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Biomedical subjects

B G Mills

Publications and source records attributed to B G Mills.

35 records · Page 2Linked to original sources
PubMed1981

Immunohistological demonstration of respiratory syncytial virus antigens in Paget disease of bone.

Respiratory syncytial virus antisera have been found to produce a positive immunohistologic response in osteoclasts in bone sections or in cells cultured from Paget disease lesions in 12 out of 12 patients tested. These experiments were carefully controlled by several means. Use of experimentally infected cells served as positive controls. Adsorption of antisera on human bone powder and KB cells did not remove the specific immunologic stain, but adsorption of the antisera by the virus did. Negative results were also obtained in osteoclasts of patients with primary or secondary hyperparathyroidism. In addition, negative results in specimens of Paget disease were found with antisera to measles; parainfluenza 1, 2, and 3; influenza A, B and C; rubella; and herpes simplex. These results are consistent with the hypothesis that the nuclear and cytoplasmic inclusions in the osteoclasts of Paget disease are a result of viral activity.

Antigens, Viral↗
PubMed1981

Comparison of the ultrastructure of a malignant tumor of the mandible containing giant cells with Paget's disease of bone.

Distinction between lesions of the jaws containing giant cells can be difficult. This study reports the results of the study of the ultrastructure of 30 patients with Paget's disease in comparison with a patient diagnosed as having malignant giant cell tumor of the mandible. The ultrastructure of the malignant giant cell tumor of the mandible was found to contain nuclear inclusions morphologically identical with the 12-15 nm tubules characteristic of the nuclei of osteoclasts in Paget's disease of bone. No clinical or laboratory signs of Paget's disease was found in this patient. A search of the literature failed to produce reports of identical nuclear inclusions in soft tissue giant cell tumors, osteosarcomas, reparative granulomas containing giant cells or in osteitis fibrosa cystica. Such nuclear inclusions have been reported in benign giant cell tumors of bone, one another in malignant giant cell tumor and cases of polymyositis. These observations raise the question of a possible virus associated with the tumor since there are recent reports of immunological evidence for the presence of a virus in Paget's disease, and viruses have been suspected in polymyositis.

Adult↗
PubMed1980

Cell cultures from bone affected by Paget's disease.

Cells obtained from Paget's bone specimens were maintained in culture for up to 8 1/2 months. The cells had several characteristics of bone cells including the presence of alkaline phosphatase, acid phosphatase, or succinic dehydrogenase as demonstrated histochemically. Electron microscopy revealed nuclear inclusions similar to those found in the osterclasts of Paget's disease in 4 or 11 cultures. Immunohistology utilizing specific antisera demonstrated the presence of respiratory syncytial virus antigen(s) in 7 or 7 patients. Negative results were obtained with antisera to a variety of paramyxoviruses.

Aged↗
PubMed1979

Long-term culture of cells from bone affected by Paget's disease.

Cells obtained from surgical bone specimens of eight patients with Paget's disease of bone were maintained in culture for up to 8 months and seven passages. The doubling time during the period of maximal cell growth ranged from 4 to 12 days. Evidence consistent with the hypothesis that many of the cells were bone cells included the following: (a) histochemical techniques demonstrated staining of some cells for alkaline phosphatase or acid phosphatase and succinic dehydrogenase; (b) parathyroid extract stimulated increased uptake of 3H-thymidine and 3H-uridine; (c) parathyroid extract suppressed and salmon calcitonin stimulated uptake of 3H-proline; and (d) crystalline calcium deposits were found within cells and extracellularly. Ultrastructural analysis revealed that three of the eight cultures contained cells whose nuclei had inclusions which were almost identical to those found in the osteoclast nuclei of all patients with Paget's disease. The maintenance of cells derived from pagetic bone in long-term culture should aid in testing the hypothesis that Paget's disease represents a slow virus infection of bone.

Aged↗
PubMed1977

The etiology of Paget's disease of bone.

The etiology of Paget's disease is not known but recent studies of the ultrastructure of bone cells in pagetic lesions have raised the possibility of a viral etiology. In 41 of 41 patients evaluated in France and Los Angeles characteristic nuclear inclusions were found in osteoclasts only. These structures were similar to nuclear inclusions found in the slow virus infection of the brain, subacute sclerosing panencephalitis. Definitive identification of a virus or viral antigens in pagetic lesions awaits future studies. Other possible etiologies of Paget's disease include an inborn error of connective tissue biosynthesis, a disorder of hormone secretion, a vascular disorder, an autoimmune state, and a neoplastic transformation of bone cells.

Bone Neoplasms↗
PubMed1976

Nuclear inclusions in Paget's disease of bone.

The ultrastructure of bone cells was examined in biopsies from 18 patients with Paget's disease of bone and from 60 patients with a variety of other bone diseases. A characteristic nuclear inclusion was found in the osteoclasts of each patient with Paget's disease. The nuclear inclusion most closely resembles viral nucleocapsids of the measles type.

Biopsy↗
PubMed1976

Florid osseous dysplasia. A clinical-pathologic study of thirty-four cases.

Thirty-four patients with florid osseous dysplasia were studied. The majority were asymptomatic Negro women: Seventeen biopsy-proven simple bone cysts were found in affected quadrants of fourteen patients. Radiographs displayed a spectrum of sclerotic and ground-glass opacities limited to alveolar processes but not to root apices. Biopsy material was studied in all cases, and biochemical analyses of serum and cyst fluid were performed on some patients. Test results and skeletal radiographs indicate that the disease is limited to the jaws. Patients have remained asymptomatic with little alteration of radiographic patterns. Three cysts failed to heal following treatment, others filled with radiographically abnormal tissue. Chronic osteomyelitis may infrequently complicate the disease. These cases appear to represent the most exuberant manifestation of this reactive fibro-osseous jaw disease.

Adult↗
PubMed1976

Acute effects of calcitonin on osteoclasts in man.

To determine the mechanism by which calcitonin acutely decreases bone resorption in man, salmon or human calcitonin was administered intravenously to five patients with Paget's disease of bone immediately after an iliac crest bone biopsy. After 30 min an adjacent bone biopsy was taken and both were evaluated by light and electron microscopy. The results indicated that calcitonin both decreases the number of osteoclasts and alters the ultrastructure of these cells. Thes acute effects of calcitonin on osteoclasts confirm findings in other species and provide evidence in man that calcitonin, at least in part, retards bone resorption by inhibiting osteoclastic activity.

Animals↗
PubMed1975

Tissue phosphatase changes following triamcinolone associated with cleft palate in rats.

One theory of the development of cleft palate in rats involves the action of lysosomal enzymes secreted by epithelial cells at the time of fusion of the palatal shelves. To test this theory we studied the biochemistry of the palates of fetal rats daily between days 14 and 19 (from 3 days before to 3 days after palate closure). Triamcinolone was administered once im on gestation day 14 to Wistar rats; 0.5 mg/kg body weight produced approximately 50% cleft palates. Pooled control palatal tissue was compared with pooled experimental tissue; that from fetuses with clefts being pooled separately from those not affected. Acid phosphatase and beta-glucuronidase were assayed. Concentration vs. time curves for both enzymes were very similar. Prior to the time of palate closure both enzymes were present in low concentration. Between days 16 and 17, the normal time of closure, there was an abrupt increased in enzyme concentration, with experimental tissue showing a significant elevation over control tissue on days 17 and 18. Alkaline phosphatase was also present in small amounts before closure and significantly higher in control tissue on day 17. Protein was depressed in palates having clefts on day 17; thus the ratio of enzyme activities to protein synthesis was significantly elevated at a critical time. Unaffected experimental palates had a normal ratio. These results suggest imbalanced acid phosphatase, beta-glucuronidase, and alkaline phosphatase activity compared with protein synthesis at the time of palate closure following triamcinolone in rats.

Acid Phosphatase↗
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↗