tbuckley/cabot-search huggingface dataset:
Clinical phenotypes in non-cystic fibrosis bronchiectasis (NCFBE)
Authors: Sara Lonni, James D. Chalmers, Angelo Bignamini, Giulia Suigo, Giulia Bonaiti, Sara Annoni, Paola Faverio, Andrea Colzani, Alberto Pesci, Adam T. Hill, Stefano Aliberti
Journal: European Respiratory Journal (2014)

Although NCFBE is a heterogeneous disease, patients may share common clinical features and could be, thus, clustered according to history, signs and symptoms. The aim of our study was to identify distinct clinical phenotypes of NCFBE patients according to clinical variables easily detectable during visits. This was an observational, prospective study of consecutive NCFBE patients attending the outpatient bronchiectasis clinic at the San Gerardo University Hospital in Monza, Italy, during 2013. A two-step cluster analysis was performed after having identified four key variables: dyspnea (evaluated by Medical Research Council –MRC- scale), daily sputum production, number of exacerbations, episodes of recurrent pneumonia (at least 1/year during the prior 3 years). Clusters were subsequently tested in a NCFBE population from Edinburgh, UK. A total of 161 patients (median age: 69 years; 42% males) were enrolled in Monza. Five clusters were identified (silhouette measure of cohesion and separation: 0.75; dimension rate: 4.00), see Figure 1.  The number of patients with at least one hospitalization per year due to exacerbation was higher in the  Poor Performance  cluster than the other clusters (p
Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation
Authors: Q Zhao, J Tao, Q Zhu, P-M Jia, A-X Dou, X Li, F Cheng, S Waxman, G-Q Chen, S-J Chen, M Lanotte, Z Chen, J-H Tong
Journal: Leukemia (2003)
Mobile Phone Use and Risk of Uveal Melanoma: Results of the Risk Factors for Uveal Melanoma Case-Control Study
Authors: Andreas Stang, Andrea Schmidt-Pokrzywniak, Timothy L. Lash, Peter Karl Lommatzsch, Gerhard Taubert, Norbert Bornfeld, Karl-Heinz Jöckel
Journal: JNCI Journal of the National Cancer Institute (2009)

We recently reported an increased risk of uveal melanoma among mobile phone users. Here, we present the results of a case-control study that assessed the association between mobile phone use and risk of uveal melanoma. We recruited 459 uveal melanoma case patients at the University of Duisburg-Essen and matched 455 case patients with 827 population control subjects, 133 with 180 ophthalmologist control subjects, and 187 with 187 sibling control subjects. We used a questionnaire to assess mobile phone use and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) of risk for uveal melanoma using conditional logistic regression. Risk of uveal melanoma was not associated with regular mobile phone use (OR = 0.7, 95% CI = 0.5 to 1.0 vs population control subjects; OR = 1.1, 95% CI = 0.6 to 2.3 vs ophthalmologist control subjects; and OR = 1.2, 95% CI = 0.5 to 2.6 vs sibling control subjects), and we observed no trend for cumulative measures of exposure. We did not corroborate our previous results that showed an increased risk of uveal melanoma among regular mobile phone users.
T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes.
Authors: G Gammon, H M Geysen, R J Apple, E Pickett, M Palmer, A Ametani, E E Sercarz
Journal: The Journal of Experimental Medicine (1991)

T lymphocytes recognize discrete regions on an antigen. The specificity of the T cell responses in three mouse strains of differing major histocompatibility complex (MHC) haplotype to a protein antigen, lysozyme, was analyzed using a series of peptides that walk the antigen in single amino acid steps. These peptide series were synthesized using the pin synthesis system, which was modified to allow the peptides to be cleaved from the pins into a physiological buffer free of toxic compounds. This methodology overcomes many of the problems associated with the production of peptides for screening proteins for antigenic determinants. The T cell determinants for the three strains were markedly different. This result points out the limitations of algorithms predicting determinants without reference to the MHC, and the importance of the empirical methodology. This analysis of the T cell response to lysozyme constitutes the most complete study of reactivity to a foreign protein to date and illustrates many important features of antigen recognition by T cells, e.g., presence of major and minor determinant regions. The outer boundaries of each immunogenic region, the determinant envelope, are difficult to define from recently immunized lymph nodes because of the heterogeneity in T cell recognition. However, core sequences common to all the immunogenic peptides in a continuous sequence can be easily defined.
Ultrasound-guided delivery of microRNA loaded nanoparticles into cancer
Authors: Tzu-Yin Wang, Jung Woo Choe, Kanyi Pu, Rammohan Devulapally, Sunitha Bachawal, Steven Machtaler, Sayan Mullick Chowdhury, Richard Luong, Lu Tian, Butrus Khuri-Yakub, Jianghong Rao, Ramasamy Paulmurugan, Jürgen K. Willmann
Journal: Journal of Controlled Release (2015)
A merged presentation of clinical and radiographic data using probability plots in a clinical trial, the JESMR study
Authors: Hideto Kameda, Katsuaki Kanbe, Eri Sato, Yukitaka Ueki, Kazuyoshi Saito, Shouhei Nagaoka, Toshihiko Hidaka, Tatsuya Atsumi, Michishi Tsukano, Tsuyoshi Kasama, Shunichi Shiozawa, Yoshiya Tanaka, Hisashi Yamanaka, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2012)

In terms of the relationship between synovial inflammation and radiographic changes, including both joint damage repair and progression,1 in rheumatoid arthritis (RA), pre-existing joint damage and persistent synovitis may promote joint destruction, while in the absence of synovitis, damaged joints may heal.2 ,3 Although presentation of radiographic results using cumulative probability plots has substantially improved understanding of clinical trial data,4 the effects of treatments on radiographic progression and improvement (regression) in individual RA patients has not yet been fully explained.

In the JESMR study,5 ,6 151 active RA patients unresponsive to treatment with methotrexate (MTX) were randomised into 1 of 2 treatment groups: etanercept (ETN) 50 mg/week with 6–8 mg/week of MTX (the E+M group), or ETN alone (the E group). Radiographs of the hands and feet before ETN (baseline) and during the first year of treatment were available from 53 (72%) and 68 (88%) patients in the E and E+M groups, respectively. Baseline characteristics of patients were comparable between those with and without available radiographic data in each treatment group (data not shown). However, most patients without data did not complete the study up to Week 52 as per protocol, chiefly due to lack of efficacy in the E group.6 The mean baseline total Sharp-van der Heijde score (TSS)7 was 114.5 in the E group and 113.1 in the E+M …
Comparative Epidemiology of Pandemic and Seasonal Influenza A in Households
Authors: Benjamin J. Cowling, Kwok Hung Chan, Vicky J. Fang, Lincoln L.H. Lau, Hau Chi So, Rita O.P. Fung, Edward S.K. Ma, Alfred S.K. Kwong, Chi-Wai Chan, Wendy W.S. Tsui, Ho-Yin Ngai, Daniel W.S. Chu, Paco W.Y. Lee, Ming-Chee Chiu, Gabriel M. Leung, Joseph S.M. Peiris
Journal: New England Journal of Medicine (2010)

There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings.We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses.Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness.Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.
Impaired gastric acidification negatively affects calcium homeostasis and bone mass
Authors: Thorsten Schinke, Arndt F Schilling, Anke Baranowsky, Sebastian Seitz, Robert P Marshall, Tilman Linn, Michael Blaeker, Antje K Huebner, Ansgar Schulz, Ronald Simon, Matthias Gebauer, Matthias Priemel, Uwe Kornak, Sandra Perkovic, Florian Barvencik, F Timo Beil, Andrea Del Fattore, Annalisa Frattini, Thomas Streichert, Klaus Pueschel, Anna Villa, Klaus-Michael Debatin, Johannes M Rueger, Anna Teti, Jozef Zustin, Guido Sauter, Michael Amling
Journal: Nature Medicine (2009)
Behavioural problems in children who weigh 1000 g or less at birth in four countries
Authors: Elysée TM Hille, A Lya den Ouden, Saroj Saigal, Dieter Wolke, Michael Lambert, Agnes Whitaker, Jennifer A Pinto-Martin, Lorraine Hoult, Renate Meyer, Judith F Feldman, S Pauline Verloove-Vanhorick, Nigel Paneth
Journal: The Lancet (2001)
Bone destruction by Th17
Authors: Ruth Williams
Journal: The Journal of Experimental Medicine (2006)

T cells that produce cytokine IL-17 activate bone-destroying osteoclasts, report Sato et al. on page 2673. The finding pinpoints a potentially powerful target for autoimmine arthritis therapy.






Figure 1

Bone destroying cells (red) flourish in the presence (top) of the IL-17 cytokine.




Autoimmune arthritis, such as rheumatoid arthritis, is a T cell–driven disease, in which bones are destroyed by hyperactive bone-resorbing osteoclasts. Activated T cells have long been implicated in arthritic inflammation and the resulting bone destruction, but exactly which type of T cell is responsible has never been confirmed. T helper (Th)-1 cells, the cells that promote cellular immunity, have received the lion's share of the blame. Yet Th1's signature cytokine, IFNγ, actually inhibits bone resorption by osteoclasts.

The study by Sato et al. helps resolve this paradox by putting the blame for inflammatory bone destruction on a recently described T cell subset called Th17. Th17 cells, named for their propensity to secrete the cytokine IL-17, have also been implicated in other models of autoimmune inflammation.

The team tested whether various T cell subsets—Th17, Th1, Th2, and regulatory T cells—affected osteoclasts. They found that only Th17 cells enhanced osteoclast differentiation—a prerequisite for bone resorption. IL-17 itself also promoted osteoclast differentiation. The induction of osteoclast differentiation was only seen when bone-forming osteoblast cells were also present in the culture. Osteoblasts provide osteoclasts with differentiation signals; thus it now appears that IL-17 might prompt the osteoblasts to release these signals.

Current treatments for autoimmune arthritis reduce inflammation by using broad-based immunosuppression. The identification of both the specific T cell subset and the cytokine responsible for promoting bone resorption might lead to a more powerful therapy that also targets skeletal damage.
EFFECT OF GRAFT PERFUSION WITH TWO CD45 MONOCLONAL ANTIBODIES ON INCIDENCE OF KIDNEY ALLOGRAFT REJECTION
Authors: Y. Brewer, D. Taube, M. Bewick, G. Hale, F. Dische, A. Palmer, K. Welsh, C. Bindon, H. Waldmann, V. Parsons, S. Snowden
Journal: The Lancet (1989)
Plasma C-reactive protein in subjects with hypo/hyperalphalipoproteinemias
Authors: Matteo Pirro, Donatella Siepi, Graziana Lupattelli, Anna Rita Roscini, Giuseppe Schillaci, Fabio Gemelli, Gaetano Vaudo, Simona Marchesi, Leonella Pasqualini, Elmo Mannarino
Journal: Metabolism (2003)
Soluble urokinase plasminogen activator receptor in plasma of patients with inflammatory rheumatic disorders: increased concentrations in rheumatoid arthritis
Authors: O. Slot, N. Brunner, H. Locht, P. Oxholm, R. W Stephens
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Urokinase type plasminogen activator (uPA) catalyses the formation of the proteolytic enzyme plasmin, which is involved in matrix degradation in the processes of tissue remodelling. Because of a surface bound uPA receptor (uPAR), expressed by some cell types (for example, macrophages, malignant cells and inflammatory activated synoviocytes), the action of uPA can be localised and intensified. uPAR seems to have a role in the mechanisms leading to invasive growth of malignant tissue and the rheumatoid pannus. uPAR may become cleaved at its cell surface anchor, thus forming a free soluble receptor (suPAR). suPAR is detectable in low but constant values in plasma of healthy people, while increased concentrations are found in patients with disseminated malignant disease, so that suPAR may be an indicator of invasive growth and tissue remodelling. suPAR concentrations in plasma have not previously been measured in rheumatic patients. A controlled cross sectional measurement was performed of suPAR in plasma of patients with various inflammatory rheumatic disorders with special reference to rheumatoid arthritis (RA). <h3>METHODS</h3> suPAR in plasma was measured by ELISA technique in patients with RA (n=51), reactive arthritis (ReA) (n=23), primary Sjögren's syndrome (PSS) (n=42) and sex and age matched healthy controls (n=53). <h3>RESULTS</h3> In the control group suPAR (median) was 0.91 (range 0.56–1.94) μg/l. Median suPAR value in RA was 1.47 (range 0.65–6.62) μg/l; in ReA 0.68 μg/l (range 0.52–1.48) and in PSS 1.12 μg/l (range 0.76–1.92); p versus controls &lt;0.001 in all patient groups. suPAR values in RA were also significantly increased compared with ReA (p&lt;0.001) and PSS (p=0.004) groups. suPAR in RA was positively correlated to C reactive protein (CRP) (p&lt;0.01) and erythrocyte sedimentation rate (p&lt;0.05) and number of swollen joints (p&lt;0.05). The ReA group had the highest CRP values of all groups, but at the same time the lowest suPAR concentrations in plasma. <h3>CONCLUSIONS</h3> Increased suPAR concentrations were found in plasma in RA, and to a smaller extent also in PSS, but not in ReA. In RA suPAR is related to disease activity. suPAR seems though not merely to be an acute phase reactant like CRP. Increased suPAR values might reflect erosive activity in RA.
Maternal age and fetal loss: population based register linkage study
Authors: A.-M. N. Andersen
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To estimate the association between maternal age and fetal death (spontaneous abortion, ectopic pregnancy, stillbirth), taking into account a woman9s reproductive history. <b>Design:</b> Prospective register linkage study. <b>Subjects:</b> All women with a reproductive outcome (live birth, stillbirth, spontaneous abortion leading to admission to hospital, induced abortion, ectopic pregnancy, or hydatidiform mole) in Denmark from 1978 to 1992; a total of 634 272 women and 1 221 546 pregnancy outcomes. <b>Main outcome measures:</b> Age related risk of fetal loss, ectopic pregnancy, and stillbirth, and age related risk of spontaneous abortion stratified according to parity and previous spontaneous abortions. <b>Results:</b> Overall, 13.5% of the pregnancies intended to be carried to term ended with fetal loss. At age 42 years, more than half of such pregnancies resulted in fetal loss. The risk of a spontaneous abortion was 8.9% in women aged 20–24 years and 74.7% in those aged 45 years or more. High maternal age was a significant risk factor for spontaneous abortion irrespective of the number of previous miscarriages, parity, or calendar period. The risk of an ectopic pregnancy and stillbirth also increased with increasing maternal age. <b>Conclusions:</b> Fetal loss is high in women in their late 30s or older, irrespective of reproductive history. This should be taken into consideration in pregnancy planning and counselling.
Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers
Authors: S Uchiyama, H Itoh, S Naganuma, K Nagaike, T Fukushima, H Tanaka, R Hamasuna, K Chijiiwa, H Kataoka
Journal: Gut (2006)

<b>Background:</b> Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. <b>Aims:</b> To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. <b>Methods:</b> Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. <b>Results:</b> In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear β-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. <b>Conclusion:</b> In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.
Superior Colliculus and Visual Spatial Attention
Authors: Richard J. Krauzlis, Lee P. Lovejoy, Alexandre Zénon
Journal: Annual Review of Neuroscience (2013)

The superior colliculus (SC) has long been known to be part of the network of brain areas involved in spatial attention, but recent findings have dramatically refined our understanding of its functional role. The SC both implements the motor consequences of attention and plays a crucial role in the process of target selection that precedes movement. Moreover, even in the absence of overt orienting movements, SC activity is related to shifts of covert attention and is necessary for the normal control of spatial attention during perceptual judgments. The neuronal circuits that link the SC to spatial attention may include attention-related areas of the cerebral cortex, but recent results show that the SC's contribution involves mechanisms that operate independently of the established signatures of attention in visual cortex. These findings raise new issues and suggest novel possibilities for understanding the brain mechanisms that enable spatial attention.
SHP2-interacting Transmembrane Adaptor Protein (SIT), A Novel Disulfide-linked Dimer Regulating Human T Cell Activation
Authors: Anne Marie-Cardine, Henning Kirchgessner, Eddy Bruyns, Andrej Shevchenko, Matthias Mann, Frank Autschbach, Sheldon Ratnofsky, Stefan Meuer, Burkhart Schraven
Journal: The Journal of Experimental Medicine (1999)

T lymphocytes express several low molecular weight transmembrane adaptor proteins that recruit src homology (SH)2 domain–containing intracellular molecules to the cell membrane via tyrosine-based signaling motifs. We describe here a novel molecule of this group termed SIT (SHP2 interacting transmembrane adaptor protein). SIT is a disulfide-linked homodimeric glycoprotein that is expressed in lymphocytes. After tyrosine phosphorylation by src and possibly syk protein tyrosine kinases SIT recruits the SH2 domain–containing tyrosine phosphatase SHP2 via an immunoreceptor tyrosine-based inhibition motif. Overexpression of SIT in Jurkat cells downmodulates T cell receptor– and phytohemagglutinin-mediated activation of the nuclear factor of activated T cells (NF-AT) by interfering with signaling processes that are probably located upstream of activation of phospholipase C. However, binding of SHP2 to SIT is not required for inhibition of NF-AT induction, suggesting that SIT not only regulates NF-AT activity but also controls NF-AT unrelated pathways of T cell activation involving SHP2.
Evaluation of the use of tyrosinase-specific and melanA/MART-1-specific reverse transcriptase-coupled-polymerase chain reaction to detect melanoma cells in peripheral blood samples from 299 patients with malignant melanoma
Authors: G.G. Brownbridge, J. Gold, M. Edward, R.M. Mackie
Journal: British Journal of Dermatology (2001)

Background There is a current need for a reliable prognostic marker for melanoma patients, particularly those with stage 2 and stage 3 disease, so that adjuvant therapies can be directed appropriately. Objectives To establish whether or not the use of tyrosinase-specific or melanA/MART-1-specific reverse transcriptase-coupled–polymerase chain reaction (RT–PCR) of peripheral blood cells detects preclinical disease progression in patients with malignant melanoma. Methods Two hundred and ninety-nine patients with melanoma in clinical stages 1–4 were observed in this study. Samples were obtained sequentially from 153 of these patients at 4-week intervals over a period of up to 2 years and correlated with clinical evidence of disease activity. Tyrosinase and melanA/MART-1 amplicons were analysed by agarose gel electrophoresis and Southern blot hybridization subsequent to a single round of amplification. Results We demonstrated a statistically significant increase in tyrosinase RT–PCR positivity with advancing stage of melanoma progression. The percentage tyrosinase positivity in 910 samples tested was: stage 1, 135 samples, 34% positive; stage 2, 196 samples, 51% positive; stage 3, 423 samples, 50% positive; and stage 4, 156 samples, 65% positive. The positivity rate for individual patients tested sequentially was higher if only one positive test was required to label a patient positive, at 42%, 65%, 82% and 81% for patients in stages 1–4, respectively. However, we did not find a clear pattern of conversion from negativity to positivity in patients who progressed during the study from stage 2 to stage 3 or stage 3 to stage 4, and found no clear evidence of increased positivity rates in the 6-week period following melanoma-related surgery in patients with stage 3 and 4 disease. The positivity rate for melanA/MART-1 was lower for both patients and samples, and no melanA/MART-1-positive sample was negative for tyrosinase. Conclusions We conclude that the presence of circulating tyrosinase-positive cells as detected by this method appears to be a discontinuous rather than a continuous phenomenon, even in patients with stage 4 disease. For this reason the assay cannot be recommended as a method of sequentially monitoring individual patients in a clinical setting.