tbuckley/cabot-search huggingface dataset:
Suppressor T-cell activity in responder x nonresponder (C57BL/10 x DBA/1)F(1) spleen cells responsive to l-glutamic acid(60)-L-alanine(30)-L-tyrosine (10)
Authors: CW Pierce, JA Kapp
Journal: The Journal of Experimental Medicine (1978)

The ability of spleen cells from (responder X nonresponder)F(1) mice immunized with various GAT-Mφ, GAT-MBSA, and soluble GAT to develop IgG GAT-specific PFC responses in vitro after stimulation with responder and nonresponder parental and F(1) GAT-Mφ, was investigated. F(1) spleen cells from mice immunized with F(1) GAT-Mφ or GAT-MBSA developed secondary responses to responder and nonresponder parental and F(1) GAT- Mφ, but not to unrelated third party GAT-Mφ. Spleen cells from F(1) mice immunized with either parental GAT-Mφ developed secondary responses to F(1) GAT-Mφ and only the parental GAT-Mφ used for immunization in vivo. Soluble GAT-primed F(1) spleen cells responded to F(1) and responder parental, but not nonresponder parental, GAT-Mφ. Simultaneous immunization in vivo with the various GAT-Mφ or GAT-MBSA plus soluble GAT modulated the response pattern of these F(1) spleen cells such that they developed secondary responses only to F(1) and parental responder GAT-Mφ regardless of the response pattern observed after immunization with the various GAT-Mφ or GAT-MBSA alone. These observations demonstrate the critical importance of the physical state of the GAT used for immunization in determining the subsequent response pattern of immune F(1) spleen cells to the parental and F(1) GAT-Mφ. Further, suppressor T cells, capable of inhibiting primary responses to GAT by virgin F(1) spleen cells stimulated by nonresponder parental GAT-Mφ, were demonstrated in spleens of F(1) mice immunized with soluble GAT, but not those primed with F(1) GAT-Mφ. Because responder parental mice develop both helper and suppressor T cells after immunization with GAT-Mφ, and soluble GAT preferentially stimulates suppressor T cells whereas GAT-Mφ stimulate helper T cells in nonresponder parental mice, these observations suggest that distinct subsets of T cells exist in F(1) mice which behave phenotypically as responder and nonresponder parental T cells after immunization with soluble GAT and GAT- Mφ.
Scaffolding Proteins DLG1 and CASK Cooperate to Maintain the Nephron Progenitor Population during Kidney Development
Authors: Sun-Young Ahn, Yeawon Kim, Sung Tae Kim, Wojciech Swat, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2013)

DLG1 (discs-large homolog 1) and CASK (calcium/calmodulin-dependent serine protein kinase) interact at membrane-cytoskeleton interfaces and function as scaffolding proteins that link signaling molecules, receptors, and other scaffolding proteins at intercellular and synaptic junctions. Dlg1-null mice exhibit hydronephrosis, hydroureter, and occasionally hypoplastic kidneys, whereas Cask-null mice do not. To investigate whether DLG1 and CASK cooperate in the developing urogenital system, we generated mice deficient in both DLG1 and CASK either 1) globally, 2) in metanephric mesenchyme, or 3) in nephron progenitors. With each approach, Dlg1;Cask double-knockout (DKO) kidneys were severely hypoplastic and dysplastic and demonstrated rapid, premature depletion of nephron progenitors/stem cells. Several cellular and molecular defects were observed in the DKO kidneys, including reduced proliferation and increased apoptosis of cells in the nephrogenic zone and a progressive decrease in the number of cells expressing SIX2, a transcription factor essential for maintaining nephron progenitors. Fgf8 expression was reduced in early-stage DKO metanephric mesenchyme, accompanied by reduced levels of components of the Ras pathway, which is activated by fibroblast growth factor (FGF) signaling. Moreover, Dlg1(+/-);Cask(-/-) (het/null) kidneys were moderately hypoplastic and demonstrated impaired aggregation of SIX2-positive cells around the ureteric bud tips. Nephron progenitor-specific het/null mice survived with small kidneys but developed glomerulocystic kidney disease and renal failure. Taken together, these results suggest that DLG1 and CASK play critical cooperative roles in maintaining the nephron progenitor population, potentially via a mechanism involving effects on FGF signaling.
Characterisation of Eubacterium cell wall: peptidoglycan structure determines arthritogenicity
Authors: X Zhang
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To elucidate factors involved in the arthritogenicity of bacterial cell walls. <h3>METHODS</h3> For characterisation of an arthritogenic <i>Eubacterium aerofaciens</i> cell wall, peptidoglycan-polysaccharide (PG-PS) polymers were isolated by removing cell wall associated proteins (CWPs), PG and PS moieties were separated, and an attempt was made to de-<i>O</i>-acetylate PG-PS. The cell wall of<i>E limosum</i> was used as a non-arthritogenic control. The chemical composition of these cell wall preparations was analysed by gas chromatography-mass spectrometry. Also, their ability to resist lysozyme degradation and to sustain experimental chronic arthritis was tested. <h3>RESULTS</h3> The observations made with the cell wall of <i>E aerofaciens</i>, an anaerobic habitant of the human intestine, were compared with those reported from a pathogenic<i>Streptococcus</i>, showing that in both strains a complex consisting of PG-PS is required for the induction of chronic arthritis. The PS moiety most probably protects PG from enzyme degradation, allowing prolonged tissue persistence and leading to the chronic synovial inflammation. CWPs attached to PG-PS are not necessary for this function. <i>O</i>-Acetylation of PG, which is required for arthritogenicity of the streptococcal cell wall, seems not to be present in the arthritogenic <i>E aerofaciens</i> PG or only occurs to a small degree; attempts to de-<i>O</i>-acylate the <i>E aerofaciens</i> cell wall did not affect its arthritogenicity or lysozyme resistance. <h3>CONCLUSION</h3> The results obtained indicate that the source of bacterial cell wall plays no part in the chemical or structural requirements for PG to induce chronic cell wall arthritis in the rats; the chemical structure of the PG moiety is decisive.
Pulmonary Vascular Shunts in Exercise-Intolerant Patients with Lymphangioleiomyomatosis
Authors: Muhammad A. Zafar, Francis X. McCormack, Shahid Rahman, Christian Tencza, Kathryn A. Wikenheiser-Brokamp, Lisa R. Young, Yukitaka Shizukuda, Jean M. Elwing
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
MicroRNA-497 increases apoptosis in MYCN amplified neuroblastoma cells by targeting the key cell cycle regulator WEE1
Authors: Laura Creevey, Jacqueline Ryan, Harry Harvey, Isabella M Bray, Maria Meehan, Adnan R Khan, Raymond L Stallings
Journal: Molecular Cancer (2013)

Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive of neuroblastoma patient survival and has been reported as a tumor suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of the cell cycle and predicted target of miR-497, has emerged as an oncogene in several cancer types and therefore represents an attractive potential target for novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate the potential tumor suppressive role of miR-497 in high-risk neuroblastoma.Expression levels of miR-497 and WEE1 in tissues and cells were determined using RT-PCR. The effect of miR-497 and siWEE1 on cell viability was evaluated using MTS assays, apoptosis levels were determined using FACS analysis of Annexin V/PI stained cells, and target protein expression was determined using western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean±S.E.M and differences were tested for significance using 2-tailed Students t-test.We determined that miR-497 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and that low miR-497 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma. Furthermore, our analysis showed that high WEE1 levels are significantly associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1 in MNA cell lines results in significant levels of apoptosis, supporting an oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR-497 over-expressing cells and WEE1 inhibited cells, resulted in a significant increase in apoptosis in MNA cells, describing a synergistic effect and therefore a potential therapeutic for high-risk neuroblastoma.Our study's results are consistent with miR-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. These findings re-enforce the proposal of WEE1 as a therapeutic target in neuroblastoma.
miR-142-3p acts as an essential modulator of neutrophil development in zebrafish
Authors: Hong-Bo Fan, Yi-Jie Liu, Lei Wang, Ting-Ting Du, Mei Dong, Li Gao, Zhao-Zheng Meng, Yi Jin, Yi Chen, Min Deng, Huang-Tian Yang, Qing Jing, Ai-Hua Gu, Ting-Xi Liu, Yong Zhou
Journal: Blood (2014)
Occurrence of large granular lymphocytes and natural killer cells in the epithelium of the gut distinguishes two different coeliac diseases.
Authors: F Hadziselimovic, L R Emmons, U Schaub, E Signer, A Burgin-Wolff, R Krstic
Journal: Gut (1992)

In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation compared with the abortive group and had to remain on a strict gluten free diet in contrast with those in the abortive group. Thus, the occurrence of intraepithelial large granular lymphocytes and natural killer cells characterises two distinctly different coeliac diseases. Based on our results neither the histological evaluation of the biopsy nor the utilisation of the revised European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) Criteria are adequate in diagnosing the two types of coeliac disease.
CD226 (DNAM-1) Is Involved in Lymphocyte Function–associated Antigen 1 Costimulatory Signal for Naive T Cell Differentiation and Proliferation
Authors: Kazuko Shibuya, Jun Shirakawa, Tomie Kameyama, Shin-ichiro Honda, Satoko Tahara-Hanaoka, Akitomo Miyamoto, Masafumi Onodera, Takayuki Sumida, Hiromitsu Nakauchi, Hiroyuki Miyoshi, Akira Shibuya
Journal: The Journal of Experimental Medicine (2003)

Upon antigen recognition by the T cell receptor, lymphocyte function–associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12–independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1–mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.
The Pragmatics of Prone Positioning
Authors: Erica Messerole, Pam Peine, Sue Wittkopp, John J. Marini, Richard K. Albert
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

1. Functional residual capacity may be higher, thereby reducing end-expiratory airspace closure (1, 2). This benefit is important relative to gas exchange as it will particularly affect the dorsal lung, and this region receives the greatest proportion of perfusion in all postures (3, 4). 2. The generally dorsal-to-ventral orientation of the major airways may allow more efficient drainage of secretions (5). 3. Regional ventilation and regional ventilation-to-perfusion relationships are more uniform (6–9) and gas exchange is improved (10–12) as a result of the anatomy of the diaphragm (13), postural differences in chest wall mechanics (14), and/or because the lungs fit into the thorax with less distortion from the heart, mediastinum, and diaphragm (15–18). 4. The effect of recruiting maneuvers on oxygenation is both increased and prolonged (19). 5. Ventilator-induced lung injury may be reduced (20, 21).
Nitric oxide contributes to oxygen demand?supply balance in hypoperfused right ventricle
Authors: S SETTY, J TUNE, H DOWNEY
Journal: Cardiovascular Research (2004)

Journal Article Nitric oxide contributes to oxygen demand–supply balance in hypoperfused right ventricle Get access Srinath Setty, Srinath Setty Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, United States Search for other works by this author on: Oxford Academic PubMed Google Scholar Johnathan D. Tune, Johnathan D. Tune Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, United States Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Fred Downey H. Fred Downey * Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, United States *Corresponding author. Tel.: +1 817 735 2078; fax: +1 817 735 5084. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 64, Issue 3, December 2004, Pages 431–436, https://doi.org/10.1016/j.cardiores.2004.07.021 Published: 01 December 2004 Article history Received: 04 May 2004 Revision received: 15 July 2004 Accepted: 27 July 2004 Published: 01 December 2004
Ultrarush versus semirush initiation of insect venom immunotherapy: A randomized controlled trial
Authors: Simon G.A. Brown, Michael D. Wiese, Pauline van Eeden, Shelley F. Stone, Christine L. Chuter, Jareth Gunner, Troy Wanandy, Michael Phillips, Robert J. Heddle
Journal: Journal of Allergy and Clinical Immunology (2012)
Estimating the Number of Potential Organ Donors in the United States
Authors: Ellen Sheehy, Suzanne L. Conrad, Lori E. Brigham, Richard Luskin, Phyllis Weber, Mark Eakin, Lawrence Schkade, Lawrence Hunsicker
Journal: New England Journal of Medicine (2003)

As the need for transplantable organs increases, waiting lists of patients become longer. We studied the size and composition of the national pool of brain-dead organ donors during a three-year period and, on the basis of these data, considered ways to increase the rate of donation.
Variation in individual responses to the cytotoxicity of cigarette smoke.
Authors: J M Hopkin, C M Steel
Journal: Thorax (1980)

There is increasing evidence that elastase may mediate pulmonary damage in emphysema and also that the release of intracellular elastase by cigarette smoke is necessarily associated with cell death. We report consistent and significant variation in response of lymphocytes from different individuals to the cytotoxic effect of cigarette smoke condensate in vitro. This variation which occurred at levels of cigarette smoke likely to be encountered in vivo and which was independent of the age, sex, or smoking habits of the subjects, may be relevant in determining the risk of developing emphysema amongst smokers.
Extracapsular tumor spread and the risk of local, axillary and supraclavicular recurrence in node-positive, premenopausal patients with breast cancer
Authors: G. Gruber, B.F. Cole, M. Castiglione-Gertsch, S.B. Holmberg, J. Lindtner, R. Golouh, J. Collins, D. Crivellari, B. Thürlimann, E. Simoncini, M.F. Fey, R.D. Gelber, A.S. Coates, K.N. Price, A. Goldhirsch, G. Viale, B.A. Gusterson
Journal: Annals of Oncology (2008)
Users' guide to detecting misleading claims in clinical research reports
Authors: Victor M Montori, Roman Jaeschke, Holger J Schünemann, Mohit Bhandari, Jan L Brozek, P J Devereaux, Gordon H Guyatt
Journal: BMJ (2004)

Plenty of advice is available to help readers identify studies with weak methods, but would you be able to identify misleading claims in a report of a well conducted study?
Quality of Care of People With Type 2 Diabetes in Eight European Countries
Authors: Margaret A. Stone, Guillaume Charpentier, Kris Doggen, Oliver Kuss, Ulf Lindblad, Christiane Kellner, John Nolan, Agnieszka Pazderska, Guy Rutten, Marina Trento, Kamlesh Khunti
Journal: Diabetes Care (2013)

We sought to determine levels of adherence in eight European countries to recommendations for the management of type 2 diabetes and to investigate factors associated with key intermediate outcomes.GUIDANCE was a cross-sectional study including retrospective data extraction from the medical records of people with type 2 diabetes recruited, using a shared protocol, from primary and specialist care sites in the following eight European countries: Belgium, France, Germany, Italy, Ireland, Sweden, the Netherlands, and the United Kingdom. The dataset for analysis comprised 7,597 cases. Proportions meeting process and outcome criteria were determined, including between-country variations. Logistic regression was used to investigate potential predictors of meeting targets for HbA1c, blood pressure, and LDL cholesterol.In the total sample, adherence to process recommendations was high for some measures, for example, HbA1c recorded in past 12 months in 97.6% of cases. Target achievement for intermediate outcome measures was lower, with only 53.6% having HbA1c <7%. Considerable between-country variation was identified for both processes and outcomes. The following characteristics were associated with an increased likelihood of meeting targets for all three measures considered (HbA1c, blood pressure, LDL cholesterol): shorter diagnosis of diabetes; having one or more macrovascular complications; lower BMI; being prescribed lipid-lowering medication; and no current antihypertensive prescribing.Compared with earlier reports, we have suggested some encouraging positive trends in Europe in relation to meeting targets for the management of people with type 2 diabetes, but there is still scope for further improvement and greater between-country consistency.
An Exercise Testing Program for Large Populations
Authors: L. Howard Hartley
Journal: JAMA (1979)

A demonstration cardiovascular evaluation and exercise testing program was assessed for feasibility, cost, and accuracy. More than 1,800 people were examined in three years. The conditions of as many as 55 people per day were examined at a cost of $60 to $70 each. Abnormalities uncovered were similar to those observed in other studies. The program was considered successful in rendering services conveniently at low cost and with accuracy.
Detection of quality of life with COPD assessment test in chronic obstructive pulmonary disease and effect of dyspnea on disease-specific quality of life in these patients
Authors: Oguzhan Okutan, Dilaver Tas, Ersin Demirer, Zafer Kartaloglu
Journal: European Respiratory Journal (2012)

Background: The measurements for level of dyspnea such as Medical Research Council (MRC) dyspnea scale or modified Borg dyspnea scale were used common in the trials. COPD assessment test (CAT) is a recently introduced to use to disease-specific quality of life and follow-up of the patients with COPD.  Objective: We aimed that assessed effect of the dyspnea on disease-specific quality of life detected by CAT score in the patients with COPD.  Methods: In this study, 90 stable patients with COPD as defined by the GOLD criteria were included. The level of dyspnea was assessed with two different scales, MRC dyspnea scale and modified Borg dyspnea scale, and disease-specific quality of life assessed with the CAT score.  Results: Patients9 mean ± SD age was 68.5±10.9 (range 41 – 97) years. A significant relationship was established among CAT score, MRC dyspnea scale, modified Borg dyspnea scale, the GOLD stage of the patients with COPD. There was a positive correlation between dyspnea scales and the GOLD stage of the patients (p
Manipulation of Cellular Excitability by Cell Fusion
Authors: Uta C. Hoppe, David C. Johns, Eduardo Marbán, Brian O’Rourke
Journal: Circulation Research (1999)

Abstract —To investigate the still-undetermined role of the Ca 2+ -independent transient outward current ( I to1 ) on repolarization of the cardiac action potential, we used cell fusion to introduce I to1 into guinea pig cardiomyocytes, which normally lack this current. This technique enables the rapid delivery of premade functional ion channels to cardiomyocytes within hours of isolation, thus eliminating the action potential alterations that complicate prolonged cell culture. Chinese hamster ovary (CHO) cells stably expressing Kv4.3 (CHO-Kv4.3) were loaded with a fluorescent dye and fused to guinea pig cardiomyocytes using polyethylene glycol. As controls, nontransfected CHO cells were fused using the same protocol. Myocytes fused with CHO-Kv4.3 cells exhibited a robust I to1 (16.5±2.6 pA/pF at +40 mV; 37°C; n=19), whereas controls had none. I to1 accelerated the early repolarization velocity ( r =−0.68; 3 ms after the overshoot) and progressively suppressed the voltage of the plateau phase ( r =−0.90) with increasing I to1 density. Reduction of the action potential duration to 50% repolarization ( r =−0.76) and to 90% repolarization ( r =−0.65) also correlated well with I to1 density. Thus, I to1 exerted a significant effect on the early repolarization phase and abbreviated action potential duration. Cell fusion is a valuable and generalizable technique to introduce preformed membrane proteins into native cells.