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Biomedical subjects

F A Meyer

Publications and source records attributed to F A Meyer.

At least 19 recordsLinked to original sources
PubMed2006

Women's perceptions of events impeding or facilitating the detection, investigation and treatment of breast cancer.

An integrated network is currently being implemented in the province of Quebec in order to improve the cancer care continuum. In this context, formal trajectories for cancer patients through healthcare services are being established. The investigation of patients' perceptions of the healthcare continuum is essential as it allows us to identify the issue of continuity/discontinuity of health services. In addition, patients' perceptions of continuity of cancer care should be documented since they could influence the implementation of optimal trajectories through the healthcare services. An exploratory qualitative study was conducted in order to identify events, based on the perceptions of women with breast cancer, that made the patient progress more rapidly, facilitating events, or more slowly, impeding events, within the cancer care continuum. Two consecutive series of women receiving adjuvant radiation therapy in 2002 and 2003 at the University Hospital of Quebec City were recruited, for a total of 120 participants. A semi-structured interview was administered in order to identify women's perceptions regarding impeding and facilitating events during the detection, investigation and treatment periods of cancer, as well as the actors and reasons involved. Overall, 64% of women reported having at least one impeding event, while 68% reported at least one facilitating event. The periods most frequently affected by impeding or facilitating events were the investigation period, followed by the treatment period. The main stages affected by impeding or facilitating events were the scheduling of an appointment, during the investigation period, and the onset of treatment. Impeding events particularly affected the scheduling of mammography, the initial exam of the investigation for breast cancer, as well as the onset of radiation treatment. On the other hand, facilitating events mainly occurred at the time of the scheduling of medical consultations with specialists, during the investigation period, and of the onset of surgery. Finally, women generally perceived that impeding events were due to a lack in the availability of services and that facilitating events resulted from human intervention. Patients' perceptions, such as those regarding the importance of human intervention in the process of continuity of care, should be taken into account by healthcare authorities in charge of implementing cancer control programmes.

Appointments and Schedules↗
PubMed1996

Differential effects of 1,25-(OH)2D3 on acyl hydrolase and cyclooxygenase activities in interleukin 1 beta-stimulated human synovial fibroblast cultures.

Effects of proinflammatory cytokines on synovial fibroblasts are considered to play a role in the accumulation of prostaglandin E2 (PGE2) in the inflamed joint in rheumatoid arthritis. We have previously shown that interleukin 1 beta (IL-1 beta) induces PGE2 production in synovial fibroblast cultures and that this effect is suppressed by the active metabolite of vitamin D3, 1,25-(OH)2D3. To study the mechanism of the inhibitory action of 1,25-(OH)2D3, its effect on acyl hydrolase (arachidonic acid (AA) release) and cyclooxygenase (COX) activities were investigated. Our findings indicate that IL-1 beta caused an increase in AA release and COX activity and that in the presence of 1,25-(OH)2D3 AA release, but not COX activity, is suppressed. In comparison, dexamethasone, which also inhibits IL-1 beta induction of PGE2, had inhibitory effects on both parameters.

Arachidonic Acid↗
PubMed1996

Salivary eicosanoid concentration in patients with Sjögren's syndrome.

OBJECTIVE: To investigate eicosanoid concentrations in the saliva of patients with primary Sjögren's syndrome (SS). METHODS: Whole mixed saliva of 36 subjects was assayed for eicosanoid concentrations using a radioimmunoassay. Patients with primary SS having positive lip biopsy served as the study group; their results were compared with data from patients with dry mouth and negative lip biopsy (dry mouth group), and with a group of normal healthy controls. RESULTS: Concentrations of thromboxane B2 were significantly (p < 0.01) increased in 18 patients with primary SS compared with 10 patients with dry mouth and eight healthy normal controls (1.95 (SD 0.51) ng/ml saliva compared with 0.52 (0.1) ng/ml and 0.3 (0.1) ng/ml, respectively). Similarly, prostaglandin E2 concentrations were also significantly increased (p < 0.01) in 11 patients with primary SS compared with five patients with dry mouth and eight normal controls (3.75 (0.82) ng/ml saliva compared with 0.32 (0.1) ng/ml and 0.41 (0.1) ng/ml, respectively). CONCLUSION: Salivary concentrations of eicosanoids are significantly increased in patients with primary SS, and this may prove helpful in the diagnosis of this disease.

Biomarkers↗
PubMed1993

Effect of 1,25-dihydroxyvitamin D3 on interleukin 1 beta actions and cell growth in human synovial fibroblast cultures.

OBJECTIVE: To investigate the effects of vitamin D3 [1,25-(OH)2D3] metabolites on interleukin 1 beta (IL-1 beta) stimulated secretory activities and on the proliferation of human synovial fibroblasts in culture. METHODS: Dose dependent effects on IL-1 beta actions were determined in nonproliferating cultures containing 1% fetal calf serum (FCS) in the culture medium. Production of prostaglandin E (PGE), collagenase and hyaluronic acid (HA) was measured respectively by radioimmunoassay, enzymatic degradation of radiolabelled collagen gels after collagenase activation and 14C-glucosamine incorporation. Effects on cell growth in 10% FCS were monitored colorimetrically, by staining cells with crystal violet. RESULTS: 1,25-(OH)2D3 inhibited the effects of IL-1 beta on PGE production by up to 90%, with half maximal inhibition at 2.0 x 10(-10) M. Inhibitory effects on stimulated collagenase and HA production and cell growth were also found but were less marked. At 10(-7) M 1,25-(OH)2D3 inhibition was 50, 21 and 50%, respectively. 24,25-dihydroxyvitamin D3 was a less potent inhibitor than 1,25-(OH)2D3. Neither metabolite influenced IL-1 beta effects on PGE or sulfated glycosaminoglycan production in human articular cartilage in tissue culture. CONCLUSION: Our results suggest that the active metabolites of vitamin D3 may modulate the behavior of synovial fibroblasts in articular inflammatory processes.

24,25-Dihydroxyvitamin D 3↗
PubMed1993

Methotrexate inhibits proliferation but not interleukin 1 stimulated secretory activities of cultured human synovial fibroblasts.

The effect of methotrexate (MTX) on proliferation and on interleukin 1 stimulated secretory activities of human synovial fibroblasts in culture was investigated. MTX caused a dose dependent inhibition of growth over the concentration range 0.07-2.2 microM with a half-maximal effect at 0.37 microM. INhibition was competitively relieved by coaddition of leucovorin. Cell growth was fully restored after MTX pretreatment of 24 h but not after 48 h, even on subsequent leucovorin addition. Cell viability was unaffected by MTX treatment. MTX had no effect on interleukin 1 stimulated production of prostaglandin E, hyaluronic acid and collagenase. Our results raise the possibility that one of the mechanisms contributing to the therapeutic effects of MTX in patients with rheumatoid arthritis may involve modulation of synovial fibroblast growth.

Arthritis, Rheumatoid↗
PubMed1990

Synergistic, additive, and antagonistic effects of interleukin-1 beta, tumor necrosis factor alpha, and gamma-interferon on prostaglandin E, hyaluronic acid, and collagenase production by cultured synovial fibroblasts.

The effects of binary combinations of the recombinant human cytokines, interleukin-1 beta (rHuIL-1 beta), tumor necrosis factor alpha (rHuTNF alpha), and gamma-interferon (rHu gamma-IFN) on the production of prostaglandin E (PGE), hyaluronic acid (HA), and collagenase by human synovial fibroblasts in culture were investigated. All 3 were stimulated by rHuIL-1 beta and rHuTNF alpha alone, but not by rHu gamma-IFN. Stimulation with rHuIL-1 beta and rHuTNF alpha occurred at femtomolar and picomolar concentrations, respectively, and maximal stimulation by rHuIL-1 beta was several times greater than that by rHuTNF alpha. Stimulation of PGE and collagenase production with rHuIL-1 beta or rHuTNF alpha was depressed by rHu gamma-IFN, depending on the concentration used. In contrast, stimulation of HA production with rHuIL-1 beta or rHuTNF alpha was unaffected or increased somewhat with rHu gamma-IFN. Combinations of rHuIL-1 beta or rHuTNF alpha had marked synergistic effects on PGE and collagenase production. However, when rHuIL-1 beta effects were maximal, rHuTNF alpha had an additive effect. These cytokines had only additive effects on HA production, however, and when rHuIL-1 beta effects were maximal, rHuTNF alpha produced no further stimulation. These data suggest that the secretory activities of synovial fibroblasts can be influenced by a combination of cytokines and is dependent on the type of cytokine present and its concentration.

Cells, Cultured↗
PubMed1990

Modulation of the effects of interleukin-1 on glycosaminoglycan synthesis by the urine-derived interleukin-1 inhibitor, but not by interleukin-6.

Interleukin-1 (IL-1) has been shown to regulate glycosaminoglycan (GAG) synthesis. We therefore investigated whether an IL-1 inhibitor or IL-6 modulates IL-1 biologic activities in human synovial cells and cultured articular cartilage. We found that in the presence of a constant amount of IL-1 beta, stimulation of hyaluronic acid (HA) synthesis by the IL-1 inhibitor was inhibited in a dose-dependent manner. Similarly, the decrease in sulfated GAG synthesis induced by IL-1 was reversed by the addition of the IL-1 inhibitor. In contrast, IL-6 did not affect the production of HA, prostaglandin E2, or collagenase in synovial cells, nor did it affect GAG in organ cultures when tested in the presence or absence of IL-1 beta. Hence, IL-6 was ineffective in modulating IL-1 bioactivities on HA or sulfated GAG synthesis. These results emphasize the importance of IL-1 and IL-1 inhibitor in connective tissue destruction and raise questions concerning the role of IL-6 in this pathogenesis.

Cartilage, Articular↗
PubMed1989

Some recombinant human cytokines stimulate glycosaminoglycan synthesis in human synovial fibroblast cultures and inhibit it in human articular cartilage cultures.

Recombinant human cytokines were compared for their effects on glycosaminoglycan (GAG) synthesis in human synovial fibroblast cultures and human articular cartilage explant cultures. In fibroblast cultures, recombinant human interleukin-1 alpha (rHuIL-1 alpha), rHuIL-1 beta, and recombinant human tumor necrosis factor alpha (rHuTNF alpha) stimulated hyaluronic acid (HA) production and, to a lesser extent, sulfated GAG production, while recombinant human gamma-interferon did not have a significant effect. Half-maximal stimulation of HA by rHuIL-1 beta was 0.14 pM, while stimulation for rHuIL-1 alpha and rHuTNF alpha was 1.6 pM and 32 pM, respectively. Indomethacin (10 micrograms/ml) had no influence on HA stimulation by cytokines, while hydrocortisone (2-10 micrograms/ml) caused a significant reduction. In articular cartilage cultures, the cytokines inhibited production of sulfated GAGs. The activity of rHuIL-1 beta was greater than that of rHuIL-1 alpha (half-maximal inhibition at 0.71 pM and 4.7 pM, respectively) and both were considerably more active than rHuTNF alpha; gamma-interferon again had no significant effect. Neither indomethacin nor hydrocortisone influenced cytokine-induced inhibition by either rHuIL-1 preparation. These studies indicate that cytokines released during an inflammatory process may affect GAG synthesis in human joint tissues and may have opposite effects on GAG synthesis in different types of connective tissues.

Biological Factors↗
PubMed1989

Effect of diclofenac on prostaglandin E and hyaluronic acid production by human synovial fibroblasts stimulated with interleukin-1.

Cultured human synovial fibroblasts were stimulated with human recombinant interleukin 1 beta to overproduce prostaglandin E (PGE) and hyaluronic acid (HA). Diclofenac, indomethacin and hydrocortisone inhibited stimulation of PGE production. Half-maximal inhibition occurred at 1.10 x 10(-9), 2.79 x 10(-8) and at 5.52 x 10(-8) M, respectively. Diclofenac or indomethacin had no effect on HA production, while hydrocortisone had an inhibitory effect (half-maximal inhibition at 2.76 x 10(-7) M). This model could be a useful in vitro indicator for the in vivo pharmacological actions of anti-inflammatory drugs.

Diclofenac↗
PubMed1987

Human recombinant interleukin-1 beta stimulates glycosaminoglycan production in human synovial fibroblast cultures.

Human recombinant interleukin-1 beta (rIL-1 beta) stimulated glycosaminoglycan (GAG) production in human synovial fibroblast cultures. A dose-dependent increase in GAG production was found, to a maximum of 500%. Increase was detected at doses as low as 1 pg/ml of rIL-1 beta, reached a maximum at 10-100 pg/ml, and was apparent 10 hours after addition of rIL-1 beta. Stimulation of GAG was always accompanied by increased accumulation of prostaglandin E (PGE) in culture media and by increased collagenase production in approximately one-half the experiments. Indomethacin (5 micrograms/ml) completely inhibited PGE stimulation by rIL-1 beta, but only partially inhibited that of GAG overproduction and had no effect on collagenase production. Hydrocortisone (2 micrograms/ml) inhibited stimulation of all 3 parameters. Stimulation of hyaluronate in synovial cultures prevailed over that of sulfated GAG, which occurred to a lesser extent. Our results support earlier suggestions that interleukin-1 is a major active mononuclear cell factor that is capable of inducing profound changes in connective tissue cell function.

Cells, Cultured↗
PubMed1987

Stimulation of collagenase production in human synovial fibroblast cultures by poly (I). poly (C).

Poly (I). poly (C) was found to induce collagenase secretion in both "normal" and "rheumatoid" synovial fibroblast cultures. Induction was time dependent, was maximal at 20-50 micrograms/ml poly (I). poly (C) and was dependent on de novo synthesis. Induction was prevented by hydrocortisone (0.1 microgram/ml) but inhibition of prostaglandin E production by diclofenac (0.2 microgram/ml) or ibuprofen (0.1 microgram/ml) did not affect collagenase production. Collagenase induction was accompanied by stimulation of hyaluronic acid and prostaglandin E production. This in vitro system may represent a model for the study of pathological secretory activities in the inflamed joint.

Cell Line↗
PubMed1983

Polymeric structure of a high-molecular-weight glycoprotein from bovine cervical mucus.

A 16 X 10(6)-Mr glycoprotein isolated from bovine oestrus cervical mucus when reduced under conditions where disulphide-bond cleavage is essentially quantitative produces chains whose Mr from light-scattering and from sedimentation and diffusion data is some 4 X 10(6)-5 X 10(6). Pronase digestion of the chains indicates that glycosylated sequences of Mr 0.3 X 10(6)-0.5 X 10(6) are interspersed with enzyme-susceptible non-glycosylated peptide sequences.

Alkylation↗
PubMed1983

The mechanism of thermal degradation of a high-molecular-weight glycoprotein complex from bovine cervical mucus.

Gel-like oestrus bovine cervical mucus can be brought to the point of dissolution by thermal treatment. The glycoprotein complex so produced was isolated on CsCl density gradients, and found to be of a size comparable with that of a complex purified from mucus that had been brought to the point of dissolution by mild mechanical stirring. The latter material (GP-S) had a mol.wt. of 15.9 X 10(6) and was used to study further the effect of thermal treatment. Time and temperature lead to a gradual breakdown of GP-S, which is characterized by a single activation energy of 93.3 kJ/mol (22.3 kcal/mol) over the temperature range of 21-99 degrees C. The process responsible is thermal hydrolysis of peptide bonds, particularly next to aspartic acid residues. This conclusion is consistent with the appearance of aspartic acid as a new N-terminal amino acid and the activation energy of the process. After thermal degradation there is an increase in the buoyant density of GP-S and a change in the amino acid composition. These findings were found to be consistent with the loss of the naked peptide region and the preponderance of aspartic acid residues in this region. Thermal degradation therefore does not involve dispersion of non-covalent bonds, and indeed GP-S is quite unaffected by media commonly used to disperse such bonds.

Amino Acids↗
PubMed1983

Evidence for a mechanical coupling of glycoprotein microfibrils with collagen fibrils in Wharton's jelly.

Wharton's jelly of human umbilical cord is known to contain hyaluronic acid and sulphated glycosaminoglycans (probably as proteoglycans) immobilized in an insoluble collagen fibril network. A secondary, independent, insoluble network based on glycoprotein microfibrils of 13 nm diameter and interpenetrated with the collagen network has now been found in amounts corresponding to 9% of the weight of collagen. Elastin, however, is absent. Tissue slices placed in physiological buffer swell to two-fold their in vivo volume. This is due to the influence of the polysaccharides since treatment with either testicular hyaluronidase, Streptomyces hyaluronidase or chondroitinase ABC, causes their quantitative removal and abolishes the swelling tendency of tissue. Tissue so treated remains close to its in vivo volume indicating that for this state the fibrillar network, overall, is in its relaxed unstressed configuration. Subsequent treatment with a protease causes the degradation of the glycoprotein microfibril network and a two-fold increase in tissue volume while treatment with bacterial collagenase, resulting in the solubilization of 46% of the collagen, causes only a slight deswelling. These results suggest that the unstressed configuration of the network system at the in vivo volume of tissue is due to the collagen network being held in compression by the microfibril network. With intact tissue protease digestion with trypsin, in addition, causes a preferential release of sulphated glycosaminoglycans. Hyaluronic acid, however, remains largely immobilized.

Amino Acids↗
PubMed1983

Macromolecular basis of globular protein exclusion and of swelling pressure in loose connective tissue (umbilical cord).

The macromolecular basis of tissue swelling pressure and of the ability of tissue to exclude globular proteins, according to size, have been investigated using human umbilical cord. Exclusion data of tissue, and tissue from which the polysaccharides had been removed by hyaluronidase were compared. Exclusion of globular proteins by the polysaccharides, obtained by difference from the two sets of data, was similar to that reported for isolated polysaccharides in solution. It can be described by a sphere/cylinder geometric exclusion model. The exclusion behavior of the polysaccharide-free tissue was accounted for in terms of the component collagen fibrils, glycoprotein microfibrils and cells. Average pore diameters of 18 and 110 nm, respectively, for the intact tissue and for the polysaccharide-free tissue were estimated. Swelling pressure measurements were performed on intact, on hyaluronidase-treated and on hyaluronidase and then Pronase-treated tissues to obtain the contributions of the polysaccharides, of collagen and of microfibrils. Close to the in vivo volume of tissue, the swelling pressure is given almost entirely by the polysaccharides and is consistent with the osmotic pressure expected from the relative amounts of hyaluronic acid and proteoglycan present and their distribution in the extrafibrillar, extracellular space. Upon swelling or deswelling a small net contribution of the fibrillar system to the swelling pressure is evident.

Collagen↗
PubMed1983

Tissue structure and macromolecular diffusion in umbilical cord. Immobilization of endogenous hyaluronic acid.

Diffusion of endogenous hyaluronic acid and 125I-labelled albumin, monitored by desorption from umbilical cord (Wharton's jelly) slices, was studied in relation to tissue structure. Diffusion of hyaluronic acid was Fickian and some two orders of magnitude slower than that in free solution. After treatment of tissue with trypsin which removes proteoglycan(s) and degrades glycoprotein microfibrils, hyaluronic acid mobility through the collagen fibril network that remains is increased by an order of magnitude. These findings indicate that the mobility of hyaluronic acid in tissue is reduced both by the collagen network and by the presence of proteoglycan(s) and/or microfibrils. Estimates of the reduction in mobility due to physical entanglements with the fibrillar networks show that these play a major role. The mobility of hyaluronic acid found for intact tissue is sufficient for it to permeate the extracellular space within its metabolic turnover time. Labelled albumin diffusion is intact tissue, on the other hand, is reduced by only some 30% relative to free solution. This is consistent with the approximate 10% reduction found for the polysaccharide-free tissue (given by the excluded volume fraction) and the approximate 20% reduction expected for the polysaccharides in the interstitial fluid. Similar effects appear to be involved in the mobility of endogenous diffusible proteins in tissue.

Connective Tissue↗
PubMed1982

Structure and function of mucus.

Discussing the available evidence a fairly strong case can be made for the existence of a basic glycoprotein unit, characterized by what may be a common protein backbone (Fig. 1). This is far less likely for the carbohydrate portion. The considerably more variability in the amount and composition of the carbohydrate coat and species and organ differences may arise because of this fact. Very large aggregates are built up from the basic unit using cross-links of disulfide bonds either intermolecularly, i.e. directly, or intramolecularly, i.e. indirectly via a possible lectin-like structure which forms its bond with some of the carbohydrate side chains. Structures of the order of 10-100 million molecular weight are to be expected which, being heavily entangled, give rise to the special rheological character of the mucus. In most instances mucus behaves rheologically like a gel. The concentration of glycoprotein in the mucus may be the most important parameter which determines the special rheological features required in a special functional context. A unified point of view, when discussing mucus structure and function, was taken. On the evidence available, it seems well justified to continue to do so.

Chemical Phenomena↗