tbuckley/cabot-search huggingface dataset:
Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD
Authors: F. Maltais
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Enzymatic and histochemical abnormalities of the peripheral muscle may play a role in exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to measure the mitochondrial enzyme activity of the vastus lateralis muscle in patients with COPD and to evaluate the relationship between enzyme activities and functional status. <h3>METHODS</h3> Fifty seven patients with COPD of mean (SD) age 66 (7) years with forced expiratory volume in one second (FEV<sub>1</sub>) 39 (15)% predicted and peak oxygen uptake (V˙o<sub>2</sub>) of 14 (4) ml/min/kg and 15 normal subjects of similar age were included in the study. Each subject performed a stepwise exercise test up to maximal capacity during which five-breath averages of V˙o<sub>2</sub>were measured. Muscle specimens were obtained by percutaneous needle biopsy of the vastus lateralis muscle and the activity of two mitochondrial enzymes (citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH)) was measured. The functional status of the patients was classified according to peakV˙o<sub>2</sub>. <h3>RESULTS</h3> CS and HADH activities were markedly reduced in patients with COPD compared with normal subjects (22.3 (2.7) versus 29.5 (7.3) μmol/min/g muscle (p&lt;0.0001) and 5.1 (2.0) versus 6.7 (1.9) μmol/min/g muscle (p&lt;0.005), respectively). The activity of CS decreased progressively with the deterioration in the functional status while that of HADH was not related to functional status. Using a stepwise regression analysis, percentage predicted functional residual capacity (FRC), the activity of CS, oxygen desaturation during exercise, age, and inspiratory capacity (% pred) were found to be significant determinants of peakV˙o<sub>2</sub>. The regression model explained 59% of the variance in peak V˙o<sub>2</sub> (p&lt;0.0001). <h3>CONCLUSIONS</h3> The oxidative capacity of the vastus lateralis muscle is reduced in patients with moderate to severe COPD compared with normal subjects of similar age. In these individuals the activity of CS correlated significantly with peak exercise capacity and independently of lung function impairment.
Suppression of antibody responses to topically applied antigens by ultraviolet light irradiation. Induction of phototolerance.
Authors: C W Spellman, W L Anderson, E J Bernhard, T B Tomasi
Journal: The Journal of Experimental Medicine (1984)

C3Hf/HeN or BALB/c mice, exposed to acute ultraviolet (UV) irradiation and skin-sensitized through the irradiated skin site with soluble protein antigens, exhibit humoral tolerance to subsequent systemic challenge with antigen. We have termed this phenomenon "phototolerance" (PT). With the doses of UV radiation used, PT induction is restricted to the irradiated skin site and is observed only if sensitization is performed via the cutaneous route. PT is antigen specific and operates at the afferent level of the immune response. While single PT induction regimens result in transient humoral suppression, multiple inductions before each systemic challenge can maintain the response at low levels. The capacity to induce PT to a variety of soluble protein antigens may have potentially important clinical applications.
Ethacrynic Acid and a Derivative Enhance Apoptosis in Arsenic Trioxide–Treated Myeloid Leukemia and Lymphoma Cells: The Role of Glutathione S-Transferase P1-1
Authors: Rui Wang, Changda Liu, Lijuan Xia, Guisen Zhao, Janice Gabrilove, Samuel Waxman, Yongkui Jing
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Arsenic trioxide (ATO) as a single agent is used for treatment of acute promyelocytic leukemia (APL) with minimal toxicity, but therapeutic effect of ATO in other types of malignancies has not been achieved. We tested whether a combination with ethacrynic acid (EA), a glutathione S-transferase P1-1 (GSTP1-1) inhibitor, and a reactive oxygen species (ROS) inducer will extend the therapeutic effect of ATO beyond APL. Experimental Design: The combined apoptotic effects of ATO plus ethacrynic acid were tested in non-APL leukemia and lymphoma cell lines. The role of ROS, GSTP1-1, glutathione (GSH), and Mcl-1 in apoptosis was determined. The selective response to this combination of cells with and without GSTP1-1 expression was compared. Results: ATO/EA combination synergistically induced apoptosis in myeloid leukemia and lymphoma cells. This treatment produced high ROS levels, activated c-jun-NH2-kinase (JNK), and reduced Mcl-1 protein. This led to the decrease of mitochondrial transmembrane potential, release of cytochrome c, and subsequently, to activation of caspase-3 and -9. Induction of apoptosis in leukemia and lymphoma cells expressing GSTP1-1 required high ethacrynic acid concentrations to be combined with ATO. Silencing of GSTP1 in leukemia cells sensitized them to ATO/EA–induced apoptosis. In a subgroup of B-cell lymphoma, which does not express GSTP1-1, lower concentrations of ethacrynic acid and its more potent derivative, ethacrynic acid butyl-ester (EABE), decreased intracellular GSH levels and synergistically induced apoptosis when combined with ATO. Conclusion: B-cell lymphoma cells lacking GSTP1-1 are more sensitive than myeloid leukemia cells to ATO/EA–induced apoptosis. Clin Cancer Res; 18(24); 6690–701. ©2012 AACR.
Cancer Cell Secretion of the DAMP Protein HMGB1 Supports Progression in Malignant Mesothelioma
Authors: Sandro Jube, Zeyana S. Rivera, Marco E. Bianchi, Amy Powers, Ena Wang, Ian Pagano, Harvey I. Pass, Giovanni Gaudino, Michele Carbone, Haining Yang
Journal: Cancer Research (2012)

Abstract Human malignant mesothelioma is an aggressive and highly lethal cancer that is believed to be caused by chronic exposure to asbestos and erionite. Prognosis for this cancer is generally poor because of late-stage diagnosis and resistance to current conventional therapies. The damage-associated molecular pattern protein HMGB1 has been implicated previously in transformation of mesothelial cells. Here we show that HMGB1 establishes an autocrine circuit in malignant mesothelioma cells that influences their proliferation and survival. Malignant mesothelioma cells strongly expressed HMGB1 and secreted it at high levels in vitro. Accordingly, HMGB1 levels in malignant mesothelioma patient sera were higher than that found in healthy individuals. The motility, survival, and anchorage-independent growth of HMGB1-secreting malignant mesothelioma cells was inhibited in vitro by treatment with monoclonal antibodies directed against HMGB1 or against the receptor for advanced glycation end products, a putative HMGB1 receptor. HMGB1 inhibition in vivo reduced the growth of malignant mesothelioma xenografts in severe-combined immunodeficient mice and extended host survival. Taken together, our findings indicate that malignant mesothelioma cells rely on HMGB1, and they offer a preclinical proof-of-principle that antibody-mediated ablation of HMBG1 is sufficient to elicit therapeutic activity, suggesting a novel therapeutic approach for malignant mesothelioma treatment. Cancer Res; 72(13); 3290–301. ©2012 AACR.
Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes
Authors: George E. Georges, Rainer Storb, Benedetto Bruno, Scott J. Brodie, Jennifer D. Thompson, Anna G. Taranova, J. Maciej Zaucha, Marie-Térèse Little, Eustacia Zellmer, Peter F. Moore, Theodore Gooley, George Sale, Hans-Peter Kiem, Brenda M. Sandmaier, Russette M. Lyons, Richard A. Nash
Journal: Blood (2001)
Genetic variation in the<i>lymphotoxin-α</i>(<i>LTA</i>)/<i>tumour necrosis factor-α</i>(<i>TNFα</i>) locus as a risk factor for idiopathic achalasia
Authors: Mira M Wouters, Diether Lambrechts, Jessica Becker, Isabelle Cleynen, Jan Tack, Ana G Vigo, Antonio Ruiz de León, Elena Urcelay, Julio Pérez de la Serna, Wout Rohof, Vito Annese, Anna Latiano, Orazio Palmieri, Manuel Mattheisen, Michaela Mueller, Hauke Lang, Uberto Fumagalli, Luigi Laghi, Giovanni Zaninotto, Rosario Cuomo, Giovanni Sarnelli, Markus M Nöthen, Séverine Vermeire, Michael Knapp, Ines Gockel, Johannes Schumacher, Guy E Boeckxstaens
Journal: Gut (2013)

<h3>Background</h3> Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors predisposing to achalasia have been poorly documented, we assessed whether single nucleotide polymorphisms (SNPs) in genes mediating immune response and neuronal function contribute to achalasia susceptibility. <h3>Methods</h3> 391 SNPs covering 190 immune and 67 neuronal genes were genotyped in an exploratory cohort from Central Europe (589 achalasia patients, 794 healthy volunteers (HVs)). 24 SNPs (p&lt;0.05) were validated in an Italian (160 achalasia patients, 278 HVs) and Spanish cohort (281 achalasia patients, 296 HVs). 16 SNPs in linkage disequilibrium (LD) with rs1799724 (r<sup>2</sup>&gt;0.2) were genotyped in the exploratory cohort. Genotype distributions of patients (1030) and HVs (1368) were compared using Cochran–Armitage trend test. <h3>Results</h3> The rs1799724 SNP located between the <i>lymphotoxin-α</i> (<i>LTA</i>) and <i>tumour necrosis factor-α</i> (<i>TNFα</i>) genes was significantly associated with achalasia and withstood correction for testing multiple SNPs (p=1.17E-4, OR=1.41 (1.18 to 1.67)). SNPs in high LD with rs1799724 were associated with achalasia. Three SNPs located in <i>myosin-5B</i>, <i>adrenergic receptor-β-2</i> and <i>interleukin-13</i> (<i>IL13</i>) showed nominally significant association to achalasia that was strengthened by replication. <h3>Conclusions</h3> Our study provides evidence for rs1799724 at the <i>LTA/TNFα</i> locus as a susceptibility factor for idiopathic achalasia. Additional studies are needed to dissect which genetic variants in the <i>LTA</i>/<i>TNFα</i> locus are disease-causing and confirm other variants as potential susceptibility factors for achalasia.
Aspirin Increases Ferritin Synthesis in Endothelial Cells
Authors: Stefanie Oberle, Tobias Polte, Aida Abate, Hans-Peter Podhaisky, Henning Schröder
Journal: Circulation Research (1998)

Abstract —Aspirin has recently been shown to increase endothelial resistance to oxidative damage. However, the mechanism underlying aspirin-induced cytoprotection is still unknown. Using cultured cells, the present study investigates the effect of aspirin on the expression of ferritin, a cytoprotective protein that sequesters free cytosolic iron, the main catalyst of oxygen radical formation. In bovine pulmonary artery endothelial cells, aspirin at low antithrombotic concentrations (0.03 to 0.3 mmol/L) induced the synthesis of ferritin protein in a time- and concentration-dependent fashion up to 5-fold over basal levels, whereas ferritin H (heavy chain) mRNA remained unaltered. Aspirin-induced cytoprotection from hydrogen peroxide toxicity was mimicked by exogenous iron-free apoferritin but not iron-loaded ferritin, demonstrating the antioxidant function of newly synthesized ferritin under these conditions. Ferritin induction by aspirin was specific in that other nonsteroidal anti-inflammatory drugs such as salicylic acid, indomethacin, or diclofenac failed to alter ferritin protein levels. Aspirin-induced ferritin synthesis was abrogated in the presence of the iron chelator desferrioxamine, pointing to an interaction of aspirin with iron-responsive activation of ferritin translation. Together, our results suggest induction of ferritin as a novel mechanism by which aspirin may prevent endothelial injury in cardiovascular disease, eg, during atherogenesis.
Bronchiectasis among hospitalised patients in Germany
Authors: Felix C. Ringshausen, AndrÃ©s de Roux, Mathias W. Pletz, Tobias Welte, Jessica Rademacher
Journal: European Respiratory Journal (2013)

Rationale:  Representative, population-based data on the epidemiology of bronchiectasis in Europe is limited.   Objective:  To investigate the current burden and the trends of bronchiectasis-associated hospitalisations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources.   Methods:  The nationwide German diagnosis-related groups hospital statistics for the years 2005–2010 were used in order to identify hospitalisations for bronchiectasis as a discharge diagnosis according to the International Classification of Diseases, tenth revision, German modification, code J47. Poisson log-linear regression was used to assess the significance of trends.   Results:  Overall 51,705 records with bronchiectasis as any hospital discharge diagnosis were extracted from 106 million hospitalisations. The average annual age-adjusted hospitalisation rate was 9.2 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period, with the highest rate of 39 hospitalisations per 100,000 population among men aged 75–84 years and the most significant average annual increase of 4.9% among females. COPD was the most frequent bronchiectasis-associated condition in up to 35.6% of subjects and showed a significantly increasing trend (p   Conclusion:  The present study provides evidence for changing trends in the epidemiology of bronchiectasis. Prospective bronchiectasis registries are needed to establish the exact prevalence of bronchiectasis according to the specific underlying condition.
Simplified stepwise management of primary spontaneous pneumothorax: a pilot study
Authors: C-H. Marquette
Journal: European Respiratory Journal (2006)

In primary spontaneous pneumothorax (PSP) requiring intervention, removal of air from the pleural space can be achieved by manual needle aspiration or by pleural drainage after insertion of a chest tube. This study aimed to evaluate the efficacy and safety of a serial-steps approach with a single system (small-calibre catheter/Heimlich valve) in a homogeneous population of patients with a first episode of PSP. All patients had an 8.5 F distally multiperforated polyurethane pigtail catheter inserted via the anterior route, at the bedside without any guidance, using the Seldinger technique. A one-way Heimlich valve was connected to the catheter, allowing the air to flow spontaneously outwards for 24-48 h. Thereafter, if the lung failed to re-expand wall suction was applied. Patients with an air leak persisting for >4 days were referred for surgery. Primary end-points were success rates at 24 h and 1 week, and 1 yr recurrence-free survival. In total, 41 consecutive patients entered the study. They were typically thin, young, smoking males. No procedure-related complications were observed. The need for pain relief medication was minimal. Within the first 24 h, most of the patients were able to walk around and half of them were able to take a shower with their catheter in place. The 24-h and 1-week success rates were 61 and 85%, respectively, and the actuarial 1-yr recurrence rate was 24%. Four patients underwent surgical pleurodesis because of a persistent air leak. The length of stay when excluding the four surgical cases was 2.3+/-1.3 days. When 24-h and 1-week success rates and recurrence at 12 months were taken as end-points, the method described here is as effective as simple manual needle aspiration or a conventional chest tube thoracotomy. These results support further studies assessing this "one system, serial-steps approach" in an outpatient management algorithm.
Small Guanine Nucleotide-Binding Proteins and Myocardial Hypertrophy
Authors: Angela Clerk, Peter H. Sugden
Journal: Circulation Research (2000)

Abstract —The small (21 kDa) guanine nucleotide-binding protein (small G protein) superfamily comprises 5 subfamilies (Ras, Rho, ADP ribosylation factors [ARFs], Rab, and Ran) that act as molecular switches to regulate numerous cellular responses. Cardiac myocyte hypertrophy is associated with cell growth and changes in the cytoskeleton and myofibrillar apparatus. In other cells, the Ras subfamily regulates cell growth whereas the Rho subfamily (RhoA, Rac1, and Cdc42) regulates cell morphology. Thus, the involvement of small G proteins in hypertrophy has become an area of significant interest. Hearts from transgenic mice expressing activated Ras develop features consistent with hypertrophy, whereas mice overexpressing RhoA develop lethal heart failure. In isolated neonatal rat cardiac myocytes, transfection or infection with activated Ras, RhoA, or Rac1 induces many of the features of hypertrophy. We discuss the mechanisms of activation of the small G proteins and the downstream signaling pathways involved. The latter may include protein kinases, particularly the mitogen-activated or Rho-activated protein kinases. We conclude that although there is significant evidence implicating Ras, RhoA, and Rac1 in hypertrophy, the mechanisms are not fully understood.
Neural Stimulation of Release of Renin
Authors: RUBEN D. BUNAG, IRVINE H. PAGE, JAMES W. MCCUBBIN
Journal: Circulation Research (1966)

Increased vasomotor discharge induced by bleeding caused renal release of renin in anesthetized dogs whether or not there was measurable change in either arterial pressure or total renal blood flow. Release of renin was prevented by ganglion blockade or local anesthesia of the renal nerves. Hemorrhage-induced release of renin occurred more consistently in dogs fed a low-sodium diet than in those fed a standard kennel diet. Stimulation of sympathetic vasomotor discharge by occlusion of the common carotid arteries, while renal perfusion pressure was kept constant, also caused release of renin, as did infusions of norepinephrine, tyramine, or DMPP. Isoproterenol, angiotensin, vasopressin, serotonin, or acetylcholine infused into the renal artery did not cause release of renin. It is concluded that neural stimuli are capable of causing release of renin in the absence of gross change in renal perfusion pressure or flow.
Abstract LB-157: A murine model of Fanconi anemia-associated head and neck cancer
Authors: Laura E. Hays, Grover C. Bagby
Journal: Cancer Research (2010)

Abstract Fanconi anemia (FA) predisposes patients to aggressive head-and-neck-squamous-cell-carcinomas (HNSCCs) early in life. These tumors are particularly difficult to treat because of the underlying hypersensitivity of all somatic cells from these patients to cross-linking agents. An in vivo model is thus badly needed to delineate the unique molecular mechanisms involved in tumor formation and to identify opportunities to exploit this mechanism therapeutically. Although mice with inactivating mutations of FA genes have been developed, these mice do not spontaneously develop HNSCCs. Therefore, we sought to develop our own model by treating wild-type (WT) and Fancc-deficient (FA-C) mice with the carcinogen 4-nitroquinoline 1-oxide for 45 weeks. Although tumor incidence, histological type and grade, and anatomical location were similar in WT and FA-C mice, cells isolated from FA-C tumors displayed higher levels of endogenous chromosomal instability compared to cells from WT tumors. None of the mice developed metastases, most likely because they required early euthanasia as tumor formation inhibited the ability to eat and drink. To compare the metastatic potential of WT and FA-C HNSCC cells, we subcutaneously injected these cells lines into the flanks of immunocompetent (C57Bl/6J) and immunodeficient (NOD/SCID) mice. Interestingly, tumors only formed in NOD/SCID mice indicating immune-mediated suppression of tumor growth in the immunocompetent mice. In NOD/SCID mice, 4 out of 6 WT and 3 out of 4 FA-C cell lines induced tumor formation. However, all of the tumor-forming FA-C lines produced aggressive tumors that penetrated into the retro-peritoneal space and/or produced hind-leg paralysis, while only 1 out of 4 WT lines invaded to this extent (a phenomenon that occurred in fewer than 25% of mice injected with this line). In addition, we found that tumor forming ability of FA-C HNSCC cell lines did not require loss of Fancc because FA-C lines transduced with wild-type Fancc remained fully tumorigenic in vivo. In conclusion, we have developed a model of FA related HNSCCs utilizing FA and WT cell lines. The model permits the outgrowth of tumors that are histologically, genomically, and biologically similar to corresponding tumors in humans. Currently we are utilizing this model to test the efficacy of small molecules in inhibiting FA tumor progression and are testing the role of the tumor microenvironment and the immune system in modulating the development of FA-related HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-157.
Pulmonary infection with Nocardia caviae in a patient with diabetes mellitus and liver cirrhosis.
Authors: B Salh, C Fegan, A Hussain, A Jaulim, K Whale, A Webb
Journal: Thorax (1988)

The first reported case of pulmonary infection with Nocardia caviae in Britain occurred in a 67 year old woman, in whom diabetes mellitus and liver cirrhosis probably contributed to impaired cell mediated immunity. She was successfully treated with gentamicin 60 mg eight hourly and sulphadimidine 500 mg six hourly for six months and then with sulphadimidine 2 g/day for a further three months. When Nocardia caviae is isolated from the sputum of a patient with chronic respiratory infection and fever, effective treatment should be started promptly.
86 CHARACTERIZATION AND SURVIVAL AFTER LIVER TRANSPLANTATION IN FAMILIAL AMYLOIDOTIC POLYNEUROPATHY: A 18 YEARS FOLLOW-UP STUDY
Authors: E. Barroso, H. Cortez-Pinto, H.P. Marques, E. Mateus, L.S. Pinheiro, M. Gouveia, J. Costa, A.V. Carneiro, M. Borges
Journal: Journal of Hepatology (2012)