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)

The pig shows a marked response to end-to-side portacaval shunt. Survival is short and levels of alkaline phosphatase and cholesterol fall. This study was designed to determine the role of the reduced food intake which follows the operation upon these results. In pair-fed, sham-operated pigs, survival was short and levels of alkaline phosphatase and cholesterol also fell. Sham-operated animals fed normally did not show this response. Reduced appetite has been recorded in many experimental animals after portacaval shunt, but the cause remains to be elucidated. Encephalopathy, bacteremia, peptic ulceration, or hormonal imbalance could be implicated. Similar alteration in appetite and weight loss have not been observed in children who have been treated by portacaval shunt for glycogen storage disease or hypercholesterolemia; however, the underlying metabolic disorder or the species difference may be a contributory cause.
 ...
PMID:Anorexia and weight loss in the portacaval-shunted pig. 106 35

Desmin and vimentin are two intermediate filaments, abundant in fetal skeletal muscle, almost undetectable in mature skeletal muscle which increase in regenerating and partially damaged skeletal muscle fibers. To determine their content in neuromuscular disorders immunohistochemical studies of desmin and vimentin were performed on 53 human muscle specimens. The labelled streptavidin biotin technique (DAKO, LSAB Kit, alkaline phosphatase) was used. Strong staining intensity was seen in regenerating and partially damaged fibers of inflammatory myopathies and muscular dystrophy. Necrotic fibers lost their reactivity for both filaments. Type II glycogenosis showed an increased reactivity for desmin and vimentin. A mild increase in desmin and vimentin staining intensity was observed in the atrophic cells of spinal muscular atrophy, but not in the atrophic fibers from other disease entities. Weaker reactivity for desmin was noted in atrophic cells of myotonic dystrophy. The immunohistochemical study of desmin and vimentin in neuromuscular disorders is helpful in detecting degeneration, or regeneration changes, of muscle fibers and may provide clues to the pathogenesis of various muscular disorders.
 ...
PMID:Immunocytochemical studies on desmin and vimentin in neuromuscular disorders. 774 34

In adults with diabetes mellitus, hepatomegaly and abnormalities of liver enzymes occur as a consequence of hepatocellular glycogen accumulation, as has been well described in children. During periods of hyperglycemia glucose freely enters the hepatocytes driving glycogen synthesis, which is augmented further by administration of insulin to supraphysiologic levels. The accumulation of excessive amounts of glycogen in the hepatocytes is a function of intermittent episodes of hyperglycemia and hypoglycemia and the use of excessive insulin. Hepatic glycogenosis occurs in patients with poorly controlled insulin-dependent type I or type II diabetes. The clinical manifestations of this phenomenon may include abdominal pain and obstructive symptoms such as early satiety, nausea, and vomiting. Ascites has rarely been reported. The typical biochemical findings are mildly to moderately elevated aminotransferases, with or without mild elevations of alkaline phosphatase. Liver synthetic function is usually normal. All these abnormalities, including the hepatomegaly, are readily reversible with sustained euglycemic control. The other major cause of hepatomegaly in patients with diabetes is steatosis. This is a function of the body habitus and state of insulin resistance rather than glycemic control. However, the distinction between steatosis and glycogenosis is important: whereas steatosis may progress to fibrosis and cirrhosis, glycogenosis does not, but reflects the need for better diabetic control. Glycogenosis and steatosis cannot be distinguished reliably on ultrasound examination. The histology, however, is definitive. In glycogenosis, as in primary glycogen storage diseases, there is excess glycogen in the cytoplasm, and often also in the nucleus, of hepatocytes. The hepatocytes throughout the lobule appear pale and swollen with clearly defined cell boundaries. Ultrastructural examination reveals cytoplasmic glycogen in clumps displacing organelles to the periphery of the cell, and there is little if any steatosis. We have shown that hepatomegaly due to glycogenosis in adults with diabetes is similar in all respects to the condition seen in children. As in children, liver enzyme abnormalities are unreliable in predicting the presence or the extent of glycogenosis. Hepatic glycogenosis can occur at any age, and therefore should be included in the differential diagnosis of hepatomegaly in all insulin-requiring diabetics.
 ...
PMID:Hepatomegaly and abnormal liver tests due to glycogenosis in adults with diabetes. 898 49

Up-to-date, most patients with serious chronic hepatic disease are best treated by liver transplantation. It has been confirmed the striking benefit of liver transplantation also for patients with glycogen storage disease or homozygous familial hypercholesterolemia who were refractory to medical treatment. Nevertheless, the advantage of achieving palliation without transplantation, thereby avoiding the need for chronic immunosuppression, is obvious. With reference to the mentioned above diseases, end-to-side portacaval shunt was used. A favourable effect was noted on body growth and a number of metabolic abnormalities. Hepatic failure did not occur, although in a few patients blood ammonia concentrations and serum alkaline phosphatase levels increased relative to preoperative values. To avoid an incomplete palliation provided by portacaval shunt, appropriate case selection is a problem. The Authors report their personal experience with portacaval shunt for the treatment of glycogenosis and familial hypercholesterolemia.
 ...
PMID:[Surgical therapy of metabolic liver diseases (glycogenosis, hypercholesterolemia)]. 957 79

Patients with glycogen storage disease (GSD) types I, III and IX show reduced bone mineral content, but there is scarce data on new serum and urine markers of bone turnover or their relationship to bone densitometry. Six GSD I, four GSD III and four GSD IX patients underwent bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry. Free pyridinoline (fPYD):creatinine and free deoxypyridinoline (fDPD):creatinine ratios were analysed on random urines. Procollagen type I C-terminal propeptide, procollagen type I N-terminal propeptide (PINP), carboxyterminal telopeptide of type I collagen and bone-specific alkaline phosphatase were analysed in serum. Some GSD I and GSD III patients had low or very low BMD. There was no difference in total body BMD z-score between the GSD types after adjusting for height (p=0.110). Bone marker analysis showed no consistent pattern. Urine fPYD:creatinine ratio was raised in four GSD I and two GSD III patients, while serum PINP was inappropriately low in some of these patients. There was no clear correlation between any markers of bone destruction and total body z-score, but the patient with the lowest total body z-score showed the highest concentrations of both urinary fPYD:creatinine and fDPD:creatinine ratios. We conclude that some GSD I and GSD III patients have very low bone mineral density. There is no correlation between mineral density and bone markers in GSD patients. The inappropriately low concentration of PINP in association with the raised urinary fPYD:creatinine and fDPD:creatinine ratios seen in two GSD I patients reflect uncoupling of bone turnover. All these findings taken together suggest that some GSD I and GSD III patients may be at an increased risk of osteoporosis.
 ...
PMID:Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX. 1497 Jul 41

Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disease caused by deficiency of glycogen debranching enzyme (GDE) in liver and muscle. The disorder is clinically heterogeneous and progressive, and there is no effective treatment. Previously, a naturally occurring dog model for this condition was identified in curly-coated retrievers (CCR). The affected dogs carry a frame-shift mutation in the GDE gene and have no detectable GDE activity in liver and muscle. We characterized in detail the disease expression and progression in eight dogs from age 2 to 16 months. Monthly blood biochemistry revealed elevated and gradually increasing serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities; serum creatine phosphokinase (CPK) activity exceeded normal range after 12 months. Analysis of tissue biopsy specimens at 4, 12 and 16 months revealed abnormally high glycogen contents in liver and muscle of all dogs. Fasting liver glycogen content increased from 4 months to 12 months, but dropped at 16 months possibly caused by extended fibrosis; muscle glycogen content continually increased with age. Light microscopy revealed significant glycogen accumulation in hepatocytes at all ages. Liver histology showed progressive, age-related fibrosis. In muscle, scattered cytoplasmic glycogen deposits were present in most cells at 4 months, but large, lake-like accumulation developed by 12 and 16 months. Disruption of the contractile apparatus and fraying of myofibrils was observed in muscle at 12 and 16 months by electron microscopy. In conclusion, the CCR dogs are an accurate model of GSD IIIa that will improve our understanding of the disease progression and allow opportunities to investigate treatment interventions.
 ...
PMID:Characterization of a canine model of glycogen storage disease type IIIa. 2273 56

Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of the glycogen debranching enzyme (GDE), which is encoded by the Agl gene. GDE deficiency leads to the pathogenic accumulation of phosphorylase limit dextrin (PLD), an abnormal glycogen, in the liver, heart, and skeletal muscle. To further investigate the pathological mechanisms behind this disease and develop novel therapies to treat this disease, we generated a GDE-deficient mouse model by removing exons after exon 5 in the Agl gene. GDE reduction was confirmed by western blot and enzymatic activity assay. Histology revealed massive glycogen accumulation in the liver, muscle, and heart of the homozygous affected mice. Interestingly, we did not find any differences in the general appearance, growth rate, and life span between the wild-type, heterozygous, and homozygous affected mice with ad libitum feeding, except reduced motor activity after 50 weeks of age, and muscle weakness in both the forelimb and hind legs of homozygous affected mice by using the grip strength test at 62 weeks of age. However, repeated fasting resulted in decreased survival of the knockout mice. Hepatomegaly and progressive liver fibrosis were also found in the homozygous affected mice. Blood chemistry revealed that alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities were significantly higher in the homozygous affected mice than in both wild-type and heterozygous mice and the activity of these enzymes further increased with fasting. Creatine phosphokinase (CPK) activity was normal in young and adult homozygous affected mice. However, the activity was significantly elevated after fasting. Hypoglycemia appeared only at a young age (3 weeks) and hyperlipidemia was not observed in our model. In conclusion, with the exception of normal lipidemia, these mice recapitulate human GSD IIIa; moreover, we found that repeated fasting was detrimental to these mice. This mouse model will be useful for future investigation regarding the pathophysiology and treatment strategy of human GSD III.
 ...
PMID:Mouse model of glycogen storage disease type III. 2461 82