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:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.
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PMID:Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves. 128 27

The effect of menaquinone-4 (MK-4, vitamin K2) was studied on des-gamma-carboxy prothrombin (DCP or PIVKA-II) levels in three subjects with vitamin K deficiency and five patients with hepatocellular carcinoma (HCC) with positive DCP. The half-life of DCP in HCC patients after intravenous MK-4 administration (50 mg daily for 14 days) was determined to be 60 hours, identical to that found in vitamin K-deficient subjects who received MK-4. When a single dose of MK-4 (10 mg) was given intravenously to three patients with HCC and elevated DCP, the levels decreased with a reduction rate identical to that in vitamin K-deficient subjects for the first 1 to 3 days, followed by an increase reaching the previous level in 7 to 10 days. Changes in plasma coagulant activity were compared between subjects with vitamin K deficiency and those with HCC before and after a single dose of MK-4 (10 mg). The activity increased in DCP-positive patients with HCC as in vitamin K-deficient subjects who received the same single dose of MK-4. The increase was greater in HCC patients with higher DCP levels. These results suggest that the level of plasma DCP in patients with HCC responded to vitamin K with the same sensitivity as that in vitamin K-deficient subjects. When patients with HCC underwent effective tumor therapy (resection or arterial embolization), the reduction rate (slope of DCP decline) was found to be identical to that in vitamin K-deficient subjects given with MK-4. In patients with less effective therapy, the reduction rate was smaller, or there was an increase in DCP. These observations strongly suggest that sequential measurements of the DCP reduction rate after treatment for HCC are useful for assessing therapeutic effects.
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PMID:Changes of plasma des-gamma-carboxy prothrombin levels in patients with hepatocellular carcinoma in response to vitamin K. 130 8

In spite of the development of various antibiotics, management of elderly patients with pneumonia remains an important problem. It is suggested that adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) often occur in elderly patients with pneumonia. Although neutrophils are suggested to be involved in the genesis of these conditions, details remain unknown. We demonstrated that a highly cytotoxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized from linoleate by human neutrophils, thus it was named leukotoxin. Leukotoxin was detected in lung lavages from patients with ARDS. In these lung lavages, increases in albumin concentration and angiotensin converting enzyme (ACE) activity were also observed. Similar results were observed in lung lavages from rats after exposure to hyperoxia for 60 hours in an experimental model of ARDS. Intravenous administration of leukotoxin (100 mumol/kg) caused lung edema. Albumin concentration and ACE activity were increased in lung lavages of rats receiving leukotoxin. In contrast, these changes were not observed in rats administered with linoleate. Furthermore, administration of leukotoxin (100 mumol/kg) caused coagulation abnormality, i.e., increase in fibrin-fibrinogen degradation products, decrease in fibrinogen, and prolongation of activated partial thromboplastin time and prothrombin time. Administration of linoleate did not induce these changes. It is indicated that O2- was produced by respiratory burst enzyme located in neutrophil plasma membrane, and that hydroxyl radicals derived from O2- by Fenton reaction were responsible for leukotoxin synthesis. From our results, leukotoxin, a product of hydroxyl radicals and linoleate, might be responsible for the genesis of ARDS and DIC.
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PMID:[Leukotoxin and pulmonary injury]. 238 90

Des-gamma-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-II and also abbreviated PIVKA-II, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.
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PMID:Plasma abnormal prothrombin (des-gamma-carboxy prothrombin) as a marker of hepatocellular carcinoma. 245 Jun 34

Over the last few years, many tumor markers have been proposed to clinicians but only a limited number of them meet the necessary criteria to be useful for either screening, diagnosis, prognosis or follow-up of gastrointestinal (GI) tumors. Both CEA and Ca 19-9 have proven to be clinically useful for the detection of recurrent tumors. AFP remains the most useful marker for the follow-up of hepatocellular carcinoma (HCC). Its interest for the early detection of primary tumor is debated. Recent data suggest that assays based on monoclonal antibodies to AFP could be used for detection HCC in high risk populations. Decarboxy-prothrombin assay may be a complement to the AFP test in this localization. In addition to GI hormones, serotonin and urinary 5HIAA, Neuron Specific Enolase appears to be a valuable marker for the follow-up of neuroendocrine tumors of the GI tract. Only a few of the new tumor-associated antigens detected by monoclonal antibodies, appear to be promising clinical ly e.g. Ca50 TAG-72, PAO. Monoclonal antibodies to tumor-associated markers have also been used with other techniques: Immunohistochemistry: this technique is useful to the pathologist for the diagnosis of undifferentiated tumors by demonstrating the presence of specific antigens on tissue samples. Immunoscintigraphy: it can be useful for the detection of either metastases of recurrences of colorectal cancer by using anti-ACE antibodies labeled with Iodine 131 iodine 123 or indium 111. However immunoscintigraphy is less sensitive than both ultrasonography and CT scan for localizing hepatic metastases. At the present time the best indication of this method remains the diagnosis of pelvic recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The value of tumor markers in digestive oncology]. 269 5

We measured plasma abnormal prothrombin (des-gamma-carboxy prothrombin; DCP) levels in normal subjects and in patients with hepatocellular carcinoma and other various diseases using the enzyme-linked immunosorbent assay developed by Motohara et al. (Pediatr Res 1985; 19: 354-357). Fifty-eight percent of 52 patients with hepatocellular carcinoma had elevated DCP levels; 24 of 28 patients with advanced or moderately advanced hepatocellular carcinoma were positive. By contrast, 50 normal controls, 13 pregnant women and 10 patients with acute hepatitis had normal levels. Three of 55 patients with chronic liver disease, and 6 of 32 patients with other malignancies, showed a slight increase. Thus, increased plasma DCP appears useful for the diagnosis of hepatocellular carcinoma. To elucidate the mechanism for the increase of DCP in hepatocellular carcinoma, we cultured a human hepatoma cell line, huH-2, and measured the levels of this abnormal prothrombin in the medium. The huH-2 cells produced large amounts of DCP in the medium without added vitamin K. It increased in a cell concentration- and time-dependent fashion. These cells produced no detectable amount of DCP in the medium with added vitamin K. Thus, human hepatoma cell line huH-2 produces DCP, and its production is dependent on the amount of vitamin K available in the medium. Des-gamma-carboxy prothrombin may be a useful tumor marker for the diagnosis of hepatocellular carcinoma.
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PMID:Production of abnormal prothrombin (des-gamma-carboxy prothrombin) by hepatocellular carcinoma. A clinical and experimental study. 303 40

To clarify the mechanism of production of des-gamma-carboxy (abnormal) prothrombin (DCP) by hepatocellular carcinoma (HCC), we measured the levels of vitamin K, DCP, immunoreactive prothrombin and the activity of gamma-glutamyl carboxylase in liver tissues from HCC patients and in the medium of cultured human hepatoma cells. There was no significant difference in vitamin K (K1, MK-4) contents between HCC and non-HCC cirrhotic liver tissues. The activity of gamma-glutamyl carboxylase per unit amount of endogenous microsomal prothrombin precursor was decreased in HCC tissue compared with non-HCC liver tissue (positive plasma DCP: 335 +/- 72 vs 372 +/- 67, negative plasma DCP: 370 +/- 84 vs 393 +/- 56 nmol/min per mg prothrombin precursor, P > 0.05), although the total incorporation of 14COOH into microsomal precursor protein was higher in the former. By contrast, levels of DCP and immunoreactive prothrombin in HCC tissue were greater (P < 0.05) than those in non-HCC cirrhotic liver tissue. Furthermore, production of large amounts of immunoreactive prothrombin was observed in human hepatoma cells huH-1 and huH-2, which produced large amounts of DCP. These results suggest that there was excessive synthesis of prothrombin precursors by human HCC tissue and hepatoma cell lines huH-1 and huH-2. Thus, excessive synthesis of prothrombin precursors seems to be the main mechanism of DCP production by HCC.
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PMID:Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. 762 Jan 13

Fosinopril is distinguished from other ACE inhibitors by a pharmacokinetic pecularity in the sense that is can be metabolized either by liver or kidney. This was the rationale of the present research the aim of which was to verify if administered to patients with liver cirrhosis the drug was liable to alter global liver function and ability to metabolize drugs. Eight cirrhotic males, mean age 56 years, also suffering from high blood pressure, were studied. In these patients, liver and kidney function tests (BUN, creatinine blood level, serum and urinary electrolytes, creatinine clearance, calcium and phosphor blood level, transaminases, alkaline phosphatase prothrombin time, cholinesterase, gamma-glutamyl-transpeptidase) were carried out at baseline and after 30 days' fosinopril treatment (1 capsule every morning in the fasting state); in addition total functioning liver mass was assessed by the galactose test, and drug-metabolizing capacity by the antipyrine test. Treatment resulted in a significant improvement of pressure values in all patients (p < 0.01) and did not alter liver and kidney function parameters. Besides, no side effects were registered, especially no case of orthostatic hypotension. The antipyrine test was not influenced by fosinopril treatment. Therefore, short-term treatment with this ACE-inhibitor can be concluded to be effective and not to cause additional alterations of liver function in patients with liver cirrhosis.
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PMID:[Evaluation of the total hepatic function after treatment with fosinopril in hypertensive patients with liver cirrhosis]. 772 Mar 55

Coumarin derivatives combine 3 unfavorable properties which make them prone to potentially life threatening drug-drug interactions: (i) high protein binding; (ii) cytochrome P450 dependent metabolism; and (iii) a narrow therapeutic range. An entire list of drugs which are supposed to interact with coumarins (mostly with warfarin) comprises about 250 different compounds. Noteworthy are the interactions with cardiovascular or antilipidaemic drugs which are often coadministered with coumarins: amiodarone, propafenone and fibrates. Cardiovascular drugs which are obviously devoid or proven to be devoid of an interaction are angiotensin converting enzyme (ACE) inhibitors, calcium antagonists, beta-blockers and cardiac glycosides. There are several other drugs which enhance the hypoprothrombinaemic response to coumarins by various mechanisms: inhibitors of the elimination of the eutomer S-(-)-warfarin (e.g. miconazole, phenylbutazone), combined with protein binding displacement (e.g., sulfinpyrazone, phenylbutazone), synergistic hypoprothrombinaemia (e.g. cefazoline). Furthermore, bleeding complications may occur with drugs affecting platelet function [aspirin (acetylsalicylic acid) and several nonsteroidal anti-inflammatories (NSAIDs)]. Strong inducers of coumarin metabolism are rifampicin (rifampin) and carbamazepine. Biphasic interactions may occur where a drug first enhances the hypoprothrombinaemic response to a coumarin but has a sustained inducing effect on coumarin metabolism (e.g. phenytoin or sulfinpyrazone). The complex response of coumarins to concomitant drug therapy makes it difficult to predict the occurrence and degree of a deterioration of anticoagulant control in individual patients. For clinical practice, it seems advisable that one should monitor for changes in prothrombin time when adding or deleting any newly approved drug or any drug suspected (e.g. on the basis of this review) to cause an interaction to patients on coumarin therapy. The onset of the adverse prothrombin time response might be from between 1 to 2 days up to 3 weeks (in case of phenprocoumon) after starting a concomitant drug regimen. With amiodarone, an adverse prothrombin time response might occur up to 2 months after initiating therapy. For heparins, only a drug interaction with aspirin or nitroglycerin seems clinically relevant due to the possibility of coadministration during acute cardiac events. Both drugs are shown to enhance the activated partial thromboplastin time response to heparin.
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PMID:Clinically important drug interactions with anticoagulants. An update. 879 56

The aim of the present study was to determine whether pretreatment with cyclosporine (CsA), or perindopril (an angiotensin converting enzyme inhibitor) would modify the ischaemia-reperfusion injury of vascular occlusion during liver resection. Rats were allocated to four groups (n = 20 for each group): (i) sham operated; (ii) liver resection only; (iii) CsA (15 mg/kg); and (iv) perindopril (4 mg/kg during the three days before ischaemia-reperfusion injury with liver resection). The ischaemia was produced by a 30 min continuous occlusion. The model was designed to study liver function tests as the principal parameter. Compared with liver resection only, bilirubin was significantly lower with perindopril on days 8 and 23, but significantly higher with CsA on days 1 and 2. The alanine aminotransferase peak (day 1) was significantly lower with both perindopril and CsA. The prothrombin time was significantly less on days 2 and 4 with perindopril and day 4 with CsA. Liver histological changes were minimal in all groups at 30 min ischaemia, but were significantly less severe in the perindopril group. There was a significant decrease in the weight of the regenerated liver at day 23 with perindopril and a significantly lower drop in weight on day 1 and the rate of gain was significantly greater. Perindopril (4 mg/kg) and CsA (15 mg/kg) significantly alter liver function tests, liver histology and bodyweight following an ischaemia-reperfusion injury associated with liver resection. These findings could limit ischaemia-reperfusion injury for major liver resections in the clinical setting.
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PMID:Premedication with cyclosporine and perindopril modifies the ischaemia-reperfusion injury during liver resection in rats. 884 Feb 41


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