tbuckley/cabot-search huggingface dataset:
Rapid Sequence Turnover at an Intergenic Locus in Drosophila
Authors: N. D. Singh
Journal: Molecular Biology and Evolution (2004)

Closely related species of Drosophila tend to have similar genome sizes. The strong imbalance in favor of small deletions relative to insertions implies that the unconstrained DNA in Drosophila is unlikely to be passively inherited from even closely related ancestors, and yet most DNA in Drosophila genomes is intergenic and potentially unconstrained. In an attempt to investigate the maintenance of this intergenic DNA, we studied the evolution of an intergenic locus on the fourth chromosome of the Drosophila melanogaster genome. This 1.2-kb locus is marked by two distinct, large insertion events: a nuclear transposition of a mitochondrial sequence and a transposition of a nonautonomous DNA transposon DNAREP1_DM. Because we could trace the evolutionary histories of these sequences, we were able to reconstruct the length evolution of this region in some detail. We sequenced this locus in all four species of the D. melanogaster species complex: D. melanogaster, D. simulans, D. sechellia, and D. mauritiana. Although this locus is similar in size in these four species, less than 10% of the sequence from the most recent common ancestor remains in D. melanogaster and all of its sister species. This region appears to have increased in size through several distinct insertions in the ancestor of the D. melanogaster species complex and has been shrinking since the split of these lineages. In addition, we found no evidence suggesting that the size of this locus has been maintained over evolutionary time; these results are consistent with the model of a dynamic equilibrium between persistent DNA loss through small deletions and more sporadic DNA gain through less frequent but longer insertions. The apparent stability of genome size in Drosophila may belie very rapid sequence turnover at intergenic loci.
Prognostic and Therapeutic Impact of the Histopathologic Definition of Parenchymal Epithelial Renal Tumors
Authors: Vincenzo Ficarra, Matteo Brunelli, Liang Cheng, Ziya Kirkali, Antonio Lopez-Beltran, Guido Martignoni, Rodolfo Montironi, Giacomo Novara, Hein Van Poppel
Journal: European Urology (2010)
Specificity of 5l Cr-Release Cytotoxicity of Lymphocytes Immune to Murine Sarcoma Virus 2
Authors: Ronald B. Herberman, Tadao Aoki, Myrthel Nunn, David H. Lavrin, N. Soares, Adi Gazdar, Howard Holden, K. S. S. Chang
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Specificity of 5lCr-Release Cytotoxicity of Lymphocytes Immune to Murine Sarcoma Virus Get access Ronald B. Herberman, Ronald B. Herberman 3Laboratory of Cell Biology, National Cancer .Institute, National Institutes of Health, Public Health Service, U.S, Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tadao Aoki, Tadao Aoki 4Viral Leukemia and Lymphoma Branch, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Myrthel Nunn, Myrthel Nunn 3Laboratory of Cell Biology, National Cancer .Institute, National Institutes of Health, Public Health Service, U.S, Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar David H. Lavrin, David H. Lavrin 5Litton Bionetics, Inc., Kensington, Md. 20795. Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Soares, N. Soares 5Litton Bionetics, Inc., Kensington, Md. 20795. Search for other works by this author on: Oxford Academic PubMed Google Scholar Adi Gazdar, Adi Gazdar 4Viral Leukemia and Lymphoma Branch, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard Holden, Howard Holden 3Laboratory of Cell Biology, National Cancer .Institute, National Institutes of Health, Public Health Service, U.S, Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar K. S. S. Chang K. S. S. Chang 3Laboratory of Cell Biology, National Cancer .Institute, National Institutes of Health, Public Health Service, U.S, Department of Health, Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 4, October 1974, Pages 1103–1111, https://doi.org/10.1093/jnci/53.4.1103 Published: 01 October 1974 Article history Received: 15 April 1974 Accepted: 20 June 1974 Published: 01 October 1974
Selection Against Deleterious LINE-1-Containing Loci in the Human Lineage
Authors: Stéphane Boissinot, Ali Entezam, Anthony V. Furano
Journal: Molecular Biology and Evolution (2001)

We compared sex chromosomal and autosomal regions of similar GC contents and found that the human Y chromosome contains nine times as many full-length (FL) ancestral LINE-1 (L1) elements per megabase as do autosomes and that the X chromosome contains three times as many. In addition, both sex chromosomes contain a ca. twofold excess of elements that are >500 bp but not long enough to be capable of autonomous replication. In contrast, the autosomes are not deficient in short (<500 bp) L1 elements or SINE elements relative to the sex chromosomes. Since neither the Y nor the X chromosome, when present in males, can be cleared of deleterious genetic loci by recombination, we conclude that most FL L1s were deleterious and thus subject to purifying selection. Comparison between nonrecombining and recombining regions of autosome 21 supported this conclusion. We were able to identify a subset of loci in the human DNA database that once contained active L1 elements, and we found by using the polymerase chain reaction that 72% of them no longer contain L1 elements in a representative of each of eight different ethnic groups. Genetic damage produced by both L1 retrotransposition and ectopic (nonallelic) recombination between L1 elements could provide the basis for their negative selection.
Effects of Blood Glucose Rate of Changes on Perceived Mood and Cognitive Symptoms in Insulin-Treated Type 2 Diabetes
Authors: Daniel J. Cox, Anthony McCall, Boris Kovatchev, Samiha Sarwat, Liza L. Ilag, Meng H. Tan
Journal: Diabetes Care (2007)

Studies indicate that diabetes affects mood, cognitive function, and motor performance (1–5). As cognitive dysfunction and depressive mood symptoms have been reported with hyperglycemia (5–7), we hypothesized that the impact of insulin on blood glucose parameters would affect mood and cognitive symptoms. Consistent with our past post hoc findings (7), we specifically hypothesized that rapid pre- to postmeal blood glucose rate of change (BGRATE) correlates with negative mood and cognitive postmeal symptoms but not with energy or positive mood. We report the results of correlation analyses of BGRATE with symptoms from a pilot investigation designed to evaluate whether improvements in glycemic control seen with basal plus prandial insulin analog regimens compared with basal insulin analog in patients with type 2 diabetes (8–10) would lead to measurable mood and cognitive differences.

A single-center, open-label, crossover, randomized, controlled clinical trial enrolled 60 adults with type 2 diabetes, A1C 7–10%, and prestudy use of metformin (with or without oral antihyperglycemic medications or once daily insulin). Pregnant or breast-feeding women and patients with a previous diagnosis of depression or treated with centrally acting medications (e.g., antidepressants or anxiolytics) were excluded.

Patients were randomly assigned to treatment with Humalog Mix 75/25 (insulin lispro mixture [75% lispro protamine suspension/25% …
Ionizing Radiation Predisposes Nonmalignant Human Mammary Epithelial Cells to Undergo Transforming Growth Factor β–Induced Epithelial to Mesenchymal Transition
Authors: Kumari L. Andarawewa, Anna C. Erickson, William S. Chou, Sylvain V. Costes, Philippe Gascard, Joni D. Mott, Mina J. Bissell, Mary Helen Barcellos-Hoff
Journal: Cancer Research (2007)

Abstract Transforming growth factor β1 (TGFβ) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFβ activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFβ-mediated epithelial to mesenchymal transition (EMT). Nonmalignant HMEC (MCF10A, HMT3522 S1, and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture or treated with a low concentration of TGFβ (0.4 ng/mL) or double treated. All double-treated (IR + TGFβ) HMEC underwent a morphologic shift from cuboidal to spindle shaped. This phenotype was accompanied by a decreased expression of epithelial markers E-cadherin, β-catenin, and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin, and vimentin. Furthermore, double treatment increased cell motility, promoted invasion, and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFβ alone elicited EMT, although IR increased chronic TGFβ signaling and activity. Gene expression profiling revealed that double-treated cells exhibit a specific 10-gene signature associated with Erk/mitogen-activated protein kinase (MAPK) signaling. We hypothesized that IR-induced MAPK activation primes nonmalignant HMEC to undergo TGFβ-mediated EMT. Consistent with this, Erk phosphorylation was transiently induced by irradiation and persisted in irradiated cells treated with TGFβ, and treatment with U0126, a MAP/Erk kinase (MEK) inhibitor, blocked the EMT phenotype. Together, these data show that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression. [Cancer Res 2007;67(18):8662–70]
European League Against Rheumatism (EULAR) Scleroderma Trial and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis: methods of elaboration and results of systematic literature research
Authors: J Avouac, O Kowal-Bielecka, R Landewe, S Chwiesko, I Miniati, L Czirjak, P Clements, C Denton, D Farge, K Fligelstone, I Földvari, D E Furst, U Müller-Ladner, J Seibold, R M Silver, K Takehara, B Garay Toth, A Tyndall, G Valentini, F van den Hoogen, F Wigley, F Zulian, M Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To describe methods and procedures used for the development of the European League Against Rheumatism (EULAR)/EULAR Scleroderma Trial and Research group (EUSTAR) recommendations for the treatment of systemic sclerosis. In particular, the results of a web-based Delphi exercise aimed at selection of research questions and evidence from systematic literature research, as parts of the development of these recommendations, are presented in detail. Methods: In agreement with the EULAR standard operating procedures a Task Force was created that consisted of the EUSTAR board members, 10 systemic sclerosis (SSc) experts invited from outside the EUSTAR board and representing Europe, the USA and Japan, a clinical epidemiologist, 2 patients with SSc and 3 fellows for literature research. All EUSTAR centres were invited to contribute to the development of recommendations through submission and preliminary selection of the research questions. The systematic literature research was performed using the Pubmed, Medline, EMBASE and Cochrane databases. Retrieved trials were evaluated according to the Jadad classification, and the level of evidence was graded from 1 to 4. Outcome data for efficacy and adverse events were abstracted and effect size, number needed to treat (NNT) and number needed to harm (NNH) were calculated when appropriate. Results: In all, 65 EUSTAR Centres provided 304 research questions concerning SSc treatment. These questions were aggregated, subdivided into 19 treatment categories and then subjected to preliminary selection by a web-based Delphi technique. The final set of 26 research questions was created by the Expert Committee based on the results of the Delphi exercise and the expert’s experience. Conclusions: This paper is a comprehensive summary of the methods we used to build recommendations for the drug treatment of systemic sclerosis, combining an evidence based approach and expert opinion.
Side Effects Related to Cancer Treatment
Authors: Wing Y. Au, Kwan Ngai Hung, Thomas S. Wan, Edmond Ma
Journal: Journal of Clinical Oncology (2005)

Radiotherapy for Recurrent MeningiomaA 70-year-old HIV-negative man presented with sudden onset of right-sided weakness.He has history of repeated craniotomy for recurrent parasagittal meningioma for 17 years, and last received surgical debulking and radiotherapy (RT; 38 Gy) 3 years ago.A computed tomography scan showed a left thalamic contrastenhancing necrotic lesion (Fig 1A, arrow), suggestive of glioblastoma multiforme.Open biopsy and debridement showed an aggressive B-cell lymphoma (Fig 1B) with high Ki67 proliferative staining (70% positive) but negative for EBER.Cytogenetic analysis showed classical c-myc translocation suggestive of Burkitt's lymphoma (Fig 1C; 46-49, XY, dup(1)(q12q42), t(8;14)(q24;q32) [3], ϩadd(6)(q11) [5], ϩX, ϩ7 [9]), and staging showed localized disease.Radiotherapy was planned, but 6 days later, fleshy tumor nodules were noted on the craniotomy sutures (Fig 1D, arrow).Biopsy showed lymphoma involvement, and the patient died shortly afterwards.Primary cerebral lymphomas in Chinese patients are mostly EBER-negative localized disease in immunocompetent hosts. 1 Primary cerebral Burkitt's lymphoma is rare, and the aggressive direct outward spread of lymphoma via the surgical tract is hitherto unreported. 2 It is unclear whether the unusual tumor is related to recurrent meningioma or previous radiotherapy.Most reports of concomi-tant or sequential cerebral lymphoma and meningioma are chance findings of small incidental meningiomas. 3,4 Lymphoma following recurrent meningioma is rare, and the older age of presentation did not favor a hereditary cancerprone syndrome.On the other hand, lymphoma is also uncommon among secondary brain cancers after cranial RT. 5,6 However, some studies suggested a wider variety of secondary cerebral cancers after cranial RT, with long latencies of up to 15 years. 7Hence, despite the long time lag, an association with previous meningioma and radiation cannot be excluded in our case.
Flow cytometric quantification of T6-positive cells in psoriatic epidermis after PUVA and methotrexate therapy
Authors: J. M. GOMMANS, S. J. T. M. HEZIK, B. E. W. L. HUYSTEE
Journal: British Journal of Dermatology (1987)

We describe a flow cytometric technique for measuring the percentage of T6-positive cells in suspensions prepared by trypsinization of human epidermis. The value obtained for healthy controls (1.55 +/- 0.52%) corresponds to about 600 T6-positive cells per mm2 of skin surface, a figure in line with histological estimates. No significant change was found in the percentage of T6-positive cells in either the uninvolved or lesional epidermis of untreated psoriatic patients. PUVA treatment resulted in a significant reduction in T6-positive cells. A cyclic fluctuation in the numbers of T6-positive cells was shown to accompany methotrexate administration on a weekly divided dose schedule.
Individualizing Targets and Tactics for High-Risk Patients With Type 2 Diabetes
Authors: Matthew C. Riddle, Diane M. Karl
Journal: Diabetes Care (2012)

Four years ago, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was stopped early as the result of increased mortality associated with intensive glycemic treatment of a population with type 2 diabetes (T2DM) and high cardiovascular (CV) risk (1). Further reports have appeared from ACCORD (2) and other studies of high-risk populations, notably the Action in Diabetes and Vascular Disease: Preterax and Diamacron MR Controlled Evaluation (ADVANCE) (3) and the Veterans Affairs Diabetes Trial (VADT) (4). These studies provide a body of evidence that intensive treatment of hyperglycemia in T2DM does not in all cases lead to an acceptable balance of benefits to risks. Although important questions remain, both the main findings and secondary and epidemiological analyses from these studies suggest possible changes of our therapeutic approach. This article summarizes the original findings of these trials, discusses recent reports from ACCORD, and describes the authors’ experiences in implementing the intensive regimen at a major ACCORD site. It will not cover all publications on CV risk in T2DM. Rather, we aim to present an updated view of challenges and opportunities in treating high-risk patients with T2DM, drawing mainly on lessons from ACCORD and including some testable hypotheses. The opinions expressed are our own and not meant to represent those of any professional or investigative group.

The UK Prospective Diabetes Study (UKPDS) (5) enrolled participants soon after diagnosis of T2DM and did not require them to have other CV risk factors. At the end of randomized comparison of intensive versus standard glycemic treatment, improvements of microvascular end points were found but not a reduction of CV events or mortality. However, the numbers of participants and the rates of CV events were relatively low and thus the statistical power was limited. Later studies were designed to test the effect of intensive …
A Recent Evolutionary Change Affects a Regulatory Element in the Human FOXP2 Gene
Authors: Tomislav Maricic, Viola Günther, Oleg Georgiev, Sabine Gehre, Marija Ćurlin, Christiane Schreiweis, Ronald Naumann, Hernán A. Burbano, Matthias Meyer, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Srećko Gajović, Janet Kelso, Wolfgang Enard, Walter Schaffner, Svante Pääbo
Journal: Molecular Biology and Evolution (2012)

The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.
Overexpression of Caspase-3s Splice Variant in Locally Advanced Breast Carcinoma Is Associated with Poor Response to Neoadjuvant Chemotherapy
Authors: Frédérique Végran, Romain Boidot, Claire Oudin, Jean-Marc Riedinger, Franck Bonnetain, Sarab Lizard-Nacol
Journal: Clinical Cancer Research (2006)

Abstract Purpose: CASP-3 gene gives rise, by alternative splicing to a caspase-3s variant, to the antagonist apoptotic property of caspase-3. Deregulation of splicing in tumor cells favoring the expression of antiapoptotic variants has been reported to contribute to both tumorigenesis and chemoresistance. Thus, we investigated the role of caspase-3 and its splice variant in breast cancer cells. Experimental Design: Breast tumor cell lines deficient (MCF-7) and proficient (HBL100) for CASP-3 gene were transfected with each transcript and were characterized for their apoptotic response to cyclophosphamide. Expression of the two transcripts were measured by reverse transcription-PCR in 130 breast carcinomas, including 90 locally advanced tumors treated with neoadjuvant chemotherapy containing cyclophosphamide, epirubicine, and 5-fluorouracil. Results: Overexpression of caspase-3s variant in caspase-3–transfected cell lines significantly inhibits apoptosis induced by cyclophosphamide (P &amp;lt; 0.0001 for both cell lines). In breast tissues, only caspase-3 levels were higher in carcinomas than in corresponding adjacent normal tissues (P = 0.0396). Locally advanced carcinomas with high levels of caspase-3 (P &amp;lt; 0.0001) and weak levels of caspase-3s (P = 0.0248) were more sensitive to treatment. Therefore, increase in caspase-3s/caspase3 ratio expression was significantly associated with chemoresistance (P = 0.01). Logistic univariate and multivariate analyses realized according to pathologic response confirm that increased caspase-3s expression was indicative of chemoresistance (P = 0.012 and P = 0.026, respectively). Conclusions: The results agree with an antagonist function between the two transcripts of caspase-3 and show that their ratio of expression levels may define a subset of locally advanced breast cancer patients who are more likely to benefit from neoadjuvant cyclophosphamide-containing chemotherapy.
Smoking and ulcer perforation
Authors: C Svanes, J A Søreide, A Skarstein, B T Fevang, P Bakke, S E Vollset, K Svanes, O Søreide
Journal: Gut (1997)

The use of ulcerogenic drugs is the only well documented risk factor for peptic ulcer perforation, but accounts for only a quarter of the events. Smoking is a well known risk factor for uncomplicated ulcer disease, and patients with ulcer bleeding have increased death rates from smoking related disorders.To assess the role of smoking in ulcer perforation.A total of 168 consecutive patients with gastroduodenal ulcer perforation and 4469 control subjects from a population based health survey.The association between ulcer perforation and smoking habits was analysed by logistic regression while adjusting for age and sex.Current smoking increased the risk for ulcer perforation 10-fold in the age group 15-74 years (OR 9.7, 95% CI 5.9 to 15.8) and there was a highly significant dose-response relationship (p < 0.001). The results were similar in men (OR 9.3, 95% CI 4.9 to 17) and women (OR 11.6, 95% CI 5.3 to 25), and for gastric (OR 10.5, 95% CI 4.5 to 25) and duodenal (OR 8.6, 95% CI 4.9 to 15.4) ulcer perforation. No increase in risk was found in previous smokers (OR 0.8, 95% CI 0.2 to 2.2).Our findings suggest that smoking is a causal factor for ulcer perforation and accounts for a major part of ulcer perforations in the population aged less than 75 years.
Whatever Happened to the Chief Complaint?
Authors: Joseph E. Hardison
Journal: JAMA (1981)

Some changes in medicine are good—some are not. Some changes are perceptible—some are not. New advances, new drugs, new treatments replace the old. Tried and unproved methods of diagnosis or treatment quietly fade away. The problem list and problem-oriented notes are useful additions to the proved and traditional methods of gathering and recording data. The format of chief complaint, present illness, past history, family history, review of systems, and physical examination has remained unchanged for many years. However, something insidious and disturbing is happening to the chief complaint. We are taught to ask the patient, "What's the main thing that's bothering you?"; "Why did you come to see the doctor?"; "What's the major problem that brought you to the hospital?". We then record the chief complaint in the patient's own words: "My chest hurts"; "My eyes itch"; "My period is late"; "I'm tired all the time"; "I believe I'm losing