bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous luminal nitric oxide exposure accelerates columnar transformation of rat esophagus
Authors: Endo Hiroyuki , Iijima Katsunori , Asanuma Kiyotaka , Ara Nobuyuki , Ito Hirotaka , Asano Naoki , Uno Kaname , Koike Tomoyuki , Imatani Akira , Shimosegawa Tooru 
Published: February 2010

AbstractExposure of the esophageal mucosa to refluxed gastroduodenal contents is recognized to be an important risk factor for Barrett's esophagus (BE). At the human gastroesophageal junction, nitric oxide is generated luminally through the enterosalivary recirculation of dietary nitrate, and in cases with gastroesophageal reflux, the site of luminal nitric oxide generation could shift to the distal esophagus. The aim of this study is to investigate whether exogenous luminal nitric oxide could promote the development of BE in rats. Sodium nitrite plus ascorbic acid were administered to a rat surgical model of BE, in which the gastroduodenal contents were refluxed into the esophagus to generate exogenous luminal nitric oxide in the esophagus by the acid‐catalyzed chemical reaction between the 2 reagents. The emergence of BE was evaluated histologically in the early phase (several weeks) after the surgery with or without exogenous nitric oxide administration. To elucidate the histogenesis of BE, CDX2, MUC2 and MUC6 expressions were investigated immunohistochemically. Coadministration of sodium nitrite plus ascorbic acid significantly accelerated the timing of emergence and increased the area of BE compared with controls. Administration of either reagent alone did not show any promotive effects on BE formation. Immunohistochemically, the columnar epithelium thus induced was similar to the specialized intestinal metaplasia in human BE. The results of this animal model study suggest that exogenous luminal nitric oxide could be involved in the pathogenesis of the columnar transformation of the esophagus. Further studies in human are warranted.
Genetic variation of PSCA gene is associated with the risk of both diffuse‐ and intestinal‐type gastric cancer in a Chinese population
Authors: Lu Yan , Chen Jianjian , Ding Yanbing , Jin Guangfu , Wu Juan , Huang Hua , Deng Bin , Hua Zhaolai , Zhou Yan , Shu Yongqian , Liu Ping , Hu Zhibin , Shen Jing , Xu Yaochu , Shen Hongbing 
Published: February 2010

AbstractProstate stem cell antigen (PSCA), a member of the LY‐6/Thy‐1 family of glycosylphosphatidylinositol‐anchored cell surface proteins, is considered to be involved in the cell‐proliferation inhibition and/or cell‐death induction activity. Two single nucleotide polymorphisms (SNPs) (rs2976392 and rs2294008) in the PSCA gene were recently identified as the susceptibility loci of gastric cancer, especially in diffuse type. Therefore, this study was to investigate whether these 2 SNPs were associated with the risk of gastric cancer in Chinese population. We genotyped rs2976392 and rs2294008 in PSCA in a case–control study including 1,053 incident gastric cancer patients and 1,100 cancer‐free controls in a high‐risk Chinese population. We found that variant genotypes of rs2976392 (GA/AA) were associated with a significantly 37% increased risk of gastric cancer (adjusted OR =1.37, 95% CI = 1.15–1.62), compared with variant homozygote GG, and the associations were all consistently significant in both intestinal and diffuse subtypes, and among different subgroups stratified by age, sex, drinking or smoking status. Interestingly, a significant multiplicative interaction between rs2976392 (GA/AA) and alcohol drinking was detected on the development of intestinal‐type gastric cancer (p = 0.009). However, rs2294008 variant genotypes (CT/TT) were associated with a nonsignificant increased risk of gastric cancer (adjusted OR = 1.14, 95% CI = 0.96–1.36). A small meta‐analysis including 5 case–control studies showed undoubtedly associations between PSCA rs2294008 and rs2976392 and gastric cancer risk (OR = 1.83, 95% CI: 1.29–2.60 and OR = 1.84, 95% CI: 1.33–2.56, respectively). These findings provide further evidence supporting that the genetic variants of PSCA gene may contribute to the gastric carcinogenesis.
MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: a comparative study on astrocytoma and glioblastoma
Authors: Christmann Markus , Nagel Georg , Horn Sigrid , Krahn Ulrike , Wiewrodt Dorothee , Sommer Clemens , Kaina Bernd 
Published: February 2010

AbstractThe DNA repair protein O6‐methylguanine‐DNA methyltransferase (MGMT) is a key player in tumor cell resistance. Promoter methylation, MGMT activity and immunohistochemistry are used for determining the MGMT status. However, it is unclear whether MGMT promoter methylation correlates with MGMT activity and whether MGMT promoter methylation of the pretreatment tumor predicts the MGMT status of recurrences. To address these questions, we determined MGMT activity promoter methylation and immunoreactivity in pretreatment and recurrent glioblastomas (GB, WHO Grade IV), and in astrocytomas (WHO Grade III). We show that GB that were promoter methylated display a range of 0–62 fmol/mg MGMT and tumors that were nonmethylated 0–423 fmol/mg protein. For astrocytomas, promoter‐methylated samples displayed 0–28 fmol/mg and, nonmethylated samples, 23–107 fmol/mg. No correlation was found between the intensity of promoter methylation and MGMT activity. Given a threshold level of 30 fmol/mg of protein, we found a correlation between promoter methylation and no/low MGMT activity in 82.4% of the tumors. This high correlation level was only observed when tumors were excluded showing a hemimethylated promoter (20%). Therefore, classification of hemimethylated tumors remains questionable. Further, we show that 39.1% of pretreatment GB and 5.3% of recurrences were promoter methylated, which is in line with the observed increase of MGMT activity in recurrences. Although individual exceptions were found, the data show an overall correlation between promoter methylation and lack/low MGMT activity in GB and astrocytomas. We also show that promoter methylation assay is superior over immunohistochemistry in determining the MGMT status defined by a given MGMT activity level.
Dramatic increase in cortical thickness induced by femoral marrow ablation followed by a 3-month treatment with PTH in rats
Authors: Zhang Qing , Carlson Jodi , Ke Hua Zhu , Li Jiliang , Kim Michael , Murphy Kieran , Mehta Nozer , Gilligan James , Vignery Agnès 
Published: February 2010

Abstract
We previously reported that following mechanical ablation of the marrow from the midshaft of rat femurs, there is a rapid and abundant but transient growth of bone, and this growth is enhanced and maintained over a 3-week period by the bone anabolic hormone parathyroid hormone (PTH). Here, we asked whether further treatment with PTH or bisphosphonates can extend the half-life of the new bone formed in lieu of marrow. We subjected the left femur of rats to mechanical marrow ablation and treated the animals 5 days a week with PTH for 3 weeks (or with vehicle as a control) to replace the marrow by bone. Some rats were euthanized and used as positive controls or treated with vehicle, PTH, or the bisphosphonate alendronate for a further 9 weeks. We subjected both femurs from each rat to soft X-ray, peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT), dynamic histomorphometry analysis, and biomechanical testing. We also determined the concentrations of serum osteocalcin to confirm the efficacy of PTH. Treatment with PTH for 3 months dramatically enhanced endosteal and periosteal bone formation, leading to a 30% increase in cortical thickness. In contrast, alendronate protected the bone that had formed in the femoral marrow cavity after marrow ablation and 3 weeks of treatment with PTH but failed to promote endosteal bone growth or to improve the biomechanical properties of ablated femurs. We further asked whether calcium-phosphate cements could potentiate the formation of bone after marrow ablation. Marrow cavities from ablated femurs were filled with one of two calcium-phosphate cements, and rats were treated with PTH or PBS for 84 days. Both cements helped to protect the new bone formed after ablation. To some extent, they promoted the formation of bone after ablation, even in the absence of any anabolic hormone. Our data therefore expand the role of PTH in bone engineering and open new avenues of investigation to the field of regenerative medicine and tissue engineering. Local bone marrow aspiration in conjunction with an anabolic agent, a bisphosphonate, or a calcium-phosphate cement might provide a new platform for rapid preferential site-directed bone growth in areas of high bone loss. © 2010 American Society for Bone and Mineral Research
Individual trabeculae segmentation (ITS)–based morphological analysis of high-resolution peripheral quantitative computed tomography images detects abnormal trabecular plate and rod microarchitecture in premenopausal women with idiopathic osteoporosis
Authors: Liu X Sherry , Cohen Adi , Shane Elizabeth , Stein Emily , Rogers Halley , Kokolus Shannon L , Yin Perry T , McMahon Donald J , Lappe Joan M , Recker Robert R , Guo X Edward 
Published: February 2010

Abstract
Idiopathic osteoporosis (IOP) in premenopausal women is a poorly understood entity in which otherwise healthy women have low-trauma fracture or very low bone mineral density (BMD). In this study, we applied individual trabeculae segmentation (ITS)–based morphological analysis to high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the distal radius and distal tibia to gain greater insight into skeletal microarchitecture in premenopausal women with IOP. HR-pQCT scans were performed for 26 normal control individuals and 31 women with IOP. A cubic subvolume was extracted from the trabecular bone compartment and subjected to ITS-based analysis. Three Young's moduli and three shear moduli were calculated by micro–finite element (µFE) analysis. ITS-based morphological analysis of HR-pQCT images detected significantly decreased trabecular plate and rod bone volume fraction and number, decreased axial bone volume fraction in the longitudinal axis, increased rod length, and decreased rod-to-rod, plate-to-rod, and plate-to-plate junction densities at the distal radius and distal tibia in women with IOP. However, trabecular plate and rod thickness did not differ. A more rod-like trabecular microstructure was found in the distal radius, but not in the distal tibia. Most ITS measurements contributed significantly to the elastic moduli of trabecular bone independent of bone volume fraction (BV/TV). At a fixed BV/TV, plate-like trabeculae contributed positively to the mechanical properties of trabecular bone. The results suggest that ITS-based morphological analysis of HR-pQCT images is a sensitive and promising clinical tool for the investigation of trabecular bone microstructure in human studies of osteoporosis. © 2010 American Society for Bone and Mineral Research
A simple method for correlative light and scanning electron microscopy of human iliac crest bone biopsies: Qualitative observations in normal and osteoporotic subjects
Authors: Dr. Dempster D. W. , Shane E. , Horbert W. , Lindsay R. 
Published: February 2010

Abstract
Despite the fact that the scanning electron microscope (SEM) offers a number of unique advantages for the investigation of bone structure, this instrument has seldom been applied in studies of the iliac crest bone biopsy. Here we describe a very simple method of preparing iliac crest biopsies for examination in the SEM after the routine histomorphometric analysis has been performed. With observations on biopsies from normal subjects and patients with osteoporosis, the paper illustrates the potential of the method for performing correlative light and scanning electron microscopical studies and for gaining new information on the three-dimensional architecture of trabecular bone.
Binding of calcitonin and calcitonin gene-related peptide to calvarial cells and renal cortical membranes
Authors: Seitz Patricia K. , Thomas Mary L. , Dr. Cooper Cary W. 
Published: February 2010

Abstract
Binding of calcitonin (CT) and calcitonin gene-related peptide (CGRP) to rat hemicalvariae and renal membranes was examined in an effort to determine whether CT and CGRP interact with the same bone cell binding site, and to see whether the binding pattern was similar for bone and renal cortex. Specific binding of 125I-salmon CT to rat calvariae was inhibited by unlabeled salmon, porcine, or human CT, but not by rat CGRP. Binding of 125I-rat CGRP to calvariae was inhibited by CGRP and high doses of salmon CT, but not by human or porcine CT. Binding of 125I-salmon CT to renal membranes was inhibited by unlabeled salmon CT or rat CGRP, but no specific binding of 125I-rat CGRP could be detected. The results suggest that separate bone cell receptors for CT and CGRP exist and that CGRP can interact with renal receptors for CT.
Effects of age and estrogen on calcium absorption in the rat
Authors: Russell Jean E. , Morimoto Shigeto , Birge Stanley J. , Fausto Aurora , Avioli Louis V. 
Published: February 2010

Abstract
In order to differentiate the relative effects of age and estrogen on rates of calcium absorption and serum levels of parathyroid hormone and calcitonin, the effect of oophorectomy with and without estrogen replacement (2 weeks) was studied in rats for 30- or 120-day periods. Whereas oophorectomy for 30 days resulted in a significant decrease in serum calcium and an increase in serum phosphate, no change in either calcium or phosphate was observed in the 120-day oophorectomized animals. iPTH decreased in both the 30- and 120-day oophorectomized animals although these changes were not significant at the .05 level. Whereas no significant change in basal circulating calcitonin occurred in the 30-day oophorectomized rats, it decreased significantly in the older animals following the ablative procedure. Forty-five days following estrogen deprivation, calcitonin release to a calcium secretagogue was significantly blunted. Intestinal calcium absorption decreased with age, and unlike the increments in calcium absorption observed in the younger estrogen-repleted, 30-day oophorectomized rat, no change in calcium absorption was observed when estrogens were administered to the older, 120-day oophorectomized rat. The accumulated data suggest that the effects of estrogen loss on the hormonal control of bone metabolism and calcium absorption are age dependent, and that estrogen contributes significantly to changes in calcium homeostasis observed in the maturing rat.
Prostaglandins change cell shape and increase intercellular gap junctions in osteoblasts cultured from rat fetal calvaria
Authors: Shen Victor , Rifas Leonard , Kohler Gail , Peck William A. 
Published: February 2010

Abstract
Mounting experimental evidence indicates that osteoblasts may be cellular intermediaries in the local activation of bone remodeling. To elucidate the role of these cells in activation, we examined the effects of prostaglandins (PGs), known resorption stimulators, on cell shape and intercellular junctional relationships in osteoblasts cultured from rat fetal calvaria. Exposure to PGE2 and PGE1, promoters of bone resorption, rapidly (within 20 min) converted the osteoblasts from a flattened to a stellate shape (shape change), and markedly increased the appearance of intercellular (gap) junctions within 10 min. Both effects were directly related to the prostaglandin concentration, as little as 1 nM being effective. PGE1, but not PGB1, PGF1α, PGD2, and PGF2α, mimicked the substantial effect of PGE2 on shape change. Shape change and gap junction formation appear to arise independently. PTH, an inducer of shape change, did not affect the number of gap junctions appreciably. Colchicine, a microtubule polymerization inhibitor, and trifluoperazine, an inhibitor of calmodulin action, blunted PGE2-mediated shape change but not the effect of PGE2 on gap junctions. Shape change and gap junction formation may be important events in local activation, shape changes in surface osteoblasts serving to expose bone surfaces which are chemotactic for osteoclasts and gap junctions propagating locally initiated activation messages.
Serum bone GLA-protein in growth hormone deficient children
Authors: Dr. Delmas Pierre D. , Chatelain Pierre , Malaval Luc , Bonne Graziela 
Published: February 2010

Abstract
Serum bone GLA-protein (BGP), a sensitive and specific marker of bone formation, was measured in 54 normal children and in 50 children with growth disorders. In normal children, the pattern of variations of serum BGP with age was similar to the pattern of variations of the growth velocity. Mean serum BGP was very high during the first year of life (25.3 ± 8.5 ng/ml), decreased to 14.8 ± 2.2 ng/ml from 2 to 6 years, increased to 18.4 ± 4.1 ng/ml from 7 to 10 years and to 18.8 ± 6.5 ng/ml from 11 to 14 years. After puberty, mean sBGP decreased to 12.9 ± 5.4 ng/ml from 15 to 18 years and to 6.5 ± 1.4 ng/ml in young adults. In 32 patients with untreated growth hormone (GH) deficiency, mean sBGP was markedly lower than in age matched controls (6.8 ± 4.4 ng/ml vs. 17.5 ± 4.9 ng/ml, p &lt; .001). In 19 patients with GH deficiency who were undergoing treatment with human GH, sBGP was higher than in untreated patients (20.5 ± 9.3 ng/ml vs. 6.8 ± 4.4 ng/ml, p &lt; .001) and was not different from controls. Repeated measurements performed in 14 GH-deficient patients under chronic GH therapy showed that serum BGP: (1) increased in most patients during treatment (p &lt; .005); (2) was correlated with the duration of treatment (p &lt; .001); (3) decreased to pretreatment values after discontinuing therapy. In conclusion, our data suggest that serum BGP is a sensitive marker of skeletal growth in normal children and in children with growth deficiency, and that measurement of serum BGP might be useful to assess the effects on bone metabolism of hormones and/or drugs that stimulate bone growth and maturation.
Effects of retinoic acid on the activation and fusion of mouse alveolar macrophages induced by 1α,25-dihydroxyvitamin D3
Authors: Miyaura Chisato , Segawa Akihisa , Nagasawa Hiroshi , Abe Etsuko , Dr. Suda Tatsuo 
Published: February 2010

Abstract
1α, 25-dihydroxyvitamin D3 [1α,25(OH)2D3] directly induces both fusion and cytotoxicity in murine alveolar macrophages. Unlike 1α,25(OH)2D3, retinoic acid per se did not induce fusion of alveolar macrophages, but it greatly enhanced the 1α,25(OH)2D3-induced fusion every time the macrophages were treated simultaneously with the two vitamins. The giant cells induced by the two vitamins were much larger than those induced by 1α,25(OH)2D3 alone. The macrophages treated with 1α,25(OH)2D3 started to fuse 36 h after the addition of the vitamin, whereas the macrophages pretreated with retinoic acid for 24 h began to fuse immediately after 1α,25(OH)2D3 was added. 1α,25(OH)2D3 and retinoic acid activated alveolar macrophages similarly, measured by the enhancement of glucose consumption and the induction of cytotoxicity against tumor cells, though 1α,25(OH)2D3 was 100 times more potent than retinoic acid on a molar basis. Simultaneous treatment with physiological concentrations of 1α,25(OH)2D3 (0.12 nM) and retinoic acid (10 nM) induced cytotoxicity additively. Morphological examinations revealed that the treated cells were enlarged and flattened with numerous filopodia. These results clearly indicate that both 1α,25(OH)2D3 and retinoic acid similarly activate alveolar macrophages, and the activated state is prerequisite to the fusion of macrophages induced by 1α,25(OH)2D3.
Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1–34) and 1,25-dihydroxyvitamin D
Authors: Dr. Slovik David M. , Rosenthal Daniel I. , Doppelt Samuel H. , Potts John T. , Daly Margaret A. , Campbell Julie A. , Neer Robert M. 
Published: February 2010

Abstract
Daily subcutaneous injection of a synthetic human parathyroid hormone fragment, combined with daily ingestion of 1,25(OH)2 vitamin D, significantly increased trabecular bone density in the spine (p &lt; .01), and improved intestinal calcium and phosphorus absorption and total body retention of dietary calcium and phosphorus in middle-aged men with idiopathic osteoporosis. The increases in spinal bone mineral were marked and progressive during a year of treatment. These results indicate that increasing intestinal absorption of dietary calcium while simultaneously stimulating new bone formation with small doses of parathyroid hormone can restore spinal bone in osteoporotic men.
Aluminum-associated bone disease in chronic renal failure: High prevalence in a long-term dialysis population
Authors: Andress Dennis L. , Maloney Norma A. , Dr. Endres David B. , Sherrard Donald J. 
Published: February 2010

Abstract
Twenty-seven asymptomatic patients treated with hemodialysis longer than 8 years (mean 12.9 ± 3.1 years) underwent bone biopsy to determine the prevalence of aluminum-associated bone disease. None had excess aluminum exposure from the dialysate. Ten patients (37%) had aluminum-associated bone disease as defined by a bone formation rate (BFR) below normal in the presence of stainable bone aluminum that covered more than 25% of the trabecular surface. The predominant type of bone histology in this group was the aplastic lesion characterized by low bone turnover, a decreased number of osteoblasts, and lack of excess unmineralized osteoid. Osteoblastic osteoid was highly correlated with stainable surface bone aluminum (r = - .82, p &lt; .001). Among the dynamic bone parameters, the double-tetracycline labeled surface was a more sensitive indicator of impaired bone function than was the bone apposition rate (BAR), since half of the patients with aluminum-associated bone disease had a normal BAR. In all of the biopsies the extent of double-labeled surfaces was inversely proportional to the amount of stainable aluminum on the bone surface (r = - .71, p &lt; .001), whereas stainable bone aluminum did not correlate with BAR. In seven of the patients with aluminum-associated bone disease, amino-terminal PTH levels were in the normal range while only one patient had a normal plasma mid-region PTH. PTH correlated directly with osteoblastic osteoid, BFR, and double-labeled surfaces. These results indicate that long-term oral aluminum intake in hemodialysis patients results in a high prevalence of aluminum-associated bone disease. The decrease in osteoblast number appears to be the major mechanism for the low bone formation. Whether aluminum adversely affects the osteoblast population directly or decreases osteoblast number indirectly via suppression of PTH secretion remains undecided.