bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue and urokinase plasminogen activators in bone tissue and their regulation by parathyroid hormone
Authors: Leloup Gaetane , Peeters-Joris Chantal , Delaisse Jean-Marie , Opdenakker Ghislain , Vaes Gilbert 
Published: February 2010

Abstract
The identification of the plasminogen activator (PA) types present in bone and the regulation of their activity by parathyroid hormone (PTH) were investigated in cultures of fetal mouse calvariae with the use of either a chromogenic substrate or a zymographic assay. PA was detected essentially in the tissue extracts of the explanted bones, with only 1–2% of the total activity released in the surrounding culture media. From their electrophoretic behavior compared to PAs of other mouse tissues and from their response to a specific antibody raised against the tissue type PA (tPA), two major molecular species, of 70 and 48 kD were identified as tPA and urokinase (uPA), respectively, a third minor species of 105 kD being likely to correspond to complexes between tPA and an inhibitor; the culture fluids, moreover, contained enzymatically active degradation products of uPA of 42 and 29 kD. The PA activity of the bone extracts was only minimally affected by the addition of fibrinogen fragments to the chromogenic assays. PTH induced bone resorption and stimulated in parallel the accumulation of PA in the tissue; other bone-resorbing agents, 1,25-dihydroxyvitamin D, and prostaglandin E2, had similar effects. Densitometric scanning of the zymograms of the bone extracts indicated that PTH stimulated only the production of tPA and had no effect on that of uPA. However, PTH also enhanced the release of uPA (both the 48 kD and the 29 kD forms) from the bones into the media. Although inhibiting bone resorption, calcitonin had no effect on the PTH-induced accumulation of PA in bone or on the release of tPA, but it prevented the PTH-induced accumulation of 29 kD uPA in the culture fluids. Thus these studies support the view that tPA and possibly also uPA may have a role in the physiology of bone; the nature of this role remains to be elucidated, however.
Bone mineral density and mass by total-body dual-photon absorptiometry in normal white and asian men
Authors: Russell-Aulet Mary , Wang Jack , Thornton John , Colt Edward W.D. , Pierson Richard N. 
Published: February 2010

Abstract
Total body bone mineral density, total body bone mineral mass (TBBM), and bone mineral densities (BMD) in seven different regions of the body were measured in 238 normal men (154 Whites and 84 Asians), age 22–94, using dual-photon absorptiometry. Although Asian men had lower TBBM and BMD in all regions (p &lt; 0.05) except the arms, when multiple regression was done with body weight, height, and age, no significant differences were found between Asians and Whites for bone measurements. Thus lower bone mineral densities and bone mineral mass in Asian males compared to White males appear to be due to differences in height and weight rather than to ethnic differences. The two groups were combined to derive multiple regression equations for TBBM, total-body BMD, and regional BMD. Age, weight, and height were significant in the multiple regression equations for TBBM, ribs BMD, and legs BMD. Age and weight, but not height, were significant for total-body BMD, trunk BMD, spine BMD, arm BMD, and pelvis BMD. Weight, but neither height nor age, was significant for head BMD. These reference normal bone mineral density and bone mineral mass standards are appropriate for both Asian and White males when adjusted for weight, height, and age.
Tallness versus shrinkage: Do women shrink with age or grow taller with recent birth date?
Authors: Davies K. Michael , Recker Robert R. , Stegman Mary Ruth , Heaney Robert P. 
Published: February 2010

Abstract
This paper presents evidence that much of the high rate of age-related height loss in women reported in cross-sectional studies is actually a cohort effect rather than an aging effect. Data from a large cross-sectional study of healthy, white American women indicate that there has been a gain in peak adult height of 1.0 cm per decade for several decades from 1900 through 1965. Data from the HES, HANES I, and HANES II studies concur on this point. By contrast, data from a longitudinal study of 191 healthy white U.S. women show only a trivial rate of decline from peak adult height in the fifth and sixth decades of life. In an unselected population, some apparent height loss with age is probably due to disease processes, such as vertebral collapse. Caution is needed in using aging to interpret differences in height and in height-dependent variables, such as bone density, in cross-sectional studies.
Expression of the osteonectin gene potentially controlled by multiple Cis- and trans-acting factors in cultured bone cells
Authors: Dominguez Pedro , Ibaraki Kyomi , Robey Pamela Gehron , Hefferan Theresa E. , Termine John D. , Young Marian F. 
Published: February 2010

Abstract
The cis-acting regulatory elements of the osteonectin gene have been studied using a chloramphenicol acetyl-transferase (CAT) promoter assay in osteonectin-expressing and nonexpressing cultured cells. When various stretches of the promoter were transiently transfected into fetal bovine bone cells, a positive element was detected in the DNA located between bases −504 and 11 (1 being the start of transcription) and a negative element between bases −900 and −504. The positive element of the promoter also conferred preferential expression of the gene, showing more activity in cells with higher levels of osteonectin mRNA expression. A 1.2 kb fragment of intron 1 displayed a negative effect on CAT expression when inserted 5′ to the promoter. An additional regulatory element was found in DNA encoding exon 1, which significantly influenced expression of the gene in fetal bovine bone cells. Gel shift analysis using positive genomic elements located 5′ to the start of transcription indicated that one of the nuclear proteins that interacts with the osteonectin promoter may be related to the transcription factor AP2.
Structure-activity relationships in calcitonin gene-related peptide: Cyclic AMP response in a preosteoblast cell line (ks-4)
Authors: Thiebaud Daniel , Akatsu Takuhiko , Yamashita Takeyoshi , Suda Tatsuo , Noda Toshiharu , Martin Rachel E. , Fletcher Ann E. , Prof. Martin T. John 
Published: February 2010

Abstract
Synthetic analogs of chicken and human CGRP were used to define structure-function relationships in a murine osteoblast precursor cell line, KS-4, that exhibits a substantial cyclic AMP response to CGRP but no response to calcitonin. Human CGRP had 40% of the activity of chicken CGRP, but [Asp-14]-human CGRP was equipotent with chicken CGRP. Similar observations were made previously for calcium- and phosphate-lowering effects. Des-1-Ala, deamino CGRP compounds of both human and chicken origin were three-fold more potent than the respective native CGRPs. The [4-F-Phe)-37]-chicken CGRP analog had a four-fold enhanced activity. In all of the 13 analogs either truncated amino-terminally or missing the (2–7)-disulfide bridge, biologic activity was greatly reduced (0.1% of chicken CGRP), as it was in chicken CGRP-(1–36)-OH, which lacks the C-terminal amino acid. The same analog has been shown to retain a hypocalcemic effect, which is most likely mediated through calcitonin receptors. In confirmation of their antagonistic effect reported in liver, analogs that lack the N-terminal ring structure exhibited significant antagonistic activity. The data illustrate the specificity of CGRP receptors in promoting cyclic AMP formation in osteoblast-like cells. Such CGRP analogs will be useful in investigating structure-function relationships of CGRP.
Impairment of gamma carboxylation of circulating osteocalcin (bone gla protein) in elderly women
Authors: Plantalech Louisa , Guillaumont Marc , Vergnaud Philippe , Leclercq Michel , Dr. Delmas Pierre D. 
Published: February 2010

Abstract
Osteocalcin, also called bone gla protein, is a unique noncollagenous protein of the extracellular matrix of bone that circulates in blood. Oseteocalcin contains three residues of the vitamin K-dependent γ-carboxyglutamic acid (gla) responsible for the affinity of osteocalcin for bone mineral. In animals treated with the vitamin K antagonist warfarin, the osteocalcin content of bone is markedly reduced and the fraction of osteocalcin released into the circulation is increased. Most studies have shown that osteocalcin increases with aging in women, reflecting an increase in bone turnover, especially after the menopause. To determine if this increase in osteocalcin could be associated with impaired carboxylation, we measured total and noncarboxylated osteocalcin in the serum of 72 women of various ages: 22 premenopausal (31 ± 7 years old), 20 early postmenopausal (54 ± 3 years), and 30 elderly women (85 ± 8 years). As previously reported, total serum osteocalcin was significantly increased in early postmenopausal and elderly women. Noncarboxylated serum osteocalcin was slightly increased in early postmenopausal women (0.95 ± 0.4 versus 0.65 ± 0.5 ng/ml in premenopausal women), markedly elevated in elderly women (1.59 ± 1.1 ng/ml, p &lt; 0.001), and correlated with age (r = 0.47, p &lt; 0.001). Elderly women had values of the same magnitude as in 10 patients on chronic warfarin therapy (1.94 ± 1.1 ng/ml). As a consequence, the increase in carboxylated serum osteocalcin was significant in early postmenopausal women but not in elderly women. Serum levels of vitamin K1 and of menaquinones 6, 7, and 8 were measured in some of the young and elderly women. No difference was found, which does not suggest a major vitamin K deficiency in elderly women. Conversely, our data may be related to an inadequate recycling of vitamin K or to an intrinsic defect of the carboxylation system within the osteoblasts of elderly people. In conclusion, we have shown that circulating osteocalcin is undercarboxylated in elderly women through an unknown mechanism, suggesting a decrease in the osteocalcin content of bone. Further studies should be conducted to determine the importance of these abnormalities in the pathogenesis of the bone loss occurring with aging.
Role of physical activity in the development of skeletal mass in children
Authors: Dr.P.H. Slemenda Charles W. , Miller Judy Z. , Hui Siu L. , Reister Teresa K. , Johnston C. Conrad 
Published: February 2010

Abstract
A group of 118 children, aged 5.3–14 years, were enrolled in a prospective study of calcium supplementation and bone mass. At entry to the study, questionnaires regarding the child's usual physical activity were administered to the children and their mothers. Repeated activity assessments at 6 month intervals indicated good within-person agreement for total activity and for most individual activities. Consistent positive associations were observed between bone mineral densities (BMD) in the radius, spine, and hip and most activities. A summary measure (total hours of weight-bearing activity) was significantly releated to BMD in the radius and hip, independently of age or gender effects. Self-reported sports and play activities were associated with BMD, but neither time spent watching television nor hours of physical education classes were associated either positively or negatively with skeletal mass. These data suggest that important increments in skeletal mass may result from physical activity during childhood.
Failure to detect paramyxovirus sequences in paget's disease of bone using the polymerase chain reaction
Authors: Ralston Stuart H. , Digiovine Francesco S. , Gallacher Stephen J. , Boyle Iain T. , Duff Gordon W. 
Published: February 2010

Abstract
It is widely believed that Paget's disease of bone is due to a “slow virus” infection of osteoclasts with one of the paramyxovirus group. Controversy continues to surround the identity of the virus involved, however, since at different times evidence has been presented implicating measles virus (MV), respiratory syncytial virus (RSV), and canine distemper virus (CDV) as putative infective agents. In this study we used the technique of reverse transcription and polymerase chain reaction (PCR) to screen for paramyxovirus sequences in ribonucleic acid (RNA) extracted from pagetic bone. We were able to detect viral amplification products of the appropriate size in RNA extracted from as few as 50 cells experimentally infected with a wide range of paramyxoviruses, including measles, canine distemper, parainfluenza 3, and respiratory syncytial virus, but we found no evidence of viral products in RNA extracts of affected bone from 10 consecutive patients with Paget's disease. This study fails to support the hypothesis that active infection with one of these or a related paramyxovirus is involved in the pathogenesis of Paget's disease.
Effects of antiestrogenic compounds on avian medullary bone formation
Authors: Dr. Williams Daniel C. , Paul Donald C , Herring Janice R. 
Published: February 2010

Abstract
Administration of estradiol to male Japanese quail induced the formation of medullary bone in the marrow cavities of the bird's femora and tibiae. This was accompanied by increased serum levels of calcium, phosphorus, and alkaline phosphatase activity. We examined the effects of two structurally distinct “antiestrogens” on the estrogen-induced formation of medullary bone in this quail model. Trioxifene (LY133314) and tamoxifen are members of a group of compounds commonly referred to as antiestrogens that elicit mixed agonist-antagonist actions on estrogen target tissues. In our experiments, these compounds did not display estrogen agonist properties with respect to medullary bone formation. They also did not elicit changes in serum calcium, phosphorus, or alkaline phosphatase activity. When given concurrently with estradiol, the compounds inhibited both the estrogen-induced formation of medullary bone and the associated changes in serum parameters. Trioxifene appears to be somewhat more potent than tamoxifen in antagonizing estrogen effects in this model.
Rapid publication TGF-β1 induces bone closure of skull defects
Authors: Beck L. Steven , Deguzman Leo , Lee Wyne P. , Xu Yvette , McFatridge Lorrie A. , Gillett Nancy A. , Amento Edward P. 
Published: February 2010

Abstract
Transforming growth factor β1 (TGF-β1) is a multifunctional regulatory protein. It is capable of inducing site-specific healing responses by increasing collagen synthesis and deposition as well as remodeling at sites of soft tissue repair. Large bony defects in the skull heal by fibrous connective tissue and never form bone unless osteoinductive bony fragments or powders are placed in the defect. We have found, however, that the single application of human recombinant TGF-β1 in a simple 3% methylcellulose gel to skull defects induced a dose-dependent increase in intramembranous bone formation. Complete bony bridging of defects occurred within 28 days after treatment with 2 μg TGF-β1. Sites treated with vehicle alone did not heal with bone formation but rather contained dense fibrous connective tissue between the defect margins.
Osteoclast-specific monoclonal antibodies coupled to magnetic beads provide a rapid and efficient method of purifying avian osteoclasts
Authors: Collin-Osdoby Patricia , Oursler Merry Jo , Webber David , Dr. Osdoby Philip 
Published: February 2010

Abstract
Osteoclasts are the major cell type responsible for normal and pathologic bone resorption. Obtaining highly purified populations of these multinucleated cells has been problematic, although such populations would greatly facilitate investigations of osteoclast regulation and activity. A new immunomagnetic protocol has been devised to surmount these difficulties, employing avian osteoclast-directed monoclonal antibodies (designated 121F, 35L, and 75B) surface coupled to uniformly small, magnetic polystyrene beads covalently conjugated with sheep antimouse IgG. Presentation of these antiosteoclast antibody-coated beads to mixed cell preparations derived from marrow-depleted, collagenase- and/or trypsin-treated chick tibiae and wing bones, followed by magnetic separation and washing, results in efficient and selective binding of osteoclasts to the immunomagnetic beads within minutes. The specific nature of this bead-cell interaction is further demonstrated by the progressive decline in antiosteoclast antibody-coated bead binding to osteoclasts pretreated with the soluble antiosteoclast antibody and also by the absence of binding to osteoclasts by uncoated beads or beads coated with an irrelevant antibody. Under optimal conditions, these isolations typically yield more than a 100-fold enrichment and greater than a 90% purification of osteoclasts from subpopulations of either predominantly nonviable or viable osteoclasts. Although scanning electron microscopy reveals that immunomagnetically purified and cultured osteoclasts internalize large numbers of the antibody-coated beads, such cells appear unimpaired in their ability to attach to tissue culture plastic or devitalized cortical bone slices and to produce resorption pits characteristic for osteoclasts. Additional studies to ascertain the most effective method for removal (desorption) of antibody-coated beads from magnetically isolated osteoclasts demonstrate that moderate physical agitation is at present the most effective protocol to dislodge antibody-coated beads from the cell surface while maintaining osteoclast viability and function. This immunomagnetic technique therefore provides a gentle method for the isolation of highly purified poplations of osteoclasts from heterogeneous bone cell populations in a rapid, efficient, and selective manner.
Journal of Bone and Mineral Research
Authors: Spiegel Allen M. 
Published: February 2010

AbstractPrimary hyperparathyroidism (PHPT) is characterized by hypersecretion of parathyroid hormone (PTH) leading to hypercalcemia and relative hypophosphatemia. PTH acts by binding to cell surface receptors coupled to G proteins. Cyclic AMP is the classic second messenger of PTH action, but substantial evidence indicates that PTH also acts to stimulate formation of the dual second messengers, inositol trisphosphate and di-acylglycerol, thereby mobilizing intracellular calcium. The physiologic actions of PTH include (1) an increase in extracellular fluid ionized calcium through direct actions on kidney and bone, the classic target organs for PTH, and (2) a decrease in extracellular fluid phosphate primarily through renal action. The pathophysiologic effects of PTH arise from (1) direct actions of PTH on bone and kidney, and possibly on nonclassic target organs, and (2) indirect effects of altered mineral homeostasis. PTH hypersecretion in PHPT can lead to bony demineralization, nephrolithiasis, and hypercalcemic crisis. PHPT may also be associated with mental disturbances, neuromuscular disease, hypertension, and glucose intolerance.
Journal of Bone and Mineral Research
Authors: Ladenson Jack H. 
Published: February 2010

Abstract
Calcium is the most closely controlled substance in the blood. The biologic variation of total calcium is ≈︁ 2% and of the biologically active free (ionized, ionic) calcium only 1%.(1–3) Thus, the monitoring of calcium in blood requires analytic procedures of high precision and accuracy. For patients with asymptomatic primary hyperparathyroidism, calcium monitoring involves the measurement of total calcium and free calcium. This review first considers the measurement of total calcium and then free calcium.
Journal of Bone and Mineral Research
Authors: Peacock Munro 
Published: February 2010

Abstract
Determination of bone mass is currently the most clinically useful measurement of bone strength and of fracture risk. Interpretation of bone mass determination as it relates to fracture has been developed largely from studies of age-related bone loss. A decrease in bone mass and an increase in fracture incidence with aging are universal phenomena that are causally related by virtue of the major contribution bone mass makes to skeletal strength. Over 70% of the skeleton's strength to resist fracture resides in its mineral content in vitro. Clinically, the relationship between trauma and fracture is complex, and in the general population, fracture appears as a random event occurring more frequently as bone mass decreases. In the individual, measurement of bone mass in relation to the range of bone mass and the fracture incidence of the reference population provides an estimate of the risk of sustaining a fracture in the future. In primary hyperparathyroidism, interpretation of a bone mass determination must take into account the effect of the disease activity on the skeleton against the background of universal age-related changes in bone mass and fracture incidence. This general relationship is likely to be altered by at least three unique effects that parathyroid hormone may have on the skeleton: (1) parathyroid hormone has a differential effect on cortical and cancellous bone; (2) it has a biphasic effect on bone that is concentration dependent; and (3) it alters bone quality and architecture. In asymptomatic patients with primary hyperparathyroidism who are considered for long-term medical follow-up, bone mass determination and fracture incidence must be part of the essential monitoring process both to provide a best estimate of fracture risk for the subject and to provide prospective data to refine the estimate of fracture risk for the disease itself.
Journal of Bone and Mineral Research
Authors: Bilezikian John P. , Silverberg Shonni J. , Shane Elizabeth , Parisien May , Dempster David W. 
Published: February 2010

Abstract
Data are presented on 97 patients with primary hyperparathyroidism who constitute a representative cohort of the disease seen today. The average calcium (11.1 ± 0.1 mg/dl; normal 8.7–10.7), phosphorus (2.8 ± 0.1 mg/dl; normal 2.5–4.5), and parathyroid hormone level by immunoradiometric assay (119 ± 7 pg/ml; normal 10–65) are typical of the modern presentation of primary hyperparathyroidism. Most patients were asymptomatic in that there was evidence for nephrolithiasis in only 18% and for radiologically evident bone disease in only 1% of patients. Nevertheless, when patients were evaluated with bone densitometry and with histomorphometric analysis of the bone biopsy specimen, evidence for the hyperparathyroid process could be shown in the majority of patients. Selective reduction of cortical bone and preservation of cancellous bone were apparent. Among patients with nephrolithiasis, no particular feature distinguished them from patients without nephrolithiasis. All biochemical data were similar between both stone and non-stone formers. The selective reduction in cortical bone was seen to the same extent among those with stones as among those without stones. The average 1,25-dihydroxyvitamin D level was not increased among those with stones. When the population was divided into groups with elevated or normal 1,25-dihydroxy vitamin D levels, the incidence of nephrolithiasis was unchanged. The results indicate that bone involvement can be demonstrated among most patients with asymptomatic primary hyperparathyroidism and that no pathophysiologic mechanisms are yet apparent to account for nephrolithiasis in primary hyperparathyroidism.