tbuckley/cabot-search huggingface dataset:
Targeting Th2-typified immune responses to prevent immunopathology in rheumatic diseases: belittled therapeutic strategies?
Authors: Frederique M Moret, Timothy R D J Radstake, Joel A G van Roon
Journal: Annals of the Rheumatic Diseases (2013)

Although Th2-associated immune responses have been well defined in atopic diseases and parasitic infections, their potential contribution to immunopathology in rheumatic diseases has scarcely been recognised. This is probably related to the clear predominance of Th1/Th17 over Th2 cells in a number of rheumatic diseases, such as rheumatoid arthritis (RA), psoriatic arthritis and primary Sjogren's syndrome (pSS). Also, whereas a clear role for Th1/Th17 activity in immunopathology has been clearly demonstrated in these diseases, Th2-related phenomena such as IgE production are hardly detected. Indeed, Th2-associated atopic conditions and Th2 cytokines like interleukin (IL)-4 and IL-10 were shown to inhibit Th1-induced inflammatory responses in these diseases.1 ,2 As a consequence the understanding of Th2-associated mediators, other than IL-4 and IgE, in these and other rheumatic conditions and the potential to target these have been underevaluated. However, recent data show that immune activation by typical Th2-associated pathways, such as mast cell activation and histamine-induced responses, or Th2-typified key regulatory molecules, such as thymic stromal lymphopoietin (TSLP), IL-33 and IL-13, contribute to inflammation and immunopathology in several rheumatic diseases.

Mast cells have been shown to have a detrimental role in allergic reactions and parasitic infections. In addition, mast cells have been shown to be increased at inflammatory sites in a plethora of rheumatic conditions, including RA, pSS, systemic sclerosis (SSc), spondyloarthropathies (SpA), dermatomyositis and eosinophilia-myalgia syndromes.3–8 Mast cells have also been shown to be important mediators in different experimental inflammatory (arthritis) models by secretion of proinflammatory mediators such as tumour necrosis factor α (TNFα), IL-6, IL-8 and IL-17. In addition, inhibitors of histamine release such as salbutamol and cromolyn were shown to prevent joint destruction in immune complex-mediated arthritis.9 ,10 Recent data suggest that targeting of mast cell-associated pathways prevents inflammatory responses driven by the innate and acquired …
Primary malignant non-Hodgkin's lymphoma of the lung arising in mucosa-associated lymphoid tissue (MALT)
Authors: A Roggeri, L Agostini, G Vezzani, E Sabattini, L Serra
Journal: European Respiratory Journal (1993)

We describe a 10 yr follow-up of a patient with a primary malignant non-Hodgkin's lymphoma of the lung, arising in mucosa-associated lymphoid tissue (MALT). Although the patient was not treated with chemotherapy or radiotherapy, no peripheral spread occurred, confirming that MALT-associated lymphomas apparently remain localized until late in the course of the disease.
Anabolic effects of a G protein–coupled receptor kinase inhibitor expressed in osteoblasts
Authors: Robert F. Spurney, Patrick J. Flannery, Sanford C. Garner, Krairerk Athirakul, Shiguang Liu, Farshid Guilak, L. Darryl Quarles
Journal: Journal of Clinical Investigation (2002)

G protein–coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs). We have selectively manipulated GRK activity in osteoblasts in vitro and in vivo by overexpressing a GRK inhibitor. We found that expression of a GRK inhibitor enhanced parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor-stimulated cAMP generation and inhibited agonist-induced phosphorylation of this receptor in cell culture systems, consistent with attenuation of receptor desensitization. To determine the effect of GRK inhibition on bone formation in vivo, we targeted the expression of a GRK inhibitor to mature osteoblasts using the mouse osteocalcin gene 2 (OG2) promoter. Transgenic mice demonstrated enhanced bone remodeling as well as enhanced urinary excretion of the osteoclastic activity marker dexoypyridinoline. Both osteoprotegrin and OPG ligand mRNA levels were altered in calvaria of transgenic mice in a pattern that would promote osteoclast activation. The predominant effect of the transgene, however, was anabolic, as evidenced by an increase in bone density and trabecular bone volume in the transgenic mice compared with nontransgenic littermate controls.
Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study
Authors: Michael J. Keating, Ian Flinn, Vinay Jain, Jacques-Louis Binet, Peter Hillmen, John Byrd, Maher Albitar, Lee Brettman, Pedro Santabarbara, Bret Wacker, Kanti R. Rai
Journal: Blood (2002)
Guidelines for the design, analysis and interpretation of ‘omics’ data: focus on human endometrium
Authors: Signe Altmäe, Francisco J. Esteban, Anneli Stavreus-Evers, Carlos Simón, Linda Giudice, Bruce A. Lessey, Jose A. Horcajadas, Nick S. Macklon, Thomas D'Hooghe, Cristina Campoy, Bart C. Fauser, Lois A. Salamonsen, Andres Salumets
Journal: Human Reproduction Update (2013)

BACKGROUND‘Omics’ high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied ‘omics’ technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The ‘omics’ technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of ‘omics’ profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such ‘omics’ data. With the expansion of ‘omics’ analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of ‘omics’ data.
Tryptophan hydroxylase-1 regulates immune tolerance and inflammation
Authors: Elizabeth C. Nowak, Victor C. de Vries, Anna Wasiuk, Cory Ahonen, Kathryn A. Bennett, Isabelle Le Mercier, Dae-Gon Ha, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (2012)

Nutrient deprivation based on the loss of essential amino acids by catabolic enzymes in the microenvironment is a critical means to control inflammatory responses and immune tolerance. Here we report the novel finding that Tph-1 (tryptophan hydroxylase-1), a synthase which catalyses the conversion of tryptophan to serotonin and exhausts tryptophan, is a potent regulator of immunity. In models of skin allograft tolerance, tumor growth, and experimental autoimmune encephalomyelitis, Tph-1 deficiency breaks allograft tolerance, induces tumor remission, and intensifies neuroinflammation, respectively. All of these effects of Tph-1 deficiency are independent of its downstream product serotonin. Because mast cells (MCs) appear to be the major source of Tph-1 and restoration of Tph-1 in the MC compartment in vivo compensates for the defect, these experiments introduce a fundamentally new mechanism of MC-mediated immune suppression that broadly impacts multiple arms of immunity.
Urinary Biomarkers Predict Brain Tumor Presence and Response to Therapy
Authors: Edward R. Smith, David Zurakowski, Ali Saad, R. Michael Scott, Marsha A. Moses
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A major difficulty in treating brain tumors is the lack of effective methods of identifying novel or recurrent disease. In this study, we have evaluated the efficacy of urinary matrix metalloproteinases (MMP) as diagnostic biomarkers for brain tumors. Experimental Design: Urine, cerebrospinal fluid, and tissue specimens were collected from patients with brain tumors. Zymography, ELISA, and immunohistochemistry were used to characterize the presence of MMP-2, MMP-9, MMP-9/neutrophil gelatinase–associated lipocalin (NGAL), and vascular endothelial growth factor (VEGF). Results were compared between age- and sex-matched controls and subjected to univariate and multivariate statistical analyses. Results: Evaluation of a specific panel of urinary biomarkers by ELISA showed significant elevations of MMP-2, MMP-9, MMP-9/NGAL, and VEGF (all P &amp;lt; 0.001) in samples from brain tumor patients compared with controls. Multiplexing MMP-2 and VEGF provided superior accuracy compared with any other combination or individual biomarker. Receiver-operating characteristics curves for MMP-2 and VEGF showed excellent discrimination. Immunohistochemistry identified these same proteins in the source tumor tissue. A subset of patients with longitudinal follow-up revealed subsequent clearing of biomarkers after tumor resection. Conclusion: We report, for the first time, the identification of a panel of urinary biomarkers that predicts the presence of brain tumors. These biomarkers correlate with presence of disease, decrease with treatment, and can be tracked from source tissue to urine. These data support the hypothesis that urinary MMPs and associated proteins are useful predictors of the presence of brain tumors and may provide a basis for a novel, noninvasive method to identify new brain tumors and monitor known tumors after treatment.
Constrictive pericarditis: etiology and cause-specific survival after pericardiectomy
Authors: Stefan C. Bertog, Senthil K. Thambidorai, Kapil Parakh, Paul Schoenhagen, Volkan Ozduran, Penny L. Houghtaling, Bruce W. Lytle, Eugene H. Blackstone, Michael S. Lauer, Allan L. Klein
Journal: Journal of the American College of Cardiology (2004)
Phase II Trial of Bexarotene Capsules in Patients With Advanced Non–Small-Cell Lung Cancer After Failure of Two or More Previous Therapies
Authors: Ramaswamy Govindan, John Crowley, Lee Schwartzberg, Peter Kennedy, Charles Williams, Bradley Ekstrand, Alan Sandler, Dinah Jaunakais, Vanessa Bolejack, Richard Ghalie
Journal: Journal of Clinical Oncology (2006)

To evaluate the effect of bexarotene on survival in patients with relapsed non-small-cell lung cancer (NSCLC).Patients with stage IIIB NSCLC with pleural effusion or stage IV NSCLC, who had Eastern Cooperative Oncology Group performance status 0 to 2, and were previously treated with > or = two different regimens that must have included a platinum and a taxane, received oral bexarotene 400 mg/m2/d plus concomitant levothyroxine and a lipid-lowering agent. Primary efficacy end point was survival.For the 146 assessable patients treated with bexarotene, median age was 66 years (range, 34 to 87 years), 51% were men, and the median number of prior regimens was three (range, one to seven). The overall median survival was 5 months (95% CI, 4 to 7 months) and the 1-year survival was 23% (95% CI, 16% to 31%). Survival was significantly longer in patients with bexarotene-induced hypertriglyceridemia and/or skin rash. In 26 patients who had both adverse effects, the median and 1-year survival rates were 12 months (95% CI, 8 to 15 months) and 48%, respectively. In 40 patients who had neither adverse effect, median and 1-year survival rates were 2 months (95% CI, 2 to 5 months) and 15%, respectively (P = .0002). Twenty patients (14%) discontinued therapy because of bexarotene-related toxicity. For the remaining patients, adverse reactions to bexarotene were generally mild to moderate.In the intent-to-treat population, bexarotene given as third or subsequent line of therapy for relapsed NSCLC did not achieve the intended median survival of 6 months. Survival may have been extended in patients who developed bexarotene-induced hypertriglyceremia and/or skin rash. It is important to confirm these observations in a randomized controlled trial.
Angiogenic cytokines in patients with idiopathic interstitial pneumonia
Authors: N R Simler
Journal: Thorax (2004)

<b>Background:</b> Angiogenesis has been implicated in the pathogenesis of idiopathic interstitial pneumonia (IIP). The aim of this study was to examine the relationship between plasma concentrations of the angiogenic cytokines interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1) and clinical parameters of disease progression over a 6 month period to identify potential aetiological mediators and prognostic markers of disease activity in patients with IIP. <b>Methods:</b> Forty nine patients with IIP (40 men) were recruited to the study. Plasma cytokine measurements, pulmonary function tests, and high resolution computed tomography (HRCT) scans were performed on recruitment and after 6 months. Plasma cytokine measurements were also performed in 15 healthy volunteers for control purposes. <b>Results:</b> Patients with IIP had significantly higher median (IQR) baseline concentrations of IL-8 and ET-1 than controls (155 (77–303) pg/ml <i>v</i> 31 (0–100) pg/ml, p&lt;0.001) and (1.21 (0.91–1.88) pg/ml <i>v</i> 0.84 (0.67–1.13) pg/ml, p&lt;0.01), respectively. Baseline concentrations of IL-8, ET-1, and VEGF were significantly related to the baseline HRCT fibrosis score (<i>r</i> = 0.42, p&lt;0.005; <i>r</i> = 0.39, p&lt;0.01; and <i>r</i> = 0.42, p&lt;0.005, respectively). Patients with IIP who developed progressive disease had significantly higher baseline levels of IL-8 (345 (270–497) pg/ml <i>v</i> 121 (73–266) pg/ml, p = 0.001) and VEGF (1048 (666–2149) pg/ml <i>v</i> 658 (438–837) pg/ml, p = 0.019). Over 6 months the change in VEGF was significantly related to the change in HRCT fibrosis score (<i>r</i> = 0.565, p = 0.035) and negatively related to the change in forced vital capacity (<i>r</i> = −0.353, p = 0.035).
From Differences in Means between Cases and Controls to Risk Stratification: A Business Plan for Biomarker Development
Authors: Nicolas Wentzensen, Sholom Wacholder
Journal: Cancer Discovery (2013)

Abstract Researchers developing biomarkers for early detection can determine the potential for clinical benefit at early stages of development. We provide the theoretical background showing the quantitative connection between biomarker levels in cases and controls and clinically meaningful risk measures, as well as a spreadsheet for researchers to use in their own research. We provide researchers with tools to decide whether a test is useful, whether it needs technical improvement, whether it may work only in specific populations, or whether any further development is futile. The methods described here apply to any method that aims to estimate risk of disease based on biomarkers, clinical tests, genetics, environment, or behavior. Significance: Many efforts go into futile biomarker development and premature clinical testing. In many instances, predictions for translational success or failure can be made early, simply based on critical analysis of case–control data. Our article presents well-established theory in a form that can be appreciated by biomarker researchers. Furthermore, we provide an interactive spreadsheet that links biomarker performance with specific disease characteristics to evaluate the promise of biomarker candidates at an early stage. Cancer Discov; 3(2); 148–57. ©2012 AACR.
EXPERIMENTAL PULMONARY PNEUMOCYSTIS CARINII INFECTION IN RABBITS
Authors: Walter H. Sheldon
Journal: The Journal of Experimental Medicine (1959)

Moderate to marked interstitial pneumonitis with many Pneumocystis organisms was found in rabbits treated with cortisone and antibiotics and instilled intranasally with a suspension of lung tissue from either a patient or a rabbit with this infection. Organisms and pulmonary lesions of similar severity and frequency were present in controls treated in the same manner but instilled with either saline or a boiled suspension of normal human lung tissue. The administration of antibiotics and infected rabbit lung suspension only produced less marked lung changes with fewer organisms. Rare organisms and minute foci of pneumonitis were encountered in normal rabbits which had received neither hormone, antibiotics, nor inoculum. The pulmonary lesions in the cortisone-treated rabbits resembled closely the findings in patients with the subclinical form of Pneumocystis pneumonitis. They did not reproduce the massive lesions of widespread Pneumocystis pneumonia in infants. The findings indicate that latent pulmonary Pneumocystis infection was widespread in these rabbits but do not establish the transmission of the disease. The activation of latent infection was dependent on an impairment of host resistance which in these experiments was produced most effectively by the administration of cortisone. The differences between the experimental lesions and those of typical Pneumocystis pneumonia in infants suggest that in man an unknown defect of host defenses other than that induced by prolonged hormone administration accounts for the increased susceptibility to the infection. It is concluded that in the presence of widespread latent Pneumocystis infection the development of active disease is a manifestation of altered host resistance.
Long-Term Effect of the Internet-Based Glucose Monitoring System on HbA1c Reduction and Glucose Stability
Authors: Jae-Hyoung Cho, Sang-Ah Chang, Hyuk-Sang Kwon, Yoon-Hee Choi, Seung-Hyun Ko, Sung-Dae Moon, Soon-Jib Yoo, Ki-Ho Song, Hyun-Shik Son, Hee-Seung Kim, Won-Chul Lee, Bong-Yun Cha, Ho-Young Son, Kun-Ho Yoon
Journal: Diabetes Care (2006)

To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes.We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI).The mean A1C and HFI were significantly lower in the intervention group (n = 40) than in the control group (n = 40). (A1C [mean +/- SD] 6.9 +/- 0.9 vs. 7.5 +/- 1.0%, P = 0.009; HFI 0.47 +/- 0.23 vs. 0.78 +/- 0.51, P = 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1C >or=7% (n = 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P = 0.022). Control patients with a basal A1C <7% (n = 15) showed the characteristic bimodal distribution of A1C levels, whereas the A1C levels in the intervention group remained stable throughout the study with low HFI.Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability.
Failure of operative treatment in a fast bowler with bilateral spondylolysis
Authors: V S Ranawat, M B Heywood-Waddington
Journal: British Journal of Sports Medicine (2004)

Modern day fast bowling places immense strain on the spine. Stress fractures of the lumbar region are common. If a period of conservative treatment fails to return a fast bowler to professional sport, surgery is considered. Good results have been reported using a direct screw repair of the spondylolytic defect. A case is presented of a failed surgical intervention with an alternative technique.
A Cancer Theory Kerfuffle Can Lead to New Lines of Research
Authors: S. G. Baker
Journal: JNCI Journal of the National Cancer Institute (2014)

The standard viewpoint that cancer is a genetic disease is often stated as a fact rather than a theory. By not acknowledging that it is a theory, namely the Somatic Mutation Theory (SMT), researchers are limiting their progress. An attractive alternative to SMT is the tissue organization field theory (TOFT), which is summarized as "development gone awry." To initiate a kerfuffle, I discuss the interpretation of various results under both TOFT and SMT, including recurrent mutations, hereditary cancers, induction of tumors in transgenic experiments, remission of tumors following the inhibition of enzymes activated by mutated genes, nongenotoxic carcinogens, denervation experiments, foreign-body carcinogenesis, transplantation experiments, and tumors with zero mutations. Thinking in terms of TOFT can spur new lines of research; examples are given related to the early detection of cancer.
Phylogeny of the genera Entamoeba and Endolimax as deduced from small- subunit ribosomal RNA sequences
Authors: J. D. Silberman, C. G. Clark, L. S. Diamond, M. L. Sogin
Journal: Molecular Biology and Evolution (1999)

We sequenced small-subunit ribosomal RNA genes (16S-like rDNAs) of 10 species belonging to the genera Entamoeba and Endolimax. This study was undertaken to (1) resolve the relationships among the major lineages of Entamoeba previously identified by riboprinting; (2) examine the validity of grouping the genera Entamoeba and Endolimax in the same family, the Entamoebidae; and (3) examine how different models of nucleotide evolution influence the position of Entamoeba in eukaryotic phylogenetic reconstructions. The results obtained with distance, parsimony, and maximum-likelihood analyses support monophyly of the genus Entamoeba and are largely in accord with riboprinting results. Species of Entamoeba producing cysts with the same number of nuclei from monophyletic groups. The most basal Entamoeba species are those that produce cysts with eight nuclei, while the group producing four-nucleated cysts is most derived. Most phylogenetic reconstructions support monophyly of the Entamoebidae. In maximum-likelihood and parsimony analyses, Endolimax is a sister taxon to Entamoeba, while in some distance analyses, it represents a separate lineage. The secondary loss of mitochondria and other organelles from these genera is confirmed by their relatively late divergence in eukaryotic 16S-like rDNA phylogenies. Finally, we show that the positions of some (fast-evolving) eukaryotic lineages are uncertain in trees constructed with models that make corrections for among-site rate variation.
Pharmacogenetics of outcome in children with acute lymphoblastic leukemia
Authors: Jose Claudio C. Rocha, Cheng Cheng, Wei Liu, Shinji Kishi, Soma Das, Edwin H. Cook, John T. Sandlund, Jeffrey Rubnitz, Raul Ribeiro, Dario Campana, Ching-Hon Pui, William E. Evans, Mary V. Relling
Journal: Blood (2005)
Remarks on the Elasticity of the Lungs and Chest-Walls: With Reference to Some Phenomena of Chest-Disease
Authors: R. D. Powell
Journal: BMJ (1878)

MR. PRESI)DEN.T ANx GENTrLE.MEN,-I musit ask for your kind indul- gence, and that of thlle mrmlmrs present, if, iii my endeavour to condense my remarks within the presciil,ed limit of tim-. (twenty minutes), I become a little disconnected(, if not incohlerent.A few preliminary considerations of a physiolgical kilnd are nec s-,ary, inasniuchli as the matter before us hangs very much upon our estin:ttion of the forces concerned in respiration.In order to illustrat,: the current views respecting the mechanism of respiration, I have taken these diagrams (Fig. i) fioun onre of our best and most mod(lern text-lookls of ph)siology.They are copied from Funlkec, but they also represent the e-sential fcatures shown in Dond(lers's well-known schema, with the additioi that here a small piece of India- rubber ( 6) is inserted to rei)rcscnt thlle elasticity of the cicst-walls.