tbuckley/cabot-search huggingface dataset:
Recombinant basic fibroblast growth factor inhibits the airway hyperresponsiveness, mucus production, and lung inflammation induced by an allergen challenge
Authors: Seong Gyu Jeon, Chun Geun Lee, Min-Hee Oh, Eun-Young Chun, Yong Song Gho, Sang-Heon Cho, Jong-Hoon Kim, Kyung-Up Min, You-Young Kim, Yoon-Keun Kim, Jack A. Elias
Journal: Journal of Allergy and Clinical Immunology (2007)
Generational Increase in Young Women’s Drinking
Authors: Rosa Alati, Kim S. Betts, Gail M. Williams, Jacob M. Najman, Wayne D. Hall
Journal: JAMA Psychiatry (2014)

Increases in alcohol use in young women over recent decades are shown by national survey data but have yet to be replicated using prospective data.To compare change in alcohol use over a generation of young women born in Australia from 1981 to 1983 at 21 years with that of their mothers at the same age.Data came from the Mater University Study of Pregnancy, a prospective prebirth cohort study that recruited all pregnant mothers attending a hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to 1053 mothers who were aged 18 to 25 years of age at the baseline measurement and their daughters who were between the same ages when assessed 21 years later.Assessing the increase in the same prospective measures of 4 levels of alcohol use between mothers and daughters.Multinomial logistic regression for clustered data indicated daughters were at greater odds of consuming high (odds ratio [OR] = 5.68 [95% CI, 4.24-7.57]) and moderate (OR = 2.81 [95% CI, 2.18-3.63]) levels of alcohol than their mothers. Not having a dependent child roughly doubled the odds of all levels of drinking in both cohorts. Undertaking or completing tertiary education had no effect on consumption. There was an interaction between mothers' or daughters' drinking and partner status (χ23 = 12.56; P = .007); having a partner doubled the daughters' odds of consuming high levels of alcohol (no partner: OR = 0.51 [95% CI, 0.31-0.80]) while the odds of drinking at the highest level were more than 5 times for mothers who were single (OR = 5.65 [95% CI, 2.99-12.35]).To our knowledge, we provide the first longitudinal evidence confirming that female alcohol use has dramatically increased over a generation, especially at higher levels of drinking. Later age at child bearing contributed to this increase and the relationship between alcohol use and having a partner was found to reverse alcohol consumption across the 2 generations.
A Case of Insulin-Dependent Diabetes Associated With Enteroviral Infections
Authors: Hidetaka Hamasaki, Hidekatsu Yanai
Journal: Diabetes Care (2012)

Enteroviruses have been reported to be a potential trigger of the development of type 1 diabetes by inducing β-cell autoantibodies and by directly destroying β-cells (1). Although the precise underlying mechanisms for enterovirus-mediated development of diabetes remain unknown, the systematic review and meta-analysis of observational molecular studies demonstrates a clinically significant association between enteroviral infections detected by molecular methods and type 1 diabetes (2). Here we report a case of juvenile-onset insulin-dependent diabetes resulting from various enteroviral infections.

A 20-year-old man was referred and admitted to our hospital because of a penile inflammation, suffering from general fatigue, and body weight loss for 2 weeks in March 2011. He had a high fever (38–39°C) at 2 weeks before the admission. …
MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2
Authors: Niamh H. Foley, Isabella M. Bray, Amanda Tivnan, Kenneth Bryan, Derek M. Murphy, Patrick G. Buckley, Jacqueline Ryan, Anne O'Meara, Maureen O'Sullivan, Raymond L. Stallings
Journal: Molecular Cancer (2010)

Neuroblastoma is a paediatric cancer of the sympathetic nervous system. The single most important genetic indicator of poor clinical outcome is amplification of the MYCN transcription factor. One of many down-stream MYCN targets is miR-184, which is either directly or indirectly repressed by this transcription factor, possibly due to its pro-apoptotic effects when ectopically over-expressed in neuroblastoma cells. The purpose of this study was to elucidate the molecular mechanism by which miR-184 conveys pro-apoptotic effects.We demonstrate that the knock-down of endogenous miR-184 has the opposite effect of ectopic up-regulation, leading to enhanced neuroblastoma cell numbers. As a mechanism of how miR-184 causes apoptosis when over-expressed, and increased cell numbers when inhibited, we demonstrate direct targeting and degradation of AKT2, a major downstream effector of the phosphatidylinositol 3-kinase (PI3K) pathway, one of the most potent pro-survival pathways in cancer. The pro-apoptotic effects of miR-184 ectopic over-expression in neuroblastoma cell lines is reproduced by siRNA inhibition of AKT2, while a positive effect on cell numbers similar to that obtained by the knock-down of endogenous miR-184 can be achieved by ectopic up-regulation of AKT2. Moreover, co-transfection of miR-184 with an AKT2 expression vector lacking the miR-184 target site in the 3'UTR rescues cells from the pro-apoptotic effects of miR-184.MYCN contributes to tumorigenesis, in part, by repressing miR-184, leading to increased levels of AKT2, a direct target of miR-184. Thus, two important genes with positive effects on cell growth and survival, MYCN and AKT2, can be linked into a common genetic pathway through the actions of miR-184. As an inhibitor of AKT2, miR-184 could be of potential benefit in miRNA mediated therapeutics of MYCN amplified neuroblastoma and other forms of cancer.
Who evaluates public health programmes? A review of the NHS Breast Screening Programme
Authors: Karsten Juhl Jørgensen, Peter C Gøtzsche
Journal: Journal of the Royal Society of Medicine (2010)

Breast screening with mammography was introduced in the UK in 1988, and the Annual Review 2008 from the NHS Breast Cancer Screening Programme (NHS BSP) summarizes the 20-year experience. Twenty years is a long time and it seems reasonable to ask what might be expected from such a review from a public health institution. First and foremost, one would expect to see an analysis that shows that screening has lowered breast cancer mortality in the UK. Secondly, one would wish to see a comparison of this benefit with a quantification of the most important harms, as this would allow the readers to judge for themselves whether the programme has been worth its large cost. If the screening programme had lived up to the expected mortality reduction that was the basis for its introduction, it should have been easy for the NHS Breast Cancer Screening Programme to demonstrate this for the politicians and other interested parties. This is not what the 26-page publication does, however. It celebrates 20 years of breast screening, as one of the headlines says. As with all good birthdays, it is the qualities of the celebrated that are mentioned, not the shortcomings. In line with the positive framing, the first sentence in the Review refers to the 20th anniversary as a ‘momentous occasion’. The Review exaggerates the benefit, omits the harms, and looks like propaganda aimed at persuasion. It comes wrapped in a beautiful layout that would pride any marketing department if it had been a sales brochure for a drug (Figure 1). The first words on the cover page are: ‘Saving lives through screening’, and the symbolism is strong. Most of the cover space is taken up by a picture of a delicate rose in the distinctive pink colour that has become iconic for the fight against breast cancer. The rose is transparent, symbolizing the scientific illumination and radiological technique through which the programme operates.
Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers
Authors: Terje Ahlquist, Guro E Lind, Vera L Costa, Gunn I Meling, Morten Vatn, Geir S Hoff, Torleiv O Rognum, Rolf I Skotheim, Espen Thiis-Evensen, Ragnhild A Lothe
Journal: Molecular Cancer (2008)

Abstract Background Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential. The methylation status of eleven genes ( ADAMTS1 , CDKN2A , CRABP1 , HOXA9 , MAL , MGMT , MLH1 , NR3C1 , PTEN , RUNX3 , and SCGB3A1 ) was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI), BRAF -, KRAS -, and TP53 mutation status. Results The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1 , MAL , and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1 , NR3C1 , RUNX3 , and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes. Conclusion Methylated ADAMTS1 , MGMT , and MAL are suitable as markers for early tumor detection.
Navigating the uncharted waters of combination therapy in pulmonary arterial hypertension: COMPASS or dead-reckoning
Authors: Jean-Luc Vachiery, Lewis J. Rubin
Journal: European Respiratory Journal (2015)

Despite substantial advances in the treatment of pulmonary arterial hypertension (PAH) over the past two decades, with 13 drugs approved by regulatory agencies worldwide, the responses to medical therapy are often incomplete or unsatisfactory [1]. As with other conditions with complex pathogenesis, PAH is probably the result of multiple stimuli, both genetic and epigenetic, whose interplay over the course of the disease is poorly understood. Combination therapy trials in cancer, heart failure and HIV infection have demonstrated the value of targeting multiple pathogenic pathways in complex diseases, and this strategy has become the therapeutic mainstay for these chronic conditions. Unlike these common diseases, however, PAH is considered an "orphan" disease, making large-scale clinical trials of multiple therapies more challenging, both logistically and practically [2, 3]. Two articles in this issue of the European Respiratory Journal provide new information regarding the effects of adding a second approved oral medication to PAH patients who are not achieving a satisfactory clinical response to initial oral monotherapy [4, 5]. Two studies in this month's ERJ report results of combination therapy for PAH <http://ow.ly/OlgID>
The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis
Authors: B Rueda, G Orozco, E Raya, J L Fernandez-Sueiro, J Mulero, F J Blanco, C Vilches, M A Gonzalez-Gay, J Martin
Journal: Annals of the Rheumatic Diseases (2008)

Recent results have shown that the IL23R gene, coding for a subunit of the interleukin-23 receptor, is strongly associated with autoimmunity. The aim of the current study was to investigate, for the first time, the possible involvement of the IL23R gene in genetic susceptibility to ankylosing spondylitis (AS).We carried out a case-control association study in which 365 patients with AS and 500 blood bank donors were included. Eight single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected as genetic markers for our association study and were genotyped using a Taqman 5' allelic discrimination assay.Interestingly, we observed association of two of eight IL23R genotyped SNPs. The strongest effect was conferred by the non-synonymous rs11209026 (Arg381Gln) SNP (odds ratio 0.46 95% confidence interval 0.2 to 0.7 p = 0.001). Similarly, the IL23R rs1343151 SNP showed association with AS genetic susceptibility (odds ratio 0.68 95% confidence interval 0.55 to 0.83 p = 0.0002). After a conditional case-control test we observed that the effect of these two genetic variants was independent of linkage disequilibrium.These results suggest that the IL23R gene seems to be involved in AS genetic predisposition.
Randomized, Double-Blind, Active-Controlled Trial of Every-3-Week Darbepoetin Alfa for the Treatment of Chemotherapy-Induced Anemia
Authors: Jean-Luc Canon, Johan Vansteenkiste, György Bodoky, M. Victoria Mateos, Laurent Bastit, Irene Ferreira, Greg Rossi, Rafael G. Amado
Journal: JNCI Journal of the National Cancer Institute (2006)

In the United States, darbepoetin alfa (Aranesp) is often used to treat patients with chemotherapy-induced anemia using weekly or every-2-week administration schedules. In Europe, darbepoetin alfa is used either weekly or in every-3-week dosing. The every-3-week schedule can be synchronized with many chemotherapy regimens, resulting in fewer visits and reducing burden to patients, but the safety and efficacy of this regimen have not been clear.A randomized, double-blind, double-dummy, active-controlled phase 3 trial was performed in 110 European centers. Eligible patients (age > or = 18 years) were anemic (hemoglobin level < 11 g/dL), had a nonmyeloid malignancy, and were to receive at least 12 weeks of chemotherapy. Patients were randomly assigned 1:1 to darbepoetin alfa treatment every 3 weeks (500-microg dose) or weekly (2.25-microg/kg) for 15 weeks. We compared red blood cell transfusion incidence among the two arms from week 5 to the end of the treatment phase using a noninferiority study design. Noninferiority was determined if the upper limit of the 95% confidence interval (CI) for the difference in blood transfusions between groups, calculated using Kaplan-Meier methods, did not exceed 12.5%, a margin based on previous placebo-controlled studies.A total of 705 patients were randomly assigned, and 672 remained in the study at week 5. Fewer patients in the every-3-week arm than in the weekly arm received blood transfusions from week 5 to the end of the treatment phase (unadjusted Kaplan-Meier estimates = 23% versus 30%, difference = -6.8%; 95% CI = -13.6 to 0.1). Percentages of patients achieving the target hemoglobin level (> or = 11 g/dL, consistent with evidence-based practice guidelines) were 84% (every 3 weeks) and 77% (weekly). The frequency of cardiovascular/thromboembolic adverse events was 8% in both groups, and safety was comparable.Patients with chemotherapy-induced anemia can safely and effectively be treated with 500 microg of darbepoetin alfa every 3 weeks.
The <i>HOXB13:IL17BR</i> Expression Index Is a Prognostic Factor in Early-Stage Breast Cancer
Authors: Xiao-Jun Ma, Susan G. Hilsenbeck, Wilson Wang, Li Ding, Dennis C. Sgroi, Richard A. Bender, C. Kent Osborne, D. Craig Allred, Mark G. Erlander
Journal: Journal of Clinical Oncology (2006)

We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility.Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models.ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007).This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.
The association of prolonged breastfeeding and allergic disease in poor urban children
Authors: C. C. Obihara, B. J. Marais, R. P. Gie, P. Potter, E. D. Bateman, C. J. Lombard, N. Beyers, J. L. L. Kimpen
Journal: European Respiratory Journal (2005)

The fact that breastfeeding may protect against allergic disease remains controversial, with hardly any reports from developing countries. This study investigated the association between allergic disease in children and prolonged breastfeeding. Data were collected from a 15% random sample of households from two poor suburbs of Cape Town, South Africa. Parents completed a validated International Study on Asthma and Allergies in Childhood questionnaire on allergic diseases for children aged 6–14 yrs. Other questions included breastfeeding duration, maternal smoking and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household. Out of the 861 children included in the study, allergic disease in general, and hay fever in particular, were significantly less frequent in those with prolonged (≥6 months) breastfeeding. There was a significant linear inverse association between breastfeeding duration and allergic disease in children without allergic parents, but not in children with an allergic predisposition. In conclusion, these results from a developing country suggest a protective effect of prolonged breastfeeding on the development of allergic disease, particularly hay fever, in children born to nonallergic parents. This protective effect was not found in children with an allergic predisposition.
STUDIES ON ANTIBODY PRODUCTION
Authors: Robert G. White, Albert H. Coons, Jeanne M. Connolly
Journal: The Journal of Experimental Medicine (1955)

After injection of ovalbumin as a water-in-oil emulsion a pronounced adjuvant effect is demonstrable following the incorporation of tubercle bacillary wax into the oily phase of the mixture. With single doses of antigen (10 mg. ovalbumin) there is a 4- to 5-fold increase in the amount of antibody at the median of 3 week serum levels in animals receiving a small dose of wax (40 microg.). With a 5 mg. dose of wax there is an 8-fold increase in serum antibody levels at the median. A striking feature of the action of wax is the stimulation of a macrophage proliferation locally at the site of injection, and the production of morphological abnormalities in these cells. As judged by staining techniques for antibody content, these locally assembled cells are not active in the formation of antibody. Wax injected in mineral oil results in a remarkable systematized stimulation of the reticulo-endothelial system. The greatly increased serum antibody levels demonstrated after the use of tubercle bacillary wax in antigen mixtures is attributed to a widespread proliferation of plasma cell elements in the lymphatic glands, spleen and liver.
Ecstasy induced pneumomediastinum.
Authors: K. Rezvani, A. S. Kurbaan, D. Brenton
Journal: Thorax (1996)

Two cases are reported of pneumomediastinum induced by the use of Ecstasy, a semi-synthetic hallucinogenic compound related to amphetamine and mescaline which has become established as a recreational drug in the UK since the late 1980s. Both cases recovered without incident, but it is important that the possible complications of this drug be publicised so that at risk subjects can be diagnosed early and managed appropriately.
Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication
Authors: Francesc Bosch, Ana Ferrer, Neus Villamor, Marcos González, Javier Briones, Eva González-Barca, Eugenia Abella, Santiago Gardella, Lourdes Escoda, Elena Pérez-Ceballos, Antoni Asensi, Ma José Sayas, Llorenç Font, Albert Altés, Ana Muntañola, Paola Bertazzoni, María Rozman, Marta Aymerich, Eva Giné, Emili Montserrat
Journal: Clinical Cancer Research (2008)

Fludarabine, cyclophosphamide, and mitoxantrone (FCM) results in a high response rate in previously treated patients with chronic lymphocytic leukemia (CLL). The aim of this study was to investigate FCM as frontline therapy in CLL.Sixty-nine patients under the age of 65 years with active CLL were treated. Patients received six cycles of fludarabine 25 mg/m(2) i.v. x 3 days, cyclophosphamide 200 mg/m(2) i.v. x 3 days, and mitoxantrone 6 mg/m(2) i.v. x 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating minimal residual disease (MRD) was also analyzed.The overall response, MRD-negative complete response (CR), MRD-positive CR, nodular partial response (PR), and PR rates were 90%, 26%, 38%, 14%, and 12%, respectively. Severe (grades 3 or 4) neutropenia developed in 10% of the patients. Major and minor infections were reported in 1% and 8% of cases, respectively. Median response duration was 37 months. Patients with del(17p) failed to attain CR. Patients achieving MRD-negative CR had a longer response duration and overall survival than patients with an inferior response. Low serum lactate dehydrogenase levels, low ZAP-70 expression, and mutated IgV(H) genes predicted longer response duration. Finally, both low ZAP-70 and CD38 expression in leukemic cells correlated with MRD-negativity achievement.FCM induces a high response rate, including MRD-negative CRs in untreated patients with active CLL. Treatment toxicity is acceptable. Both high ZAP-70 and increased CD38 expression predict failure to obtain MRD-negative response. Patients in whom MRD can be eradicated have longer response duration and overall survival than those with inferior response. These results indicate that FCM can be an ideal companion for chemoimmunotherapy of patients with CLL.