tbuckley/cabot-search huggingface dataset:
Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood
Authors: J Henderson, R Granell, J Heron, A Sherriff, A Simpson, A Woodcock, D P Strachan, S O Shaheen, J A C Sterne
Journal: Thorax (2008)

Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals.Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function (forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age.Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mumol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 %FEV(1) per mumol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes.The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.
SYSTEMIC BLASTOMYCOSIS, WITH REPORT OF A FATAL CASE
Authors: D. C. SMITH, H. C. TURNER, E. S. SANDERSON
Journal: British Journal of Dermatology (1928)

Journal Article SYSTEMIC BLASTOMYCOSIS, WITH REPORT OF A FATAL CASE Get access D. C. SMITH, M.D., D. C. SMITH, M.D. Front the Department of Dermatology and Syphilology and the Department of Pathology and Bacteriology, School of Medicine, University of Virginia, Charlottesville, Va Search for other works by this author on: Oxford Academic Google Scholar H. C. TURNER, M.D., H. C. TURNER, M.D. Front the Department of Dermatology and Syphilology and the Department of Pathology and Bacteriology, School of Medicine, University of Virginia, Charlottesville, Va Search for other works by this author on: Oxford Academic Google Scholar E. S. SANDERSON, Ph.D. E. S. SANDERSON, Ph.D. Front the Department of Dermatology and Syphilology and the Department of Pathology and Bacteriology, School of Medicine, University of Virginia, Charlottesville, Va Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 40, Issue 8-9, 1 August 1928, Pages 344–359, https://doi.org/10.1111/j.1365-2133.1928.tb09272.x Published: 01 August 1928
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies
Authors: Gillian F Black, Rosemary E Weir, Sian Floyd, Lyn Bliss, David K Warndorff, Amelia C Crampin, Bagrey Ngwira, Lifted Sichali, Bernadette Nazareth, Jenefer M Blackwell, Keith Branson, Steven D Chaguluka, Linda Donovan, Elizabeth Jarman, Elizabeth King, Paul EM Fine, Hazel M Dockrell
Journal: The Lancet (2002)
Renal Calcium Metabolism and Diuretics
Authors: C T Stier, H D Itskovitz
Journal: The Annual Review of Pharmacology and Toxicology (1986)

Diuretic agents have variable effects on calcium excretion as studied in vivo and in isolated kidneys and nephron segments. Generally, by increasing sodium and water excretion, diuretics will cause a concomitant increase in calcium excretion. As they diminish blood volume and alter renal hemodynamics, diuretics enhance calcium reabsorption in the proximal tubule, modulating their usual effects on calcium excretion. These general effects can be further modulated by additional metabolic actions. For instance, chronic administration of thiazide diuretics may diminish calcium excretion on the basis of altered levels of or responsiveness to PTH. Agents such as acetazolamide, which diminish bicarbonate reabsorption in the proximal tubule, will cause a modest calciuria, if any, because of reabsorption of the increased delivery of calcium, but not sodium, at the distal nephron. Agents acting in the loop of Henle that increase chloride excretion relative to sodium tend to cause greater calcium excretion. Finally, agents that act beyond the loop of Henle, which have their primary effects on cation excretion, tend to cause lesser degrees of calcium excretion, especially relative to sodium. These principles indicate that it may be appropriate to select a specific diuretic agent for different patients, depending upon the state of their calcium balance. It also may be possible to predict alterations in calcium balance, so that these may be anticipated and compensated for with patients on long-term therapy with various diuretic agents.
Meta-Analysis of Hepatic Arterial Infusion for Unresectable Liver Metastases From Colorectal Cancer: The End of an Era?
Authors: Simone Mocellin, Pierluigi Pilati, Mario Lise, Donato Nitti
Journal: Journal of Clinical Oncology (2007)

The treatment of unresectable liver-confined metastatic disease from colorectal cancer (CRC) is a challenging issue. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomized controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT).To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves.HAI regimens were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT, fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU + leucovorin, or a miscellany of FU and best supportive care in three, one, four, and two studies, respectively. Pooling the data, tumor response rate was 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively; the meta-risk of death was not statistically different between the two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24).Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.
Low Dopamine D<sub>2</sub> Receptor Binding Potential in Social Phobia
Authors: Franklin R. Schneier, Michael R. Liebowitz, Anissa Abi-Dargham, Yolanda Zea-Ponce, Shu-Hsing Lin, Marc Laruelle
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study compared dopamine D2 receptor binding potential in patients with social phobia and healthy comparison subjects. METHOD: Dopamine D2 receptor binding potential was assessed in 10 unmedicated subjects with generalized social phobia and no significant lifetime psychiatric comorbidity and 10 healthy comparison subjects matched for age and sex. Binding potential was measured in the striatum by using single photon emission computerized tomography and constant infusion of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM). RESULTS: Mean D2 receptor binding potential was significantly lower in the subjects with social phobia than in the comparison subjects. Within the social phobia group, there was a nonsignificant correlation of binding potential with the Liebowitz Social Anxiety Scale score. CONCLUSIONS: Generalized social phobia may be associated with low binding of [123I]IBZM to D2 receptors in the striatum.
Signaling impairments in maternal T cells engrafted in an infant with a novel IL-2 receptor γ mutation
Authors: Aaruni Khanolkar, Jeffrey D. Wilks, Lawrence J. Jennings, Jessica L. Davies, Joshua A. Zollett, Loren L. Lott, Erin R. Fullmer, Nicolas E. Bensen, Katrin M. Carlson-Leuer, William T. Tse, Ramsay L. Fuleihan
Journal: Journal of Allergy and Clinical Immunology (2015)
Comprehensive clinical electrophysiologic studies in the investigation of documented or suspected tachycardias. Time, staff, problems and costs.
Authors: D L Ross, J Farre, F W Bar, E J Vanagt, W R Dassen, I Wiener, H J Wellens
Journal: Circulation (1980)

To assess time, staff, problems and costs involved in clinical electrophysiologic studies for documented or suspected tachycardia, 33 consecutive cases were analyzed prospectively. At least seven staff members were used for each study. Insertion of catheters required 24--105 minutes (mean 63 +/- 20 minutes). Programmed stimulation required 12--210 minutes (mean 87 +/- 38 minutes). Total fluoroscopy times were 6--67 minutes (mean 22 +/- 15 minutes). Each study used 360--2100 feet (mean 1260 +/- 390 feet) of recording paper. Detailed analysis of tracing took 1--11 hours (mean 5 +/- 2.5 hours). Delays occurred during electrophysiologic study in 25 cases (76%), with multiple causes of delay in 14 cases (42%). These were caused by 1) difficulty in obtaining venous access (five patients); 2) difficult initial catheter placement (15 cases); 3) repositioning of catheters during stimulation (17 cases); 4) sustained atrial fibrillation (four cases). Coronary sinus catheterization was achieved from the groin in 21 of 27 cases (78%) in whom a sustained attempt was made. The approximate cost of each study was greater than $800. Our data show that clinical electrophysiologic studies in the investigation and management of tachycardia are difficult, time-consuming and expensive.
A Novel Two-Stage, Transdisciplinary Study Identifies Digoxin as a Possible Drug for Prostate Cancer Treatment
Authors: Elizabeth A. Platz, Srinivasan Yegnasubramanian, Jun O. Liu, Curtis R. Chong, Joong Sup Shim, Stacey A. Kenfield, Meir J. Stampfer, Walter C. Willett, Edward Giovannucci, William G. Nelson
Journal: Cancer Discovery (2011)

Identification of novel indications for commonly prescribed drugs could accelerate translation of therapies. We investigated whether any clinically-used drugs might have utility for treating prostate cancer by coupling an efficient, high-throughput laboratory-based screen and a large, prospective cohort study. In stage 1, we conducted an in vitro prostate cancer cell cytotoxicity screen of 3,187 compounds. Digoxin emerged as the leading candidate given its potency in inhibiting proliferation in vitro (mean IC₅₀=163 nM) and common use. In stage 2, we evaluated the association between the leading candidate drug from stage 1 and prostate cancer risk in 47,884 men followed 1986-2006. Regular digoxin users (versus nonusers: RR=0.76, 95% CI 0.61-0.95), especially users for ≥ 10 years (RR=0.54, 95% CI 0.37-0.79, P-trend<0.001), had a lower prostate cancer risk. Digoxin was highly potent in inhibiting prostate cancer cell growth in vitro and its use was associated with a 25% lower prostate cancer risk.Our two-stage transdisciplinary approach for drug repositioning provides compelling justification for further mechanistic and possibly clinical testing of the leading nonchemotherapy candidate, digoxin, a cardiac glycoside, as a drug for prostate cancer treatment. Perhaps of equal importance, our study illustrates the power of the transdisciplinary approach in translational cancer research. By coupling laboratory and epidemiologic methods and thinking, we reduced the probability of identifying false-positive candidate drugs for the next steps in testing.
Epilepsy, Hyperalgesia, Impaired Memory, and Loss of Pre- and Postsynaptic GABAB Responses in Mice Lacking GABAB(1)
Authors: Valérie Schuler, Christian Lüscher, Christophe Blanchet, Norman Klix, Gilles Sansig, Klaus Klebs, Markus Schmutz, Jakob Heid, Clive Gentry, Laszlo Urban, Alyson Fox, Will Spooren, Anne-Lise Jaton, Jean-Marie Vigouret, Mario Pozza, Peter H. Kelly, Johannes Mosbacher, Wolfgang Froestl, Edgar Käslin, Reinhard Korn, Serge Bischoff, Klemens Kaupmann, Herman van der Putten, Bernhard Bettler
Journal: Neuron (2001)
Comparison study of growth plate fusion using MRI versus plain radiographs as used in age determination for exclusion of overaged football players
Authors: John George, Jayaselvi Nagendran, Khairul Azmi
Journal: British Journal of Sports Medicine (2010)

Background MRI of distal radius fusion is currently being used in the U17 World Cup to exclude overaged players. Developing countries that cannot afford to perform MRI on their players are using plain radiographs based on the same MRI criteria of fusion. Objective The aim of this study is to compare the grade of fusion of the left wrist distal radial growth plate between MRI and plain radiographs. Methods 150 healthy male football players were grouped into five age groups ranging from 15 to 19 years old. Each participant had coronal T1-weighted MRI and plain radiograph of the left wrist. The degree of distal radius fusion was rated randomly by three radiologists using a six-stage grading system proposed by the FIFA Research Centre. Results MRI assessment of distal radial growth plate fusion has good correlation with plain radiograph fusion (r=0.949). The mean of x-ray grading is higher than the MRI grading in the 15, 16, 17, 18 and 19 years old age groups with p=0.443, 0.001, 0.009, &lt;0.001 and 0.003, respectively, using Wilcoxon signed ranked test. Intraobserver and interobserver correlations were high (r=0.9). T1 MRI correlation with chronological age (r=0.771) was close to plain radiographs (r=0.821) with p value of &lt;0.001. Conclusion This article is of major importance as it is the first to show that x-rays significantly overrate the grading of fusion in this age group and therefore should not be used to exclude overaged players as is occurring now to the distress of many genuinely eligible players.
Low-dose theophylline enhances the anti-inflammatory effects of steroids during exacerbations of COPD
Authors: B G Cosio, A Iglesias, A Rios, A Noguera, E Sala, K Ito, P J Barnes, A Agusti
Journal: Thorax (2009)

<h3>Background:</h3> Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised that HDAC activity is further reduced during ECOPD and that theophylline, an HDAC activator, potentiates the anti-inflammatory effect of steroids in these patients. A study was performed to investigate HDAC activity during ECOPD and the effects of theophylline on the anti-inflammatory effects of steroids in a randomised single-blind controlled study. <h3>Methods:</h3> 35 patients hospitalised with ECOPD and treated according to international guidelines (including systemic steroids) were randomised to receive or not to receive low-dose oral theophylline (100 mg twice daily). Before treatment and 3 months after discharge, HDAC and nuclear factor-κB (NF-κB) activity in sputum macrophages, the concentration of nitric oxide in exhaled air (eNO) and total antioxidant status (TAS), tumour necrosis factor α (TNFα), interleukin (IL)-6 and IL8 levels in sputum supernatants were measured. <h3>Results:</h3> Patients receiving standard therapy showed decreased NF-κB activity, eNO concentration and sputum levels of TNFα, IL6 and IL8, as well as increased TAS during recovery of ECOPD, but HDAC activity did not change. The addition of low-dose theophylline increased HDAC activity and further reduced IL8 and TNFα concentrations. <h3>Conclusions:</h3> During ECOPD, low-dose theophylline increases HDAC activity and improves the anti-inflammatory effects of steroids. <h3>Trial registration number:</h3> NCT00671151
Evidence of a Role for Ki-RAS in the Stimulated Proliferation of Renal Fibroblasts
Authors: CLAIRE C. SHARPE, MARK E. C. DOCKRELL, RIZALDY SCOTT, MAZHAR I. NOOR, LEX M. COWSERT, BRETT P. MONIA, BRUCE M. HENDRY
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Progressive renal fibrosis is driven by a range of cytokines that act via membrane receptors and intracellular signaling cascades to evoke gene transcription events and related responses. The Ras family of GTPases has been implicated in many of these signaling cascades in model systems such as 3T3 fibroblasts. However, the role of the specific Ras isoforms Ki, Ha, and N in the stimulation of renal fibroblasts has not been defined. In this study, Ras has been inhibited in primate renal fibroblasts (vero cells) using specific phosphorothioate oligodeoxynucleotides (oligos) targeting the three isoforms. Lipofectin transfection with 200 to 400 nM Ki-Ras oligo inhibited the epidermal growth factor- and fibroblast growth factor-stimulated proliferation of vero cells by 25 to 35% with a lesser effect on serum-stimulated growth. Oligos against Ha-Ras and N-Ras were inactive with respect to control oligo. Total cellular Ras protein (estimated by Western blotting) was reduced by 60 to 90% 24 h after transfection with Ki-Ras oligo. N-Ras, Ha-Ras, and control oligos were inactive. Total Ras synthesis over 4 h measured using [ 35 S]-cys/met pulse chase was reduced by approximately 70% by Ki-Ras oligo and not altered by other oligos. The fractional prenylation of Ras was quantified from the discrete bands on polyacrylamide gel electrophoresis and was increased by the Ki-Ras oligo alone. These data demonstrate that these renal fibroblasts predominantly express the Ki isoform of Ras and that this GTPase plays a role in the stimulated proliferation of these cells. Ras GTPases may be a target for the inhibition of processes leading to renal fibrosis.
Interaction with Vascular Endothelium Enhances Survival in Primary Chronic Lymphocytic Leukemia Cells via NF-κB Activation and<i>De novo</i>Gene Transcription
Authors: Andrea G.S. Buggins, Chris Pepper, Piers E.M. Patten, Saman Hewamana, Satyen Gohil, Jane Moorhead, Najeem'deen Folarin, Deborah Yallop, N. Shaun B. Thomas, Ghulam J. Mufti, Chris Fegan, Stephen Devereux
Journal: Cancer Research (2010)

Chronic lymphocytic leukemia (CLL) cells rapidly undergo apoptosis in vitro, suggesting that the in vivo microenvironment provides crucial antiapoptotic signals. Overexpression of the antiapoptotic proteins Bcl-2 and Mcl-1 is a hallmark of CLL, and their expression is further enhanced in the lymphoid tissues. However, the high levels of Mcl-1 found in peripheral blood samples, coupled with its short half-life, led us to hypothesize that it must be actively maintained in the peripheral circulation. Coculture of CLL cells with human vascular endothelial cells significantly enhanced tumor cell survival, an effect that was not observed with normal B cells. This was associated with elevated levels of the antiapoptotic proteins Bcl-2, Mcl-1, and Bcl-X(L) and marked increased expression of CD38 and CD49d, both of which are associated with clinically aggressive disease. Because CD38, CD49d, and some Bcl-2 family genes are transcriptional targets for NF-κB, we assessed NF-κB activation following coculture with endothelial cells. DNA binding of the NF-κB subunit Rel A was significantly increased and strongly correlated with changes in transcription of CD38, CD49d, BCL2, MCL1, and BCLXL, effects that were reversed by a peptide inhibitor of Rel A. These effects were not observed following coculture with nonendothelial cell lines. Therefore, CLL cells receive specific survival signals following interaction with endothelial cells mediated through the activation of NF-κB and the induction of downstream target genes. This type of interaction in the peripheral vasculature may explain the constitutive NF-κB activation and the overexpression of Bcl-2 family proteins commonly seen in this disease.
994 HEPATOCYTE NUCLEAR SIZE, A RELIABLE MARKER OF HEPATOCELLULAR AGING, IS USEFUL TO IDENTIFY THE HIGH RISK GROUP OF HEPATOCARCINOGENESIS IN NON-B NON-C NON-ALCOHOLIC LIVER DISEASE
Authors: T. Nakajima, J. Yamaoka, A. Shibuya, T. Nakashima, Y. Itoh, T. Yoshikawa
Journal: Journal of Hepatology (2011)
RALBP1/RLIP76 Depletion in Mice Suppresses Tumor Growth by Inhibiting Tumor Neovascularization
Authors: Seunghyung Lee, Jeremy G. T. Wurtzel, Sharad S. Singhal, Sanjay Awasthi, Lawrence E. Goldfinger
Journal: Cancer Research (2012)

RalBP1/RLIP76 is a widely expressed multifunctional protein that binds the Ral and R-Ras small GTPases. In the mouse, RLIP76 is nonessential but its depletion or blockade promotes tumorigenesis and heightens the sensitivity of normal and tumor cells to radiation and cytotoxic drugs. However, its pathobiologic functions, which support tumorigenesis, are not well understood. Here, we show that RLIP76 is required for angiogenesis and for efficient neovascularization of primary solid tumors. Tumor growth from implanted melanoma or carcinoma cells was blunted in RLIP76(-/-) mice. An X-ray microcomputed tomography-based method to model tumor vascular structures revealed defects in both the extent and form of tumor angiogenesis in RLIP76(-/-) mice. Specifically, tumor vascular volumes were diminished and vessels were fewer in number, shorter, and narrower in RLIP76(-/-) mice than in wild-type mice. Moreover, we found that angiogenesis was blunted in mutant mice in the absence of tumor cells, with endothelial cells isolated from these animals exhibiting defects in migration, proliferation, and cord formation in vitro. Taken together, our results establish that RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.