tbuckley/cabot-search huggingface dataset:
Regulation of sperm function by reactive oxygen species
Authors: W.C.L. Ford
Journal: Human Reproduction Update (2004)

Sperm capacitation can be increased by the addition of reactive oxygen species (ROS) and decreased by antioxidants. Broadly consistent results have been achieved with a wide variety of methods and across different species. Exposure to ROS increases protein tyrosine phosphorylation consequent on an increase in cAMP and activation of tyrosine kinase and inhibition of tyrosine phosphatase. The measurement of ROS production by sperm is complicated by contamination of suspensions by leukocytes, laying many studies open to doubt. In human sperm the observation that extracellular NADPH could support superoxide production detected with the chemiluminescent probe lucigenin and had physiological effects similar to hydrogen peroxide led to the suggestion that they contained NADPH oxidase activity to generate ROS to support capacitation. However, the realization that lucigenin can signal superoxide artefactually, combined with failure to detect superoxide production using spin trapping techniques or to detect NADPH oxidase components in mature sperm, and confirmation of old reports that NADPH solution contains substantial amounts of hydrogen peroxide due to autoxidation, have undermined this hypothesis. Although the presence of significant NADPH oxidase activity in mature human sperm now seems less likely, other observations continue to suggest that they can make ROS in some way. There is stronger evidence that animal sperm can make ROS although these may be mainly of mitochondrial origin.
Comparative efficacy of endoscopic ultrasound-guided fine-needle aspiration using different needle gauge in mediastinal lymphadenopathies
Authors: Ilya Sivokozov, Olga Lovacheva, Irina Shumskaya, Galina Evgushenko, Larisa Lepekha
Journal: European Respiratory Journal (2013)

RATIONALE. Still there is no direct comparison of 19G vs 22G needles for EUS.

METHODS. 23 patients (14 males) with mediastinal lymphadenopathy w/o pulmonary lesions undergone EUS-FNA using Olympus echobronchoscope via esophagus. Target lymphnodes (LN) in station 7 and/or 4L were punctured using dedicated 22G (Olympus) and 19 G ProCore (Cook) needles with prior randomization on which type will be used first. If EUS-FNA was nondiagnostic, patient referred to surgery. Diagnostic yield depending on disease and type of specimen (histology and/or cytology) were analyzed.

RESULTS. There were no complications. Mean LN size was 2.4 cm, mean number of passes for 22G needle of 2.7, and for 19G needle of 1.5 passes. Final diagnosis was established by EUS-FNA in 19/23 (82.6%) pts: sarcoidosis in 10/23 (43.5%), non-specific inflammation in 2/23 (8.7%), tuberculosis in 2/23 (8.7%), Hodgkin's lymphoma in 3/23 (13%), B-cell non-Hodgkin lymphoma in 1/23 (4.3%), adenocarcinoma in 1/23 (4.3%). Among patients referred to surgery: 2/23 (8.7%) Hodgkin lymphoma, 1/23 (4.3%) - adenocarcinoma and 1/23 (4.3%) sarcoidosis. Efficacy of 22G by cytology for benign diseases was 11/15 (73.3%), for malignancies - 1/8 (12.5%), no samples for histology. For 19G, efficacy in benign diseases by cytology: 12/15 (80%), in malignancy 3/8 (37.5%). Histology specimens were retrieved by 19G in 19/23 (82.6%), diagnostic yield benign diseases 14/15 (93.3%), and 5/8 (62.5%) in malignancy.

CONCLUSION. Diagnostic yield for 22G and 19G needle is equal by cytology in benign diseases, but it favours 19G for malignancy. For histology, 19G is more efficient vs 22G, especially for lymphoma.
Coronary Heart Disease Mortality After 5 Years of Adjuvant Tamoxifen Therapy: Results from a Randomized Trial
Authors: Bo Nordenskjöld, Johan Rosell, Lars-Erik Rutqvist, Per-Olof Malmström, Jonas Bergh, Nils-Olof Bengtsson, Thomas Hatschek, Arne Wallgren, John Carstensen
Journal: JNCI Journal of the National Cancer Institute (2005)

From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94; P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed.
Integrating real-life studies in the global therapeutic research framework
Authors: Nicolas Roche, Helen K Reddel, Alvar Agusti, Eric D Bateman, Jerry A Krishnan, Richard J Martin, Alberto Papi, Dirkje Postma, Mike Thomas, Guy Brusselle, Elliot Israel, Cynthia Rand, Alison Chisholm, David Price
Journal: The Lancet Respiratory Medicine (2013)
Quantification of baroreceptor influence on arterial pressure changes seen in primary angiotension-induced hypertension in dogs.
Authors: A W Cowley, J W DeClue
Journal: Circulation Research (1976)

We studied the role of the sino-aortic baroreceptors in the gradual development of hypertension induced by prolonged administration of small amounts of angiotensin II (A II) in intact dogs and dogs with denervated sino-aortic baroreceptors. Short-term 1-hour infusions of A II(1.0-100 ng/kg per min) showed that conscious denervated dogs had twice the pressor sensitivity of intact dogs. Long-term infusions of A II at 5.0 ng/kg per min (2-3 weeks) with continuous 24-hour recordings of arterial pressure showed that intact dogs required 28 hours to reach the same level of pressure attained by denervated dogs during the 1st hour of infusion. At the 28th hour the pressure in both groups was 70% of the maximum value attained by the 7th day of infusion. Both intact and denervated dogs reached nearly the same plateau level of pressure, the magnitude being directly related both the the A II infusion rate and the daily sodium intake. Cardiac output in intact dogs initially decreased after the onset of A II infusion, but by the 5th day of infusion it was 38% above control, whereas blood volume was unchanged. Heart rate returned to normal after a reduction during the 1st day of infusion in intact dogs. Plasma renin activity could not be detected after 24 hours of A II infusion in either intact or denervated dogs. The data indicate that about 35% of the hypertensive effect of A II results from its acute pressor action, and an additional 35% of the gradual increase in arterial pressure is in large measure a result of baroreceptor resetting. We conclude that the final 30% increase in pressure seems to result from increased cardiac output, the cause of which may be decreased vascular compliance. since the blood volume remains unaltered.
Combined Neoplastic Effects of Vaccinia Virus and 3-Methylcholanthrene. II. Genetic Factors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lilly, Frank, Duran-Reynals, Maria L.
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Combined Neoplastic Effects of Vaccinia Virus and 3-Methylcholanthrene. II. Genetic Factors Get access Frank Lilly, Frank Lilly Departments of Genetics and of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461 Search for other works by this author on: Oxford Academic PubMed Google Scholar Maria L. Duran-Reynals Maria L. Duran-Reynals Departments of Genetics and of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 1, January 1972, Pages 105–112, https://doi.org/10.1093/jnci/48.1.105 Published: 01 January 1972 Article history Received: 01 December 1970 Revision received: 10 September 1971 Accepted: 21 September 1971 Published: 01 January 1972
World Health Organization‐defined eosinophilic disorders: 2014 update on diagnosis, risk stratification, and management
Authors: Jason Gotlib
Journal: American Journal of Hematology (2014)

Disease overview : The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end‐organ damage. Diagnosis : Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1,500/mm 3 and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ hybridization, flow immunocytometry, and T‐cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder. Risk stratification : Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2008 World Health Organization establishes a semimolecular classification scheme of disease subtypes including “myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA , PDGFRB , or FGFR1 ', chronic eosinophilic leukemia, not otherwise specified” (CEL, NOS), lymphocyte‐variant HE, and idiopathic hypereosinophilic syndrome (HES), which is a diagnosis of exclusion. Risk‐adapted therapy : The goal of therapy is to mitigate eosinophil‐mediated organ damage. For patients with milder forms of eosinophilia (e.g., &lt;1,500/mm 3 ) without symptoms or signs of organ involvement, a watch and wait approach with close‐follow‐up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first‐line therapy for patients with lymphocyte‐variant HE and HES. Hydroxyurea and interferon‐alpha have demonstrated efficacy as initial treatment and steroid‐refractory cases of HES. In addition to hydroxyurea, second‐line cytotoxic chemotherapy agents and hematopoietic cell transplant have been used for aggressive forms of HES and CEL with outcomes reported for limited number of patients. Although clinical trials have been performed with anti‐IL‐5 (mepolizumab) and anti‐CD52 (alemtuzumab) antibodies, their therapeutic role in primary eosinophilic diseases and HES has yet to be established. Am. J. Hematol. 89:326–337, 2014. © 2014 Wiley Periodicals, Inc.
Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation
Authors: Zhengguo Xiao, Matthew F. Mescher, Stephen C. Jameson
Journal: The Journal of Experimental Medicine (2007)

CD8 is critical for T cell recognition of peptide/class I major histocompatability complex ligands, yet is down-regulated during activation of CD8 T cells. We report that loss of CD8 expression early during in vivo responses to vaccinia virus or Listeria monocytogenes (LM) correlates with decreased T cell staining with specific class I/peptide tetramers and reduced CD8 T cell sensitivity for antigen. Loss of CD8 cell surface expression occurs despite sustained mRNA expression, and CD8 levels return to normal levels during differentiation of memory cells, indicating a transient effect. We determined that during response to LM, CD8 down-regulation is regulated by T cell reactivity to type I interferon (IFN-I) because CD8 loss was averted on IFN-I receptor–deficient T cells. IFN-I alone was not sufficient to drive CD8 down-regulation, however, as antigen was also required for CD8 loss. These results suggest that CD8 effector T cell differentiation involves a transient down-regulation of antigen sensitivity (CTL “detuning”), via reduced CD8 expression, a feature that may focus the effector response on target cells expressing high levels of antigen (e.g., infected cells), while limiting collateral damage to bystander cells.
Impact of acute admissions and readmissions in patients with lung cancer for patients and the hospital
Authors: Conal Hayton, Venencia Sibanda, Imran Aziz, Ram Sundar
Journal: European Respiratory Journal (2014)

Background: It has been shown that 40% of patients with lung cancer attend the emergency department at least once during their illness and this leads to admission in more than 60% (Gorham J.et al. Lung Cancer. 2013; 80: 203-208). Locally we have observed that patients with lung cancer have multiple admissions.

Aim: To determine the frequency and reasons for acute admissions in patients with a diagnosis of lung cancer.

Methods: We performed a retrospective case note review of all patients with lung cancer diagnosis admitted to a district general hospital between 1/8/2011 and 31/12/2013.

Results: 204 patients (108 male, median age 73) had 399 admissions. There were 37 primary presenting symptoms. Dyspnoea was the commonest (39.1%), followed by general deterioration (10.3%) and chest pain (7.0%). 77 primary conditions were treated. The most common was community acquired pneumonia (11.0%) followed by lower respiratory tract infection (8.5%). 8.5% of patients were admitted for end of life care. 42.9% of admissions were attributable to the underlying malignancy and 5.5% to effects of oncological treatment. 29.6% of admissions were due to another respiratory disease. 22.1% were unrelated to lung malignancy or respiratory disease. Median length of stay was 5 days (range 1 to 65). 53.4% of patients had more than 1 admission. Median time between admissions was 29 days (range 0-691). 51.5% of re-admissions were within 30 days.

Conclusions: As 50% of admissions were directly attributable to the lung malignancy or treatment, a structured community based lung cancer service with enhanced communication could have a bigger impact on patient experience and health economy.
Randomized Phase I/II Study of Troxacitabine Combined With Cytarabine, Idarubicin, or Topotecan in Patients With Refractory Myeloid Leukemias
Authors: Francis J. Giles, Stefan Faderl, Deborah A. Thomas, Jorge E. Cortes, Guillermo Garcia-Manero, Dan Douer, Alexandra M. Levine, Charles A. Koller, Sima S. Jeha, Susan M. O’Brien, Elihu H. Estey, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2003)

Troxacitabine has significant single-agent activity. This study was conducted to define the dose-limiting toxicities (DLTs) of its combination with cytarabine (ara-C), idarubicin, or topotecan.Patients with refractory acute myeloid leukemia (AML), advanced myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP) were initially randomly assigned to receive troxacitabine 5.0 mg/m(2) by intravenous (IV) infusion over 30 minutes on days 1 to 5 with ara-C 1.0 g/m(2)/d IV [DOSAGE ERROR CORRECTED] over 2 hours on days 1 to 5, idarubicin 12 mg/m(2) by 5 minute IV infusion on days 1 to 3, or topotecan 1.0 mg/m(2) as an continuous IV infusion on days 1 to 5. Doses were then adjusted to define DLT for each combination.Eighty-seven patients (68 AML, eight MDS, 11 CML-BP) were treated. DLTs were hepatic transaminitis, hyperbilirubinemia, and hand foot syndrome (HFS) on the troxacitabine plus ara-C combination. The recommended phase II doses were 6 mg/m(2) once a day for 5 days and 1.0g/m(2) once a day for 5 days, respectively. DLTs were diarrhea, rash, and mucositis on the troxacitabine plus topotecan combination. The recommended phase II doses were 4 mg/m(2) once a day for 5 days and 0.75 mg/m(2) once a day for 5 days, respectively. DLTs were HFS, rash, and mucositis on the troxacitabine plus idarubicin combination. The recommended phase II doses were 4 mg/m(2) once a day for 5 days and 9 mg/m(2) once a day for 3 days, respectively. Among 74 evaluable patients with AML or MDS, 10 (13%) achieved complete remission and four (5%) had hematologic improvement. Two of 11 (18%) evaluable patients with CML-BP returned to chronic phase.Troxacitabine-based combinations had significant antileukemic activity.
TB and M/XDR-TB infection control in European TB reference centres: the Achilles' heel?
Authors: G. Sotgiu, L. D'Ambrosio, R. Centis, G. Bothamley, D. M. Cirillo, S. De Lorenzo, G. Guenther, K. Kliiman, R. Muetterlein, V. Spinu, M. Villar, J. P. Zellweger, A. Sandgren, E. Huitric, C. Lange, D. Manissero, G. B. Migliori
Journal: European Respiratory Journal (2011)

TB infection control in European TB reference centres: the Achilles' heel?To the Editors:The emergence of multidrug-resistant (MDR) tuberculosis (TB), defined as in vitro resistance to isoniazid and rifampicin, and extensively drug-resistant (XDR)-TB, defined as in vitro drug resistance to isoniazid and rifampicin plus any fluoroquinolone and at least one of the injectable drugs (amikacin, capreomycin or kanamycin), represents a major threat to TB control at the global level [1][2][3][4][5].XDR-TB is a manmade product, resulting, in essence, from clinical mismanagement of newly diagnosed susceptible and resistant TB cases [2][3][4][5].Moreover, existing MDR/XDR-TB cases must be promptly detected and treated, and the transmission from infectious source cases has to be prevented, particularly in nosocomial settings [2][3][4][5][6].
REGULATION OF GENE EXPRESSION BY REACTIVE OXYGEN
Authors: Timothy P. Dalton, Howard G. Shertzer, Alvaro Puga
Journal: The Annual Review of Pharmacology and Toxicology (1999)

▪ Abstract Reactive oxygen intermediates are produced in all aerobic organisms during respiration and exist in the cell in a balance with biochemical antioxidants. Excess reactive oxygen resulting from exposure to environmental oxidants, toxicants, and heavy metals perturbs cellular redox balance and disrupts normal biological functions. The resulting imbalance may be detrimental to the organism and contribute to the pathogenesis of disease and aging. To counteract the oxidant effects and to restore a state of redox balance, cells must reset critical homeostatic parameters. Changes associated with oxidative damage and with restoration of cellular homeostasis often lead to activation or silencing of genes encoding regulatory transcription factors, antioxidant defense enzymes, and structural proteins. In this review, we examine the sources and generation of free radicals and oxidative stress in biological systems and the mechanisms used by reactive oxygen to modulate signal transduction cascades and redirect gene expression.
Staging of digestive endocrine tumours using helical computed tomography and somatostatin receptor scintigraphy
Authors: F. Panzuto, M. Falconi, S. Nasoni, S. Angeletti, A. Moretti, M. Bezzi, G. Gualdi, E. Polettini, R. Sciuto, A. Festa, F. Scopinaro, V.D. Corleto, C. Bordi, P. Pederzoli, G. Delle Fave
Journal: Annals of Oncology (2003)
Phase II Study of Gefitinib, Fluorouracil, Leucovorin, and Oxaliplatin Therapy in Previously Treated Patients With Metastatic Colorectal Cancer
Authors: Timothy Kuo, Cheryl D. Cho, Joanne Halsey, Heather A. Wakelee, Ranjana H. Advani, James M. Ford, George A. Fisher, Branimir I. Sikic
Journal: Journal of Clinical Oncology (2005)

To investigate the gefitinib, fluorouracil (FU), leucovorin, and oxaliplatin regimen (IFOX) in previously treated patients with metastatic colorectal cancer.Eligible patients had stage IV colorectal adenocarcinoma and had demonstrated progression or intolerance to a prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin 85 mg/m2 intravenously (IV) during 2 hours on day 1, hours 0 to 2; leucovorin 200 mg/m2 IV on days 1 and 2, hours 0 to 2; FU 400 mg/m2 IV push on days 1 and 2; and FU 600 mg/m2 IV on days 1 and 2, hours 2 to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg/d administered orally throughout the 14-day cycle.Twenty-seven patients were enrolled onto the study. The median number of prior chemotherapy regimens was two, and 74% of all patients received prior irinotecan. Nine of the 27 patients (33%) and six of the 20 patients (30%) who had prior FU and irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors Group criteria. Median overall survival was 12.0 months. Median event-free survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%), diarrhea (48%), nausea (22%), and vomiting (15%).IFOX is an active regimen in patients with previously treated metastatic colorectal adenocarcinoma, demonstrating higher response rates than those reported with FOLFOX-4 alone in a similar patient population.
Chronic Inflammation: A Common and Important Factor in the Pathogenesis of Neoplasia
Authors: D. Schottenfeld, J. Beebe-Dimmer
Journal: CA A Cancer Journal for Clinicians (2006)

A causal link between chronic inflammation and carcinogenesis is explored by reviewing illustrative examples of specific cancers and causal agents and mechanisms. The causal agents or pathologic conditions include microbial agents, gastroesophageal reflux, chronic cholecystitis and cholelithiasis, inflammatory bowel disease, and specific agents that cause chronic obstructive or diffuse interstitial lung disease. The proportion of total cancer deaths attributable to infectious agents is estimated to be about 20% to 25% in developing countries and 7% to 10% in more industrialized countries. Recurrent or persistent inflammation may induce, promote, or influence susceptibility to carcinogenesis by causing DNA damage, inciting tissue reparative proliferation, and/or creating a stromal “soil” that is enriched with cytokines and growth factors. Future research on the complex cascade of cellular and humoral factors participating in the chronic inflammatory process will further understanding of the pathogenesis of various cancers and potentially provide a rationale for targeted chemopreventive interventions.
The α3 Isoform Protein of the Na <sup>+</sup> ,K <sup>+</sup> -ATPase Is Associated With the Sites of Cardiac and Neuromuscular Impulse Transmission
Authors: Raphael Zahler, Wei Sun, T. Ardito, Zhong-ting Zhang, Jeffery D. Kocsis, Michael Kashgarian
Journal: Circulation Research (1996)

The alpha (catalytic) subunit of the Na+ pump (Na+, K(+)-ATPase) has three isoforms; alpha1 is ubiquitous, skeletal muscle expresses predominantly alpha2, and alpha3 has been localized to specific types of neurons and, possibly, to axonal processes. The alpha3 isoform mRNA is also expressed in the rat cardiac conduction system. Thus, we studied rat heart and quadriceps muscles by immunohistochemistry using isoform-specific antibodies to the Na+ pump alpha subunit and labeled alpha-bungarotoxin as a probe for the neuromuscular junction (NMJ). We found that alpha3 pump protein is localized to three sites important for impulse transmission: the junctional complex between cardiac myocytes, the heart conduction system, and the NMJ. Specifically, all levels of the conduction system expressed alpha3 immunoreactive protein, as assessed by two isoform-specific antibodies and histological conduction system markers. Specific expression at the junctional complex was confirmed by immuno-EM. Double-labeling and denervation analysis indicated that alpha3-positive areas in skeletal muscle were presynaptic and adjacent to postsynaptic bungarotoxin-positive regions, which had the classic morphology of NMJs. Thus, specific Na+,K(+)-ATPase pump isoforms may be adapted to maintenance of membrane potential and/or intracellular ion concentrations required for impulse transmission in both heart and presynaptic motor terminals contacting skeletal muscle.