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C C Chen

Publications and source records attributed to C C Chen.

At least 631 records · Page 35Linked to original sources

Mechanisms of proteoglycan inhibition of hydroxyapatite growth.

Purified bovine nasal cartilage proteoglycans (aggregate and subunit containing fractions) and to a lesser degree, chondroitin 4-sulfate of physiological size, retard seeded hydroxyapatite (HA) growth in vitro. The large hydrodynamic size and high charge density of these macromolecules are believed to be associated with the ability of proteoglycans to inhibit HA formation and growth. We now demonstrate the involvement of the negative charges of proteoglycans in this inhibition by comparing the inhibitory ability of chondroitin 4-sulfate and its desulfated analog, and by comparing the growth of HA seed crystals coated either with proteoglycan aggregates or chondroitin 4-sulfate to that of uncoated crystals. In the desulfation experiments, desulfated chondroitin sulfate was a less efficient HA growth inhibitor than untreated, undesulfated chondroitin sulfate of similar molecular size. Dextran sulfate showed higher inhibitory effectiveness than unchanged neutral dextran. Both experiments suggest that sulfate groups play an important role in the regulation of mineral deposition by proteoglycans. In the coating experiment, precoating of HA seed crystals with proteoglycan aggregates decreased the amount of HA precipitated as a function of time, suggesting proteoglycans may block the active nucleating sites on HA surface and slow down the growth process. Chondroitin 4-sulfate had a similar but weaker coating effect. Neutral dextran, having little affinity for HA, had no effect.

Animals↗

Echocardiographic study of cardiac abnormalities in families of patients with Marfan's syndrome.

Twelve patients (5 male and 7 female; mean age 17.7 +/- 12.3 years, range 5 to 42) with Marfan's syndrome and 48 of their first degree relatives (16 male and 22 female; mean age 29.8 +/- 17.3 years, range 4 to 60) were evaluated for cardiac abnormalities by echocardiography. Of the patients with Marfan's syndrome, aortic valve prolapse was present in 1, tricuspid valve prolapse in 4, mitral valve prolapse in 12 and aortic root dilation in 10. Of the 48 first degree relatives of these 12 patients, tricuspid valve prolapse was diagnosed in 3, mitral valve prolapse in 15 and aortic root dilation in 12; aortic valve prolapse was not observed in any of these subjects. Of the 60 persons studied in these 12 kindreds, 28 (47%) had cardiac involvement. Among the 28 with cardiac involvement, aortic valve prolapse was observed in 1 (3.5%), tricuspid valve prolapse in 7 (25%), mitral valve prolapse in 27 (96%) and aortic root dilation in 22 (79%). Mitral valve prolapse was also present in the seven subjects with tricuspid valve prolapse and one with aortic valve prolapse. In 32 of the 60 persons studied in the 12 families, at least one abnormality of the cardiac, skeletal or ophthalmologic system was observed. Nineteen subjects were younger than 18 years of age; all had cardiac involvement associated with Marfan's syndrome. The notably earlier presentation of cardiac involvement in young persons may be responsible for a shorter life span in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Inhibitors of poly(adenosine diphosphoribose) synthetase, examination of metabolic perturbations, and enhancement of radiation response in Chinese hamster cells.

3-Aminobenzamide, a specific inhibitor of poly(adenosine diphosphoribose) synthesis, has been shown to enhance the response of mammalian cells to ionizing radiation and alkylating agents. Observations such as these usually have been taken to be an indication of the involvement of poly(adenosine diphosphoribose) in the repair of DNA damage. It has been reported that some inhibitors of adenosine diphosphoribosyl transferase (ADPRT) affect cell viability, glucose metabolism, and DNA synthesis when present at low concentrations in the growth medium for extended periods (e.g., lymphoid cells exposed to a few millimolar for 24 h [Milam, K. M., and Cleaver, J. E. Science (Wash. DC), 223: 589, 1984]). The latter report questioned previous interpretations of radiation results based on the use of ADPRT inhibitors which enhance cell killing. We have studied the enhanced radiation lethality of Chinese hamster cells using higher concentrations of these inhibitors, but for shorter periods, in an effort to determine if metabolic perturbations are produced and if they are relatable to enhanced cell killing. The compounds used were 2-aminobenzamide, 3-aminobenzamide, 4-aminobenzamide, benzamide, and nicotinamide, compounds which show a large variation in their potency as inhibitors of ADPRT. It was found that none of the compounds was toxic at the highest doses used (20 mM for 2 h) and that, during a 2-h period, the potent inhibitor 3-aminobenzamide had little or no effect on DNA synthesis. Two h is long enough to yield a near-maximum radiosensitization with 3-aminobenzamide. Although glucose metabolism was affected to varying degrees (up to a 50% inhibition by 4-aminobenzamide in 2 h), there was no correlation between effectiveness in inhibiting ADPRT and effectiveness in inhibiting glucose metabolism. A correlation was observed, however, between the inhibitory potential of ADPRT and the enhancement of radiation response. When used for sufficiently short times, we conclude that the effects at even high concentrations of a potent inhibitor of ADPRT (e.g., 3-aminobenzamide) are consistent with an involvement of poly(adenosine diphosphoribose) synthesis in the expression of a radiation-induced end point like cell killing.

Animals↗

The phospholipid requirement for activity of the lactose carrier of Escherichia coli.

The transport activity of the lactose carrier of Escherichia coli has been reconstituted in proteoliposomes composed of different phospholipids. The maximal activity was observed with the natural E. coli lipid as well as mixtures containing phosphatidylethanolamine or phosphatidylserine. Phosphatidylcholine or mixtures of phosphatidylcholine with phosphatidylglycerol, phosphatidic acid, or cardiolipin showed low activity. The lactose carrier reconstituted with amino phospholipids of increasing degrees of methylation (dioleoylphosphatidylethanolamine, dioleoylmonomethylphosphatidylethanolamine, dioleoyldimethylphosphatidylethanolamine, and dioleoylphosphatidylcholine) revealed a progressive decrease in both counterflow and proton motive force-driven lactose uptake activities. Trinitrophenylation of phosphatidylethanolamine in the E. coli proteoliposomes resulted in a marked reduction in lactose carrier activity. Partial restitution of transport activity was obtained by detergent extraction of the carrier from these inactive proteoliposomes and reconstitution of the carrier into proteoliposomes containing normal E. coli lipid. These results suggest that the amino group of the amino phospholipids (e.g. phosphatidylethanolamine and phosphatidylserine) is required for the full function of the lactose carrier from E. coli.

Escherichia coli↗

The inhibitory effect of cartilage proteoglycans on hydroxyapatite growth.

The calcification of connective tissues, including cartilage, is under the control of many interacting systems. Proteoglycans are thought to retard the deposition of hydroxyapatite crystals, and modification of the proteoglycans presumably facilitates mineralization in those tissues that are actively calcifying. The mechanism underlying these regulations remains speculative. This study investigates this question by comparing the inhibitory effectiveness of several macromolecules at neutral pH and approximately physiological ionic strengths. Inhibitors tested include bovine nasal proteoglycan monomer A1D1D1 and aggregate-containing A1 fractions, glycosaminoglycan chains (chondroitin 4-sulfate), and neutral dextran (as an uncharged analog). Hydroxyapatite growth was assessed either by measuring the time-dependent decreases in solution calcium and phosphate concentrations, or by determining utilization of hydroxyl ion in a pH-Stat. All species studied inhibit hydroxyapatite growth, and the extent of inhibition for each class is concentration-dependent. The proteoglycan aggregate-containing A1 fraction is more effective than the proteoglycan monomer at the same concentration, and the proteoglycan monomer is more effective than chondroitin 4-sulfate. Neutral dextran inhibits hydroxyapatite growth less effectively than proteoglycans. These results suggest that inhibition of hydroxyapatite growth by proteoglycans critically depends on both status (aggregate, monomer, etc.) and hydrodynamic size of this macromolecule, supporting the hypothesis that modification of proteoglycans in vivo functions to modulate the effectiveness of proteoglycans as a hydroxyapatite growth inhibitor.

Animals↗