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Biomedical subjects

M A Denne

Publications and source records attributed to M A Denne.

15 recordsLinked to original sources
PubMed1995

Bone resorption at the femoral neck is dependent on local factors in nonosteoporotic late postmenopausal women: an in vitro-in vivo study.

Local mediators of bone resorption may be involved in bone loss in recently postmenopausal women and in osteoporosis. In the present study, we investigated the production of cytokines and the formation of osteoclast-like cells in marrow cultures from 16 late postmenopausal nonosteoporotic women (mean age: 66 +/- 8 years; time after menopause: 15 +/- 8 years) undergoing hip replacement for arthrosis. Marrow adherent mononuclear cells (MMNC) isolated from femoral diaphysis marrow were cultured for 10 days in the absence or in the presence of 1,25(OH)2D3. In vivo bone resorption was concomitantly assessed by histomorphometry on femoral neck bone sections. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultured in the presence of 1,25(OH)2D3 correlated with the number of osteoclasts measured on the bone femoral neck biopsies (r = 0.65, p < 0.01), suggesting that the formation of multinucleated cells in vitro could reflect the osteoclast differentiation in vivo. Furthermore, the number of osteoclasts was related to the eroded volume and the trabecular separation of the femoral neck bone biopsies. Finally, the release of interleukin-1 (IL-1), IL-6, and TNF-alpha by cultures of peripheral blood mononuclear cells (PBMC) and MMNC was measured by radioimmunoassay. The cytokine levels of basal and 1,25(OH)2D3-treated MMNC decreased from days 2 to 5 and then reached a plateau to day 10. The number of TRAP+ multinucleated cells obtained after 10 days in MMNC cultures correlated with the basal IL-6 release in the same cultures determined at day 2 (r = 0.55, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome.

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disorder characterized by increased serum immunoglobulin E levels. Bone fragility is part of this syndrome, which has recently been reported to be also associated with an imbalance in cytokine-secreting lymphocyte subpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investigated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible involvement of cytokines in causing the bone fragility associated with this disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal radius was two standard deviations below that of the aged-matched controls. Urinary pyridinoline excretion, a marker of bone resorption, was markedly increased in the two youngest patients. Adherent mononuclear cells derived from these patients were cultured in vitro and the bone resorbing activity (BRA) of the culture supernatant was measured by means of a fetal rat long bone assay. The BRA was up to 28% above the basal value. We compared the BRA and the cytokine production by the mononuclear cells of these patients to that of postmenopausal women. The BRA, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of interferon-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is similar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading to bone loss in HIES, which could be related to IgE-dependent mechanisms.

Adolescent↗
PubMed1995

1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone related protein secretion.

Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.

Animals↗
PubMed1993

Peripheral monocyte culture supernatants of menopausal women can induce bone resorption: involvement of cytokines.

Increased bone resorption is a mechanism contributing to bone loss in the postmenopausal period. Cytokines are involved in osteoclastic differentiation and, therefore, may play a role in the regulation of bone resorption. Several previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This study determines the concomitant production of the three cytokines and tests the bone-resorbing activity of peripheral monocyte supernatants. Four groups of women were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr). Assignment to clinical groups was verified by plasma FSH and estradiol determinations. Lumbar spine bone mineral density was significantly higher in the premenopausal women group than in the three postmenopausal groups. Peripheral blood monocytes were cultured for 48 h with 20% autologous plasma, and after stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were measured by RIA in the monocyte surpernatants. The three cytokines were highly correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The mean levels of the three cytokines could not be compared because of the variations in the values. However, a trend toward lower levels in the three cytokines was noted in estrogen-treated women compared to the untreated postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed by fetal long bone-resorbing assay, increased in untreated postmenopausal compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P < 0.05). In estrogen-treated patients, this activity decreased to premenopausal levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor antagonist and TNF alpha antibodies to the supernatant bone culture medium induced a significant decrease in the calcium release. Those data show the involvement of several cytokines in the bone resorption process after estrogen deficiency.

Bone Resorption↗
PubMed1991

Cyclosporin-A in vitro decreases bone resorption, osteoclast formation, and the fusion of cells of the monocyte-macrophage lineage.

We studied the in vitro effect of cyclosporin-A (CyA) on bone resorption using a fetal rat long bone-resorbing assay. CyA inhibited both PTH-stimulated and unstimulated bone resorption. The inhibitory effect of CyA on basal resorption was dose dependent, and it was more pronounced during the second period (less than or equal to 0.1 microgram/ml) of culture (days 5-7) than during the first period (days 2-4). A cytotoxic effect was ruled out by the absence of decrease in [3H]thymidine incorporation into bones up to a concentration of 5 micrograms/ml CyA. Histomorphometry performed after 4 and 7 days of culture showed that CyA (1 microgram/ml) decreased the number of osteoclasts per bone section after 7 days of culture (23.5 +/- 4.0 vs. 41.7 +/- 2.9 osteoclasts/bone section; P less than 0.05), but not after 4 days (25.6 +/- 3.3 vs. 23.0 +/- 2.5). These data suggested an effect of CyA on osteoclastic differentiation rather than on the function of mature osteoclasts. We further assessed the mechanisms of the inhibitory effect of CyA on osteoclastic differentiation in order to determine 1) the level of this action (proliferation and/or fusion of osteoclast precursors), and 2) if this action is direct or indirect. Autoradiographic studies were performed on bone sections after incubation of bones with [3H]thymidine for the last 48 h of culture. CyA decreased slightly but significantly the percentage of labeled nuclei per osteoclast and the number of osteoclasts containing at least one labeled nucleus (20.2 +/- 0.7 vs. 33.2 +/- 3.5; P less than 0.02). Moreover the number of nuclei per osteoclast was decreased after 7 days in CyA-treated bones (2.4 +/- 0.05 vs. 3.0 +/- 0.1; P less than 0.02). Taken together these results demonstrate that CyA slightly decreased the proliferation of osteoclast precursors, but markedly decreased their fusion. Similar effects were observed in cultures of rat marrow macrophages. CyA (1 microgram/ml) inhibited the fusion of macrophages into multinucleated cells elicited by 1 nM 1,25-dihydroxyvitamin D3, but had only a slight effect on the proliferation of these cells, as assessed by autoradiography. CyA also inhibited the formation of multinucleated cells and the fusion index in long term cultures of human cord blood monocytes, a cellular model for osteoclastic differentiation. By contrast, CyA had no effect on the formation of myotubes by fusion of cultured mononucleated rat myoblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Osteocalcin and bone morphometric parameters in adults without bone disease.

Serum bone Gla-protein (s-BGP or osteocalcin) and other serum biochemical parameters were measured in 19 subjects (8 women and 11 men, aged 20-82 years) without any bone disease. Each subject simultaneously underwent an iliac crest biopsy; tetracycline double-labeling was performed in 11 subjects, allowing correlations between s-BGP and bone histomorphometric parameters. s-BGP was significantly correlated with static bone parameters: trabecular bone volume (r = 0.74; P less than 0.001), osteoid surfaces (r = 0.69; P less than 0.001), osteoblastic surfaces (r = 0.68; P less than 0.002); dynamic bone formation parameters: total labeled surfaces (r = 0.72; P less than 0.01); and the bone formation rate (r = 0.69; P less than 0.01). We conclude that s-BGP is a valuable marker for evaluating bone formation in healthy adult subjects.

Adult↗
PubMed1986

Relationship between bone GLA-protein (BGP) and calcidiol (25-hydroxycalciferol) in serum of breast-fed infants.

The aim of this investigation was to study the bone metabolism in early infancy by establishing the relationship between serum osteocalcin levels and the hormonal vitamin D status of exclusively breast-fed infants during their first month of life. Calcium, phosphorus, alkaline phosphatase, 25-hydroxycalciferol (calcidiol), 1,25-dihydroxycalciferol (calcitriol) and osteocalcin (BGP or GLA-protein) were measured in 22 healthy lactating women and their paired breast-fed infants before and after supplementation (400 IU vitamin D per day). Prior to supplementation calcidiol, calcitriol and osteocalcin remained unchanged. Following supplementation there was an increase in all the parameters with the exception of calcitriol. The administration of vitamin D to breast-fed infants should in fact have an effect on bone activity as reflected by the increase in osteocalcin levels.

25-Hydroxyvitamin D 2↗
PubMed1982

[Serum ceruloplasmin levels and cetrimonium tests in pregnancy].

Serum ceruloplamin levels were measured and Badin's cetrimonium tests (selective precipitation of serum glycoproteins with cetrimonium bromide) were performed after delivery in 72 out of 350 sera previously collected during the 4th-5th months of pregnancy. Thirty-six of the 72 sera were obtained from women whose pregnancy ended with toxaemia, and 36 from women chosen at random whose pregnancy ended normally. In women who developed toxaemia at 8-9 months, ceruloplasmin levels and cetrimonium test values were often higher at 4-5 months than in correlation between assays and tests. Ceruloplasmin determinations and cetrimonium tests therefore provide different types of information on the latent pathological condition which precedes toxaemia, but their predictive values must be taken jointly.

Ceruloplasmin↗
PubMed1981

[beta-Lipoprotein serum levels in the months preceeding pregnancy toxemia and its relationship with the Cetrimonium test (author's transl)].

beta-Lipoprotein determination and selective serum protein precipitation with Cetrimonium bromide (Badin's Cetrimonium test) were carried out retroactively (after delivery) on sera selected out of 700 sera collected from women at 4-5 months and 6-7 months of pregnancy. The selected sera were those from 36 women in the first group and 37 in the second group, who had ended pregnancy with toxemia. The sera were matched to sera collected at the same period from women whose pregnancy had been normal until the end. In both the 4-5 month and the 6-7 month groups, women with toxemia at the end of pregnancy had significantly higher levels of beta-lipoprotein and higher Cetrimonium tests but the two data were not correlated. The information they provide on the abnormal condition preceeding toxemia symptoms are different : hyperlipoproteinemia would be a predisposing factor and the Cetrimonium test an evidence of some latent inflammatory process.

Cetrimonium↗
PubMed1976

Clinical and immunochemical study of the serum IgG fraction not precipitated in a zinc-sodium salicylate reagent.

A reagent made of zinc sulphate (0-08 M) in a 0-4 M sodium salicylate solution at pH 7-3 precipitated most of the IgG when a small volume of human serum was added. Sera with normal IgG levels or polyclonal hyperglobulinaemia showed a close correlation between total IgG and zinc-precipitated IgG (r = + 0-95). In clinical material, not including IgG myeloma, zinc-soluble IgG varied between 0 and 6 mg/ml and was independent of the IgG serum concentration. In 31 normal subjects the average IgG concentration, as determined by the Technicon immunonephelometric method, was 10-2 +/- 1-7 mg/ml for total IgG and 2-2 +/- 1-0 mg/ml for the soluble fraction. Among 173 sera, including 24 from cord blood, 16 from pregnant women, and 133 from patients with miscellaneous diseases, no pathological conditions except three cases of IgG myeloma were found with a zinc-soluble IgG definitely above the normal values; zinc-soluble IgG levels were often low in patients with hyperglobulinaemia, and the difference was highly significant in liver disease. kappa and gamma light chains as well as the four IgG-Hp chain subclasses were found in both zinc-soluble fractions of normal IgG. A study of myeloma monoclonal IgG showed that globulins of classes 1, 3, and 4 could be either soluble or insoluble in the zinc reagent. One, G2, was mainly insoluble. Hexose and antistreptolysin contents per milligram normal IgG were not significantly different in either fraction. It is suggested that zinc-soluble IgG consists of the recently synthesized molecules, the zinc-solubility of which has not yet been decreased by protein association, lipid interaction, antigen binding, or enzymatic denaturation. Within this hypothesis, a low level of soluble IgG would mean either an increased precatabolic protein or a decreased synthesis.

Chemical Precipitation↗