tbuckley/cabot-search huggingface dataset:
Caesarean section and asthma
Authors: P Merkus
Journal: Thorax (2009)

Role of breathing exercises in hyperventilating subjectsThomas and colleagues reported breathing training leading to improvements in asthmaspecific health status and other patientcentred measures. 1These included Asthma Quality of Life Questionnaire (AQLQ) scores, Hospital Anxiety and Depression (HAD) anxiety, HAD depression, Nijmegen scores and Asthma Control Questionnaire (ACQ) scores.The significant improvement in all the above stated scores except the last one at 6 months after the intervention could be due to a few inherent biases.This was discussed in our weekly journal club.First, most of the population studied were hyperventilating subjects, as evidenced by the mean Nijmegen scores in both groups of .23.Breathing training might therefore have helped these hyperventilating subjects.Second, as stated in the article, most subjects with chronic disease would like to try alternative forms of treatment. 2If this ''alternative form'' was mentioned during the invitation to take part in the study (which is not stated in the article), then all the subjects could have been self-motivated, which is not representative of the general population and hence the results cannot be generalised.Last, the subjects who underwent breathing training were encouraged to do the breathing exercises throughout the 6-month period whereas the control group had three sessions of asthma education with no such ongoing ''controlling effect''.A significant improvement in forced expiratory volume in 1 s and a significant fall in exhaled nitric oxide 1 month after the intervention in the control group shows the beneficial effect of patient education.Hence, effective pharmacotherapy with asthma education continues to be the core of asthma treatment.The role of breathing training is possibly present in subjects who have a tendency to hyperventilate, which need not be due just to asthma but to any cause.
Short-term renal hemodynamic effects of tolvaptan in subjects with autosomal dominant polycystic kidney disease at various stages of chronic kidney disease
Authors: Wendy E. Boertien, Esther Meijer, Paul E. de Jong, Stephan J.L. Bakker, Frank S. Czerwiec, Joachim Struck, Dorothee Oberdhan, Susan E. Shoaf, Holly B. Krasa, Ron T. Gansevoort
Journal: Kidney International (2013)
EFFECT OF HIGH DOSE OF ATORVASTATIN VERSUS MODERATE DOSE ON ENDOTHELIAL FUNCTION AND INFLAMMATORY BIOMARKERS IN PATIENTS WITH STEMI
Authors: Riccardo Raddino, Paolo Della Pina, Mara Gavazzoni, Elio Gorga, Alberto Madureri, Marco Metra
Journal: Journal of the American College of Cardiology (2013)
MiR-490-3p modulates the proliferation of vascular smooth muscle cells induced by ox-LDL through targeting PAPP-A
Authors: Yufa Sun, Deyou Chen, Lijuan Cao, Rongrong Zhang, Jie Zhou, Haiyan Chen, Yinyin Li, Minglong Li, Jian Cao, Zhe Wang
Journal: Cardiovascular Research (2013)

Oxidized low-density lipoprotein (ox-LDL) can induce vascular smooth muscle cell (VSMC) proliferation and differentiation, which is the important mechanism of the pro-atherogenic effects of ox-LDL. Although miRNAs are crucial regulators of the ox-LDL effects on VSMC, the detailed mechanisms are not fully elucidated. So, we investigated the miRNAs changes in the proliferation of human coronary artery smooth muscle cells (hCASMCs) induced by ox-LDL and the functional significance of some miRNAs, which were regulated significantly. Using miRNA microarray, real-time PCR, and luciferase reporter assay, our study showed that miR-490-3p and insulin-like growth factor-1 (IGF1) expression were down-regulated, whereas pregnancy-associated plasma protein A (PAPP-A) and IGF2 expression were up-regulated significantly in hCASMC treated by ox-LDL and/or in human atherosclerotic plaque. Further studies indicated PAPP-A was the target gene of miR-490-3p. The miR-490-3p mimic could inhibit the up-regulation of PAPP-A induced by ox-LDL in hCASMC, which resulted in the suppression of the metalloprotease effect of PAPP-A on IGF-binding protein-4 (IGFBP-4). All these effects led to the inhibition of the proliferation of hCASMC induced by ox-LDL. Ox-LDL could inhibit the expression of miR-490-3p and IGF1, whereas increase IGF2 expression. The inhibition of miR0-490-3p up-regulated its target gene PAPP-A and then increased the proteolysis of IGFBP-4. The increased expression of IGF2 and proteolysis of IGFBP-4 might activate pathways independent or dependent on IGF axis by autocrine and paracrine mechanisms and resulted in the VSMC proliferation. Our results could help us to understand the mechanisms of the pro-atherogenic effects of ox-LDL and the effects of PAPP-A on atherosclerosis development.
Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment
Authors: Gareth J. Morgan, Faith E. Davies, Walter M. Gregory, Susan E. Bell, Alexander J. Szubert, Gordon Cook, Mark T. Drayson, Roger G. Owen, Fiona M. Ross, Graham H. Jackson, J. Anthony Child
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Medical Research Council (MRC) Myeloma IX was a phase III trial evaluating bisphosphonate and thalidomide-based therapy for newly diagnosed multiple myeloma. Results were reported previously after a median follow-up of 3.7 years (current controlled trials number: ISRCTN68454111). Survival outcomes were reanalyzed after an extended follow-up (median, 5.9 years). Experimental Design: At first randomization, patients (N = 1,970) were assigned to bisphosphonate (clodronic acid or zoledronic acid) and induction therapies [cyclophosphamide–vincristine–doxorubicin–dexamethasone (CVAD) or cyclophosphamide–thalidomide–dexamethasone (CTD) followed by high-dose therapy plus autologous stem cell transplantation for younger/fitter patients (intensive pathway), and melphalan–prednisone (MP) or attenuated CTD (CTDa) for older/less fit patients (nonintensive pathway)]. At second randomization, patients were assigned to thalidomide maintenance therapy or no maintenance. Interphase FISH (iFISH) was used to analyze cytogenics. Results: Zoledronic acid significantly improved progression-free survival (PFS; HR, 0.89; P = 0.02) and overall survival (OS; HR, 0.86; P = 0.01) compared with clodronic acid. In the intensive pathway, CTD showed noninferior PFS and OS compared with CVAD, with a trend toward improved OS in patients with favorable cytogenics (P = 0.068). In the nonintensive pathway, CTDa significantly improved PFS (HR, 0.81; P = 0.007) compared with MP and there was an emergent survival benefit after 18 to 24 months. Thalidomide maintenance improved PFS (HR, 1.44; P &amp;lt; 0.0001) but not OS (HR, 0.96; P = 0.70), and was associated with shorter OS in patients with adverse cytogenics (P = 0.01). Conclusions: Long-term follow-up is essential to identify clinically meaningful treatment effects in myeloma subgroups based on cytogenetics. Clin Cancer Res; 19(21); 6030–8. ©2013 AACR.
Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments
Authors: Yong-Jie Zhang, Tania F Gendron, Ya-Fei Xu, Li-Wen Ko, Shu-Hui Yen, Leonard Petrucelli
Journal: Molecular Neurodegeneration (2010)

Abstract Background Inclusions of TAR DNA binding protein-43 (TDP-43) are the defining histopathological feature of several neurodegenerative diseases collectively referred to as TDP-43 proteinopathies. These diseases are characterized by the presence of cellular aggregates composed of abnormally phosphorylated, N-terminally truncated and ubiquitinated TDP-43 in the spinal cord and/or brain. Recent studies indicate that C-terminal fragments of TDP-43 are aggregation-prone and induce cytotoxicity. However, little is known regarding the pathways responsible for the degradation of these fragments and how their phosphorylation contributes to the pathogenesis of disease. Results Herein, we established a human neuroblastoma cell line (M17D3) that conditionally expresses an enhanced green fluorescent protein (GFP)-tagged caspase-cleaved C-terminal TDP-43 fragment (GFP-TDP 220-414 ). We report that expression of this fragment within cells leads to a time-dependent formation of inclusions that are immunoreactive for both ubiquitin and phosphorylated TDP-43, thus recapitulating pathological hallmarks of TDP-43 proteinopathies. Phosphorylation of GFP-TDP 220-414 renders it resistant to degradation and enhances its accumulation into insoluble aggregates. Nonetheless, GFP-TDP 220-414 inclusions are reversible and can be cleared through the ubiquitin proteasome system. Moreover, both Hsp70 and Hsp90 bind to GFP-TDP 220-414 and regulate its degradation. Conclusions Our data indicates that inclusions formed from TDP-43 C-terminal fragments are reversible. Given that TDP-43 inclusions have been shown to confer toxicity, our findings have important therapeutic implications and suggest that modulating the phosphorylation state of TDP-43 C-terminal fragments may be a promising therapeutic strategy to clear TDP-43 inclusions.
Binding of C4b-Binding Protein to Porin
Authors: Sanjay Ram, Meabh Cullinane, Anna M. Blom, Sunita Gulati, Daniel P. McQuillen, Brian G. Monks, Catherine O'Connell, Ryan Boden, Christopher Elkins, Michael K. Pangburn, Björn Dahlbäck, Peter A. Rice
Journal: The Journal of Experimental Medicine (2001)

We screened 29 strains of Neisseria gonorrhoeae and found 16/21 strains that resisted killing by normal human serum and 0/8 serum sensitive strains that bound the complement regulator, C4b-binding protein (C4bp). Microbial surface–bound C4bp demonstrated cofactor activity. We constructed gonococcal strains with hybrid porin (Por) molecules derived from each of the major serogroups (Por1A and Por1B) of N. gonorrhoeae, and showed that the loop 1 of Por1A is required for C4bp binding. Por1B loops 5 and 7 of serum-resistant gonococci together formed a negatively charged C4bp-binding domain. C4bp–Por1B interactions were ionic in nature (inhibited by high salt or by heparin), whereas the C4bp–Por1A bond was hydrophobic. Only recombinant C4bp mutant molecules containing the NH2-terminal α-chain short consensus repeat (SCR1) bound to both Por1A and Por1B gonococci, suggesting that SCR1 contained Por binding sites. C4bp α-chain monomers did not bind gonococci, indicating that the polymeric form of C4bp was required for binding. Using fAb fragments against C4bp SCR1, C4bp binding to Por1A and Por1B strains was inhibited in a complement-dependent serum bactericidal assay. This resulted in complete killing of these otherwise fully serum resistant strains in only 10% normal serum, underscoring the importance of C4bp in mediating gonococcal serum resistance.
CYP3A Phenotyping Approach to Predict Systemic Exposure to EGFR Tyrosine Kinase Inhibitors
Authors: Jing Li, Mats O. Karlsson, Julie Brahmer, Avery Spitz, Ming Zhao, Manuel Hidalgo, Sharyn D. Baker
Journal: JNCI Journal of the National Cancer Institute (2006)

Gefitinib is an orally active inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) with activity in non-small-cell lung cancer. The response to gefitinib is variable, possibly because of interindividual variation in the activity of cytochrome P450 3A (CYP3A), the principal enzyme that metabolizes gefitinib. We prospectively assessed the influence of CYP3A activity on gefitinib disposition and toxicity.Twenty-seven patients with advanced cancer were treated with daily oral gefitinib at 250 mg (n = 13) or 500 mg (n = 14) for 28 days. Concentration-time profiles of midazolam and geftinib were constructed based on measurement of their concentration in serial blood samples using high-performance liquid chromatography and mass spectroscopy. CYP3A activity was determined at baseline by assessment of midazolam apparent oral clearance. Pharmacokinetic studies were performed for a period of 28 days, and population modeling was performed using NONMEM software. A structural pharmacokinetic model was developed to describe the concentration-time profiles of unbound and total gefitinib plasma concentrations, and patient-specific covariates were added to the model to account for unexplained interindividual variability in pharmacokinetic parameters. Statistical tests were two-sided.Gefitinib pharmacokinetics exhibited wide interindividual variability (interindividual variability on total and unbound gefitinib apparent oral clearance was 79% and 74%, respectively). Midazolam clearance (mean = 40 L/h, range = 10-111) was highly correlated with that of total and unbound gefitinib (R2 = .60 and R2 = .68, respectively) and with steady-state plasma trough concentrations of gefitinib (R2 = .58 and R2 = .60, respectively), and it accounted for approximately 40% of interindividual variability in gefitinib clearance in the pharmacokinetic model. Both total and unbound gefitinib steady-state plasma trough concentrations were associated with the development of diarrhea (P<.05), but not skin rash. At a dose of 250 mg gefitinib, 11 of 13 patients achieved steady-state plasma trough concentrations above the IC50 for inhibition of mutant EGFR in vitro (0.015 microM), but only one achieved a steady-state plasma trough concentration above the IC50 for inhibition of wild-type EGFR (0.1 microM).As an in vivo phenotypic probe of CYP3A, midazolam oral clearance may have utility for prediction of gefitinib exposure and dose selection. A pharmacokinetic model incorporating this indicator of CYP3A activity has potential for optimization of treatment with gefitinib and other TK inhibitors that are metabolized in a similar manner.
Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial
Authors: Caterina P Minniti, Alexander M Gorbach, Dihua Xu, Yuen Yi Hon, Kara-Marie Delaney, Miles Seidel, Nitin Malik, Marlene Peters-Lawrence, Carly Cantilena, James S Nichols, Laurel Mendelsohn, Anna Conrey, George Grimes, Gregory J Kato
Journal: The Lancet Haematology (2014)
ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis
Authors: Enrico Garattini, Edoardo Parrella, Luisa Diomede, Maurizio Gianni', Yesim Kalac, Lucio Merlini, Daniele Simoni, Romina Zanier, Fabiana Fosca Ferrara, Ilaria Chiarucci, Paolo Carminati, Mineko Terao, Claudio Pisano
Journal: Blood (2003)
Spontaneous achlorhydria with atrophic gastritis in the Zollinger-Ellison syndrome
Authors: H. G. Desai, F. P. Antia
Journal: Gut (1969)

This case report describes the occurrence of spontaneous, persistent achlorhydria in a patient with markedly raised basal acid secretion and diarrhoea for over two years (Zollinger-Ellison syndrome). Achlorhydria was due to the rapid development of severe atrophic gastritis in a gastric mucosa that had previously shown markedly increased numbers of parietal cells.
Autofluorescence Bronchoscopy in the Detection of Squamous Metaplasia and Dysplasia in Current and Former Smokers
Authors: J. M. Kurie, J. S. Lee, F. R. Khuri, A. Broxson, R. Yu, W. K. Hong, R. C. Morice, G. L. Walsh, J. Y. Ro, W. A. Franklin
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: New methods are needed to detect precancerous lesions in lung tissue. We conducted a study to determine the utility of LIFE™ (laserinduced fluorescence emission) autofluorescence bronchoscopy for the detection of squamous metaplasia and dysplasia in current and former smokers. Methods: In this prospective, single-center study, 53 participants underwent standard white-light bronchoscopy and 39 underwent both white-light and LIFE bronchoscopy Bronchial biopsy specimens were obtained from all participants at six predetermined sites using white-light bronchoscopy and from all other sites that appeared to be abnormal in participants who underwent LIFE bronchoscopy. Relationships between LIFE imaging and histologic findings were examined for 245 biopsy specimens obtained from those participants who had undergone LIFE bronchoscopy. Results: LIFE imaging revealed abnormalities designated as either class II or class III in 89 (36.3 %) and 16 (6.5 %) of the 245 sites examined, respectively, and histopathologic examination showed dysplasia and metaplasia in eight (3.3%) and in 52 (21.2%) of the 245 specimens, respectively. Among the 105 biopsy specimens obtained from sites with abnormal LIFE imaging, only 26 (24.8%) exhibited squamous metaplasia and/or dysplasia, similar to the findings for sites with normal LIFE imaging (34 [24.3%] of 140). Comparison of individuals examined by LIFE imaging with those who underwent white-light bronchoscopy alone revealed no increase in the detection of dysplasia or metaplasia with LIFE bronchoscopy. Conclusion: In this population of current and former smokers, abnormalities detected by LIFE bronchoscopy did not improve the detection of squamous metaplasia or dysplasia. [J Nall Cancer Inst 1998; 90:991–5]
Persistent calcium elevation correlates with the induction of surface immunoglobulin-mediated B cell DNA synthesis.
Authors: H Yamada, C H June, F Finkelman, M Brunswick, M S Ring, A Lees, J J Mond
Journal: The Journal of Experimental Medicine (1993)

Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ([Ca2+]i). These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low-level but persistent sustained or cyclic elevations in [Ca2+]i. In marked contrast, early and nonsustained elevations in [Ca2+]i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran-anti-Ig conjugate which induced very high levels of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in [Ca2+]i as detected by flow cytometry. Finally, B cells from X-linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in [Ca2+]i, but do not show persistent calcium elevations. These data suggest that the rapid and large increases of [Ca2+]i seen in lymphocytes within seconds after antigen receptor ligation may be associated with entry in G1, whereas low-level but persistent elevations may be the hallmark of a cell destined to synthesize DNA.
Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome
Authors: Alessandra Moretti, Milena Bellin, Andrea Welling, Christian Billy Jung, Jason T. Lam, Lorenz Bott-Flügel, Tatjana Dorn, Alexander Goedel, Christian Höhnke, Franz Hofmann, Melchior Seyfarth, Daniel Sinnecker, Albert Schömig, Karl-Ludwig Laugwitz
Journal: New England Journal of Medicine (2010)

Long-QT syndromes are heritable diseases associated with prolongation of the QT interval on an electrocardiogram and a high risk of sudden cardiac death due to ventricular tachyarrhythmia. In long-QT syndrome type 1, mutations occur in the KCNQ1 gene, which encodes the repolarizing potassium channel mediating the delayed rectifier IKs current.
The laminin A4 is expressed in interstitial lung disease associated with lupus and scleroderma
Authors: S. Kielhauser, E. Stacher, F. Furst, M. Kremser, M. Stradner, H. Popper, W. Graninger
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Interstitial lung disease (ILD) is a major complication of the rheumatic diseases systemic sclerosis (SSc), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). ILD is the consequence of tissue remodelling with increased collagen production in the interstitium and around blood vessels. The laminin LAMA4 is involved in tissue remodelling. LAMA4 mutant mice develop myocardial and renal fibrosis. The authors studied LAMA4 expression in lung tissue of ILD patients suffering from SLE, SSc and RA. <h3>Material and methods</h3> Lung biopsy specimens were obtained from ILD patients who fulfilled the criteria for SLE (n=7), SSc (n=4) and RA (n=5). As negative controls lung tissue from patients without any signs of ILD and a single metastasis of colon cancer (n=5) were used. Immunohistochemistry on paraffin embedded slides was performed for LAMA4 using the monoclonal antibody 2A3. Intensity of staining was scored semiquantitatively. <h3>Results</h3> LAMA4 was overexpressed in lung tissue from SLE, SSc and RA patients with ILD. The LAMA4 staining was enhanced in areas around the vessels and around the peripheral alveolar cells. In normal lung tissue LAMA4 expression was hardly detectable. <h3>Conclusion</h3> LAMA 4 is expressed in lung tissue from patients with ILD secondary to SLE, SSC and RA. LAMA4 may be a major player in the development of fibrosis. It also may be important for the development of pulmonary arterial hypertension.
Body Weight and Leptin Plasma Levels During Treatment With Antipsychotic Drugs
Authors: Thomas Kraus, Monika Haack, Andreas Schuld, Dunja Hinze-Selch, Martin Kï¿½hn, Manfred Uhr, Thomas Pollmï¿½cher
Journal: American Journal of Psychiatry (1999)

Leptin is produced by fat cells and is presumed to signal the size of the adipose tissue to the brain. The authors investigated whether antipsychotic drugs that often induce weight gain affect circulating levels of leptin.Weight, body mass index, and leptin plasma level were measured weekly over 4 weeks in psychiatric inpatients who received clozapine (N = 11), olanzapine (N = 8), haloperidol (N = 13), or no psychopharmacological treatment (N = 12).In patients receiving clozapine or olanzapine, significant increases in weight, body mass index, and leptin level were found, whereas these measures remained stable in patients who received haloperidol or no pharmacological treatment.Weight gain induced by clozapine or olanzapine appears to be associated with an increase in leptin level that cannot be attributed to dietary changes upon hospitalization.