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D J Simmons

Publications and source records attributed to D J Simmons.

At least 73 records · Page 4Linked to original sources
PubMed1985

In vitro evaluation of circadian patterns of bone collagen formation.

The circadian patterns of bone collagen formation were studied in vitro to ascertain whether the biorhythmic profiles previously measured in vivo reflect true differences in collagen synthesis. Alteration of amino acid pool sizes did not negate the circadian-stage differences in bone collagen production. Evaluations of proline uptake and transport, as well as collagenous protein turnover, demonstrated that the intracellular assembly and secretion of bone collagenous protein during the dark span is truly decreased relative to that during the light period. It was further affirmed that PTH is essential for maintenance of the normal circadian collagen synthesis rhythms.

Animals↗
PubMed1985

Fracture healing perspectives.

This paper reviews the sequence of histomorphologic changes that occur in and around a fracture site, and discusses recent concepts about the roles of the cells and bone matrical moieties in promoting specific cell transformations during the phases of callus tissue formation and consolidation of the bony cortex. Current knowledge about the roles of autocrine, paracrine, and endocrine polypeptide growth and transforming factors lends new perspectives about this classic problem in bone physiology.

Animals↗
PubMed1985

Effect of fixation devices on radiostrontium clearance in the intact canine femur.

Femoral metaphyseal/diaphyseal blood flow was studied by 85Sr clearance in unfractured segments of dog femurs following compression plating and various control procedures (drilling with and without application of screws). The animals were tested as early as seven days and as late as two months after surgery. The only statistically significant change in strontium clearance (SrC) was an increase produced by the application of stainless-steel bone screws, with or without plates. The presence or absence of compression had no consistent effect on changes in the rate of SrC. During the period of study, no changes in bone mineralization, haversian porosity, or cortical bone thickness accompanied the SrC alterations.

Animals↗
PubMed1984

From bone lining cell to osteocyte--an SEM study.

We describe the SEM appearance of the rat endosteal bone lining cell ( BLC ) population, and the sequence of morphological changes of these cells as they self-incorporate into unmineralized bone matrix (osteoid), establish intercellular connections, and construct lacunae. The osteoblast/nascent osteocyte series was progressively unsheathed by gentle digestion of the osteoid with 0.25% collagenase. The osteoblasts which leave the polygonally packed BLC compartment rapidly develop numerous complexly branched processes that contact the processes elaborated by previous generations of maturing and mature osteocytes. As osteoblasts mature and approach the mineralization front, they appear to lose processes. The mature cells begin to form osteocyte lacunae by depositing an asymmetric perimeter of woven collagen fibrils, such that as the cells roof-over, the lacunae appear as pocketlike constructions. The collagen fibrils on the perilacunar matrix are oriented in a tangential or circular pattern, while those in the more distal matrix are arranged in a parallel pattern. With the completion of a lacuna, its wall appears to mineralize quickly, for lacunae could be recognized only when they are forming.

Animals↗
PubMed1984

Intestinal microflora as potential modifiers of sensitizer activity in vivo.

Treatment of mice (some bearing Lewis Lung tumors), with penicillin (PEN) at 500 mg/l drinking water for one week prior to treatment with misonidazole (MIS), resulted in: the elimination of their anaerobic cecal flora; a decrease in MIS-induced neurotoxicity; an increase in pharmacological exposure to MIS; a decrease in MIS chemopotentiation; a probable increase in MIS radiosensitization; an increase in MIS induced hypothermia. Assuming no chemical interaction between PEN and MIS, these observations indicate that the intestinal microflora can influence the activity of MIS in vivo. Therefore their influence should be considered in all sensitizer-related studies in vivo. The observed reduction in the neurotoxic but not the radiosensitizing potential of MIS following PEN treatment indicates a therapeutic benefit.

Animals↗
PubMed1984

Adrenal/parathyroid regulation of DNA, collagen and protein synthesis in rat epiphysial cartilage and bone.

Young, growing rats which had been chronically (2 weeks) adrenalectomized or parathyroidectomized were used to define the roles of the adrenal and parathyroid glands on the maintenance of normal circadian rhythms of DNA, collagen and non-collagen protein synthesis in the skeleton. The animals were conditioned to food being available ad libitum and to 12 h light: 12 h darkness (lights on from 08.00 to 20.00 h). The pace of DNA, collagen and non-collagen protein synthesis in different regions of the tibia (tibial growth cartilage, metaphysial bone and diaphysial bone) was measured by the in-vivo incorporation of tritiated thymidine (1 h) and radioactive proline (48 h). In intact rats there were no regional differences in the phasing of the circadian profiles; peak DNA and non-collagen protein synthesis occurred at the onset of the dark period while peak collagen synthesis occurred during the middle of the period of light. Adrenalectomy selectively abolished the regional DNA synthesis rhythms without altering the phases of the serum Ca and phosphorus (P) rhythms, which peak at mid-day and at the onset of darkness respectively. Parathyroidectomy abolished the regional rhythms for collagen and non-collagen protein synthesis and serum Ca rhythms, without altering the phase of the serum P and corticosterone rhythms. Dietary Ca-lactate supplements, which raised serum Ca levels towards normal in parathyroidectomized rats, were able to correct serum corticosterone values but did not normalize bone collagen and non-collagen protein synthesis values. These data indicate that the adrenal rhythm governs the proliferative activities of bone and cartilage cells, and that parathyroid hormone is essential to maintain normal collagen and non-collagen protein synthesis rhythms.

Adrenal Glands↗
PubMed1984

The effects of spaceflight on the mineralization of rat incisor dentin.

The lower incisors of Male Wistar rats flown for 18.5 days on the Soviet Cosmos-1129 Biosatellite were sectioned and chemically analyzed with an electron microprobe in order to determine whether there were specific effects of spaceflight on dentin formation/mineralization. Control tissues were obtained from rats housed under identical conditions in a land-based mock-up of the Biosatellite. The profiles of calcium (Ca), phosphorus (P), and sulfur (S) concentrations in dentin were measured in continuous traverses (1.0 micron intervals) from the pulp to the dentinoenamel junction. The incisor dentin formed during spaceflight had higher than normal (at 1G) concentrations of Ca (+ 10-15%) and P (+ 20-30%), particularly in the temporally youngest tissues within 80 micron of the pulp which had been least affected by secondary mineralization. The S-concentration profiles tended to decrease with tissue age. Fourier analysis (to determine the growth rhythms) revealed abnormal distributional patterns of S in the recently formed dentin from the Flight rats. The sulfur fluctuations in Flight animals alone periodically peaked above the irregular background fluctuations. These observations indicate that spaceflight has measureable effects on dentinogenesis, and they may also bear on the problem of the regulatory role of proteoglycans in mineralization and in the maturation of mineral and matrix moieties in skeletal tissue.

Animals↗
PubMed1984

Mineralization in rat metaphyseal bone exhibits a circadian stage dependency.

Density gradient fractionation analysis of rat metaphyseal bone was used to delineate the biorhythmic changes in bone matrix mineralization. Seventy-two 4-week-old rats were entrained to 12-hr light, 12-hr dark cycles (light, 0800-2000 hr; darkness, 2000-0800 hr) for 4 weeks. All animals were fed ad lib. on Purina laboratory rat chow and tap water. Groups of 10-12 rats were killed by cervical dislocation at 4-hr intervals during a 24-hr period, and the tibias were then biopsied and frozen in liquid N2. Metaphyseal bone was fractionated via bromoformtoluene density gradients into specific gravity fractions ranging from 1.7 to 2.8. Density gradient fractions were analyzed for concentrations of calcium and inorganic phosphorus. Chronograms indicated that the accumulation of both calcium and inorganic phosphorus into the newly forming/least-dense mineral moieties of bone (1.3-1.7 sp grav) showed a single peak in the biorhythm of the rat. A statistically significant circadian rhythm of mineralization was detected for calcium (P less than 0.001) and inorganic phosphorus (P less than 0.039), with peaks during the environmental dark span. These results suggest that the physiological phasing of bone mineralization in the light-dark synchronized rat, is similar to that previously noted for cartilage mineralization and is antiphasal to the midday peak in bone collagen synthesis.

Animals↗
PubMed1984

Salter innominate osteotomy. The effect of blood supply to the roof of the acetabulum.

Quantitative studies of blood flow (hydrogen washout technique) and bone mineralization rate (tetracycline labeling) were performed in the ilium of 23 immature dogs before and after Salter innominate osteotomy. The vascular anatomy, blood flow rate, and mineralization rate (appositional bone growth) on the roof of the acetabulum were disturbed after operation. Radiographic healing and normal patterns of circulation to the ilium were partially restored within two weeks and completely restored after six weeks. The data suggest that a single iliac osteotomy is without long-term consequence to the viability of acetabular bone.

Acetabulum↗
PubMed1983

Plugged haversian canals and local dose in radium cases.

Haversian canal plugging is a common lesion in bone from human radium cases, signaling vascular damage. Its incidence is correlated with the whole body radium dose. However, since the vascular supply to bone forms an extensive anastomotic plexus facilitating propagation of vascular damage from a primary site of high radium content, we do not know if the degree of plugging is related to the local bone dose. In this report, we compare the incidence of plugging of osteons in different regions (16 sections) of humeri of three radium cases with terminal 226Ra body contents of 0.203, 1.03 and 15.4 muCi to the local dose of radium in adjacent bone sections. While the first and third subjects had received 226Ra only, the second had had a large intake of 228Ra as well. The background incidence of plugging in 35 "normal" humeri from dissecting room populations (45-90 yr) ranged from 0 to 1%, with an average of 0.3%. The least squares linear regression equation for the relation between the percent of canals plugged (PCP) and dose, PCP = (0.00214 +/- 0.00014) rad + (3.26 +/- 3.6), predicts for our three radium cases a development of about 0.002% plugs/rad. The correlation coefficient was very high (r = 0.97, n = 16, P less than 0.01). When normalized to radiation dose from the two decay series, 226Ra and 228Ra appear to be equally effective in producing plugged canals.

Adult↗
PubMed1983

Effect of spaceflight on the non-weight-bearing bones of rat skeleton.

Male Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellite. They were injected with tetracycline for a second and third time on the 6th and 27th days, respectively, after recovery of the Biosatellite. Spaceflight did not alter the rate of periosteal bone formation in the non-weight-bearing ribs and regions of the mandibles, which were covered by masticatory muscles. Bone formation-calcification rates were impaired at those sites in the jaw that had no contiguous muscle (molar region). The remodeling activity on the alveolar bone around the buccal roots of the molar teeth was significantly reduced but without creating a negative balance between formative and resorptive activities. Total Ca, P, and hydroxyproline concentrations in the jaws, incisors, and ribs were normal after spaceflight, but gravity density fractionation studies indicated that in the jaws alone, O-G conditions caused a delay in the maturation of bone mineral and matrix. A 29-day postflight recovery period at earth's gravity was sufficient to fully correct these anomalies. Relative to tooth formation, relatively normal circadian and infradian biorhythmic periodicities of Ca and P in dentin and enamel were maintained during spaceflight. We conclude that most of the non-weight-bearing bones of the rat skeleton are at risk to the effects of hypogravity.

Animals↗
PubMed1983

Meal timing as a Zeitgeber for skeletal deoxyribonucleic acid and collagen synthesis rhythms.

Meal timing protocols were used to probe the circadian regulation of DNA and protein synthesis in the rat tibia. Two groups of 4-week-old rats were entrained to 12-h light, 12-h dark cycles (light, 0800-2000 h; darkness, 2000-0800 h) for 4 weeks. One group was fed for 4 h at the onset of the light span (EL). The other group was fed for 4 h at the onset of the dark span (ED). Forty-eight hours before death, the rats were injected ip with 0.015 microCi/g BW [14C]proline [collagen and noncollagen protein (NCP) synthesis], and they received 0.25 microCi/g BW [3H] thymidine (DNA synthesis) 1 h before death. Groups of 10-12 rats were bled from the abdominal aorta at 4-h intervals under light ether anesthesia (1-2 min/rat) during 2 consecutive 24-h periods, and the tibias were then biopsied and frozen in liquid N2. Serum samples were analyzed for calcium, inorganic phosphorus, and immunoassayable levels of corticosterone (CS), PTH, and calcitonin. Epiphyseal cartilage and metaphyseal and diaphyseal bone were analyzed for DNA and acidic pepsin-digestible collagen. Chronograms indicated that DNA synthesis in cartilage and bone, along with serum CS, showed two approximately equal and positively correlated peaks, with the cycles for rats fed EL vs. ED being in approximate antiphase. The fit of a 12-h cosine curve was statistically significant in all cases (P less than 0.01). The acrophase peaks were: EL, 0800 and 2000 h; and ED, 1600 and 0400 h. These patterns were unrelated to those for NCP and collagen synthesis. EL and ED relationships for NCP synthesis were also antiphasal. A statistically significant circadian rhythm of collagen synthesis was detected in cartilage and bone of ED-fed rats (peak, 0800 h; nadir, 2400 h). In EL-fed rats, the 0800 h peak alone was muted. No consistent correlations were observed between serum calcium and phosphorus chronograms and those of cartilage and bone collagen and DNA synthesis. The results suggest that physiological alterations of CS in vivo serve to modulate cartilage and bone cell proliferation, but they do not seem to regulate the phasing of the net collagen synthetic rhythm.

Animals↗
PubMed1983

The effect of protracted tetracycline treatment on bone growth and maturation.

Mature female rhesus monkeys were used to evaluate the effects of a one-year course of tetracycline (50 mg/kg/day, intramuscularly) on the formation, maturation, and mineralization of mandibular bone. The bones from the treated group contained normal concentrations of calcium (Ca), inorganic phosphorus (Pi), and hydroxyproline (HO-Pr), and the treatment schedule did not alter the distribution (percentage) of total osteons into slightly, moderately, and highly mineralization classes. Tetracycline impairs bone mineralization and the subsequent maturation of the mineral and matrix moieties. The percentage of highly mineralized osteons labeled with tetracycline is subnormal. Density gradient fractionation studies indicate the presence of abnormally high Ca/Pi ratios in the temporally young newly formed bone mineral and somewhat higher ratios in the most mature bone fraction. Protracted tetracycline treatment at high dosages impairs bone growth and maturation in adult rhesus monkeys.

Animals↗
PubMed1983

Healing of canine femoral osteotomies. Effects of compression plates versus Eggers' plates.

The effects of rigid self-compressing plates were compared with the effects of less rigid internal contact splints on the healing characteristics of osteotomized canine femora. Radiographically, the rigid fixation afforded by the compression plate produced accelerated healing as compared with the less rigid fixation obtained with splints at two to four months. At six months there was little or no difference between the two groups. Comparison of the material biomechanical properties of the healing femora suggested that the repair tissue formed early after compression plating was stronger than the callus tissue that surrounded the less rigidly fixed femora. A comparison of the structural biomechanical properties of the bones suggested, conversely, that a stronger whole bone resulted from the less rigid fixation splint. The histomorphometric data showed that some cortical bone was lost under both types of fixation plates. However, the patterns of loss were not comparable. Use of rigid internal fixation led to loss of cortical bone after four to six months, while the less rigid fixation obtained with the Eggers splint produced mild intracortical resorption only. These observations point to the desirability of rigid internal fixation early in the healing process and the possible benefit of decreasing the rigidity of the fixation device as healing proceeds.

Animals↗
PubMed1983

Simulating certain aspects of hypogravity: effects on bone maturation in the non-weight bearing skeleton.

This study reports the effects of simulation of certain aspects of hypogravity (via partial skeletal unloading) on the growth and maturation of the non-weight bearing mandibles of 41-d and 1-yr-old rats. Partial skeletal unloading was effected by elevating the hindquarters (PULEH), and this simulation was controlled with normally loaded animals fed either ad libitum or the average amount of food consumed by the the experimental group (group-mean fed). The chemical status of the mandibles after 10 d or 14 d PULEH closely resembled that of control rats. The younger PULEH rats and their group-mean fed controls demonstrated a trend toward impaired maturation of mineral and matrix moieties; yet the concentrations of calcium (Ca) and phosphorus (P) expressed as a ratio to collagen hydroxyproline content were normally distributed within a density gradient profile which separates the mineral and matrix moieties into various age-dependent fractions. These data demonstrate that 10 d or 14 d PULEH in young or old rats, respectively, is not sufficient to elicit the maturation deficit observed in the mandibles of rats flown for 18.5 d in the Soviet Biosatellite Cosmos-1129. Unless the duration of PULEH is critical, the cephalad fluid shift which is common to PULEH and spaceflight animals cannot be solely responsible for the flight-induced maturation deficit. Because the mandibles of the PULEH rats remain antigravity-postured, the results emphasize the importance of gravity unloading to the impairment of mandibular bone matrix/mineral maturation during spaceflight. Decreased gravity and, hence, gravity unloading cannot be mimicked in ground-based models of hypokinesia.

Age Factors↗
PubMed1982

A cellular investment of bone marrow.

We describe a method for clearly separating the cell layers at the bone-marrow interface, which reveals that the myeloid tissue is invested by an epithelial-like layer of specialized squamous cells we call the marrow sac. The scanning electron microscope showed that the sac was fenestrated and that some of its cells pass as perivascular elements with the marrow capillaries that penetrate the bony cortex. The transmission electron microscope (TEM) showed that the cells comprising the marrow sac are less than 0.1 micrometer thick, overlap at their margins without specialized cell junctions, and are more electron dense than the reticular or fibroblastic cells of the marrow stroma. The fenestrations in the sac were intercellular and were usually occupied by cells having an ultrastructure compatible with an osteoprogenitor cell (OPC) lineage. The observation of a close proximity between the cells of the marrow sac and the osteogenic cells that line the endosteal surfaces of bone suggest that the sac cells, along with the OPCs of the superficial marrow stroma, should be included in any morphological or functional definition of an endosteum.

Animals↗