Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.
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PMID:Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. 1098 61

We have shown, in animal models as well as in retrospective human study, that some degree of decreased thyroid function is beneficial for subjects with liver damage of various etiologies. Therefore, we herein present the results of a cohort population study. Between 1991 and 1994, 18 patients (12 women and 6 men; mean age, 59 +/- 24 years) with both biopsy-proven active cirrhosis (5 hepatitis C virus, 4 hepatitis B virus, 1 immunocompromised host, 2 primary biliary cirrhosis, 1 alcoholic, and 5 cryptogenic; Child's-Pugh criteria: A-8, B-8, C-2) and primary or induced (by either drug or surgery) thyroxine-treated hypothyroidism were prospectively followed. Each patient was examined at least twice yearly and served as their own control. The thyroid of the profiled patients ranged between euthyroidism and subclinical hypothyroidism. Liver function tests were evaluated and compared in states of normal versus increased thyroid-stimulating hormone (TSH) blood levels. A significant improvement in alanine aminotransferase (p < 0.001), alkaline phosphatase (p < 0.0001), albumin (p < 0.001), and bilirubin (p < 0.01) was found in the increased TSH group. Prothrombin time was also found to be significantly better (p < 0.001). We conclude that euthyroid patients with liver cirrhosis might benefit from a controlled hypothyroidism.
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PMID:The effects of hypothyroidism on liver status of cirrhotic patients. 1099 36

We herein describe a patient with autoimmune cholangiopathy complicated with rheumatoid arthritis. A 58-year-old female was admitted to our hospital due to complications of arthralgia in her fingers, shoulders, elbows, knees and ankles. She presented with abnormally elevated levels of transaminases, alkaline phosphatase and was also negative for hepatitis B virus, hepatitis C virus and the serum mitochondrial antibody test, but had high titers of serum antinuclear antibody, rheumatoid factor and rheumatoid arthritis hemagglutination. A liver biopsy specimen showed chronic non-suppurative destructive cholangitis. She was thus diagnosed to have autoimmune cholangiopathy and rheumatoid arthritis. She began treatment with prednisolone 40 mg per day. After 20 days of steroid therapy, her hepatic function tests improved and the arthralgia symptoms disappeared. This is, to our knowledge, the first case of autoimmune cholangiopathy associated with rheumatoid arthritis, in which both symptoms improved with steroid therapy.
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PMID:Autoimmune cholangiopathy associated with rheumatoid arthritis. 1114 95

Some studies suggest that the hepatitis C virus (HCV) internal ribosome entry site (IRES) requires downstream 5' viral polyprotein-coding sequence for efficient initiation of translation, but the role of this RNA sequence in internal ribosome entry remains unresolved. We confirmed that the inclusion of viral sequence downstream of the AUG initiator codon increased IRES-dependent translation of a reporter RNA encoding secretory alkaline phosphatase, but found that efficient translation of chloramphenicol acetyl transferase (CAT) required no viral sequence downstream of the initiator codon. However, deletion of an adenosine-rich domain near the 5' end of the CAT sequence, or the insertion of a small stable hairpin structure (deltaG = -18 kcal/mol) between the HCV IRES and CAT sequences (hpCAT) substantially reduced IRES-mediated translation. Although translation could be restored to both mutants by the inclusion of 14 nt of the polyprotein-coding sequence downstream of the AUG codon, a mutational analysis of the inserted protein-coding sequence demonstrated no requirement for either a specific nucleotide or amino acid-coding sequence to restore efficient IRES-mediated translation to hpCAT. Similar results were obtained with the structurally and phylogenetically related IRES elements of classical swine fever virus and GB virus B. We conclude that there is no absolute requirement for viral protein-coding sequence with this class of IRES elements, but that there is a requirement for an absence of stable RNA structure immediately downstream of the AUG initiator codon. Stable RNA structure immediately downstream of the initiator codon inhibits internal initiation of translation but, in the case of hpCAT, did not reduce the capacity of the RNA to bind to purified 40S ribosome subunits. Thus, stable RNA structure within the 5' proximal protein-coding sequence does not alter the capacity of the IRES to form initial contacts with the 40S subunit, but appears instead to prevent the formation of subsequent interactions between the 40S subunit and viral RNA in the vicinity of the initiator codon that are essential for efficient internal ribosome entry.
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PMID:The influence of downstream protein-coding sequence on internal ribosome entry on hepatitis C virus and other flavivirus RNAs. 1134 37

In 30 patients with mononucleosis-like syndrome (MLS) caused by cytomegalovirus (CMV), diagnosed on the basis of clinical symptoms, haematological & serological changes (after excluding Epstein-Barr virus, HAV, HBV and HCV infections), the following measurements were done weekly during consecutive two months': bilirubin concentration, aspartate & alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), beta-glucuronidase (B-GR), and gamma-glutamyltranspeptidase (GGTP) activity. Increase in bilirubin concentration was found in 6% of patients, increase of AST and ALT activity--in 70%, GGTP--in 50%, ALP--in 25%, and of B-GR--in 16% of the subjects. The highest bilirubin concentration, and high levels of AST, ALT, and B-GR were noted in the 2nd week of infection, whereas the peak activity of ALP and GGTP was found in the 3rd week of the disease. In all patients normalization of bilirubin concentration was earliest (5th week of infection); followed by decrease of AST, ALT, B-GR, and ALP activity (7th week), and subsequently--that of GGTP (8th week of the disease). The results of the investigations have shown that in the course of MLS the changes of hepatic activity are limited and transient; they return to normal synchronously with the withdrawal of clinical symptoms (4th-6th week of the disease), without permanent measurable consequences. In patients with MLS and increase AST & ALT activity (400-600 iu) as well as slight increased of bilirubin concentrations hepatitis C,A and B should be excluded. In has not been established so far whether the changes of hepatic function during MLS are the consequence of direct infection by CMV, reactivation of the primary occult infection (asymptomatic), or re-infection by a different serotype.
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PMID:[Biochemical changes of liver damage factors in the course of mononucleosis like syndrome caused by cytomegalovirus]. 1134 95

Fifteen male patients with acute hepatitis C aged 16-44 years were treated with neovir, an interferon inducer, administered intramuscularly in a daily dose of 250 mg 2-3 times a week for 3 months. By the end of this therapy the RNA of hepatitis C virus could still be detected in 84.6% of the patients, the characteristics of ALT, AST and alkaline phosphatase exceeded the norm more than twofold. The results of neovir therapy are regarded as ineffective.
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PMID:[Effect of neovir in the treatment of acute hepatitis C]. 1155 May 70

Bile duct lesions are observed in the livers of chronic hepatitis C patients, but are inconstant and rarely associated with other features of chronic cholestasis and progressive bile duct injury or loss. We aimed to identify the clinical and biochemical characteristics of patients with chronic hepatitis C from our patient database presenting with prominent cholestatic features to determine if there is a correlation between histological evidence of bile duct injury and clinical or biochemical features observed in these patients. We retrospectively reviewed a hepatitis C database including 620 patients to identify those who presented with either alkaline phosphatase (AP) > or = 400 units/liter (normal 30-126 units/liter) or AP > or = 250 units/liter with pruritus. All patients were negative for anti-mitochondrial antibody (AMA). Appropriate exclusion criteria were used to exclude patients with other confounding factors. Histological features were compared with age- and sex-matched controls selected randomly from our hepatitis C database. Thirty-two patients were identified as meeting the above criteria. Twenty-four were excluded for the presence of other confounding factors and two for lack of liver biopsy. There were two men and four women. The mean age was 47 +/- 9 years. Four of the six presented with pruritus, which was severe in three. Liver biopsy showed evidence of moderate to severe fibrosis in all but one patient. Evidence of bile duct injury was seen in all patients and tended to be more severe than in controls. Bile ductular proliferation and mild ductopenia were the most commonly observed findings. A subset of patients with chronic hepatitis C may present with prominent cholestatic features. The majority of these patients present with pruritus and have histological evidence of bile duct injury, which may be progressive.
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PMID:Cholestatic presentation of chronic hepatitis C: a clinical and histological study with a review of the literature. 1168 May 77

The pathogenesis of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is poorly understood, but the cellular immune response is likely to have a major role. Daclizumab, an interleukin-2 receptor (IL-2R) antibody that blunts T-cell activation, leading to a decreased risk for cellular rejection, is used frequently in transplant recipients. The aim of this study is to evaluate the effect of daclizumab therapy on the incidence and severity of recurrent HCV. Forty-one liver transplant recipients (21 patients, HCV positive; 20 patients, HCV negative) at high risk for neurological or renal complications of calcineurin inhibitors were administered daclizumab, mycophenolate mofetil (MMF), and steroids in the early post-LT period, followed by tacrolimus and a steroid taper. All patients were followed up prospectively for graft function and disease recurrence with protocol liver biopsies day 7, month 4, and yearly. Compared with patients without HCV, patients with HCV administered daclizumab had greater 4-month serum alkaline phosphatase, total bilirubin, and alanine aminotransferase (ALT) levels. These biochemical differences resolved by 12 months, except for persistent elevation of ALT levels. Compared with a well-matched HCV control population, patients with HCV administered daclizumab were more likely to have an earlier onset of hepatitis, jaundice, and greater histological activity. Recurrent hepatitis progressed more rapidly in the daclizumab group; 45% developed advanced disease within 1 year. HCV viral load in the daclizumab group was significantly greater at both 4 months and 1 year. Results of this study suggest that the use of adjuvant IL-2R antibodies in combination with MMF in the early peritransplantation period may be associated with early recurrence of hepatitis C and more rapid histological progression of disease.
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PMID:Anti-interleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. 1175 8

We investigated the prevalence of positive viral hepatitis titres in sickle cell disease (SCD) and the relationship of abnormal liver function tests (LFTs) to transfusions and ferritin levels. Charts from 141 patients with SCD were reviewed and recent laboratory data on serum ferritin, hepatitis serology, units of packed red blood cells transfused and LFTs were collected. Hepatitis B core antibodies were positive in 14% of patients (12/86) and Hepatitis C viral antibody titres were positive in 16.5% (15/91). There was a relationship of positive serologies to transfusion for hepatitis C virus (HCV), but not for hepatitis B virus (HBV). Hepatitis C antibody negative (HCVAb-) patients had fewer packed red blood cells (pRBC) transfused than Hepatitis C antibody positive (HCVAb+) (6.4 vs. 20.3, P=0.08). Patients with ferritins < 500 ng/ml compared to those with > 1000 ng/ml also showed a difference in units transfused (P < 0.003). Steady state LFTs, with the exception of alkaline phosphatase, had no relationship to serum ferritin or hepatitis serologies. Males were twice as likely to have positive serology as females but more females had elevated ferritin levels. Paired analysis of LFTs in steady state and crisis failed to demonstrate deterioration during crisis. We conclude that: (1) there is a relationship of positive Hepatitis C serology, but not Hepatitis B serology, to transfusion; (2) ferritin levels correlate with transfusion number but not with LFTs; (3) in our population, LFTs in SCD are usually normal and do not increase in vaso-occlusive crises.
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PMID:Liver function tests in sickle cell disease. 1184 94

Hepatitis C virus (HCV) is transmitted primarily by direct percutaneous exposures to blood. Since HCV RNA has been found in saliva, it has been suggested that saliva might also be a source of infection. HCV RNA in saliva from plasma HCV RNA positive patients was tested by a highly sensitive PCR method. HCV RNA was detected in 32 out of 61 saliva specimens (52.4%). No correlation was found between the presence of HCV in saliva and age, sex, identified risk factors for HCV infection, time lapsed since the diagnosis, transaminases and alkaline phosphatase values and stimulated salivary flow. A statistically significant relation between plasma HCV RNA viral load and saliva HCV RNA detection was observed (P<0.001). In conclusion, HCV RNA is often present in saliva of HCV infected patients, with plasma viral load being the only known predictable factor. Further studies on salivary HCV RNA are needed.
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PMID:Detection of HCV RNA in saliva of patients with hepatitis C virus infection by using a highly sensitive test. 1184 81


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