bluuebunny/crossref_metadata_2025 huggingface dataset:
Amelin: An enamel-related protein, transcribed in the cells of epithelial root sheath
Authors: Fong Cheng Dan , Slaby Ivan , Hammarström Lars
Published: February 2010

Since 1974, when Slavkin and his collaborators proposed the epithelial origin of cementum, many experiments have been carried out to provide evidence for deposition of enamel-related proteins along the root surface. However, neither amelogenin nor other proteins have fully satisfied expectations. In previous studies, we have identified a novel mRNA coding for an extracellular-like protein which we called amelin. It was expressed at high levels in secretory and postsecretory ameloblasts in rat molars and incisors. In situ hybridization experiments described in the present study also localized the amelin message to epithelial cells adjacent to the peripheral surface of newly deposited dentin in the root end and to cells embedded in cellular cementum in molars. In incisors, the amelin RNA positive cells were detected in the area where cementum formation had been initiated. No amelogenin RNA signal was found in the cells at the root surface. We postulate that the epithelial cells of the root sheath as well as the ameloblasts are synthesizing amelin which might be one of the key proteins coupled to the process of cementogenesis. (J Bone Miner Res 1996;11:892-898)
Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro
Authors: Almaden Yolanda , Canalejo Antonio , Hernandez Alexis , Ballesteros Evaristo , Garcia-Navarro Socorro , Torres Armando , Rodriguez Mariano , Rodriguez Mariano
Published: February 2010

Phosphorus retention is an important factor in the development of hyperparathyroidism secondary to renal failure. In vivo manipulation of phosphorus is associated with changes in serum calcium and calcitriol levels which in turn can modify parathyroid hormone synthesis and secretion. The present in vitro study evaluates whether high extracellular phosphorus has a direct effect on parathyroid hormone secretion. Fresh rat parathyroid glands were incubated in a media with phosphorus concentrations of 1, 2, 3, and 4 mM and subsequently exposed to calcium levels ranging from 0.4 to 1.35 mM. In 1.25 mM calcium, the parathyroid hormone secretion rate was similar in 1 and 2 mM phosphorus; however, a phosphorus concentration of 3 and 4 mM produced a 3- and 4-fold increase in the parathyroid hormone secretion, respectively, as compared with 1 mM phosphorus. While in 1 or 2 mM phosphorus an increase in calcium from 0.6 to 1.35 mM reduced parathyroid hormone secretion to 37%, in 4 mM phosphorus the same increase in calcium only inhibited parathyroid hormone secretion to 75%. Furthermore, the addition of arachidonic acid 20 μM, a substrate for inhibitory intracellular signal pathway, to the 4 mM phosphorus-1.35 mM calcium incubation media reduced the parathyroid hormone secretion to 34.5% (p < 0.05). In conclusion, our results indicate that in vitro, high phosphorus directly increases parathyroid hormone secretion. (J Bone Miner Res 1996;11:970-976)
Dual-energy X-ray absorptiometry studies of bone mineral status in newborn infants
Authors: Dr. Koo Winston W. K. , Walters Jocelyn , Bush Andrew J. , Chesney Russell W. , Carlson Susan E.
Published: February 2010

We studied bone mineral status using dual-energy X-ray absorptiometry (DXA) on 150 singleton newborn infants with birth weights 1002–3990 g and gestational ages (GA) 27–42 weeks. Eighty-five infants were preterm (<38 weeks), and 79 infants were low birth weight (≤2500 g). In addition, we aimed to determine the predictive value of anthropometric measurements, race, and gender on variability in bone mineral status. Data were acquired using a whole body DXA scanner with a pediatric platform. Scan analyses were performed with software version V5.64P. Results showed a highly significant (p < 0.001 for all comparisons) correlation among the continuous independent variables, gestational age, birth weight, study weight, study bare weight, and study length, and between independent and each of the dependent variables, total body bone mineral content (TB BMC), TB area, and TB bone mineral density (TB BMD). The best single determinant of bone mineral status is body weight, accounting for 95% of TB BMC and TB area and for 86% of TB BMD variation. Body length was the only additional significant predictor of TB area. Inclusion of postnatal age (during the first week after birth), race, gender, or season, either individually or in combination, failed to improve bone mineral status explanation. By term (GA 38–42 weeks, birth weight 2700–3990 g), the mean TB BMC was 68.2 g, TB area 307.6 cm2, and TB BMD 0.221 g/cm2. We conclude that DXA can be performed even in small preterm infants during the newborn period. Our results can be used as a basis for further studies in physiologic and pathologic situations that might affect bone mineralization in infants. (J Bone Miner Res 1996;11:997-1002)
Low bone mineral content is common but osteoporotic fractures are rare in elderly rural Gambian women
Authors: Dr. Aspray Terence J. , Prentice Ann , Cole Timothy J. , Sawo Yankuba , Reeve Jonathon , Francis Roger M.
Published: February 2010

Osteoporosis is reported to be rare in Black Africa. The low fracture incidence among North American black women is explained by a high peak bone mass and preservation of bone mineral into old age. To assess whether this is the case among Black African women, we measured bone mineral content (BMC) and bone mineral density (BMD), using single- and dual-photon absorptiometry, in 195 rural Gambian women aged over 44 years and 391 white women of comparable age from three centers in the U.K. Measurements were made at the midshaft of the radius, distal radius, lumbar spine, and femoral neck. The influence of height, weight, and nationality on BMC and BMD was analyzed. BMC and BMD decreased with age at all sites. Age, decreasing weight, but not height were independently associated with lower BMC at all sites. BMC in Gambian women was lower than in British women by 31% at the lumbar spine and 16% at the midshaft of the radius. After adjustment for age, height, and weight, BMC among Gambian women remained 24% lower at the lumbar spine and 10% lower at the radius. In women aged over 64 years, BMC at the lumbar spine was 42% lower and BMD was 31% lower in The Gambia (for all comparisons, p > 0.005). We conclude that bone mineral mass is not preserved in elderly Gambian women. However, minimal trauma fractures are rare in this population. These results challenge the concept of BMC as a primary determinant of fracture risk. (J Bone Miner Res 1996;11:1019–1025)
Vertebral fractures and other predictors of back pain among older women
Authors: Dr. Huang Chun , Ross Philip D. , Wasnich Richard D.
Published: February 2010

We examined the prevalence and predictors of back pain (BKP) among 645 postmenopausal Japanese-American women in Hawaii with a mean age of 73.9 years (ranging from 55 to 93 years) and serial spine radiographs during the preceding 12 years. The overall prevalence of BKP was 32.9% and appeared to be constant up to age 80, with an increase thereafter. At most ages, pain in the lower back was the most common, upper BKP was less so, and mid-BKP was the least common. The overall prevalence of BKP among Japanese-American women in Hawaii was about half of that reported for U.S. Caucasians. Vertebral fractures were divided into three categories based on the length of time since the fracture was identified on radiographs. BKP was only associated with recent vertebral fractures (during the previous 4 years, on average) and increased progressively with the number and severity of fractured vertebrae. A history of a single recent fracture was associated with a 2.8-fold increase in the odds of BKP; two recent fractures with a 7.8-fold increase and three recent fractures with a 21.7-fold increase in the odds of BKP. In addition, self-reported disk problems, body mass index, and the number of other painful joints also showed independent associations with BKP. Height, spine bone mineral density (BMD), calcaneus BMD, smoking, and number of live births were not significantly associated with BKP. (J Bone Miner Res 1996;11:1026–1032)
Single cell enzyme activity and proliferation in the growth plate: Effects of growth hormone
Authors: Dr. Gevers E.F. , Milne J. , Robinson I.C.A.F. , Loveridge N.
Published: February 2010

Longitudinal growth is a result of proliferation and differentiation of chondrocytes in the growth plate. Growth hormone (GH) stimulates longitudinal growth, and GH receptors have been shown on growth plate chondrocytes, but the effects of GH on chondrocytes of different cell layers are not clear. To study the effect of GH on chondrocyte activity, in situ biochemical techniques were used to measure enzyme activities, which are associated with cell differentiation (alkaline phosphatase [ALP]) and osteoclast activity (tartrate-resistant acid phosphatase [TRAP]), within single cells of the growth plate. Uptake of bromodeoxyuridine (BrdU) was used as a parameter for proliferative activity. In addition, glucose-6-phosphate dehydrogenase (G6PD) was measured since increased proliferation has been associated with increased G6PD activity. The role of GH was studied in a model of isolated GH deficiency (dwarf rat) and complete pituitary deficiency (hypophysectomized rat). Groups of GH-deficient dwarf rats were infused with recombinant human GH in either a continuous or a pulsatile manner, since the pattern of GH secretion is an important regulator of growth in the rat. After 7 days, G6PD activity in proliferative chondrocytes and TRAP activity in osteoclasts was increased, while ALP activity in hypertrophic chondrocytes was decreased. GH not only increased the number of chondrocytes that incorporated BrdU but also the total number of chondrocytes in the proliferative zone; therefore, its ratio, the labeling index (an indicator of proliferative rate), was not increased. The widths of the proliferative and hypertrophic zones were increased by both patterns of GH administration. The width of the resting zone was unaffected by continuous GH but decreased by pulsatile GH. ALP and TRAP activities were, respectively, higher and lower in hypophysectomized rats compared with the GH-deficient animals. Hypophysectomized rats had smaller growth plates than dwarf rats with a disproportionally wide resting zone, which, like BrdU uptake, was not affected by GH. GH treatment resulted in increased TRAP and decreased ALP activity. These results indicate that GH stimulates the commitment of chondrocytes within the resting/germinal layer to a proliferative phenotype (as opposed to stimulating the rate of chondrocyte proliferation) but only in the presence of other pituitary hormones. Furthermore, this study shows that enzyme activities within single chondrocytes and osteoclasts are GH-sensitive. The extent to which these effects are direct or mediated by systemic or local growth factors remains to be clarified.
Ultrastructural, enzyme-, lectin-, and immunohistochemical studies of the erosion zone in rat tibiae
Authors: Nakamura Hiroaki , Ozawa Hidehiro
Published: February 2010

To clarify the process of endochondral ossification, we used ultrastructural, enzyme-, lectin-, and immunohistochemical techniques to study perivascular cells located in the erosion zones of rat tibiae. In growth plate erosion zones, perivascular cells directly connected to blood capillaries were seen invading cartilage. These cells contained a well-developed rough endoplasmic reticulum and Golgi apparatus in their cytoplasm and formed finger-like cytoplasmic processes toward uncalcified transverse cartilage walls. These processes were seen to stretch as far as the degenerated chondrocytes located in the calcified layer of the growth plate. Interestingly, these perivascular cells showed neither alkaline phosphatase activity nor tartrate-resistant acid phosphatase activity. Lectin histochemistry revealed specific staining by Dolichos Biflorus agglutinin (DBA) on the perivascular cells. No reactivity for DBA was detected on either endothelial cells, osteoblasts, chondroclasts, or osteoclasts. In addition, immunohistochemical studies showed that the perivascular cells neither expressed CD44, which was localized on the plasma membrane of chondroclasts, osteoclasts, and osteocytes, nor were surrounded by laminin. These results suggest that the perivascular cells in the erosion zone are distinct from endothelial cells, osteoblasts, chondroclasts, and osteoclasts; that they may resorb uncalcified cartilage matrix and degenerated chondrocytes; and that perivascular cells may play an important role in the capillary invasion during the process of endochondral ossification.
Comparison of biochemical markers of bone turnover in paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links
Authors: Mr. Randall A.G. , Kent G.N. , Garcia-Webb P. , Bhagat C.I. , Pearce D.J. , Gutteridge D.H. , Prince R.L. , Stewart G. , Stuckey B. , Will R.K. , Retallack R.W. , Price R.I. , Ward L.
Published: February 2010

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyproline excretion (HypE) levels (i.e., group 1, HypE < 5.0 μmol/1 of glomerular filtrate [GF]; group 2, HypE of 5.0–9.9 μmol/1 of GF; group 3, HypE < 10 μmol/1 of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.
Hysteresis of the PTH-calcium curve during hypocalcemia in the dog: Effect of the rate and linearity of calcium decrease and sequential episodes of hypocalcemia
Authors: Aguilera-Tejero E. , Sánchez J. , Almadén Y. , Mayer-Valor R. , Rodríguez M. , Felsenfeld A. J.
Published: February 2010

Several studies have shown the presence of hysteresis of the parathyroid hormone (PTH)-calcium relationship in both normal humans and hemodialysis patients; for hypocalcemia, hysteresis is defined as a lower PTH level for the same serum calcium during the recovery from than the induction of hypocalcemia. However, some have questioned whether hysteresis is only a function of the rate and/or direction of change in calcium, and others have proposed that hysteresis is due to depletion of PTH stores. To address these issues, two groups of dogs were studied. To induce hypocalcemia, sodium EDTA (50 mg/kg) was infused either over 60 (termed slow) or 30 (termed fast) minutes; immediately after the cessation of the ethylenediamine tetracetate (EDTA) infusion, calcium chloride (0.75 mEq/kg) was infused over 60 or 30 minutes, respectively, to correct the hypocalcemia. The EDTA infusion produced a linear decrease in serum calcium by progressively increasing the infusion rate at regular intervals. A second cycle of hypocalcemia and recovery using the same protocol was started immediately after the completion of the first cycle. To determine whether a nonlinear decrease in the serum calcium affected the PTH response to hypocalcemia, a third group of dogs, termed superfast, was studied; in this group, EDTA was infused for 30 minutes at a constant rate of 50 mg/kg. The hysteretic loops of PTH produced by the two sequential slow and fast cycles and the superfast cycle during the induction of and recovery from hypocalcemia were similar. Moreover, the maximal PTH level for the two sequential slow and fast cycles and the superfast cycle was not different even though the rates of calcium decrease varied and the calcium decrease was nonlinear in the superfast cycle. In conclusion, (1) since hysteresis was reproducible and the maximal PTH was not different during two sequential cycles of hypocalcemia, hysteresis is not due to PTH depletion; (2) the PTH-calcium curve is not affected by the rate at which hypocalcemia is induced: and (3) the maximal PTH level is not influenced by either the rate or linearity of the reduction in serum calcium.
A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density
Authors: Dr. Uitterlinden André G. , Pols Huibert A. P. , Burger Huibert , Huang Qiuju , van Daele Paul L. A. , van Duijn Cornelia M. , Hofman Albert , Birkenhäger Jan C. , van Leeuwen Johannes P. T. M.
Published: February 2010

Conflicting results have been reported on the association between restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus (i.e., for BsmI, ApaI, and TaqI) and bone mineral density (BMD). We analyzed this association in a large population-based sample (n = 1782) of men and women aged 55–80 years using a novel direct haplotyping polymerase chain reaction (PCR) test to monitor the three polymorphic sites simultaneously. The direct haplotyping test we developed demonstrated a larger degree of genetic polymorphism at the VDR gene locus than described until now. None of the individual RFLPs were associated with BMD at the proximal femur. By analyzing allele dose effects, we identified a VDR haplotype allele weakly associated with low BMD. This allele, as one representative of the group of b alleles, is different from the BsmI allele previously reported by other groups to be associated with low BMD. This suggests allelic heterogeneity at the VDR locus in relation to BMD. Our results indicate at most a small effect of the VDR genotype on BMD in this elderly population. Since anonymous polymorphisms were analyzed, alternative explanations for our results include linkage to another nearby bone-metabolism related gene.
Prediction of fracture load at different skeletal sites by geometric properties of the cortical shell
Authors: Augat P. , Reeb H. , Claes L. E.
Published: February 2010

Quantitative bone assessment today is primarily based on the analysis of bone mineral density (BMD). The geometric properties of bone, which are an important parameter for skeletal strength, are generally not considered in the routine clinical assessment of osteoporosis. This study combined the geometric properties and the BMD values determined by peripheral quantitative computed tomography (pQCT) at the distal radius and at the femoral neck to predict fracture loads of the radius, femur, and lumbar vertebrae of 20 cadavers. Generalized osteopenia reduced the fracture loads at all three sites (p < 0.001). The strength of the radius and the femoral neck could best be predicted by considering either the second moment of inertia and trabecular BMD (R = 0.93) or the moment of inertia and the cortical BMD (R = 0.91). The geometric properties at the distal radius were highly correlated with the fracture load at the same skeletal site (R = 0.89) and were also used to estimate the fracture risk at the lumbar vertebrae (R = 0.75) and at the femoral neck (R = 0.87). We conclude that both geometry and density contribute substantially to the strength of the skeleton. The screening for osteoporosis and the prediction of fracture risk can be improved, therefore, by an additional consideration of the geometric properties of the cortex.
Effects of progesterone on serum levels of IGF-1 and on femur IGF-1 mRNA in ovariectomized rats
Authors: Barengolts E.I. , Kouznetsova T. , Segalene A. , Lathon P. , Odvina C. , Kukreja S.C. , Unterman T.G.
Published: February 2010

Local and systemic insulin-like growth factors (IGFs) may be involved in the regulation of bone formation by sex hormones. The present studies describe the in vivo effects of estradiol, progesterone, or both on IGF-1 mRNA abundance in bone, serum IGF-1 levels, and bone formation. Rats were sham-operated (SHAM) or ovariectomized (OVX) at 12 weeks of age and used a week later in three experiments. First, OVX rats were treated with vehicle, estradiol, and/or medroxyprogesterone (MPA) for 3 weeks, and bone formation was assessed in the tibial metaphysis. Second, OVX rats were treated in the same manner and serum IGF-1 levels measured. Third, OVX rats were treated with an injection of vehicle, estradiol, and/or progesterone, and 24 h later, levels of IGF-1 mRNA in the femur were analyzed. The mineralized surface, mineral apposition rate, and bone formation rate (BFR) were higher in OVX than in SHAM rats. The BFR was decreased in estrogen-treated but increased in MPA-treated rats compared with vehicle-treated OVX rats. Circulating levels of IGF-1 were higher in OVX than in SHAM rats but were not affected by sex hormones in a 3-week experiment, whereas these levels were not different among groups in a 24-h experiment. Northern analysis detected 7.5 and 0.8 kb IGF-1 mRNA transcripts. The abundance of IGF-1 mRNA was higher in OVX than in SHAM rats. IGF-1 transcripts 7.5 and 0.8 kb were decreased by 72 and 29%, respectively, in estrogen-treated and increased by 44 and 43%, respectively, in progesterone-treated rats compared with vehicle-treated OVX rats. We conclude that in the short term, estrogen lowers and progesterone raises bone IGF-1 mRNA and these changes are followed by coordinated changes in bone formation rate.
Dissociation of binding and antiresorptive properties of hydroxybisphosphonates by substitution of the hydroxyl with an amino group
Authors: van Beek Ermond , Löwik Clemens , Que Ivo , Papapoulos Socrates
Published: February 2010

The purpose of this study was to examine the role of the R1 moiety of bisphosphonates in binding to bone mineral and for antiresorptive action. For this, the R1 chain of three clinically useful hydroxybisphosphonates (etidronate, pamidronate, and olpadronate) was substituted with an amino group. The effects of the aminosubstituted bisphosphonates were compared with those of their hydroxy counterparts in a crystal growth assay and in fetal mouse long bone cultures which are representative of bisphosphonate actions in vivo. It was found that all three aminosubstituted compounds and their hydroxy analogs bound with similar affinity to bone mineral and inhibited the growth of calcium oxalate crystals to the same extent. Surprisingly, the antiresorptive effect of olpadronate was totally abolished by the amino substitution of the hydroxyl group while that of pamidronate was reduced by about six-fold and that of etidronate did not change. These studies demonstrate the involvement of the entire bisphosphonate molecule in the cellular mechanism of antiresorptive action. In addition, the aminosubstituted analog of olpadronate, which lacks any antiresorptive action but retains all other properties of olpadronate, provides an excellent tool for the study of specific cellular effects involved in bisphosphonate action.
Bisphosphonates clodronate and etidronate in the prevention of ovariectomy-induced osteopenia in growing rats
Authors: Lepola Vesa T. , Kippo Katriina , Hannuniemi Ritva , Laurén Leena , Virtamo Teija , Österman Thua , Jalovaara Pekka , Sellman Raija , Väänänen H. Kalervo
Published: February 2010

The aim of this study was to evaluate the ability of the bisphosphonate compounds clodronate and etidronate to prevent ovariectomy-induced bone changes. Three-month-old Sprague-Dawley rats were either ovariectomized (OVX) or sham-operated (SHAM) and further divided into groups receiving either vehicle (n = 30), 25 mg/kg/week of clodronate (n = 25) or 25 mg/kg/week of etidronate (n = 25). The subcutaneous drug administration was started immediately after the surgery and was continued for 12 weeks. OVX rats had accelerated bone turnover rates compared with the SHAM animals, as indicated by the results of dynamic histomorphometry and biochemical markers in serum and urine. Femoral and vertebral mineralized trabecular bone volume and maximum loads in compressions of the femoral neck and lumbar vertebra were lower after OVX compared with the SHAM operation. Both clodronate and etidronate prevented the decrease in trabecular bone volume and suppressed the increase in the bone turnover rate. Clodronate and etidronate also blocked the loss of bone strength in the femoral neck and lumbar vertebra of OVX rats. Both compounds resulted in an absence of double fluorochrome labels on the endocortical surface of the femoral metaphysis, which seemed, however, to be a dose-dependent response. Furthermore, etidronate also lowered serum osteocalcin and diaphyseal endocortical bone formation below the vehicle level both in the OVX and SHAM rats. In conclusion, clodronate and etidronate were effective in preventing the estrogen deficiency-induced decreases in trabecular bone volume and bone strength in rats. Treatment with a high dose of clodronate induced minor signs of abnormally low bone formation but not any impairment of bone mineralization, whereas both of these events were seen with high-dose etidronate administration.
Evaluation of cortical bone by computed tomography
Authors: Hangartner Thomas N. , Gilsanz Vicente
Published: February 2010

The purpose of this study was to determine the minimum thickness of cortical bone required for the accurate measurement of cortical material density by computed tomography (CT) and to establish normal reference values. A phantom with several wall thicknesses of bone-like material was constructed to simulate various cortical widths. The CT density at each level of thickness was measured on a GE 9800 CT scanner and on the OsteoQuant, a special CT scanner optimized for the measurement of bone in the extremities. The minimum width required to attain the correct material density was determined for each scanner. Additionally, the material density and width of the cortex in the radius and/or femur were measured by CT in 761 healthy subjects, ages 4-84 years. The minimum thickness necessary for an accurate density evaluation of the walls of the phantom by CT was 2-2.5 mm; below these thresholds the values fell in a linear way relative to width. In humans, the material density of cortical bone in the appendicular skeleton was not influenced by height or weight, and the values were similar for all subjects, as long as the cortical width was above 2-2.5 mm. The cortical width increased with age up to 30 years and decreased from 50 years on. We conclude that the material density of cortical bone in the appendicular skeleton can be measured accurately by CT if the thickness of the cortex exceeds 2-2.5 mm.
The mechanism of β-glycerophosphate action in mineralizing chick limb-bud mesenchymal cell cultures
Authors: Boskey Adele L. , Guidon Peter , Doty Stephen B. , Stiner Dalina , Leboy Phoebe , Binderman Itzhak
Published: February 2010

Differentiating chick limb-bud mesenchymal cells plated in micromass culture form a cartilage matrix that can be mineralized in the presence of 4 mM inorganic phosphate (Pi) and 1 mM calcium. Previous studies showed that when β-glycerophosphate (βGP) is used in place of Pi, the mineral crystals formed are larger and differ in distribution. The present study shows that the difference in distribution is not associated with alterations in cell proliferation, protein synthesis, or with collagen, proteoglycan core protein, or alkaline phosphatase gene expression. Cultures with 2.5, 5, and 10 mM βGP did show different levels of alkaline phosphatase activity, and in the presence of low (0.3 mM) Ca had different Pi contents (4, 6, and 9 mM, respectively), indicating that the increase in CaxP product may in part be responsible for the altered pattern of mineralization. However, cultures with βGP in which alkaline phosphatase activity was inhibited with levamisole still had an altered mineral distribution as revealed by Fourier transform-infrared (FT-IR) microspectroscopy. The presence of a casein kinase II-like activity in the mineralizing cultures, the ability of specific inhibitors of this enzyme to block mineralization, and the known ability of βGP to block phosphoprotein phosphatase activity suggests that altered patterns of matrix protein phosphorylation may influence mineral deposition in these cultures. (J Bone Miner Res 1996;11:1694-1702)
Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factor
Authors: Vargas Socorro J. , Naprta Anica , Glaccum Moira , Lee Sun Kyeong , Kalinowski Judith , Dr. Lorenzo Joseph A.
Published: February 2010

We examined the roles of interleukin-1 Type I receptor (IL-1R1) and tumor necrosis factor receptor 1 (TNFR1) in bone metabolism using mice rendered deficient in these receptors by gene targeting. Sections of decalcified paraffin-embedded calvariae and humeri from 11- to 12-week-old mice deficient in IL-1 Type I receptor (IL-1R1-/-) or TNF receptor 1 (TNFR1-/-) were examined by histomorphometry. Wild-type mice (C57BL/6J X 129/J, WILD) served as controls. Interleukin-6 (IL-6) production in primary osteoblastic and bone marrow stromal cell cultures in response to parathyroid hormone (PTH, 100 ng/ml), IL-1α (10 ng/ml), and TNF-α (10 ng/ml) was also examined. IL-1R1-/- and TNFR1-/- mice were viable and appeared phenotypically normal. However, the body weights of the IL-1R1-/- mice were 30% less than WILD, while the TNFR1-/- mice weighed 30% more than WILD mice of equivalent age. Calvariae and humeri of IL-1R1-/- and TNFR1-/- mice were normal with respect to trabecular bone volume, osteoclast number, osteoclast surface, growth plate widths, and cortical thickness. Receptor deficiency was confirmed by determining the ability of PTH, IL-1α, and TNF-α to stimulate IL-6 in the media of primary calvaria-derived osteoblastic cell cultures from CD-1 and cytokine receptor-deficient mice. After 24 h of treatment, IL-1α and TNF-α did not stimulate IL-6 production in osteoblasts from IL-1R1-/- and TNFR1-/- mice, respectively. In contrast, PTH increased IL-6 levels in the cells from all mice. IL-6 protein levels in bone marrow supernatants and conditioned media from untreated bone marrow stromal cells were undetectable in WILD, IL-1R1-/-, and TNFR1-/- mice. PTH, IL-1α, and TNF-α increased IL-6 mRNA and protein production in the WILD bone marrow stromal cells. In contrast, PTH and TNF-α increased IL-6 mRNA and protein levels in IL-1R1-/- bone marrow stromal cells while IL-1α had no effect. These findings demonstrate that normal bone development in mice can occur in the absence of IL-1R1 or TNFR1 expression. (J Bone Miner Res 1996;11:1736-1744)
In vivo reproducibility of three-dimensional structural properties of noninvasive bone biopsies using 3D-pQCT
Authors: Dr. Müller R. , Hildebrand T. , Häuselmann H. J. , Rüegsegger P.
Published: February 2010

Trabecular bone architecture is one of the main factors influencing the mechanical behavior of cancellous bone. To assess the three-dimensional trabecular microstructure of intact bones, we introduced the concept of noninvasive bone biopsy, a method to assess and analyze cancellous bone based upon three-dimensional peripheral quantitative computed tomography in vivo (3D-pQCT). The aim of this work was to demonstrate the potential of noninvasive bone biopsies as a basis for structural and mechanical analysis of trabecular bone in the process of rapid bone loss. A group of six healthy young male volunteers was measured to provide data on the reproducibility of structural parameters. Baseline and 1-month follow-up measurements were performed to provide data on short-term precision of the procedure, and three of the controls were reanalyzed within 3–6 months to estimate long-term precision. Prior to structural evaluation, the baseline and follow-up measurements were repositioned three-dimensionally to ensure matching volumes of interest (VOI). Trabecular bone density (TBD) as well as structural indices were analyzed for all measurements. The VOIs were analyzed morphometrically by evaluating bone volume (BV/TV) and trabecular number (Tb.N) based on a direct three-dimensional approach. Trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were derived from these two indices. The data of the measurements at 1 month to determine the short-term precision was in excellent agreement with the baseline measurements. The results showed that structural parameters can be reproduced in vivo with a coefficient of variation of less than 0.5%. With a typical spread of 4% for the structural indices within the group of healthy volunteers, an intraclass correlation of better than 0.98 was reached. We conclude that high-resolution 3D-pQCT has the potential to detect structural changes in trabecular bone during therapeutic and diagnostic trials. (J Bone Miner Res 1996;11:1745-1750)
Blinded reading of radiographs increases the frequency of errors in vertebral fracture detection
Authors: Dr. Ross Philip D. , Huang Chun , Karpf David , Lydick Eva , Coel Marc , Hirsch Laurence , Wasnich Richard D.
Published: February 2010

We examined the effect of blinding X-rays to film sequence and patient identity on vertebral fracture detection. A sample of 50 postmenopausal women with low bone density and two sets of spine X-rays 3.6 years apart was selected; based on prior morphometric studies, about half of the women had experienced new fractures after the initial film. New morphometric and semiquantitative radiologist readings were each performed twice: blinded and unblinded. For morphometry, incident fractures were defined as vertebral height decreases of more than 15% compared with the initial film. The incidence was slightly higher when blinded versus unblinded (5.6 vs. 5.3% of all vertebrae for morphometry, and 9.7 vs. 8.7% for the radiologist), but these differences were not significant. The error rate was investigated by examining the frequency of “fracture reversals”—vertebrae identified as fractured on the initial film but not on the later film. Agreement between blinded and unblinded readings was generally greater than 80% for fractures but less than 10% for “fracture reversals,” suggesting that reversals are not true events but random errors. The number of reversals was higher when the radiologist was blinded (2.1% of all vertebrae vs. 0.8% when unblinded; p = 0.07). The number of vertebrae with increases greater than 15% in size over time was also greater when morphometry readings were blinded versus unblinded: 0.8 versus 0% (p < 0.05). Although these errors are small, they are similar in magnitude to the annual fracture incidence in many populations. These data show that blinding X-rays to sequence offers no advantages, increases the frequency of errors, and may inflate incidence rates. We conclude that the assessment of X-rays for vertebral fractures in clinical trials should not be performed with the evaluator blinded to the sequence of the X-rays. (J Bone Miner Res 1996;11:1793–1800)
The aqueous Raman optical activity spectra of 4(R)‐hydroxyproline: theory and experiment
Authors: Pecul Magdalena , Deillon Christine , Thorvaldsen Andreas J. , Ruud Kenneth
Published: February 2010

Vibrational Raman optical activity (ROA) spectra have been measured for aqueous solutions of 4(R)‐hydroxyproline at three different pH values and are compared with theoretical results calculated for several conformations of anionic, cationic and zwitterionic 4(R)‐hydroxyproline using density functional theory (DFT) and the polarizable continuum model (PCM). The experimental ROA bands have been ascribed to the normal modes by comparison of the experimental and calculated vibrational frequencies and ROA intensities. Overall, using PCM for geometry optimization and force field calculations gives simulated Raman and ROA spectra that agree with the main features of the experimental spectra, whereas using PCM also in the calculations of optical tensors seems more problematic. Copyright © 2010 John Wiley & Sons, Ltd.
The effects of L‐ to D‐isomerization and C‐terminus deamidation on the secondary structure of antimicrobial peptide Anoplin in aqueous and membrane mimicking environment
Authors: Pripotnev Stahs , Won Amy , Ianoul Anatoli
Published: February 2010

UV resonance Raman spectra of the antimicrobial peptide (AMP) Anoplin (L‐Anoplin‐NH2) and two of its derivatives (enantiomer D‐Anoplin‐NH2 and C‐terminus deamidated L‐Anoplin‐OH) were measured in aqueous buffer solution and in membrane‐mimetic environments including 2,2,2‐trifluoro ethanol (TFE), zwitterionic lipid dipalmitoylglycerophosphocholine (DPPC) and anionic lipid dipalmitoylglycerophosphoglycerol (DPPG) vesicle solutions. All three peptides were found to adopt random‐coil/β turn‐like conformation in aqueous solution over the temperature range of 1–60 °C. The conformation was found to become more α‐helical in membrane‐mimetic solutions such as TFE and DPPG but not in DPPC for all Anoplin derivatives. The data demonstrate that Anoplin preferentially binds to the anionic over the zwitterionic model cell membranes. Results also showed that deamidation does not change the conformation of L‐Ano‐NH2 very significantly, but does alter membrane rupturing and antimicrobial activities thus confirming that it is the physicochemical properties rather than the peptide conformation that define the mechanism of AMP action. Copyright © 2010 John Wiley & Sons, Ltd.
An assessment of sinonasal anatomic variants potentially associated with recurrent acute rhinosinusitis
Authors: Alkire Blake C. , Bhattacharyya Neil
Published: February 2010

Objectives/Hypothesis:

To examine sinonasal anatomic variants that may predispose toward recurrent acute rhinosinusitis (RARS).

Study Design:

Retrospective case‐control.

Methods:

Sinus computed tomography (CT) scans from a consecutive series of adult patients meeting strict diagnostic criteria for RARS were retrospectively reviewed. A control group was assembled from patients who underwent pituitary or temporal bone CT for a nonrhinosinusitis indication. CT scans were scored for the presence of Haller cells, concha bullosa, and impinging septal spurs. Maximal septal deviation (degrees), infundibular widths, and Lund staging were also assessed. The prevalence of these anatomic variants was statistically compared between the RARS and control groups.

Results:

Thirty‐six patients met diagnostic criteria for RARS (mean age, 47.2 years; 2:1 female preponderance); 42 control patients were identified. The mean Lund score for patients with RARS was 2.25 versus 1.27 for the control group (P < .001). Although RARS patients were more likely to manifest concha bullosa (41.7% vs. 28.6%) or impinging septal spurs (27.8% vs. 19.0%), these differences were not statistically significant (P = .165 and P = .260, respectively). However, patients with RARS were significantly more likely to radiographically demonstrate Haller cells (39.9% vs. 11.9%, respectively, P = .006). Finally, patients with RARS had significantly smaller mean infundibular widths when compared with control patients (0.591 mm vs. 0.823 mm, respectively, P < .001).

Conclusions:

The presence of Haller cells and smaller infundibular widths were statistically associated with RARS when compared to control patients. Our data suggest that anatomy could play a role in the pathogenesis of RARS. Further prospective study is warranted. Laryngoscope, 2010
The impact of cotton geotextiles on soil and water losses from Mediterranean rainfed agricultural land
Authors: Giménez‐Morera A. , Sinoga J. D. Ruiz , Cerdà A.
Published: February 2010

High soil erosion risk of Mediterranean cultivated soils is due to steep slopes, high rainfall intensities and low vegetation cover. Traditional land management as ploughing and herbicides give rise to high soil erosion rates. This paper reports on the use of a cotton geotextiles to control soil and water losses on agricultural land under Mediterranean climatic conditions. Eight paired plots (1, 2, 4 and 16 m2) were studied during 1‐year period under natural rainfall. Forty rainfall simulations under wet and dry climatic conditions, and water drop penetration time (WDPT) tests, were carried out in order to analyze the effect of a geotextile on soil and water losses on a typical rainfed orchard in Eastern Spain. Results showed that an 8 mm thick cotton geotextile reduced soil loss to negligible values (from 14 to 0·1 Mg ha−1 y−1) due to the low sediment concentration as geotextile covered 100% of the soil. However, infiltration rates decreased and runoff increased due to the hydrophobic response of the cotton material. The runoff discharge increased from 8% to 16% for the 2004 period under natural rainfall and from 27% to 87% under simulated rainfall when summer dry conditions were reached. The cotton geotextile reduced local soil losses at plot‐scale, but increased runoff. Copyright © 2010 John Wiley & Sons, Ltd.
Impact of belief in neuroprotection on therapeutic intervention in Parkinson's disease
Authors: Elble Rodger J. , Suchowersky Oksana , Shaftman Stephanie , Weiner William J. , Huang Peng , Tilley Barbara ,   On Behalf of the NINDS NET‐PD Investigators
Published: February 2010

We explored the hypotheses that an investigator's belief in a putative neuroprotective agent might influence the timing of symptomatic intervention and the assessment of signs and symptoms of patients with Parkinson's disease with the Unified Parkinson's Disease Rating Scale (UPDRS). These hypotheses were tested with Cox and general linear modeling, using data from a previously published double‐blind placebo‐controlled futility trial of coenzyme Q10 and GPI‐1485. We found the investigators' level of confidence in these agents had no effect on the time to symptomatic therapy or on the change in UPDRS during 12 months of treatment. © 2010 Movement Disorder Society
Glucocerebrosidase Gene L444P mutation is a risk factor for Parkinson's disease in Chinese population
Authors: Sun Qi‐Ying , Guo Ji‐Feng , Wang Lei , Yu Ren‐He , Zuo Xing , Yao Ling‐Yan , Pan Qian , Xia Kun , Tang Bei‐Sha
Published: February 2010

An association between mutations in the glucocerebrosidase (GBA) gene and Parkinson's disease (PD) has been reported in several populations. We searched for four common GBA mutations (L444P, F213I, R353W, and N370S) in 402 Chinese PD patients and 413 age‐ and sex‐matched controls. In the PD cohort, 11 patients were found carrying a heterozygous GBA mutation and all of them had the L444P mutation. Heterozygous GBA mutations were detected none in controls. The GBA gene L444P mutation was detected at a significantly higher frequency among PD patients (11/402 = 2.74%), when compared with the control group (0/413): P = 0.0007. To evaluate the possible role of the GBA gene L444P mutation in PD in Ashkenazi Jewish and non‐Jewish populations, we conducted a meta‐analysis on the topic. In the Chinese population, the GBA gene L444P mutation was detected at a significantly higher frequency among PD patients, when compared with the control group: Z = 3.83, P = 0.0001, OR = 8.42, confidence interval = 95%, 2.83–25.06. In the non‐Jewish populations, the difference was obviously significant: Z = 5.76, P < 0.00001, OR = 8.82, confidence interval = 95%, 4.21–18.48. The results suggest that the GBA gene L444P mutation appears to be a risk factor for PD in Chinese population. © 2010 Movement Disorder Society
Clinical and dual‐tasking aspects in frequent and infrequent fallers with progressive supranuclear palsy
Authors: Lindemann Ulrich , Nicolai Simone , Beische Denis , Becker Clemens , Srulijes Karin , Dietzel Elisabeth , Bauer Sarah , Berg Daniela , Maetzler Walter
Published: February 2010

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with no sufficient therapeutic options to date. Falls are the most devastating feature. The causes of these falls are not well understood. To test the impact of PSP‐associated motor and cognitive features on falls, 26 PSP patients were prospectively recruited and divided into frequent fallers (> one fall/month, 18 patients) and infrequent fallers (≤ one fall/month, 8 patients). Further parameters were assessed by clinical investigation and biomechanical gait and balance analysis with and without dual‐task paradigms. Physical activity was measured through an ambulatory device. Frequent fallers scored higher on the total PSP rating scale and the subscales “history,” “mental,” “bulbar,” “supranuclear ocular motor,” and “gait/midline exam” but not on disease duration, the subscale “limb exam,” the UPDRS motor score and the sway analysis. Frequent fallers also showed an increased probability of an altered walking pattern with shortened step lengths and increased cadence under a dual‐task situation. It is concluded that the occurrence of falls in PSP seems strongly associated with the deterioration of bulbar function, but not relevantly with typical parkinsonian features like rigidity and bradykinesia. The decreased ability to deal with distraction of attention under a dual‐task situation points to a relevant impact of cortical and subcortical dysfunction on the frequency of falls. © 2010 Movement Disorder Society
Sulfonated carbon nanotubes/sulfonated poly(ether sulfone ether ketone ketone) composites for polymer electrolyte membranes
Authors: Zhou Weihua , Xiao Jichun , Chen Yiwang , Zeng Rong , Xiao Shuqin , Nie Huarong , Li Fan , Song Caisheng
Published: February 2010

A series of composite membranes consisting of sulfonated carbon nanotubes (sCNTs) and sulfonated poly(ether sulfone ether ketone ketone) were successfully fabricated via the solution casting method. The chemical structure, as well as the long‐term stability of the sCNTs in different solvents, was investigated by Fourier transform infrared (FTIR) analysis and solubility experiment, respectively. The morphology, tensile strength, proton conductivity, and methanol permeability of the composite membranes were also investigated. The scanning electron microscope (SEM) observation indicated the good dispersion of the carbon nanotubes in polymer matrix as well as the strong interfacial bonding between the sulfonated poly(ether sulfone ether ketone ketone) (SPESEKK) matrix and sCNTs. The addition of either pristine carbon nanotubes or modified carbon nanotubes significantly enhanced the tensile strength of the SPESEKK membrane. The proton conductivity of the SPESEKK membrane increased while the methanol permeability decreased as the sCNTs content increased, showing a strong interaction between the modified nanotubes and SPESEKK. Copyright © 2010 John Wiley & Sons, Ltd.