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F R Singer

Publications and source records attributed to F R Singer.

161 records · Page 9Linked to original sources
PubMed1972

An evaluation of antibodies and clinical resistance to salmon calcitonin.

21 patients with Paget's disease of bone and one with osteoporosis were studied to detect development of antibodies to salmon calcitonin during chronic therapy. Antibody titers ranged from 1:40 to 1:30,000 in plasma obtained after treatment of 11 patients. Radio-immunoelectrophoresis revealed that the antibodies were restricted to the gammaG class. One patient, W. O., with Paget's disease initially responded to treatment with a decrease in bone turnover, but later became resistant to the hormone in association with the appearance of a very high titer (1:30,000) of antibody against salmon calcitonin. A 1:10 dilution of his plasma was shown to completely inactivate 20 mMRC units/ml of salmon calcitonin as detected by bioassay in rats; slight inactivation was detected at a 1:200 dilution. All other patients continued to respond to salmon calcitonin despite the development of antibody to the hormone in ten cases. No evidence of systemic allergic reactions or other toxicity was found in any patient. The data suggest that although antibody formation may occur in as many as 50% of patients treated with salmon calcitonin, this antibody response is unlikely to be of clinical significance in most patients. However, in an occasional patient, a marked antibody response may occur which interferes with the therapeutic use of the hormone.

Adult↗
PubMedDate not supplied

Multinucleated cells formed in vitro from Paget's bone marrow express viral antigens.

Paget's disease of bone is characterized by large numbers of osteoclasts that have viral-like nuclear and/or cytoplasmic inclusions. Pagetic osteoclasts express respiratory syncytial viral (RSV) and measles viral (MV) nucleocapsid antigens. The data suggest a possible viral etiology for Paget's disease. However, studies to characterize further the putative viral inclusions in Paget's osteoclasts have been severely hampered by the extreme difficulty in isolating large numbers of osteoclasts from pagetic bone. The recent demonstration that osteoclast-like multinucleated cells (MNC), that had certain characteristics of pagetic osteoclasts formed in marrow cultures from Paget's patients, may permit studies to describe this virus further. Therefore, we have cultured marrow samples from involved and uninvolved bones from Paget's patients and from normal subjects to determine if the MNC formed in these cultures express viral antigens. RSV and/or MV antigens were expressed in the mononuclear cells and/or the MNC formed in 12 of 12 marrow cultures from active lesions of patients with Paget's disease, with 40-50% of the cells expressing viral antigens. In contrast, less than 5% of cells isolated from cultures from normal subjects expressed RSV and/or MV. These results suggest that MNC formed in long-term marrow cultures from patients with Paget's disease frequently express paramyxoviral antigens and are very similar to pagetic osteoclasts. Thus, these marrow cultures may be useful for further characterizing the virus in Paget's disease.

Aged↗
PubMedDate not supplied

In vivo morphologic changes in the rat osteoclast induced by gallium nitrate: the result of toxicity or other effects?

Gallium nitrate, an approved antitumor drug, has found clinical application in the treatment of cancer-related hypercalcemia and of Paget's disease; the exact mechanism of its action, however, remains unknown. The present study utilized rats in a 7-day exposure to gallium at doses similar to those used clinically. Quantitative histomorphometry and ultrastructural examination of osteoclast fine structure were carried out on specimens from animals with documented hypocalcemia. Gallium exposure produced striking changes in the osteoclast. The number of nuclei/osteoclast increased, and the ruffled borders of the osteoclasts were markedly decreased along the length of the Howship's lacunar cavity. The absence of a decrease in osteoclast number and the types of changes seen in ultrastructure suggest that the mechanism of action of gallium seen here may differ from that of calcitonin, a nontoxic, reversible antiresorbing agent. Results underscore the difficulty in assessing the toxicity of agents such as gallium on the osteoclast, a mature differentiated cell which does not divide and which does not produce a characteristic extracellular matrix component.

Animals↗
PubMedDate not supplied

Paget's disease. Reversal of severe paraparesis using calcitonin.

Relatively short-term treatment of paraparesis due to Paget's disease with subcutaneous salmon calcitonin alone produced dramatic relief of sensory loss, pain, and paraparesis. The successful outcomes in 2 patients, one with spinal cord and one with cauda equina compression, indicate a potential alternative to surgery in reversing mild-to-severe neural dysfunction in Pagets disease. The proposed mechanisms of action of calcitonin include reduction of a direct bony impingement on the neural tissue and/or a decrease of neural ischemia. It is suggested that even if paraparesis does not improve with calcitonin alone, the medication given preoperatively would probably serve a useful adjunctive role by decreasing intraoperative bone bleeding. However, those patients whose pagetic bone is already metabolically inactive would probably not benefit from calcitonin therapy.

Calcitonin↗