tbuckley/cabot-search huggingface dataset:
Genetically Encoded Ca <sup>2+</sup> Indicators in Cardiac Myocytes
Authors: Lars Kaestner, Anke Scholz, Qinghai Tian, Sandra Ruppenthal, Wiebke Tabellion, Kathrina Wiesen, Hugo A. Katus, Oliver J. Müller, Michael I. Kotlikoff, Peter Lipp
Journal: Circulation Research (2014)

Genetically encoded Ca(2+) indicators constitute a powerful set of tools to investigate functional aspects of Ca(2+) signaling in isolated cardiomyocytes, cardiac tissue, and whole hearts. Here, we provide an overview of the concepts, experiences, state of the art, and ongoing developments in the use of genetically encoded Ca(2+) indicators for cardiac cells and heart tissue. This review is supplemented with in vivo viral gene transfer experiments and comparisons of available genetically encoded Ca(2+) indicators with each other and with the small molecule dye Fura-2. In the context of cardiac myocytes, we provide guidelines for selecting a genetically encoded Ca(2+) indicator. For future developments, we discuss improvements of a broad range of properties, including photophysical properties such as spectral spread and biocompatibility, as well as cellular and in vivo applications.
Nurse care for patients with chest drainage and creation of local procedural standards
Authors: Renata Sabova, Zuzana Taligova, Jan Plutinsky, Daniel Magula, Dalibor Petras
Journal: European Respiratory Journal (2011)

Introduction:  Drain is simple or complicated device or entire system, which serves to evacuate unwanted secretions or air from the pleural space. Today, the chest drainage (CD) is frequently used in pneumology. Its application is pathophysiologically favourable, because the accumulation of fluid/air in body cavities prevents oxygenation of the cells, slows down mobilisation of collagen, prevents lymphatic drainage and creates a bounded space, resulting to delay the healing process.   Aims:  Upon nurse assistance during CD to share own experience with formation the local procedural standards.   Methods:  From 2007 to 2009 CD was performed on 159 patients (pts). Empyema had 88 pts, malignant pleural effusion 58 pts and pneumothorax 13 pts.   Results:  CD was without complications in 134 pts (84.3%). The complications occurred in 31 pts (19.5%). In 7 pts (4.4%) occurred trapped lungs; pain occurred in 6 pts (3.8%); the CD had to be repeated in 6 pts (3.8%), in 4 pts (2.5%) occurred clogging of the drain by fibrin clot. Leakage pleural effusion/empyema into skin was in 3 pts (1.9%), in one patient (0.6%) it was necessary to change the place of the drain. Collapse during CD had 7 pts (4.4%).   Conclusions:  Our experiences from nursing assistance in CD helped us to create the local procedural standards. For successful CD is necessary to meet several conditions. Maintain clear and airtight connection between chest cavity drainage and collection device, reduce inequalities between chest cavity volume and lung tissue and eliminated unwanted the aerodynamic situation.
Phase II study of gemcitabine concurrent with radiation in locally advanced squamous cell carcinoma of head and neck: Trial of the Cancer Research Group Pakistan
Authors: A. A. Javed, A. Shaharyar, I. H. Shah, M. A. Shah, T. N. Ansari, M. Faheem, H. Mehmood, M. S. Khan, M. A. Afridi, S. Rasool
Journal: Journal of Clinical Oncology (2006)

15520 Background: The optimum radiosensitizing dose and schedule of gemcitabine for squamous cell carcinoma of head and neck are not known. The objectives of this study were to evaluate the efficacy and toxicity of weekly gemcitabine as a radiosensitizer concurrent with radical radiotherapy in locally advanced head and neck cancer. Method: Thirty-nine patients with stage III or IV B inoperable carcinoma of head and neck were enrolled. Eligible patients had histopathologically confirmed squamous cell carcinoma with age between 18–70 years. Patients had a KPS &gt;70 with an adequate marrow, hepatic and renal function. No prior chemotherapy or radiotherapy was allowed. Patients with nasopharyngeal, glottic or sub-glottic cancer were excluded. Gemcitabine 150 mg/m 2 or a total dose not exceeding 200 mg was given on day 1,8,15,22,29, and 36 during radiation treatment. Gemcitabine was infused in 200 ml of normal saline in 2 hours and radiation was delivered two hours after the completion of gemcitabine infusion. Conventional fractionation was used to deliver a total dose of 66 Gy. CTC version 2.0 of NCI and RTOG/EORTC Late Radiation Morbidity Scoring Scheme were used for evaluation of toxicity and RECIST was used for response evaluation. Results: Only 35 patients were considered evaluable for response. Complete response was seen in 8 (22.9%) (95% CI; 10.4–40.1%), partial response in 25 (71.4%), with an overall response rate of 94.3% (95% CI; 80.8–99.3%). All the thirty-nine patients were evaluable for toxicity. Grade 3 and 4 mucositis was seen in 28 (71.8%) and 2 (5.1%) patients respectively. Grade 3 pharyngeal toxicity was seen in 6 (15.4%). One patient developed pharyngo-cutaneous fistula. Despite vigorous symptomatic and supportive care acute toxicities led to treatment interruption in 16 (41%) of patients. Conclusion: Weekly gemcitabine at a dose of 150mg/m 2 concurrent with radiation therapy gives a high overall response rate and a high rate of acute toxicity. No significant financial relationships to disclose.
C1 fixation and classical complement pathway activation by a fragment of the Cmu4 domain of IgM.
Authors: M M Hurst, J E Volanakis, R M Stroud, J C Bennett
Journal: The Journal of Experimental Medicine (1975)

A 56 residue fragment derived from a Waldenströme IgM protein and consisting of 24 residues of the amino-terminal portion of the Cmu4 domain disulfide bonded to 32 residues of the carboxy-terminal region of the loop has been shown to fix active C1 (C1) in a C1-fixation assay. Cleavage of the disulfide bond within the CH4 fragment resulted in a marked decrease of C1-fixing ability, although the isolated A and B fragments did retain a limited ability to fix C1. Upon incubation with normal human serum the intact CH4 fragment and equal molar amounts of the isolated A and B peptides consumed C4 suggesting that the C1-activating determinant of IgM remains intact in these three fragments. Furthermore, on a molar basis the intact or the reduced CH4 fragment consumed C4 as effectively as each of its component chains suggesting that transient binding of C1 by the individual A and B peptide chains is sufficient to activate C1. On the basis of these observations it is proposed that a classical complement fixation function, i.e. C1 binding and activation, can be localized within a region of the IgM molecule corresponding to the Cmu4 domain.
Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study
Authors: H.H. van der Zee, J.D. Laman, L. de Ruiter, W.A. Dik, E.P. Prens
Journal: British Journal of Dermatology (2011)

Background Hidradenitis suppurativa (HS) is a difficult‐to‐manage disease. Randomized controlled trials with antitumour necrosis factor (TNF)‐α biologics have been conducted and in most studies disease activity was reduced. However, the mechanism of action in HS skin is so far unknown. Objectives To assess whether anti‐TNF‐α treatment affects in situ cytokine production and frequency of inflammatory cell populations in HS lesional skin. Methods Nine patients with HS, participating in a larger placebo‐controlled, double‐blind phase IIb clinical trial on the efficacy and safety of adalimumab in patients with moderate to severe HS (M10‐467), were randomized and treated for 16 weeks. In a mechanism‐of‐action substudy, biopsies were obtained at fixed time points pre‐ and post‐treatment. One part of the biopsy was cultured for 24 h for cytokine release in the culture medium, while another part was used for in situ analysis. Results Secretion of cytokines, including interleukin (IL)‐1β, CXCL9 [monokine induced by interferon‐γ (MIG)], IL‐10, IL‐11, B‐lymphocyte chemoattractant (BLC) and IL‐17A, was significantly elevated in HS. Adalimumab treatment was associated with decreased production of cytokines in HS skin, especially IL‐1β, CXCL9 (MIG) and BLC. Treatment significantly reduced the number of CD11c+, CD14+ and CD68+ cells in HS lesional skin. The numbers of CD3+ and CD4+ T cells, and CD20+ and CD138+ B cells were also reduced by adalimumab treatment. Conclusions Adalimumab treatment inhibits important cytokines and inflammatory cell numbers in lesional HS skin, especially levels of IL‐1β and numbers of inflammatory CD11c+ dendritic cells.
SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE
Authors: Harvey Cantor, Richard Asofsky
Journal: The Journal of Experimental Medicine (1972)

Two types of thymus-derived (T) lymphocytes have been shown to cooperate in the induction of graft-versus-host responses. One cell type is found in highest concentrations in the peripheral blood and lymph node, is extremely sensitive to anti-thymocyte serum (ATS) in vivo, and is probably part of the recirculating lymphoid cell pool (3). The second cell type, found in highest concentrations in the thymus and spleen, is relatively resistant to small doses of ATS in vivo. Both cell types are substantially depleted after neonatal thymectomy. Moreover, since synergism was also obtained using appropriate mixtures of cells from either parental strain in F(1) hosts, it was possible to show that the nonrecirculating cells determined the specificity of the response and were probably the precursors of effector cells in this response. The recirculating T cell appeared to amplify this response. The implications of these data are discussed.
New Risk Score for Patients With Acute Chest Pain, Non-ST-Segment Deviation, and Normal Troponin Concentrations
Authors: Juan Sanchis, Vicent Bodí, Julio Núñez, Vicente Bertomeu-González, Cristina Gómez, María José Bosch, Luciano Consuegra, Xavier Bosch, Francisco J. Chorro, Àngel Llàcer
Journal: Journal of the American College of Cardiology (2005)
Association of Type and Duration of Diabetes With Erectile Dysfunction in a Large Cohort of Men
Authors: Constance G. Bacon, Frank B. Hu, Edward Giovannucci, Dale B. Glasser, Murray A. Mittleman, Eric B. Rimm
Journal: Diabetes Care (2002)

Differences in risk of erectile dysfunction (ED) by characteristics of diabetes among older men are not well understood. We examined the association of type and duration of diabetes with erectile function in men >50 years of age in a large prospective cohort study.Subjects included 31,027 men aged 53-90 years in the Health Professionals Follow-Up Study cohort. On a questionnaire mailed in 2000, participants rated their ability (without treatment) in the past 5 years to have and maintain an erection sufficient for intercourse. Men who reported poor or very poor function were considered to have ED. Diabetes information was ascertained via self-report and documented with supplementary medical data.Men with diabetes had an age-adjusted relative risk (RR) of 1.32 (95% CI 1.3-1.4) for having ED compared with men without diabetes. In multivariable regression analyses, men with type 1 and type 2 diabetes were at a significantly higher risk for ED (type 1 diabetes RR = 3.0, 95% CI 1.5-5.9; type 2 diabetes RR = 1.3, 1.1-1.5) than nondiabetic men. Men with type 2 diabetes had an increasingly greater risk of ED with increased duration since diagnosis (trend test P value <0.0001) (RR = 1.7, 95% CI 1.1-2.7, for men diagnosed >20 years previously).For men over age 50 years, increasing duration of diabetes was positively associated with increased risk of ED relative to nondiabetic subjects. This association persisted despite the higher prevalence of other comorbid conditions. ED prevention and diabetes management efforts are likely to go hand-in-hand.
Maintenance Therapy with Certolizumab Pegol for Crohn's Disease
Authors: Stefan Schreiber, Mani Khaliq-Kareemi, Ian C. Lawrance, Ole Østergaard Thomsen, Stephen B. Hanauer, Juliet McColm, Ralph Bloomfield, William J. Sandborn
Journal: New England Journal of Medicine (2007)

Certolizumab pegol is a pegylated humanized Fab' fragment with a high binding affinity for tumor necrosis factor alpha that does not induce apoptosis of T cells or monocytes.In our randomized, double-blind, placebo-controlled trial, we evaluated the efficacy of certolizumab pegol maintenance therapy in adults with moderate-to-severe Crohn's disease. As induction therapy, 400 mg of certolizumab pegol was administered subcutaneously at weeks 0, 2, and 4. Patients with a clinical response (defined as reduction of at least 100 from the baseline score on the Crohn's Disease Activity Index [CDAI]) at week 6 were stratified according to their baseline C-reactive protein level and were randomly assigned to receive 400 mg of certolizumab pegol or placebo every 4 weeks through week 24, with follow-up through week 26.Among patients with a response to induction therapy at week 6 (428 of 668 [64%]), the response was maintained through week 26 in 62% of patients with a baseline C-reactive protein level of at least 10 mg per liter (the primary end point) who were receiving certolizumab pegol (vs. 34% of those receiving placebo, P<0.001) and in 63% of patients in the intention-to-treat population who were receiving certolizumab pegol (vs. 36% receiving placebo, P<0.001). Among patients with a response to induction therapy at week 6, remission (defined by a CDAI score of < or =150) at week 26 was achieved in 48% of patients in the certolizumab group and 29% of those in the placebo group (P<0.001). The efficacy of certolizumab pegol was also shown in patients taking and those not taking glucocorticoids or immunosuppressants and in patients who had and those who had not previously taken infliximab. Infectious serious adverse events (including one case of pulmonary tuberculosis) occurred in 3% of patients receiving certolizumab pegol and in less than 1% of patients receiving placebo. Antinuclear antibodies developed in 8% of the patients in the certolizumab group; antibodies against certolizumab pegol developed in 9% of all patients who entered the induction phase.Patients with moderate-to-severe Crohn's disease who had a response to induction therapy with 400 mg of certolizumab pegol were more likely to have a maintained response and a remission at 26 weeks with continued certolizumab pegol treatment than with a switch to placebo. (ClinicalTrials.gov number, NCT00152425 [ClinicalTrials.gov].).
Liver Damage Preferentially Results from CD8+ T Cells Triggered by High Affinity Peptide Antigens
Authors: Jennifer Q. Russell, Gregory J. Morrissette, Mark Weidner, Chirag Vyas, Deborah Aleman-Hoey, Ralph C. Budd
Journal: The Journal of Experimental Medicine (1998)

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate. Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatibility complex (MHC)–restricted ovalbumin-specific T cell antigen receptor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4−CD8−B220+ T cells occurs more frequently from a CD8+ precursor than from CD4+ T cells. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8+ cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of serum aspartate transaminase. This was not observed in mice bearing a class II MHC–restricted TCR. The findings show that CD4−CD8−B220+ T cells preferentially derive from a CD8+ precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.
Breast Feeding, Cow Milk Feeding, and Allergy
Authors: M.‐R. Ståhlberg
Journal: Allergy (1985)

Information about every 10th child aged 14 to 38 months was collected by means of a questionnaire in Turku, Finland in March, 1983. This paper reports on the occurrence of allergy in relation to the duration of breast feeding and to the age of the child when cow milk feeding was started. The average duration of breast feeding was 5.7 months and the average age at the introduction of cow milk-based products was 4.3 months. Allergy was reported in family members of 47.6% of the children. In 30.3% the child himself was reported allergic. The occurrence of allergy was unaffected by the duration of breast feeding and the age at introduction of cow milk feeding.
A single pre-B cell can give rise to antigen-specific B cells that utilize distinct immunoglobulin gene rearrangements.
Authors: A J Caton
Journal: The Journal of Experimental Medicine (1990)

A group of hybridomas that express antibodies with related specificities for the influenza virus hemagglutinin (HA), that represent B cells that were the clonal progeny of a single pre-B cell, and that utilized distinct L chain gene rearrangements have been characterized. The clonal relationship was established by the sharing of H chain gene rearrangements at both the productive and the nonproductive alleles. Among these hybridomas, one group had rearranged only one of its kappa alleles, having joined a V kappa 24 gene to the J kappa 2 gene segment. The other group utilized the same V kappa 24 gene segment in productive rearrangement to the J kappa 5 gene segment, and shared an aberrant rearrangements among members of the same B cell clone can normally occur, and can contribute to the generation and diversification of the immune repertoire that is available for the recognition of foreign antigens. Mechanisms by which the distinct rearrangements expressed by the hybridomas might have been generated are discussed.
Association Between Gait Speed as a Measure of Frailty and Risk of Cardiovascular Events After Myocardial Infarction
Authors: Yasushi Matsuzawa, Masaaki Konishi, Eiichi Akiyama, Hiroyuki Suzuki, Naoki Nakayama, Masayoshi Kiyokuni, Shinichi Sumita, Toshiaki Ebina, Masami Kosuge, Kiyoshi Hibi, Kengo Tsukahara, Noriaki Iwahashi, Mitsuaki Endo, Nobuhiko Maejima, Kenichiro Saka, Katsutaka Hashiba, Kozo Okada, Masataka Taguri, Satoshi Morita, Seigo Sugiyama, Hisao Ogawa, Hironobu Sashika, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2013)
Simultaneous measurements of lactate turnover rate and umbilical lactate uptake in the fetal lamb.
Authors: J W Sparks, W W Hay, D Bonds, G Meschia, F C Battaglia
Journal: Journal of Clinical Investigation (1982)

Lactic acid represents a major exogenous nutrient for the developing fetal lamb in utero. Our study was undertaken (a) to quantitate the net consumption of lactate by the fetus, (b) to quantitate the net lactate production and metabolism by the placenta, and (c) to compare the net fetal lactate consumption with fetal lactate use, measured simultaneously with radioactive tracers. 14 pregnant sheep were prepared with catheters in the maternal femoral artery and uterine vein and in the fetal aorta and umbilical vein. By simultaneous application of the Fick principle to the uterine and umbilical circulations, placental glucose consumption and placental lactate production were rapid, averaging 39.8 +/- 5.1 and 11.8 +/- 0.7 mg.min-1. Net lactate umbilical uptake averaged 1.95 +/- 0.16 mg-1.kg.min-1. During infusion of L-[14C(U)]lactate, fetal lactate turnover was much more rapid, averaging 6.5 +/- 0.8 mg.kg-1.min-1, and lactate utilization within the anatomic fetus was 5.9 +/- 0.7 mg.kg-1.min-1. During infusion of tracer glucose, endogenous fetal lactate production from glucose and nonglucose substrates averaged 3.0 and 1.5 mg.kg-1.min-1, respectively. The present studies have quantitated under well oxygenated, steady-state conditions, the rapid placental metabolism and production of lactate, the net fetal consumption of lactate, and the rapid endogenous fetal lactate production from glucose and nonglucose substrates.
Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31
Authors: Karen A. Gelmon, Frances M. Boyle, Bella Kaufman, David G. Huntsman, Alexey Manikhas, Angelo Di Leo, Miguel Martin, Lee S. Schwartzberg, Julie Lemieux, Samuel Aparicio, Lois E. Shepherd, Susan Dent, Susan L. Ellard, Katia Tonkin, Kathleen I. Pritchard, Timothy J. Whelan, Dora Nomikos, Arnd Nusch, Robert E. Coleman, Hirofumi Mukai, Sergei Tjulandin, Rustem Khasanov, Shulamith Rizel, Anne P. Connor, Sergio L. Santillana, Judith-Anne W. Chapman, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2015)

The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown.The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors.From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03).As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.
Relationship Between Moderate Alcohol Consumption and Adiponectin and Insulin Sensitivity in a Large Heterogeneous Population
Authors: Claus Thamer, Michael Haap, Andreas Fritsche, Hans Haering, Michael Stumvoll
Journal: Diabetes Care (2004)

In the January issue of Diabetes Care , Sierksma et al. (1) reported that moderate alcohol consumption increased adiponectin serum levels and improved insulin sensitivity in a small group of insulin-resistant middle-aged men using a longitudinal study. This finding prompted us to examine the effect of moderate alcohol consumption on these parameters in our large heterogeneous group of nondiabetic subjects with and without family history of type 2 diabetes (2,3). Subjects with clinically suspected alcohol abuse were excluded from the study. Data on alcohol …