malignancies in fatty liver. PMID:26725923

  19. Functional Human Liver Preservation and Recovery by Means of Subnormothermic Machine Perfusion

    PubMed Central

    Weeder, Pepijn D.; Sridharan, Gautham V.; Uygun, Basak E.; Karimian, Negin G.; Porte, Robert J.; Markmann, James F.; Yeh, Heidi; Uygun, Korkut

    2015-01-01

    There is currently a severe shortage of liver grafts available for transplantation. Novel organ preservation techniques are needed to expand the pool of donor livers. Machine perfusion of donor liver grafts is an alternative to traditional cold storage of livers and holds much promise as a modality to expand the donor organ pool. We have recently described the potential benefit of subnormothermic machine perfusion of human livers. Machine perfused livers showed improving function and restoration of tissue ATP levels. Additionally, machine perfusion of liver grafts at subnormothermic temperatures allows for objective assessment of the functionality and suitability of a liver for transplantation. In these ways a great many livers that were previously discarded due to their suboptimal quality can be rescued via the restorative effects of machine perfusion and utilized for transplantation. Here we describe this technique of subnormothermic machine perfusion in detail. Human liver grafts allocated for research are perfused via the hepatic artery and portal vein with an acellular oxygenated perfusate at 21 °C. PMID:25938299

  20. A fully automated, quantitative test of upper limb function.

    PubMed

    Prochazka, Arthur; Kowalczewski, Jan

    2015-01-01

    The Rehabilitation Joystick for Computerized Exercise (ReJoyce, Rehabtronics Inc., Edmonton, Alberta, Canada), is a workstation on which participants exercise dexterous movement tasks in the guise of computer games. The system incorporates the ReJoyce Arm and Hand Function Test (RAHFT). Here the authors evaluate the RAHFT against the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FMA). All 3 tests were performed in 36 separate sessions in 13 tetraplegic individuals. Concurrent and criterion validities of the RAHFT were supported by a high level of correlation with the ARAT (r2 = .88). Regarding responsiveness, the effect size of the RAHFT at week 6 of 1 hr/day exercise training was 1.8. Regarding reliability, the mean test-retest difference in RAHFT baseline scores was 0.67% ± 3.6%, which was not statistically significant. The RAHFT showed less ceiling effect than either ARAT or FMA. These data help validate the RAHFT as a quantitative, automated alternative to the ARAT and FMA. The RAHFT is the first comprehensive test of arm and dexterous hand function that does not depend on human judgment. It offers a standardized, quantitative outcome evaluation, which can be performed not only in the clinic, but also in the participant's home, administered by a remote therapist over the Internet. PMID:25575220

  1. [Effect of hepatophyt on the choleretic function of the liver damaged by tetracycline].

    PubMed

    Nikolaev, S M; Sambueva, Z G; Chekhirova, G V; Tsyrenzhalov, A V

    2003-01-01

    In experimental injury of the liver in Wistar-line white rats induced by tetracycline the course therapeutic and prophylatic administration of the dry extract "Hepatophyt" in a dose of 0.1 g/kg inhibits the negative effect of tetracycline and promotes stimulation of choleretic and antitoxic functions of the liver. The dry extract was derived from the herbal mix of the same name, used in the practice of Tibetan medicine against liver diseases. PMID:13677134

  2. Quantitative Analysis of the Effective Functional Structure in Yeast Glycolysis

    PubMed Central

    De la Fuente, Ildefonso M.; Cortes, Jesus M.

    2012-01-01

    The understanding of the effective functionality that governs the enzymatic self-organized processes in cellular conditions is a crucial topic in the post-genomic era. In recent studies, Transfer Entropy has been proposed as a rigorous, robust and self-consistent method for the causal quantification of the functional information flow among nonlinear processes. Here, in order to quantify the functional connectivity for the glycolytic enzymes in dissipative conditions we have analyzed different catalytic patterns using the technique of Transfer Entropy. The data were obtained by means of a yeast glycolytic model formed by three delay differential equations where the enzymatic rate equations of the irreversible stages have been explicitly considered. These enzymatic activity functions were previously modeled and tested experimentally by other different groups. The results show the emergence of a new kind of dynamical functional structure, characterized by changing connectivity flows and a metabolic invariant that constrains the activity of the irreversible enzymes. In addition to the classical topological structure characterized by the specific location of enzymes, substrates, products and feedback-regulatory metabolites, an effective functional structure emerges in the modeled glycolytic system, which is dynamical and characterized by notable variations of the functional interactions. The dynamical structure also exhibits a metabolic invariant which constrains the functional attributes of the enzymes. Finally, in accordance with the classical biochemical studies, our numerical analysis reveals in a quantitative manner that the enzyme phosphofructokinase is the key-core of the metabolic system, behaving for all conditions as the main source of the effective causal flows in yeast glycolysis. PMID:22393350

  3. Functional Nanoparticles Activate a Decellularized Liver Scaffold for Blood Detoxification.

    PubMed

    Xu, Fen; Kang, Tianyi; Deng, Jie; Liu, Junli; Chen, Xiaolei; Wang, Yuan; Ouyang, Liang; Du, Ting; Tang, Hong; Xu, Xiaoping; Chen, Shaochen; Du, Yanan; Shi, Yujun; Qian, Zhiyong; Wei, Yuquan; Deng, Hongxin; Gou, Maling

    2016-04-01

    Extracorporeal devices have great promise for cleansing the body of virulence factors that are caused by venomous injuries, bacterial infections, and biological weaponry. The clinically used extracorporeal devices, such as artificial liver-support systems that are mainly based on dialysis or electrostatic interaction, are limited to remove a target toxin. Here, a liver-mimetic device is shown that consists of decellularized liver scaffold (DLS) populated with polydiacetylene (PDA) nanoparticles. DLS has the gross shape and 3D architecture of a liver, and the PDA nanoparticles selectively capture and neutralize the pore-forming toxins (PFTs). This device can efficiently and target-orientedly remove PFTs in human blood ex vivo without changing blood components or activating complement factors, showing potential application in antidotal therapy. This work provides a proof-of-principle for blood detoxification by a nanoparticle-activated DLS, and can lead to the development of future medical devices for antidotal therapy. PMID:26914158

  4. Functional Immune Anatomy of the Liver-As an Allograft.

    PubMed

    Demetris, A J; Bellamy, C O C; Gandhi, C R; Prost, S; Nakanuma, Y; Stolz, D B

    2016-06-01

    The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system. PMID:26848550

  5. Hepatic function in hypothermically stored porcine livers: comparison of hypothermic machine perfusion vs cold storage.

    PubMed

    Jain, S; Lee, C Y; Baicu, S; Duncan, H; Xu, H; Jones, J W; Clemens, M G; Brassil, J; Taylor, M J; Brockbank, K G M

    2005-01-01

    Hypothermic machine perfusion (HMP) has a potential to relieve the current donor liver crisis by providing an improved and extended preservation method. This study examined the effect of HMP on hepatocellular functions, using a prototype liver transporter capable of preserving livers for 24 hours. Livers obtained from adult farm pigs (28 to 32 kg body weight) were divided into three groups: fresh control, HMP, and simple cold storage (n = 4 each). A 4-hour normothermic reperfusion of livers was conducted to assess hepato-metabolic and cellular functions. The hepatic transport function, as indicated by canalicular excretion of indocyanine green, was improved in the HMP group than in the SCS group. The overall tissue viability, as indicated by oxygen consumption levels, was notably improved in HMP and control livers as compared to the SCS group. Higher bile production in both the preserved groups as compared to the fresh control livers could be a result of biliary edema and leakage of plasma into the canaliculus. The hepato-cellular injury, measured by ALT, release was significantly greater in the SCS group as compared to the HMP and control groups. These findings suggest that HMP could be a better method to preserve hepatic function and overall tissue viability as compared to SCS. Improved hepatic functions are indirect indicators of superior microcirculation and sinusoidal endothelial cell functions. Further studies in progress will evaluate these functions to confirm the significance of these observations. PMID:15808637

  6. Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

    PubMed

    Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

    2016-04-01

    To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes. PMID:27104857

  7. Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits

    PubMed Central

    Xie, Dan; Liang, Meimei; Xiong, Momiao

    2016-01-01

    To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI’s Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes. PMID:27104857

  8. Developing a Causal Model from Liver Function Test Data

    NASA Astrophysics Data System (ADS)

    Inada, Masanori; Terano, Takao

    As Active Mining is a new concept among data mining and/or knowledge discovery in databases communities, in order to validate the effectiveness, it is important to carry out empirical studies using practical data. Based on the concept of Active User Reaction, this paper develops a causal model from liver function test data in a medical domain. To develop the model, we have set a problem to predict the values of ICG (indocyanine green) test from given observation data and experts' background knowledge. We therefore employ a framework of meta-learning and structural equation modeling. In this paper meta-learning means learning about mined results from multiple data-mining techniques. Structural equation modeling enables us to describe flexible models from background knowledge. The construction of the causal model contains two phases: meta-learning and the model building. The meta-learning phase utilizes both the linear regression and the neural network as data mining techniques, then examines the predictability on the given data set. Mining models are n-folded learned from the training data set. Each of the prediction accuracy of the mining models is compared using with the testing data. On the model building phase, we use structural equation modeling to develop a causal model based on results of meta-learning and background knowledge. We again compare the accuracy of the causal model with each of the mining models. Consequently we have developed the causal model, which is comprehensible and have good predictive performance, via the meta-learning phase. Through the empirical study, we have got the conclusion that the framework of meta-learning is effective in data mining in a difficult medical domain.

  9. Quantitative imaging of lymphatic function with liposomal indocyanine green.

    PubMed

    Proulx, Steven T; Luciani, Paola; Derzsi, Stefanie; Rinderknecht, Matthias; Mumprecht, Viviane; Leroux, Jean-Christophe; Detmar, Michael

    2010-09-15

    Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. PMID:20823159

  10. Quantitative Trait Loci Identify Functional Noncoding Variation in Cancer

    PubMed Central

    Heyn, Holger

    2016-01-01

    The interpretation of noncoding alterations in cancer genomes presents an unresolved problem in cancer studies. While the impact of somatic variations in protein-coding regions is widely accepted, noncoding aberrations are mostly considered as passenger events. However, with the advance of genome-wide profiling strategies, alterations outside the coding context entered the focus, and multiple examples highlight the role of gene deregulation as cancer-driving events. This review describes the implication of noncoding alterations in oncogenesis and provides a theoretical framework for the identification of causal somatic variants using quantitative trait loci (QTL) analysis. Assuming that functional noncoding alterations affect quantifiable regulatory processes, somatic QTL studies constitute a valuable strategy to pinpoint cancer gene deregulation. Eventually, the comprehensive identification and interpretation of coding and noncoding alterations will guide our future understanding of cancer biology. PMID:26938653

  11. Physical exercise and quantitative lower limb collateral function

    PubMed Central

    Stoller, Michael; Stoller, David; Seiler, Christian

    2016-01-01

    Objective This study tested the hypothesis that global physical activity and physical performance parameters are directly related to invasively obtained left superficial femoral artery (SFA) collateral flow index (CFI). Background So far, the association between different measures of physical exercise activity and quantitative lower limb collateral function has not been investigated. Methods The primary study end point was pressure-derived CFI as obtained during a 3 min left SFA balloon occlusion. CFI is the ratio of simultaneously recorded mean SFA distal occlusive pressure divided by mean aortic pressure, both subtracted by central venous pressure. As independent variables, the items of the Global Physical Activity Questionnaire (GPAQ) and physical exercise performance (maximal workload in watts) as achieved during a bicycle or treadmill exercise test were determined. The secondary study end point was transcutaneous left calf partial oxygen pressure (PO2 in mm Hg) divided by transcutaneous PO2 at a non-ischaemic reference site as obtained simultaneously to CFI measurement. Results Of the 110 study patients undergoing diagnostic coronary angiography, 79 belonged to the group without and 31 with engagement in regular intensive leisure time physical activity according to GPAQ. Left SFA CFI tended to be lower in the group without than with intensive leisure time physical activity: 0.514 ±0.141 vs 0.560 ±0.184 (p =0.0566). Transcutaneous PO2 index was associated with simultaneous left SFA CFI: CFI =018 +0.57 PO2 index; p<0.0001. Maximal physical workload was directly associated with left SFA CFI: CFI =0.40 +0.0009 maximal workload; p =0.0044. Conclusions Quantitative left SFA collateral function is directly reflected by maximal physical workload as achieved during an exercise test. Trial registration number NCTO02063347. PMID:26977310

  12. Functional activity of sphingomyelin cycle in rat liver in chronic toxic hepatitis.

    PubMed

    Serebrov, V Yu; Kuzmenko, D I; Burov, P G; Novitsky, S V

    2008-12-01

    Activities of sphingomyelinase and ceramidase decreased in the liver in chronic toxic hepatitis and the balance between the levels of proapoptotic ceramide and antiapoptotic sphyngosine-1-phosphate shifts towards the latter substance. Pronounced changes in the qualitative and quantitative composition of fatty acids in the sphingomyelin cycle effector molecules were revealed. PMID:19513367

  13. Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function

    PubMed Central

    2013-01-01

    Background Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression. Results In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development. Conclusions Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity. PMID:23958281

  14. Evaluation of liver function using gadoxetate disodium (Gd-EOB-DTPA) enhanced MR imaging

    NASA Astrophysics Data System (ADS)

    Yamada, Akira; Hara, Takeshi; Li, Feng; Doi, Kunio

    2010-03-01

    Indocyanine green (ICG) is widely used for its clearance test in the evaluation of liver function. Gadoxetate disodium (Gd-EOB-DTPA) is a targeted MR contrast agent partially taken up by hepatocytes. The objective of this study was to evaluate the feasibility of an estimation of the liver function corresponding to plasma disappearance rate of indocyanine green (ICG-PDR) by use of the signal intensity of the liver alone in Gd-EOB-DTPA enhanced MR imaging (EOB-MRI). We evaluated fourteen patients who had EOB-MRI and ICG clearance test within 1 month. 2D-GRE T1 weighted images were obtained at pre contrast, 3 min (equilibrium phase) and 20 min (hepatobiliary phase) after the intravenous administration of Gd-EOB-DTPA, and the mean signal intensity of the liver was measured. The correlation between ICG-PDR and many parameters derived from the signal intensity of the liver in EOB-MRI was evaluated. The correlation coefficient between ICG-PDR and many parameters derived from the signal intensity of the liver in EOBMRI was low and not significant. The estimation of the liver function corresponding to ICG-PDR by use of the signal intensity of the liver alone in EOB-MRI would not be reliable.

  15. Quantitative Proteomic Profiles of Androgen Receptor Signaling in the Liver of Fathead Minnows Pimephalus promelas

    EPA Science Inventory

    Androgenic chemicals are present in the environment at concentrations that impair reproductive processes in fish. The objective of this experiment was to identify proteins altered by an androgen receptor agonist (17â-trenbolone) and antagonist (flutamide) in the liver. Female fa...

  16. Quantitative analysis of site-specific N-glycans on sera haptoglobin β chain in liver diseases.

    PubMed

    Zhang, Shu; Jiang, Kai; Sun, Chun; Lu, Haojie; Liu, Yinkun

    2013-12-01

    The site-specific characterization of N-glycans in glycoproteins with the potential of clinical application is important. In our previous report, the overall N-glycans of sera haptoglobin (Hp) β chain were found to be different in liver diseases. Hp β chain contains four potential sites of N-glycosylation. In this study, we investigated the potential change of N-glycans on Hp β chain in a site-specific fashion. Sera Hp β chain in healthy individuals as well as patients with hepatitis B virus (HBV), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were purified, digested and subjected to liquid chromatography-electrospray ionization-higher energy collision dissociation mass spectrometry, which allowed identification and structure determination of the glycopeptide, as well as the relative quantification of glycans present on each glycopeptide. The quantitative results revealed that the sialylation of NLFLN(207)HSEN(211)ATAK and the fucosylated structure at all glycopeptides increased significantly in LC and HCC patients compared with those in HBV patients and healthy individuals. A set of different N-glycan patterns of Hp β chain in various liver diseases has been determined. Thus, the sialylated and fucosylated glycoforms of Hp β chain might be related to early hepatocarcinogenesis and also might be useful as novel differential markers for LC and HCC patients. PMID:24103369

  17. Quantitative Assessment of Neuromotor Function in Adolescents with High Functioning Autism and Asperger Syndrome

    ERIC Educational Resources Information Center

    Freitag, Christine M.; Kleser, Christina; Schneider, Marc; von Gontard, Alexander

    2007-01-01

    Background: Motor impairment in children with Asperger Syndrome (AS) or High functioning autism (HFA) has been reported previously. This study presents results of a quantitative assessment of neuromotor skills in 14-22 year old HFA/AS. Methods: 16 HFA/AS and 16 IQ-matched controls were assessed by the Zurich Neuromotor Assessment (ZNA). Results:…

  18. [Respiratory functional impairment in patients with liver cirrhosis].

    PubMed

    Siemieniako, Andrzej; Łapiński, Tadeusz Wojciech; Flisiak, Robert

    2010-04-01

    Liver pathologies have negative influence on numerous organs including pulmonary system. Liver failure, which often results from cirrhosis, may lead to the hepatopulmonary syndrome and portopulmonary hypertension. The hepatopulmonary syndrome is characterized by increased alveolar-capillary oxygen gradient, presence of intrapulmonary leak and diminished retention of the carbon dioxide from arterial blood. Two types of the hepatopulmonary syndrome are distinguished: the type 1 connected with pre-capillary and capillaries extension, what shortens the time of the blood flow by the pulmonary vessels. The type 2 hepatopulmonary syndrome results from the formation of arteriovenous anastomoses and anatomical "shunt" connections. Most patients with hepatopulmonary syndrome demonstrate both types. Patients with liver failure may develop portopulmonary hypertension, independently from hepatopulmonary syndrome. If not treated, hypertension might lead to the death of 50 to 90% patients in the 5-year follow up. The patients with the serious damage of the liver have hiperdynamic circulation with the increased heart capacity and lowered systemic vascular resistance. The hepatopulmonary syndrome is characterized by the growth of the pulmonary artery pressure and the presence of portal hypertension. The mechanism how the portal hypertension leads to the pulmonary hypertension is not clear. PMID:20491346

  19. How to interpret liver function tests in heart failure patients?

    PubMed

    Çağlı, Kumral; Başar, Fatma Nurcan; Tok, Derya; Turak, Osman; Başar, Ömer

    2015-05-01

    Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder. PMID:26006191

  20. Cognitive and Adaptive Functioning after Liver Transplantation for Maple Syrup Urine Disease: A Case Series

    PubMed Central

    Shellmer, D. A.; Dabbs, A. DeVito; Dew, M. A.; Noll, R. B.; Feldman, H.; Strauss, K.; Morton, D. H.; Vockley, G.; Mazariegos, G. V.

    2011-01-01

    MSUD is a complex metabolic disorder that has been associated with central nervous system damage, developmental delays, and neurocognitive deficits. Although liver transplantation provides a metabolic cure for MSUD, changes in cognitive and adaptive functioning following transplantation have not been investigated. In this report we present data from 14 patients who completed cognitive and adaptive functioning testing pre- and one year and/or three years post-liver transplantation. Findings show either no significant change or improvement in IQ scores pre- to post-liver transplantation. Greater variability was observed in adaptive functioning scores, but the majority of patients evidenced either no significant change or improvement in adaptive scores. In general, findings may indicate that liver transplantation curtails additional central nervous system damage and neurocognitive decline providing an opportunity for stabilization or improvement in functioning. PMID:20946191

  1. An accurate method of extracting fat droplets in liver images for quantitative evaluation

    NASA Astrophysics Data System (ADS)

    Ishikawa, Masahiro; Kobayashi, Naoki; Komagata, Hideki; Shinoda, Kazuma; Yamaguchi, Masahiro; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2015-03-01

    The steatosis in liver pathological tissue images is a promising indicator of nonalcoholic fatty liver disease (NAFLD) and the possible risk of hepatocellular carcinoma (HCC). The resulting values are also important for ensuring the automatic and accurate classification of HCC images, because the existence of many fat droplets is likely to create errors in quantifying the morphological features used in the process. In this study we propose a method that can automatically detect, and exclude regions with many fat droplets by using the feature values of colors, shapes and the arrangement of cell nuclei. We implement the method and confirm that it can accurately detect fat droplets and quantify the fat droplet ratio of actual images. This investigation also clarifies the effective characteristics that contribute to accurate detection.

  2. Effect of Non-speckle Echo Signals on Tissue Characteristics for Liver Fibrosis using Probability Density Function of Ultrasonic B-mode image

    NASA Astrophysics Data System (ADS)

    Mori, Shohei; Hirata, Shinnosuke; Yamaguchi, Tadashi; Hachiya, Hiroyuki

    To develop a quantitative diagnostic method for liver fibrosis using an ultrasound B-mode image, a probability imaging method of tissue characteristics based on a multi-Rayleigh model, which expresses a probability density function of echo signals from liver fibrosis, has been proposed. In this paper, an effect of non-speckle echo signals on tissue characteristics estimated from the multi-Rayleigh model was evaluated. Non-speckle signals were determined and removed using the modeling error of the multi-Rayleigh model. The correct tissue characteristics of fibrotic tissue could be estimated with the removal of non-speckle signals.

  3. Functional Implications of Biochemical and Molecular Characteristics of Donation After Circulatory Death Livers

    PubMed Central

    Masuzaki, Ryota; Yu, Hui; Kingsley, Philip; Marnett, Lawrence; Zhao, Zhongming; Karp, Seth J.

    2015-01-01

    Background In aggregate, livers donated after circulatory death (DCD) provide lower rates of graft and patient survival compared to brain dead donors (DBD). A method to identify DCD livers likely to perform well would lead to better decision-making regarding which livers to use and which to discard and is an important unmet clinical need. We hypothesized that the ischemic time between extubation and cold perfusion in the donor leads to immediate and unique biochemical and molecular changes that could be used to predict subsequent function. Methods Biopsies from normal perfused liver, immediately after cold perfusion during DCD or DBD liver procurement, and during subsequent cold storage were analyzed and compared. Biochemical analysis included adenosine triphosphate (ATP), adenosine diphosphate, adenosine monophosphate, hypoxanthine, xanthine, inosine, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. Levels of these metabolites were compared to peak posttransplant aspartate aminotransferase as a marker of ischemic injury. Molecular analysis was performed by transcriptional profiling using high throughput sequencing. Results Immediately after cold perfusion in the donor, biochemical analysis revealed lower levels of ATP and adenosine diphosphate in DCD versus DBD liver samples (P < 0.01 in both cases). The ATP levels showed high negative correlation with peak aspartate aminotransferase levels in recipients (P = 0.029). Four hundred seventy genes showed differential expression in DCD but not DBD samples immediately after cold perfusion compared with normal liver samples. Upregulated genes function in inflammation and immunity, whereas downregulated genes function in translation. During cold storage, samples were transcriptionally inactive with no consistent changes in messenger RNA expression. Conclusion The ATP content of liver samples taken immediately postperfusion correlates with ischemic injury. Transcriptional profiling identifies biological

  4. True versus mild hyperthermia during isolated hepatic perfusion: effects on melphalan pharmacokinetics and liver function.

    PubMed

    Pilati, Pierluigi; Mocellin, Simone; Rossi, Carlo R; Ori, Carlo; Innocente, Federico; Scalerta, Romano; Ceccherini, Mauro; Da Pian, Pier Paolo; Nitti, Donato; Lise, Mario

    2004-08-01

    Hyperthermic antiblastic isolated hepatic perfusion (IHP) with melphalan has been recently proposed as an alternative therapeutic option for patients with unresectable liver tumors. Although melphalan-heat antiblastic synergism is at a maximum at temperatures higher than 41 degrees C, IHP has so far been performed in humans at lower temperatures. In this experimental work, we compared IHP under mild versus true hyperthermic conditions in terms of drug pharmacokinetics and liver function. Ten pigs were submitted to IHP with melphalan 1.5 mg/kg at a mean temperature of 40 degrees C (group A, n = 5) or 42 degrees C (group B, n = 5). After a 60-minute perfusion, a 15-minute washout was performed. Perfusate-to-plasma leakage was monitored using scintigraphy. Throughout perfusion, samples from the systemic blood, perfusate, and liver parenchyma were obtained to measure melphalan concentrations. Liver function was assessed using standard blood tests and the indocyanine green-based test. No deaths related to the IHP procedure were recorded. All animals had transient liver function impairment, with all liver function test results returning to normal within the observation period. At histologic examination, liver damage was similar under both hyperthermic conditions. Melphalan levels in the perfusate were not significantly different in the two study groups (the mean perfusate/plasma area under the curve from 0 to 60 minutes ratios were 463 and 501, respectively). These results correlated well with those obtained using the scintigraphic method. Liver drug concentrations remained unchanged after true hyperthermia IHP. Under true hyperthermic conditions, neither an increase in liver parenchyma toxicity nor changes in melphalan pharmacokinetics were observed. These findings support the use of true hyperthermia in the clinical setting to exploit fully the antitumor synergism between melphalan and heat. PMID:15457357

  5. Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

    SciTech Connect

    Cao Yue; Wang Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2013-01-01

    Purpose: To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials: Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results: There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions: This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

  6. Prediction of Liver Function by Using Magnetic Resonance-based Portal Venous Perfusion Imaging

    PubMed Central

    Cao, Yue; Wang, Hesheng; Johnson, Timothy D.; Pan, Charlie; Hussain, Hero; Balter, James M.; Normolle, Daniel; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2013-01-01

    Purpose To evaluate whether liver function can be assessed globally and spatially by using volumetric dynamic contrast-enhanced magnetic resonance imaging MRI (DCE-MRI) to potentially aid in adaptive treatment planning. Methods and Materials Seventeen patients with intrahepatic cancer undergoing focal radiation therapy (RT) were enrolled in institution review board-approved prospective studies to obtain DCE-MRI (to measure regional perfusion) and indocyanine green (ICG) clearance rates (to measure overall liver function) prior to, during, and at 1 and 2 months after treatment. The volumetric distribution of portal venous perfusion in the whole liver was estimated for each scan. We assessed the correlation between mean portal venous perfusion in the nontumor volume of the liver and overall liver function measured by ICG before, during, and after RT. The dose response for regional portal venous perfusion to RT was determined using a linear mixed effects model. Results There was a significant correlation between the ICG clearance rate and mean portal venous perfusion in the functioning liver parenchyma, suggesting that portal venous perfusion could be used as a surrogate for function. Reduction in regional venous perfusion 1 month after RT was predicted by the locally accumulated biologically corrected dose at the end of RT (P<.0007). Regional portal venous perfusion measured during RT was a significant predictor for regional venous perfusion assessed 1 month after RT (P<.00001). Global hypovenous perfusion pre-RT was observed in 4 patients (3 patients with hepatocellular carcinoma and cirrhosis), 3 of whom had recovered from hypoperfusion, except in the highest dose regions, post-RT. In addition, 3 patients who had normal perfusion pre-RT had marked hypervenous perfusion or reperfusion in low-dose regions post-RT. Conclusions This study suggests that MR-based volumetric hepatic perfusion imaging may be a biomarker for spatial distribution of liver function, which

  7. Analysis of liver connexin expression using reverse transcription quantitative real-time polymerase chain reaction

    PubMed Central

    Maes, Michaël; Willebrords, Joost; Crespo Yanguas, Sara; Cogliati, Bruno; Vinken, Mathieu

    2016-01-01

    Summary Although connexin production is mainly regulated at the protein level, altered connexin gene expression has been identified as the underlying mechanism of several pathologies. When studying the latter, appropriate methods to quantify connexin mRNA levels are required. The present chapter describes a well-established reverse transcription quantitative real-time polymerase chain reaction procedure optimized for analysis of hepatic connexins. The method includes RNA extraction and subsequent quantification, generation of complementary DNA, quantitative real-time polymerase chain reaction and data analysis. PMID:27207283

  8. Analysis of Liver Connexin Expression Using Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction.

    PubMed

    Maes, Michaël; Willebrords, Joost; Crespo Yanguas, Sara; Cogliati, Bruno; Vinken, Mathieu

    2016-01-01

    Although connexin production is mainly regulated at the protein level, altered connexin gene expression has been identified as the underlying mechanism of several pathologies. When studying the latter, appropriate methods to quantify connexin RNA levels are required. The present chapter describes a well-established reverse transcription quantitative real-time polymerase chain reaction procedure optimized for analysis of hepatic connexins. The method includes RNA extraction and subsequent quantification, generation of complementary DNA, quantitative real-time polymerase chain reaction, and data analysis. PMID:27207283

  9. Differential proteomic analysis of STAT6 knockout mice reveals new regulatory function in liver lipid homeostasis.

    PubMed

    Iff, Joël; Wang, Wei; Sajic, Tatjana; Oudry, Nathalie; Gueneau, Estelle; Hopfgartner, Gérard; Varesio, Emmanuel; Szanto, Ildiko

    2009-10-01

    Increased inflammatory signaling is a key feature of metabolic disorders. In this context, the role of increased pro-inflammatory signals has been extensively studied. By contrast, no efforts have been dedicated to study the contrasting scenario: the attenuation of anti-inflammatory signals and their role in metabolic homeostasis. IL-4 and IL-13 are anti-inflammatory cytokines signaling through the Signal Transducer and Activator of Transcription 6 (STAT6). Our study was aimed at evaluating the lack of STAT6 signaling on liver homeostasis. To this end we analyzed the liver proteome of wild type and STAT6 knock-out mice using 2D nanoscale LC-MS/MS with iTRAQ labeling technique. The coordinated changes in proteins identified by this quantitative proteome analysis indicated disturbed lipid homeostasis and a state of hepatocellular stress. Most significantly, the expression of the liver fatty acid binding protein (FABP1) was increased in the knock-out mice. In line with the elevated FABP1 expression we found latent liver lipid accumulation in the STAT6-deficient mice which was further aggravated when mice were challenged by a high fat diet. In conclusion, our study revealed a so far uncharacterized role for STAT6 in regulating liver lipid homeostasis and demonstrates the importance of anti-inflammatory signaling in the defense against the development of liver steatosis. PMID:19663508

  10. Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

    PubMed

    Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

    2016-07-01

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy. PMID:27224003

  11. Radiometric assay for direct quantitation of rat liver cytochrome P-450b using monoclonal antibodies.

    PubMed

    Rothwell, C E; Khazaeli, M B; Bernstein, I A

    1985-08-15

    A simple and sensitive assay has been developed that is capable of detecting as little as 0.2 ng of the major isozyme of cytochrome P-450 (P-450b) isolated from the livers of phenobarbital-induced rats. This assay employs monoclonal antibodies generated against cytochrome P-450b to directly quantify the levels of this enzyme in various tissues. Separation of bound from free labeled antibody is achieved by using 6,9-diaminoacridine lactate (Rivanol). The useful range of the assay is between 1 and 100 ng of P-450b. PMID:3935002

  12. Detection of Recurrent Hepatocellular Carcinoma in Cirrhotic Liver after Transcatheter Arterial Chemoembolization: Value of Quantitative Color Mapping of the Arterial Enhancement Fraction of the Liver

    PubMed Central

    Lee, Dong Ho; Klotz, Ernst; Kim, Soo Jin; Kim, Kyung Won; Han, Joon Koo; Choi, Byung Ihn

    2013-01-01

    Objective To investigate the additional diagnostic value of color mapping of the hepatic arterial enhancement fraction (AEF) for detecting recurrent or residual hepatocellular carcinoma (HCC) in patients treated with transcatheter arterial chemoembolization (TACE). Materials and Methods Seventy-six patients with 126 HCCs, all of whom had undergone previous TACE, and subsequently, underwent follow-up multiphasic liver CT scans, were included in this study. Quantitative color maps of the AEF of the whole liver were created, by using prototype software with non-rigid registration. The AEF was defined as the ratio of the attenuation increment during the arterial phase to the attenuation increment during the portal phase. Two radiologists independently analyzed the two image sets at a two-week interval, i.e., the multiphasic CT image set and the second image set of the AEF color maps and the CT images. The additional diagnostic value of the AEF color mapping was determined, by the use of the jackknife-alternative free-response receiver-operating-characteristic analysis. The sensitivity and positive predictive values for detecting HCCs of each image set were also evaluated and compared. Results The reader-averaged figures of merit were 0.699 on the initial interpretation of the MDCT image set, and 0.831 on the second interpretation of the combined image set; the difference between the two interpretations was significant (p value < 0.001). The mean sensitivity for residual or recurrent HCC detection increased from 62.7% on the initial analysis to 82.1% on the second analysis using the AEF color maps (p value < 0.001). The mean positive predictive value for HCC detection was 74.5% on the initial analysis using MDCT, and 71.6% on the second analysis using AEF color mapping. Conclusion Quantitative color mapping of the hepatic AEF may have the possibility to increase the diagnostic performance of MDCT for the detection of recurrent or residual HCC without the potential risk

  13. Long-term quantitative evaluation of liver transplantation in familial amyloid polyneuropathy (Portuguese V30M).

    PubMed

    de Carvalho, Mamede; Conceição, Isabel; Bentes, Carla; Luís, M L Sales

    2002-06-01

    Familial amyloid polyneuropathy (FAP) is associated with massive endoneurial and extracellular deposition of amyloid, which isformed from a mutated transthyretin (TTR) protein. Ninety percent of TTR protein is produced in liver. Liver transplantation (LT) is the only treatment that can halt FAP clinical progression. We studied 35 LT patients. The mean age of the first symptoms was 36.6 years (ranging from 27 to 56), 19 were males, and 16 females, they underwent LT after a mean time of 5 years of symptomatic disease. Fifteen patients followed for more than 24 months after LT had periodic evaluations with clinical and neurophysiological scores (CS and NS). Ten were first evaluated before LT (mean follow-up time of 44 months after LT), and 5 were evaluated only after LT (or a mean time of 41 months). Five patients were followed periodically before LT (mean time of 44 months) to study the natural course of this condition. The mortality rate was of 14% in the first 6 months and was related to known complications of the surgery. No deaths occurred in the period 6 months to 1 year after LT. Five patients (14%) died 1-2 years after LT, 4 of whom were transplanted in advance stages. In the survival group, CS tended to stabilize shortly after LT and to remain invariable later on. The NSprogressed in the first year following LT, and subsequently it did not increase significantly. LT changed the natural course of FAP-I. PMID:12440485

  14. The Evaluation of Liver Function and Surgical Influence by ICGR15 after Chemotherapy for Colorectal Liver Metastases

    PubMed Central

    Hiwatashi, Kiyokazu; Ueno, Shinichi; Sakoda, Masahiko; Iino, Satoshi; Minami, Koji; Mori, Shinichiro; Kita, Yoshiaki; Baba, Kenji; Kurahara, Hiroshi; Mataki, Yuko; Maemura, Kosei; Shinchi, Hiroyuki; Natsugoe, Shoji

    2016-01-01

    Background; Approximately 60% of patients with colorectal cancer develop liver metastasis at some point after diagnosis. The aim of this study is to investigate whether the evaluation of ICGR15 preoperatively is a useful clinical indicator of hepatic injury following chemotherapy and to investigate the influence of multiple chemotherapies on liver function. Results; Mean ICGR15 values were higher in patients ≥65 years (P = 0.047) and in patients with ≥3 cycles (P = 0.022) and ≥6 cycles (P = 0.001) of systemic chemotherapy. ICGR15 values tended to be higher in patients with postoperative complications (P = 0.085). Patients receiving systemic chemotherapy for ≥6 cycles had higher levels of AST (P = 0.003), ALT (P = 0.015), and alkaline phosphatase (ALP) (P = 0.041). Patients receiving systemic chemotherapy for ≥3 cycles had higher levels of AST (P = 0.015) and ALP (P = 0.015). Conclusions; Because the pathological diagnosis is usually established only after operation, preoperative evaluation such as the identification of sinusoidal injury is difficult. Based on this study, higher ICGR15 values may provide an indication of surgical complications and be a predictor of liver dysfunction following frequent cycles of chemotherapy. Hepatectomy should be performed with the utmost care in such patients, and the number of cycles of preoperative chemotherapy should probably be as low as possible. PMID:27053958

  15. Quantitative CT for volumetric analysis of medical images: initial results for liver tumors

    NASA Astrophysics Data System (ADS)

    Behnaz, Alexander S.; Snider, James; Chibuzor, Eneh; Esposito, Giuseppe; Wilson, Emmanuel; Yaniv, Ziv; Cohen, Emil; Cleary, Kevin

    2010-03-01

    Quantitative CT for volumetric analysis of medical images is increasingly being proposed for monitoring patient response during chemotherapy trials. An integrated MATLAB GUI has been developed for an oncology trial at Georgetown University Hospital. This GUI allows for the calculation and visualization of the volume of a lesion. The GUI provides an estimate of the volume of the tumor using a semi-automatic segmentation technique. This software package features a fixed parameter adaptive filter from the ITK toolkit and a tumor segmentation algorithm to reduce inter-user variability and to facilitate rapid volume measurements. The system also displays a 3D rendering of the segmented tumor, allowing the end user to have not only a quantitative measure of the tumor volume, but a qualitative view as well. As an initial validation test, several clinical cases were hand-segmented, and then compared against the results from the tool, showing good agreement.

  16. Mechanical Model Analysis for Quantitative Evaluation of Liver Fibrosis Based on Ultrasound Tissue Elasticity Imaging

    NASA Astrophysics Data System (ADS)

    Shiina, Tsuyoshi; Maki, Tomonori; Yamakawa, Makoto; Mitake, Tsuyoshi; Kudo, Masatoshi; Fujimoto, Kenji

    2012-07-01

    Precise evaluation of the stage of chronic hepatitis C with respect to fibrosis has become an important issue to prevent the occurrence of cirrhosis and to initiate appropriate therapeutic intervention such as viral eradication using interferon. Ultrasound tissue elasticity imaging, i.e., elastography can visualize tissue hardness/softness, and its clinical usefulness has been studied to detect and evaluate tumors. We have recently reported that the texture of elasticity image changes as fibrosis progresses. To evaluate fibrosis progression quantitatively on the basis of ultrasound tissue elasticity imaging, we introduced a mechanical model of fibrosis progression and simulated the process by which hepatic fibrosis affects elasticity images and compared the results with those clinical data analysis. As a result, it was confirmed that even in diffuse diseases like chronic hepatitis, the patterns of elasticity images are related to fibrous structural changes caused by hepatic disease and can be used to derive features for quantitative evaluation of fibrosis stage.

  17. Self-assembling functionalized nanopeptides for immediate hemostasis and accelerative liver tissue regeneration

    NASA Astrophysics Data System (ADS)

    Cheng, Tzu-Yun; Wu, Hsi-Chin; Huang, Ming-Yuan; Chang, Wen-Han; Lee, Chao-Hsiung; Wang, Tzu-Wei

    2013-03-01

    Traumatic injury or surgery may trigger extensive bleeding. However, conventional hemostatic methods have limited efficacy and may cause surrounding tissue damage. In this study, we use self-assembling peptides (SAPs) and specifically extend fragments of functional motifs derived from fibronectin and laminin to evaluate the capability of these functionalized SAPs in the effect of hemostasis and liver tissue regeneration. From the results, these peptides can self-assemble into nanofibrous network structure and gelate into hydrogel with pH adjustment. In animal studies, the efficacy of hemostasis is achieved immediately within seconds in a rat liver model. The histological analyses by hematoxylin-eosin stain and immunohistochemistry reveal that SAPs with these functionalized motifs significantly enhance liver tissue regeneration. In brief, these SAPs may have potential as pharmacological tools to extensively advance clinical therapeutic applications in hemostasis and tissue regeneration in the field of regenerative medicine.Traumatic injury or surgery may trigger extensive bleeding. However, conventional hemostatic methods have limited efficacy and may cause surrounding tissue damage. In this study, we use self-assembling peptides (SAPs) and specifically extend fragments of functional motifs derived from fibronectin and laminin to evaluate the capability of these functionalized SAPs in the effect of hemostasis and liver tissue regeneration. From the results, these peptides can self-assemble into nanofibrous network structure and gelate into hydrogel with pH adjustment. In animal studies, the efficacy of hemostasis is achieved immediately within seconds in a rat liver model. The histological analyses by hematoxylin-eosin stain and immunohistochemistry reveal that SAPs with these functionalized motifs significantly enhance liver tissue regeneration. In brief, these SAPs may have potential as pharmacological tools to extensively advance clinical therapeutic applications

  18. What Is Liver Cancer?

    MedlinePlus

    ... Topic Key statistics about liver cancer What is liver cancer? Cancer starts when cells in the body ... structure and function of the liver. About the liver The liver is the largest internal organ. It ...

  19. Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

    PubMed Central

    Honda, Koichi; Seike, Masataka; Oribe, Junya; Endo, Mizuki; Arakawa, Mie; Syo, Hiroki; Iwao, Masao; Tokoro, Masanori; Nishimura, Junko; Mori, Tetsu; Yamashita, Tsutomu; Fukuchi, Satoshi; Muro, Toyokichi; Murakami, Kazunari

    2016-01-01

    AIM: To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS: A total of 123 patients with hepatitis B virus- or hepatitis C virus-related hepatocellular car-cinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS: CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as signi-ficant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION: Long-term liver function following RFA was dependent on liver functional reserve, the degree of fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. PMID:27168872

  20. [Liver and artificial liver].

    PubMed

    Chamuleau, R A

    1998-06-01

    Despite good results of orthotopic liver transplantation in patients with fulminant hepatic failure the need still exists for an effective and safe artificial liver, able to temporarily take over the complex liver function so as to bridge the gap with transplantation or regeneration. Attempts to develop non-biological artificial livers have failed, mostly when controlled clinical trials were performed. In the last decade several different types of bioartificial livers have been devised, in which the biocomponent consists of freshly isolated porcine hepatocytes or a human hepatoblastoma cell line. The majority use semipermeable hollow fibers known from artificial kidney devices. The liver cells may lie either inside or outside the lumen of these fibers. In vitro analysis of liver function and animal experimental work showing that the bioartificial liver increases survival justify clinical application. Bioartificial livers are connected to patients extracorporeally by means of plasmapheresis circuit for periods of about 6 hours. In different trials about 40 patients with severe liver failure have been treated. No important adverse effects have not been reported in these phase I trials. Results of controlled studies are urgently needed. As long as no satisfactory immortalised human liver cell line with good function is available, porcine hepatocytes will remain the first choice, provided transmission of porcine pathogens to man is prevented. PMID:9752034

  1. Novel strategy to decrease reperfusion injuries and improve function of cold-preserved livers using normothermic ex vivo liver perfusion machine.

    PubMed

    Banan, Babak; Xiao, Zhenyu; Watson, Rao; Xu, Min; Jia, Jianluo; Upadhya, Gundumi A; Mohanakumar, Thalachallour; Lin, Yiing; Chapman, William

    2016-03-01

    Normothermic extracorporeal liver perfusion (NELP) can decrease ischemia/reperfusion injury to the greatest degree when cold ischemia time is minimized. Warm perfusion of cold-stored livers results in hepatocellular damage, sinusoidal endothelial cell (SEC) dysfunction, and Kupffer cell activation. However, the logistics of organ procurement mandates a period of cold preservation before NELP. The aim of this study was to determine the beneficial effects of gradual rewarming of cold-stored livers by placement on NELP. Three female porcine livers were used for each group. In the immediate NELP group, procured livers were immediately placed on NELP for 8 hours. In the cold NELP group, livers were cold-stored for 4 hours followed by NELP for 4 hours. In rewarming groups, livers were cold-stored for 4 hours, then gradually rewarmed in different durations to 38°C and kept on NELP for an additional 4 hours. For comparison purposes, the last 4 hours of NELP runs were considered to be the evaluation phase. Immediate NELP livers had significantly lower concentrations of liver transaminases, hyaluronic acid, and β-galactosidase and had higher bile production compared to the other groups. Rewarming livers had significantly lower concentrations of hyaluronic acid and β-galactosidase compared to the cold NELP livers. In addition, there was a significant decline in international normalized ratio values, improved bile production, reduced biliary epithelial cell damage, and improved cholangiocyte function. Thus, if a NELP machine is not available at the procurement site and livers will need to undergo a period of cold preservation, a gradual rewarming protocol before NELP may greatly reduce damages that are associated with reperfusion. In conclusion, gradual rewarming of cold-preserved livers upon NELP can minimize the hepatocellular damage, Kupffer cell activation, and SEC dysfunction. PMID:26439190

  2. Prediction of liver disease in patients whose liver function tests have been checked in primary care: model development and validation using population-based observational cohorts

    PubMed Central

    McLernon, David J; Donnan, Peter T; Sullivan, Frank M; Roderick, Paul; Rosenberg, William M; Ryder, Steve D; Dillon, John F

    2014-01-01

    Objective To derive and validate a clinical prediction model to estimate the risk of liver disease diagnosis following liver function tests (LFTs) and to convert the model to a simplified scoring tool for use in primary care. Design Population-based observational cohort study of patients in Tayside Scotland identified as having their LFTs performed in primary care and followed for 2 years. Biochemistry data were linked to secondary care, prescriptions and mortality data to ascertain baseline characteristics of the derivation cohort. A separate validation cohort was obtained from 19 general practices across the rest of Scotland to externally validate the final model. Setting Primary care, Tayside, Scotland. Participants Derivation cohort: LFT results from 310 511 patients. After exclusions (including: patients under 16 years, patients having initial LFTs measured in secondary care, bilirubin >35 μmol/L, liver complications within 6 weeks and history of a liver condition), the derivation cohort contained 95 977 patients with no clinically apparent liver condition. Validation cohort: after exclusions, this cohort contained 11 653 patients. Primary and secondary outcome measures Diagnosis of a liver condition within 2 years. Results From the derivation cohort (n=95 977), 481 (0.5%) were diagnosed with a liver disease. The model showed good discrimination (C-statistic=0.78). Given the low prevalence of liver disease, the negative predictive values were high. Positive predictive values were low but rose to 20–30% for high-risk patients. Conclusions This study successfully developed and validated a clinical prediction model and subsequent scoring tool, the Algorithm for Liver Function Investigations (ALFI), which can predict liver disease risk in patients with no clinically obvious liver disease who had their initial LFTs taken in primary care. ALFI can help general practitioners focus referral on a small subset of patients with higher predicted risk

  3. Functional renal failure (FRF) in cirrhosis of the liver and liver carcinoma

    PubMed Central

    Vesin, P.; Traverso, H.

    1975-01-01

    The term ‘functional renal failure’ has been used to describe the renal failure developing in advanced cirrhosis in which tubular function and structure remain intact. It may develop spontaneously, in which case prognosis is poor, but may be secondary to gastro-intestinal haemorrhage or excessive use of diuretics, in which case correction of the precipitating factor leads to improvement in renal function. It is suggested that the renal failure is due to a reduction in effective circulating plasma volume. PMID:1234327

  4. Pathological and ultrastructural observations and liver function analysis of Eimeria stiedai-infected rabbits.

    PubMed

    Jing, Jin; Liu, Chun; Zhu, Shun-Xing; Jiang, Ying-Mei; Wu, Liu-Cheng; Song, Hong-Yan; Shao, Yi-Xiang

    2016-06-15

    To study the pathogenicity of Eimeria stiedai, sporulated oocysts were given orally to coccidian-free two-month-old New Zealand rabbits(1000±20g). After 30days, blood samples from the rabbit hearts were collected for routine blood tests, liver functions and four characteristics of blood coagulation. Additionally, specimens of the liver, bile duct and duodenum were collected to observe the changes in pathology and ultrastructure. E. stiedai severely restricted the growth and development of rabbits. Blood tests showed that glutamine transferase (GGT) and serum cholinesterase (ChE) were significantly different from the non-infected controls. Other extremely significant differences were observed in the biochemical indices of routine blood tests, liver function and four blood coagulation characteristics, indicating that the liver functions were significantly affected. Staining showed that, compared with the negative control group, the liver, bile duct and duodenum contained significant numbers of lesions, and organs and cell structures suffered severe damage in ultrastructure, which greatly affecting bodily functions. E. stiedai-infected rabbits model was successfully established, which might provide a theoretical basis for research on the pathogenesis of rabbit coccidia, and the diagnosis and prevention of coccidiosis in rabbits. PMID:27198796

  5. Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

    PubMed Central

    Donnan, Peter T; McLernon, David; Steinke, Douglas; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

    2007-01-01

    Background Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs. Methods/Design A population-based retrospective cohort study will follow up all those who have had an incident liver function test (LFT) in primary care to subsequent liver disease or mortality over a period of 15 years (approx. 2.3 million tests in 99,000 people). The study is set in Primary Care in the region of Tayside, Scotland (pop approx. 429,000) between 1989 and 2003. The target population consists of patients with no recorded clinical signs or symptoms of liver disease and registered with a GP. The health technologies being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside (ELDIT) database to determine the outcomes of liver disease. These are based on hospital admission data (Scottish Morbidity Record 1), dispensed medication records, death certificates, and examination of medical records from Tayside hospitals. A sample of patients (n = 150) with recent initial ALF tests or invitation to biopsy will complete questionnaires to obtain quality of life data and anxiety measures. Cost-effectiveness and cost utility Markov model analyses will be performed from health service and patient perspectives using standard NHS costs. The findings will also be used to develop a computerised clinical decision support tool. Discussion

  6. Quantitative alterations in the liver and adrenal gland in pregnant rats induced by Pyralene 3000

    SciTech Connect

    Vreci, M.; Sek, S.; Lorger, J.; Bavdek, S.; Pogacnik, A.

    1995-06-01

    Polychlorinated biphenyls (PCBs) are among the most widespread environmental pollutants known in the world. The half-life of PCBs is very long and, therefore, once released into the environment, they accumulate in food chains and tissues of various mammals, including man. Their presence can cause numerous toxic effects, e.g., hepatotoxicity, immunotoxicity, dermatotoxicity, neurotoxicity, and disorders of the reproductive system, among others. These effects depend on the distribution route in the organism, the rate of metabolism and excretion. Their characteristics are closely associated with the number and position of the chlorine atoms in the molecule. Previous studies of trichlorobiphenyl distributions in various tissues demonstrated that low chlorinated trichlorobiphenyls do no accumulate in endocrine organs, whereas higher chlorinated biphenyls, such as hexa- and octachlorobiphenyl, are deposited and retained in the adrenal gland. A selective distribution of radioabelled tetrachlorobiphenyl to the zona fasciculata, accompanied by morphometric evidence of the hypertrophy of the zona fasciculata, was also noted. The purpose of this study was to examine changes in the tissue structure of the pregnant rat liver and adrenal gland induced experimentally by Pyralene 3000 administration. We chose this commercial low chlorinated PCB because it was in use in Slovenia and, discharged from the electroindustrial plants, caused a serious incidence of environmental pollution in the region of Bela Krajina. Our further aim was to research the transplacental influences of Pyralene 3000 in rats. 17 refs., 1 fig., 3 tabs.

  7. Quantitative evaluation of six graph based semi-automatic liver tumor segmentation techniques using multiple sets of reference segmentation

    NASA Astrophysics Data System (ADS)

    Su, Zihua; Deng, Xiang; Chefd'hotel, Christophe; Grady, Leo; Fei, Jun; Zheng, Dong; Chen, Ning; Xu, Xiaodong

    2011-03-01

    Graph based semi-automatic tumor segmentation techniques have demonstrated great potential in efficiently measuring tumor size from CT images. Comprehensive and quantitative validation is essential to ensure the efficacy of graph based tumor segmentation techniques in clinical applications. In this paper, we present a quantitative validation study of six graph based 3D semi-automatic tumor segmentation techniques using multiple sets of expert segmentation. The six segmentation techniques are Random Walk (RW), Watershed based Random Walk (WRW), LazySnapping (LS), GraphCut (GHC), GrabCut (GBC), and GrowCut (GWC) algorithms. The validation was conducted using clinical CT data of 29 liver tumors and four sets of expert segmentation. The performance of the six algorithms was evaluated using accuracy and reproducibility. The accuracy was quantified using Normalized Probabilistic Rand Index (NPRI), which takes into account of the variation of multiple expert segmentations. The reproducibility was evaluated by the change of the NPRI from 10 different sets of user initializations. Our results from the accuracy test demonstrated that RW (0.63) showed the highest NPRI value, compared to WRW (0.61), GWC (0.60), GHC (0.58), LS (0.57), GBC (0.27). The results from the reproducibility test indicated that GBC is more sensitive to user initialization than the other five algorithms. Compared to previous tumor segmentation validation studies using one set of reference segmentation, our evaluation methods use multiple sets of expert segmentation to address the inter or intra rater variability issue in ground truth annotation, and provide quantitative assessment for comparing different segmentation algorithms.

  8. Quantitative analysis of aberrant protein glycosylation in liver cancer plasma by AAL-enrichment and MRM mass spectrometry.

    PubMed

    Ahn, Yeong Hee; Shin, Park Min; Kim, Yong-Sam; Oh, Na Ree; Ji, Eun Sun; Kim, Kwang Hoe; Lee, Yeon Jung; Kim, Sung Ho; Yoo, Jong Shin

    2013-11-01

    A lectin-coupled mass spectrometry (MS) approach was employed to quantitatively monitor aberrant protein glycosylation in liver cancer plasma. To do this, we compared the difference in the total protein abundance of a target glycoprotein between hepatocellular carcinoma (HCC) plasmas and hepatitis B virus (HBV) plasmas, as well as the difference in lectin-specific protein glycoform abundance of the target glycoprotein. Capturing the lectin-specific protein glycoforms from a plasma sample was accomplished by using a fucose-specific aleuria aurantia lectin (AAL) immobilized onto magnetic beads via a biotin-streptavidin conjugate. Following tryptic digestion of both the total plasma and its AAL-captured fraction of each HCC and HBV sample, targeted proteomic mass spectrometry was conducted quantitatively by a multiple reaction monitoring (MRM) technique. From the MRM-based analysis of the total plasmas and AAL-captured fractions, differences between HCC and HBV plasma groups in fucosylated glycoform levels of target glycoproteins were confirmed to arise from both the change in the total protein abundance of the target proteins and the change incurred by aberrant fucosylation on target glycoproteins in HCC plasma, even when no significant change occurs in the total protein abundance level. Combining the MRM-based analysis method with the lectin-capturing technique proved to be a successful means of quantitatively investigating aberrant protein glycosylation in cancer plasma samples. Additionally, it was elucidated that the differences between HCC and control groups in fucosylated biomarker candidates A1AT and FETUA mainly originated from an increase in fucosylation levels on these target glycoproteins, rather than an increase in the total protein abundance of the target glycoproteins. PMID:24027776

  9. Role of Gut Barrier Function in the Pathogenesis of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Dai, Xin; Wang, Bangmao

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver disease, and its incidence is increasing year by year. Many efforts have been made to investigate the pathogenesis of this disease. Since 1998 when Marshall proposed the conception of “gut-liver axis,” more and more researchers have paid close attention to the role of gut barrier function in the pathogenesis of NAFLD. The four aspects of gut barrier function, including physical, chemical, biological, and immunological barriers, are interrelated closely and related to NAFLD. In this paper, we present a summary of research findings on the relationship between gut barrier dysfunction and the development of NAFLD, aiming at illustrating the role of gut barrier function in the pathogenesis of this disease. PMID:25945084

  10. Quantitative Reasoning and the Sine Function: The Case of Zac

    ERIC Educational Resources Information Center

    Moore, Kevin C.

    2014-01-01

    A growing body of literature has identified quantitative and covariational reasoning as critical for secondary and undergraduate student learning, particularly for topics that require students to make sense of relationships between quantities. The present study extends this body of literature by characterizing an undergraduate precalculus…

  11. Sleep deprivation predisposes liver to oxidative stress and phospholipid damage: a quantitative molecular imaging study

    PubMed Central

    Chang, Hung-Ming; Mai, Fu-Der; Chen, Bo-Jung; Wu, Un-In; Huang, Yi-Lun; Lan, Chyn-Tair; Ling, Yong-Chien

    2008-01-01

    Sleep disorders are associated with an increased rate of various metabolic disturbances, which may be related to oxidative stress and consequent lipid peroxidation. Since hepatic phosphatidylcholine plays an important role in metabolic regulation, the aim of the present study was to determine phosphatidylcholine expression in the liver following total sleep deprivation. To determine the effects of total sleep deprivation, we used adult rats implanted for polygraphic recording. Phosphatidylcholine expression was examined molecularly by the use of time-of-flight secondary ion mass spectrometry, along with biochemical solid-phase extraction. The parameters of oxidative stress were investigated by evaluating the hepatic malondialdehyde levels as well as heat shock protein 25 immunoblotting and immunohistochemistry. In normal rats, the time-of-flight secondary ion mass spectrometry spectra revealed specific peaks (m/z 184 and 224) that could be identified as molecular ions for phosphatidylcholine. However, following total sleep deprivation, the signals for phosphatidylcholine were significantly reduced to nearly one-third of the normal values. The results of solid-phase extraction also revealed that the phosphatidylcholine concentration was noticeably decreased, from 15.7 µmol g–1 to 9.4 µmol g–1, after total sleep deprivation. By contrast, the biomarkers for oxidative stress were drastically up-regulated in the total sleep deprivation-treated rats as compared with the normal ones (4.03 vs. 1.58 nmol mg–1 for malondialdehyde levels, and 17.1 vs. 6.7 as well as 1.8 vs. 0.7 for heat shock protein 25 immunoblotting and immunoreactivity, respectively). Given that phosphatidylcholine is the most prominent component of all plasma lipoproteins, decreased expression of hepatic phosphatidylcholine following total sleep deprivation may be attributed to the enhanced oxidative stress and the subsequent lipid peroxidation, which would play an important role in the formation

  12. Deranged liver function tests in pregnancy: the importance of postnatal follow-up

    PubMed Central

    Stone, Sophia; Girling, Joanna C

    2009-01-01

    We report an asymptomatic 40-year-old woman with persistently deranged liver function tests found incidentally in the first trimester of her second pregnancy. No cause was apparent clinically, serologically or with imaging studies until a new finding of hepatomegaly led to a repeat ultrasound scan six weeks following delivery. A mass in the region of the common hepatic duct was confirmed to be a cholangiocarcinoma, with vascular invasion precluding curative surgical resection. This case highlights the need for close vigilance of patients with unexplained and persistently abnormal liver function tests, antenatally and postdelivery.

  13. Abnormal Liver Function Tests in an Anorexia Nervosa Patient and an Atypical Manifestation of Refeeding Syndrome

    PubMed Central

    Vootla, Vamshidhar R.; Daniel, Myrta

    2015-01-01

    Refeeding syndrome is defined as electrolyte and fluid abnormalities that occur in significantly malnourished patients when they are refed orally, enterally, or parenterally. The principal manifestations include hypophosphatemia, hypokalemia, vitamin deficiencies, volume overload and edema. This can affect multiple organ systems, such as the cardiovascular, pulmonary, or neurological systems, secondary to the above-mentioned abnormalities. Rarely, patients may develop gastrointestinal symptoms and show abnormal liver function test results. We report the case of a 52-year-old woman with anorexia nervosa who developed refeeding syndrome and simultaneous elevations of liver function test results, which normalized upon the resolution of the refeeding syndrome. PMID:26351414

  14. The functional role of some tomato products on lipid profile and liver function in adult rats.

    PubMed

    Ibrahim, Hoda Salama; Ahmed, Lamiaa Ali; El-din, Maha Mohamed Essam

    2008-09-01

    This study was carried out to investigate the functional role of lycopene obtained from powder prepared from fresh tomato, tomato paste, and ketchup that contained equal amounts of lycopene based on levels of intake on body weight gain (BWG), feed intake, feed efficiency ratio (FER), lipid profiles, atherogenic index, and liver enzymes of hyperlipidemic rats. Forty-eight male albino rats were divided into two main groups: the first group (n = 6 rats) was kept on the basal diet as a normal control, while the second group (n = 42 rats) was fed a hyperlipidemic diet for 5 weeks to induce hyperlipidemia. The latter group was divided into seven subgroups: the first subgroup was the positive control group, while the others were supplemented with one of the tomato products at one of two levels (10 or 20 mg of lycopene/kg of diet). BWG, feed intake, and FER were calculated, and blood samples were collected to determine total lipids, total cholesterol, triglycerides, lipoprotein fractions, atherogenic index, and liver function in sera. Relative organ weights were also calculated. Results revealed that administration of various tomato products produced a significant reduction in feed intake except for the hyperlipidemic group that supplemented with the lower lycopene level from tomato paste. In addition, BWG and FER were not influenced by addition of tomato products at any level of intake. Hyperlipidemic rats supplemented with tomato powder, tomato paste, or ketchup showed significant improvement in almost all the parameters studied compared to the positive control group. Results showed that the higher lycopene level from tomato paste produced significant improvement in all lipid parameters, followed by 10 mg of lycopene/kg from tomato paste, which caused significant elevation in high-density lipoprotein cholesterol comparable to that of the negative control group. The lowest atherogenic index was achieved by addition of the lower lycopene level from tomato paste followed by

  15. The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers.

    PubMed

    Takeshita, T; Yang, X; Morimoto, K

    2000-06-01

    A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (<100). The subjects completed a questionnaire on alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males. PMID:10942105

  16. The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases

    PubMed Central

    Liu, Wei-hui; Song, Fu-qiang; Ren, Li-na; Guo, Wen-qiong; Wang, Tao; Feng, Ya-xing; Tang, Li-jun; Li, Kun

    2015-01-01

    Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesodermal mesenchyme. MSCs can be obtained from a variety of tissues, including bone marrow, umbilical cord tissue, umbilical cord blood, peripheral blood and adipose tissue. Under certain conditions, MSCs can differentiate into many cell types both in vitro and in vivo, including hepatocytes. To date, four main strategies have been developed to induce the transdifferentiation of MSCs into hepatocytes: addition of chemical compounds and cytokines, genetic modification, adjustment of the micro-environment and alteration of the physical parameters used for culturing MSCs. Although the phenomenon of transdifferentiation of MSCs into hepatocytes has been described, the detailed mechanism is far from clear. Generally, the mechanism is a cascade reaction whereby stimulating factors activate cellular signalling pathways, which in turn promote the production of transcription factors, leading to hepatic gene expression. Because MSCs can give rise to hepatocytes, they are promising to be used as a new treatment for liver dysfunction or as a bridge to liver transplantation. Numerous studies have confirmed the therapeutic effects of MSCs on hepatic fibrosis, cirrhosis and other liver diseases, which may be related to the differentiation of MSCs into functional hepatocytes. In addition to transdifferentiation into hepatocytes, when MSCs are used to treat liver disease, they may also inhibit hepatocellular apoptosis and secrete various bioactive molecules to promote liver regeneration. In this review, the capacity and molecular mechanism of MSC transdifferentiation, and the therapeutic effects of MSCs on liver diseases are thoroughly discussed. PMID:25534251

  17. Dual function microscope for quantitative DIC and birefringence imaging

    NASA Astrophysics Data System (ADS)

    Li, Chengshuai; Zhu, Yizheng

    2016-03-01

    A spectral multiplexing interferometry (SXI) method is presented for integrated birefringence and phase gradient measurement on label-free biological specimens. With SXI, the retardation and orientation of sample birefringence are simultaneously encoded onto two separate spectral carrier waves, generated by a crystal retarder oriented at a specific angle. Thus sufficient information for birefringence determination can be obtained from a single interference spectrum, eliminating the need for multiple acquisitions with mechanical rotation or electrical modulation. In addition, with the insertion of a Nomarski prism, the setup can then acquire quantitative differential interference contrast images. Red blood cells infected by malaria parasites are imaged for birefringence retardation as well as phase gradient. The results demonstrate that the SXI approach can achieve both quantitative phase imaging and birefringence imaging with a single, high-sensitivity system.

  18. Patterns and predictors of sexual function after liver donation: The Adult-to-Adult Living Donor Liver Transplantation Cohort study.

    PubMed

    DiMartini, Andrea F; Dew, Mary Amanda; Butt, Zeeshan; Simpson, Mary Ann; Ladner, Daniela P; Smith, Abigail R; Hill-Callahan, Peg; Gillespie, Brenda W

    2015-05-01

    Although sexual functioning is an important facet of a living donor's quality of life, it has not received an extensive evaluation in this population. Using data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, we examined donor sexual functioning across the donation process from the predonation evaluation to 3 months and 1 year after donation. Donors (n = 208) and a comparison group of nondonors (n = 155) completed self-reported surveys with specific questions on sexual desire, satisfaction, orgasm, and (for men) erectile function. Across the 3 time points, donor sexual functioning was lower at the evaluation phase and 3 months after donation versus 1 year after donation. In the early recovery period, abdominal pain was associated with difficulty reaching orgasm [odds ratio (OR), 3.98; 95% confidence interval (CI), 1.30-12.16], concerns over appearance were associated with lower sexual desire (OR, 4.14; 95% CI, 1.02-16.79), and not feeling back to normal was associated with dissatisfaction with sexual life (OR, 3.58; 95% CI, 1.43-8.99). Efforts to educate donors before the surgery and prepare them for the early recovery phase may improve recovery and reduce distress regarding sexual functioning. PMID:25779554

  19. Characterization of liver-specific structure and function during hepatocyte spheroid self-assembly: Implications for a bioartificial liver device

    NASA Astrophysics Data System (ADS)

    Friend, Julie Renee

    A hollow fiber bioreactor containing collagen-entrapped hepatocytes has been developed as a bioartificial liver device. For clinical application, further scale-up of the device is desirable. This may be achieved through the use of hepatocyte spheroids, which are compacted aggregates that exhibit prolonged viability, higher liver-specific function and a more tissue-like ultrastructure compared to hepatocytes cultured as monolayers. In order to gain a better understanding of structural changes in spheroids over the course of their self-assembly, confocal microscopy was used to optically section spheroids and monitor changes in situ. Channels within spheroids hypothesized to be bile canaliculi were first evaluated by monitoring the diffusion of a fluorescent tracer, FITC-dextran, into spheroids. Three-dimensional reconstruction of spheroids showed that a continuous network of channels was forming within spheroids. Functionality of these channels as bile canaliculi was demonstrated by monitoring secretion of a fluorescently tagged bile acid, FITC-glycocholate, by hepatocytes in spheroids. Secretion of FITC-glycocholate could be seen in both rat and porcine hepatocyte spheroids. To elucidate changes in metabolism occurring during spheroid self-assembly, metabolic flux analysis was applied to hepatocyte spinner cultures. Glucose, lactate, amino acid, albumin and urea concentration in culture medium were measured and used to estimate intracellular fluxes within hepatocytes. Metabolism before and after spheroid formation was compared. Overall, little difference was seen in metabolism before and after spheroid self-assembly. As the BAL approaches clinical trials, methods of bioreactor storage for shipping and inventory purposed need to be developed. Storage conditions were tested in various hepatocyte culture systems. A protocol for storing reactors for 24 hours without significant loss in function was developed. Further optimization will be necessary for storage for longer

  20. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    PubMed Central

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). DDC is metabolized mainly by cytochrome P450 (Cyp)3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC. PMID:26967735

  1. Expression and function of the atypical cadherin FAT1 in chronic liver disease

    SciTech Connect

    Valletta, Daniela; Czech, Barbara; Thasler, Wolfgang E.; Mueller, Martina; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer The expression of the atypical cadherin FAT1 is increased in chronic liver disease. Black-Right-Pointing-Pointer FAT1 expression goes up during the activation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Activated HSCs are the cellular source of enhanced FAT1 expression in diseased livers. Black-Right-Pointing-Pointer FAT1 enhanced NFkB activity and resistance to apoptosis in activated HSCs. Black-Right-Pointing-Pointer FAT1 is a new therapeutic target for prevention and treatment of hepatic fibrosis. -- Abstract: Hepatic fibrosis can be considered as wound healing process in response to hepatocellular injury. Activation of hepatic stellate cells (HSCs) is a key event of hepatic fibrosis since activated HSCs are the cellular source of enhanced extracellular matrix deposition, and reversion of liver fibrosis is accompanied by clearance of activated HSCs by apoptosis. The atypical cadherin FAT1 has been shown to regulate diverse biological functions as cell proliferation and planar cell polarity, and also to affect wound healing. Here, we found increased FAT1 expression in different murine models of chronic liver injury and in cirrhotic livers of patients with different liver disease. Also in hepatic tissue of patients with non-alcoholic steatohepatitis FAT1 expression was significantly enhanced and correlated with collagen alpha I(1) expression. Immunohistochemistry revealed no significant differences in staining intensity between hepatocytes in normal and cirrhotic liver tissue but myofibroblast like cells in fibrotic septa of cirrhotic livers showed a prominent immunosignal. Furthermore, FAT1 mRNA and protein expression markedly increased during in vitro activation of primary human and murine HSCs. Together, these data indicated activated HSCs as cellular source of enhanced FAT1 expression in diseased livers. To gain insight into the functional role of FAT1 in activated HSCs we suppressed FAT1 in these

  2. CT/99mTc-GSA SPECT fusion images demonstrate functional differences between the liver lobes

    PubMed Central

    Sumiyoshi, Tatsuaki; Shima, Yasuo; Tokorodani, Ryoutarou; Okabayashi, Takehiro; Kozuki, Akihito; Hata, Yasuhiro; Noda, Yoshihiro; Murata, Yoriko; Nakamura, Toshio; Uka, Kiminori

    2013-01-01

    AIM: To evaluate the functional differences between the 2 liver lobes in non-cirrhotic patients by using computed tomography/99mTc-galactosyl human serum albumin (CT/99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODS: Between December 2008 and March 2012, 264 non-cirrhotic patients underwent preoperative liver function assessment using CT/99mTc-GSA SPECT fusion images. Of these, 30 patients, in whom the influence of a tumor on the liver parenchyma was estimated to be negligible, were selected. Specifically, the selected patients were required to meet either of the following criteria: (1) the presence of an extrahepatic tumor; or (2) presence of a single small intrahepatic tumor. These 30 patients were retrospectively analyzed to calculate the percentage volume (%Volume) and the percentage function (%Function) of each lobe. The ratio between the %Function and %Volume (function-to-volume ratio) of each lobe was also calculated, and the ratios were compared between the 2 lobes. Furthermore, the correlations between the function-to-volume ratio and each of 2 liver parameters [lobe volume and diameter ratio of the left portal vein to the right portal vein (LPV-to-RPV diameter ratio)] were investigated. RESULTS: The median values of %Volume and %Function were 62.6% and 67.1% in the right lobe, with %Function being significantly higher than %Volume (P < 0.01). The median values of %Volume and %Function were 31.0% and 28.7% in the left lobe, with %Function being significantly lower than %Volume (P < 0.01). The function-to-volume ratios of the right lobe (1.04-1.14) were significantly higher than those of the left lobe (0.74-0.99) (P < 0.01). The function-to-volume ratio showed no significant correlation between the lobe volume in either lobe. In contrast, the function-to-volume ratio showed significant correlations with the LPV-to-RPV diameter ratio in both lobes (right lobe: negative correlation, rs = -0.37, P = 0.048; left lobe: positive

  3. Measuring Markers of Liver Function Using a Micro-Patterned Paper Device Designed for Blood from a Fingerstick

    PubMed Central

    Vella, Sarah J.; Beattie, Patrick; Cademartiri, Rebecca; Laromaine, Anna; Martinez, Andres W.; Phillips, Scott T.; Mirica, Katherine A.

    2012-01-01

    This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase ALP, and aspartate aminotransferase AST) and total serum protein. A device consists of four components: i) a top plastic sheet, ii) a filter membrane, iii) a patterned paper chip containing the reagents necessary for analysis, and iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and “spiked” standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings. PMID:22390675

  4. Assessment of portal contribution to liver perfusion by quantitative sequential scintigraphy and Doppler ultrasound in alcoholic cirrhosis. Diagnostic value in the detection of portal hypertension.

    PubMed

    Dao, T; Elfadel, S; Bouvard, G; Bouvard, N; Lecointe, I; Jardin-Grimaux, I; Verwaerde, J C; Valla, A

    1993-03-01

    To assess the portal contribution to liver perfusion, we carried out quantitative sequential scintigraphy in 110 patients with alcoholic cirrhosis (22 Child-Pugh class A, 39 class B, 49 class C) and 15 normal subjects. Duplex Doppler ultrasound found a type of intrahepatic circulation that made the standard scintigraphic procedure inaccurate in four cases of cirrhosis, which were reevaluated. Portal contribution to liver perfusion was lower in cirrhotics than in normal subjects (48.7 +/- 29% versus 78.4 +/- 6%; p < 0.001). The sensitivity of scintigraphy in detecting portal hypertension, based on portal contribution < or = 66%, was 61.8% (with a 100% specificity) compared with 66.7% for endoscopy (diagnosis based on existence of varices). The overall sensitivity of the two tests together was 86.1%. Portal contribution to liver perfusion was inversely correlated to Child-Pugh score (r = 0.53; p < 0.001), to prothrombin time (r = 0.52; p < 0.001), and to hepatic venous pressure gradient (r = 0.43; p < 0.001) and positively correlated to albuminemia (r = 0.42; p < 0.001). Concurrent alcoholic hepatitis and the existence of large portosystemic collaterals were related to a decrease in portal contribution to liver perfusion. We conclude that quantitative sequential scintigraphy, which shows a direct relationship between portal contribution to liver perfusion, on the one hand, and the amount of portosystemic shunting, the progression of liver disease, and/or acute liver injury, on the other, could serve as a diagnostic test for portal hypertension. The addition of scintigraphy improves the overall sensitivity of endoscopy. PMID:8463621

  5. Prep1 Controls Insulin Glucoregulatory Function in Liver by Transcriptional Targeting of SHP1 Tyrosine Phosphatase

    PubMed Central

    Oriente, Francesco; Iovino, Salvatore; Cabaro, Serena; Cassese, Angela; Longobardi, Elena; Miele, Claudia; Ungaro, Paola; Formisano, Pietro; Blasi, Francesco; Beguinot, Francesco

    2011-01-01

    OBJECTIVE We investigated the function of the Prep1 gene in insulin-dependent glucose homeostasis in liver. RESEARCH DESIGN AND METHODS Prep1 action on insulin glucoregulatory function has been analyzed in liver of Prep1-hypomorphic mice (Prep1i/i), which express 2–3% of Prep1 mRNA. RESULTS Based on euglycemic hyperinsulinemic clamp studies and measurement of glycogen content, livers from Prep1i/i mice feature increased sensitivity to insulin. Tyrosine phosphorylation of both insulin receptor (IR) and insulin receptor substrate (IRS)1/2 was significantly enhanced in Prep1i/i livers accompanied by a specific downregulation of the SYP and SHP1 tyrosine phosphatases. Prep1 overexpression in HepG2 liver cells upregulated SYP and SHP1 and inhibited insulin-induced IR and IRS1/2 phosphorylation and was accompanied by reduced glycogen content. Consistently, overexpression of the Prep1 partner Pbx1, but not of p160MBP, mimicked Prep1 effects on tyrosine phosphorylations, glycogen content, and on SYP and SHP1 expression. In Prep1 overexpressing cells, antisense silencing of SHP1, but not that of SYP, rescued insulin-dependent IR phosphorylation and glycogen accumulation. Both Prep1 and Pbx1 bind SHP1 promoter at a site located between nucleotides −2,113 and −1,778. This fragment features enhancer activity and induces luciferase function by 7-, 6-, and 30-fold, respectively, in response to Prep1, Pbx1, or both. CONCLUSIONS SHP1, a known silencer of insulin signal, is a transcriptional target of Prep1. In liver, transcriptional activation of SHP1 gene by Prep1 attenuates insulin signal transduction and reduces glucose storage. PMID:20864515

  6. All-Trans-Retinoic Acid Enhances Mitochondrial Function in Models of Human Liver.

    PubMed

    Tripathy, Sasmita; Chapman, John D; Han, Chang Y; Hogarth, Cathryn A; Arnold, Samuel L M; Onken, Jennifer; Kent, Travis; Goodlett, David R; Isoherranen, Nina

    2016-05-01

    All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. The liver is the main storage organ of vitamin A, but activation of the retinoic acid receptors (RARs) in mouse liver and in human liver cell lines has also been shown. AlthoughatRA treatment improves mitochondrial function in skeletal muscle in rodents, its role in modulating mitochondrial function in the liver is controversial, and little data are available regarding the human liver. The aim of this study was to determine whetheratRA regulates hepatic mitochondrial activity.atRA treatment increased the mRNA and protein expression of multiple components of mitochondrialβ-oxidation, tricarboxylic acid (TCA) cycle, and respiratory chain. Additionally,atRA increased mitochondrial biogenesis in human hepatocytes and in HepG2 cells with and without lipid loading based on peroxisome proliferator activated receptor gamma coactivator 1αand 1βand nuclear respiratory factor 1 mRNA and mitochondrial DNA quantification.atRA also increasedβ-oxidation and ATP production in HepG2 cells and in human hepatocytes. Knockdown studies of RARα, RARβ, and PPARδrevealed that the enhancement of mitochondrial biogenesis andβ-oxidation byatRA requires peroxisome proliferator activated receptor delta. In vivo in mice,atRA treatment increased mitochondrial biogenesis markers after an overnight fast. Inhibition ofatRA metabolism by talarozole, a cytochrome P450 (CYP) 26 specific inhibitor, increased the effects ofatRA on mitochondrial biogenesis markers in HepG2 cells and in vivo in mice. These studies show thatatRA regulates mitochondrial function and lipid metabolism and that increasingatRA concentrations in human liver via CYP26 inhibition may increase mitochondrial biogenesis and fatty acidβ-oxidation and provide therapeutic benefit in diseases associated with mitochondrial dysfunction. PMID:26921399

  7. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes

    PubMed Central

    TANAKA, Hiroshi; TAKEO, Shun; ABE, Takahito; KIN, Airi; SHIRASUNA, Koumei; KUWAYAMA, Takehito; IWATA, Hisataka

    2016-01-01

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  8. Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes.

    PubMed

    Tanaka, Hiroshi; Takeo, Shun; Abe, Takahito; Kin, Airi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2016-06-17

    The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

  9. Synthesis of functionalized magnetite nanoparticles to use as liver targeting MRI contrast agent

    NASA Astrophysics Data System (ADS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe3O4 nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe3O4-SiO2-mebrofenin composite is an effective MRI contrast agent for liver targeting.

  10. Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology

    PubMed Central

    2014-01-01

    The liver is a central immunological organ. Liver resident macrophages, Kupffer cells (KC), but also sinusoidal endothelial cells, dendritic cells (DC) and other immune cells are involved in balancing immunity and tolerance against pathogens, commensals or food antigens. Hepatic stellate cells (HSCs) have been primarily characterized as the main effector cells in liver fibrosis, due to their capacity to transdifferentiate into collagen-producing myofibroblasts (MFB). More recent studies elucidated the fundamental role of HSC in liver immunology. HSC are not only the major storage site for dietary vitamin A (Vit A) (retinol, retinoic acid), which is essential for proper function of the immune system. This pericyte further represents a versatile source of many soluble immunological active factors including cytokines [e.g., interleukin 17 (IL-17)] and chemokines [C-C motif chemokine (ligand) 2 (CCL2)], may act as an antigen presenting cell (APC), and has autophagy activity. Additionally, it responds to many immunological triggers via toll-like receptors (TLR) (e.g., TLR4, TLR9) and transduces signals through pathways and mediators traditionally found in immune cells, including the Hedgehog (Hh) pathway or inflammasome activation. Overall, HSC promote rather immune-suppressive responses in homeostasis, like induction of regulatory T cells (Treg), T cell apoptosis (via B7-H1, PDL-1) or inhibition of cytotoxic CD8 T cells. In conditions of liver injury, HSC are important sensors of altered tissue integrity and initiators of innate immune cell activation. Vice versa, several immune cell subtypes interact directly or via soluble mediators with HSC. Such interactions include the mutual activation of HSC (towards MFB) and macrophages or pro-apoptotic signals from natural killer (NK), natural killer T (NKT) and gamma-delta T cells (γδ T-cells) on activated HSC. Current directions of research investigate the immune-modulating functions of HSC in the environment of liver

  11. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    PubMed Central

    Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2014-01-01

    Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues. PMID:24876909

  12. The Complex Myeloid Network of the Liver with Diverse Functional Capacity at Steady State and in Inflammation

    PubMed Central

    Eckert, Christoph; Klein, Niklas; Kornek, Miroslaw; Lukacs-Kornek, Veronika

    2015-01-01

    In recent years, it has been an explosion of information regarding the role of various myeloid cells in liver pathology. Macrophages and dendritic cell (DC) play crucial roles in multiple chronic liver diseases such as fibrosis and non-alcoholic fatty liver disease (NAFLD). The complexity of myeloid cell populations and the missing exclusive marker combination make the interpretation of the data often extremely difficult. The current review aims to summarize the multiple roles of macrophages and DCs in chronic liver diseases, especially pointing out how these cells influence liver immune and parenchymal cells thereby altering liver function and pathology. Moreover, the review outlines the currently known marker combinations for the identification of these cell populations for the study of their role in liver immunology. PMID:25941527

  13. Complete resection of unresectable liver metastases from colorectal cancer without deterioration of liver function after cetuximab and irinotecan: two case reports.

    PubMed

    Karasaki, Takahiro; Sano, Keiji; Takamoto, Taketumi; Kinoshita, Hiroto; Tateishi, Ryosuke; Takemura, Tamiko; Makuuchi, Masatoshi

    2010-01-01

    Complete resection for colorectal metastases is the only treatment that can provide long-term survival and may lead to cure. Recent reports have shown that liver resection following systemic chemotherapy in patients with initially unresectable metastases from colorectal cancer may also result in a good long-term survival, and rescue surgery after chemotherapy has become a strategy of choice. A 29-year-old male and a 35-year-old female with unresectable liver metastases from colorectal cancer underwent complete resection after administration of third-line combination therapy of cetuximab and irinotecan. Although systemic chemotherapy may decrease liver function, which may make liver resection unfeasible, in the two cases reported, liver function did not deteriorate after cetuximab plus irinotecan. The indocyanine green retention rate at 15 minutes, which is useful in deciding the safe limit of hepatectomy, was optimal after the administration of cetuximab plus irinotecan in both patients. Cetuximab plus irinotecan may be beneficial as neoadjuvant chemotherapy for metastatic colorectal cancer, not only because of its oncological efficacy but also for preservation of liver function. PMID:21443115

  14. Quantitative analysis of ultrasonographic images and cytology in relation to histopathology of canine and feline liver: An ex-vivo study.

    PubMed

    Banzato, Tommaso; Gelain, Maria Elena; Aresu, Luca; Centelleghe, Cinzia; Benali, Silvia Lucia; Zotti, Alessandro

    2015-12-01

    The aims of the present study were to investigate, in a standardized experimental condition, the usefulness of histogram analysis on ex-vivo ultrasonographic images of the liver of dogs and cats compared with histological alterations and to evaluate whether the combination of histogram parameters and cytology might improve diagnostic accuracy referring to optical microscopy as gold standard. Histogram-based parameters were calculated on ultrasonographic images of liver tissue samples collected from the cadavers of 68 dogs and 31 cats. Standard deviation of the histogram (SDH) had a higher sensitivity and specificity in the detection of the lesions in cat compared with dog. Matched results of cytology and SDH improved sensitivity and specificity in dog where as no substantial improvement was evident in cat. Quantitative analysis of ultrasonographic images of the liver in dog and cat could become a potentially useful tool in the distinction between normal and pathological organs. PMID:26679812

  15. Complete and rapid response to FOLFIRI plus bevacizumab in a patient presenting with impaired liver function and poor performance status from colon cancer liver metastases.

    PubMed

    Belda-Iniesta, Cristóbal; Sáenz, Enrique Casado; de Castro-Carpeño, Javier; Hernández, Elena; Barón, Manuel González

    2009-04-01

    Impaired liver function is a final complication of hepatic metastases from colon cancer. This disease status is of critical importance at first clinical presentation because of the tight therapeutic window for chemotherapy. A rapid response to treatment is required as other means of supportive care for hepatic function are limited. New targeted therapies including monoclonal antibodies directed against several proteins with key roles in colon cancer biology are now available, allowing new treatment options for this group of patients. Here, we present a patient with highly impaired liver function secondary to hepatic metastases from colon cancer that showed clinical and radiological improvement after systemic treatment including bevacizumab. PMID:19352108

  16. Quantitative Evaluation of the Reticuloendothelial System Function with Dynamic MRI

    PubMed Central

    Liu, Ting; Choi, Hoon; Zhou, Rong; Chen, I-Wei

    2014-01-01

    Purpose To evaluate the reticuloendothelial system (RES) function by real-time imaging blood clearance as well as hepatic uptake of superparamagnetic iron oxide nanoparticle (SPIO) using dynamic magnetic resonance imaging (MRI) with two-compartment pharmacokinetic modeling. Materials and Methods Kinetics of blood clearance and hepatic accumulation were recorded in young adult male 01b74 athymic nude mice by dynamic T2* weighted MRI after the injection of different doses of SPIO nanoparticles (0.5, 3 or 10 mg Fe/kg). Association parameter, Kin, dissociation parameter, Kout, and elimination constant, Ke, derived from dynamic data with two-compartment model, were used to describe active binding to Kupffer cells and extrahepatic clearance. The clodrosome and liposome were utilized to deplete macrophages and block the RES function to evaluate the capability of the kinetic parameters for investigation of macrophage function and density. Results The two-compartment model provided a good description for all data and showed a low sum squared residual for all mice (0.27±0.03). A lower Kin, a lower Kout and a lower Ke were found after clodrosome treatment, whereas a lower Kin, a higher Kout and a lower Ke were observed after liposome treatment in comparison to saline treatment (P<0.005). Conclusion Dynamic SPIO-enhanced MR imaging with two-compartment modeling can provide information on RES function on both a cell number and receptor function level. PMID:25090653

  17. HepatoProteomics: Applying Proteomic Technologies to the Study of Liver Function and Disease

    SciTech Connect

    Diamond, Deborah L.; Proll, Sean; Jacobs, Jon M.; Chan, Eric Y.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2006-08-01

    The wealth of human genome sequence information now available, coupled with technological advances in robotics, nanotechnology, mass spectrometry, and information systems, has given rise to a method of scientific inquiry known as functional genomics. By using these technologies to survey gene expression and protein production on a near global scale, the goal of functional genomics is to assign biological function to genes with currently unknown roles in physiology. This approach carries particular appeal in disease research, where it can uncover the function of previously unknown genes and molecular pathways that are directly involved in disease progression. With this knowledge may come improved diagnostic techniques, prognostic capabilities, and novel therapeutic approaches. In this regard, the continuing evolution of proteomic technologies has resulted in an increasingly greater impact of proteome studies in many areas of research and hepatology is no exception. Our laboratory has been extremely active in this area, applying both genomic and proteomic technologies to the analysis of virus-host interactions in several systems, including the study of hepatitis C virus (HCV) infection and HCV-associated liver disease. Since proteomic technologies are foreign to many hepatologists (and to almost everyone else), this article will provide an overview of proteomic methods and technologies and describe how they're being used to study liver function and disease. We use our studies of HCV infection and HCV-associated liver disease to present an operational framework for performing high throughput proteome analysis and extracting biologically meaningful information.

  18. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique.

    PubMed

    Sun, Di; Wei, Cong; Shen, E; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

  19. Quantitative Study of Elasticity of Rabbit VX2 Liver Tumor with Alternated Cooling and Heating Treatment based on ARFI Ultrasound Imaging Technique

    PubMed Central

    Sun, Di; Wei, Cong; Shen, E.; Ying, Tao; Hu, Bing

    2016-01-01

    Acoustic radiation force impulse (ARFI) ultrasound imaging technique is used to quantitatively evaluate the elasticity of rabbit VX2 liver tumor with alternated cooling and heating treatment (ACHT). ACHT was performed on fifteen VX2 liver tumor models established in fifteen male New Zealand white rabbits with open tumor plant. ARFI was performed on day 0, 1, 7 and 14 after ACHT and shear wave velocity (SWV) in ARFI was recorded to evaluate the elasticity of the treated area. The SWV value of the lesion on day 0, 1, 7 and 14 was 2.33 ± 0.19 m/s, 3.09 ± 0.40 m/s, 2.64 ± 0.37 m/s and 2.26 ± 0.24 m/s, respectively, indicating the treated areas get stiffer on day 1 and then get softer gradually by day. All the difference between adjacent time points was statistically significant. The SWV value of different parts on day 7 approved that the hardness of the treated area is heterogenous: the treated area in the center >the peripheral strip-shaped area >normal liver tissues, consistent with pathological changes. Meanwhile, ARFI combined with conventional US imaging can qualitatively and quantitatively exam the healing process of rabbit VX2 liver tumor after ACHT, and corresponds well to the pathological results. PMID:27381362

  20. The use of DWI to assess spleen and liver quantitative ADC changes in the detection of liver fibrosis stages in chronic viral hepatitis.

    PubMed

    Cece, Hasan; Ercan, Abdulbasit; Yıldız, Sema; Karakas, Ekrem; Karakas, Omer; Boyacı, Fatıma Nurefsan; Aydogan, Timucin; Karakas, Emel Yigit; Cullu, Nesat; Ulas, Turgay

    2013-08-01

    This study aimed to evaluate the changes in spleen and liver diffusion-weighted magnetic resonance imaging (DWI) in chronic viral hepatitis patients. The study comprised 47 patients and 30 healthy volunteers. DWIs were obtained. Apparent Diffusion Coefficient (ADC) measurements were made by transferring the images to the workstation. The measurements of value b 1000 were made from a total of five points of the liver and three points of the spleen. Liver biopsy was performed on the 47 patients. The fibrosis stages of the patients were defined according to the METAVIR scoring system. Student's t-test was used in the comparison of mean ages, liver and spleen ADC values between the patient and the control group. Kruskal-Wallis followed by Mann-Whitney U Test with Bonferroni adjustment was performed in the comparison of mean ADC values of the patients at different stages and the control group. A statistically significant difference was determined between the patient and control group in respect of liver and spleen mean ADC values (P<0.05). F3 group showed a significant difference compared to control and F1 and F4 group showed a significant difference compared to control, F1, F2 and F3 group in terms of the mean liver ADC value (P<0.01). F3 and F4 group showed a significant difference compared to control and F1 group in terms of the mean spleen ADC value (P<0.01). As a result we believe that the measurement of liver and spleen ADC values may be an indicator in the determination of the level of fibrosis. PMID:23518145

  1. A quantitative overview of biophysical forces impinging on neural function

    NASA Astrophysics Data System (ADS)

    Mueller, Jerel K.; Tyler, William J.

    2014-10-01

    The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction.

  2. A quantitative overview of biophysical forces impinging on neural function.

    PubMed

    Mueller, Jerel K; Tyler, William J

    2014-01-01

    The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction. PMID:25156965

  3. Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

    SciTech Connect

    Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki; Fukuda, Kuniaki; Oshiro, Yoshiko; Fukumitsu, Nobuyoshi; Abei, Masato; Kawaguchi, Atsushi; Hayashi, Yasutaka; Ohkawa, Ayako; Hashii, Haruko; Kanemoto, Ayae; Moritake, Takashi; Tohno, Eriko; Tsuboi, Koji; Sakae, Takeji; Sakurai, Hideyuki

    2012-03-01

    Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effect of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.

  4. Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey

    PubMed Central

    Cappello, Maria; Randazzo, Claudia; Bravatà, Ivana; Licata, Anna; Peralta, Sergio; Craxì, Antonio; Almasio, Piero Luigi

    2014-01-01

    BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. MATERIALS AND METHODS A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as an increase in aspartate aminotransferase, (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), or total bilirubin. RESULTS A cohort of 335 patients (179 males, mean age 46.0 ± 15.6 years) was analyzed. Abnormal LFTs were detected in 70 patients (20.9%). In most cases, the alterations were mild and spontaneously returned to normal values in about 60% of patients. Patients with abnormal LFTs were less frequently on treatment with aminosalicylates (22.8 vs. 36.6%, P = 0.04). The most frequent cause for transient abnormal LFTs was drug-induced cholestasis (34.1%), whereas fatty liver was the most frequent cause of persistent liver damage (65.4%). A cholestatic pattern was found in 60.0% of patients and was mainly related to older age, longer duration of disease, and hypertension. CONCLUSIONS The prevalence of LFT abnormalities is relatively high in IBD patients, but the development of severe liver injury is exceptional. Moreover, most alterations of LFTs are mild and spontaneously return to normal values. Drug-induced hepatotoxicity and fatty liver are the most relevant causes of abnormal LFTs in patients with IBD. PMID:24966712

  5. Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization

    PubMed Central

    Boas, F. Edward; Brody, Lynn A.; Erinjeri, Joseph P.; Yarmohammadi, Hooman; Shady, Waleed; Kishore, Sirish; Sofocleous, Constantinos T.

    2016-01-01

    Objective Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. Materials and Methods We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4–8 weeks after treatment. Results A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. Conclusion Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT. PMID:27248430

  6. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  7. Liver transplant - series (image)

    MedlinePlus

    The liver is in the right upper abdomen. The liver serves many functions, including the detoxification of substances delivered ... A liver transplant may be recommended for: liver damage due to alcoholism (Alcoholic cirrhosis) primary biliary cirrhosis long-term ( ...

  8. Quantitative evaluation of phonetograms in the case of functional dysphonia.

    PubMed

    Airainer, R; Klingholz, F

    1993-06-01

    According to the laryngeal clinical findings, figures making up a scale were assigned to vocally trained and vocally untrained persons suffering from different types of functional dysphonia. The different types of dysphonia--from the manifested hypofunctional to the extreme hyperfunctional dysphonia--were classified by means of this scale. Besides, the subjects' phonetograms were measured and approximated by three ellipses, what rendered possible the definition of phonetogram parameters. The combining of selected phonetogram parameters to linear combinations served the purpose of a phonetographic evaluation. The linear combinations were to bring phonetographic and clinical evaluations into correspondence as accurately as possible. It was necessary to use different kinds of linear combinations for male and female singers and nonsingers. As a result of the reclassification of 71 and the new classification of 89 patients, it was possible to graduate the types of functional dysphonia by means of computer-aided phonetogram evaluation with a clinically acceptable error rate. This method proved to be an important supplement to the conventional diagnostics of functional dysphonia. PMID:8353627

  9. Estimating Functional Liver Reserve Following Hepatic Irradiation: Adaptive Normal Tissue Response Models

    PubMed Central

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and Methods From 2005–2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1−(ICG-R15pre-RT/ICG-R15post-RT)] where no toxicity was observed using a beta distribution function. Results Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ≥78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p<0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation. PMID:24813090

  10. Boron determination in liver tissue by combining quantitative neutron capture radiography (QNCR) and histological analysis for BNCT treatment planning at the TRIGA Mainz.

    PubMed

    Schütz, C; Brochhausen, C; Altieri, S; Bartholomew, K; Bortolussi, S; Enzmann, F; Gabel, D; Hampel, G; Kirkpatrick, C J; Kratz, J V; Minouchehr, S; Schmidberger, H; Otto, G

    2011-09-01

    The typical primary malignancies of the liver are hepatocellular carcinoma and cholangiocarcinoma, whereas colorectal liver metastases are the most frequently occurring secondary tumors. In many cases, only palliative treatment is possible. Boron neutron capture therapy (BNCT) represents a technique that potentially destroys tumor tissue selectively by use of externally induced, locally confined secondary particle irradiation. In 2001 and 2003, BNCT was applied to two patients with colorectal liver metastases in Pavia, Italy. To scrutinize the rationale of BNCT, a clinical pilot study on patients with colorectal liver metastases was carried out at the University of Mainz. The distribution of the (10)B carrier (p-borono-phenylalanine) in the liver and its uptake in cancerous and tumor-free tissue were determined, focusing on a potential correlation between the uptake of p-borono-phenylalanine and the biological characteristics of cancerous tissue. Samples were analyzed using quantitative neutron capture radiography of cryosections combined with histological analysis. Methodological aspects of the combination of these techniques and results from four patients enrolled in the study are presented that indicate that the uptake of p-borono-phenylalanine strongly depends on the metabolic activity of cells. PMID:21692653

  11. Cognitive functions in patients with liver cirrhosis: A tendency to commit more memory errors

    PubMed Central

    Ciećko-Michalska, Irena; Wójcik, Jan; Senderecka, Magdalena; Wyczesany, Mirosław; Binder, Marek; Szewczyk, Jakub; Dziedzic, Tomasz; Słowik, Agnieszka; Mach, Tomasz

    2013-01-01

    Background Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE). For diagnostic purposes, 2 alternative batteries of psychometric screening tests are recommended. They differ from each other in terms of the cognitive domains assessed. The research was designed to provide a profile of cognitive functioning in patients with liver cirrhosis, using an assessment that covers a wider range of cognitive functions than the usual screening battery. Material/Methods We examined 138 persons, including 88 with liver cirrhosis and 50 healthy volunteers. The Mini Mental State Examination (MMSE) was used for screening and excluding advanced cognitive impairment. Then, to assess cognitive functions in more detail, the following tests were used: Auditory Verbal Learning Test (AVLT), Letter and Semantic Fluency Tests (LF and SF), Trail Making Test (TMT A&B), Digit Symbol Test (DST), Block Design Test (BDT), and Mental Rotation Test (MRT). The MRT task has not been used in MHE diagnosis so far. Finally, 57 patients and 48 controls took part in the entire study. Results Patients with liver cirrhosis commit significantly more errors of intrusions in the AVLT during the delayed free recall trial. Results significantly deviating from the norm in at least 2 tests were found only in 7 cirrhosis patients. Conclusions The results do not provide any specific profile of cognitive disturbances in MHE, but suggest that cirrhosis patients have a tendency to commit more memory errors, probably due to subtle impairments of executive function. PMID:23598598

  12. Image Registration for Quantitative Analysis of Kidney Function using MRI

    NASA Astrophysics Data System (ADS)

    Sance, Rosario; Ledesma-Carbayo, María J.; Lundervold, Arvid; Santos, Andrés

    2006-10-01

    The aim of the present study is to analyze the possibilities of registration algorithms to compensate respiratory motion and deformation in abdominal DCE-MRI 3D temporary series. The final objective is that from registered data, appropriate intensity curves of local renal activity along the time could be represented for each kidney voxel. Assuming a relation between the voxel intensity and the contrast media concentration, this non-invasive renographic method could be used to evaluate the local renal function, and to calculate typical renal parameters like glomerular filtration rate.

  13. Quantitative analysis of contrast-enhanced ultrasonography in acute radiation-induced liver injury: An animal model

    PubMed Central

    FENG, JUN; CHEN, SHU-BO; WU, SHU-JUN; SUN, PING; XIN, TIAN-YOU; CHEN, YING-ZHEN

    2015-01-01

    The aim of the present study was to examine and assess contrast-enhanced ultrasound in the early diagnosis of acute radiation-induced liver injury in a rat model. Sixty female rats were used, with 50 rats being utilized to produce an animal model of liver injury with a single dose of stereotactic X-ray irradiation of 20 Gy. Ten rats from the injury group and 2 rats from the control group were randomly selected on days 3, 7, 14, 21 and 28, and examined by contrast-enhanced ultrasound and histopathology of liver specimens. The rats were divided into four groups: the normal control group, mild, moderate, and severe radioactive liver injury groups based on the histopathological examination results. Hepatic artery arriving time (HAAT) and hepatic vein arriving time (HVAT) were recorded, and hepatic artery to vein transit time (HA-HVTT) was calculated. The time-intensity curve of liver parenchyma, the time to peak (TTP) and peak intensity (PI) were also obtained. Significant differences were observed between liver injury and control groups for PI and HA-HVTT (P<0.05). PI and HA-HVTT were shorter in the severe liver injury group compared to the mild and moderate liver injury groups (P<0.05). Compared to the control group, higher TTP was recorded in all the liver injury groups (P<0.05), and the highest TTP level was observed in the severe liver injury group compared to the mild or moderate group (P<0.05). However, no significant difference was observed between the mild and moderate groups for PI, HA-HVTT and TTP. In conclusion, the results showed that contrast-enhanced ultrasonography is useful for an earlier diagnosis in a rat model of acute radiation-induced liver injury. PMID:26640553

  14. Restoration of Liver Function and Portosystemic Pressure Gradient after TIPSS and Late TIPSS Occlusion

    SciTech Connect

    Maedler, U.; Hansmann, J.; Duex, M.; Noeldge, G.; Sauer, P.; Richter, G.M.

    2002-03-15

    TIPSS (transjugular intrahepatic portosystemic shunt) may be indicated to control bleeding from esophageal and gastric varicose veins, to reduce ascites, and to treat patients with Budd-Chiari syndrome and veno-occlusive disease. Numerous measures to improve the safety and methodology of the procedure have helped to increase the technical and clinical success. Follow-up of TIPSS patients has revealed shunt stenosis to occur more often in patients with preserved liver function (Child A, Child B). In addition, the extent of liver cirrhosis is the main factor that determines prognosis in the long term. Little is known about the effects of TIPSS with respect to portosystemic hemodynamics. This report deals with a cirrhotic patient who stopped drinking 7 months prior to admission. He received TIPSS to control ascites and recurrent esophageal bleeding. Two years later remarkable hypertrophy of the left liver lobe and shunt occlusion was observed. The portosystemic pressure gradient dropped from 24 mmHg before TIPSS to 11 mmHg and remained stable after shunt occlusion. The Child's B cirrhosis prior to TIPSS turned into Child's A cirrhosis and remained stable during the follow-up period of 32 months. This indicates that liver function of TIPSS patients may recover due to hypertrophy of the remaining non-cirrhotic liver tissue. In addition the hepatic hemodynamics may return to normal. In conclusion, TIPSS cannot cure cirrhosis but its progress may be halted if the cause can be removed. This may result in a normal portosystemic gradient, leading consequently to shunt occlusion.

  15. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis.

    PubMed

    Karsdal, Morten A; Manon-Jensen, Tina; Genovese, Federica; Kristensen, Jacob H; Nielsen, Mette J; Sand, Jannie Marie B; Hansen, Niels-Ulrik B; Bay-Jensen, Anne-Christine; Bager, Cecilie L; Krag, Aleksander; Blanchard, Andy; Krarup, Henrik; Leeming, Diana J; Schuppan, Detlef

    2015-05-15

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. PMID:25767261

  16. Novel insights into the function and dynamics of extracellular matrix in liver fibrosis

    PubMed Central

    Manon-Jensen, Tina; Genovese, Federica; Kristensen, Jacob H.; Nielsen, Mette J.; Sand, Jannie Marie B.; Hansen, Niels-Ulrik B.; Bay-Jensen, Anne-Christine; Bager, Cecilie L.; Krag, Aleksander; Blanchard, Andy; Krarup, Henrik; Leeming, Diana J.; Schuppan, Detlef

    2015-01-01

    Emerging evidence suggests that altered components and posttranslational modifications of proteins in the extracellular matrix (ECM) may both initiate and drive disease progression. The ECM is a complex grid consisting of multiple proteins, most of which play a vital role in containing the essential information needed for maintenance of a sophisticated structure anchoring the cells and sustaining normal function of tissues. Therefore, the matrix itself may be considered as a paracrine/endocrine entity, with more complex functions than previously appreciated. The aims of this review are to 1) explore key structural and functional components of the ECM as exemplified by monogenetic disorders leading to severe pathologies, 2) discuss selected pathological posttranslational modifications of ECM proteins resulting in altered functional (signaling) properties from the original structural proteins, and 3) discuss how these findings support the novel concept that an increasing number of components of the ECM harbor signaling functions that can modulate fibrotic liver disease. The ECM entails functions in addition to anchoring cells and modulating their migratory behavior. Key ECM components and their posttranslational modifications often harbor multiple domains with different signaling potential, in particular when modified during inflammation or wound healing. This signaling by the ECM should be considered a paracrine/endocrine function, as it affects cell phenotype, function, fate, and finally tissue homeostasis. These properties should be exploited to establish novel biochemical markers and antifibrotic treatment strategies for liver fibrosis as well as other fibrotic diseases. PMID:25767261

  17. New Trends in Quantitative Assessment of the Corneal Barrier Function

    PubMed Central

    Guimerà, Anton; Illa, Xavi; Traver, Estefania; Herrero, Carmen; Maldonado, Miguel J.; Villa, Rosa

    2014-01-01

    The cornea is a very particular tissue due to its transparency and its barrier function as it has to resist against the daily insults of the external environment. In addition, maintenance of this barrier function is of crucial importance to ensure a correct corneal homeostasis. Here, the corneal epithelial permeability has been assessed in vivo by means of non-invasive tetrapolar impedance measurements, taking advantage of the huge impact of the ion fluxes in the passive electrical properties of living tissues. This has been possible by using a flexible sensor based in SU-8 photoresist. In this work, a further analysis focused on the validation of the presented sensor is performed by monitoring the healing process of corneas that were previously wounded. The obtained impedance measurements have been compared with the damaged area observed in corneal fluorescein staining images. The successful results confirm the feasibility of this novel method, as it represents a more sensitive in vivo and non-invasive test to assess low alterations of the epithelial permeability. Then, it could be used as an excellent complement to the fluorescein staining image evaluation. PMID:24841249

  18. Vicarious liver visualization in solitary functioning kidney with technetium-99m ethylenedicysteine renal scintigraphy

    PubMed Central

    Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Gupta, Nitin; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2015-01-01

    We present a case of 3-year-old boy who was incidentally diagnosed to have single left kidney on ultrasonography. Dynamic technetium-99m ethylenedicysteine renal scintigraphy was acquired for assessing the existing kidney function showed the tracer localization in bilateral renal fossae during the entire study. The single-photon emission computerized tomography/computerized tomography study revealed activity in the right renal fossa to be in the enlarged right lobe of the liver, which was mimicking as impaired functioning right kidney in planar images. The hybrid imaging helped in accurate delineation of tracer uptake by confirming it to be the false appearance of the right kidney in planar imaging. This case report also highlights the possible mechanism of renal tracer uptake in the liver parenchyma. PMID:26170576

  19. Quantitative simulation of intracellular signaling cascades in a Virtual Liver: estimating dose dependent changes in hepatocellular proliferation and apoptosis

    EPA Science Inventory

    The US EPA Virtual Liver (v-Liver™) is developing an approach to predict dose-dependent hepatotoxicity as an in vivo tissue level response using in vitro data. The v-Liver accomplishes this using an in silico agent-based systems model that dynamically integrates environmental exp...

  20. Long Term Liver Engraftment of Functional Hepatocytes Obtained from Germline Cell-Derived Pluripotent Stem Cells

    PubMed Central

    Fagoonee, Sharmila; Famulari, Elvira Smeralda; Silengo, Lorenzo; Tolosano, Emanuela; Altruda, Fiorella

    2015-01-01

    One of the major hurdles in liver gene and cell therapy is availability of ex vivo-expanded hepatocytes. Pluripotent stem cells are an attractive alternative. Here, we show that hepatocyte precursors can be isolated from male germline cell-derived pluripotent stem cells (GPSCs) using the hepatoblast marker, Liv2, and induced to differentiate into hepatocytes in vitro. These cells expressed hepatic-specific genes and were functional as demonstrated by their ability to secrete albumin and produce urea. When transplanted in the liver parenchyma of partially hepatectomised mice, Liv2-sorted cells showed regional and heterogeneous engraftment in the injected lobe. Moreover, approximately 50% of Y chromosome-positive, GPSC-derived cells were found in the female livers, in the region of engraftment, even one month after cell injection. This is the first study showing that Liv2-sorted GPSCs-derived hepatocytes can undergo long lasting engraftment in the mouse liver. Thus, GPSCs might offer promise for regenerative medicine. PMID:26323094

  1. [Structuro-functional changes in dog liver and regional lymph node lysosomes in toxic hepatitis].

    PubMed

    Borodin, Iu I; Korolenko, T A; Malygin, A E; Pupyshev, A B; Sharaĭkina, E O

    1978-10-01

    Structural and functional changes in the dog liver and regional lymph nodes lysosomes were studied during toxic hepatitis induced by CCl4 administration (single and repeated). Total activity of lysosomal enzymes (acid RNA-ase and beta-galactosidase) was higher in the regional lymph nodes than in the liver, reflecting the barrier, protective function of the organ. During acute toxic hepatitis the specific activities of acid RNA-ase and cathepsin D displayed a sharp rise. No normalization of the indices under study occurred during the observation period (from 8 to 30 days). At the same time there was a rise of the regional lymph node weight and an elevation of the relative macrophage and neutrophil content in the sinuses. The increased activity of the lysosome enzymes in the regional lymph nodes in injury of the liver was connected with greater functional load on the lymph nodes effecting hydrolysis of biopolymeres which penetrated into the regional lymphatic node with the lymph. PMID:708870

  2. A quantitative confidence signal detection model: 1. Fitting psychometric functions.

    PubMed

    Yi, Yongwoo; Merfeld, Daniel M

    2016-04-01

    Perceptual thresholds are commonly assayed in the laboratory and clinic. When precision and accuracy are required, thresholds are quantified by fitting a psychometric function to forced-choice data. The primary shortcoming of this approach is that it typically requires 100 trials or more to yield accurate (i.e., small bias) and precise (i.e., small variance) psychometric parameter estimates. We show that confidence probability judgments combined with a model of confidence can yield psychometric parameter estimates that are markedly more precise and/or markedly more efficient than conventional methods. Specifically, both human data and simulations show that including confidence probability judgments for just 20 trials can yield psychometric parameter estimates that match the precision of those obtained from 100 trials using conventional analyses. Such an efficiency advantage would be especially beneficial for tasks (e.g., taste, smell, and vestibular assays) that require more than a few seconds for each trial, but this potential benefit could accrue for many other tasks. PMID:26763777

  3. Generation and functional significance of CXC chemokines for neutrophil-induced liver injury during endotoxemia.

    PubMed

    Dorman, Robert B; Gujral, Jaspreet S; Bajt, Mary Lynn; Farhood, Anwar; Jaeschke, Hartmut

    2005-05-01

    The hypothesis that the neutrophil chemoattractant CXC chemokines KC and macrophage inflammatory protein-2 (MIP-2) are involved in neutrophil transmigration and liver injury was tested in C3Heb/FeJ mice treated with galactosamine (Gal, 700 mg/kg), endotoxin (ET, 100 microg/kg), or Gal + ET (Gal/ET). Hepatic KC and MIP-2 mRNA levels and plasma CXC chemokine concentrations were dramatically increased 1.5 h after Gal/ET or ET alone and gradually declined up to 7 h. Murine recombinant cytokines (TNF-alpha, IL-1 alpha, and IL-1 beta), but not Gal/ET, induced CXC chemokine formation in the ET-resistant C3H/HeJ strain. To assess the functional importance of KC and MIP-2, C3Heb/FeJ mice were treated with Gal/ET and control IgG or a combination of anti-KC and anti-MIP-2 antibodies. Anti-CXC chemokine antibodies did not attenuate hepatocellular apoptosis, sinusoidal neutrophil sequestration and extravasation, or liver injury at 7 h. Furthermore, there was no difference in liver injury between BALB/cJ wild-type and CXC receptor-2 gene knockout (CXCR2-/-) mice treated with Gal/ET. The higher neutrophil count in livers of CXCR2-/- than in wild-type mice after Gal/ET was caused by the elevated number of neutrophils located in sinusoids of untreated CXCR2-/- animals. The pancaspase inhibitor Z-Val-Ala-Asp-fluoromethylketone eliminated Gal/ET-induced apoptosis and neutrophil extravasation and injury but not CXC chemokine formation. Thus Gal/ET induced massive, cytokine-dependent CXC chemokine formation in the liver. However, neutrophil extravasation and injury occurred in response to apoptotic cell injury at 6-7 h and was independent of CXC chemokine formation. PMID:15576625

  4. Quantitative Liquid Chromatography-Mass Spectrometry-Multiple Reaction Monitoring (LC-MS-MRM) Analysis of Site-specific Glycoforms of Haptoglobin in Liver Disease*

    PubMed Central

    Sanda, Miloslav; Pompach, Petr; Brnakova, Zuzana; Wu, Jing; Makambi, Kepher; Goldman, Radoslav

    2013-01-01

    Development of liver disease is associated with the appearance of multiply fucosylated glycoforms of haptoglobin. To analyze the disease-related haptoglobin glycoforms in liver cirrhosis and hepatocellular carcinoma, we have optimized an LC-MS-multiple reaction monitoring (MRM) workflow for glycopeptide quantification. The final quantitative analysis included 24 site-specific glycoforms generated by treatment of a tryptic digest of haptoglobin with α(2–3,6,8)-neuraminidase and β(1–4)-galactosidase. The combination of LC-MS-MRM with exoglycosidase digests allowed resolution of isobaric glycoforms of the haptoglobin-T3 glycopeptide for quantification of the multiply fucosylated Lewis Y-containing glycoforms we have identified in the context of liver disease. Fourteen multiply fucosylated glycoforms of the 20 examined increased significantly in the liver disease group compared with healthy controls with an average 5-fold increase in intensity (p < 0.05). At the same time, two tri-antennary glycoforms without fucoses did not increase in the liver disease group, and two tetra-antennary glycoforms without fucoses showed a marginal increase (at most 40%) in intensity. Our analysis of 30 individual patient samples (10 healthy controls, 10 cirrhosis patients, and 10 hepatocellular carcinoma patients) showed that these glycoforms were substantially increased in a small subgroup of liver disease patients but did not significantly differ between the groups of hepatocellular carcinoma and cirrhosis patients. The tri- and tetra-antennary singly fucosylated glycoforms are associated with a MELD score and low platelet counts (p < 0.05). The exoglycosidase-assisted LC-MS-MRM workflow, optimized for the quantification of fucosylated glycoforms of haptoglobin, can be used for quantification of these glycoforms on other glycopeptides with appropriate analytical behavior. PMID:23389048

  5. Quantitative chemical proteomics for investigating the biomarkers of dioscin against liver fibrosis caused by CCl4 in rats.

    PubMed

    Zhang, Xiaoling; Xu, Lina; Yin, Lianhong; Qi, Yan; Xu, Youwei; Han, Xu; Peng, Jinyong

    2015-07-14

    In the present work, the effect of dioscin against liver fibrosis in rats caused by carbon tetrachloride (CCl4) was confirmed. Then, the differentially expressed proteins from rat liver were identified using two-dimensional differential in-gel electrophoresis technology. Ten new biomarkers including protein disulfide isomerase A3, selenium-binding protein 1, glutamine synthetase, senescence marker protein 30, hemopexin, keratin 8, keratin 18, vimentin, Annexin A5 and dermatopontin associated with liver fibrosis were found and validated, and new insights through affecting multiple drug targets and biological processes were also provided to reveal the mechanisms of dioscin against hepatic fibrosis for the first time. PMID:26069897

  6. Function of the liver and bile ducts in humans exposed to lead.

    PubMed

    Kasperczyk, A; Dziwisz, M; Ostałowska, A; Swietochowska, E; Birkner, E

    2013-08-01

    Lead is very common in the environment, and it is therefore important to characterize its possible adverse health effects. The aim of this study was to evaluate the impact of lead exposure on selected functions of the liver and bile ducts in people who are chronically exposed to the metal because of their occupations. To provide this information, the activity of specific enzymes and the bilirubin concentration were determined in blood serum, and morphological parameters of the liver and bile ducts were evaluated using the ultrasonic imaging method. Healthy male employees of a lead-zinc processing facility (n = 145) who were occupationally exposed to lead were divided into two subgroups as a function of the lead concentrations in blood (PbB): low lead exposure (PbB = 20-35 μg/dl; n = 57) and high lead exposure (PbB = 35-60 μg/dl; n = 88). Human exposure to lead compounds was found to cause liver enlargement and to activate inflammatory reactions with the characteristics of moderate cholestasis within the bile ducts, while no characteristics of necrotic damage of hepatic cells were noted. It seems that lipid peroxidation can be one of the toxic mechanisms of lead which induce moderate cholestasis. The effects depend on the extent of the lead exposure and were greater in subjects with higher exposure levels, particularly subjects with PbB values greater than 35 μg/dl. PMID:23529799

  7. Assessment of liver function in dogs using the 13C-galactose breath test.

    PubMed

    Silva, S; Wyse, C A; Goodfellow, M R; Yam, P S; Preston, T; Papasouliotis, K; Hall, E J

    2010-08-01

    The aim of this study was to evaluate the application of the 13C-galactose breath test (13C-GBT) in assessing canine liver function by applying it to a group of healthy dogs, and to a group with clinicopathological evidence of liver dysfunction. Breath samples were collected 30 min before ingestion of 13C-galactose, and then at regular intervals thereafter for 6 h. The proportion of 13CO2/12CO2 in the breath samples was measured by isotope-ratio mass spectrometry. There was no significant difference in recovery of 13CO2 in the diseased group, compared to the healthy controls, but there was considerable inter-subject variation in both groups, possibly due to differences in the rate of gastric emptying, which could preclude detection of alterations in hepatic metabolism of galactose. The results of this study do not support the application of the 13C-GBT for assessment of canine liver function. PMID:19546016

  8. In vitro gene regulatory networks predict in vivo function of liver

    PubMed Central

    2010-01-01

    Background Evolution of toxicity testing is predicated upon using in vitro cell based systems to rapidly screen and predict how a chemical might cause toxicity to an organ in vivo. However, the degree to which we can extend in vitro results to in vivo activity and possible mechanisms of action remains to be fully addressed. Results Here we use the nitroaromatic 2,4,6-trinitrotoluene (TNT) as a model chemical to compare and determine how we might extrapolate from in vitro data to in vivo effects. We found 341 transcripts differentially expressed in common among in vitro and in vivo assays in response to TNT. The major functional term corresponding to these transcripts was cell cycle. Similarly modulated common pathways were identified between in vitro and in vivo. Furthermore, we uncovered the conserved common transcriptional gene regulatory networks between in vitro and in vivo cellular liver systems that responded to TNT exposure, which mainly contain 2 subnetwork modules: PTTG1 and PIR centered networks. Interestingly, all 7 genes in the PTTG1 module were involved in cell cycle and downregulated by TNT both in vitro and in vivo. Conclusions The results of our investigation of TNT effects on gene expression in liver suggest that gene regulatory networks obtained from an in vitro system can predict in vivo function and mechanisms. Inhibiting PTTG1 and its targeted cell cyle related genes could be key machanism for TNT induced liver toxicity. PMID:21073692

  9. Lipid Profiling and Transcriptomic Analysis Reveals a Functional Interplay between Estradiol and Growth Hormone in Liver

    PubMed Central

    Fernández-Pérez, Leandro; Santana-Farré, Ruymán; de Mirecki-Garrido, Mercedes; García, Irma; Guerra, Borja; Mateo-Díaz, Carlos; Iglesias-Gato, Diego; Díaz-Chico, Juan Carlos; Flores-Morales, Amilcar; Díaz, Mario

    2014-01-01

    17β-estradiol (E2) may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a marked influence on

  10. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk. PMID:27106140