tbuckley/cabot-search huggingface dataset:
Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele
Authors: P. G Vlachoyiannopoulos
Journal: Annals of the Rheumatic Diseases (2000)

Description of Greek patients with scleroderma with reference to (a) major organ disease, (b) autoantibodies, (c) survival rate, and (d) HLA associations.The clinical files of 254 patients were analysed retrospectively and a standardised clinical chart was completed with age at disease onset, sex, date of first and last visit, clinical and serological findings, organs affected, reasons for death, and HLA class II alleles. HLA class II alleles (DRB1, DQA1, DQB1, DPB1) were determined by polymerase chain reaction amplification using oligopeptide probes. DNA was extracted from 98 patients and 130 Greek controls.124 patients (49%) had limited systemic sclerosis (lSSc), 114 (45%) had diffuse systemic sclerosis (dSSc), and 16 (6%) had overlap syndromes. Patients with dSSc, compared with lSSc, were characterised by a higher prevalence of lung disease (p=0.0011), oesophageal, heart, and peripheral vessel disease (p=0.027, p=0.0025, and p=0.012, respectively). Anticentromere antibodies (ACA) occurred exclusively in lSSc (34%), whereas antibodies to topoisomerase I (anti-topo I) were associated with dSSc (p<0.0001). Anti-topo I were associated with interstitial pulmonary fibrosis, oesophageal and peripheral vessel disease (p=0.028, p=0.012, and p=0.01, respectively). The HLA-DRB1*1104 allele was associated with the disease (p<0.0001) and anti-topo I (p<0.001), whereas it was not associated with ACA serum reactivity (p<0.001). Renal disease occurred in 4% of patients with SSc. The estimated survival probability for this cohort of patients with SSc, four years after the first visit, is 94.8%.SSc among Greek subjects has the same pattern of organ disease as in other white populations. However, the prevalence of kidney disease is low. The HLA class II DRB1*1104 allele is associated with the disease, with anti-topo I, and not associated with ACA serum reactivity.
INFECTIVE ENDOCARDITIS CAUSED BY HACEK MICROORGANISMS
Authors: M. Das, MD, A.D. Badley, MD, F.R. Cockerill, MD, J.M. Steckelberg, MD, W. R. Wilson, MD
Journal: Annual Review of Medicine (1997)

The HACEK group of fastidious gram-negative organisms is a recognized but unusual cause of infective endocarditis, responsible for approximately 3% of cases. We report our experience with 45 cases of endocarditis caused by HACEK organisms. In Olmsted County, Minnesota, the incidence of HACEK endocarditis was 0.14 per 100,000 person-years. In patients with native valves, 33 cases occurred, and in patients with prosthetic valves, 12 cases occurred. The most common presenting symptoms were fever, splenomegaly, new or changing murmur, and microvascular phenomena. Symptoms were present in the majority of patients anywhere from two weeks to six months prior to diagnosis. Blood cultures became positive in a mean 3.375 days, and therapy with a beta-lactam alone or as part of a combination was given for anywhere between three and six weeks. Within the first month of diagnosis, surgery was performed for 13 regurgitant valves in 11 patients (24%). Echocardiography was an insensitive predictor of subsequent major arterial embolization (odds ratio, 1.33; 95% confidence interval, 0.31-5.67). The overall survival in our cohort of patients was 87%. These results confirm previous reports that HACEK endocarditis portends a favorable prognosis.
Receptor interacting protein kinase 2–mediated mitophagy regulates inflammasome activation during virus infection
Authors: Christopher Lupfer, Paul G Thomas, Paras K Anand, Peter Vogel, Sandra Milasta, Jennifer Martinez, Gonghua Huang, Maggie Green, Mondira Kundu, Hongbo Chi, Ramnik J Xavier, Douglas R Green, Mohamed Lamkanfi, Charles A Dinarello, Peter C Doherty, Thirumala-Devi Kanneganti
Journal: Nature Immunology (2013)
Advances in Breast Conservation Therapy
Authors: Lisa A. Newman, Henry M. Kuerer
Journal: Journal of Clinical Oncology (2005)

Breast conservation therapy (BCT) is now well established as oncologically safe treatment for primary breast cancer, and in fact has been deemed the preferable surgical option in a 1991 National Cancer Institute (NCI) position statement on management of early-stage disease. This consensus was reached after the completion of several prospective, randomized clinical trials confirming survival equivalence in breast cancer patients randomly assigned to receive BCT versus mastectomy. Follow-up as long as 20 years has been reported (Table 1) as well as a metaanalysis of all trials, with stability of the outcome results.
Electrophysiological Characteristics of Canine Atrial Plateau Fibers
Authors: PERRY M. HOGAN, LARRY D. DAVIS
Journal: Circulation Research (1971)

Right atria from dog hearts were immersed in Tyrode's solution with the endocardial surface of the anterior wall exposed. Glass microelectrodes were used to impale fibers in different anatomical areas of this preparation. Electrical characteristics of atrial plateau fibers located along the caval border of the crista terminalis were compared with those of regular atrial fibers from other sites. The former conducted at a rate (0.803±0.110 M/sec) two to three times more rapidly than pathways composed of regular atrial fibers. A period of supernormal excitability was demonstrated for plateau fibers but not for regular fibers. Graded premature responses could be elicited in plateau fibers by both electrical stimulation and propagated action potentials. Duration of the effective refractory period of plateau fibers (196.1±2.5 msec) was longer than that of regular fibers (147.8±5.4 msec). Plateau fibers required a lower level of membrane potential (-62.1 ± 0.8 mv) to generate a propagated action potential than did regular fibers (-65.5 ± 1.3 mv). Regular atrial fibers could respond at faster rates to high frequency stimulation than plateau fibers.
Characterization of the Endothelium-Specific Murine Vascular Endothelial Growth Factor Receptor-2 (Flk-1) Promoter
Authors: Volker Rönicke, Werner Risau, Georg Breier
Journal: Circulation Research (1996)

Flk-1, a high-affinity signaling receptor for vascular endothelial growth factor (VEGF), is strongly and specifically expressed on endothelial cells during embryonic development of the vascular system and during tumor angiogenesis. Disruption of Flk-1 gene function has recently been shown to prevent completely endothelial cell differentiation during murine embryonic development. To gain insights into the mechanisms that regulate the endothelium-specific Flk-1 expression, we have isolated the 5'-flanking region of the murine Flk-1 gene. RNase protection and primer extension analyses revealed a single transcriptional start site located 299 bp upstream from the translational start site in an initiator-like pyrimidine-rich sequence. The 5'-flanking region is rich in GC residues and lacks a typical TATA or CAAT box. A luciferase reporter construct containing a fragment from nucleotides -1900 to +299 showed strong endothelium-specific activity in transfected bovine aortic endothelial cells. Deletion analyses revealed that endothelium-specific Flk-1 expression is stimulated by the 5'-untranslated region of the first exon, which contains an activating element between nucleotides +137 and +299. In addition, two endothelium-specific negative regulatory elements were identified between nucleotides -4100 and -623. Two strong general activating elements were present in the region between nucleotides -96 and -37, which contains one potential NF kappa B and three potential AP-2 binding sites. This study shows that Flk-1 expression in endothelial cells is mainly regulated by an endothelium-specific activating element in the long 5'-untranslated region of the first exon and by negative regulatory elements located further upstream.
Evolution of Bone Disease over 10 Years in 135 Patients with Terminal Renal Failure
Authors: G. L. V. Tatler, R. A. Baillod, Z. Varghese, W. B. Y. S. Farrow, M. R. Wills, J. F. Moorhead
Journal: BMJ (1973)

An objective radiographic study of erosions, fractures, and periarticular and vascular calcification was made in a series of 135 patients over 10 years of maintenance haemodialysis therapy. The four lesions progressed at different rates, consistent with variation in the response of tissues to a changing biochemical milieu and deficiency in vitamin D metabolites. The half time for development of individual radiographic signs was 3.4 years for vascular calcification, 9 years for fractures, 16 years for periarticular calcification, and 22.9 years for erosions. Calcification of the dorsalis pedis artery seen as a developing ring or tube was an early and valuable sign of disturbed calcium metabolism. In these patients renal osteodystrophy is a chronic condition with a prolonged time course.
Both <i>XPD</i> alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients
Authors: Takahiro Ueda, Emmanuel Compe, Philippe Catez, Kenneth H. Kraemer, Jean-Marc Egly
Journal: The Journal of Experimental Medicine (2009)

Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP). Many XP patients are compound heterozygotes with a “causative” XPD point mutation R683W and different second mutant alleles, considered “null alleles.” However, there is marked clinical heterogeneity (including presence or absence of skin cancers or neurological degeneration) in these XPD/R683W patients, thus suggesting a contribution of the second allele. Here, we report XP patients carrying XPD/R683W and a second XPD allele either XPD/Q452X, /I455del, or /199insPP. We performed a systematic study of the effect of these XPD mutations on several enzymatic functions of TFIIH and found that each mutation exhibited unique biochemical properties. Although all the mutations inhibited the nucleotide excision repair (NER) by disturbing the XPD helicase function, each of them disrupted specific molecular steps during transcription: XPD/Q452X hindered the transactivation process, XPD/I455del disturbed RNA polymerase II phosphorylation, and XPD/199insPP inhibited kinase activity of the cdk7 subunit of TFIIH. The broad range and severity of clinical features in XP patients arise from a broad set of deficiencies in NER and transcription that result from the combination of mutations found on both XPD alleles.
Pulmonary Lymphangioleiomyomatosis in a Karyotypically Normal Man without Tuberous Sclerosis Complex
Authors: Mario Schiavina, Valerio Di Scioscio, Paola Contini, Alberto Cavazza, Andrea Fabiani, Marco Barberis, Alessandro Bini, Annalisa Altimari, Robin M. T. Cooke, Walter F. Grigioni, Antonia D'Errico-Grigioni
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

The three previously reported cases of conclusively documented pulmonary lymphangioleiomyomatosis (LAM) in men were associated with definite or probable tuberous sclerosis complex (TSC).To describe an unequivocal case of pulmonary LAM occurring in a man with no clinical or genotypic evidence of TSC.At high-resolution computed tomography, a 37-year-old phenotypically and karyotypically normal man with left pneumothorax and massive pulmonary collapse had widespread thin-walled cysts throughout both lungs. Histological diagnosis of LAM was performed on biopsy material, and immunohistochemically confirmed with the HMB-45 monoclonal antibody.Remarkably, the HMB-45-positive cells lining the cysts also showed strong reactivity for estrogen and progesterone receptor proteins. TSC was clinically excluded, and TSC1 and TSC2 germline mutations were not detected at DNA analysis.This article indicates that occurrence of LAM may be possible in a chromosomally normal man unaffected by TSC. On diagnostic grounds, the possibility of LAM should be borne in mind when diffuse cystic lung disease occurs in a man, even in the absence of signs of TSC.
Single Geographic Origin of a Widespread Autotetraploid Arabidopsis arenosa Lineage Followed by Interploidy Admixture
Authors: Brian Arnold, Sang-Tae Kim, Kirsten Bomblies
Journal: Molecular Biology and Evolution (2015)

Whole-genome duplication, which leads to polyploidy, has been implicated in speciation and biological novelty. In plants, many species exhibit ploidy variation, which is likely representative of an early stage in the evolution of polyploid lineages. To understand the evolution of such multiploidy systems, we must address questions such as whether polyploid lineage(s) had a single or multiple origins, whether admixture occurs between ploidies, and the timescale over which ploidy variation affects the evolution of populations. Here we analyze three genomic data sets using nonparametric and parametric analyses, including coalescent-based methods, to study the evolutionary history of a geographically widespread autotetraploid variant of Arabidopsis arenosa, a new model system for understanding the molecular basis of autopolyploid evolution. Autotetraploid A. arenosa populations are widely distributed across much of Northern and Central Europe, whereas diploids occur in Eastern Europe and along the southern Baltic coast; the two ploidies overlap in the Carpathian Mountains. We find that the widespread autotetraploid populations we sampled likely arose from a single ancestral population approximately 11,000–30,000 generations ago in the Northern Carpathians, where its closest extant diploid relatives are found today. Afterward, the tetraploid population split into at least four major lineages that colonized much of Europe. Reconstructions of population history suggest that substantial interploidy admixture occurred in both directions, but only among geographically proximal populations. We find two cases in which selection likely acted on an introgressed locus, suggesting that persistent interploidy gene flow has a local influence on patterns of genetic variation in A. arenosa.
Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study
Authors: Ahmad Awada, Agustin A Garcia, Stephen Chan, Guy H M Jerusalem, Robert E Coleman, Manon T Huizing, Aminder Mehdi, Sue M O'Reilly, John T Hamm, Peter J Barrett-Lee, Veronique Cocquyt, Kostandinos Sideras, David E Young, Carol Zhao, Yen Lin Chia, Ute Hoch, Alison L Hannah, Edith A Perez
Journal: The Lancet Oncology (2013)
Extent, patterns, and burden of uncontrolled disease in severe or difficult‐to‐treat asthma
Authors: S. D. Sullivan, L. Rasouliyan, P. A. Russo, T. Kamath, B. E. Chipps
Journal: Allergy (2007)

Background: Characterization of uncontrolled asthma burden in a natural treatment setting can influence treatment recommendations and clinical practice. The objective was to characterize and compare the economic burden of severe or difficult‐to‐treat asthma in uncontrolled and controlled patients. Methods: Baseline patient data (age ≥ 13 years; n = 3916) were obtained from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. Disease control was assessed using two approaches: (i) applying criteria for control based on the Gaining Optimal Asthma ControL study, and (ii) using the Asthma Therapy Assessment Questionnaire (ATAQ) to identify the number of asthma control problems. Assessments were performed at baseline, and at months 12 and 24. Monetary values were assigned to productivity loss and medical resource use. Direct and indirect costs were aggregated over 24 months and compared using Student's t ‐test for continuous measures and chi‐squared for categorical variables. Results: Throughout the study, most patients had uncontrolled asthma (83% uncontrolled; 16% inconsistent control; 1.3% controlled). Controlled patients experienced fewer work or school absences and less healthcare resource use than uncontrolled patients at all study time points. Using the multilevel ATAQ control score, asthma costs increased directly with the number of asthma control problems. Costs for uncontrolled patients were more than double those of controlled patients throughout the study ($14 212 vs $6452; adjusted to 2002 dollars; P &lt; 0.0001). Conclusions: This study demonstrated that few severe or difficult‐to‐treat asthma patients achieved control over a 2‐year period and the economic consequence of uncontrolled disease is substantial.
Effects of CCR5-Δ 32, CCR2-64I, and SDF-1 3′A Alleles on HIV-1 Disease Progression: An International Meta-Analysis of Individual-Patient Data
Authors: J P Ioannidis, P S Rosenberg, J J Goedert, L J Ashton, T L Benfield, S P Buchbinder, R A Coutinho, J Eugen-Olsen, T Gallart, T L Katzenstein, L G Kostrikis, H Kuipers, L G Louie, S A Mallal, J B Margolick, O P Martinez, L Meyer, N L Michael, E Operskalski, G Pantaleo, G P Rizzardi, H Schuitemaker, H W Sheppard, G J Stewart, I D Theodorou, H Ullum, E Vicenzi, D Vlahov, D Wilkinson, C Workman, J F Zagury, T R O'Brien
Journal: Annals of Internal Medicine (2001)

Background: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. Objective: To examine postulated associations of genetic alleles with HIV-1 disease progression. Design: Meta-analysis of individual-patient data. Setting: 19 prospective cohort studies and case–control studies from the United States, Europe, and Australia. Patients: Patients with HIV-1 infection who were of European or African descent. Measurements: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. Results: Both the CCR5-Δ 32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74; P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, −0.18 log10 copies/mL and −0.14 log10 copies/mL; P < 0.05 for both). Having the CCR5-Δ32 or CCR2-64I allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast, SDF-1 3′A homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). Conclusions: The CCR5-Δ 32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3′A homozygosity carried no such protection.
Positive selection for colicin diversity in bacteria.
Authors: M A Riley
Journal: Molecular Biology and Evolution (1993)

To examine the hypothesis that colicin proteins are subject to diversity-enhancing selection, we studied the rates of synonymous, nonsynonymous, and intergenic nucleotide substitution in three pairs of closely related colicin clusters. The results indicate that the immunity gene and the immunity-binding domain of the colicin gene, which interact to provide specific immunity from the lethal action of the colicin toxin, accumulate substitutions at synonymous and nonsynonymous sites several times more rapidly than does the remainder of the colicin cluster. We suggest that this increased level of divergence, centered at the immunity protein, may be the result of the combined action of recombination and positive selection acting to increase colicin diversity in natural populations of Escherichia coli.
Experimental Design and Analysis of Antibody Microarrays: Applying Methods from cDNA Arrays
Authors: Jeanette E. Eckel-Passow, Antje Hoering, Terry M. Therneau, Irene Ghobrial
Journal: Cancer Research (2005)

Abstract Protein expression microarrays, also called antibody arrays, represent a new technology that allows the expression level of proteins to be assessed directly. As is also the case with gene expression microarrays, it is hoped that protein expression microarrays will aid in biomarker discovery, predicting disease outcomes and response to treatments, and detecting molecular mechanisms and/or pathways associated with a particular disease state. However, accurately achieving these aims is dependent upon suitable experimental designs, normalization procedures that eliminate systematic bias, and appropriate statistical analyses to assess differential expression or expose expression patterns. In the last five years, a large amount of research has been devoted to two-color cDNA arrays to improve experimental design, normalization and statistical analyses to assess differential expression and classification. These methods are directly applicable to two-color antibody arrays. The objective of this article is to discuss statistical methods that have been developed for cDNA arrays and describe how the methods can be directly applied to antibody arrays.
Response to: Domiciliary long term non-invasive ventilation in COPD: should we select subgroups with a better likelihood to respond to NIV in subsequent randomised controlled trials?
Authors: F M Struik, P J Wijkstra
Journal: Thorax (2014)

Response to: Domiciliary long term non-invasive ventilation in COPD: should we select subgroups with a better likelihood to respond to NIV in subsequent randomised controlled trials?Dear editor, We thank Borel et al 1 for their comments on our paper. 2Borel and colleagues suggest that future studies should focus on specific COPD subgroups who have better likelihood of response to chronic noninvasive ventilation (NIV).They recently showed that obese COPD patients respond better to NIV compared with non-obese patients. 3We completely agree with their suggestion about focusing on COPD subgroups for future studies and in fact we tried to do so as well.In our study, we investigated the benefits of chronic NIV in COPD patients after they received ventilatory support due to acute respiratory failure.However, we focused on a more specific COPD group (in the letter by Borel and colleagues called 'respiratory COPD') and as we expected chronic NIV to be more beneficial in those patients with obstructive sleep apnoea (OSA), we excluded the latter group.The mean Body Mass Index of our study population was 25 kg/m 2 suggesting that obesity/OSA was not the major factor in their respiratory failure.In short, we focused on a group with more pure COPD who were being treated for acute respiratory failure but who showed no response to chronic NIV.The outcome of PostScript
HIV Infection and Smoking Behavior
Authors: George Davey Smith
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Halsey et al<sup>1</sup>reported an association between cigarette smoking and the risk of HIV-1 infection in Haitian women that remained after adjustment for "all known risk factors." The authors suggest two alternative explanations for their results: First, that there is a "hidden" or "unrecognized" confounder that has not been accounted for and, second, that there is a biologic effect of cigarette smoking on the risk of HIV transmission. We would like to suggest a third possibility, namely, that the association is not due to an unknown confounder, but rather the inability to properly measure a well-known confounder—frequency of unprotected sexual intercourse with an HIV-infected man or men. The dichotomous variable "≥3 lifetime sexual partners" that was used in the study is only a poor proxy measure of this true confounder and thus considerably underestimates its association with risk of HIV infection.<sup>2-4</sup>The underestimation of the
821 Effects of Mepolizumab, an Anti-Interleukin-5 Monoclonal Antibody, on Blood Eosinophil Counts in Patients With Hypereosinophilic Syndrome
Authors: P.F. Weller, G.J. Gleich, W.W. Busse, M.E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2007)