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Biomedical subjects

A M Prieur

Publications and source records attributed to A M Prieur.

At least 91 records · Page 5Linked to original sources

CD44 contributes to T cell activation.

We demonstrate here that the CD44 molecule, which mediates lymphocyte adhesion to high endothelial venules (HEV), is also involved in the delivery of an activation signal to the T cell. We have produced a CD44 mAb (H90) which is able to block the binding of lymphocytes to high endothelial venules. H90 had no effect on [3H]TdR incorporation of whole PBL stimulated by lectins, allogeneic cells, or CD3 mAb in the soluble phase; in contrast, it strongly increased [3H]TdR incorporation of PBL stimulated by CD2 pairs of mAb or by CD3 mAb linked to the plastic culture plates, when purified T cells were used, H90 mAb could efficiently induce them to proliferate after a primary signal of activation delivered via cross-linked CD3 or via CD2, an effect mediated by Il-2 synthesis and Il-2R expression. Thus, the effect of H90 mAb resembles the mitogenic effect of CD28 "9.3" mAb. However, several results show that CD28 and CD44 mediate different signals to the T cells: i) in contrast to CD28 mAb, CD44 mAb cannot complement the signal delivered by a soluble CD3 mAb, lectins, or PMA; ii) CD44 mAb, at the difference of CD28 mAb, cannot induce CD3+ thymocytes to proliferate in conjunction with a first signal provided via cross-linked CD3 or via CD2; iii) F(ab) fragments of H90 were efficient, whereas divalent fragments of CD29 9.3 mAb are required to produce activation signals; and iv) CD44 and CD28 mAb produce a very strong synergistic effect on T cell proliferation. These results fit with previous ones showing that endothelial cells can play the role of accessory cell in T cell activation and that a hierarchy of signaling can be delivered to T cells via CD3 and CD2.

Adjuvants, Immunologic↗

D-penicillamine in juvenile chronic arthritis.

Juvenile chronic arthritis (JCA) is a heterogeneous disease, differing in most instances from adult rheumatoid arthritis. The diagnostic criteria generally used in Europe are those proposed in Oslo in 1977. There are three main types of onset: systemic, polyarticular and pauciartricular. However, when we observe patients during the course of the disease, this proposed classification seems too simple and does not reflect the reality of outcome. To be more efficient for therapeutic studies, we think that it should be more accurate to consider the type of course, rather than the type of onset. Thus, we will discuss in a first part of this paper subdivisions of the disease according to course, biology and genetics, and indicate in which circumstances a slow acting drug such as pencillamine should be a realistic therapeutic indication. In the second part of this paper, we will give the results of already published observations and of personal data on the effect and tolerance of D-penicillamine, and discuss a way of improving drug evaluation in JCA.

Adolescent↗

Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis.

Interleukin-1 (IL-1) activity and inhibition were studied in serum and urine from nine patients with systemic juvenile chronic arthritis (S-JCA). In afebrile patients IL-1 activity was normal or high. Serum from two afebrile S-JCA patients taken during a period of severe disease activity had an enhancing effect on the activity of exogenous IL-1. Secondary amyloidosis subsequently developed in one of these patients. In contrast, in febrile patients' serum and urine IL-1 activity was low, apparently reflecting the presence of a strong inhibitor of IL-1 activity measured by the inhibition of prostaglandin E2 production by synovial cells. This inhibition was greatest at the time of peak temperature, suggesting the possibility of feedback regulation during fever. This novel identification in S-JCA of a specific IL-1 inhibitor that competes at the IL-1 receptor level may be an important step in the understanding of the pattern of fever and the evaluation of disease in patients with S-JCA.

Adolescent↗

Renal involvement in juvenile chronic arthritis: clinical and pathologic features.

Over an 18-year period, renal involvement was diagnosed in 13 patients, who represent 1% of the total juvenile chronic arthritis population referred to us. All had severe arthritis. This study illustrates the importance of renal biopsy and indicates that renal involvement in juvenile chronic arthritis is a heterogeneous group of diseases, with a variety of causes. In eight patients with nephrotic syndrome, renal biopsy revealed amyloidosis. One rapidly died of diffuse amyloidosis and infection. The other seven received chlorambucil. Disappearance of proteinuria was noted in three of them. Four patients have persistent proteinuria but normal serum creatinine. It is suggested that, despite the long-term oncogenic risk of the drug, chlorambucil may be beneficial in patients with amyloid deposits. In one patient, the nephrotic syndrome was attributed to systemic lupus erythematosus, and in another, the chance association of an arthritis and nephrotic syndrome with minimal glomerular changes was considered. Although drug responsibility is difficult to determine in these patients receiving several medications in association, the renal involvement presented by the remaining three patients was probably related to drug(s). Moreover, it is possible that the effect of the association of medications is deleterious to the kidney. Drug-induced nephropathy is usually reversible when drugs are stopped. Unfortunately, because of persistent joint pain, these patients will continue to require pain-relieving drugs over prolonged periods.

Amyloidosis↗

HLA B27 associated chronic arthritis in children: review of 65 cases.

The study of sixty-five children with antigen HLA B27 associated chronic rheumatism was performed. There was a male preponderance, and mean age at onset was ten. A family history was available in half patients. After a 5-year follow up study, 32% of the patients were diagnosed as having ankylosing spondylitis or Reiter's syndrome or psoriatic arthritis or arthritis associated to inflammatory bowel disease. The other patients should be considered as having an HLA B27 associated juvenile chronic arthritis with special features such as enthesopathy, acute joint pain or sausage-like digits. Three patients had a very severe outcome with considerable joint lesion seen on X Ray.

Adolescent↗

A chronic, infantile, neurological, cutaneous and articular (CINCA) syndrome. A specific entity analysed in 30 patients.

We have studied the clinical presentation and course of a chronic inflammatory disease occurring in childhood and observed in 30 patients. The first symptoms were generally present at birth, except in a few patients where they were first noticed in early infancy. All the patients had the association of three main symptoms: neurological, cutaneous and articular. The skin rash was the first symptom observed in all the patients and looked like a chronic non pruritic urticaria varying during the day. The articular manifestations involved knees, ankles and feet, elbows, wrists and hands unaffecting the other joints. They could be mild giving arthritis during flare-ups or severe with major radiological modifications affecting the epiphysis, metaphysis and growth cartilage. The neurological manifestations were characterized by a chronic meningitis and symptoms indicating meningeal irritation: headaches, seizures, spasticity of legs. Most patients had a cerebral atrophy and a low IQ. Sensory organ involvement occurred progressively during the follow-up: ocular inflammation with optic atrophy, deafness and hoarseness. Common morphological features characterized these patients with short stature, head enlargement, saddle back nose and short and thick extremities with clubbing of fingers. The course was that of a chronic inflammatory disease with numerous flare-ups associating fever, splenomegaly and adenomegaly. Except for a high level of eosinophils in blood, CSF and tissues, the biology was non specific and only exhibited features of inflammation. Except for two families, the disease was sporadic. A high frequency of prematurity with features resembling a foetal infection was observed but no proof of a possible causal virus has so far been found so that etiology remains unknown.

Adolescent↗

[Retrospective study of the possible role of injuries in the genesis of ankylosing spondylitis, Fiessinger-Leroy-Reiter syndrome and other reactive arthritis, unclassified B27 rheumatism in adults and chronic B27 arthritis in children].

If the revealing or aggravating effect of traumas is known in the course of ankylosing spondylarthritis, their etiological role is debatable. We have reviewed 370 files of patients with ankylosing spondylarthritis, 11 of which were mentioning a post-traumatic onset, without being able to find a single case which could satisfy irrefutably the criteria of imputability. It was the same for 51 cases of the Fiessinger Leroy Reiter syndrome 29 cases of reactional arthritis and 42 cases of unclassifiable Rheumatism HLA B27+, and all affections that could develop into an ankylozing spondylarthritis. On the contrary, in 53 cases of chronic juvenile arthritis HLA B27+, we found 5 cases which satisfied the criteria attributable to a trauma. The critical review of the literature also leads us to question the causal role of trauma in cases of ankylosing spondylarthritis and the Fiessinger Leroy Reiter syndrome where trauma is presented as such.

Adult↗

Evaluation of D-penicillamine in juvenile chronic arthritis. A double-blind, multicenter study.

Seventy-four children with juvenile chronic arthritis were entered into a 6-month, multicenter, comparative double-blind study of the efficacy of D-penicillamine versus placebo. The results were evaluated in 70 patients, 55 of whom completed 6 months of the study. Improvement was observed in the total number of stiff joints, total number of painful joints, and total severity index measuring joint pain. There was also a significant reduction in the concurrent use of nonsteroidal anti-inflammatory drugs. D-penicillamine was well-tolerated in all but 2 patients. Some children in the placebo group exhibited definite improvement; however, relapses that were observed were mainly in that group. These results confirm the efficacy of D-penicillamine for the treatment of joint involvement in juvenile chronic arthritis.

Adolescent↗

Acute hemorrhagic, hepatic, and neurologic manifestations in juvenile rheumatoid arthritis: possible relationship to drugs or infection.

Seven children with juvenile rheumatoid arthritis had a syndrome characterized by hemorrhage and neurologic, hepatic, hematologic, and metabolic manifestations. The disease did not seem to conform clearly to the characteristics of Reye syndrome or any other well-known entity. This severe complication may be induced by macrophage activation secondary to a drug or intercurrent infection. Our data suggest that a sudden fall in erythrocyte sedimentation rate or in platelet and fibrinogen levels may mark the start of this complication and may be an indication for rapid steroid therapy.

Acute Disease↗

[Functional, social and professional outcome of patients with juvenile chronic arthritis seen again 12 years after a 1st evaluation].

The authors assessed the outcome of children with juvenile rheumatoid arthritis following an average of 18 years since the onset of the illness. Two-thirds of the patients with the systemic form were asymptomatic. Juvenile rheumatoid arthritis which began with pauciarticular involvement and progressed to polyarticular involvement had the most severe disability, affecting 25% of these patients. Social and professional pursuits were most often satisfactory in spite of numerous problems encountered during the school years.

Adolescent↗

[Juvenile chronic arthritis. Double-blind study of the efficacy and tolerance of D-penicillamine].

Seventy-four children with juvenile chronic arthritis were admitted to a 6-month multicentric double blind comparative study of the efficiency of D-Penicillamine or placebo. The results evaluated in 55 patients who completed the study, indicated an improvement in the total number of stiff joints and in the total index of severity measuring joint pain and inflammation. A significant reduction of the concurrent use of non steroidal antiinflammatory drugs was also observed. The tolerance was good except in two patients. Some children in the placebo group exhibited a definite improvement.

Arthritis, Juvenile↗