tbuckley/cabot-search huggingface dataset:
A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa.
Authors: B S Coller, E I Peerschke, L E Scudder, C A Sullivan
Journal: Journal of Clinical Investigation (1983)

To define better the role of the fibrinogen receptor in platelet physiology and to characterize it biochemically, a murine monoclonal antibody that completely blocks the binding of fibrinogen to the platelet surface was produced by the hybridoma technique with the aid of a functional screening assay. Purified F(ab')2 fragments and/or intact antibody completely blocked aggregation induced by ADP, thrombin, or epinephrine and the binding of radiolabeled fibrinogen to platelets induced by ADP. The antibody did not block agglutination of formaldehyde-fixed platelets by ristocetin or shape change induced by either ADP or thrombin. ADP- and epinephrine-induced release of ATP was completely inhibited by the antibody, but inhibition of release induced by collagen and thrombin was dose dependent and partial. The antibody also dramatically inhibited platelet retention in glass-bead columns, platelet adhesion to glass, and clot retraction. Thus, the antibody induced a thrombasthenic-like state. Immunofluorescent studies confirmed the specificity of the antibody for normal platelets and megakaryocytes and suggested that there is a marked decrease in detectable antigen in thrombasthenic platelets. Radiolabeled antibody bound to an average of approximately 40,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets of a patient with thrombasthenia. The antibody immunoprecipitated both glycoproteins IIb and IIIa, and both glycoproteins bound to an affinity column of the antibody. These studies indicate that there is probably a single anatomic site that is crucial to the binding of all fibrinogen molecules and that this site is most likely on the glycoprotein IIb/IIIa complex. It also suggests that the thrombasthenic phenotype can be completely accounted for on the basis of the inhibition of fibrinogen binding to platelets.
ROENTGEN RAY INTOXICATION
Authors: S. L. Warren, G. H. Whipple
Journal: The Journal of Experimental Medicine (1922)

Exposure to large doses of x-rays will cause notable increase in the speed of autolysis of the crypt or secretory epithelium of the dog's small intestine. These changes can be demonstrated readily in material obtained from dogs killed 2, 24, 48, 72, or 96 hours after the initial radiation (Text-figs. 1 and 2). In the radiated dogs the secretory crypt epithelium of the small intestine autolyzes first and the epithelium of the villi last, while the reverse is true in the normal control small intestine. These abnormalities of autolysis associated with lethal Roentgen ray exposures can be demonstrated for the small intestine over the whole 4 day period subsequent to radiation. The colon shows little change and the stomach no demonstrable changes in autolysis under like conditions. The kidney likewise is negative. The spleen, lymph glands, liver, and pancreas show a moderate increase in speed of autolysis in tissues taken from radiated animals within 48 hours of the initial exposure. What the significance of this disturbance of cell ferments in the intestinal mucosa may be, we cannot pretend to say. At least these observations strengthen one's confidence in the profound functional disturbance of this important intestinal epithelium-a disturbance which we believe is responsible for the clinical abnormalities and fatal intoxication.
Changes in airway resistance induced by nasal or oral intermittent positive pressure ventilation in normal individuals
Authors: P. Fontanari, H. Burnet, M.C. Zattara-Hartmann, M. Badier, Y. Jammes
Journal: European Respiratory Journal (1999)

Nasal intermittent positive-pressure ventilation (nIPPV) is used for the treatment of respiratory failure in patients with neuromuscular disease. The aim of the present study was to demonstrate that nIPPV may activate nose receptors, the consequence of which being reflex changes in lung resistance. The changes in interrupter resistances (Rint) in response to nIPPV were tested before and after local anaesthesia of the nasal mucosa in normal subjects. They were compared to the Rint changes induced by oral intermittent positive-pressure ventilation (oIPPV) in the same individuals. Rint was measured during 10-min periods of nIPPV or oIPPV at a constant rate (15 L x min(-1)), but at two different stroke volumes (0.8 and 1.2 L). Inspired temperature and relative humidity were held constant. nIPPV with 1.2 L (17 mL x kg(-1)) significantly increased the Rint value (+22%). This effect disappeared after nose anaesthesia or after inhalation of a cholinergic antagonist. oIPPV never changed Rint, even though the associated hypocapnia was present and more accentuated than during nIPPV. Adding CO2 to the inspired gas during nIPPV and oIPPV trials suppressed the Rint changes. The present study suggests the existence of a nasopulmonary bronchoconstrictor reflex elicited through the stimulation of nasal mechanoreceptors, their activity being markedly influenced by the changes in expired CO2 concentration.
Mitochondrial aldehyde dehydrogenase and cardiac diseases
Authors: Che-Hong Chen, Lihan Sun, Daria Mochly-Rosen
Journal: Cardiovascular Research (2010)

Numerous conditions promote oxidative stress, leading to the build-up of reactive aldehydes that cause cell damage and contribute to cardiac diseases. Aldehyde dehydrogenases (ALDHs) are important enzymes that eliminate toxic aldehydes by catalysing their oxidation to non-reactive acids. The review will discuss evidence indicating a role for a specific ALDH enzyme, the mitochondrial ALDH2, in combating oxidative stress by reducing the cellular 'aldehydic load'. Epidemiological studies in humans carrying an inactive ALDH2, genetic models in mice with altered ALDH2 levels, and small molecule activators of ALDH2 all highlight the role of ALDH2 in cardioprotection and suggest a promising new direction in cardiovascular research and the development of new treatments for cardiovascular diseases.
The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44
Authors: Can Liu, Kevin Kelnar, Bigang Liu, Xin Chen, Tammy Calhoun-Davis, Hangwen Li, Lubna Patrawala, Hong Yan, Collene Jeter, Sofia Honorio, Jason F Wiggins, Andreas G Bader, Randy Fagin, David Brown, Dean G Tang
Journal: Nature Medicine (2011)
CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens
Authors: Mariolina Salio, Michael J. Palmowski, Ann Atzberger, Ian F. Hermans, Vincenzo Cerundolo
Journal: The Journal of Experimental Medicine (2004)

Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor–deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-γ and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.
Simvastatin Lowers C-Reactive Protein Within 14 Days
Authors: Julie K. Plenge, Teri L. Hernandez, Kathleen M. Weil, Paul Poirier, Gary K. Grunwald, Santica M. Marcovina, Robert H. Eckel
Journal: Circulation (2002)

Background— The early response of C-reactive protein to initiation of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) is not known. The purpose of this study was to determine the rate at which highly sensitive C-reactive protein (hsCRP) levels change after initiation of simvastatin and whether this occurs independently of the change in LDL cholesterol. Methods and Results— The study was a crossover, double-blind design including 40 subjects with elevated LDL cholesterol. Subjects were randomly assigned to 1 of 2 groups: simvastatin 40 mg for 14 days, then placebo for 14 days, or placebo first, then simvastatin. Simvastatin decreased LDL cholesterol by 56±4 mg/dL ( P &lt;0.0001) at day 7 and by an additional 8±3 mg/dL ( P =0.02) at day 14. Baseline log(hsCRP) levels were similar in the 2 groups. By day 14, log(hsCRP) was significantly lower in patients on simvastatin when compared with placebo ( P =0.011). Although there was no significant difference in fibrinogen levels, simvastatin produced a modest increase in log[lipoprotein(a)] ( P =0.03) at days 7 and 14. There were no relationships between the decrease in LDL cholesterol and the decrease in hsCRP. Conclusions— Simvastatin lowers hsCRP by 14 days, independent of its effect on LDL cholesterol. This rapid impact of a statin on hsCRP has potential implications in the management of acute coronary syndromes.
Randomised controlled trial of transcutaneous electrical muscle stimulation of the lower extremities in patients with chronic obstructive pulmonary disease
Authors: G Bourjeily-Habr
Journal: Thorax (2002)

<b>Background:</b> Although exercise training improves exercise tolerance in most patients with chronic obstructive pulmonary disease (COPD), some patients with severe disease may not be able to tolerate exercise training due to incapacitating breathlessness. Transcutaneous electrical muscle stimulation (TCEMS) has been shown to improve muscle strength, muscle mass, and performance in paraplegics, patients with knee ligament injury, and patients with peripheral vascular disease. We hypothesised that TCEMS of the lower extremities can improve muscle strength and exercise tolerance in patients with moderate to severe COPD. <b>Methods:</b> A randomised controlled trial of TCEMS of the lower extremities was performed in 18 medically stable patients of mean (SD) age 60.0 (1.5) years with a mean forced expiratory volume in 1 second (FEV<sub>1</sub>) of 1.03 (0.10) l (38% predicted) and residual volume/total lung capacity (RV/TLC) of 59 (2)%. Stimulation of the lower extremities was performed three times a week, 20 minutes each session, for six continuous weeks. Quadriceps and hamstring muscle strength, exercise capacity, and peak oxygen uptake were measured at baseline and after 6 weeks of stimulation. <b>Results:</b> TCEMS improved both the quadriceps strength (by 39.0 (20.4)% <i>v</i> 9.0 (8.1)%, p=0.046) and hamstring muscle strength (by 33.9 (13.0)% <i>v</i> 2.9 (4.7)%, p=0.038) in the treated (n=9) and sham treated (n=9) groups, respectively. The improvement in muscle strength carried over to better performance in the shuttle walk test in the treated group (36.1% <i>v</i> 1.6% in the treated and sham groups respectively, p=0.007, Mann-Whitney U test). There was no significant change in lung function, peak workload, or peak oxygen consumption in either group. Muscle stimulation was well tolerated by the patients with no dropouts and better than 95% compliance with the protocol. <b>Conclusions:</b> TCEMS of peripheral muscles can be a useful adjunct to the comprehensive pulmonary rehabilitation of patients with COPD.
Clinical Breast Examination: Practical Recommendations for Optimizing Performance and Reporting
Authors: D. Saslow, J. Hannan, J. Osuch, M. H. Alciati, C. Baines, M. Barton, J. K. Bobo, C. Coleman, M. Dolan, G. Gaumer, D. Kopans, S. Kutner, D. S. Lane, H. Lawson, H. Meissner, C. Moorman, H. Pennypacker, P. Pierce, E. Sciandra, R. Smith, R. Coates
Journal: CA A Cancer Journal for Clinicians (2004)

Clinical breast examination (CBE) seeks to detect breast abnormalities or evaluate patient reports of symptoms to find palpable breast cancers at an earlier stage of progression. Treatment options for earlier-stage cancers are generally more numerous, include less toxic alternatives, and are usually more effective than treatments for later-stage cancers. For average-risk women aged 40 and younger, earlier detection of palpable tumors identified by CBE can lead to earlier therapy. After age 40, when mammography is recommended, CBE is regarded as an adjunct to mammography. Recent debate, however, has questioned the contributions of CBE to the detection of breast cancer in asymptomatic women and particularly to improved survival and reduced mortality rates. Clinicians remain widely divided about the level of evidence supporting CBE and their confidence in the examination. Yet, CBE is practiced extensively in the United States and continues to be recommended by many leading health organizations. It is in this context that this report provides a brief review of evidence for CBE's role in the earlier detection of breast cancer, highlights current practice issues, and presents recommendations that, when implemented, could contribute to greater standardization of the practice and reporting of CBE. These recommendations may also lead to improved evidence of the nature and extent of CBE's contribution to the earlier detection of breast cancer.
Alcohol in the Navy.
Authors: C. F. Stokes
Journal: JAMA (1907)

San Juan, Porto Rico, March 6, 1907. <h3>To the Editor:</h3> —The substance of your editorial on this subject inThe Journal, February 16, 1907, is so at variance with my experience that I can not let it go unchallenged, even though your deductions are drawn from the paper of my friend, Dr. Lovering. After a service of nearly twenty years, comprising duty on all stations and in many ships, I feel safe in saying that I know of no more generally abstemious class of men than naval officers, no type more keenly appreciative of their responsibilities, no type better qualified for their duties. Conscientiousness in the matter of duty is a characteristic of the service. When you see a naval officer, no matter what the conditions he is under, nor where he may be placed, you will find that he will ring true ninety-nine times out of a hundred. There
Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial
Authors: G. Mustacchi, R. Ceccherini, S. Milani, A. Pluchinotta, A. De Matteis, L. Maiorino, A. Farris, A. Scanni, F. Sasso
Journal: Annals of Oncology (2003)
Surface expression of Fc gamma receptor III (CD16) on chemoattractant-stimulated neutrophils is determined by both surface shedding and translocation from intracellular storage compartments.
Authors: M F Tosi, H Zakem
Journal: Journal of Clinical Investigation (1992)

Stimulation of neutrophils (PMN) with chemoattractants markedly increases surface expression of several membrane proteins, including the complement receptors, CR1 and CR3, by translocation from intracellular storage compartments to the cell surface. When we stimulated freshly-isolated PMN with FMLP, we observed little net change in surface Fc gamma receptor (R) III expression. However, if elastase was first used to cleave most (85-90%) of the Fc gamma R III from the PMN surface, subsequent treatment with FMLP induced a rapid renewal of surface Fc gamma R III, achieving levels of approximately 70% of that originally present on the cell surface after 15 min, suggesting translocation of intracellular receptors. This was confirmed by demonstrating concomitant depletion of greater than 80% of the intracellular Fc gamma R III. Studies of density gradient fractions of N2-cavitated PMN indicated at least two distinct intracellular membrane fractions that contain Fc gamma R III. Shedding of Fc gamma R III induced by FMLP was about half-maximal by 15 min and nearly complete by 60 min. Stoichiometric assessment of FMLP-induced changes in PMN surface and intracellular Fc gamma R III showed a marked depletion in intracellular Fc gamma R III, little net change in surface Fc gamma R III, and a large overall loss of total cell Fc gamma R III that could be attributed to shedding. We conclude that stimulation by chemoattractants causes a rapid translocation of intracellular Fc gamma R III to the PMN surface that is roughly balanced by the concomitant FMLP-induced shedding of this receptor.
In Vitro Growth Promotion of Human Mammary Carcinoma Cells by Steroid Hormones, Tamoxifen, and Prolactin23
Authors: Wolfgang E. Simon, Michael Albrecht, Günter Trams, Manfred Dietel, Fritz Hölzel
Journal: JNCI Journal of the National Cancer Institute (1984)

Journal Article In Vitro Growth Promotion of Human Mammary Carcinoma Cells by Steroid Hormones, Tamoxifen, and Prolactin Get access Wolfgang E. Simon, Wolfgang E. Simon Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Albrecht, Michael Albrecht Search for other works by this author on: Oxford Academic PubMed Google Scholar Günter Trams, Günter Trams Search for other works by this author on: Oxford Academic PubMed Google Scholar Manfred Dietel, Manfred Dietel Search for other works by this author on: Oxford Academic PubMed Google Scholar Fritz Hölzel Fritz Hölzel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 73, Issue 2, August 1984, Pages 313–321, https://doi.org/10.1093/jnci/73.2.313 Published: 01 August 1984 Article history Received: 05 May 1983 Revision received: 13 March 1984 Accepted: 23 March 1984 Published: 01 August 1984
The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-α
Authors: Shu Zhu, Wen Pan, Xinyang Song, Yan Liu, Xinrui Shao, Yuanjia Tang, Dong Liang, Dongyi He, Honglin Wang, Wenjun Liu, Yufang Shi, John B Harley, Nan Shen, Youcun Qian
Journal: Nature Medicine (2012)
Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease
Authors: Juan F. Navarro-González, Carmen Mora-Fernández, Mercedes Muros de Fuentes, Jesús Chahin, María L. Méndez, Eduardo Gallego, Manuel Macía, Nieves del Castillo, Antonio Rivero, María A. Getino, Patricia García, Ana Jarque, Javier García
Journal: Journal of the American Society of Nephrology (2014)

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3–4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m2 in the PTF group compared with 6.5±0.4 ml/min per 1.73 m2 in the control group, with a between-group difference of 4.3 ml/min per 1.73 m2 (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m2; P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m2 per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, −0.3% to 11.1%) in the control group and −14.9% (95% CI, −20.4% to −9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11–20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2–18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.
Cystine Deficiency and Cholesterol Metabolism in Primates
Authors: George V. Mann
Journal: Circulation Research (1966)

Cebus and Rhesus monkeys suppress the in vivo production of cholesterol when fed cholesterol. This suppression is less than that observed in rats and it did not occur in Lagothrix monkeys. Cebus monkeys deficient in cystine lose their efficiency in removing cholesterol when the body pool is large. One result is an elevation of the plasma level of cholesterol.
Effects of beta-blockers on lung function in bronchial asthma patients
Authors: Olga Agapova, Ludmila Ratova, Badreddin Nazarov, Yuliya Dolgusheva, Irina Chazova, Kirill Zykov
Journal: European Respiratory Journal (2014)

Introduction 

Significant numbers of patients with bronchial asthma (BA) have cardiovascular diseases (CVD) which require beta-blockers (BB). It was shown, that the use of selective BB in selected patients is possible, however there is a high risk of side effects (bronchoobstruction).

Objective 

Evaluate the possibility of identifying of the patients with high risk of bronchoobstruction due to BB.

Methods 

23 patients (mean age 60,0±9,8 years) with BA and CVD were included in the study and received single dose selective BB (bisoprolol) 1.25 mg. The FEV1 and FVC were assessed initially, after 30, 90, 150, 240 min after BB and after 30 min of salbutamol 400 mcg.

Results 

Initially FEV1 was 85,8±13,7%, FVC 97,0±13,3% and didn't change significantly after 30, 90, 150 and 240 min (FEV1 was 88,5±13,3%; 87,3±11,8; 85,8±13,1; and 85,2±13,3% respectively). Minimal FEV1 in one patient was after 30 min, in 4 patients – after 90 min, in 4 patients – after 150 min and in 9 patients – after 240 min. In two patients after 240 min FEV1 decreased on 10% and 200 ml compared with initial FEV1. After use of salbutamol there was significant increase of FEV1.The FVC did not significantly change.

Conclusion 

Patients with BA and CVD had no significant decrease FEV1 after the single dose of bisoprolol 1.25 mg. But in some patients ΔFEV1 was -10% and 200 ml after 240 min after beta-blocker. This allows to recommend the 4-hours acute test with bisoprolol to select the patients with bronchoobstruction.
Induced Abortion, Bias, and Breast Cancer: Why Epidemiology Hasn't Reached Its Limit
Authors: D. L. Weed, B. S. Kramer
Journal: JNCI Journal of the National Cancer Institute (1996)

Once again we are faced with the difficult task of judging a body of epidemiologic evidence. The issue, induced abortion and breast cancer, is about as thorny as it gets in modern American medicine (7). For us, the task at hand is more a matter of separating statistical association from spurious coincidence than of separating causal associations from noncausal. Making these judgments in the face of considerable uncertainty and complexity is a serious matter, requiring prudence and the superimposition of qualitative methods on quantitative. And it is a necessary matter, underscoring the importance of epidemiology for public health and for the practice of medicine.
The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: A comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia
Authors: Ali Saklamaz, Abdurrahman Comlekci, Aysegul Temiz, Sezer Caliskan, Cengiz Ceylan, Ahmet Alacacioglu, Sena Yesil
Journal: Metabolism (2005)