tbuckley/cabot-search huggingface dataset:
Tobacco smoking prevalence and patterns in Croatian pupils in year 2011 - Results of Croatian national Global Youth Tobacco Survey (GYTS)
Authors: Dijana Mayer, Ivana Pavic Simetin, Divo Ljubicic
Journal: European Respiratory Journal (2012)

Introduction: Important changes have occurred in the prevalence and patterns of cigarette smoking by young people. Given the known consequences of smoking for morbidity and mortality and the nature of smoking habits established during adolescence, changes in smoking behaviors carry extraordinary implications for the health of these youngsters throughout their lives.  Aims and objectives: to investgate the prevalence and pattern of cigarette smoking among Croatian pupils.  Methods: The Croatia GYTS (Global Youth Tobacco Survey) was a school-based survey of pupils in 7 th  and 8 th  grade primary, and 1 st  grade secondary school conducted in year 2011. A two-stage cluster sample design was used to produce representative data for all of Croatia. A total of 3,551 students aged 13-15 participated in study.  Results: The overall response rate was 90.1%. Any form of tobacco is currently used by 28.6% pupils (boys = 28.6%, girls = 27.9%); 66.5% of pupils had ever smoked cigarettes (boys = 66.6%, girls = 65.9%). More than one-quarter (27.2%) currently smoke cigarettes (boys = 26.7%, girls = 27.0%); 12.0% smoke daily manufactured cigarettes (boys = 12.1%, girls = 11.2%); 14.9% currently smoke cigars (boys = 15.2%, girls = 14.1%). Almost one quarter of ever smokers initiated smoking before age ten (boys = 30.4%, girls = 16.3%). Of never smokers, even 22.1% are likely to initiate smoking next year.  Conclusions: The results of Croatian GYTS 2011 indicate significant tobacco use and exposure to tobacco among pupils in Croatia. There is an urgent need to prevent tobacco smoke prevalence among these individuals and reduce morbidity and mortality throughout their lives.
Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome
Authors: Su-Jiang Zhang, Raajit Rampal, Taghi Manshouri, Jay Patel, Nana Mensah, Andrew Kayserian, Todd Hricik, Adriana Heguy, Cyrus Hedvat, Mithat Gönen, Hagop Kantarjian, Ross L. Levine, Omar Abdel-Wahab, Srdan Verstovsek
Journal: Blood (2012)
Long-Term Lithium Use and Risk of Renal and Upper Urinary Tract Cancers
Authors: Anton Pottegård, Jesper Hallas, Boye L Jensen, Kirsten Madsen, Søren Friis
Journal: Journal of the American Society of Nephrology (2015)

Lithium induces proliferation in the epithelium of renal collecting ducts. A recent small-scale cohort study reported a strong association between use of lithium and increased risk of renal neoplasia. We therefore conducted a large-scale pharmacoepidemiologic study of the association between long-term use of lithium and risk of upper urinary tract cancer, including renal cell cancer and cancers of the renal pelvis or ureter. We identified all histologically verified upper urinary tract cancer cases in Denmark between 2000 and 2012 from the Danish Cancer Registry. A total of 6477 cases were matched by age and sex to 259,080 cancer-free controls. Data on lithium use from 1995 to 2012 were obtained from the Danish Prescription Registry. We estimated the association between long-term use of lithium (≥5 years) and risk of upper urinary tract cancer using conditional logistic regression with adjustment for potential confounders. Long-term use of lithium was observed among 0.22% of cases and 0.17% of controls. This yielded an overall nonsignificant adjusted odds ratio (OR) of 1.3 (95% confidence interval [95% CI], 0.8–2.2) for upper urinary tract cancer associated with long-term use of lithium. Analyses stratified by stage and subtype of upper urinary tract cancer revealed slight but nonsignificant increases in the ORs for localized disease (OR, 1.6; 95% CI, 0.8–3.0) and for renal pelvis/ureter cancers (OR, 1.7; 95% CI, 0.5–5.4). In conclusion, in our nationwide case-control study, use of lithium was not associated with an increased risk of upper urinary tract cancer.
A Decision Tree for Tuberculosis Contact Investigation
Authors: Lynn B. Gerald, Shenghui Tang, Frank Bruce, David Redden, Michael E. Kimerling, Nancy Brook, Nancy Dunlap, William C. Bailey
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The University of Alabama at Birmingham and the Alabama Department of Public Health recently developed a logistic regression model showing those variables that are most likely to predict a positive tuberculin skin test in contacts of tuberculosis cases. However, translating such a model into field application requires a stepwise approach. This article describes a decision tree developed to assist public health workers in determining which contacts are most likely to have a positive tuberculin skin test. The Classification and Regression Tree analysis was performed on 292 consecutive cases and their 2,941 contacts seen by the Alabama Department of Public Health from January 1, 1998, to October 15, 1998. Several decision trees were developed and were then tested using prospectively collected data from 366 new tuberculosis cases and their 3,162 contacts from October 15, 1998, to April 30, 2000. Testing showed the trees to have sensitivities of 87–94%, specificities of 22–28%, and false-negative rates between 7 and 10%. The use of the decision trees would decrease the number of contacts investigated by 17–25% while maintaining a false-negative rate that was close to that of the presumed background rate of latent tuberculosis infection in the state of Alabama.
Pathogenic VCP Mutations Induce Mitochondrial Uncoupling and Reduced ATP Levels
Authors: Fernando Bartolome, Hsiu-Chuan Wu, Victoria S. Burchell, Elisavet Preza, Selina Wray, Colin J. Mahoney, Nick C. Fox, Andrea Calvo, Antonio Canosa, Cristina Moglia, Jessica Mandrioli, Adriano Chiò, Richard W. Orrell, Henry Houlden, John Hardy, Andrey Y. Abramov, Helene Plun-Favreau
Journal: Neuron (2013)

Valosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%-2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death.
Recirculating, suppressor T cells in transplantation tolerance.
Authors: S Dorsch, R Roser
Journal: The Journal of Experimental Medicine (1977)

An adoptive transfer system was used to examine the capacity of cellular inocula from rats fully tolerant of Ag-B antigens to transfer tolerance to irradiated recipients. Permanent tolerance in these irradiated recipients involved specific suppression of the regenerating immune response. Cells obtained from tissues rich in recirculating lymphocytes were the most effective suppressors. Highly purified inocula of T cells from tolerant donors were potent suppressors in irradiated hosts, but were not capable of direct suppression of peripheral antigen-sensitive T cells.. The role of the thymus in maintaining the complement of recirculating suppressor T cells in tolerant animals was examined after adult thymectomy. Thymectomized tolerant rats did not reject their tolerated grafts, and the longevity of the suppression in tolerant rats was confirmed by showing that adoptive transfer of cells from thymectomized tolerant donors was effective in suppressing irradiated recipients up to 180 days after thymectomy. Cellular inocula from these donors appeared to lose their suppressor function marginally faster than they lost effector function (as measured by their capacity to mediate rejection of third party control grafts). Thymectomy made tolerant rats more vulnerable to the termination of tolerance by challenge with normal cells. Transplantation tolerance is maintained in adult rats by long-lived rapidly recirculating suppressor T cells. The target for the suppressor action of these cells is probably the precursor of alloantigen-sensitive lymphocytes, and the effect of suppression may be deletion or inactivation of the relevant clone of these cells.
Pulmonary interstitial fibrosis associated with alveolar proteinosis.
Authors: H W Clague, A C Wallace, W K Morgan
Journal: Thorax (1983)

Alveolar proteinosis is characterised by the presence of an amorphous lipoproteinaceous material that fills the alveolar space and stains positively by the periodic acid Schiff.(PAS) method.'Alveolar walls are usually normal or only slightly thickened by cellular infiltrate, and interstitial fibrosis is unusual.We report a patient in whom severe interstitial fibrosis occurred early in the course of the dis- ease and led to a delay in correct diagnosis and to inappropriate treatment with corticosteroids. Case reportA 54 year old man who worked as a forklift truck driver presented with a two month history of effort dyspnoea, recurrent painful pleurisy, and fever with cough and sputum production.Physical examination revealed nothing abnormal but a chest radiograph showed basal interstitial nodular shadowing.A needle lung biopsy specimen2 (fig 1) from the left lower lobe was reported as showing intersti- tial fibrosis with considerable numbers of both interstitial and intra-alveolar macrophages.Despite treatment with oral prednisone (15 mg daily) the patient's dyspnoea
The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity
Authors: Maya Remington, Jana Chtchetinin, Karen Ancheta, Phioanh Leia Nghiemphu, Timothy Cloughesy, Albert Lai
Journal: Neuro-Oncology (2008)

First-line therapy for patients with glioblastoma multiforme includes treatment with radiation and temozolomide (TMZ), an oral DNA alkylating chemotherapy. Sensitivity of glioma cells to TMZ is dependent on the level of cellular O(6)-methylguanine-DNA methyltransferase (MGMT) repair activity. Several common coding-region polymorphisms in the MGMT gene (L84F and the linked pair I143V/K178R) modify functional characteristics of MGMT and cancer risk. To determine whether these polymorphic changes influence the ability of MGMT to protect glioma cells from TMZ, we stably overexpressed enhanced green fluorescent protein (eGFP)-tagged MGMT constructs in U87MG glioma cells. We confirmed that the wild-type (WT) eGFP-MGMT protein is properly localized within the nucleus and found that L84F, I143V/K178R, and L84F/I143V/K178R eGFP-MGMT variants exhibited nuclear localization patterns indistinguishable from WT. Using MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] proliferation and clonogenic survival assays, we confirmed that WT cells expressing eGFP-MGMT are resistant to TMZ treatment compared with control U87MG cells, and that each of the polymorphic eGFP-MGMT variants confers similar resistance to TMZ. However, upon exposure to O(6)-benzylguanine (O(6)-BG), a synthetic MGMT inhibitor, the L84F and L84F/I143V/K178R variants were degraded more rapidly than WT or I143V/K178R in a proteasome-dependent manner. Despite the increased O(6)-BG- stimulated protein turnover caused by the L84F alteration, cells expressing L84F eGFP-MGMT did not exhibit altered sensitivity to the combination of O(6)-BG and TMZ compared with WT cells. In conclusion, we demonstrated that the L84F polymorphic variant has altered protein turnover without modifying sensitivity of U87MG cells to TMZ or combined TMZ and O(6)-BG. These findings may provide a clue to determining the clinical significance of MGMT coding-region polymorphisms.
Village Settlements for the Consumptive
Authors: P. C. Varrier-Jones
Journal: BMJ (1927)

Lg 1. 1, LMzDicAL Jo=xAL~~~~~~~~~~~~~~~~~~~~~~of the normal rather than of the abnormal.It cannot be repeated too often that thep symptoms of disease are only the prenmatur-e occurrence of the signs' of exhaustion due to over-exertion of the organ when in 'a state of heatth.It will be a gr;eatL, gain when the experimental physiologist gets into the habit of leaving his laboratorv from time to time in order to visit the wards, the dispensary, and the operat- ing theatre under the guidance of the physician and the surgeon-.A new clinical physiologyis much to be desired-a physiol-ogy wlhich deals u ith the symptoms of ill lhealth and tries lhonestly to estimate the functional activity of every organ of the body.The more those apparently simple matters are investigated the greater will be the regret and astonislhment to find so many gaps in our owln knowledlge.Mackenzie never tired of tryinig to drive that fact llomle.He took a delight in astoniishing his visit-ors by such questions as the following: Why does cancer kill a man?What is it that kills him?WIhy does he die?At those times his conversationl was fakcinating and stim'ulating, but sometimnles very puzzling anid bewildelring.It was necessary to admit that usually the questions he asked although going to the very root of the matter and provinlg how ignorfant we are of some of the most fundanmelntal problems of life, are in tlhe present state of our kniowledge unhnswerable.Doubtless, by the advance of science anid tho increase of knowledge, those p)roblems will oiie day lie solved, and I venture to predict that the familv doctor will play an important part ill their sol'ution.
Modulation of the oestrogen receptor: a process with distinct susceptible steps
Authors: A. Cano
Journal: Human Reproduction Update (2000)

The selective oestrogen receptor modulators (SERMs) constitute a group of substances which are capable of regulating the agonistic/antagonistic profile of the oestrogen receptor in distinct tissues. Their potential utility is considerable since, among the pleiotropic range of effects that oestrogens exert on their target tissues, they may provide a selective profile that better suits each clinical necessity. This review summarizes the principal steps of oestrogen action where modifications have resulted in changes of the effect profile. Three different steps of oestrogen action have been highlighted as being susceptible to modulation: type of ligand, particular species of oestrogen receptor, and particulars at the target tissue. Two main families of SERMs, the triphenylethylene derivatives, with tamoxifen as the main actor, and the benzothiophene derivatives, mainly represented by raloxifene, provide much of the basic and clinical knowledge on the influence of the type of ligand. Two types of oestrogen receptor, and , add the second variable susceptible to modulating the response to receptor activation. Finally, the ligand–receptor complex may define particular events in its interaction with DNA, such as binding to promoters other than the oestrogen response element, recruitment of concrete sets of local transcription factors, or other options.
The Ligand Status of the Aromatic Hydrocarbon Receptor Modulates Transcriptional Activation of BRCA-1 Promoter by Estrogen
Authors: Jennifer K. Hockings, Patricia A. Thorne, Michael Q. Kemp, Sherif S. Morgan, Ornella Selmin, Donato F. Romagnolo
Journal: Cancer Research (2006)

Abstract In sporadic breast cancers, BRCA-1 expression is down-regulated in the absence of mutations in the BRCA-1 gene. This suggests that disruption of BRCA-1 expression may contribute to the onset of mammary tumors. Environmental contaminants found in industrial pollution, tobacco smoke, and cooked foods include benzo(a)pyrene [B(a)P] and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which have been shown to act as endocrine disruptors and tumor promoters. In previous studies, we documented that estrogen (E2) induced BRCA-1 transcription through the recruitment of an activator protein-1/estrogen receptor-α (ERα) complex to the proximal BRCA-1 promoter. Here, we report that activation of BRCA-1 transcription by E2 requires occupancy of the BRCA-1 promoter by the unliganded aromatic hydrocarbon receptor (AhR). The stimulatory effects of E2 on BRCA-1 transcription are counteracted by (a) cotreatment with the AhR antagonist 3′-methoxy-4′-nitroflavone; (b) transient expression in ERα-negative HeLa cells of ERα lacking the protein-binding domain for the AhR; and (c) mutation of two consensus xenobiotic-responsive elements (XRE, 5′-GCGTG-3′) located upstream of the ERα-binding region. These results suggest that the physical interaction between the unliganded AhR and the liganded ERα plays a positive role in E2-dependent activation of BRCA-1 transcription. Conversely, we show that the AhR ligands B(a)P and TCDD abrogate E2-induced BRCA-1 promoter activity. The repressive effects of TCDD are paralleled by increased recruitment of the liganded AhR and HDAC1, reduced occupancy by p300, SRC-1, and diminished acetylation of H4 at the BRCA-1 promoter region flanking the XREs. We propose that the ligand status of the AhR modulates activation of the BRCA-1 promoter by estrogen. (Cancer Res 2006; 66(4): 2224-32)
Low levels of sequence divergence in rock wallabies (Petrogale) suggest a lack of positive directional selection in SRY
Authors: R. J. O'Neill, M. D. Eldridge, R. H. Crozier, J. A. Graves
Journal: Molecular Biology and Evolution (1997)

The rate of nucleotide mutation traditionally has been considered uniform over the entire genome, and any variations in substitution rate are deemed functions of differential selective constraints (Wolfe, Sharp, and Li 1989). Previous studies of sequence divergence of SRY, the mammalian male sex determining gene (Sinclair et al. 1990), in two eutherian groups of mammals suggested that the rapid evolution of the gene may indicate positive directional selection. Among pair-wise comparisons between human and seven primate species (Whitfield, Lovell-Badge, and Goodfellow 1993), and between Mus musculus and six species of Old World mice and rats (Tucker and Lundrigan 1993), low amino acid identity led the authors to conclude that SRY was evolving rapidly. To examine the relative rates of evolution within these pair-wise comparisons, K,IK, values were determined for SRY, where KA is the rate of nonsynonymous substitutions per nonsynonymous site and Ks is the rate of synonymous substitutions per synonymous site. K,IK, values in the primate study ranged from 0.47 to 1.88 and values in the mouse study ranged from 0.33 to 0.45. A comparison of 363 genes between mouse and rat estimated an average KA/KS value of 0.14 within a range of 0.05-0.2, although Y-linked genes were not involved in this study (Wolfe and Sharp 1993). Neutral, or unconstrained, evolution would predict a K*/ KS value of 1 (Lee, Ota, and Vacquier 1995; Rosenberg et al. 1995), yet a value of 1.88 found in primates indicated a deviation from this and evidence of selective drive on the sequence. This drive has been suggested to be positive directional selection, which may promote reproductive isolation by causing disruption of sexual development in hybrids (Hale, Washburn, and Either 1993; Tucker and Lundrigan 1993; Whitfield, LovellBadge, and Goodfellow 1993; Hurst 1994). While these studies suggest a plausible model for the directional selection of SRY, these species diverged several million years ago and any selective constraint, or lack thereof, on the sequence may have been masked by other nonselective or episodic events. To test for any directional selection or functional constraint on SRY, we have examined the nucleic acid and amino acid sequences and compared the substitution rates in a recently diverged and rapidly speciating group of mammals. The results of studies of sequence evolution over relatively
Sustained disease remission and inhibition of radiographic progression in methotrexate-naive patients with rheumatoid arthritis and poor prognostic factors treated with abatacept: 2-year outcomes
Authors: J. Bathon, M. Robles, A. C. Ximenes, S. Nayiager, J. Wollenhaupt, P. Durez, J. Gomez-Reino, W. Grassi, B. Haraoui, W. Shergy, S.-H. Park, H. Genant, C. Peterfy, J.-C. Becker, A. Covucci, D. Moniz Reed, R. Helfrick, R. Westhovens
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To assess the efficacy and safety of abatacept plus methotrexate versus methotrexate alone in early erosive rheumatoid arthritis (RA). <h3>Methods</h3> The AGREE was a 2-year phase IIIb multinational study in early (≤2 years) RA. During the double-blind period (year 1), patients were randomly assigned 1:1 to receive abatacept+methotrexate or methotrexate alone; all patients received open-label abatacept+methotrexate during year 2. Clinical outcomes assessed included 28-joint disease activity score (DAS28) defined remission, low disease activity score (LDAS), American College of Rheumatology (ACR) responses and physical function. Radiographic outcomes were assessed using the Genant-modified Sharp total score (TS). Safety was monitored throughout. <h3>Results</h3> Of the 459 patients completing year 1, 433 patients (94.3%) completed year 2. DAS28-defined remission, LDAS, ACR and physical function were sustained through year 2 in the original abatacept+methotrexate group, with 55.2% in remission at 2 years. Upon introduction of abatacept in the methotrexate-alone group, additional patients achieved DAS28-defined remission (44.5% vs 26.9%), LDAS (60.4% vs 43.2%) and improved ACR 70 (49.8% vs 31.7%) for year 2 versus year 1. Less radiographic progression was observed at 2 years in the original abatacept+methotrexate group than the methotrexate-alone group (change in TS 0.84 vs 1.75, p&lt;0.001). No new safety issues were seen. Similar rates of serious adverse events, serious infections and autoimmune events were observed in years 1 and 2. <h3>Conclusions</h3> The AGREE trial was the first to examine the impact of T-cell co-stimulation modulation with abatacept in patients with early erosive RA. Early treatment with abatacept+methotrexate resulted in greater sustainable clinical, functional and radiographic benefits than methotrexate alone, with acceptable safety and tolerability. <h3>Trial Registration:</h3> NCT00122382
VICTOR: A PHASE III PLACEBO-CONTROLLED TRIAL OF ROFECOXIB IN COLORECTAL CANCER PATIENTS FOLLOWING SURGICAL RESECTION
Authors: Midgley Rsj., C C McConkey, M J Langman, J L Smith, P Julier, C Iveson, E Johnstone, Chen X-H., J A Dunn, D J Kerr, Grp Victort.
Journal: Annals of Oncology (2008)