Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disorders in lipoprotein metabolism (dyslipidemia) can result in premature atherosclerosis or pancreatitis. Dyslipidemias can be classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low density lipoprotein cholesterol and decreased levels of HDL cholesterol predispose to premature atherosclerosis. Triglyceride levels greater than 1,000 mg/dL increase the risk for pancreatitis. In the appraisal of the dyslipidemias, measurement of serum cholesterol, triglycerides, HDL-cholesterol and obtaining the LDL cholesterol by Friedewald equation is usually sufficient in the majority of patients. However, in some cases, such as the diagnosis of the Type III dyslipidemia and when triglycerides are > or = 400 mg/dL, ultracentrifugation is required to determine the VLDL or LDL cholesterol. Lipoprotein electrophoresis can be useful in the diagnosis of Type III dyslipidemia (broad beta band) and also to detect chylomicrons. In young subjects with coronary artery disease with a normal LDL cholesterol an apolipoprotein B-100 level may be a useful test. In children and young adults with severe hypertriglyceridemia, measurement of lipoprotein lipase activity or assaying apolipoprotein C-II levels can be useful in elucidating the cause. Also, laboratory tests are useful in excluding a secondary cause of dyslipidemia (urinalysis, plasma creatinine, TSH, glucose, protein electrophoresis, alkaline phosphatase and transaminases). Thus, laboratory investigations play an important role in the management of dyslipidemia.
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PMID:A practical approach to the laboratory diagnosis of dyslipidemia. 870 23

A woman with primary lipoprotein lipase (LPL) deficiency developed marked hypertriglyceridemia, pancreatitis, eruptive xanthomas, and unusual palmar xanthomas during pregnancy. Hypotheses to account for the palmar xanthomas were that oxidative modification of triglyceride (TG)-rich lipoproteins occurred due to increased plasma residence time, or that their apolipoprotein E (apoE) content was abnormally elevated. Indices of oxidation of her TG-rich lipoproteins did not support the hypothesis that oxidative changes were a causative factor for her xanthomata. However, degradation of her TG-rich lipoproteins by macrophages was markedly increased (1844 ng/mg protein) during pregnancy as compared to hypertriglyceridemic (with normal LPL) and normotriglyceridemic controls (352 and 126 ng/mg protein, respectively). Post pregnancy the degradation of the subject's TG-rich lipoproteins fell to 289 ng/mg protein. Compositional analysis showed significant enrichment of the particles with apoE (0.97 mass ratio of apoE:apoB during pregnancy, in contrast to 0.38 for normolipidemic controls), and was correlated with the rate of degradation of the TG-rich lipoproteins. Thus, the increased uptake of the TG-rich lipoproteins by macrophages appears to be the result of an unusual enrichment of these lipoproteins with apoE.
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PMID:ApoE enhances lipid uptake by macrophages in lipoprotein lipase deficiency during pregnancy. 872 50

Familial lipoprotein lipase (LPL) deficiency is an inherited disorder of lipoprotein metabolism characterized by hypertriglyceridemia and recurrent episodes of abdominal pain and pancreatitis. We have studied the genetic basis of LPL deficiency in a 62-year-old black male with undetectable pre- and post-heparin plasma LPL mass and activity, DNA sequence analysis of the patient's LPL cDNA and gene as well as digestion with Bcl I and Asu I revealed that the proband is a homozygote for two separate gene defects. One mutation changed a G to an A, resulting in the conversion of amino acid 9 of the mature protein, aspartic acid (GAC), to asparagine (AAC). The second substitution, a C for a T, replaced tyrosine (TAC) at residue 262 with histidine (CAC). Northern blot analysis of monocyte-derived macrophage RNA demonstrated the presence of LPL mRNA of approximately normal size and quantity when compared to control. Expression of both mutations separately (pCMV-9 and pCMV-262) or in combination (pCMV-9+262) in human embryonal kidney-293 cells demonstrated that LPL-9 had approximately 80% the specific activity of wild type LPL, but LPL-262 and LPL-9+262 had no enzymic activity, thus establishing the functional significance of the LPL-262 defect. Despite an absolute deficiency of LPL mass and activity demonstrated by analysis of patient post-heparin plasma, in vitro expression of both LPL mutants was normal, suggesting that the absence of LPL in patient post-heparin plasma was a result of altered in vivo processing. Analysis of the heparin binding properties of the mutant enzymes by heparin-Sepharose affinity chromatography indicated that most of the LPL-262 mass was present in an inactive peak, which like the normal LPL monomer, eluted at 0.8 M NaCl. Thus, the Tyr262 --> His mutation may alter the stability of the LPL dimer, leading to the formation of inactive LPL-262 monomer which exhibits reduced heparin affinity. Based on these results, we propose that, in vivo, enhanced formation of LPL-9+262 monomer leads to abnormal binding of the mutant lipase to endothelial glycosaminoglycans ultimately resulting in enhanced catabolism of the mutant enzyme and lower enzyme mass in post-heparin plasma.
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PMID:Homozygosity for two point mutations in the lipoprotein lipase (LPL) gene in a patient with familial LPL deficiency: LPL(Asp9-->Asn, Tyr262-->His). 872 26

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.
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PMID:Lipoprotein lipase deficiency with pancreatitis in mink: biochemical characterization and pathology. 918 2

We have studied the underlying molecular defect in a patient presenting with recurrent pancreatitis, hypertriglyceridemia, and virtually undetectable postheparin plasma lipoprotein lipase (LPL) mass and activity, who normalized her triglycerides 3 to 6 months after initiation of either medium-chain triglyceride (MCT) oil or omega-3 fatty acid (omega-3-FA) therapy. After treatment, postheparin plasma LPL activity and mass ranged from 24% to 39% of normal and LPL specific activity was normal (1.0 nmol.ng-1.min-1). On discontinuation of MCT oil or omega-3-FA, plasma triglyceride increased to > 2000 mg/dL. Northern blotting revealed both normal size and abundance of LPL mRNA isolated from adipocytes as well as macrophages. Sequence analysis of the LPL gene, which included all 10 exons, intron-exon splice junctions, and 1.7 kb of the 5'-flanking region, and of LPL cDNA failed to identify any mutations. ApoC-II activity and mass assays revealed the presence of normal levels of a fully functional cofactor as well as the absence of circulating plasma inhibitors of lipase function. In summary, we describe a unique patient presenting with classical features of the familial chylomicronemia syndrome who manifests an unusually beneficial therapeutic response to MCT oil and omega-3-FA therapy. Unlike that in most patients with LPL deficiency, the chylomicronemia in this patient is not caused by a mutation in the structural LPL gene but possibly by a posttranscriptional defect. Thus, a subset of LPL-deficient patients with unique genetic defects respond to therapy by normalizing fasting plasma triglycerides; a therapeutic trial with MCT oil should be considered in all patients presenting with the familial chylomicronemia syndrome.
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PMID:Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome. 926 Dec 73

Tamoxifen, a nonsteroidal estrogen antagonist, has been widely used in a hormonal treatment for breast cancer. The side effects of tamoxifen are generally recognized to be mild. However, we experienced three cases of severe hypertriglyceridemia and/or hyperglycemia induced by tamoxifen. For normalization of their hypertriglyceridemia we need to stop giving tamoxifen. In one of three cases we analyzed her lipoprotein profile in detail with lipoprotein lipase activities and apolipoprotein E phenotype. The case was a 49 year-old woman. After 15 months of tamoxifen administration, she was diagnosed as severe hypertriglyceridemia. Consecutively, severe hyperglycemia was occurred to need insulin therapy. After tamoxifen withdrawal, her triglyceride and glucose levels improved. Her lipolytic enzyme was reduced during tamoxifen treatment. Apolipoprotein E phenotype was uncommon E4/2. Although hypertriglyceridemia was not considered to be a risk factor for coronary heart disease, a marked hypertriglyceridemia might occasionally produce severe lethal pancreatitis. We recommend that a periodic plasma lipid analysis is needed for patients treated with tamoxifen, especially for diabetic and hypertriglyceridemic patients, to avoid such complications.
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PMID:Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery. 946 33

Severe hypertriglyceridemia is an uncommon pathological finding in pregnant women if there is no prior history of hyperlipidemia. A partial reduction in lipoprotein lipase (LPL) activity due to a mutation in the LPL gene, is often an associating factor. Here we report a novel LPL gene mutation (Glu421Lys), in a previously healthy primigravid woman who died from hypertriglyceridemia-induced pancreatitis during the last trimester of pregnancy. The patient was heterozygous for this mutation which a charge inversion in the C-terminal domain of LPL resulting in a moderate reduction in catalytic activity, both in vivo and in vitro. These data support the role of partial LPL deficiency in the pathogenesis of severe gestational hypertriglyceridemia.
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PMID:A novel Glu421Lys substitution in the lipoprotein lipase gene in pregnancy-induced hypertriglyceridemic pancreatitis. 949 99

We herein report a case of a 40-year-old Japanese woman (patient IT) with a history of recurrent aggravation of hypertriglyceridaemia, pancreatitis and miscarriages in three previous pregnancies. However, strict dietary intervention was applied during a fourth pregnancy. As a result, acute pancreatitis was avoided, and the patient gave birth to a healthy infant. In patient IT, the underlying etiology of the recurrent aggravation of hypertriglyceridaemia during pregnancy was a lipoprotein lipase (LPL) gene aberration. She was homozygous for LPL deficiency due to a nonsense mutation (TGG1401 --> TGA/Trp382 --> Stop) in exon 8 of the LPL gene, which resulted in the absence of LPL activity and immunoreactive LPL mass. Our findings indicate that, in LPL deficiency, pregnancy seriously exacerbates hypertriglyceridaemia and increases the risk of acute pancreatitis, which endangers both the mother and fetus. Early diagnosis of LPL deficiency and appropriate management thereof are essential for normal childbirth.
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PMID:Identification of homozygous lipoprotein lipase gene mutation in a woman with recurrent aggravation of hypertriglyceridaemia induced by pregnancy. 962 47

Familial apolipoprotein (apo) CII deficiency is a rare autosomal recessive inborn error of metabolism clinically resembling lipoprotein lipase deficiency. A number of mutations of the apo CII gene are known to date; they are located in the promoter region, the coding exons, or in the splice junctions. We present a simple assay based on PCR and denaturing gradient gel electrophoresis, which allows scanning of the promoter, the entire coding sequence, and the splice junctions of the apo CII gene for sequence variants. All gene fragments are amplified using a common PCR protocol and are examined for mutations on a single gradient gel. Using this method and direct sequencing, we identified homozygosity for a donor splice-site mutation in the second intron, previously designated apo CII-Hamburg, as the genetic cause of apo CII deficiency in a 9-year-old boy presenting with chylomicronemia, eruptive xanthoma, and pancreatitis. In addition, the method allowed us to detect all of six different other known mutations of the apo CII gene. We conclude, therefore, that our assay is highly sensitive; in addition, it is easy to perform and may facilitate the differential diagnosis of disorders of lipoprotein metabolism at the genetic level.
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PMID:Detection of mutations in the apolipoprotein CII gene by denaturing gradient gel electrophoresis. Identification of the splice site variant apolipoprotein CII-Hamburg in a patient with severe hypertriglyceridemia. 966 14

Atherogenic risk is accurately defined by the turnover of the lipoprotein classes that transport cholesterol and triglycerides, and by the apolipoproteins that determine the fate of these particles. Post-prandial triglyceride levels have also been shown to be an accurate predictor of atherogenic risk. The post-prandial triglyceride levels and conversion of very low density lipoprotein (VLDL) to intermediate density lipoprotein (IDL) are controlled by a dynamic metabolic process involving lipoprotein lipase (LPL) and hepatic lipase. The interaction between the two enzymes modulates triglyceride transport through the plasma and influences the structure and serum concentrations of the denser cholesterol-rich low density lipoproteins (LDL) and high density lipoproteins (HDL). Inadequate LPL function, a consequence either of impaired enzyme function or simply post-prandial overloading, can have profound pathophysiological consequences. High levels of large HDL2 reflect effective catabolism of triglyceride-rich lipoproteins by LPL whereas low levels of this lipoprotein reflect inadequate LPL activity or elevated hepatic lipase activity. Individuals with low levels of HDL2 are prone to coronary artery disease. Overloading of LPL can occur in insulin resistance due to the absence of normal insulin-mediated suppression of VLDL secretion and the consequence is hypertriglyceridaemia. In addition, a deficiency in LPL can arise from a genetic defect which, in the homozygous state, results in pronounced hypertriglyceridaemia and pancreatitis. The correct management for patients with inadequate LPL activity is to optimize triglyceride metabolism, particularly in the post-prandial state.
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PMID:Influence of lipolysis on chylomicron clearance and HDL cholesterol levels. 971 57


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