bluuebunny/crossref_metadata_2025_split huggingface dataset:
RANKL Treatment Releases the Negative Regulation of the Poly(ADP-Ribose) Polymerase-1 on Tcirg1 Gene Expression During Osteoclastogenesis
Authors: Beranger Guillaume E , Momier David , Rochet Nathalie , Quincey Danielle , Guigonis Jean-Marie , Samson Michel , Carle Georges F , Scimeca Jean-Claude 
Published: September 2006

Abstract
The Tcirg1 gene encodes the osteoclast-specific a3 isoform of the V-ATPase a subunit. Using the mouse osteoclastic model RAW264.7 cells, we studied Tcirg1 gene expression, and we identified PARP-1 as a transcriptional repressor negatively regulated by RANKL during osteoclastogenesis.
Introduction: The TCIRG1 gene encodes the a3 isoform of the V-ATPase a subunit, and mutations at this locus account for ∼60% of infantile malignant osteopetrosis cases. Using RAW264.7 cells as an osteoclastic differentiation model, we undertook a transcriptional study of the mouse Tcirg1 gene focused on the 4-kb region upstream of the transcription starting point.
Materials and Methods: The promoter activity of serial-deletion fragments of the Tcirg1 gene promoter was monitored throughout the RAW264.7 cell differentiation process. We next performed EMSA, UV cross-linking, affinity purification, mass spectrometry analysis, gel supershift, and siRNA transfection experiments to identify the factor(s) interacting with the promoter.
Results: The −3946/+113 region of the mouse Tcirg1 gene displayed a high basal promoter activity, which was enhanced by RANKL treatment of RAW264.7 cells. Constructs deleted up to −1589 retained this response to RANKL. A deletion up to −1402 induced a 3-fold enhancement of the basal activity, whereas RANKL response was not affected. EMSA experiments led us to identify within the −1589/−1402 region, a 10-nucleotide sequence, which bound a nuclear protein present in nondifferentiated RAW264.7 cells. This interaction was lost using nuclear extracts derived from RANKL-treated cells. Affinity purification followed by mass spectrometry analysis and gel supershift assay allowed the identification of poly(ADP-ribose) polymerase-1 (PARP-1) as this transcriptional repressor, whereas Western blot experiments revealed the cleavage of the DNA-binding domain of PARP-1 on RANKL treatment. Finally, both PARP-1 depletion after siRNA transfection and RAW264.7 cell treatment by an inhibitor of PARP-1 activity induced an increase of a3 mRNA expression.
Conclusions: We provide evidence that the basal transcription activity of the Tcirg1 gene is negatively regulated by the binding of PARP-1 protein to its promoter region in mouse pre-osteoclast. On RANKL treatment, PARP-1 protein is cleaved and loses its repression effect, allowing an increase of Tcirg1 gene expression that is critical for osteoclast function.
Enhanced Osteoclastogenesis in 4-1BB—Deficient Mice Caused by Reduced Interleukin-10
Authors: Shin Hyun-Hee , Lee Ji-Eun , Lee Eun A , Kwon Byoung Se , Choi Hye-Seon 
Published: September 2006

Abstract
Enhanced osteoclastogenesis was observed in bone marrow—derived macrophage cells from 4-1BB—deficient mice than in those from wildtype mice. 4-1BB and 4-1BB ligand interaction may play a role at a certain stage of osteoclast formation through increased level of IL-10, a negative regulator of osteoclastogenesis.
Introduction: 4-1BB is an inducible T-cell costimulatory molecule and a member of the TNF receptor family. The expression pattern of 4-1BB and 4-1BB ligand (4-1BBL) has suggested that 4-1BB plays a role not only in various responses related to innate immunity but also in bone metabolism.
Materials and Methods: Osteoclast formation was evaluated in bone marrow—derived macrophage cells (BMMs) from wildtype and 4-1BB—deficient (4-1BB−/−) mice. Expression of interleukin-10 (IL-10) during osteoclast formation was analyzed at the mRNA and protein levels.
Results: Expression of IL-10 was higher in RANKL-stimulated wildtype BMMs than 4-1BB−/− BMMs. When 4-1BBL was stimulated with 4-1BB—Fc fusion protein, the expression of IL-10 in BMMs increased. Neutralization of IL-10 was not as effective in preventing inhibition by IL-10 of osteoclast differentiation in 4-1BB−/− BMMs as in wildtype BMMs. When IL-10 was added to the culture medium, osteoclast formation was inhibited more efficiently in the 4-1BB−/− BMMs than in the wildtype BMMs.
Conclusions: Interaction of 4-1BB and 4-1BBL stimulates IL-10 production through 4-1BBL signaling. 4-1BBL plays a role at a certain stage of osteoclast formation, and IL-10 may mediate this effect. The elevated level of osteoclastogenesis in 4-1BB−/− BMMs may thus be caused, in part, by a lower level of IL-10.
Volumetric BMD and Vascular Calcification in Middle-Aged Women: The Study of Women's Health Across the Nation
Authors: Farhat Ghada N , Cauley Jane A , Matthews Karen A , Newman Anne B , Johnston Janet , Mackey Rachel , Edmundowicz Daniel , Sutton-Tyrrell Kim 
Published: September 2006

Abstract
The association of spine vBMD with AC and CAC was studied in a biracial cohort of 490 middle-aged women in the Study of Women's Health Across the Nation. Lower vBMD was related to high AC, but not to CAC, independent of age and shared risk factors between osteoporosis and cardiovascular disease.
Introduction: This analysis studied the association of spine volumetric BMD (vBMD) with aortic (AC) and coronary artery (CAC) calcification in middle-aged women and evaluated whether such associations were independent of age and shared risk factors between osteoporosis and cardiovascular disease (CVD) or explained by endogenous estradiol levels.
Materials and Methods: Vascular calcification and trabecular vBMD of the spine were measured using electron-beam CT in 490 women free from clinical CVD in the Study of Women's Health Across the Nation. Women were 45–58 years of age, 61% were white, and 64% were perimenopausal. Calcification scores were categorized into three levels (no AC, N =146; moderate AC, scores =1–74, N =221; high AC, N =123; no CAC, N =256; moderate CAC, score =1–7.54, N =111; high CAC, N =123). The highest categories were set at the 75th percentiles. Multinomial logistic regression was used to assess the association between vBMD (per SD) and the AC and CAC levels, with no calcification as the reference group.
Results: AC and CAC were detected in 70% and 48% of the population, respectively. Mean vBMD was 161.6 ± 37.2 (SD) mg/ml. vBMD was associated with high AC in unadjusted, age-adjusted, and risk factor—adjusted analysis. Per 1 SD decrease in vBMD, the adjusted odds of high AC compared with no AC was significantly increased by 68% (95% CI, 1.06–2.68). Estradiol did not influence this association. vBMD was related to high CAC in unadjusted (OR =1.35; 95% CI, 1.08–1.70) but not adjusted models. No associations of vBMD with moderate AC or CAC were observed.
Conclusion: Lower vBMD was related to high AC, but not to CAC, in a biracial cohort of healthy middle-aged women independent of age and shared risk factors between osteoporosis and CVD. Further research should study possible pathophysiological links between the two conditions and the potential for common preventive and therapeutic interventions.
Size-Corrected BMD Decreases During Peak Linear Growth: Implications for Fracture Incidence During Adolescence
Authors: Faulkner Robert A , Davison K Shawn , Bailey Donald A , Mirwald Robert L , Baxter-Jones Adam DG 
Published: September 2006

Abstract
Peak adolescent fracture incidence at the distal end of the radius coincides with a decline in size-corrected BMD in both boys and girls. Peak gains in bone area preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting the theory that the dissociation between skeletal expansion and skeletal mineralization results in a period of relative bone weakness.
Introduction: The high incidence of fracture in adolescence may be related to a period of relative skeletal fragility resulting from dissociation between bone expansion and bone mineralization during the growing years. The aim of this study was to examine the relationship between changes in size-corrected BMD (BMDsc) and peak distal radius fracture incidence in boys and girls.
Materials and Methods: Subjects were 41 boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent growth period and again in young adulthood. Ages of peak height velocity (PHV), peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were determined for each child. To control for maturational differences, subjects were aligned on PHV. BMDsc was calculated by first regressing the natural logarithms of BMC and BA. The power coefficient (pc) values from this analysis were used as follows: BMDsc =BMC/BApc.
Results: BMDsc decreased significantly before the age of PHV and then increased until 4 years after PHV. The peak rates in radial fractures (reported from previous work) in both boys and girls coincided with the age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls.
Conclusions: There is a clear dissociation between PBMCV and PBAV in boys and girls. BMDsc declines before age of PHV before rebounding after PHV. The timing of these events coincides directly with reported fracture rates of the distal end of the radius. Thus, the results support the theory that there is a period of relative skeletal weakness during the adolescent growth period caused, in part, by a draw on cortical bone to meet the mineral demands of the expanding skeleton resulting in a temporary increased fracture risk.
Premedication for Nonemergent Neonatal Intubations: A Randomized, Controlled Trial Comparing Atropine and Fentanyl to Atropine, Fentanyl, and Mivacurium
Authors: Roberts Kari D. , Leone Tina A. , Edwards William H. , Rich Wade D. , Finer Neil N. 
Published: October 2006

OBJECTIVE. The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure.
PATIENTS/METHODS. This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of ≤85%, ≤75%, ≤60%, and ≤40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium.
RESULTS. Analysis of 41 infants showed that incidence of oxygen saturation ≤60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration ≤85%, 75%, and 40%; cumulative time ≥30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in ≤2 attempts significantly more often in the mivacurium group (35% vs 71%).
CONCLUSIONS. Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.
N-Cadherin Is Expressed by Putative Stem/Progenitor Cells and Melanocytes in the Human Limbal Epithelial Stem Cell Niche
Authors: Hayashi Ryuhei , Yamato Masayuki , Sugiyama Hiroaki , Sumide Taizo , Yang Joseph , Okano Teruo , Tano Yasuo , Nishida Kohji 
Published: September 2006

Abstract
Corneal epithelial stem cells are known to be localized to the basal layer of the limbal epithelium, providing a model system for epithelial stem cell biology; however, the mechanisms regarding the maintenance of these stem cells in their specialized niche remain poorly understood. N-cadherin is a member of the classic cadherin family and has previously been demonstrated to be expressed by hematopoietic stem cells. In the present study, we demonstrate that N-cadherin is expressed by putative stem/progenitor cells, as well as melanocytes, in the human limbal epithelial stem cell niche. In addition, we demonstrate that upon in vitro culture using 3T3 feeder layers, loss of N-cadherin expression occurs with cell proliferation. These results indicate that N-cadherin may be a critical cell-to-cell adhesion molecule between corneal epithelial stem/progenitor cells and their corresponding niche cells in the limbal epithelium.
The Cell Surface Glycosphingolipids SSEA-3 and SSEA-4 Are Not Essential for Human ESC Pluripotency
Authors: Brimble Sandii N. , Sherrer Eric S. , Uhl Elizabeth W. , Wang Elaine , Kelly Samuel , Merrill Alfred H. , Robins Allan J. , Schulz Thomas C. 
Published: September 2006

Abstract
Pluripotent cells can be isolated from the human blastocyst and maintained in culture as self-renewing, undifferentiated, human ESCs (hESCs). These cells are a valuable model of human development in vitro and are the focus of substantial research aimed at generating differentiated populations for cellular therapies. The extracellular markers that have been used to characterize hESCs are primarily carbohydrate epitopes on proteoglycans or sphingolipids, such as stage-specific embryonic antigen (SSEA)-3 and -4. The expression of SSEA-3 and -4 is tightly regulated during preimplantation development and on hESCs. Although this might imply a molecular function in undifferentiated cells, it has not yet been tested experimentally. We used inhibitors of sphingolipid and glycosphingolipid (GSL) biosynthesis to block the generation of SSEA-3 and -4 in hESCs. Depletion of these antigens and their precursors was confirmed using immunostaining, flow cytometry, and tandem mass spectroscopy. Transcriptional analysis, immunostaining, and differentiation in vitro and in teratomas indicated that other properties of pluripotency were not noticeably affected by GSL depletion. These experiments demonstrated that the GSLs recognized as SSEA-3 and -4 do not play critical functional roles in maintaining the pluripotency of hESCs, but instead suggested roles for this class of molecules during cellular differentiation.
Basal Cells of the Human Adult Airway Surface Epithelium Retain Transit-Amplifying Cell Properties
Authors: Hajj Rodolphe , Baranek Thomas , Le Naour Richard , Lesimple Pierre , Puchelle Edith , Coraux Christelle 
Published: September 2006

AbstractIn numerous airway diseases, such as cystic fibrosis, the epithelium is severely damaged and must regenerate to restore its defense functions. Although the human airway epithelial stem cells have not been identified yet, we have suggested recently that epithelial stem/progenitor cells exist among both human fetal basal and suprabasal cell subsets in the tracheal epithelium. In this study, we analyzed the capacity of human adult basal cells isolated from human adult airway tissues to restore a well-differentiated and functional airway epithelium. To this end, we used the human-specific basal cell markers tetraspanin CD151 and tissue factor (TF) to separate positive basal cells from negative columnar cells with a FACSAria cell sorter. Sorted epithelial cells were seeded into epithelium-denuded rat tracheae that were grafted subcutaneously in nude mice and on collagen-coated porous membranes, where they were grown at the air-liquid interface. Sorted basal and columnar populations were also analyzed for their telomerase activity, a specific transit-amplifying cell marker, by the telomeric repeat amplification protocol assay. After cell sorting, the pure and viable CD151/TF-positive basal cell population proliferated on plastic and adhered on epithelium-denuded rat tracheae, as well as on collagen-coated porous membranes, where it was able to restore a fully differentiated mucociliary and functional airway epithelium, whereas viable columnar negative cells did not. Telomerase activity was detected in the CD151/TF-positive basal cell population, but not in CD151/TF-negative columnar cells. These results demonstrate that human adult basal cells are at least airway surface transit-amplifying epithelial cells.
Assessment of collagen genes involved in fragmented medial coronoid process development in Labrador Retrievers as determined by affected sibling-pair analysis
Authors: Salg Katja G. , Temwitchitr Jedee , Imholz Sandra , Hazewinkel Herman A. W. , Leegwater Peter A. J. 
Published: October 2006

Abstract
Objective—To evaluate the involvement of various collagen genes in the development of fragmented medial coronoid process (FCP) in Labrador Retrievers.
Sample Population—93 dogs originating from 13 litters were used in the study; FCP was diagnosed in 35 dogs, and each affected dog had at least 1 sibling that was also affected. Twelve dams and sires were included in the analysis. All dogs were purebred Labrador Retrievers except for 2 litters (offspring of a female Golden Retriever-Labrador Retriever mixed-breed dog).
Procedures—For each dog, DNA was isolated from blood samples. Polymorphic microsatellite markers adjacent to 14 candidate genes (ie, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL6A3, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1, COL11A2, and COL24A1) were analyzed by use of PCR assays; genotypes were determined via automated detection of DNA products. The level of allele sharing between pairs of affected siblings was assessed.
Results—Among the 93 dogs, allele sharing of the 14 collagen genes was determined as follows: COL1A1, 45%; COL1A2, 47%; COL2A1, 37%; COL3A1, 32%; COL5A1, 43%; COL5A2, 32%; COL6A3, 36%; COL9A1, 45%; COL9A2, 49%; COL9A3, 38%; COL10A1, 46%; COL11A1, 52%; COL11A2, 47%; and COL24A1, 47%.
Conclusions and Clinical Relevance—Because siblings share 50% of their genome at random, the fact that the percentages of allele sharing among the analyzed collagen genes were not significantly > 50% indicates that these genes are not determinant candidates for FCP in Labrador Retrievers. The gene for the vitamin D receptor could also be excluded because of its proximity to COL2A1.
Absence of FTL3 mutations in patients with JAK2V617F mutation negative essential thrombocythemia
Authors: Medeiros Bruno C. , Zhang Tong , Lipton Jeffrey H. , Kamel‐Reid Suzanne 
Published: September 2006

AbstractA common point mutation in the JAK2 tyrosine kinase leads to constitutive hematopoietic growth factor receptor signaling and was recently described in many patients with myeloproliferative disorders (MPDs). However, this JAK2 mutation is present in only a subset (35–50%) of patients with essential thrombocythemia (ET). Thus, the proliferative signals responsible for MPDs in the absence of JAK2 mutations remain largely unknown. Despite intriguing pre‐clinical data, where transgenic mice overexpressing FLT3‐ITD developed a MPD resembling ET, none of the patient samples from ET patients who were JAK2V617F‐negative demonstrated the presence of activating mutations in the FLT3 receptor. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: Association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity, and damage accrual
Authors: Vilá Luis M. , Alarcón Graciela S. , McGwin Gerald , Bastian Holly M. , Fessler Barri J. , Reveille John D. 
Published: September 2006

AbstractObjectiveTo determine if lymphopenia is associated with clinical/immunologic manifestations, disease activity, and disease damage in systemic lupus erythematosus (SLE).MethodsThe study group comprised 591 patients with SLE participating in a multiethnic, longitudinal outcome study. Cumulative clinical/immunologic (per American College of Rheumatology criteria) and pharmacologic treatment variables were obtained at enrollment (T0) and last visit (TL). Lymphopenia (<1,500/mm3) was scored only when clinically attributable to SLE and not to medications or other causes. Lymphocyte counts were expressed in 4 categories per the Systemic Lupus Activity Measure (SLAM): normal (≥1,500/mm3), mild (1,000–1,499/mm3), moderate (500–999/mm3), and marked (<500/mm3). Disease activity was assessed with the SLAM and the Physician's Global Assessment (PGA). Disease damage was determined with the Systemic Lupus International Collaborating Clinics Damage Index (SLICC‐DI). The relationship of lymphopenia with cumulative clinical/immunologic and pharmacologic treatment variables was first examined, then the association between the SLAM, PGA, and SLICC‐DI scores with different categories of lymphopenia was examined by generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered into all regression models.ResultsAt T0 and TL, lymphopenia was found to be positively associated with renal involvement, leukopenia, anti–double‐stranded DNA antibodies, anti‐Ro antibodies, and the use of glucocorticoids, azathioprine, and methotrexate, but was negatively associated with photosensitivity. On GEE analyses, marked lymphopenia at T0 and moderate and marked lymphopenia for all visits were independently associated with higher SLAM, PGA, and SLICC‐DI scores.ConclusionLymphopenia is associated with several clinical/immunologic manifestations in SLE. Moderate and marked lymphopenia are associated with higher disease activity and damage accrual.
Patient treatment preferences for osteoporosis
Authors: Fraenkel Liana , Gulanski Barbara , Wittink Dick 
Published: September 2006

AbstractObjectiveTo examine patient preferences for currently available and promising osteoporosis treatment options.MethodsWe recruited patients who had recently (within 2 weeks) undergone bone densitometry and were found to have osteoporosis. Consenting participants completed an Adaptive Conjoint Analysis questionnaire to determine their treatment preferences for oral bisphosphonates taken once per week, intravenous bisphosphonates administered every 3 months, intravenous bisphosphonates administered once per year, and subcutaneous recombinant human parathyroid hormone (rhPTH). We performed simulations based on respondents' values for route of administration, absolute reduction in risk of vertebral and hip fractures over 5 years, and risk of adverse effects to predict each respondent's treatment choice.ResultsThe study sample included 201 women and 11 men (median age 73). Patients' treatment preferences were strongly influenced by route of administration. Patients' preferred treatment option, across all simulations, was bisphosphonates. Among 80 treatment‐naive participants, 52 (65%) preferred an annual infusion over oral weekly bisphosphonates. Participants with poorer perceived health status, those with a high perceived risk of future fracture, and participants preferring to treat health problems without doctors or prescription drugs were more likely to prefer an annual infusion over weekly pills.ConclusionPatient preferences for osteoporosis treatment options are strongly influenced by route of administration. Therefore, despite the added benefits of rhPTH, patients' preferred treatment option for osteoporosis is bisphosphonates. Among those preferring bisphosphonates, many preferred annual infusions over weekly oral medications, emphasizing the need to incorporate individual patient preferences into treatment decisions for osteoporosis. The latter is especially important given the poor rates of long‐term adherence to osteoporosis medications.