tbuckley/cabot-search huggingface dataset:
B-1a B Cells that Link the Innate and Adaptive Immune Responses Are Lacking in the Absence of the Spleen
Authors: Hedda Wardemann, Thomas Boehm, Neil Dear, Rita Carsetti
Journal: The Journal of Experimental Medicine (2002)

Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.
FoxO3 Coordinately Activates Protein Degradation by the Autophagic/Lysosomal and Proteasomal Pathways in Atrophying Muscle Cells
Authors: Jinghui Zhao, Jeffrey J. Brault, Andreas Schild, Peirang Cao, Marco Sandri, Stefano Schiaffino, Stewart H. Lecker, Alfred L. Goldberg
Journal: Cell Metabolism (2007)
Effect of Azithromycin on Pulmonary Function in Patients With Cystic Fibrosis Uninfected With &lt;emph type="ital"&gt;Pseudomonas aeruginosa&lt;/emph&gt;&lt;subtitle&gt;A Randomized Controlled Trial&lt;/subtitle&gt;
Authors: Lisa Saiman
Journal: JAMA (2010)

A VICIOUS CYCLE OF INFECTIONand inflammation causes progressive lung destruction and premature death in patients with cystic fibrosis (CF).Treatment strategies have therefore included both antimicrobial and anti-inflammatory agents. 1,2Over the past decade, there has been increasing evidence that azithromycin, an antibiotic with both antimicrobial and anti-inflammatory activity, benefits individuals with CF.4][5][6] These studies demonstrated that azithromycin was associated with reduced pulmonary exacerbations, increased weight gain, or both, and improved lung function.Thus, azithro-
Cancer Immunotherapy Based on Killing of <i>Salmonella</i>-Infected Tumor Cells
Authors: Francesca Avogadri, Chiara Martinoli, Liljana Petrovska, Claudia Chiodoni, Pietro Transidico, Vincenzo Bronte, Renato Longhi, Mario P. Colombo, Gordon Dougan, Maria Rescigno
Journal: Cancer Research (2005)

Abstract A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella–specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.
The effectiveness of supported employment for people with severe mental illness: a randomised controlled trial
Authors: Tom Burns, Jocelyn Catty, Thomas Becker, Robert E Drake, Angelo Fioritti, Martin Knapp, Christoph Lauber, Wulf Rössler, Toma Tomov, Jooske van Busschbach, Sarah White, Durk Wiersma
Journal: The Lancet (2007)
Diaphragm Dysfunction on Admission to the Intensive Care Unit. Prevalence, Risk Factors, and Prognostic Impact—A Prospective Study
Authors: Alexandre Demoule, Boris Jung, Hélène Prodanovic, Nicolas Molinari, Gerald Chanques, Catherine Coirault, Stefan Matecki, Alexandre Duguet, Thomas Similowski, Samir Jaber
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans.Objectives: To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission.Methods: Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim).Measurements and Main Results: Eighty-five consecutive patients aged 62 (54–75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44–68]). On Day 1, Ptr,stim was 8.2 (5.9–12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, −3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, −0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3–13.8] vs. 7.3 [5.5–9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3–13.5] vs. 7.8 [5.5–10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar.Conclusions: A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis.Clinical trial registered with www.clinicaltrials.gov (NCT 00786526).
A need for greater reporting of socioeconomic status and race in clinical trials
Authors: S J Lee
Journal: Annals of the Rheumatic Diseases (2004)

Comprehensive data about new treatments for rheumatoid arthritis (RA), including their potential for disease remission, efficacy, and safety, are derived from clinical research.Often these studies can significantly influence management strategies for patients with RA.Virtually all recent studies on RA report disease characteristics relevant to outcome.Factors such as the presence of rheumatoid factor, the number of tender and swollen joints, measurements of acute phase reactants, the presence of radiographic erosions, and prior treatments with disease modifying antirheumatic drugs define the severity of disease, and also, the potential for responses to treatments.The age and sex of the study population are also reported in every study, although their effect on disease outcome is less clear.However, many clinical studies, including some landmark studies that have dramatically shaped our approach to RA, fail to report other key demographic information.9][20] Although the data on RA are limited, studies in systemic lupus erythematosus and in non-rheumatological conditions have shown that race can be associated with worse disease prognosis, a more aggressive disease, and a
Multicenter Core Laboratory Comparison of the Instantaneous Wave-Free Ratio and Resting P /P With Fractional Flow Reserve
Authors: Allen Jeremias, Akiko Maehara, Philippe Généreux, Kaleab N. Asrress, Colin Berry, Bernard De Bruyne, Justin E. Davies, Javier Escaned, William F. Fearon, K. Lance Gould, Nils P. Johnson, Ajay J. Kirtane, Bon-Kwon Koo, Koen M. Marques, Sukhjinder Nijjer, Keith G. Oldroyd, Ricardo Petraco, Jan J. Piek, Nico H. Pijls, Simon Redwood, Maria Siebes, Jos A.E. Spaan, Marcel van 't Veer, Gary S. Mintz, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2013)
Interleukin-2 and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures.
Authors: E Arzt, G Stelzer, U Renner, M Lange, O A Müller, G K Stalla
Journal: Journal of Clinical Investigation (1992)

The production of IL-1 and IL-6 by pituitary cells has recently been demonstrated. In this study we investigated the expression of IL-2 and its receptor (IL-2R) by pituitary cells of different species. In Northern blots, a single hybridizing band of 1 kb, identical to that in normal stimulated lymphocytes, was obtained with specific IL-2 probes. In the mouse AT-20 pituitary tumor cell line, IL-2 mRNA expression was detected after stimulation with corticotropin-releasing hormone or phorbol myristate acetate. In human corticotrophic adenoma cells, basal IL-2 mRNA expression as well as IL-2 secretion were further stimulated by phorbol myristate acetate. Both adenoma and AtT-20 cells showed detectable amounts of IL-2R mRNA and by immunofluorescence, IL-2R membrane expression. In addition, dual immunofluorescence studies in rat anterior pituitary cells demonstrated colocalization of IL-2R with ACTH-positive cells and other cell types expressing the receptor. In addition to the action of lymphocyte-produced IL-2, this cytokine may have a paracrine or autocrine regulatory role within the pituitary. It remains to be established whether IL-2 production occurs in the normal pituitary or is intrinsic to the process of tumor development of these cells. IL-2 may be involved in the growth control of pituitary cells.
REAL-TIME NMR IMAGING OF CORONARY VESSELS
Authors: M. Stehling, B. Chapman, P. Glover, R.J. Ordidge, P. Mansfield, D. Dutka, A. Howseman, R. Coxon, R. Turner, G. Jaroszkiewicz, G.K. Morris, B.S. Worthington, R.E. Coupland
Journal: The Lancet (1987)
CYTODYNAMICS OF THE IMMUNE RESPONSE IN TWO LINES OF MICE GENETICALLY SELECTED FOR "HIGH" AND "LOW" ANTIBODY SYNTHESIS
Authors: G. Biozzi, C. Stiffel, D. Mouton, Y. Bouthillier, C. Decreusefond
Journal: The Journal of Experimental Medicine (1972)

Two lines of mice have been separated by selective breeding for the character "agglutinin production to heterologous erythrocytes." Around the 18th generation of selection the two lines could be considered as homozygous for the character investigated. This trait is under the control of a group of additive genes. The interline difference in the production of anti-SE agglutinins was verified for the range of antigen doses from subimmunogenic to maximal. After intravenous immunization with an optimal dose of SE, the duration of the exponential rise in serum antibody was 4-5 days in both lines. At this time most of the interline difference in responsiveness is already expressed. A cytodynamic study carried out in terms of plaque-forming cells (PFC) and rosette-forming cells (RFC) in the spleen during the exponential phase showed that the principal interline difference is found in the doubling time of cells engaged in the immune response. More precise cytodynamic analysis made in terms of RFC showed that the doubling time of RFC is 9 hr in high responder and 16 hr in low responder mice. The duration of the exponential rise and the number of target cells stimulated by antigen is the same in both lines. The interline difference at the end of the exponential rise (4 days postimmunization) is larger in terms of serum antibody (30-40-fold) than in terms of PFC or RFC (20- and 11-fold, respectively). A morphological study of RFC in nonimmunized mice showed that about 90% of rosettes were formed by small lymphocytes in both lines. The remainder were medium-sized lymphocytes. At the peak of the cellular response the RFC have differentiated into large lymphocytes, blast cells, and plasma cells. The contribution of plasma cells to RFC is much greater in the high than in the low line. The cytodynamic and morphologic results presented in this article are compatible with the hypothesis that the group of genes segregated in each line during the selective breeding control and regulate the rate of multiplication and differentiation of the antibody-producing cells.
The Coevolution of Insect Muscle TpnT and TpnI Gene Isoforms
Authors: Raúl Herranz, Jesús Mateos, José A. Mas, Elena García-Zaragoza, Margarita Cervera, Roberto Marco
Journal: Molecular Biology and Evolution (2005)

In bilaterians, the main regulator of muscle contraction is the troponin (Tpn) complex, comprising three closely interacting subunits (C, T, and I). To understand how evolutionary forces drive molecular change in protein complexes, we have compared the gene structures and expression patterns of Tpn genes in insects. In this class, while TpnC is encoded by multiple genes, TpnT and TpnI are encoded by single genes. Their isoform expression pattern is highly conserved within the Drosophilidae, and single orthologous genes were identified in the sequenced genomes of Drosophila pseudoobscura, Anopheles gambiae, and Apis mellifera. Apis expression patterns also support the equivalence of their exon organization throughout holometabolous insects. All TpnT genes include a previously unidentified indirect flight muscle (IFM)–specific exon (10A) that has evolved an expression pattern similar to that of exon 9 in TpnI. Thus, expression patterns, sequence evolution trends, and structural data indicate that Tpn genes and their isoforms have coevolved, building species- and muscle-specific troponin complexes. Furthermore, a clear case can be made for independent evolution of the IFM-specific isoforms containing alanine/proline-rich sequences. Dipteran genomes contain one tropomyosin gene that encodes one or two high–molecular weight isoforms (TmH) incorporating APPAEGA-rich sequences, specifically expressed in IFM. Corresponding exons do not exist in the Apis tropomyosin gene, but equivalent sequences occur in a high–molecular weight Apis IFM-specific TpnI isoform (TnH). Overall, our approach to comparatively analyze supramolecular complexes reveals coevolutionary trends not only in gene families but in isoforms generated by alternative splicing.
RNA sequencing reveals sexually dimorphic gene expression before gonadal differentiation in chicken and allows comprehensive annotation of the W-chromosome
Authors: Katie L Ayers, Nadia M Davidson, Diana Demiyah, Kelly N Roeszler, Frank Grützner, Andrew H Sinclair, Alicia Oshlack, Craig A Smith
Journal: Genome biology (2013)

Abstract Background Birds have a ZZ male: ZW female sex chromosome system and while the Z-linked DMRT1 gene is necessary for testis development, the exact mechanism of sex determination in birds remains unsolved. This is partly due to the poor annotation of the W chromosome, which is speculated to carry a female determinant. Few genes have been mapped to the W and little is known of their expression. Results We used RNA-seq to produce a comprehensive profile of gene expression in chicken blastoderms and embryonic gonads prior to sexual differentiation. We found robust sexually dimorphic gene expression in both tissues pre-dating gonadogenesis, including sex-linked and autosomal genes. This supports the hypothesis that sexual differentiation at the molecular level is at least partly cell autonomous in birds. Different sets of genes were sexually dimorphic in the two tissues, indicating that molecular sexual differentiation is tissue specific. Further analyses allowed the assembly of full-length transcripts for 26 W chromosome genes, providing a view of the W transcriptome in embryonic tissues. This is the first extensive analysis of W-linked genes and their expression profiles in early avian embryos. Conclusion Sexual differentiation at the molecular level is established in chicken early in embryogenesis, before gonadal sex differentiation. We find that the W chromosome is more transcriptionally active than previously thought, expand the number of known genes to 26 and present complete coding sequences for these W genes. This includes two novel W-linked sequences and three small RNAs reassigned to the W from the Un_Random chromosome.
Central Challenges Facing the National Clinical Research Enterprise
Authors: Nancy S. Sung, William F. Crowley, Myron Genel, Patricia Salber, Lewis Sandy, Louis M. Sherwood, Stephen B. Johnson, Veronica Catanese, Hugh Tilson, Kenneth Getz, Elaine L. Larson, David Scheinberg, E. Albert Reece, Harold Slavkin, Adrian Dobs, Jack Grebb, Rick A. Martinez, Allan Korn, David Rimoin
Journal: JAMA (2003)

Medical scientists and public health policy makers are increasingly concerned that the scientific discoveries of the past generation are failing to be translated efficiently into tangible human benefit. This concern has generated several initiatives, including the Clinical Research Roundtable at the Institute of Medicine, which first convened in June 2000. Representatives from a diverse group of stakeholders in the nation's clinical research enterprise have collaborated to address the issues it faces. The context of clinical research is increasingly encumbered by high costs, slow results, lack of funding, regulatory burdens, fragmented infrastructure, incompatible databases, and a shortage of qualified investigators and willing participants. These factors have contributed to 2 major obstacles, or translational blocks: impeding the translation of basic science discoveries into clinical studies and of clinical studies into medical practice and health decision making in systems of care. Considering data from across the entire health care system, it has become clear that these 2 translational blocks can be removed only by the collaborative efforts of multiple system stakeholders. The goal of this article is to articulate the 4 central challenges facing clinical research at present--public participation, information systems, workforce training, and funding; to make recommendations about how they might be addressed by particular stakeholders; and to invite a broader, participatory dialogue with a view to improving the overall performance of the US clinical research enterprise.
Blood doping: potential of blood and urine sampling to detect autologous transfusion
Authors: J Segura, C Lundby
Journal: British Journal of Sports Medicine (2014)

The collection of blood, its storage as red blood cell (RBC) concentrates and its reinjection is prohibited; until now, the practice cannot be reliably detected. A recent innovation—the haematological module of the athlete's biological passport—can provide authorities with indications towards autologous blood transfusion. In situations where a given athlete has been exposed to altitude, heat stress, sickness, etc, additional evidence may be needed to establish beyond any reasonable doubt that a blood transfusion may actually have occurred. Additional evidence may be obtained from at least three different approaches using parameters related to blood and urine matrices.Genomics applied to mRNA or miRNA is one of the most promising analytical tools. Proteomics of changes associated with RBC membranes may reveal the presence of cells stored for some time, as can an abnormal pattern of size distribution of aged cells. In urine, high concentrations of metabolites of plasticisers originating from the blood storing bags strongly suggest a recent blood transfusion. We emphasise the usefulness of simultaneously obtaining and then analysing blood and urine for complementary evidence of autologous blood transfusion (‘blood doping’).
Constitutive Activation of Myosin-Dependent Contractility Sensitizes Glioma Tumor-Initiating Cells to Mechanical Inputs and Reduces Tissue Invasion
Authors: Sophie Y. Wong, Theresa A. Ulrich, Loic P. Deleyrolle, Joanna L. MacKay, Jung-Ming G. Lin, Regina T. Martuscello, Musa A. Jundi, Brent A. Reynolds, Sanjay Kumar
Journal: Cancer Research (2015)

Abstract Tumor-initiating cells (TIC) perpetuate tumor growth, enable therapeutic resistance, and drive initiation of successive tumors. Virtually nothing is known about the role of mechanotransductive signaling in controlling TIC tumorigenesis, despite the recognized importance of altered mechanics in tissue dysplasia and the common observation that extracellular matrix (ECM) stiffness strongly regulates cell behavior. To address this open question, we cultured primary human glioblastoma (GBM) TICs on laminin-functionalized ECMs spanning a range of stiffnesses. Surprisingly, we found that these cells were largely insensitive to ECM stiffness cues, evading the inhibition of spreading, migration, and proliferation typically imposed by compliant ECMs. We hypothesized that this insensitivity may result from insufficient generation of myosin-dependent contractile force. Indeed, we found that both pharmacologic and genetic activation of cell contractility through RhoA GTPase, Rho-associated kinase, or myosin light chain kinase restored stiffness-dependent spreading and motility, with TICs adopting the expected rounded and nonmotile phenotype on soft ECMs. Moreover, constitutive activation of RhoA restricted three-dimensional invasion in both spheroid implantation and Transwell paradigms. Orthotopic xenotransplantation studies revealed that control TICs formed tumors with classical GBM histopathology including diffuse infiltration and secondary foci, whereas TICs expressing a constitutively active mutant of RhoA produced circumscribed masses and yielded a 30% enhancement in mean survival time. This is the first direct evidence that manipulation of mechanotransductive signaling can alter the tumor-initiating capacity of GBM TICs, supporting further exploration of these signals as potential therapeutic targets and predictors of tumor-initiating capacity within heterogeneous tumor cell populations. Cancer Res; 75(6); 1113–22. ©2015 AACR.
The motivational self is more than the sum of its goals
Authors: Ayelet Fishbach
Journal: Behavioral and Brain Sciences (2014)

I present evidence in favor of an overarching motivational self: a mental function that regulates expression of multiple goals. Goals often conflict with each other, and the role of a motivational self is to consciously or unconsciously prioritize pursuit of these goals. When observing inconsistency in expression of goals, it is therefore useful to consider whether the motivational self is attempting to balance between conflicting goals or if such inconsistency results from temporary self-control weakness.