tbuckley/cabot-search huggingface dataset:
Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patients
Authors: D. Usener, A. Gerhardt, D. Schadendorf, S. Eichmuller
Journal: British Journal of Dermatology (2003)

Summary Background Cancer-testis antigens exemplify a growing number of tumour antigens which are expressed in a variety of malignancies, but not in normal tissues other than germ cells, primarily those of the testis. Objectives To investigate the humoral response to known cancer-testis antigens in melanoma patients. Methods We used phage clones coding for seven different melanoma antigens MAGE-A or LAGE-1A proteins. These clones were isolated using the newly developed DNA hybridization analysis of recombinantly expressed cDNA libraries (HYREX) approach. HYREX combines the advantage of a nonradioactive library screening method with the possibility of subsequently analysing the serological response to the recombinant proteins. We isolated clones coding for MAGE-A1, -A3, -A4b, -A6, -A9 and -A12, as well as LAGE-1A. Additionally, we correlated gene expression and seroreactivity. Results Between 13% and 27% of sera (n = 15) were reactive against individual tumour antigens. We found the presence of specific antibodies was, with only two exceptions, generally correlated with mRNA expression of the antigen within cell lines derived from the same patient. While cross-reactivity of patients' IgG might play a role in these cases, antibodies from patients' sera were able to distinguish even the closely related MAGE-A3 and -A6. In general, the mRNA expression frequency was higher than the detected IgG responses. Conclusions Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes.
Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain
Authors: Florian Heidel, Fian K. Solem, Frank Breitenbuecher, Daniel B. Lipka, Stefan Kasper, M. H. Thiede, Christian Brandts, Hubert Serve, Johannes Roesel, Francis Giles, Eric Feldman, Gerhard Ehninger, Gary J. Schiller, Stephen Nimer, Richard M. Stone, Yanfeng Wang, Thomas Kindler, Pamela S. Cohen, Christoph Huber, Thomas Fischer
Journal: Blood (2005)
Complete genome sequence of the industrial bacterium Bacillus licheniformis and comparisons with closely related Bacillusspecies
Authors: Michael W Rey, Preethi Ramaiya, Beth A Nelson, Shari D Brody-Karpin, Elizabeth J Zaretsky, Maria Tang, Alfredo Lopez de Leon, Henry Xiang, Veronica Gusti, Ib Groth Clausen, Peter B Olsen, Michael D Rasmussen, Jens T Andersen, Per L Jørgensen, Thomas S Larsen, Alexei Sorokin, Alexander Bolotin, Alla Lapidus, Nathalie Galleron, S Dusko Ehrlich, Randy M Berka
Journal: Genome biology (2004)

Abstract Background Bacillus licheniformis is a Gram-positive, spore-forming soil bacterium that is used in the biotechnology industry to manufacture enzymes, antibiotics, biochemicals and consumer products. This species is closely related to the well studied model organism Bacillus subtilis , and produces an assortment of extracellular enzymes that may contribute to nutrient cycling in nature. Results We determined the complete nucleotide sequence of the B. licheniformis ATCC 14580 genome which comprises a circular chromosome of 4,222,336 base-pairs (bp) containing 4,208 predicted protein-coding genes with an average size of 873 bp, seven rRNA operons, and 72 tRNA genes. The B. licheniformis chromosome contains large regions that are colinear with the genomes of B. subtilis and Bacillus halodurans , and approximately 80% of the predicted B. licheniformis coding sequences have B. subtilis orthologs. Conclusions Despite the unmistakable organizational similarities between the B. licheniformis and B. subtilis genomes, there are notable differences in the numbers and locations of prophages, transposable elements and a number of extracellular enzymes and secondary metabolic pathway operons that distinguish these species. Differences include a region of more than 80 kilobases (kb) that comprises a cluster of polyketide synthase genes and a second operon of 38 kb encoding plipastatin synthase enzymes that are absent in the B. licheniformis genome. The availability of a completed genome sequence for B. licheniformis should facilitate the design and construction of improved industrial strains and allow for comparative genomics and evolutionary studies within this group of Bacillaceae.
Dose-intensive chemotherapy with doxorubicin, cyclophosphamide and GM-CSF fails to improve survival of metastatic breast cancer patients
Authors: A.H. Honkoop, K. Hoekman, Wagstaff J., E. Boven, C.J. van Groeningen, G. Giaccone, J.B. Vermorken, H.M. Pinedo
Journal: Annals of Oncology (1996)
ASPIRIN IN THE TREATMENT AND PREVENTION OF CARDIOVASCULAR DISEASE
Authors: Charles H. Hennekens
Journal: Annual Review of Public Health (1997)

▪ Abstract Aspirin irreversibly inhibits cyclooxygenase in platelets for their entire lifespan, raising the possibility of clinical benefits by decreasing risks of occlusive vascular events. In secondary prevention among patients with a wide range of prior occlusive vascular events, including myocardial infarction (MI), stroke, transient ischemic attacks (TIAs), as well as unstable and chronic stable angina, aspirin therapy is associated with a reduction in risks of subsequent MI, stroke, and vascular deaths. In acute MI, aspirin also confers clear benefits on subsequent MI, stroke, and vascular deaths. In primary prevention, the available randomized trial data, which to date are limited to men, indicate a clear reduction in risk of a first MI; the current data are inconclusive concerning aspirin's effect on stroke and total vascular mortality. A currently ongoing trial among 40,000 apparently healthy women will provide reliable data concerning the balance of benefits and risks of aspirin in primary prevention.
Platelet-Derived Growth Factor Receptor Inhibitor Imatinib Mesylate and Docetaxel: A Modular Phase I Trial in Androgen-Independent Prostate Cancer
Authors: Paul Mathew, Peter F. Thall, Donnah Jones, Cherie Perez, Corazon Bucana, Patricia Troncoso, Sun-Jin Kim, Isaiah J. Fidler, Christopher Logothetis
Journal: Journal of Clinical Oncology (2004)

Purpose To study the platelet-derived growth factor receptor (PDGFR) inhibitor imatinib mesylate in androgen-independent prostate cancer (AIPC), alone and in combination with docetaxel, we designed a modular phase I trial. Our goals were to (1) evaluate the toxicity and maximum-tolerated dose of docetaxel with imatinib, and (2) evaluate the decline of prostate-specific antigen (PSA) induced by imatinib alone, and imatinib and docetaxel. Patients and Methods Twenty-eight men with AIPC and bone metastases were enrolled to receive imatinib 600 mg daily lead-in for 30 days, then imatinib 600 mg daily and one of six possible doses of docetaxel weekly for 4 weeks every 6 weeks. Results During the imatinib lead-in module, one dose-limiting toxicity (DLT) event was observed, while two (7%) of 28 had PSA decline (both &lt; 50%). With imatinib and docetaxel, cycle 1 DLT was found in three of 12 patients at docetaxel 30 mg/m 2 , in three of four patients at docetaxel 45 mg/m 2 , and in five of six patients at docetaxel 35 mg/m 2 . DLTs (n = 40 total events) were principally fatigue (35%) and nausea (20%). Eight (38%) of 21 had PSA decline greater than 50%, and six (29%) of 21 had PSA decline less than 50%. Serial PSA declines beyond 18 months were observed. PDGFR-expressing tumor declined on serial bone marrow biopsies with combination therapy alone. Conclusion With imatinib 600 mg daily, the maximum-tolerated dose of docetaxel was determined to be 30 mg/m 2 weekly for 4 weeks every 6 weeks. Long-term responses were observed. The role of imatinib in modulating outcomes to docetaxel in AIPC is being tested in a randomized phase II trial.
Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-α Expression
Authors: Akiko Higuchi, Koji Ohashi, Shinji Kihara, Kenneth Walsh, Noriyuki Ouchi
Journal: Circulation Research (2009)

The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypoxia. When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was exacerbated in adiponectin-knockout (APN-KO) mice compared with wild-type mice (neovascular area: 17.0+/-1.0% versus 11.7+/-0.6%, respectively). APN-KO mice also exhibited increased leukocyte adhesion (2.3+/-0.4-fold) and tumor necrosis factor (TNF)-alpha expression (2.6+/-0.2-fold) in hypoxic retina. Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF-alpha production. TNF-alpha blockade diminished the enhanced pathological neovascularization in APN-KO mice by 34%, and the inhibitory effects of adiponectin overexpression on retinal neovascularization and leukocyte adhesion were abolished in mice lacking TNF-alpha. These data provide evidence that adiponectin protects against retinal vessel injury following pathological stimuli through modulation of TNF-alpha inflammatory responses.
Basil Frank Clarke
Authors: I. W. C. B. M. Frier
Journal: BMJ (2014)

After junior medical jobs and a period in general practice in New Zealand, Basil Frank Clarke came to Edinburgh to study for the MRCP exam, which he passed in 1960. His intention had been to return to work in New Zealand, but he obtained a medical post with Professor Sir Derrick Dunlop in the Royal …
Caterpillars and moths
Authors: Eric W. Hossler
Journal: Journal of the American Academy of Dermatology (2009)

Caterpillars and moths (order Lepidoptera) are uncommonly recognized causes of adverse cutaneous reactions, such as localized stings, papular dermatitis, and urticarial wheals. These reactions are typically mild and self-limited; however, in South America, the sting of Lonomia caterpillars can cause a potentially fatal hemorrhagic diathesis related to massive fibrinolysis. In addition, ocular inflammation and prominent arthralgias have been reported to be caused by caterpillar exposures. Therapies for mucocutaneous reactions to Lepidoptera are largely empiric, with the exception of antivenin against Lonomia obliqua envenomation. Part II of this two-part series on caterpillars and moths reviews the varied symptoms caused by Lepidopteran exposures, reviews the differential diagnosis, and discusses appropriate treatment algorithms.
Health department refuses plea for private PIP implants to be replaced on NHS
Authors: A. O'Dowd
Journal: BMJ (2012)

<h3>Abstracts</h3> <h3>Background</h3> Emergence of COVID-19 caught the world off-guard and unprepared, initiating a global pandemic. In the absence of evidence, individual communities had to take timely action to reduce the rate of disease spread and avoid overburdening their healthcare systems. Although a few predictive models have been published to guide these decisions, most have not taken into account spatial differences and have included assumptions that do not match the local realities. Access to reliable information that is adapted to local context is critical for policymakers to make informed decisions during a rapidly evolving pandemic. <h3>Objective</h3> The goal of this study was to develop an adapted susceptible-infected-removed (SIR) model to predict the trajectory of the COVID-19 pandemic in North Carolina and the Charlotte metropolitan region and to incorporate the effect of a public health intervention to reduce disease spread, while accounting for unique regional features and imperfect detection. <h3>Methods</h3> Three SIR models were fit to prevalence data from the state and the greater Charlotte region and then rigorously compared. One of these models (SIR-Int) accounted for a stay-at-home intervention and imperfect detection of COVID-19 cases. <h3>Results</h3> Presently, the COVID-19 outbreak is rapidly decelerating in NC and the Charlotte region. Infection curves are flattening at both the state and regional level. Relatively speaking, the greater Charlotte region has responded more favorably to the stay-at-home intervention than NC as a whole. While an initial basic SIR model served the purpose of informing decision making in the early days of the pandemic, its forecast increasingly did not fit the data over time. However, as the pandemic and local conditions evolved, the SIR-Int model provided a good fit to the data. <h3>Conclusions</h3> Using local data and continuous attention to model adaptation, our findings have enabled policymakers, public health officials and health systems to do capacity planning and evaluate the impact of a public health intervention. Our SIR-Int model for estimated latent prevalence was reasonably flexible, highly accurate, and demonstrated the efficacy of a stay-at-home order at both the state and regional level. Our results highlight the importance of incorporating local context into pandemic forecast modeling, as well as the need to remain vigilant and informed by the data as we enter into a critical period of the outbreak.
MicroRNAs in pediatric central nervous system embryonal neoplasms: the known unknown
Authors: Maria Braoudaki, George I Lambrou
Journal: Journal of Hematology & Oncology (2015)

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that repress post-transcriptional regulation of gene expression, while embryonal central nervous system tumors are the foremost cause of mortality in children suffering from a neoplasm. MiRNAs and their regulatory mechanisms are new to understand, while pediatric CNS tumors are difficult to comprehend. Therefore, identification of the link between them composes a major scientific challenge. The present study, reviewed the current knowledge on the role of miRNA in pediatric CNS embryonal tumors, attempting to collect the existing information in one piece of work that could ideally be used as a guide for future reference and research.
Lipopolysaccharide modulation of normal enterocyte turnover by toll-like receptors is mediated by endogenously produced tumour necrosis factor alpha
Authors: F M Ruemmele
Journal: Gut (2002)

Circulating levels of endotoxin (or lipopolysaccharide (LPS)) and anti-endotoxin antibodies are increased in patients with inflammatory bowel disease, supporting the hypothesis of a role for endogenous bacterial products in the pathogenesis of these disorders.The aim of this study was to analyse the direct effects of LPS on intestinal epithelial cell turnover.LPS significantly inhibited growth of the human non-transformed immature crypt cell line (HIEC), whereas IEC-6 cell proliferation was stimulated by LPS. As LPS is a physiological inducer of tumour necrosis factor alpha (TNFalpha) in various cell systems and this cytokine exerted similar anti-proliferative (HIEC) or growth stimulatory (IEC-6 cells) effects, the study thus tested the hypothesis that endogenously produced TNFalpha in response to LPS mediates this growth modulatory effect in an autoparacrine/paracrine way. Therefore, during LPS stimulation, the biological activity of TNFalpha was blocked using neutralising anti-TNFalpha antibodies, as well as inhibitory, antagonistic antibodies directed against the p55 TNF receptor, signalling the antimitotic TNFalpha effect in HIEC. Both experimental approaches completely abolished the growth modulatory effects of LPS in HIEC/IEC-6 cells. Production and secretion of TNFalpha by HIEC/IEC-6 cells in response to LPS was confirmed on mRNA and protein level by reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay. LPS signalling was independent of CD14 in HIEC, as these cells lack this receptor. However, HIEC expressed TLR4 and MD2 resulting in a fully functional signalling complex as demonstrated by RT-PCR, western blot, and immunofluorescence analyses.These results support the hypothesis that LPS induced changes of intestinal epithelial cell turnover may directly contribute to the pathogenesis of inflammatory epithelial cell lesions by endogenous TNFalpha production by enterocytes.
Monitoring of pulmonary function in Pompe disease: a muscle disease with new therapeutic perspectives
Authors: A. T. van der Ploeg
Journal: European Respiratory Journal (2005)

Monitoring of pulmonary function and timely initiation of noninvasive ventilation should be a focus in supportive care for patients with muscular disorders. In the current issue of the European Respiratory Journal , Pellegrini et al. 1 focus on this aspect in patients with late-onset Pompe disease (glycogenosis type II, acid maltase deficiency) 1. In Pompe disease, correct monitoring of pulmonary function and initiation of supportive care is even more relevant since new therapeutic developments are underway. The first reports on the effects of enzyme therapy for this disease are promising 2–4.

Pompe disease is an autosomal, recessive, metabolic myopathy caused by deficiency of the lysosomal enzyme α-glucosidase, which is involved in the degradation of glycogen. The disease has an estimated frequency of one in 40,000 and may present at any age 5, 6. Disease severity relates to the level of enzyme activity. Infants with a virtual absence of α-glucosidase show symptoms shortly after birth. They do not reach major motor milestones, such as sitting and standing, due to progressive muscle weakness. A hypertrophic cardiomyopathy is characteristically present and classic infantile patients generally die before 1 yr of age due to cardiorespiratory failure. Pompe disease may also occur in older children and adults. In this late-onset or nonclassic form of the disease, progression is much slower and patients finally become wheelchair bound and ventilator dependent. …
Serotyping for an extended anti-citrullinated peptide autoantibody panel does not add value to CCP2 testing for diagnosing RA in an early undifferentiated arthritis cohort
Authors: A. G. Pratt, P. J. Charles, M. Chowdhury, G. Wilson, P. J. Venables, J. D. Isaacs
Journal: Annals of the Rheumatic Diseases (2011)

The now widely employed CCP2 assay, which detects circulating autoantibodies to a panel of synthetic, cyclic citrullinated peptides, carries a positive predictive value of 0.93 for rheumatoid arthritis (RA) among early undifferentiated arthritis (UA) patients,1 thus providing a cornerstone of recently evolved scoring systems that predict and classify early RA.2 However, approximately 80% of newly presenting UA patients are anti-CCP2- negative 3 and a quarter of these evolve into RA within 3 years,1 thus experiencing diagnostic delay. The peptides used in the CCP2 assay do not necessarily correspond to in vivo generated proteins, yet citrullinated antigens of putative pathophysiological relevance have recently been described in association with specific circulating autoantibodies in RA.4 Therefore, we hypothesised that the detection of one or any such autoantibodies, as well as those against filaggrin components of the CCP1 assay,5 IgA or IgM rheumatoid factor (RF), might add to the diagnostic utility of CCP2 testing alone in predicting RA progression among early UA patients.

Consecutive adult UA patients with …
Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD
Authors: S. Santos, V.I. Peinado, J. Ramírez, T. Melgosa, J. Roca, R. Rodriguez-Roisin, J.A. Barberà
Journal: European Respiratory Journal (2002)

Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV 1 ), 66±10% predicted) and smokers without airflow obstruction (n=7; FEV 1 , 86±6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p&lt;0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.
Survival benefit of combined curative resection of the stomach (D2 resection) and liver in gastric cancer patients with liver metastases
Authors: S.H. Cheon, S.Y. Rha, H.-C. Jeung, C.-K. Im, S.H. Kim, H.R. Kim, J.B. Ahn, J.K. Roh, S.H. Noh, H.C. Chung
Journal: Annals of Oncology (2008)
A 10 year asthma programme in Finland: major change for the better
Authors: T Haahtela
Journal: Thorax (2006)

A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society.The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched.The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were 218 million euro which had fallen to 213.5 million euro in 2003. Costs per patient per year have decreased 36% (from 1611 euro to 1031 euro).It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.