tbuckley/cabot-search huggingface dataset:
THE EFFECT OF NUTRITIONAL DISTURBANCES ON THE SUSCEPTIBILITY OF MICE TO STAPHYLOCOCCAL INFECTIONS
Authors: J. Maclean Smiths, René J. Dubos
Journal: The Journal of Experimental Medicine (1956)

The susceptibility of mice to intravenous injection of coagulase-positive hemolytic staphylococci was estimated by (a) observing the extent and time of mortality of infected animals; (b) determining the number of colonies of cocci that could be recovered from the liver and spleen at various intervals of time after infection. Complete deprival of food for 36 to 48 hours immediately before infection was found to increase susceptibility. This infection-enhancing effect was further increased by allowing the animals to drink a 5 per cent glucose solution instead of water or saline during the fasting period. In contrast, sodium lactate partially corrected the effect of fasting. The infection-enhancing effect of fasting was reversible. Mice prevented from gaining weight for several weeks either by restricting their daily food intake, or by feeding them ad lib. an inadequate diet, appeared just as resistant to staphylococcal infection as did mice that gained weight rapidly on an unrestricted, complete diet.
A Pilot Study of Bacterial Genes with Disrupted ORFs Reveals a Surprising Profusion of Protein Sequence Recoding Mediated by Ribosomal Frameshifting and Transcriptional Realignment
Authors: V. Sharma, A. E. Firth, I. Antonov, O. Fayet, J. F. Atkins, M. Borodovsky, P. V. Baranov
Journal: Molecular Biology and Evolution (2011)

Bacterial genome annotations contain a number of coding sequences (CDSs) that, in spite of reading frame disruptions, encode a single continuous polypeptide. Such disruptions have different origins: sequencing errors, frameshift, or stop codon mutations, as well as instances of utilization of nontriplet decoding. We have extracted over 1,000 CDSs with annotated disruptions and found that about 75% of them can be clustered into 64 groups based on sequence similarity. Analysis of the clusters revealed deep phylogenetic conservation of open reading frame organization as well as the presence of conserved sequence patterns that indicate likely utilization of the nonstandard decoding mechanisms: programmed ribosomal frameshifting (PRF) and programmed transcriptional realignment (PTR). Further enrichment of these clusters with additional homologous nucleotide sequences revealed over 6,000 candidate genes utilizing PRF or PTR. Analysis of the patterns of conservation apparently associated with nontriplet decoding revealed the presence of both previously characterized frameshift-prone sequences and a few novel ones. Since the starting point of our analysis was a set of genes with already annotated disruptions, it is highly plausible that in this study, we have identified only a fraction of all bacterial genes that utilize PRF or PTR. In addition to the identification of a large number of recoded genes, a surprising observation is that nearly half of them are expressed via PTR—a mechanism that, in contrast to PRF, has not yet received substantial attention.
Osteopontin: a new player in regulating hepatic ductular reaction and hepatic progenitor cell responses during chronic liver injury
Authors: Mario Strazzabosco, Luca Fabris, Emanuele Albano
Journal: Gut (2014)

In recent years, an increasing number of reports have shown the involvement of osteopontin (OPN), a pleiotropic cytokine and an important component of the extracellular matrix (ECM), in the pathogenesis of liver injury and the development of fibrosis.1 ,2 OPN is also frequently overexpressed in hepatocellular carcinoma (HCC), where it modulates HCC growth, invasion and metastasis,2 and in cholangiocarcinoma, where its expression bears prognostic significance. Previous studies3 have shown that in injured livers OPN is expressed by hepatic stellate cells (HSC) and upregulates collagen I production. Interestingly, in HSC, OPN expression appears to be downstream of SOX9, a Hedgehog- and Notch-controlled transcription factor that is expressed also in biliary cells and hepatic progenitor cells (HPC)/hepatocytes committed to the biliary fate.4–6 In this issue of Gut , two papers investigate the role of OPN in HPC-driven ductular reaction (DR) in relation to the progression of liver fibrosis.7 ,8

DR, a histological lesion present in most chronic liver diseases, is a dynamic, multicellular complex characterised by the presence of ‘reactive’ ductular epithelial cells, arranged in irregular strings along the margins of the portal tract in close contact with mesenchymal, inflammatory and endothelial cells. Reactive ductular cells acquire novel functions including the secretion of cytokines, chemokines, growth factors and angiogenic factors, enabling them to establish intense paracrine communications with …
Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases
Authors: Marta Rusmini, Silvia Federici, Francesco Caroli, Alice Grossi, Maurizia Baldi, Laura Obici, Antonella Insalaco, Alberto Tommasini, Roberta Caorsi, Eleonora Gallo, Alma Nunzia Olivieri, AngeloValerio Marzano, Domenico Coviello, Roberto Ravazzolo, Alberto Martini, Marco Gattorno, Isabella Ceccherini
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing a primary dysfunction of the innate immune system. More than 50% of patients with SAID does not show any mutation at gene(s) tested because of lack of precise clinical classification criteria and/or incomplete gene screening. To improve the molecular diagnosis and genotype interpretation of SAIDs, we undertook the development of a next-generation sequencing (NGS)-based protocol designed to simultaneous screening of 10 genes. <h3>Methods</h3> Fifty patients with SAID, already genotyped for the respective causative gene(s), were massively sequenced for the coding portions of <i>MEFV</i>, <i>MVK</i>, <i>TNFRSF1A</i>, <i>NLRP3</i>, <i>NLRP12</i>, <i>NOD2</i>, <i>PSTPIP1</i>, <i>IL1RN</i>, <i>LPIN2</i> and <i>PSMB8</i>. Three different bioinformatic pipelines (Ion Reporter, CLC Bio Genomics Workbench, GATK-based in-house workflow) were compared. <h3>Results</h3> Once resulting variants were compared with the expected mutation list, no workflow turned out to be able to detect all the 79 variants known in the 50 DNAs. Additional variants were also detected, validated by Sanger sequencing and compared to assess true and false positive detection rates of the three workflows. Finally, the overall clinical picture of 34 patients was re-evaluated in the light of the new mutations found. <h3>Conclusions</h3> The present gene panel has resulted suitable for molecular diagnosis of SAIDs. Moreover, genotype–phenotype correlation has confirmed that the interpretation of NGS data in patients with an undefined inflammatory phenotype is remarkably difficult, thus supporting the need of evidence-based and validated clinical criteria to be used concurrently with the genetic analysis for the final diagnosis and classification of patients with SAIDs.
Evaluation of aid to diagnosis of pigmented skin lesions in general practice: controlled trial randomised by practice
Authors: D. R English
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To determine whether an aid to the diagnosis of pigmented skin lesions reduces the ratio of benign lesions to melanomas excised in general practice. <b>Design</b> Controlled trial randomised by practice. <b>Setting</b> General practices in Perth, Western Australia. <b>Participants</b> 468 general practitioners in 223 practices. <b>Interventions</b> Intervention practices were given an algorithm and instant camera to assist with the diagnosis of pigmented skin lesions. All practices were given national guidelines on managing melanoma. <b>Main outcome measures</b> Ratio of benign pigmented lesions to melanomas excised. Analyses conducted with and without inclusion of seborrhoeic keratoses. <b>Results</b> At baseline the ratios of benign to malignant lesions were lower in the intervention group than in the control group. During the trial period the ratios were higher in the intervention group (19:1 <i>v</i> 17:1 without seborrhoeic keratoses and 29:1 <i>v</i> 26:1 with seborrhoeic keratoses). After adjustment for patients9 age, sex, and socioeconomic status, the ratio was 1.02 times higher (95% confidence interval 0.68 to 1.51, P = 0.94) in the intervention group when seborrhoeic keratoses were not included and 1.03 times higher (0.71 to 1.50, P = 0.88) when seborrhoeic keratoses were included. General practitioners in the intervention group were less likely than those in the control group to excise the most recent pigmented skin lesion they managed (22% <i>v</i> 48%, P &lt; 0.001) and to refer the patient to a specialist (16% <i>v</i> 27%, P = 0.06). <b>Conclusions</b> Provision of the algorithm and camera did not decrease the ratio of benign pigmented skin lesions to melanomas excised by general practitioners.
GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice
Authors: C Plater-Zyberk, L A B Joosten, M M A Helsen, J Hepp, P A Baeuerle, W B van den Berg
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> In this study, we identify the nature of the immunological response of human peripheral blood mononuclear cells (PBMC) and lamina propria gastric lymphocytes (LPL) to two <i>Helicobacter pylori</i> antigens, the neutrophil activating protein (NapA) and alkyl hydroperoxide reductase (AphC). These antigens were identified and selected for study based on the observation that serological recognition of these proteins was associated with <i>H pylori</i> negative status in humans. <b>Aims:</b> The aim was to study the serological, proliferative, and cytokine responses of PBMC and LPL, obtained from <i>H pylori</i> infected and uninfected individuals, to these antigens. <b>Methods:</b> Patient serum, PBMC, and LPL were used to determine antibody isotype, and proliferative and cytokine responses to recombinant forms of NapA and AphC using western blotting and ELISA. <b>Results:</b> Western blotting revealed antibody reactivity to recombinant NapA and AphC among the <i>H pylori</i> negative population studied. Both the proliferative and interferon γ responses of PBMC and LPL to NapA and AphC were significantly higher in <i>H pylori</i> negative compared with <i>H pylori</i> positive subjects. Analysis of the IgG subclass profiles to both antigens revealed a T helper 1 associated IgG3 antibody response in uninfected individuals. However, interleukin 10 production was greater in <i>H pylori</i> positive individuals in response to these antigens. <b>Conclusions:</b> Taken together these data are consistent with an immune response to these antigens skewed towards a T helper 1 response in the uninfected cohort.
STUDIES ON THE MECHANISM OF ADAPTATION OF INFLUENZA VIRUS TO MICE
Authors: George K. Hirst
Journal: The Journal of Experimental Medicine (1947)

1. When strains of influenza A virus which have been isolated in chick embryos are introduced into the mouse lung, the virus multiplies readily and achieves initially a titer which is as high as is even obtained, even after repeated passage. The high initial titer of virus may be unaccompanied by any lethal or visible pathogenic effects; but with four or five mouse passages the agent becomes lethal in high titer and causes extensive pulmonary consolidation, though its capacity to multiply in the lung has not increased. In one example the adaptation to mouse lung was accompanied by increasing capacity to agglutinate guinea pig red cells without a corresponding increase in agglutinating power for chicken cells. Influenza B virus, in preliminary tests, did not behave in a similar fashion. 2. The adaptation of influenza A virus to mice is accompanied by changes in antigenic pattern, as detected by cross-tests with the agglutination inhibition method. Two strains, initially similar, with passage, changed in pattern along divergent paths so that they became not only unlike the parent strains but unlike each other. This finding has important implications for the interpretation of the strain difference problem in human influenza.
P7 Assessing the intuitive ease of use of a novel dry powder inhaler, the Forspiro™ device, for asthma and COPD: Abstract P7 Table 1
Authors: S Jones, T Weuthen, QJ Harmer, JC Virchow
Journal: Thorax (2012)

<h3></h3> Poor inhaler technique has been recognised as a significant contributor to poor control.(1) A number of authors have attempted to identify desirable attributes of an inhaler.(2,3) “Ease of use” is an important characteristic but is often determined after instructed training. Whilst the importance of initial and repeat correct inhaler technique training cannot be overlooked, a dry powder inhaler (DPI) device that is intuitively easy to use may be more beneficial for those patients with poor technique recall or with barriers to access adequate training. An intuitively easy to use inhaler such as the Sandoz Forspiro™ device may facilitate correct patient handling. A 28 day study to assess the intuitive ease of use of the Forspiro device was conducted in 24 Accuhaler® users (≥ 1 year use), aged 20–86 years (mean age = 53.8). Participants were separated into 2 groups of 12 and received either limited written instructions about the use of the device (Uninstructed) or were given fully illustrated instructions for use (Instructed). See table 1. The correlation of the ease of use assessment by Uninstructed and Instructed subjects has shown that the new Forspiro DPI is intuitive to use, even in patients that had received minimal instructions for use. The introduction of innovative generic versions of inhaled medications enables the much needed economic rationalisation of drug use in these times of austerity within the NHS. Benefitting from advanced design technology, drawn from years of patient feedback, generic versions of inhaled medications may be more readily adopted by patients and HCPs if the device is intuitive to use. The importance of initial and repeat correct inhaler technique training cannot be overlooked, however intuitively easy to use inhalers, such as the Forspiro device, may facilitate correct patient handling. Refs: 1. Giraud 2002; 2. Virchow 2008; 3. Chrystyn 2007
The Role of Cardiac MRI Stress Testing
Authors: Gerald M. Pohost, Robert W. W. Biederman
Journal: Circulation (1999)

ear the turn of the 20th century, Ralph Waldo Emerson said, "If a man can make a better mouse trap than his neighbor, the world will make a beaten path to his door."In the 1900s, we have seen particularly illuminating examples of this prediction: from the model T Ford, which in one decade eliminated the horse-and-buggy era, to the introduction of the heart-lung machine by John Gibbon, Jr, in 1953, which indelibly changed medicine, and, more recently, Andreas Gruentzig's intrepid introduction of intracoronary angioplasty, revolutionizing the treatment of coronary artery disease (CAD).
Uptake of cystic fibrosis testing in primary care: supply push or demand pull?
Authors: H Bekker, M Modell, G Denniss, A Silver, C Mathew, M Bobrow, T Marteau
Journal: BMJ (1993)

OBJECTIVE--To determine the acceptability and feasibility of screening for carriers of cystic fibrosis in a primary care setting. DESIGN--Follow up study over 15 months of patients offered carrier testing by mouthwash. SETTING--A general practice in inner London. SUBJECTS--5529 patients aged 18-45 invited by various methods and combinations of methods (letter, booklet, personal approach) for testing. MAIN OUTCOME MEASURES--Uptake of screening, anxiety, and knowledge of test. RESULTS--957 (17%) invitees were screened over the 15 months. 28 carriers and no carrier couples were detected. Uptake rates were 12% (59/502 patients) among patients invited by letter and tested by appointment; 9% (47/496) among patients invited by letter, with leaflet, and tested by appointment; 4% (128/2953) among patients invited by letter six weeks before the end of the study and tested by appointment; 17% (81/471) among patients offered passive opportunistic testing; 70% (453/649) among patients offered active opportunistic testing; and 25% (22/88) among patients offered active opportunistic testing by appointment. A short term rise in anxiety among those given a positive test result had dissipated by three months. At three months about one fifth and one third of those given positive and negative results respectively did not understand their results correctly. CONCLUSION--These results suggest that the strongest variable in determining uptake of screening is the active approach by a health professional offering immediate testing. It remains to be resolved whether the high uptake rates achieved by active recruitment indicate a supply push for this new test rather than a demand from the population.
A phase II trial of neoadjuvant cisplatin–fluorouracil followed by postoperative intraperitoneal floxuridine–leucovorin in patients with locally advanced gastric cancer
Authors: B. Brenner, M.A. Shah, M.S. Karpeh, M. Gonen, M.F. Brennan, D.G. Coit, D.S. Klimstra, L.H. Tang, D.P. Kelsen
Journal: Annals of Oncology (2006)
Validity and reliability of the St George's Respiratory Questionnaire after adaptation to a different language and culture: the Spanish example
Authors: M Ferrer, J Alonso, L Prieto, V Plaza, E Monso, R Marrades, MC Aguar, A Khalaf, JM Anto
Journal: European Respiratory Journal (1996)

We describe the adaptation into Spanish of the St George's Respiratory Questionnaire (SGRQ), a self-administered questionnaire developed by Jones et al. (1991) covering three domains of health in airways disease patients: symptoms, activity and impacts. For the adaptation, the forward and back-translation method by bilinguals was used, together with professional committee and lay panel. Once tested for feasibility and comprehension, 318 male chronic obstructive pulmonary disease (COPD) patients with a wide range of disease severity completed the Spanish version of the SGRQ. The clinical status of the patients was evaluated concurrently with the measurement of health status. Lung function was assessed in the 2 months before or after the questionnaire administration. The Spanish version of the SGRQ was acceptable and easy to understand. Cronbach's alpha reliability coefficient was 0.94 for the overall scale and 0.72 for "Symptoms", 0.89 for "Activity", and 0.89 for "Impacts" subscales. Correlation coefficients between the overall score and dyspnoea and % forced expiratory volume in one second (FEV1) were 0.59 and -0.45, respectively, and these correlations were higher than those observed between the clinical variables and the Nottingham Health Profile, a generic measure of health-related quality of life. Results of the study suggest that the Spanish version of the SGRQ is conceptually equivalent to the original, and similarly reliable and valid. Although further studies should complete the adaptation work, results suggest that the SGRQ may already be used in Spain and in international studies involving Spanish respiratory patients. According to the present approach, it appears to be feasible to adapt a specific questionnaire on health-related quality of life in respiratory disease to another language and culture.
Genetics and pulmonary medicine bullet 1: The genetics of cystic fibrosis lung disease
Authors: D. J Davidson, D. J Porteous
Journal: Thorax (1998)

Since the isolation of the gene responsible for cystic fibrosis in 1989 we have witnessed rapid progress in our understanding of this common genetic disorder. Progressively more detailed knowledge of the disease causing mutations, the gene expression patterns, the protein structure, and its function as an ion channel has allowed the development of reliable screening programmes, the creation of animal models, and the design of novel therapeutic approaches. The biological basis of many aspects of the disease phenotype are becoming clearer, including recent significant advances in understanding the pathogenesis of the characteristic and ultimately fatal lung disease. While this great expansion of knowledge has started to bridge the gap between our understanding of the genetic defect and the well documented clinical sequelae, it has also served to demonstrate the mechanistic complexity of this “simple” single gene defect.

Cystic fibrosis is the most common lethal autosomal recessive genetic disorder in Caucasian populations with a carrier frequency of one in 25. It affects about one in 2500 live births and has a median life expectancy of 28 years.1 

The characteristic manifestations are due primarily to dysfunction of exocrine glands, producing viscid, dehydrated secretions. The resultant phenotype is of salty sweat, pancreatic insufficiency (with consequent malabsorption and failure to thrive), intestinal obstruction (with meconium ileus in 10–20% of patients in the first few days of life), infertility and severe pulmonary disease. The electrophysiological profile of affected tissues shows characteristic abnormalities in the transport of chloride and sodium ions across the apical membrane.2 

The recent advancement of our knowledge was sparked by the cloning, in 1989, of the gene responsible for the disease—the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. Located on the long arm of human chromosome 7, it spans over 250 kb, contains 27 exons, and encodes a 1480 residue …
Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans.
Authors: J W Murphy, M R Hidore, S C Wong
Journal: Journal of Clinical Investigation (1993)

Lymphocytes, especially CD4+ T cells, are essential for clearance of the yeast-like organism Cryptococcus neoformans from the infected host. The mechanism(s) by which the lymphocytes facilitate elimination of cryptococci has not been elucidated. It is generally thought, however, that lymphocytes reactive with C. neoformans indirectly function by production of lymphokines to enhance clearance of the organism by natural effector cells such as macrophages. In the present study, we assessed the ability of freshly isolated human lymphocytes to interact directly with C. neoformans and to limit the growth of the organism in vitro. We found that large granular lymphocytes (LGL) as well as T cells bound to cryptococcal cells when the lymphocytes were mixed with the cryptococcal cells at a 2:1 ratio. The physical binding interactions of the two lymphocyte populations were different. LGL attached to the cryptococcal cells by many microvilli; T lymphocytes associated with the yeast through broad areas of membrane attached to the cryptococcal cell surface. The two types of lymphocyte interactions did not result in phagocytosis but resulted in direct inhibition of cryptococcal growth, making these lymphocyte interactions with cryptococci distinctly different from interactions of monocytes with cryptococci. With the human natural killer (NK) cell line, NK 3.3, we confirmed that NK cells that were present in the LGL population were capable of limiting the growth of C. neoformans. Through immunoelectron microscopy, human CD3+ lymphocytes were seen attached to cryptococcal cells and by mass cytolysis, human CD3+ lymphocytes were shown to be responsible for inhibition of C. neoformans growth. The direct inhibitory interactions of NK cells and T lymphocytes with cryptococcal cells may be important means of host defense against this ubiquitous organism that frequently causes life-threatening disease in AIDS patients.