tbuckley/cabot-search huggingface dataset:
Estimating the Neutral Rate of Nucleotide Substitution Using Introns
Authors: M. M. Hoffman, E. Birney
Journal: Molecular Biology and Evolution (2006)

Evolutionary biologists frequently rely on estimates of the neutral rate of evolution when characterizing the selective pressure on protein-coding genes. We introduce a new method to estimate this value based on intron nucleotide substitutions. The new method uses a metascript model that considers alternative splicing forms and an algorithm to pair orthologous introns, which we call Introndeuce. We compare the intron method with a widely used method that uses observed substitutions in synonymous coding nucleotides, by using both methods to estimate the neutral rate for human–dog and mouse–rat comparisons. The estimates of the 2 methods correlate strongly (rS = 0.75), but cannot be considered directly equivalent. We also investigate the effect of alignment error and G + C content on the variance in the intron method: in both cases there is an effect, and it is species-pair specific. Although the intron method may be more useful for shorter evolutionary distances, it is less useful at longer distances due to the poor alignment of less-conserved positions.
Guidelines for Teaching Rounds
Authors: D.A. VAUGHAN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 November 1982Guidelines for Teaching RoundsD.A. VAUGHAN, M.D.D.A. VAUGHAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-5-782_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial by Frame (1) contained several helpful guidelines for organizing teaching rounds for internal medicine residents.During the past 5 years, I have served as attending physician for a rural community outreach program for senior residents from an urban teaching hospital. I have tried to improve the quality of teaching rounds, but have found these rounds to be time-consuming.After reading the editorial, I drew up new guidelines for teaching rounds that I gave to the residents and have followed for the past several months. We have saved enough time to allow for more bedside teaching...References1. FRAME B. Interaction between housestaff and attending physicians [Editorial]. Ann Intern Med. 1982;96:372-3. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Bethel Clinic Newton, KS 67114 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOrganic electrosyntheses in industry 1 November 1982Volume 97, Issue 5Page: 782-782 Issue Published: 1 November 1982 PDF downloadLoading ...
Clinical Reporting to Primary Care Physicians Leads to Increased Use and Understanding of Bone Densitometry and Affects the Management of Osteoporosis
Authors: John L. Stock
Journal: Annals of Internal Medicine (1998)

Background: A major barrier to wider use of bone densitometry has been a lack of reports that are comprehensible to primary care physicians. Objective: To compare the effect of short technical reports and longer clinical reports on use, understanding, and acceptance of bone densitometry by primary care physicians and on management of osteoporosis. Design: Randomized trial. Setting: Osteoporosis center of a community teaching hospital. Subjects: 57 primary care physicians ordering bone mineral density tests with dual x-ray absorptiometry. Intervention: Physicians were randomly assigned to receive short technical reports or long clinical reports written by endocrinologists with access to clinical information. Measurements: Physicians were interviewed by telephone after receiving at least two reports. Results: Before being interviewed, physicians receiving short reports ordered a mean ±SD of 0.72 ± 0.71 tests per month; those receiving long reports ordered 1.30 ± 1.21 tests per month (P = 0.002). At the first interview, 30% of physicians receiving short reports and 86% of those receiving long reports understood the bone mineral density definition of osteoporosis (P < 0.001). Receiving long reports led to more modifications in the pharmacologic treatment of osteoporosis by gynecologists (19% of patients whose reports were short and 61% of patients whose reports were long; P = 0.021) and less confusion about reports by all physicians (36% of physicians receiving short reports and 1% of those receiving long reports; P = 0.003). Conclusions: Clinical reporting of bone densitometry to primary care physicians increased use and understanding of bone densitometry, changed management of osteoporosis, and was well accepted. It may help achieve appropriate use of bone densitometry and may allow convenient dissemination of information on osteoporosis.
Effect of Acute Metabolic Stress on Pituitary-Adrenal Axis Activation in Patients With Schizophrenia
Authors: Igor Elman, Caleb M. Adler, Anil K. Malhotra, Christopher Bir, David Pickar, Alan Breier
Journal: American Journal of Psychiatry (1998)

Although several lines of evidence suggest that stress plays a role in the course of schizophrenia, studies that have assessed stress-relevant neurobiological measures have not produced consistent results. The authors examined the effects of acute metabolic stress induced by 2-deoxy-D-glucose (2-DG) on pituitary-adrenal axis activation.Thirteen patients with schizophrenia and 11 healthy comparison subjects were administered pharmacological doses of 2-DG (40 mg/kg). The subjects' arterial plasma was then assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol.2-DG induced significant increases in the measured hormones in both groups, and ACTH elevations were significantly greater in patients with schizophrenia than in comparison subjects.Patients with schizophrenia have an exaggerated ACTH response to acute metabolic stress exposure.
Estimation of regional gas and tissue volumes of the lung in supine man using computed tomography.
Authors: D M Denison, M D Morgan, A B Millar
Journal: Thorax (1986)

This study was intended to discover how well computed tomography could recover the volume and weight of lung like foams in a body like shell, and then how well it could recover the volume and weight of the lungs in supine man. Model thoraces were made with various loaves of bread submerged in water. Computed tomography scans recovered the volume of the model lungs (true volume range 250-12,500 ml) within +0.2 (SD 68) ml and their weights (true range 72-3125 g) within +30 (78) g. Scans also recovered successive injections of 50 ml of water, within +/- 5 ml. Scans in 12 healthy supine men recovered their vital capacities, total lung capacities (TLC), and predicted tissue volumes with comparable accuracy. At total lung capacity the mean tissue volume of single lungs was 431 (64) ml and at residual volume (RV) it was 427 (63) ml. Tissue volume was then used to match inspiratory and expiratory slices and calculate regional ventilation. Throughout the mid 90% of lung the RV/TLC ratio was fairly constant--mean 21% (5%). New methods of presenting such regional data graphically and automatically are also described.
Residential Proximity to Agricultural Pesticide Use and Incidence of Breast Cancer in California, 1988–1997
Authors: Peggy Reynolds, Susan E. Hurley, Robert B. Gunier, Sauda Yerabati, Thu Quach, Andrew Hertz
Journal: Environmental Health Perspectives (2005)

California is the largest agricultural state in the United States and home to some of the world’s highest breast cancer rates. The objective of our study was to evaluate whether California breast cancer rates were elevated in areas with recent high agricultural pesticide use. We identified population-based invasive breast cancer cases from the California Cancer Registry for 1988–1997. We used California’s pesticide use reporting data to select pesticides for analysis based on use volume, carcinogenic potential, and exposure potential. Using 1990 and 2000 U.S. Census data, we derived age- and race-specific population counts for the time period of interest. We used a geographic information system to aggregate cases, population counts, and pesticide use data for all block groups in the state. To evaluate whether breast cancer rates were related to recent agricultural pesticide use, we computed rate ratios and 95% confidence intervals using Poisson regression models, adjusting for age, race/ethnicity, and neighborhood socioeconomic status and urbanization. This ecologic (aggregative) analysis included 176,302 invasive breast cancer cases and 70,968,598 person-years of observation. The rate ratios did not significantly differ from 1 for any of the selected pesticide categories or individual agents. The results from this study provide no evidence that California women living in areas of recent, high agricultural pesticide use experience higher rates of breast cancer.
miR-200 Expression Regulates Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Reverses Resistance to Epidermal Growth Factor Receptor Therapy
Authors: Liana Adam, Meng Zhong, Woonyoung Choi, Wei Qi, Milena Nicoloso, Ameeta Arora, George Calin, Hua Wang, Arlene Siefker-Radtke, David McConkey, Menashe Bar-Eli, Colin Dinney
Journal: Clinical Cancer Research (2009)

The epithelial-to-mesenchymal transition (EMT) is a cell development-regulated process in which noncoding RNAs act as crucial modulators. Recent studies have implied that EMT may contribute to resistance to epidermal growth factor receptor (EGFR)-directed therapy. The aims of this study were to determine the potential role of microRNAs (miRNA) in controlling EMT and the role of EMT in inducing the sensitivity of human bladder cancer cells to the inhibitory effects of the anti-EGFR therapy.miRNA array screening and real-time reverse transcription-PCR were used to identify and validate the differential expression of miRNAs involved in EMT in nine bladder cancer cell lines. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200b and miR-200c was expressed in UMUC3 and T24 cells using a retrovirus or a lentivirus construct, respectively. Protein expression and signaling pathway modulation, as well as intracellular distribution of EGFR and ERRFI-1, were validated through Western blot analysis and confocal microscopy, whereas ERRFI-1 direct target of miR-200 members was validated by using the wild-type and mutant 3'-untranslated region/ERRFI-1/luciferse reporters.We identified a tight association between the expression of miRNAs of the miR-200 family, epithelial phenotype, and sensitivity to EGFR inhibitors-induced growth inhibition in bladder carcinoma cell lines. Stable expression of miR-200 in mesenchymal UMUC3 cells increased E-cadherin levels, decreased expression of ZEB1, ZEB2, ERRFI-1, and cell migration, and increased sensitivity to EGFR-blocking agents. The changes in EGFR sensitivity by silencing or forced expression of ERRFI-1 or by miR-200 expression have also been validated in additional cell lines, UMUC5 and T24. Finally, luciferase assays using 3'-untranslated region/ERRFI-1/luciferase and miR-200 cotransfections showed that the direct down-regulation of ERRFI-1 was miR-200-dependent because mutations in the two putative miR-200-binding sites have rescued the inhibitory effect.Members of the miR-200 family appear to control the EMT process and sensitivity to EGFR therapy in bladder cancer cells and the expression of miR-200 is sufficient to restore EGFR dependency at least in some of the mesenchymal bladder cancer cells. The targets of miR-200 include ERRFI-1, which is a novel regulator of EGFR-independent growth.
Missense dopamine transporter mutations associate with adult parkinsonism and ADHD
Authors: Freja H. Hansen, Tina Skjørringe, Saiqa Yasmeen, Natascha V. Arends, Michelle A. Sahai, Kevin Erreger, Thorvald F. Andreassen, Marion Holy, Peter J. Hamilton, Viruna Neergheen, Merete Karlsborg, Amy H. Newman, Simon Pope, Simon J.R. Heales, Lars Friberg, Ian Law, Lars H. Pinborg, Harald H. Sitte, Claus Loland, Lei Shi, Harel Weinstein, Aurelio Galli, Lena E. Hjermind, Lisbeth B. Møller, Ulrik Gether
Journal: Journal of Clinical Investigation (2014)

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.
Early diagnosis of acute myocardial infarction
Authors: M C Bateson, J Ratcliffe
Journal: BMJ (1990)

REPLY,-My article made clear that single enzyme measurements are rarely diagnostic in the first 12 hours.Serial measurements are more useful, but in the real world of a busy hospital and an understaffed biochemistry laboratory this is unlikely to find much favour, particularly when the method requires four hourly blood sampling and construction of a "log creatine kinase slope."Even if the method were practicable it would not permit diagnosis until 12 hours or more after admission (perhaps 16 hours after infarction), when the benefits of thrombolytic treatment are considerably diminished and when electrocardiography often shows unequivocal changes.Practical considerations aside, I am less enthusiastic than Dr Mullen about the validity of this method.The main differential diagnosis in patients with cardiac chest pain is between unstable angina and acute infarction.Difficulties arise only if the electrocardiogram taken on ad- mission to hospital is non-diagnostic, and an additional test may be required.Collinson et al gave no information about admission electro- cardiograms, and in the 1989 study only one patient had unstable angina compared with 34 with acute infarction-which makes it difficult to assess the test's discriminatory value.Indeed, they seem to acknowledge this difficulty by diagnosing five patients as "ischaemia ?infarction," a conundrum
Corynebacterium haemolyticum as Human Pathogen
Authors: ROGER I. CEILLEY
Journal: Annals of Internal Medicine (1977)

Comments and Correction1 February 1977Corynebacterium haemolyticum as Human PathogenROGER I. CEILLEY, M.D.ROGER I. CEILLEY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-2-239_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Hande and associates have expanded the list of diphtheroids that can cause serious infection with an interesting report, "Sepsis with a New Species ofCorynebacterium" in the October issue (Ann Intern Med85:423-426, 1976). In Table 1, page 425, however, they incorrectly state thatCorynebacterium haemolyticumhas not been reported as a pathogen in man. Indeed, MacLean, Liebow, and Rosenberg (1), who first named the organismC. haemolyticum, were describing an organism that they first isolated from nasopharyngeal and cutaneous infections occurring in natives and U.S. military personnel in the South Pacific. Ryan (2) and others have...References1. MACLEANLIEBOWROSENBERG PAA: A haemolytic corynebacterium resembling Corynebacterium ovis and Corynebacterium pyogenes in man. J Infect Dis 79:69-90, 1946 CrossrefMedlineGoogle Scholar2. RYAN W: Throat infection and rash associated with an unusual corynebacterium. Lancet 1:1345, 1972 CrossrefGoogle Scholar3. WASHINGTONMARTINSPIEKERMAN JWR: Brain abscess with Corynebacterium hemolyticum: report of a case. Am J Clin Pathol 56:212-215, 1971 CrossrefMedlineGoogle Scholar4. CEILLEY R: Foot ulceration and vertebral osteomyelitis with C. haemolyticum. Arch Dermatol, in press Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Dermatology and Syphilology University of Iowa Hospitals and Clinics Iowa City, IA 52242 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1977Volume 86, Issue 2Page: 239-239KeywordsArmed forcesPathogensSepsis Issue Published: 1 February 1977 PDF downloadLoading ...
Time to study another variant of endothelial progenitor cells?
Authors: E. Rheaume
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Immune privilege of endothelial cells differentiated from endothelial progenitor cells’ by J. Ladhoff et al ., pp. 121–129, this issue. 

There is considerable interest in exploiting the functions of bone marrow-derived endothelial progenitor cells (EPC) for tissue repair and engineering.1 However, with all the potential that EPC-based therapy may bring for vascular and organ repair, a major problem lies with the fact that patients who potentially need the most EPC-related cell therapy are those in which EPC levels and functions are the lowest, such as type II diabetic patients.2 Allogeneic EPC therapy would thus be a suitable approach if it could be established that endothelial cells derived from EPC can survive within an allogeneic host. This may be a plausible proposal, as a novel study in Cardiovascular Research presents results demonstrating protection of allogeneic EPC-derived endothelial cells used in an aortic graft transplantation model.3 Although long-term survival of EPC in an autologous graft model has been shown,4 this new study shows survival of endothelial cells (EC) derived from EPC, up to 14 days post-transplantation, in a major histocompatibility complex (MHC)-mismatched allogeneic transplantation rat model. Ladhoff et al. used decellularized rat aortic grafts that were seeded with EPC-derived EC. … 

*Corresponding author. Tel: +1 514 376 3330 ext. 3091; fax: +1 514 376 1355, Email: eric.rheaume{at}icm-mhi.org
Functional and Metabolic Imaging of the Cardiovascular System in Young Healthy South Asians and Caucasians Unveils Early Differences
Authors: Linda D. van Schinkel, Leontine E.H. Bakker, Jacqueline T. Jonker, Albert de Roos, Hanno Pijl, A. Edo Meinders, Ingrid M. Jazet, Johannes W.A. Smit, Hildo J. Lamb
Journal: Diabetes Care (2013)

South Asians, representing one-fifth of the world’s population, have a higher risk of developing cardiovascular disease (CVD) than Caucasians (1). Moreover, CVD is more aggressive in this population (1). Traditional risk factors per se do not explain these between-ethnic group differences (1,2). Insulin resistance (IR) and type 2 diabetes are also highly prevalent in South Asians (3). Because the mortality risk of CVD associated with type 2 diabetes is higher in South Asians than in Caucasians (2,4), the excess CVD risk in South Asians might be due to inherent ethnicity-associated structural cardiac features and/or a higher cardiac susceptibility to metabolic disorders. Because it is unknown whether differences already exist in cardiac dimensions and function at a young age between these ethnicities, we studied these features in young South Asians and Caucasians and subjected both groups to a short-term high-fat, high-caloric (HFHC) diet to study cardiac response to metabolic stress.

Cardiac dimensions, cardiovascular function, and fat distribution were assessed with a 1.5-T magnetic resonance imaging/magnetic resonance spectroscopy scanner in young, healthy male South Asians and Caucasians ( n = 12 for each ethnicity; mean age 22.1 ± 0.4 years; BMI 20.9 ± 0.4 vs. 22.2 ± 0.6 kg/m2, respectively; P = 0.11) …
What happened to the Croydon trainees of 1977-81?
Authors: C B Floyd
Journal: BMJ (1983)

Questionnaires were sent to the 58 doctors during the last two months of 1981. Second letters with duplicate questionnaires were posted to non-responders, and telephone calls were made as a final reminder. Forty eight questionnaires were collected over nine months ?a response rate of 85 5,.?from 27 United Kingdom graduates and 21 overseas graduates. Some information was collected from trainers about the two United Kingdom and eight overseas graduates who did not respond.
Quality of Physicians' Office-Care Performance
Authors: Thomas F. Lyons
Journal: JAMA (1974)

Office records of 904 patient visits during six weeks in 1970 were examined for conformance to predetermined optimal standards of physician performance in seven categories of diagnoses or conditions. No overall evidence was found that primary-care physicians performed differently for the elderly than for younger adult patients in the office setting.  ( JAMA 229:1621-1622, 1974)
Use of FDG-PET in the Differential Diagnosis of a Single Bone Lesion in Ovarian Cancer
Authors: Thomas Leitha, Robert Cesnik, Erich Steiner, Franz Frühwald
Journal: Clinical Nuclear Medicine (2004)

Bone scanning has a high sensitivity but low specificity for the differential diagnosis of bone lesions in oncology. FDG-PET has been investigated in the differential diagnosis between acute benign and metastatic fractures in the past but its use is still under debate (1–9). We report a case with a true negative result with FDG-PET. Magnetic resonance imaging and bone scintigraphy suggested metastatic disease in a patient with ovarian cancer in remission but with recent onset of left-sided pelvic pain. In contrast, FDG-PET showed only faint tracer uptake in the lesion, insinuating a benign process. Histology confirmed osteopenia and microfractures and excluded malignancy.