Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An ELISA has been developed for detection of auto-antibodies against calmodulin. There was a significantly increased frequency (63.1%) of autoantibodies against calmodulin in 103 patients with chronic liver diseases as compared to that (30%) of patients with systemic lupus erythematosus and to that (6.9%) of normal subjects (p less than 0.01). IgG autoantibodies against calmodulin were detected in the patients with acute hepatitis (37.9%), chronic liver disease (45.6%) and also in the patients with systemic lupus erythematosus (30%). IgM autoantibodies against calmodulin were frequently found in patients with liver cirrhosis (52.2%), primary biliary cirrhosis (50%) and autoimmune chronic active hepatitis (38.7%), but rarely in patients with acute hepatitis (13.8%), chronic persistent hepatitis (9.5%) and systemic lupus erythematosus (0%). IgA autoantibodies against calmodulin were frequently found in liver cirrhosis (33.3%), primary biliary cirrhosis (42.9%) and autoimmune chronic active hepatitis (53.6%), but rarely in chronic persistent hepatitis (15.8%), chronic active hepatitis (14.3%) and systemic lupus erythematosus (0%). The occurrences of autoantibodies against calmodulin correlated neither with those of antismooth muscle antibody, antinuclear antibody and antimitochondrial antibody, nor with serum IgG concentrations. Autoantibodies against calmodulin did not cross-react with troponin, myosin light chain, calf thymus DNA and actin. The titer of autoantibodies against calmodulin was decreased by absorption of serum with calmodulin and the liver plasma membrane fraction. The immunoblotting experiment revealed the binding of autoantibodies against calmodulin to calmodulin. IgG fraction from a patient with autoimmune chronic active hepatitis inhibited the activation of phosphodiesterase by calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticalmodulin autoantibody in liver diseases: a new antibody against a cytoskeleton-related protein. 355 8

2,131 coded sera were obtained and tested according to the new 5'-NPDase-V isozyme test. On decoding, 99/126 (79%) samples of primary hepatoma, from the United States and other countries, were positive. In the U. S. group, 51/58 (88%) were positive, 23/58 (40%) had AFP higher than 20 ng/ml. In the non-U. S. group, 48/68 (71%) were positive for 5'-NPDase-V, as compared with AFP elevation in 45/68 (66%). 236/268 (88%) cases of cancer with known liver metastases were positive for 5'-NPDase-V. Of 1,040 cancer patients without liver scan or biopsy evidence of metastasis, 316 were positive. In a follow-up of this group of 316 cases, 109 underlying liver metastases were demonstrated by repeat scan or at autopsy within 3--6 months. All 166 sera from normal healthy persons were negative for 5'-NADase-V. Based on this large panel, 5'-NPDase-V test is a sensitive and an important diagnostic aid for cancer patients, both as an early predictor for liver metastases, and a useful marker for primary hepatoma when no other primary sites are found and when there is no evidence of severe chronic liver disease such as cirrhosis.
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PMID:Serum 5'--nucleotide phosphodiesterase isozyme--V test for human liver cancer. 615 48

Insulin action is approximately doubled following a meal. The mechanism of postprandial insulin sensitization is dependent on hepatic parasympathetic nerves regulated by the prandial status. The nerves provide a permissive signal to the liver that allows insulin to cause the release of a putative hepatic insulin sensitizing substance (HISS) that selectively stimulates glucose uptake into skeletal muscle but not liver or adipose tissue. The parasympathetic signal has several steps identified in the regulatory pathway; acetylcholine acts on muscarinic receptors leading to activation of nitric oxide synthase and generation of HISS. The meal-induced insulin (MIS) sensitization requires hepatic GSH, which decreases with fasting and several disease states. Interfering with the MIS process results in severe insulin resistance with the response to insulin being reduced by approximately 50% to levels seen in the fasted state. A wide range of conditions have been shown to be associated with insulin resistance attributed to lack of the MIS process including insulin resistance; in chronic liver disease produced by chemical damage or bile duct ligation, hepatic denervation, sucrose fed rats, aging, spontaneously hypertensive rats, fetal alcohol exposed adult offspring, spontaneously insulin resistant rats, animals with pharmacological blockade of hepatic muscarinic receptors, NO synthase, cyclooxygenase, hepatic cGMP, and hepatic GSH levels. Pharmaceutical reversal of insulin resistance has been shown in several models using a variety of approaches including mimicking or potentiating the parasympathetic signal using cholinergic agonists, NO donors, cholinesterase antagonists, phosphodiesterase antagonists, and replenishment of hepatic GSH levels. These compounds are being evaluated for therapeutic application by our international academic/industry collaborative team. The MIS process has now been demonstrated in mice, rats, guinea pigs, cats, dogs, and humans, and has been demonstrated by independent laboratories.
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PMID:Pharmaceutical reversal of insulin resistance. 1563 5

Pulmonary arterial hypertension (PAH) is a disease that leads to characteristic vascular wall remodeling and hemodynamic alterations. Consequently, this pulmonary vascular disease contributes to substantial morbidity and mortality in afflicted patients. PAH may be idiopathic in nature or associated with connective tissue disease, chronic liver disease, human immunodeficiency virus, congenital heart disease, and a growing list of other conditions. There are currently nine Food and Drug Administration-approved therapies for specific PAH treatment. Therapeutic targets include prostacyclin replacement, endothelin-1 antagonism, and phosphodiesterase-5 inhibition. This article focuses on the prostanoid treprostinil and explores its role in the management of patients with PAH.
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PMID:Clinical utility of treprostinil and its overall place in the treatment of pulmonary arterial hypertension. 2287 90

Liver disease is a significant health problem worldwide with mortality reaching around 2 million deaths a year. Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are the major causes of chronic liver disease. Pathologically, NAFLD and ALD share similar patterns of hepatic disorders ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. It is becoming increasingly important to identify new pharmacological targets, given that there is no FDA-approved therapy yet for either NAFLD or ALD. Since the evolution of liver diseases is a multifactorial process, several mechanisms involving parenchymal and non-parenchymal hepatic cells contribute to the initiation and progression of liver pathologies. Moreover, certain protective molecular pathways become repressed during liver injury including signaling pathways such as the cyclic adenosine monophosphate (cAMP) pathway. cAMP, a key second messenger molecule, regulates various cellular functions including lipid metabolism, inflammation, cell differentiation and injury by affecting gene/protein expression and function. This review addresses the current understanding of the role of cAMP metabolism and consequent cAMP signaling pathway(s) in the context of liver health and disease. The cAMP pathway is extremely sophisticated and complex with specific cellular functions dictated by numerous factors such abundance, localization and degradation by phosphodiesterases (PDEs). Furthermore, because of the distinct yet divergent roles of both of its effector molecules, the cAMP pathway is extensively targeted in liver injury to modify its role from physiological to therapeutic, depending on the hepatic condition. This review also examines the behavior of the cAMP-dependent pathway in NAFLD, ALD and in other liver diseases and focuses on PDE inhibition as an excellent therapeutic target in these conditions.
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PMID:Role of cAMP and phosphodiesterase signaling in liver health and disease. 3004 53