Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage
Patent
1986-09-02
1990-11-13
Marantz, Sidney
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving virus or bacteriophage
437 7, 437810, 436518, 436536, 436545, 436546, 436547, 436823, 530327, 530328, 530387, 530807, G01N 33532, G01N 33543, G01N 3368, G01N 3392
Patent
active
049701444
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention is directed to the discovery that certain apolipoprotein (ALP) peptide fragments (or domains or moieties) are immunogenically active and can be used to produce type-specific antibodies that recognize ALP's. The resulting fragments and ALP type-specific antibodies are useful in another aspect of the invention, assay systems for quantitating ALP levels.
BACKGROUND ART
Lipoproteins are aggregates of lipids and protein which circulate in the blood and are the means by which lipids are transported within the body. The lipid portions of these aggregates consist essentially of cholesterol and triglyceride. Serum lipoproteins are classified according to their density. These classes include very low density lipoproteins (VLDL), also known as pre-beta lipoproteins; low density lipoproteins (LDL), also known as beta-lipoproteins; and high density lipoproteins (HDL), also known as alpha-lipoproteins. A fourth class of lipoproteins is chylomicron (CHYLO), stable droplets containing 86% triglyceride fat, 3% cholesterol, 9% phospholipids, and 2% protein. Chylomicrons are found in the intestinal lymphatics and blood during and after meals, and are the form in which absorbed long-chain fats and cholesterol are transported from the intestine.
One of the functions of lipoproteins is to carry water insoluble substances, such as cholesterol and cholesterol esters, for eventual cellular utilization. While all cells require cholesterol for growth, excess accumulation of cholesterol by cells is known to lead to certain diseases, including atherosclerosis. It is now known that the amount of total serum cholesterol can be correlated with the incidence of atherosclerosis. However, since all lipoprotein classes contain varying amounts of cholesterol, total serum cholesterol determination is a complex average of the amount that each lipoprotein class contributes to the total lipoprotein population of the serum.
Recent studies have implicated LDL as the class of lipoproteins responsible for the accumulation of cholesterol in cells, whereas HDL has been shown to be important in the removal of excess cholesterol from cells. Additionally, the correlation of atherosclerosis and the levels of LDL cholesterol is much higher than a similar correlation between atherosclerosis and total serum cholesterol levels. Conversely, there seems to be a negative correlation of atherosclerosis and HDL cholesterol levels. See Goffman, J. W. et al , Circulation, 2: 161-178 (1950); Barr, D. P. et al., Am. J. Med., 11: 480-493 (1951); Nikkala, E., Scand. J. Clin. Lab. Invest. Supplement, 5: 1-101 (1952); Jencks, W. P. et al., J. Clin. Invest., 35: 980-990 (1956), and Miller, G. J. et al., Lancet, 1(7897): 16-19 (1975).
Thus, because the various classes of lipoproteins contain cholesterol and triglyceride in different proportions, determination of only total cholesterol and total triglyceride is not sufficient to differentiate abnormal lipoprotein patterns. Recognition of this fact has led investigators to various procedures designed to determine concentrations of specific lipoproteins rather than just lipids. U.S. Pat. No. 4,126,416 to Sears describes a method for determining the level of LDL cholesterol in blood plasma, the LDL cholesterol being separated from other soluble cholesterol fractions by selectively agglutinating LDL with a plant lectin, followed by detection of the amount of cholesterol associated with the agglutinated LDL.
U.S. Pat. No. 4,167,467 to Golias describes an electrophoresis method for determining the concentration of HDL free cholesterols in body fluids and simultaneously determining the concentration of VLDL and LDL free cholesterols in the fluid sample. The method includes applying a direct current across the fluid medium, applying a developing substrate to the electrophoresed lipoproteins, and quantitatively determining the concentration of each lipoprotein free cholesterol. The method of Golias purports to be an improvement over the prior art in that direct and simultaneous measurement of each li
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Fareed George
Sen Arup
International Genetic Engineering
Marantz Sidney
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