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Biomedical subjects

C W Castor

Publications and source records attributed to C W Castor.

At least 73 records · Page 4Linked to original sources
PubMed1975

Rheumatoid behavior in normal human synovial fibroblasts induced by extracts of Gram-negative bacteria.

We have previously shown that exposure of normal human synovial cells to whole extracts of Gram-negative bacteria or purified endotoxins results in increased synthesis of hyaluronic acid, and increased glucose uptake and lactate output. Derivatives of Gram-negative bacteria, therefore, duplicate the major known actions of connective tissue activating peptide (CTAP). The studies presented here demonstrate that, in addition to the hypermetabolic changes, extract-treated synovial cells become hyposensitive to CTAP and acquire accelerated growth rates. Furthermore, the cellular alterations which occur following a short bacterial product-synovial fibroblast interaction period (72 hours) persist for varying lengths of time, in some cases for as long as the cells are followed in culture (up to 38 days). Additional data presented suggest that bacterial products induce CTAP formation or activation within synovial fibroblasts. Pre-incubation of bacterial endotoxin in fresh normal human serum does not alter its ability to activate synovial cells. Many of the cellular alterations induced by bacterial products and endotoxin (derivatives of infectious agents) resemble the abnormal metabolism of rheumatoid synovium in vivo and are characteristic of the behavior of rheumatoid connective tissue fibroblasts grown in vitro. Furthermore, the persistence of the bacterial extract-induced behavior resembles the semi-autonomy of the cultured rheumatoid synovial cell, at least for a limited period of observation.

Animals↗
PubMed1975

Connective tissue activation. VII. Evidence supporting a role for prostaglandins and cyclic nucleotides.

Prostaglandins added to synovial cultures stimulated hyaluronic acid (HA) synthesis and glycolysis. The order of potency of the prostaglandins was: PGE1 greater than PGE2 greater than PGF2alpha greater than PGF1alpha, PGE1 and PGE2, 1.0 mug per milliliter, stimulated synovial cells, whereas F-series prostaglandins required 5 mug per milliliter for stimulation. Connective tissue-activating peptide (CTAP) activation of synovial cells was markedly potentiated by all four prostaglandins, and by PGE1 in concentrations as low as 0.01 mug per milliliter. Exogenous prostaglandins caused a prompt and marked increment in synovial cell cyclic-AMP, while CTAP caused a delayed peak of cyclic-AMP of lesser magnitude. Treatment of synovial cultures with cortisol (1.0 mug per milliliter), cycloheximide (10 mug per milliliter), or indomethacin (15.0 mug per milliliter) failed to block stimulation by PGE1, 7-OXA-13-Prostynoic acid, a prostaglandin antagonist, substantially inhibited the action of PGE1 and suppressed the effect of CTAP on synovial cells. It is possible that both exogenous and endogenous (synovial prostaglandins are involved in the connective tissue activation sequence.

Animals↗
PubMed1972

The effect of bacterial products on synovial fibroblast function: hypermetabolic changes induced by endotoxin.

The effects of bacterial products on selected synovial fibroblast functions were studied. Extracts of commonly encountered microorganisms were prepared by sonic or mechanical disruption. "Purified" endotoxins were prepared from selected organisms, and in some cases were purchased commercially. Normal fibroblasts were derived from synovial connective tissue obtained from amputations or arthrotomy. The cells were grown as a monolayer on glass and were nourished by a semisynthetic nutrient medium. Extracts of Gram-negative bacteria, applied to fibroblast cultures, markedly increased hyaluronic acid production, glucose utilization, and lactate output. Treatment of the extracts with heat at 100 degrees C for (1/2) hr decreased their effectiveness by approximately 40%. Purified Gram-negative bacterial endotoxin stimulated synovial fibroblasts to an extent comparable to that caused by heat-treated whole extracts. The lipid moiety of the endotoxin molecule appeared to account for much of the stimulatory activity of the endotoxin. Extracts of commonly encountered Gram-positive cocci, yeast, and Mycoplasma had no stimulating capabilities. Corynebacterial extracts, however, had definite stimulating potential. Endotoxin-synovial cell interaction experiments demonstrated that endotoxin was bound to fibroblasts. Reassay of the endotoxin after extraction from the cells showed that it retained its stimulatory potential. The metabolic phenomena stimulated by bacterial products duplicate the major known actions of connective tissue-activating peptide (CTAP). The observations made in this study suggest that bacterial products may participate in a fundamental way in the activation process, and indicate a possible role for bacterial products in synovial inflammation in humans.

Cells, Cultured↗
PubMed1968

Regional distribution of acid mucopolysaccharides in the kidney.

Kidneys from 20 dogs were dissected into cortical and medullary components and analysed for acid mucopolysaccharide content. Heparitin sulfate accounted for approximately 80% of cortical acid mucopolysaccharide, 10% was chondroitin sulfate B, and 10% was low molecular weight hyaluronic acid. Medullary tissue exhibited a 4- to 5-fold higher concentration of acid mucopolysaccharide than did cortical tissue, and the dominant compound was moderately highly polymerized hyaluronic acid. While chondroitin sulfates A and (or) C were not detected in this study, the presence of minor amounts of these substances could not be excluded. A model experiment indicated that hyaluronic acid retards sodium diffusion, apparently due to its viscous properties rather than its electronegativity.

Animals↗