tbuckley/cabot-search huggingface dataset:
T cell recognition of major histocompatibility complex class II complexes with invariant chain processing intermediates.
Authors: S Morkowski, A W Goldrath, S Eastman, L Ramachandra, D C Freed, P Whiteley, Rudensky AYu
Journal: The Journal of Experimental Medicine (1995)

Peptides from the lumenal portion of invariant chain (Ii) spanning residues 80-106 (class II-associated Ii peptide [CLIP]) are found in association with several mouse and human major histocompatibility complex (MHC) class II allelic variants in wild-type and presentation-deficient mutant cells. The ready detection of these complexes suggests that such an intermediate is essential to the MHC class II processing pathway. In this study, we demonstrate that T cells recognize CLIP/MHC class II complexes on the surface of normal and mutant cells in a manner indistinguishable from that of nominal antigenic peptides. Surprisingly, T cell hybrids specific for human CLIP bound to murine MHC class II molecule I-Ab and a new monoclonal antibody 30-2 with the same specificity, recognize two independent epitopes expressed on this peptide/class II complex. T cell recognition is dependent on a Gln residue (position 100) in CLIP, whereas the 30-2 antibody recognizes a Lys residue-at position 90. These two residues flank the 91-99 sequence that is conserved among human, mouse, and rat Ii, potentially representing an MHC class II-binding site. Our results suggest that the COOH-terminal portion of CLIP that includes TCR contact residue Gln 100 binds in the groove of I-Ab molecule. Moreover, both T cells and the antibody recognize I-Ab complexed with larger Ii processing intermediates such as the approximately 12-kD small leupeptin-induced protein (SLIP) fragments. Thus, SLIP fragments contain a CLIP region bound to MHC class II molecule in a conformation identical to that of a free CLIP peptide. Finally, our data suggest that SLIP/MHC class II complexes are precursors of CLIP/MHC class II complexes.
MIB-1 and p27(Kip1) expression in nephroblastoma
Authors: C Jones, K. Pritchard-Jones
Journal: Clinical Cancer Research (2004)

blastemal MIB-1 and p27 Kip1 were significant independent prognostic variables for clinical progression in the Cox proportional hazards model. The potential of such markers to identify those patients who may go on to relapse is an attractive one, and studies such as this one are welcome. However, we feel that there are several points in the study that ought to be addressed. The authors’ cohort of 62 patients were treated according to the International Society of Pediatric Oncology protocols 9 or 93-01, i.e., they received neoadjuvant chemotherapy before nephrectomy. Although it is stated that the samples showed the presence of blastemal, epithelial, and stromal cells, and that careful assessment of the immunohistochemical staining in these different cellular components of the tumor was carried out, nowhere is the actual histologic subtype given. This is of direct clinical relevance because the data from these trials demonstrated the prognostic significance of histologic subtype, with those tumors exhibiting a
Role of Blood Doping in the Coronary Vasoconstrictor Response to Cocaine
Authors: Richard P. Shannon, W. Thomas Manders, You-Tang Shen
Journal: Circulation (1995)

Background The mechanism by which cocaine induces myocardial ischemia remains controversial. Most prior studies have postulated that cocaine-induced coronary vasoconstriction limits myocardial oxygen delivery during times of increased myocardial oxygen demand. Methods and Results To determine the contribution of altered myocardial metabolic demands to the coronary vasoconstrictor effects of intravenous cocaine (COC 1 mg/kg), we studied 13 conscious, chronically instrumented dogs in the intact state and with heart rate held constant with atrial pacing in the presence and absence of β-adrenergic blockade with propranolol (2 mg/kg) to limit the inotropic and chronotropic effects of cocaine on associated increases in myocardial oxygen consumption. In the intact state, COC caused a prompt increase in coronary blood flow (+30±3%, P &lt;.01) that returned rapidly to baseline within 10 minutes, whereas coronary vascular resistance did not increase significantly (+17±6%, P &lt;.05) until 15 minutes after COC. Notably, myocardial oxygen consumption increased (+57±4%, P &lt;.01) to a greater extent than oxygen delivery (+42±3%, P &lt;.01) during the first 2.5 minutes, requiring increased oxygen extraction (from 75±1% to 80±1%, P &lt;.01), although only transiently. Thereafter, enhanced oxygen delivery matched the required oxygen consumption without further need to extract additional oxygen. Surprisingly, the enhanced oxygen delivery associated with COC in conscious dogs did not depend on persistent increases in coronary blood flow but rather was due to enhanced arterial oxygen content (+22±4%, P &lt;.01) as a result of a significant “blood doping” effect with associated increases in circulating hemoglobin from 12.1±0.4 to 14.2±0.6 g/dL ( P &lt;.01), which persisted for 60 minutes. Conclusions The myocardial oxygen requirements associated with COC administration have a significant impact on both the magnitude and the mechanism of the coronary vasoconstrictor effects of COC in conscious dogs. Furthermore, the enhanced myocardial oxygen delivery associated with COC administration is not dependent solely on coronary blood flow responses but is due to a significant “blood doping” effect associated with COC.
POINTS FROM LETTERS: Advertising Literature
Authors: W. S. Sykes
Journal: BMJ (1957)

<h3>Objective</h3> To describe temperature change throughout the workday in an enclosed vehicle in Austin, Texas across the calendar year while accounting for heat index. <h3>Methods</h3> In this observational study, vehicular temperature was measured 1 day per month during 2012 in Austin, Texas. Data were recorded at 5-min intervals via an EL-USB-1-PRO digital temperature sensor from 8:00 to 16:00. Selected days were primarily cloud-free (with ‘clear’ or ‘few clouds’) with a predicted ambient temperature high within ±20°F of the 30-year normal high. Referent temperature and 30-year normal data were collected via the nearest National Weather Service (NWS) weather station. The NWS heat index and corresponding hazard levels were used as a guideline for this study. <h3>Results</h3> Per NWS guidelines, the enclosed vehicle temperature rose to ‘danger’ levels of ≥105°F (41°C) in all months except January and December and to ‘extreme caution’ levels of ≥90°F (32°C) in every month of the year. In June, the vehicle rose to ≥105°F (41°C) by 9:25. The hottest vehicular temperature achieved was 137°F (58°C). In 9 months of the year, the vehicle reached ≥90°F (32°C) by noon. We also found that an ambient temperature as low as 68°F was associated with vehicular temperatures ≥105°F (41°C). <h3>Conclusions</h3> Infants and children in states that experience mild winter temperatures face the threat of vehicular hyperthermia disability and death across the calendar year. Prevention efforts that focus on awareness of a childhood heat vulnerability, parental perception of susceptibility to forgetting a child in a vehicle and universal availability of vehicular safety devices may reduce paediatric vehicular hyperthermia death.
Perceptual objects may have nonphysical properties
Authors: Aaron Ben-Ze’ev
Journal: Behavioral and Brain Sciences (2003)

Abstract Byrne &amp; Hilbert defend color realism, which assumes that: (a) colors are properties of objects; (b) these objects are physical; hence, (c) colors are physical properties. I accept (a), agree that in a certain sense (b) can be defended, but reject (c). Colors are properties of perceptual objects – which also have underlying physical properties – but they are not physical properties.
Community involvement in dengue vector control: cluster randomised trial
Authors: V Vanlerberghe, M E Toledo, M Rodriguez, D Gomez, A Baly, J R Benitez, P Van der Stuyft
Journal: BMJ (2009)

<b>Objective</b> To assess the effectiveness of an integrated community based environmental management strategy to control <i>Aedes aegypti</i>, the vector of dengue, compared with a routine strategy. <b>Design</b> Cluster randomised trial. <b>Setting</b> Guantanamo, Cuba. <b>Participants</b> 32 circumscriptions (around 2000 inhabitants each). <b>Interventions</b> The circumscriptions were randomly allocated to control clusters (n=16) comprising routine <i>Aedes</i> control programme (entomological surveillance, source reduction, selective adulticiding, and health education) and to intervention clusters (n=16) comprising the routine <i>Aedes</i> control programme combined with a community based environmental management approach. <b>Main outcome measures</b> The primary outcome was levels of <i>Aedes</i> infestation: house index (number of houses positive for at least one container with immature stages of <i>Ae aegypti</i> per 100 inspected houses), Breteau index (number of containers positive for immature stages of <i>Ae aegypti</i> per 100 inspected houses), and the pupae per inhabitant statistic (number of <i>Ae aegypti</i> pupae per inhabitant). <b>Results</b> All clusters were subjected to the intended intervention; all completed the study protocol up to February 2006 and all were included in the analysis. At baseline the <i>Aedes</i> infestation levels were comparable between intervention and control clusters: house index 0.25% <i>v</i> 0.20%, pupae per inhabitant 0.44×10<sup>−3</sup><i>v</i> 0.29×10<sup>−3</sup>. At the end of the intervention these indices were significantly lower in the intervention clusters: rate ratio for house indices 0.49 (95% confidence interval 0.27 to 0.88) and rate ratio for pupae per inhabitant 0.27 (0.09 to 0.76). <b>Conclusion</b> A community based environmental management embedded in a routine control programme was effective at reducing levels of <i>Aedes</i> infestation. <b>Trial registration</b> Current Controlled Trials ISRCTN88405796.
Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size and Estrogen-Receptor Status
Authors: Ju-Hyun Park, William F. Anderson, Mitchell H. Gail
Journal: Journal of Clinical Oncology (2015)

Breast cancer mortality began declining in many Western countries during the late 1980s. We estimated the proportion of improvements in stage- and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status.We estimated hazard ratios for breast cancer-specific death from time of invasive breast cancer diagnosis in the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database from 1973 to 2010, with and without stratification by tumor size and ER status.Hazards from breast cancer-specific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age ≥ 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age ≥ 70 years within 5 years after diagnosis.Most stage-specific survival improvement in women younger than age 70 years old is unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women ≥ 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age ≥ 70 years.
THE RADIOLOGICAL MANIFESTATIONS OF SCLERODERMA (DIFFUSE SYSTEMIC SCLEROSIS)
Authors: G. M. FRASER
Journal: British Journal of Dermatology (1966)

Journal Article THE RADIOLOGICAL MANIFESTATIONS OF SCLERODERMA (DIFFUSE SYSTEMIC SCLEROSIS) Get access G. M. FRASER, M.B., Ch.B., D.M.R.D., F.F.R. G. M. FRASER, M.B., Ch.B., D.M.R.D., F.F.R. Formerly Senior Registrar, Radiodiagnostic Department, Cardiff Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 1, 1 January 1966, Pages 1–14, https://doi.org/10.1111/j.1365-2133.1966.tb12126.x Published: 01 January 1966
Generation of PRL-3- and PRL-1-Specific Monoclonal Antibodies as Potential Diagnostic Markers for Cancer Metastases
Authors: Jie Li, Ke Guo, Vicki Wei Chyi Koh, Jing Ping Tang, Bin Qi Gan, Hong Shi, Hui Xiang Li, Qi Zeng
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The PRL-3 mRNA is consistently elevated in metastatic samples derived from colorectal cancers. We sought to generate a specific PRL-3 monoclonal antibody (mAb) that might serve as a potential diagnostic marker for colorectal cancer metastasis. Experimental Design: PRL-3 is one of three members (PRL-1, PRL-2, and PRL-3) in a unique protein-tyrosine phosphatase family. Because the three PRLs are 76% to 87% identical in their amino acid sequences, it poses a great challenge to obtain mAbs that are specific for respective phosphatase of regenerating liver (PRL) but not for the other two in the family. We screened over 1,400 hybridoma clones to generate mAbs specific to each PRL member. Results: We obtained two hybridoma clones specifically against PRL-3 and another two clones specifically against PRL-1. These antibodies had been evaluated by several critical tests to show their own specificities and applications. Most importantly, the PRL-3 mAbs were assessed on 282 human colorectal tissue samples (121 normal, 17 adenomas, and 144 adenocarcinomas). PRL-3 protein was detected in 11% of adenocarcinoma samples. The PRL-3- and PRL-1-specific mAbs were further examined on 204 human multiple cancer tissues. The differential expressions of PRL-3 and PRL-1 confirmed the mAbs' specificity. Conclusions: Using several approaches, we show that PRL-3- or PRL-1-specific mAbs react only to their respective antigen. The expression of PRL-3 in &amp;gt;10% of primary colorectal cancer samples indicates that PRL-3 may prime the metastatic process. These mAbs will be useful as markers in clinical diagnosis for assessing tumor aggressiveness.
Minor acute effect of an inhaled corticosteroid (budesonide) on bronchial hyperresponsiveness to methacholine in children with asthma
Authors: EE van Essen-Zandvliet, WC Hop, H de Jong, A Ferwerda, KF Kerrebijn
Journal: European Respiratory Journal (1993)

Several studies have shown that long-term administration of inhaled corticosteroid reduces airway hyperresponsiveness. This study was performed in order to exclude an acute effect of inhaled corticosteroid. In a double-blind, randomized, cross-over study, children with asthma, who had never used inhaled or oral corticosteroid, received a single dose of 0.8 mg budesonide or placebo on two separate days, with an interval of at least 48 h. On each test day, baseline forced expiratory volume in one second (FEV1) and methacholine responsiveness (expressed as provocative dose producing a 20% fall in FEV1 (PD20) to methacholine, in doubling dose) were measured. Both measurements were repeated 2 and 5 h after administration of the drug. Twenty children were included in the study. FEV1 showed a mean increase of 1% at 5 h on the budesonide day, and a decrease of 2% on the placebo day (p = 0.01). PD20 increased by 0.1 doubling dose on the budesonide day, and decreased by 0.4 doubling dose on the placebo day. These changes are within the measurement variation (p = 0.06). We conclude that a single dose of 0.8 mg budesonide has a minor effect on methacholine responsiveness 5 h after administration in children with asthma. It is unlikely that such an effect interferes with the interpretation of data collected in long-term studies.
Genetic linkage analysis of pulmonary fibrotic response to silica in mice
Authors: Y. Ohtsuka, X-T. Wang, J. Saito, T. Ishida, M. Munakata
Journal: European Respiratory Journal (2006)

Inter-individual variations in the development of silicosis, even within the same environments, have been reported, which suggest the contribution of genetic factors in silicosis aetiology. The aim of the present study was to determine whether there is any significant genetic influence on the development of silicosis. Furthermore, which genetic loci are responsible for the pulmonary response to silica exposure? Eight strains of inbred mice were used to examine the genetic influence on the lung fibrotic response to silica exposure. After intercross-breeding between the most susceptible and most resistant strains, a genome-wide linkage analysis of quantitative trait loci (QTL) was performed. Hydroxyproline was applied as an index, and genotypes of 167 marker genes were analysed by fragment analysis using a capillary-type sequencer. There was significant inter-strain difference in the mean concentration of hydroxyproline contents among the eight strains of mice. Breeding studies were conducted between the most susceptible, C57BL/6J, and the most resistant strain, CBA/J. A genome-wide linkage analysis of silica-exposed intercrossed cohorts identified significant QTL on chromosome 4 and suggestive QTL on chromosomes 3 and 18. The present study demonstrates that genetic factors may play a significant role in fibrotic-lung responses to silica; one significant and two suggestive quantitative trait loci were identified.
Selective enhancement of multipotential hematopoietic progenitors in vitro and in vivo by IL-20
Authors: Ling Liu, Chunjin Ding, Wei Zeng, Josef G. Heuer, Jonathan W. Tetreault, Timothy W. Noblitt, Giao Hangoc, Scott Cooper, Kellie A. Brune, Ganesh Sharma, Niles Fox, Scott W. Rowlinson, Danise P. Rogers, Derrick R. Witcher, Peter K. Lambooy, Victor J. Wroblewski, James R. Miller, Hal E. Broxmeyer
Journal: Blood (2003)
An integrative probabilistic model for identification of structural variation in sequencing data
Authors: Suzanne S Sindi, Selim Önal, Luke C Peng, Hsin-Ta Wu, Benjamin J Raphael
Journal: Genome biology (2012)

Abstract Paired-end sequencing is a common approach for identifying structural variation (SV) in genomes. Discrepancies between the observed and expected alignments indicate potential SVs. Most SV detection algorithms use only one of the possible signals and ignore reads with multiple alignments. This results in reduced sensitivity to detect SVs, especially in repetitive regions. We introduce GASVPro, an algorithm combining both paired read and read depth signals into a probabilistic model that can analyze multiple alignments of reads. GASVPro outperforms existing methods with a 50 to 90% improvement in specificity on deletions and a 50% improvement on inversions. GASVPro is available at http://compbio.cs.brown.edu/software .
Managing adult patients who need home parenteral nutrition
Authors: G. Wanten, P. C. Calder, A. Forbes
Journal: BMJ (2011)

#### Summary points

Patients with intestinal failure—defined as failure to maintain protein-energy balance, fluid balance, electrolyte balance, or micronutrient balance when eating a normal diet as a result of surgery, bowel disease, or a congenital defect—require parenteral nutrition (see box 1 for full definition). Since its introduction in 1967, intravenous nutrition administered in the home has been the mainstay of treatment for patients with long term intestinal failure. Home parenteral nutrition is a clinically important way to supply certain patients with their long term nutritional requirements, but high rates of complications are a worry. Although patients’ survival largely depends on the underlying disease, adverse events related to venous access and metabolic disturbances associated with the delivery of parenteral nutrition may compromise quality of life. We provide an overview of the indications for and delivery of home parenteral nutrition and discuss advances that promise to limit complications and improve treatment outcomes. This review is based largely on recent guidelines and on observational evidence.

#### Sources and selection criteria

We searched PubMed for articles in English on home parenteral nutrition. We also consulted guidelines issued by the European Society for Clinical Nutrition and Metabolism (ESPEN) that are based on grade A (randomised controlled trials), grade B (non-randomised studies), and grade C (expert opinion) evidence.1

#### Box 1 Definition of intestinal failure and short bowel syndrome2

Intestinal failure is caused …
Improving identification of differentially expressed genes in microarray studies using information from public databases.
Authors: Richard D Kim, Peter J Park
Journal: Genome biology (2004)

We demonstrate that the process of identifying differentially expressed genes in microarray studies with small sample sizes can be substantially improved by extracting information from a large number of datasets accumulated in public databases. The improvement comes from more reliable estimates of gene-specific variances based on other datasets. For a two-group comparison with two arrays in each group, for example, the result of our method was comparable to that of a t-test analysis with five samples in each group or to that of a regularized t-test analysis with three samples in each group. Our results are further improved by weighting the results of our approach with the regularized t-test results in a hybrid method.
Lipoprotein (a). Heterogeneity and biological relevance.
Authors: A M Scanu, G M Fless
Journal: Journal of Clinical Investigation (1990)

Lipoprotein (a), or Lp(a),' discovered by KAre Berg (1) more than 25 years ago, remains today a fascinating subject of re- search both because of its presumed association with athero- sclerotic cardiovascular disease (ASCVD) (2-14) and the many challenges it is offering to geneticists, structural biolo- gists, physiologists, epidemiologists, cardiologists, and clini- cians in general.Among these challenges is the elucidation of the remarkable heterogeneity exhibited by this lipoprotein particle, which is a key for understanding its biology.We will examine the various aspects of this heterogeneity and attempt to provide a global view on past and current knowledge on Lp(a) and identify those controversial areas where intensified research efforts are likely to provide important new advances. Physicochemical basis ofheterogeneityThe heterogeneity of Lp(a) went largely unrecognized until Harvie and Schultz (15) reported that their preparations of Lp(a) had a rather broad sedimentation coefficient distribu- tion, and that 25% of them exhibited a bimodal Schlieren peak.The first systematic study on Lp(a) heterogeneity was carried out in 1984 by Fless et al. ( 16), who not only confirmed the findings of Harvey and Schultz but by studying individual rather than pooled human blood samples also found that Lp(a) exhibits both inter-and intra-individual density heterogeneity, and that this heterogeneity is accounted for by differences in protein and lipid composition.In the same study, they also observed that apolipoprotein(a) [apo(a)], the specific marker of Lp(a), exhibits size heterogeneity owing to species that have electrophoretic mobility either less than, equal to, or greater than that of apo B100, the protein moiety of low density lipo- protein (LDL).In those studies it was also shown that apo(a) mass contributed to Lp(a) density in that the larger apo(a) was the main component of the denser particles and the smaller apo(a) was preferentially associated to Lp(a) particles of a low buoyant density.The importance of these studies did not be-