tbuckley/cabot-search huggingface dataset:
Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells.
Authors: R Witzgall, D Brown, C Schwarz, J V Bonventre
Journal: Journal of Clinical Investigation (1994)

The mechanisms leading to the recovery of the kidney after ischemic acute renal failure are poorly understood. To explore the role played by mitogenesis and dedifferentiation in this repair process and to identify whether the genetic response of the nephron segments reflects the level of susceptibility to injury, the temporal and nephron segment expressions of various proteins implicated in mitogenesis, differentiation, and injury were determined. Proliferating cell nuclear antigen (PCNA), a marker for the G1-S transition in the cell cycle and hence mitogenesis, was detected primarily in the S3 segment of the proximal tubule, with maximal expression at 2 d postischemia. Vimentin, normally present in mesenchymal cells but not epithelial cells, and hence a marker for the state of differentiation, was prominently expressed in the S3 segment 2-5 d postischemia. In the S3 segments in the outer stripe of the medulla cells that stained positively for PCNA also stained positively for vimentin. Clusterin, a marker for cell injury, was expressed primarily in the S3 segment and in the distal tubule with distinct staining patterns in each segment. None of the cells that stained with clusterin antibodies were positively stained with PCNA or vimentin antibodies. Likewise, none of the PCNA or vimentin-positive cells expressed clusterin at detectable levels. Thus, in the S3 segment, where there is significant ischemic injury, surviving cells express markers indicating that they undergo mitogenesis and dedifferentiate in the postischemic period. While there is some expression of c-Fos in the S3 segment, c-Fos was expressed predominantly, at 1 and 3 h postischemia, in the nuclei of the distal nephron, particularly in the thick ascending limb. The data support the view that the mature renal S3 segment epithelial cell can be a progenitor cell.
Time to Insulin Initiation Cannot Be Used in Defining Latent Autoimmune Diabetes in Adults
Authors: Sinead Brophy, Knud Yderstræde, Didac Mauricio, Stephen Hunter, Mohammed Hawa, Paolo Pozzilli, Guntram Schernthaner, Nanette Schoot, Raffaella Buzzetti, Helen Davies, David Leslie, Rhys Williams
Journal: Diabetes Care (2008)

Latent autoimmune diabetes in adults is type 1 diabetes presenting as non-insulin dependent diabetes. One feature of the selection criteria is time independent of insulin treatment. We examine the validity of this criterion.Patients were recruited in nine European centers, and clinicians reported on criteria for initiating insulin. All patients were tested for GAD antibodies (GADAs) in a central laboratory. We examined time to insulin treatment for GADA-positive patients in six participating centers.There was intercenter variation in the criteria used to initiate insulin. Median time to insulin was 16.15 months (interqartile range 6.7-25.5) in centers with GADA testing compared with 45.6 months (29.5-61.8) in centers without routine GADA testing (P < 0.002).Time to insulin should not be used to define patients with LADA because it is dependent on local clinical judgment and the use of laboratory tests for GADA.
Combination Antibody Therapy With Epratuzumab and Rituximab in Relapsed or Refractory Non-Hodgkin's Lymphoma
Authors: John P. Leonard, Morton Coleman, Jamie Ketas, Michelle Ashe, Jennifer M. Fiore, Richard R. Furman, Ruben Niesvizky, Tsiporah Shore, Amy Chadburn, Heather Horne, Jacqueline Kovacs, Cliff L. Ding, William A. Wegener, Ivan D. Horak, David M. Goldenberg
Journal: Journal of Clinical Oncology (2005)

To explore the safety and therapeutic activity of combination anti-B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL).Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate-risk or high-risk International Prognostic Index scores. All patients were rituximab naïve.Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months.The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.
Bioluminescence imaging of leukemia cell lines in vitro and in mouse xenografts: effects of monoclonal and polyclonal cell populations on intensity and kinetics of photon emission
Authors: Sandra Christoph, Jennifer Schlegel, Francesca Alvarez-Calderon, Yong-Mi Kim, Luis N Brandao, Deborah DeRyckere, Douglas K Graham
Journal: Journal of Hematology & Oncology (2013)

Abstract Background We investigated the utility of bioluminescence imaging (BLI) using firefly luciferase in monoclonal and polyclonal populations of leukemia cells in vitro and in vivo . Methods Monoclonal and polyclonal human lymphoid and myeloid leukemia cell lines transduced with firefly luciferase were used for BLI. Results Kinetics and dynamics of bioluminescence signal were cell line dependent. Luciferase expression decreased significantly over time in polyclonal leukemia cells in vitro. Transplantation of polyclonal luciferase-tagged cells in mice resulted in inconsistent signal intensity. After selection of monoclonal cell populations, luciferase activity was stable, equal kinetic and dynamic of bioluminescence intensity and strong correlation between cell number and light emission in vitro were observed. We obtained an equal development of leukemia burden detected by luciferase activity in NOD-scid-gamma mice after transplantation of monoclonal populations. Conclusion The use of monoclonal leukemia cells selected for stable and equal luciferase activity is recommended for experiments in vitro and xenograft mouse models. The findings are highly significant for bioluminescence imaging focused on pre-clinical drug development.
Eosinophil extracellular trap cell death–derived DNA traps: Their presence in secretions and functional attributes
Authors: Shigeharu Ueki, Yasunori Konno, Masahide Takeda, Yuki Moritoki, Makoto Hirokawa, Yoshinori Matsuwaki, Kohei Honda, Nobuo Ohta, Shiori Yamamoto, Yuri Takagi, Atsushi Wada, Peter F. Weller
Journal: Journal of Allergy and Clinical Immunology (2015)
Lineage relationships and developmental kinetics of immature thymocytes: CD3, CD4, and CD8 acquisition in vivo and in vitro.
Authors: H T Petrie, P Hugo, R Scollay, K Shortman
Journal: The Journal of Experimental Medicine (1990)

T lymphocytes develop in the thymus from immunologically naive bone marrow precursors. Based on T cell receptor rearrangement and transcription, and thymic reconstitution potential, we have deduced a developmental sequence among immature thymocytes, before the acquisition of the lineage markers CD3, CD4, and CD8. In the current study, we have followed the ontogenic progression of the latter stages in this sequence, using two different systems: (a) in vivo, by direct injection into the thymus of nonirradiated, congenic recipients; and (b) in vitro, using culture medium without mitogens or cytokines. In vivo, the less mature Pgp-1- interleukin 2 receptor alpha-positive (IL-2R alpha+) CD3-4-8- subset (also heat-stable antigen high) requires 3 d before becoming predominantly IL-2R alpha- CD3lo4+ 8+ typical cortical-type cells, and at least 5 d before the appearance of any mature single-positive cells (CD3hi4+ 8- or CD3hi4-8+). However, these Pgp-1- IL-2R alpha+ precursors do not differentiate further in unstimulated culture. The more mature Pgp-1- IL-2R alpha- CD3-4-8- subset becomes primarily CD3lo4+ 8+ within 1 d after transplantation, and some mature single-positive progeny are evident by day 3. By 5 d, most of these Pgp-1-IL-2R alpha- precursor cells have become CD3hi, and have lost or are downregulating either CD4 or CD8. In culture, these Pgp-1- IL-2R alpha- cells also acquire high levels of CD4 and CD8 within 1 d, and low levels of CD3 by 2 d. However, they do not progress further to mature single positives in vitro, and most of them die by day 3. These experiments directly confirm our previously proposed developmental sequence, and demonstrate the kinetics of T lymphocyte production in a low-stress, steady-state environment.
Respiratory symptoms, bronchitis and asthma in children of Central and Eastern Europe
Authors: G.S. Leonardi, D. Houthuijs, B. Nikiforov, J. Volf, P. Rudnai, J. Zejda, E. Gurzau, E. Fabianova, T. Fletcher, B. Brunekreef
Journal: European Respiratory Journal (2002)

The multicentre Central European Study of Air Pollution and Respiratory Health (CESAR) aimed to measure the respiratory health of schoolchildren using a standardised questionnaire in six countries of Central and Eastern Europe (CEE), allowing comparisons within this region and with other European countries. A cross-sectional study was conducted in 25 urban areas of Bulgaria, Czech Republic, Hungary, Poland, Romania, and Slovakia in 1996. Parents of 21,743 schoolchildren of age 7–11 yrs completed a questionnaire based on items from the World Health Organization and International Study of Asthma and Allergies in Childhood questions on cough and wheeze symptoms, as well as on diagnoses by doctors. Life-time prevalence of bronchitis was 55.9%, asthma 3.9%, and asthmatic, spastic or obstructive bronchitis 12.3%. In CEE countries the prevalence of bronchitis is higher and prevalence of asthma appears lower than in Western Europe. However, if asthma is defined as a diagnosis of either asthma or asthmatic, spastic or obstructive bronchitis, then its prevalence is comparable to Western Europe, or higher. In this region, within-country variation for most respiratory parameters is less than between-country variation. Between-country comparisons in doctors9 diagnoses appear dependent on the choice of definition of asthma. Europe-wide comparisons in prevalence of respiratory symptoms and diagnosis are reported in this study. Some of the East-West difference in asthma prevalence may be attributable to differences in diagnostic practice.
THE REGULATION OF CD4 AND CD8 CORECEPTOR GENE EXPRESSION DURING T CELL DEVELOPMENT
Authors: Wilfried Ellmeier, Shinichiro Sawada, Dan R. Littman
Journal: Annual Review of Immunology (1999)

▪ Abstract The two major subsets of T lymphocytes in the peripheral immune system, the helper and cytotoxic T cells, are defined by their expression of either the CD4 or the CD8 glycoproteins, respectively. Expression of these molecules, which serve as coreceptors by interacting specifically with either MHC class II or class I molecules, also defines discrete stages of T cell development within the thymus. Thus, CD4 + and CD8 + single-positive (SP) thymocytes arise from common progenitor double positive (DP) cells that express both CD4 and CD8, during a process known as positive selection. The molecular mechanisms underlying the developmental choice toward the helper or cytotoxic lineage remain poorly understood. Because regulation of coreceptor gene expression appears to be coupled to the phenotypic choice of the differentiating T cell, it is likely that shared signaling pathways direct CD4 and CD8 transcription and the development of an uncommited DP thymocyte toward either the helper or cytotoxic lineage. Therefore, an understanding of how CD4 and CD8 expression is regulated will not only provide insights into transcriptional control mechanisms in T cells, but may also result in the identification of molecular factors that are involved in lineage choices during T cell development. In this review, we summarize recent progress that has been made toward an understanding of how CD4 and CD8 gene expression is regulated.
Congestive Heart Failure in Type 2 Diabetes
Authors: Gregory A. Nichols, Teresa A. Hillier, John R. Erbey, Jonathan B. Brown
Journal: Diabetes Care (2001)

OBJECTIVE—To estimate the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and to identify risk factors for diabetes-associated CHF. RESEARCH DESIGN AND METHODS—We searched the inpatient and outpatient electronic medical records of 9,591 individuals diagnosed with type 2 diabetes before 1 January 1997 and those of an age- and sex-matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, we searched forward for 30 months for incident cases of CHF. We constructed multiple logistic regression models to identify risk factors for both prevalent and incident CHF. RESULTS—CHF was prevalent in 11.8% (n = 1,131) of diabetic subjects and 4.5% (n = 435) of control subjects at baseline. We observed incident cases of CHF in 7.7% of diabetic subjects free of CHF at baseline (650 of 8,460) and in 3.4% of control subjects (314 of 9,156). In diabetic subjects, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline, and improved glycemic and blood pressure control at follow-up predicted the development of CHF. CONCLUSIONS—Despite controlling for age, duration of diabetes, presence of ischemic heart disease, and presence of hypertension, insulin use was associated with both prevalent and incident CHF. Why insulin use and better glycemic control both at baseline and follow-up independently predicted CHF deserves further study.
Phase II Clinical Trial Design: Methods in Translational Research from the Genitourinary Committee at the Eastern Cooperative Oncology Group
Authors: Robert Gray, Judith Manola, Scott Saxman, John Wright, Jan Dutcher, Michael Atkins, Michael Carducci, William See, Christopher Sweeney, Glenn Liu, Mark Stein, Robert Dreicer, George Wilding, Robert S. DiPaola
Journal: Clinical Cancer Research (2006)

Abstract Given the increase in novel agents and difficulty with planning and completing many phase III studies, various phase II trial design options should be considered to more effectively guide phase III trial plans. The need for novel phase II trial designs has increased, given the number of novel molecular targeted therapies now available for testing, an abundance of cytostatic agents, and limited resources to conduct phase III studies for all interesting agents or combinations. This review will focus on options for phase II trial designs. We review randomized phase II designs with placebo control, randomized selection designs, and randomized discontinuation designs. As agents become available for testing in the clinic, the strengths and weaknesses of different phase II trial designs should be considered to optimize a trial development plan that guides phase III trial decisions more effectively.
A case-control study of lifestyle risk factors associated with tuberculosis in Liverpool, North-West England
Authors: K. Tocque, M.A. Bellis, N.J. Beeching, Q. Syed, T. Remmington, P.D.O. Davies
Journal: European Respiratory Journal (2001)

The aim of this study was to identify the subtle influences of exposure and individual lifestyles on the risk of developing tuberculosis. A retrospective case-control study (with matching by sex, age, postcode and ethnicity) of all tuberculosis cases notified over a 7-yr period in Liverpool, UK, was carried out. Multiple logistic regression showed that, before diagnosis, cases were 7.4 times more likely to have had visitors from abroad; 4.0 times more likely to have been born abroad; and 3.8 times more likely to have lived with someone with tuberculosis. Subtle socioeconomic factors were also evident with cases 4.0 times less likely to have additional bathrooms. Lifestyle factors emerged with cases 2.3 times more likely to have smoked for at least 30 yrs, 3.8 times less likely to eat dairy products every week and 2.6 times less likely to have had high blood pressure. At interview, these factors were still evident, but cases, unlike controls, had reduced their smoking and alcohol consumption and were less likely to go out of the home or exercise than before their illness. Within individuals, lifestyle consequences of tuberculosis lead to a “healthier” lifestyle on the one hand (less smoking and alcohol consumption), but a reduced quality of life (social activity) on the other.
Association of RhoGDIα with Rac1 GTPase mediates free radical production during myocardial hypertrophy
Authors: F CUSTODIS, M EBERL, H KILTER, M BOHM, U LAUFS
Journal: Cardiovascular Research (2006)

Journal Article Association of RhoGDIα with Rac1 GTPase mediates free radical production during myocardial hypertrophy Get access Florian Custodis, Florian Custodis Klinik und Poliklinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcel Eberl, Marcel Eberl Klinik und Poliklinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Heiko Kilter, Heiko Kilter Klinik und Poliklinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Böhm, Michael Böhm Klinik und Poliklinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Ulrich Laufs Ulrich Laufs * Klinik und Poliklinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany * Corresponding author. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, 66424 Homburg/Saar, Germany. Tel.: +49 6841 1623000. Email address: [email protected] Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 71, Issue 2, July 2006, Pages 342–351, https://doi.org/10.1016/j.cardiores.2006.04.005 Published: 15 July 2006 Article history Received: 20 December 2005 Revision received: 28 March 2006 Accepted: 06 April 2006 Published: 15 July 2006
Real World Effectiveness of Population-Based Roll Out of Human Papillomavirus Vaccination Against Rates of Genital Warts
Authors: J. S. Smith, E. Weiderpass
Journal: JNCI Journal of the National Cancer Institute (2013)

Dr Leval and colleagues present novel data on the real-world effectiveness of population-based roll-out of human papillomavirus (HPV) vaccination against rates of genital warts among more than 2 million female residents of Sweden aged 10 to 44 years (1).The ability of the Swedish public health system to link unique personal identification numbers of residents to multiple registries allows an norms for TL values by populations.Future studies comparing ethnic groups are needed to understand if and why longer TLs are observed in African Americans ( 16).This could lead to insights into different cancer risk profiles between distinct ethnic groups.Because telomere shortening is observed in the aging process, several studies have pursued a likely connection between TL and mortality.In a prospective, population-based study using qPCR, short telomere length at baseline was associated with higher cancer risk and mortality with a higher hazards ratio for the latter (3.1 and 11.1, respectively) (17).Weischer et al. found that individuals with shorter telomeres were more likely to die from cancer than those who had cancer and longer telomeres.In the Cardiovascular Health Study, shorter telomeres were associated with 60% risk of death, mainly from infectious or cardiovascular cause, but interestingly, not cancer (16).Although these prospective studies suggest a connection between short telomeres and mortality, there is more to investigate.It is possible that individuals with telomeres shorter than average could be at risk of dying sooner than those with longer telomeres, regardless of the cause of death, because of more limited cellular replicative capacity.Until even larger studies are done, preferably in prospective cohorts, it will be difficult to separate which causes of death are clearly linked to shorter TL.In conclusion, association studies of TL and cancer have likely suffered from important methodological issues, including reverse causation bias, lack of interlaboratory comparisons of TL measurements, and limited reporting of DNA extraction and handling methods.Because therapeutic interventions can affect telomere lengths, it will be important to integrate clinical data in future studies.If telomere lengths are to be used as effective biomarkers for cancer prevention or intervention, it will be necessary to more thoroughly understand the connection between telomere biology, cancer, chronic disease, and mortality in the general population.
Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)
Authors: Jeffrey B Washam, Susanna R Stevens, Yuliya Lokhnygina, Jonathan L Halperin, Günter Breithardt, Daniel E Singer, Kenneth W Mahaffey, Graeme J Hankey, Scott D Berkowitz, Christopher C Nessel, Keith A A Fox, Robert M Califf, Jonathan P Piccini, Manesh R Patel
Journal: The Lancet (2015)
THE POSITIVE CONDITIONAL SALIVARY REFLEX IN PSYCHONEUROTIC PATIENTS
Authors: JACOB E. FINESINGER, GEORGE F. SUTHERLAND, FRANCES F. MCGUIRE
Journal: American Journal of Psychiatry (1942)

1. A positive conditional salivary reflex to an auditory stimulus was developed in 10 psychoneurotic patients. The stimulus was a metronome 150 beats per minute reenforced by lemon juice. 2. The salivary responses were designated as positive when the action of the metronome was accompanied by an increase in salivation over the rate immediately preceding the stimulus 3. When the results for the first prolonged stimulus of the day were studied for each patient, the positive responses appeared in from 67 to 83 per cent of the cases, the mean value of the positive reflex for the 10 patients being 77 per cent. 4. The mean value of the positive response for 15 seconds was 4.9 drops or 0.1 cc.