tbuckley/cabot-search huggingface dataset:
Does parental smoking influence the adoption of this habit among their children
Authors: Maria Malik, Umair Misbah
Journal: European Respiratory Journal (2012)

Hypothesis/Background:  Parental smoking is likely to influence adoption of the habit by their children. There is a positive correlation between parents smoking and their children developing this habit.   Objective:  To find out if there is a correlation between parental smoking and their children adopting this habit.   Methods:  Primary and secondary researches were undertaken. Primary research comprised of a questionnaire, filled by 256 participants aged between 16 to 25 years from different private schools and colleges all over Pakistan. Interviews of 30 people were also conducted for further collection of information as a part of secondary research.   Results:  Literature review supported our hypothesis. Children were 5 percent less likely to smoke if parents did not smoke; children both whose parents smoked were 2.69 times more likely to smoke by 12thgrade compared to those whose parents did not smoke. Primary research showed that indigenous data also corresponds to the hypothesis. The chi-squared test of association, X2 > X2 (0.05, 1, 1), shows there is association between parental smoking and children smoking.   Conclusions:  The effect of parental smoking cannot be ignored, however since smoking habit is caused by a variety of factors, only a correlation can be developed. Prevention from and negative attitudes of parents are the most effective way of preventing or atleast reducing smoking habits among children.
Adrenomedullin Gene Transfer Induces Therapeutic Angiogenesis in a Rabbit Model of Chronic Hind Limb Ischemia
Authors: Noriyuki Tokunaga, Noritoshi Nagaya, Mikiyasu Shirai, Etsuro Tanaka, Hatsue Ishibashi-Ueda, Mariko Harada-Shiba, Munetake Kanda, Takefumi Ito, Wataru Shimizu, Yasuhiko Tabata, Masaaki Uematsu, Kazuhiro Nishigami, Shunji Sano, Kenji Kangawa, Hidezo Mori
Journal: Circulation (2004)

Background— Earlier studies have shown that adrenomedullin (AM), a potent vasodilator peptide, has a variety of cardiovascular effects. However, whether AM has angiogenic potential remains unknown. This study investigated whether AM gene transfer induces therapeutic angiogenesis in chronic hind limb ischemia. Methods and Results— Ischemia was induced in the hind limb of 21 Japanese White rabbits. Positively charged biodegradable gelatin was used to produce ionically linked DNA-gelatin complexes that could delay DNA degradation. Human AM DNA (naked AM group), AM DNA-gelatin complex (AM-gelatin group), or gelatin alone (control group) was injected into the ischemic thigh muscles. Four weeks after gene transfer, significant improvements in collateral formation and hind limb perfusion were observed in the naked AM group and AM-gelatin group compared with the control group (calf blood pressure ratio: 0.60±0.02, 0.72±0.03, 0.42±0.06, respectively). Interestingly, hind limb perfusion and capillary density of ischemic muscles were highest in the AM-gelatin group, which revealed the highest content of AM in the muscles among the three groups. As a result, necrosis of lower hind limb and thigh muscles was minimal in the AM-gelatin group. Conclusions— AM gene transfer induced therapeutic angiogenesis in a rabbit model of chronic hind limb ischemia. Furthermore, the use of biodegradable gelatin as a nonviral vector augmented AM expression and thereby enhanced the therapeutic effects of AM gene transfer. Thus, gelatin-mediated AM gene transfer may be a new therapeutic strategy for the treatment of peripheral vascular diseases.
DETECTION OF BREAST CARCINOMA METASTASES IN BONE: RELATIVE MERITS OF X-RAYS AND SKELETAL SCINTIGRAPHY
Authors: DavidJ. Perez, Jonathan Milan, H.T. Ford, JamesS. Macdonald, TrevorJ. Powles, J.C. Gazet, V. Ralph Mccready, R. Charles Coombes
Journal: The Lancet (1983)
Focal Atrial Tachycardia From the Ostium of the Coronary Sinus
Authors: Peter M. Kistler, Simon P. Fynn, Haris Haqqani, Irene H. Stevenson, Jitendra K. Vohra, Joseph B. Morton, Paul B. Sparks, Jonathan M. Kalman
Journal: Journal of the American College of Cardiology (2005)
Grape Exosome-like Nanoparticles Induce Intestinal Stem Cells and Protect Mice From DSS-Induced Colitis
Authors: Songwen Ju, Jingyao Mu, Terje Dokland, Xiaoying Zhuang, Qilong Wang, Hong Jiang, Xiaoyu Xiang, Zhong-Bin Deng, Baomei Wang, Lifeng Zhang, Mary Roth, Ruth Welti, James Mobley, Yan Jun, Donald Miller, Huang-Ge Zhang
Journal: Molecular Therapy (2013)

Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5+ stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5+ stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking β-catenin–mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5+ stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers. Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5+ stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5+ stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking β-catenin–mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5+ stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers.
Possible pitfalls in the identification of glycophorin-binding proteins of Plasmodium falciparum.
Authors: M R van Schravendijk, R J Wilson, C I Newbold
Journal: The Journal of Experimental Medicine (1987)

Plasmodium falciparum proteins that bind to the putative erythrocyte receptor (glycophorin) have been identified in several laboratories by their ability to bind to glycophorin immobilized on aminoethyl-BioGel (AE-BioGel). We here report that several parasite proteins bind to AE-BioGel in the absence of coupled glycophorin. Binding is apparently due to the strong ion-exchange properties of the matrix, and is sensitive to ionic conditions such as the degree of equilibration of the matrix and the pH. The parasite proteins that bind to the blank column under appropriate conditions include proteins with the serological activities of S-antigen and Ag 23, which also bind to glycophorin-coupled AE-BioGel. In the light of these results, the glycophorin-binding specificity of these and other proteins reported to bind to glycophorin-coupled AE-BioGel will have to be reevaluated, preferably using a different support matrix.
Cancer Stem Cell Analysis and Clinical Outcome in Patients with Glioblastoma Multiforme
Authors: Roberto Pallini, Lucia Ricci-Vitiani, Giuseppe Luigi Banna, Michele Signore, Dario Lombardi, Matilde Todaro, Giorgio Stassi, Maurizio Martini, Giulio Maira, Luigi Maria Larocca, Ruggero De Maria
Journal: Clinical Cancer Research (2008)

Cancer stem cells (CSC) are thought to represent the population of tumorigenic cells responsible for tumor development. The stem cell antigen CD133 identifies such a tumorigenic population in a subset of glioblastoma patients. We conducted a prospective study to explore the prognostic potential of CSC analysis in glioblastoma patients.We investigated the relationship between the in vitro growth potential of glioblastoma CSCs and patient death or disease progression in tumors of 44 consecutive glioblastoma patients treated with complete or partial tumorectomy followed by radiotherapy combined with temozolomide treatment. Moreover, we evaluated by immunohistochemistry and immunofluorescence the prognostic value of the relative presence of CD133+ and CD133+/Ki67+ cells in patient tumors.In vitro CSC generation and the presence of > or = 2% CD133+ cells in tumor lesions negatively correlated with overall (P = 0.0001 and 0.02, respectively) and progression-free (P = 0.0002 and 0.01, respectively) survival of patients. A very poor overall (P = 0.007) and progression-free (P = 0.001) survival was observed among patients whose tumors contained CD133+ cells expressing Ki67. Taking into account symptom duration, surgery type, age, O6-methylguanine-DNA methyltransferase promoter methylation, and p53 status, generation of CSCs and CD133/Ki67 coexpression emerged as highly significant independent prognostic factors, with an adjusted hazard ratio of 2.92 (95% confidence interval, 1.37-6.2; P = 0.005) and 4.48 (95% confidence interval, 1.68-11.9; P = 0.003), respectively.The analysis of CSCs may predict the survival of glioblastoma patients. In vitro CSC generation and presence of CD133+/Ki67+ cells are two considerable prognostic factors of disease progression and poor clinical outcome.
Humoral Immune Response to -Methylacyl-CoA Racemase and Prostate Cancer
Authors: A. Sreekumar, B. Laxman, D. R. Rhodes, S. Bhagavathula, J. Harwood, D. Giacherio, D. Ghosh, M. G. Sanda, M. A. Rubin, A. M. Chinnaiyan
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Although prostate-specific antigen (PSA) is a prototypic biomarker for prostate cancer, it has poor specificity. Expression of α-methylacyl-CoA racemase (AMACR), which is involved in the conversion of R-stereoisomers of branched-chain fatty acids to S-stereoisomers, has been shown to be specifically increased in prostate cancer epithelia. However, attempts to detect AMACR in circulation have not been successful. Hence, we determined whether an immune response to AMACR could be used as a serum biomarker for prostate cancer. Methods: Sera from patients with biopsy-proven prostate cancer and from control subjects were screened for a humoral immune response to selected tumor antigens, including AMACR, by using protein microarrays (46 patients, 28 control subjects). Humoral immune response to AMACR was then validated using high-throughput immunoblot analysis (151 patients, 259 control subjects) and enzyme-linked immunosorbent assay (ELISA) (54 patients, 55 control subjects). Receiver operating characteristic curves were used to determine the sensitivity and specificity of the immune response to AMACR to detect prostate cancer. Results: Immunoreactivity against AMACR was statistically significantly higher in sera from patients with prostate cancer than in control subjects by all three techniques (Pprotein microarray = .009, Pimmunoblot<.001, PELISA = .011). High-throughput immunoblot analysis revealed that, in subjects with intermediate PSA levels (4–10 ng/mL), the immune response against AMACR was more sensitive and specific than was PSA in distinguishing sera from prostate cancer patients relative to control subjects (sensitivity and specificity of 77.8% and 80.6% versus 45.6% and 50%, respectively; area under the curve of 0.789 versus 0.492; P<.001). Conclusion: Assays to detect a humoral immune response against AMACR may have the potential to supplement PSA screening in identifying patients with clinically significant prostate cancer, especially those with intermediate PSA levels.
A missense mutation in <i>FIC1</i> is associated with greenland familial cholestasis
Authors: Leo W.J. Klomp, Laura N. Bull, Alexander S. Knisely, Marjolein A.M. van der Doelen, Jenneke A. Juijn, Ruud Berger, Sylviane Forget, Inge-Merete Nielsen, Hans Eiberg, Roderick H.J. Houwen
Journal: Hepatology (2000)

Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G-->A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation.
Ubiquitin-Specific Protease 8 Links the PTEN-Akt-AIP4 Pathway to the Control of FLIPS Stability and TRAIL Sensitivity in Glioblastoma Multiforme
Authors: Amith Panner, Courtney A. Crane, Changjiang Weng, Alberto Feletti, Shanna Fang, Andrew T. Parsa, Russell O. Pieper
Journal: Cancer Research (2010)

The antiapoptotic protein FLIP(S) is a key suppressor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human glioblastoma multiforme (GBM) cells. We previously reported that a novel phosphatase and tensin homologue (PTEN)-Akt-atrophin-interacting protein 4 (AIP4) pathway regulates FLIP(S) ubiquitination and stability, although the means by which PTEN and Akt were linked to AIP4 activity were unclear. Here, we report that a second regulator of ubiquitin metabolism, the ubiquitin-specific protease 8 (USP8), is a downstream target of Akt, and that USP8 links Akt to AIP4 and the regulation of FLIP(S) stability and TRAIL resistance. In human GBM xenografts, levels of USP8 correlated inversely with pAkt levels, and genetic or pharmacologic manipulation of Akt regulated USP8 levels in an inverse manner. Overexpression of wild-type USP8, but not catalytically inactive USP8, increased FLIP(S) ubiquitination, decreased FLIP(S) half-life, decreased FLIP(S) steady-state levels, and decreased TRAIL resistance, whereas short interfering RNA (siRNA)-mediated suppression of USP8 levels had the opposite effect. Because high levels of the USP8 deubiquitinase correlated with high levels of FLIP(S) ubiquitination, USP8 seemed to control FLIP(S) ubiquitination through an intermediate target. Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIP(S) E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIP(S) interaction, whereas siRNA-mediated suppression of USP8 increased AIP4 ubiquitination. Furthermore, the suppression of FLIP(S) levels by USP8 overexpression was reversed by the introduction of siRNA targeting AIP4. These results show that USP8, a downstream target of Akt, regulates the ability of AIP4 to control FLIP(S) stability and TRAIL sensitivity.
Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.
Authors: M Ciofetta, C Lalli, P Del Sindaco, E Torlone, S Pampanelli, L Mauro, D L Chiara, P Brunetti, G B Bolli
Journal: Diabetes Care (1999)

OBJECTIVE: To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied. RESULTS: The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P &amp;lt; 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P &amp;lt; 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P &amp;lt; 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P &amp;lt; 0.05). Frequency of hypoglycemia was greater in group 2 (P &amp;lt; 0.05), but not in group 3 (NS) vs. group 1.
Serial PEF measurement is superior to cross-shift change in diagnosing occupational asthma
Authors: D. Park, V. C. Moore, C. B. S. G. Burge, M. S. Jaakkola, A. S. Robertson, P. S. Burge
Journal: European Respiratory Journal (2009)

Cross-shift measurements of peak expiratory flow (PEF) are commonly employed in the diagnosis of occupational asthma, although evidence for this approach is lacking. The current paper presents an evaluation of the technique. Mean changes in PEF across morning/day shifts were compared between workers with occupational asthma, confirmed using specific challenge testing, and non-working asthmatics. Individuals were divided into a development set, used to identify the optimum cross-shift change for diagnosing occupational asthma, and an evaluation set, used to test the sensitivity and specificity of this value. Comparative analysis of serial PEF records was performed using the Oasys-2 computerised system. A cross-shift decrease in PEF of 5 L·min −1 achieved acceptable specificity in the development set. Applied to the evaluation set, this cut-off had a specificity of 90.9% and a sensitivity of 50%. Sensitivity could not be improved without unacceptable compromise to specificity. Analysis of serial PEF records using linear discriminant analysis identified occupational asthma with a sensitivity of 83.3% and a specificity of 90.9%. Serial analysis using mean work/rest day PEF comparison had a sensitivity of 66.7% and a specificity of 100%. Cross-shift changes in PEF in morning/day-shift workers have poor sensitivity in diagnosing occupational asthma, and are inferior to serial techniques.
Th17 cell paradox in sarcoidosis
Authors: Jonas Schupp, Benedikt Jäger, Joachim Müller-Quernheim, Antje Prasse
Journal: European Respiratory Journal (2013)

Background:   Sarcoidosis is a systemic granulomatous disorder with a still unknown cause. Muliple evidence shows that saroidosis is associated with a strong Th1 immune response. Up to date, only few studies evaluated the potential role of Th17 cells. While immunohistochemistry data showed IL-17 upregulation in sarcoid granuloma, IL-17 overproduction by BAL cells has not been demonstrated.   Objectives:   To compare the gene expression profiles of BAL cells from sarcoid patients with healthy volunteers focused on the Th17 signature.   Methods:   50 patients with sarcoidosis and 20 healthy volunteers underwent bronchoscopy with bronchoalveolar lavage. BAL cells were isolated using a standard protocol. Gene expression was quantified by using Human Gene 1.0 ST Arrays (Affymetrix, Santa Clara, USA), as analysis software we used the BRB tool developed by Richard Simon.   Results:   Gene expression of BAL cells of patients with sarcoidosis differed in >10000 genes (with a FDR    Conclusion:   Gene expression of BAL cells from sarcoid patients differs highly compared to healthy volunteers. Th17 cells seem to be elevated, but functionally repressed. Confirmation via flow cytometry, ELISA and immunohistochemistry are in progress and will be available at the ERS conference 2013.
NLRP3 Suppresses NK Cell–Mediated Responses to Carcinogen-Induced Tumors and Metastases
Authors: Melvyn T. Chow, Jaclyn Sceneay, Christophe Paget, Christina S.F. Wong, Helene Duret, Jürg Tschopp, Andreas Möller, Mark J. Smyth
Journal: Cancer Research (2012)

The NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response upon infectious insults or tissue injury and damage. However, the role of the NLRP3 inflammasome in natural killer (NK) cell-mediated control of tumor immunity is poorly understood. Here, we show in a model of chemical-induced carcinogenesis and a series of experimental and spontaneous metastases models that mice lacking NLRP3 display significantly reduced tumor burden than control wild-type (WT) mice. The suppression of spontaneous and experimental tumor metastases and methylcholanthrene (MCA)-induced sarcomas in mice deficient for NLRP3 was NK cell and IFN-γ-dependent. Focusing on the amenable B16F10 experimental lung metastases model, we determined that expression of NLRP3 in bone marrow-derived cells was necessary for optimal tumor metastasis. Tumor-driven expansion of CD11b(+)Gr-1(intermediate) (Gr-1(int)) myeloid cells within the lung tumor microenvironment of NLRP3(-/-) mice was coincident with increased lung infiltrating activated NK cells and an enhanced antimetastatic response. The CD11b(+)Gr-1(int) myeloid cells displayed a unique cell surface phenotype and were characterized by their elevated production of CCL5 and CXCL9 chemokines. Adoptive transfer of this population into WT mice enhanced NK cell numbers in, and suppression of, B16F10 lung metastases. Together, these data suggested that NLRP3 is an important suppressor of NK cell-mediated control of carcinogenesis and metastases and identify CD11b(+)Gr-1(int) myeloid cells that promote NK cell antimetastatic function.
Assessment of outcome in dyspepsia: has progress been made?
Authors: S J O Veldhuyzen van Zanten
Journal: Gut (2002)

There is a lack of consensus among researchers on how to best measure outcome in functional dyspepsia trials and more importantly a lack of validated outcome measures. If symptoms resolve completely, treatment has been successful but with partial improvement interpretation is less straightforward. It is most likely that these issues will only be resolved if unequivocally efficacious treatments emerge to which the different outcome measures can be compared. Recently, a few validated outcome measures have been developed which look promising.