tbuckley/cabot-search huggingface dataset:
The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease
Authors: D. DIAT‐SANCHEZ
Journal: Allergy (1997)

The increase in allergic airway disease has paralleled the increase in the use of fossil fuels. Studies were undertaken to examine whether extracts of polyaromatic hydrocarbons (PAH) from diesel exhaust particles (DEP) (PAH-DEP) acted as mucosal adjuvants to help initiate or enhance immunoglobulin E (IgE) production in response to common inhaled allergens. In vitro studies demonstrated that PAH-DEP enhanced IgE production by tonsillar B-cells in the presence of interleukin-4 (IL-4) and CD40 monoclonal antibody, and altered the nature of the IgE produced, i.e. a decrease in the CH4'-CHe5 variant, a marker for differentiation of IgE-producing B-cells, and an increase in the M2' variant. In vivo nasal provocation studies using 0.30 mg DEP in saline also showed enhanced IgE production in the human upper respiratory mucosa, accompanied by a reduced CH4'-CHe5 mRNA splice variant. The effects of DEP were also isotype-specific, with no effect on IgG, IgA, IgM, or albumin, but it produced a small increase in the IgG4 subclass. The ability of DEP to act as an adjuvant to the ragweed allergen Amb a I was examined by nasal provocation in ragweed allergic subjects using 0.3 mg DEP, Amb a I, or both. Although allergen and DEP each enhanced ragweed-specific IgE, DEP plus allergen promoted a 16-times greater antigen-specific IgE production. Nasal challenge with DEP also influenced cytokine production. Ragweed challenge resulted in a weak response, DEP challenge caused a strong but non-specific response, while allergen plus DEP caused a significant increase in the expression of mRNA for TH0 and TH2-type cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) with a pronounced inhibitory effect on IFN-gamma gene expression. These studies suggest that DEP can enhance B-cell differentiation, and by initiating and elevating IgE production, may play an important role in the increased incidence of allergic airway disease.
Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus.
Authors: H Volkmer, C Bertholet, S Jonjić, R Wittek, U H Koszinowski
Journal: The Journal of Experimental Medicine (1987)

The murine immediate-early (IE) protein pp89 is a nonstructural virus-encoded phosphoprotein residing in the nucleus of infected cells, where it acts as transcriptional activator. Frequency analysis has shown that in BALB/c mice the majority of virus-specific CTL recognize IE antigens. The present study was performed to assess whether pp89 causes membrane antigen expression detected by IE-specific CTL. Site-directed mutagenesis has been used to delete the introns from gene ieI, encoding pp89, for subsequent integration of the continuous coding sequence into the vaccinia virus genome. After infection with the vaccinia recombinant, the authentic pp89 was expressed in cells that became susceptible to lysis by an IE-specific CTL clone. Priming of mice with the vaccinia recombinant sensitized polyclonal CTL that recognized MCMV-infected cells and transfected cells expressing pp89. Thus, a herpesviral IE polypeptide with essential function in viral transcriptional regulation can also serve as a dominant antigen for the specific CTL response of the host.
Biochemical properties of membranes isolated from calcium-depleted rabbit hearts.
Authors: J M Lamers, J T Stinis, T J Ruigrok
Journal: Circulation Research (1984)

The purpose of this study was to define the biochemical properties of sarcolemma from the calcium-depleted rabbit heart. Calcium repletion after calcium-free perfusion results in irreversible damage to the heart (calcium paradox). No difference was found in specific activity of the Na+ -Ca++ antiporter in a crude preparation of sarcolemmal vesicles that was isolated from calcium-depleted hearts, compared with control perfused hearts. Likewise, the passive calcium efflux from sarcolemmal vesicles, preloaded with calcium via the Na+ -Ca++ antiporter, showed rates that were identical with control values. This indicates that the sarcolemma calcium permeability is not affected by calcium-free perfusion of the heart. Na+,K+ -ATPase activity in sarcolemma isolated from calcium-depleted hearts was reduced by 75% (P less than 0.005) compared with the control activity. Sarcolemmal phosphoproteins, whether produced by endogenous cyclic AMP- or calcium-calmodulin-dependent protein kinase, were not altered by calcium-free perfusion of the heart. The content of an important calcium-binding site in the myocardial cell, the sialic acid residues, was also estimated. Only a long period (60 minutes) of calcium-free perfusion resulted in a significant decrease (by 68%, P less than 0.025) of sialic acid content in the homogenate but not in the sarcolemma preparation. In hearts that were reperfused for 15 minutes with a normal calcium concentration (1.3 mM), sarcolemmal Na+,K+ -ATPase remained depressed and calcium permeability was still unchanged. It is possible that the sarcolemma isolation method selected a distinct part of the sarcolemma from the calcium-depleted and repleted heart that had no modified glycocalyx and permeability barriers to calcium ions, and that another part of the sarcolemma with altered properties was lost during the isolation procedure. Another possibility is that reconstitution processes during isolation affected membrane permeability properties. The results of the Na+,K+ -ATPase measurements provide evidence that the net calcium gain of the cells after calcium repletion may be associated, in part, with a loss in ability of the sarcolemma to remove calcium from the cytosol.
Overnight Closed-Loop Insulin Delivery in Young People With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial
Authors: Roman Hovorka, Daniela Elleri, Hood Thabit, Janet M. Allen, Lalantha Leelarathna, Ranna El-Khairi, Kavita Kumareswaran, Karen Caldwell, Peter Calhoun, Craig Kollman, Helen R. Murphy, Carlo L. Acerini, Malgorzata E. Wilinska, Marianna Nodale, David B. Dunger
Journal: Diabetes Care (2014)

OBJECTIVE To evaluate feasibility, safety, and efficacy of overnight closed-loop insulin delivery in free-living youth with type 1 diabetes. RESEARCH DESIGN AND METHODS Overnight closed loop was evaluated at home by 16 pump-treated adolescents with type 1 diabetes aged 12–18 years. Over a 3-week period, overnight insulin delivery was directed by a closed-loop system, and on another 3-week period sensor-augmented therapy was applied. The order of interventions was random. The primary end point was time when adjusted sensor glucose was between 3.9 and 8.0 mmol/L from 2300 to 0700 h. RESULTS Closed loop was constantly applied over at least 4 h on 269 nights (80%); sensor data were collected over at least 4 h on 282 control nights (84%). Closed loop increased time spent with glucose in target by a median 15% (interquartile range −9 to 43; P &amp;lt; 0.001). Mean overnight glucose was reduced by a mean 14 (SD 58) mg/dL (P &amp;lt; 0.001). Time when glucose was &amp;lt;70 mg/dL was low in both groups, but nights with glucose &amp;lt;63 mg/dL for at least 20 min were less frequent during closed loop (10 vs. 17%; P = 0.01). Despite lower total daily insulin doses by a median 2.3 (interquartile range −4.7 to 9.3) units (P = 0.009), overall 24-h glucose was reduced by a mean 9 (SD 41) mg/dL (P = 0.006) during closed loop. CONCLUSIONS Unsupervised home use of overnight closed loop in adolescents with type 1 diabetes is safe and feasible. Glucose control was improved during the day and night with fewer episodes of nocturnal hypoglycemia.
Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis
Authors: Nicola Low, Matthew F. Chersich, Kurt Schmidlin, Matthias Egger, Suzanna C. Francis, Janneke H. H. M. van de Wijgert, Richard J. Hayes, Jared M. Baeten, Joelle Brown, Sinead Delany-Moretlwe, Rupert Kaul, Nuala McGrath, Charles Morrison, Landon Myer, Marleen Temmerman, Ariane van der Straten, Deborah Watson-Jones, Marcel Zwahlen, Adriane Martin Hilber
Journal: PLoS Medicine (2011)

Background Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. Methods and Findings We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I2 values 0.0%–16.1%). Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18–1.83), insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00–1.71), and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01–1.53) remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04–1.47). Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001) or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001), respectively. Conclusions This study provides evidence to suggest that some intravaginal practices increase the risk of HIV acquisition but a direct causal pathway linking intravaginal cleaning with soap, disruption of vaginal flora, and HIV acquisition has not yet been demonstrated. More consistency in the definition and measurement of specific intravaginal practices is warranted so that the effects of specific intravaginal practices and products can be further elucidated. Please see later in the article for the Editors' Summary
Risk of Fractures Following Cataract Surgery in Medicare Beneficiaries
Authors: Victoria L Tseng, Fei Yu, Flora Lum, Anne L Coleman
Journal: JAMA (2012)

Visual impairment is a known risk factor for fractures. Little is known about the association of cataract surgery with fracture risk.To determine the association of cataract surgery with subsequent fracture risk in US Medicare beneficiaries with a diagnosis of cataract.Retrospective study of 1-year fracture incidence in a 5% random sample of Medicare Part B beneficiaries with cataract who received and did not receive cataract surgery from 2002 through 2009.One-year incidence of hip fractures. Analyses were adjusted for age; sex; race/ethnicity; US region of residence; systemic comorbidities, including Charlson Comorbidity Index (CCI) score; ocular comorbidities; cataract severity; and presence of physically limiting conditions. Adjusted odds ratios (ORs) of hip fractures were calculated using logistic regression modeling.There were 1,113,640 US Medicare beneficiaries 65 years and older with a diagnosis of cataract between 2002 and 2009 in the 5% random sample; of these patients, 410,809 (36.9%) received cataract surgery during the study period. There were 13,976 patients (1.3%) who sustained a hip fracture during the study period. The most common fracture-related comorbidity was osteoporosis (n = 134,335; 12.1%). The most common ocular comorbidity was glaucoma (n = 212,382; 19.1%). Compared with 1-year hip fracture incidence in patients with cataract who did not have cataract surgery, adjusted OR of hip fracture within 1 year after cataract surgery was 0.84 (95% CI, 0.81-0.87) with an absolute risk difference of 0.20%. Compared with matched subgroups of patients who did not receive cataract surgery, patient subgroups that experienced lower odds of hip fracture after cataract surgery included patients with severe cataract, patients most likely to receive cataract surgery based on propensity score, patients 75 years and older, and patients with a CCI score of 3 or greater.In a cohort of US Medicare beneficiaries aged 65 years and older with a diagnosis of cataract, patients who had cataract surgery had lower odds of hip fracture within 1 year after surgery compared with patients who had not undergone cataract surgery.
Malignant proliferating trichilemmal tumour associated with human papillomavirus type 21 in epidermodysplasia verruciformis
Authors: S. Motegi, A. Tamura, Y. Endo, G. Kato, A. Takahashi, I. Negishi, O. Ishikawa
Journal: British Journal of Dermatology (2003)

Journal Article Malignant proliferating trichilemmal tumour associated with human papillomavirus type 21 in epidermodysplasia verruciformis Get access S. Motegi, S. Motegi Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Tamura, A. Tamura Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Endo, Y. Endo Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar G. Kato, G. Kato Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Takahashi, A. Takahashi Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar I. Negishi, I. Negishi Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa O. Ishikawa Department of Dermatology, Gunma University School of Medicine, 3‐39‐22 Showa‐machi, Maebashi, Gunma 371–8511, Japan E‐mail: smotegi@showa.gunma‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 1, 1 January 2003, Pages 180–182, https://doi.org/10.1046/j.1365-2133.2003.510110.x Published: 01 January 2003
Non–Glycemic-Dependent Reduction of Late Pregnancy A1C Levels in Women With Type 1 Diabetes
Authors: Lucrecia Herranz, Lourdes Saez-de-Ibarra, Cristina Grande, Luis F. Pallardo
Journal: Diabetes Care (2007)

Areduction of A1C levels during pregnancy in women without diabetes has been reported (1–6), suggesting that the goal for A1C during pregnancy complicated with diabetes should be lowered. The decrease in fasting blood glucose levels during the first trimester of normal pregnancy (7,8) may explain the lower A1C levels found in early pregnancy (1,2,3,5). A further decrease of A1C in late pregnancy in women without diabetes has been reported by Nielsen et al. (3), which may be related to decreased erythrocyte life span (9,10).

In women with type 1 diabetes, strict glycemic control during pregnancy leads to a reduction in A1C levels, which may be insufficient to prevent the complications of pregnancy in type 1 diabetes (11,12). Since the decrease in A1C during normal pregnancy is related to lower blood glucose and to decreased erythrocyte lifespan (6–10), some of the reduction of A1C observed in pregnant women with type 1 diabetes will not be related to improved glycemic control. Therefore, A1C levels in pregnancies complicated by diabetes can be misleading when evaluating the degree of glycemic control. The aim of this study was to quantify the decrease in A1C levels during late pregnancy in women with type 1 diabetes who were not dependent on glycemic control.

This study was performed at the Hospital Universitario La Paz, Madrid, Spain. Ethical approval …
Evidence That IGF Binding Protein-5 Functions as a Ligand-Independent Transcriptional Regulator in Vascular Smooth Muscle Cells
Authors: Qijin Xu, Shenghua Li, Yang Zhao, Travis J. Maures, Ping Yin, Cunming Duan
Journal: Circulation Research (2004)

Insulin-like growth factor binding protein (IGFBP)-5 is a conserved protein synthesized and secreted by vascular smooth muscle cells (VSMCs). IGFBP-5 binds to extracellular IGFs and modulates IGF actions in regulating VSMC proliferation, migration, and survival. IGFBP-5 also stimulates VSMC migration through an IGF-independent mechanism, but the molecular basis underlying this ligand-independent action is unknown. In this study, we show that endogenous IGFBP-5 or transiently expressed IGFBP-5-EGFP, but not IGFBP-4-EGFP, is localized in the nuclei of VSMCs. Using a series of IGFBP-4/5 chimeras and IGFBP-5 points mutants, we demonstrated that the IGFBP-5 C-domain is necessary and sufficient for its nuclear localization, and residues K206, K208, K217, and K218 are particularly critical. Intriguingly, inhibition of protein secretion abolishes IGFBP-5 nuclear localization, suggesting the nuclear IGFBP-5 is derived from the secreted protein. When added exogenously, 125 I- or Cy3-labeled IGFBP-5 is capable of cellular entry and nuclear translocation. To identify potential transcriptional factor(s) that interact with IGFBP-5, a human aorta cDNA library was screened by a yeast two-hybrid screening strategy. Although this screen identified many extracellular and cytosolic proteins that are known to interact with IGFBP-5, no known transcription factors were found. Further motif analysis revealed that the IGFBP-5 N-domain contains a putative transactivation domain. When fused to GAL-4 DNA dinging domain and tested, the IGFBP-5 N-domain has strong transactivation activity. Mutation of the IGF binding domain or treatment of cells with IGF-I has little effect on transactivation activity. These results suggest that IGFBP-5 is localized in VSMC nucleus and possesses transcription-regulatory activity that is IGF independent. The full text of this article is available online at http://circres.ahajournals.org.
β-Adrenergic Stimulation of L-type Ca <sup>2+</sup> Channels in Cardiac Myocytes Requires the Distal Carboxyl Terminus of α <sub>1C</sub> but Not Serine 1928
Authors: Anand N. Ganesan, Christoph Maack, David C. Johns, Agnieszka Sidor, Brian O’Rourke
Journal: Circulation Research (2006)

Beta-adrenoceptor stimulation robustly increases cardiac L-type Ca2+ current (ICaL); yet the molecular mechanism of this effect is still not well understood. Previous reports have shown in vitro phosphorylation of a consensus protein kinase A site at serine 1928 on the carboxyl terminus of the alpha1C subunit; however, the functional role of this site has not been investigated in cardiac myocytes. Here, we examine the effects of truncating the distal carboxyl terminus of the alpha1C subunit at amino acid residue 1905 or mutating the putative protein kinase A site at serine 1928 to alanine in adult guinea pig myocytes, using novel dihydropyridine-insensitive alpha1C adenoviruses, coexpressed with beta2 subunits. Expression of alpha1C truncated at 1905 dramatically attenuated the increase of peak ICaL induced by isoproterenol. However, the point mutation S1928A did not significantly attenuate the beta-adrenergic response. The findings indicate that the distal carboxyl-terminus of alpha1C plays an important role in beta-adrenergic upregulation of cardiac L-type Ca2+ channels, but that phosphorylation of serine 1928 is not required for this effect.
Unilateral absence of a pulmonary artery: congenital disease or embolic occlusion?
Authors: J M Arriero, J Gil, C Martín, V Mainar, S Romero
Journal: European Respiratory Journal (1991)

A young man with congenital absence of the left pulmonary artery is reported. A right aortic arch and normal pulmonary pressures essentially rule out an alternate diagnosis of occlusive chronic thrombus in the central pulmonary arteries. Recurrent or massive haemoptysis makes an exact knowledge of the pulmonary circulation advisable.
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from<i>BRCA</i>Mutation Carriers
Authors: Peter C. Fong, David S. Boss, Timothy A. Yap, Andrew Tutt, Peijun Wu, Marja Mergui-Roelvink, Peter Mortimer, Helen Swaisland, Alan Lau, Mark J. O'Connor, Alan Ashworth, James Carmichael, Stan B. Kaye, Jan H.M. Schellens, Johann S. de Bono
Journal: New England Journal of Medicine (2009)

The inhibition of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) is a potential synthetic lethal therapeutic strategy for the treatment of cancers with specific DNA-repair defects, including those arising in carriers of a BRCA1 or BRCA2 mutation. We conducted a clinical evaluation in humans of olaparib (AZD2281), a novel, potent, orally active PARP inhibitor.This was a phase 1 trial that included the analysis of pharmacokinetic and pharmacodynamic characteristics of olaparib. Selection was aimed at having a study population enriched in carriers of a BRCA1 or BRCA2 mutation.We enrolled and treated 60 patients; 22 were carriers of a BRCA1 or BRCA2 mutation and 1 had a strong family history of BRCA-associated cancer but declined to undergo mutational testing. The olaparib dose and schedule were increased from 10 mg daily for 2 of every 3 weeks to 600 mg twice daily continuously. Reversible dose-limiting toxicity was seen in one of eight patients receiving 400 mg twice daily (grade 3 mood alteration and fatigue) and two of five patients receiving 600 mg twice daily (grade 4 thrombocytopenia and grade 3 somnolence). This led us to enroll another cohort, consisting only of carriers of a BRCA1 or BRCA2 mutation, to receive olaparib at a dose of 200 mg twice daily. Other adverse effects included mild gastrointestinal symptoms. There was no obvious increase in adverse effects seen in the mutation carriers. Pharmacokinetic data indicated rapid absorption and elimination; pharmacodynamic studies confirmed PARP inhibition in surrogate samples (of peripheral-blood mononuclear cells and plucked eyebrow-hair follicles) and tumor tissue. Objective antitumor activity was reported only in mutation carriers, all of whom had ovarian, breast, or prostate cancer and had received multiple treatment regimens.Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCA2 mutation. (ClinicalTrials.gov number, NCT00516373.)
Radiographic appearances of mycoplasma pneumonia.
Authors: O C Finnegan, S J Fowles, R J White
Journal: Thorax (1981)

The chest radiographs of 60 adult patients with serologically proven mycoplasma pneumonia were reviewed. Confluent or patchy consolidation was most commonly seen, and involved one lobe only in 40% of patients. Widespread nodular opacities were seen much less frequently (7%). Pleural fluid was rare. Complete resolution was almost invariable, 40% of radiographs having cleared by four weeks and 96% by eight weeks.