Familial homozygous cells

Incorporation of radioactivity derived from [%] Galactose into the individual glycosphingolipids of co-cultured normal and familial hypercholesterolemic homozygous cells and a familial hypercholesterolemic heterozygous fibroblast line... 

Here, we Illustrate how analysis of the cellular defects underlying familial hypercholesterolemia can illuminate normal cellular processes. First let s consider typical cell-culture experiments in which the interactions of LDL with normal and FH homozygous cells were examined as a function of LDL concentration, which defined the high-affinity LDL receptor, and incubation temperature, which established the temperature dependence of LDL uptake. In these experiments, purified LDL was first labeled by the covalent attachment of radioactive I to the side chains of tyrosine residues in apoB-100 on the surfaces of the LDL particles. Cultured cells from normal persons and FH patients were incubated for several hours with the labeled LDL. Investigators then de-... 

Deficiency of GC-S is extremely rare only five cases from four unrelated families have been reported so far (B18, HI7, K23). This enzyme deficiency appears to be inherited as an autosomal recessive and has been clearly associated with a moderate chronic hemolytic anemia and a marked decrement of red blood cell GSH. Spinocerebellar degeneration and aminoaciduria were present in both homozygous siblings in the first family, whereas no neurologic deficit was noted in the other three families. 

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.

Incorporation of Radioactivity Derived from [3H] Galactose into the Individual Glycosphingolipids of Normal and Familial Hypercholesterolemic Homozygous (FH) Cells Cultured in Fetal Bovine Serum... 

Low Density Lipoprotein Binding and Degradation in Normal, Familial Hypercholesterolemic Homozygous, and Co-cultured Cells... 

A low-density lipoprotein binding in normal (A), co-cuhured (O), and familial hyper-cholesterolemic homozygous (A.) cells. B low density lipoprotein degradation in normal (A), co-cuhured (O), and familial hypercholesterolemic homozygous (A) cells... 

Schneider, R. G., and Galveston, T., Incidence of Hemoglobin C trait in 505 normal negroes a family with homozygous hemoglobin C and sickle cell trait union. J. Lab. Clin. Med. 44, 133 (1954). 

In 1922,V R. Mason (Mason, 1992) published a case review in the Journal of the American Medical Association entitled Sickle Cell Anemia, and the homozygous condition has since then been referred to by the description of the shape of the red cells seen by Dr. Irons a decade earlier In his review article, Dr. Mason promulgated the misconception that this disease was exclusively seen in persons of African origin. In 1923, Sydenstricked and colleagues reviewed the cases of two children with sickle cell disease and observed the blood smears of Caucasian and African Americans and concluded, with Mason, that sickle cell anemia was a condition peculiar to people of African descent. Neel (1949) reviewed blood smears of families with sickle cell disease over a 2-year period and correctly concluded that sickle cell anemia was a disease with Mendelian inheritance. 

In 1969 Schwartz (S29) described an Albanian family of two children with mild j8-thalassemia major. Their mother had a classical j8-thalassemia heterozygosity, but the father had a normal red cell morphology and normal levels of Hb-A, and Hb-F. The synthesis of /8 chains in this individual was impaired, although to a lesser extent than is usually observed in the classical jS-thalassemia. Interaction of this type of j8-thalassemia with the classical type results in a thalassemia major of reduced severity because the apparent homozygous children from this marriage are only mildly affected with levels of Hb-F of less than 12%. 

Despite inhibition of HMG-CoA reductase by statins, cells compensate by increasing enzyme expression several fold. However, the total body cholesterol is reduced by 20-40% due to increased expression of LDL-receptors after statin administration this enhances LDL (the major cholesterol carrying lipoprotein) clearance from serum with a net reduction of serum cholesterol (Chapter 20). Individuals who lack functional LDL-receptors (homozygous familial hypercholesterolemia. Chapter 20) do not benefit from statin therapy. However, statin therapy is useful in the treatment of heterozygous familial hypercholesterolemia. Since HMG-CoA reductase plays a pivotal role in the synthesis of many products vital for cellular metabolism, inhibitors of the enzyme may have toxic effects. Monitoring of liver and muscle function may be necessary to detect any toxicity of statin drug therapy. A decreased risk of bone fractures with statin therapy has been observed in subjects age 50 years or older, who are being treated for hypercholesterolemia. The mechanism of action of statins in bone metabolism may involve inhibition of prenylation... 

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. 

All effects of GH result from its interactions with the GH receptor, as evidenced by the severe phenotype of rare patients with homozygous mutations of the GH receptor gene (the Laron syndrome of GH-resistant dwarfism). The GH receptor is a widely distributed cell-surface receptor that belongs to the cytokine receptor superfanuly. Like other members of the cytokine receptor family, the GH receptor contains an extracellular domain that binds GH, a single membrane-spanning... 

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