Nancy L. Noble

The Marfan Syndrome: A Deficiency in Chemically Stable Collagen Cross-Links

THE reduced tensile strength of tissues supporting the ocular lenses, cardiac valves, and aorta in heritable connective-tissue diseases is probably due to a defective organization of collagen. Sinc...

Histamine, norepinephrine, and bradykinin stimulation of fibroblast growth and modification of serotonin response.

Summary Histamine and norepinephrine have a concentration-dependent growth-enhancing effect on fibroblast growth in vitro that is different from the response to serotonin. These distinct dose-response curves suggest different mechanisms of action. Furthermore, histamine depresses growth of human embryo lung fibroblasts while enhancing growth of an established cell line (3T6) and serially cultured strains of mouse skin fibroblasts. The acquired nature of the histamine response is in contrast to the consistent growth-enhancing effect of serotonin and norepinephrine on all fibroblast lines or strains. At micromolar concentrations, histamine, norepinephrine, and bradykinin antagonize the action of serotonin, while at a nanomolar level norepinephrine potentiates the effect of serotonin. The spatial configuration of bradykinin is critical for the fibroblast growth response. Prostaglandin E2 inhibits fibroblast growth. The authors gratefully acknowledge the assistance of Mr. T. Ralph Alvarez and the gift of prostaglandin E2 from Dr. Vincent A. Ziboh.

Biochemical observations of human atheromatosis: analysis of aortic intima.

Atherosclerosis develops chiefly in the intima of the artery. Biochemical changes associated with atheromatosis were studied serially in human aortic intima by a gross division of the intima into normal tissue, early and advanced atheromata. Earliest alterations observed are increases in collagen concentration and in binding of hexosamine with scleroprotein. Elevation of lipids occurs only after development of the atherosclerotic lesion. There appear to be more biochemical alterations in female intima with atheromatosis and age than in male tissue. Calcium concentration does not increase with age in normal intimal tissue.

Lipids of the Serum and Connective Tissue of the Rat and Rabbit

The lipicl profile of connective tissue, isolated from the rat and the rabbit, by the sponge-implantation technique, is presented. This tissue is rich in cholesterol, phospholipid, and neutral fat. Several sex, age, and species differences in the concentration of its lipids are reported. Simultaneous determination of serum lipids indicates that there is no significant correlation between the lipid values of the serum and connective tissue. The relationship of these findings in connective tissue, the chief constituent of the intima, to the problem of atherosclerosis is discussed.

Similarity of aortic pathology in Marfan's syndrome, copper deficiency in chicks and B-aminopropionitrile toxicity in Turkeys

Abstract The abdominal aortas of a human with Marfans syndrome, chicks fed a copper-deficient diet and turkeys fed B-aminopropionitrile (BAPN) were studied by light- and electron microscopy. The alterations in the aortic media in all three conditions were similar. The degenerative changes included shrinkage of smooth muscle cells, swelling and fragmentation of elastic fibers, scattering of collagenous fibers, pooling of mucopolysaccharide, and dilatation of extracellular spaces. Only in Marfans syndrome was there thickening of the basement membrane of smooth muscle cells. The microscopic lesions agree with the biochemical changes of connective tissue reported to occur in the three conditions.

Biochemical Studies on Cholesterol in in vivo Cultivated Connective Tissue

In vivo cultivated connective tissue is rich in lipids. That obtained from man and chicken has larger concentrations of neutral fat and cholesterol than connective tissue of other species. Connective tissue synthesizes cholesterol and possesses a striking avidity for retention of either endogenous or exogenous cholesterol. The fibrous portion of sponge-connective tissue of the rabbit incorporates cholesterol at a characteristic rate, indicating some inherent inter-relationship between the lipid and the scleroprotein. Marked reduction of a previously elevated serum cholesterol in the rabbit does not lower connective tissue cholesterol concentration. Connective tissue of the rabbit intima requires prolonged exposure to an elevated serum cholesterol before increased cholesterol incorporation occurs.

Serotonin and ribonucleic acid and collagen metabolism of fibroblasts in vitro.

Summary Serotonin when added to mouse (3T6) and human embryo lung fibroblasts in culture at a medium concentration of 10-6 M affects RNA and collagen syntheses. The effect differs depending upon the stage of cell culture when serotonin is added. During rapid cell growth, serotonin reduces the uptake of 3H-uridine into RNA and 3H-proline into protein, while serotonin added to the cells after the logarithmic growth phase stimulates the synthesis of RNA and protein. In stimulating RNA synthesis, serotonin seems to affect predominantly the species of RNA that are involved in protein synthesis, the 30s and tRNA. At no time did serotonin affect protein or collagen synthesis without a parallel response in RNA synthesis. The authors are pleased to acknowledge the review of the manuscript and helpful comments of Dr. Antero So.

Considerations of aortic elastin chemistry in the genesis of the intimal plaque (Broad-Breasted White turkey)

Abstract Fragmentation of internal and external elastic membranes occurs in the abdominal but not in the thoracic aorta of the Broad-Breasted White turkey during the early developmental period. In this early period, isolated elastin from the abdominal aorta contains more polar amino acid residues than elastin of the thoracic aorta. Additionally, the relative amount of a chemically unstable elastin cross-link, dehydrolysinonorleucine, is greater in the abdominal as compared to the thoracic aorta during the early developmental and adult periods. Cells of the abdominal aorta exposed to a higher arterial pressure and a greater rate of arterial pressure rise ( dp dt ) and in a region with a higher collagen:elastin ratio (reduced compliance to pulse-pressure-volume deformations) may synthesize a chemically unstable elastin which breaks down in regions of accentuated wall stress. Though these breaks of the internal elastic membranes, modified smooth muscle cells may migrate, proliferate and ultimately synthesize new elastin in forming the intimal plaque.

The Conjugated Lipids of Connective Tissue of the Rat and Rabbit

The conjugated lipids of connective tissue of the rat and rabbit obtained by the sponge-biopsy technic and the aortic intima of the rabbit were divided into two portions by differential saline solubility and the saline-soluble portion was further fractionated into the alpha and beta fractions of Cohn. No apparent relationship was observed between the protein, amino acids or lipids of the serum and the connective tissue of the rabbit. The sponge-connective tissue differed from the aortic intima in certain respects but appeared to be similar in the saline-insoluble fractions of amino acid and cholesterol. The effects of sex and age upon connective tissue of the rat is described.

Variations in 35SO4 incorporation into glycosaminoglycans along canine coronary arteries. A possible index of artery wall stress.

Focal areas of accentuated waO stress along the course of canine coronary arteries may be revealed by the level of 35SO4 incorporation into grycosamlnogrycans (GAG). In the anterior descending artery, 35SO4 incorporation is higher in the proximal than in the distal region and may be extraordinarily high as the vessel enters a proximally located muscle bridge and at the takeoff region of multidirectional branches. In the circumflex artery, the incorporation also is higher in the proximal than in the distal region and is high at the genn where the posterior descending artery forms. There are differences in uptake of 25SO4 in vessels even when the arteries arise from the same vascular bed. This was shown by the higher incorporation in the left coronary artery than in the right coronary artery. A general anatomical agreement exists between these sites of high 35SO4 incorporation and previously described locations of Internal elastic disruption and proliferation of intimal connective tissue in the dog.