bluuebunny/crossref_metadata_2025_split huggingface dataset:
BK Virus as a Cofactor in the Etiology of Prostate Cancer in Its Early Stages
Authors: Das Dweepanita , Wojno Kirk , Imperiale Michael J. 
Published: December 2007

ABSTRACT

Prostate cancer has been projected to cause almost 10% of all male cancer deaths in the United States in 2007. The incidence of mutations in the tumor suppressor genes
Rb1
and
p53
, especially in the early stages of the disease, is low compared to those for other cancers. This has led to the hypothesis that a human virus such as BK virus (BKV), which establishes a persistent subclinical infection in the urinary tract and encodes oncoproteins that interfere with these tumor suppressor pathways, is involved. Previously, we detected BKV DNA in the epithelial cells of benign and proliferative inflammatory atrophy ducts of cancerous prostate specimens. In the present report, we demonstrate that BKV is present at a much lower frequency in noncancerous prostates. Additionally, in normal prostates, T-antigen (TAg) expression is observed only in specimens harboring proliferative inflammatory atrophy and prostatic intraepithelial neoplasia. We further demonstrate that the
p53
gene from atrophic cells expressing TAg is wild type, whereas tumor cells expressing detectable nuclear p53 contain a mix of wild-type and mutant
p53
genes, suggesting that TAg may inactivate p53 in the atrophic cells. Our results point toward a role for BKV in early prostate cancer progression.
High Level of PD-1 Expression on Hepatitis C Virus (HCV)-Specific CD8
+
and CD4
+
T Cells during Acute HCV Infection, Irrespective of Clinical Outcome
Authors: Kasprowicz Victoria , Schulze zur Wiesch Julian , Kuntzen Thomas , Nolan Brian E. , Longworth Steven , Berical Andrew , Blum Jenna , McMahon Cory , Reyor Laura L. , Elias Nahel , Kwok William W. , McGovern Barbara G. , Freeman Gordon , Chung Raymond T. , Klenerman Paul , Lewis-Ximenez Lia , Walker Bruce D. , Allen Todd M. , Kim Arthur Y. , Lauer Georg M. 
Published: December 2007

ABSTRACT

We monitored expression of PD-1 (a mediator of T-cell exhaustion and viral persistence) on hepatitis C virus (HCV)-specific CD8
+
and CD4
+
T cells from blood and liver during acute and chronic infections and after the resolved infection stage. PD-1 expression on HCV-specific T cells was high early in acute infection irrespective of clinical outcome, and most cells continued to express PD-1 in resolved and chronic stages of infection; intrahepatic expression levels were especially high. Our results suggest that an analysis of PD-1 expression alone is not sufficient to predict infection outcome or to determine T-cell functionality in HCV infection.
INFINITE DIVISIBILITY FOR THE CONDITIONALLY FREE CONVOLUTION
Authors: KRYSTEK ANNA DOROTA 
Published: December 2007

Infinite divisibility for the free additive convolution was studied in Ref. 20. A complete characterization of [Formula: see text]-infinitely divisible distributions was given, and it was explained in Ref. 21 that this characterization is an analogue of the classical Lévy–Khintchine characterization. In fact, the analogue of the Gaussian distribution appeared even earlier, when the central limit theorem for free additive convolution was proven in Ref. 19. In this paper we define the notion of [Formula: see text]-infinitely divisibility and give the description of infinitely divisible compactly supported probability measures relative to the conditionally free convolution. We also show that the Lévy–Khintchine measures associated with a [Formula: see text]-infinitely divisible distribution μ can be calculated, as in the classical or free case, as a weak limit of measures related with the convolution semigroup generated by (μ, φ) for [Formula: see text]-infinitely divisible.
Reflections and Commentary From the Field: Connecting the Reform of Administrator Preparation to the Reform of Teacher Preparation
Authors: Monk David H. 
Published: December 2007

Purpose: Attention is drawn in this article to the presence and dysfunctional nature of a disconnection between professional preparation programs for administrators and for teachers. Findings: A case is made for achieving greater alignment between the work going on in these areas, particularly in light of the growing efforts to hold schools accountable for pupil performance gains. A case is also made for balancing reform efforts so that disproportionate attention is not paid to one area relative to the other.
“Living on Barbed Wire”: Resilient Women Administrators in Educational Leadership Programs
Authors: Christman Dana , McClellan Rhonda 
Published: December 2007

Background: Despite access for women administrators in educational leadership departments, the longevity of their service within them is tenuous. Women administrators are caught in the social constructions of gender and leadership. Purpose: To explore how some women administrators in educational leadership programs have sustained their administrative roles; to evaluate whether their resiliency rests on a feminine type of leadership. Participants: A group of seven diverse women administrators in educational leadership programs who were peer nominated, are accomplished scholars, and have an average of 11.25 years of experience. Research Design: A computer-based qualitative Delphi technique using an online asynchronous mode and ensuring anonymity. Data Collection and Analysis: Several iterations focused on the identification of resiliency markers and components, descriptions of episodes denoting the participants' overcoming difficult situations, proposals for adapting educational leadership programs to foster better women leaders, and the reflection and interpretation of data. Findings: The participants' rankings and narratives indicate that gender identity and leadership are more complex than to simply fit them into one gender construction model or another. When interacting in particular episodes, resilient women leaders embrace or disclaim one gender norm for another to varying degrees. A multidimensional-gendered leadership model is provided. Conclusions: Faculty and students should not expect the socially constructed norms in women leaders. These resilient participants suggest that gendered leadership norms are too simplistic and that women leaders must be willing to shift into multidimensional gender and traverse conventional borders.
Who or What Creates? A Conceptual Framework for Social Creativity
Authors: Watson Elizabeth 
Published: December 2007

Creativity is increasingly understood as a social phenomenon, especially in organizational contexts. This article offers a conceptual framework for social creativity that integrates perspectives from published literature. The foundational questions that structured the literature review are twofold. First, because both individuals and entities, such as teams, can be agents of creativity, who or what creates? Second, through what sites of action or contexts does creative engagement by individuals, groups, and organizations occur? An integrative review of the literature reveals that the engagement occurs in individuals, in individuals interacting, in group work, and in complex multilevel systems. A concept map is used to represent the literature in this domain. This is then discussed with reference to the representative authors in each of the identified sectors. A set of names for the outcomes of the creative process is suggested, including individually generated creative outcomes, socially influenced creative outcomes, socially constructed creative outcomes, and socially generated creative outcomes.
Identification of somatic JAK1 mutations in patients with acute myeloid leukemia
Authors: Xiang Zhifu , Zhao Yu , Mitaksov Vesselin , Fremont Daved H. , Kasai Yumi , Molitoris AnnaLynn , Ries Rhonda E. , Miner Tracie L. , McLellan Michael D. , DiPersio John F. , Link Daniel C. , Payton Jacqueline E. , Graubert Timothy A. , Watson Mark , Shannon William , Heath Sharon E. , Nagarajan Rakesh , Mardis Elaine R. , Wilson Richard K. , Ley Timothy J. , Tomasson Michael H. 
Published: December 2007

Abstract
Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1T478S, and JAK1V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.
Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
Authors: Maurissen Lisbeth F. A. , Thomassen M. Christella L. G. D. , Nicolaes Gerry A. F. , Dahlbäck Björn , Tans Guido , Rosing Jan , Hackeng Tilman M. 
Published: December 2007

AbstractProtein S expresses cofactor activity for activated protein C (APC) by enhancing the APC-catalyzed proteolysis at R306 in factor Va. It is generally accepted that only free protein S is active and that complex formation with C4b-binding protein (C4BP) inhibits the APC-cofactor activity of protein S. However, the present study shows that protein S-C4BP expresses APC-cofactor activity and stimulates APC-catalyzed proteolysis at R306 more than 10-fold, but instead inhibits proteolysis at R506 by APC 3- to 4-fold. Free protein S stimulates APC-catalyzed cleavage at R306 approximately 20-fold and has no effect on cleavage at R506. The resulting net effect of protein S-C4BP complex formation on APC-catalyzed factor Va inactivation is a 6- to 8-fold reduction in factor Va inactivation when compared with free protein S, which is not explained by inhibition of APC-cofactor activity of protein S at R306, but by generation of a specific inhibitor for APCcatalyzed proteolysis at R506 of factor Va. These results are of interest for carriers of the factor VLeiden mutation (R506Q), as protein S-C4BP effectively enhances APC-catalyzed factor Va (R306) inactivation in plasma containing factor VLeiden.
A large-scale proteomic analysis of human embryonic stem cells
Authors: Schulz Thomas C , Swistowska Anna Maria , Liu Ying , Swistowski Andrzej , Palmarini Gail , Brimble Sandii N , Sherrer Eric , Robins Allan J , Rao Mahendra S , Zeng Xianmin 
Published: December 2007

Abstract

Background
Much of our current knowledge of the molecular expression profile of human embryonic stem cells (hESCs) is based on transcriptional approaches. These analyses are only partly predictive of protein expression however, and do not shed light on post-translational regulation, leaving a large gap in our knowledge of the biology of pluripotent stem cells.

Results
Here we describe the use of two large-scale western blot assays to identify over 600 proteins expressed in undifferentiated hESCs, and highlight over 40 examples of multiple gel mobility variants, which are suspected protein isoforms and/or post-translational modifications. Twenty-two phosphorylation events in cell signaling molecules, as well as potential new markers of undifferentiated hESCs were also identified. We confirmed the expression of a subset of the identified proteins by immunofluorescence and correlated the expression of transcript and protein for key molecules in active signaling pathways in hESCs. These analyses also indicated that hESCs exhibit several features of polarized epithelia, including expression of tight junction proteins.

Conclusion
Our approach complements proteomic and transcriptional analysis to provide unique information on human pluripotent stem cells, and is a framework for the continued analyses of self-renewal.
Pancreatectomy for non-pancreatic malignancies results in improved survival after R0 resection
Authors: Varker Kimberly A , Muscarella Peter , Wall Kristian , Ellison Christopher , Bloomston Mark 
Published: December 2007

AbstractBackgroundPancreatectomy has a high morbidity but remains the only chance of cure for pancreatic cancer. Its efficacy for non-pancreatic malignancies is less clear. We reviewed our experience with pancreatectomy for non-pancreatic malignancies to determine outcomes and identify predictors of survival.Patients and methodsThe records of patients who underwent pancreatectomy for non-pancreatic malignancies between 1990 and 2005 were reviewed. Survival curves were constructed using the Kaplan-Meier method and compared using log-rank analysis. Cox proportional hazards was used to identify predictors of survival.Results29 patients (18 M/11 F) with a mean age of 59.9 years (range 29–86) underwent pancreatectomy for non-pancreatic malignancies. 19 (66%) primary malignancies were GI in origin. Most operations were undertaken with curative intent (76%), whereas the remainder was for symptom palliation. Pancreatectomy was completed for metastatic disease in 7 patients (24%) or en bloc to achieve negative margins in 22 patients (76%). Complete (i.e., R0) resection was achieved in 17 (59%). Perioperative mortality was 3%. Median follow-up was 15 months (range 7–172). Median overall survival was 12 months with 1-year survival of 48%. Significant predictors of improved survival by univariate analysis were R0 resection, non-GI primary, and pancreatic metastasectomy (vs. en bloc resection). Only R0 resection was predictive of long-term survival by multivariate analysis (median 21 months vs. 6).ConclusionPancreatic resection for non-pancreatic malignancies can be completed with minimal mortality. However, incomplete resection results in poor overall survival. Pancreatectomy for non-pancreatic malignancies should only be undertaken if complete resection is possible.
The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation
Authors: Gribar Steven C , Anand Rahul J , Sodhi Chhinder P , Hackam David J 
Published: December 2007

AbstractEmerging evidence suggests that the innate immune system, comprised of Toll-like receptors (TLRs) and their associated molecules, plays a pivotal role in the regulation of intestinal inflammation and in the response to invading pathogens. Although TLRs are thought to have predominantly beneficial effects in pathogen recognition and bacterial clearance by leukocytes, their dysregulation and unique signaling effects within intestinal epithelia in the setting of inflammation may have devastating consequences. For instance, activation of TLR4 in enterocytes leads to an inhibition of enterocyte migration and proliferation as well as the induction of enterocyte apoptosis—factors that would be expected to promote intestinal injury while inhibiting intestinal repair. TLR signaling has been shown to be abnormal in several intestinal inflammatory diseases, including Crohn’s disease, ulcerative colitis, and necrotizing enterocolitis. This review serves to examine the evidence regarding the patterns of expression and signaling of TLRs in the intestinal mucosa at basal levels and during physiologic stressors to gain insights into the pathogenesis of intestinal inflammation. We conclude that the data reviewed suggest that epithelial TLR signaling—acting in concert with TLR signaling by leukocytes—participates in the development of intestinal inflammation. We further conclude that the evidence reviewed provides a rationale for the development of novel, epithelial-specific, TLR-based agents in the management of diseases of intestinal inflammation.
The re-emerging role of the intestinal microflora in critical illness and inflammation: why the gut hypothesis of sepsis syndrome will not go away
Authors: Alverdy John C , Chang Eugene B 
Published: December 2007

AbstractRecent advances in the ability to genetically interrogate microbial communities within the intestinal tract of humans have revealed many striking findings. That there may be as many as 300 unculturable and unclassified microbes within the human intestinal tract opens the possibility that yet-unidentified microbes may play a role in various human diseases [1]. Technologically, the regional and spatial aspects of intestinal microbial communities can now be better appreciated by emerging genetic and in vivo imaging systems using a bioinformatics approach [2]. Finally, in situ PCR of tissues and blood now allows the detection of microbes at concentrations that would otherwise remain undetected by culture alone [3]. In the aggregate, these studies have empowered clinicians to readdress the issue of how our microbial partners are affected by extreme states of physiologic stress and antibiotic use through the course of critical illness. The role of microbes in systemic inflammatory states, such as systemic inflammatory response syndrome, as well as in primary intestinal mucosal diseases, such as necrotizing enterocolitis, inflammatory bowel disease, and ischemia-reperfusion injury, can now be more completely defined, and the microbial genes that mediate the immune activation during these disorders can be identified. The 2008 roadmap initiative at the National Institutes of Health to fully define the human microbiome is further testament to the power of this technology and the importance of understanding how intestinal microbes, their genes, and their gene products affect the course of human disease and inflammation.
Effects of Previous Antiresorptive Therapy on the Bone Mineral Density Response to Two Years of Teriparatide Treatment in Postmenopausal Women with Osteoporosis
Authors: Boonen Steven , Marin Fernando , Obermayer-Pietsch Barbara , Simões Maria E. , Barker Clare , Glass Emmett V. , Hadji Peyman , Lyritis George , Oertel Heide , Nickelsen Thomas , McCloskey Eugene V. 
Published: December 2007

Abstract
Introduction: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 μg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr.
Methods: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n = 107), risedronate (n = 59), etidronate (n = 30), and non-bisphosphonate (n = 49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months.
Results: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide.
Conclusions: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.
Kallmann’s Syndrome: A Comparison of the Reproductive Phenotypes in Men Carrying KAL1 and FGFR1/KAL2 Mutations
Authors: Salenave Sylvie , Chanson Philippe , Bry Hélène , Pugeat Michel , Cabrol Sylvie , Carel Jean Claude , Murat Arnaud , Lecomte Pierre , Brailly Sylvie , Hardelin Jean-Pierre , Dodé Catherine , Young Jacques 
Published: December 2007

Abstract
Context: Kallmann’s syndrome (KS) is a genetically heterogeneous disorder consisting of congenital hypogonadotropic hypogonadism (CHH) with anosmia or hyposmia.
Objective: Our objective was to compare the reproductive phenotypes of men harboring KAL1 and FGFR1/KAL2 mutations.
Design and Patients: We studied the endocrine features reflecting gonadotropic-testicular axis function in 39 men; 21 had mutations in KAL1 and 18 in FGFR1/KAL2, but none had additional mutations in PROK-2 or PROKR-2 genes.
Results: Puberty failed to occur in the patients with KAL1 mutations, all of whom had complete CHH. Three patients with FGFR1/KAL2 mutations had normal puberty, were eugonadal, and had normal testosterone and gonadotropin levels. Cryptorchidism was more frequent (14 of 21 vs. 3 of 15; P &lt; 00.1) and testicular volume (2.4 ± 1.1 vs. 5.4 ± 2.4 ml; P &lt; 0.001) was smaller in CHH subjects with KAL1 mutations than in subjects with FGFR1/KAL2 mutations. The mean basal plasma FSH level (0.72 ± 0.47 vs. 1.48 ± 0.62 IU/liter; P &lt; 0.05), serum inhibin B level (19.3 ± 10.6 vs. 39.5 ± 19.3 pg/ml; P &lt; 0.005), basal LH plasma level (0.57 ± 0.54 vs. 1.0 ± 0.6 IU/liter; P &lt; 0.01), and GnRH-stimulated LH plasma level (1.2 ± 1.0 vs. 4.1 ± 3.5 IU/liter; P &lt; 0.01) were significantly lower in the subjects with KAL1 mutations. LH pulsatility was studied in 13 CHH subjects with KAL1 mutations and seven subjects with FGFR1/KAL2 mutations; LH secretion was nonpulsatile in all the subjects, but mean LH levels were lower in those with KAL1 mutations.
Conclusion: KAL1 mutations result in a more severe reproductive phenotype than FGFR1/KAL2 mutations. The latter are associated with a broader spectrum of pubertal development and with less severe impairment of gonadotropin secretion.
Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men
Authors: Coviello Andrea D. , Kaplan Beth , Lakshman Kishore M. , Chen Tai , Singh Atam B. , Bhasin Shalender 
Published: December 2007

Abstract
Context: Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men.
Objective: Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels.
Design: We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg im) for 20 wk.
Setting: The study took place at a General Clinical Research Center.
Participants: Participants included 60 older men aged 60–75 yr and 61 young men aged 19–35 yr.
Outcome Measures: Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels.
Results: Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P &lt; 0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels.
Conclusions: Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.