tbuckley/cabot-search huggingface dataset:
Carbon monoxide pollution is associated with decreased lung function in asthmatic adults
Authors: C. Canova, S. Torresan, L. Simonato, M. L. Scapellato, R. Tessari, A. Visentin, M. Lotti, P. Maestrelli
Journal: European Respiratory Journal (2009)

The aim of the present study was to test the effects of exposure to air pollutants on lung function. A panel of 19 adult asthmatics living in Padua (Italy) was followed for five 30-day periods during 2 yrs consecutively (1,492 morning and 1,434 evening measures analysed). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV 1 ) were measured using a pocket electronic meter. Daily levels of air pollutants and meteorological variables were collected at outdoor city monitoring sites. Significant inverse associations were observed between morning and evening PEF and carbon monoxide level (p = 0.01–0.03), without clear differences between lags (0–3 days). An increment of 1 mg·m −3 CO was associated with a PEF variation ranging -2.6– -2.8%. All effect estimates on PEF for CO remained significant and even increased after controlling for particles with a 50% cut-off aerodynamic diameter of 10 μm (PM 10 ), nitrogen dioxide and sulphur dioxide in single and multi-pollutant models. A similar trend was observed for FEV 1 , but the associations were nonsignificant. A nonsignificant inverse relationship between evening PEF and SO 2 was also detected. PEF and FEV 1 were not related to PM 10 and NO 2 concentrations. The present results indicate that, in this panel of adult asthmatics, the worsening of lung function is associated with exposure to gaseous pollutants and occurs at levels of CO and SO 2 lower than current European standards.
Altered pattern of cannabinoid type 1 receptor expression in adipose tissue of dysmetabolic and overweight patients
Authors: Riccardo Sarzani, Marica Bordicchia, Pierfrancesco Marcucci, Samuele Bedetta, Silvia Santini, Andrea Giovagnoli, Lorena Scappini, Daniele Minardi, Giovanni Muzzonigro, Paolo Dessì-Fulgheri, Alessandro Rappelli
Journal: Metabolism (2009)
Everolimus in patients with rheumatoid arthritis receiving concomitant methotrexate: a 3-month, double-blind, randomised, placebo-controlled, parallel-group, proof-of-concept study
Authors: G A W Bruyn, G Tate, F Caeiro, J Maldonado-Cocco, R Westhovens, H Tannenbaum, M Bell, O Forre, O Bjorneboe, P P Tak, K H Abeywickrama, P Bernhardt, P L C van Riel
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Everolimus, a proliferation signal inhibitor with disease-modifying properties, may be useful in treating rheumatoid arthritis (RA). This proof-of-concept study assessed efficacy and safety of everolimus in combination with methotrexate (MTX) in patients with refractory RA. <h3>Methods:</h3> A multi-centre, randomised, double-blind, placebo-controlled trial was performed in 121 patients with active RA receiving MTX. Patients were randomised to receive everolimus (6 mg/day) or placebo. The primary endpoint was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR20) at 12 weeks. <h3>Results:</h3> There was a rapid onset of action and at 12 weeks the ACR20 response rate was significantly higher in the everolimus group (36.1%) than in the placebo group (16.7%; p = 0.022). Improvements from baseline in tender and swollen joint counts, patient's assessment of pain, and patient's and physician's global assessment of disease activity were significantly greater after treatment with everolimus. The most common adverse events (AEs) in the everolimus group were gastrointestinal (52.5% vs 31.7% in the placebo group), skin (29.5% vs 8.3%), and nervous system disorders (21.3% vs 10.0%); AEs leading to treatment discontinuation were reported for 16.4% and 10.0% of patients, respectively. Changes in haematological parameters, liver function tests, and lipid levels occurred more frequently with everolimus compared to placebo, but were mild and reversible. <h3>Conclusions:</h3> The study indicates that everolimus plus MTX provides clinical benefit with an acceptable safety and tolerability profile. It may offer a new treatment option in RA patients with inadequate response to MTX.
Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease
Authors: D Fina, M Sarra, R Caruso, G Del Vecchio Blanco, F Pallone, T T MacDonald, G Monteleone
Journal: Gut (2007)

In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon gamma (IFNgamma) and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T-bet and promote the Th1 cell response are unknown.To examine whether interleukin 21 (IL21), a cytokine that regulates T cell activation, has a role in CD.Duodenal mucosal samples were taken from CD patients and normal controls. IL21 and T-bet were examined by real-time PCR and western blotting, and IFNgamma was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated CD patients. Finally, the role of IL21 in controlling T-bet and IFNgamma was also evaluated in cultures of biopsies taken from treated CD patients and cultured with a peptic-tryptic digest of gliadin (PT) in the presence or absence of a neutralising IL21 antibody.Enhanced IL21 RNA and protein expression was seen in duodenal samples from untreated CD patients. Blockade of IL21 activity in biopsies of untreated CD patients reduced T-bet and IFNgamma secretion. Stimulation of treated CD biopsies with PT enhanced IL21 expression, and neutralisation of IL21 largely prevented PT-driven T-bet and IFNgamma induction.IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNgamma production.
Gene Expression Profile of <i>BRCA</i>ness That Correlates With Responsiveness to Chemotherapy and With Outcome in Patients With Epithelial Ovarian Cancer
Authors: Panagiotis A. Konstantinopoulos, Dimitrios Spentzos, Beth Y. Karlan, Toshiyasu Taniguchi, Elena Fountzilas, Nancy Francoeur, Douglas A. Levine, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2010)

Purpose To define a gene expression profile of BRCAness that correlates with chemotherapy response and outcome in epithelial ovarian cancer (EOC). Methods A publicly available microarray data set including 61 patients with EOC with either sporadic disease or BRCA½ germline mutations was used for development of the BRCAness profile. Correlation with platinum responsiveness was assessed in platinum-sensitive and platinum-resistant tumor biopsy specimens from six patients with BRCA germline mutations. Association with poly-ADP ribose polymerase (PARP) inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones. The BRCAness profile was validated in 70 patients enriched for sporadic disease to assess its association with outcome. Results The BRCAness profile accurately predicted platinum responsiveness and mutation status in eight of 10 patient-derived tumor specimens and between PARP-inhibitor sensitivity and resistance in four of four Capan-1 clones. When applied to the 70 patients with sporadic disease, patients with the BRCA-like (BL) profile had improved disease-free survival (34 months v 15 months; log-rank P = .013) and overall survival (72 months v 41 months; log-rank P = .006) compared with patients with a non–BRCA-like (NBL) profile, respectively. The BRCAness profile maintained independent prognostic value in multivariate analysis, which controlled for other known clinical prognostic factors. Conclusion The BRCAness profile correlates with responsiveness to platinum and PARP inhibitors and identifies a subset of sporadic patients with improved outcome. Additional evaluation of this profile as a predictive tool in patients with sporadic EOC is warranted.
Inflammation-induced subventricular zone dysfunction leads to olfactory deficits in a targeted mouse model of multiple sclerosis
Authors: Vanja Tepavčević, Françoise Lazarini, Clara Alfaro-Cervello, Christophe Kerninon, Kazuaki Yoshikawa, José Manuel Garcia-Verdugo, Pierre-Marie Lledo, Brahim Nait-Oumesmar, Anne Baron-Van Evercooren
Journal: Journal of Clinical Investigation (2011)

Neural stem cells (NSCs) persist in defined brain niches, including the subventricular zone (SVZ), throughout adulthood and generate new neurons destined to support specific neurological functions. Whether brain diseases such as multiple sclerosis (MS) are associated with changes in adult NSCs and whether this might contribute to the development and/or persistence of neurological deficits remains poorly investigated. We examined SVZ function in mice in which we targeted an MS-like pathology to the forebrain. In these mice, which we refer to herein as targeted EAE (tEAE) mice, there was a reduction in the number of neuroblasts compared with control mice. Altered expression of the transcription factors Olig2 and Dlx2 in the tEAE SVZ niche was associated with amplification of pro-oligodendrogenic transit-amplifying cells and decreased neuroblast generation, which resulted in persistent reduction in olfactory bulb neurogenesis. Altered SVZ neurogenesis led to impaired long-term olfactory memory, mimicking the olfactory dysfunction observed in MS patients. Importantly, we also found that neurogenesis was reduced in the SVZ of MS patients compared with controls. Thus, our findings suggest that neuroinflammation induces functional alteration of adult NSCs that may contribute to olfactory dysfunction in MS patients.
Sensitivity of Squamous Cell Carcinoma Lymph Node Metastases to Herpes Oncolytic Therapy
Authors: Zhenkun Yu, Sen Li, Yu-Yao Huang, Shu-Fu Lin, Yuman Fong, Richard J. Wong
Journal: Clinical Cancer Research (2008)

Cancer metastases may have phenotypic and genetic differences from their primary cancers of origin. Engineered, replication-competent, attenuated viruses based on herpes simplex virus-1 (HSV-1) have shown potent oncolytic effects in treating primary tumors in animal tumor models, but their efficacy in treating lymph node metastases is poorly understood. We compared the efficacy of an attenuated oncolytic HSV-1 (NV1023) in treating a series of murine squamous carcinoma cell lines derived from serial implantation and harvest from metastatic lymph nodes.The auricles of C3H/HeJ mice were implanted with SCCVII. Cervical nodal metastases were isolated, expanded in vitro, and reimplanted into new mice. A series of cell lines (LN1-LN7) were generated through seven serial passages. Cells from higher LN passages showed consistent trends toward increased migratory and invasive ability, increased cell surface nectin-1 (an HSV-1 receptor) expression, and increased glycoprotein D binding. Exposure to NV1023 showed increased viral entry, replication, and cytotoxicity with higher LN passages. Intratumoral injection of NV1023 in a murine flank tumor model caused significantly greater tumor regression and increased viral infection of LN7 compared with SCCVII.These results show that lymph node metastases may undergo selection for characteristics, including increased nectin-1 expression, that make them more sensitive targets for herpes oncolytic therapy. These findings support the clinical application of these agents for the treatment of lymph node metastases.
Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations
Authors: Keith T. Flaherty, Jeffery R. Infante, Adil Daud, Rene Gonzalez, Richard F. Kefford, Jeffrey Sosman, Omid Hamid, Lynn Schuchter, Jonathan Cebon, Nageatte Ibrahim, Ragini Kudchadkar, Howard A. Burris, Gerald Falchook, Alain Algazi, Karl Lewis, Georgina V. Long, Igor Puzanov, Peter Lebowitz, Ajay Singh, Shonda Little, Peng Sun, Alicia Allred, Daniele Ouellet, Kevin B. Kim, Kiran Patel, Jeffrey Weber
Journal: New England Journal of Medicine (2012)

Resistance to therapy with BRAF kinase inhibitors is associated with reactivation of the mitogen-activated protein kinase (MAPK) pathway. To address this problem, we conducted a phase 1 and 2 trial of combined treatment with dabrafenib, a selective BRAF inhibitor, and trametinib, a selective MAPK kinase (MEK) inhibitor.
Control of T-Cell–Mediated Immune Response by HLA Class I in Human Pancreatic Carcinoma
Authors: Eduard Ryschich, Tanja Nötzel, Ulf Hinz, Frank Autschbach, James Ferguson, Ioan Simon, Jürgen Weitz, Boris Fröhlich, Ernst Klar, Markus W. Büchler, Jan Schmidt
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cell surface HLA class I molecules present peptides derived from human cellular proteins to T cells. In the present study, we investigated the expression of HLA class I in human pancreatic carcinoma. Experimental Design: The expression of HLA class I antigen and the extent of tumor infiltration by T cells were investigated in 46 primary tumors and in 14 metastases of pancreatic cancer by standard immunohistochemistry. Results: The locus-specific expression of HLA I was reduced in 61% of primary tumors and in 93% of metastases. The total loss of this molecule complex was detected in 6% of primary tumors and in 43% of metastases. Pancreatic carcinoma and peritumoral tissue showed a significantly higher infiltration by CD3+, CD4+, and CD8+ T-cells compared with the tumor-distant pancreatic tissue. The negative expression of HLA class I was uniformly accompanied by a low density of tumor-infiltrating cytotoxic T-cells whereas the HLA class I–positive tumors were characterized by a substantial lymphocyte accumulation. However, the infiltration by cytotoxic T-cells was not correlated with the density of tumor cells. Patients with a high accumulation of cytotoxic cells showed a longer median survival. Conclusions: Pancreatic carcinoma frequently induces a cellular immune response that results in intratumoral and peritumoral T-cell infiltration. The expression of HLA class I is frequently lost in pancreatic carcinoma, which represents an effective mechanism to escape the tumor infiltration by cytotoxic T-cells. However, the infiltration by cytotoxic cells represents a favorable prognostic sign in pancreatic cancer patients.
ACTIVE SUPPRESSION OF IMMUNOGLOBULIN ALLOTYPE SYNTHESIS
Authors: E. B. Jacobson, Leonore A. Herzenberg
Journal: The Journal of Experimental Medicine (1972)

Long-term (chronic) allotype suppression, previously reported only in rabbits, is shown here to occur in at least one strain combination of mice as well. Close to 50% of the offspring of SJL (Ig(b)) males mated to BALB/c (Ig(a)) females immunized against the paternal allotype were found to be suppressed for Ig-1b (gammaG(2a)) at 6 months of age. These mice are called "chronically" suppressed. The percentage of offspring in this strain combination suppressed for the paternal allotype at 8 wk of age is the same as that seen in an earlier strain combination tested, [(C57 x BALB/c)F(1)], in which all mice recover from suppression by 10-12 wk. After 8 wk, two distinct patterns of long-term (chronic) suppression emerge in (SJL x BALB/c)F(1) mice: a small number of these mice never produce detectable amounts of Ig-1b throughout their lives, while the majority produce detectable Ig-1b sporadically, sometimes over a period of several weeks, the level of which eventually falls below detectability. Attempts to "cure" suppression by destroying the existent lymphoid population and forcing endogenous repopulation in chronically suppressed animals were unsuccessful. Furthermore, attempts to restore Ig-1b production by injection of cells from syngeneic Ig(a)/Ig(b) donors into irradiated, chronically suppressed recipients were also unsuccessful, although the same cell inocula, when injected into irradiated BALB/c (Ig(a)/Ig(a)) mice produced high levels of gamma globulin carrying the allotype. These results suggest that long-term allotype suppression resulting from perinatal exposure of offspring to specific anti-allotype antibody (anti-Ig-1b), is not due merely to an absence of Ig-1b-producing cells or their progenitors, but appears to be an active process, which dominates physiologically over normal production.
Outcomes with Esophageal Cancer Radiation Therapy
Authors: Zhen Zhang, Yuan Chen, Yanzhi Chen, Melenda Jeter, Wayne L. Hofstetter, Jaffer Ajani, Stephen G. Swisher, Joe Y. Chang, Pamela K. Allen, James D. Cox, Ritsuko Komaki, Zhongxing X. Liao
Journal: Journal of Thoracic Oncology (2009)
Insecticide impregnated curtains to control domestic transmission of cutaneous leishmaniasis in Venezuela: cluster randomised trial
Authors: A. Kroeger
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective</b>: To measure the impact on transmission of leishmaniasis of curtains impregnated with insecticide. <b>Design</b>: Cluster randomised controlled trial: household interview survey, observational study of people9s behaviour, entomological study with light trap captures of sandflies inside houses. <b>Setting</b>: 14 urban sectors in Trujillo, Venezuela. <b>Participants</b>: 2913 inhabitants of 569houses. <b>Intervention</b>: Sectors were paired according to their 12month cumulative incidence of cutaneous leishmaniasis, one sector in each pair was randomly allocated to receive polyester curtains impregnated with lambdacyhalothrin (intervention group) while the other sector received curtains without insecticide or no curtains (control groups). After 12 months a follow up household survey was conducted. <b>Main outcome measures</b>: Reduction in abundance of sandflies indoors and 12 month incidence of clinical cases of cutaneous leishmaniasis. <b>Results</b>: Transmission of cutaneous leishmaniasis occurred mainly in the domestic setting, with the incidence over 12 months of 4%. The mean number of sandflies per trap per night was 16.After follow up the 12 month incidence of cutaneous leishmaniasis was 0% in the intervention group and 8% in the six pairs in the control group that received unimpregnated curtains (mean difference 8, 95% confidence interval 4.22 to 11.78; P=0.001). There were significantly fewer sandflies in the intervention group (2 <i>v</i> 15,mean difference 13 sandflies per trap; 9 to 17; P&lt;0.001). <b>Conclusion</b>: Curtains impregnated with insecticide provide a high degree of protection against indoor transmission of cutaneous leishmaniasis.
PTH-033 A Specialist Iron Deficiency Anaemia Clinic Significantly Reduces The Need For Secondary Care Follow Up
Authors: E Taylor, J Campbell, M Donnelly, J Hebden
Journal: Gut (2014)

<h3>Introduction</h3> BSG guidelines provide clear recommendations for the investigation and management of iron deficiency anaemia (IDA). The algorithm lends itself to a ‘one stop’ new patient clinic in secondary care with further follow-up in primary care. We set up a dedicated IDA clinic aiming to streamline patients’ management and reduce unnecessary follow-up visits. <h3>Methods</h3> A ‘one stop’ IDA clinic was set up and run by a single gastroenterologist from November 2013. Data was collected prospectively for the first 60 patients referred with IDA (Group A). Patients without confirmed IDA (10, [17%]) were analysed separately. A second group of proven IDA referrals seen in unselected gastroenterology clinics in 2011 was identified (Group B). Rates of clinic follow up were recorded and the two groups compared. Additional data collected included demographics, haemoglobin, MCV, ferritin and other iron indices (Fe/TIBC) as well as radiology and endoscopy reports. Iron deficiency was defined as isolated microcytosis and/or low ferritin. <h3>Results</h3> Fifty patients fulfilled diagnostic criteria for IDA in group A (35 female, median age 69.0, range 35–91). Group B comprised 50 IDA patients (28 female, median age 72.0, range 38–83). All patients in Group A were seen by a single, UKconsultant compared to 80% seen by consultants in Group B. Four patients were diagnosed with colorectal cancers in group A. Two patients were diagnosed with oesophago-gastric tumours and 4 with colorectal cancers in group B. One new diagnosis of coeliac disease was made in each group. Group A contained five females with gynaecological pathology responsible for IDA (1 advanced cervical cancer and 4 menorrhagia). Despite confirmation of IDA with a low ferritin, 11 (22%) in Group A and 6 (12%) in Group B had undergone additional serum iron/TIBC measurements before referral. Only 3/17 (18%) iron studies were congruent with the ferritin result. Significantly more patients in Group A (94%) were discharged back to primary care after their initial consultation and investigations compared to Group B (26%, p &lt; 0.0001). <h3>Conclusion</h3> A specialist IDA clinic leads to appropriate discharge to primary care virtually eliminating secondary care follow up. Clinical assessment allows identification of a significant proportion of non-IDA referrals requiring alternative management. Measurement of serum iron/TIBC should be discouraged. <h3>Disclosure of Interest</h3> None Declared.
Absence of Antibodies to HTLV-III in Health Workers After Hepatitis B Vaccination
Authors: Jules L. Dienstag
Journal: JAMA (1985)

A proportion of the plasma for the triply inactivated, plasma-derived hepatitis B vaccine produced in the United States is obtained from homosexual men. Because homosexual men are a high-risk group for the acquired immunodeficiency syndrome (AIDS), concern has emerged that the vaccine could harbor the AIDS agent. To evaluate this risk, we tested 15-month postvaccination serum samples for antibodies to human T-cell lymphotropic virus type III in 100 health care workers who had received inactivated hepatitis B vaccine lots made from plasma collected between 1977 and 1979 and 100 who had received placebo injections. None of the 200 health workers had serological evidence of human T-cell lymphotropic virus type III infection. These serological findings lend additional support to earlier epidemiologic and immunologic observations suggesting that hepatitis B vaccine does not transmit infection with an AIDS virus. (<i>JAMA</i>1985;254:1064-1066)
Management of the Metabolic Syndrome and Type 2 Diabetes Through Lifestyle Modification
Authors: Faidon Magkos, Mary Yannakoulia, Jean L. Chan, Christos S. Mantzoros
Journal: Annual Review of Nutrition (2009)

Sustainable lifestyle modifications in diet and physical activity are the initial, and often the primary, component in the management of diabetes and the metabolic syndrome. An energy-prudent diet, coupled with moderate levels of physical activity, favorably affects several parameters of the metabolic syndrome and delays the onset of diabetic complications. Weight loss, albeit not an absolute prerequisite for improvement, is a major determinant and maximizes effectiveness. Adopting a healthy lifestyle pattern requires a series of long-term behavioral changes, but evidence to date indicates low long-term adherence to diet and physical activity recommendations. This calls for greater research and public health efforts focusing on strategies to facilitate behavior modification.
Preschool As Palliative Care
Authors: Mary Elizabeth Ross, Judith Hicks, Wayne L. Furman
Journal: Journal of Clinical Oncology (2008)

One privilege of caring for children with cancer is witnessing the courage with which families face life despite the disease. We don’t often think of attending preschool as either palliative or as an act of courage; in this case, it was both. A courageous mother advocated for her child to attend school, the care team facilitated school enrollment, and courageous teachers did more than simply accept him into their classroom.