tbuckley/cabot-search huggingface dataset:
Moderately Preterm Children Have More Respiratory Problems during Their First 5 Years of Life Than Children Born Full Term
Authors: Elianne J. L. E. Vrijlandt, Jorien M. Kerstjens, Eric J. Duiverman, Arend F. Bos, Sijmen A. Reijneveld
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Pulmonary outcomes of moderate-preterm children (MP) are unknown.To investigate the prevalence of respiratory symptoms during infancy and at preschool age of MP compared with full-term (FT) and early preterm children (EP) and to determine factors associated with respiratory symptoms of MP at school age.Prospective cohort study.number of rehospitalizations caused by respiratory problems, prevalence of respiratory symptoms determined by ISAAC Questionnaires, and factors associated with respiratory symptoms determined by univariate and multivariate analyzes.A total of 988 MP, 551 EP, and 573 FT children were included. The number of hospitalizations caused by respiratory problems during the first year of life was doubled in MP compared with FT (6% vs. 3%; P < 0.001). At preschool age, compared with FT, MP reported more cough or wheeze during a cold (63% vs. 50%; P < 0.001); cough or wheeze without a cold (23% vs. 15%; P = 0.001); nocturnal cough (33% vs. 26%; P = 0.005); dyspnea (8% vs. 4%; P = 0.011); and use of medication (inhaled steroids, 9% vs. 6%; P = 0.042) (antibiotics, 12% vs. 7%; P = 0.002). Factors associated with respiratory symptoms at 5 years among MP were respiratory problems, eczema, rehospitalization in infancy, passive smoking in infancy, family history of asthma, and higher social class. Multivariate analyzes showed the same results except for rehospitalization in infancy.MP have more respiratory symptoms than FT during early childhood. Factors associated with respiratory symptoms at school age are early respiratory problems, family history of asthma, higher social class, and passive smoking.
Onset of Angina Pectoris in Relation to Circulatory Adaptation during Arm and Leg Exercise
Authors: JOHN WAHREN, STELLAN BYGDEMAN
Journal: Circulation (1971)

The circulatory adaptation to arm and leg exercise was studied with stepwise increased work loads in 10 patients with signs of coronary artery disease. Both arm and leg exercise elicited angina pectoris in all patients. Anginal pain appeared at the same level of pressure-time per minute (PTM) in the two forms of exercise, but at a smaller work load and a lower pulmonary oxygen uptake during arm exercise than during leg exercise. Heart rate, PTM, and peak systolic, systolic mean, diastolic, and mean arterial pressures all increased more steeply in relation to work load during arm exercise than during leg exercise. The differences in circulatory adaptation during arm and leg exercise are attributed in part to a lower mechanical efficiency and a higher sympathetic outflow during arm exercise. These factors may in turn reflect the involvement of smaller muscle groups and a larger component of static work with trunk muscles during arm exercise. The pattern of response to exercise resembles that seen in healthy subjects and provides a pathophysiologic background for the earlier appearance of anginal symptoms during arm than leg exercise in patients with coronary artery disease.
Human rheumatoid factors with restrictive specificity for rabbit immunoglobulin G: auto- and multi-reactivity, diverse VH gene segment usage and preferential usage of V lambda IIIb.
Authors: Q Fang, C C Kannapell, F Gaskin, A Solomon, W J Koopman, S M Fu
Journal: The Journal of Experimental Medicine (1994)

To determine the molecular and functional properties of human rheumatoid factors (RF), we established stable hybridomas and Epstein-Barr virus-transformed B cell lines from the synovial fluid or peripheral blood of three patients with rheumatoid arthritis and one patient with systemic lupus erythematosus. 17 cell lines were obtained that produced high-titer immunoglobulin M (IgM) RF that reacted exclusively with rabbit but not human IgG or IgG of other mammalian species. Certain anti-rabbit IgG RF also had specificity for other mammalian antigens (Ag), including cytoskeletal proteins and intracellular proteins found in HeLa cells, as well as for Ag present in an extract prepared from the cell wall of group A streptococci. 13 of the 17 RF contained lambda-type light (L) chains, of which 12 were classified serologically as members of the lambda-L chain variable region (V lambda) subgroup, designated V lambda III. The heavy chain V region (VH) and V lambda sequences of nine of these IgM lambda RF were determined at the cDNA level. Five VH genes in three VH families were used by these antibodies (Ab), including VH1 (dp21/1-4b and dp10 [51p1]/hv1051), VH3 (dp38/3-15 and dp77/13-21), and VH4 (dp70/4-4b). The deduced V gene-encoded amino acid sequences of the lambda chains of these IgM lambda RF confirmed their serological classification as lambda III, and they were further classified as members of the relatively uncommon V lambda III subgroup, designated V lambda IIIb. Based on cDNA analyses, nine were the product of three different V lambda III b germline genes. Two such genes, designated hsiggll150 and hsiggll295, were cloned and sequenced from genomic DNA. Unique combinations of these VH and V lambda III b genes could be related to distinctive patterns of reactivity among the IgM lambda RF. Although the VH and V lambda regions of these Abs were expressed primarily as germline-encoded sequences, four of nine multireactive Abs had extensive V region mutation, indicative of an Ag-driven process. The finding that lambda IIIb L chains are preferentially found among anti-rabbit IgG RF, and that some of these Ab have specificity for other protein, cellular, and bacterial Ag, provides new insight into the pathogenesis of RA and related diseases.
The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve
Authors: Marc B. Goldstein, F. John Gennari, William B. Schwartz
Journal: Journal of Clinical Investigation (1971)

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.
Lung Volume Reduction by Bronchoscopic Administration of Steam
Authors: Michael J. Emery, Randy L. Eveland, Kelly Eveland, Laurent L. Couetil, Jacob Hildebrandt, Erik R. Swenson
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

At present, bronchoscopic approaches to lung volume reduction (LVR) create airway obstruction to achieve parenchyma collapse, avoiding many risks of surgical LVR. However, LVR by these methods is limited by temporary or incomplete collapse and/or residual atelectatic and scarred tissue volumes. Heat-induced ablation of lung tissue is currently under investigation as an alternative LVR methodology. We hypothesized that bronchoscopic steam injection can produce safe and effective LVR, and explored potential mechanisms for the effects. Steam treatments were applied bilaterally to six cranial lobe segments of large dogs. For series 1, 14 dogs received one of three target heat dose levels (1, 4, or 8 cal · ml⁻¹ segment volume), and then 3 months of follow-up including pulmonary function testing and monitoring for complications. For series 2, 12 dogs received a single target dose (4 cal · ml⁻¹) or sham, similar follow-up, and then assessment of lobar mass, volume, and blood flow. Vapor content of series 2 steam was 40% greater than for series 1 (similar heat dose) to attempt more peripheral heat delivery. Nineteen of 20 treatment animals survived with minimal evidence of serious risks or reduced pulmonary function testing volumes, but 1 died from pneumothorax 5 days post-treatment. Postmortem processing of animals that survived as planned revealed obvious dose-dependent lobe reductions, additional evidence of risks, and blood flow reduction that occurred immediately post-treatment. Bronchoscopic administration of steam is a potentially safe means to achieve LVR, but substantial risks are present and further research is recommended.
Beneficial Effects of a Soy-Based Dietary Supplement on Lipid Levels and Cardiovascular Risk Markers in Type 2 Diabetic Subjects
Authors: Kjeld Hermansen, Mette Søndergaard, Lars Høie, Marius Carstensen, Birgitte Brock
Journal: Diabetes Care (2001)

OBJECTIVE— Consumption of soy protein has recently been shown to improve the blood lipid levels in nondiabetic subjects. The purpose of this study was to evaluate if a dietary supplement of soy protein, isoflavones, and cotyledon fiber (Abalon) affects cardiovascular risk markers, blood glucose,and insulin levels in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS— Twenty type 2 diabetic subjects participated in a crossover trial. They were randomized to double-blind supplementation for 6 weeks with Abalon (soy protein [50 g/day] with high levels of isoflavones [minimum 165 mg/day] and cotyledon fiber [20 g/day]) or placebo (casein [50 g/day] and cellulose [20 g/day]), separated by a 3-week wash-out period. RESULTS— The results are expressed as means ± SD. The percentage mean treatment difference between Abalon and placebo demonstrated significantly lower mean values after Abalon for LDL cholesterol (10 ±15%, P &amp;lt; 0.05), LDL/HDL ratio (12 ± 18%, P &amp;lt;0.05), apolipoprotein (apo) B100 (30 ± 38%, P &amp;lt; 0.01),triglycerides (22 ± 10%, P &amp;lt; 0.05), and homocysteine (14± 21%, P &amp;lt; 0.01), whereas the total cholesterol value tended to be less significant but still lower (8 ± 15%, P &amp;lt;0.08). No change occurred in HDL cholesterol, apo B100/apo A1 ratio,plasminogen activator inhibitor 1, factor VIIc, von Willebrand factor,fibrinogen, lipoprotein(a), glucose, HbAlc, or 24-h blood pressure. CONCLUSIONS— These results indicate beneficial effects of dietary supplementation with Abalon on cardiovascular risk markers in type 2 diabetic subjects. This improvement is seen even in individuals with near-normal lipid values.
CXCL16 Recruits Bone Marrow-Derived Fibroblast Precursors in Renal Fibrosis
Authors: Gang Chen, Song-Chang Lin, Jiyuan Chen, Liqun He, Feixia Dong, Jing Xu, Shuhua Han, Jie Du, Mark L. Entman, Yanlin Wang
Journal: Journal of the American Society of Nephrology (2011)

Although fibroblasts are responsible for the production and deposition of extracellular matrix in renal fibrosis, their origin is controversial. Circulating fibroblast precursors may contribute to the pathogenesis of renal fibrosis, but the signaling mechanisms underlying the recruitment of bone marrow-derived fibroblast precursors into the kidney in response to injury are incompletely understood. Here, in the unilateral ureteral obstruction model of renal fibrosis, tubular epithelial cells upregulated the chemokine CXCL16 in obstructed kidneys, and circulating fibroblast precursors expressed the CXCL16 receptor, CXCR6. Compared with wild-type mice, CXCL16-knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors in obstructed kidneys. CXCL16-knockout mice also exhibited significantly fewer CD45-, collagen I-, and CXCR6-triple-positive fibroblast precursors in injured kidneys. Furthermore, targeted deletion of CXCL16 inhibited myofibroblast activation, reduced collagen deposition, and suppressed expression of collagen I and fibronectin. In conclusion, CXCL16 contributes to the pathogenesis of renal fibrosis by recruiting bone marrow-derived fibroblast precursors.
Introducing ‘Putting Papers into Practice’
Authors: S.M. Langan, J.M. Batchelor
Journal: British Journal of Dermatology (2011)

The BJD aims to advance the understanding, management and treatment of skin disease and to improve patient outcomes. Although the BJD hopes to achieve this by publishing high-quality research, we also recognize that what is published in the BJD represents only part of the research output from the field of dermatology. In the recent BJD reader survey, many readers said they were keen to be kept up to date with recent important research published in other journals. Readers may manage to read their monthly copy of the BJD, but it is almost impossible to find the time to read other dermatology and general medical journals, which may contain important articles relating to the field of dermatology. In this month’s issue we are therefore delighted to introduce a new section entitled ‘Putting Papers into Practice’. The main aim of this new section will be to alert busy readers to important papers from the wider dermatological and general medical literature that are relevant to clinical practice or research in the field of dermatology, highlighting any impact the paper may have on clinical practice. We will also cover important new developments in research methodology, such as STROBE and CONSORT. It will not be possible to cover all relevant papers, but we will aim to select ones which we consider to be clinically important and of interest to the BJD readership. We are keen to make this section educationally useful, and the main educational themes will include critical appraisal and application of research knowledge to clinical practice. Where appropriate, the section will critically appraise a selected paper, assessing the quality, internal validity and generalizability (external validity) of the research. Developing skills in critical appraisal of medical papers is important for all clinicians, trainees and researchers and is fundamental to basing clinical practice on the best available evidence.1 The section will mainly focus on randomized controlled trials, observational studies on dermatology-related topics and important developments in research reporting, e.g. new guidelines for reporting of research. Important definitions of terms relating to epidemiological studies and clinical trials, together with any key references, will be maintained in an accompanying section on the BJD website for interested readers. The main points we would aim to cover in an appraisal are outlined in Table 1. If any readers wish to identify potential articles of interest or to contribute appraisals of articles to this section, we are very happy to be contacted via the BJD editorial office. Where possible, we will also aim to include comments from expert clinicians or researchers in the relevant field. We will also offer authors of critically appraised articles the opportunity to respond to any comments made. As this new section develops, we would also appreciate any feedback from readers and suggestions as to how it might be improved. We wish to thank Professor Hywel Williams for his helpful comments on our initial plans for this new section.
Screening Mammograms by Community Radiologists: Variability in False-Positive Rates
Authors: J. G. Elmore
Journal: JNCI Journal of the National Cancer Institute (2002)

Previous studies have shown that the agreement among radiologists interpreting a test set of mammograms is relatively low. However, data available from real-world settings are sparse. We studied mammographic examination interpretations by radiologists practicing in a community setting and evaluated whether the variability in false-positive rates could be explained by patient, radiologist, and/or testing characteristics.We used medical records on randomly selected women aged 40-69 years who had had at least one screening mammographic examination in a community setting between January 1, 1985, and June 30, 1993. Twenty-four radiologists interpreted 8734 screening mammograms from 2169 women. Hierarchical logistic regression models were used to examine the impact of patient, radiologist, and testing characteristics. All statistical tests were two-sided.Radiologists varied widely in mammographic examination interpretations, with a mass noted in 0%-7.9%, calcification in 0%-21.3%, and fibrocystic changes in 1.6%-27.8% of mammograms read. False-positive rates ranged from 2.6% to 15.9%. Younger and more recently trained radiologists had higher false-positive rates. Adjustment for patient, radiologist, and testing characteristics narrowed the range of false-positive rates to 3.5%-7.9%. If a woman went to two randomly selected radiologists, her odds, after adjustment, of having a false-positive reading would be 1.5 times greater for the radiologist at higher risk of a false-positive reading, compared with the radiologist at lowest risk (95% highest posterior density interval [similar to a confidence interval] = 1.17 to 2.08).Community radiologists varied widely in their false-positive rates in screening mammograms; this variability range was reduced by half, but not eliminated, after statistical adjustment for patient, radiologist, and testing characteristics. These characteristics need to be considered when evaluating false-positive rates in community mammographic examination screening.
Trafficking of G Protein–Coupled Receptors
Authors: Matthew T. Drake, Sudha K. Shenoy, Robert J. Lefkowitz
Journal: Circulation Research (2006)

G protein-coupled receptors (GPCRs) play an integral role in the signal transduction of an enormous array of biological phenomena, thereby serving to modulate at a molecular level almost all components of human biology. This role is nowhere more evident than in cardiovascular biology, where GPCRs regulate such core measures of cardiovascular function as heart rate, contractility, and vascular tone. GPCR/ligand interaction initiates signal transduction cascades, and requires the presence of the receptor at the plasma membrane. Plasma membrane localization is in turn a function of the delivery of a receptor to and removal from the cell surface, a concept defined most broadly as receptor trafficking. This review illuminates our current view of GPCR trafficking, particularly within the cardiovascular system, as well as highlights the recent and provocative finding that components of the GPCR trafficking machinery can facilitate GPCR signaling independent of G protein activation.
C-Jun Nh2-Terminal Kinase 1 in Hepatocytes: An Essential Mediator of Insulin Resistance
Authors: Francisco Javier Cubero, Oliver Drvarov, Christian Trautwein
Journal: Hepatology (2010)

Abstract Nonalcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH2-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This finding has potential implications for the design of JNK1-selective drugs for the treatment of metabolic syndrome.
Models of β-amyloid induced Tau-pathology: the long and “folded” road to understand the mechanism
Authors: Ilie-Cosmin Stancu, Bruno Vasconcelos, Dick Terwel, Ilse Dewachter
Journal: Molecular Neurodegeneration (2014)

The amyloid cascade hypothesis has been the prevailing hypothesis in Alzheimer’s Disease research, although the final and most wanted proof i.e. fully successful anti-amyloid clinical trials in patients, is still lacking. This may require a better in depth understanding of the cascade. Particularly, the exact toxic forms of Aβ and Tau, the molecular link between them and their respective contributions to the disease process need to be identified in detail. Although the lack of final proof has raised substantial criticism on the hypothesis per se, accumulating experimental evidence in in vitro models, in vivo models and from biomarkers analysis in patients supports the amyloid cascade and particularly Aβ-induced Tau-pathology, which is the focus of this review. We here discuss available models that recapitulate Aβ-induced Tau-pathology and review some potential underlying mechanisms. The availability and diversity of these models that mimic the amyloid cascade partially or more complete, provide tools to study remaining questions, which are crucial for development of therapeutic strategies for Alzheimer’s Disease.
Identification of the Lateral Interaction Surfaces of Human Histocompatibility Leukocyte Antigen (HLA)-DM with HLA-DR1 by Formation of Tethered Complexes That Present Enhanced HLA-DM Catalysis
Authors: Efstratios Stratikos, Lidia Mosyak, Dennis M. Zaller, Don C. Wiley
Journal: The Journal of Experimental Medicine (2002)

Human histocompatibility leukocyte antigen (HLA)-DM is a major histocompatibility complex (MHC)-like protein that catalyzes exchange of antigenic peptides from MHC class II molecules. To investigate the molecular details of this catalysis we created four covalent complexes between HLA-DM and the MHC class II allele DR1. We introduced a disulfide bond between the naturally occurring cysteine β46 on HLA-DM and an engineered cysteine on the end of a linker attached to either the NH2- or the COOH terminus of an antigenic peptide that is tightly bound on DR1. We find that when DM is attached to the NH2 terminus of the peptide, it can, for all linker lengths tested, catalyze exchange of the peptide with a half-life a few minutes (compared with uncatalyzed t1/2 &amp;gt; 100 h). This rate, which is several orders of magnitude greater than the one we obtain in solution assays using micromolar concentrations of HLA-DM, is dominated by a concentration independent factor, indicating an intramolecular catalytic interaction within the complex. A similar complex formed at the COOH terminus of the peptide shows no sign of DM-specific intramolecular catalysis. Restrictions on the possible interaction sites imposed by the length of the linkers indicate that the face of DR1 that accommodates the NH2 terminus of the antigenic peptide interacts with the lateral face of HLA-DM that contains cysteine β46.