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Biomedical subjects

S Innis

Publications and source records attributed to S Innis.

5 recordsLinked to original sources

Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets.

Endogenous ligands of cannabinoid receptors have been discovered recently and include some N-acylethanolamines (NAEs; e.g., N-arachidonoylethanolamine) and some 2-acylglycerols (e.g., sn-2-arachidonoylglycerol). Previously, we found these compounds to be active biologically when administered per os in large quantities to mice. In the present work, piglets were fed diets with and without 20:4n-6 and 22:6n-3 fatty acid precursors of NAEs, in levels similar to those found in porcine milk, during the first 18 days of life, and corresponding brain NAEs were assessed. In piglets fed diets containing 20:4n-6 and 22:6n-3, there were increases in several biologically active NAEs in brain homogenates-20:4n-6 NAE (4-fold), 20:5n-3 NAE (5-fold), and 22:5n-3 and 22:6n-3 NAE (9- to 10-fold). These results support a mechanism we propose for dietary long-chain polyunsaturated fatty acids influences on brain biochemistry with presumed functional sequelae. This paradigm will enable targeted investigations to determine whether and why specific populations such as infants, elderly, or persons suffering from certain clinical conditions may benefit from dietary long-chain polyunsaturated fatty acids.

Animals↗

Lipid and lipoprotein analysis of cats with lipoprotein lipase deficiency.

BACKGROUND: We have previously described a colony of domestic cats with a naturally occurring mutation in the lipoprotein lipase (LPL) gene. We have now further characterized cats homozygous for LPL deficiency (LPL -/-, homozygotes), and have contrasted these with heterozygotes (LPL +/-) and normal cats (LPL +/+). MATERIALS AND METHODS: Density gradient ultracentrifugation with subsequent lipid analysis, agarose and polyacrylamide gel electrophoresis was used to examine detailed liproprotein differences between the genotypes. Oral fat loading studies and breast milk fatty acid analysis were also performed to further characterize the phenotypic expression of LPL deficiency in this model system. RESULTS: Several lipid abnormalities associated with homozygosity for LPL deficiency were evident. Triglyceride-rich lipoprotein-triglycerides (TRL-TG) and cholesterol (TRL-C) were higher (TRL-TG 2.09 +/- 1.14 vs. 0.15 +/- 0.04 mmol L-1, P < 0.001; TRL-C 0.42 +/- 0.30 vs. 0.11 +/- 0.16 mmol L-1, P < 0.05) in male -/- than in male +/+ cats, as was HDL-cholesterol (HDL-C, 1.75 +/- 0.24 vs. 1.41 +/- 0.14 mmol L-1, P < 0.05). LDL-C levels were lower in homozygous cats than in control cats, similar to what is seen in human LPL deficiency. Oral fat loading studies revealed that homozygous cats have a marked reduced ability to clear plasma TGs in terms of peak time (7 h vs. 3 h), peak height (9.36 vs. 1.1 mmol L-1), area under the TG clearance curve (AUC, 280.3 vs. 2.2 h mmol L-1) and time to return to baseline. Fasting lipid and lipoprotein levels were not significantly different between heterozygous and normal cats. However, oral fat loading in heterozygotes revealed an intermediate phenotype (peak of 2.35 mmol L-1 at 5 h, AUC 13.1 h mmol L-1), highlighting the impaired TG clearance in these animals. CONCLUSION: Thus, LPL deficiency in the cat results in a lipid and lipoprotein phenotype that predominantly parallels human LPL deficiency, further validating the use of these animals in studies on the pathobiology of LPL.

Animals↗

Factors associated with response to platelet transfusion following hematopoietic stem cell transplantation.

We studied 526 consecutive post-transplant platelet transfusions to determine the factors associated with response to platelet transfusion in the BMT setting. Poor responses to platelet transfusions occurred frequently, with 310 of the 484 evaluable transfusions (64%) resulting in post-infusion corrected count increments of less than 7500. Factors associated with poor response to platelet transfusion by both univariate and multivariate analysis included, (1) presence of serum lymphocytotoxic antibodies; (2) male sex; (3) body surface area greater than 1.7 m2; (4) transfusion of red cells on the day of the platelet infusion; (5) concurrent administration of steroids; (6) major ABO mismatch between the recipient and the platelet product; and (7) (among women) a history of one or more pregnancies prior to transplant. Paradoxically, a history of greater than 25 blood product exposures prior to transplant, and evidence of prior CMV infection in either the bone marrow donor or recipient were associated with higher CCIs by both univariate and multivariate analysis. Factors that showed little correlation with response to platelet transfusion included, (1) age of the infused platelet product; (2) concurrent fever; (3) recent administration of intravenous immunoglobulin; and (4) absolute neutrophil count at the time of the infusion. The factors associated with response to platelet transfusion in BMT patients appear to be different from those observed in the non-transplant setting.

ABO Blood-Group System↗

Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition.

BACKGROUND: The pathogenesis of Schnyder dystrophy is thought to be a primary abnormality of corneal lipid metabolism resulting in opacification secondary to lipid accumulation. Histochemical investigations have suggested the accumulated lipid includes unesterified cholesterol; however, quantitative analysis has not been done. METHODS: Quantitative biochemical analysis was performed on a corneal button obtained from a patient with clinically and pathologically proven Schnyder dystrophy. Results were compared with four age-, sex-, and size-matched corneal buttons obtained from cadaveric eyes. RESULTS: Corneal lipid accumulated in Schnyder dystrophy predominantly is composed of phospholipid, free cholesterol, and cholesterol ester. These constituents were markedly elevated in the Schnyder cornea when compared with cadaveric control corneas as follows: (1) phospholipid, 23.6 versus 4.05 mg/g; (2) unesterified cholesterol, 6.99 versus 0.52 mg/g; and (3) cholesterol ester, 3.16 versus 0.26 mg/g. CONCLUSION: Phospholipid, unesterified cholesterol and cholesterol ester are the predominant lipids in Schnyder dystrophy. The pathogenesis may be a primary disorder of corneal lipid metabolism.

Chromatography, Gas↗