bluuebunny/crossref_metadata_2025_split huggingface dataset:
When is a mouse basophil not a basophil?
Authors: Lee James J. , McGarry Michael P. 
Published: September 2006

AbstractThe identification and characterization of mouse basophils have historically been hampered by the extreme rarity of this cell type. Virtually no photomicrographs of hematologically stained (eg, Wright-Giemsa) examples of mouse basophils exist in the literature. However, 4 recent studies in the past 2 years have used flow cytometry and a defined set of cell-surface markers to identify and subsequently isolate mouse “basophils,” including the publication of stained cytospin preparations of these cells. Surprisingly, a reevaluation of the data from all 4 of the studies revealed several issues of concern that suggest that the cells under study are not necessarily basophils. Nonetheless, we propose that these studies do provide the foundation for a reevaluation of the defining characteristics of a basophil and/or provide support for the provocative conclusion that a new previously overlooked leukocyte subtype has been identified. The purpose of this commentary is to revisit these previously published studies, highlight the relevant issues, and provide a different perspective in the hope of developing a consensus within the research community as to the true identity of the “basophils” described in these studies.
Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment
Authors: Anjos-Afonso Fernando , Bonnet Dominique 
Published: September 2006

AbstractIt is believed that a primitive cell type that maintains the mesenchymal compartment exists in the bone marrow. However, this putative mesenchymal stem/progenitor cell is yet to be identified and isolated. We are reporting the identification, isolation, and detailed characterization of the most primitive mesenchymal progenitor cells in the adult murine bone marrow, based on the expression of stage-specific embryonic antigen–1 (SSEA-1). This primitive subset can be identified in mesenchymal cell cultures and also directly in the bone marrow, thus ascertaining for the first time their existence in an adult organism. Characterization of SSEA-1+ mesenchymal cells revealed that upon purification these cells gave rise to SSEA-1− mesenchymal cells, whereas the reverse could not be observed. Also, these SSEA-1+ cells have a much higher capacity to differentiate than their negative counterparts, not only to several mesenchymal cell types but also to unconventional cell types such as astrocyte-, endothelial-, and hepatocyte-like cells in vitro. Most importantly, a single-cell–derived population was capable of differentiating abundantly into different mesenchymal cell types in vivo. Altogether we are proposing a hierarchical organization of the mesenchymal compartment, placing SSEA-1+ cells at the apex of this hierarchy.
Altered intercellular communication in lung fibroblast cultures from patients with idiopathic pulmonary fibrosis
Authors: Trovato-Salinaro Angela , Trovato-Salinaro Elisa , Failla Marco , Mastruzzo Claudio , Tomaselli Valerio , Gili Elisa , Crimi Nunzio , Condorelli Filippo Daniele , Vancheri Carlo 
Published: September 2006

Abstract

Rationale
Gap junctions are membrane channels formed by an array of connexins which links adjacent cells realizing an electro- metabolic synapse. Connexin-mediated communication is crucial in the regulation of cell growth, differentiation, and development. The activation and proliferation of phenotypically altered fibroblasts are central events in the pathogenesis of idiopathic pulmonary fibrosis. We sought to evaluate the role of connexin-43, the most abundant gap-junction subunit in the human lung, in the pathogenesis of this condition.

Methods
We investigated the transcription and protein expression of connexin-43 and the gap-junctional intercellular communication (GJIC) in 5 primary lung fibroblast lines derived from normal subjects (NF) and from 3 histologically proven IPF patients (FF).

Results
Here we show that connexin-43 mRNA was significantly reduced in FF as demonstrated by standard and quantitative RT-PCR. GJIC was functionally evaluated by means of flow-cytometry. In order to demonstrate that dye spreading was taking place through gap junctions, we used carbenoxolone as a pharmacological gap-junction blocker. Carbenoxolone specifically blocked GJIC in our system in a concentration dependent manner. FF showed a significantly reduced homologous GJIC compared to NF. Similarly, GJIC was significantly impaired in FF when a heterologous NF line was used as dye donor, suggesting a complete defect in GJIC of FF.

Conclusion
These results suggest a novel alteration in primary lung fibroblasts from IPF patients. The reduced Cx43 expression and the associated alteration in cell-to-cell communication may justify some of the known pathological characteristic of this devastating disease that still represents a challenge to the medical practice.
Comparative assessment of performance and genome dependence among phylogenetic profiling methods
Authors: Snitkin Evan S , Gustafson Adam M , Mellor Joseph , Wu Jie , DeLisi Charles 
Published: September 2006

AbstractBackgroundThe rapidly increasing speed with which genome sequence data can be generated will be accompanied by an exponential increase in the number of sequenced eukaryotes. With the increasing number of sequenced eukaryotic genomes comes a need for bioinformatic techniques to aid in functional annotation. Ideally, genome context based techniques such as proximity, fusion, and phylogenetic profiling, which have been so successful in prokaryotes, could be utilized in eukaryotes. Here we explore the application of phylogenetic profiling, a method that exploits the evolutionary co-occurrence of genes in the assignment of functional linkages, to eukaryotic genomes.ResultsIn order to evaluate the performance of phylogenetic profiling in eukaryotes, we assessed the relative performance of commonly used profile construction techniques and genome compositions in predicting functional linkages in both prokaryotic and eukaryotic organisms. When predicting linkages inE. coliwith a prokaryotic profile, the use of continuous values constructed from transformed BLAST bit-scores performed better than profiles composed of discretized E-values; the use of discretized E-values resulted in more accurate linkages when usingS. cerevisiaeas the query organism. Extending this analysis by incorporating several eukaryotic genomes in profiles containing a majority of prokaryotes resulted in similar overall accuracy, but with a surprising reduction in pathway diversity among the most significant linkages. Furthermore, the application of phylogenetic profiling using profiles composed of only eukaryotes resulted in the loss of the strong correlation between common KEGG pathway membership and profile similarity score. Profile construction methods, orthology definitions, ontology and domain complexity were explored as possible sources of the poor performance of eukaryotic profiles, but with no improvement in results.ConclusionGiven the current set of completely sequenced eukaryotic organisms, phylogenetic profiling using profiles generated from any of the commonly used techniques was found to yield extremely poor results. These findings imply genome-specific requirements for constructing functionally relevant phylogenetic profiles, and suggest that differences in the evolutionary history between different kingdoms might generally limit the usefulness of phylogenetic profiling in eukaryotes.
How a well-grounded minimal important difference can enhance transparency of labelling claims and improve interpretation of a patient reported outcome measure
Authors: Brożek Jan L , Guyatt Gordon H , Schünemann Holger J 
Published: September 2006

Abstract
The evaluation and use of patient reported outcome (PRO) measures requires detailed understanding of the meaning of the outcome of interest. The Food and Drug Administration (FDA) recently presented its draft guidance and view on the use of PRO measures as endpoints in clinical trials. One section of the guidance document specifically deals with advice about the use of the minimal important difference (MID) that we redefined as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important. The advice, however, is short, indeed much too short. We believe that expanding the section and making it more specific will benefit all stakeholders: patients, clinicians, other clinical decision makers, those designing trials and making claims, payers and the FDA.
There is no "gold standard" methodology of estimating the MID or achieving the meaningfulness of clinical trial results based on patient reported outcomes. There are many methods of estimating the MID usually grouped into two distinct categories: anchor-based methods, that examine the relationship between scores on the target instrument and some independent measure, and distribution-based methods resorting to the statistical characteristics of the obtained scores.
Estimation of an MID and interpretation of clinical trial results that present patient important outcomes is demanding but vital for informing the decision to recommend approve a given intervention. Investigators are encouraged to use reliable and valid methods to achieve meaningfulness of their results, preferably those that rely on patients to estimate what constitutes a minimal important, small, moderate, or large difference. However, acquiring the meaningfulness of PRO measures transcends beyond a concept of the MID and we advocate that dichotomizing the scores of patient-reported outcome measures facilitate interpretability of clinical trial results for those who need to understand trial results after a labelling claim has been granted. Irrespective of the strategy investigators use to estimate these values, from the individual patient perspective it is much more relevant if investigators report both the estimated thresholds and the proportion of patients achieving that benefit.
Individual freedoms versus collective responsibility: immunization decision-making in the face of occasionally competing values
Authors: Salmon Daniel A , Omer Saad B 
Published: September 2006

AbstractModern public health strives for maximizing benefits for the highest number of people while protecting individual rights. Restrictions on individual rights are justified for two reasons-for the benefit of the individual or the benefit of the community.In extreme situations there may be a need to protect the health of an individual and particularly a child; even by overriding individual/parental autonomy. However, The American Academy of Pediatrics recently concluded that "Continued (vaccine) refusal after adequate discussion should be respected unless the child is put at significant risk of serious harm (as, for example, might be the case during an epidemic). Only then should state agencies be involved to override parental discretion on the basis of medical neglect".Many countries have compulsory immunization requirements. These laws curtail individual autonomy in order to protect the community from infectious diseases because unvaccinated individuals pose risk to the community – including vaccinated individuals (since vaccines are not 100% efficacious), children too young to be vaccinated, and persons who have medical vaccine contraindications. There are situations where there can be a real or perceived divergence between individual and community benefits of vaccination. This divergence may occasionally be based upon current scientific evidence and may exemplify the need for overriding individual autonomy. A divergence between individual and community benefits may also exist when there are ideological beliefs incongruent with vaccination or individuals are unaware of or do not accept available scientific evidence.When the state curtails individual freedoms for the collective good, it should address several issues including the magnitude of the individual and community risk, the strength of the individual's conviction, wider and long-term consequences of restricting individual autonomy, effective risk communication, best available scientific evidence, and transparency of the decision making process.
Multiple effects govern endogenous retrovirus survival patterns in human gene introns
Authors: van de Lagemaat Louie N , Medstrand Patrik , Mager Dixie L 
Published: September 2006

Abstract
Background
Endogenous retroviruses (ERVs) and solitary long terminal repeats (LTRs) have a significant antisense bias when located in gene introns, suggesting strong negative selective pressure on such elements oriented in the same transcriptional direction as the enclosing gene. It has been assumed that this bias reflects the presence of strong transcriptional regulatory signals within LTRs but little work has been done to investigate this phenomenon further.

Results
In the analysis reported here, we found significant differences between individual human ERV families in their prevalence within genes and degree of antisense bias and show that, regardless of orientation, ERVs of most families are less likely to be found in introns than in intergenic regions. Examination of density profiles of ERVs across transcriptional units and the transcription signals present in the consensus ERVs suggests the importance of splice acceptor sites, in conjunction with splice donor and polyadenylation signals, as the major targets for selection against most families of ERVs/LTRs. Furthermore, analysis of annotated human mRNA splicing events involving ERV sequence revealed that the relatively young human ERVs (HERVs), HERV9 and HERV-K (HML-2), are involved in no human mRNA splicing events at all when oriented antisense to gene transcription, while elements in the sense direction in transcribed regions show considerable bias for use of strong splice sites.

Conclusion
Our observations suggest suppression of splicing among young intronic ERVs oriented antisense to gene transcription, which may account for their reduced mutagenicity and higher fixation rate in gene introns.
Increased Visfatin Messenger Ribonucleic Acid and Protein Levels in Adipose Tissue and Adipocytes in Women with Polycystic Ovary Syndrome: Parallel Increase in Plasma Visfatin
Authors: Tan Bee K. , Chen Jing , Digby Janet E. , Keay Stephen D. , Kennedy C. Richard , Randeva Harpal S. 
Published: September 2006

AbstractContext: Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Recent studies have shown that plasma levels of the insulin-mimetic adipokine visfatin increase with obesity. Currently, no data exist on the relative expression of visfatin in either plasma or adipose tissue of PCOS women.Objectives: We investigated the mRNA expression of visfatin from sc and omental (om) adipose tissue and sc adipocytes in women with PCOS compared with matched normal women, as well as visfatin protein in adipose tissue; plasma visfatin was also assessed.Design: Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. Biochemical measurements were performed.Results: There was significant up-regulation of visfatin mRNA in both sc (P &lt; 0.05) and om (P &lt; 0.05) adipose tissue of PCOS women, when compared with normal controls; these findings were also reflected in isolated sc adipocytes (PCOS &gt; controls; P &lt; 0.05). In addition to elevated plasma visfatin levels in women with PCOS (mean ± sd, 30.2 ± 10.4 vs. 11.2 ± 6.2 ng/ml; P &lt; 0.01) when compared with normal controls, visfatin protein levels were significantly greater in both sc and om adipose tissue of PCOS women (P &lt; 0.05 and P &lt; 0.01, respectively).Conclusions: The precise reason for the up-regulation of visfatin seen in women with PCOS, a proinflammatory state, is unknown. Additional studies are needed to clarify the potential role of visfatin in the pathophysiology of PCOS.
Mutational Analysis of the Vitamin D Receptor Does Not Support Its Candidacy as a Tumor Suppressor Gene in Parathyroid Adenomas
Authors: Samander Elizabeth Hanna , Arnold Andrew 
Published: September 2006

AbstractContext: The vitamin D receptor gene (VDR) is a compelling candidate tumor suppressor gene for parathyroid adenomas based on existing evidence of the vitamin D system’s antiproliferative actions in parathyroid and other tissues, its reported inhibition of PTH gene transcription, and the decreased expression of VDR mRNA and VDR protein observed in parathyroid adenomas.Objective: Because demonstration of intragenic mutations is required to establish the authenticity and primary role in pathogenesis for any candidate tumor suppressor gene, we examined the VDR gene in parathyroid adenomas for the presence of such mutations and other loss-of-function abnormalities.Methods and Results: Genomic DNA samples from 37 sporadic parathyroid adenomas and matched normal control DNA from the same individuals were subjected to direct sequencing of the entire VDR coding region and all intron-exon boundaries. No VDR coding region or junctional mutations were identified. The tumors were also analyzed for loss of heterozygosity, a frequent mechanism of tumor suppressor gene inactivation, by molecular allelotyping at three microsatellite markers located near the VDR gene, D12S85, D12S96, and D12S368, and a polymorphism within VDR itself. In all 37 cases, at least one marker was informative and no tumor-specific loss of heterozygosity was observed.Conclusion: We found no evidence of allelic loss within or near the VDR locus and no mutations within the splice junctions and coding regions of the VDR gene in 37 typical sporadic parathyroid adenomas. Thus, VDR is most unlikely to commonly serve as a classical tumor suppressor gene in sporadic parathyroid adenomas.
One-step Preparation of ZnSe Nanorod Aggregates
Authors: Zhao Qingchun , Xu Wenzong 
Published: September 2006

Abstract
ZnSe semiconductor aggregations were prepared via γ-ray irradiation method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the products clearly show that ZnSe possesses an aggregation structure, and these aggregations were found to form through the aggregation of ZnSe nanorods. The length and the diameter of the ZnSe nanorods are about 500–1000 and 30–60 nm, respectively. Electron diffraction patterns of an individual ZnSe nanorod and X-ray diffraction (XRD) analysis were used to examine the crystal structure of the products. The obtained product is pure-phase hexagonal system ZnSe. The composition of the products was analyzed by X-ray photoelectron spectroscopy (XPS). Effect of the pH value on product morphology was investigated.
Light-induced Electron Transfer on the Single Wall Carbon Nanotube Surrounded in Anthracene Dendron in Aqueous Solution
Authors: Sandanayaka Atula S D , Takaguchi Yutaka , Uchida Tetsuya , Sako Yuuki , Morimoto Yu , Araki Yasuyuki , Ito Osamu 
Published: September 2006

Abstract
Light illumination of single-wall carbon nanotubes (SWCNTs) dispersed with anthracene (An) dendrons afforded the accumulation of the reduced form of methyl viologen in the presence of a hole shifter. With the helps of the fluorescence lifetime and transient absorption measurements, the charge-separation process from the excited state of the hybrides of An dendrimer to SWCNT was confirmed.
Interpretation of the short Synacthen test in the presence of low cortisol-binding globulin: two case reports
Authors: Moisey Robert , Wright Dianne , Aye Mo , Murphy Elaine , Peacey Steven R 
Published: September 2006

Context: Ten percent of serum total cortisol (TC) is unbound; the remainder is bound to cortisol-binding globulin (CBG) and, to a lesser extent, albumin. CBG concentrations can drop significantly, particularly in critical illness, resulting in a low TC although the free, active, cortisol may be normal or increased. In the context of a low CBG, the diagnosis of pituitary-adrenal insufficiency with measurements of TC is difficult. Objective: To remind clinicians of the difficulty in interpreting TC when the CBG is low, the circumstances when CBG concentrations may decrease and that measurement of CBG and calculation of the free cortisol index can help in the assessment of pituitary-adrenal reserve. Case: We present two patients at risk of primary and secondary adrenal insufficiency with a poor response to 250 μg Synacthen. In both cases we confirmed low CBG concentrations but a normal free cortisol index (FCI), confirming normal pituitary-adrenal reserve. Intervention: In case one, we have been able to avoid long-term steroid replacement therapy. We continue to reduce the steroid dose in case 2 but have been limited by the need for high-dose steroid treatment for exacerbations of the patient's airways disease. Conclusion: The use of TC in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis may give rise to misleading results if the CBG concentration is low. The FCI may be a better marker of pituitary-adrenal reserve in these subjects. Clinicians should be cautious when interpreting abnormal cortisol results and we emphasize the importance of good clinical assessment.
Whole-blood thiopurine S-methyltransferase activity with genotype concordance: a new, simplified phenotyping assay
Authors: Ford Loretta , Graham Valerie , Berg Jonathan 
Published: September 2006

Background: We have developed a new thiopurine S-methyltransferase (TPMT) phenotyping method that measures TPMT activity in whole blood. To evaluate this assay, we compared it with conventional TPMT phenotyping, which uses a red blood cell (RBC) lysate and genotyping for analysis of common TPMT mutations. Methods: Whole-blood and RBC lysates were prepared from 402 patients' samples received for routine analysis. The TPMT activity of lysates was determined using 6-thioguanine as substrate with high-performance liquid chromatographic (HPLC) analysis and fluorimetric detection. DNA was extracted from buffy coats using phenol-chloroform extraction. A multiplex amplification refractory mutation system (ARMS) strategy was used to screen for the common TPMT mutations TPMT*2 and TPMT*3 (TPMT*3A, TPMT*3C and TPMT*3D). Results: TPMT activities were higher in the whole-blood (mean TPMT activity 51 nmol 6-MTG/gHb/h) compared with the RBC lysate (37 nmol 6-MTG/gHb/h). Overall, concordance with TPMT genotypic analysis was 97% for both the new whole-blood and standard RBC lysate methods. Between low TPMT activity and heterozygotes, both phenotypic methods gave a concordance of 79%. Conclusion: Using multiplex ARMS testing for TPMT*2 and 3*C mutations to define the cut-off between low and normal TPMT activity, we have demonstrated that the new whole-blood TPMT phenotyping method performs as well as the conventional RBC lysate assay. This new method overcomes the need to prepare a RBC lysate, a process which is time consuming and increases analytical variation. The resulting assay is better suited to a regional or national TPMT phenotyping service.
Reflective testing: what do patients think?
Authors: Paterson Sarah G , Robson Jean E , McMahon Michael J , Baxter Gwen , Murphy Michael J , Paterson John R 
Published: September 2006

Introduction: Reflective testing refers to the practice of adding on tests by laboratory staff. Little is known about what patients think of this practice. Methods: We surveyed patients attending a general practice surgery and patients attending hospital outpatient clinics. We sought their views about the practice of adding on tests and about the information they received from requesting clinicians about their investigations. Results: In both groups of patients, large majorities favoured an approach in which relevant additional tests are performed without consulting the requesting clinician or patient first. Most patients also felt that the requesting clinicians had provided a satisfactory explanation about what tests were to be performed and why. Conclusion: Most patients are content to let NHS professionals add on relevant tests if this is felt to be in their interest.