Goldstein (Goldstein), Joseph L.

genus. April 18, 1940
American geneticist Joseph Leonard Goldstein was born in Sumter (South Carolina) from Isadora E. and Fanny A. Goldstein. He received a bachelor of science degree from the University of Washington and Lee in Lexington (Va.) in 1962. and four years later - the degree of doctor of medicine in the south-western Medical School, University of Texas at Dallas. G. distinguished himself as a brilliant student, even before graduating from the University received from the head of the medical department of the University, Dr. Donald Seldina proposal to stay and work in it. In the internship, Massachusetts General Hospital in Boston, where he practiced from 1966 to 1968, Mr.. met with Michael. Brown, administrator of the hospital.
After internship G. spent two years in a researcher in the Laboratory of Clinical Genetics, National Institutes of Health, led by Marshall. Nirenberg. From 1970 to 1972. G. held an internship in medical genetics at the University of Washington in Seattle. There, working under the guidance of Mr. Arnault. Motulski, he discovered a new disease - a family combined hyperlipidemia form. In 1972. G. returns to the Southwestern Medical School, to head the department of Medical Genetics and become an assistant professor in the department of internal medicine therapy. Two years later he was promoted to Associate Professor, . then a senior attending physician in Parklendskoy Memorial Hospital (1974), . professor of internal therapy of diseases (1976), . professor and head of molecular genetics, . Professor of Medicine and Genetics (1977), . visiting member of the Board Solkovskogo Institute in San Diego (California) (1983),
. Michael Brown had already moved to the south-western medical school, and two scientists have begun to work together on the study of cholesterol metabolism.
. Cholesterol is necessary for human life connection, is a major component part of the structure of cell membranes and serves for the production of bile acids and steroid hormones
. In that case, however, if too much cholesterol, it is postponed to the walls of blood vessels, impeding blood flow and causing heart attacks and strokes. Part cholesterol comes from food fats, partially synthesized in the body. Transfer of cholesterol in the blood is carried primarily by particles of low density lipoprotein (LDL).
Family form hypercholesterolemia - a hereditary disease characterized by extremely high blood cholesterol and LDL. Approximately 1 in 500 Americans and Europeans have less severe heterozygous (one abnormal gene) form of the disease and often carries a heart attack at age 30 ... 50 years. In 85% of this group, mostly men, myocardial inevitably arises to 60 years. In people suffering from more severe homozygous form of the disease, which develops due to the inheritance of two mutant genes and occurs in about 1 person per 1 million, circulatory disorders begin in childhood.
. Studying the formation of cholesterol and its regulation, G
. and Brown used a tissue culture method for growing skin cells taken from individuals with a family form of hypercholesterolemia. It was found that these cells contain excessive amount of 3-hydroxy-3-methyl-glyutaril-coenzyme A-reductase (HMG-CoA reductase), an enzyme that controls the rate of cholesterol synthesis. Due to the excessive activity of the enzyme produced the cells much more cholesterol than it disposed.
Then G. and Brown found that the surface of cells, especially the liver, have specific receptors for the complex of LDL-cholesterol. Together with his colleague, Richard D. Anderson, they found that LDL receptors are located teams in the pits of the cell surface, lined the protein clathrin. During the so-called receptor-mediated endocytosis containment cell membranes absorb LDL and detached, forming bubbles for the transfer of particles inside the cells. The receptor then separated from LDL and returned to the cell surface. In cell LDL destroyed, releasing cholesterol. Excess cholesterol inhibits the activity of HMG-CoA reductase (and consequently the synthesis of new cholesterol) while at the same time it activates acyl-CoA or cholesterol Acyltransferase (ADAT-over), an enzyme responsible for intracellular stores of cholesterol. With the increase of intracellular cholesterol also stops the formation of new LDL receptors. So healthy cell to maintain a balance between incoming dietary cholesterol and the intracellular synthesis of this substance. However, an excess of cholesterol in the cells inside the blood vessels are formed atherosclerotic deposits.
. In patients with a family form of hypercholesterolemia LDL receptors are different from normal so that they are not able to remove from the bloodstream sufficient cholesterol
. In 1984. G. and Brown described several mutations of the gene responsible for the LDL receptor. Familial hypercholesterolemia may be caused by defective synthesis of the receptor, . defective binding of LDL, . inadequate endocytosis or transport of the receptor inside the cell and, . Finally, . inability to migrate to the surface receptor protein inlay deepening.,
. In some patients with the heterozygous form of familial hypercholesterolemia, . having only one functional gene for the LDL receptor, . treatment of such preparations, . as kompaktin or mevinolin, . increases the number of LDL receptors, . produced a functional gene, . thereby reducing the content of LDL and cholesterol in the blood,
. This form of therapy, however, is ineffective in homozygous patients lacking a functioning gene for LDL receptor. In 1984. 6-year-old girl with homozygous form of familial hypercholesterolemia was a liver transplant, and in accordance with projections based on the theory of G. and Brown, the presence of a transplant of normal LDL receptors led to a marked decrease in the concentration of cholesterol in the blood.
G. and Brown received the Nobel Prize in Physiology or Medicine 1985. for research, which, according to the Karolinska Institute in Stockholm, 'significantly deepened our understanding of cholesterol metabolism and increased the possibilities of prevention and treatment of atherosclerosis. "
. G., who remained unmarried, with pleasure in their spare time listening to classical music.
. However, Mr. Brown
. Pfitserovskoy also won awards for his research on the chemistry of enzymes of the American Chemical Society (1976), awards Launsberi National Academy of Sciences (1979), an international award Gardner Fund (1981), awards VD. Mattia Institute of Molecular Biology (1984), Louisa Gross Prize-Horvitz of Columbia University (1984). A member of numerous medical and scientific societies, Mr.. also actively participates in the American Federation of Clinical Research, . National Advisory Committee of mammalian cell lines, . Physiological Chemistry Study Section of the American Heart Association, . American Society of Clinical Research (president in 1985 ... 1986.) And the Medical Advisory Committee of Howard Hughes Medical Institute,
. He is a permanent part of the editorial board of the journals 'Aterosklerozis revyuz' ( 'Atherosclerosis Reviews'), 'Arteriosklerozis, Sell, Molekyular Bayolodzhi End of Medicine' ( 'Arteriosclerosis, Cell, Molecular Biology and Medicine') and 'Sains' ( 'Science'). G. is also one of the editors 'office Inherited metabolic Bayzis Dizis' ( 'The Metabolic Basis of Inherited Disease').