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M Cohen-Solal

Publications and source records attributed to M Cohen-Solal.

86 records · Page 5Linked to original sources
PubMedDate not supplied

Biologic, histologic and densitometric effects of oral risedronate on bone in patients with multiple myeloma.

Recent studies have shown that treatment with bisphosphonates could be effective against the myelomatous skeletal deterioration. However, the mechanisms of action of these drugs in multiple myeloma (MM) have been poorly studied. In the present study, 11 patients with MM and bone lesions were treated orally with 30 mg/day of risedronate for 6 months, and monitored for 6 additional months. Mean serum calcium decreased from day 4, with a concomitant increase in circulating levels of PTH (1-84) and 1,25-(OH)2D. These parameters reached their nadir on day 7 and returned to baseline value during the treatment period. Markers of bone resorption, pyridinoline and deoxypyridinoline decreased from day 7; they were at 50% and 78% of their basal value at the end of treatment and follow-up periods, respectively. A significant reduction of estimates of bone formation (serum alkaline phosphatase and osteoclacin) appeared at month 3 and persisted for the remainder of the 9-month period. Histomorphometric analysis showed a significant reduction of activation frequency, number of osteoclasts and erosion depth. Bone turnover was high at baseline, and normal after treatment, without mineralisation defects. Mean wall thickness was not different before and after treatment. Spinal bone mineral density measured by dual energy X-ray absorptiometry increased (5.3%) at the end of treatment. We conclude that oral risedronate in multiple myeloma induces a noticeable and rapid inhibition of bone resorption.

Absorptiometry, Photon↗
PubMedDate not supplied

Osteoprotegerin and inflammation.

RANK, RANKL, and OPG have well established regulatory effects on bone metabolism. RANK is expressed at very high levels on osteoclastic precursors and on mature osteoclasts, and is required for differentiation and activation of the osteoclast. The ligand, RANKL binds to its receptor RANK to induce bone resorption. RANKL is a transmembrane protein expressed in various cells type and particularly on osteoblast and activated T cells. RANKL can be cleaved and the soluble form is active. Osteoprotegerin decoy receptor (OPG), a member of the TNF receptor family expressed by osteoblasts, strongly inhibits bone resorption by binding with high affinity to its ligand RANKL, thereby preventing RANKL from engaging its receptor RANK. This system is regulated by the calciotropic hormones. Conversely, the effects of RANKL, RANK, and OPG on inflammatory processes, most notably on the bone resorption associated with inflammation, remain to be defined. The RANK system seems to play a major role in modulating the immune system. Activated T cells express RANKL messenger RNA, and knock-out mice for RANKL acquire severe immunological abnormalities and osteopetrosis. RANKL secretion by activated T cells can induce osteoclastogenesis. These mechanisms are enhanced by cytokines such as TNF-alpha, IL-1, and IL-17, which promote both inflammation and bone resorption. Conversely, this system is blocked by OPG, IL-4, and IL-10, which inhibit both inflammation and osteoclastogenesis. These data may explain part of the abnormal phenomena in diseases such as rheumatoid arthritis characterized by both inflammation and destruction. Activated T cells within the rheumatoid synovium express RANKL. Synovial cells are capable of differentiating to osteoclast-like cells under some conditions, including culturing with M-CSF and RANKL. This suggests that the bone erosion seen in rheumatoid arthritis may result from RANKL/RANK system activation by activated T cells. This opens up the possibility that OPG may have therapeutic effects mediated by blockade of the RANKL/RANK system.

Animals↗
PubMedDate not supplied

[Hemoglobin J. Broussais alpha-2 90 Lys leads to Asn beta-2A (FG2) discovered in a Martinique family. Comparison of several analytical technics].

We report a new case of hemoglobin J. Broussais, present in its heterozygote form in a seven year old child from Martinque. The structural characteristics of this abnormal hemoglobin have been compared by three methods: 1. By analytical and preparative finger-printing on silica gel thin layer plates after tryptic digestion. 2. By a programmed separation of tryptic peptides on various ion exchange resins. 3. And by automatic sequencing of the peptides obtained following CNBr cleavage and separation by gel filtration chromatography. The functional behaviour of this hemoglobin was not modified by the substitution of an Asn for a Lys residue at position 90, although its presence induced slight hematological disorders in the patient. Abnormal hemoglobins which have been identified in Martinique and Guadeloupe are reviewed.

Amino Acid Sequence↗
PubMedDate not supplied

Secretion of parathyroid hormone-related peptide in patients with multiple myeloma.

Stimulation of bone resorption by local factors, the cytokines, is key to the development of hypercalcemia in multiple myeloma patients. Parathyroid hormone-related peptide, the systemic factor found in humoral hypercalcemia, has rarely been incriminated in myeloma. We report a case of myeloma with hypercalcemia and elevated serum level of parathyroid hormone-related peptide. Bisphosphonate therapy was rapidly effective in correcting serum calcium levels despite persistent high levels of the peptide. Seven other cases of myeloma with hypercalcemia and high serum parathyroid hormone-related peptide levels have been reported. Expression by myeloma plasmocytes of the messenger RNA for this peptide has also been demonstrated. These data suggest that parathyroid hormone-related peptide may contribute to the development of hypercalcemia in some myeloma patients.

Antineoplastic Agents↗