Familial homozygous fibroblasts

Degradation in Normal, Familial Hypercholesterolemic, Homozygous Fibroblasts and Co-cultured Fibroblasts... 

Metabolic Labeling Pattern of Glycosphinqolipids in Familial Hypercholesterolemic Heterozygous Fibroblasts and Co-cultured Normal and Familial Hypercholesterolemic Homozygous Fibroblasts... 

Incorporation of radioactivity derived from [14C] Leucine, [3H] Thymidine and [3H]2-deoxy glucose into normal and familial hypercholesterolemic homozygous fibroblasts incubated in fetal calf serum and lipoprotein deficient serum containing medium... 

Effects of incubation of normal and familial hypercholesterolemic homozygous fibroblasts in lipoprotein deficient medium on the incorporation of radioactivity derived from [%] galactose into cellular glycosphingolipids and culture medium... 

In homozygous FH patients, specific LDL binding to fibroblasts is reduced by more than 90% compared to that for control fibroblasts from normolipidemic individuals. Heterozygous carriers of a FH mutation have significantly reduced LDL binding compared to normolipidemic individuals like unaffected family members. 

ApoA-I-mediated cholesterol efflux from fibroblasts of homozygous Tangier patients is reduced by more than 90% compared to normal control fibroblasts. Heterozygous carriers show significantly reduced cholesterol efflux from fibroblasts compared to unaffected family members. 

These interrelationships may occur in the plasma compartment, on the surface of cells, or within the cell. Our purpose here will be to review briefly some of the previous work in the above area and to present some of our recent, preliminary data on GSL and lipoprotein metabolism. Our approach has been to study simultaneously cultured human fibroblasts derived from both normal subjects and those heterozygous or homozygous for familial hypercholesterolemia (FH), a relatively common disorder of cholesterol and low density lipoprotein (LDL) metabolism. 

Figure 1. Pedigree pattern of the B family. Relationship of the proband (T.B.) with the clinical phenotype of homozygous familial hypercholesterolemia to her other relatives whom we studied is shown. Lipoprotein patterns were determined after ultracentrifugation using NIH outpoints (51). F indicates that fibroblast cell lines were established from skin biopsies. Males, H Females, O.

Goldstein, J. L., and M. S. Brown. 1974. Binding and degradation of low density lipoproteins by cultured human fibroblasts comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J. Biol. Chem. 249 5153-5162. 

The cell-surface glycosphingolipids and other lipids in the fibroblasts from a family with familial hypercholesterolemia have been examined after they had been oxidized with D-galactose oxidase and then reduced with sodium borotritide. Comparisons of the radiolabel incorporated by homozygous, heterozygous, and normal fibroblast cells suggested that the defective metabolism of lipids in this disease is more extensive than previously realized. Gangliosides and asialo-G j have been shown to accumulate in the cerebrospinal fluid of a patient with SandhofTs disease. ... 

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