1/15. A newly identified lipoprotein lipase (LPL) gene mutation (F270L) in a Japanese patient with familial LPL deficiency.We have systematically investigated the molecular defects resulting in a primary lipoprotein lipase (LPL) deficiency in a Japanese male infant (proband SH) with fasting hyperchylomicronemia. Neither LPL activity nor immunoreactive LPL mass was detected in pre- or postheparin plasma from proband SH. dna sequence analysis of the LPL gene of proband SH revealed homozygosity for a novel missense mutation of F270L (Phe(270)-->Leu/TTT(1065)-->TTG) in exon 6. The function of the mutant F270L LPL was determined by both biochemical and immunocytochemical studies. in vitro expression experiments on the mutant F270L LPL cDNA in COS-1 cells demonstrated that the mutant LPL protein was synthesized as a catalytically inactive form and its total amount was almost equal to that of the normal LPL. Moreover, the synthesized mutant LPL was non-releasable by heparin because the intracellular transport of the mutant LPL to the cell surface - by which normal LPL becomes heparin-releasable - was impaired due to the abnormal structure of the mutant LPL protein. These findings explain the failure to detect LPL activities and masses in pre- and postheparin plasma of the proband. The mutant F270L allele generated an XcmI restriction enzyme site in exon 6 of the LPL gene. The carrier status of F270L in the proband's family members was examined by digestion with XcmI. The proband was ascertained to be homozygous for the F270L mutation and his parents and sister were all heterozygous. The LPL activities and masses of the parents and the sister (carriers) were half or less than half of the control values. Regarding the phenotype of the carriers, the mother with a sign of hyperinsulinemia manifested hypertriglyceridemia (type IV hyperlipoproteinemia), whereas the healthy father and the sister were normolipidemic. Hyperinsulinemia may be a strong determinant of hypertriglyceridemia in subjects with heterozygous LPL deficiency.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
2/15. Unusual finding in a water-logged corpse--hyperchylomicronemia or pulmonary fat embolism?During excavation work at the bank of the River Inn the corpse of a 32-year-old alcoholic male was recovered. head injuries suggested a crime of violence. Postmortem examination demonstrated conspicuous milky turbidity of the blood, which was found by laboratory testing to be due to hyperchylomicronemia. The findings are interpreted and their relevance to the determination of postmortal head injuries is discussed. The inadequacy of double-edged knife specimens and frozen-section biopsies for the estimation of pulmonary fat embolism as a vital reaction is considered.- - - - - - - - - - ranking = 5keywords = fat (Clic here for more details about this article) |
3/15. Management of lipoprotein-x accumulation in severe cholestasis by semi-selective LDL-apheresis.liver disorders characterized by prolonged bile stasis are often associated with the accumulation of an abnormal lipoprotein, lipoprotein-x (LP-X), in plasma. LP-X is separated in the low-density lipoprotein (LDL) density range, but lacks apolipoprotein B and does not interact with the LDL receptor; LP-X can cause hyperlipidemia, cutaneous xanthomas, and worsening of arterial disease. We report the case of a patient with severe cholestasis, markedly elevated plasma cholesterol levels (26.8 to 31.5 mmol/L), mainly due to a massive accumulation of LP-X in plasma, and diffuse xanthomas. To reduce the elevated cholesterol levels, the patient was given extracorporeal treatment aimed at removing atherogenic lipoprotein (LDL-apheresis). LDL-apheresis was performed at weekly or bi-weekly intervals, either by a semi-selective technique using filters with a defined pore diameter (double filtration, DF) or by a more selective technique using dextran-sulfate-cellulose (DSC) columns able to bind LDL. The semi-selective DF technique proved more effective than DSC, removing 48% of total cholesterol (compared to 30% with DSC), and lowering cholesterol levels to 11.1 mmol/L in 6 weeks. DF removed both LDL and LP-X from plasma, whereas DSC selectively decreased the LDL content. The reduction of plasma cholesterol levels was associated with a complete regression of the xanthomas, supporting DF apheresis as a first-choice treatment for patients with massive LP-X accumulation due to cholestasis.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
4/15. Identification and characterization of a new variant of apolipoprotein E (apo E-Kochi).A new variant of apolipoprotein E (apo E), named apo E-Kochi, was identified in the sera of a 29-year-old male with hyperlipoproteinemia as characterized by a broad-beta band. The characteristic double bands of apo E were seen in the isoelectric focusing gel of very low density lipoprotein from the proband and three members of his family. Of the double bands from the probands, the more cationic component was identical to ordinary apo E3 and the other anionic band was located at approximately a distance of one-half charge to the anode side. This anionic band is a new electrophoretical isoform of apo E (apo E-Kochi), and the molecular weight by sodium dodecyl sulfate electrophoresis and its antigenicity against anti apo E serum are the same as apo E3. sequence analysis of lysyl endopeptidase fragments showed that apo E-Kochi differs from normal apo E3 at residue 145, where an arginine residue is substituted for histidine.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
5/15. hyperlipoproteinemia type i in a patient with active lipoprotein lipase in adipose tissue and indications of defective transport of the enzyme.This paper presents a case of typical hyperlipoproteinemia type i in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein b-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of normal). Southern blot analysis suggested no major defect in her LPL gene and Northern blot analysis of adipose tissue rna showed normal-sized LPL-mRNA. A 2-h [35S]methionine incorporation experiment with adipose tissue pieces in vitro showed that she produced normal-sized LPL and had LPL catalytic activity in the tissue. The amounts were, however, only 5-10% of control. No detectable LPL radioactivity or catalytic activity was released from patient tissue even in the presence of heparin in the incubations. Immunofluorescent staining of adipose tissue biopsies from the patient showed LPL immunoreactivity only in adipocytes and little or none within the capillaries. Treatment of immunoprecipitated labeled LPL with endoglycosidase H showed that the oligosaccharide chains on her enzyme were of the high-mannose type and not processed as in controls. Taken together the data suggest that the patient synthesizes a relatively normal LPL protein which is core-glycosylated and folded into active enzyme as in normal subjects, but is not effectively transported via the Golgi to the cell surface.- - - - - - - - - - ranking = 1224.8623009263keywords = adipose (Clic here for more details about this article) |
6/15. Primary type I hyperlipoproteinaemia--a metabolic and family study.Primary Type I Hyperlipoproteinaemia is the rarest phenotype of the inherited hyperlipidaemias. A study of the plasma lipids, lipoprotein distribution and apoprotein concentrations has been carried out in a propositus and in three generations of her immediate family, as has associated post heparin lipolytic activity (PHLA). The propositus presented in infancy with spontaneous bruising and abdominal pain. She has gross chylomicronaemia in the presence of depressed PHLA, which is due to deficiency of lipoprotein lipase. Apo Al and B levels are depressed in concert with low density and high density lipoproteins. Introduction of a low fat diet has resulted in loss of symptoms but plasma lipids remain abnormal. Within her immediate family, six of nine members have depressed PHLA. Two such members have elevated plasma triglycerides, one associated with hypercholesterolaemia and peripheral vascular disease. Low PHLA in this family is then associated with different lipoprotein phenotypes.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
7/15. An incomplete form of familial lipoprotein lipase deficiency presenting with type I hyperlipoproteinemia.The author reports the case of a patient with an incomplete form of familial lipoprotein lipase deficiency associated with type I hyperlipoproteinemia manifesting an autosomal recessive pattern of inheritance. The patient presented with hepatosplenomegaly, abdominal pain, and fasting chylomicronemia. A Western diet elicited a steep increase in plasma triglyceride concentration and the appearance of floating chylomicrons over a clear infranatant in fasting plasma. Postheparin lipoprotein lipase activity was moderately reduced to 38% of control values. adipose tissue lipoprotein lipase activity was 10% of normal, whereas his muscle enzyme activity was within the reference range. Two-dimensional electrophoresis of plasma apolipoproteins revealed the presence of normal activator (apolipoprotein c-ii). These results confirm the importance of the adipose tissue enzyme for the clearance of diet-derived plasma triglycerides.- - - - - - - - - - ranking = 174.98032870375keywords = adipose (Clic here for more details about this article) |
8/15. Lipoprotein disorder, cirrhosis, and olivopontocerebellar degeneration in two siblings.Two siblings had olivopontocerebellar degeneration, failure to thrive, hepatic fatty change and cirrhosis, and a dyslipoproteinemia characterized by low cholesterol and elevated triglycerides. This condition was distinct from other cerebellar atrophies and ataxias and was not due to malabsorption or malnutrition. Cerebellar degeneration progressed rapidly during the first year of life, and both children died from intercurrent infections and surgical complications at 11 and 17 months. Stereotyped clinical and pathologic findings in the two patients suggest a previously unreported genetic metabolic disorder affecting the liver and the CNS.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
9/15. milk and plasma lipid composition in a lactating patient with type I hyperlipoproteinemia.This report describes studies on the plasma and milk lipid composition of a patient with primary Type I hyperlipoproteinemia who had been followed through her second pregnancy. Post-partum she lactated, supplying milk for assay. It was abnormal in the low content of its total lipid and in the bizarre composition of its fatty acids. The proportion of long chain fatty acids was unusually low, and that of medium chain fatty acids unusually high. Furthermore, the fatty acids of the patient's milk differed greatly from those of her plasma triglycerides. This was in marked contrast to normal nursing mothers' milk, in which the fatty acid composition is comparable to that of plasma triglycerides. The patient's milk fatty acids were shorter in chain length and deficient in essential fatty acids. During the time of lactation, the patient remained hyperlipidemic and her post-heparin plasma had no lipolytic activity. These data and the differences between the plasma and milk fatty acids suggested that in the patient the circulating triglyceride fatty acids did not enter the mammary gland. Without preformed fatty acids entering it from plasma or adipose tissue, the lactating breast apparently synthesized fatty acids de novo. These newly synthesized fatty acids were of medium, rather than long chain length. This accounted for the abundance of medium chain length triglycerides in the patient's milk. The studies suggested that the deficit of lipoprotein lipase in Type I hyperlipoproteinemia extended to the mammary gland.- - - - - - - - - - ranking = 186.98032870375keywords = adipose, fat (Clic here for more details about this article) |
10/15. Lipaemia retinalis in a 29-day-old infant with type 1 hyperlipoproteinaemia.A 29-day-old infant born of consanguineous parents had type 1 hyperlipoproteinaemia associated with lipaemia retinalis. Biochemical analyses disclosed hypertriglyceridaemia, hyperchylomicronaemia, and lipoprotein lipase deficiency. Ophthalmoscopically all retinal vessels had the creamy appearance of lipaemia retinalis. The plasma lipoprotein levels and fundus condition became normal after her ingestion of fat was limited. To our knowledge this is the youngest patient reported with type 1 hyperlipoproteinaemia associated with lipaemia retinalis.- - - - - - - - - - ranking = 1keywords = fat (Clic here for more details about this article) |
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