bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feline aminopeptidase N is not a functional receptor for avian infectious bronchitis virus
Authors: Chu Victor C , McElroy Lisa J , Aronson Jed M , Oura Trisha J , Harbison Carole E , Bauman Beverley E , Whittaker Gary R 
Published: February 2007

Abstract

Background
Coronaviruses are an important cause of infectious diseases in humans, including severe acute respiratory syndrome (SARS), and have the continued potential for emergence from animal species. A major factor in the host range of a coronavirus is its receptor utilization on host cells. In many cases, coronavirus-receptor interactions are well understood. However, a notable exception is the receptor utilization by group 3 coronaviruses, including avian infectious bronchitis virus (IBV). Feline aminopeptidase N (fAPN) serves as a functional receptor for most group 1 coronaviruses including feline infectious peritonitis virus (FIPV), canine coronavirus, transmissible gastroenteritis virus (TGEV), and human coronavirus 229E (HCoV-229E). A recent report has also suggested a role for fAPN during IBV entry (Miguel B, Pharr GT, Wang C: The role of feline aminopeptidase N as a receptor for infectious bronchitis virus. Brief review. Arch Virol 2002, 147:2047–2056.

Results
Here we show that, whereas both transient transfection and constitutive expression of fAPN on BHK-21 cells can rescue FIPV and TGEV infection in non-permissive BHK cells, fAPN expression does not rescue infection by the prototype IBV strain Mass41. To account for the previous suggestion that fAPN could serve as an IBV receptor, we show that feline cells can be infected with the prototype strain of IBV (Mass 41), but with low susceptibility compared to primary chick kidney cells. We also show that BHK-21 cells are slightly susceptible to certain IBV strains, including Ark99, Ark_DPI, CA99, and Iowa97 (<0.01% efficiency), but this level of infection is not increased by fAPN expression.

Conclusion
We conclude that fAPN is not a functional receptor for IBV, the identity of which is currently under investigation.
Quantitative image analysis of immunohistochemical stains using a CMYK color model
Authors: Pham Nhu-An , Morrison Andrew , Schwock Joerg , Aviel-Ronen Sarit , Iakovlev Vladimir , Tsao Ming-Sound , Ho James , Hedley David W 
Published: February 2007

AbstractBackgroundComputer image analysis techniques have decreased effects of observer biases, and increased the sensitivity and the throughput of immunohistochemistry (IHC) as a tissue-based procedure for the evaluation of diseases.MethodsWe adapted a Cyan/Magenta/Yellow/Key (CMYK) model for automated computer image analysis to quantify IHC stains in hematoxylin counterstained histological sections.ResultsThe spectral characteristics of the chromogens AEC, DAB and NovaRed as well as the counterstain hematoxylin were first determined using CMYK, Red/Green/Blue (RGB), normalized RGB and Hue/Saturation/Lightness (HSL) color models. The contrast of chromogen intensities on a 0–255 scale (24-bit image file) as well as compared to the hematoxylin counterstain was greatest using the Yellow channel of a CMYK color model, suggesting an improved sensitivity for IHC evaluation compared to other color models. An increase in activated STAT3 levels due to growth factor stimulation, quantified using the Yellow channel image analysis was associated with an increase detected by Western blotting. Two clinical image data sets were used to compare the Yellow channel automated method with observer-dependent methods. First, a quantification of DAB-labeled carbonic anhydrase IX hypoxia marker in 414 sections obtained from 138 biopsies of cervical carcinoma showed strong association between Yellow channel and positive color selection results. Second, a linear relationship was also demonstrated between Yellow intensity and visual scoring for NovaRed-labeled epidermal growth factor receptor in 256 non-small cell lung cancer biopsies.ConclusionThe Yellow channel image analysis method based on a CMYK color model is independent of observer biases for threshold and positive color selection, applicable to different chromogens, tolerant of hematoxylin, sensitive to small changes in IHC intensity and is applicable to simple automation procedures. These characteristics are advantageous for both basic as well as clinical research in an unbiased, reproducible and high throughput evaluation of IHC intensity.
Ethnoveterinary medicines used for ruminants in British Columbia, Canada
Authors: Lans Cheryl , Turner Nancy , Khan Tonya , Brauer Gerhard , Boepple Willi 
Published: February 2007

AbstractBackgroundThe use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock.MethodsIn 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop.ResultsThere are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses:Berberis aquifolium/Mahonia aquifolium Echinacea purpurea,Symphytum officinale,Bovista pila,Bovista plumbea,Achillea millefoliumandUsnea longissima.Curcuma longaL.,Salix scoulerianaandSalix lucidaare used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalisandMatricaria chamomillaare used for eye problems.Wounds and injuries are treated withBovistaspp.,Usnea longissima,Calendula officinalis,Arnicasp.,Malvasp.,Prunella vulgaris,Echinaceapurpurea,Berberis aquifolium/Mahonia aquifolium,Achillea millefolium,Capsella bursa-pastoris,Hypericum perforatum,Lavandula officinalis,Symphytum officinaleandCurcuma longa.Syzygium aromaticumandPseudotsuga menziesiiare used for coccidiosis. The following plants are used for diarrhea and scours:Plantago major,Calendula officinalis,Urtica dioica,Symphytum officinale,Pinus ponderosa,Potentilla pacifica,Althaea officinalis,Anethum graveolens,Salix albaandUlmus fulva.Mastitis is treated withAchillea millefolium,Arctiumlappa,Salix alba,Teucrium scorodoniaandGalium aparine.Anethum graveolensandRubussp., are given for increased milk production.Taraxacum officinale,Zea mays, andSymphytum officinaleare used for udder edema. Ketosis is treated withGaultheria shallon,Vacciniumsp., andSymphytum officinale.Hedera helixandAlchemilla vulgarisare fed for retained placenta.ConclusionSome of the plants showing high levels of validity wereHedera helixfor retained placenta andEuphrasia officinalisfor eye problems. Plants with high validity for wounds and injuries includedHypericum perforatum,Malva parvifloraandPrunella vulgaris. Treatments with high validity against endoparasites included those withJuniperus communisandPinus ponderosa. Anxiety and pain are well treated withMelissa officinalisandNepeta caesarea.
Functional intercomparison of intraoperative radiotherapy equipment – Photon Radiosurgery System
Authors: Armoogum Kris S , Parry John M , Souliman Salam K , Sutton David G , Mackay Colin D 
Published: February 2007

Abstract
Background
Intraoperative Radiotherapy (IORT) is a method by which a critical radiation dose is delivered to the tumour bed immediately after surgical excision. It is being investigated whether a single high dose of radiation will impart the same clinical benefit as a standard course of external beam therapy. Our centre has four Photon Radiosurgery Systems (PRS) currently used to irradiate breast and neurological sites.

Materials and methods
The PRS comprises an x-ray generator, control console, quality assurance tools and a mobile gantry. We investigated the dosimetric characteristics of each source and its performance stability over a period of time. We investigated half value layer, output diminution factor, internal radiation monitor (IRM) reproducibility and depth-doses in water. The half value layer was determined in air by the broad beam method, using high purity aluminium attenuators. To quantify beam hardening at clinical depths, solid water attenuators of 5 and 10 mm were placed between the x-ray probe and attenuators. The ion chamber current was monitored over 30 minutes to deduce an output diminution factor. IRM reproducibility was investigated under various exposures. Depth-dose curves in water were obtained at distances up to 35 mm from the probe.

Results
The mean energies for the beam attenuated by 5 and 10 mm of solid water were derived from ICRU Report 17 and found to be 18 and 24 keV. The average output level over a period of 30 minutes was found to be 99.12%. The average difference between the preset IRM limit and the total IRM count was less than 0.5%. For three x-ray sources, the average difference between the calculated and actual treatment times was found to be 0.62% (n = 30). The beam attenuation in water varied by approximately 1/r3.

Conclusion
The x-ray sources are stable over time. Most measurements were found to lie within the manufacturer's tolerances and an intercomparison of these checks suggests that the four x-ray sources have similar performance characteristics.
Gene promoter hypermethylation in ductal lavage fluid from healthy BRCAgene mutation carriers and mutation-negative controls
Authors: Locke Imogen , Kote-Jarai Zsofia , Jo Fackler Mary , Bancroft Elizabeth , Osin Peter , Nerurkar Ashutosh , Izatt Louise , Pichert Gabriella , Gui Gerald PH , Eeles Rosalind A 
Published: February 2007

Abstract
Introduction
Female germline BRCA gene mutation carriers are at increased risk for developing breast cancer. The purpose of our study was to establish whether healthy BRCA mutation carriers demonstrate an increased frequency of aberrant gene promoter hypermethylation in ductal lavage (DL) fluid, compared with predictive genetic test negative controls, that might serve as a surrogate marker of BRCA1/2 mutation status and/or breast cancer risk.

Methods
The pattern of CpG island hypermethylation within the promoter region of a panel of four genes (RAR-β, HIN-1, Twist and Cyclin D2) was assessed by methylation-specific polymerase chain reaction using free DNA extracted from DL fluid.

Results
Fifty-one DL samples from 24 healthy women of known BRCA mutation status (7 BRCA1 mutation carriers, 12 BRCA2 mutation carriers and 5 controls) were available for methylation analysis. Eight of 19 (42.1%) BRCA mutation carriers were found to have at least one hypermethylated gene in the four-gene panel. Two BRCA mutation carriers, in whom aberrant methylation was found, also had duct epithelial cell atypia identified. No hypermethylation was found in DL samples from 5 negative controls(p = 0.13).

Conclusion
We found substantial levels of aberrant methylation, with the use of a four-gene panel, in the fluid from the breasts of healthy BRCA mutation carriers compared with controls. Methylation analysis of free DNA in DL fluid may offer a useful surrogate marker for BRCA1/2 mutation status and/or breast cancer risk. Further studies are required for the evaluation of the specificity and predictive value of aberrant methylation in DL fluid for future breast cancer development in BRCA1/2 mutation carriers.
DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies
Authors: Hovatta Iiris , Zapala Matthew A , Broide Ron S , Schadt Eric E , Libiger Ondrej , Schork Nicholas J , Lockhart David J , Barlow Carrolee 
Published: February 2007

Abstract
Background
Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies.

Results
Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements.

Conclusion
Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest.
Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma
Authors: Kleinrath Thomas , Gassner Christoph , Lackner Peter , Thurnher Martin , Ramoner Reinhold 
Published: February 2007

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.
Clinical Activity and Immune Modulation in Cancer Patients Treated With CP-870,893, a Novel CD40 Agonist Monoclonal Antibody
Authors: Vonderheide Robert H. , Flaherty Keith T. , Khalil Magi , Stumacher Molly S. , Bajor David L. , Hutnick Natalie A. , Sullivan Patricia , Mahany J. Joseph , Gallagher Maryann , Kramer Amy , Green Stephanie J. , O'Dwyer Peter J. , Running Kelli L. , Huhn Richard D. , Antonia Scott J. 
Published: February 2007

PurposeThe cell-surface molecule CD40 activates antigen-presenting cells and enhances immune responses. CD40 is also expressed by solid tumors, but its engagement results in apoptosis. CP-870,893, a fully human and selective CD40 agonist monoclonal antibody (mAb), was tested for safety in a phase I dose-escalation study.Patients and MethodsPatients with advanced solid tumors received single doses of CP-870,893 intravenously. The primary objective was to determine safety and the maximum-tolerated dose (MTD). Secondary objectives included assessment of immune modulation and tumor response.ResultsTwenty-nine patients received CP-870,893 in doses from 0.01 to 0.3 mg/kg. Dose-limiting toxicity was observed in two of seven patients at the 0.3 mg/kg dose level (venous thromboembolism and grade 3 headache). MTD was estimated as 0.2 mg/kg. The most common adverse event was cytokine release syndrome (grade 1 to 2) which included chills, rigors, and fever. Transient laboratory abnormalities affecting lymphocytes, monocytes, platelets, D-dimer and liver function tests were observed 24 to 48 hours after infusion. Four patients with melanoma (14% of all patients and 27% of melanoma patients) had objective partial responses at restaging (day 43). CP-870,893 infusion resulted in transient depletion of CD19+ B cells in blood (93% depletion at the MTD for < 1 week). Among B cells remaining in blood, we found a dose-related upregulation of costimulatory molecules after treatment.ConclusionThe CD40 agonist mAb CP-870,893 was well tolerated and biologically active, and was associated with antitumor activity. Further studies of repeated doses of CP-870,893 alone and in combination with other antineoplastic agents are warranted.
Tumor-Infiltrating Lymphocytes Predict Sentinel Lymph Node Positivity in Patients With Cutaneous Melanoma
Authors: Taylor Rebecca C. , Patel Ami , Panageas Katherine S. , Busam Klaus J. , Brady Mary S. 
Published: February 2007

Purpose Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution. Patients and Methods All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL. Results Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival. Conclusion The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.
International Comparison of C-Peptide Measurements
Authors: Wiedmeyer Hsiao-Mei , Polonsky Kenneth S , Myers Gary L , Little Randie R , Greenbaum Carla J , Goldstein David E , Palmer Jerry P 
Published: March 2007

Abstract
Background: C-peptide measurement has been widely used as a marker of insulin secretion in patients with diabetes. We assessed the comparability of C-peptide results obtained with different methods and by different laboratories and determined whether C-peptide results could be harmonized by normalization with a WHO reference reagent or with plasma.
Methods: We sent 16 different heparin plasma samples to 15 laboratories in 7 countries. The samples were analyzed with 10 different assay methods. A WHO C-peptide standard was also sent to each laboratory and used to determine the feasibility of normalizing results. To assess the impact of calibrator matrix on the comparability of results, we also used the mean results of all laboratories for 4 of the samples to normalize the remaining sample results.
Results: Between-laboratory variability increased with increasing C-peptide concentrations. Normalization of results with WHO reference reagents did not improve comparability, but normalization with samples significantly improved comparability among laboratories and methods. The 95% confidence interval estimate for the SD for the lab/method effect (0.0–0.061) using sample-normalized values did not overlap with the 95% CI estimate with the raw data (0.090–0.225).
Conclusions: C-peptide results generated by different methods and different laboratories do not always agree, especially at higher concentrations of C-peptide. These data support the concept of using a single laboratory for multisite studies and support efforts to harmonize C-peptide measurements by use of calibrators prepared in the sample matrix.
Longitudinal Analyses of Affect, Temperament, and Childhood Psychopathology
Authors: Goldsmith H. Hill , Lemery-Chalfant Kathryn , Schmidt Nicole L. , Arneson Carrie L. , Schmidt Cory K. 
Published: February 2007

AbstractThe Wisconsin Twin Panel utilizes the resources of state birth records to study the etiology and developmental course of early emotions, temperament, childhood anxiety and impulsivity, the autism spectrum, and related psychobiological and behavioral phenotypes. The panel currently supports 5 active research studies which involve twins from birth to early adolescence. A range of research methods are employed, including questionnaires and structured interviews with caregivers, home and laboratory-based behavioral batteries, observer ratings, child self-report, psychophysiology, neuroendocrine measures, birth records, genotyping, and cognitive testing. The panel is in the early stages of generating longitudinal findings.
Stability of Genetic and Environmental Effects from Adolescence to Young Adulthood: Results of Croatian Longitudinal Twin Study of Personality
Authors: Bratko Denis , Butkovic Ana 
Published: February 2007

AbstractThe primary aim of this study was to conduct a bivariate genetic analysis investigating the extent to which genetic and environmental factors contribute to stability and change in personality factors in the period from adolescence to young adulthood on a sample of Croatian twins. The sample used in this research was formed in 1992 based on a register of citizens of Zagreb and data was collected for 160 twin pairs (75 monozygotic and 85 dizygotic twin pairs). Twins were tested twice, 4 years apart with the Eysenck Personality Questionnaire (mean age at first time point was 17 years). Univariate analyses indicate that the best fitting model for extraversion, neuroticism, psychoticism and lie scale at both time points includes additive genetic (A) and nonshared environmental (E) influences, with heritability estimates in the .40 to .50 range. Longitudinal analyses using AE correlated factors model indicate that genetic factors contribute mainly to stability, while environmental factors contribute mainly to change in personality during that 4-year period of transition from adolescence to young adulthood.