tbuckley/cabot-search huggingface dataset:
Chemosensitization and Delayed Androgen-Independent Recurrence of Prostate Cancer With the Use of Antisense Bcl-2 Oligodeoxynucleotides
Authors: H. Miayake, A. Tolcher, M. E. Gleave
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND: Increased expression of the bcl-2 gene has been observed in prostate cancer cells after androgen withdrawal and has been associated with the development of androgen independence and chemoresistance. The objective of this study was to determine whether antisense Bcl-2 oligodeoxynucleotides could enhance paclitaxel cytotoxicity and delay androgen-independent progression. METHODS: Northern and western blot analyses were used to measure changes in Bcl-2 expression in mouse Shionogi tumor cells after treatment with antisense Bcl-2 oligodeoxynucleotides and/or paclitaxel. Growth inhibition and induction of apoptotic cell death were assessed with the use of standard methods. All P values are two-sided. RESULTS: Treatment of Shionogi tumor cells with 500 nM antisense Bcl-2 oligodeoxynucleotides decreased expression of Bcl-2 messenger RNA (mRNA) by approximately 85%. Paclitaxel treatment induced Bcl-2 protein phosphorylation but did not alter Bcl-2 mRNA expression. Antisense Bcl-2 oligodeoxynucleotide treatment substantially enhanced paclitaxel chemosensitivity in a dose-dependent manner. Characteristic apoptotic DNA laddering and cleavage of poly(adenosine diphosphate-ribose) polymerase were demonstrated only after combined treatment. Adjuvant in vivo administration of antisense Bcl-2 oligodeoxynucleotides and micellar paclitaxel following castration resulted in a statistically significant delay of androgen-independent, recurrent tumors compared with administration of either agent alone (P<.001, Mantel-Cox log-rank test). Combination therapy also statistically significantly inhibited the growth of established hormone-refractory tumors compared with treatment with either agent alone (P<.001, Student's t test). CONCLUSIONS. Combined treatment with antisense Bcl-2 oligodeoxynucleotides and paclitaxel could be a novel and attractive strategy to inhibit progression to androgen-independent disease as well as growth of hormone-refractory prostate cancer through deprivation of Bcl-2 function.
Assessment of health state utilities of controlled and uncontrolled psoriasis and atopic eczema: a population-based study
Authors: J. Schmitt, M. Meurer, M. Klon, K.D. Frick
Journal: British Journal of Dermatology (2007)

Health utilities are used to express relevant trade-offs for resource allocation. The absence of valid and generalizable utilities for atopic eczema (AE) and psoriasis limits the validity of previous cost-utility analyses.(i) To assess health utilities of standardized scenarios of controlled and uncontrolled AE and psoriasis in participants from the general population and in patients using the time trade-off (TTO) method; (ii) to test the association of the utilities obtained with demographic and patient characteristics; and (iii) to compare these utilities with other health economic outcomes [utilities assessed on visual analogue scale (VAS), willingness to pay (WTP)].A single-centre study conducted in 2006 at the Department of Dermatology, Dresden, Germany. Standardized interactive computer-assisted interviews in a random sample from the general population (n=139), and patients with AE (n=58) and psoriasis (n=62). Information on health states included characteristic clinical pictures and a short text explaining aetiology, signs, symptoms and quality of life impact.In participants from the general population median utilities (TTO) of controlled and uncontrolled AE were 0.97 and 0.64, respectively. For psoriasis the corresponding utilities were 0.93 and 0.56. Utilities were independent of sex and socioeconomic position, and tended to be lower in patients with psoriasis. Correlations between TTO, VAS and WTP responses were weak.To avoid uncontrolled psoriasis or eczema participants chose an approximately 40% shorter life expectancy. This indicates that severe chronic inflammatory skin diseases may be considered as severe as angina pectoris, chronic anxiety, rheumatoid arthritis, multiple sclerosis or regional oesophageal cancer. The different economic outcomes assessed are not interchangeable.
Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition
Authors: G Zoli, G R Corazza, S Wood, R Bartoli, G Gasbarrini, M J G Farthing
Journal: Gut (1998)

Background —Reticuloendothelial system function is impaired in humans receiving lipid regimens. Aims —To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function. Methods —Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn’s disease who were not receiving intravenous nutrition, and 50 healthy controls. Results —Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p&lt;0.001) than in healthy controls (0.6%) and in patients with Crohn’s disease (0.9%). No difference was found between healthy controls and patients with Crohn’s disease. There was a correlation ( r =0.50; p&lt;0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p&lt;0.01) and healthy volunteers (17.8%, p&lt;0.001) . An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition ( r s =−0.44, p&lt;0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12 months. Conclusions —Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection.
Whole-genome single nucleotide polymorphism-based linkage analysis in spondyloarthritis multiplex families reveals a new susceptibility locus in 13q13
Authors: Félicie Costantino, Emmanuel Chaplais, Tifenn Leturcq, Roula Said-Nahal, Ariane Leboime, Elena Zinovieva, Diana Zelenika, Ivo Gut, Céline Charon, Gilles Chiocchia, Maxime Breban, Henri-Jean Garchon
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> Spondyloarthritis (SpA) is a chronic inflammatory disorder with high heritability but with complex genetics. Apart from HLA-B27, most of the underlying genetic components remain to be identified. We conducted a whole-genome high-density non-parametric linkage analysis to identify new genetic factors of susceptibility to SpA. <h3>Methods</h3> 914 subjects including 462 with SpA from 143 multiplex families were genotyped using Affymetrix 250K microarrays. After quality control, 189 368 single nucleotide polymorphisms (SNPs) were kept for further analyses. Both non-parametric and parametric linkage analyses were performed using Merlin software. Association was tested with Unphased. <h3>Results</h3> Non-parametric linkage analysis identified two regions significantly linked to SpA: the major histocompatibility complex (LOD<sub>max</sub>=24.77) and a new 13q13 locus (LOD<sub>max</sub>=5.03). Additionally, eight loci achieved suggestive LOD scores, including the previously identified SPA2 locus at 9q33 (LOD<sub>max</sub>=3.51). Parametric analysis supported a codominant model in 13q13 with a maximum heterogeneity LOD, 'HLOD' score of 3.084 (α=0.28). Identification of meiotic recombination events around the 13q13 linkage peak in affected subjects from the 43 best-linked families allowed us to map the disease interval between 38.753 and 40.040 Mb. Family-based association analysis of the SNPs inside this interval in the best-linked families identified a SNP near <i>FREM2</i> (rs1945502) which reached a p value close to statistical significance (corrected p=0.08). <h3>Conclusion</h3> We report here for the first time a significant linkage between 13q13 and SpA. Identification of susceptibility factor inside this chromosomal region through targeted sequencing in linked families is underway.
Prospective Study of Quantitation of Plasma DNA Levels in the Diagnosis of Malignant versus Benign Prostate Disease
Authors: Jane L. Boddy, Shira Gal, Peter R. Malone, Adrian L. Harris, Jim S. Wainscoat
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of this study was to determine the potential of cell-free DNA levels as a diagnostic marker for prostate cancer, having first established the effect that blood sample processing has on this measurement. Experimental Design: A total of 152 blood samples were collected prospectively from patients before their prostate biopsy and 25 from men in two distinct control groups. Blood was processed to yield three components: one-spin plasma (n = 68), two-spin plasma (n = 152), and serum (n = 56) samples. Results: Having established the effect of sample preparation on the measured DNA level, the more reliable two-spin plasma sample was used to determine the relationship between DNA and the presence of prostate cancer. Those patients with cancer (n = 78) had a significantly higher level of DNA compared with the control groups (P &amp;lt; 0.0001 and P &amp;lt; 0.0001). However, DNA levels in patients with a benign biopsy (n = 74) were significantly higher than the 78 patients confirmed to have cancer (P = 0.02). Conclusions: We conclude that the sample type used in the quantitation of cell-free DNA has an effect on the level reported. Elevated levels are present in the two-spin plasma samples of patients with prostate cancer compared with healthy controls but are not of diagnostic value during the management of prostate cancer.
Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial
Authors: Maria J Wawer, Nelson K Sewankambo, David Serwadda, Thomas C Quinn, Noah Kiwanuka, Chuanjun Li, Thomas Lutalo, Fred Nalugoda, Charlotte A Gaydos, Lawrence H Moulton, Saifuddin Ahmed, Ronald H Gray, Lynn A Paxton, Fred Wabwire-Mangen, Mary O Meehan
Journal: The Lancet (1999)

The study tested the hypothesis that community-level control of sexually transmitted disease (STD) would result in lower incidence of HIV-1 infection in comparison with control communities.This randomised, controlled, single-masked, community-based trial of intensive STD control, via home-based mass antibiotic treatment, took place in Rakai District, Uganda. Ten community clusters were randomly assigned to intervention or control groups. All consenting residents aged 15-59 years were enrolled; visited in the home every 10 months; interviewed; asked to provide biological samples for assessment of HIV-1 infection and STDs; and were provided with mass treatment (azithromycin, ciprofloxacin, metronidazole in the intervention group, vitamins/anthelmintic drug in the control). Intention-to-treat analyses used multivariate, paired, cluster-adjusted rate ratios.The baseline prevalence of HIV-1 infection was 15.9%. 6602 HIV-1-negative individuals were enrolled in the intervention group and 6124 in the control group. 75.0% of intervention-group and 72.6% of control-group participants provided at least one follow-up sample for HIV-1 testing. At enrolment, the two treatment groups were similar in STD prevalence rates. At 20-month follow-up, the prevalences of syphilis (352/6238 [5.6%]) vs 359/5284 [6.8%]; rate ratio 0.80 [95% CI 0.71-0.89]) and trichomoniasis (182/1968 [9.3%] vs 261/1815 [14.4%]; rate ratio 0.59 [0.38-0.91]) were significantly lower in the intervention group than in the control group. The incidence of HIV-1 infection was 1.5 per 100 person-years in both groups (rate ratio 0.97 [0.81-1.16]). In pregnant women, the follow-up prevalences of trichomoniasis, bacterial vaginosis, gonorrhoea, and chlamydia infection were significantly lower in the intervention group than in the control group. No effect of the intervention on incidence of HIV-1 infection was observed in pregnant women or in stratified analyses.We observed no effect of the STD intervention on the incidence of HIV-1 infection. In the Rakai population, a substantial proportion of HIV-1 acquisition appears to occur independently of treatable STD cofactors.
High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset
Authors: M. Mullazehi, L. Mathsson, J. Lampa, J. Ronnelid
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To investigate whether the cytokine-inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC), which were reported earlier, have any clinical impact. <b>Methods:</b> Anti-CII serology was analysed in 274 patients with early rheumatoid arthritis (RA). Patients with increased levels of anti-CII were followed serially for 1–5 years with regard to anti-CII IC-induced levels of tumour necrosis factor (TNF)α, interleukin (IL)1β and IL8. Levels of antibodies and IC-induced cytokines were compared with clinical indices over 5 years of follow-up. <b>Results:</b> 5/100 healthy controls and 24/274 (8.8%) patients with RA exhibited increased levels (&gt;29 arbitrary units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274 (3.3%) patients with RA and no controls comprised a discrete group with high anti-CII levels &gt;450 AU/ml. These high anti-CII level sera were associated with induction of pro-inflammatory cytokines by anti-CII-containing IC formed in vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel decline in antibody levels, IC-induced cytokines, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had significantly increased levels of CRP and ESR at baseline, but not later during the follow-up. <b>Conclusions:</b> Anti-native CII-positive patients with RA have a distinct clinical phenotype characterised by an early acute phase response that might be driven by anti-CII-containing IC in joint cartilage.
IMP3 signatures of fallopian tube: a risk for pelvic serous cancers
Authors: Yiying Wang, Yue Wang, Dake Li, Lingmin Li, Wenjing Zhang, Guang Yao, Zhong Jiang, Wenxin Zheng
Journal: Journal of Hematology & Oncology (2014)

Recent advances suggest fallopian tube as the main cellular source for women’s pelvic serous carcinoma (PSC). In addition to TP53 mutations, many other genetic changes are involved in pelvic serous carcinogenesis. IMP3 is an oncofetal protein which has recently been observed to be overexpressed in benign-looking tubal epithelia. Such findings prompted us to examine the relationship between IMP3 over-expression, patient age and the likelihood of development of PSC. Fallopian tubes from three groups (low-risk, high-risk, and PSC) of patients with matched ages were studied. Age was recorded in 10 years intervals ranging from age 20 to older than 80. The number of IMP3 signatures (defined by 10 or more tubal secretory cells stained positively and continuously in benign appearing tubal mucosa) from both tubal fimbria and ampulla segments was measured. The data was analyzed by standard contingency table and Poisson distribution methods after age adjustment. IMP3 overexpression was also examined in serous tubal intraepithelial carcinoma and PSC. The positive IMP3-stained cells are mainly tubal secretory cells. The absolute number of tubal IMP3 signatures increased significantly within each age group. Age remained a significant risk factor for serous neoplasia after age adjustment. IMP3 signatures were more frequent in the patients of both high-risk and PSC groups. The presence of IMP3 signatures in tubal mucosa was significantly associated with tubal or pelvic serous carcinogenesis (p < 0.001). The findings suggest that tubal secretory cells with IMP3 signatures showing growth advantage could potentially serve as a latent precancer biomarker for tubal or pelvic serous carcinomas in women.
Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Authors: Aart J. van der Lely, Matthias Tschöp, Mark L. Heiman, Ezio Ghigo
Journal: Endocrine Reviews (2004)

Ghrelin is a peptide predominantly produced by the stomach. Ghrelin displays strong GH-releasing activity. This activity is mediated by the activation of the so-called GH secretagogue receptor type 1a. This receptor had been shown to be specific for a family of synthetic, peptidyl and nonpeptidyl GH secretagogues. Apart from a potent GH-releasing action, ghrelin has other activities including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, and influence on pancreatic exocrine and endocrine function as well as on glucose metabolism. Cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system, are other actions of ghrelin. Therefore, we consider ghrelin a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis. So, there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.
Capsule endoscopy in patients with suspected Crohn's disease - is the PillCam worth the swallow?
Authors: R. Kalla, M. E. McAlindon, K. Drew, R. Sidhu
Journal: Gut (2011)

Introduction Capsule endoscopy (CE) has developed an important role in the investigation pathway of patients with suspected Crohn's disease. However there is paucity of data on the long term outcome in this cohort. We investigated the utility of CE in patients with suspected Crohn's disease and impact on subsequent management. Methods All patients with suspected Crohn's disease referred routinely for CE between 2003 and 2009 were identified. Data was collected for patient demographics, previous investigations, findings at CE and subsequent follow up. Results A total of 265 patients were identified, 68% females, mean age 41 years (range 17–82 years). The majority of patients had symptoms of diarrhoea (80%) and abdominal pain (83%),while 33% (n=86) had weight loss. Raised inflammatory markers were present in 65% (n=172) and 18% (n=47) were iron deficient. Nine per cent (n=25) of patients were on non-steroidal anti-inflammatory drugs (NSAID). 94% of patients had colonoscopy prior to CE with TI biopsies in 60% (n=159). Although 20% (n=31/159) were macroscopically abnormal, 18 patients had normal TI histology with 13 showing non specific changes. Small bowel radiology was performed in 90% (n=239) prior to CE where 87% (n=207) were normal and 13% showed non-specific small bowel changes. CE was suggestive of Crohn's disease with the presence of ulcers (>3), oedema, petechiae and erythema in 17% (n=45). On logistic regression, abdominal pain (p=0.01), diarrhoea (p=0.002) and hypoalbuminaemia (p=0.014) were predictive of Crohn's disease on CE. Management was altered in 62% (n=164) of patients. Thirteen percent underwent therapy change (n=21; azathioprine/ methotrexate (n=6), steroids (n=7), infliximab (n=2) or mesalazine (n=6)). 49% (n=81) were discharged after a normal CE and 3% (n=5) were treated for irritable bowel syndrome. 42 patients (26%) had repeat histology post CE, 5 patients had their NSAIDs stopped and ten patients underwent other investigations/radiology post CE. An eventual diagnosis of Crohn's disease was made in 12% (n=31) after a mean follow up of 15 months (range 1–84). 14 patients had repeat histology of which 4 were confirmed Crohn's disease on biopsy and the other 10 were non-specific changes but with evidence of macroscopic ulceration and/or stricturing on enteroscopy. A further 14 patients were confirmed on the basis of their CE findings and their clinical response to treatment. In 3 patients management was unchanged either because of symptom resolution or treatment initiation prior to CE. Conclusion CE is a useful tool in patients with suspected Crohn's disease with a positive impact on patient management. Abdominal pain, diarrhoea and hypoalbuminaemia appear to be highly predictive of a yield with CE. CE also helps to rationalise management in those with normal findings.
Mutationally Activated BRAFV600E Elicits Papillary Thyroid Cancer in the Adult Mouse
Authors: Roch-Philippe Charles, Gioia Iezza, Elena Amendola, David Dankort, Martin McMahon
Journal: Cancer Research (2011)

Abstract Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAFV600E. One month following BRAFV600E expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAFV600E-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling. Cancer Res; 71(11); 3863–71. ©2011 AACR.
Sexual function problems and help seeking behaviour in Britain: national probability sample survey
Authors: Catherine H Mercer, Kevin A Fenton, Anne M Johnson, Kaye Wellings, Wendy Macdowall, Sally McManus, Kiran Nanchahal, Bob Erens
Journal: BMJ (2003)

Although similar findings have been reported in men who report same sex behaviour, 21 to our knowledge no other population study has focused specifically on sexual problems in bisexual as distinct from homosexual men.We thank Josephine Woolf for her collaboration in obtaining funding; Alice Gladwin, Monique Cloherty, and Üta Drescher for their assistance in collecting the data; and Bob Blizard