Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With respect to liver disease, the primary function of the laboratory is to identify its presence. Tests are not available that permit a specific diagnosis and an accurate prognosis. Several tests should be present in a minimum data base that can help identify hepatobiliary disease. They are ALT, SAP, total serum bilirubin, urine bilirubin, cholesterol, albumin, BUN, glucose, red cell morphology, and urine sediment. It is sometimes possible to tentatively identify whether a disease is primarily hepatocellular or biliary from the pattern of changes that occur in these tests. In addition, an estimate of the severity is sometimes possible when abnormal values are extreme. The keys are to avoid overinterpretation, use serial evaluations, and rely on a liver biopsy when definitive answers are needed. If liver disease is suspected but there are only marginal changes in the routine tests, the more sensitive tests of function, BSP retention and ammonia tolerance, are warranted. In the future, as more knowledge is gained about the responses of ARG, GGT, and ICG retention to naturally occurring diseases, these tests may join or replace some of those currently used. Also, as the ability to accurately and economically measure the various bile acids improves, a sensitive, yet noninvasive, method to detect and define modest changes in hepatobiliary function may result.
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PMID:Laboratory evaluation of liver disease. 387 5

IGF-I is the best marker of GH secretory status but it also depends on the nutritional status and peripheral hormones such as insulin, glucocorticoids, thyroid hormones and gonadal steroids. Though monitoring IGF-I levels is the best way for evaluating appropriate GH replacement, the usefulness of IGF-I assay in the diagnosis of adult GH deficiency (GHD) is still matter of debate. To clarify this point in a large population of GHD adults (no. = 135, 61 women and 74 men; age, mean +/- SE: 43.8 +/- 1.4 yr, range 20-80 yr) we studied IGF-I levels, their reproducibility and association to peak GH response to GHRH + arginine (GHRH + ARG) test and insulin tolerance test (ITT). The results in GHD were compared with those in a large population of normal subjects (no. = 336, 233 women and 103 men, aged 20-80 yr). Mean IGF-I levels in GHD (77.8 +/- 4.9 micrograms/l) were clearly lower (p < 0.001) than those in normal subjects (170.2 +/- 4.7 micrograms/l). In Childhood Onset GHD (CO-GHD; no. = 40; age, mean +/- SE: 27.8 +/- 1.5 yr) IGF-I levels were lower than those in Adult Onset GHD (AO-GHD; no. = 95, age, mean +/- SE: 50.7 +/- 1.4 yr) (56.6 +/- 9.7 vs 87.1 +/- 5.4 micrograms/l, p < 0.0003). In both GHD and normal subjects IGF-I levels showed good, reproducibility (r = 0.92, p < 0.00001 and r = 0.62, p < 0.00001, respectively). In GHD, but not in normal subjects, IGF-I levels were positively associated to peak GH responses to GHRH + ARG (r = 0.57, p < 0.00001); on the other hand, the GH peak after ITT was not associated to IGF-I in GHD. In normal subjects, but not in GHD, IGF-I levels were negatively associated to age (r = -0.60, p < 0.00001). Considering individual IGF-I levels there was a clear overlap between GHD and normal subjects. However, this overlap was strongly dependent on age. In fact, in the third and fourth decade of life 83.6% of GHD had IGF-I levels below the 3rd centile of normal values; on the other hand, in the fifth-sixth decade and in ageing 47% and only 12% of GHD, respectively, had IGF-I levels low for age. In conclusion, our results demonstrate that IGF-I levels represent a reproducible marker of GH status and are reduced more in CO-GHD than in AO-GHD adults. An overlap exists between GHD and normal subjects, however this is small up to the 4th decade of life. Thus, though normal IGF-I levels do not rule out the existence of GHD, up to 40 yr low IGF-I levels strongly point to GHD if malnutrition and liver disease have been ruled out.
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PMID:Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults. 980 91

The ability of ethanol to inhibit regenerative processes in the liver is thought to play a key role in the development of alcoholic liver disease. To understand the underlying mechanisms, we investigated the effects of ethanol on the Janus kinasesignal transducer and activator transcription factor (JAK-STAT) signaling pathways in hepatocytes. Treatment of freshly isolated adult rat hepatocytes with 10-100 mM ethanol rapidly (< 3 min) inhibits interleukin-6 (IL-6)-induced STAT3 activation, tyrosine and serine phosphorylation and IL-6-induced CCAAT enhancer binding protein (C/EBP) alpha and beta mRNA expression. Western analyses, in vitro kinase assays and in vivo cell labelling assays indicate that this inhibitory effect is not due to blocking the upstream-located JAK1, JAK2 or Tyk2 activation. On the contrary, acute ethanol exposure significantly potentiates IL-6-induced JAK1 autophosphorylation in vitro and in vivo. Pretreatment with sodium vanadate, a non-selective tyrosine phosphatase inhibitor, or with MG132 and lactacystin, proteasome inhibitors, does not abolish the ethanol inhibition of IL-6-induced STAT3 activation, suggesting that activation of protein tyrosine phosphatases or the ubiquitin-proteasome pathway is not involved. In view of the critical role of IL-6 signaling in liver regeneration, these findings suggest that the ability of biologically relevant concentrations of ethanol to markedly inhibit IL-6-induced STAT3 phosphorylation is one of the cellular mechanisms involved in the pathogenesis and progression of alcoholic liver diseases.
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PMID:Ethanol rapidly inhibits IL-6-activated STAT3 and C/EBP mRNA expression in freshly isolated rat hepatocytes. 1048 86

HIV accelerates progression of hepatitis C virus (HCV)-related liver disease. There are conflicting data on the effect of HCV on the risk of HIV progression and CD4 response to highly active antiretroviral therapy (HAART). Long-term prospective cohort studies are clearly required to resolve these issues. The optimal management of the co-infected patient is also unclear. For the co-infected patient, the optimal HAART regimen for best immune CD4 recovery and least adverse reactions remains unclear. Unfortunately, current HCV treatment is associated with significant side effects and a considerable proportion of HIV co-infected patients are poor candidates for HCV treatment. Better and more effective treatment for HCV (preferably not based on interferon) is urgently required for this group of patients. Patients with good CD4 cell count and with HCV genotypes 2 and 3 are likely to have a reasonable response to treatment.
Int J STD AIDS 2004 May
PMID:Hepatitis C and HIV co-infection. 1511 93

The importance of sexual transmission in the epidemiology of hepatitis G virus (HGV) and hepatitis C virus (HCV) was evaluated in two groups of HIV-1-positive Lebanese patients. Members of one group (90 patients) were HIV-1-infected via sexual route and denied intravenous drug (IVD) use, while members of the other group (28 patients) became HIV-1-infected parenterally and confessed frequent IVD use. The overall prevalence of HGV infection was relatively high in both groups and with no statistically significant difference between them (28% among IVD users vs 32% among the non-IVD users) despite the fact that non-IVD users were significantly older (32.7 +/- 1.7 years) than the IVD users (24.0 +/- 1.4 years) (P < 0.01). Conversely, there was a clear association between IVD use and HCV infection (25% for IVD users vs 7% for non-IVD users) despite the significantly lower age of the IVD users. These results point to the efficient transmission of HGV via the sexual route, while the transmission of HCV is mainly via the parenteral route. CD4+ lymphocyte counts were known on only 82 HIV1-infected patients. Although the number of HGV-RNA-positive patients (three) was small compared with anti-HGV-positive patients (24), a relationship was not found between CD4+ lymphocyte counts and the presence of HGV-RNA in the HIV-1-positive patients. The role of HGV in causing significant liver disease is still under dispute.
Int J STD AIDS 2004 Jul
PMID:Exposure rates to hepatitis C and G virus infections among HIV-infected patients: evidence of efficient transmission of HGV by the sexual route. 1522 31

Tumor necrosis factor alpha (TNF) is known to be one of the primary causative cytokines inflicting the characteristic damage to hepatocytes seen in alcoholic liver disease. TNF activates both cell survival and death-inducing signaling pathways. The balance between these two prongs determines the fate of the cell and the onset of disease. Ethanol exposure has been shown to alter mitochondrial function, decreasing their threshold for injury. Importantly, mitochondrial injury is a necessary end point of TNF-induced cell killing. It has been shown that ethanol exposure increases the sensitivity of hepatocytes and HepG2E47 cells to TNF-mediated death. The cumulative and terminal effect of the increased sensitivity to TNF caused by ethanol is an induction of a mitochondrial permeability transition. TNF brings about the mitochondrial permeability transition in ethanol-exposed cells due to amplification in the activity of the p38 stress kinase and a diminution in the activity of the antiapoptotic Akt/PKB kinase. The present report identifies an increase of PTEN expression in ethanol-exposed cells as the main causative factor in altering the balance between prosurvival and prodeath signals initiated by TNF. Suppression of the elevated PTEN levels found in ethanol-exposed HepG2E47 cells through the use of RNA interference reversed the ethanol-induced alterations to TNF signaling, resulting in a preservation of mitochondrial function and cell viability.
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PMID:Elevated PTEN levels account for the increased sensitivity of ethanol-exposed cells to tumor necrosis factor-induced cytotoxicity. 1562 31

Before the advent of highly active antiretroviral therapy (HAART), the vast majority of HIV-infected patients died from AIDS-related diseases. But, amongst those with access to HAART, AIDS is no longer the leading cause of death. Instead, liver disease is fast becoming the commonest cause of death in HIV-infected patients, particularly in those who have a co-infection with hepatitis C (HCV). The four recent comparative trials of peginterferon and ribavirin in HIV/HCV coinfected patients have provided valuable new information about the most appropriate treatment of this difficult group of patients. As with HIV-negative patients, it is clear that peginterferon alpha has advantages over non-pegylated treatment, with superior efficacy, in the form of higher sustained virological responders and comparable safety. Discontinuation rates were higher than reported in HCV mono-infected patients but comparable for most treatment arms. Furthermore, in about half the patients, treatments were not stopped during the first months of treatment because of side effects, but due to non-early virological response.
Int J STD AIDS 2005 Jan
PMID:Treatment of hepatitis C in HIV/hepatitis C co-infected patients: what is the evidence? 1570 63

Hepatocyte growth factor (HGF) is crucial for the development and regeneration of the liver and offers a possible new therapeutic strategy for the treatment of canine liver disease. In this study, the in vitro and in vivo bioactivity of recombinant canine HGF (rcHGF) produced with a baculoviral expression system in insect cells was measured. In vitro rcHGF induced mitogenesis, motogenesis, and phosphorylated the HGF receptor c-MET and its downstream mediators PKB and ERK1/2 in two canine epithelial cell lines. After a partial hepatectomy (phx) in dogs, rcHGF increased phosphorylation of c-MET, PKB and ERK1/2. A moderate increase was seen with the cell cycle protein PCNA in rcHGF treated livers, but no HGF-induced increase in liver weight was seen 7 days after phx. Furthermore, rcHGF treated livers showed lower levels of the key mediator of apoptosis, caspase-3, at 7days after phx. It is concluded that rcHGF is a biologically active protein in vitro and in vivo and the baculoviral expression system supplies sufficient amounts of rcHGF for future clinical studies in dogs.
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PMID:In vitro and in vivo bioactivity of recombinant canine hepatocyte growth factor. 1831 58

The presence of hepatitis B virus (HBV) serological markers have been investigated in 101 Lebanese patients (69 men, 32 women; mean age 32.7 +/- 1.7 years) infected with human immunodeficiency virus type 1 (HIV-1). Seven patients (6.9%) were HBsAg carriers compared with 54 patients (53.5%) who had no evidence of exposure to HBV infection. Twenty-four patients (23.8%) had anti-HBc alone as a serological marker compared with four patients who were positive for anti-HBs alone and 12 patients (11.9%) who were anti-HBc and anti-HBs-positive. Occult HBV infection (presence of HBV DNA in the absence of HBsAg) is found to be relatively high (28.7%) in HIV-infected Lebanese patients and the overwhelming majority (83.3%) of those who were positive for anti-HBc alone had a detectable HBV DNA in their serum. However, none of our HIV-positive patients with occult HBV infection had abnormal alanine aminotransferase level, which also raises the question as to whether occult HBV plays a role in the aetiology of liver disease in HIV-infected patients. Further, studies on the association between HBV DNA levels and markers of liver function in addition to data on liver biopsy would help in answering this question.
Int J STD AIDS 2008 Mar
PMID:Occult hepatitis B virus infection in HIV-infected Lebanese patients with isolated antibodies to hepatitis B core antigen. 1839 62

There has been significant progress in the understanding of the pathophysiologic basis of common haematological problems like cytopenias, coagulopathies and thrombophilic disorders in the background of liver disease. Diagnosis has improved with newer tests like detection of JAK2 mutation and better radiological imaging. Additionally, therapeutic options have expanded with availability of drugs like activated factor VII and eltrombopeg and improved expertise in procedures like TIPSS for treatment of the Budd-Chiari syndrome. Thus, there is increasing need for coordinated management of these problems by the hematologist and gastroenterologist. This article overviews the interface between hepatology and hematology and elaborates on some of the common problems encountered.
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PMID:Hematological problems and liver disease. 1976 Sep 87


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