bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical Assessment of Paget's Disease of Bone
Authors: Shankar Subramanian , Hosking David J 
Published: January 2007

Abstract
Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best characterized of the bone turnover markers and reflects the extent and activity of Paget's disease. However, in addition to bone-specific alkaline phosphatase (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) as formation markers. A variety of telopeptides (C-terminal telopeptide of type I collagen, [CTX], N-telopeptide of type I collagen [NTX]) or cross-link breakdown products of type 1 collagen can be used to assess bone resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all perform similarly in diagnosis and in evaluating the response to treatment, but the general availability, low interassay variation, and inexpensiveness of Total ALP makes it the best test for routine use. Measurement of the biological variability of the different markers in stable, untreated Paget's disease indicates how great a change (critical difference) is needed to define a true alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy induced change/critical difference ratio during antiresorptive treatment. Some of the resorption markers show more complex changes in response to treatment. Pyridinoline (PYD) or deoxypyridinoline (DPD) cross-links of type 1 collagen are excreted in urine either as free or as peptide bound moieties, but it is the latter which decrease by the greatest amount in response to bisphosphonate therapy. Newly formed type 1 collagen contains an aspartyl-glycine motif (αCTX), which undergoes spontaneous isoaspartyl formation to βCTX as the bone ages. In untreated Paget's disease, the αCTX is raised proportionately more (16-fold) than βCTX (3-fold) and decreases in response to bisphosphonate therapy to a greater extent than βCTX (measured in the sCTX assay). As bisphosphonates have become more potent, the aim of treatment has shifted toward the achievement of a rate of bone turnover in the lower part of the reference range. This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover.
Contribution of Genetic Factors to the Pathogenesis of Paget's Disease of Bone and Related Disorders
Authors: Lucas Gavin JA , Daroszewska Anna , Ralston Stuart H 
Published: January 2007

Abstract
Paget's disease of bone (PDB) is a common condition with a strong genetic component that is characterized by focal increases in bone turnover, leading to bone deformity, pathological fractures, and various other complications. Several rare disorders have also been described that show phenotypic overlap with PDB. Genome-wide searches have identified several susceptibility loci for PDB and PDB-like disorders, and mutations that cause these disorders have now been identified in four genes, all of which are involved in the RANK-NF-κB signaling pathway. Mutations in SQSTM1, which encodes an important scaffold protein in this pathway, have been found to be a common cause of classical PDB. Thus far, all disease-causing mutations in SQSTM1 affect the ubiquitin-associated (UBA) domain of the gene product and cause loss of ubiquitin binding. The rare PDB-like disorders of familial expansile osteolysis, early-onset familial PDB, and expansile skeletal hyperphosphatasia are caused by duplication mutations in exon 1 of the TNFRSF11A gene, which encodes the RANK receptor. This gene does not seem to be involved in the pathogenesis of classical PDB. Inactivating mutations in the TNFRSF11B gene, which encodes osteoprotegerin, cause juvenile PDB, and TNFRSF11B polymorphisms seem to increase the risk of classical PDB. The rare syndrome of hereditary inclusion body myopathy, PDB, and frontotemporal dementia (IBMPFD) is caused by mutations in the VCP gene, which is involved in regulating I-κB degradation by the proteasome. The disease-causing mutations in VCP cluster in and around a domain involved in ubiquitin binding. Whereas SQSTM1 has emerged as an important gene for classical PDB, most kindreds with familial PDB do not carry SQSTM1 mutations, indicating that additional genes for PDB remain to be discovered. In light of the molecular defects that have been identified thus far, it seems likely that these genes will also be involved in the RANK-NF-κB signaling pathway or its interactions with the ubiquitin-proteasome system.
Medical Therapy in Adults With Fibrous Dysplasia of Bone
Authors: Chapurlat Roland D 
Published: January 2007

Abstract
In open studies, bisphosphonate therapy (pamidronate, alendronate) reduced bone pain associated with fibrous dysplasia of bone and was associated to some radiological improvement. Calcium, vitamin D, and phosphorus supplements may be useful in patients with deficiency. We are awaiting results from controlled trials testing bisphosphonates.
Introduction: Fibrous dysplasia of bone (FD), a rare disease caused by osteoblastic lineage differentiation defects, is associated with bone pain, fracture, and bone deformity, but few therapeutic options are available.
Materials and Methods: We reviewed published data on the treatment of FD with bisphosphonates (pamidronate, alendronate), calcium, vitamin D, and phosphorus. We also present new results on FD therapy with a more potent bisphosphonate, zoledronic acid, given intravenously at the dose of 4 mg every 6 months.
Results: Pamidronate therapy, given intravenously every 6 months at a dose of 180 mg in adults, relieved bone pain, decreased bone resorption, and improved the radiological aspect (filling of lytic lesions and/or thickening of cortices) in ∼50% of patients. BMD in affected sites was also significantly increased after pamidronate treatment. Those results have been obtained only in open studies, without controls, by several research groups. In a series of nine patients on long-term pamidronate treatment, but resisting to this medication and switched to intravenous zoledronic acid, no substantial improvement was observed. There is some biological rationale supporting the use of calcium and vitamin D in patients with deficiency to improve FD lesions by limiting secondary hyperparathyroidism. Phosphorus supplementation may prevent mineralization defects in those patients who have both FD and renal phosphate wasting. However, we are lacking clinical evidence for the efficacy of such supplements.
Conclusions: Bisphosphonate treatment reduces increased osteoclastic activity in FD and probably improves bone pain, but their use should be better studied in randomized controlled trials.
FGF23 Concentrations Vary With Disease Status in Autosomal Dominant Hypophosphatemic Rickets
Authors: Imel Erik A , Hui Siu L , Ecibs Michael J 
Published: January 2007

Abstract
We measured FGF23 concentrations in subjects with ADHR. FGF23 and serum phosphate correlated positively in controls and negatively in subjects with ADHR. Elevated FGF23 concentrations were associated with lower phosphate values. The variable phenotype in ADHR may be caused by fluctuations in FGF23.
Introduction: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disorder of phosphaturia, hypophosphatemia, inappropriately low/normal calcitriol, and rickets/osteomalacia. ADHR is caused by mutations in a circulating peptide, fibroblast growth factor 23 (FGF23). We present the first report of FGF23 concentrations in subjects with ADHR. The aim was to test the hypotheses that subjects with ADHR have elevated FGF23 concentrations and that FGF23 concentrations are associated with disease severity.
Materials and Methods: This was an observational study at a tertiary referral center. Subjects were from three kindreds with FGF23 mutations causing ADHR (n = 42). Controls were participants from these families without mutations (n = 55). Fasting blood and urine samples were obtained. Biochemistries were determined, and FGF23 concentrations were measured using two ELISAs.
Results: Three cases are presented illustrating activity of disease and FGF23 concentrations. One case shows persistent hypophosphatemia and elevation of FGF23 concentrations, whereas another shows remission of hypophosphatemia corresponding to a decrease in previously elevated FGF23 concentrations. Overall cross-sectional group differences were nonsignificant for serum phosphate and FGF23 concentrations. C-terminal FGF23 concentration in controls was 61.0 ± 28.6 (SD) RU/ml (median, 52.5 RU/ml), and in subjects with mutations was 148.8 ± 374.5 RU/ml (median, 63.1 RU/ml). Mean intact FGF23 concentration in controls was 44.7 ± 14.9 pg/ml (median, 40.4 pg/ml), and in subjects with mutations was 83.2 ± 233.0 pg/ml (median, 39.0 pg/ml). C-terminal FGF23 concentrations were at least +2 SD in 10/42(24%), and intact FGF23 concentrations were at least +2 SD in 3/34(9%). Phosphate correlated positively with C-terminal and intact FGF23 in both controls and in subjects with mutations with phosphate &gt;2.5 mg/dl but correlated significantly negatively with C-terminal and intact FGF23 in ADHR subjects with phosphate ≤2.5 mg/dl.
Conclusions: Elevated FGF23 concentrations are associated with hypophosphatemia in ADHR, and remission of the phenotype is associated with lower FGF23 concentrations. FGF23 has an opposite relationship with phosphate in ADHR compared with controls. We conclude that ADHR symptoms and disease severity likely fluctuate with FGF23 concentrations.
Functional Involvement of PHOSPHO1 in Matrix Vesicle–Mediated Skeletal Mineralization
Authors: Roberts Scott , Narisawa Sonoko , Harmey Dympna , Millán José Luis , Farquharson Colin 
Published: January 2007

Abstract
PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional involvement in mineralization through the use of novel small molecule inhibitors. PHOSPHO1 expression was present within matrix vesicles, and inhibition of enzyme action caused a decrease in the ability of matrix vesicles to calcify.
Introduction: The novel phosphatase, PHOSPHO1, belongs to the haloacid dehalogenase superfamily of hydrolases and is capable of cleaving phosphoethanolamine (PEA) and phosphocholine to generate inorganic phosphate. Our aims in this study were to examine the expression of PHOSPHO1 in murine mineralizing cells and matrix vesicles (MV) and to screen a series of small-molecule PHOSPHO1-specific inhibitors for their ability to pharmacologically inhibit the first step of MV-mediated mineralization.
Materials and Methods: q-PCR and immunohistochemistry were used to study the expression and localization profiles of PHOSPHO1. Inhibitors of PHOSPHO1's PEA hydrolase activity were discovered using high-throughput screening of commercially available chemical libraries. To asses the efficacy of these inhibitors to inhibit MV mineralization, MVs were isolated from TNAP-deficient (Akp2−/−) osteoblasts and induced to calcify in their presence.
Results: q-PCR revealed a 120-fold higher level of PHOSPHO1 expression in bone compared with a range of soft tissues. The enzyme was immunolocalized to the early hypertrophic chondrocytes of the growth plate and to osteoblasts of trabecular surfaces and infilling primary osteons of cortical bone. Isolated MVs also contained PHOSPHO1. PEA hydrolase activity was observed in sonicated MVs from Akp2−/− osteoblasts but not intact MVs. Inhibitors to PHOSPHO1 were identified and characterized. Lansoprazole and SCH202676 inhibited the mineralization of MVs from Akp2−/− osteoblasts by 56.8% and 70.7%, respectively.
Conclusions: The results show that PHOSPHO1 localization is restricted to mineralizing regions of bone and growth plate and that the enzyme present within MVs is in an active state, inhibition of which decreases the capacity of MVs to mineralize. These data further support our hypothesis that PHOSPHO1 plays a role in the initiation of matrix mineralization.
Minimally Invasive Approaches for Diagnosis and Treatment of Early-Stage Breast Cancer
Authors: Vlastos Georges , Verkooijen Helena M. 
Published: January 2007

Learning Objectives
After completing this course, the reader will be able to: Describe the minimally invasive approaches to breast cancer diagnosis and treatment.List the strengths and weaknesses of minimally invasive diagnostic and treatment procedures.Select appropriate patients for minimally invasive approaches to breast cancer diagnosis and treatment.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Disseminated Malignancy Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Report of 10 Patients and a Systematic Review of Published Cases
Authors: Francis Kristin K. , Kalyanam Nalini , Terrell Deirdra R. , Vesely Sara K. , George James N. 
Published: January 2007

Learning Objectives
After completing this course, the reader will be able to: List the diagnostic criteria for thrombotic thrombocytopenic purpura.Describe how occult disseminated malignancy can mimic the clinical features of thrombotic thrombocytopenic purpura.Identify the clinical clues that indicate additional diagnostic evaluation for possible malignancy in a patient with suspected thrombotic thrombocytopenic purpura.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Cancer Statistics, Trends, and Multiple Primary Cancer Analyses from the Surveillance, Epidemiology, and End Results (SEER) Program
Authors: Hayat Matthew J. , Howlader Nadia , Reichman Marsha E. , Edwards Brenda K. 
Published: January 2007

Learning Objectives
After completing this course, the reader will be able to: Discuss the evolving changes in the following cancer-related measures: median age at diagnosis, incidence rate, death rate, lifetime risk, survival, and prevalence.Explain important concepts affecting occurrence of multiple primary cancers at various cancer sites.Describe the impact of the growing and aging population on the future number of cancer cases by age at diagnosis.
CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
The Continuum of Care: A Paradigm for the Management of Metastatic Colorectal Cancer
Authors: Goldberg Richard M. , Rothenberg Mace L. , Van Cutsem Eric , Benson Al B. , Blanke Charles D. , Diasio Robert B. , Grothey Axel , Lenz Heinz-Josef , Meropol Neal J. , Ramanathan Ramesh K. , Becerra Carlos H. Roberto , Wickham Rita , Armstrong Delma , Viele Carol 
Published: January 2007

Learning ObjectivesAfter completing this course, the reader should be able to: Discuss recent progress in the treatment of patients with advanced colorectal cancer.Define the continuum-of-care approach and how it may differ from our current approach to the treatment of patients with advanced colorectal cancer.Identify key factors in treatment selection for patients with advanced colorectal cancer.Explain the impact of each active drug in the treatment of advanced colorectal cancer and the impact of treatment with multiple agents over the course of the disease.CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Increased expression of HSP70 by colon cancer cells is not always associated with access to the dendritic cell cross-presentation pathway
Authors: Matera Lina , Forno Sarah , Galetto Alessandra , Moro Francesco , Garetto Stefano , Mussa Antonio 
Published: January 2007

AbstractDendritic cells (DCs) are highly specialized antigen-presenting cells endowed with the unique ability to not only present exogenous antigens upon exposure to MHC II, but also to cross-present these upon exposure to MHC I. This property was exploited to generate the tumor-specific CD8 cytotoxic lymphocyte (CTL) response in DCs-based cancer vaccine protocols. In this context, the source of tumor antigens remains a critical challenge. A crude tumor in the context of danger signals is believed to represent an efficient source of tumor antigens (TAs) for DCs loading. In our previous work, increased DCs cross-presentation of antigens from necrotic gastric carcinoma cells paralleled up-regulation of the heat shock protein hsp70. We studied the expression of hsp70 on primary colon carcinoma cells and its relevance in the cross-priming of anti-tumor CTL by tumor-loaded DCs. Hsp70 was expressed on all three of the tumors studied, but was never detected in the peritumoral normal mucosa (NM). The uptake of the tumor induced a trend towards down-modulation of the monocyte-specific marker CD14, but had no effect on the chemokine receptors CCR4 and CCR7. The IFN-γ enzyme-linked immunospot assay (ELIspot) showed cross-priming of CTL by tumor-loaded but not NM-loaded DCs in four of the six cases studied. The CTL response generated in DC+tumor cultures was directed towards the tumor, but not towards NM, and it was characterized by refractoriness to polyclonal (Ca ionophores, PKC activators) stimuli. Of the three CTL-generating tumors, only one expressed hsp70. This data indicates a tumor-specific expression of hsp70, but does not support its relevance in the DC cross-presentation of TAs.
Reassessment of holoprosencephaly–diencephalic hamartoblastoma (HDH) association
Authors: Castori Marco , Douzgou Sofia , Silvestri Evelina , Encha‐Razavi Férechté , Dallapiccola Bruno 
Published: January 2007

AbstractWe report on a 23‐week fetus with a hypothalamic hamartoma, lobar holoprosencephaly, right anophthalmia, and facial asymmetry, features which are consistent with theholoprosencephaly–diencephalichamartoblastoma (HDH) association. In an attempt to better delineate HDH, we reviewed 19 published patients with similar features. The HDH clinical spectrum ranges from classic holoprosencephaly with micro/anophthalmia, multiple additional findings in non‐contiguous structures and early lethality, to isolated microforms of holoprosencephaly. Associated cephalic features mainly include cortical/neuronal migration defects (39%), meningeal anomalies (28%), brainstem/posterior fossa malformations (22%), dysmorphic ears (41%), facial asymmetry (35%), and hypoplastic mandible (29%). Fifty‐three percent of patients have additional extra‐cephalic malformations, for example, vertebral/rib segmentation defects (50%), hypo/aplastic lungs (38%), congenital heart defect (29%), and urinary anomalies (29%). HDH shows etiological heterogeneity, that is, teratogenic exposure, chromosome imbalances, autosomal recessive as well as dominant “de novo” mutations. Several features could directly result from a disruptive sequence caused by an early hamartoma which alters the development of forebrain, hindbrain, meninges, and 1st–2nd branchial arches, although the pleiotropic action of genetic/environmental factors cannot be excluded. HDH does not emerge as a distinct syndrome, but other hypotheses, including separate conditions within a common pathway and the developmental field defect theory, are discussed. © 2007 Wiley‐Liss, Inc.
Family‐based and case‐control studies reveal no association oflipocalin‐type prostaglandin D2 synthasewith schizophrenia
Authors: Ruano Dina , Macedo António , Soares Maria João , Valente José , Azevedo Maria Helena , Pato Carlos , Hutz Mara Helena , Gama Clarissa S. , Lobato Maria Inês , Belmonte‐de‐Abreu Paulo , Heutink Peter , Palha Joana Almeida 
Published: January 2007

AbstractSeveral observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin‐type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2‐mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants ofPTGDSare involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case‐control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents‐offspring sample from the Azorean Islands. Our data do not support the involvement of thePTGDSgene in the etiology of schizophrenia. © 2007 Wiley‐Liss, Inc.
Kling and the “critical”: Social informatics and critical informatics
Authors: Day Ronald E. 
Published: January 2007

AbstractThe article discusses Rob Kling's notion of the critical and how this term is embodied in Kling's social informatics and in works of other authors, which we identify as belonging to critical informatics. Issues of method and the notion of the empirical are discussed. The importance of such analyses in regard to social life and professional education is discussed.
Regulation of male traits by testosterone: implications for the evolution of vertebrate life histories
Authors: Hau Michaela 
Published: January 2007

AbstractThe negative co‐variation of life‐history traits such as fecundity and lifespan across species suggests the existence of ubiquitous trade‐offs. Mechanistically, trade‐offs result from the need to differentially allocate limited resources to traits like reproduction versus self‐maintenance, with selection favoring the evolution of optimal allocation mechanism. Here I discuss the physiological (endocrine) mechanisms that underlie optimal allocation rules and how such rules evolve. The hormone testosterone may mediate life‐history trade‐offs due to its pleiotropic actions in male vertebrates. Conservation in the actions of testosterone in vertebrates has prompted the ‘evolutionary constraint hypothesis,’ which assumes that testosterone signaling mechanisms and male traits evolve as a unit. This hypothesis implies that the actions of testosterone are similar across sexes and species, and only the levels of circulating testosterone concentrations change during evolution. In contrast, the ‘evolutionary potential hypothesis’ proposes that testosterone signaling mechanisms and male traits evolve independently. In the latter scenario, the linkage between hormone and traits itself can be shaped by selection, leading to variation in trade‐off functions. I will review recent case studies supporting the evolutionary potential hypothesis and suggest micro‐evolutionary experiments to unravel the mechanistic basis of life‐history evolution. BioEssays 29: 133–144, 2007. © 2007 Wiley Periodicals, Inc.
DNA barcoding in animal species: progress, potential and pitfalls
Authors: Waugh John 
Published: January 2007

AbstractDespite 250 years of work in systematics, the majority of species remains to be identified. Rising extinction rates and the need for increased biological monitoring lend urgency to this task. DNA sequencing, with key sequences serving as a “barcode”, has therefore been proposed as a technology that might expedite species identification. In particular, the mitochondrial cytochrome c oxidase subunit 1 gene has been employed as a possible DNA marker for species and a number of studies in a variety of taxa have accordingly been carried out to examine its efficacy. In general, these studies demonstrate that DNA barcoding resolves most species, although some taxa have proved intractable. In some studies, barcoding provided a means of highlighting potential cryptic, synonymous or extinct species as well as matching adults with immature specimens. Higher taxa, however, have not been resolved as accurately as species. Nonetheless, DNA barcoding appears to offer a means of identifying species and may become a standard tool. BioEssays 29: 188–197, 2007. © 2007 Wiley Periodicals, Inc.