bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental Models of Paget's Disease
Authors: Kurihara Noriyoshi , Zhou Hua , Reddy Sakamuri V , Garcia Palacios Veronica , Subler Mark A , Dempster David W , Windle Jolene J , Roodman G David 
Published: January 2007

Abstract
We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo.
Introduction: Paget's disease (PD) is one of the most exaggerated examples of abnormal bone remodeling, with increased bone resorption and excessive new bone formation. However, its etiology is unclear. A viral etiology for PD has been suggested based on the presence of paramyxoviral-like nuclear inclusions, detection of measles virus nucleocapsid (MVNP) mRNA or protein in osteoclasts (OCLs) from PD lesions, and in vitro studies showing that transfection of normal OCL precursors with the MVNP gene results in formation of OCLs that express a pagetic phenotype (increased numbers of OCLs; increased responsivity to 1,25(OH)2D3, RANKL, and TNF-α; increased expression of the TAFII-17 gene, and increased bone resorption capacity).
Materials and Methods: We targeted MVNP to cells in the OCL lineage in transgenic mice using the TRACP promoter.
Results: Histomorphometric analysis showed that there was a 64% increase in OCL perimeter (p = 6.0002) and 37% increase in osteoblast (OBL) perimeter in MVNP mice. In a mouse that was 14 months of age, there was a 225% increase in OBL perimeter and 149% in OBL perimeter. This was accompanied by increased cancellous bone volume (83%) and trabecular width (47%) and number (25%), with a marked increase in the amount of woven bone. In contrast, cancellous bone volume decreased between 3 and 12 months in wildtype (WT) mice, whereas cancellous bone volume in MVNP mice increased over the same time period. Ex vivo studies showed that the numbers of OCLs formed in marrow cultures from MVNP mice were increased, and the OCLs were hyper-responsive to 1,25(OH)2D3 and had an increased bone resorbing capacity compared with WT cultures.
Conclusion: These results show that expression of MVNP in OCL in vivo results in a bone phenotype that is characteristic of PD.
Surgical Management of Paget's Disease of Bone
Authors: Parvizi Javad , Klein Gregg R , Sim Franklin H 
Published: January 2007

Abstract
Paget's disease is a chronic nonmetabolic bone disorder that is characterized by increased bone resorption, bone formation, and remodeling. This unbalanced process may lead to osseous deformities, structural weakness, and altered joint biomechanics, all of which can make surgical reconstruction difficult. Although few patients with Paget's disease ever need surgical treatment, successful surgical management of orthopedic manifestations of the disease has improved the quality of life for these patients. Surgical options include corrective osteotomy for long bone deformity, fracture fixation, joint arthroplasty, spinal decompression, and tumor resection. Patients are at increased risk for surgical complications such as blood loss and heterotopic bone formation. Issues relating to the surgical management of patients with Paget's disease such as appropriate preoperative diagnosis, technical challenges of surgery, and strategies to improve the long-term outcome of surgical intervention are discussed.
Effects Of a One-Month Treatment With PTH(1–34) on Bone Formation on Cancellous, Endocortical, and Periosteal Surfaces of the Human Ilium
Authors: Lindsay Robert , Zhou Hua , Cosman Felicia , Nieves Jeri , Dempster David W , Hodsman Anthony B 
Published: January 2007

Abstract
Using bone histomorphometry, we found that a 1-month treatment with PTH(1–34) [hPTH(1–34)] stimulated new bone formation on cancellous, endocortical, and periosteal bone surfaces. Enhanced bone formation was associated with an increase in osteoblast apoptosis.
Introduction: The precise mechanisms by which hPTH(1–34) increases bone mass and improves bone structure are unclear. Using bone histomorphometry, we studied the early effects of treating postmenopausal women with osteoporosis with hPTH(1–34).
Materials and Methods: Tetracycline-labeled iliac crest bone biopsies were obtained from 27 postmenopausal women with osteoporosis who were treated for 1 month with hPTH(1–34), 50 μg daily subcutaneously. The results were compared with tetracycline-labeled biopsies from a representative control group of 13 postmenopausal women with osteoporosis.
Results: The bone formation rate on the cancellous and endocortical surfaces was higher in hPTH(1–34)–treated women than in control women by factors of 4.5 and 5.0, respectively. We also showed a 4-fold increase in bone formation rate on the periosteal surface, suggesting that hPTH(1–34) has the potential to increase bone diameter in humans. On the cancellous and endocortical surfaces, the increased bone formation rate was primarily caused by stimulation of formation in ongoing remodeling units, with a modest amount of increased formation on previously quiescent surfaces. hPTH(1–34)–stimulated bone formation was associated with an increase in osteoblast apoptosis, which may reflect enhanced turnover of the osteoblast population and may contribute to the anabolic action of hPTH(1–34).
Conclusions: These findings provide new insight into the cellular basis by which hPTH(1–34) improves cancellous and cortical bone architecture and geometry in patients with osteoporosis.
Genetic and Environmental Determinants of Volumetric and Areal BMD in Multi-Generational Families of African Ancestry: The Tobago Family Health Study
Authors: Wang Xiaojing , Wheeler Victor W , Patrick Alan L , Bunker Clareann H , Zmuda Joseph M 
Published: January 2007

Abstract
BMD is higher and fracture risk is lower among individuals of African versus European descent, but little is known about the genetic architecture of BMD in the former group. Heritabilities of areal and volumetric BMD were moderate in our large families of African descent but differed for trabecular and cortical BMD.
Introduction: Populations of African ancestry have lower osteoporotic fracture risk and higher BMD than other ethnic groups. However, there is a paucity of information regarding the genetic and environmental influences on bone health among populations of African heritage.
Materials and Methods: We dissected the genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar spine, and whole body and volumetric BMD measured by pQCT at the distal and proximal radius and tibia in 283 women and 188 men ≤18 years of age (mean, 43 years) from eight multigenerational Afro-Caribbean families (mean family size &gt; 50). Using quantitative genetic methods, we estimated the residual heritability and the effects of anthropometric, demographic, lifestyle, and medical variables on areal and volumetric BMD.
Results: Compared with U.S. non-Hispanic blacks and whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and women at all ages. Trabecular volumetric BMD decreased linearly with increasing age, whereas cortical volumetric BMD did not decrease until age 40–49, especially in women. Anthropometric, lifestyle, and medical factors accounted for 12–32% of the variation in areal and volumetric BMD, and residual heritabilities (range, 0.23–0.52) were similar to those reported in other ethnic groups. Heritability of cortical BMD was substantially lower than that of areal or trabecular volumetric BMD, although the measured covariates accounted for a similar proportion of the total phenotypic variation.
Conclusions: Our study is the first comprehensive genetic epidemiologic analysis of volumetric BMD measured by QCT and the first analysis of these traits in extended families of African descent. Genes account for as much or more of the total variation in areal and volumetric BMD than do environmental factors, but these effects seem to differ for trabecular and cortical bone.
Food and Drug Administration Drug Approval Summary: Sunitinib Malate for the Treatment of Gastrointestinal Stromal Tumor and Advanced Renal Cell Carcinoma
Authors: Rock Edwin P. , Goodman Vicki , Jiang Janet X. , Mahjoob Kooros , Verbois S. Leigh , Morse David , Dagher Ramzi , Justice Robert , Pazdur Richard 
Published: January 2007

Learning Objectives
After completing this course, the reader will be able to: Discuss the mechanism of action of the newly approved targeted cancer drug sunitinib.List the current approved oncology indications for this agent.Describe the pharmacology, metabolism, and side effect profile of sunitinib.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Final Report of Toxicity and Efficacy of a Phase II Study of Oral Cyclophosphamide, Thalidomide, and Prednisone for Patients with Relapsed or Refractory Multiple Myeloma: A Hoosier Oncology Group Trial, HEM01-21
Authors: Suvannasankha Attaya , Fausel Christopher , Juliar Beth E. , Yiannoutsos Constantin T. , Fisher William B. , Ansari Rafat H. , Wood Lisa L. , Smith Gina G. , Cripe Larry D. , Abonour Rafat 
Published: January 2007

Abstract
Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per 28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The median follow-up time was 25.3 months (95% confidence interval [CI] 23.2–27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease, and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8–10.9) and 13.2 months (95% CI 9.4–21.0), respectively. The median number of treatment cycles was seven (range 1–12 cycles). Grade III to IV toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future development of such an approach in MM.
Phenol red in the culture medium strongly affects the susceptibility of human MCF-7 cells to roscovitine
Authors: Węsierska-Gądek Józefa , Schreiner Tanja , Maurer Margarita , Waringer Astrid , Ranftler Carmen 
Published: January 2007

AbstractEstrogens play an important role in the growth and terminal differentiation of the mammary gland. Prolonged exposure to estrogens seems to predispose women to breast cancer. It recently became evident that not only the intrinsic hormonal status but also external factors such as the occurrence of pharmaceuticals and chemicals with hormone activity in the environment may put women at greater risk of developing breast cancer. We focused on the interference of endocrine disruptors in breast cancer therapy. We observed that phenol red added to the culture medium strongly promoted the cell proliferation and cell cycle progression of human cells expressing the estrogen receptor, and affected their susceptibility to chemotherapy.
Microarray analysis reveals the role of matrix metalloproteinases in mouse experimental autoimmune myocarditis induced by cardiac myosin peptides
Authors: Tang Qizhu , Huang Ji , Qian Haiyan , Xiong Ran , Shen Difei , Wu Hui , Bian Zhouyan , Wei Xiaohong 
Published: January 2007

AbstractAutoimmune myocarditis develops after the presentation of heart-specific antigens to autoaggressive CD4+ T cells and after inflammation has infiltrated the tissues. To shed light on global changes in the gene expression of autoimmune myocarditis and to gain further insight into the molecular mechanisms underlying the genesis of myocarditis, we conducted a comprehensive microarray analysis of mRNA using an experimental mouse autoimmune myocarditis model via immunization with α-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a high density oligonucleotide microarray, 466 were under-expressed and 241 over-expressed by ≥ 1.5-fold compared with the controls in BALB/C mouse with autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes related to the immune response. These altered genes encode for leukocyte-specific markers and receptors, the histocompatibility complex, cytokines/receptors, chemokines/receptors, adhesion molecules, components of the complement cascade, and signal transduction-related molecules. Interestingly, matrix metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. This indicates that MMPs may act as major regulators of the cytokine profile. Together, these findings provide new insight into the molecular events associated with the mechanism of the autoimmune genesis of myocarditis.
Detection of the status of tumour-infiltrating CD4+ T-cell subpopulations in squamous cell carcinoma of the head and neck (HNSCC) using real-time RT-PCR detection of CD4 mRNA
Authors: Smerkolj Sava , Volavšek Metka , Glavač Damjan 
Published: January 2007

AbstractSeveral studies have reported tumour infiltrating CD4+ T cells as a favourable prognostic factor in some types of cancer. We investigated 37 head and neck squamous cell carcinomas (HNSCC) at different stages, using immunohistochemical staining for CD4+ infiltrates and real-time reverse transcription polymerase chain reaction (RT-PCR) detection of CD4 mRNA. The CD4+ infiltrates were evaluated and expressed as a percentage according to the ratio of CD4+ T cells to epithelial cells in the cancer cell nests and to the overall inflammatory cell infiltrate in the tumor stroma. The CD4 mRNA expression level strongly correlated with the CD4+ infiltration score in the cancer epithelium (rs = 0.858, P < 0.001) and in the cancer stroma (rs = 0.797, P < 0.001). These results indicate that the real-time RT-PCR assay is a sensitive and reliable method for the detection of CD4 mRNA, and that it could be used to reassess CD4+ infiltration status in resected specimens from patients with HNSCC.
Market power in tobacco: Measuring multiple markets
Authors: Raper Kellie Curry , Love H. Alan 
Published: January 2007

AbstractTraditional market power analyses of the U.S. cigarette manufacturing industry consider monopoly power exertion by manufacturers in selling cigarettes to consumers. Market characteristics combined with government policy make it plausible that manufacturers exert monopsony market power in procuring tobacco. We investigate this possibility in the U.S. and international tobacco markets by extending nonparametric tests to include simultaneously potential monopoly market power with potential monopsony market power in multiple input markets, allowing both Hicks‐neutral and biased technical change. We use annual data from the cigarette manufacturing industry from 1977 to 1993. Results indicate substantial departures from competitive pricing in the procurement of domestic tobacco, supporting the postulate that cigarette manufacturers appropriate monopsony rents despite, and perhaps at times through, U.S. tobacco farm policy. Results are less clear with respect to monopsony market power exertion in imported leaf tobacco procurement by cigarette manufacturers. Finally, results indicate that monopoly market power exertion is relatively small and that, when the possibility of monopsony market power exertion is admitted, monopoly market power exertion is no longer problematic.[EconLit citations: L100, L660]. © 2007 Wiley Periodicals, Inc. Agribusiness 23: 35–55, 2007.
Development of gastroschisis: Review of hypotheses, a novel hypothesis, and implications for research
Authors: Feldkamp Marcia L. , Carey John C. , Sadler Thomas W. 
Published: January 2007

AbstractGastroschisis, a ventral body wall defect, is a continuing challenge and concern to researchers, clinicians, and epidemiologists seeking to identify its cause(s) and pathogenesis. Concern has been renewed in recent years because, unlike most other birth defects, rates of gastroschisis are reportedly increasing in many developed and developing countries. No tenable explanation or specific causes have been identified for this trend. Rates of gastroschisis are particularly high among pregnancies of very young women. Such an intriguing association, not observed to this degree with other birth defects, may afford clues to the defect's cause. Understanding the causes of gastroschisis may provide insight to the defect's origin. In pursuing such causal studies, it would be helpful to understand the embryogenesis of gastroschisis. To date, four main embryologic hypotheses have been proposed: (1) Failure of mesoderm to form in the body wall; (2) Rupture of the amnion around the umbilical ring with subsequent herniation of bowel; (3) Abnormal involution of the right umbilical vein leading to weakening of the body wall and gut herniation; and (4) Disruption of the right vitelline (yolk sac) artery with subsequent body wall damage and gut herniation. Although based on embryological phenomena, these hypotheses do not provide an adequate explanation for how gastroschisis would occur. Therefore, we propose an alternative hypothesis, based on well described embryonic events. Specifically, we propose that abnormal folding of the body wall results in a ventral body wall defect through which the gut herniates, leading to the clinical presentation of gastroschisis. This hypothesis potentially explains the origin of gastroschisis as well as that of other developmental defects of the ventral wall. © 2007 Wiley‐Liss, Inc.
Strukturen von RNA‐Schaltern: Einblick in molekulare Erkennung und Tertiärstruktur
Authors: Schwalbe Harald , Buck Janina , Fürtig Boris , Noeske Jonas , Wöhnert Jens 
Published: January 2007

AbstractRNA‐Schalter erfüllen wichtige Funktionen in der Genregulation. Sie bestehen aus einer Aptamerdomäne, die eine spezifische und hochaffine Bindung mit einem Liganden eingeht, und einer Expressionsplattform, die durch eine allosterische Umorientierung auf den Ligandbindungszustand der Aptamerdomäne reagiert. Die Genexpression kann sowohl während der Transkription wie auch während der Translation reguliert werden, außerdem wurde postuliert, dass RNA‐Schalter die Prozessierung von mRNA steuern. Dieser Kurzaufsatz fasst den Kenntnisstand über die Strukturen und Regulationsmechanismen von RNA‐Schaltern zusammen. Besonderes Augenmerk gilt sekundären und tertiären Wechselwirkungen, die die Faltung der globulären RNA‐Struktur stabilisieren und so die Funktion der Aptamerdomänen bestimmen.
Physiological relevance of telomeric G‐quadruplex formation: a potential drug target
Authors: Oganesian Liana , Bryan Tracy M. 
Published: January 2007

AbstractThe concept of a G‐quartet, a unique structural arrangement intrinsic to guanine‐rich DNA, was first introduced by Gellert and colleagues1 over 40 years ago. For decades, it has been uncertain whether the G‐quartet and the structure that it gives rise to, the G‐quadruplex, are purely in vitro phenomena. Nevertheless, the presence of signature G‐rich motifs in the eukaryotic genome, and the plethora of proteins that bind to, modify or resolve this nucleic acid structure in vitro have provided circumstantial evidence for its physiological relevance. More recently, direct visualisation of G‐quadruplex DNA at native telomeres was achieved, bolstering the evidence for its existence in the cell. Furthermore, G‐quadruplex folded telomeric DNA has been found to perturb telomere function and to impede the action of telomerase, an enzyme overexpressed in >85% of human cancers, hence opening up a novel avenue for cancer therapy in the form of G‐quadruplex stabilising agents. BioEssays 29: 155–165, 2007. © 2007 Wiley Periodicals, Inc.
BDNF variant linked to anxiety‐related behaviors
Authors: Hashimoto Kenji 
Published: January 2007

AbstractBrain‐derived neurotrophic factor (BDNF) is the most‐abundant neurotrophin in the brain. In mammals, it is synthesized as a precursor called proBDNF, which is proteolytically cleaved to generate mature BDNF. The BDNF gene is located on chromosome 11p13, and a functional single nucleotide polymorphism (SNP) of this gene has been shown to produce a valine (Val)‐to‐methionine (Met) substitution in the proBDNF protein at codon 66 (Val66Met). Several papers suggest that this SNP is related to decreased hippocampal volume and hippocampus‐mediated memory performance in humans. Recently, Chen et al.1 generated a variant BDNF mouse (BDNFMet/Met) that reproduces the phenotypic hallmarks in humans with a variant Met allele. In the behavioral analysis, BDNFMet/Met mice show increased anxiety‐related behaviors. This mini‐review examines the impact of Met substitution of proBDNF on anxiety‐related behaviors. BioEssays 29: 116–119, 2007. © 2007 Wiley Periodicals, Inc.
Quantification of pseudoephedrine in human plasma by LC‐MS/MS using mosapride as internal standard
Authors: Nirogi Ramakrishna V. S. , Kandikere Vishwottam N. , Shukla Manoj , Mudigonda Koteshwara , Maurya Santosh , Komarneni Prashanth 
Published: January 2007

AbstractA simple, sensitive and rapid high‐performance liquid chromatography/positive ion electrospray tandem mass spectrometry (LC‐MS/MS) method was developed and validated for the quantification of pseudoephedrine in human plasma using mosapride as internal standard. Following solid‐phase extraction, the analytes were separated using an isocratic mobile phase on a reverse‐phase column and analyzed by MS/MS in the multiple‐reaction monitoring mode using the respective [M + H]+ ions, m/z 166/148 for pseuoephedrine and m/z 422/198 for the IS. The method exhibited a linear dynamic range of 2–1000 ng/mL pseudoephedrine in human plasma. The lower limit of quantification was 2 ng/mL with a relative standard deviation of less than 9% for pseudoephedrine. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 2 min for each sample made it possible to analyze more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies. Copyright © 2007 John Wiley & Sons, Ltd.