Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxyhemoglobin dissociation curves were performed from blood of subjects with pancreatitis associated with Type V and Type I hyperlipoproteinemia. The hemoglobin-oxygen affininty was markedly increased with P50 varying from 22.3 to 17.7 mmHg. As the hyperlipoproteinemia subsided the clinical and laboratory signs of pancreatic affection disappeared. The increased hemoglobin-oxygen affinity and decreased flow of red cells due to hyperchylomicronemia in the microcirculation may lead to tissue hypoxia, which may act as a precipitating injurious factor leading to pancreatitis during severe hyperlipemia.
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PMID:Increased hemoglobin-oxygen affinity in patients with pancreatitis associated with type I and V hyperlipoproteinemia. 2 74

Primary type V hyperlipoproteinemia was identified in two preadolescent children. The propositus (kindred N) was a 10-year-old girl with severely creamy plasma, lipemia retinalis, hypertriglyceridemia (triglyceridelevel, 6,800 mg/100 ml), and ypercholesterolemia (cholesterol level, 490 mg/100 ml). Her parents and an 8-year-old sister all had endogenous hypertriglyceridemia (type IV hyperlipoproteinemia). In kindred A, an 11-year-old boy had triglyceride levels as high as 1,100 mg/100 ml and recurrent abdominal pain. His father had type V hyperlipoproteinemia; his mother was normal. All three of his older teenage siblings had type IV hyperlipoproteinemia. The enzymatic activities of lipoprotein lipase (LPL), hepatic triglyceride lipase (HTL), and histaminase (H) were studied in postheparin plasma. The LPL level was low in the children and both parents in kindred N. LPL level in kindred A was normal, except for one child with type IV hyperlipoproteinemia. HTL level was normal to above normal in both kindreds. Most patients had a normal H level, but one parent (kindred N) had no preheparin H and very low levels of postheparin H. There was a strong correlation (r = 0.58, significant at less than 1% level) between release of LPL and H but not between HTL and H (r= 0.22). The mean (+/- 1 S.D.) levels of the enzymes were as follows: LPL, 2.8 +/- 0.7 micronmol/ml/hr in kindred N and 5.4 +/- 2.2 micronmol/ml/hr in kindred A; H, 13.4 +/- 6.8 units/ml in kindred N and 22.0 +/- 11.9 units/ml in kindred A; and HTL, 18.0 +/- 7.1 micronmol/ml/hr in kindred N and 14.9 +/- 6.3 micronmol/ml/hr in kindred A. The enzymatic activities of kindreds N and A were significantly different for LPL (P less than .001) and H (.025 less than P less than .05) but not for HTL. All but one child had at least one high insulin level, which was accompanied by hyperglycemia in two children. The hypertriglyceridemia in all but one child was ameliorated on therapeutic diets. These data suggest that the genetic basis of the hypertriglyceridemia in these two families is different and that hyperchylomicronemia in childhood is not confined to the rara type I hyperliporproteinemia.
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PMID:The clinical, biochemical, and familial presentation of type V hyperlipoproteinemia in childhood. 19 90

The role of triglycerides in cardiovascular disease is a controversial subject. Despite differences of opinion, present data allow a certain number of conclusions to be drawn. Hyperchylomicronemia is not associated with atherosclerosis, whereas type III hyperlipidemia is very atherogenic. These two abnormalities are, however, rare, and the majority of hypertriglyceridemias are, in practice, associated with increased very low density lipoproteins. Many epidemiological trials do not identify hypertriglyceridemia as an independent risk factor when the cholesterol and, in particular, the HDL cholesterol levels, are taken into consideration. Nevertheless, these results must be interpreted with caution as hypertriglyceridemia represents a very heterogeneous entity which is closely related to many factors which affect coronary risk (hypertension, insulin resistance, sedentarity, and even tobacco consumption). Therefore, hypertriglyceridemia and hypo-HDL-emia may be the result of the same primary abnormality; as the HDL-cholesterol level is more stable, it is the parameter which will be identified as a protective factor in epidemiological trials. The available data is insufficient to affirm that therapeutic lowering of triglycerides is accompanied by a reduced coronary risk because none of the large scale trials were designed to analyse this problem. Despite these epidemiological data, the measurement of serum triglyceride levels remains important in patients with hyperlipidemia.
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PMID:[Role of triglycerides in cardiovascular diseases]. 129 43

We have identified the molecular basis for familial lipoprotein lipase (LPL) deficiency in two unrelated families with the syndrome of familial hyperchylomicronemia. All 10 exons of the LPL gene were amplified from the two probands' genomic DNA by polymerase chain reaction. In family 1 of French descent, direct sequencing of the amplification products revealed that the patient was heterozygous for two missense mutations, Gly188----Glu (in exon 5) and Asp250----Asn (in exon 6). In family 2 of Italian descent, sequencing of multiple amplification products cloned in plasmids indicated that the patient was a compound heterozygote harboring two mutations, Arg243----His and Asp250----Asn, both in exon 6. Studies using polymerase chain reaction, restriction enzyme digestion (the Gly188----Glu mutation disrupts an Ava II site, the Arg243----His mutation, a Hha I site, and the Asp250----Asn mutation, a Taq I site), and allele-specific oligonucleotide hybridization confirmed that the patients were indeed compound heterozygous for the respective mutations. LPL constructs carrying the three mutations were expressed individually in Cos cells. All three mutant LPLs were synthesized and secreted efficiently; one (Asp250----Asn) had minimal (approximately 5%) catalytic activity and the other two were totally inactive. The three mutations occurred in highly conserved regions of the LPL gene. The fact that the newly identified Asp250----Asn mutation produced an almost totally inactive LPL and the location of this residue with respect to the three-dimensional structure of the highly homologous human pancreatic lipase suggest that Asp250 may be involved in a charge interaction with an alpha-helix in the amino terminal region of LPL. The occurrence of this mutation in two unrelated families of different ancestries (French and Italian) indicates either two independent mutational events affecting unrelated individuals or a common shared ancestral allele. Screening for the Asp250----Asn mutation should be included in future genetic epidemiology studies on LPL deficiency and familial combined hyperlipidemia.
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PMID:A missense (Asp250----Asn) mutation in the lipoprotein lipase gene in two unrelated families with familial lipoprotein lipase deficiency. 161 66

The hyperlipoproteinemias are disturbances in the metabolism of lipoproteins. Elevated levels of total and low density lipoprotein-cholesterol, and low levels of high density lipoprotein-cholesterol are proven risk factors for atherosclerosis. The significance of hypertriglyceridemia as an independent risk factor for atherosclerosis is controversial, however, at high levels triglycerides are a major risk factor for pancreatitis. Lipoprotein abnormalities can be divided into dietary, primary (genetic), and secondary disorders. The major causes of moderate and severe hypercholesterolemia are familial hypercholesterolemia, familial combined hyperlipidemia, severe primary (polygenic) hypercholesterolemia, and familial dysbetalipoproteinemia. Causes of hypertriglyceridemia include familial hypertriglyceridemia, familial lipoprotein lipase deficiency, sporadic hypertriglyceridemia, and secondary causes.
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PMID:Hyperlipoproteinemias: Part I. Lipoprotein classification and abnormalities. 194 97

We examined 56 French Canadians, aged 1 week to 54 years, from eastern Quebec who were referred to the Laval University Lipid Research Centre and in whom coincidental finding (in 46% of the cases), abdominal pain (in 32%) or family screening (in 22%) led to the diagnosis of primary lipoprotein-lipase-activity deficiency (familial hyperchylomicronemia). Half of the patients had one or more of the following signs: lipemia retinalis, eruptive xanthomas, splenomegaly and hepatomegaly; the plasma triglyceride concentrations were significantly higher (greater than 40 mmol/L) among these patients than among those without clinical signs (mean 21.7 [standard deviation 13.5] mmol/L). The prevalence rate of this disorder was 30 times higher than the previously published rate and was highest in the counties of Charlevoix and Saguenay-Lac-St-Jean (200 and 100 cases per million respectively) because of the distinct demographic history of these areas. Because of a founder effect an autosomal recessive gene involved in lipoprotein-lipase expression or activation has probably been disseminated among this isolated French Canadian population.
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PMID:Primary lipoprotein-lipase-activity deficiency: clinical investigation of a French Canadian population. 291 62

The major atherosclerosis risk factors hypertension, diabetes, hyperlipidemia and cigarette smoking are examined along with blood vessel anatomy, hemodynamics, histopathology and known experimental results. A common factor of blood vessel hypoxia, specifically endothelial and intimal hypoxia, is shown to exist. Arguments are presented suggesting endothelial hypoxia as the commonest initiating event for atherosclerosis. Cholesterol appears to be a secondary and opportunistic villain. Explanations are given for the lack of increased atherosclerosis risk in familial lipoprotein lipase deficiency (type I hyperlipoproteinemia) and for the increased incidence and severity of atherosclerosis in the human abdominal aorta in comparison with the thoracic aorta. It is suggested that effective prevention of atherosclerosis can be accomplished by lowering blood pressure and blood glucose, among others, even though these may be within acceptable normal limits. Suggestions are given for experiments to test the hypothesis of hypoxia being the major initiating factor in atherosclerosis.
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PMID:Mechanisms of atherogenesis: endothelial hypoxia proposed as the major initiator. 385 84

Of 311 patients with primary acute pancreatitis, seven revealed major and seven minor lipid abnormalities on hospital admission. One pregnant woman suffered acute pancreatitis associated with Fredrickson type I hyperlipoproteinaemia. Twelve of the 13 men with types IV and V hyperlipoproteinaemia suffered alcohol abuse pancreatitis and represented 13.2 per cent of this aetiological group. However, only one of the 157 patients (0.6 per cent) with biliary disease had lipid abnormalities. Two of the 13 men died--the oldest, who had gallstones, and one with alcohol related disease. The remaining 11 were subject to follow-up (5-10 years). Six, who had improvement of their lipid abnormalities, had abstained from alcohol. The other five had a persistent lipid disorder, and all admitted continuing heavy alcohol ingestion. The clinical diagnosis of acute pancreatitis was supported by serum amylase elevation in only nine of the fourteen patients. Urinary amylase levels were consistent with the diagnosis in 11 of the 12 patients. Estimation of both serum and urinary amylase gave 100 per cent support to the clinical diagnosis of acute pancreatitis. Hyperlipidaemia associated with acute pancreatitis may be secondary to alcohol abuse but the possible role of HLP cannot be discounted. Urinary amylase is useful in diagnosing acute pancreatitis in the presence of hyperlipidaemia.
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PMID:Hyperlipidaemia, alcohol abuse and acute pancreatitis. 620 8

We have studied the large nonconsanguineous pedigree of a proband with Type I hyperlipoproteinemia (HL) and lipoprotein lipase (LPL) deficiency. Within the nuclear family, the mother and two of the proband's five siblings had fasting hypertriglyceridemia or low-normal tissue adipose LPL activities or both. Retention of lipoprotein retinyl esters after vitamin A feeding was present only in the propositus. The maternal side of the extended pedigree contained individuals with Types IIA, IV, and V hyperlipoproteinemia, findings most consistent with autosomal dominant multiple lipoprotein-type hyperlipidemia (familial combined hyperlipidemia). This family and previously reported pedigrees of Type I HL probands have demonstrated phenotypic heterogeneity. Without specific genetic markers, homozygous LPL deficiency and complex multiple-gene mechanisms cannot be distinguished unambiguously. Parental hyperlipidemia in nuclear pedigrees of Type I HL probands should not be equated with heterozygous LPL deficiency in the absence of extended pedigree data or more informative markers. The possibility that the complex inheritance of two different genetic defects in lipoprotein transport can produce the Type I HL phenotype must be considered.
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PMID:Phenotypic heterogeneity in the extended pedigree of a proband with lipoprotein lipase deficiency. 664 61

Two children with congenital nephrosis of the Finnish type were studied successively at the three stages of the disease: (A) nephrosis, (B) renal insufficiency/peritoneal dialysis and (C) post-transplantation; two additional patients were studied at two stages. Plasma lipoprotein profiles were determined by density gradient ultracentrifugation and lipids by enzymatic methods. Stage A was characterized by hyperchylomicronemia, low high density lipoprotein (HDL) cholesterol and the presence of dense low density lipoprotein (LDL) and HDL particles. Total cholesterol and triglycerides showed great daily variation (5-14 and 5-33 mmol/l, respectively). During stage B, hyperlipidemia weakened. Yet HDL concentration remained low and the concentration of intermediate density lipoproteins (IDL) increased. At stage C, hyperlipidemia had almost subsided, but the presence of IDL persisted. In conclusion, severe hyperlipoproteinemia of congenital nephrosis at the nephrotic stage is attenuated during renal insufficiency and dialysis, and essentially normalizes after kidney transplantation. Yet the presence of IDL implies an increased risk of atherosclerosis.
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PMID:Severe hyperlipoproteinemia in congenital nephrotic syndrome of the Finnish type: effect of dialysis and kidney transplantation. 824 75


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