tbuckley/cabot-search huggingface dataset:
Tuberculin positive children.
Authors: L O Larsson, B E Skoogh, A Lind
Journal: Thorax (1993)

Cohabiting with domestic mitesDr IH Feather and colleagues have reviewed the central role of house dust mites in the aetiology of allergic asthma (January 1993;43:5-9).In my personal series of 744 consecutive asthmatic children aged 5-15 years compiled over the years 1985-91, positive skin prick test reactions to Dermatophagoides pteronyssinus (ALK, Copenhagen) were nevertheless found in only 180 subjects (24%) and more often among those from rural domiciles, large families, cramped dwellings, and blue collar social classes (table ).The mite population in homes is depen- dent on the supply of food-that is, human skin scales-and air humidity.Since there is generally no shortage of the former it is the humidity that is the decisive factor for mite survival.In many regions the circumstances are ideal for mite growth, and bedrooms in particular are universally infested with mites.In Scandinavia, however, the relative humidity indoors is low during the long cold season from September to May when the houses are heated continuously, and conditions are therefore unsuitable for mites.Modern energy saving with heat insulation and poor ventilation have caused a change in the traditional indoor climate and a rapid rise in mite concentrations and hypersensitivity to mites has resulted in Stockholm,l2 but in northern Scandinavia (for example, Finland) hypersensitivity to mites still remains more or less a social problem.Crowded living conditions pro- vide a food supply for mites and an addi- tional water vapour load which together provide conditions suitable for mite sur- vival.In view of the limited efficiency of acaricides and vacuum cleaning, I agree with the opinion that the mite problem can- not be solved without a change of housing conditions in general.
The Impact of Low Serum Sodium on Treatment Outcome of Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Cancer Database Consortium
Authors: Fabio A.B. Schutz, Wanling Xie, Frede Donskov, Monica Sircar, David F. McDermott, Brian I. Rini, Neeraj Agarwal, Sumanta Kumar Pal, Sandy Srinivas, Christian Kollmannsberger, Scott A. North, Lori A. Wood, Ulka Vaishampayan, Min-Han Tan, Mary J. Mackenzie, Jae Lyun Lee, Sun-Young Rha, Takeshi Yuasa, Daniel Y.C. Heng, Toni K. Choueiri
Journal: European Urology (2013)
Somatic mutations identify a subgroup of aplastic anemia patients who progress to myelodysplastic syndrome
Authors: Austin G. Kulasekararaj, Jie Jiang, Alexander E. Smith, Azim M. Mohamedali, Syed Mian, Shreyans Gandhi, Joop Gaken, Barbara Czepulkowski, Judith C. W. Marsh, Ghulam J. Mufti
Journal: Blood (2014)
Increased Expression of Apoptosis Inhibitor Protein XIAP Contributes to Anoikis Resistance of Circulating Human Prostate Cancer Metastasis Precursor Cells
Authors: Olga Berezovskaya, Aaron D. Schimmer, Anna B. Glinskii, Clemencia Pinilla, Robert M. Hoffman, John C. Reed, Gennadi V. Glinsky
Journal: Cancer Research (2005)

Abstract Survival in lymph or blood is an essential prerequisite for metastasis of carcinoma cells to distant organs. Recently, we reported isolation and initial biological characterization of circulating metastatic cells in a fluorescent, orthotopic, metastatic nude-mouse model of human prostate cancer. Here we show that the metastatic human prostate carcinoma cells selected for survival in the circulation have increased resistance to anoikis, which is apoptosis induced by cell detachment. Using gene silencing and gene transfer techniques, we show that increased expression of the apoptosis inhibitory protein XIAP contributes to anoikis resistance of the circulating metastatic human prostate carcinoma cells. We also provide initial preclinical data on the antimetastatic efficacy of recently discovered small-molecule antagonists of XIAP.
Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production induced by anti-CD58 monoclonal antibody.
Authors: H Kimata, M Fujimoto, C Ishioka, A Yoshida
Journal: The Journal of Experimental Medicine (1996)

We studied the effects of histamine on human immunoglobulin (IgE) and IgG4 production. Histamine selectively enhanced IgE and IgG4 production in purified surface IgE and IgG4 negative (sIgE-sIgG4-) B cells from normal donors stimulated with interleukin (IL)-4 plus anti-CD58 or IL-13 plus anti-CD58 monoclonal antibody (mAb) without affecting production of IgG1, IgG2, IgG3, IgM, IgA1, or IgA2. In cultures with IL-4 plus anti-CD58 mAb, histamine-induced enhancement of IgE and IgG4 production was specifically blocked by thioperamide (H3 receptor antagonist), and was inhibited by anti-IL-10 antibody (Ab). In contrast, in cultures with IL-13 plus anti-CD58 mAb, histamine-induced enhancement was blocked by dimaprit (H1 receptor antagonist), and was inhibited by anti-IL-6 mAb. Histamine also enhanced IgE and IgG4 production by in vivo-generated sIgE+ and sIgG4+ B cells, respectively, from atopic patients; enhancement was blocked by dimaprit and thioperamide, and was inhibited by anti-IL-6 mAb and anti-IL-10 Ab. In sIgE-sIgG4- B cells, IL-4 plus anti-CD58 mAb induced IL-10 production and IL-10 receptor expression, whereas IL-13 plus anti-CD58 mAb induced IL-6 production and IL-6 receptor expression. Histamine increased IL-10 and IL-6 production without affecting IL-10 and IL-6 receptor expression, in cultures with IL-4 plus anti-CD58 mAb and with IL-13 plus anti-CD58 mAb, respectively, which was blocked by thioperamide and dimaprit, respectively. In contrast, sIgE+ and sIgG4+ B cells spontaneously produced both IL-6 and IL-10 and constitutively expressed IL-6 and IL-10 receptors, and histamine increased IL-6 and IL-10 production without affecting IL-6 or IL-10 receptor expression, which was blocked by thioperamide and dimaprit. These results indicate that histamine enhanced IgE and IgG4 production by increasing endogenous IL-6 and IL-10 production via H1 and H3 receptors, respectively.
Occupational asthma caused by aluminium welding
Authors: O Vandenplas, JP Delwiche, ML Vanbilsen, J Joly, D Roosels
Journal: European Respiratory Journal (1998)

Work-related asthma has been documented in workers employed in the primary aluminium industry and in the production of aluminium salts. The role of aluminium in the development of occupational asthma has, however, never been convincingly substantiated. We investigated a subject who experienced asthmatic reactions related to manual metal arc welding on aluminium. Challenge exposure to aluminium welding with flux-coated electrodes, as well as with electrodes without flux, elicited marked asthmatic reactions. Manual metal arc welding on mild steel did not cause significant bronchial response. The results of inhalation challenges combined with exposure assessments provided evidence that aluminium can cause asthmatic reactions in the absence of fluorides. Awareness of this possibility may be relevant to the investigation of asthma in workers exposed to aluminium.
Is operational research delivering the goods? The journey to success in low-income countries
Authors: Rony Zachariah, Nathan Ford, Dermot Maher, Karen Bissell, Rafael Van den Bergh, Wilma van den Boogaard, Tony Reid, Kenneth G Castro, Bertrand Draguez, Johan von Schreeb, Jeremiah Chakaya, Rifat Atun, Christian Lienhardt, Don A Enarson, Anthony D Harries
Journal: The Lancet Infectious Diseases (2012)
Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A
Authors: Fiorenza Lotti, Awad M. Jarrar, Rish K. Pai, Masahiro Hitomi, Justin Lathia, Adam Mace, Gerald A. Gantt, Kumar Sukhdeo, Jennifer DeVecchio, Amit Vasanji, Patrick Leahy, Anita B. Hjelmeland, Matthew F. Kalady, Jeremy N. Rich
Journal: The Journal of Experimental Medicine (2013)

Many solid cancers display cellular hierarchies with self-renewing, tumorigenic stemlike cells, or cancer-initiating cells (CICs) at the apex. Whereas CICs often exhibit relative resistance to conventional cancer therapies, they also receive critical maintenance cues from supportive stromal elements that also respond to cytotoxic therapies. To interrogate the interplay between chemotherapy and CICs, we investigated cellular heterogeneity in human colorectal cancers. Colorectal CICs were resistant to conventional chemotherapy in cell-autonomous assays, but CIC chemoresistance was also increased by cancer-associated fibroblasts (CAFs). Comparative analysis of matched colorectal cancer specimens from patients before and after cytotoxic treatment revealed a significant increase in CAFs. Chemotherapy-treated human CAFs promoted CIC self-renewal and in vivo tumor growth associated with increased secretion of specific cytokines and chemokines, including interleukin-17A (IL-17A). Exogenous IL-17A increased CIC self-renewal and invasion, and targeting IL-17A signaling impaired CIC growth. Notably, IL-17A was overexpressed by colorectal CAFs in response to chemotherapy with expression validated directly in patient-derived specimens without culture. These data suggest that chemotherapy induces remodeling of the tumor microenvironment to support the tumor cellular hierarchy through secreted factors. Incorporating simultaneous disruption of CIC mechanisms and interplay with the tumor microenvironment could optimize therapeutic targeting of cancer.
Age-related alterations in the phosphorylation of sarcoplasmic reticulum and myofibrillar proteins and diminished contractile response to isoproterenol in intact rat ventricle.
Authors: M T Jiang, M P Moffat, N Narayanan
Journal: Circulation Research (1993)

Previous studies have shown that the inotropic response of the heart to beta-adrenergic stimulation declines with aging. This alteration has been attributed partly to an age-related impairment in the activation of the beta-adrenoceptor-G protein-adenylate cyclase complex. To further understand the mechanisms underlying the age-related deficit, the present study compared beta-adrenergic-mediated contractile response, cAMP accumulation, and phosphorylation of sarcoplasmic reticulum and myofibrillar proteins in isolated perfused hearts from adult (6-8 months) and aged (28-30 months) Fischer 344 rats. In isometrically contracting, electrically paced (240 beats per minute) hearts perfused at constant flow rate (9 ml/min per gram ventricle), the baseline contractile performance differed significantly between adult and aged hearts. Thus, contraction duration was prolonged (approximately 15%, p &lt; 0.001) in the aged relative to the adult heart, and this was due to increases in time to peak tension and relaxation time. Further, developed peak tension, normalized per gram ventricular wet weight, was significantly lower (approximately 20%, p &lt; 0.05) in the aged compared with the adult heart. In these isolated perfused heart preparations, beta-adrenergic stimulation with isoproterenol (ISO, 0.001-1 microM) evoked concentration-dependent positive inotropic and lusitropic responses, both of which were significantly lower (15-20%, p &lt; 0.05-0.001) in the aged compared with the adult heart. These age-related differences were manifested as relatively smaller ISO-induced increases in 1) developed peak tension, 2) maximum rate of tension development (+dT/dt), and 3) maximum rate of relaxation (-dT/dt) in the aged compared with the adult heart. The ISO-induced abbreviation of time to half relaxation was also less marked in the aged heart. Under similar experimental conditions, ISO (0.1 microM)-induced increase in tissue cAMP content was also lower (approximately 18%, p &lt; 0.05) in the aged heart. ISO (0.1 microM)-induced phosphorylation of the sarcoplasmic reticulum protein phospholamban and myofibrillar protein troponin I was significantly diminished (approximately 38% and 25% decline, respectively, for phospholamban and troponin I; p &lt; 0.05-0.001) in the aged compared with the adult heart. No significant age-related difference was, however, evident in ISO-induced phosphorylation of C protein of myofibrils. These data suggest that age-related decrements in beta-adrenergic-mediated cAMP accumulation and phosphorylation of phospholamban and troponin I contribute to the diminished contractile responses of the aged heart to beta-adrenergic stimulation.
Reply: CXCL13 in Tertiary Lymphoid Tissues: Sites of Production Are Different from Sites of Functional Localization
Authors: Eleni Litsiou, Maria Semitekolou, Ioanna Galani, Ioannis Morianos, Aikaterini Tsoutsa, Panagiota Kara, Dimitra Rontogianni, Ion Bellenis, Maria Konstantinou, Konstantinos Potaris, Evangelos Andreakos, Paschalis Sideras, Spyros Zakynthinos, Maria Tsoumakidou
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
FLUOROSCOPY-FREE ABLATION OF PAROXYSMAL AND PERSISTENT ATRIAL FIBRILLATION
Authors: Georg Nö;lker, Klaus J. Gutleben, Johannes Heintze, Jürgen Homberger, Ameera Yalda, Vanessa Pütz, Dieter Horstkotte, Jürgen Vogt
Journal: Journal of the American College of Cardiology (2010)
The Effects of Dipeptidyl Peptidase-4 Inhibition on Microvascular Diabetes Complications
Authors: Angelo Avogaro, Gian Paolo Fadini
Journal: Diabetes Care (2014)

We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: (“diabetes” OR “diabetic”) AND (“retinopathy” OR “retinal” OR “nephropathy” OR “renal” OR “albuminuria” OR “microalbuminuria” OR “neuropathy” OR “ulcer” OR “wound” OR “bone marrow”); (“dipeptidyl peptidase-4” OR “dipeptidyl peptidase-IV” OR “DPP-4” OR “DPP-IV”); and (“inhibition” OR “inhibitor”). Experimentally, DPP4-I appears to improve inflammation, endothelial function, blood pressure, lipid metabolism, and bone marrow function. Several experimental studies report direct potential beneficial effects of DPP4-I on all microvascular diabetes-related complications. These drugs have the ability to act either directly or indirectly via improved glucose control, GLP-1 bioavailability, and modifying nonincretin substrates. Although preliminary clinical data support that DPP4-I therapy can protect from microangiopathy, insufficient evidence is available to conclude that this class of drugs directly prevents or decreases microangiopathy in humans independently from improved glucose control. Experimental findings and preliminary clinical data suggest that DPP4-I, in addition to improving metabolic control, have the potential to interfere with the onset and progression of diabetic microangiopathy. Further evidence is needed to confirm these effects in patients with diabetes.
Assessing the Probability That a Positive Report is False: An Approach for Molecular Epidemiology Studies
Authors: Sholom Wacholder, Stephen Chanock, Montserrat Garcia-Closas, Laure El ghormli, Nathaniel Rothman
Journal: JNCI Journal of the National Cancer Institute (2004)

Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.
Patterns of interaction between anthraquinone drugs and the calcium-release channel from cardiac sarcoplasmic reticulum.
Authors: S R Holmberg, A J Williams
Journal: Circulation Research (1990)

We have studied the effects of clinically useful anthraquinones on the cardiac sarcoplasmic reticulum calcium-release channel. Micromolar concentrations of doxorubicin and other anthracyclines at the cytosolic face of the channel significantly and reversibly increase the open probability of single channels in artificial phospholipid bilayers. Lifetime analysis shows that anthracyclines and calcium are synergistic activators of the calcium-release channel. Radiolabeled ryanodine binding suggests that all the anthracyclines studied are equally potent as channel activators in vitro. Mitoxantrone, an anthracenedione derivative, variably increases channel open probability at low (1-10 microM) concentrations. Higher concentrations are associated with the appearance of channel currents with lower amplitudes than the fully open state, and normal openings are reduced in frequency. At these concentrations, the interaction of mitoxantrone with the channel reduces the level of ryanodine binding. Abnormal function of the cardiac calcium-release channel will alter calcium handling within the myocyte and may be the basis for anthraquinone-related cardiotoxicity.
Plasma and Cerebrospinal Fluid Pharmacokinetics of Intravenous Oxaliplatin, Cisplatin, and Carboplatin in Nonhuman Primates
Authors: Shana S. Jacobs, Elizabeth Fox, Christopher Dennie, Lindsey B. Morgan, Cynthia L. McCully, Frank M. Balis
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Describe and compare the central nervous system pharmacology of the platinum analogues, cisplatin, carboplatin, and oxaliplatin and develop a pharmacokinetic model to distinguish the disposition of active drug from inert platinum species. Experimental Design: Oxaliplatin (7 or 5 mg/kg), cisplatin (2 mg/kg), or carboplatin (10 mg/kg) was given i.v. Serial plasma and cerebrospinal fluid (CSF) samples were collected over 24 hours. Plasma ultrafiltrates were prepared immediately. Platinum concentrations were measured using atomic absorption spectrometry. Areas under the concentration × time curve were derived using the linear trapezoidal method. CSF penetration was defined as the CSF AUC0-24/plasma ultrafiltrate AUC0-24 ratio. A four-compartment model with first-order rate constants was fit to the data to distinguish active drug from inactive metabolites. Results: The mean ± SD AUCs in plasma ultrafiltrate for oxaliplatin, cisplatin, and carboplatin were 61 ± 22, 18 ± 6, and 211 ± 64 μmol/L hour, respectively. The AUCs in CSF were 1.2 ± 0.4 μmol/L hour for oxaliplatin, 0.56 ± 0.08 μmol/L hour for cisplatin, and 8 ± 2.2 μmol/L hour for carboplatin, and CSF penetration was 2.0%, 3.6%, and 3.8%, respectively. For oxaliplatin, cisplatin, and carboplatin, the pharmacokinetic model estimated that active drug accounted for 29%, 79%, and 81% of platinum in plasma ultrafiltrate, respectively, and 25%, 89%, and 56% of platinum in CSF, respectively. The CSF penetration of active drug was 1.6% for oxaliplatin, 3.7% for cisplatin, and 2.6% for carboplatin. Conclusions: The CSF penetration of the platinum analogues is limited. The pharmacokinetic model distinguished between active drug and their inactive (inert) metabolites in plasma and CSF.
Heart rate responses of women aged 23–67 years during competitive orienteering
Authors: S Bird, M George, J Balmer, R C R Davison
Journal: British Journal of Sports Medicine (2003)

To compare the heart rate responses of women orienteers of different standards and to assess any relation between heart rate responses and age.Eighteen competitive women orienteers completed the study. They were divided into two groups: eight national standard orienteers (ages 23-67 years); 10 club standard orienteers (ages 24-67 years). Each participant had her heart rate monitored during a race recognised by the British Orienteering Federation. Peak heart rate (HR(PEAK)), mean heart rate (HR(MEAN)), standard deviation of her heart rate during each orienteering race (HR(SD)), and mean change in heart rate at each control point (DeltaHR(CONTROL)) were identified. The data were analysed using analysis of covariance with age as a covariate.National standard orienteers displayed a lower within orienteering race standard deviation in heart rate (6 (2) v 12 (2) beats/min, p<0.001) and a lower DeltaHR(CONTROL) (5 (1) v 17 (4) beats/min, p<0.001). The mean heart rate during competition was higher in the national standard group (170 (11) v 158 (11) beats/min, p = 0.025). The HR(MEAN) for the national and club standard groups were 99 (8)% and 88 (9)% of their age predicted maximum heart rate (220-age) respectively. All orienteers aged >55 years (n = 4) recorded HR(MEAN) greater than their age predicted maximum.The heart rate responses indicate that national and club standard women orienteers of all ages participate in the sport at a vigorous intensity. The higher DeltaHR(CONTROL) of club standard orienteers is probably due to failing to plan ahead before arriving at the controls and this, coupled with slowing down to navigate or relocate when lost, produced a higher HR(SD).
New Long-Acting Insulin Analogs: From Clamp Studies to Clinical Practice
Authors: Geremia B. Bolli, J. Hans DeVries
Journal: Diabetes Care (2015)

The NPH era started in 1946 and ended nearly 60 years later with the introduction to the market of the long-acting analogs, glargine in 2000 (1) and detemir in 2004 (2). More recently, a second-generation acylated long-acting insulin analog, degludec (3), has become available in some countries outside the U.S. In this issue of the journal, Becker et al. (4) report on pharmacokinetics (PK) and pharmacodynamics (PD) of a new long-acting insulin analog, glargine U300 (Gla-300). This is the same glargine molecule concentrated three times (300 units in 1 mL). It was approved by the U.S. Food and Drug Administration and received a positive opinion from the European Medicines Agency at the end of February 2015.

Becker et al. (4) compared Gla-300 to the original glargine (Lantus, U-100; Gla-100) in a clamp experiment in subjects with type 1 diabetes (T1D). They studied the right population (absent endogenous insulin secretion) in which the observed PK/PD after subcutaneous (s.c.) injection of an insulin preparation are specifically attributable to the injected insulin. When clamp studies are instead run in subjects without diabetes or with type 2 diabetes (T2D), the PK/PD results are confounded by endogenous insulin secretion. Becker et al. (4) correctly studied the subjects after 1 week of treatment at “steady state.” However, they did use a fixed dose of basal insulin (0.4 units/kg/day glargine, either Gla-300 or Gla-100). This approach has the advantage of simplicity but the disadvantage of inducing a pharmacological overinsulinization with risk of hypoglycemia as the previously daily basal insulin dose used by the subjects with T1D was lower (mean 0.30 units/kg/day). Indeed, the majority of subjects needed a robust glucose infusion rate (GIR) during the 6 h prior to injection of glargine (time zero) to prevent hypoglycemia, and several subjects had baseline plasma insulin concentrations higher before …