tbuckley/cabot-search huggingface dataset:
Inhibition of legumain:integrin complex at the invasive cell front surface blocks angiogenesis and metastasis
Authors: Yuan Liu, Fang Guo, Wenyuan Wu, zhiyong chen, Sunny Abraham, Subhash Sinha, Cheng Liu
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3090 

The unique asparaginyl endopeptidases, legumain, is induced by hypoxia and transported to the front of invading cells. Legumain forms complex with integrins exclusively on the cell surface of lamellipodia and invadopodia. Binding of legumain to its cofactor integrins significantly enhances its ability to activate pro-MMP2 and pro-cathepsin L. Therefore the legumain:integrin complex physically and functionally define an invasive cell front surface (ICFS) where it regulates a network of matrix-processing enzymes. Inhibition of legumain:integrin affects matrix remodeling locally and suppresses angiogenesis and cell invasion. Importantly, systemic administration of a potent, cell impermeable asparaginyl endopepidase inhibitor (AEPI-1) inhibits tumor angiogenesis and invasive growth. The treated tumors demonstrated profound disorganization of collagens and elastic fiber. This treatment prevented both spontaneous and experimental lung metastasis suggesting the activity of legumain:integrin is required for metastasis. Our findings indicate legumain:integrin is an important regulator of cell invasion and matrix remodeling as well as an effective therapeutic target for cancer.
Effect of Anesthetic Drugs on Myocardial Performance in Man
Authors: R G Merin
Journal: Annual Review of Medicine (1977)

All potent CNS depressant drugs can depress cardiac function in man in a dose-dependent manner. The dose-effect curve is considerably flatter with several drugs (diethyl ether, cyclopropane, fluroxene, isoflurane, and ketamine), presumably from sympathetic nervous-system activation. Potent analgesics and tranquilizers appear to produce less depression, but have been incompletely studied. Neuromuscular blocking drugs and regional anesthesia produce minimal effects on the heart in healthy people. However, not as much is known about diseased man. For instance, nitrous oxide produces more depression in "muscle" function in IHD patients (43), while diazepam (28) and morphine (44) do not adversely affect pump function in this class of patients. Fluroxene (45) is more depressant in VHD patients, but nitrous oxide (46), morphine (30), fetanyl (46), and droperidol-fentanyl (46) seem to have equivalent effects to those seen in health patients. In any given patient, therefore, accurate prediction of the effect of any anesthetic drug on cardiac performance is not possible. Adequate monitoring and careful titration of drug dose offer the safest method of assuring a satisfactory response.
Viruses of the Upper Respiratory Tract
Authors: George Gee Jackson
Journal: Annual Review of Medicine (1956)

The influence of tissue culture techniques, especially the serial propaga­ tion of various cell lines in vitro as suspended cell cultures, upon our knowl­ edge in the field of infectious diseases and in particular virology, promises to be comparable to the development of semisolid media for the propagation of bacteria. Just as the latter innovation ushered in a period of great atten­ tion to etiologic identification, laboratory diagnosis, and taxonomy of bac­ teria, the use of tissue cultures has already provided a glimpse of a similar prospective era for viral diseases. In this context the subject of viruses of the upper respiratory tract is appropriate for review. Such a title is noncom­ mital regarding the question of the pathologic importance of any particular virus recovered by these ne'w techniques, although commendable epidemio­ logical studies which relate some of the newly recognized viruses to disease entities already have been performed. Neither can this review discuss with any completeness all of the known viruses for which the respiratory tract may serve as a portal of entry, but an attempt will be made to examine the recent contributions to our knowledge of common upper respiratory ill­ nesses and those viruses for which the upper respiratory tract appears to be the principal habitat. Where viral agents have not been cultivated success­ fully from patients with respiratory diseases that are presumed to have a viral etiology, recent clinical observations will be reported. Although the number of such publications is meager compared to those concerned with the laboratory aspects of viruses from the upper respiratory tract, it must be emphasized that the majority of common upper respiratory illnesses still must be classified upon the basis of clinical observations and epidemiology. Also, the broad application of laboratory procedures that deal with the pres­ ently known viruses is not yet practical. Repetition of material discussed in the comprehensive review of viral diseases by T. F. McNair Scott in the Annual Review of Medicine, vol. 6, May, 1955 (1) will be avoided except to supplement and enlarge upon certain aspects related to respiratory diseases. Also, in agreement with the advice to reviewers of scientific literature re­ corded by Arnon (2), only material that has been published or presented will be noted. There is an inevitable lag in such communications and the author knows of additional reports of recent and continuing research upon the common respiratory diseases that can be expected to.appear in the near fu­ ture. It is hoped, therefore, that this review will serve the reader by enabling him to iiltegrate some of the current information with past and future publications. .
CpG expedites regression of local and systemic tumors when combined with activatable nanodelivery
Authors: Azadeh Kheirolomoom, Elizabeth S. Ingham, Lisa M. Mahakian, Sarah M. Tam, Matthew T. Silvestrini, Spencer K. Tumbale, Josquin Foiret, Neil E. Hubbard, Alexander D. Borowsky, William J. Murphy, Katherine W. Ferrara
Journal: Journal of Controlled Release (2015)
Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy
Authors: Annelies W. Turksma, Veerle M.H. Coupé, Marc C. Shamier, Kevin L.H. Lam, Vincent A. de Weger, Jeroen A.M. Belien, Alfons J. van den Eertwegh, Gerrit A. Meijer, Chris J.L.M. Meijer, Erik Hooijberg
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To determine the prognostic and predictive value of tumor-infiltrating lymphocytes (TIL) in colon cancer in a cohort of patients who previously took part in a trial on adjuvant active specific immunotherapy (ASI). Experimental Design: We determined the number and location of CD3 and CD8 positive T cells in archival tumor samples of 106 colon cancers. We correlated stromal and epithelial TIL numbers with tumor stage and treatment and determined the effects on disease-specific survival (DSS) and recurrence-free interval (RFI). Results: On the basis of the data presented, we concluded that (i) high numbers of stromal CD3 T cells have positive prognostic value measured as DSS for patients with stage II microsatellite-stable tumors and (ii) high numbers of epithelial CD8-positive T cells have positive prognostic value measured as RFI for the group of patients with stage II microsatellite-stable tumors as well as for the whole group (so stage II plus stage III together). Furthermore, we concluded that high numbers of pre-existing stromal CD3-positive T cells are of positive predictive value in adjuvant ASI treatment measured as DSS as well as RFI. Conclusions: ASI therapy may contribute to an improved DSS and RFI in patients with microsatellite-stable colon tumors harboring high numbers of pre-existing stromal CD3+ TIL. Validation in future clinical trials is awaited. Clin Cancer Res; 22(2); 346–56. ©2015 AACR.
Erratum. Improving Diabetes Management and Cardiovascular Risk Factors Through Peer-Led Self-management Support Groups in Western Kenya. Diabetes Care 2015;38:e110–e111
Authors: Paul H. Park, Charity K. Wambui, Sabina Atieno, Joseph R. Egger, Lawrence Misoi, Jack S. Nyabundi, Sonak D. Pastakia, Gerald S. Bloomfield, Jemima H. Kamano
Journal: Diabetes Care (2015)
Physiological Bases for New Approaches to Mechanical Ventilation
Authors: A F Saari, T H Rossing, J M Drazen
Journal: Annual Review of Medicine (1984)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Recommendations for the Establishment of Stroke Systems of Care
Authors: Lee H. Schwamm, Arthur Pancioli, Joe E. Acker, Larry B. Goldstein, Richard D. Zorowitz, Timothy J. Shephard, Peter Moyer, Mark Gorman, S. Claiborne Johnston, Pamela W. Duncan, Phil Gorelick, Jeffery Frank, Steven K. Stranne, Renee Smith, William Federspiel, Katie B. Horton, Ellen Magnis, Robert J. Adams
Journal: Circulation (2005)
The Pulmonary Uptake, Accumulation, and Metabolism of Xenobiotics
Authors: J R Bend, C J Serabjit-Singh, R M Philpot
Journal: The Annual Review of Pharmacology and Toxicology (1985)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
The Biologic Roles of CD2, CD4, and CD8 in T-Cell Activation
Authors: B E Bierer, B P Sleckman, S E Ratnofsky, S J Burakoff
Journal: Annual Review of Immunology (1989)

The Biologic Roles of CD2, CD4, and CD8 in T-Cell Activation, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/immunol/7/1/annurev.iy.07.040189.003051-1.gif
Luminescent Dual Sensors Reveal Extracellular pH-Gradients and Hypoxia on Chronic Wounds That Disrupt Epidermal Repair
Authors: Stephan Schreml, Robert J. Meier, Michael Kirschbaum, Su Chii Kong, Sebastian Gehmert, Oliver Felthaus, Sarah Küchler, Justin R. Sharpe, Kerstin Wöltje, Katharina T. Weiß, Markus Albert, Uwe Seidl, Josef Schröder, Christian Morsczeck, Lukas Prantl, Claus Duschl, Stine F. Pedersen, Martin Gosau, Mark Berneburg, Otto S. Wolfbeis, Michael Landthaler, Philipp Babilas
Journal: Theranostics (2014)

Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.
Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases
Authors: Ahmed Ghallab, Géraldine Cellière, Sebastian G. Henkel, Dominik Driesch, Stefan Hoehme, Ute Hofmann, Sebastian Zellmer, Patricio Godoy, Agapios Sachinidis, Meinolf Blaszkewicz, Raymond Reif, Rosemarie Marchan, Lars Kuepfer, Dieter Häussinger, Dirk Drasdo, Rolf Gebhardt, Jan G. Hengstler
Journal: Journal of Hepatology (2015)

Recently, spatial-temporal/metabolic mathematical models have been established that allow the simulation of metabolic processes in tissues. We applied these models to decipher ammonia detoxification mechanisms in the liver.An integrated metabolic-spatial-temporal model was used to generate hypotheses of ammonia metabolism. Predicted mechanisms were validated using time-resolved analyses of nitrogen metabolism, activity analyses, immunostaining and gene expression after induction of liver damage in mice. Moreover, blood from the portal vein, liver vein and mixed venous blood was analyzed in a time dependent manner.Modeling revealed an underestimation of ammonia consumption after liver damage when only the currently established mechanisms of ammonia detoxification were simulated. By iterative cycles of modeling and experiments, the reductive amidation of alpha-ketoglutarate (α-KG) via glutamate dehydrogenase (GDH) was identified as the lacking component. GDH is released from damaged hepatocytes into the blood where it consumes ammonia to generate glutamate, thereby providing systemic protection against hyperammonemia. This mechanism was exploited therapeutically in a mouse model of hyperammonemia by injecting GDH together with optimized doses of cofactors. Intravenous injection of GDH (720 U/kg), α-KG (280 mg/kg) and NADPH (180 mg/kg) reduced the elevated blood ammonia concentrations (>200 μM) to levels close to normal within only 15 min.If successfully translated to patients the GDH-based therapy might provide a less aggressive therapeutic alternative for patients with severe hyperammonemia.
Primary or delayed debulking surgery and chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide in stage III-IV epithelial ovarian carcinoma.
Authors: J Wils, G Blijham, A Naus, C Belder, F Boschma, H Bron, T Ceelen, A Eekhout, J von Erp, P Geelen
Journal: Journal of Clinical Oncology (1986)

Eighty-eight previously untreated patients with stage III and IV epithelial ovarian carcinoma were treated with primary or delayed (secondary) optimal debulking surgery unless impossible, and combination chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide intravenously (IV) on day 1, every 4 weeks (CAP-I). In patients with no evidence of disease after six cycles of chemotherapy, a second-look laparotomy was performed. A pathologically confirmed complete response (CR) was obtained in 39% of the patients. The median progression-free survival period of all patients was 18 months and the median survival time 24 months. CAP-I is an effective chemotherapy schedule that can be administered with moderate toxicity and appears to enhance the cure rate in advanced ovarian carcinoma. The role of secondary surgery must be further defined.
Intensive induction chemotherapy and radiation for organ preservation in patients with advanced resectable head and neck carcinoma.
Authors: S G Urba, A A Forastiere, G T Wolf, R M Esclamado, P W McLaughlin, A F Thornton
Journal: Journal of Clinical Oncology (1994)

We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the head and neck. The regimen consisted of intensive chemotherapy followed by radiation therapy alone for patients with good response to treatment. The end points of the study were response rate, organ preservation, toxicity, and survival.Forty-two eligible patients with carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, and paranasal sinuses were enrolled. Induction chemotherapy consisted of three cycles of mitoguazone, fluorouracil (5-FU), and high-dose continuous infusion cisplatin. Patients who had a complete response to chemotherapy, or whose tumor was downstaged to T1N1, were treated with definitive radiation therapy, to a total dose of 66 to 73.8 Gy. Patients with residual disease greater than T1N1 underwent surgery and postoperative radiation.The overall response rate to chemotherapy was 84%, with a 43% complete response rate, and a 68% complete response rate at the primary tumor site. Sixty-nine percent of patients (29 of 42) were initially spared surgery to the primary tumor site, and four of these patients (14%) required neck dissection only, after radiation therapy. These tumor sites included oral cavity, oropharynx, hypopharynx, larynx, and sinuses. Eventually, five of these patients (17%) required salvage surgery and eight patients (28%) had unresectable or metastatic relapses. With a median follow-up duration of 38.5 months, 36% of all patients have had preservation of the primary tumor site and remain disease-free. The median survival duration is 26.8 months. Toxicity was substantial, with a 70% incidence of grade 3 to 4 granulocytopenia and two septic deaths.Organ preservation without apparent compromise of survival was achieved in patients with selected nonlaryngeal sites of head and neck carcinoma. Larger site-specific trials with less toxic regimens conducted in randomized fashion are required to extend these data.
How to Accurately Establish Pharmacokinetics/Pharmacodynamics of Long-Acting Insulins in Humans: Relevance to Biosimilar Insulins
Authors: Francesca Porcellati, Paola Lucidi, Geremia B. Bolli, Carmine G. Fanelli
Journal: Diabetes Care (2015)

In this issue of Diabetes Care , Linnebjerg et al. (1) compare the pharmacokinetics (PK) and pharmacodynamics (PD) of a Lilly synthetized insulin glargine (LY IGlar) with the insulin glargine Lantus (IGlar) based on a series of clamp studies in healthy volunteers and conclude for PK/PD that there is similarity of the LY IGlar vs. IGlar. The strengths of the study should be discussed along with its limitations.

The strengths of the study are several. First, there are consistent rate ratios of geometric means of the several PK/PD parameters of LY IGlar and IGlar examined, which are all close to 1.0, with the 90% CIs contained in the prespecified acceptance limits of 0.80–1.25. Second, there is an elevated number of subjects studied with the technique of euglycemic clamp ( N = 211) and the study design (randomized, double-blind, two-treatment, four periods, crossover) is strong. Third, the comparison between LY IGlar and IGlar is repeated twice (one time vs. European Union [EU]-approved IGlar, the other time vs. US-approved IGlar), and there is the unique comparison between EU-approved IGlar and US-approved IGlar. Of note, the authors not only demonstrate PK/PD similarity between LY IGlar and IGlar but also originally prove the intraindividual similarity (reproducibility) of different batches of IGlar (EU- and US-approved IGlar both originate from the same manufacturer, Sanofi in Frankfurt, Germany).

The limitations of the study by Linnebjerg et al. (1) derive from study design and population studied. The conclusions are correct in the specific conditions examined in this study, i.e., normal volunteers without diabetes, a single insulin injection, a dose of 0.5 units/kg (supra-therapeutic, at least for subjects with type 1 diabetes [T1D]), and an insulin dose given in the morning. It is our opinion that one should be cautious regarding the results when extrapolating to the general population of …
Response to Open Peer Commentaries on “Bioethical Considerations in Translational Research: Primate Stroke”
Authors: Michael E. Sughrue, J. Mocco, Willam J. Mack, Andrew F. Ducruet, Ricardo J. Komotar, Ruth L. Fischbach, Thomas E. Martin, E. Sander Connolly
Journal: The American Journal of Bioethics (2009)
WHO’s role in Ebola crisis is criticised by all sides
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Clinicians, a government minister, and public health experts have all criticised the World Health Organization during a parliamentary evidence session on its handling of the recent Ebola virus outbreak in west Africa.

MPs on the House of Commons Science and Technology Committee heard from various witnesses that WHO had failed to act quickly enough and had “actively downplayed” the scale of the problem initially, leading to more deaths.

The criticisms came during an evidence session for the committee’s inquiry into science in emergencies and what lessons the United Kingdom could draw from the recent Ebola outbreak. The outbreak in west Africa, which began in late 2013 but was first reported in March 2014, led to the deaths of more than 11 000 people in Guinea, Liberia, and Sierra Leone.

MPs asked about a report published in …
Heritability and confirmation of genetic association studies for childhood asthma in twins
Authors: V. Ullemar, P. K. E. Magnusson, C. Lundholm, A. Zettergren, E. Melén, P. Lichtenstein, C. Almqvist
Journal: Allergy (2015)

Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases.In a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases.The heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8) ; other significant associations all below P = 3.5*10(-4) ). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6) ).Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.
A primary care pedometer-based walking intervention with and without practice nurse support: PACE-UP cluster-randomised controlled trial
Authors: Tess Harris, Sally M Kerry, Elizabeth Limb, Christina R Victor, Steve Iliffe, Sunil M Shah, Michael Ussher, Peter Whincup, Ulf Ekelund, Julia Fox-Rushby, Judith Ibison, Stephen DeWilde, Lee David, Cheryl Furness, Emma Howard, Rebecca Dale, Jaime Smith, Derek G Cook
Journal: The Lancet (2015)