tbuckley/cabot-search huggingface dataset:
Cellular changes in denervated tissue during wound healing in a rat model
Authors: None Richards, None Floyd, None Terenghi, None McGrouther
Journal: British Journal of Dermatology (1999)

There is increasing evidence that innervation, possibly mediated via neuropeptides, promotes wound healing. This study presents data on the early cellular events during healing in denervated tissue. Free oblique groin flaps were raised on 25 adult Sprague-Dawley rats. Excisional wounds were placed within the flap and in two control sites, the contralateral inguinal region and the thorax. The absence of innervation in the free flap wounds was confirmed 10 days after surgery by indirect immunofluorescence with a pan-neuronal marker. The cellular infiltrate of the wounds was analysed immunohistochemically with a panel of antibodies to rat macrophages and monocytes (ED1), rat B lymphocytes (CD45R) and T lymphocytes (CD2). The immunostained cellular infiltrate was quantified at 2, 4, 7 and 10 days postoperatively. Our results show that denervated wounds have a significantly lower macrophage and T-lymphocyte count at day 4 of wound healing (P < 0.05). Inflammatory cells, particularly macrophages, are known to play an important part in wound healing and their reduced chemotaxis in denervated tissue may be related to the observed delay in wound closure.
Long-term safety and efficacy of ivacaftor in subjects with CF who have the G551D-CFTR mutation
Authors: Edward McKone, Sally Rodriguez, Karl Yen, Jane Davies
Journal: European Respiratory Journal (2012)

Objectives:  Ivacaftor was evaluated in 2 48-week Phase 3 studies. This 96-week open-label extension (PERSIST) evaluated the safety and efficacy of long-term ivacaftor in subjects who completed the prior trials (STRIVE and ENVISION).   Methods:  192 subjects who completed treatment in STRIVE or ENVISION enrolled in PERSIST. All subjects received ivacaftor 150 mg q12h in addition to prescribed therapies. Here we report the results of 96 weeks of treatment for subjects who were in STRIVE (n=144) and 72 weeks for those in ENVISION (n=48).   Results:  For subjects who received ivacaftor in the placebo-controlled studies, the FEV 1  improvements were sustained in PERSIST. For STRIVE subjects, the mean (SD) absolute change from STRIVE baseline in % predicted FEV 1  was 9.4% (8.3%) on Day 1 of PERSIST (Week 48 in STRIVE), 10.3% (9.3%) at Week 72, and 9.5% (10.1%) at Week 96. For ENVISION subjects, the mean (SD) absolute change from ENVISION baseline was 10.2% (15.7%) on Day 1 of PERSIST, 9.1% (15.6%) at Week 60, and 10.1% (14.2%) at Week 72. For placebo subjects in STRIVE or ENVISION, the FEV 1  improvements in PERSIST were similar to those observed in ivacaftor subjects during the placebo-controlled studies. The mean (SD) absolute change from PERSIST baseline was 9.4% (8.5%) at Week 96 for STRIVE placebo subjects and 8.1% (12.5%) at Week 72 for ENVISION placebo subjects. The safety profile observed in PERSIST was generally consistent with the safety profile observed during ivacaftor treatment in STRIVE and ENVISION.   Conclusions:  Ivacaftor-related improvements in lung function were sustained with additional ivacaftor treatment. No new clinically important safety concerns were identified.  Sponsored by Vertex.
Genotypic analysis of genes associated with transmission and drug resistance in the Beijing lineage of Mycobacterium tuberculosis
Authors: J-R. Chang, C-H. Lin, S-F. Tsai, I-J. Su, F-C. Tseng, Y-T. Chen, T-S. Chiueh, J-R. Sun, T-S. Huang, Y-S. Chen, H-Y. Dou
Journal: Clinical Microbiology and Infection (2010)
Abstract 15768: Mitochondria-Targeted DNA Repair Glycosylase Ogg1 Suppresses Early Stage of Atherogenesis in Ogg1 Deficient Mice
Authors: Mykhaylo V Ruchko, Sergiy Sukhanov, Olena M Gorodnya, Lyudmila I Rachek, Svitlana D Danchuk, Patrick Delafontaine, Mark N Gillespie
Journal: Circulation (2014)

Introduction: Reactive oxygen species (ROS) play a key role in the development of atherosclerosis. Mitochondria are a main source of endogenous ROS in the cell. Mitochondrial DNA (mtDNA) is sensitive to oxidation and our previous results from cultured cell and intact animal models suggest that increasing mtDNA repair prevents both oxidative mtDNA damage and associated cytotoxicity and cellular dysfunction. Involvement of oxidative mtDNA damage in disorders characterized by chronic oxidative stress has been less thoroughly studied. Hypothesis: In the present study we tested the hypothesis that transgenic modulation of Ogg1, a DNA glycosylase mediating the first step in the base excision repair of oxidative mtDNA damage, coordinately regulates atherogenesis in mice fed a high fat diet. Methods: Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KO-Tg) were fed pro-atherogenic Western type diet for 14 weeks and analyzed for mtDNA damage and signs of atherogenesis. Results: KO mice fed a high fat diet had increased oxidative mtDNA damage in cardiac tissue, whereas KO-Tg animals did not differ from WT mice (WT: 0.18 ± 0.04; KO: 0.35 ± 0.04; KO-Tg: 0.15 ± 0.01 lesions per 10 4 bp; n=3, P&lt;0.05; quantitative Southern blot analysis). We did not observe significant atherosclerotic plaque formation in the aortic valve of animals from any group; however appearance of fatty streaks, indicative of early plaque development, was more evident in KO mice (WT: 179 ± 20; KO: 384 ± 59 pixels, n=4, P&lt;0.05; immunohistochemistry for Fc receptor - general marker of inflammatory cells). This effect was completely blocked in KO-Tg mice. We found increased number of apoptotic cells in the aortic valve of KO, but not KO-Tg mice (WT: 2.00 ± 0.50; KO: 4.25 ± 0.48; KO-Tg: 2.14 ± 0.85 apoptotic cells, n=4, P&lt;0.05; TUNEL assay). Conclusion: Our data demonstrate that Ogg1 deficiency in mice fed a high fat diet leads to increased oxidative mtDNA damage, appearance of fatty streaks and cell apoptosis. In contrast, enhancement of mtDNA repair with mitochondria-targeted Ogg1 reduces fatty streaks formation and apoptosis induced by a high fat diet. These results suggest mtDNA damage and repair could be important targets for atheroprotection.
Local inhibition of IL-4 and IL-13 protects lung function in OVA mouse model
Authors: Nicole Stowell, Michael Baumann, Sandra Bruckmaier, Andreas Cornelius, Colleen Kane, Cassandra Lowenstein, Kristen Picha, Gaby Sennhauser, Edward Yurkow, Zhao Zhou, Michael Stumpp, Karyn O'Neil
Journal: European Respiratory Journal (2011)

DARPinsTM (Designed Ankyrin Repeat Proteins) are a novel class of proteins that combine the affinity and specificity properties of antibodies with the solubility and tissue penetration properties of small molecules. The excellent biophysical properties of DARPin domains allows for simple engineering of multispecificity by linking domains that target different ligands. DARPin134 is a bispecific DARPin that inhibits binding of murine IL-13 and IL-4 to their receptors.  The bispecific molecule (DARPin134) or either of the mono-specific molecules was delivered to the lungs of mice via intra-tracheal instillation during an acute ovalbumin sensitization and challenge model. Free IL-4 and IL-13 levels were reduced in the BAL following treatment with DARPin134. While the anti-IL-4 and anti-IL-13 DARPins each showed a trend towards reducing eosinophils in the lungs of mice, the bi-specific DARPin significantly reduced eosinophil infiltration. In addition, an improvement airway hyper-responsiveness in mice treated with DARPin134 was observed.  A variety of studies have confirmed the unique and overlapping roles for IL-13 and IL-4 in the pathology of asthma. Molecules inhibiting IL-4 alone have failed in clinical trials of asthma and a variety of clinical studies with molecules targeting IL-13 are ongoing. In contrast, DARPin134 targets both IL-4 and IL-13 and in vitro data demonstrate the bispecific DARPin has high potency, affinity and excellent biophysical properties. Blockade of both IL-4 and IL-13 in the pulmonary compartment could provide a therapeutic option in pulmonary diseases without disruption of either cytokine systemically.
A three miRNA signature regulates the CF transmembrane conductance regulator (CFTR) in cystic fibrosis airway epithelium
Authors: Irene Oglesby, Shane O'Neill, Noel McElvaney, Catherine Greene
Journal: European Respiratory Journal (2011)

Expression profiling studies have identified altered miRNA patterns in several human diseases, however little is known of the role miRNA play in cystic fibrosis (CF). Here we examined the impact of altered miRNA expression in CF bronchial epithelium on CFTR expression.  We performed miRNA expression profiling on bronchial brushings taken from five CF and five non-CF individuals by qRT-PCR using Taqman Low Density Arrays (TLDAs). Expression of altered miRNA was validated by qRT-PCR in additional brushings and  in vitro  in CF and non-CF bronchial epithelial cell lines. CFTR gene expression was also measured. miRNA inhibition and over-expression studies were performed in CFBE41o– and 16HBE14o– cell lines respectively  in vitro  and CFTR mRNA and protein was detected by qRT-PCR and western blot.  Of the 667 miRNA examined 56 were down-regulated and 36 up-regulated in CF. Using  in silico  analysis we identified miRNAs predicted to target the CFTR gene that were collectively up-regulated in the CF samples e.g. a three miRNA signature consisting of miR-145, miR-223 and miR-494. Knockdown of miR145, -223 and -494 in CFBE41o– cells led to an increase in CFTR protein production. Conversely a decrease in CFTR expression was observed following miRNA over-expression in 16HBE14o– cells. CFTR mRNA expression was significantly decreased in CF vs. non-CF bronchial brushings.  These data show that miRNA are differentially expressed in the CF airway epithelium, miRNA targeting CFTR are up-regulated and CFTR is reciprocally down-regulated. The regulation of CFTR by miRNA may represent an additional endogenous level of control over mutant CFTR in classes I, II or V CFTR mutations.
Allogeneic Marrow Transplantation for Chronic Granulocytic Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Fefer, R A Clift, E D Thomas
Journal: JNCI Journal of the National Cancer Institute (1986)

A retrospective analysis is presented of results obtained with allogeneic bone marrow transplantation (BMT) in three phases of Philadelphia chromosome-positive chronic granulocytic leukemia. At BMT, 23 patients were in blastic phase (BP), 33 were in accelerated phase (AP), and 45 were in chronic phase (CP). With a follow-up time of 1-8 years after BMT, the probability of long-term survival was 14, 10, and 58%, respectively, for patients transplanted in BP, AP, or CP. The probability of cytogenetic relapse with or without clinical hematologic relapse at 3 years after BMT was 80, 38, and 31%, respectively, for patients transplanted in BP, AP, or CP. Splenectomy did not influence posttransplant survival. Given the dismal prognosis on conventional therapy, patients younger than 50 in BP or AP should be considered for BMT. For the patient in CP, BMT offers the possibility of cure but with a significant risk of early death. Patients under 40 who fully understand the risks and potential benefits of BMT should be offered BMT early in CP before any change to AP occurs.
CT scan derived emphysema scores correlate with spirometry and gas exchange but not acute exacerbation rates (AER) or COPD assessment test (CAT) in COPD subjects with and without alpha-1-antitrypsin (AAT) deficiency
Authors: Ronald Dandurand, Tomás Carroll, Raúl San José Estépar, Jean Bourbeau, David Eidelman
Journal: European Respiratory Journal (2013)

We previously reported 24 patients with AAT deficiency (AATD) and found them not different from non-AATD subject in terms of lung function, AER and CAT scores. We aimed to expand our observations to include emphysema scores derived from thoracic CT scans. 23 genotyped subjects with serum AAT levels    group may have null or rare alleles and require  SERPINA1  gene sequencing. Lung emphysema was determined using a threshold of -950 HU to define the low attenuation area percentage (LAA% (-950 HU)) and measured with  Airway Inspector  (www.airwayinspector.org). Demographics, physiology, AERs, CAT scores and LAA% (-950 HU) did not differ between groups. LAA% correlated with FEV 1  (r=-0.42, p Lco  (r=-0.50, p 1 /FVC (r=-0.73, p -8 , Figure 1) but not AER (r=0.08, p=0.61) or CAT scores (r=-0.02, p=0.89).  In this small group of COPD patients emphysema scores did not differ between those with and without AATD and correlated with the FEV 1 , FEV 1 /FVC and D Lco . These results support the notion that airway-parenchymal interdependence is an important determinant of airflow obstruction in both AATD and non-AATD COPD patients.
Carcinoma of Hard Palate in India in Relation to Reverse Smoking of Chuttas
Authors: C. R. R. M. Reddy
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Carcinoma of Hard Palate in India in Relation to Reverse Smoking of Chuttas Get access C. R. R. M. Reddy, M.D., Ph.D. C. R. R. M. Reddy, M.D., Ph.D. 2Professor of Pathology, Andhra Medical College, Visakhapatnam, S. India. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 3, September 1974, Pages 615–619, https://doi.org/10.1093/jnci/53.3.615 Published: 01 September 1974 Article history Received: 04 February 1974 Accepted: 13 May 1974 Published: 01 September 1974
Expansion depends on rigorous control of numbers in training and non-consultant career grades
Authors: A. G Hobart
Journal: BMJ (1995)

EDITOR,—Stephen Brearley identifies the principal influences on the duration of training for junior doctors in Britain: the rate of entry to and exit from the training grades.1 He does not, however, consider fully how those rates may be varied and regulated.

The rate of outflow from the training grades is influenced mainly by the number of consultant posts. If purchasers wish to buy more or better quality services they must finance more consultant posts—unless, that is, trusts employ other doctors at lower salaries. Staff …
Randomized double-blinded placebo-controlled intra-individual trial on topical treatment with a 1,25-dihydroxyvitamin D3 analogue in polymorphic light eruption
Authors: A. Gruber-Wackernagel, I. Bambach, F.J. Legat, A. Hofer, S.N. Byrne, F. Quehenberger, P. Wolf
Journal: British Journal of Dermatology (2011)

Journal Article Randomized double‐blinded placebo‐controlled intra‐individual trial on topical treatment with a 1,25‐dihydroxyvitamin D3 analogue in polymorphic light eruption Get access A. Gruber‐Wackernagel, A. Gruber‐Wackernagel Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A‐8036 Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar I. Bambach, I. Bambach Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A‐8036 Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar F.J. Legat, F.J. Legat Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A‐8036 Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar A. Hofer, A. Hofer Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A‐8036 Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar S.N. Byrne, S.N. Byrne Department of Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Search for other works by this author on: Oxford Academic Google Scholar F. Quehenberger, F. Quehenberger Institute for Medical Informatics, Statistics, and Documentation, Medical University of Graz, Graz, Austria Search for other works by this author on: Oxford Academic Google Scholar P. Wolf P. Wolf Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Auenbrugger Platz 8, A‐8036 Graz, Austria Peter Wolf. E‐mail: peter.wolf@medunigraz.at Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 152–163, https://doi.org/10.1111/j.1365-2133.2011.10333.x Published: 01 July 2011
Prostat Biyopsisinin Tekrar Edilmesinin Planlandığı Avrupalı Erkeklerde PCA3 İdrar Testinin Klinik Rolü
Authors: Alexander Haese, Alexandre de la Taille, Hendrik van Poppel, Michael Marberger, Arnulf Stenzl, Peter F.A. Mulders, Hartwig Huland, Clément-Claude Abbou, Mesut Remzi, Martina Tinzl, Susan Feyerabend, Alexander B. Stillebroer, Martijn P.M.Q. van Gils f, Jack A. Schalken f
Journal: European Urology (2009)
Developing a postgraduate medical oncology training program in Taipei, Taiwan, Republic of China.
Authors: P P Carbone
Journal: Journal of Clinical Oncology (1991)

Because cancer is the number one cause of mortality in Taiwan, a governmental decision was made to develop an experiment in medical oncology education using a United States-style training program in medical oncology in three Taipei, Taiwan, university hospitals. In the past, trainees from developing countries came to the United States or other foreign countries to receive specialty training. In doing so, the training did not necessarily prepare the individuals with skills to treat the indigenous cancers, nor did they work with other related specialists or support staff such as nursing and pharmacy, so important to providing good cancer care. This program involved 13 fellows with significant laboratory experience working with American faculty on-site. The major benefits of this model for oncology training are that the trainees developed important interdisciplinary relationships with local staff at each of the hospitals; they were involved in the treatment of the major cancer diseases of Taiwan such as nasopharyngeal, hepatocellular, and cervical cancers as well as breast, lung, and colon cancers; and they completed a certification process involving written and oral tests by two senior American oncologist examiners. Oncology services have been established at each of the hospitals and most of the fellows have expressed an interest or made arrangements to come to the United States to get additional research experience.
Sustaining a chronic obstructive pulmonary disease (COPD) discharge care bundle on the respiratory ward in an acute district general hospital
Authors: Bhupinder Mann, Essam Ramhamadany, Leonel Flores, Almie Mngadi, Leny Eapen, Haidee Venturina, Sandra Wilson, Muhammad Pasha, Robert Tidswell
Journal: European Respiratory Journal (2012)

A COPD discharge care bundle was previously piloted on the respiratory ward at our hospital in May 2010. At 1 year there were significant improvements in patient care and a reduction in 28 day COPD readmission rate from 25% to 18.4% (p=0.06).  Objective  To look at the current level of sustainability of the bundle, and to assess patient and staff experience. In addition, we implemented the bundle on our medical day unit (MAU).  Methods  To maintain sustainability, a programme of regular education and training was provided. Patient experience was assessed by the response of 40 patients to a telephone call post discharge, and ward staff (n=21) completed a questionnaire.  Results  Compliance with the bundle on the respiratory ward from May 2010 to January 2012 (21 months) has remained high at 99%. Compliance with all 4 elements of the bundle was 93%. Improvement in patient care continues to remain significantly higher than baseline. The 28 day COPD readmission rate is currently 18%.  85% of patients found the bundle useful or very useful. In the staff survey, 81% of staff thought that the bundle improved patient care and 71% found it easy to complete. 67% said that it improved their knowledge and skills about COPD, while 24% were unsure. 95% felt it should be carried out on other wards.  Compliance on the MAU was disappointing at 24% over the last 6 months. Reasons for poor compliance included a change in the MAU bed model, low nursing numbers and high patient turnover.  Conclusion  The improvement in patient care using the COPD bundle is sustainable on a specialist ward. Patient and staff experience was positive. Roll out on the MAU remains a challenge.
The effects of diesel exhausted particles on the oxidative systems in smoking-induced emphysema model
Authors: Soo-Taek Uh, So My Koo, Do Jin Kim, Sung Woo Park, An Soo Jang, Choon Sik Park, Yong Hoon Kim
Journal: European Respiratory Journal (2013)

Introduction: Diesel exhausted particles (DEP) is one of major constituent in air pollution which has been known as an important cause of acute exacerbation of COPD. The role of oxidative stress is unknown in acute exacerbation of COPD. We hypothesized the responses of DEP are different between in emphysema and non-emphysema murine model in terms of oxidative systems. Methods: Smoking-induced emphysema models were exposed to cigarettes for 6 months. Suspended DEP were given intratracheally after 0, 2, 4, 6 days after last expose to smoking. The mice were sacrificed 3 days after last DEP instillation. Bronchoalveolar lavage (BAL), mean liner intercept (MLI), ELISA for TNF-α and IL-8, Western blot for PCNA, HNE, Nrf-2, and Tunnel assay were performed. Results: MLI significantly more increased in emphysema group compared to those in control group (36.7±3.5 vs 26.5±6.5 μm, respectively) and significantly distended alveoli were observed in emphysema group. Total cell count and percentages of lymphocyte and neutrophil in BAL fluid significantly increased by DEP treatment. The amounts of IL-8 and TNF-α in BAL fluid were not different by treatment of DEP. The expressions of PCNA were increased and expressions of Nrf-2 were depressed by treatment of DEP in both emphysema and control group. The expression of PCNA and Nrf-2 were more increased by treatment of DEP in emphysema group compared to that in control group. The expressions of HNE were depressed by treatment of DEP in both emphysema and control group. Apoptosis were significantly increased in emphysema group by treatment of DEP. Conclusion: The oxidative systems are more exaggerated by DEP in emphysema model.
RECIPROCAL CHANGES IN PLASMA PROTEIN AND PLASMA ACACIA AS RESULT OF HIGH AND LOW PROTEIN DIETS
Authors: R. E. Knutti, J. B. Goetsch, R. A. Warrick
Journal: The Journal of Experimental Medicine (1950)

Dogs were made hypoproteinemic by repeated injections of gum acacia, and the acacia injections were discontinued. Diets of varying protein content were then given. When a high protein diet is provided the plasma protein concentration increases; with a low protein diet, or under conditions of fasting, the plasma protein concentration diminishes. Similarly, plasma acacia concentration shows increases and decreases which are reciprocal to the protein variations. Total circulating plasma protein and total circulating plasma acacia show similar changes. In all instances total circulating colloid (acacia plus protein) concentration adds up to an amount within normal limits for protein alone. The results indicate that under these conditions, acacia stored in the body (principally in the liver) can be removed from its site of deposit and returned to the blood. The data also show that dogs in which acacia is deposited in large quantities, require a larger amount of protein in the diet to maintain a constant plasma protein content than do normal dogs. It appears that the mechanism for maintenance of peripheral colloidal material may be dependent on differences in intracellular and extracellular colloidal osmotic pressure. The experiments also support the idea that plasma protein molecules, as well as gum acacia, may pass in and out of cells through the cell membranes.