Differentiation of human dendritic cell subsets for immune tolerance induction.

OBJECTIVES: Since no further progress was achieved, in order to improve the long-term organ transplantation outcome, the immune tolerance appears as an interesting therapeutic goal. Dendritic cells (DCs) are specialized cells participating in the homeostasis of the immune response. Moreover, subsets of DCs, identified in humans, appear to have their respective competences in immune response modulation. Our objective is to purify from PBMC or to differentiate DC subsets from monocytes using several strategies and evaluate their IL10 secretion. METHODS: CD14+ cells were purified from peripheral blood mononuclear cell (PBMC) by affinity beads and cultured with cytokines up to 7 days. The pDCs were purified with anti-BDCA-2 beads from PBMC fraction enriched by Percoll® gradient. The moDCs, pDCs and moLCs subsets were analyzed by phenotype labelling and FACS analyses and IL10 secretion measured by ELISA. RESULTS: The moDCs were characterized by the CD209 expression and a lower expression of CD1a markers. Expression of CD207 and CD1a markers characterized moLCs and CD123+/BDCA-2+ pDCs. Variable IL-10 secretions were shown between the three DC subsets, both at basal and activated levels. CONCLUSIONS: As the several DC populations studied have different capacities of IL-10 synthesis, they might play, among others, distinct roles in the induction of immune tolerance.

Generation and validation of a normative, age-specific reference curve for lumbar spine trabecular bone score (TBS) in French women.

UNLABELLED: Age-related changes in lumbar vertebral microarchitecture are evaluated, as assessed by trabecular bone score (TBS), in a cohort of 5,942 French women. The magnitude of TBS decline between 45 and 85 years of age is piecewise linear in the spine and averaged 14.5%. TBS decline rate increases after 65 years by 50%. INTRODUCTION: This study aimed to evaluate age-related changes in lumbar vertebral microarchitecture, as assessed by TBS, in a cohort of French women aged 45-85 years. METHODS: An all-comers cohort of French Caucasian women was selected from two clinical centers. Data obtained from these centers were cross-calibrated for TBS and bone mineral density (BMD). BMD and TBS were evaluated at L1-L4 and for all lumbar vertebrae combined using GE-Lunar Prodigy densitometer images. Weight, height, and body mass index (BMI) also were determined. To validate our all-comers cohort, the BMD normative data of our cohort and French Prodigy data were compared. RESULTS: A cohort of 5,942 French women aged 45 to 85 years was created. Dual-energy X-ray absorptiometry normative data obtained for BMD from this cohort were not significantly different from French prodigy normative data (p = 0.15). TBS values at L1-L4 were poorly correlated with BMI (r = -0.17) and weight (r = -0.14) and not correlated with height. TBS values obtained for all lumbar vertebra combined (L1, L2, L3, L4) decreased with age. The magnitude of TBS decline at L1-L4 between 45 and 85 years of age was piecewise linear in the spine and averaged 14.5%, but this rate increased after 65 years by 50%. Similar results were obtained for other region of interest in the lumbar spine. As opposed to BMD, TBS was not affected by spinal osteoarthrosis. CONCLUSION: The age-specific reference curve for TBS generated here could therefore be used to help clinicians to improve osteoporosis patient management and to monitor microarchitectural changes related to treatment or other diseases in routine clinical practice.

Load-sensitive adhesion factor expression in the elderly with skiing: relation to fiber type and muscle strength.

We hypothesized that 12 weeks of downhill skiing mitigates the functional deficits of knee extensor muscles in elderly subjects due to the specific recruitment of fast motor units during forceful turns on the slope. Downhill skiing led to a 1.4-fold increase in the mean cross-sectional area of slow (P=0.04)- and fast (P=0.08)-type muscle fibers. Fold changes in the expression of the structural component of focal adhesions, gamma-vinculin, were correlated with alterations in concentric force (r=0.64). Hypertrophy of fast fibers was more pronounced in women than in men (1.7 vs 1.1). Gender-specific structural-functional adjustments of knee extensor muscles and attached patellar tendon were reflected by altered expression of pro- vs de-adhesive proteins and a number of correlations. The de-adhesive protein tenascin-C was selectively increased in women compared with men (1.7 vs 1.1) while the content of the adhesive collagen XII was specifically reduced in women. The pro-adhesive focal adhesion kinase showed a specific increase in men compared with women (1.9 vs 1.1). Our findings indicate that quantitatively matched adaptations in slow and fast motor units of extensor muscle underlie the preventive effect of skiing against sarcopenia and support that hypertrophy and reinforcement of fiber adhesion operate in the improvement of muscle strength.

[Biceps crural myositis after an insect bite]. / Myosite du biceps crural après piqûre d'insecte.

INTRODUCTION: It can be difficult to diagnose focal muscular disease. We report a case of crural biceps focal myositis after an insect bite. DISCUSSION: We then discuss diagnostics of one or a small number of muscle injury. Focal inflammatory myositis has been described. We emphasize the role of pathology. In our case, pathological examination rules out inflammatory or tumoral disease and access likely toxical etiology. Muscle injury can appear, most frequently around the bite of venomous animal. CONCLUSION: Hymenopters are often responsible for such stings in France. Venoms are toxic for muscle cells membrane.

Apoptosis in normal and osteoarthritic human articular cartilage.

OBJECTIVES: To investigate whether apoptosis occurs in osteoarthritis (OA), and if this phenomenon is modulated by human recombinant interleukin 1beta (hrIL1beta). METHODS: Human articular cartilage samples were obtained at the time of hip arthroplasty because of femoral neck fracture (normal cartilage) (n=4) or advanced coxarthrosis (OA cartilage) (n=14). Apoptotic chondrocytes, isolated by collagenase digestion and cultivated for 24 hours, or present in situ in frozen cartilage sections, were quantified by fluorescent microscopy using two apoptosis markers: the TUNEL reaction, which detects nuclear DNA fragmentation, and Annexin-V-fluos, which labels at the membrane level the externalisation of phosphatidylserine. RESULTS: In OA cartilage 18-21% of chondrocytes showed apoptotic features, compared with 2-5% in normal cartilage. The results were similar for the two comparative studies (in situ and in vitro) and for both apoptosis markers. Moreover, hrIL1beta increased the apoptosis rate in vitro in a dose dependent manner in OA and normal chondrocytes. CONCLUSION: These results suggest that apoptosis may be an important factor in the evolution of OA and may be a new target for treatment of OA.

[Condensing myeloma. Apropos of 2 cases with bone histomorphometric study]. / Myélome condensant. A propos de deux cas avec étude histomorphométrique osseuse.

Two cases of myeloma with roentgenographic evidence of bone sclerosis confirmed by iliac histomorphometric measurements are reported. In one patient, increased resorption, major depression of osteoblast activity, initial intense myelofibrosis, and myeloid deposits were found. The other patient had both increased resorption and increased osteoblast activity with clinical manifestations suggestive of POEMS syndrome. These two cases are compared with 116 cases previously published in the occidental medical literature and with five histomorphometric studies demonstrating increased bone trabecula volume (BTV). Conventional histologic studies suggest several mechanisms as possible explanations for the occurrence of bone sclerosis, including increased modeling unit activity, isolated osteoblast activation, metamorphic neoosteogenesis in myelofibrosis foci, and, in exceptional cases, inhibition of resorption due to increased production of calcitonin. The diversity of bone modeling patterns evidenced by the seven histomorphometric studies reviewed in this article is striking. Bone modeling patterns provide only a snapshot of bone modeling units and may vary over time in a given patient. Reported cases are too few to allow conclusions but emphasize the need for performing further histomorphometric investigations.

[HLA-B and psoriatic rheumatism. Study of 193 cases]. / HLA-B et rhumatisme psoriasique. Etude de 193 cas.

Study of the HLA-B grouping of 193 patients with psoriatic arthropathy (PA), compared with that of a control series consisting of 2,706 healthy subjects representative of the French population, revealed a statistically significant link between PA and antigens B27, B17 and B16. In contrast to reported findings of earlier studies, the authors found no link between an HLA-B antigen and any particular topographical or anatomical form of PA. Antigen B27 was not statistically significantly linked with axial forms of PA nor did it protect against peripheral forms. There were neither more cases of peripheral involvement nor less of axial involvement among non-B27 PA patients. The only statistically significant link which could be shown was that between antigen B27 and sacroiliac involvement in recent PA, present for less than 10 years. The authors conclude that in 60 per cent of cases, PA is associated with a particular antigen: B16, B17 or B27. Involvement of the sacroiliac joints is more common in cases of B27 PA and above all occurs earlier than in others. Regardless of its HLA group, PA as it progresses shows an increasingly clear mixture of spinal, peripheral and sacroiliac lesions, which forms the basis of the originality of this condition.

Acute mononeuropathy with angiotropic lymphoma.

Angiotropic lymphoma can present as a vascular disease in the central nervous system. The patient described in this report had a sudden pain in the region of the right superficial peroneal nerve and a nerve biopsy showed tumoral cells in the lumen of most small blood vessels. This pathology, first described in the skin as malignant angioendotheliomatosis, can be compared with the occurrence of multiple emboli in the vasa nervorum. In recent cases, tumoral markers have evidenced a lymphomatous origin, generally of the B type.

[Serum, synovial and intra-articular pharmacokinetics of naproxen after one-gram oral administration in patients with rheumatoid polyarthritis]. / Pharmacocinétique plasmatique, synoviale et intra-articulaire du naproxène après administration orale d'un gramme chez des sujets atteints de polyarthrite rhumatoïde.

After a reminder of the major points of the pharmacokinetics of non-steroid anti-inflammatory drugs, the authors report the results of a multicentric study of the kinetics of naproxen after oral intake of one single dose of 1 gram in patients with rheumatoid arthritis. The half-life is longer in the synovial fluid than in the serum, 23 hours versus 17 hours. The balance point is obtained at the 24th hour and, at that time, the naproxen level in the synovium and the joint fluid are 32 and 60 p. cent, respectively, of the corresponding maximum concentrations.