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

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic findings. Our goal was to characterize the disease prospectively by application of uniform diagnostic criteria. Twenty patients were identified and compared with 242 patients with conventional forms of autoimmune liver disease. Patients with autoimmune cholangitis were distinguished from type 1 autoimmune hepatitis (AIH) by lower serum levels of aspartate transaminase (AST), gamma-globulin, and immunoglobulin G; higher serum levels of alkaline phosphatase; and lower frequencies of autoantibodies. They were distinguished from primary biliary cirrhosis (PBC) by higher serum levels of AST and bilirubin, lower serum concentrations of immunoglobulin M, and greater occurrence of autoantibodies. Their female predominance, lower serum alkaline phosphatase levels, higher frequency of autoantibodies, and absence of inflammatory bowel disease differentiated them from primary sclerosing cholangitis (PSC). Laboratory findings ranged widely and did not characterize individual patients. HLA risk factors were similar to those of type 1 AIH and PBC, and different from those of PSC. Treatment responses to corticosteroids or ursodeoxycholic acid were poor. Composite histological patterns resembled mainly PBC or PSC. We conclude that autoimmune cholangitis diagnosed by prospective analysis cannot be assimilated into a single, conventional, diagnostic category. It may represent variant forms of diverse conditions, a transition stage, or a separate entity with varying manifestations.
...
PMID:Autoimmune cholangitis within the spectrum of autoimmune liver disease. 1207 15

The overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis is a rare condition and only few cases have been published, partly associated with ulcerative colitis, but not with Crohn's disease. We report an autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome in a female patient with Crohn's disease. In addition, a second case of overlap syndrome is reported in a man without inflammatory bowel disease. A 24-year-old woman was referred with a 10-month history of diarrhoea and biochemical changes including elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and immunoglobulin G. Enzyme linked immunosorbent assay showed that antinuclear autoantibodies were elevated. Immunofluorescence for perinuclear-staining antineutrophil cytoplasmatic antibodies was positive. Diagnostic criteria of definite autoimmune hepatitis according to the International Autoimmune Hepatitis Group were fulfilled. Liver biopsy simultaneously showed criteria of autoimmune hepatitis and primary sclerosing cholangitis. Endoscopic retrograde cholangiography demonstrated features of primary sclerosing cholangitis. Colonoscopy and colonoscopic biopsies indicated an active Crohn's disease affecting the terminal ileum and the ascending and transverse colon. Furthermore, we report the case of a 28-year-old man with known primary sclerosing cholangitis for the previous 6 years, and who developed jaundice and a marked increase of aspartate aminotransferase, alanine aminotransferase and immunoglobulin G, leading to the diagnosis of definite autoimmune hepatitis. A review of the literature revealed only 16 cases of an autoimmune hepatitis/primary sclerosing cholangitis syndrome in patients without inflammatory bowel disease or in association with ulcerative colitis. We report two additional cases, one case showing an association with Crohn's disease.
...
PMID:Overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis in two cases. 1083 1

Over the past decade, the outcome of liver transplantation in primary sclerosing cholangitis (PSC) patients with end-stage liver disease has improved significantly with many centres reporting 1-year patient and graft survival of 90-97% and 85-88%, respectively. Based on these results, liver transplantation has emerged as the treatment of choice for PSC patients. Specific complications related to PSC remain problematical. Inflammatory bowel disease (IBD) occurs in 70% of patients, and there is a distinctly increased risk of colorectal neoplasia both pre- and post-transplantation. Furthermore, symptoms related to IBD post-transplantation can become severe and lead to the need for proctocolectomy. Cholangiocarcinoma remains a major risk facing the PSC patient and develops in 15-30% of patients. Markers to detect the early neoplastic changes of cholangiocarcinoma are not available. To date, outcome following liver transplantation in PSC patients who have associated cholangiocarcinoma has been dismal. However, those patients who are found to have an incidental cholangiocarcinoma have an acceptable low incidence of recurrence of disease. To assess optimal timing of liver transplantation, natural history risk scores have been developed and utilized. Utilizing such risk scores, estimated survival for the individual PSC patient can be obtained. Finally, there is an increased incidence of both acute and chronic rejection, hepatic artery thrombosis and biliary stricturing in PSC patients undergoing liver transplantation. A late rise in serum alkaline phosphatase level is almost always indicative of biliary stricturing and recurrence of disease. Approximately 20% of patients followed for 5 years or more will have recurrence of PSC documented both on cholangiography and histology.
...
PMID:Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease. 1149 75

The present studies were designed to determine whether recombinant human growth hormone (rhGH) can counteract some of the catabolic effects of glucocorticosteroid therapy in children chronically treated with glucocorticosteroids. Whether rhGH can safely improve short-term linear growth was also investigated. The effect of rhGH on disease activity was also assessed. Ten children (6 boys, 4 girls) with inflammatory bowel disease (IBD) on oral prednisone for at least 4 months prior to these studies were recruited (mean +/- SE, 11.9 +/- 0.9 years). Leucine and glucose isotope studies, body composition, substrate oxidation and energy expenditure rates, and growth factors were measured at baseline (D1) and at 4 months after treatment with rhGH (0.05 mg/ kg. d subcutaneously [SC]) while continuing oral prednisone. Dual-emission x-ray absorptiometry (DEXA) and calcium kinetic analysis ((42)Ca/(46)Ca) were performed also. rhGH was continued for 6 months to assess linear growth in all 10 subjects, 7 of whom continued rhGH for 12 months. Body composition changed favorably with increased fat free mass (+3 kg, P =.001) and decreased percent fat mass (-3.5%, P =.001) after 4 months of treatment. Rates of whole body protein turnover, oxidation, and synthesis remained invariant, with no changes in substrate oxidation or resting energy expenditure rates. Linear growth velocity increased from 3.5 +/- 0.4 cm/yr when the patients were treated with prednisone only, to 7.7 +/- 0.9 after 6 months of combined prednisone/rhGH (P =.001). The growth velocity was sustained in the 7 patients treated with rhGH for 12 months. Plasma insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations also increased significantly while on rhGH treatment. No changes in calcium absorption were observed but there was a significant increase in kinetic rates of bone calcium accretion (P =.045) as well as in bone-specific alkaline phosphatase concentrations, a measure of bone formation (P =.03). Fasting and 2-hour postprandial glucose concentrations, fasting insulin levels, and HbA(1C) were invariant during combined rhGH/prednisone treatment. The Crohn's disease activity score was unchanged with rhGH therapy. In summary, rhGH treatment of corticosteroid-dependent patients with IBD was associated with positive changes in body composition, bone metabolism, and linear growth, without deterioration of carbohydrate tolerance or intermediate metabolism of substrates. We conclude that treatment with rhGH has beneficial effects in prednisone-dependent growing children. Larger studies will be needed to assess the long-term safety and efficacy of this approach.
...
PMID:Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. 1178 84

Anti-galactosyl alpha1-3-galactosyl (anti-Gal) is a natural serum antibody abundantly produced in humans in response to immune stimulation by enteric bacteria. Marked elevation of its titer has been detected in parasitic diseases and in some autoimmune disorders. Because persistent intestinal infection and defective mucosal barrier have been suggested as potential etiologic agents of inflammatory bowel disease, the aim of this study was to analyze the sera levels of anti-Gal antibodies in patients with Crohn's disease and ulcerative colitis. An ELISA assay was performed to analyze circulating antibody using the disaccharide Gal (alpha 1-3)Gal coupled to human serum albumin as antigen and alkaline phosphatase-conjugated rabbit anti-human immunoglobulin G, A, M as antibody. Immunoglobulin classes were assayed using class-specific antibodies. The optical densities of sera from Crohn's disease (1.83 +/- 0.63) and ulcerative colitis (1.45 +/- 0.7) were significantly higher (P < 0.0001 and P < 0.0005, respectively) than those of the control group (0.97 +/- 0.39). In Crohn's disease the increase was distributed among the three immunoglobulin classes; in ulcerative colitis a significant increase was observed only for immunoglobulin A. The increased levels of circulating antibodies against Gal (alpha 1-3)Gal in the presence of intestinal bacterial strains expressing antigenic epitopes and breakdown of mucosal barrier could contribute to the dysregulated immune response observed in inflammatory bowel disease.
...
PMID:Alterations in serum anti-alpha-galactosyl antibodies in patients with Crohn's disease and ulcerative colitis. 1198 86

Recruitment of peripheral leukocytes to intestine is an essential process for intestinal inflammation. This study examined the localization of a novel molecule, 4C8 antigen, in inflammatory bowel disease; this molecule is involved in the transendothelial migration of T lymphocytes. Surgical specimens of human intestine were obtained from nine patients with ulcerative colitis, 13 with Crohn's disease, and eight controls. Immunohistological staining was performed using antibodies against 4C8 antigen, and CD3, CD4, CD8, CD20, CD68, CD45RA, CD45RO, CD11a, and CD62 (E- and P-selectin) by the peroxidase method. Immunological double staining was subsequently performed for the same specimens stained with anti-4C8 antibody using the alkaline phosphatase method. In normal controls, 4C8-positive cells were mainly found in lamina propria. 4C8-positive cells were increased in lamina propria and submucosa of specimens with Crohn's disease. Accumulation of 4C8-positive cells surrounding CD62-positive vessels was found in the submucosa of specimens with inflammatory bowel disease, but not in controls. Immunohistological double staining revealed that the major subsets of 4C8-positive cells were positive for CD3, CD4, CD45RO, and CD11a. 4C8-positive cells in human intestine belong to the subset of helper/inducer memory T cells newly recruited from the peripheral pool. Inhibition of the 4C8-ligand system could have potentially uses in the treatment of inflammatory bowel disease.
...
PMID:Expression of 4C8 antigen, a novel transendothelial migration-associated molecule on activated T lymphocytes, in inflammatory bowel disease. 1221 77

Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 +/- 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated gamma-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P <.001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P =.2) or medical therapy (P =.2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome.
...
PMID:Primary sclerosing cholangitis in children: a long-term follow-up study. 1283 4

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin, characterized by inflammation, fibrosis, and obliteration of bile ducts, which ultimately results in biliary cirrhosis. The condition most commonly affects intrahepatic and extrahepatic bile ducts together, but sometimes only intrahepatic or extrahepatic ducts are involved. PSC is often associated with inflammatory bowel disease, especially ulcerative colitis. The majority of patients are initially asymptomatic, and identified on the basis of elevated serum levels of alkaline phosphatase or gamma-glutamyl transpeptidase, especially while screening patients with ulcerative colitis. Diagnosis is based on characteristic cholangiographic appearance with focal bile duct dilatations proximal to areas of stricturing that produce a beaded appearance. Ursodeoxycholic acid is most effective medical therapy, with other symptomatic measures, while liver transplantation is the treatment of choice for patients with advanced liver disease.
...
PMID:[Primary sclerosing cholangitis--diagnosis and therapy]. 1458 67

Six dogs were entered into a 30-day, prospective, nonrandomized, uncontrolled clinical trial evaluating the effects of an oral preparation of budesonide on the hypothalamic-pituitary-adrenal (HPA) axis during therapeutic management of active inflammatory bowel disease. Oral budesonide, at a dose of 3 mg/m(2), was administered once daily. Upon entry and completion of the trial, serum basal cortisol, adrenocorticotropic (ACTH)-stimulated cortisol, endogenous ACTH concentration, serum alkaline phosphatase (SAP) activity, and urine specific gravity were evaluated, as well as owner assessment of glucocorticoid-associated side effects. Significant suppression of the HPA axis occurred. No significant differences in SAP activity, urine specific gravity, or owner-subjective assessments were detected.
...
PMID:Clinical effects of short-term oral budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease. 1500 47

It is unknown why some patients with inflammatory bowel disease develop primary sclerosing cholangitis. We have recently shown that patients with primary sclerosing cholangitis have an increased prevalence of mutations in the gene responsible for cystic fibrosis (CFTR) compared with individuals with inflammatory bowel disease alone. Our aim was to examine whether induction of colitis by oral dextran leads to bile duct injury in mice heterozygous or homozygous for mutations in CFTR. The effect of oral administration of docosahexaenoic acid to correct a fatty acid imbalance associated with cystic fibrosis was also examined to determine whether this would prevent bile duct inflammation. Wild-type mice and mice heterozygous and homozygous for CFTR mutations were given dextran orally for 14 days to induce colitis. Bile duct injury was quantitated by blinded histological scoring and measurement of serum alkaline phosphatase activity. The effect of pretreatment with docosahexaenoic acid for 7 days was examined. Treatment of mice with 100 mg dextran/day for 9 days followed by 85 mg/day for 5 days resulted in a significant increase in bile duct injury as determined by histological scoring in homozygous cystic fibrosis mice compared with wild-type mice (P = 0.005). The bile duct injury seen in cystic fibrosis mice was reflected in a threefold increase in serum alkaline phosphatase (P = 0.0006). Pretreatment with oral docosahexaenoic acid decreased both histological evidence of bile duct injury and serum alkaline phosphatase levels. In the setting of colitis, loss of CFTR function leads to bile duct injury.
...
PMID:Induction of colitis in cftr-/- mice results in bile duct injury. 1506 32


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---