tbuckley/cabot-search huggingface dataset:
Peripheral airway findings in chronic obstructive pulmonary disease using an ultrathin bronchoscope
Authors: M. Kikawada, Y. Ichinose, D. Miyamoto, K. Minemura, M. Takasaki, K. Toyama
Journal: European Respiratory Journal (2000)

The authors performed bronchoscopic examination using an ultrathin bronchoscope to determine the characteristics of the peripheral airways in chronic obstructive pulmonary disease (COPD). The study population comprised 13 healthy control subjects, 10 patients with chronic bronchitis without airflow limitation, and 20 patients with COPD. The COPD patients were divided clinically into 10 with chronic bronchitis and 10 with pulmonary emphysema. The peripheral airways were examined using an ultrathin bronchoscope. In chronic bronchitis, peripheral airways of the 11th or 12th generation showed a high frequency of obstruction and mucosal changes such as granulation. In pulmonary emphysema, the peripheral airways frequently showed a net-like appearance of the bronchial epithelium and obstruction at the 11th or 12th generation. Morphological changes of the small airways in chronic obstructive pulmonary disease can be detected by an ultrathin bronchoscope, and this method is likely to be useful for investigating the small airways in vivo.
Ceramide-1-phosphate attenuates cigarette smoke induce lung inflammation
Authors: Kristin Baudiß, Sanja Cicko, Korcan Ayata, Marco Idzko
Journal: European Respiratory Journal (2013)

Introduction:  Sphingolipids are playing an essential role in normal cell und tissue homeostasis as well as in the development and progress of various diseases and disorders. The central molecule in the sphingolipid metabolism is ceramide, which can be converted into Shingosine-1-Phosphate (S1P) and Ceramide-1-Phosphate (C1P). While the role of S1P in the pathogenesis of airway inflammation has been extensively studied, little is known about C1P.   Aim:  To elucidate the role of C1P in the pathogenesis of cigarette smoke (CS)-induced lung inflammation and lung emphysema in mice.   Methods:  An acute and chronic cigarette smoke induced lung inflammation model in C57/BL6 mice (6-8 weeks old) were used. BALF was collected and the distribution of different cells analysed by flow cytometer. The cytokine content in BAL fluid was measured by Elisa. The internal surface area of the lung was calculated. Parametric test were applied for statistical analysis.   Results:  Intrapulmonary application of C1P suppressed airway inflammation of acute and chronic CS-induced mice models in vivo. C1P significantly reduced inflammatory cell numbers (p   Conclusion:  In summary, C1P reduces the development of lung emphysema in a chronic smoke model. Our results suggest that C1P may have a role in limiting CS-induced lung inflammation and lung emphysema.
Mortality Results from a Randomized Prostate-Cancer Screening Trial
Authors: Gerald L. Andriole, E. David Crawford, Robert L. Grubb, Saundra S. Buys, David Chia, Timothy R. Church, Mona N. Fouad, Edward P. Gelmann, Paul A. Kvale, Douglas J. Reding, Joel L. Weissfeld, Lance A. Yokochi, Barbara O'Brien, Jonathan D. Clapp, Joshua M. Rathmell, Thomas L. Riley, Richard B. Hayes, Barnett S. Kramer, Grant Izmirlian, Anthony B. Miller, Paul F. Pinsky, Philip C. Prorok, John K. Gohagan, Christine D. Berg
Journal: New England Journal of Medicine (2009)

The effect of screening with prostate-specific–antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality.
Psoriasis and the risk of incident diabetes mellitus: a population-based study
Authors: Y.B. Brauchli, S.S. Jick, C.R. Meier
Journal: British Journal of Dermatology (2008)

Cross-sectional studies, mostly in hospitalized patients, reported a possible positive association between psoriasis and diabetes mellitus (DM). However, information on the temporal relation is scarce, and incidence rates of new-onset DM in patients with psoriasis are lacking.To assess and compare incidence rates of new-onset DM between patients with psoriasis and a comparison group without psoriasis, and to explore the role of psoriasis severity and body mass index (BMI).We conducted a follow-up study with a nested case-control analysis within the U.K.-based General Practice Research Database. The study population consisted of patients with a first-time diagnosis of psoriasis between 1994 and 2005 and a matched group of psoriasis-free patients. We used psoriasis duration and treatment as proxy for disease severity, and we applied conditional logistic regression to obtain odds ratios (ORs) with 95% confidence intervals (CIs).Within the study population of 65 449 patients we identified 1061 incident cases of DM. Of these, 59% had a history of psoriasis, yielding a crude incidence rate ratio of 1.36 (95% CI 1.20-1.53). The adjusted OR for patients with >or=2 years disease duration and >2 prescriptions per year for oral psoriasis treatment was 2.56 (95% CI 1.11-5.92). In an analysis restricted to patients with normal BMI, the adjusted OR was 2.02 (95% CI 1.31-3.10).In this large observational study the risk of incident DM was increased for patients with psoriasis as compared with a psoriasis-free comparison group. The risk increased with psoriasis duration and severity and was not driven by high BMI alone.
Subcellular Localization of p27kip1 Expression Predicts Poor Prognosis in Human Ovarian Cancer
Authors: Daniel G. Rosen, Gong Yang, Kathy Qi Cai, Robert C. Bast, David M. Gershenson, Elvio G. Silva, Jinsong Liu
Journal: Clinical Cancer Research (2005)

The cyclin-dependent kinase inhibitor p27(kip1) regulates cellular progression from G(1) to S phase. Several studies have shown that loss of p27(kip1) protein expression is associated with disease progression in various malignancies. The purpose of this study was to evaluate the subcellular localization of this cyclin-dependent kinase inhibitor in a large cohort of primary ovarian carcinomas and compare the results with clinicopathologic variables and overall survival.Subcellular localization of p27(kip1) was first assessed by Western blotting in nuclear and cytoplasmic extract from 13 cases of ovarian carcinoma. Subcellular localization of the p27(kip1) protein was evaluated using tissue microarrays containing 421 cases of ovarian carcinoma.The presence of p27(kip1) in the cytoplasm regardless of the nuclear stain correlated strongly with late-stage disease (P < 0.03), extent of cytoreduction (P = 0.03), and shorter disease-specific survival (P < 0.0001).Cytoplasmic localization of p27(kip1) predicts poorer prognosis in ovarian carcinoma, particularly in late-stage disease.
Plasminogen activator secreted by cultured human melanocytes
Authors: K. HASHIMOTO, T. HORIKOSHI, K. NISHIOKA, K. YOSHIKAWA, D.M. CARTER
Journal: British Journal of Dermatology (1986)

A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator.
Sodium-lithium exchange and sodium-proton exchange are mediated by the same transport system in sarcolemmal vesicles from bovine superior mesenteric artery.
Authors: A M Kahn, J C Allen, E J Cragoe, H Shelat
Journal: Circulation Research (1989)

Several laboratories have reported that Na+-Li+ countertransport activities are increased in red blood cells from patients with essential hypertension. It has been proposed that the activity of this red blood cell transport system might reflect the activity of a similar system in vascular smooth muscle. We previously demonstrated Na+-Li+ exchange in sarcolemmal vesicles from canine artery and proposed that this transport function might be mediated by the Na+-H+ exchanger. In the present studies, however, we were unable to demonstrate Na+-Li+ countertransport in canine red blood cells. Since bovine red blood cells have a vigorous Na+-Li+ exchanger and we previously demonstrated Na+-H+ exchange in sarcolemmal vesicles from bovine artery, we wished to determine whether bovine sarcolemmal vesicles mediate Na+-Li+ exchange and whether this transport function is mediated via the Na+-H+ exchanger. We found that an outwardly directed proton or Li+ gradient stimulated 22Na+ uptake in sarcolemmal vesicles from bovine superior mesenteric artery. Li+ gradient-stimulated Na+ uptake was not due to electrical coupling between the two ions, was not affected by a change in membrane potential, and could not be explained by the parallel operation of Li+-H+ and Na+-H+ exchange. External Li+ inhibited proton gradient-stimulated Na+ uptake, and external protons inhibited Li+ gradient-stimulated Na+ uptake. Na+ efflux from vesicles was stimulated by inwardly directed gradients for Li+ or protons, and these effects were not additive. Proton efflux from vesicles was stimulated by inwardly directed gradients for Na+ or Li+, and these effects were not additive. Finally, Na+-H+ exchange and Na+-Li+ exchange in sarcolemmal vesicles were inhibited by 5-(N-ethyl-N-isopropyl)amiloride in an identical dose-dependent manner. In conclusion, Na+-Li+ countertransport could not be demonstrated in canine red blood cells, but as is the case with bovine red blood cells, sarcolemmal vesicles from bovine artery mediate Na+-Li+ countertransport. This transport function and sarcolemmal Na+-H+ exchange are mediated via a single 5-(N-ethyl-N-isopropyl)amiloride-sensitive cation exchanger with affinity for Na+, Li+, and protons. The cow, as opposed to the dog, may be a good animal model to test whether the activity of red blood cell Na+-Li+ countertransport is predictive of the activity of Na+-Li+ (and Na+-H+) exchange in vascular smooth muscle.
In Autoimmune Diabetes the Transition from Benign to Pernicious Insulitis Requires an Islet Cell Response to Tumor Necrosis Factor α
Authors: Syamasundar V. Pakala, Marylee Chivetta, Colleen B. Kelly, Jonathan D. Katz
Journal: The Journal of Experimental Medicine (1999)

The islet-infiltrating and disease-causing leukocytes that are a hallmark of insulin-dependent diabetes mellitus produce and respond to a set of cytokine molecules. Of these, interleukin 1β, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ are perhaps the most important. However, as pleiotropic molecules, they can impact the path leading to β cell apoptosis and diabetes at multiple points. To understand how these cytokines influence both the formative and effector phases of insulitis, it is critical to determine their effects on the assorted cell types comprising the lesion: the effector T cells, antigen-presenting cells, vascular endothelium, and target islet tissue. Here, we report using nonobese diabetic chimeric mice harboring islets deficient in specific cytokine receptors or cytokine-induced effector molecules to assess how these compartmentalized loss-of-function mutations alter the events leading to diabetes. We found that islets deficient in Fas, IFN-γ receptor, or inducible nitric oxide synthase had normal diabetes development; however, the specific lack of TNF- α receptor 1 (p55) afforded islets a profound protection from disease by altering the ability of islet-reactive, CD4+ T cells to establish insulitis and subsequently destroy islet β cells. These results argue that islet cells play a TNF-α–dependent role in their own demise.
A volume-independent component to postdiuretic sodium retention in humans.
Authors: K Almeshari, N G Ahlstrom, F E Capraro, C S Wilcox
Journal: Journal of the American Society of Nephrology (1993)

Net sodium (Na) loss during diuretic administration is limited by postdiuretic renal salt retention. This could be a homeostatic response to extracellular fluid volume (ECV) depletion. However, rats infused with loop diuretics develop structural and functional adaptations in the distal nephron that enhance NaCl reabsorption. Therefore, the hypothesis that postdiuretic Na retention in humans contains a volume-independent component was tested. Normal volunteers were equilibrated to a 120 mmol/24 h Na intake. For the first protocol, subjects received, in random order, a placebo, bumetanide (B), or bumetanide accompanied by an infusion of an electrolyte solution at a rate adjusted to match urine flow and thereby to obviate Na losses (bumetanide plus volume replacement; B + VR). After the completion of B diuresis, there was a positive Na balance that restored 70% of the Na loss within 42 h. However, this positive Na balance was prevented by volume replacement (B + VR). For the second protocol, subjects received, in random order, a placebo injection and a 100-mmol NaCl load (P + NaCl) or a bumetanide injection plus volume replacement in addition to a 100-mmol NaCl load (B + VR + NaCl). Over the ensuing 42 h, 94% of the load was eliminated when it was infused alone (P + NaCl). In contrast, only 9% was eliminated when it was given with bumetanide and volume replacement (B + VR + NaCl). It was concluded that postdiuretic Na retention in normal human subjects is due both to ECV depletion and to volume-independent Na retention manifest as an inability to excrete a modest NaCl load.(ABSTRACT TRUNCATED AT 250 WORDS)
Is CRP a reliable diagnostic tool for infective exacerbations of COPD
Authors: Numbere Numbere, Milan Bhattacharya, Ajikumar Kavidasan
Journal: European Respiratory Journal (2013)

CRP, a marker of infection and inflammation, is often used to help type COPD exacerbations as infective or non-infective and so decide need for sputum cultures and antibiotics. This is more so if other signs of infection e.g. fever, sputum purulence are absent.  Bacterial growth from sputum reflects infection or colonisation and can greatly alter immediate and long-term management of COPD patients.  We looked at how predictive CRP levels are of bacterial growth from sputum culture in patients admitted to a district hospital with COPD exacerbations. We posed 2 questions:  1. Is there a difference in CRP between positive and negative sputum groups?  2. Is a particular CRP level predictive of positive sputum culture?  METHOD  We cross-referenced positive sputum cultures from 2008 to 2010 with discharges from the same time coded with keywords “COPD”, “exacerbation”. Only patients with CRP levels and sputum sent within 24 hours of admission were included.  RESULTS  We found 122 cases: 79 male, 43 female, mean age 70.8 years. 67 / 122 had positive sputum cultures. Though the sputum positive CRP mean was higher, we found no significant difference between the groups: mean CRP for sputum positives was 89.6 (CI 62.4 - 116.7) and for sputum negatives 70.6 (CI 49.1 - 92.1); P = 0.29.  With CRP at 100 as a screen, sensitivity for positive sputum was 28.4%, specificity 72.7%, positive predictive value (PPV) 55.9% and negative predictive value (NPV) 45.5%. With a CRP of 50, sensitivity was 50%, specificity 58.2%, PPV 58.9% and NPV 49.2%.  CONCLUSION  We contend that CRP is not a reliable predictor of sputum positivity in COPD exacerbations and so there must be more reliance on clinical findings to decide need for sputum cultures and antibiotics.
Microparticles and vascular dysfunction in obstructive sleep apnoea
Authors: Wojciech Trzepizur, Maria Carmen Martinez, Pascaline Priou, Ramaroson Andriantsitohaina, Frédéric Gagnadoux
Journal: European Respiratory Journal (2014)

Obstructive sleep apnoea (OSA) is independently associated with various cardiovascular diseases, including myocardial infarction and stroke. OSA may promote atherosclerosis risk factors such as hypertension, diabetes and dyslipidaemia, and may have direct proatherogenic effects on the vascular wall. A growing number of studies have recently focused on the role of microparticles (MPs) in the atherogenic process. MPs are small plasma membrane vesicles that can be released by a variety of vascular or blood cells, and contain both membrane and cytosolic elements. Case–control studies have shown that platelet-, endothelium- and leukocyte-derived MP levels are increased in OSA. Experimental evidence has demonstrated that MPs from OSA patients induce endothelial dysfunction, inflammation and vascular hyperreactivity when injected into mice. In this review, we provide an overview of the main characteristics of MPs, their expression in OSA and their potential role in the atherogenic process associated with OSA.
Impaired Glycemia and Diabetic Polyneuropathy
Authors: Peter J. Dyck, Vicki M. Clark, Carol J. Overland, Jenny L. Davies, John M. Pach, P. James B. Dyck, Christopher J. Klein, Robert A. Rizza, L. Joseph Melton, Rickey E. Carter, Ronald Klein, William J. Litchy
Journal: Diabetes Care (2012)

OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.
Anomalous Origin of the Left Coronary Artery from the Pulmonary Trunk
Authors: HADWIG WESSELHOEFT, J. S. FAWCETT, ARNOLD L. JOHNSON
Journal: Circulation (1968)

The congenital anomaly in which the left coronary artery arises from the main pulmonary artery is infrequent, but lethal, and since it can be alleviated surgically, its recognition and hemodynamic consequences are important. On the basis of 140 reported cases and our seven cases, it seems to present in one of four ways: (1) in infancy with angina-like symptoms or as cardiomyopathy, and later (2) as mitral insufficiency, (3) continuous murmur, or in adults (4) by sudden death. Visualization of the coronary arteries provides the definitive diagnosis, and the problem is the selection for this procedure. The electrocardiogram, the most helpful laboratory aid, is diagnostic of infarction in 80% of the infant group; in the remainder other forms of cardiomyopathy may be confused. Although blood flows directly into the pulmonary artery in the majority of cases, it flows in the reverse direction in a few and this must be determined preoperatively. Some unanswered questions are the subject of discussion: Why the majority of infants have onset of symptoms at about 8 weeks of age, and why some survive to childhood and adult life. The pathological findings are reviewed. Although the greatest surgical therapy experience has been with obliteration of the anomalous left coronary artery (ALCA) at its connection with the pulmonary artery, anastomosis between aorta and ALCA provides an additive supply for both the present and the future.
Death Certificate Completion by Physicians
Authors: John M. Hoffer
Journal: JAMA (1996)

To the Editor.  —Surely Drs Messite and Stellman1are jesting when they suggest a new medical school course in how to fill out  certificate forms. Fifty years ago when I began medical school, the department of medicine taught me the etiology, sequences, and sequelae of diseases, and the department of pathology demonstrated this graphically at the autopsy table. Even though autopsy rates are not as high today as 50 years ago, I assume the modern-day medical student does spend some time at the side of the autopsy table and does read autopsy reports, which by tradition and protocol are finalized with cause of death written in the same manner as is required on most  certificates. I also assume that clinical pathological conferences and morbidity and mortality conferences are attended at many teaching hospitals. In these educational conferences, the diagnosis is arrived at by the process of medical
Hypertrophic osteoarthropathy associated with gastrointestinal stromal tumour
Authors: L Silva
Journal: Annals of the Rheumatic Diseases (2006)

Hypertrophic osteoarthropathy (HOA) is a condition characterised by digital clubbing, polyarthralgias, periostosis, occasionally arthritis,1,2 and cutaneous signs of autonomic disorders (sweating, flushing, blanching).3 HOA is classified as either primary (hereditary or occasionally idiopathic in adults) or secondary (often associated with neoplastic or infectious diseases).4 In the industrialised world, 90% of cases are associated with an underlying malignancy, usually a pulmonary neoplasm,1 but also cardiovascular and gastrointestinal diseases.4 Here, we describe the case of a patient presenting with HOA as the first manifestation of a gastrointestinal stromal tumour (GIST).

A 47 year old white man consulted the rheumatologist in January 2005 with a 2 month history of fatigue and bilateral ankle and knee arthritis. Physical examination was normal, except for arthritis in knees and ankles. Blood and urine routine …
Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury
Authors: Yu-Chin Lien, Teresa Noel, Hua Liu, Arnold J. Stromberg, Kuey-Chu Chen, Daret K. St. Clair
Journal: Cancer Research (2006)

Abstract The clinical application of adriamycin, an exceptionally good chemotherapeutic agent, is limited by its dose-related cardiomyopathy. Our recent study showed that tumor necrosis factor-α (TNF-α) receptors mediated cytoprotective signaling against adriamycin-induced mitochondrial injury and cardiomyocyte apoptosis. In the present study, we investigated the potential targets of TNF receptor–mediated cytoprotective signaling by global genome microarray analysis using wild-type and TNF receptor–deficient mice. Microarray analysis revealed that adriamycin treatment induced the down-regulation of several mitochondrial functions and energy production–related genes in double TNF receptor–deficient mice, notably, phospholipase C-δ1, a protein involved in fatty acid metabolism and calcium regulation. The role of phospholipase C-δ1 in TNF receptor–mediated cardioprotection against adriamycin-induced injury was evaluated by measuring changes in cardiac function using high-frequency ultrasound biomicroscopy. Selective inhibition of phospholipase C activity in wild-type mice by its inhibitor, U73122, exacerbated adriamycin-induced cardiac dysfunction. Inhibition of phospholipase C-δ1 resulted in the significant decrease of left ventricular ejection fraction and fractional shortening, and the decreased levels were similar to those observed in adriamycin-treated double TNF receptor–deficient mice. The data derived from the global genome analysis identified phospholipase C-δ1 as an important target for TNF receptors and revealed the critical role of TNF receptor signaling in the protection against adriamycin-induced cardiotoxicity. (Cancer Res 2006; 66(8): 4329-38)