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S C Marks

Publications and source records attributed to S C Marks.

At least 181 records · Page 10Linked to original sources
PubMed1987

Tartrate-resistant acid phosphatase in mononuclear and multinuclear cells during the bone resorption of tooth eruption.

Tartrate-resistant acid phosphatase (TRAP) has been used as a cytochemical marker for the cell mediators of bone resorption, osteoclasts and their mononuclear precursors. We have applied a cytochemical method for TRAP to study the dependence of the osteoclast-mediated bone resorption of tooth eruption on the dental follicle, a connective tissue investment of the developing tooth, by analyzing the TRAP activity of mononuclear cells in the dental follicle before and during pre-molar eruption in dogs. The percentage of TRAP-positive monocyte cells increases until mid-eruption, slightly preceding a previously demonstrated rise in numbers of osteoclasts on adjacent bone surfaces. These data suggest an ontogenetic relationship between follicular mononuclear cells and osteoclasts on adjacent alveolar bone surfaces during tooth eruption. However, because TRAP occurs in other tissues and is not an exclusive indicator of pre-osteoclasts, proof of their relationship will have to await application of more definitive techniques.

Acid Phosphatase↗
PubMed1987

Osteopetrosis--multiple pathways for the interception of osteoclast function.

Osteopetrosis is a metabolic bone disease inherited in a number of species including human beings and characterized by a generalized increase in skeletal density detected radiographically. This condition results primarily from reduced osteoclast function which produces partial or complete absence of marrow spaces, a variable compensatory hepatosplenomegaly, interferences with tooth eruption and certain neurological complications. Experimental investigations of some mutations have shown that restoration of bone resorption and recovery from the disease follow bone marrow transplantation. These data indicate that in these mutations, including some children, the defect is intrinsic to osteoclasts or their stem cells. In other mutations in animals and children, bone marrow transplants do not restore bone resorption and the defect is believed to be one of local environmental products or signals whose importance in cell differentiation and regulation is becoming increasingly appreciated. These data, reviewed with respect to the emerging cell biology of the osteoclast, indicate that osteopetrotic mutations have much to teach us about the regulation of bone metabolism.

Animals↗
PubMed1987

Elevated serum 1,25-dihydroxyvitamin D in osteopetrotic mutations in three species.

Osteopetrosis is an inherited bone disease in which bone mass accumulates due to a reduction in bone resorption. We have examined serum levels of vitamin D metabolites in seven mutations from three species and found that serum 1,25-dihydroxyvitamin D is markedly elevated in each. In some mutations, these findings cannot be solely explained by the known stimulators of this hormone; namely hypophosphatemia and hyperparathyroidism, and suggest a compensatory adjustment to an end-organ resistance to this hormone. These data, taken together with known alterations in osteoclast structure and function in congenital osteopetrosis and the effects of this hormone on monocyte differentiation and bone resorption, indicate that resistance to 1,25-dihydroxyvitamin D could be a unifying concept to explain the osteoclast heterogeneities in osteopetrosis. Furthermore, this may be an ideal system in which to examine the effects of this hormone on the proliferation, differentiation and function of bone cells.

Animals↗
PubMed1987

Osteopetrosis in the toothless rat: failure of osteoclast differentiation and function.

Toothless is an osteopetrotic mutation in the rat characterized by reduced bone resorption, few osteoclasts and failure to be cured by bone marrow transplants from normal littermates. The latter could be due to the production of bone that cannot recruit or activate normal osteoclasts or their precursors. We tested this hypothesis using a metatarsal organ culture system in which metatarsals are cultured with various tissues which act as sources of osteoclast precursors. Mutant metatarsals cultured alone or with mutant tissue had numerous large mononuclear cells, few osteoclasts, no marrow spaces and no evidence of bone resorption. Culture of mutant metatarsals with normal liver or spleen caused no changes in osteoclast number or bone resorption. Cultures of normal metatarsals had large osteoclasts, bone resorption and marrow spaces. Histochemical analyses demonstrated that strong tartrate-resistant acid phosphatase (TRAP) staining was present in all osteoclasts and in some mononuclear cells in normal metatarsals. Mutant metatarsals before or after culture contained no TRAP-positive osteoclasts and an occasional, weakly staining mononuclear cell only when co-cultured with normal spleen which contained TRAP-positive mononuclear cells. We interpret these data to mean that the mutant skeletal environment is unable to support the development and differentiation of normal osteoclasts. These observations are consistent with the failure of toothless rats to be cured by bone marrow transplants from normal littermates.

Animals↗
PubMed1987

Tooth eruption: the regulation of a localized, bilaterally symmetrical metabolic event in alveolar bone.

Tooth eruption is a complicated process by which developing teeth are moved within the jaws to their functional position. The usual model chosen to study this process, the erupted rodent incisor, differs both structurally and functionally from the human dentition and conclusions drawn from these studies are not directly applicable to tooth eruption in human beings. We have studied the eruption of developing permanent premolars in dogs and present evidence by scanning electron microscopy for regional differences in metabolic activities on bone surfaces of the crypt during eruption. We review evidence that these polarization of alveolar bone metabolism are cell-mediated, dependent upon the dental follicle, independent of root formation or the tooth itself and that tooth eruption depends on coordination of these activities by the dental follicle. We conclude that tooth eruption is a localized, bilaterally symmetrical event in alveolar bone and that this is an excellent model system in which to study the regulation of alveolar bone metabolism.

Animals↗
PubMed1986

Ultrastructure of alveolar bone during tooth eruption in the dog.

Previous work from our laboratories has established that eruption of the permanent mandibular premolars in dogs is dependent upon the presence of the dental follicle and that it involves resorption of alveolar bone and the roots of the deciduous predecessor above and formation of alveolar bone below the developing crown. This study illustrates the topography of the bone surfaces of the crypt by scanning electron microscopy and the ultrastructure of the cells on alveolar bone surfaces during tooth eruption. Above the developing crown where the eruption pathway forms, the bone surface is a pitted sheet, the characteristic topographic feature of bone resorption; between the crown and the mandibular canal, the bone surface has numerous interconnecting trabeculae. Transmission electron microscopy of bone cells lining the eruption pathway area of the crypt showed numerous osteoclasts with adjacent mononuclear cells. Both cell types contained specific, membrane-bound cytoplasmic vesicles shown by the work of others to be characteristic features of osteoclasts and their precursors. Basal trabeculated bone in the crypt was covered by plump osteoblasts. These data show that the metabolic events in alveolar bone associated with tooth eruption have the appropriate cellular and bony surface correlates and that the suspected control of alveolar bone resorption by the dental follicle may be mediated by its recruiting and directing to adjacent bone surfaces the mononuclear precursors of osteoclasts.

Alveolar Process↗
PubMed1986

Ultrastructure of the giant cell infiltrate of subcutaneously implanted bone particles in rats and mice.

The giant cells of soft tissues and those of mineralized tissues (osteoclasts) have distinctly different cell surface receptors and ultrastructural characteristics. Recently, the removal of dead bone particles in a subcutaneous environment has been described as a prototype of bone resorption, and a major issue is whether the giant cells that surround these ectopic bone implants and the processes involved in the disruption of bone surfaces are the same as those in the skeleton. We have compared the cytology and ultrastructure of giant cells recruited to subcutaneously implanted isogeneic bone particles with similar features of osteoclasts in metaphyseal bone of young normal rats and mice. Giant cells on surfaces of bone particles 2, 3, and 4 weeks after implantation were multinucleated, had a homogeneous, nonvacuolated cytoplasm, and had a bone surface interface unremarkable by light microscopy. In a few cells randomly distributed, small cytoplasmic vacuoles were present and large vacuoles were noted next to the bone surface at high magnification. By transmission electron microscopy, folded membrane configurations forming extensive interdigitations with adjacent cells were prominent features on most surfaces of giant cells. In instances where these interdigitations abutted bone surfaces, configuration resembling a ruffled border were noted, but these regions were always part of two different cells when examined at lower magnification or in serial sections. Breakdown of bone particles appeared to be by phagocytosis of small pieces and subsequent intracellular digestion in electron-dense cytoplasmic vacuoles. Osteoclasts from these same young animals were smaller with fewer nuclei, had cytoplasmic vacuoles concentrated next to bone surfaces, and had characteristic ruffled borders and clear zones. These results confirm those of others that native osteoclasts and multinucleated giant cells on dead bone particles are distinctly different with respect to both ultrastructure and mechanism of disruption of bone surfaces.

Animals↗
PubMed1986

Calcitonin receptor binding as a marker of osteoclast heterogeneity in osteopetrotic rodents.

We have employed a radioautographic technique to examine in vivo receptor binding of calcitonin to osteoclasts in four rodent mutants with osteopetrosis. 125I-Labeled calcitonin was injected intravenously alone or with excess unlabeled calcitonin to osteopetrotic (op/op), osteosclerotic (oc/oc), and microphthalmic (mi/mi) mice and to incisor absent (ia/ia) rats. Similar experiments were performed simultaneously in phenotypically normal littermates. Specific binding of calcitonin to receptors on osteoclasts and osteoclast morphology were then examined by light and electron microscope radioautography. Calcitonin binding was increased in mi/mi mice, where osteoclasts were abundant but reduced in size, and was also increased in op/op mice in association with an undulated and redundant osteoclast cell membrane. Binding of the hormone was markedly diminished on osteoclasts of oc/oc mice and ia/ia rats. Thus, in these rodent models of osteopetrosis all of which manifest reduced skeletal remodeling and share a recessive pattern of inheritance, considerable heterogeneity of osteoclast characteristics was demonstrable. Although calcitonin may play no primary pathogenetic role in most forms of this disease, calcitonin receptor binding is a morphological and functional marker of osteoclasts that can be used in assessing the pathophysiology of disorders of bone remodeling.

Animals↗
PubMed1986

The anatomical basis for retrorenal extensions of pancreatic effusions: the role of the renal fasciae.

Retrorenal extension of pancreatic inflammatory processes are considered to involve invasion of the posterior pararenal space. Analysis of computed tomographic (CT) images demonstrates preservation of posterior pararenal fat in most patients, implicating some other mechanism. We have examined the anatomical basis for these retrorenal extensions in static and functional studies of 12 cadavers using CT imaging, dissection and histological techniques. We observed that the posterior renal fascia was thicker than the anterior, that it could be easily separated into two layers by manual dissection and injections of liquid latex, that the inner (anterior) layer of the posterior fascia was continuous with the anterior fascia and the outer layer continuous with the lateroconal fascia. The point at which the two layers of the posterior fascia separated laterally and the medial extent of the posterior fascia varied considerably in CT scans of 100 patients. These data are interpreted to mean that pancreatic effusions extend posterior to the kidney by separating the two layers of the posterior renal fascia.

Fascia↗
PubMed1986

Bone particles from osteopetrotic mice not cured by bone marrow transplants are resorbed in normal littermates.

Osteosclerotic (oc/oc) and osteopetrotic (op/op) mice are not cured by bone marrow transplantation from normal littermates. The possibility that this is due to production of poorly resorbable bone was examined by comparing the fate of mutant and normal bone particles implanted subcutaneously in normal hosts. Bone, removed aseptically from calvarial and tibial sites of normal littermates and mutants, was cleaned of adherent soft tissue, ground and sieved to a particle size of 70-300 micron. Aliquots (17-20 mg) of bone from each phenotype of each stock were pelleted and implanted beneath the anterior thoracic skin of normal littermates for two weeks. Particle density in tissue sections was determined as percent of field by a point-counting method. Giant cell response was recorded as number per high-power field. Percent bone present initially was determined in pellets implanted for less than 24 hr. Bone particles were reduced in each pellet with time, about 25% of the original volume being removed in two weeks. No statistically significant differences were noted in the rates of disappearance of mutant and normal bone or in the percentage or number of giant cells in implants of mutant and normal bone in either stock. Furthermore, these values were not different from identical studies in microphthalmic mice, an osteopetrotic stock cured by bone marrow transplantation. These data suggest that the failure of osteopetrotic and osteosclerotic mice to be cured by bone marrow transplants from normal littermates is not due to the presence of unresorbable bone.

Animals↗
PubMed1986

The osteopetrotic rabbit: general and skeletal features of a new outbred stock.

Stock of the lethal osteopetrotic mutation in the rabbit has been outbred to robust New Zealand White stock. Features of this new stock include skeletal sclerosis and failure of tooth eruption characteristic of osteopetrosis, together with hypocalcemia, hypophosphatemia, and osteoclasts of reduced numbers and abnormal cytology. No abnormalities of carbonic anhydrase II were detectable by electrophoresis. The commercial availability of mutants of this new stock makes them a potentially important source of information about both osteopetrosis and osteoclast biology.

Animals↗
PubMed1986

Lack of effect of citric acid treatment of root surfaces on the formation of new connective tissue attachment.

Previous reports have described an accelerated induction of new attachment and repair of furcations in dogs after treatment of roots surfaces with citric acid, but few controlled clinical studies have examined its usefulness in surgical treatments for periodontitis. This study compared the effects of a comprehensive surgical plaque control procedure with or without citric acid treatment for generalized and localized effects on gingival height, probing pocket depth and attachment level in 72 teeth in 3 patients who were treated surgically for moderate periodontitis and examined every 3 months for 1 year. No statistically significant differences in the effects of the 2 treatments were observed. These observations suggest that there is no clinical advantage of citric acid conditioning of the root surface during surgical treatment of periodontitis.

Adult↗
PubMed1986

The metaphyseal lesion in abused infants: a radiologic-histopathologic study.

The metaphyseal lesions in abused infants have highly distinctive radiologic characteristics. The so-called "bucket-handle" and "corner" fractures often form the basis for the diagnosis of abuse. However, despite the great familiarity with the radiologic appearances, no systematic histopathologic study of the metaphyseal lesions in abused infants has been carried out. An in-depth study of pre- and postmortem radiologic features combined with histologic analyses of the metaphyses from a group of four abused infants provides new insights into the nature of these peculiar lesions. The basic histologic alteration is a subepiphyseal planar series of microfractures through the most immature portion of metaphyseal bone. This fracture results in the isolation of a mineralized disc or portion of a disc that is identifiable radiographically. Depending upon the size of the injury, the degree of involvement of the periphery of the bone, and the radiographic projection, a bucket-handle lesion, corner fracture, or metaphyseal lucency will result. In some cases, the radiographs may be normal even though there is significant histologic alteration. Although cartilaginous injuries may play a role in infant abuse, none of the specimens examined in this study evidenced injury through the germinal layers of cartilage. On the basis of the findings described here, it is recommended that postmortem analysis of all radiographically suspicious metaphyses be carried out in cases of suspected infant homicide. If there are other clinical or pathologic indications to support abuse, a strong argument can be made for removal of radiologically normal but high-risk metaphyses. Instituting these procedures will require closer cooperation between the radiologist and the medical examiner, but the potential for reducing the number of infant homicides demands this enlightened approach.

Autopsy↗
PubMed1986

Pediatric hypertrophic gastropathy.

Four previously healthy children presented in a 6-week period with marked hypoproteinemia without liver disease, malnutrition, or significant proteinuria. They all had strikingly similar radiographic findings consisting of enlarged folds confined to the fundus and body of the stomach. Three of the children had prodromal symptoms suggesting a viral illness. Cytomegalovirus was cultured from the urine in all cases and from the gastric biopsy specimens in three patients. Two of these patients also showed intranuclear inclusions in their biopsy specimens compatible with cytomegalovirus. It is not certain if cytomegalovirus was the cause of the illness.

Child, Preschool↗
PubMed1986

Bone particles from toothless (tl/tl) osteopetrotic rats not cured by bone marrow transplantation are resorbed in normal littermates.

We examined the possibility that the failure of toothless (osteopetrotic) rats to be cured by bone marrow transplantation from a normal littermate is due to the production of poorly resorbable bone. Mineralized bone particles from mutants (tl/tl) and normal littermates were implanted subcutaneously in normal rats of this stock. The removal of bone and recruitment of multinucleated giant cells were evaluated by histomorphometry. No differences were found between mutant and normal bone from this stock or from two other osteopetrotic rat stocks, incisors-absent and osteopetrosis, known to be cured by bone marrow transplantation. Subject to the limitations of this method, these data suggest that the failure of tl/tl rats to be cured by bone marrow transplants from normal littermates is not due to the production of unresorbable bone or a bone matrix deficient in its ability to recruit multinucleated giant cells and presumably osteoclasts.

Animals↗
PubMed1985

Morphological evidence of reduced bone resorption in the osteosclerotic (oc) mouse.

Osteopetrosis, a metabolic bone disease characterized by a generalized sclerosis of the skeleton, is inherited as an autosomal recessive in a number of mammalian species. The pathogenesis of congenital osteopetrosis is mediated by a reduction in bone resorption as a result of decreased osteoclast function. This hypothesis is based on both functional and structural evidence of reduced bone resorption in all mutations examined to date. The present study examined the histology of cartilage and bone, the ultrastructure of osteoclasts, and the morphology of mineralized bone surfaces in a lethal osteopetrotic mutation, the osteosclerotic (oc) mouse. Histologically, epiphyseal cartilage growth plates, especially the hypertrophic zone, are markedly thickened in oc mice and metaphyses contain excessive osteoid, features characteristic of rickets. Transmission electron microscopy revealed that less than one-quarter of osteoclasts in oc mice demonstrated evidence of ruffled border formation compared with three-quarters of the osteoclasts in normal littermates. In mutants, ruffled borders were less elaborate and cytoplasmic processes penetrated into bone surfaces, suggesting that bone may be removed by mechanical rather than by enzymatic means. There was little morphological evidence of cartilage degradation and broad laminae limitantes persisted in mutants. Mineralized surfaces that undergo resorption in normal mice showed no evidence of bone resorption by scanning EM in mutants. The presence of a rachitic condition, the observations of reduced bone resorption, and the possible contribution of undermineralized matrices to decreased bone resorption are characteristics of the osteosclerotic mutation which suggest that it is a unique osteopetrotic mutant in which to study both the development and regulation of skeletal metabolism.

Animals↗
PubMed1985

Mineral and matrix alterations in the bones of incisors-absent (ia/ia) osteopetrotic rats.

The bones of incisors-absent (ia/ia) osteopetrotic rats differ from those of their normal littermates (ia/+) in histologic and radiographic appearance and in mechanical properties. This study examined how the mineral and matrices of osteopetrotic metaphyses and calvaria differed from normal controls. Bones of 11-day-old and 52-day-old osteopetrotic animals had higher ash (mineral) contents that age-matched controls; osteopetrotic metaphyses had elevated hexosamine contents, indicative of the persistence of cartilage. Calcium acidic phospholipid phosphate complexes, involved in initiation of hydroxyapatite formation in vivo and in vitro, were significantly reduced in content in all osteopetrotic bones. These results suggest that in the osteopetrotic rat, where osteoclast activity is defective, new mineral formation is reduced and replaced by accretion of mineral on existing crystals. Fractionation of osteopetrotic bone particles by density centrifugation demonstrated that the osteopetrotic bone was much more mineralized than that of age-matched controls. X-ray diffraction analysis of the mineralized fractions indicated a lack of growth of mineral crystals during maturation of the osteopetrotic animals. The absence of remodeling was apparent from the elevated Ca:P ratios of the highly mineralized osteopetrotic bone fractions, and from the high hexosamine content of these dense fractions. These observations may explain some of the unusual mechanical properties of osteopetrotic bone.

Animals↗