tbuckley/cabot-search huggingface dataset:
Anginal chest pain in sarcoidosis.
Authors: J L Wait, A Movahed
Journal: Thorax (1989)

Of 43 consecutive black patients (42 male) with sarcoidosis, 12 (28%) complained of chest pain that met the clinical criteria for typical (four patients) or atypical (eight patients) angina pectoris. These patients underwent cardiopulmonary assessment, which included exercise and redistribution thallium-201 scans and, if indicated, coronary angiography. Nine control patients with sarcoidosis matched for age and duration of disease, but without chest pain, were also studied by thallium-201 scintigraphy. Six of the 12 patients with chest pain had thallium scans indicative of myocardial ischaemia, but all had normal coronary angiograms; no patient from the control group had evidence of ischaemia on the thallium scan. Four additional patients with chest pain and one from the control group had other (non-specific) abnormalities on the thallium scan, so that scans were abnormal in 10 of the 12 patients with sarcoidosis who had chest pain. Most patients with anginal chest pain reported partial or complete relief of symptoms with nitrates. Anginal chest pain appears to be common in black male patients with sarcoidosis, is associated with abnormal myocardial perfusion scans, and may result from myocardial sarcoidosis.
1093-145 Assessment of aortic valve calcification by electrocardiogram-gated multislice spiral computed tomography as a marker for severe aortic stenosis
Authors: Ralf Koos, Andras Horst Mahnken, Anil Martin Sinha, Joachim Ernst Wilberger, Harald Peter Kühl, Rainer Hoffmann
Journal: Journal of the American College of Cardiology (2004)
Viral, bacterial or both? Regardless, we need to treat infection in COPD
Authors: Tobias Welte, Marc Miravitlles
Journal: European Respiratory Journal (2014)

Guidelines indicate that pharmacological treatment of chronic obstructive pulmonary disease (COPD) is based on bronchodilators with the addition of inhaled corticosteroids (ICS) in frequent exacerbators [1]. Although this recommendation is in accordance with the best evidence available, it does not take into account that more than half of the exacerbations are infective and infections are not adequately prevented or treated by ICS. In fact, no pharmacological treatment has been able to suppress all exacerbations and, on the contrary, the long-term use of ICS has been associated with higher airway bacterial load in stable COPD [2], and increased risk of pneumonia [3] and tuberculosis [4].

Clinicians have always been aware that not all exacerbations of COPD are alike. Some must be treated with anti-infective agents while others respond better to systemic corticosteroids. Markers such as sputum colour and C-reactive protein levels are useful to differentiate exacerbations and guide therapy [5, 6]. Recent studies have further characterised these different types of exacerbations, and identified bacterial, viral, inflammatory (eosinophilic) and pauci-inflammatory phenotypes of exacerbations, with the majority (59%) of exacerbations being bacterial or viral. Interestingly, the phenotype of the exacerbation remains constant in a given patient [7]. However, despite these different phenotypes of exacerbations, no studies have attempted to investigate whether different treatments would be more effective in preventing one type of exacerbation or another.

Both the high bacterial load in the airways in stable COPD and an increased frequency of exacerbations have been associated with a more rapid decline in lung function and an impairment in quality of life [8–10]. More recently, the presence of bronchiectasis in patients with COPD [11] and the persistent colonisation by unusual microorganisms [12] have also …
Changes in joint laxity occurring during pregnancy.
Authors: M Calguneri, H A Bird, V Wright
Journal: Annals of the Rheumatic Diseases (1982)

We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies.
Experience-Dependent Specialization of Receptive Field Surround for Selective Coding of Natural Scenes
Authors: Michael Pecka, Yunyun Han, Elie Sader, Thomas D. Mrsic-Flogel
Journal: Neuron (2014)

Highlights•V1 firing is more selective to natural than phase-scrambled surround stimuli•Improved selectivity is caused by Vm hyperpolarisation prior to RF-spiking events•Natural surround sensitivity is experience dependent, absent in immature/deprived V1•Vision shapes circuits to improve V1 coding of natural scenes across RF and surroundSummaryAt eye opening, neurons in primary visual cortex (V1) are selective for stimulus features, but circuits continue to refine in an experience-dependent manner for some weeks thereafter. How these changes contribute to the coding of visual features embedded in complex natural scenes remains unknown. Here we show that normal visual experience after eye opening is required for V1 neurons to develop a sensitivity for the statistical structure of natural stimuli extending beyond the boundaries of their receptive fields (RFs), which leads to improvements in coding efficiency for full-field natural scenes (increased selectivity and information rate). These improvements are mediated by an experience-dependent increase in the effectiveness of natural surround stimuli to hyperpolarize the membrane potential specifically during RF-stimulus epochs triggering action potentials. We suggest that neural circuits underlying surround modulation are shaped by the statistical structure of visual input, which leads to more selective coding of features in natural scenes.
Regulation of the Growth Arrest and DNA Damage-Inducible Gene 45 (GADD45) by Peroxisome Proliferator-Activated Receptor γ in Vascular Smooth Muscle Cells
Authors: Dennis Bruemmer, Fen Yin, Joey Liu, Joel P. Berger, Toshiyuki Sakai, Florian Blaschke, Eckart Fleck, Andre J. Van Herle, Barry M. Forman, Ronald E. Law
Journal: Circulation Research (2003)

Peroxisome proliferator-activated receptor (PPAR) gamma is activated by thiazolidinediones (TZDs), widely used as insulin-sensitizing agents for the treatment of type 2 diabetes. TZDs have been shown to induce apoptosis in a variety of mammalian cells. In vascular smooth muscle cells (VSMCs), proliferation and apoptosis may be competing processes during the formation of restenotic and atherosclerotic lesions. The precise molecular mechanisms by which TZDs induce apoptosis in VSMCs, however, remain unclear. In the present study, we demonstrate that the TZDs rosiglitazone (RSG), troglitazone (TRO), and a novel non-TZD partial PPARgamma agonist (nTZDpa) induce caspase-mediated apoptosis of human coronary VSMCs. Induction of VSMC apoptosis correlated closely with an upregulation of growth arrest and DNA damage-inducible gene 45 (GADD45) mRNA expression and transcription, a well-recognized modulator of cell cycle arrest and apoptosis. Using adenoviral-mediated overexpression of a constitutively active PPARgamma mutant and the irreversible PPARgamma antagonist GW9662, we provide evidence that PPARgamma ligands induce caspase-mediated apoptosis and GADD45 expression through a receptor-dependent pathway. Deletion analysis of the GADD45 promoter revealed that a 153-bp region between -234 and -81 bp proximal to the transcription start site, containing an Oct-1 element, was crucial for the PPARgamma ligand-mediated induction of the GADD45 promoter. PPARgamma activation induced Oct-1 protein expression and DNA binding and stimulated activity of a reporter plasmid driven by multiple Oct-1 elements. These findings suggest that activation of PPARgamma can lead to apoptosis and growth arrest in VSMCs, at least in part, by inducing Oct-1-mediated transcription of GADD45. The full text of this article is available online at http://www.circresaha.org.
Worldwide variations in the prevalence of atopic symptoms: what does it all mean?
Authors: J. O. Warner
Journal: Thorax (1999)

Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC The International Study of Asthma and Allergies in Childhood (ISAAC) Steering CommitteeBackground.Systematic international comparisons of the prevalences of asthma and other allergic disorders in children are needed for better understanding of their global epidemiology, to generate new hypotheses, and to assess existing hypotheses of possible causes.We investigated worldwide prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema.Methods.We studied 463 801 children aged 13-14 years in 155 collaborating centres in 58 countries.Children self-reported, through one-page questionnaires, symptoms of these three atopic disorders.In 99 centres in 42 countries, a video asthma questionnaire was also used for 304 796 children.Findings.We found differences of between 20-fold and 60-fold between centres in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema, with four-fold to 12-fold variations between the 10th and 90th percentiles for the different disorders.For asthma symptoms, the highest 12-month prevalences were from centres in the UK.Australia, New Zealand, and Republic of Ireland, followed by most centres in North, Central, and South America; the lowest prevalences were from centres in several Eastern European countries, Indonesia, Greece, China, Taiwan, Uzbekistan, India, and Ethiopia.For allergic rhinoconjunctivitis, the centres with the highest prevalences were scattered across the world.The centres with the lowest prevalences were similar to those for asthma symptoms.For atopic eczema, the highest prevalences came from scattered centres, including some from Scandinavia and Africa that were not among centres with the highest asthma prevalences; the lowest prevalence rates of atopic eczema were similar in centres, as for asthma symptoms.Interpretation.The variation in the prevalences of asthma, allergic rhinoconjunctivitis, and atopic-eczema symptoms is striking between different centres throughout the world.These findings will form the basis of further studies to investigate factors that potentially lead to these international patterns.(
Enhanced Absorption of Insulin Aspart as the Result of a Dispersed Injection Strategy Tested in a Randomized Trial in Type 1 Diabetic Patients
Authors: Julia K. Mader, Thomas Birngruber, Stefan Korsatko, Sigrid Deller, Gerd Köhler, Susanne Boysen, Thomas Augustin, Selma I. Mautner, Frank Sinner, Thomas R. Pieber
Journal: Diabetes Care (2012)

We investigated the impact of two different injection strategies on the pharmacokinetics and pharmacodynamics of insulin aspart in vivo in an open-label, two-period crossover study and verified changes in the surface-to-volume ratio ex vivo.Before the clinical trial, insulin aspart was injected ex vivo into explanted human abdominal skin flaps. The surface-to-volume ratio of the subcutaneous insulin depot was assessed by microfocus computed tomography that compared 1 bolus of 18 IU with 9 dispersed boluses of 2 IU. These two injection strategies were then tested in vivo, in 12 C-peptide-negative type 1 diabetic patients in a euglycemic glucose clamp (glucose target 5.5 ± 1.1 mmol/L) for 8 h after the first insulin administration.The ex vivo experiment showed a 1.8-fold higher mean surface-to-volume ratio for the dispersed injection strategy. The maximum glucose infusion rates (GIR) were similar for the two strategies (10 ± 4 vs. 9 ± 4; P = 0.5); however, times to reach maximum GIR and 50% and 10% of the maximum GIR were significantly reduced by using the 9 × 2 IU strategy (68 ± 33 vs. 127 ± 93 min; P = 0.01; 38 ± 9 vs. 49 ± 16 min; P < 0.01; 23 ± 6 vs. 30 ± 10 min; P < 0.05). For 9 × 2 IU, the area under the GIR curve was greater during the first 60 min (219 ± 89 vs. 137 ± 75; P < 0.01) and halved until maximum GIR (242 ± 183 vs. 501 ± 396; P < 0.01); however, it was similar across the whole study period (1,361 ± 469 vs. 1,565 ± 527; P = 0.08).A dispersed insulin injection strategy enhanced the effect of a fast-acting insulin analog. The increased surface-to-volume ratio of the subcutaneous insulin depot can facilitate insulin absorption into the vascular system.
Target interaction profiling of midostaurin and its metabolites in neoplastic mast cells predicts distinct effects on activation and growth
Authors: B Peter, G E Winter, K Blatt, K L Bennett, G Stefanzl, U Rix, G Eisenwort, E Hadzijusufovic, M Gridling, C Dutreix, G Hoermann, J Schwaab, D Radia, J Roesel, P W Manley, A Reiter, G Superti-Furga, P Valent
Journal: Leukemia (2015)
Are house dust mite allergen levels influenced by cold winter weather?
Authors: U. Gehring, B. Brunekreef, B. Fahlbusch, H.‐E. Wichmann, J. Heinrich
Journal: Allergy (2005)

Background: Moisture is vitally important for house dust mites and they cannot survive in cold or hot‐dry climates. Aims of the study: To investigate the influence of two extraordinarily cold and dry winters in 1995/1996 and 1996/1997 on house dust mite levels in German homes. Methods: Dust samples were collected between June 1995 and December 2001 on the mattresses of 655 adults and 454 schoolchildren living in five different areas of Germany. We compared house dust mite allergen Dermatophagoides pteronyssinus (Der p 1) levels before and during the winters of 1995/1996 and 1996/1997 with levels after these winters. Results: D. pteronyssinus (Der p 1) levels in samples taken after the cold winters of 1995/1996 and 1996/1997 were approximately two times lower than Der p 1 levels in dust samples collected before or during these respective winters (Geometric means: Erfurt 89 vs 33 ng/g; Hamburg 333 vs 219 ng/g; Bitterfeld, Hettstedt, and Zerbst 296 vs 180 ng/g). Except for Hamburg, the decrease in Der p 1 levels was statistically significant. D. pteronyssinus levels measured in dust samples collected in 2001 (i.e. 3 years after the two cold winters) show a statistically non‐significant increase (Geometric means: Erfurt 33 vs 39 ng/g; Hamburg 219 vs 317 ng/g), suggesting that it may take a long time for mite allergen levels to increase again after a sudden decrease. Conclusion: We conclude that Der p 1 levels in German mattress dust samples have been approximately reduced by a factor of three to four by the two consecutive cold winters of 1995/1996 and 1996/1997.
Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1 expansion cohort study
Authors: David Olmos, Sophie Postel-Vinay, L Rhoda Molife, Scott H Okuno, Scott M Schuetze, M Luisa Paccagnella, Gretchen N Batzel, Donghua Yin, Kathryn Pritchard-Jones, Ian Judson, Francis P Worden, Antonio Gualberto, Michelle Scurr, Johann S de Bono, Paul Haluska
Journal: The Lancet Oncology (2009)
Efficacy of ruxolitinib on hepatomegaly in patients with myelofibrosis
Authors: S Verstovsek, E Atallah, J Mascarenhas, H Sun, M Montgomery, V Gupta, R Mesa, J Gotlib
Journal: Leukemia (2015)

The Janus kinase 1/2 inhibitor ruxolitinib has been shown in a pivotal placebo-controlled phase III study (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment I (COMFORT-I)) to significantly reduce splenomegaly and symptoms in patients with intermediate-2 or high-risk myelofibrosis (MF). Although splenomegaly is the most common manifestation of MF-associated extramedullary hematopoiesis, up to 65% of patients may also have hepatomegaly,1, 2 which is often highly symptomatic and can lead to serious complications.3 Here, we present the results from a COMFORT-I post hoc analysis that assessed changes in liver volume and their relationship with concomitant changes in splenomegaly and measures of metabolic status.
Variation in bronchial responsiveness in the European Community Respiratory Health Survey (ECRHS)
Authors: S Chinn, P Burney, D Jarvis, C Luczynska
Journal: European Respiratory Journal (1997)

Attempts to compare bronchial responsiveness between populations have been hampered by between-study differences in the pharmacological agent of provocation, the method of administration and the summary statistic employed. The European Community Respiratory Health Survey used methacholine challenge delivered by Mefar dosimeter according to a standardized protocol used in 35 centres in 16 countries. Data were obtained from 13,161 men and women, aged 20-44 yrs at the start of the study. The dose of methacholine producing a 20% fall in forced expiratory volume in one second (FEV1) (PD20) and the regression coefficient of percentage decline in FEV1 with log dose, were calculated ("slope", after transformation), with and without calibration of nebulizers by weight and adjustment for nonresponse bias. Standardization for baseline lung function and variation in smoking prevalence was applied to slope. Results were robust to whichever summary measure was used, and to the various adjustments. Responsiveness was low in Iceland and Switzerland, and in most centres in Sweden, Italy and Spain, and high in New Zealand, Australia, the USA, Britain, France, Denmark and Germany. Bronchial responsiveness varies considerably in Europe, and high levels are not confined to the English-speaking world.
Some Intraspecies Differences in Antigens on the Surface of Certain Living Human Cells&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Nelda B. Holmgren, Francis E. Payne
Journal: JNCI Journal of the National Cancer Institute (1966)

Surface antigens of several types of living cells of human origin were partially characterized with hyperimmune antisera prepared in the rabbit against living HeLa cells and living, uncultured, full-term, human amnion cells. Hemagglutination, mixed-agglutination, and direct and indirect immunofluorescence (FAB) techniques were employed. With these techniques and fractional absorption procedures, common and specific cell antigens were detected on the surface of several human living cells: uncultured and primary amnion, two established human cell lines (RP Am 1 and U amnion) of presumed normal origin and two (HeLa and HEp-2) of presumed malignant origin, and human erythrocytes. None of the antigens were found on NCTC 2555 mouse cells. The human cells possessed species-related antigens demonstrable by hemagglutination. After removal of the hemagglutinins by absorption with human erythrocytes, antibody in high titer for the homologous cells was detected by FAB methods. In addition, some changes in antigens on the surface of amnion cells during primary culture were observed. Finally, an antigen was Found on HeLa and HEp-2 cells, by use of anti-HeLa serum absorbed with human erythrocytes and RP Am 1 cells, that was not found on either human erythrocytes, uncultured amnion cells, or on the cells of the two established amnion cell lines. At the dilutions used in the tests, antibodies to the ABO blood group isoantigens, Forssman hapten, or adsorbed serum proteins could not account for the antigens detected. The possibility that Mycoplasma sp. antigens were responsible for the reactions was inconsistent with the results. The specificity of the FAB methods on living cells was confirmed.
Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact
Authors: J.M. Nabholtz, C. Abrial, M.A. Mouret-Reynier, M.M. Dauplat, B. Weber, J. Gligorov, A.M. Forest, O. Tredan, L. Vanlemmens, T. Petit, S. Guiu, I. Van Praagh, C. Jouannaud, P. Dubray-Longeras, N. Tubiana-Mathieu, K.E. Benmammar, S. Kullab, M.R.K. Bahadoor, N. Radosevic-Robin, F. Kwiatkowski, A. Desrichard, A. Cayre, N. Uhrhammer, N. Chalabi, P. Chollet, F. Penault-Llorca
Journal: Annals of Oncology (2014)
Promoting new approaches for cancer care in the Middle East
Authors: M. Silbermann, D.E. Epner, H. Charalambous, L. Baider, C.M. Puchalski, L. Balducci, M. Gultekin, R.F. Abdalla, M. Daher, M.R. Al-Tarawneh, T.J. Smith
Journal: Annals of Oncology (2013)
Glomerular and Tubular Damage Markers Are Elevated in Patients With Diabetes
Authors: Ferdau L. Nauta, Wendy E. Boertien, Stephan J.L. Bakker, Harry van Goor, Wim van Oeveren, Paul E. de Jong, Henk Bilo, Ron T. Gansevoort
Journal: Diabetes Care (2011)

We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid-binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR).Damage markers were measured in triplicate in fresh morning urine samples and in plasma.Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87; all P ≤ 0.001). All urinary damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between -0.38 and -0.21; all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β -0.26; P = 0.037).Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease.
Transmission of male infertility to future generations: lessons from the Y chromosome
Authors: S. J. Silber
Journal: Human Reproduction Update (2002)

The introduction of ICSI and testicular sperm extraction (TESE) has allowed many infertile men to father children. The biggest concern about the wide use of these techniques is the health of the resulting offspring, in particular their fertility status. If the spermatogenic defect is genetic in origin, there is potential risk of transmitting this defect to future offspring. The most frequently documented genetic cause of male infertility is a Y chromosome deletion. The Y chromosome has acquired a large number of testis-specific genes during recent evolution, and deletions causing infertility take out a number of these genes. These deletions have been shown to be transmitted to 100% of male offspring. Also, absence of an aberration on the Y chromosome does not rule out a genetic cause of the infertility phenotype, as there are many other genes involved in spermatogenesis elsewhere in the genome, and current mapping techniques–-especially on the Y chromosome–-can miss many aberrations. More detailed studies of these spermatogenesis genes, which are now possible because of more precise sequence-based mapping, will lead to improved understanding of the genetic basis of male infertility and enable proper counselling of patients undergoing ICSI in the future.