tbuckley/cabot-search huggingface dataset:
A novel submaximal cycle test to monitor fatigue and predict cycling performance
Authors: R P Lamberts, J Swart, T D Noakes, M I Lambert
Journal: British Journal of Sports Medicine (2009)

Objective The purpose of this study was to determine the reliability and predictive value of performance parameters, measured by a new novel submaximal cycle protocol, on peak power and endurance cycling performance in well-trained cyclists. Methods Seventeen well-trained competitive male road racing cyclists completed four peak power output (PPO) tests and four 40-km time trials (40-km TT). Before each test, all cyclists performed a novel submaximal cycle test (Lamberts and Lambert Submaximal Cycle Test (LSCT)). Parameters associated with performance such as power, speed, cadence and rating of perceived exertion (RPE) were measured during the three stages of the test when cyclists rode at workloads coinciding with fixed predetermined heart rates. Heart rate recovery (HRR) was measured after the last stage of the test. Results Parameters measured during the second and third stages of the LSCT were highly reliable (intraclass correlation range: R=0.85−1.00) with low typical error of measurements (range: 1.3−4.4%). Good relationships were found between the LSCT and cycling performance measured by the PPO and 40-km TT tests. Mean power had stronger relationships with measures of cycling performance during the second (r=0.80−0.89) and third stages (r=0.91−0.94) of the LSCT than HRR (r=0.55−0.68). Conclusions The LSCT is a reliable novel test which is able to predict peak and endurance cycling performance from submaximal power, RPE and HRR in well-trained cyclists. As these parameters are able to detect meaningful changes more accurately than VO 2max , the LSCT has the potential to monitor cycling performance with more precision than other current existing submaximal cycle protocols.
Threshold Values for Preserved Viability With a Noninvasive Measurement of Collateral Blood Flow During Acute Myocardial Infarction Treated by Direct Coronary Angioplasty
Authors: Timothy F. Christian, Peter B. Berger, Michael K. O’Connor, David O. Hodge, Raymond J. Gibbons
Journal: Circulation (1999)

Background —Quantitative measures of myocardial perfusion defect severity from acute 99m Tc-sestamibi tomographic images (nadir) have correlated closely with collateral and residual antegrade blood flow during acute myocardial infarction. The purpose of this study was to determine whether a viability threshold could be identified from this measure in patients with acute myocardial infarction treated in a homogeneous manner with successful reperfusion therapy. Methods and Results —The study group consisted of 61 patients with acute myocardial infarction with a risk area of &gt;6% LV treated with primary angioplasty between 120 and 240 minutes after symptom onset. All patients were injected with 20 to 30 mCi of 99m Tc-sestamibi before primary angioplasty and imaged after the procedure. Acute myocardium at risk (MAR) and subsequent infarct size (IS) were quantified by a threshold program. Severity (nadir) from the acute image was the lowest ratio of minimal/maximum counts from 5 short-axis slices. Infarct location was anterior in 22 and inferior in 39 patients. MAR was 33±15% LV and IS was 13±15% LV: 23 patients had no infarction despite MAR similar to those with infarction. Receiver-operator characteristic curve analysis identified a nadir value of 0.26 as providing the best separation of patients with and without infarction (sensitivity, 74%; specificity, 74%). This nadir threshold varied by infarct location: anterior defect, 0.21; inferior defect, 0.31. The sensitivity and specificity for absent infarction for these values were anterior, 69% and 67%, and inferior, 88% and 84%, respectively. Conclusions —In a time frame in which the presence of residual blood flow is important, the severity of the acute 99m Tc-sestamibi defect can be used to predict whether infarction will develop despite successful reperfusion.
Early-Stage Lung Cancer Mimicking Pulmonary Arteriovenous Malformation
Authors: Kyoung Hwa Choi, Seoung Ju Park, Kyung Hoon Min, So Ri Kim, Min Hee Lee, Chi Ryang Chung, Hyo Jin Han, Young Min Han, Myung Ja Chung, Yong Chul Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Slowing down with age: lung DCs do it too
Authors: Thomas J. Braciale, Taeg S. Kim
Journal: Journal of Clinical Investigation (2011)

Decline in immune function with age has been attributed to defects or alterations in both the innate and the adaptive immune system. In this issue of the JCI, Zhao and coworkers provide evidence for a novel mechanism of immune dysfunction in aging mice. They show that migration of respiratory DCs from the site of virus replication to the draining lymph nodes in response to infection with several different respiratory viruses is markedly diminished with increasing age. The impaired DC migration was a result of increased levels of the lipid mediator prostaglandin D2 (PGD2) in the respiratory tract with age and could be partially reversed by blockade of PGD2 synthesis or action.
A Switch from E-Cadherin to N-Cadherin Expression Indicates Epithelial to Mesenchymal Transition and Is of Strong and Independent Importance for the Progress of Prostate Cancer
Authors: Karsten Gravdal, Ole J. Halvorsen, Svein A. Haukaas, Lars A. Akslen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cell adhesion molecules are of crucial importance in cancer invasion and metastasis. Epithelial to mesenchymal transition, characterized by reduced E-cadherin and increased N-cadherin expression, has been recognized as a feature of aggressive tumors, but the importance of this phenotype has not been settled in human prostate cancer. We here present novel data, with special focus on the independent relationship between an E-cadherin to N-cadherin switch (EN-switch) and patient prognosis. Experimental Design: Tissue microarray sections from a consecutive series of 104 radical prostatectomies during 1988 to 1994 with detailed clinicopathologic data and long follow-up were studied immunohistochemically for the expression of E-cadherin, N-cadherin, P-cadherin, β-catenin, and p120CTN. Results: Low E-cadherin expression was significantly associated with adverse clinicopathologic features, whereas other biomarkers were mostly related to Gleason score. In univariate survival analyses, cadherin switching (high N-cadherin and low E-cadherin) showed strong and significant associations with multiple end points of progression and cancer-specific death. Expression of the “basal cell marker” P-cadherin was associated with shorter time to skeletal metastasis (P = 0.036). In multivariate analysis of time to clinical recurrence, the “EN-switch” (hazard ratio, 4.3; P &amp;lt; 0.0005) had strong and independent prognostic effect, together with Gleason score. Conclusion: These novel data unravel the importance of epithelial to mesenchymal transition for prostate cancer progression, and demonstration of a switch from E-cadherin to N-cadherin expression could have significant effect on the care of prostate cancer patients.
Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice
Authors: John Falardeau, Wilson C.J. Chung, Andrew Beenken, Taneli Raivio, Lacey Plummer, Yisrael Sidis, Elka E. Jacobson-Dickman, Anna V. Eliseenkova, Jinghong Ma, Andrew Dwyer, Richard Quinton, Sandra Na, Janet E. Hall, Celine Huot, Natalie Alois, Simon H.S. Pearce, Lindsay W. Cole, Virginia Hughes, Moosa Mohammadi, Pei Tsai, Nelly Pitteloud
Journal: Journal of Clinical Investigation (2008)

Idiopathic hypogonadotropic hypogonadism (IHH) with anosmia (Kallmann syndrome; KS) or with a normal sense of smell (normosmic IHH; nIHH) are heterogeneous genetic disorders associated with deficiency of gonadotropin-releasing hormone (GnRH). While loss-of-function mutations in FGF receptor 1 (FGFR1) cause human GnRH deficiency, to date no specific ligand for FGFR1 has been identified in GnRH neuron ontogeny. Using a candidate gene approach, we identified 6 missense mutations in FGF8 in IHH probands with variable olfactory phenotypes. These patients exhibited varied degrees of GnRH deficiency, including the rare adult-onset form of hypogonadotropic hypogonadism. Four mutations affected all 4 FGF8 splice isoforms (FGF8a, FGF8b, FGF8e, and FGF8f), while 2 mutations affected FGF8e and FGF8f isoforms only. The mutant FGF8b and FGF8f ligands exhibited decreased biological activity in vitro. Furthermore, mice homozygous for a hypomorphic Fgf8 allele lacked GnRH neurons in the hypothalamus, while heterozygous mice showed substantial decreases in the number of GnRH neurons and hypothalamic GnRH peptide concentration. In conclusion, we identified FGF8 as a gene implicated in GnRH deficiency in both humans and mice and demonstrated an exquisite sensitivity of GnRH neuron development to reductions in FGF8 signaling.
Manifestations of three HHV-8-related diseases in an HIV-negative patient: Immunoblastic variant multicentric Castleman's disease, primary effusion lymphoma, and Kaposi's sarcoma
Authors: Shlomi Codish, Mahmoud Abu-Shakra, Samuel Ariad, Howard J. Zirkin, Tikva Yermiyahu, Nicolas Dupin, Chris Boshoff, Shaul Sukenik
Journal: American Journal of Hematology (2000)

We describe a 73-year-old HIV negative patient who presented with symptomatic hypoglycemia. Over the course of several months she was diagnosed with three human herpesvirus-8 related diseases: multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. No improvement was observed following cytotoxic therapy and she died 16 months after her initial presentation. The etiology of the hypoglycemia remained obscure over the course of this patient's disease. This case is the first report of a patient with three human herpesvirus-8 related diseases, and the first report of severe hypoglycemia as the presenting symptom of any of these diseases. Am. J. Hematol. 65:310–314, 2000. © 2000 Wiley-Liss, Inc.
LL-37 is expressed in the inflamed synovium in patients with rheumatoid arthritis and downregulated by TNF inhibitors
Authors: Petra Neregård, Marianne Engström, Birgitta Agerberth, Anca Irinel Catrina
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background/objectives</h3> LL-37, a member of the cathelicidin family of host defense peptides, has a broad range of immunomodulatory and anti-infective effects that are known to selectively alter innate immunity. The authors aimed to investigate a potential role of LL-37 in rheumatoid arthritis (RA). <h3>Materials and methods</h3> Thirty-eight patients meeting the 1987 American College of Rheumatology (ACR) criteria for RA were recruited for this study. The authors evaluated LL-37 and CD-68 expression by immunohistochemistry in synovial biopsy samples obtained before and after a mean of 8 weeks of treatment from 15 patients treated with adalimumab, 12 patients treated with etanercept and 11 patients treated with Methotrexate. The authors also evaluated LL-37 expression in 10 healthy controls. Microscopic analysis was performed and stained synovial biopsy sections were evaluated semiquantitatively in random order by two independent observers (ME and PN) using a four-point scale (0=no positive cells, 1=occasional positive cells, 2=scattered positive cells and/or focal positive cells, 3=extensive positive cells). The observers were unaware of patient identity. Statistical analysis was performed using Wilcoxon paired test. <h3>Results</h3> LL-37 was expressed in most of the RA synovial biopsies, both in close proximity to blood vessels and in the lining and sublining layers. Serial immunostaining for cell surface markers identifies macrophages and granulocytes as main cells expressing LL-37 in the inflamed joint. Lower expression of LL-37 was observed in the healthy controls. Interestingly the authors were able to demonstrate a significant downregulation of LL-37 following adalimumab and etanercept but not methotrexate treatment. <h3>Conclusion</h3> Our results suggest a role for LL-37 in the synovial inflammation and show specific regulation of this molecule by distinct antirheumatic agents.
Type 3 deiodinase is critical for the maturation and function of the thyroid axis
Authors: A. Hernandez
Journal: Journal of Clinical Investigation (2006)

Developmental exposure to appropriate levels of thyroid hormones (THs) in a timely manner is critical to normal development in vertebrates. Among the factors potentially affecting perinatal exposure of tissues to THs is type 3 deiodinase (D3). This enzyme degrades THs and is highly expressed in the pregnant uterus, placenta, and fetal and neonatal tissues. To determine the physiological role of D3, we have generated a mouse D3 knockout model (D3KO) by a targeted inactivating mutation of the Dio3 gene in mouse ES cells. Early in life, D3KO mice exhibit delayed 3,5,3'-triiodothyronine (T3) clearance, a markedly elevated serum T3 level, and overexpression of T3-inducible genes in the brain. From postnatal day 15 to adulthood, D3KO mice demonstrate central hypothyroidism, with low serum levels of 3,5,3',5'-tetraiodothyronine (T4) and T3, and modest or no increase in thyroid-stimulating hormone (TSH) concentration. Peripheral tissues are also hypothyroid. Hypothalamic T3 content is decreased while thyrotropin-releasing hormone (TRH) expression is elevated. Our results demonstrate that the lack of D3 function results in neonatal thyrotoxicosis followed later by central hypothyroidism that persists throughout life. These mice provide a new model of central hypothyroidism and reveal a critical role for D3 in the maturation and function of the thyroid axis.
Variation in the ribosomal internal transcribed spacers and 5.8S rDNA among five species of Acropora (Cnidaria; Scleractinia): patterns of variation consistent with reticulate evolution
Authors: D. M. Odorico, D. J. Miller
Journal: Molecular Biology and Evolution (1997)

The ITS sequences of Acropora spp. are the shortest so far identified in any metazoan and are among the shortest seen in eukaryotes; ITS1 was 70-80 bases, and ITS2 was 100-112 bases. The ITS sequences were also highly variable, but base composition and secondary structure prediction indicate that divergent sequence variants are unlikely to be pseudogenes. The pattern of variation was unusual in several other respects: (1) two distinct ITS2 types were detected in both A. hyacinthus and A. cytherea, species known to hybridize in vitro with high success rates, and a putative intermediate ITS2 form was also detected in A. cytherea; (2) A. valida was found to contain highly (29%) diverged ITS1 variants; and (3) A. longicyathus contained two distinct 5.8S rDNA types. These data are consistent with a reticulate evolutionary history for the genus Acropora.
PRIOR CORONARY ARTERY BYPASS GRAFT SURGERY IS ASSOCIATED WITH INCREASED MORTALITY IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Puja Parikh, Allen Jeremias, Srihari S. Naidu, Richard Shlofmitz, Sorin J. Brener, Thomas Pappas, Kevin P. Marzo, David L. Brown, Luis Gruberg
Journal: Journal of the American College of Cardiology (2011)
Immunologic recognition of a 25-amino acid repeat arrayed in tandem on a major antigen of Blastomyces dermatitidis.
Authors: B S Klein, L H Hogan, J M Jones
Journal: Journal of Clinical Investigation (1993)

A 120-kD glycoprotein antigen abundantly expressed on Blastomyces dermatitidis yeasts is a target of cellular and humoral immune responses in human infection. To investigate the antigen and immune response more carefully at the molecular level, we screened an expression library from B. dermatitidis to identify clones that encode this antigen, designated WI-1. A 942-bp cDNA was isolated by immunologic screening with polyclonal, rabbit anti-WI-1 antiserum. Northern hybridization analysis showed that the cDNA hybridized to yeast message approximately equal to 3.9 kb. DNA and deduced protein sequence analysis of the clone demonstrated a 25-amino acid repeat arrayed in tandem, present in 4.5 copies near the 5' end, and rich in predicted antigenic epitopes. Further analysis showed strong homology in these tandem repeats with invasin, an adhesin of Yersiniae. Cloned cDNA was used to express a 30-kD fusion protein strongly recognized in western blots by rabbit anti-WI-1 antiserum, and by sera from all 35 blastomycosis patients studied. The fusion protein product of subcloned cDNA encoding only the tandem repeat also was strongly recognized in western blots by sera from the 35 blastomycosis patients, but not by sera from 10 histoplasmosis and 5 coccidioidomycosis patients. An antigen-inhibition radioimmunoassay showed that the tandem repeat alone completely eliminated rabbit and human anti-WI-1 antibody binding to radiolabeled native WI-1. From these results, we conclude that the 25-amino acid repeat of WI-1 displays an immunodominant B cell epitope, and that the carboxyl-terminus of the molecule exhibits an architecture that may promote adhesion of Blastomyces yeasts to host cells or extracellular matrix proteins and ultimately provide a clearer picture of the molecular pathogenesis of blastomycosis.
Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity
Authors: Paul J. Tacken, Ingrid S. Zeelenberg, Luis J. Cruz, Maaike A. van Hout-Kuijer, Gerline van de Glind, Remco G. Fokkink, Annechien J. A. Lambeck, Carl G. Figdor
Journal: Blood (2011)
Expression Profiling of t(12;22) Positive Clear Cell Sarcoma of Soft Tissue Cell Lines Reveals Characteristic Up-Regulation of Potential New Marker Genes Including <b> <i>ERBB3</i> </b>
Authors: Karl-Ludwig Schaefer, Kristin Brachwitz, Daniel H. Wai, Yvonne Braun, Raihanatou Diallo, Eberhard Korsching, Martin Eisenacher, Reinhard Voss, Frans van Valen, Claudia Baer, Barbara Selle, Laura Spahn, Shuen-Kuei Liao, Kevin A. W. Lee, Pancras C. W. Hogendoorn, Guido Reifenberger, Helmut E. Gabbert, Christopher Poremba
Journal: Cancer Research (2004)

Abstract Clear cell sarcoma of soft tissue (CCSST), also known as malignant melanoma of soft parts, represents a rare lesion of the musculoskeletal system usually affecting adolescents and young adults. CCSST is typified by a chromosomal t(12;22)(q13;q12) translocation resulting in a fusion between the Ewing sarcoma gene (EWSR1) and activating transcription factor 1 (ATF1), of which the activity in nontransformed cells is regulated by cyclic AMP. Our aim was to identify critical differentially expressed genes in CCSST tumor cells in comparison with other solid tumors affecting children and young adults to better understand signaling pathways regulating specific features of the development and progression of this tumor entity. We applied Affymetrix Human Genome U95Av2 oligonucleotide microarrays representing ∼12,000 genes to generate the expression profiles of the CCSST cell lines GG-62, DTC-1, KAO, MST2, MST3, and Su-CC-S1 in comparison with 8 neuroblastoma, 7 Ewing tumor, and 6 osteosarcoma cell lines. Subsequent hierarchical clustering of microarray data clearly separated all four of the tumor types from each other and identified differentially expressed transcripts, which are characteristically up-regulated in CCSST. Statistical analysis revealed a group of 331 probe sets, representing ∼300 significant (P &amp;lt; 0.001) differentially regulated genes, which clearly discriminated between the CCSST and other tumor samples. Besides genes that were already known to be highly expressed in CCSST, like S100A11 (S100 protein) or MITF (microphthalmia-associated transcription factor), this group shows an obvious portion of genes that are involved in cyclic AMP response or regulation, in pigmentation processes, or in neuronal structure and signaling. Comparison with other expression profile analyses on neuroectodermal childhood tumors confirms the high robustness of this strategy to characterize tumor entities based on their gene expression. We found the avian erythroblastic leukemia viral oncogene homologue 3 (ERBB3) to be one of the most dramatically up-regulated genes in CCSST. Quantitative real-time PCR and Northern blot analysis verified the mRNA abundance and confirmed the absence of the inhibitory transcript variant of this gene. The protein product of the member of the epidermal growth factor receptor family ERBB3 could be shown to be highly present in all of the CCSST cell lines investigated, as well as in 18 of 20 primary tumor biopsies. In conclusion, our data demonstrate new aspects of the phenotype and the biological behavior of CCSST and reveal ERBB3 to be a useful diagnostic marker.
Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in childhood chordomas
Authors: R. Yadav, M. C. Sharma, P. B. Malgulwar, P. Pathak, E. Sigamani, V. Suri, C. Sarkar, A. Kumar, M. Singh, B. S. Sharma, A. Garg, S. Bakhshi, M. Faruq
Journal: Neuro-Oncology (2013)

Chordomas are slow-growing tumors and most commonly involve the sacrum and clivus. Multiple recurrences are frequent. Childhood chordomas are rare and often show exceptionally aggressive behavior, resulting in short survival and a high incidence of metastatic spread.This study examined the histologic features and immunohistochemical profile of pediatric chordomas and compared them with their adult counterparts.Nine pediatric and 13 adult cases were included in the study. Childhood chordomas were classified into conventional, atypical, and poorly differentiated types. Immunohistochemistry was performed for cytokeratin, epithelial membrane antigen, vimentin, S100, brachyury, p53, INI1, epidermal growth factor receptor (EGFR), and CD117. Cytogenetic analyses were performed in a subset of tumors for SMARCB1/INI1 locus on 22q chromosome by fluorescent in situ hybridization (FISH) and analysis of the SMARCB1/INI1 gene sequence.All tumors showed expression of cytokeratin, epithelial membrane antigen, S100, vimentin, brachyury, and EGFR. Atypical morphology, p53 expression, higher MIB-1 labelling index (LI), and INI1 loss were more frequently seen in pediatric chordomas as compared with adults. None of the tumors showed CD117 expression. No point mutation in the SMARCB1/INI1 gene was noted in the tumors examined; however, 4 pediatric and 1 adult chordoma showed loss of this locus on FISH analysis.A subset of pediatric chordomas with atypical histomorphologic features needs to be identified, as they behave in an aggressive manner and require adjuvant therapy. Pediatric chordomas more frequently show p53 expression, INI1 loss, and higher MIB-1 LI as compared with adults, whereas EGFR expression is common to both.