tbuckley/cabot-search huggingface dataset:
A Randomised Trial Comparing Holmium Laser Enucleation Versus Transurethral Resection in the Treatment of Prostates Larger Than 40Grams: Results at 2 Years
Authors: Liam C. Wilson, Peter J. Gilling, Andrew Williams, Katie M. Kennett, Chris M. Frampton, Andre M. Westenberg, Mark R. Fraundorfer
Journal: European Urology (2006)
A model for the release of adsorbed molecules from the surfaces of airborne particulate matter based on liquid-phase desorption from amorphous carbon blacks.
Authors: T H Risby, S S Sehnert, L Jiang, B S Dhingra
Journal: Environmental Health Perspectives (1988)

The release of molecules adsorbed on the surfaces of amorphous carbon blacks has been studied using liquid-solid chromatography. Adsorbate molecules, adsorbents, and mobile phases were selected on the basis of their relevance as models for the release of toxic agents adsorbed on inhalable environmental particulate matter that originates from the incomplete combustion of organic materials. The presence of surface active groups on the carbon blacks has been shown to adsorb and retain adsorbate molecules selectively, and this selectivity can be reduced by competition for these active groups by the displacing solvent. Release is also governed by the surface coverage of the particles and increases as coverage approaches the monolayer.
Counteracting Autophagy Overcomes Resistance to Everolimus in Mantle Cell Lymphoma
Authors: Laia Rosich, Sílvia Xargay-Torrent, Mónica López-Guerra, Elías Campo, Dolors Colomer, Gaël Roué
Journal: Clinical Cancer Research (2012)

Mantle cell lymphoma (MCL) is an aggressive B-lymphoid neoplasm with poor response to conventional chemotherapy and short survival. The phosphatidylinositol 3-kinase/Akt/mTOR survival pathway is constitutively activated in MCL cells, thereby making the mTOR inhibition an attractive therapeutic strategy. The first clinical studies of everolimus (RAD001), an mTOR inhibitor, in relapsed MCL patients have reported a significant response. Our aim was to analyze the mechanism related to everolimus resistance/sensitivity in MCL cells.Sensitivity to everolimus was analyzed in MCL cell lines and primary MCL cells. Everolimus mechanism of action was determined by flow cytometry and Western blot. Particularly, autophagy was studied by LC3BI/II expression, autophagolysosomes detection by flow cytometry and fluorescence microscopy, and siRNA-mediated gene silencing.Everolimus exerted antitumoral effect on MCL cells while sparing normal cells. In MCL cell lines, this phenomenon was associated to G(1) cell-cycle arrest, dephosphorylation of the mTOR downstream targets, 4E-BP1 and S6RP, and rephosphorylation of Akt. A synergistic cytotoxic effect was observed between everolimus and an Akt inhibitor, which overcame the compensatory reactivation within the mTOR signaling pathway. Interestingly, MCL cells with low response to this combination showed high levels of autophagy. Accordingly, selective triple knockdown of the autophagy genes ATG7, ATG5 and ATG3, and pretreatment with the autophagy inhibitor hydroxychloroquine, efficiently overcame the resistance to Akt/mTOR inhibitors, leading to the activation of the mitochondrial apoptotic pathway.These results suggest that autophagy induction protects MCL cells from Akt/mTOR targeting and counteracting autophagy may represent an attractive strategy for sensitizing MCL cells to everolimus-based therapy.
Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction
Authors: Christian A. Bauer, Edward Y. Kim, Francesco Marangoni, Esteban Carrizosa, Natalie M. Claudio, Thorsten R. Mempel
Journal: Journal of Clinical Investigation (2014)

Tregs control various functions of effector T cells; however, where and how Tregs exert their immunomodulatory effects remain poorly understood. Here we developed a murine model of adoptive T cell therapy and found that Tregs induce a dysfunctional state in tumor-infiltrating CTLs that resembles T cell exhaustion and is characterized by low expression of effector cytokines, inefficient cytotoxic granule release, and coexpression of coinhibitory receptors PD-1 and TIM-3. Induction of CTL dysfunction was an active process, requiring local TCR signals in tumor tissue. Tregs infiltrated tumors only subsequent to Ag-dependent activation and expansion in tumor-draining LNs; however, Tregs also required local Ag reencounter within tumor tissue to induce CTL dysfunction and prevent tumor rejection. Multiphoton intravital microscopy revealed that in contrast to CTLs, Tregs only rarely and briefly interrupted their migration in tumor tissue in an Ag-dependent manner and formed unstable tethering-interactions with CD11c+ APCs, coinciding with a marked reduction of CD80 and CD86 on APCs. Activation of CTLs by Treg-conditioned CD80/86lo DCs promoted enhanced expression of both TIM-3 and PD-1. Based on these data, we propose that Tregs locally change the costimulatory landscape in tumor tissue through transient, Ag-dependent interactions with APCs, thus inducing CTL dysfunction by altering the balance of costimulatory and coinhibitory signals these cells receive.
Successful treatment of inflammatory linear verrucous epidermal naevus with topical natural vitamin D3 (calcitriol)
Authors: M. Bohm, T.A. Luger, H. Traupe
Journal: British Journal of Dermatology (2003)

Journal Article Successful treatment of inflammatory linear verrucous epidermal naevus with topical natural vitamin D3 (calcitriol) Get access M. Böhm, M. Böhm Department of Dermatology, University of Münster, Von Esmarch‐Str. 58, D‐48149 Münster, Germany E‐mail: bohmm@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar T.A. Luger, T.A. Luger Department of Dermatology, University of Münster, Von Esmarch‐Str. 58, D‐48149 Münster, Germany E‐mail: bohmm@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar H. Traupe H. Traupe Department of Dermatology, University of Münster, Von Esmarch‐Str. 58, D‐48149 Münster, Germany E‐mail: bohmm@uni‐muenster.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 4, 1 April 2003, Pages 824–825, https://doi.org/10.1046/j.1365-2133.2003.05194.x Published: 01 April 2003
Determining Risk for Severe Leptospirosis by Molecular Analysis of Environmental Surface Waters for Pathogenic Leptospira
Authors: Christian A Ganoza, Michael A Matthias, Devon Collins-Richards, Kimberly C Brouwer, Calaveras B Cunningham, Eddy R Segura, Robert H Gilman, Eduardo Gotuzzo, Joseph M Vinetz
Journal: PLoS Medicine (2006)

Background Although previous data indicate that the overall incidence of human leptospirosis in the Peruvian Amazon is similar in urban and rural sites, severe leptospirosis has been observed only in the urban context. As a potential explanation for this epidemiological observation, we tested the hypothesis that concentrations of more virulent Leptospira would be higher in urban than in rural environmental surface waters. Methods and Findings A quantitative real-time PCR assay was used to compare levels of Leptospira in urban and rural environmental surface waters in sites in the Peruvian Amazon region of Iquitos. Molecular taxonomic analysis of a 1,200-bp segment of the leptospiral 16S ribosomal RNA gene was used to identify Leptospira to the species level. Pathogenic Leptospira species were found only in urban slum water sources (Fisher's exact test; p = 0.013). The concentration of pathogen-related Leptospira was higher in urban than rural water sources (~103 leptospires/ml versus 0.5 × 102 leptospires/ml; F = 8.406, p < 0.05). Identical 16S rRNA gene sequences from Leptospira interrogans serovar Icterohaemorrhagiae were found in urban slum market area gutter water and in human isolates, suggesting a specific mode of transmission from rats to humans. In a prospective, population-based study of patients presenting with acute febrile illness, isolation of L. interrogans-related leptospires from humans was significantly associated with urban acquisition (75% of urban isolates); human isolates of other leptospiral species were associated with rural acquisition (78% of rural isolates) (chi-square analysis; p < 0.01). This distribution of human leptospiral isolates mirrored the distribution of leptospiral 16S ribosomal gene sequences in urban and rural water sources. Conclusions Our findings data support the hypothesis that urban severe leptospirosis in the Peruvian Amazon is associated with higher concentrations of more pathogenic leptospires at sites of exposure and transmission. This combined quantitative and molecular taxonomical risk assessment of environmental surface waters is globally applicable for assessing risk for leptospiral infection and severe disease in leptospirosis-endemic regions.
Fibrinogen-Coated Droplets of Olive Oil for Delivery of Docetaxel to a Fibrin(ogen)-Rich Ascites Form of a Murine Mammary Tumor
Authors: Charity M. Einhaus, Andrew C. Retzinger, Andre O. Perrotta, Michael D. Dentler, Abhijeet S. Jakate, Pankaj B. Desai, Gregory S. Retzinger
Journal: Clinical Cancer Research (2004)

Abstract Micronized droplets of olive oil loaded with docetaxel and coated with functional fibrinogen were administered intraperitoneally to mice bearing the fibrin(ogen)-rich ascites form of the TA3/St mammary tumor. When compared with docetaxel administered intraperitoneally as its commercial formulation (i.e., Taxotere), docetaxel-loaded oil droplets coated with murine fibrinogen prolonged the median survival time of tumor-bearing mice from 14.5 to 29.5 days. Drug-free oil droplets provided no therapeutic benefit. Significantly more docetaxel was associated with tumor cells 24 and 48 hours after administration of the drug in fibrinogen-coated oil droplets than after its administration as Taxotere. Consistent with a role for thrombin in the retention of fibrinogen-coated oil droplets within the tumor microenvironment, hirudin significantly reduced the association of tumor cells with docetaxel delivered in fibrinogen-coated oil droplets and, at the same time, reduced the therapeutic efficacy of the droplets to that of Taxotere. Importantly, fibrinogen-coated oil droplets formed rosettes with tumor cells in vivo, a process prevented by hirudin. Although mice treated with oil droplets developed antifibrinogen antibodies, those antibodies seemed to be inconsequential. Taken together, our results and observations indicate fibrinogen-coated oil droplets markedly improve the therapeutic efficacy of docetaxel for the treatment of a mammary tumor grown in ascites form, a consequence of thrombin-mediated retention of the drug-loaded droplets within the tumor microenvironment.
Circulating haemopoietic and endothelial progenitor cells are decreased in COPD
Authors: P. Palange, U. Testa, A. Huertas, L. Calabrò, R. Antonucci, E. Petrucci, E. Pelosi, L. Pasquini, A. Satta, G. Morici, M. A. Vignola, M. R. Bonsignore
Journal: European Respiratory Journal (2006)

Circulating CD34+ cells are haemopoietic progenitors that may play a role in tissue repair. No data are available on circulating progenitors in chronic obstructive pulmonary disease (COPD). Circulating CD34+ cells were studied in 18 patients with moderate-to-severe COPD (age: mean± sd 68±8 yrs; forced expiratory volume in one second: 48±12% predicted) and 12 controls, at rest and after endurance exercise. Plasma concentrations of haematopoietic growth factors (FMS-like tyrosine kinase 3 (Flt3) ligand, kit ligand), markers of hypoxia (vascular endothelial growth factor (VEGF)) and stimulators of angiogenesis (VEGF, hepatocyte growth factor (HGF)) and markers of systemic inflammation (tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8) were measured. Compared with the controls, the COPD patients showed a three-fold reduction in CD34+ cell counts (3.3±2.5 versus 10.3±4.2 cells·µL −1 ), and a 50% decrease in AC133+ cells. In the COPD patients, progenitor-derived haemopoietic and endothelial cell colonies were reduced by 30–50%. However, four COPD patients showed progenitor counts in the normal range associated with lower TNF-α levels. In the entire sample, CD34+ cell counts correlated with exercise capacity and severity of airflow obstruction. After endurance exercise, progenitor counts were unchanged, while plasma Flt3 ligand and VEGF only increased in the COPD patients. Plasma HGF levels were higher in the COPD patients compared with the controls and correlated inversely with the number of progenitor-derived colonies. In conclusion, circulating CD34+ cells and endothelial progenitors were decreased in chronic obstructive pulmonary disease patients and could be correlated with disease severity.
Expression of the functional cone phototransduction cascade in retinoblastoma.
Authors: R L Hurwitz, E Bogenmann, R L Font, V Holcombe, D Clark
Journal: Journal of Clinical Investigation (1990)

Retinoblastoma is a malignant intraocular tumor that primarily affects small children. These tumors are primitive neuroectodermal malignancies, however some of them show morphologic evidence of differentiation into photoreceptors. Phototransduction cascades are a series of biochemical reactions that convert a photon of light into a neural impulse in rods and cones. The components of these cascades are uniquely expressed in photoreceptors and, although functionally similar, distinct components of these cascades are expressed in rods and cones. Using HPLC anion exchange chromatography, Western blot analysis, and specific monoclonal and polyclonal antibodies, we found that the cone but not the rod cGMP phosphodiesterase is functionally expressed in all six primary retinoblastomas examined and in three continuous retinoblastoma cell lines. Morphologic evidence of differentiation did not correlate with the expression of the enzyme. Furthermore, GTP analogues could activate the phosphodiesterase activity suggesting that an intact phototransduction cascade is present in the tumors. The presence of the cone phototransduction cascade in retinoblastoma confirms that this tumor has biochemically differentiated along the cone cell lineage.
Text messaging as a new method for injury registration in sports - a methodological study in elite female football
Authors: A Nilstad, R Bahr, T E Andersen
Journal: British Journal of Sports Medicine (2011)

Background Injury registration is a necessary first step of injury prevention research in sports. However, inconsistencies in injury definitions and recording methods may have contributed to discrepancies in injury rates reported. Previous studies have traditionally been based on injury reporting by team medical staff. Objective To evaluate a novel methodology employing text messaging (SMS) by players to record injuries, comparing it to routine injury registration by team medical staff. Design Prospective study. Methods All teams in the Norwegian elite female football league (N=12, 205 players) reported injuries and exposure in training and matches throughout the 2009 football season (April-November). For the individual registration, we used a new SMS tracking system; all players received three messages once weekly with questions on exposure and injuries. Players reporting time-loss injuries were contacted to complete an injury form through a telephone interview. A designated member of the team medical staff also recorded injuries and team exposure throughout the season. Results We compared data from teams with complete registrations (n=9, 159 players). A total of 232 time-loss injuries were reported; 62% were recorded by individual registration only, 28% by both methods, and 10% by medical staff only. Knee injuries dominated (26%), but only 41% were captured through medical staff reports. The most frequent injury type was ligament injuries (22%), of which 38% were reported by the medical staff. Of the severe injuries (absence &gt;28 days), 31 (50%) were identified from medical staff reports. Discussion The medical staff reports underestimated the incidence of time-loss injuries by two-thirds in our setting, which emphasises the importance of individual registration to increase the accuracy of injury incidence in team sports. Conclusion A new method employing text messaging by players to record injuries gave a more complete picture of injuries to elite female football players than team medical staff registration.
Screening Adults for Type 2 Diabetes: A Review of the Evidence for the U.S. Preventive Services Task Force
Authors: Susan L. Norris, Devan Kansagara, Christina Bougatsos, Rongwei Fu
Journal: Annals of Internal Medicine (2008)

Background: More than 19 million Americans are affected by type 2 diabetes mellitus, which is undiagnosed in one third of these persons. In addition, it is estimated that more than 54 million adults have prediabetes. Debate continues over the benefits and harms of screening and then treating adults who have asymptomatic diabetes or prediabetes. Purpose: To update the 2003 U.S. Preventive Services Task Force review on the evidence for potential benefits and harms of screening adults for type 2 diabetes and prediabetes in primary care settings. Data Sources: MEDLINE and the Cochrane Library for relevant studies and systematic reviews published in English between March 2001 and July 2007. Study Selection: Trials and observational studies that directly addressed the effectiveness and adverse effects of screening interventions were included. Randomized, controlled trials were used to assess the effectiveness of diabetes and prediabetes treatments. For diabetes interventions, trials of patients with disease for 1 year or less were included, as well as trials comparing outcomes among diabetic and nondiabetic patients. Data Extraction: Relevant data were abstracted in duplicate into a standardized template. Data Synthesis: Data were synthesized in a qualitative manner, and a random-effects meta-analysis of the effects of interventions in prediabetes on the incidence of diabetes was performed. Limitations: Most of the data on diabetes treatment were not from primary trial data but from subgroup analyses. Participants in intensive lifestyle interventions for prediabetes may not be representative of general prediabetic populations. Conclusion: Direct evidence is lacking on the health benefits of detecting type 2 diabetes by either targeted or mass screening, and indirect evidence also fails to demonstrate health benefits for screening general populations. Persons with hypertension probably benefit from screening, because blood pressure targets for persons with diabetes are lower than those for persons without diabetes. Intensive lifestyle and pharmacotherapeutic interventions reduce the progression of prediabetes to diabetes, but few data examine the effect of these interventions on long-term health outcomes.
Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin–Cohort Study in Ontario, Canada
Authors: Harvey A Risch, John R McLaughlin, David E C Cole, Barry Rosen, Linda Bradley, Isabel Fan, James Tang, Song Li, Shiyu Zhang, Patricia A Shaw, Steven A Narod
Journal: JNCI Journal of the National Cancer Institute (2006)

BRCA1 and BRCA2 mutations in general populations and in various types of cancers have not been well characterized. We investigated the presence of these mutations in unselected patients with newly diagnosed incident ovarian cancer in Ontario, Canada, with respect to cancers reported among their relatives.A population series of 1171 unselected patients with incident ovarian cancer diagnosed between January 1, 1995, and December 31, 1999, in Ontario, Canada, was screened for germline mutations throughout the BRCA1 and BRCA2 genes. Screening involved testing for common variants, then protein truncation testing of long exons, and then denaturing gradient gel electrophoresis or denaturing high-performance liquid chromatography for the remainder of BRCA1 and BRCA2, respectively. Cox regression analysis was used to examine cancer outcomes reported by the case probands for their 8680 first-degree relatives. Population allele frequencies and relative risks (RRs) were derived from the regression results by an extension of Saunders-Begg methods. Age-specific Ontario cancer incidence rates were used to estimate cumulative incidence of cancer to age 80 years by mutation status.Among 977 patients with invasive ovarian cancer, 75 had BRCA1 mutations and 54 had BRCA2 mutations, for a total mutation frequency of 13.2% (95% confidence interval [CI] = 11.2% to 15.5%). Higher risks for various cancer types in the general Ontario population were associated with BRCA1 mutation carriage than with noncarriage, including ovarian (RR = 21, 95% CI = 12 to 36), female breast (RR = 11, 95% CI = 7.5 to 15), and testis (RR = 17, 95% CI = 1.3 to 230) cancers. Higher risks were also associated with BRCA2 mutation carriage than with noncarriage, particularly for ovarian (RR = 7.0, 95% CI = 3.1 to 16), female and male breast (RR = 4.6, 95% CI = 2.7 to 7.8, and RR = 102, 95% CI = 9.9 to 1050, respectively), and pancreatic (RR = 6.6, 95% CI = 1.9 to 23) cancers. Cancer risks differed according to the mutation's position in the gene. Estimated cumulative incidence to age 80 years among women carrying BRCA1 mutations was 24% for ovarian cancer and 90% for breast cancer and among women carrying BRCA2 mutations was 8.4% for ovarian cancer and 41% for breast cancer. For the general Ontario population, estimated carrier frequencies of BRCA1 and BRCA2 mutations, respectively, were 0.32% (95% CI = 0.23% to 0.45%) and 0.69% (95% CI = 0.43% to 1.10%).BRCA1 and BRCA2 mutations may be more frequent in general populations than previously thought and may be associated with various types of cancers.
Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction
Authors: Giancarlo Paradisi, Helmut O. Steinberg, Annette Hempfling, Jessica Cronin, Ginger Hook, Marguerite K. Shepard, Alain D. Baron
Journal: Circulation (2001)

Background —We recently reported endothelial dysfunction as a novel cardiovascular risk factor associated with insulin resistance/obesity. Here, we tested whether hyperandrogenic insulin-resistant women with polycystic ovary syndrome (PCOS) who are at increased risk of macrovascular disease display impaired endothelium-dependent vasodilation and whether endothelial function in PCOS is associated with particular metabolic and/or hormonal characteristics. Methods and Results —We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) and to euglycemic hyperinsulinemia in 12 obese women with PCOS and in 13 healthy age- and weight-matched control subjects (OBW). LBF increments in response to MCh were 50% lower in the PCOS group than in the OBW group ( P &lt;0.01). Euglycemic hyperinsulinemia increased LBF above baseline by 30% in the PCOS and 60% in OBW group ( P &lt;0.05 between groups). Across all subjects, the maximal LBF response to MCh exhibited a strong inverse correlation with free testosterone levels ( r =−0.52, P &lt;0.007). This relationship was stronger than with any other parameter, including insulin sensitivity. Conclusions —PCOS is characterized by (1) endothelial dysfunction and (2) resistance to the vasodilating action of insulin. This endothelial dysfunction appears to be associated with both elevated androgen levels and insulin resistance. Given the central vasoprotective role of endothelium, these findings could explain, at least in part, the increased risk for macrovascular disease in women with PCOS.