Search PubMed⌕ Search

Biomedical subjects

D D Thompson

Publications and source records attributed to D D Thompson.

At least 55 records · Page 3Linked to original sources
PubMed1992

The bisphosphonate, alendronate, prevents bone loss in ovariectomized baboons.

We examined the effect of the amino bisphosphonate alendronate, administered IV every 2 weeks at 0.05 and 0.25 mg/kg for 1 year, on bone loss and parameters related to bone metabolism in ovariectomized baboons. Relative to non-OVX animals, the OVX baboons experienced increased bone turnover, reflected in biochemical and histomorphometric measurements, and bone loss assessed by dual-beam absorptiometry in the lumbar spine, which was similar to changes observed in ovariectomized women. Alendronate treatment maintained all parameters of bone turnover at control (nonovariectomized) levels and prevented the bone loss in a dose-dependent manner. We concluded that ovariectomized baboons offer a suitable model for the bone changes observed in ovariectomized women and that these changes can be prevented by sustained administration of an appropriate dose of this aminobisphosphonate.

Acid Phosphatase↗
PubMed1991

Method for transilial bone biopsy in baboons.

A surgical method for obtaining transilial bone biopsy specimens in baboons that provides adequate amounts of trabecular and cortical bone for histomorphometric analysis was developed. Biopsy specimens were removed from a site on the craniodorsal portion of the ilium by use of an 8-mm trephine.

Animals↗
PubMed1991

The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats.

Estrogen deficiency in mammals is known to increase bone turnover and result in reduced bone mass. The bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphophonic acid disodium salt, alendronate (MK-217), is a potent inhibitor of bone resorption and was evaluated in this study for its ability to inhibit bone loss following ovariectomy in rats. Alendronate was administered sc in doses of 0.0, 0.056, 0.28, 1.40, and 7.0 mg P/kg/month, divided into two, four, or eight monthly subcutaneous injections for each dose, to female Sprague-Dawley rats (250-280 g) that underwent bilateral ovariectomy. Rats were sacrificed 12 weeks postovariectomy, the femora ashed, and the tibiae prepared for static and dynamic histomorphometric analyses. Femoral bone mass in vehicle-treated rats was reduced by 12% 12 weeks after ovariectomy compared to the nonovariectomized control group. In MK-217-treated rats femoral bone mass was significantly increased in a dose-dependent manner compared to either ovariectomized or nonovariectomized controls. Histomorphometric analysis showed significant increases in tibial trabecular bone volume with no decrease in osteoclast number. Doses delivered twice per month or eight times per month were equally effective in achieving the peak bone volume 12 weeks after ovariectomy. In conclusion, alendronate (MK-217) was effective in inhibiting bone loss due to estrogen deficiency in rats, and the magnitude of its effect was related primarily to the total amount of compound administered rather than the frequency of its administration.

Alendronate↗
PubMed1991

Depression of osteoblastic activity in immobilized limbs of suckling rats.

Recently we characterized the immobilization-related osteopenia in adult rats and showed that it is caused by increased bone resorption and decreased bone formation (Weinreb et al. 1989 Bone 10:187). To assess the effect of age on disuse osteopenia, this study investigated the effects of immobilization on bone turnover in very young, suckling rats. The 15-day-old rats underwent unilateral hind limb immobilization by sciatic neurectomy; the contralateral limb was left intact and served as control. Experimental or sham-operated animals were killed after 0, 2, 4, or 12 days postsurgery. Dry, fat-free weight and ash weight were determined in both femora, and both tibiae were subjected to static and dynamic histomorphometry. Immobilization caused a progressive deficit in bone mass in the immobilized limb compared to the contralateral intact limb but did not affect femoral longitudinal growth. The total mineral content in the immobilized femora was 13.6% less than that in the intact limb by day 12. Concomitantly, tibial cancellous bone area and perimeter declined in the immobilized limb by 37.3 and 32.2%, respectively. This reduction in bone mass in the tibiae of immobilized limbs was associated with increased bone resorption, expressed as osteoclast perimeter, number of osteoclasts per mm surface, and number of osteoclasts per mm2 tissue area. Bone formation was reduced as a result of impaired osteoblast activity as evidenced by (1) decreased endocortical and trabecular mineral apposition rate; (2) reduced trabecular mineral formation rate; (3) decreased percentage of ash of the femoral dry weight; and (4) increased volume of unmineralized osteoid in the tibial metaphysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Immobilization-related bone loss in the rat is increased by calcium deficiency.

The object of this study was to investigate whether a calcium-deficient diet increases the bone loss produced by mechanical hypofunction (disuse) in the rat. Male Sprague-Dawley rats of approximately 150 g were placed on either a normal diet or a calcium-deficient diet. After 7 days, all rats underwent unilateral hind-limb immobilization by sciatic neurectomy and were sacrificed 30 hours, 72 hours, or 10 days postsurgery. Femora were ashed and the total mineral content (ash weight) was determined. Tibiae were embedded, sectioned, and stained. The metaphyseal secondary spongiosa and the diaphyseal cortical bone were subjected to histomorphometric analysis. Femoral length and serum calcium were not affected by calcium intake or immobilization. Serum parathyroid hormone levels were elevated in rats on the calcium-deficient diet compared to those on the normal diet. Calcium deficiency caused a significant reduction in femoral ash weight (20-35%), tibial cortical thickness (16-20%), and trabecular bone volume (TBV) (33-39%) at 72 hours and 10 days postsurgery. Additional loss of bone mass occurred in the immobilized limb compared to the contralateral intact limb of both dietary groups. This loss occurred earlier (30 hours postsurgery versus 72 hours) in the animals on a calcium-deficient diet and was larger compared to animals on a normal diet (10.6% versus 4.8% at 72 hours and 17.9% versus 12.45% at 10 days). The total bone loss induced by the combination of a calcium-deficient diet and immobilization in this experiment was estimated to equal 46% of femoral ash weight and 79% of tibial TBV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts.

Alendronate↗
PubMed1990

Patterns of skeletal histologic change through time: comparison of an archaic native American population with modern populations.

This paper compares patterns of histologic change in an archaic Native American population with those in modern white populations. Histologic sections were removed from core biopsies taken from the anterior femoral cortex of an archeologic sample of Pecos Indians. The data demonstrate many microstructural similarities between the Pecos and modern populations, even though they were genetically and culturally distinct. Pecos women had small Haversian canals and large osteon mean wall thickness, with no clear evidence of an intracortical bone volume deficit even in the older age groups, although significant marrow cavity expansion occurred in both males and females with age. No striking relationships were found between bone tissue changes and gross geometric changes with age. The data suggest that a more active life-style is associated with greater osteon mean wall thickness or osteon population density, but that it alone does not protect against significant bone loss on the cortical-endosteal surface.

Adult↗
PubMed1990

Aminohydroxybutane bisphosphonate inhibits bone loss due to immobilization in rats.

The purpose of this study was to document the effects of aminobutane bisphosphonate (AHBuP) on bone remodeling during immobilization in rats. Male Sprague-Dawley rats underwent unilateral sciatic neurectomy after receiving two daily subcutaneous injections of 0, 0.01, 0.10, or 1.0 mg P per kg AHBuP. Rats were sacrificed at 24 h or 10 or 20 days postimmobilization. Femora were ashed and tibiae were prepared for histomorphometric analysis. AHBuP was effective in inhibiting bone loss due to immobilization in a dose-dependent manner. The percentage loss of femoral ash weight due to immobilization decreased in a dose-dependent manner. In vehicle-treated rats, there was a significant decrease in trabecular bone volume (TBV) in the immobilized tibiae compared to the normal tibiae; in AHBuP-treated rats there was a dose-dependent increase in TBV both in the immobilized and control tibiae. The osteoid surface extent was decreased in AHBuP-treated rats in a dose-dependent manner. The mineral apposition rate was altered only in the intact leg of rats treated with 0.1 and 1.0 mg P AHBuP per kg compared to vehicle treated. Osteoclast number per mm was reduced by AHBuP treatment. In conclusion, aminohydroxybutane bisphosphonate effectively prevented the bone loss due to immobilization in this system.

Alendronate↗
PubMed1989

Osteopenia in the immobilized rat hind limb is associated with increased bone resorption and decreased bone formation.

The lack of mechanical function (disuse) caused by paralysis, immobilization or weightlessness, leads to osteopenia. This study examines the contribution of bone resorption and bone formation to osteopenia of disuse, during six weeks of limb-immobilization in the growing rat. Male Sprague-Dawley rats of approximately 200 g underwent unilateral hind-limb immobilization by either tenotomy at the knee joint or sciatic neurectomy, while control rats were sham-operated. Animals were sacrificed at 30 and 72 hours, 10, 26 and 42 d postsurgery. Femora were ashed to determine the total mineral content and histomorphometric parameters, static and dynamic, were measured in the secondary spongiosa of the proximal tibial metaphysis. No difference was found in the femoral length of the immobilized legs. Bone loss in the immobilized leg versus the nonimmobilized one, at 10, 26 and 42 d post-surgery was 18.0, 14.0 and 11.2% of femoral mineral content in the tenotomy group, respectively, and 12.4, 16.1 and 15.7% in the neurectomy group. Loss of metaphyseal trabecular bone volume at 10, 26 and 42 days amounted to 67.8, 49.3 and 52.9% in the tenotomy group, respectively, and 70.5, 59.0 and 72.9% in the neurectomy group. The bone loss was caused by: (a) A rapid surge in bone resorption, reflected in a significant increase in the number of osteoclasts per mm bone surface at 30 and 72 h and in the osteoclast surface at 72 h but not at later times, and (b) a sustained decrease in bone mineral apposition rate and bone formation rate (osteoblast-referent) throughout the 42-day immobilization period suggesting osteoblastic hypofunction (reduced activity).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Indomethacin inhibition of tenotomy-induced bone resorption in rats.

Loss of biomechanical function results in rapid bone loss. This study assesses the role of arachidonic acid metabolites in immobilization-related osteopenia. A hind limb of the rat was immobilized by knee tenotomy and bone resorption and formation parameters were quantitated by histological methods in indomethacin-treated (0.5 mg/kg per day) and vehicle-treated animals. Control animals sacrificed 30, 72, and 240 hr post-tenotomy revealed a significant increase in osteoclast number (30 hr) and resorption surfaces (72 hr) and a decrease in trabecular bone volume (240 hr) in the tenotomized tibiae. In the indomethacin-treated tibial metaphysis, no significant differences were noted for these parameters by comparison to the nontenotomized leg. Bone formation parameters remained reduced in the tenotomized legs of both the indomethacin and vehicle-treated groups compared to the control legs. Indomethacin inhibited bone resorption, but did not prevent the decrease in bone formation produced by immobilization over the 10 days of these experiments.

Animals↗
PubMed1988

Direct action of the parathyroid hormone-like human hypercalcemic factor on bone.

Peptides containing residues 1-34 of the human parathyroid hormone (PTH)-like hypercalcemic factor (hHCF), termed hHCF-(1-34)-NH2, produce effects similar to those of PTH in several biological systems in vitro and in vivo. However, there is conflicting evidence regarding the potency of hHCF on bone and, by implication, its role in calcium mobilization and the skeletal contribution to tumor-associated hypercalcemia. To resolve this conflict, the effects of infusing either hHCF-(1-34)-NH2 or a peptide containing residues 1-34 of bovine PTH [bPTH-(1-34)] into unrestrained thyroparathyroidectomized rats on a low calcium diet were compared. Direct effects on bone histology and serum calcium levels, which are totally dependent on calcium mobilization from bone in these animals, were examined. bPTH-(1-34) and hHCF-(1-34)-NH2 were equipotent in producing dose-dependent calcium mobilization from bone. At an infusion rate of 0.1 nmol/hr, both peptides produced hypercalcemia and extensive nephrocalcinosis. Histomorphometric analysis of tibiae from these animals after 48 hr of peptide infusion showed a dose-related increase in osteoclast number from 3-5 cells per mm2 at 0.01 nmol/hr to approximately equal to 32 cells per mm2 at 0.1 nmol/hr of hHCF or bovine PTH. These findings indicate that hHCF has a direct PTH-like effect on bone and, in this model system, the hHCF-(1-34)-NH2 is equipotent to bPTH-(1-34).

Animals↗
PubMed1988

Male fertility and the undescended testis in Down syndrome. How to counsel parents.

Evaluation of fertility in male patients with Down syndrome has generally revealed poor psychosexual adaptation and markedly abnormal semen quality, which have thus far been uniformly associated with sterility. Up to 50% of male patients with Down syndrome have undescended testes. Life-table analysis of survival among patients with Down syndrome, as well as the low incidence of testicular tumors, would suggest that orchidopexy may be unnecessary in some patients. In most patients, however, orchidopexy is appropriate to allow for subsequent testicular examination. Parents of children with Down syndrome must be appropriately counseled regarding the fertility of their children and the treatment options for cryptorchidism.

Counseling↗
PubMed1988

A tumor-secreted protein associated with human hypercalcemia of malignancy. Biology and molecular biology.

This investigation addresses a theoretical concept of tumor pathogenesis proposed over 40 years ago, namely that malignancy-associated hypercalcemia can result from endocrine secretion by tumors of a PTH-like factor. These studies demonstrate that a fragment of hHCF alone, without added or tumor-secreted cofactors or hormones, can produce hypercalcemia and other biochemical abnormalities associated with HHM. The hypercalcemia can be generated by hHCF-(1-34)NH2 action on bone, although kidney and gut could contribute to the HHM syndrome when it occurs naturally. No other tumor-secreted peptide displays this biological profile. These studies establish one (PTH-like) mechanism by which human tumors could produce hypercalcemia. Furthermore, the finding that hHCF-(1-34)NH2 is more potent than PTH in some systems is of considerable interest for the future design of hormone analogs. A broad spectrum of biological properties of hHCF-(1-34)NH2, including production of components of the HHM syndrome, can be inhibited by a PTH antagonist. Because [Tyr-34]bPTH-(7-34)NH2 selectively and competitively occupies PTH receptors, our studies demonstrate formally that hHCF-(1-34)NH2 mediates some (and perhaps all) of its actions via receptors conventionally regarded as intended for interaction with PTH, but which actually may be present to allow for expression of bioactivity of both secreted proteins. Although some structural homology is shared by the two hormones and many contribute to interaction with receptors, the disparity in structure, especially within the 1-34 domains responsible for bioactivity in both hormones, is more pronounced. The similarity in biological profiles despite structural differences between hHCF and PTH is emphasized by the inhibitory action of [Tyr-34]bPTH-(7-34)NH2 against the tumor peptide even in the absence of much of the homologous region in the PTH antagonist. This investigation provides impetus for designing more potent antagonists, which must now be regarded more appropriately as inhibitors of both PTH and hHCF. Such antagonists may best be generated from hybrid structures of the two hormones. In any case, these studies establish a promising new approach to therapy of tumor-associated hypercalcemia.

Base Sequence↗
PubMed1987

Femoral diaphyseal histomorphometric age determinations for the Shanidar 3, 4, 5, and 6 Neandertals and Neandertal longevity.

Histomorphometric analysis of femoral diaphyseal fragments from the Shanidar 3, 4, 5, and 6 Neandertals provide age at death estimates of 41 (+/- 6.7), 36 (+/- 6.7), 40 (+/- 6.7), and 24 (+/- 6.7) years. These determinations are in agreement with previous macroscopic age assessments. Since the Shanidar 3, 4, and 5 (and slightly younger Shanidar 1) individuals are among the oldest known Neandertals, these age determinations suggest that significant postreproductive survival was rare among the Neandertals and a phenomenon primarily of anatomically modern humans.

Adult↗