SYNOVIAL CELL ACTIVATION INDUCED BY A POLYPEPTIDE MEDIATOR *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73993/1/j.1749-6632.1975.tb36057.x.pd

Light curves for bump Cepheids computed with a dynamically zoned pulsation code

The dynamically zoned pulsation code developed by Castor, Davis, and Davison was used to recalculate the Goddard model and to calculate three other Cepheid models with the same period (9.8 days). This family of models shows how the bumps and other features of the light and velocity curves change as the mass is varied at constant period. The use of a code that is capable of producing reliable light curves demonstrates that the light and velocity curves for 9.8 day Cepheid models with standard homogeneous compositions do not show bumps like those that are observed unless the mass is significantly lower than the 'evolutionary mass.' The light and velocity curves for the Goddard model presented here are similar to those computed independently by Fischel, Sparks, and Karp. They should be useful as standards for future investigators

Connective Tissue Activation. I. The Nature, Specificity, Measurement and Distribution of Connective Tissue Activating Peptide

A polypeptide which induces hypermetabolism in normal synovial fibroblasts in tissue culture is described. The metabolic changes induced included a marked increase in hyaluronate formation, lactate formation and glucose uptake; formation of soluble and fibrous collagen was depressed. An assay method is presented which permits quantitative comparisons of samples for connective tissue activating peptide (CTAP) activity. The CTAP appeared to be widely distributed in human tissues, the amount of activity being a function of cell density. A role for CTAP in rheumatoid inflammation is proposed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37716/1/1780140107_ftp.pd

Connective tissue activation

Connective tissue a ctivating p eptides from lymphocytes (CTAP-I) and platelets (CTAP-III) are known to stimulate glycosaminoglycan synthesis, glycolysis, and mitogenesis in connective tissue cell cultures. Direct evidence suggested that increased accumulation of cyclic AMP was involved in the action of these peptide agonists, and increased prostaglandin E synthesis was postulated on the basis of indirect evidence. In the present experiments, CTAP-I and -III were incubated with human and murine cells in culture, and prostaglandin E was measured by radioimmunoassay using antibody directed primarily to prostaglandin E2. Both CTAP-I and -III markedly stimulated the elaboration of prostaglandin E into culture medium, the earliest evidence of increased synthesis occurring at 4 hours with maximal concentrations found at 24 hours. Substantial residual stimulation persisted at least through 48 hours. Indo-methacin (13.0 Mg/ml) obliterated basal and incremental synthesis of prostaglandin in the presence of mediators. Cycloheximide (8.7 Mg/ml) did not affect the stimulation of prostaglandin synthesis by CTAP-I and -III. Three nonrheumatoid and 3 rheumatoid synovial cell strains showed similar basal levels of prostaglandin E and similar responses to CTAP-I. A murine fibroblast cell strain (3T3) showed increased prostaglandin E synthesis on exposure to CTAP-I, and the KB tumor cell strain was markedly stimulated by CTAP-III. These studies confirm the increased synthesis of E series prostaglandins postulated to occur in human connective tissue cells on exposure to CTAP-I and -III, and clarify the mechanism of action of these agonists on “activated” target cells. The importance of elevated extracellular concentrations of prostaglandins is uncertain, although they may act directly on sensitive cell types as well as potentiate the actions of CTAP-I and -III on neighboring cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37752/1/1780240309_ftp.pd

Connective tissue activation

Connective tissue activating peptide-III (CTAP-III) isolated from human platelets is a potent mitogen for human connective tissue cells in culture in addition to stimulating glycosaminoglycan synthesis, glucose consumption, and lactate formation. The amino acid composition of apparently homogeneous CTAP-III was determined, confirming the presence of two disulfide links and providing a calculated molecular weight of 11,633 daltons. Comparison of the mitogenic activity of serum and plasma-serum suggests that CTAP-III is a major mitogenic component of human serum. Seventeen strains of human connective tissue cells (synovial, cartilage, dermal and thyroid) incorporated [ 3 H]-thymidine at up to 30 times control at levels under the influence of microgram quantities of CTAP-III and caused detectable increases in thymidine incorporation at levels as low as 10–29 ng/ml. Prostaglandin E 1 (0.01 Μg/ml) and dibutyryl cyclic AMP (25 Μg/ml) potentiated the glycosaminoglycan stimulating effect of CTAP-III, but not its mitogenic effect. Cycloheximide and actinomycin D blocked the biologic actions of CTAP-III. Cortisol and penicillamine had little effect on the mitogenic activity of CTAP-III, whereas antirheumatic agents such as acetylsalicylic acid and phenylbutazone opposed the mitogenic activity when added to cultures at clinically relevant concentrations. A weak antiheparin factor secreted by platelets, low affinity platelet factor 4 (LA-PF 4 ), was shown to be similar to CTAP-III in biologic actions, electrophoretic mobility, amino acid composition, and antigenic determinants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37739/1/1780220308_ftp.pd

Hyaluronic acid in human synovial effusions; A sensitive indicator of altered connective tissue cell function during inflammation

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37705/1/1780090606_ftp.pd

Connective Tissue Activation. II. Abnormalities of Cultured Rheumatoid Synovial Cells

Rheumatoid synovial cells grown in vitro demonstrated: a) increased rate of lactate formation, b) increased rate of glucose uptake, c) increased rate of hyaluronate synthesis, d) decreased sensitivity to exogenous activator and e) increased concentrations of an endogenous activator. Exogenous activator was shown to be capable of inducing cortisol unresponsiveness in relation to suppression of hyaluronate synthesis. Evidence that exogenous activator is not long retained by synovial cells suggests that elevated levels in rheumatoid cells are due to accentuated endogenous formation. Elevated activator peptide content of rheumatoid synovial cells provides an explanation for many of the differences between normal and rheumatoid synovial cells in vitro.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37717/1/1780140108_ftp.pd

Integrating Viral Hepatitis Screening and Prevention Services into an Urban Chemical Dependency Treatment Facility for American Indians and Alaska Natives

American Indian/Alaska Natives (AI/AN) patients at an urban residential chemical dependency treatment center participated in a viral hepatitis prevention project. Project activities integrated into patients’ treatment programs included viral hepatitis and human immunodeficiency virus (HIV) risk factor screening, education and counseling, laboratory testing, and hepatitis A and B vaccination. Of 928 AI/AN admissions, 585 (63%) completed risk factor screening assessment. Of these, 436 (75%) received at least one vaccination, viral hepatitis testing, or both. Of 322 patients tested, 91 (28%) were hepatitis C virus (HCV) antibody positive. Lack of pre-existing immunity to vaccine-preventable viral hepatitis infection was common: 132 (45%) were susceptible to hepatitis A and 224 (70%) were susceptible to hepatitis B infection. Chemical dependency treatment centers serving urban AI/AN provide important opportunities for implementing viral hepatitis prevention programs for high-risk populations and for improving ongoing efforts to reduce the disparate impact of chronic liver disease in AI/ AN people

Connective tissue activation. xxxv. detection of connective tissue activating peptide–iii isoforms in synovium from osteoarthritis and rheumatoid arthritis patients: patterns of interaction with other synovial cytokines in cell culture

Objective. To determine whether extracts of unincubated osteoarthritis (OA) and rheumatoid arthritis (RA) synovial tissue contain connective tissue activating peptide–III (CTAP-III) isoforms and prostaglandin E 2 (PGE 2 ), and whether such extracts have growth-promoting activity, and to determine whether binary combinations of CTAP-III with other cytokines reported to be present in synovial tissue lead to synergistic, additive, or inhibitory effects on growth. Methods. Acid–ethanol extracts of human synovium were examined for growth-promoting activity by measuring formation of 14 C-glycosaminoglycan ( 14 CGAG) and 3 H-DNA in synovial cell cultures; PGE 2 was measured by enzyme immunoassay, and CTAP-III isoforms were identified by Western blotting of extracted proteins separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Growth-promoting activity of CTAP-III and other cytokines was tested in synovial cultures treated with the agonists singly and in binary combination, by measuring changes in synthesis of 14 C-GAG and 3 H-DNA. Results. Platelet-derived CTAP-III and a cleavage isoform with the electrophoretic mobility of CTAP-III–des 1–15/neutrophil-activating peptide–2 (NAP-2) and PGE 2 were found in biologically active extracts of synovial samples from patients with RA and OA. Five growth factors (recombinant epidermal growth factor [rEGF], recombinant interleukin-1Β [rIL-1Β], basic fibroblast growth factor [bFGF], PGE 1 , and PGE 2 ) in binary combination with CTAP-III showed synergism in stimulating GAG synthesis; two (recombinant platelet-derived growth factor type BB [rPDGF-BB] and recombinant transforming growth factor Β [rTGFΒ]) had an additive effect. In combination with CTAP-III, rEGF and rPDGF-BB had a synergistic effect in promoting DNA synthesis, rTGFΒ and rbFGF had an additive effect, and rIL-1Β, PGE 1 , and PGE 2 were antagonistic. Conclusions. The results suggest that, in addition to endogenous factors, CTAP-III and other plateletderived cytokines may play roles in regulating synovial cell metabolism in RA and OA, and that combinations of growth factors may be more significant than single agents in amplification or suppression of important cell functions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37793/1/1780350712_ftp.pd