tbuckley/cabot-search huggingface dataset:
mRNA Retrotransposition Coupled with 5' Inversion as a Possible Source of New Genes
Authors: K. K. Kojima, N. Okada
Journal: Molecular Biology and Evolution (2009)

Human long interspersed nuclear element-1 (L1) occupies one-sixth of our genome and has contributed to genome evolution in various ways. Approximately 10% of human L1 copies are composed of two L1 segments; the 5′ segment and 3′ segment are in head-to-head (i.e., 5′-inverted) orientation. Besides mediating their own retrotransposition, L1 has the ability to mobilize mRNA "in trans," and the number of retrotransposed mRNA sequences (retrocopies) is estimated to be >6,000. In this study, we identified 48 human-specific retrocopies and 95 chimpanzee-specific retrocopies by comparing the human and chimpanzee genomes. Among these retrocopies, 12 were 5′-inverted. The characteristics of these 5′-inverted retrocopies were similar to those of 5′-inverted L1 copies, indicating that the 5′ inversion is generated by the same mechanism. With these findings, we examined the possibility that 5′ inversion of the retrocopy generates a new gene that codes for a peptide with a different N terminus. We identified several potential 5′-inverted retrogenes, including those of thymopoietin beta (TMPO) and eukaryotic translation initiation factor 3 subunit 5 (EIF3F). The most interesting candidate was the 5′-inverted retrocopy of small nuclear ribonucleoprotein polypeptide N (SNRPN). This retrocopy was transcribed in the reverse orientation in several organs, had multiple transcript variants, and encoded a protein containing a peptide fragment derived from the N-terminal portion of SNRPN. Our results suggest that mRNA retrotransposition coupled with 5′ inversion may be a mechanism to generate new genes distinct from parental genes.
Prognostic Value of Myocardial Perfusion Studies in Patients with End-Stage Renal Disease Assessed for Kidney or Kidney-Pancreas Transplantation
Authors: Christian G. Rabbat, Darin J. Treleaven, J. David Russell, David Ludwin, Deborah J. Cook
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The prognostic utility of myocardial perfusion studies (MPS) such as thallium scintigraphy and dobutamine stress echocardiography (DSE) for stratifying cardiac risk among candidates for kidney or kidney-pancreas transplantation is uncertain. This study is a meta-analysis to determine the prognostic significance of MPS results on future myocardial infarction (MI) and cardiac death (CD) in patients with end-stage renal disease (ESRD) assessed for kidney or kidney-pancreas transplantation. MEDLINE was searched using combinations of MeSH headings and text words for transplantation, coronary artery disease, prognosis, end-stage renal disease, and noninvasive cardiac testing (nuclear scintigraphy and DSE) for primary studies. Studies were included if they reported MPS results and cardiac events in patients assessed for kidney or kidney-pancreas transplantation. Methodologic study quality and outcome data were independently abstracted in duplicate by two researchers. The relative risks (RR) of MI and CD were calculated using a random effects model. Twelve articles met all inclusion criteria; 12 studies reported CD, and 9 reported MI. In eight studies, thallium scintigraphy was used (four with pharmacologic stress, four with exercise stress), whereas four used DSE. When compared with negative tests, positive tests had a significantly increased RR of MI (2.73 [95% CI, 1.25 to 5.97]; P = 0.01) and CD (2.92 [95% CI, 1.66 to 5.12]; P < 0.001). Subgroup analyses of studies of diabetic patients indicated that positive tests were associated with a RR of CD 3.95 (95% CI, 1.48 to 10.5; P = 0.006) and a RR of MI 2.68 (95% CI, 0.95 to 7.57; P = 0.06) when compared with negative tests. In studies evaluating mixed populations of diabetic and nondiabetic patients, positive tests were associated with a RR of CD 2.52 (95% CI, 1.25 to 5.08; P = 0.01) and with a RR of MI 2.79 (95% CI, 0.85 to 9.21; P = 0.09) when compared with a negative test. The presence of reversible defects was associated with an increased risk of MI in diabetic patients and of CD in both subgroups; fixed defects were associated with an increased risk of CD but not MI. It is concluded that positive MPS are useful in identifying patients with significantly increased risk of future MI and CD in both diabetic and nondiabetic ESRD patients. E-mail: [email protected]
A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG)—the 4th study
Authors: M. Nakagawa, F. Tanaka, N. Tsubota, M. Ohta, M. Takao, H. Wada
Journal: Annals of Oncology (2004)
The effect of a chemically defined diet on the faecal flora and faecal steroid concentration
Authors: J. S. Crowther, B. S. Drasar, P. Goddard, M. J. Hill, K. Johnson
Journal: Gut (1973)

The consumption of a chemically defined diet altered both the faecal flora and faecal steroids. Enterobacteria increased while enterococci and other lactic acid bacteria decreased in number. No other obvious change occurred. However, the alteration in the degree of degradation of the faecal neutral steroids may reflect some alteration in the anaerobic flora. Total excretion of both acid and neutral steroids was also reduced. On cessation of the diet both faecal flora and faecal steroids reverted to levels before the diet.
Hepatic Changes in Young Women Ingesting Contraceptive Steroids
Authors: E. Truman Mays
Journal: JAMA (1976)

Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role.
Diminished Insulin Secretory Response to Glucose but Normal Insulin and Glucagon Secretory Responses to Arginine in a Family With Maternally Inherited Diabetes and Deafness Caused by Mitochondrial tRNALEU(UUR) Gene Mutation
Authors: Michael Brändle, Roger Lehmann, Friedrich E. Maly, Christoph Schmid, Giatgen A. Spinas
Journal: Diabetes Care (2001)

The effects of glucose, arginine, and glucagon on beta-cell function as well as alpha-cell response to arginine were studied in a family with mitochondrial diabetes.The function of alpha- and beta-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test.The glucose disappearance constant (K(g)) value (mean +/- SEM 0.61 +/- 0.04 vs. 1.1 +/- 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0-10 min, 77.7 +/- 50.7 vs. 1,352.3 +/- 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 +/- 111.4 vs. 1,526.7 +/- 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 +/- 710.8 vs. 1,083.2 +/- 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 +/- 47.5 vs. 90.0 +/- 21.1 pmol/l, P = 0.099).This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.
The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma
Authors: Satoshi Shimizu, Tetsuo Takehara, Hayato Hikita, Takahiro Kodama, Takuya Miyagi, Atsushi Hosui, Tomohide Tatsumi, Hisashi Ishida, Takehiro Noda, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, Norio Hayashi
Journal: Journal of Hepatology (2010)
Lymphangioma: a rare cause of a mediastinal mass
Authors: R J Parker
Journal: Thorax (2004)

A chest radiograph performed on an asymptomatic 47 year old man under investigation for hypertension was suspicious of a retrocardiac mass. Contrast enhanced computed tomographic (CT) scanning demonstrated a large low attenuation mass encasing the oesophagus. It extended from the carina to the diaphragm and measured 15 × 7 cm in diameter (fig 1). The air space …
GPI-anchored complement regulatory proteins in seminal plasma. An analysis of their physical condition and the mechanisms of their binding to exogenous cells.
Authors: I A Rooney, J E Heuser, J P Atkinson
Journal: Journal of Clinical Investigation (1996)

We analyzed and compared the properties of three glycosylphosphatidylinositol (GPI)-anchored proteins. CD59, CD55 (both C regulators), and CDw52, and of the transmembrane C regulator CD46 in seminal plasma (SP). We demonstrated previously that anchor-intact SP CD59 is present on the membranes of vesicles (prostasomes) and that cells acquire this protein during incubation with SP. We now report that this acquisition is due partly to adherence of prostasomes to cells and partly to a second mechanism which may involve micellar intermediates. Using fluorescent labeling, ultracentrifugation, and density gradient centrifugation, virtually all CD46 was present on prostasomes whereas CD59, CD55, AND CDw52 were also detected in a form which remained in the 200,000 g supernatant and equilibrated at higher density than prostasomes in gradients. All three GPI-linked proteins eluted at high molecular mass during size exclusion chromatography of this nonprostasome fraction. As documented by videomicroscopy and biochemical analysis, cells acquired new copies of the GPI-linked proteins during incubation with the nonprostasome fraction as well as with prostasomes. These data demonstrate the presence in SP of a stable population of membrane-free, GPI-linked proteins available for transfer to cells. Binding of these proteins to spermatozoa and pathogens in SP may confer new properties on their membranes including increased resistance to C attack. Finally, our data raise the possibility that lipid-associated GPI-linked proteins may be suitable for therapeutic applications.
Asymmetric Division and Lineage Commitment at the Level of Hematopoietic Stem Cells
Authors: Hina Takano, Hideo Ema, Kazuhiro Sudo, Hiromitsu Nakauchi
Journal: The Journal of Experimental Medicine (2004)

How hematopoietic stem cells (HSCs) commit to a particular lineage is unclear. A high degree of HSC purification enabled us to address this issue at the clonal level. Single-cell transplantation studies revealed that 40% of the CD34−/low, c-Kit+, Sca-1+, and lineage marker− (CD34−KSL) cells in adult mouse bone marrow were able, as individual cells, to reconstitute myeloid and B- and T-lymphoid lineages over the long-term. Single-cell culture showed that &amp;gt;40% of CD34−KSL cells could form neutrophil (n)/macrophage (m)/erythroblast (E)/megakaryocyte (M) (nmEM) colonies. Assuming that a substantial portion of long-term repopulating cells can be detected as nmEM cells within this population, we compared differentiation potentials between individual pairs of daughter and granddaughter cells derived in vitro from single nmEM cells. One of the two daughter or granddaughter cells remained an nmEM cell. The other showed a variety of combinations of differentiation potential. In particular, an nmEM cell directly gave rise, after one cell division, to progenitor cells committed to nm, EM, or M lineages. The probability of asymmetric division of nmEM cells depended on the cytokines used. These data strongly suggest that lineage commitment takes place asymmetrically at the level of HSCs under the influence of external factors.
Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load
Authors: M. Yanina Pepino, Courtney D. Tiemann, Bruce W. Patterson, Burton M. Wice, Samuel Klein
Journal: Diabetes Care (2013)

OBJECTIVE Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects. RESEARCH DESIGN AND METHODS Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m2) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics. RESULTS Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P &amp;lt; 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P &amp;lt; 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose. CONCLUSIONS These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS.
Quality of Chart Review for Quality of Care
Authors: A. Russell Localio
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Dr Ellerbeck and colleagues<sup>1</sup>support the accuracy of their abstraction of clinical indicators from medical records using κ statistics based on duplicate reviews of 912 records. However, the κ statistic is inappropriate and uninformative in this application, since κ measures agreement, corrected for chance, between reviewers when the true finding is not known,<sup>2</sup>whereas in chart abstraction the presence or absence of an indicator can be ascertained with certainty. More appropriate measures of accuracy are sensitivity and specificity.<sup>3</sup>In this setting, sensitivity is the proportion of cases correctly identified when the indicator is present in the medical record, while specificity is the proportion of cases correctly identified as having no indicator present. Using κ can mislead. For example, suppose the prevalence of the indicator is 10% in a sample of 1000 records, the sensitivity of the record abstraction is 75% (75 correct of 100
Risk Factors for Locoregional Recurrence Among Breast Cancer Patients: Results From International Breast Cancer Study Group Trials I Through VII
Authors: A. Wallgren, M. Bonetti, R.D. Gelber, A. Goldhirsch, M. Castiglione-Gertsch, S.B. Holmberg, J. Lindtner, B. Thürlimann, M. Fey, I.D. Werner, J.F. Forbes, K. Price, A.S. Coates, J. Collins
Journal: Journal of Clinical Oncology (2003)

To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies.The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years.In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women.LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
Prevalence of Retinopathy in People With Diabetes, Impaired Glucose Tolerance, and Normal Glucose Tolerance
Authors: Ulla Rajala, Mauri Laakso, Qing Qiao, Sirkka Keinänen-Kiukaanniemi
Journal: Diabetes Care (1998)

Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based studyThe population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%).There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information.The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.
COPD prognosis in relation to diagnostic criteria for airflow obstruction in smokers
Authors: Reinier P. Akkermans, Marion Biermans, Bas Robberts, Gerben ter Riet, Annelies Jacobs, Chris van Weel, Michel Wensing, Tjard Schermer
Journal: European Respiratory Journal (2013)

The aim of this study was to establish which cut-off point for the forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio ( i.e. fixed 0.70 or lower limit of normal (LLN) cut-off point) best predicts accelerated lung function decline and exacerbations in middle-aged smokers. We performed secondary analyses on the Lung Health Study dataset. 4045 smokers aged 35–60 years with mild-to-moderate obstructive pulmonary disease were subdivided into categories based on presence or absence of obstruction according to both FEV 1 /FVC cut-off points. Post-bronchodilator FEV 1 decline served as the primary outcome to compare subjects between the categories. 583 (14.4%) subjects were nonobstructed and 3230 (79.8%) subjects were obstructed according to both FEV 1 /FVC cut-off points. 173 (4.3%) subjects were obstructed according to the fixed cut-off point, but not according to the LLN cut-off point (“discordant” subjects). Mean± se post-bronchodilator FEV 1 decline was 41.8±2.0 mL·year −1 in nonobstructed subjects, 43.8±3.8 mL·year −1 in discordant subjects and 53.5±0.9 mL·year −1 in obstructed subjects (p&lt;0.001). Our study showed that FEV 1 decline in subjects deemed obstructed according to a fixed criterion (FEV 1 /FVC &lt;0.70), but non-obstructed by a sex- and age-specific criterion (LLN) closely resembles FEV 1 decline in subjects designated as non-obstructed by both criteria. Sex and age should be taken into account when assessing airflow obstruction in middle-aged smokers.
Glycosylation, Hypogammaglobulinemia, and Resistance to Viral Infections
Authors: Mohammed A. Sadat, Susan Moir, Tae-Wook Chun, Paolo Lusso, Gerardo Kaplan, Lynne Wolfe, Matthew J. Memoli, Miao He, Hugo Vega, Leo J.Y. Kim, Yan Huang, Nadia Hussein, Elma Nievas, Raquel Mitchell, Mary Garofalo, Aaron Louie, Derek C. Ireland, Claire Grunes, Raffaello Cimbro, Vyomesh Patel, Genevieve Holzapfel, Daniel Salahuddin, Tyler Bristol, David Adams, Beatriz E. Marciano, Madhuri Hegde, Yuxing Li, Katherine R. Calvo, Jennifer Stoddard, J. Shawn Justement, Jerome Jacques, Debra A. Long Priel, Danielle Murray, Peter Sun, Douglas B. Kuhns, Cornelius F. Boerkoel, John A. Chiorini, Giovanni Di Pasquale, Daniela Verthelyi, Sergio D. Rosenzweig
Journal: New England Journal of Medicine (2014)

Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.