tbuckley/cabot-search huggingface dataset:
Resistance to penicillin among the<i>Streptococcus pneumoniae</i>in Turkey
Authors: A.S. Yurdakul, H.C. Çalişir, M. Atasever, L. Ordulu, M. Öğretensoy
Journal: European Respiratory Journal (2001)

To the Editor: 

Streptococcus pneumoniae is the most common micro-organism which causes respiratory tract diseases affecting all age groups. The increasing frequency of pneumococcal strains resistant to penicillin has been reported all over the world. The emergence of drug-resistant strains threatens to complicate the management of respiratory infections due to pneumococcus. Ataturk Chest Disease and Thoracic Surgery Centre is one of the biggest training hospitals for pulmonary disease in Turkey. Nine-thousand inpatients and 60,000 outpatients with respiratory diseases are treated every year. Bacteriological examinations of materials obtained from …
Endomysium antibodies in coeliac disease: an improved method.
Authors: B Ladinser, E Rossipal, K Pittschieler
Journal: Gut (1994)

The ultra structural binding sites of endomysium antibodies have been studied on human umbilical cord tissue. The sensitivity and specificity of IgA endomysium antibodies were compared with recently described methods using basement membrane of smooth muscle of monkey oesophagus. Thirty adults affected by coeliac disease (10 in remission) and 75 healthy adult controls with normal intestinal mucosa (35 false antigliadin positive) were investigated. Sensitivity and correlation of endomysium antibodies with total villous atrophy in untreated coeliac disease patients were 100% on the human umbilical cord smooth muscles, and only 90% on the muscular layer of primate oesophagus. Indirect immunofluorescence was superior to peroxidase staining in detecting these IgA antibodies. The easy availability and enhanced testing sensitivity of the umbilical cord is an advance towards a better diagnostic tool for coeliac disease.
Transgenic and gene-targeted mice as models for chronic obstructive pulmonary disease
Authors: S. D. Shapiro
Journal: European Respiratory Journal (2007)

Animal models play an important role in the understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD). The applicability of findings to human COPD depends upon several factors, including the disease model, and similarities in mouse structure and function between species. There are many examples in the literature of transgenic mice that have contributed to the understanding of COPD. Several studies demonstrate the complexity of inflammatory networks and how unexpected findings in animal models have led to the search for new potential mediators in human disease. Gene-targeting studies into alpha(1)-antitrypsin (alpha(1)-AT) and emphysema in mice have demonstrated that the genetic locus for alpha(1)-AT in mice is very complex and that the loss of one gene is lethal in embryo lung development. This underlines the differences between mice and humans that limit the ability to translate between systems in some instances. Gene targeting has also highlighted complex roles for transforming growth factor-beta in COPD and has been used to determine important molecules and pathways in COPD. Both transgenic and gene-targeted models suffer limitations and their applicability to human chronic obstructive pulmonary disease may be dependant on several factors, some of which are still being learnt. The more that is known about similarities and differences, the better the knowledge will be that is gained to develop for chronic obstructive pulmonary disease.
Reversible Kinetic Analysis of Myc Targets <i>In vivo</i> Provides Novel Insights into Myc-Mediated Tumorigenesis
Authors: Elizabeth R. Lawlor, Laura Soucek, Lamorna Brown-Swigart, Ksenya Shchors, C. Uli Bialucha, Gerard I. Evan
Journal: Cancer Research (2006)

Abstract Deregulated expression of the Myc transcription factor is a frequent causal mutation in human cancer. Thousands of putative Myc target genes have been identified in in vitro studies, indicating that Myc exerts highly pleiotropic effects within cells and tissues. However, the complexity and diversity of Myc gene targets has confounded attempts at identifying which of these genes are the critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of Myc in a reversibly switchable transgenic model of Myc-mediated β cell tumorigenesis induces rapid tumor onset, whereas subsequent Myc deactivation triggers equally rapid tumor regression. Thus, sustained Myc activity is required for tumor maintenance. We have used this reversibly switchable kinetic tumor model in combination with high-density oligonucleotide microarrays to develop an unbiased strategy for identifying candidate Myc-regulated genes responsible for maintenance of Myc-dependent tumors. Consistent with known Myc functions, some Myc-regulated genes are involved in cell growth, cycle, and proliferation. In addition, however, many Myc-regulated genes are specific to β cells, indicating that a significant component of Myc action is cell type specific. Finally, we identify a very restricted cadre of genes with expression that is inversely regulated upon Myc activation-induced tumor progression and deactivation-induced tumor regression. By definition, such genes are candidates for tumor maintenance functions. Combining reversibly switchable, transgenic models of tumor formation and regression with genomic profiling offers a novel strategy with which to deconvolute the complexities of oncogenic signaling pathways in vivo. (Cancer Res 2006; 66(9): 4591-601)
Patellar taping for patellofemoral pain: a systematic review and meta-analysis to evaluate clinical outcomes and biomechanical mechanisms
Authors: Christian Barton, Vivek Balachandar, Simon Lack, Dylan Morrissey
Journal: British Journal of Sports Medicine (2013)

Patellar taping is frequently used to treat patellofemoral pain (PFP). This systematic review and meta-analysis (1) evaluates the efficacy of patellar taping for patients with PFP, (2) compares the efficacy of various taping techniques and (3) identifies potential biomechanical mechanisms of action.The MEDLINE, CINAHL, SPORTSDiscus, Web of Science and Google Scholar databases were searched in January 2013 for studies evaluating the effects of patellar taping on pain and lower-limb biomechanics in individuals with PFP. Three independent reviewers assessed each paper for inclusion and two assessed for quality. Means and SDs were extracted from each included study to allow effect size calculations.Twenty studies were identified. There is moderate evidence that (1) tailored (customised to the patient to control lateral tilt, glide and spin) and untailored patellar taping provides immediate pain reduction of large and small effect, respectively and (2) tailored patellar taping promotes earlier onset of vastus medialis oblique (VMO) contraction (relative to vastus lateralis contraction). There is limited evidence that (1) tailored patellar taping combined with exercise provides superior pain reduction compared to exercise alone at 4 weeks, (2) untailored patellar taping added to exercise at 3-12 months has no benefit and (3) tailored patellar taping promotes increased internal knee extension moments.Tailoring patellar taping application (ie, to control lateral tilt, glide and spin) to optimise pain reduction is important for efficacy. Evaluation of tailored patellar taping beyond the immediate term is limited and should be a research priority. Possible mechanisms behind patellar taping efficacy include earlier VMO onset and improved knee function capacity (ie, ability to tolerate greater internal knee extension moments).
Treatment of childhood nephrotic syndrome.
Authors: S A Mendoza, B M Tune
Journal: Journal of the American Society of Nephrology (1992)

This review examines selected aspects of the treatment of the nephrotic syndrome in children. Particular attention has been paid to two groups of nephrotic children. First, children with steroid-responsive nephrotic syndrome are discussed. Recently, a series of controlled studies have provided important information regarding the optimal duration of steroid therapy. Initial episodes of the nephrotic syndrome are best treated with "long" courses of prednisone therapy (6 wk of high-dose daily prednisone followed by 6 wk of alternate-day prednisone). In contrast, relapses do as well with "short" courses (about 2 wk of daily prednisone and 2 wk of alternate-day therapy). Some children who are steroid responsive require high doses of prednisone to remain in remission. These patients may require alkylating agent therapy. The most common cause of steroid-resistant nephrotic syndrome is focal segmental glomerulosclerosis. Over the past 10 yr, these patients have been treated with an intensive protocol involving multiple infusions of high-dose methylprednisolone and, in many cases, oral alkylating agent therapy. Current experience with this treatment is presented. The protocol appears to improve the outcome in children with focal segmental glomerulosclerosis, although it is believed that it is essential that these observations be confirmed by a controlled trial. There is also interest in the use of angiotensin-converting enzyme inhibitors and cyclosporine in the treatment of childhood nephrotic syndrome. The experience with these agents is briefly reviewed, but the current data are inadequate to indicate their role(s) in this condition.
Heavy chain variable (VH) region diversity generated by VH gene replacement in the progeny of a single precursor cell transformed with a temperature-sensitive mutant of Abelson murine leukemia virus.
Authors: T Shirasawa, I Miyazoe, S Hagiwara, H Kimoto, K Shigemoto, M Taniguchi, T Takemori
Journal: The Journal of Experimental Medicine (1992)

Sequence analysis of a large number of DNA clones containing a functional heavy chain variable, diversity, and joining (VHDJH) complex generated by VH to VHDJH joining (VH gene replacement) in the progeny derived from a common precursor cell transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A-MuLV) indicates that endogenous VH gene replacement in vitro generates immunoglobulin gene joints distinct from those generated by the usual VH to DJH joining. Such joints keep the pentamer CAAGA at the 3' end of the donor VH segment and lack a recognizable D segment, as can be seen also in vivo. The results suggest that VH gene replacement participates in generating VH region diversity in vivo, as previously postulated. During the joining process, a unique VH gene was selected in all progeny cells, together with a single A nucleotide dominantly added to the junctional boundaries. The basis of these regulatory processes is discussed.
The use of abatacept in debilitating cavitating lung disease associated with rheumatoid arthritis, bronchocentric granulomatosis and aspergillosis
Authors: K. Neff, J. Stack, S. Harney, M. Henry
Journal: Thorax (2010)

A case of debilitating cavitating lung disease associated with rheumatoid arthritis and bronchocentric granulomatosis, which failed to respond to conventional medical or surgical treatment, is described. The patient was treated over 10 years with steroids, antimicrobial agents, disease-modifying antirheumatoid drugs and surgery. Lung function continued to decline and the patient presented for admission with recurrent pneumonia. Abatacept was initiated to modify the underlying immunopathology. Following 12 months of treatment with abatacept the patient has demonstrable improvement in lung function and lung anatomy, and has not presented to hospital with pneumonia. She has tolerated the treatment without complication. The use of abatacept has stabilised the lung disease in this case in the medium term and prevented readmission to hospital. These results suggest a larger role for abatacept in those with such disease in the future and may warrant further investigation.
Dual Receptor T Cells Mediate Pathologic Alloreactivity in Patients with Acute Graft-Versus-Host Disease
Authors: Gerald P. Morris, Geoffrey L. Uy, David Donermeyer, John F. DiPersio, Paul M. Allen
Journal: Science Translational Medicine (2013)

Acute graft-versus-host disease (aGVHD) results from a robust response of donor T cells transferred during hematopoietic stem cell transplantation (HSCT) to allogeneic peptide-major histocompatibility complex antigens. Previous investigations have not identified T cell subsets that selectively mediate either protective immunity or pathogenic alloreactivity. We demonstrate that the small subset of peripheral T cells that naturally express two T cell receptors (TCRs) on the cell surface contributes disproportionately to aGVHD in patients after allogeneic HSCT. Dual TCR T cells from patients with aGVHD demonstrate an activated phenotype and produce pathogenic cytokines ex vivo. Dual receptor clones from a patient with symptomatic aGVHD responded specifically to mismatched recipient human leukocyte antigens (HLAs), demonstrating pathologic alloreactivity. Human dual TCR T cells are strongly activated and expanded by allogeneic stimulation in vitro, and disproportionately contribute to the repertoire of T cells recognizing both major (HLA) and minor histocompatibility antigens, providing a mechanism for their observed activity in vivo in patients with aGVHD. These results identify dual TCR T cells as a target for focused analysis of a T cell subset mediating GVHD and as a potential prognostic indicator.
Bioluminescence Imaging of Prenylation Inhibition–Letter
Authors: Philippe Clezardin
Journal: Clinical Cancer Research (2012)

We read with great interest the recent article by Chinault and colleagues (1), providing evidence that aminobisphosphonate zoledronic acid (ZOL) does not exert a direct antitumor activity against breast cancer cells in vivo. There is extensive preclinical evidence suggesting that aminobisphosphonates exhibit antitumor effects in addition to their therapeutic activity in preserving bone tissue. The underlying inhibitory mechanisms of aminobisphosphonates against tumor cells are primarily through the blockade of the enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway, which prevents prenylation of signaling proteins (e.g., Rho, Ras, Cdc42), leading to the inhibition of tumor cell adhesion, migration, invasion, and proliferation in vitro (2). Whether aminobisphosphonates exhibit direct and/or indirect antitumor effects in animal models remains a matter of intense discussion. Here, the authors used a bioluminescence-based imaging reporter system that is inducible by prenylation inhibitors, such as aminobisphosphonates, and they showed that the treatment of animals with ZOL fails to induce the reporter in human MDA-MB-231 breast tumor xenografts, indicating that the aminobisphosphonate does not directly target cancer cells in vivo (1). However, we would like to point out an aspect of tumor xenograft experiments not adequately addressed by Chinault and colleagues (1), which deserves a remark.The inhibition of FPPS activity by aminobisphosphonates leads to the intracellular accumulation of IPP/ApppI mevalonate metabolites (2). We recently provided in vivo evidence that ZOL (administered at a dose compatible with clinical dosing regimens) induces accumulation of IPP/ApppI in human breast tumors implanted subcutaneously in animals and that human Vγ9Vδ2 T cells (a subset of human T cells) infiltrate and inhibit growth of these tumors producing high IPP/ApppI levels, but not those expressing low IPP/ApppI levels (3). IPP and ApppI are recognized by human Vγ9Vδ2 T cells as tumor phosphoantigens. Importantly, we showed that estrogen receptor–positive breast tumors (T47D, MCF-7) were more likely to produce IPP/ApppI after ZOL treatment because of a higher cellular uptake of ZOL and a higher activity of the mevalonate pathway compared with estrogen receptor–negative breast tumors (MDA-MB-231, MDA-MB-435; ref. 3). We believe these findings (3) may likely explain results obtained by Chinault and colleagues (1). It would be therefore very interesting to determine whether ZOL induces bioluminescence-based reporter activity in estrogen receptor–positive breast cancer cells in vivo.See the Response, p. 6078P. Clezardin has served on advisory boards for Novartis and Amgen and has received lecture fees and a research grant from Novartis and Amgen. P. Clezardin also has other commercial research support and a honoraria from Speakers Bureau from Novartis and AMGEN.
Postnatal human lung growth.
Authors: W M Thurlbeck
Journal: Thorax (1982)

Standard morphometric methods were applied to the lungs of 36 boys and 20 girls aged from 6 weeks to 14 years, dying as a result of trauma or after short illnesses. Individual lung units, alveolar dimensions, and number of alveoli per unit area and volume did not differ between boys and girls, but boys had bigger lungs than girls for the same stature. This resulted in a larger total number of alveoli and a larger aveolar surface area in boys than in girls for a given age and stature. There may be more respiratory bronchioles in boys than girls. There was rapid alveolar multiplication during the first two years of life and alveolar dimensions and number of alveoli per unit area and volume did not change much during this period. There was little or no increase in the total number of alveoli after the age of 2 years but the data are hard to interpret. There is a wide scatter of the total number of alveoli in the growing lung, in keeping with the observation that the total number of alveoli is very variable in adults. Prediction data are given for the various morphometric variables studied.
Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases
Authors: C. N Bernstein, F. Shanahan
Journal: Gut (2008)

Few would contest that advances in uncovering genetic risk factors for Crohn’s disease and ulcerative colitis over the past decade have changed the way we think about inflammatory bowel diseases (IBDs). Perhaps the most important message has been that much of the genetically determined risk lies in how the host interprets its microbial environment.1–3 However, the primacy of environmental factors was already evident from several sources; notably, studies of genetically identical twins showing a relatively low concordance rate for both Crohn’s disease (<50%) and ulcerative colitis (<10%), and the increased frequency of both disorders in many countries during a period too short to involve significant changes in the population gene pool.4 What are the environmental or lifestyle risk factors for IBD? How do they collude with genetic susceptibility?

The lesson of Helicobacter pylori and peptic ulcer disease was that the solution to some chronic disorders cannot be found by studying the human host alone. Rather, the answer may lie at the interface with the microbial environment. A more sobering lesson was the failure of conventional epidemiological studies to recognise that peptic ulcer disease is caused by a transmissible agent. How did disparate epidemiological observations miss this association and fail to guide medical scientists toward this conclusion? Could IBDs (or a subset thereof) be due to an infectious agent, waiting to be identified? Or is the relationship between host susceptibility and the microbial environment a more subtle one? While the complexity and heterogeneity of these diseases surely accounts for some of this dilemma, it seems reasonable to ask whether several decades of epidemiological studies have directed or distracted researchers seeking clues to the cause of IBD.

Some of the false leads and false promises of epidemiology have been highlighted elsewhere, with the most vigorous attacks in the …
Is Helicobacter pylori associated with non-ulcer dyspepsia and will eradication improve symptoms? A meta-analysis
Authors: R L. Jaakkimainen, E. Boyle, F. Tudiver
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To examine the association between <i>Helicobacter pylori</i> infection and non-ulcer dyspepsia, and to assess the effect of eradicating <i>H pylori</i> on dyspeptic symptoms in patients with non-ulcer dyspepsia. <b>Design:</b> Systematic review and meta-analysis of <i>(a)</i> observational studies examining the association between <i>Helicobacter pylori</i> infection and non-ulcer dyspepsia (association studies), and <i>(b)</i> therapeutic trials examining the association between eradication of <i>H pylori</i> and dyspeptic symptoms in patients with non-ulcer dyspepsia (eradication trials). <b>Data sources:</b> Randomised controlled trials and observational studies conducted worldwide and published between January 1983 and March 1999. <b>Main outcome measures:</b> Summary odds ratios and summary symptom scores. <b>Results:</b> 23 association studies and 5 eradication trials met the inclusion criteria. In the association studies the summary odds ratio for <i>H pylori</i> infection in patients with non-ulcer dyspepsia was 1.6 (95% confidence interval 1.4 to 1.8). In the eradication trials the summary odds ratio for improvement in dyspeptic symptoms in patients with non-ulcer dyspepsia in whom <i>H pylori</i> was eradicated was 1.9 (1.3 to 2.6). <b>Conclusions:</b> Some evidence shows an association between <i>H pylori</i> infection and dyspeptic symptoms in patients referred to gastroenterologists. An improvement in dyspeptic symptoms occurred among patients with non-ulcer dyspepsia in whom <i>H pylori</i> was eradicated.
Reduced risk of next exacerbation and mortality associated with antibiotic use in COPD
Authors: B. M. Roede, P. Bresser, J. M. Prins, F. Schellevis, T. J. M. Verheij, P. J. E. Bindels
Journal: European Respiratory Journal (2008)

The long-term risk of a subsequent exacerbation of chronic obstructive pulmonary disease (COPD) after treatment with oral corticosteroids without (OS) or with antibiotics (OSA) was compared in a historical general practice-based cohort. Eligible patients were >/=50 yrs of age, had a registered diagnosis of COPD, were on maintenance respiratory drugs, and had experienced at least one exacerbation defined as a prescription OS or OSA. Times to second and third exacerbations were assessed using Kaplan-Meier survival analysis; the risk of a subsequent exacerbation was assessed in a Cox proportional hazards analysis; and all-cause mortality was assessed using Kaplan-Meier survival and Cox proportional hazards analyses. A total of 842 patients had one or more exacerbations. The median time from first to second exacerbation was comparable for the OS and OSA groups, but the time from second to third exacerbation differed: 189 versus 258 days, respectively. The protective effect of OSA was most pronounced during the first 3 months following treatment (hazards ratio 0.72, 95% confidence interval 0.62-0.83). Exposure to antibiotics unrelated to a course of oral corticosteroids almost halved the risk of a new exacerbation. Mortality during follow-up was considerably lower in the OSA group. Adding antibiotics to oral corticosteroids was associated with: reduced risk of subsequent exacerbation, particularly in patients with recurrent exacerbations; and reduced risk of all-cause mortality.