tbuckley/cabot-search huggingface dataset:
Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis
Authors: P.A. de Jong, Y. Nakano, M.H. Lequin, J.R Mayo, R. Woods, P.D. Paré, H.A.W.M. Tiddens
Journal: European Respiratory Journal (2003)

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease. CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). "Sensitivity" was defined as the ability to detect disease progression. In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function. These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.
Effects of exogenous free radicals on electromechanical function and metabolism in isolated rabbit and guinea pig ventricle. Implications for ischemia and reperfusion injury.
Authors: J I Goldhaber, S Ji, S T Lamp, J N Weiss
Journal: Journal of Clinical Investigation (1989)

Oxygen-derived free radicals have been implicated in the pathogenesis of cardiac dysfunction during ischemia, postischemic myocardial "stunning," and reperfusion injury. We investigated the effects of oxygen-derived free radicals on cardiac function in intact isolated rabbit hearts and single guinea pig ventricular myocytes. In the intact rabbit ventricle, exposure to free radical-generating systems caused increased cellular K+ efflux, shortening of the action potential duration, changes in tension, and depletion of high energy phosphates similar to ischemia and metabolic inhibition. In patch-clamped single ventricular myocytes, free radical-generating systems activated ATP-sensitive K+ channels, decreased the calcium current, and caused cell shortening by irreversibly inhibiting glycolytic and oxidative metabolism. The results suggest that free radicals generated during ischemia and reperfusion may contribute to electrophysiologic abnormalities and contractile dysfunction by inhibiting glycolysis and oxidative phosphorylation. Inhibition of metabolism by free radicals may be an important factor limiting functional recovery from an ischemic insult after reestablishment of effective blood flow.
Longitudinal Assessment of Chemotherapy-Induced Alterations in Brain Activation During Multitasking and Its Relation With Cognitive Complaints
Authors: Sabine Deprez, Mathieu Vandenbulcke, Ronald Peeters, Louise Emsell, Ann Smeets, Marie-Rose Christiaens, Frederic Amant, Stefan Sunaert
Journal: Journal of Clinical Oncology (2014)

Purpose To examine whether cognitive complaints after treatment for breast cancer are associated with detectable changes in brain activity during multitasking. Patients and Methods Eighteen patients who were scheduled to receive chemotherapy performed a functional magnetic resonance imaging multitasking task in the scanner before the start of treatment (t1) and 4 to 6 months after finishing treatment (t2). Sixteen patients who were not scheduled to receive chemotherapy and 17 matched healthy controls performed the same task at matched intervals. Task difficulty level was adjusted individually to match performance across participants. Statistical Parametric Mapping 8 (SPM8) software was used for within-group, between-group, and group-by-time interaction image analyses. Results Voxel-based paired t tests revealed significantly decreased activation (P &lt; .05) from t1 to t2 at matched performance in the multitasking network of chemotherapy-treated patients, whereas no changes were noted in either of the control groups. At baseline, there were no differences between the groups. Furthermore, in contrast to controls, the chemotherapy-treated patients reported a significant increase in cognitive complaints (P &lt; .05) at t2. Significant (P &lt; .05) correlations were found between these increases and decreases in multitasking-related brain activation. Moreover, a significant group-by-time interaction (P &lt; .05) was found whereby chemotherapy-treated patients showed decreased activation and healthy controls did not. Conclusion These results suggest that changes in brain activity may underlie chemotherapy-induced cognitive complaints. The observed changes might be related to chemotherapy-induced damage to the brain or reduced connectivity between brain regions rather than to changes in effort or changes in functional strategy. To the best of our knowledge, this is the first longitudinal study providing evidence for a relationship between longitudinal changes in cognitive complaints and changes in brain activation after chemotherapy.
Blocking Hedgehog Survival Signaling at the Level of the GLI Genes Induces DNA Damage and Extensive Cell Death in Human Colon Carcinoma Cells
Authors: Tapati Mazumdar, Jennifer DeVecchio, Akwasi Agyeman, Ting Shi, Janet A. Houghton
Journal: Cancer Research (2011)

Canonical Hedgehog (HH) signaling is characterized by Smoothened (Smo)-dependent activation of the transcription factors Gli1 and Gli2, which regulate HH target genes. In human colon carcinoma cells, treatment with the Gli small-molecule inhibitor GANT61 induces extensive cell death in contrast to the Smo inhibitor cyclopamine. Here we elucidate cellular events upstream of cell death elicited by GANT61, which reveal the basis for its unique cytotoxic activity in colon carcinoma cells. Unlike cyclopamine, GANT61 induced transient cellular accumulation at G(1)-S (24 hours) and in early S-phase (32 hours), with elevated p21(Cip1), cyclin E, and cyclin A in HT29 cells. GANT61 induced DNA damage within 24 hours, with the appearance of p-ATM and p-Chk2. Pharmacologic inhibition of Gli1 and Gli2 by GANT61 or genetic inhibition by transient transfection of the Gli3 repressor (Gli3R) downregulated Gli1 and Gli2 expression and induced γH2AX, PARP cleavage, caspase-3 activation, and cell death. GANT61 induced γH2AX nuclear foci, while transient transfection of Gli3R showed expression of Gli3R and γH2AX foci within the same nuclei in HT29, SW480, and HCT116. GANT61 specifically targeted Gli1 and Gli2 substantiated by specific inhibition of (i) direct binding of Gli1 and Gli2 to the promoters of target genes HIP1 and BCL-2, (ii) Gli-luciferase activity, and (iii) transcriptional activation of BCL-2. Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells.
The aldehyde dehydrogenase ALDH2*2 allele exhibits dominance over ALDH2*1 in transduced HeLa cells.
Authors: Q Xiao, H Weiner, T Johnston, D W Crabb
Journal: Journal of Clinical Investigation (1995)

Individuals heterozygous or homozygous for the variant aldehyde dehydrogenase (ALDH2) allele (ALDH2*2), which encodes a protein differing only at residue 487 from the normal protein, have decreased ALDH2 activity in liver extracts and experience cutaneous flushing when they drink alcohol. The mechanisms by which this allele exerts its dominant effect is unknown. To study this effect, the human ALDH2*1 cDNA was cloned and the ALDH2*2 allele was generated by site-directed mutagenesis. These cDNAs were transduced using retroviral vectors into HeLa and CV1 cells, which do not express ALDH2. The normal allele directed synthesis of immunoreactive ALDH2 protein (ALDH2E) with the expected isoelectric point. Extracts of these cells contained increased aldehyde dehydrogenase activity with low Km for the aldehyde substrate. The ALDH2*2 allele directed synthesis of mRNA and immunoreactive protein (ALDH2K), but the protein lacked enzymatic activity. When ALDH2*1-expressing cells were transduced with ALDH2*2 vectors, both mRNAs were expressed and immunoreactive proteins with isoelectric points ranging between those of ALDH2E and ALDH2K were present, indicating that the subunits formed heteromers. ALDH2 activity in these cells was reduced below that of the parental ALDH2*1-expressing cells. Thus, the ALDH2*2 allele is sufficient to cause ALDH2 deficiency in vitro.
Altered muscle activation following hamstring injuries
Authors: Gisela Sole, Stephan Milosavljevic, Helen Nicholson, S John Sullivan
Journal: British Journal of Sports Medicine (2011)

The purpose of this study was to compare the electromyographic (EMG) activity of gluteal and thigh muscles of sportspeople with a recent hamstring injury with uninjured controls during a weight-bearing task.Cross-sectional.University laboratory.16 participants with a hamstring injury (hamstring-injured group, HG) and 18 control participants (control group (CG)) participated in the study.The EMG activity of gluteal, quadriceps and hamstring muscles was recorded during a movement from double- to single-leg movement using surface electrodes.The EMG onsets of biceps femoris and medial hamstrings were significantly earlier for the HG injured and the uninjured sides in preparation for single-leg standing when compared with the CG average. There were no differences in onsets for the gluteal and quadriceps muscles when comparing the injured or uninjured legs of the HG to the bilateral average of the CG.The earlier onset of the injured and the uninjured hamstrings in preparation for single leg stance of the HG in comparison with the CG suggests an alteration in the motor control of these muscles. Altered neuromuscular control following a hamstring injury may be a factor to be considered in the rehabilitation of hamstring injuries.
The efficacy of a custom-fabricated nasal mask on gas exchange during nasal intermittent positive pressure ventilation
Authors: T Tsuboi, M Ohi, H Kita, N Otsuka, H Hirata, T Noguchi, K Chin, M Mishima, K Kuno
Journal: European Respiratory Journal (1999)

Commercially available nasal masks have a large mask volume and give rise to considerable air leaks around the mask during nasal intermittent positive pressure ventilation (NIPPV) which may reduce alveolar ventilation (VA per breath). The effects of a custom-fabricated nasal mask (F-mask) versus a commercially available mask (C-mask) on arterial blood gas measurements, dead space including both physiological and apparatus dead space (VD), air leak and VA per breath were compared in patients with restrictive thoracic disease during short-term NIPPV sessions while using a volume cycled ventilator with equivalent settings for both masks. The mask volume of the C-mask was significantly larger than that of the F-mask (p&lt;0.003). The arterial carbon dioxide tension (Pa,CO2) during NIPPV with either the F-mask (5.56+/-1.35 kPa) (mean+/-SD) or the C-mask (6.87+/-0.96 kPa) was significantly lower than during spontaneous breathing (7.75+/-0.81 kPa; p&lt;0.003), but the Pa,CO2 decreased more during NIPPV with the F-mask than with the C-mask (p&lt;0.003). The VD was significantly smaller (p&lt;0.03), the air leak was significantly less (p&lt;0.03), and the VA per breath was significantly larger (p&lt;0.03) during NIPPV with the F-mask than with the C-mask. In conclusion, nasal intermittent positive pressure ventilation with the F-mask was more effective than nasal intermittent positive pressure ventilation with the commercially available mask due to its smaller dead space and less air leak. Further studies are needed to extend these results to all the commercially available-masks.
Insulin-like Growth Factor-I Receptor Signaling Blockade Combined with Radiation
Authors: Gregory W. Allen, Corey Saba, Eric A. Armstrong, Shyh-Min Huang, Sergio Benavente, Dale L. Ludwig, Daniel J. Hicklin, Paul M. Harari
Journal: Cancer Research (2007)

Abstract Signaling through the insulin-like growth factor-I receptor (IGF-IR) is implicated in cellular proliferation, apoptosis, carcinogenesis, metastasis, and resistance to cytotoxic cancer therapies. Targeted disruption of IGF-IR signaling combined with cytotoxic therapy may therefore yield improved anticancer efficacy over conventional treatments alone. In this study, a fully human anti–IGF-IR monoclonal antibody A12 (ImClone Systems, Inc., New York, NY) is examined as an adjunct to radiation therapy. IGF-IR expression is shown for a diverse cohort of cell lines, whereas targeted IGF-IR blockade by A12 inhibits IGF-IR phosphorylation and activation of the downstream effectors Akt and mitogen-activated protein kinase. Anchorage-dependent proliferation and xenograft growth is inhibited by A12 in a dose-dependent manner, particularly for non–small cell lung cancer lines. Clonogenic radiation survival of H226 and H460 cells grown under anchorage-dependent conditions is impaired by A12, demonstrating a radiation dose-enhancing effect for IGF-IR blockade. Postradiation anchorage-independent colony formation is inhibited by A12 in A549 and H460 cells. In the H460 xenograft model, combining A12 and radiation significantly enhances antitumor efficacy compared with either modality alone. These effects may be mediated by promotion of radiation-induced, double-stranded DNA damage and apoptosis as observed in cell culture. In summary, these results validate IGF-IR signal transduction blockade as a promising strategy to improve radiation therapy efficacy in human tumors, forming a basis for future clinical trials. [Cancer Res 2007;67(3):1155–62]
Effects of Donor Pretreatment With Dopamine on Graft Function After Kidney Transplantation
Authors: Peter Schnuelle, Uwe Gottmann, Simone Hoeger, Detlef Boesebeck, Werner Lauchart, Christel Weiss, Michael Fischereder, Karl-Walter Jauch, Uwe Heemann, Martin Zeier, Christian Hugo, Przemyslaw Pisarski, Bernhard K. Krämer, Kai Lopau, Axel Rahmel, Urs Benck, Rainer Birck, Benito Antonio Yard
Journal: JAMA (2009)

Kidney graft function after transplantation can be improved through pharmacological donor pretreatment to limit organ injury from cold preservation.To determine whether pretreatment of brain-dead donors with low-dose dopamine improves early graft function in human renal transplant recipients.Randomized, open-label, multicenter, parallel-group trial of 264 deceased heart-beating donors and 487 subsequent renal transplants performed at 60 European centers between March 2004 and August 2007 (final follow-up, December 31, 2008). Eligible donors were stable under low-dose norepinephrine with a normal serum creatinine concentration on admission.Donors were randomized to receive low-dose dopamine (4 mug/kg/min).Dialysis requirement during first week after transplantation.Dopamine was infused for a median of 344 minutes (IQR, 215 minutes). Dialysis was significantly reduced in recipients of a dopamine-treated graft. Fewer recipients in the treatment group needed multiple dialyses (56/227; 24.7%; 95% CI, 19.0%-30.3%; vs 92/260; 35.4%; 95% CI, 29.5%-41.2%; P = .01). The need for multiple dialyses posttransplant was associated with allograft failure after 3 years (HR, 3.61; 95% CI, 2.39-5.45; P < .001), whereas a single dialysis was not (HR, 0.67; 95% CI, 0.21-2.18; P = .51). Besides donor dopamine (OR, 0.54; 95% CI, 0.35-0.83; P = .005), cold ischemic time (OR, 1.07; 95% CI, 1.02-1.11 per hour; P = .001), donor age (OR, 1.03; 95% CI, 1.01-1.05 per year; P < .001), and recipient body weight (OR, 1.02; 95% CI, 1.01-1.04 per kg; P = .009) were independent explanatory variables in a multiple logistic regression model. Dopamine resulted in significant but clinically meaningless increases in the donor's systolic blood pressure (3.8 mm Hg; 95% CI, 0.7-6.9 mm Hg; P = .02) and urine production before surgical recovery of the kidneys (29 mL; 95% CI, 7-51 mL; P = .009) but had no influence on outcome.Donor pretreatment with low-dose dopamine reduces the need for dialysis after kidney transplantation.clinicaltrials.gov Identifier: NCT00115115.
Use of inhaled corticosteroids and the risk of tuberculosis
Authors: Chang-Hoon Lee, Kyungjoo Kim, Min Kyung Hyun, Eun Jin Jang, Na Rae Lee, Jae-Joon Yim
Journal: Thorax (2013)

<h3>Background</h3> Inhaled corticosteroid (ICS) use could decrease local immunity of the lung. Concerns have been raised regarding the risk of tuberculosis (TB) development among ICS users. The aim of this study was to elucidate the association between ICS use and development of TB among patients with various respiratory diseases in South Korea, an intermediate-TB-burden country. <h3>Methods</h3> A nested case-control study based on the Korean national claims database was performed. The eligible cohort consisted of 853 439 new adult users of inhaled respiratory medications between 1 January 2007 and 31 December 2010. Patients diagnosed as having TB after initiation of inhaled medication were included as cases. For each case individual, up to five control individuals matched for age, sex, diagnosis of asthma or chronic obstructive pulmonary disease (COPD) and initiation date of inhaler use were selected. <h3>Results</h3> From the cohort population, we matched 4139 individuals diagnosed as having TB with 20 583 controls. ICS use was associated with increased rate of TB diagnosis (adjusted OR (aOR), 1.20; 95% CI 1.08 to 1.34). The association was dose dependent (p for trend &lt;0.001). A subgroup analysis revealed that ICS use increased the risk of TB development among non-users of oral corticosteroid (OCS) but not among OCS users. <h3>Conclusions</h3> ICS use increases the risk of TB in an intermediate-TB-burden country. Clinicians should be aware of the possibility of TB development among patients who are long-term high-dose ICS users.
Impact of c-MYC Protein Expression on Outcome of Patients with Early-Stage HER2+ Breast Cancer Treated with Adjuvant Trastuzumab NCCTG (Alliance) N9831
Authors: Amylou C. Dueck, Monica M. Reinholz, Xochiquetzal J. Geiger, Kathleen Tenner, Karla Ballman, Robert B. Jenkins, Darren Riehle, Beiyun Chen, Ann E. McCullough, Nancy E. Davidson, Silvana Martino, George W. Sledge, Peter A. Kaufman, Leila A. Kutteh, Julie Gralow, Lyndsay N. Harris, James N. Ingle, Wilma L. Lingle, Edith A. Perez
Journal: Clinical Cancer Research (2013)

This study investigated the association between tumor MYC protein expression and disease-free survival (DFS) of patients randomized to receive chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2(+) trastuzumab breast cancer trial.This analysis included 1,736 patients randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was determined in tissue microarray sections containing three biopsies per patient or whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor was considered positive for MYC protein overexpression (MYC(+)) if the nuclear 3+ staining percentage was more than 30%.Five hundred and seventy-four (33%) tumors were MYC(+). MYC(+) was associated with hormone receptor positivity (χ(2), P = 0.006), tumors 2 cm or more (χ(2), P = 0.02), and a higher rate of nodal positivity (χ(2), P < 0.001). HRs for DFS (median follow-up: 6.1 years) for Arm C versus A were 0.52 (P = 0.006) and 0.65 (P = 0.006) for patients with MYC(+) and MYC(-) tumors, respectively (P(interaction) = 0.40). For Arm B versus A, HRs for patients with MYC(+) and MYC(-) tumors were 0.79 (P = 0.21) and 0.74 (P = 0.04), respectively (P(interaction) = 0.71). For Arm C versus B, HRs for patients with MYC(+) and MYC(-) tumors were 0.56 (P = 0.02) and 0.89 (P = 0.49), respectively (P(interaction) = 0.17).Our data do not support an impact of tumor MYC protein expression on differential benefit from adjuvant trastuzumab.
HISTOCHEMICAL STUDIES ON CUTANEOUS LEIOMYOMATOSIS. II: DEHYDROGENASES, HYDROLASES AND PHOSVHORYLASE.
Authors: M. NIEMI, E. LEVONEN, K.K. MUSTAKALLIO
Journal: British Journal of Dermatology (1964)

Journal Article HISTOCHEMICAL STUDIES ON CUTANEOUS LEIOMYOMATOSIS. II: DEHYDROGENASES, HYDROLASES AND PHOSVHORYLASE. Get access M. NIEMI, M. NIEMI Department of Pathology Search for other works by this author on: Oxford Academic Google Scholar E. LEVONEN, E. LEVONEN Department of Forensic Medicine Search for other works by this author on: Oxford Academic Google Scholar K.K. MUSTAKALLIO K.K. MUSTAKALLIO Department of Dermatology, University of Helsinki, Snellmaninkatu 14, Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 76, Issue 7, 1 July 1964, Pages 341–345, https://doi.org/10.1111/j.1365-2133.1964.tb14539.x Published: 01 July 1964
Pathogenesis of chronic persistent cough associated with gastroesophageal reflux.
Authors: A J Ing, M C Ngu, A B Breslin
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
How can a migraine cause faecal incontinence?
Authors: K Honein
Journal: Gut (2005)

During the past three decades, prolonged monitoring of oesophageal pH has become increasingly popular among physicians.Most of the studies carried out with this technique focused on oesophageal acid exposure, defined as percentage of time with pH below 4.However, in most cases acid exposure variables are not very useful in the evaluation of patients with symptoms and signs of gastro-oesophageal reflux disease (GORD).An often neglected aspect of 24 hour pH recording is assessment of the temporal relation between reflux and symptoms.Various methods to quantify this relationship were developed.Here, we review these methods and the contribution of symptom association analysis to the evaluation of patients with symptoms suggestive of GORD.www.gutjnl.
Prediction of Myocardial Viability by MRI
Authors: Charles B. Higgins
Journal: Circulation (1999)

evascularization interventions in evolving myocardial infarctions have their rationale in the assumption that viable myocardial cells persist in the ischemically injured area.Consequently, intensive work has been directed over the past decade toward the development of noninvasive imaging methods to identify and quantify myocardial viability.