tbuckley/cabot-search huggingface dataset:
Altered pulmonary microvascular reactivity to norepinephrine in canine pacing-induced heart failure.
Authors: M I Townsley, V H Pitts, J L Ardell, Z Zhao, W H Johnson
Journal: Circulation Research (1994)

Pulmonary hypertension in congestive heart failure causes medial hypertrophy in pulmonary vessels and thickening of the endothelial basement membrane. In this study, the functional consequences of such pulmonary vascular adaptations were evaluated. Heart failure was induced in dogs by rapid ventricular pacing (240 beats per minute) for 28 days, at which time left ventricular shortening fraction was decreased by 57% compared with that at baseline. Lung lobes from paced (n = 56) and control dogs (n = 68) were isolated and perfused with autologous blood. Total, arterial (Ra), and venous (Rv) vascular resistances were significantly increased and vascular capacitance decreased in lobes from paced animals compared with controls. Increments in Ra and Rv after intra-arterial boluses of norepinephrine were measured before and after sequential addition of the alpha 1- and alpha 2-receptor antagonists prazosin (16 mumol/L) and yohimbine (0.1 mumol/L) in the presence or absence of propranolol (5 mumol/L). Norepinephrine (1 to 40 micrograms) had little effect on Ra in the absence of propranolol, a pattern that persisted in control lobes after propranolol. However, when lobes from paced animals were pretreated with propranolol, norepinephrine increased Ra, Rv was increased after norepinephrine in control lobes, an effect that was enhanced in the paced group. In both groups, the increment in Rv was greater after propranolol. Irrespective of propranolol pretreatment, prazosin significantly attenuated, if not abolished, the response to norepinephrine. The enhancement in venous vascular reactivity in lobes from paced animals remained when venous pressure was elevated to 20 cm H2O. In control lobes under conditions of elevated tone or when endothelium-dependent relaxing factor was blocked, responses to norepinephrine did not mimic those observed in the paced group. Microvascular permeability, as measured by the capillary filtration coefficient, was not altered in the paced group. We conclude that the pulmonary adaptations to 4 weeks of rapid ventricular pacing include functional changes in pulmonary hemodynamics and vascular reactivity but not in microvascular permeability.
Inhaled fluticasone in bronchiectasis: a 12 month study
Authors: K W Tsang
Journal: Thorax (2005)

The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation.After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion.35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency </=2/year (p = 0.04), and sputum purulence score >5 (p = 0.03).ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.
Recurrent Comas Due to Secret Self-Administration of Insulin in Adolescents With Type 1 Diabetes
Authors: Pascal Boileau, Brigitte Aboumrad, Pierre Bougnères
Journal: Diabetes Care (2006)

The incidence of severe hypoglycemia ranges from 0.02 to 0.07 per patient-month in a large series of adolescents with type 1 diabetes (1–4). Parents and physicians usually attribute these hypoglycemic accidents to mistakes in the management of diabetes: excessive insulin dosage, unusual exercise, meal omission, etc. In one-third of these episodes, however, the circumstances of hypoglycemia remain unclear (5,6). The fear of recurrence usually prompts the patient or his parents to decrease insulin doses and increase glucose monitoring (7). In few cases, however, severe hypoglycemia repeats, leading physicians to search for an organic cause. These investigations are almost always negative. Because lack of compliance is frequent among adolescents, we hypothesized that recurrent comas could be due to self-administration of insulin of which parents and physicians are not aware, a cause that has received little attention in literature (8–10) but carries a high risk of medical and judicial errors, morbidity, or even mortality.

Since 1990, we investigated 322 cases of recurring hypoglycemic comas in 149 adolescents with type 1 diabetes. All went through careful interviews and medical examinations. Plasma …
Cah or Sle?
Authors: B. Leggett, R. Collins, R. Prentice, L. W. Powell, Lawrence E. Gurian, Thomas M. Rogoff, Athol J. Ware, Burton Combes
Journal: Hepatology (1986)

real.The opposing point of view championed by Morgan et al. yields KZs/Ko = L Y ~/ C Y ~~ = 5.7 (6.3 -4.1) for both models.This last result is free of the numerical uncertainty inherent in computing 1 -E from values of E that are close to 1.The model assumptions outlined above predict that K2s/K0 = 1.The "lumped" analysis yields data that include this prediction but that can neither confirm or deny it.If we choose the "distributed model or accept Morgan's claim that E is independent of CY, on the other hand, we must conclude that at least one of the underlying assumptions is false.But which one?Do cul-acid glycoprotein-propranolol complexes participate in cell surface-mediated dissociation?Are the binding reactions between propranolol and LY, -acid glycoprotein and between propranolol and erythrocytes fast enough to be considered at equilibrium during propranolol uptake?Could propranolol-protein complexes have been removed intact?Is the uptake of free propranolol truly first order?These questions envision possible explanations for the finding that no matter which model we choose, the best, albeit uncertain, estimate of K25/K0 is at least twice the predicted value.Others bear importantly on the interpretation of the actual magnitude of KZs/Ko.Does the binding of propranolol meet the distributed model requirement for first-order binding?To what extent do differences in the interstitial diffusion of nl-acid glyco-protein and free propranolol distort one's estimate of K,,/K,?What is the role of erythrocyte-propranolol complexes?All of these queries are answerable in principle.In one way or another, all of them have been answered in studies of' how binding to albumin influences the uptake of other ligands ( 1-4).For propranolol and al-acid glycoprotein, however, none of them appear answerable from the data at hand.
Cyclooxygenase-2-Dependent Expression of Angiogenic CXC Chemokines ENA-78/CXC Ligand (CXCL) 5 and Interleukin-8/CXCL8 in Human Non-Small Cell Lung Cancer
Authors: Mehis Põld, Li X. Zhu, Sherven Sharma, Marie D. Burdick, Ying Lin, Peter P. N. Lee, Anu Põld, Jie Luo, Kostyantyn Krysan, Mariam Dohadwala, Jenny T. Mao, Raj K. Batra, Robert M. Strieter, Steven M. Dubinett
Journal: Cancer Research (2004)

Abstract Elevated tumor cyclooxygenase (COX)-2 activity plays a multifaceted role in non-small cell lung cancer (NSCLC). To elucidate the role of COX-2 in the in vitro and in vivo expression of two known NSCLC angiogenic peptides, CXC ligand (CXCL) 8 and CXCL5, we studied two COX-2 gene-modified NSCLC cell lines, A549 and H157. COX-2 overexpression enhanced the in vitro expression of both CXCL8 and CXCL5. In contrast, specific COX-2 inhibition decreased the production of both peptides as well as nuclear translocation of nuclear factor κB. In a severe combined immunodeficient mouse model of human NSCLC, the enhanced tumor growth of COX-2-overexpressing tumors was inhibited by neutralizing anti-CXCL5 and anti-CXCL8 antisera. We conclude that COX-2 contributes to the progression of NSCLC tumorigenesis by enhancing the expression of angiogenic chemokines CXCL8 and CXCL5.
Outcomes of Older Patients Receiving Chronic Dialysis
Authors: A. Peter Lundin
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Two articles in<i>JAMA</i>would have untutored readers believe that the low functional status and high death rate occurring in elderly dialysis patients resulted solely from dialysis treatment.<sup>1,2</sup>Those more knowledgeable will note instead the absence of data on other factors that could have led to the same result. The authors may be reporting things as they appear to be but not as they can or should be. Readers are given no indication of the level of dialysis efficiency provided for the patients studied. Underdialyzed patients are chronically uremic; complications of uremia include weakness and premature death. It is striking that the authors, reviewers, and editors have overlooked the need to report on the adequacy of the dialysis treatments, especially since evidence is available that a majority of hemodialysis patients in the United States have been receiving less than minimal treatment and may be dying as
Deficiency in neuronal TGF-β signaling promotes neurodegeneration and Alzheimer’s pathology
Authors: Ina Tesseur, Kun Zou, Luke Esposito, Frederique Bard, Elisabeth Berber, Judith Van Can, Amy H. Lin, Leslie Crews, Patrick Tremblay, Paul Mathews, Lennart Mucke, Eliezer Masliah, Tony Wyss-Coray
Journal: Journal of Clinical Investigation (2006)

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration and cerebral accumulation of the β-amyloid peptide (Aβ), but it is unknown what makes neurons susceptible to degeneration. We report that the TGF-β type II receptor (TβRII) is mainly expressed by neurons, and that TβRII levels are reduced in human AD brain and correlate with pathological hallmarks of the disease. Reducing neuronal TGF-β signaling in mice resulted in age-dependent neurodegeneration and promoted Aβ accumulation and dendritic loss in a mouse model of AD. In cultured cells, reduced TGF-β signaling caused neuronal degeneration and resulted in increased levels of secreted Aβ and β-secretase–cleaved soluble amyloid precursor protein. These results show that reduced neuronal TGF-β signaling increases age-dependent neurodegeneration and AD-like disease in vivo. Increasing neuronal TGF-β signaling may thus reduce neurodegeneration and be beneficial in AD.
Quality of Life Following Localized Prostate Cancer Treated Initially with Androgen Deprivation Therapy or No Therapy
Authors: Arnold L Potosky, Bryce B Reeve, Limin X Clegg, Richard M Hoffman, Robert A Stephenson, Peter C Albertsen, Frank D Gilliland, Janet L Stanford
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Many men diagnosed with clinically localized prostate cancer are initially treated conservatively, receiving neither surgery nor radiotherapy for the first year. Treatment patterns and quality-of-life outcomes have not been previously reported for a population-based sample of such men. Methods: A population-based random sample of men (n = 661) from six geographic regions who had been newly diagnosed with clinically localized prostate cancer from 1994 through 1995 were followed for up to 1 year. Eligible subjects received neither surgery nor radiotherapy within 1 year of initial diagnosis. We assessed disease-specific and generic quality-of-life outcomes in men receiving androgen deprivation therapy (ADT) compared with men receiving no therapy. All statistical tests were two-sided. Results: Two hundred and forty-five study patients received ADT and the remaining 416 patients received no therapy. Approximately two thirds of the patients (n = 159) receiving ADT had either baseline Gleason scores greater than six or serum prostate-specific antigen values above 20 ng/mL. Among men who were sexually potent before diagnosis (ADT = 88 patients; no therapy = 223 patients), 80% of those on ADT reported being impotent after 1 year compared with 30% of those receiving no treatment (P < .001). Patients receiving ADT reported more physical discomfort 1 year after diagnosis than did men who had received no therapy. However, patients receiving ADT, compared with those receiving no therapy, were more likely to be satisfied with their treatment decision (56% pleased versus 45.3%; P = .001). Patients on ADT also experienced a statistically significant decline in vitality, but not in physical function, after adjustment for the confounding factors (P = .05). Conclusion: ADT is a commonly used primary therapy for clinically localized prostate cancer. Therefore, men considering ADT as an initial treatment should be aware that sexual function and some aspects of physical well-being are likely to be affected in the first year following this treatment.
Skewed balance in basal expression and regulation of activating v inhibitory Fcgamma receptors in macrophages of collagen induced arthritis sensitive mice
Authors: A B Blom
Journal: Annals of the Rheumatic Diseases (2003)

Recently, it has been found that collagen type II arthritis susceptible mouse strains are hyperreactive to immune complexes (ICs), locally deposited into their knee joints.To investigate whether this strain specific knee joint hyperreactivity is related to a disturbed regulation of activatory and inhibitory FcgammaR on their macrophages before and after stimulation with ICs.Macrophages from collagen induced arthritis susceptible strains (DBA/1 and B10.RIII) and non-susceptible strains (C57BL/6 and BALB/c) were compared. FcgammaR levels on macrophages were detected at protein level by flow cytometric analysis and at mRNA level by reverse transcriptase-polymerase chain reaction. Macrophages were stimulated with ICs, and production of cytokines and enzymes was measured at different times.On synovial and peritoneal macrophages of DBA/1 mice a higher basal FcgammaRII and III expression was found, which was skewed towards the activating FcgammaRIII. In B10.RIII macrophages, however, FcgammaRIII levels were much lower. Regulation of FcgammaR mRNA levels in macrophages was tested after stimulation with ICs for one and three days. DBA/1 and B10.RIII macrophages showed a prolonged up regulation of activating FcgammaRI and III, whereas the inhibiting FcgammaRII was significantly down regulated compared with non-susceptible strains. In line with this, DBA/1 and B10.RIII macrophages showed a higher interleukin 1 (IL1) and matrix metalloproteinase (MMP) production after IC exposure, whereas IL6 production was significantly reduced.This study indicates that macrophages derived from collagen type II arthritis susceptible mice show a disregulated FcgammaR expression before, and even more clearly, after activation by ICs involved in inflammation and cartilage degradation, resulting in prolonged expression of activatory FcgammaRI and III, down regulation of inhibitory FcgammaRII and increased release of IL1 and MMP.
Transcription analysis in the MeLiM swine model identifies RACK1 as a potential marker of malignancy for human melanocytic proliferation
Authors: Giorgia Egidy, Sophia Julé, Philippe Bossé, Florence Bernex, Claudine Geffrotin, Silvia Vincent-Naulleau, Vratislav Horak, Xavier Sastre-Garau, Jean-Jacques Panthier
Journal: Molecular Cancer (2008)

Metastatic melanoma is a severe disease. Few experimental animal models of metastatic melanoma exist. MeLiM minipigs exhibit spontaneous melanoma. Cutaneous and metastatic lesions are histologically similar to human's. However, most of them eventually spontaneously regress. Our purpose was to investigate whether the MeLiM model could reveal markers of malignancy in human melanocytic proliferations. We compared the serial analysis of gene expression (SAGE) between normal pig skin melanocytes and melanoma cells from an early pulmonary metastasis of MeLiM minipigs. Tag identification revealed 55 regulated genes, including GNB2L1 which was found upregulated in the melanoma library. In situ hybridisation confirmed GNB2L1 overexpression in MeLiM melanocytic lesions. GNB2L1 encodes the adaptor protein RACK1, recently shown to influence melanoma cell lines tumorigenicity. We studied the expression of RACK1 by immunofluorescence and confocal microscopy in tissues specimens of normal skin, in cutaneous and metastatic melanoma developped in MeLiM minipigs and in human patients. In pig and human samples, the results were similar. RACK1 protein was not detected in normal epidermal melanocytes. By contrast, RACK1 signal was highly increased in the cytoplasm of all melanocytic cells of superficial spreading melanoma, recurrent dermal lesions and metastatic melanoma. RACK1 partially colocalised with activated PKCαβ. In pig metastases, additional nuclear RACK1 did not associate to BDNF expression. In human nevi, the RACK1 signal was low. RACK1 overexpression detected in situ in human melanoma specimens characterized cutaneous and metastatic melanoma raising the possibility that RACK1 can be a potential marker of malignancy in human melanoma. The MeLiM strain provides a relevant model for exploring mechanisms of melanocytic malignant transformation in humans. This study may contribute to a better understanding of melanoma pathophysiology and to progress in diagnosis.
A scientific fix for the classical account of addiction
Authors: Jeffrey Foss
Journal: Behavioral and Brain Sciences (1996)

Abstract Heyman's two crucial theses are that people over-value immediate rewards, and that addictive substances “subvert the value of competing commodities.” These perennial ideas were discussed by Plato. Whereas Heyman provides scientific clarification and support for the first, the second remains problematic. I outline how this deficiency might be remedied via evolutionary considerations.
Determination of the Critical Concentration of Neutrophils Required to Block Bacterial Growth in Tissues
Authors: Yongmei Li, Arthur Karlin, John D. Loike, Samuel C. Silverstein
Journal: The Journal of Experimental Medicine (2004)

We showed previously that the competition between bacterial killing by neutrophils and bacterial growth in stirred serum-containing suspensions could be modeled as the competition between a first-order reaction (bacterial growth) and a second-order reaction (bacterial killing by neutrophils). The model provided a useful parameter, the critical neutrophil concentration (CNC), below which bacterial concentration increased and above which it decreased, independent of the initial bacterial concentration. We report here that this model applies to neutrophil killing of bacteria in three-dimensional fibrin matrices and in rabbit dermis. We measured killing of 103–108 colony forming units/ml Staphylococcus epidermidis by 105–108 human neutrophils/ml in fibrin gels. The CNC was ∼4 × 106 neutrophils/ml gel in the presence of normal serum and ∼1.6 × 107 neutrophils/ml gel in the presence of C5-deficient serum. Application of our model to published data of others on killing of ∼5 × 107 to 2 × 108 E. coli/ml rabbit dermis yielded CNCs from ∼4 × 106 to ∼8 × 106 neutrophils/ml dermis. Thus, in disparate tissues and tissuelike environments, our model fits the kinetics of bacterial killing and gives similar lower limits (CNCs) to the neutrophil concentration required to control bacterial growth.
Characterization and quantification of tumor infiltrating lymphocytes in breast cancer
Authors: Shahinaz Bedri, Mahmoud Mohamed, Hina Sarwath, Konduru Sastry
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Tumor infiltrating lymphocytes (TILs) are a significant component of the tumor microenvironment [[1][1]]. In breast cancer the prognostic and predictive value of TIL is under active investigation [[2][2]]. The goal of our study was to define specific TIL subtypes and regional
Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11)(q11.2;p15.1) translocation
Authors: Maria Corsignano Guastadisegni, Angelo Lonoce, Luciana Impera, Francesco Albano, Pietro D'Addabbo, Sebastiano Caruso, Isabella Vasta, Ioannis Panagopoulos, Anna Leszl, Giuseppe Basso, Mariano Rocchi, Clelia Tiziana Storlazzi
Journal: Molecular Cancer (2008)

Abstract Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL) is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11)(q11.2;p15.1) translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 (Hermansky Pudlak syndrome 5) intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ)-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692 . Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation.
Liver X receptor β and peroxisome proliferator-activated receptor δ regulate cholesterol transport in murine cholangiocytes
Authors: Xuefeng Xia, Dongju Jung, Paul Webb, Aijun Zhang, Bin Zhang, Lifei Li, Stephen D. Ayers, Chiara Gabbi, Yoshiyuki Ueno, Jan-Åke Gustafsson, Gianfranco Alpini, David D. Moore, Gene D. LeSage
Journal: Hepatology (2012)

Nuclear receptors (NRs) play crucial roles in the regulation of hepatic cholesterol synthesis, metabolism, and conversion to bile acids, but their actions in cholangiocytes have not been examined. In this study, we investigated the roles of NRs in cholangiocyte physiology and cholesterol metabolism and flux. We examined the expression of NRs and other genes involved in cholesterol homeostasis in freshly isolated and cultured murine cholangiocytes and found that these cells express a specific subset of NRs, including liver X receptor (LXR) β and peroxisome proliferator-activated receptor (PPAR) δ. Activation of LXRβ and/or PPARδ in cholangiocytes induces ATP-binding cassette cholesterol transporter A1 (ABCA1) and increases cholesterol export at the basolateral compartment in polarized cultured cholangiocytes. In addition, PPARδ induces Niemann-Pick C1-like L1 (NPC1L1), which imports cholesterol into cholangiocytes and is expressed on the apical cholangiocyte membrane via specific interaction with a peroxisome proliferator-activated response element (PPRE) within the NPC1L1 promoter.We propose that (1) LXRβ and PPARδ coordinate NPC1L1/ABCA1-dependent vectorial cholesterol flux from bile through cholangiocytes and (2) manipulation of these processes may influence bile composition with important applications in cholestatic liver disease and gallstone disease, two serious health concerns for humans.