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D J Simmons

Publications and source records attributed to D J Simmons.

At least 55 records · Page 3Linked to original sources

Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887.

We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

Animals↗

Long-term effects of tissue expansion on cranial and skeletal bone development in neonatal miniature swine: clinical findings and histomorphometric correlates.

Progressive tissue expansion induces significant gross, histologic, and bony changes in skulls and long bones of neonatal miniature swine. These bony changes consist of erosion underlying tissue expanders, with bony lipping and bone deposition at the periphery of the expander. Cranial suture lines underneath expanders appear effaced and convoluted. Serial CT scans reveal decreased bone thickness and volume (p less than 0.02) but identical bone density (p = 0.60) beneath expanders. Increased bone volume and thickness occur at the periphery of expanders (p less than 0.02). Bone density (CT number) is unaffected by tissue expansion in both cranial and long bones. These findings have histomorphometric correlates: Osteoclastic bone resorption occurs underneath expanders with periosteal reaction at the periphery of expanders. Cranial sutures are similarly affected, but no cranial synostosis results. No changes to the inner table of the skull or stigmata of increased intracranial pressure were observed either in CT scans or in behavioral changes in long-term animals. The pathophysiology of bony changes is a remodeling effect, not one of simple pressure deformation. Increased bone resorption and complete inhibition of bone formation occur until the pressure is removed. Cranial bone is significantly more affected than long bone. After removal of the expanders, reparative bone remodeling begins within 5 days and nearly complete healing of the cranial defects occurs within 2 months (p less than 0.02). No plagiocephaly results despite early coronal suture changes. On the basis of this study, we conclude that tissue expansion causes significant but reversible effects, readily monitored by high-resolution CT scans, on neonatal and infant cranial and long bones.

Animals↗

Calcitonin: chronotherapeutic effect on osteopenia in the ovariectomized rat.

This chronotherapeutic study has revealed no clear evidence to support the concept that calcitonin promotes bone formation in intact or OVX'd rats. Rather, the efficacy of CT-impaired bone resorption appeared to be optimal in OVX'd rats treated during the daytime, and least effective during the first half of the environmental dark span. These findings indicate a benefit for calcitonin chronotherapy in this animal model where the cellular kinetics resemble those documented in early development of postmenopausal osteoporosis.

Animals↗

Effect of dihydrotachysterol on bone induction in ovariectomized rats.

We have demonstrated via marrow stromal cell cultures and the osteoinductive response to demineralized bone grafts (DBM) that the cortical bone deficit in the ovariectomized (OVX) rat (6 weeks postop) is primarily due to impaired osteoprogenitor cell proliferation, and that dihydrotachysterol (DHT) treatment can be protective. In cultured marrow stromal cells from OVX rats, short-term DHT-Rx exaggerated the already subnormal pattern of marrow stromal cell proliferation. However, in DBM grafts, DHT treatment benefited the time-course of mesenchymal cell DNA synthesis as measured by tritiated thymidine incorporation and osteogenic cell maturation as measured by alkaline phosphatase concentration, and established a suggestive trend toward normalization of bone formation/mineralization (24 h 45Ca incorporation). The data from this animal model infer that DHT could moderate the bone loss normally seen in ovariectomized rats via an activation of the osteoprogenitor cell population.

Alkaline Phosphatase↗

Correlation of MRI images with histology in avascular necrosis in the hip. A preliminary study.

The role of MRI in identifying the tissue level changes in the femoral head was investigated in five patients diagnosed as having avascular necrosis by radiology, scintigraphy, and MRI (0.35 Telsa). Radiographic scoring by the Ficat and Arlet system showed one hip with stage I, one stage II, two stage III, and one stage IV changes. The histologic features of core biopsy specimens obtained during decompression of the femoral heads were compared to the preoperative T1 and mixed T1/T2-weighted MR images. The cores varied with respect to their distance from the subchondral bone (7-23 mm) and length (19-45 mm). At the subchondral end of the core tract, low T1-weighted images corresponded to marrow fibrosis (5 cases) and in three of five cases to increased trabecular bone volume (TBV = 44-50%). Subjacent areas of diffusely decreased MR signal corresponded to marrow fibrosis and necrosis, with a relatively normal TBV (17-28%). The distal ends of the core tracts showed normal fatty marrow and a normal MR signal. The observations affirm that the MR signal intensity is largely reduced as a function of marrow degeneration and loss of fat content, but the signal is not predictive of particular histotypic morphologic patterns.

Adult↗

Bone cell populations and histomorphometric correlates to function.

A circadian context has been used to develop information about the proliferative and functional behavior of the cell populations that function to model the long bones of growing rats. We asked: Are the proliferating cells in the growth cartilages and diaphyseal bone of young adult growing rats distributed within single or multiple populations? Can cytomorphometry (TEM-C) be used to determine ultrastructural correlates to the well-defined circadian rhythm of matrix formation displayed by functionally synchronous populations of metaphyseal osteoblasts? Can TEM-C reveal changes in osteoclast ultrastructure that could index a biological rhythm for osteoclastic bone mineralysis/resorption? Kinetic results derived from multiple radiothymidine labeling (DNA synthesis) support the single population model for chondrocytes and diaphyseal osteoprogenitor cells. TEM-C studies at the midpoints of the daily light and dark spans show that osteoblast RER-membrane development and cysternal volumes are maximal at the recorded daytime peak of net collagen synthesis. The extent of metaphyseal osteoclast surface ruffling (mineralysis) is also twofold greater during the day than the night--an observation supporting the concept that bone formation and resorption activities are coupled.

Animals↗

Charged beads: generation of bone and giant cells.

Based on reports of electrically induced bone formation and findings that some materials used to promote bone ingrowth are stimulatory in bead form, the osteogenic potential of beads with different surface charges was examined. In this preliminary study, three types of Sephadex beads were injected into chick femora: type I, DEAE beads, positively charged; type II, CM beads, negatively charged; type III, G-25, uncharged. Beads were injected into the femoral midshaft, and after 3 days, 4 days, and 1 week, birds were sacrificed and femora were processed for histology. Type I beads: at 3 days, were surrounded by multinucleated giant cells; by 4 days, patches of bead-associated new bone were present along with giant cells; after 1 week, occasional bead-associated multinucleated cells were seen, but now most beads were surrounded by new intramedullary bone, forming an extensive bead-bone lattice. With bead types II and III, bead-associated new bone was seen at 3 days and 4 days only when beads lodged near the endosteum or in the metaphysis. At 7 days, no bone was seen with either of these two bead types. The response to the type I beads may be likened to a remodeling phenomenon with large numbers of giant cells at 3 days, new bone and giant cells at 4 days, and evidence only of bone formation at 7 days.

Animals↗

Pull-out strengths of bone screws at various sites about the pelvis--a preliminary study.

The pull-out strength of both cortical and cancellous screws from bone at various sites about cadaveric pelves was examined. No significant differences were seen between cortical or cancellous screws at similar sites with the possible exception of the sacroiliac joint. Pull-out strengths were best correlated to the depth of bone at a particular screw hole. For practical purposes, the strongest sites are in the thick buttress of bone along the iliopubic column.

Acetabulum↗

Regional alterations in long bone produced by internal fixation devices. Part I. 85Sr clearance.

We examined the effect of rigid plate application on the radiostrontium clearance of the intact canine femur at 6 months. We examined each of the component surgical steps. We calculated the clearance both for the whole bone and for each of the five transverse sections of the whole bone. Screw application, but not drilling, increased the clearance in the segment about the screw holes. Plate application produced an increase in the segment beneath the plate as well as around the screws and in the whole bone. These changes are accomplished not only by an absolute increase in clearance to the middle three segments, but by a relative diminution in clearance by the most proximal and distal segments. The histomorphometric changes in long bones following rigid plating may be accompanied by regional increases in bone blood flow.

Animals↗

Regional alterations in long bone 85Sr clearance produced by internal fixation devices. Part II. Histomorphometry.

The effects of each of the surgical stages involved in compression plating on the development of cortical thinning and porosity were assessed in the intact midshaft, stress-shielded femoral segments of adult mongrel dogs 6 months postoperatively. The data were evaluated in terms of a postsurgical tetracycline-based measure of remodeling and terminal 85Sr clearance (SrC) values for the plated segments of bone. Drilling had no effect on any parameter. Screw application was associated with minimal cortical thinning (p less than 0.05), while plate fixation clearly promoted thinning (p less than 0.01) and porosity (p less than 0.05). The percentage of labeled osteons, a measure of remodeling activity, increased only after plate fixation (p less than 0.05), and the labeling patterns suggested that most osteons had formed during the first 4 postsurgical months. That none of these changes were correlated with the 6-month SrC values suggests that the development of plate-induced osteopenia involves disparate histomorphometric time constants, rather than lack of any association.

Animals↗

The effect of low dietary calcium and calcium supplementation on calcium metabolism and bone in the immature, growing rat.

The data presented here were obtained from a series of experiments designed to determine 1) whether normal growth and bone development could be maintained in young, growing rats (3-9 weeks of age) on a diet containing 0.1% Ca, and 2) whether Ca presented in a bolus would be utilized as effectively as the same amount of Ca distributed throughout the diet. Weanling female rats were raised to 9 weeks of age on diets containing 0.4% P and either 0.5% or 0.1% Ca. One group of animals on the 0.1% Ca diet was given oral supplements of CaCO3 twice each day to supply the same amount of Ca consumed by age-matched animals on the 0.5% Ca diet. We found that animals consuming diet containing 0.1% Ca grew at the same rate as animals receiving 0.5% Ca, or 0.1% Ca + supplement for up to 9 weeks of age when the experiment was terminated. Measurement of femur length indicated that long bone length was the same for all animals. However, the 0.1% Ca group exhibited mild hypocalcemia (9.1 mg/dl vs 10.4 for controls), a 2.6-fold elevation in immunoreactive parathyroid hormone, and an increase of similar magnitude in circulating levels of 1,25-dihydroxyvitamin D. Bones from the 0.1% Ca group contained less than half as much Ca as bones from the 0.5% Ca group, and exhibited significant decreases in mid-shaft diaphyseal thickness, % trabecular volume of the distal metaphysis and breaking strength (torsion testing). These results suggest that while a diet containing 0.1% Ca is able to maintain normal growth, bone mineralization is compromised.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Subcapital fracture of the hip following an intertrochanteric fracture. A case report and literature review.

A 42-year-old alcoholic man who had a normal femoral head histologically incurred a subcapital fracture four months after surgical treatment of an intertrochanteric fracture of the same hip. Subcapital fracture of the hip following intertrochanteric fracture is an unusual occurrence, with possibly as few as 11 cases documented in the literature. Affected persons are usually elderly females with severe osteoporosis. Though unusual, the fracture is obvious and not difficult to treat.

Adult↗

Radiostrontium clearance and bone formation in response to simulated internal screw fixation.

Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling.

Animals↗

The changes in quality of mandibular bone mineral in otherwise totally immobilized rhesus monkeys.

The status of bone mineral and osteocalcin in the young adult Rhesus monkey mandible was assessed following a 14-day period of postcranial immobilization, and after 7- and 28-day recovery periods. Specimens of cortical bone taken from the compact bone at the inferior border of the jaws were ground in liquid nitrogen and sieved to a particular size below 20 micron. The bone powder was then fractionated in a bromoform-toluene density gradient to determine its mineralization profile (Ca, P, CO3, and osteocalcin), and X-ray diffraction was used to determine apatite crystal size in some fractions. There was no change in the chemistry of the mandibular bone from the immobilized animals. However, the mineralization profile in that group showed a significant shift toward the higher density fractions, indicating the presence of a greater than normal content of mature well-mineralized bone. While this trend was accentuated in the jaws following a 7-day postimmobilization recovery period, partial recovery of the normal profile was observed after a 28-day recovery period. The osteocalcin profile shifted like the mineralization profile during the immobilization and recovery periods. X-ray diffraction analyses showed that the shift in the mineralization profile during the immobilization period was associated with a decrease in apatite crystal size.

Animals↗

Bone deficit in ovariectomized rats. Functional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment.

This study investigates the proliferative and osteogenic role of marrow stromal/osteoprogenitor cells in the development of the cortical bone deficit in ovariectomized (OVX) female rats. In vitro, clonal growth of marrow stromal cells from OVX rats was significantly impaired (vs. sham-operated controls). Yet in vivo, cells from sham-operated and OVX rats had equal osteogenic potential in several in vivo experimental situations, such as in intraperitoneally implanted millipore diffusion chambers and in intramuscular implants of marrow plus osteoinductive bone matrix (composite grafts). Long-term (6 mo) dihydrotachysterol (DHT) treatment of OVX rats enhanced their in vitro proliferative potential and clonal growth, as well as their osteogenic expression in composite grafts. The observation that the in vivo osteogenic performance of OVX rat marrow stromal cells was normal at extraosseous sites suggests that the mechanisms leading to osteopenia may involve an abnormality in cell-matrix interactions.

Animals↗

Bone maturation and quality of bone material in rats flown on the space shuttle 'Spacelab-3 Mission'.

The maturation profiles of calcium, phosphorus, magnesium and hydroxyproline in the femoral trabecular and cortical bone and in the thoracic vertebrae from male rats flown on the 7-day 'Spacelab-3 Mission' were measured by density gradient analysis. In rats exposed to a spaceflight environment, profiles of the matrix and mineral moieties were shifted toward both the lower (vertebrae) and higher density fractions (femurs and vertebrae), patterns indicating a decrease in bone growth/turnover. X-Ray diffraction of vertebrae indicated that spaceflight is associated with a decrease in apatite crystal size/perfection.

Animals↗

Effect of rotopositioning on the growth and maturation of mandibular bone in immobilized rhesus monkeys.

As part of an ongoing effort to mimic the hypokinesia and hypogravity of spaceflight, the effects of 14 d immobilization and rotopositioning on mandibular bone osteon growth (= radial rate of closure) was assessed in 12 juvenile Rhesus monkeys by tetracycline labeling. The monkeys had been restrained in a supine position and rotated 908 every 30 min through a full 3608 arc for 14 d. Osteon growth was also assessed after the immobilized/rotopositioned animals had been permitted to recover in metabolism cages for periods of 28 and 56 d. The closure rates of osteons in the cortex of the inferior border of the mandible were not abnormal during immobilization/rotopositioning or during recovery. The regression line plots yielded slopes of: Controls = 0.946-1.000; Immobilized/Rotopositioned = 1.045; 28 d Recovery = 0.833; 56 d Recovery = 0.829. Microradiographs indicated a normal distribution of osteons of different mineral density: lowly (28%), moderately (53%), and highly mineralized (18%). Bone porosity values also remain within the normal range (18.3 6 4.1%). These results suggested that 14 d immobilization/rotopositioning did not effect abnormal changes in the rates of bone formation and mineralization in the mandibular cortex of the juvenile Rhesus monkey.

Animals↗

Effect of an adrenocorticotropin analogue, ACTH 1-17, on DNA synthesis in murine metaphyseal bone.

The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six different timepoints, 4 hr apart, during a single 24-hr span with either a low (0.02 I.U./kg) or a high (20 I.U./kg) dose of ACTH 1-17. Control groups received injections of a placebo at corresponding timepoints. Subgroups of mice were injected with [3H]thymidine ([3H]Tdr) to follow the changes in DNA labeling in the proximal tibial metaphysis at 15 min and 2, 4, 8, 12 and 24 hr after ACTH 1-17 or placebo treatment. All mice were injected with the isotope 30 min before killing, except for those killed 15 min after Rx administration where the isotope had been injected 14 min before killing. The data were analyzed both by analysis of variance and by the cosinor method, the latter of which tests the fit of a 24-hr cosine curve to the data. The effect of ACTH 1-17 on the target cell population was dependent not only upon the dose but upon the time of administration. Both doses exerted time-dependent action, ranging from stimulation to inhibition of DNA labeling. Inhibition was noted when the ACTH 1-17 was administered at 2 hr after the beginning of the daily dark span when nocturnal animals become active. When administered at this circadian stage, the larger dose in particular was associated with an inhibition of DNA labeling lasting for 24 hr. The inhibitory effect was much shorter when the same dose was injected 4 hr earlier. Moreover, the large ACTH 1-17 dose had a stimulatory effect lasting for 24 hr when it was administered 2 hr after the onset of the daily light span, with a much shorter stimulation following administration of the large dose at 6 hr after the beginning of the daily dark span. A circadian stage-dependent stimulation or inhibition of DNA labeling at 2 or 14 hr after light onset, respectively, was thus complemented by an initial inhibition followed by stimulation and vice versa at 10 and 18 hr after light onset respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗