tbuckley/cabot-search huggingface dataset:
Prevalence of Psoriasis in Polyarthritic Patients and their Relatives
Authors: Harvey Baker
Journal: Annals of the Rheumatic Diseases (1966)

<h3>Abstract</h3> Selective inhibition of CDK8 could be a promising strategy for reducing mitogenic signals in cancer cells with reduced toxic effects on normal cells. As compared with type I ligands, binding of a type II compound often achieves longer residence time. We developed a novel virtual drug screening package which takes advantage of two energy evaluation methods: Superposition and Single-Point Energy Evaluation, and VM2 free energy calculation, and applied it to the discovery of new CDK8 type II ligands. In this research we analyzed binding thermodynamics of 11 published CDK8 type II ligands, and extracted the key binding information to assist virtual drug screening for new ligands. The free energy and MD calculations on the reference CDK8-ligand complexes revealed the important factors in the binding. The urea moiety was found to be the critical structural contributor of the reference ligands. Starting with the urea moiety we implemented virtual drug screening and singled out three compounds for bio-assay testing. The ranking from the experimental result for the three compounds is completely consistent with the predicted rankings by both energy evaluation methods. A potent drug-like compound was discovered to have a K<sub>d</sub> value of 42.5 nM with CDK8, which is comparable to the most potent reference ligands and provided a good starting point to design and synthesize a series of highly selective and potent CDK8 ligands. Therefore, our novel virtual drug screening package is accurate and efficient enough to be used in drug design projects. We believe this work has significant impact to the field of drug discovery.
Acquired Immunological Tolerance and Carcinogenesis by the Mammary Tumor Virus. I. Influence of Neonatal Infection With the Mammary Tumor Virus on the Growth of Spontaneous Mammary Adenocarcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Donald L. Morton
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article Acquired Immunological Tolerance and Carcinogenesis by the Mammary Tumor Virus. I. Influence of Neonatal Infection With the Mammary Tumor Virus on the Growth of Spontaneous Mammary Adenocarcinomas Get access Donald L. Morton Donald L. Morton Cancer Research Institute and Department of Surgery, University of California Medical Center, San Francisco, California 94122, and Surgery Branch, National Cancer Institute,6Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 42, Issue 2, February 1969, Pages 311–320, https://doi.org/10.1093/jnci/42.2.311 Published: 01 February 1969 Article history Received: 07 October 1968 Accepted: 18 November 1968 Published: 01 February 1969
Formation of typical vascular lesions in a new experimental model of pulmonary arterial hypertension
Authors: Max-Paul Winter, Arman Alimohammadi, Adelheid Panzenboeck, Maria Sibilia, Felix Nagel, David Santer, Bruno Podesser, Sherin Alias, Maria Frey, Irene Lang
Journal: European Respiratory Journal (2013)

Background:  Pulmonary arterial hypertension (PAH) is a progressive disease characterized by obstruction of small pulmonary arteries leading to increased pulmonary vascular resistance. The key pathologic finding is a negative vascular remodeling process with total vessel occlusion and a monoclonal expansion of endothelial cells. Vascular endothelial growth factor (VEGF) signaling plays a significant role in this process. Aim of our study was to investigate whether inhibition of VEGFR-2 (KDR) by gene manipulation may replicate classical pulmonary vasculopathy.  Methods:  We utilized mice with conditional KDR knock-out in endothelial cells (KDR-/-). KDRflox/flox/Tie-2Cre and KDRflox/flox/Tie-2 mice were injected intraperitoneally with tamoxifen for 3 weeks to induce knock-out. KDR-/- mice and wild type littermates were held in an environmental chamber with FiO2 of 0.1 or under normoxia for 2, 4, and 6 weeks. We investigated the effect of KDR deletion and chronic normobaric hypoxia on pulmonary hemodynamics and right ventricular hypertrophy.  Results:  KDR-/- mice showed significantly increased right ventricular pressures (RVSP’s) and Fulton indices after 2, 4, and 6 weeks under normoxic conditions, compared with wild type controls. Both KDR-/- and wild type mice showed increased RVSP’s under normobaric hypoxia. KDR-/- mice revealed significantly higher RVSP’s and Fulton indices than controls after 4 and 6 weeks. Lung histologies demonstrated neointimal thickening and vessel occlusions in lungs of KDR-/- mice resembling human pulmonary arteriopathy.  Conclusion  Classical pulmonary arterial hypertension was induced in C57/BL6J mice by direct ablative gene manipulation of KDR.
Inflammation-induced formation of fat-associated lymphoid clusters
Authors: Cécile Bénézech, Nguyet-Thin Luu, Jennifer A Walker, Andrei A Kruglov, Yunhua Loo, Kyoko Nakamura, Yang Zhang, Saba Nayar, Lucy H Jones, Adriana Flores-Langarica, Alistair McIntosh, Jennifer Marshall, Francesca Barone, Gurdyal Besra, Katherine Miles, Judith E Allen, Mohini Gray, George Kollias, Adam F Cunningham, David R Withers, Kai Michael Toellner, Nick D Jones, Marc Veldhoen, Sergei A Nedospasov, Andrew N J McKenzie, Jorge H Caamaño
Journal: Nature Immunology (2015)
Importance of Adding Neomycin to Metronidazole for Bowel Preparation<sup>1</sup>
Authors: S Vallance, Y Arabi, B Jones, M R B Keighley
Journal: Journal of the Royal Society of Medicine (1980)

A prospective randomized trial has investigated whether it is necessary to add oral neomycin to oral metronidazole as a means of preventing sepsis in elective colonic resection. Seventy-three patients completed the study; 41 received metronidazole and placebo neomycin and 32 received metronidazole and active neomycin. There was a significant reduction in the incidence of wound infection in patients receiving neomycin and metronidazole (22%) compared with metronidazole alone (51%, P &lt; 0.02). There was also a significant reduction in anaerobic infections in the group receiving metronidazole and neomycin compared with metronidazole alone (P &lt; 0.05). These results indicate that oral metronidazole alone is of no benefit for patients requiring elective colonic operations and that if oral metronidazole is advised it should always be given in combination with oral neomycin.
Particularities of tuberculosis in pregnant women and women during of the first 3 years after childbirth
Authors: Ecaterina Evstratii, Valentina Vilc
Journal: European Respiratory Journal (2013)

Background: Unfavorable epidemiological situation of tuberculosis (TB) in Moldova led to the spread of TB in pregnant and women after childbirth.  Aim: to characterise clinical evolution of TB in pregnant women and women during of the first 3 years after childbirth, evaluation of risk factors in the development TB.  Methods: This was a retrospective study (2001-2010) of 66 women which divided in two groups: I – 33 cases of pregnancy associated with TB and II – 33 cases of TB in women during of the first 3 years after childbirth.  Results: TB in pregnant women were detected more frequently by active method (72,7%), in II group – 57,6% cases. In I group detected a higher degree of presence Pulmonary TB (39,4%) and Pleural TB (39,4%), in II group predominated Pulmonary TB – 84,8%. In 33,3% in I group and 27,3% in II group TB developed with complications. According to the results, more than half of pregnant women with pulmonary TB was detected in the third trimester of pregnancy – 57,6% of cases. In 72,7% of cases TB were detected during the pregnancy, in 27,3% cases pregnancy was detected in women with active TB. The majority of women lead the pregnancy at term – 87,9% and 12,1% finished with abortion. In II group TB was found more frequently in the first 6 months after birth - 39.5%. The main risk factor in the development of TB in I and II groups birth was the presence of comorbidities, while second place at pregnant women were social factors and women in II group - contact with TB patients.  Conclusions: Pregnant and women after childbirth must be included in the risk group of development of TB, and in relation to this population should have maximum caution.
Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins
Authors: M.S. de Oliveira, D.B. de Assis, M.P. Freire, G.V. Boas do Prado, A.S. Machado, E. Abdala, L.C. Pierrotti, C. Mangini, L. Campos, H.H. Caiaffa Filho, A.S. Levin
Journal: Clinical Microbiology and Infection (2014)
Microbiological impact of regular colistin use in a population of lung transplant recipients
Authors: Mohamed Al-Aloul, Bashar Al-Sheklly, Jamal Salai, Barbara Isalska
Journal: European Respiratory Journal (2012)

Long term outcomes of lung transplantation (LTx) are partly limited by infection. Due to increasing prevelance of multiresistant Pseudomonas aeruginosa (Pa) isolates we use colistin regularly in our LTx recipients and we now present its impact on microbiological surveillance.

Population: 3 groups between June 2005 and December 2011. Gp1: IV colistin for new and past LTx with confirmed or suspected gram negative infection not responding to treatment with tazocin (n=171). Gp 2: Prophylaxis in CF recipients with previous Pa to prevent/delay graft colonisation (n=32): colistin/TOBI nebs alternate months for 1 year then withdraw. Gp 3: Eradication of new Pa isolates in Pa naive recipients (n=29): 2 weeks of IV B-lactam+colistin followed by 3 months of nebulised colistin. Gp 2 and 3 had sputum/bronchial lavage tested 3 monthly for 1 year after treatment.

Results: Gp1- 443 courses of IV colistin, median dose 3 mu/day for a median 16 days; pathogens were confirmed in 69%. Gp2- continued growth, no growth and intermittent growth of Pa was seen in 23, 7 and 2 patients during surveillance. Pa was re-isolated from 4 at 4 months post prophylaxis. Gp3: 22 did not grow Pa after treatment and 17 showed no further isolates during follow up. 1141 sputa/lavages were analysed. Colistin resistance was not seen in any Pa isolates on E-test. New isolates of Stenotrophomas (x2), Ralstonia (x1) and Proteus (x1) were seen during colistin. 4 B. cepacia cases was seen in 2009, only 1 had received colistin.

Conclusion: Colistin can be used for various indications in LTx recipients with satisfactory outcomes. its regular application did not appear to induce resistance in pseudomonas nor select new resistant pathogens.
Predicting Factors Associated With Comorbidity Remission Following Bariatric Surgery
Authors: Scott Kahan
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 16718: The Long Noncoding RNA H19 Controls Vascular Ageing and Inflammation
Authors: Patrick Hofmann, Katharina M Michalik, Anuradha Doddaballapur, Stefanie Dimmeler, Reinier Boon
Journal: Circulation (2014)

Long noncoding RNAs (lncRNAs) are endogenously expressed noncoding RNAs with a length of more than 200 nucleotides, which can regulate gene expression through various mechanisms. Laminar shear stress and the expression of the flow-induced transcription factor Kruppel like factor 2 (KLF2) decrease with ageing. We hypothesize that protective factors like shear stress and detrimental factors like ageing and inflammation regulate the expression of lncRNAs that in turn regulate endothelial cell (EC) functions. Using next generation sequencing, we identified differentially regulated lncRNAs in several tissues of young and aged mice. The most profoundly regulated lncRNA was H19. Microarray profiling of lung ECs from 2 and 18 months old mice revealed a downregulation of H19 with ageing (-4.1 ± 1.2 fold), qPCR analysis of the same tissue from Ku80+/- progeria mice showed similar effects (-1.7 ± 0.4 fold) compared to WT littermates. In the aortic intima of 20 months old C57BL/6J mice, H19 was also downregulated (-3...
APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults
Authors: Wendy E Hoy, Michael D Hughson, Jeffrey B Kopp, Susan A Mott, John F Bertram, Cheryl A Winkler
Journal: Journal of the American Society of Nephrology (2015)

APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans.
Irritative effects of respirable particles and chromium in non-smoking welders
Authors: Martin Lehnert, Volker Harth, Frank Hoffmeyer, Rolf Merget, Katarzyna Gawrych, Kendzia Benjamin, Hans Berresheim, Evelyn Heinze, Monika Raulf-Heimsoth, Tobias Weiss, Beate Pesch, Thomas Brüning
Journal: European Respiratory Journal (2011)

Introduction: Welding fumes are known to contain chromium (Cr) compounds. Particulate matter, Cr and other constituents of welding fume may induce inflammatory reactions.

Aims and objectives: We studied irritative effects of welding fume and Cr in non-smoking welders using spirometry and fractional exhaled nitric oxide (FeNO).

Methods: Shift exposure to respirable particles in the welding fume was measured with personal samplers in the breathing zone of 119 non-smoking welders. The Cr concentration in these fume samples was determined by inductively coupled plasma mass spectrometry. Post-shift spirometry was performed with pneumotachography. FeNO was determined with a handheld device (NIOX Mino®). A potential irritative effect of Cr and welding fume was evaluated with multiple regression models.

Results: Lung function measurements revealed normal average values standardized to European Community of Coal and Steel. (median of forced vital capacity (FVC): 111.2%; forced expiratory volume in on second (FEV1):104.7%; Tiffeneau index (FEV1/FVC): 77%). Median of FeNO was 17.5 ppb. Cr, respirable welding fume and use of dust masks together explained less than 10% of the variance of the variables under study. We found no effect of any of these potential predictors measured during a single working shift on FeNO or Tiffeneau index.

Conclusion: Our data analysis did not reveal an acute irritative effect of Cr and welding fumes in non-smoking welders assessed with spirometry and FeNO. Nevertheless, further investigations with the implementation of non-invasive methods to assess inflammatory processes in the upper airways are necessary to make final conclusions.
Bronchiolitis obliterans organizing pneumonia (BOOP): the cytological and immunocytological profile of bronchoalveolar lavage
Authors: U Costabel, H Teschler, J Guzman
Journal: European Respiratory Journal (1992)

The cytological and immunocytological profile of bronchoalveolar lavage (BAL) was studied in 10 patients with idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) and compared with the data in idiopathic pulmonary fibrosis (IPF) (n = 22), chronic eosinophilic pneumonia (CEP) (n = 9), and extrinsic allergic alveolitis (EAA) (n = 24). Lymphocyte subsets were enumerated using an immunoperoxidase slide assay. The BAL pattern in BOOP patients was characterized by several features: 1) colorful cell differentials with an increase in all cell types, most markedly in lymphocytes, and more moderately in neutrophils, eosinophils and mast cells, as well as the presence of foamy macrophages and, occasionally, of plasma cells; 2) decreased CD4/CD8 ratio; 3) normal percentage of CD57+ cells; and 4) increase in activated T-cells in terms of human leucocyte antigen-DR (HLA-DR) expression, and occasionally also interleukin-2 receptor (CD25) expression. The findings were most similar to those in EAA except for the CD25 expression, which was always normal, and the CD57+ cells, which were increased in EAA. The increase in lymphocytes discriminated best between BOOP and IPF. The eosinophils were significantly higher in CEP than in BOOP with little overlap. In conclusion, BAL may be of value to distinguish between BOOP and other interstitial lung disease.
Mammary Gland Hyperplastic Alveolar Noduligenesis in the LEW/Mai Rat in Relation to Mitotic Activity, Estrous Cycle Status, and Age2
Authors: Dallas M. Purnell, Deborah J. Stowers
Journal: JNCI Journal of the National Cancer Institute (1978)

Spontaneous mammary hyperplastic alveolar noduligenesls was studied in nulliparous female LEW/Mal rats In relation to age, estrous cycle status, and mammary gland mitotic activity. The morphometric composition of the mammary gland and the incidence of hyperplastic alveolar nodules (HAN) and dysplaslas were determined by examination of stained whole-mount preparations of one of the Inguinal mammary glands. Mitotic activity In the contralateral mammary gland rose almost linearly from 30 to 108 days of age and then fell progressively thereafter, although mitotic activity remained significantly elevated compared to that in mammary glands of rats less than 100 days old. Mitotic activity was nonrandomly distributed in the mammary glands of young pubertal rats in contrast to that in glands of prepubertal rats and in rats In persistent estrus, In which it tended to be randomly distributed. HAN were present In some rats by 150 days of age and were frequent in the mammary glands of most rats older than 200 days. All animals with HAN were in persistent vaginal estrus and had Significantly Increased pituitary weights. This association suggested that hormone imbalance may be an important etiologic factor in spontaneous hyperplastic alveolar noduligenesls in the rat.
HER2/neu-directed therapy for biliary tract cancer
Authors: Milind Javle, Chaitanya Churi, HyunSeon C. Kang, Rachna Shroff, Filip Janku, Rakesh Surapaneni, Mingxin Zuo, Christian Barrera, Humaid Alshamsi, Sunil Krishnan, Lopa Mishra, Robert A. Wolff, Ahmed O. Kaseb, Melanie B. Thomas, Abby B. Siegel
Journal: Journal of Hematology & Oncology (2015)

Biliary cancers are highly aggressive tumors that are often diagnosed an advanced disease stage and have a poor outcome with systemic therapy. Recent efforts towards molecular characterization have identified a subset of biliary patients that have HER2/neu amplification or mutation. HER2/neu amplification is associated with response to HER2/neu-directed therapy in breast and gastric cancers. However, the efficacy of HER2/neu-targeted therapy in biliary cancers is unknown.We retrospectively reviewed cases of advanced gallbladder cancer and cholangiocarcinoma with HER2/neu genetic aberrations or protein overexpression who received HER2/neu-directed therapy between 2007 and 2014. Clinical data were retrieved from medical records, and imaging studies were independently reviewed.Nine patients with gallbladder cancer and five patients with cholangiocarcinoma had received HER2/neu-directed therapy (trastuzumab, lapatinib, or pertuzumab) during the study period. In the gallbladder cancer group, HER2/neu gene amplification or overexpression was detected in eight cases. These patients experienced disease stability (n = 3), partial response (n = 4), or complete response (n = 1) with HER2/neu-directed therapy. One patient had HER2/neu mutation and experienced a mixed response after lapatinib therapy. The duration of response varied from 8+ to 168 weeks (median 40 weeks), and three patients are still on therapy. One patient developed HER2/neu amplification as a secondary event after FGFR-directed therapy for FGF3-TACC3 gene fusion. The cholangiocarcinoma cases treated in this series had a higher proportion of HER2/neu mutations, and no radiological responses were seen in these patients despite HER2/neu-directed therapy.HER2/neu blockade is a promising treatment strategy for gallbladder cancer patients with gene amplification and deserves further exploration in a multi-center study.
ABC of learning and teaching in medicine: Creating teaching materials
Authors: R. Farrow
Journal: BMJ (2003)

The nature and qualities of the teaching materials that you use can have a substantial effect on the educational experience of your students. Teaching materials can often distract learners rather than help them to learn. Common avoidable problems include overcrowded or illegible slides, irrelevant or badly prepared handouts, and incompatible multimedia equipment. It is important therefore to know how to create effective teaching materials.

Five basic principles apply to preparing teaching materials, irrespective of the type of material you choose: links, intelligibility, general style, highlighting, and targeting (LIGHT). You may sometimes decide to ignore one or more of these principles, but if you do, think carefully about what you are trying to achieve.

### Links

Your teaching materials should have obvious and direct links to your talk, discussion, or presentation. Handouts are the main offenders in this category, and it is not unusual for handouts to have little in common with the talk. It is quite acceptable for the teaching materials to give some additional information, but this should not be excessive.

#### Preparing overhead transparencies

##### Do

##### Don't

### Intelligibility

The teaching material should be easy to understand and learn from. How this is achieved will depend on the medium used and the venue of the talk or presentation. Use simple language and avoid overlong sentences or statements. Diagrams can help to clarify a complex message. If you are using slides or overhead transparencies, the size of the print needs to be large enough …