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Biomedical subjects

R T Turner

Publications and source records attributed to R T Turner.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effects of short-term spaceflight and recombinant human growth hormone (rhGH) on bone growth in young rats.

The purpose of this study was to characterize the effects of short-term spaceflight and recombinant human growth hormone (rhGH) on bone growth in rapidly growing male rats. Bone growth was determined by dynamic bone histomorphometry and rhGH was administered using implanted ALZET osmotic pumps. Treatment with rhGH for 5 d had no effect on body weight but a 4-d spaceflight resulted in a small reduction in the rate of weight gain. Neither spaceflight nor rhGH altered bone length or the rate of bone elongation. In contrast, rhGH and spaceflight each resulted in site- and bone-specific increases (periosteal) and decreases (endocortical) in formation of cortical bone. The results demonstrate that: a) inhibition of periosteal bone formation observed during longer spaceflight is not apparent during a 4-d spaceflight; and b) infusion of rhGH stimulates cortical bone formation in weightless as well as in weight bearing animals.

Animals↗
PubMed1995

Spaceflight results in depressed cancellous bone formation in rat humeri.

Two experiments investigating the effects of short-term spaceflight on cancellous bone turnover were carried out: Physiological Systems Experiment-1 (PSE-1) (a 4-d orbital spaceflight) and PSE-2 (a 10-d flight). Cancellous bone area was not significantly altered by spaceflight in the humerus during either flight. The calculated bone formation rate was unchanged during the 4-d flight but decreased during the 10-d flight. The decrease in calculated bone formation during the longer flight was due to a combination of a statistically significant decrease in mineral apposition rate and a nonsignificant decrease in double label perimeter. The dynamic measurements suggest that spaceflight results in decreases in osteoblast number and activity. Further, the decreases in osteoblast perimeter and osteoid perimeter indicate that a 2-d reloading period was insufficient to restore bone formation to normal. Resorption of the preflight fluorochrome label was not influenced by spaceflight, suggesting that there was no net change in bone resorption. This conclusion is supported by the unremarkable effects of spaceflight on osteoclast number and osteoclast perimeter. Our findings indicate that short-term spaceflight results in depressed osteoblast number and/or activity. Continued decreases in bone formation with normal bone resorption could ultimately lead to cancellous osteopenia and reduced bone strength.

Animals↗
PubMed1994

The effect of long-term ovarian hormone deficiency on transforming growth factor-beta and bone matrix protein mRNA expression in rat femora.

Estrogen deficiency results in increased bone turnover and osteopenia. Decreased transforming growth factor beta (TGF-beta) has been implicated as having a role in ovariectomy (OVX)-induced bone loss; however the decrease in TGF-beta mRNA may simply be due to the reduction in cancellous bone volume that occurs following OVX. This investigation characterized the effect of long-term OVX (11.5 months) on mRNA levels for TGF-beta, osteocalcin (OC), and type I collagen (TYPE I) and expressed these data relative to the amount of cancellous bone surface. Additionally, the short-term effect of estrogen administration on TGF-beta, OC, and TYPE I mRNA was evaluated. OVX resulted in a 56% loss of bone surface. At the tissue level, TGF-beta was reduced, OC was increased, and TYPE I was unchanged. Expressed relative to bone surface, TGF-beta was unchanged and OC and TYPE I were significantly elevated. Four hours after estrogen administration, TGF-beta mRNA was unchanged compared to vehicle-treated controls. The data suggest that bone turnover is elevated after long-term OVX, but do not suggest a direct role of TGF-beta in OVX-induced bone loss.

Aging↗
PubMed1994

Cancellous bone turnover in growing rats: time-dependent changes in association between calcein label and osteoblasts.

Calcein was given to growing male rats to label mineralizing bone, and groups of animals were sacrificed from 6 h to 12 days later. Fluorochrome-labeled perimeter and osteoblast perimeter were determined in a growth-adjusted sampling site in the secondary spongiosa of the proximal tibial metaphysis. The best correspondence between calcein-labeled perimeter and osteoblast-lined perimeter was during the initial 24 h following administration of the label. This association decreased progressively thereafter because of (1) cessation of bone formation on fluorochrome-labeled surfaces and (2) initiation of new foci of bone formation. The time-dependent decline in osteoblast-lined trabeculae with adjacent calcein label exceeded the increase in osteoblast perimeter on nonfluorochrome-labeled trabeculae, indicating that there was a net decrease in osteoblast number. Fluorochrome-labeled perimeter and bone area showed parallel decreases with time after labeling, as a result of bone resorption. Interestingly, the decrease in cancellous bone was caused exclusively by a reduction in trabecular number. There was no change in trabecular thickness. The findings suggest that the decreased osteoblast number and progressive bone resorption resulted in complete erosion of trabeculae most distal to the growth plate. As a result of the nearly equal growth and destruction of trabeculae, there was no change in the length of the cancellous metaphysis with time. It is concluded that cancellous bone turnover in growing rats represents a maturation process that differs fundamentally from bone turnover in adults.

Animals↗
PubMed1994

Reduced chondroclast differentiation results in increased cancellous bone volume in estrogen-treated growing rats.

These studies were designed to investigate the role of altered growth processes in mediating estrogen-induced changes in cancellous bone volume in growing female rats. Ovariectomy resulted in an increase in the longitudinal growth rate of the tibia throughout the growth period and estrogen treatment of ovariectomized (OVX) rats resulted in a dose-dependent decrease in longitudinal growth. Estrogen treatment also resulted in decreases in growth plate thickness, chondroclast number in the zone of vascular invasion, and osteoclast number in the secondary spongiosa. There were simultaneous increases in mineralized cartilage in the zone of vascular invasion; total mineralized tissue, mineralized cartilage, and bone in the primary spongiosa; and bone in the secondary spongiosa. Ovariectomy increased and estrogen treatment of OVX rats decreased [3H]thymidine-labeled nuclei in chondroclasts after 24 h, but after 7 days, the labeling indices were similar in the OVX and intact groups and only slightly decreased in the estrogen-treated rats. We interpret these results as evidence that estrogen impairs chondroclast differentiation. We propose that this impairment leads to decreased chondroclast number and reduced resorption of mineralized cartilage in the zone of vascular invasion, which, in turn, results in an increased cancellous bone volume.

Aging↗
PubMed1994

The effects of raloxifene on tibia histomorphometry in ovariectomized rats.

Tissue-specific estrogen agonists may be useful in protecting against osteoporosis and the increased risk of coronary heart disease in postmenopausal women with minimal undesired effects on reproductive tissues. The actions of the mixed estrogen agonist/antagonist raloxifene on selected estrogen target tissues were determined in ovariectomized (OVX) rats immediately postovariectomy. Five groups of 75-day-old Sprague-Dawley rats were studied; baseline controls, sham-operated controls, OVX controls, OVX animals treated with estrogen (0.1 mg 17 alpha-ethynyl estradiol/kg.day), and OVX animals treated with raloxifene (3 mg/kg.day). Fluorochrome labels were given on days 1, 28, and 34. The baseline controls were killed on day 2, and the remaining groups on day 35. Ovariectomy increased tibial longitudinal growth rate as well as measurements related to radial growth and cancellous bone turnover. Ovariectomy decreased cancellous bone area and uterine weight, and increased serum cholesterol, bone elongation, and radial bone growth. Estrogen treatment prevented these changes in OVX rats. Raloxifene prevented cancellous osteopenia as well as the changes in radial bone growth, bone resorption, and blood cholesterol, but was less effective in reducing cancellous bone formation and did not prevent uterine atrophy. These findings suggest that raloxifene is a target-specific, mixed estrogen agonist/antagonist. At the concentration studied, raloxifene had potent estrogenic activity on bone resorption and serum cholesterol, a lesser effect on bone formation, and minimal activity on uterine wet weight.

Aging↗
PubMed1993

Mechanism of action of estrogen on cancellous bone balance in tibiae of ovariectomized growing rats: inhibition of indices of formation and resorption.

Ovariectomy results in cancellous osteopenia in rat long bones, a condition that is prevented by treatment with estrogens. The purpose of these studies was to clarify the effects of estrogen on cancellous bone turnover using dynamic bone histomorphometry. Treatment of ovariectomized rats with diethylstilbestrol (DES) reduced the mineral apposition rate, double-label perimeter, osteoblast number, and osteoclast number, suggesting that the hormone had inhibitory effects on bone formation as well as bone resorption. However, we could not estimate the bone formation rate because of rapid resorption of tetracycline-labeled bone in the ovariectomized rat. The magnitude of loss was documented by a time course study: 58% of the tetracycline initially incorporated into the secondary spongiosa of the tibial metaphysis was resorbed after 11 days and 89% was resorbed after 22 days. Similarly, cancellous bone area was decreased by 67% after 11 days and by 88% after 22 days. Administration of either DES or tamoxifen (TAM) dramatically reduced resorption of tetracycline as well as the decrease in cancellous bone area. These results demonstrate that (1) estrogen prevents osteopenia in ovariectomized (OVX) rats, in part by inhibiting bone turnover, (2) TAM is an estrogen agonist on bone resorption, and (3) resorption of tetracycline-labeled bone leads to serious underestimation of the bone formation rate in OVX rats.

Animals↗
PubMed1993

Prostaglandin E2 administered by subcutaneous pellets causes local inflammation and systemic bone loss: a model for inflammation-induced bone disease.

The effects of prostaglandin E2 (PGE2) given in controlled-release pellets or by daily sc injection for 21 days on mineral homeostasis and bone histomorphometry were compared in 7-week-old female rats. Sham operation and ovariectomy were performed at the beginning of the studies. In experiment 1, 7.5 mg PGE2 or drug-free, controlled-release pellets were implanted sc at the back of the neck on day 7. In experiment 2, 3 mg/kg body weight of PGE2 or vehicle was injected sc daily beginning on day 7. The animals were sacrificed on day 28 of the two experiments, and the tibiae were removed for histomorphometric analysis of the diaphysis and metaphysis. When administered by pellets in experiment 1, PGE2 lowered serum 1,25-dihydroxyvitamin D and did not influence weight gain, serum calcium, phosphorus, or magnesium, cross-sectional or medullary areas, periosteal bone formation and apposition rates, endosteal bone formation and apposition rates, or endosteal tetracycline-labeled perimeter. PGE2 lowered cancellous bone area and cancellous bone perimeter in both the sham-operated and ovariectomized rats. In contrast, when administered by sc injection in experiment 2, PGE2 reduced weight gain, increased serum magnesium, increased cortical area, and reduced medullary area without changing cross-sectional area, increased periosteal bone formation and apposition rates and endosteal bone and apposition rates, did not alter endosteal tetracycline-labeled perimeter, and increased cancellous bone area and cancellous bone perimeter in both sham-operated and ovariectomized animals. PGE2 produced local inflammation when given by pellets, and the serum concentration of 13,14-dihydro-15-ketoprostaglandin E2, the major metabolite of PGE2, increased when PGE2 was given by sc injection but not when administered by pellets. Thus, PGE2 given sc by controlled-release pellets (1) produces local inflammation and systemic bone loss without increasing PGE2 systemically and (2) provides a model for inflammation-induced loss of cancellous bone. The results also indicate that the pellet is not a valid means for the delivery of PGE2 to the general circulation.

Analysis of Variance↗
PubMed1993

Fate of ultrahigh molecular weight polyethylene (UHMW-PE) wear debris in patients with hip implants.

The process of ultrahigh molecular weight polyethylene (UHMW-PE) breakdown, started at the articular surface of the cup, continues in small fragments after generation. An assiduous interaction between the UHMW-PE particles and the host cells leads to oxidative changes of the UHMW-PE and to size reduction of the particles simultaneous with transporting them toward, and finally by, lymphatic or blood vessels. The particles are mobilized by means of enzymatic, extracellular matrix-degrading activity of cells that have phagocytosed them or adhered to them. Together, these characteristics indicate an attempt by the natural cellular immunity system to eliminate the implant wear debris. Macrophages are the main effector cells acting as scavengers; however, excessive amount of the wear debris evokes phagocytic activity of cells other than macrophages as well.

Alloys↗
PubMed1993

Restriction-site PCR: a direct method of unknown sequence retrieval adjacent to a known locus by using universal primers.

Fast acquisition of unknown nucleotide sequences around a known sequence has important implication in molecular biology, especially in genome mapping. We have developed a method, termed restriction site polymerase chain reaction (RS-PCR), that utilizes specially designed primers that recognize, anneal, and sustain PCR. These primers, termed restriction site oligonucleotides (oligonucleotide primers specific for a given restriction enzyme recognition sequence or RSOs), could be generated corresponding to any restriction enzyme irrespective of the length of the recognition site and used as PCR primers corresponding to the unknown region of a DNA segment. In this method a first round of PCR is carried out in different tubes with a set of RSOs and a primer specific to the known region. A second round of PCR is then performed on the products of the first PCR with the same RSOs and another specific primer internal to the first one. Subsequently, the products of the last round of PCR are transcribed with an appropriate RNA polymerase and sequenced with a reverse transcriptase with an end-labeled specific primer internal to the second specific PCR primer. To demonstrate the applicability of RS-PCR in retrieving unknown sequences around a known sequence, we have used a set of four RSOs and three specific primers representing the known sequence and have successfully obtained hitherto unknown factor IX sequences (12 of 12 times) from three species starting from genomic DNA. The sequences obtained indicate the presence of a conserved stretch of 20 nucleotides in the 3' noncoding region of the factor IX gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Estrogen does not increase bone formation in growing rats.

The purpose of these experiments was to test the hypothesis that estrogen has an anabolic effect on cancellous bone formation in long bones of growing rats. In the present studies, estrogen decreased measurements related to cancellous bone formation, including osteoblast number, fluorochrome-labeled bone perimeter, and incorporation of [3H]proline into osteoid. Steady state mRNA levels for bone matrix proteins and mineral apposition rate were unchanged or reduced. The [3H]thymidine labeling index for osteoblasts was very low and was reduced by estrogen treatment. Finally, estrogen decreased the rate of removal of tetracycline previously incorporated into cancellous bone as well as the growth-dependent decrease in cancellous bone area, indicating that hormone treatment reduced net bone resorption. In summary, no evidence was secured to support the hypothesis that estrogen has an anabolic action on bone formation; the results obtained in these studies consistently demonstrated a pronounced inhibitory action of the hormone on bone turnover.

Animals↗
PubMed1993

Evidence that estrogen binding sites are present in bone cells and mediate medullary bone formation in Japanese quail.

Studies were carried out in Japanese quail to characterize the binding of estrogen to bone cells and to determine whether induction of medullary bone by estrogen is mediated by estrogen receptors. First, attempts were made to identify specific, high affinity nuclear binding sites for estrogen with a nuclear exchange assay in oviduct and femora from laying female quail and in liver, kidney, and femora from adult male quail treated with estradiol valerate (2 mg per bird). High-affinity nuclear estrogen binding sites were detected in each of the tissues except femora. Second, estrogen binding sites in femora from male quail were localized by radioautography after treatment with 100 microCi of [3H]-17 beta-estradiol ([3H]-E). Estrogen binding sites were present at 1 and 3 h after administration of [3H]-E, and binding of the radiolabeled hormone was prevented by the simultaneous administration of an excess of radioinert estrogen. Third, estradiol valerate (.4 mg) was given as a bolus to adult male Japanese quail. Five days later, the quail had hypercalcemia due to accumulation of phosvitin in serum, had an extensive network of medullary bone at the femur midshaft, and had reduced cortical bone area. The nonsteroidal, anti-estrogen tamoxifen (2 mg/day) prevented estrogen-induced hypercalcemia, medullary bone formation, and reduction of cortical bone area. Fourth, the estrogen target cells in femora from adult male quail that were induced to differentiate to osteoblasts by estrogen treatment were located by [3H]-proline radioautography as early as 12 h following administration of the hormone. These results are interpreted as evidence that induction of medullary bone is a process mediated by estrogen receptor.

Animals↗
PubMed1992

Effects of gallium on bone in the rat.

Gallium nitrate lowers the serum calcium in patients with hypercalcemia caused by malignancy and is available for clinical use. The mechanism for the hypocalcemic action is unknown, however. The present studies were undertaken to determine the effects of gallium on bone metabolism. Normal male rats were implanted subcutaneously with mineralized allogeneic bone matrix. Histomorphometry of the implants and of tibiae was determined after three doses of tetracycline administered at intervals of 1 week. Gallium as nitrate was administered daily by intraperitoneal injection at doses of 0.9, 1.8, and 3.6 mg elemental gallium per kg body weight for 21 days in one study and at 3.5 mg/kg for 33 days in a second study. All the gallium-treated rats gained weight. Rats given gallium at doses of 3.5 mg/kg or more grew at a lower rate than untreated controls (-7 and -10% at doses of 3.5 and 3.6 mg/kg, respectively; p less than 0.05). At a dose of 0.9 mg/kg, gallium did not inhibit bone resorption or lower serum calcium but inhibited bone formation by 32% and bone apposition by 36% at the endosteal surface of the tibia. At a dose of 1.8 mg/kg, gallium produced modest hypocalcemia, prevented a rise in circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D], inhibited bone resorption in implants, and inhibited bone formation by 19% and bone apposition by 18%. At a dose of 3.5 mg/kg, gallium lowered the serum calcium and serum 1,25-(OH)2D, inhibited growth, and accentuated the antiresorptive and antiformative effects seen at the two lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Tissue-specific expression of bone proteins in femora of growing rats.

Total cellular RNA was extracted from bone cells of three different femoral compartments of 2-mo-old rats. The intact femora were first incubated with collagenase to obtain periosteal cells. The bisected periosteum-free diaphyses and metaphyses were then incubated with collagenase to obtain enriched populations of endosteal and cancellous bone cells, respectively. The total cellular RNA from these three tissues was separated by size using agarose gel electrophoresis, transferred to nylon filters, hybridized to 32P-labeled cDNA probes for glyceraldehyde-3-phosphate dehydrogenase (GAP), pre-pro-alpha (I) type I collagen (collagen), osteocalcin (BGP), and alkaline phosphatase (AP), and the cDNA/mRNA hybrids were visualized by radioautography. Bone matrix deposition was measured in each tissue compartment by tetracycline-based dynamic bone histomorphometry. The bone formation and apposition rates were greatest in the periosteum and least in metaphysis. Mean mRNA levels for collagen and BGP were positively correlated with mean bone formation and mineral apposition rates. Interestingly, mean AP mRNA levels were not correlated with indexes of bone formation. These results demonstrate that the steady-state mRNA levels for bone matrix proteins in femora show pronounced site specificity and correlate with the rates of bone matrix deposition.

Animals↗
PubMed1992

Disuse osteopenia is accompanied by downregulation of gene expression for bone proteins in growing rats.

Unilateral sciatic neurectomy (USN) resulted in cortical osteopenia in tibiae from the sciatic nerve-sectioned limb of growing rats. The bone deficit resulted from decreased periosteal addition; there were no changes in the indexes of bone resorption. The periosteal bone formation rate was reduced in the nerve-sectioned limb within 7 days of sciatic neurectomy, and this decrease persisted for at least 56 days. Steady-state mRNA levels for bone proteins were determined in periosteum isolated from tibiae and femurs 7 and 14 days after sciatic nerve section. Nerve section resulted in decreased levels of mRNA for osteocalcin, alkaline phosphatase, and possibly the prepro-alpha (I)-subunit of type I collagen (collagen). The effects were more pronounced in tibiae than femurs, corresponding to the greater degree of immobility induced by USN in the former bone. The results demonstrate that decreased bone formation precedes establishment of disuse cortical osteopenia in growing rats with no evidence for a change in bone resorption. Furthermore, the decreased bone formation is associated with, and may be due to, reduced mRNA levels for matrix proteins and other important bone proteins.

Aging↗