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Biomedical subjects

G Loyau

Publications and source records attributed to G Loyau.

At least 73 records · Page 4Linked to original sources

In vitro production of collagen by synovial fibroblasts from D-penicillamine-treated arthritic rabbits.

In order to get further insight into the mechanism of D-penicillamine action on synovial tissue collagen synthesis, fibroblasts derived from drug-treated arthritic rabbits were cultured and labelled with radioactive proline. No evident correlation was found between the amount of newly synthesized collagen and the previous treatment of animals. In contrast, the prolyl-hydroxylase activity was reduced in cells from rabbits receiving D-penicillamine. This finding suggests that culture conditions may influence the collagen-synthesizing potentiality of the synovial fibroblasts without changing the level of enzyme activity. Therefore, the prolyl-hydroxylase activity could be considered here as a more reliable reflection of the in vivo situation. The ratio of type III to type I procollagens, as estimated by DEAE-cellulose chromatography, showed a rise in cultures from D-penicillamine-treated rabbits as compared to controls. This result indicates that long-term administration of the drug may alter the collagen composition of synovial tissue matrix in rheumatoid arthritis. The question remains, however, whether this alteration contributes to the beneficial effect of the drug.

Animals↗

D-penicillamine inhibition of interleukin-1 production: a possible mechanism for its effect on synovial collagen synthesis?

Collagen production was investigated in cultured rabbit synovial fibroblasts exposed in vitro to D-penicillamine (D-Pen). The results show that these cells are rather insensitive to the drug since only a slight increase of the collagen amount secreted was observed for 48-h exposure to concentrations of 200-400 micrograms/ml. However, fibroblasts derived from the synovium of arthritic rabbits proved to be more susceptible to D-Pen, responding by a marked increase of collagen secretion even for concentrations of 50 micrograms/ml. This finding suggests that synovial fibroblasts of arthritic patients, probably stimulated by the inflammation process, could be target cells for the D-Pen action. The activities of 4-prolyl-hydroxylase (4-PH) and galactosylglucosyl-transferase (GGT) were assayed in the same cultures. A correlation has been found between the 4-PH activity and the collagen amount produced. In contrast, no alteration in the level of GGT on exposure to D-Pen was detected. Finally, D-Pen was shown to reduce in vitro the production of collagen-inhibiting factors by phytohaemagglutinin-stimulated mononuclear cells. This effect was associated with an inhibition of the release of monocyte cell factor (MCF/interleukin-1), suggesting that D-Pen could indirectly affect synovial collagen synthesis by interfering with interleukin-1 secretion.

Animals↗

[Collagenases in rheumatology].

An important role is supposed to be played by the collagenases in the physiological or pathological degradation of collagen. However, their exact effects in rheumatic diseases, especially in rheumatoid arthritis is still controversial. The aim of the authors is to give facts and datas up to date, about this important question of the pathogenic role of collagenases in rheumatoid arthritis, osteoarthritis and in several other rheumatic diseases.

Arthritis, Rheumatoid↗

Interleukin-1 inhibits the synthesis of collagen by fibroblasts.

Human dermal fibroblasts, exposed to human or porcine Interleukin-1, responded by an inhibition of collagen synthesis in a dose dependent manner. Incubation with Il-1 for more than 8 h was required to see an appreciable effect. The phenomenon was not dependent on the presence of serum in the culture medium. Since a stimulation of prostaglandin E2 secretion was also observed in presence of Il-1, we investigated the eventual role of arachidonic acid metabolites in the phenomenon. Inhibitors interfering with arachidonate metabolism, namely indomethacin, acetyl salicylic acid, BW 755 C and NDGA had no influence on the inhibition of collagen synthesis caused by Il-1. These data suggest that both cyclooxygenase and lipoxygenase derived metabolites of arachidonic acid are unlikely to play a role in the mechanism.

Animals↗

Effect of ascorbic acid on secreted proteoglycans from rabbit articular chondrocytes.

Addition of ascorbic acid (25, 50 100 micrograms/ml) to cultures of rabbit articular chondrocytes did not change the total amount of proteoglycans produced. However, it induced an increased retention of these macromolecules in the pericellular fraction. The size of the proteoglycan subunits and the length of glycosaminoglycan chains, released in the medium, were not modified on exposure to ascorbic acid (25 micrograms/ml). On the other hand, the rate of non-sulfated chondroitin was increased 2.5-fold, whereas chondroitin-4-sulfate was depressed 1.5-fold.

Animals↗

Mononuclear cell-mediated modulation of synovial cell metabolism. II. Increased hyaluronic acid synthesis by a monocyte cell factor (MCF).

Treatment of cultured human synovial cells with a mononuclear cell factor (MCF) enhanced their ability to synthesize glycosaminoglycans (GAG), but GAG repartition between extracellular, pericellular and intracellular compartments was found to be the same as in control. Hyaluronic acid (HA) production, which represents 80-90% of all secreted GAG, was stimulated 2 1/2-3-fold, but the HA molecular weight was not modified. The MCF increased the hyaluronate synthetase activity of synovial cells in similar proportions. Actinomycin D inhibited the increase in hyaluronate synthetase activity produced by MCF, indicating that this increase involves new synthesis of mRNA. Stimulation of both HA synthesis and hyaluronate synthetase activity by MCF was suppressed by 10(-4)-10(-5) M indomethacin (an inhibitor of cyclo-oxygenase), suggesting that MCF effect is prostaglandin-dependent.

Aged↗

Mononuclear cell-mediated modulation of synovial cell metabolism. I. Collagen synthesis.

Human PHA-stimulated mononuclear cells produce a factor which inhibits synovial cell collagen and non-collagen protein synthesis, whereas it enhances hyaluronic acid (HA) production. Indomethacin (10(-4)-10(-6) M), a cyclo-oxygenase inhibitor, suppresses this effect, suggesting that the mechanism is prostaglandin-mediated. The active material, of apparent molecular weight 12 000-20 000, also displays the properties of the mononuclear cell factor (MCF) previously described by others, since its stimulates collagenase and PGE2 release by the cultured synovial cells. Furthermore, it co-purifies with interleukin 1 (IL 1) as shown by lymphocyte-activating factor activity. This strongly suggests that IL 1 could be responsible for some (or all) the effects observed on MCF-exposed synovial cells. From these data, we deduce the possibility that mononuclear cells may participate in limiting synovial collagen deposition in rheumatoid arthritis.

Cells, Cultured↗

[Cardiac manifestations of atrophying polychondritis. Apropos of a case disclosed by pericardial effusion and auricular flutter].

We report the case of a 50 year old patient, hospitalised with a clinical record suggestive of acute pericarditis and disturbance of auricular rhythm of the flutter type. The consciousness of muscular pain, subcutaneous peri-articular nodules developing over periods of 10 to 15 days and the appearance of chondritis of the right auricle on the 2nd day of hospitalisation led to a diagnosis of atrophying polychondritis. A two-dimensional, TM echocardiographic examination confirms the presence of a discrete, pericardial effusion and presents evidence for a concentric hypertrophy and a heterogeneous aspect of the left ventricular myocardium. In atrophying polychondritis, a rare systemic disease the diagnosis for which is essentially clinical, complications readily set in the form of cardiovascular attacks, sometimes lethal (valvulopathies essentially aortic, aneurysm of the ascending aorta, disturbances of rhythm and conduction, myocardial necrosis, etc). A pericardial attack has already been reported for this condition but uniquely according to electrocardiographic criteria, the lack of specificity of which is known. Our case report confirms the possibility of a pericardial reaction and, in addition, permits the observation of a hypertrophy and a heterogeneous aspect of the myocardium which has not yet been reported in the literature.

Atrial Flutter↗

[Spinal biphotonic absorptiometry].

Spinal biphotonic absorptiometry allows a quantitative investigation of bone mineralisation. The study of a control and an osteoporotic population allowed the definition of the fracture threshold independent of age and the curve of the variation in the mineral content with aging. A good correlation was observed with computed tomography. The criteria of definition of a population at risk for the purposes of a longitudinal study are proposed. Biphotonic absorptiometry is an excellent examination for the detection of demineralisation and for the monitoring of treated subjects.

Adult↗

[Multiple myeloma of the bones. Treatment by 2-stage whole-body irradiation. 7 cases].

Seven patients with high tumoral burden myeloma of bones were treated by two successive hemicorporeal irradiations. This treatment was strikingly effective in providing pain relief which was durable in 3 cases. It might also have reduced the tumoral mass, since partial remission was obtained in 2 cases and lasting normalization of calcaemia in one patient with a non-excreting myeloma. Its haematological side-effects did not seem to exceed those of combined chemotherapy, and its pulmonary toxicity was reduced by using corrected doses.

Aged↗

Effect of a monocyte cell factor (MCF) on collagen production in cultured articular chondrocytes: role of prostaglandin E2.

A monocyte cell factor (MCF) inhibited the incorporation of (3H)proline into collagen of rabbit articular chondrocytes in culture, without significant effect on non-collagen protein. In addition, MCF produced a new compartmental repartition of collagen between cell layer and medium. No MCF-induced shift was observed in the relative proportion of collagens synthesized, type II remaining the major collagenous product. The inhibitory effect of MCF was not completely suppressed when prostaglandin synthesis was blocked by indomethacin. Addition of PGE2 at 12.5-25 micrograms/ml to the cultures resulted in a decrease of total collagen. Lower concentrations (0.42-0.85 microgram/ml) did not affect the total synthesis of collagen but changed its distribution between cells and medium in the same way as MCF. These results suggest that the MCF-stimulated release of PGE2 may be partially involved in the inhibitory effect observed on collagen synthesis.

Animals↗

[Cleidocranial dysostosis. Contribution to its study apropos of 2 personal cases (an isolated and a familial form)].

Cleidocranial dysostosis is a rare embryopathy affecting the whole osseous system. Anomalies predominate on skull, chest and dentition but the whole skeleton can be affected especially pelvic girdle and spine. An autosomal transmission is often demonstrable; isolated forms are very uncommon. We present two cases fortuitously diagnosed in our ward: a familial cleidocraniopelvic major form and an incomplete isolated form. The treatment must be especially oriented towards dental malformations.

Adolescent↗

[Clinical study of Bi-Profenid in rheumatologic practice].

The effectiveness and tolerance of Bi-Profenid as 150 mg tablets were analyzed in a multicenter study. Each of the 288 patients entered in the study had one of the main conditions found in rheumatologic practice: arthrosis of the hip or knee, rheumatoid arthritis or ankylosing spondylarthritis. Each patient was given one 150 mg Bi-Profenid tablet twice daily for 30 days. Overall effectiveness, as assessed by the pain scale test, produced improvement in 87.3% of cases. In degenerative rheumatic diseases, nocturnal pain, pain upon mobilization and walking distance were very significantly improved. In inflammatory rheumatic diseases, the significantly improved parameters were nocturnal pain, morning stiffness and functional indexes of rheumatoid arthritis. Tolerance was outstanding or very good in 77.1% of cases and the dropout rate was only 7.6%.

Adult↗

[Ankylosing spondylitis. Comparative trial of two non-steroidal anti-inflammatory agents: pirprofen and ketoprofen].

In this double blind, crossover trial, 40 patients with ankylosing spondylitis were treated during two successive periods of 4 weeks each with either pirprofen 800 mg/day or ketoprofen 300 mg/day administered orally in a randomized order. The efficacy of pirprofen and ketoprofen was comparable, the results, as assessed by the clinician, were excellent or satisfactory in 53% of both groups. Pirprofen was well tolerated by 71% of the patients and ketoprofen by 59%.

Adult↗