tbuckley/cabot-search huggingface dataset:
Temozolomide downregulates P-glycoprotein expression in glioblastoma stem cells by interfering with the Wnt3a/glycogen synthase-3 kinase/ -catenin pathway
Authors: C. Riganti, I. C. Salaroglio, V. Caldera, I. Campia, J. Kopecka, M. Mellai, L. Annovazzi, A. Bosia, D. Ghigo, D. Schiffer
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme stem cells display a highly chemoresistant phenotype, whose molecular basis is poorly known. We aim to clarify this issue and to investigate the effects of temozolomide on chemoresistant stem cells. A panel of human glioblastoma cultures, grown as stem cells (neurospheres) and adherent cells, was used. Neurospheres had a multidrug resistant phenotype compared with adherent cells. Such chemoresistance was overcome by apparently noncytotoxic doses of temozolomide, which chemosensitized glioblastoma cells to doxorubicin, vinblastine, and etoposide. This effect was selective for P-glycoprotein (Pgp) substrates and for stem cells, leading to an investigation of whether there was a correlation between the expression of Pgp and the activity of typical stemness pathways. We found that Wnt3a and ABCB1, which encodes for Pgp, were both highly expressed in glioblastoma stem cells and reduced by temozolomide. Temozolomide-treated cells had increased methylation of the cytosine–phosphate–guanine islands in the Wnt3a gene promoter, decreased expression of Wnt3a, disrupted glycogen synthase-3 kinase/β-catenin axis, reduced transcriptional activation of ABCB1, and a lower amount and activity of Pgp. Wnt3a overexpression was sufficient to transform adherent cells into neurospheres and to simultaneously increase proliferation and ABCB1 expression. On the contrary, glioblastoma stem cells silenced for Wnt3a lost the ability to form neurospheres and reduced at the same time the proliferation rate and ABCB1 levels. Our work suggests that Wnt3a is an autocrine mediator of stemness, proliferation, and chemoresistance in human glioblastoma and that temozolomide may chemosensitize the stem cell population by downregulating Wnt3a signaling.
Small Airway Function Improvement after Smoking Cessation in Smokers without Airway Obstruction
Authors: Sylvia Verbanck, Daniël Schuermans, Manuel Paiva, Marc Meysman, Walter Vincken
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Studying smokers with normal spirometry requires monitoring tools of the peripheral lung. A validated multiple breath washout technique was used to assess possible recovery of smoking-induced small airway malfunction in acinar and conductive lung zones.Eighty-seven smokers with a smoking history of at least 10 pack-years but absence of spirometric airflow obstruction were invited for assessment of lung function and small airway function at baseline and after 1 wk, 3 mo, 6 mo, and 12 mo of smoking cessation. A control group of 16 persistent smokers was studied at the same time intervals.Of the 87 smokers, 66, 32, 28, and 21% successfully ceased smoking for 1 wk, 3 mo, 6 mo, and 12 mo, respectively. Lung function parameters remained essentially unaffected by smoking cessation. Ventilation heterogeneity showed transient improvements after 1 wk in the acinar lung compartment with a return to baseline afterwards. By contrast, there were persistent improvements in the conductive airway compartment; for example, smokers who successfully quit smoking for 12 mo (n=18) showed a 30 and 42% reduction of conductive airways abnormality after 1 wk and 1 yr, respectively.Smokers with early signs of small airway malfunction who successfully quit smoking show sustained improvements of conductive airway malfunction. In contrast, acinar airway malfunction quickly returns to baseline after a transient improvement.
Acquired cystic disease in chronically rejected renal transplants.
Authors: W Y Chung, C C Nast, R B Ettenger, G M Danoviton, H J Ward, A H Cohen
Journal: Journal of the American Society of Nephrology (1992)

Acquired cystic disease has been documented to complicate most forms of chronic renal damage; it has only infrequently been described in transplanted kidneys. Five patients with noncystic ESRD and chronically rejected transplants in which acquired cystic disease arose are reported. The diagnosis of acquired cystic disease was established in examination of transplant nephrectomies from four patients and a core biopsy from the fifth. The allografts were in place from 44 to 80 months; three patients were treated with hemodialysis before the diagnosis of acquired cystic disease, whereas two received peritoneal dialysis. Three of the four patients evaluated had cysts in the native kidneys. Although papillary hyperplasia of lining epithelium was evident in four specimens, only one kidney was the site of neoplasms in the form of multiple small tubular adenomas. No malignant neoplasms were noted in this study or in the few similar previous ones; however, it is possible that chronically rejected transplanted kidneys may harbor neoplasms with the same malignant potential as those in acquired cystic disease in native kidneys.
Constitutively active HIF-1α improves perfusion and arterial remodeling in an endovascular model of limb ischemia
Authors: T PATEL, H KIMURA, C WEISS, G SEMENZA, L HOFMANN
Journal: Cardiovascular Research (2005)

Objective: Hypoxia-inducible factor 1 (HIF-1) regulates the expression of angiogenic growth factors. We analyzed the effect of intramuscular (i.m.) delivery of AdCA5, an adenovirus encoding a constitutively active form of the HIF-1α subunit, in a novel model of limb ischemia. Methods: AdCa5 or AdLacZ (6 × 108 pfu) was injected into male New Zealand White rabbits that were untreated or subjected to occlusion of the left superficial femoral artery by endovascular coils. Expression of mRNAs was quantified 1, 3, and 7 days after adenovirus injection into rabbits without occlusion. Calf blood pressure (BP), angiography, and immunohistochemical analyses were performed 14 days after arterial occlusion and adenovirus injection. Results: AdCA5 increased the expression of HIF-1α, monocyte chemotactic protein-1, placental growth factor, platelet-derived growth factor B, stromal-derived factor 1α, and vascular endothelial growth factor (VEGF) mRNA as well as HIF-1α and VEGF protein. On day 14, AdCA5-injected limbs showed improved calf BP ratios (0.89 ± 0.13 vs. 0.51 ± 0.05, p = 0.02), angiographic perfusion scores (3.50 ± 0.56 vs. 8.33 ± 1.31, p = 0.007), and distal deep femoral artery diameter ratio (1.84 ± 0.25 vs. 0.93 ± 0.22, p = 0.02) relative to those receiving AdLacZ. The capillary/myocyte ratio (0.93 ± 0.03 vs. 0.78 ± 0.06, p = 0.04) and arterial luminal area (0.32 ± 0.05 mm2 vs. 0.21 ± 0.03 mm2, p = 0.04) were significantly increased in the AdCA5 group. Conclusion: In a model that resembles atherosclerotic obstruction of peripheral arteries in patients, the i.m. administration of AdCA5 promoted arteriogenic and angiogenic responses.
Pruritic folliculitis of pregnancy
Authors: George Kroumpouzos, Lisa M. Cohen
Journal: Journal of the American Academy of Dermatology (2000)

Pruritic folliculitis of pregnancy is a rare pregnancy dermatosis that clears spontaneously in the postpartum period. We describe a patient with characteristic clinical and histopathologic features of this dermatosis. (J Am Acad Dermatol 2000;43:132-4.)
White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review
Authors: E. A. Hu, A. Pan, V. Malik, Q. Sun
Journal: BMJ (2012)

<b>Objectives</b> To summarise evidence on the association between white rice consumption and risk of type 2 diabetes and to quantify the potential dose-response relation. <b>Design</b> Meta-analysis of prospective cohort studies. <b>Data sources</b> Searches of Medline and Embase databases for articles published up to January 2012 using keywords that included both rice intake and diabetes; further searches of references of included original studies. <b>Study selection</b> Included studies were prospective cohort studies that reported risk estimates for type 2 diabetes by rice intake levels. <b>Data synthesis</b> Relative risks were pooled using a random effects model; dose-response relations were evaluated using data from all rice intake categories in each study. <b>Results</b> Four articles were identified that included seven distinct prospective cohort analyses in Asian and Western populations for this study. A total of 13 284 incident cases of type 2 diabetes were ascertained among 352 384 participants with follow-up periods ranging from 4 to 22 years. Asian (Chinese and Japanese) populations had much higher white rice consumption levels than did Western populations (average intake levels were three to four servings/day versus one to two servings/week). The pooled relative risk was 1.55 (95% confidence interval 1.20 to 2.01) comparing the highest with the lowest category of white rice intake in Asian populations, whereas the corresponding relative risk was 1.12 (0.94 to 1.33) in Western populations (P for interaction=0.038). In the total population, the dose-response meta-analysis indicated that for each serving per day increment of white rice intake, the relative risk of type 2 diabetes was 1.11 (1.08 to 1.14) (P for linear trend&lt;0.001). <b>Conclusion</b> Higher consumption of white rice is associated with a significantly increased risk of type 2 diabetes, especially in Asian (Chinese and Japanese) populations.
Temporary Disruption of the Blood–Brain Barrier by Use of Ultrasound and Microbubbles: Safety and Efficacy Evaluation in Rhesus Macaques
Authors: Nathan McDannold, Costas D. Arvanitis, Natalia Vykhodtseva, Margaret S. Livingstone
Journal: Cancer Research (2012)

The blood-brain barrier (BBB) prevents entry of most drugs into the brain and is a major hurdle to the use of drugs for brain tumors and other central nervous system disorders. Work in small animals has shown that ultrasound combined with an intravenously circulating microbubble agent can temporarily permeabilize the BBB. Here, we evaluated whether this targeted drug delivery method can be applied safely, reliably, and in a controlled manner on rhesus macaques using a focused ultrasound system. We identified a clear safety window during which BBB disruption could be produced without evident tissue damage, and the acoustic pressure amplitude where the probability for BBB disruption was 50% and was found to be half of the value that would produce tissue damage. Acoustic emission measurements seem promising for predicting BBB disruption and damage. In addition, we conducted repeated BBB disruption to central visual field targets over several weeks in animals trained to conduct complex visual acuity tasks. All animals recovered from each session without behavioral deficits, visual deficits, or loss in visual acuity. Together, our findings show that BBB disruption can be reliably and repeatedly produced without evident histologic or functional damage in a clinically relevant animal model using a clinical device. These results therefore support clinical testing of this noninvasive-targeted drug delivery method.
A cellular screening assay to test the ability of PKR to induce cell death in mammalian cells
Authors: Inbar Friedrich, Menahem Eizenbach, Julia Sajman, Hannah Ben-Bassat, Alexander Levitzki
Journal: Molecular Therapy (2005)

Long double-stranded RNA (>30 bp), usually expressed in cells infected with RNA viruses, triggers antiviral responses that induce apoptosis of the infected cells. PKR can be selectively activated in glioblastoma cells by in situ generation of dsRNA following introduction of antisense RNA complementary to an RNA expressed specifically in these cells. Harnessing PKR for the selective killing of cancer cells is potentially a powerful strategy for treating cancer, but we were unable to induce apoptosis by this approach in a T cell lymphoma. We therefore established a cellular screening assay to test the ability of PKR to induce death in cell lines, especially those originating from human cancers. This "PKR killing screen" is based on the infection of cells with an adenoviral vector encoding GyrB-PKR, followed by coumermycin treatment. Cancers represented by cell lines in which PKR activation leads to cell death are good candidates for the dsRNA killing approach, using antisense to RNA molecules specifically expressed in these cells. The PKR killing screen may also serve as a tool for exploring PKR signaling and other related pathways, by identifying new cases in which PKR signaling is inhibited or impaired.
Positional Identification of an Asthma Susceptibility Gene on Human Chromosome 5q33
Authors: Emiko Noguchi, Yukako Yokouchi, Jiang Zhang, Kazuko Shibuya, Akira Shibuya, Makoto Bannai, Katsushi Tokunaga, Hitomi Doi, Mayumi Tamari, Makiko Shimizu, Taro Shirakawa, Masanao Shibasaki, Kunio Ichikawa, Tadao Arinami
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Asthma is a common respiratory disease with complex genetic components. We previously reported strong evidence for linkage between mite-sensitive asthma and markers on chromosome 5q33. This area of linkage includes a region homologous to a mouse area that contains a locus involved in regulation of airway hyperreactivity. Objective: The aim of the present study is to identify asthma susceptibility genes on chromosome 5q33. Methods and Results: We performed mutation screening and association analyses of genes in the 9.4-Mb human linkage region. Transmission disequilibrium test analysis of 105 polymorphisms in 155 families with asthma revealed that six polymorphisms in cytoplasmic fragile X mental retardation protein (FMRP)–interacting protein 2 gene were associated significantly with the development of asthma (p = 0.000075; odds ratio, 5.9). These six polymorphisms were in complete linkage disequilibrium. In real-time quantitative polymerase chain reaction analysis, subjects homozygous for the haplotype overtransmitted to asthma-affected offspring showed significantly increased level of cytoplasmic FMRP interacting protein 2 gene expression in lymphocytes compared with ones heterozygous for the haplotype (p = 0.038). Conclusions: Our data suggest that cytoplasmic FMRP interacting protein 2 are associated with the development of atopic asthma in humans, and that targeting cytoplasmic FMRP interacting protein 2 could be a novel strategy for treating atopic asthma.
Negative Regulation of Myofibroblast Differentiation by PTEN (Phosphatase and Tensin Homolog Deleted on Chromosome 10)
Authors: Eric S. White, Rachelle G. Atrasz, Biao Hu, Sem H. Phan, Vuk Stambolic, Tak W. Mak, Cory M. Hogaboam, Kevin R. Flaherty, Fernando J. Martinez, Christopher D. Kontos, Galen B. Toews
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Myofibroblasts are primary effector cells in idiopathic pulmonary fibrosis (IPF). Defining mechanisms of myofibroblast differentiation may be critical to the development of novel therapeutic agents.To show that myofibroblast differentiation is regulated by phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity in vivo, and to identify a potential mechanism by which this occurs.We used tissue sections of surgical lung biopsies from patients with IPF to localize expression of PTEN and alpha-smooth muscle actin (alpha-SMA). We used cell culture of pten(-/-) and wild-type fibroblasts, as well as adenoviral strategies and pharmacologic inhibitors, to determine the mechanism by which PTEN inhibits alpha-SMA, fibroblast proliferation, and collagen production.In human lung specimens of IPF, myofibroblasts within fibroblastic foci demonstrated diminished PTEN expression. Furthermore, inhibition of PTEN in mice worsened bleomycin-induced fibrosis. In pten(-/-) fibroblasts, and in normal fibroblasts in which PTEN was inhibited, alpha-SMA, proliferation, and collagen production was upregulated. Addition of transforming growth factor-beta to wild-type cells, but not pten(-/-) cells, resulted in increased alpha-SMA expression in a time-dependent fashion. In pten(-/-) cells, reconstitution of PTEN decreased alpha-SMA expression, proliferation, and collagen production, whereas overexpression of PTEN in wild-type cells inhibited transforming growth factor-beta-induced myofibroblast differentiation. It was observed that both the protein and lipid phosphatase actions of PTEN were capable of modulating the myofibroblast phenotype.The results indicate that in IPF, myofibroblasts have diminished PTEN expression. Inhibition of PTEN in vivo promotes fibrosis, and PTEN inhibits myofibroblast differentiation in vitro.
Kidney Disease and Increased Mortality Risk in Type 2 Diabetes
Authors: Maryam Afkarian, Michael C. Sachs, Bryan Kestenbaum, Irl B. Hirsch, Katherine R. Tuttle, Jonathan Himmelfarb, Ian H. de Boer
Journal: Journal of the American Society of Nephrology (2013)

Type 2 diabetes associates with increased risk of mortality, but how kidney disease contributes to this mortality risk among individuals with type 2 diabetes is not completely understood. Here, we examined 10-year cumulative mortality by diabetes and kidney disease status for 15,046 participants in the Third National Health and Nutrition Examination Survey (NHANES III) by linking baseline data from NHANES III with the National Death Index. Kidney disease, defined as urinary albumin/creatinine ratio ≥30 mg/g and/or estimated GFR ≤60 ml/min per 1.73 m2, was present in 9.4% and 42.3% of individuals without and with type 2 diabetes, respectively. Among people without diabetes or kidney disease (reference group), 10-year cumulative all-cause mortality was 7.7% (95% confidence interval [95% CI], 7.0%–8.3%), standardized to population age, sex, and race. Among individuals with diabetes but without kidney disease, standardized mortality was 11.5% (95% CI, 7.9%–15.2%), representing an absolute risk difference with the reference group of 3.9% (95% CI, 0.1%–7.7%), adjusted for demographics, and 3.4% (95% CI, −0.3% to 7.0%) when further adjusted for smoking, BP, and cholesterol. Among individuals with both diabetes and kidney disease, standardized mortality was 31.1% (95% CI, 24.7%–37.5%), representing an absolute risk difference with the reference group of 23.4% (95% CI, 17.0%–29.9%), adjusted for demographics, and 23.4% (95% CI, 17.2%–29.6%) when further adjusted. We observed similar patterns for cardiovascular and noncardiovascular mortality. In conclusion, those with kidney disease predominantly account for the increased mortality observed in type 2 diabetes.
Metabolic Syndrome Is Associated With Adherence to an Unhealthy Diet
Authors: Parvin Mirmiran, Azita Hekmatdoost, Fereidoun Azizi
Journal: Diabetes Care (2007)

We read with interest the article by Freire et al. (1), which implicates that total dietary fat might increase the risk for metabolic syndrome. Conversely, they discovered an inverse relationship between linoleic acid intake and the metabolic syndrome. These data add to the mounting evidence describing the association between high dietary fat intake and features of metabolic syndrome either alone or in combination (2,3).

We evaluated dietary nutrient intakes and features of metabolic syndrome in a population-based cross-sectional study of 671 subjects (297 …
ESR/ERS white paper on lung cancer screening
Authors: Hans-Ulrich Kauczor, Lorenzo Bonomo, Mina Gaga, Kristiaan Nackaerts, Nir Peled, Mathias Prokop, Martine Remy-Jardin, Oyunbileg von Stackelberg, Jean-Paul Sculier
Journal: European Respiratory Journal (2015)

Lung cancer is the most frequently fatal cancer, with poor survival once the disease is advanced. Annual low dose computed tomography has shown a survival benefit in screening individuals at high risk for lung cancer. Based on the available evidence, the European Society of Radiology and the European Respiratory Society recommend lung cancer screening in comprehensive, quality-assured, longitudinal programmes within a clinical trial or in routine clinical practice at certified multidisciplinary medical centres. Minimum requirements include: standardised operating procedures for low dose image acquisition, computer-assisted nodule evaluation, and positive screening results and their management; inclusion/exclusion criteria; expectation management; and smoking cessation programmes. Further refinements are recommended to increase quality, outcome and cost-effectiveness of lung cancer screening: inclusion of risk models, reduction of effective radiation dose, computer-assisted volumetric measurements and assessment of comorbidities (chronic obstructive pulmonary disease and vascular calcification). All these requirements should be adjusted to the regional infrastructure and healthcare system, in order to exactly define eligibility using a risk model, nodule management and quality assurance plan. The establishment of a central registry, including biobank and image bank, and preferably on a European level, is strongly encouraged.
Dutch smokers are "alarmingly" ignorant of harms of passive smoking, study finds
Authors: T. Sheldon
Journal: BMJ (2011)

Tobacco control experts are urging the Dutch government to launch information campaigns funded by a doubling of the price of cigarettes, after a new study showed an “alarming” ignorance of the dangers of passive smoking.

The study, by researchers at Maastricht University for the International Tobacco Control Policy Evaluation Project, coincides with this week’s European conference on tobacco and health in Amsterdam, aimed at putting tobacco control higher on the political and social agenda.

In addition, the latest Tobacco Control Scale , a report on measures to combat smoking by the Association of European Cancer Leagues, placed the Netherlands joint 13th out of 30 …
THE MIXED LYMPHOCYTE REACTION: AN IN VITRO TEST FOR TOLERANCE
Authors: M. Roy Schwarz
Journal: The Journal of Experimental Medicine (1968)

Tolerance, as defined by an inability to produce runt disease and the failure to elicit a normal lymphocyte transfer reaction, was induced in Lewis and Brown Norway rats by the neonatal injection of bone marrow from the opposite strain. When thymus, thoracic duct lymph, or lymph node cells from such tolerant Lewis and Brown Norway rats were cultured together, or were individually cultured with similar cells from an F(1) hybrid of these strains, transformation was suppressed to the levels observed in nonmixed control cultures. In contrast, mixtures of cells involving nontolerant donors demonstrated significant transformation as measured by per cent enlarged cells and thymidine-(3)H uptake. The specificity of the tolerance was confirmed by the presence of transformed cells in mixtures involving cells from a tolerant donor and an unrelated or a partially related third strain of rats. From these results, it is suggested that the mixed lymphocyte reaction may be used as a simple test for tolerance and that it most likely represents an in vitro immune response.