tbuckley/cabot-search huggingface dataset:
The evolutionary history of the amylase multigene family in Drosophila pseudoobscura
Authors: A Popadić, R A Norman, W W Doanet, W W Anderson
Journal: Molecular Biology and Evolution (1996)

In Drosophila pseudoobscura, the amylase (Amy) multigene family is contained within a series of inversions, or gene arrangements, on the third chromosome. The Standard (ST), Santa Cruz (SC), and Tree Line (TL) inversions are central to the phylogeny of arrangements, and have clusters of other arrangements derived from them. The gene arrangements belonging to each of these three clusters have a characteristic number of Amy genes, ranging from three in ST to two in SC to one in TL. This distribution pattern can reflect a history of either duplications or deletions, although the data available in the past did not permit a decision between these alternatives. We provide unambiguous evidence that three Amy genes were present before the divergence of the ST, SC, and TL arrangements. Thus, the current status of the Amy multigene family is the result of deletions in the TL and SC arrangements, which created three new pseudogenes: TL Amy2-psi, TL Amy3-psi, and SC Amy3-psi. Analysis of pseudogene sequences revealed that, in the SC and ST arrangements, pseudogene evolution has been retarded, most likely due to the homogenization effect of gene conversion. Finally, by determining the original copy number, we have reconstructed the evolutionary history of the Amy multigene family and linked it with the evolution of the central gene arrangements.
CYP17 Promoter Polymorphism and Breast Cancer in Australian Women Under Age Forty Years
Authors: A. B. Spurdle
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: The cytochrome P450c17α enzyme functions in the steroid biosynthesis pathway, and altered endogenous steroid hormone levels have been reported to be associated with a T to C polymorphism in the 5′ promoter region of the CYP17 gene. Because steroid hormone exposure is known to influence breast cancer risk, we conducted a population-based, case–control-family study to assess the relationship between the CYP17 promoter polymorphism and early-onset breast cancer. Methods: Case subjects under 40 years of age at diagnosis of a first primary breast cancer, population-sampled control subjects, and the relatives of both case and control subjects were interviewed to record family history of breast cancer and other risk factors. CYP17 genotype was determined in 369 case subjects, 284 control subjects, and 91 relatives of case subjects. Genotype distributions were compared by logistic regression, and cumulative risk was estimated by a modified segregation analysis. All statistical tests were two-tailed. Results: Compared with the TT genotype (i.e., individuals homozygous for the T allele), the TC genotype was not associated with increased breast cancer risk (P = .7). Compared with the TT and TC genotypes combined, the CC genotype was associated with a relative risk of 1.81 (95% confidence interval [CI] = 1.15–2.86; P = .01) before adjustment for measured risk factors and 1.63 (95% CI = 1.00–2.64; P = .05) after adjustment. There was an excess of CC genotypes in case subjects who had at least one affected first- or second-degree relative, compared with control subjects unstratified by family history of breast cancer (23% versus 11%; P = .006), and these case subjects had a threefold to fourfold higher risk than women of other groups defined by genotype and family history of breast cancer. Analysis of breast cancer in first- and second-degree relatives of case subjects with the CC genotype, excluding two known carriers of a deleterious mutation in BRCA1 or BRCA2, gave a relative hazard in women with the CC genotype of 3.48 (95% CI = 1.13–10.74; P = .04), which is equivalent to a cumulative risk of 16% to age 70 years. Conclusions: The CC genotype may modify the effect of other familial risk factors for early-onset breast cancer.
Reply
Authors: Kathie Beland, Fernando Alvarez
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. B cells are a diverse and multifaceted cell population comprising both regulatory and effector cells. This diversity could allow B cells to be both friend and foe in autoimmune hepatitis (AIH). Similar to CD4+ T cells, which can be either T‐helper or regulatory T cells, B‐cell subpopulations can be either pathologic (e.g., presenting autoantigens) or protective (e.g., interleukin‐10 secreting B cells). In our recent article, we showed that B‐cell depletion in a mouse model leads to remission of AIH,1 a result also observed in patients.2 These results may seem to conflict with the data of Liu et al.,4 in which a subset of regulatory B cells (interleukin‐10‐dependent CD11b+ B cells) inhibited pathogenic CD4 T cells in a different model of AIH. In their model, the absence of B cells exacerbates the disease and regulatory B cells improve it. This apparent discrepancy may stem, as discussed in their article,4 from the S100 experimental AIH model that is based on complete Freund adjuvant administration, a model in which the pathogenesis is considerably different from that of AIH patients or from the type 2 AIH model. While a role of regulatory B cells in our murine model and AIH patients cannot be excluded, clinical and laboratory evidence suggests a predominant role for a pathological subset(s) of B cells. As pointed out, sustained B‐cell depletion raises concerns as to increased risk of infections and deleterious side effects. Our study provided preclinical data on the efficacy and mechanism of B‐cell depletion in AIH and did not aim to address safety issues. However, the data suggest that rituximab is well tolerated in AIH patients,2 and the rate of severe infection during multiple courses of rituximab is between four and six cases per 100 patients, comparable to that of anti‐tumor necrosis factor‐α therapy.5 Rituximab is used to treat various conditions and has an established safety profile and a treatment regimen that minimizes serious side effects. Because B‐cell depletion seems to effectively induce remission of AIH, it would be interesting to develop new therapies able to target pathological, while sparing regulatory, B‐cell subsets to see if treatment efficacy could be improved and side effects minimized.
Impact of Co-Occurring Posttraumatic Stress Disorder on Suicidal Women With Borderline Personality Disorder
Authors: Melanie S. Harned, Shireen L. Rizvi, Marsha M. Linehan
Journal: American Journal of Psychiatry (2010)

The authors examined the impact of co-occurring posttraumatic stress disorder (PTSD) on women with borderline personality disorder who had attempted suicide in the preceding year.Female borderline personality disorder outpatients (N=94) either with (N=53, 56.4%) or without PTSD (N=41, 43.6%) and with recent and repeated suicidal or self-injurious behavior were compared in nine areas of functioning.Borderline personality disorder patients with and without PTSD differed in the lethality, intent, and triggers for intentional self-injury, trauma history, emotion regulation, and axis I comorbidity. The two groups did not differ in borderline personality disorder severity, axis II comorbidity, psychosocial functioning, or mental health or medical treatment utilization.The results indicate greater impairment among individuals with both disorders and suggest that there are some unique features associated with co-occurring borderline personality disorder and PTSD that require further attention in assessment and treatment.
<i>Micrococcus</i>folliculitis in HIV-1 disease
Authors: None Smith, None Neafie, None Yeager, None Skelton
Journal: British Journal of Dermatology (1999)

Organisms with little pathogenic potential in immunocompetent hosts may produce disease in HIV-1 + patients. We describe three HIV-1 + patients in late disease who presented with pruritic papules with central ulceration over the face and arms. In all the patients the eruptions had been present for months, and the patients did not develop sepsis. Biopsy specimens in all the patients showed large Gram-positive cocci, forming tetrads. Colony morphology, catalase positivity and coagulase negativity, and resistance to nitrofurantoin were used to separate micrococci from staphylococci. Micrococcus species are usually considered normal inhabitants of the skin; however, in patients with HIV-1 disease, Micrococcus species can produce localized cutaneous infections.
Combination Antiretroviral Therapy and the Risk of Myocardial Infarction
Authors: Nina Friis-Møller, Caroline A Sabin, Rainer Weber, Antonella d'Arminio Monforte, Wafaa M El-Sadr, Peter Reiss, Rodolphe Thiébaut, Linda Morfeldt, Stephane De Wit, Christian Pradier, Gonzalo Calvo, Matthew G Law, Ole Kirk, Andrew N Phillips, Jens D Lundgren
Journal: New England Journal of Medicine (2003)

It remains controversial whether exposure to combination antiretroviral treatment increases the risk of myocardial infarction. methodsIn this prospective observational study, we enrolled 23,468 patients from 11 previously established cohorts from December 1999 to April 2001 and collected follow-up data until February 2002.Data were collected on infection with the human immunodeficiency virus and on risk factors for and the incidence of myocardial infarction.Relative rates were calculated with Poisson regression models.Combination antiretroviral therapy was defined as any combination regimen of antiretroviral drugs that included a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. resultsOver a period of 36,199 person-years, 126 patients had a myocardial infarction.The incidence of myocardial infarction increased with longer exposure to combination antiretroviral therapy (adjusted relative rate per year of exposure, 1.26 [95 percent confidence interval, 1.12 to 1.41]; P<0.001).Other factors significantly associated with myocardial infarction were older age, current or former smoking, previous cardiovascular disease, and male sex, but not a family history of coronary heart disease.A higher total serum cholesterol level, a higher triglyceride level, and the presence of diabetes were also associated with an increased incidence of myocardial infarction.conclusions Combination antiretroviral therapy was independently associated with a 26 percent relative increase in the rate of myocardial infarction per year of exposure during the first four to six years of use.However, the absolute risk of myocardial infarction was low and must be balanced against the marked benefits from antiretroviral treatment.
Magnetic Nanoparticles and microNMR for Diagnostic Applications
Authors: Huilin Shao, Changwook Min, David Issadore, Monty Liong, Tae-Jong Yoon, Ralph Weissleder, Hakho Lee
Journal: Theranostics (2012)

Sensitive and quantitative measurements of clinically relevant protein biomarkers, pathogens and cells in biological samples would be invaluable for disease diagnosis, monitoring of malignancy, and for evaluating therapy efficacy.Biosensing strategies using magnetic nanoparticles (MNPs) have recently received considerable attention, since they offer unique advantages over traditional detection methods.Specifically, because biological samples have negligible magnetic background, MNPs can be used to obtain highly sensitive measurements in minimally processed samples.This review focuses on the use of MNPs for in vitro detection of cellular biomarkers based on nuclear magnetic resonance (NMR) effects.This detection platform, termed diagnostic magnetic resonance (DMR), exploits MNPs as proximity sensors to modulate the spin-spin relaxation time of water molecules surrounding the molecularly-targeted nanoparticles.With new developments such as more effective MNP biosensors, advanced conjugational strategies, and highly sensitive miniaturized NMR systems, the DMR detection capabilities have been considerably improved.These developments have also enabled parallel and rapid measurements from small sample volumes and on a wide range of targets, including whole cells, proteins, DNA/mRNA, metabolites, drugs, viruses and bacteria.The DMR platform thus makes a robust and easy-to-use sensor system with broad applications in biomedicine, as well as clinical utility in point-of-care settings.
Abstract IA20: Epigenetic deregulation of gene expression
Authors: Ari Melnick
Journal: Cancer Research (2013)

Abstract Epigenetic deregulation of gene expression through aberrant DNA methylation or histone modification plays an important role in the malignant transformation of hematopoietic cells. In particular, acute myeloid leukemias (AMLs) can be classified according to epigenetic signatures affecting DNA methylation or histone modifications affecting specific gene sets. Heterozygous somatic mutations in the loci encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in ~20% of AMLs and are accompanied by global DNA hypermethylation and hypermethylation and silencing of a number of specific gene promoters. IDH1/2 mutations are almost completely mutually exclusive with somatic loss of function mutations in TET2, which hydroxylates methylcytosine (mCpG). DNA hydroxymethylation can function as an intermediate step in mCPG demethylation. TET2 mutant de novo AMLs also display global and promoter specific hypermethylation partially overlapping with IDH1/2 mutant cases. Mutations in the IDH1/2 loci result in a neomorphic enzyme that generates the aberrant oncometabolite 2-hydroxyglutarate (2HG) using alpha-ketoglutarate (aKG) as a substrate. 2HG can disrupt the activity of enzymes that use aKG as a cofactor, including TET2 and the Jumonji family of histone demethylases. Expression of mutant IDH isoforms inhibit TET2 hydroxymethylation and Jumonji histone demethylase functions. IDH and TET2 mutant AMLs accordingly exhibit reduced levels of hydroxymethylcytosine and a trend towards reduced histone methylation. Mutant IDH or TET2 loss of function causes differentiation blockade and expansion of hematopoietic stem cells and TET2 knockout results in a myeloproliferative phenotype in mice. Hydroxymethylcytosine is abundance in hematopoietic stem cells, and displays specific distribution patterns, and yet the function of this covalent modification is not fully understood. Recent data link TET2 with the function of cytosine deaminases as a pathway towards DNA demethylation, which has implications as well for B-cell lymphomas and CML lymphoid blast crisis, which are linked with the actions of activation induced cytosine deaminase. Altogether, the available data implicate mutations in IDH1/2 and TET2 in promoting malignant transformation in several tissues, by disrupting epigenomics programming and altering gene expression patterning. Citation Format: Ari Melnick. Epigenetic deregulation of gene expression. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA20.
Ambrisentan for pulmonary fibrosis
Authors: Ravi Punwani
Journal: Thorax (2013)

Ambrisentan for pulmonary fibrosisThis randomised, double-blind, placebo-controlled study is one of the largest multicentre studies investigating whether ambrisentan (an endothelin A receptor antagonist) reduces the rate of idiopathic pulmonary fibrosis (IPF) progression.The investigators compared ambrisentan (more commonly used in the treatment of pulmonary hypertension (PH)) with placebo on the basis of preclinical studies suggesting endothelin receptor blockade decreased the severity of pulmonary fibrosis.The primary endpoint was time to IPF progression defined as either death, respiratory hospitalisation or prespecified decrease in lung function (whichever came first).Target recruitment was 660 over 18 months.However, at 75% of enrolment (492) the study was terminated due to a low likelihood of showing efficacy by the study end.However, more worryingly ambrisentan-treated patients were more likely to have disease progression, more likely to suffer lung function decline, more likely to suffer respiratory hospitalisations and more likely to die when compared with placebo.One reason given for the worse outcomes is worse baseline IPF severity.However, even allowing for this does not fully explain the differences seen.In addition, they used patients with <5% honeycombing on CT, which would suggest less severe disease, and also therefore less likely to have PH (approximately 10% in each group as determined by right heart catheterisation), a patient group which one may speculate would do better with ambrisentan.The authors concluded that ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and hospitalisation.
COOH-Terminal Binding Protein Regulates Expression of the p16INK4A Tumor Suppressor and Senescence in Primary Human Cells
Authors: Edmund A. Mroz, Abigail H. Baird, William A. Michaud, James W. Rocco
Journal: Cancer Research (2008)

Abstract The p16/pocket-protein pathway sets a balance between tumor suppression and capacity for tissue regeneration. Understanding the upstream signaling pathway that turns on the expression of p16 is required both for knowing the tumorigenic stresses from which this pathway provides protection and for appreciating the selective pressure that leads to the loss of this pathway in most human tumors. We report that COOH-terminal binding protein (CtBP), a physiologically regulated transcriptional corepressor that dimerizes to hold together repressive complexes, regulates p16 expression in primary human fibroblasts and keratinocytes. Interfering with CtBP-mediated repression increased p16 expression and accelerated senescence. CtBP had little influence on the expression of the alternate product of the CDKN2A tumor-suppressor gene, p14ARF. Loss of CtBP-mediated repression diminished the Polycomb-based epigenetic histone mark that is reported to favor silencing of p16 via DNA methylation. Enhancing CtBP-mediated repression by growing cells in low oxygen increased the association of CtBP with the p16 promoter, as assessed by chromatin immunoprecipitation, and reduced p16 expression. Stresses and stimuli that reduce CtBP-mediated repression are associated with increased p16 expression; therefore, CtBP may provide a common final target for regulating the balance among tumor suppression, regenerative capacity, and senescence. [Cancer Res 2008;68(15):6049–53]
Epidermal Growth Factor Receptor Inhibitors: A Moving Target?
Authors: Susan E. Bates, Tito Fojo
Journal: Clinical Cancer Research (2005)

It has been over 20 years since the first agents targeting the epidermal growth factor receptor (EGFR) pathway were developed by Mendelsohn and Baselga ([1][1]). In vitro studies demonstrating that antibodies inhibiting the pathway could retard cell growth, and markedly so in some cell lines, led
Relationship between blood hydroxychloroquine and desethylchloroquine concentrations and cigarette smoking in treated patients with connective tissue diseases
Authors: G. Leroux, N. Costedoat-Chalumeau, J.-S. Hulot, Z. Amoura, C. Frances, G. Aymard, P. Lechat, J.-C. Piette
Journal: Annals of the Rheumatic Diseases (2007)

Cigarette smoking has been suspected to increase the risk and the activity of systemic lupus erythematosus (SLE)1 2 and cutaneous lupus.3 4 Some data indicate that cigarette smoking might interfere with the effectiveness of hydroxychloroquine and chloroquine in cutaneous lupus.3 4 As these antimalarial agents are partly metabolised via the cytochrome P450 enzyme system and as the constituents of cigarette smoke are known potent inducers of cytochrome P450, it has been hypothesised that the resistance of cutaneous lupus might be explained by a modification of the metabolism of these …
Cancer Incidence in a Religious Isolate of Alberta, Canada, 1953–74 2 3
Authors: L. A. Gaudette, T. M. Holmes, L. M. Laing, K. Morgan, M. G. A. Grace
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Cancer Incidence in a Religious Isolate of Alberta, Canada, 1953–74 Get access L. A. Gaudette, L. A. Gaudette Search for other works by this author on: Oxford Academic PubMed Google Scholar T. M. Holmes, T. M. Holmes Search for other works by this author on: Oxford Academic PubMed Google Scholar L. M. Laing, L. M. Laing Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Morgan, K. Morgan Search for other works by this author on: Oxford Academic PubMed Google Scholar M. G. A. Grace M. G. A. Grace 7 7Address reprint requests to Dr. Grace. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 6, June 1978, Pages 1233–1238, https://doi.org/10.1093/jnci/60.6.1233 Published: 01 June 1978 Article history Received: 09 August 1977 Accepted: 11 January 1978 Published: 01 June 1978
Relationship between cancer and allergy.
Authors: Bruno Gustavo Muzzi Carvalho Carneiro, Andy Petroianu, Rafael Augusto Ribeiro Carvalho, Thiago Neto Ribeiro, Ana Maria Santos Rodrigues
Journal: Journal of Clinical Oncology (2012)

e12018 Background: Many studies have suggested an inverse association between allergies and cancer, while others have found no relation between them, and still others have shown an increased risk of cancer in allergy patients. The conflicting findings from prior studies are partially due to the chosen research method, such as different definitions and measures for atopy, in addition to variations in the control of confusion factors, such as smoking and obesity. Objectives: Verify if there is a relation between certain types of cancer and allergies; investigate if there is a difference between individuals with and without cancer in relation to allergies. Methods: Case-control study carried out at the Alberto Cavalcanti Hospital of the Hospital Foundation of the State of Minas Gerais (FHEMIG), Brazil, from 2009 to 2011. The study included patients over 18 years of age, from both genders, who presented a diagnosis of cancer, as compared to healthy individuals, paired by gender and age. An anamnesis was gathered considering the medical history of the allergy, as diagnosed by a doctor, as well as the patients’ habits, associated illnesses, and the use of medications. For cancer patients, data concerning the tumor were recorded. Subsequently, an allergy percutaneous test was performed in each group to detect allergic hyperreactivity toward common inhalable, bacterial, and food antigens within our everyday environment. A blood sample was collected to quantitatively evaluate the eosinophils. Results: Both groups were paired according to interest variables, and eventual deviations were adjusted by means of multivariate analysis. Reports of allergies occurred in 30% of the patients in the cancer group, as compared to 53% in the control group (p&lt;0.05), whereas in the cutaneous tests, a greater positivity occurred in the cancer group (69%) than in the control group (51%, p&lt;0.05). No difference in the eosinophil values could be observed within the groups. Conclusions: Cancer patients present fewer allergies. By contrast, in cancer patients, positive cutaneous tests detected allergies which did not correspond to the clinical findings. Therefore, in cancer patients, the positive cutaneous test for allergies does not present a direct relation to the presence of clinically detectable allergies.