bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Ankle Taping on Detection of Inversion-Eversion Movements in Participants with Recurrent Ankle Sprain
Authors: Refshauge Kathryn M. , Raymond Jacqueline , Kilbreath Sharon L. , Pengel Liset , Heijnen Inger 
Published: October 2008

Background Taping is often used to counter the proprioceptive deficit after joint injury such as ankle sprain. However, the effect of taping on proprioceptive acuity at the ankle is unclear, with conflicting findings. Hypothesis Application of tape improves detection of inversion and eversion movements at the ankle. Study Design Controlled laboratory study. Methods The 70% threshold for movement detection was measured in 16 participants with recurrent ankle sprain under 2 conditions: with the ankle taped or untaped. The threshold for movement detection was examined at 3 velocities (0.1 deg/s, 0.5 deg/s, and 2.5 deg/s) and in 2 directions (inversion and eversion). Results Application of tape significantly decreased the ability to detect movements at the ankle (P <. 023). For example, at 0.5 deg/s, the 70% detection threshold was 3.40° ± 1.05° in inversion and 3.49° ± 1.15° in eversion at the untaped ankle, and 4.02° ± 0.86° in inversion and 4.04° ± 0.89° in eversion at the taped ankle. Conclusion Taping the ankle decreased the ability to detect movement in the inversion-eversion plane in participants with recurrent ankle sprain. Clinical Relevance The findings suggest that the efficacy of taping is unlikely to be explained by an enhanced ability to detect inversion or eversion movements. However, because it has been found effective in reducing the incidence of ankle sprain, clinicians should continue taping to reduce the likelihood of resprain.
Phase I study of obatoclax mesylate (GX15-070), a small molecule pan–Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia
Authors: O'Brien Susan M. , Claxton David F. , Crump Michael , Faderl Stefan , Kipps Thomas , Keating Michael J. , Viallet Jean , Cheson Bruce D. 
Published: October 2008

Abstract
Obatoclax mesylate is a small molecule pan–Bcl-2 antagonist with in vitro activity against chronic lymphocytic leukemia (CLL) cells. Obatoclax was administered to patients with advanced CLL at doses ranging from 3.5 to 14 mg/m2 as a 1-hour infusion and from 20 to 40 mg/m2 as a 3-hour infusion every 3 weeks. Twenty-six patients received a total of 74 cycles. Dose-limiting reactions were neurologic (somnolence, euphoria, ataxia) and associated with the infusion. The maximum tolerated dose (MTD) was 28 mg/m2 over 3 hours every 3 weeks. One (4%) of 26 patients achieved a partial response. Patients with anemia (3/11) or thrombocytopenia (4/14) experienced improvements in hemoglobin and platelet counts. Circulating lymphocyte counts were reduced in 18 of 26 patients with a median reduction of 24%. Overall, the maximum plasma concentration (Cmax) and area under the curve (AUC) values of obatoclax were dose proportional. Activation of Bax and Bak was demonstrated in peripheral blood mononuclear cells, and induction of apoptosis was related to overall obatoclax exposure, as monitored by the plasma concentration of oligonucleosomal DNA/histone complexes. Obatoclax mesylate has biologic activity and modest single-agent activity in heavily pretreated patients with advanced CLL. Further evaluation in less heavily pretreated patients and in combination with other therapeutic agents is warranted. This trial has been registered with http://clinicaltrials.gov under identifier NCT00600964.
Integrin αvβ3 on human endothelial cells binds von Willebrand factor strings under fluid shear stress
Authors: Huang Jing , Roth Robyn , Heuser John E. , Sadler J. Evan 
Published: October 2008

AbstractAcutely secreted von Willebrand factor (VWF) multimers adhere to endothelial cells, support platelet adhesion, and may induce microvascular thrombosis. Immunofluorescence microscopy of live human umbilical vein endothelial cells showed that VWF multimers rapidly formed strings several hundred micrometers long on the cell surface after stimulation with histamine. Unexpectedly, only a subset of VWF strings supported platelet binding, which depended on platelet glycoprotein Ib. Electron microscopy showed that VWF strings often consisted of bundles and networks of VWF multimers, and each string was tethered to the cell surface by a limited number of sites. Several approaches implicated P-selectin and integrin αvβ3 in anchoring VWF strings. An RGDS peptide or a function-blocking antibody to integrin αvβ3 reduced the number of VWF strings formed. In addition, integrin αv decorated the VWF strings by immunofluorescence microscopy. Furthermore, lentiviral transduction of shRNA against the αv subunit reduced the expression of cell-surface integrin αvβ3 and impaired the ability of endothelial cells to retain VWF strings. Soluble P-selectin reduced the number of platelet-decorated VWF strings in the absence of Ca2+ and Mg2+ but had no effect in the presence of these cations. These results indicate that VWF strings bind specifically to integrin αvβ3 on human endothelial cells.
Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis
Authors: Serwold Thomas , Richie Ehrlich Lauren I. , Weissman Irving L. 
Published: October 2008

AbstractOngoing thymopoiesis requires continual seeding from progenitors that reside within the bone marrow (BM), but the identity of the most proximate prethymocytes has remained controversial. Here we take a comprehensive approach to prospectively identify the major source of thymocyte progenitors that reside within the BM and blood, and find that all thymocyte progenitor activity resides within a rare Flk2+CD27+ population. The BM Flk2+CD27+ subset is predominantly composed of common lymphoid progenitors (CLPs) and multipotent progenitors. Of these 2 populations, only CLPs reconstitute thymopoiesis rapidly after intravenous injection. In contrast, multipotent progenitor-derived cells reconstitute the thymus with delayed kinetics only after they have reseeded the BM, self-renewed, and generated CLPs. These results identify CLPs as the major source of thymocyte progenitors within the BM.
Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays
Authors: Gardina Paul J , Lo Ken C , Lee Walter , Cowell John K , Turpaz Yaron 
Published: October 2008

Abstract

Background
Genomic hybridization platforms, including BAC-CGH and genotyping arrays, have been used to estimate chromosome copy number (CN) in tumor samples by detecting the relative strength of genomic signal. The methods rely on the assumption that the predominant chromosomal background of the samples is diploid, an assumption that is frequently incorrect for tumor samples. In addition to generally greater resolution, an advantage of genotyping arrays over CGH arrays is the ability to detect signals from individual alleles, allowing estimation of loss-of-heterozygosity (LOH) and allelic ratios to enhance the interpretation of copy number alterations. Copy number events associated with LOH potentially have the same genetic consequences as deletions.

Results
We have utilized allelic ratios to detect patterns that are indicative of higher ploidy levels. An integrated analysis using allelic ratios, total signal and LOH indicates that many or most of the chromosomes from 24 glioblastoma tumors are in fact aneuploid. Some putative whole-chromosome losses actually represent trisomy, and many apparent sub-chromosomal losses are in fact relative losses against a triploid or tetraploid background.

Conclusion
These results suggest a re-interpretation of previous findings based only on total signal ratios. One interesting observation is that many single or multiple-copy deletions occur at common putative tumor suppressor sites subsequent to chromosomal duplication; these losses do not necessarily result in LOH, but nonetheless occur in conspicuous patterns. The 500 K Mapping array was also capable of detecting many sub-mega base losses and gains that were overlooked by CGH-BAC arrays, and was superior to CGH-BAC arrays in resolving regions of complex CN variation.
SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys
Authors: Humbert Michael , Rasmussen Robert A , Song Ruijiang , Ong Helena , Sharma Prachi , Chenine Agnès L , Kramer Victor G , Siddappa Nagadenahalli B , Xu Weidong , Else James G , Novembre Francis J , Strobert Elizabeth , O'Neil Shawn P , Ruprecht Ruth M 
Published: October 2008

Abstract

Background
Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide.

Results
We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123–270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis.

Conclusion
These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.
Human prion disease with a G114V mutation and epidemiological studies in a Chinese family: a case series
Authors: Ye Jing , Han Jun , Shi Qi , Zhang Bao-Yun , Wang Gui-Rong , Tian Chan , Gao Chen , Chen Jian-Min , Li Cun-Jiang , Liu Zheng , Li Xian-Zhang , Zhang Lai-Zhong , Dong Xiao-Ping 
Published: October 2008

Abstract

Introduction
Transmissible spongiform encephalopathies are a group of neurodegenerative diseases of humans and animals. Genetic Creutzfeldt-Jakob diseases, in which mutations in the PRNP gene predispose to disease by causing the expression of abnormal PrP protein, include familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia.

Case presentation
A 47-year-old Han-Chinese woman was hospitalized with a 2-year history of progressive dementia, tiredness, lethargy and mild difficulty in falling asleep. On neurological examination, there was severe apathy, spontaneous myoclonus of the lower limbs, generalized hyperreflexia and bilateral Babinski signs. A missense mutation (T to G) was identified at the position of nt 341 in one PRNP allele, leading to a change from glycine (Gly) to valine (Val) at codon 114. PK-resistant PrPSc was detected in brain tissues by Western blotting and immunohistochemical assays. Information on pedigree was collected notably by interviews with family members. A further four suspected patients in five consecutive generations of the family have been identified. One of them was hospitalized for progressive memory impairment at the age of 32. On examination, he had impairment of memory, calculation and comprehension, mild ataxia of the limbs, tremor and a left Babinski sign. He is still alive.

Conclusion
This family with G114V inherited prion disease is the first to be described in China and represents the second family worldwide in which this mutation has been identified. Three other suspected cases have been retrospectively identified in this family, and a further case with suggestive clinical manifestations has been shown by gene sequencing to have the causal mutation.
Evidence that molecular changes in cells occur before morphological alterations during the progression of breast ductal carcinoma
Authors: Castro Nadia P , Osório Cynthia ABT , Torres César , Bastos Elen P , Mourão-Neto Mário , Soares Fernando A , Brentani Helena P , Carraro Dirce M 
Published: October 2008

Abstract
Introduction
Ductal carcinoma in situ (DCIS) of the breast includes a heterogeneous group of preinvasive tumors with uncertain evolution. Definition of the molecular factors necessary for progression to invasive disease is crucial to determining which lesions are likely to become invasive. To obtain insight into the molecular basis of DCIS, we compared the gene expression pattern of cells from the following samples: non-neoplastic, pure DCIS, in situ component of lesions with co-existing invasive ductal carcinoma, and invasive ductal carcinoma.

Methods
Forty-one samples were evaluated: four non-neoplastic, five pure DCIS, 22 in situ component of lesions with co-existing invasive ductal carcinoma, and 10 invasive ductal carcinoma. Pure cell populations were isolated using laser microdissection. Total RNA was purified, DNase treated, and amplified using the T7-based method. Microarray analysis was conducted using a customized cDNA platform. The concept of molecular divergence was applied to classify the sample groups using analysis of variance followed by Tukey's test.

Results
Among the tumor sample groups, cells from pure DCIS exhibited the most divergent molecular profile, consequently identifying cells from in situ component of lesions with co-existing invasive ductal carcinoma as very similar to cells from invasive lesions. Additionally, we identified 147 genes that were differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma, which can discriminate samples representative of in situ component of lesions with co-existing invasive ductal carcinoma from 60% of pure DCIS samples. A gene subset was evaluated using quantitative RT-PCR, which confirmed differential expression for 62.5% and 60.0% of them using initial and partial independent sample groups, respectively. Among these genes, LOX and SULF-1 exhibited features that identify them as potential participants in the malignant process of DCIS.

Conclusions
We identified new genes that are potentially involved in the malignant transformation of DCIS, and our findings strongly suggest that cells from the in situ component of lesions with co-existing invasive ductal carcinoma exhibit molecular alterations that enable them to invade the surrounding tissue before morphological changes in the lesion become apparent.
A candidate molecular signature associated with tamoxifen failure in primary breast cancer
Authors: Vendrell Julie A , Robertson Katherine E , Ravel Patrice , Bray Susan E , Bajard Agathe , Purdie Colin A , Nguyen Catherine , Hadad Sirwan M , Bieche Ivan , Chabaud Sylvie , Bachelot Thomas , Thompson Alastair M , Cohen Pascale A 
Published: October 2008

Abstract
Introduction
Few markers are available that can predict response to tamoxifen treatment in estrogen receptor (ER)-positive breast cancers. Identification of such markers would be clinically useful. We attempted to identify molecular markers associated with tamoxifen failure in breast cancer.

Methods
Eighteen initially ER-positive patients treated with tamoxifen requiring salvage surgery (tamoxifen failure [TF] patients) were compared with 17 patients who were disease free 5 years after surgery plus tamoxifen adjuvant therapy (control patients). cDNA microarray, real-time quantitative PCR, and immunohistochemistry on tissue microarrays were used to generate and confirm a gene signature associated with tamoxifen failure. An independent series of 33 breast tumor samples from patients who relapsed (n = 14) or did not relapse (n = 19) under tamoxifen treatment from a different geographic location was subsequently used to explore the gene expression signature identified.

Results
Using a screening set of 18 tumor samples (from eight control patients and 10 TF patients), a 47-gene signature discriminating between TF and control samples was identified using cDNA arrays. In addition to ESR1/ERα, the top-ranked genes selected by statistical cross-analyses were MET, FOS, SNCG, IGFBP4, and BCL2, which were subsequently validated in a larger set of tumor samples (from 17 control patients and 18 TF patients). Confirmation at the protein level by tissue microarray immunohistochemistry was observed for ER-α, γ-synuclein, and insulin-like growth factor binding protein 4 proteins in the 35 original samples. In an independent series of breast tumor samples (19 nonrelapsing and 14 relapsing), reduced expression of ESR1/ERα, IGFBP4, SNCG, BCL2, and FOS was observed in the relapsing group and was associated with a shorter overall survival. Low mRNA expression levels of ESR1/ERα, BCL2, and FOS were also associated with a shorter relapse-free survival (RFS). Using a Cox multivariate regression analysis, we identified BCL2 and FOS as independent prognostic markers associated with RFS. Finally, the BCL2/FOS signature was demonstrated to have more accurate prognostic value for RFS than ESR1/ERα alone (likelihood ratio test).

Conclusions
We identified molecular markers including a BCL2/FOS signature associated with tamoxifen failure; these markers may have clinical potential in the management of ER-positive breast cancer.
Selective Elevation of Adiponectin Production by the Natural Compounds Derived from a Medicinal Herb Alleviates Insulin Resistance and Glucose Intolerance in Obese Mice
Authors: Xu Aimin , Wang Hongbing , Hoo Ruby L. C. , Sweeney Gary , Vanhoutte Paul. M. , Wang Yu , Wu Donghai , Chu Wenjing , Qin Guowei , Lam Karen S. L. 
Published: October 2008

Adiponectin is an adipocyte-derived insulin-sensitizing hormone with antidiabetic, antiinflammatory, and antiatherosclerotic properties. A decreased serum level of adiponectin in obesity has been identified as an independent risk factor for diabetes and cardiovascular complications, suggesting that pharmacological intervention aimed at elevating adiponectin production might hold promise for the treatment and/or prevention of these diseases. Here we report the identification of two structurally related natural compounds (astragaloside II and isoastragaloside I) from the medicinal herb Radix Astragali that possess such an activity. Astragaloside II and isoastragaloside I selectively increased adiponectin secretion in primary adipocytes without any obvious effects on a panel of other adipokines. Furthermore, an additive effect on induction of adiponectin production was observed between these two compounds and rosiglitazone, a thiazolidinedione class of insulin-sensitizing drugs. Chronic administration of astragaloside II and isoastragaloside I in both dietary and genetic obese mice significantly elevated serum levels of total adiponectin and selectively increased the composition of its high molecular weight oligomeric complex. These changes were associated with an alleviation of hyperglycemia, glucose intolerance, and insulin resistance. By contrast, the beneficial effects of these two compounds on insulin sensitivity and glucose metabolism were diminished in adiponectin knockout mice. In conclusion, our results suggest that pharmacological elevation of circulating adiponectin alone is sufficient to ameliorate insulin resistance and diabetes and support the use of adiponectin as a biomarker for future drug discovery. The two natural compounds might provide the lead as a novel class of therapeutics for obesity-related diseases.
Natural compounds alleviate insulin resistance by inducing adiponectin production.
Pharmacokinetics and pharmacodynamics of Phor21-βCG(ala), a lytic peptide conjugate
Authors: Jia Lee , Noker Patricia E , Piazza Gary A , Leuschner Carola , Hansel William , Gorman Gregory S , Coward Lori U , Tomaszewski Joseph 
Published: October 2008

Abstract
Phor21-βCG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the β-chain of chorionic gonadotropin (βCG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-βCG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.luc). Plasma stability, protease hydrolysis and pharmacokinetics of Phor21-βCG(ala) were measured by using liquid chromatography mass spectrometry (LC/MS/MS). Phor21-βCG(ala) selectively inhibited proliferation in-vitro and in-vivo metastases of PC-3 cells. Phor21-βCG(ala) was relatively stable in mouse, rat, dog and human plasma. Its degradation was partially due to protease hydrolysis and thermodynamic catalysis. Intravenous administration of Phor21-βCG(ala) showed its blood Cmax and AUC0→∞ around the in-vitro effective levels. In the tested rodents, Phor21-βCG(ala) displayed a moderate volume of distribution at steady state (VdSS) and slow clearance (Cl) in the rodents. In conclusion, Phor21-βCG(ala) displayed promising in-vitro and in-vivo anti-cancer activity with favourable pharmacokinetics, and may offer a novel approach to metastatic cancer chemotherapy.
The response of the honeybee dance to uncertain rewards
Authors: Seefeldt Sandra , De Marco Rodrigo J. 
Published: October 2008

SUMMARYThis work focuses on the responses of dancing bees to uncertain rewards. We varied the distribution of a fixed amount of sugar solution among the several flowers of a patch and recorded the foraging and subsequent dance behaviour of single honeybees collecting such a reward at that patch. Concurrently, we aimed to minimize the well-known modulatory effects of sugar reward on both the probability and the strength of a honeybee's dance. It was under these circumstances that we conceived the honeybee dance as an autonomous information-processing system and asked whether or not such a system is sensitive to uncertainty of reward. Our results suggest that bees can tune their dancing according to the distribution of sugar reward among the several flowers of a patch, and that they seemingly do this based on the number– or the frequency – of their non-rewarding inspections to these flowers: the higher the number of non-rewarding inspections the lower the probability of dancing. As a result, a honeybee's dance appears as`risk-averse', meaning that dances for uncertain resources are less likely. Presumably, the ultimate result of having `risk-averse' dances is a colony's ability to diminish delayed rewards and the effects of competition with other flower visitors for limited resources. We conclude that a systems approach to the honeybee dance will help to further analyse the regulation of a honeybee's threshold for dancing, and that theoretical accounts of `risk-sensitive'dances would prove fruitful in broader studies of honeybee foraging,particularly if one were to examine how recruitment actually translates into fitness.