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See detailEffects of oral contraception with ethinylestradiol and drospirenone on oxidative stress in women 18-35 years old.
De Groote, D.; PERRIER d'HAUTERIVE, Sophie ULg; Pintiaux, Axelle ULg et al

in Contraception (2009), 80(2), 187-93

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ... [more ▼]

Background Oral contraceptives (OCs) with estrogens and progestins may affect oxidative stress (OS) status. Study design A group of 32 women using oral contraceptives (OCU) containing 0.03 mg ethinylestradiol and 3 mg drospirenone have been compared to a matched control group of 30 noncontraception users (NCU). Blood levels of antioxidants, trace elements and markers of lipid peroxidation were assessed by biochemical methods. A microarray analysis of whole blood mRNA levels of 200 genes involved in OS-dependant pathway was also performed. Results Levels of zinc, vitamin E and antibodies to oxidized low-density lipoproteins (LDLs) were not significantly different between the two groups. On the other hand, significant increases in the mean levels of lipid peroxides (+176%, p<.001), oxidized LDLs (+145%, p<.002), copper (+103%, p<.001), Cu/Zn ratio (+100%, p<.001) and a significant decrease in the mean level of β-carotene (−41%, p<.01) were observed in the OCU compared to NCU. There was a highly significant positive correlation between the lipid peroxide levels and the copper-to-zinc ratio. From the 200 genes tested by microarray, one coding for HSP70 was significantly up-regulated (log2 fold change=+ 0.45, p<.02) and one coding for inducible nitric oxide synthase significantly down-regulated (log2 fold change=−0.24, p<.05) in the OCU compared to the NCU. Conclusions The recently introduced combination of ethinylestradiol and drospirenone induced the heightening of lipid peroxidation correlated with high levels of copper, a situation that could be associated with increased cardiovascular risk. [less ▲]

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See detailOral contraception and lipid peroxidation
De Groote, D.; Pincemail, Joël ULg; Defraigne, Jean-Olivier ULg et al

in Clinical Chemistry (2007, June), 53(6, Suppl. S), 30-30

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See detailCytokine Production from Peripheral Whole Blood in Atopic and Nonatopic Asthmatics: Relationship with Blood and Sputum Eosinophilia and Serum Ige Levels
Bettiol, J.; Bartsch, Pierre ULg; Louis, Renaud ULg et al

in Allergy (2000), 55(12), 1134-41

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is ... [more ▼]

BACKGROUND: The cytokine network is thought to be essential in orchestrating airway inflammation in asthma. Although evidence has accumulated to suggest that atopic asthma is a Th2 disease, much less is known about nonatopic asthma. METHODS: We have compared the production of IL-4, IL-6, IFN-gamma, and TNF-alpha from peripheral blood leukocytes between atopic (n=21) and nonatopic (n=22) asthmatics and healthy nonatopic subjects (n=20). Peripheral blood was incubated for 24 h either without stimulus or with LPS or PHA. Cytokines were measured by the immunotrapping technique (Dynamic Immunoassay). RESULTS: When compared to healthy nonatopic subjects, both atopic and nonatopic asthmatics showed increased blood and sputum eosinophilia associated with raised total serum IgE levels. Similarly, both asthma groups displayed spontaneous, endotoxin-induced overproduction of IL-6. Enhanced spontaneous, endotoxin-induced release of IL-4 combined with reduced spontaneous IFN-gamma production was seen only in atopic asthma. In this group of patients, the production of IL-4 was related to the extent of blood and sputum eosinophilia. In nonatopic asthmatics, serum levels of IgE were inversely related to the production of IFN-gamma. CONCLUSIONS: Both atopic and intrinsic asthma display raised blood and airway eosinophilia, raised total serum IgE, and overproduction of IL-6 from peripheral blood. Atopic asthma is also characterized by impaired spontaneous release of IFN-gamma and increased production of IL-4 that correlates with the magnitude of eosinophilic inflammation. [less ▲]

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See detailIncreased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
Louis, Edouard ULg; Ribbens, Clio ULg; Barreto Dos Santos, Amelia ULg et al

in Clinical & Experimental Immunology (2000), 120(2), 241-246

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were ... [more ▼]

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10. [less ▲]

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See detailIncreased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA).
Ribbens, Clio ULg; Bonnet, V.; Kaiser, Marie-Joëlle ULg et al

in Clinical & Experimental Immunology (2000), 120(1), 194-199

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control ... [more ▼]

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest. [less ▲]

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See detailIncreased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune arthropathies
Ribbens, Clio ULg; Andre, Béatrice ULg; Kaye, O. et al

in European Cytokine Network (2000), 11(4), 669-676

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different ... [more ▼]

The assessment of cytokines and their soluble receptors in the synovial fluid (SF) of inflammatory arthropathies may be useful in studying pathogenetic and immunoregulatory mechanisms underlying different diseases. The aim of this work was to study the cytokine network occurring in inflammatory arthropathies and to identify a cytokine profile which is characteristic of an immune-mediated synovitis. Levels of IL-12, as well as IL-4, IL-8, IL-10, IFN-gamma, sCD25, TNF-alpha and its soluble receptors were measured in the SF of various arthropathies, i.e. non-inflammatory arthropathies: "control" meniscus pathology (n = 21), osteoarthritis (n = 22) and chronic crystal arthritis (n = 9); a non-immune inflammatory arthropathy: acute crystal arthritis (n = 11); 2 immune inflammatory arthropathies: reactive arthritis (ReA) (n = 23) and rheumatoid arthritis (RA) (n = 44). SF levels of IL-10, TNF-alpha and sTNF-RII were found to be increased in the three inflammatory arthropathies compared to the "control" meniscus group. Within the inflammatory group, acute crystal arthritis was characterized by a significantly higher sTNF-RI/TNF-alpha ratio and ReA by a significantly lower sTNF-RII/TNF-alpha ratio compared to the two other diseases. The two immune arthropathies, RA and ReA, were characterized by increased SF levels of IL-12, sCD25 and of the sTNF-RII/sTNF-RI ratio. ReA differed however from RA by showing lower IL-8 and IL-4 levels, higher IFN-gamma levels and a higher IL-12/IL-10 ratio, suggesting a more prevalent Th1 profile in ReA SF. Our data indicate that the measurement of SF cytokines and soluble receptors may discriminate between each inflammatory arthropathy and might be useful in clinical practice. [less ▲]

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See detailSynovial fluid matrix metalloproteinase-3 levels are increased in inflammatory arthritides whether erosive or not
Ribbens, Clio ULg; Andre, Béatrice ULg; Kaye, O. et al

in Rheumatology (2000), 39(12), 1357-1365

OBJECTIVE: To study the levels of matrix metalloproteinase-3 (MMP-3) in the knee synovial fluid (SF) of inflammatory arthropathies (rheumatoid arthritis whether erosive or not, reactive arthritis, acute ... [more ▼]

OBJECTIVE: To study the levels of matrix metalloproteinase-3 (MMP-3) in the knee synovial fluid (SF) of inflammatory arthropathies (rheumatoid arthritis whether erosive or not, reactive arthritis, acute crystal arthritis) and degenerative arthropathies [chronic crystal disease, osteoarthritis and (control) meniscus pathology] and to correlate them with the degree of joint destruction, local inflammatory and immune parameters and systemic markers of inflammation. METHODS: SF levels of MMP-3 (precursor, active and tissue inhibitor of MMP-bound forms), tumour necrosis factor (TNF) alpha, soluble TNF receptors I and II, interleukin (IL)-6 and soluble IL-6 receptor were measured by ELISA in 107 inflammatory and 53 degenerative arthropathies. RESULTS: MMP-3 levels in SF were (i) significantly higher in inflammatory than in degenerative arthropathies; (ii) not related to the degree of joint destruction; (iii) significantly correlated with the levels of all SF markers tested and with erythrocyte sedimentation rate and serum levels of C-reactive protein and fibrinogen. CONCLUSION: Increased MMP-3 levels in SF are found in inflammatory arthropathies and are not specific for erosive joint diseases. MMP-3 in SF is therefore a potential candidate for the assessment of the inflammatory process in joints. However, the exclusive determination of the active form could indicate the degree of joint destruction. [less ▲]

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See detailMatrix metalloproteinase-3 serum levels are correlated with disease activity and predict clinical response in rheumatoid arthritis
Ribbens, Clio ULg; Andre, Béatrice ULg; Jaspar, J. M. et al

in Journal of Rheumatology (2000), 120(1), 888-893

OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 ... [more ▼]

OBJECTIVE: To demonstrate that serum matrix metalloproteinase-3 (MMP-3) is a variable associated with disease activity and with the response to treatment in rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured and compared to biological and clinical disease activity variables in 20 patients with active RA assessed serially during a one year prospective open label trial with methotrexate or tenidap. RESULTS: MMP-3 levels were significantly correlated with C-reactive protein (CRP) and interleukin 6 serum levels as well as with the disease activity score (DAS), not only at start in untreated patients but also during the 12 month followup period in both treated groups. Early changes (after 0.5, 1, 2, or 3 months) in MMP-3 levels were significantly associated with change in DAS observed 4 to 6 months later. CONCLUSION: In addition to CRP, a systemic marker of inflammation, serum MMP-3 may serve as a consistent synovial derived marker of RA disease activity, early changes of which predict disease outcome. [less ▲]

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See detailEffects of Dexamethasone on the Profile of Cytokine Secretion in Human Whole Blood Cell Cultures
Franchimont, Denis; Louis, Edouard ULg; Dewé, Walthère ULg et al

in Regulatory Peptides (1998), 73(1), 59-65

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit ... [more ▼]

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion. [less ▲]

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See detailTumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.
Louis, Edouard ULg; Franchimont, D.; Piron, Anne ULg et al

in Clinical & Experimental Immunology (1998), 113(3), 401-406

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some ... [more ▼]

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals. [less ▲]

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See detailA High Serum Concentration of Interleukin-6 Is Predictive of Relapse in Quiescent Crohn's Disease
Louis, Edouard ULg; Belaiche, Jacques ULg; Van Kemseke, Catherine ULg et al

in European Journal of Gastroenterology & Hepatology (1997), 9(10), 939-44

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as ... [more ▼]

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease. PATIENTS/METHODS: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters. RESULTS: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found. CONCLUSION: Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease. [less ▲]

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See detailThe effect of avocado and soybean unsaponifiables on freshly isolated human articular chondrocytes
Henrotin, Yves ULg; Labasse, A; Zheng, S et al

in Rheumatology in Europe (1997), 26(S2), 280

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See detailCytokine Production by Human Thymic Epithelial Cells: Control by the Immune Recognition of the Neurohypophysial Self-Antigen
Martens, Henri ULg; Malgrange, Brigitte ULg; Robert, F. et al

in Regulatory Peptides (1996), 67(1), 39-45

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after ... [more ▼]

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein, is integrated within the plasma membrane of TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of mAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared from human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1 beta (IL-1 beta), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-1 beta) were detected in the supernatants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the neurohypophysial family. [less ▲]

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See detailIs IL-6 capable to modify chondrocyte metabolism ?
Henrotin, Yves ULg; Labasse, A; Jaspar, JM et al

in Clinical Rheumatology (1996), 15

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See detailEffects of three avocado/soybean unsaponifiable mixtures on human chondrocytes metabolism
Henrotin, Yves ULg; Labasse, A; Zheng, SX et al

in Arthritis and Rheumatism (1996), 39

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See detailIncrease in IL-1bêta, IL-6, and TNF-alpha production in postmenopausal osteoporosis
Zheng, SX; Geenen, Vincent ULg; Vrindts, Y et al

in Osteoporosis International (1996), 6(S1), 101

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See detailCytokines and cartilage degradation
Henrotin, Yves ULg; De Groote, D; Labasse, A et al

in Mediators of Inflammation (1995), 4

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See detailDirect stimulations of cytokines (IL1-Beta, IL2, IL6, TNF-Alpha, IFN-Gamma, GM-CSF, LIF) in whole blood. Differences between normal and osteoporotic postmenopausal women.
Zheng, X; Vrindts, Y; de Groote, D et al

in Journal of Bone and Mineral Research (1994), 9(S1), 322

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