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S C Marks

Publications and source records attributed to S C Marks.

At least 199 records · Page 11Linked to original sources
PubMed1985

The lifespan of osteoclasts: experimental studies using the giant granule cytoplasmic marker characteristic of beige mice.

Osteoclasts are large multinucleated skeletal cells that form by fusion of bloodborne mononuclear precursors. Fusion with mononuclear precursors occurs throughout life, and survival of osteoclasts is believed to be dependent upon continued replenishment by fusion. This study examined osteoclast lifespan, defined as maximal survival without fusion, in normal mice irradiated to eliminate host stem cells and rescued with stem cells from beige (bg) mice whose osteoclasts have a distinctive phenotype. Osteoclasts of donor phenotype appeared during the second week and progressively increased so that by the sixth week no osteoclasts of host phenotype were present. Radiation alone did not produce any change in osteoclast phenotype. These data are interpreted to indicate that the maximal survival of osteoclasts without fusion of precursors is less than 6 weeks.

Animals↗
PubMed1985

Humanities in medical education: rationale and resources for the dissection laboratory.

Dissection of a human body during an anatomy course raises for first-year medical students questions about invasion of privacy, cadaver sources, dying and death. Emotions evoked are often heightened by the fear and uneasiness each student experiences when dissecting the body of a human being. Providing curricular resources for identification and discussion of reactions to death and dissection early in the first year can demonstrate to students the humanity of having such reactions, and that these reactions can be understood and managed more or less appropriately. An elective course has been offered to first-year medical students at the University of Massachusetts Medical School for 10 years; the students' reception of this evolving programme has been enthusiastic. The rationale, content, resources and responses of such a course are presented.

Attitude to Death↗
PubMed1985

Ultrastructural features of the dental follicle associated with formation of the tooth eruption pathway in the dog.

The dental follicle is a loose connective tissue layer that surrounds the developing and erupting tooth. The follicle is necessary for tooth eruption in dogs and specific cellular changes occur in the follicle at the onset of tooth eruption. In particular, within the coronal region of the follicle next to areas of subsequent bone resorption there is an increase in mononuclear cells which have the ultrastructure features of monocytes and contain specific granules characteristic of preosteoclasts. The follicle has an extensive microvasculature and monocytes are often seen adjacent to capillaries and venules. Monocytes increase in number in direct proportion to the increase in osteoclasts that form the eruption pathway and decrease in number as soon as this activity is completed. It is postulated that monocytes enter the follicle from the microvasculature and then migrate to the walls of the bony crypt to participate in the formation of the eruption pathway.

Age Factors↗
PubMed1985

Rickets and osteopetrosis: the osteosclerotic (oc) mouse.

A new mouse osteopetrotic mutation, osteosclerosis, has been examined with respect to rickets. These osteopetrotic mice were hypocalcemic and hypophosphatemic, and had greatly thickened epiphyseal plates with abnormalities in matrix vesicles when compared with normal littermates. Such biochemic and morphologic manifestations of rickets in this osteopetrotic mutation may explain the failure of osteosclerotic mice to be cured by transplantation of bone marrow from normal littermates and indicate that vitamin D metabolism and matrix vesicle biochemistry warrant further study.

Animals↗
PubMed1984

Experimental study in the dog of the non-active role of the tooth in the eruptive process.

The role of the tooth in eruption was studied radiographically and histologically after experimental manipulations of the crowns of permanent mandibular premolars in dogs. Crowns were removed and dead crown shells or metal or silicone replicas were substituted into dental follicles just prior to scheduled eruption. These replacements erupted on schedule after formation of the usual eruption pathways and formation of trabecular bone from the base of the bony crypt. Removal of crowns, but without adding replacements, also exhibited these same hallmarks of eruption. We conclude that tooth eruption is a series of metabolic events in alveolar bone characterized by bone resorption and formation on opposite sides of the dental follicle and the tooth does not contribute to this process.

Alveolar Process↗
PubMed1984

Congenitally osteopetrotic (oplop) mice are not cured by transplants of spleen or bone marrow cells from normal littermates.

Congenital mammalian osteopetrosis is characterized by a generalized skeletal sclerosis due to reduced bone resorption by osteoclasts. This condition can be cured in several mutant strains of mice and rats by transplantation of spleen or bone marrow cells from normal littermates. The ability of this regimen to cure osteopetrosis in oplop mice was examined in 23 mice treated with spleen or bone marrow cells from normal littermates and followed for up to 80 days. In no instance was there radiographic or histologic evidence of removal of the excessive skeletal mass characteristic of the disease. These data show that spleen or bone marrow cells do not cure osteopetrosis in this mutation. Recent demonstrations that not all children with congenital osteopetrosis are cured by bone marrow transplants from HLA-matched donors suggest that the oplop mouse mutation may be a useful model system in which to develop alternate treatments.

Animals↗
PubMed1984

Osteoclast populations in congenital osteopetrosis: additional evidence of heterogeneity.

Osteopetrosis is a metabolic bone disease characterized by excessive accumulation of skeletal mass due to a reduction in bone resorption. The pathogenesis of osteopetrosis is reduced osteoclast function. Reports of osteoclast numbers in several mammalian mutations exhibiting osteopetrosis have shown them to be increased, decreased, or normal in numbers. The present investigation quantitated the osteoclast populations and examined the cytology of osteoclasts by light microscopy in calvarial and tibial sites in one rabbit and two mouse mutations and compared them with their normal littermates. Our observations show that osteoclast numbers are, depending on the particular mutation, increased, decreased, or comparable to those found in normal littermates. In each mutation, however, osteoclasts fail to exhibit the cytoplasmic vacuolization next to bone surfaces seen in normal osteoclasts. These data provide additional evidence of heterogeneity in the congenital mammalian osteopetrosis and suggest that these mutations may be significant sources of new information about the biology of osteoclasts.

Animals↗
PubMed1984

Congenital osteopetrotic mutations as probes of the origin, structure, and function of osteoclasts.

Progress has been made in recent years on the cell biology of the osteoclast and the pathogenesis of congenital osteopetrosis. New information is critically evaluated and summarized with respect to the origin, structure, and function of osteoclasts with special reference to osteopetroses. A broader perspective emerges from which to consider the biology of osteoclasts, the heterogeneities in the osteopetroses, and the value of each in elucidating the other, along with treatment of the disorder.

Adult↗
PubMed1983

The cytology of the dental follicle and adjacent alveolar bone during tooth eruption in the dog.

Previous studies from our laboratories have shown that premolar eruption in dogs depends upon the presence of the dental follicle and is independent of root or crown growth or attachment to the oral epithelium. The present study is an analysis of the cellular composition of the dental follicle and the cellular investment of the adjacent walls of the bony crypt before and during eruption of the third and fourth mandibular permanent premolars in young beagle dogs. Four premolar follicles and their adjacent bony crypts were examined at 2-week intervals over 12 weeks before and during eruption of these teeth. Tissues were removed, fixed, processed, and oriented so that each follicle and the adjacent crypt wall could be reproducibly examined in vertical and horizontal planes. Mononuclear cells with abundant cytoplasm, euchromatic nuclei, and prominent nucleoli were present in juxtavascular location in the coronal part of the dental follicle; and these cells increased in number immediately preceding and during tooth eruption in parallel with an increase in osteoclasts on the adjacent crypt wall. These data are interpreted to mean that the coronal part of the dental follicle may coordinate the alveolar bone resorption required for tooth eruption by attracting and directing to the crypt wall a population of mononuclear cells, which either become osteoclasts and/or direct osteoclastic activity during tooth eruption.

Alveolar Process↗
PubMed1983

The origin of osteoclasts: evidence, clinical implications and investigative challenges of an extra-skeletal source.

Recent evidence for an extraskeletal origin of osteoclasts and the historical record of the genesis of osteoclasts are examined critically. Reviews of the structure, function and development of osteoclasts from mononuclear precursors, the local regulation of bone resorption and the coupling of bone formation to preceding resorption are presented as a background for discussing the clinical implications for management of osteolytic bone diseases. The roles of osteoclasts and macrophages as phagocytes are compared and contrasted, and recent evidence for macrophage heterogeneity resulting from site-specific monoblastic precursors is reviewed. The implications of these recent developments in macrophage biology are extrapolated to osteoclasts and the existence of site-specific, extraskeletal osteoclast precursors is proposed. Finally, the investigative challenges inherent in these perspectives are discussed.

Alveolar Process↗
PubMed1983

Inhibition by dithionite and reactivation by iron of the tartrate-resistant acid phosphatase in bone of osteopetrotic (ia) rats.

The staining intensity and inhibitor sensitivity of acid phosphatase activity was determined histochemically in various tissues of normal and ia rat pups by the use of freeze-dried whole body sections. Activity was determined using alpha-naphthylphosphate as substrate and hexazonium pararosaniline as coupler. Sections from ia rats (6 and 24 days old) showed markedly higher enzyme activity in bone than sections from normal littermates. However, there were no differences between ia and normal pups in acid phosphatase activity in soft tissues and developing teeth. Preincubation of sections with 1-100 mM sodium dithionite (an iron-binding agent) caused a dose-related inhibition of enzyme activity in bone of ia and normal pups, but only slight inhibition of activity in soft tissues. Partial restoration of the dithionite-inhibited activity in bone was achieved by subsequent preincubation in 1 mM FeCl2. Addition of 100 mM sodium tartrate to the staining solution of non-preincubated sections caused almost complete inhibition of activity in soft tissues and the developing teeth but no inhibition of the activity in bone that was sensitive to sodium dithionite. These data indicate a) that sodium dithionite can be used as a specific histochemical inhibitor of the tartrate-resistant acid phosphatase and b) that the source of increased acid phosphatase activity in bone from ia rats is mostly from the tartrate-resistant acid phosphatase.

Acid Phosphatase↗
PubMed1982

Morphological evidence of reduced bone resorption in osteopetrotic (op) mice.

Osteopetrosis, a metabolic bone disease in which a generalized accumulation of bone mass reduces or obliterates marrow cavities, is inherited as an autosomal recessive in several mammalian species. A recently discovered mutation in mice, the osteopetrosic (op) mutation, exhibits an elevation in bone matrix synthesis and a resistance to the hypercalcemic effects of exogenous parathyroid extract when young mutants are compared with normal littermates. This investigation examined the number, cytology, and ultrastructure of osteoclasts and the structure of bone surfaces in op mice in a morphologic assessment of bone resorption. Compared with normal littermates, op mice have a severe deficiency of osteoclasts, which also contain unusual toluidine blue-positive and electron-dense cytoplasmic inclusions and hypertrophy of clear zones and ruffled borders. Marrow spaces in op mice contained large numbers of megakaryocytes and large lipoid masses. Bone surfaces exhibiting evidence of resorption by scanning electron microscopy in normal littermates showed no evidence of resorption in op mice. Instead, these areas were characterized by morphologic features of bone formation. These data offer morphologic evidence of a reduction of bone resorption in this mutation. They are interpreted to mean 1) that op mice have a severe reduction in numbers or proliferative capacity of osteoclast precursors, which may be related to the cellular inclusions in the osteoclast population, and 2) that hypertrophy of the ruffled borders and clear zones of op osteoclasts is a compensatory attempt to increase bone resorption.

Animals↗
PubMed1982

Chronology and histology of exfoliation and eruption of mandibular premolars in dogs.

Exfoliation of third deciduous mandibular premolars and their replacement by the third permanent premolars were compared in young dogs of purebred beagle and mongrel stock. Radiographic and histologic studies showed that eruption of the permanent premolar begins during the 16th postnatal week and is completed in 7 weeks. Root elongation proceeds with eruption, but fibers of the periodontal ligaments are not anchored in alveolar bone and do not attain their final orientation with respect to the long axis of the tooth until final phase of the eruptive period. These data define a predictable system in which various stages in the mechanism of eruption of noncontinuously erupting teeth may be examined experimentally. Furthermore, the observation that these processes are identical in timing and sequence in beagle and mongrel dogs suggests that less expensive, more readily available mongrel dogs can be used for these studies.

Animals↗
PubMed1982

Transformations of osteoclast phenotype in ia rats cured of congenital osteopetrosis.

The reduced bone resorption characteristic of osteopetrosis is accompanied in the incisors-absent (ia) rat mutation by a significant increase in osteoclasts of inactive (mutant) phenotype. Restoration of bone resorption in ia rats by transfer of spleen cells from normal littermates is preceded by a transformation of osteoclasts from mutant to normal phenotype. In this investigation the proportions of osteoclasts of normal phenotype have been determined by light microscopy in untreated ia and normal rats and in ia rats treated with various cell populations from normal rats. Significant increases in numbers of osteoclasts of normal phenotype were seen in the mutant skeleton soon after cell treatments that eventually restored bone resorption and cured the disease. No changes in osteoclast phenotype were seen after cell transfers that did not cure the disease. These data establish transformation of osteoclast phenotype as an early event in the recovery from osteopetrosis and suggest that determination of osteoclast phenotype is a reliable predictor of the success of normal cell populations to restore bone resorption in this mutation.

Animals↗
PubMed1982

Osteoclast kinetics in osteopetrotic (ia) rats cured by spleen cell transfers from normal littermates.

Excessive skeletal mass and reduced bone resorption characteristic of osteopetrosis in young ia rats can be corrected by irradiation and transfer of spleen cells from normal littermates. Cell population analyses and 3H-thymidine (3H-TdR) autoradiographic methods were used to determine osteoclast population dynamics and kinetics of incorporation of nuclei following whole-body irradiation and spleen cell transfer in ia/ia rats and in untreated ia rats and their (ia/+) normal littermates. The numbers of osteoclasts per metaphyseal area were greater in ia rats than in (ia/+) normal littermates. Untreated ia rats had greater rates of incorporation of 3H-TdR-labeled nuclei into osteoclasts but were reduced to near normal values following irradiation and spleen cell transfer. Labeled osteoclast nuclei were first seen in the primary spongiosa of the femoral metaphysis and with increasing time appeared at greater distances from the epiphyseal growth plate as the bones grew In length. These sites of osteoclast neogenesis correspond to sites where restoration of bone resorption is initially seen following bone marrow and splenic transplants in the treatment of osteopetrosis.

Animals↗