tbuckley/cabot-search huggingface dataset:
Phenotypic Anchoring of Gene Expression Changes during Estrogen-Induced Uterine Growth
Authors: Jonathan G. Moggs, Helen Tinwell, Tracey Spurway, Hur-Song Chang, Ian Pate, Fei Ling Lim, David J. Moore, Anthony Soames, Ruth Stuckey, Richard Currie, Tong Zhu, Ian Kimber, John Ashby, George Orphanides
Journal: Environmental Health Perspectives (2004)

A major challenge in the emerging field of toxicogenomics is to define the relationships between chemically induced changes in gene expression and alterations in conventional toxicologic parameters such as clinical chemistry and histopathology. We have explored these relationships in detail using the rodent uterotrophic assay as a model system. Gene expression levels, uterine weights, and histologic parameters were analyzed 1, 2, 4, 8, 24, 48, and 72 hr after exposure to the reference physiologic estrogen 17β-estradiol (E2). A multistep analysis method, involving unsupervised hierarchical clustering followed by supervised gene ontology–driven clustering, was used to define the transcriptional program associated with E2-induced uterine growth and to identify groups of genes that may drive specific histologic changes in the uterus. This revealed that uterine growth and maturation are preceded and accompanied by a complex, multistage molecular program. The program begins with the induction of genes involved in transcriptional regulation and signal transduction and is followed, sequentially, by the regulation of genes involved in protein biosynthesis, cell proliferation, and epithelial cell differentiation. Furthermore, we have identified genes with common molecular functions that may drive fluid uptake, coordinated cell division, and remodeling of luminal epithelial cells. These data define the mechanism by which an estrogen induces organ growth and tissue maturation, and demonstrate that comparison of temporal changes in gene expression and conventional toxicology end points can facilitate the phenotypic anchoring of toxicogenomic data.
Prophylaxis Against Pneumocystis carinii Pneumonia at Higher CD4+ T-Cell Counts
Authors: Susan Y. Chu
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Current recommendations for the prevention of first episodes of<i>Pneumocystis carinii</i>pneumonia (PCP) in human immunodeficiency virus (HIV)—infected adults and adolescents state that prophylaxis should begin when the CD4<sup>+</sup>count falls below 0.200 × 10<sup>9</sup>/L (200/μL).<sup>1</sup>However, the risk of PCP in patients with CD4<sup>+</sup>counts greater than 0.200 × 10<sup>9</sup>/L, although low, is not zero, and some experts on the US Public Health Service Task Force that made the current recommendations felt that prophylaxis could also be considered in patients with higher CD4<sup>+</sup>counts.<sup>1</sup> We have estimated the number of cases of primary PCP that could potentially be prevented if the recommended CD4<sup>+</sup>threshold for initiating prophylaxis were raised to 0.300 × 10<sup>9</sup>/L, using data from a large multisite project in which medical records of HIV-infected patients are reviewed at regular intervals.<sup>2</sup>Between January 1990 and April
Unilateral Absence of Ventilation and Perfusion Due to Thoracic Aortic Aneurysm
Authors: ROBERT A. DUKE, MILTON R. BARRETT, JAMES D. MASSIE, JORGE E. SALAZAR, MORRIS L. GAVANT, STEVEN D. PAYNE
Journal: Clinical Nuclear Medicine (1988)

An elderly man presented with progressive atelectasis of the left lung, a mediastinal mass, and dilatation of the thoracic aorta. Ventilation and perfusion radionuclide lung scans revealed the complete absence of ventilation in the left lung and near-complete absence of perfusion. Evaluation by MRI and angiography showed an obstructing mediastinal “mass” to be a saccular aortic aneursym. A thoracic aortic aneurysm should be a consideration in the differential diagnosis for unilateral decrease or absence of ventilation and perfusion with a history or findings of mediastinal mass or aneurysm.
Group A Streptococcus Septicemia in Children-Reply
Authors: Mary C. Wheeler
Journal: JAMA (1992)

In Reply.  —There are several ways to demonstrate a real increase in group A streptococcal sepsis in children based on data from our article. We demonstrated a significant increase in group A streptococcal bacteremia from 1980 through 1990 based on a comparison of cases per 10 000 discharges. At the same time, the rate ofHaemophilus influenzaebacteremia went down, and the rate ofStreptococcus pneumoniaewas unchanged. Dr Hexter suggests several other relevant comparisons. Because the 1980 through 1982 data on the average lengths of stay were not easily accessible, comparison of the periods 1983 through 1984 and 1989 through 1990 was made.  In order to control for lengths of stay, the incidence density for positive blood cultures for 1983 through 1984 was calculated to be 0.007 positive cultures per patient-day, whereas the 1989 through 1990 data indicated a rate of 0.008. The intensity of discovery as it relates
Correlation of the CD8+ AND CD4+ T cell response during spontaneous clearance of hepatitis C virus
Authors: N.H. Gruener, M.C. Jung, H.M. Diepolder, J.T. Gerlach, R. Zachoval, R. Hoffmann, W. Schraut, C.A. Schirren, T. Santantonio, G.R. Pape
Journal: Journal of Hepatology (2000)
GPs must be encouraged to test out new approaches to primary care, report says
Authors: Gareth Iacobucci
Journal: BMJ (2013)

NHS England must take action to ease the “significant strain” on UK general practitioners to encourage primary care to focus more on population health, a report has concluded.1

The report, by health think tanks the Nuffield Trust and the King’s Fund, said that NHS England should work with clinical commissioning groups to give GPs “support, incentives, and permission” to test out new approaches to delivering and organising primary care.

It added that it was “a pressing priority” to help GPs develop larger scale organisations or networks that provide a wider range of services, with a different skill mix and new leadership opportunities.

New measures proposed include wider access to “high quality” organisational development and planning support, and the introduction of a new alternative contract alongside the existing general medical services (GMS) contract to encourage groups of practices to …
Transforming Growth Factor-β-Induced Differentiation of Smooth Muscle From a Neural Crest Stem Cell Line
Authors: Shiyou Chen, Robert J. Lechleider
Journal: Circulation Research (2004)

During vascular development, nascent endothelial networks are invested with a layer of supporting cells called pericytes in capillaries or smooth muscle in larger vessels. The cellular lineage of smooth muscle precursors and factors responsible for regulating their differentiation remain uncertain. In vivo, cells derived from the multipotent neural crest can give rise to vascular smooth muscle in parts of the head and also the cardiac outflow tract. Although transforming growth factor-beta (TGF-beta) has previously been shown to induce some smooth muscle markers from primary cultures of neural crest stem cells, the extent of the differentiation induced was not clear. In this study, we demonstrate that TGF-beta can induce many of the markers and characteristics of vascular smooth muscle from a neural crest stem cell line, Monc-1. Within 3 days of in vitro treatment, TGF-beta induces multiple smooth muscle-specific markers, while downregulating epithelial markers present on the parent cells. Treatment with TGF-beta also induces a contractile phenotype that responds to the muscarinic agonist carbachol and is not immediately reversed on TGF-beta withdrawal. Examination of the signaling pathways involved revealed that TGF-beta activation of Smad2 and Smad3 appear to be essential for the observed differentiation. Taken together, this system provides a novel model of smooth muscle differentiation that reliably recapitulates the process observed in vivo and allows for dissection of the pathways and processes involved in this process.
1026 Histologic findings in potential living liver donor biopsies
Authors: M KAMAL, C LASSMAN, R GHOBRIAL, S SAAB, K MARKS, R BUSUTTIL
Journal: Hepatology (2003)

Recipient-derived cells integrate into renal allografts inducing organ-specific microchimerism. Circulating pluripotent progenitor cells with high plasticity for differentiation were suggested as a potential source of allograft chimerism. Whether or not these cells also contribute to tumor formation in renal transplants is unknown. We analyzed six histologically different tumors in renal allografts for the presence of recipient-derived cells. To circumvent dependency on gender mismatch, a polymerase chain reaction assay for highly polymorphic short tandem repeat marker (DNA fingerprinting) in combination with laser microdissection was applied. Pure tumor cell populations were harvested by laser microdissection after immunohistochemical (CD45/CD68) marking of contaminating leukocytes. In cases of gender mismatch (n = 2), results were confirmed by sex chromosome in situ hybridization. Two metanephric adenomas demonstrated microchimerism comprising both donor- and recipient-derived tumor cells. Two clear cell carcinomas, one transitional cell carcinoma, and one renal cortical adenoma were all of donor origin without chimerism. We conclude that except for metanephric adenomas, tumors arising in renal transplants originate completely from graft cells. The mixed derivation of metanephric adenomas indicates an incorporation of recipient-derived progenitor cells. This finding suggests that adult stem cells can assume neoplastic phenotypes.
Positive Contribution of Pathogenic Mutations in the Mitochondrial Genome to the Promotion of Cancer by Prevention from Apoptosis
Authors: Yujiro Shidara, Kumi Yamagata, Takashi Kanamori, Kazutoshi Nakano, Jennifer Q. Kwong, Giovanni Manfredi, Hideaki Oda, Shigeo Ohta
Journal: Cancer Research (2005)

The role of mitochondrial dysfunction in cancer has been a subject of great interest and much ongoing investigation. Although most cancer cells harbor somatic mutations in mitochondrial DNA (mtDNA), the question of whether such mutations contribute to the promotion of carcinomas remains unsolved. Here we used trans-mitochondrial hybrids (cybrids) containing a common HeLa nucleus and mtDNA of interest to compare the role of mtDNA against the common nuclear background. We constructed cybrids with or without a homoplasmic pathogenic point mutation at nucleotide position 8,993 or 9,176 in the mtDNA ATP synthase subunit 6 gene (MTATP6) derived from patients with mitochondrial encephalomyopathy. When the cybrids were transplanted into nude mice, the MTATP6 mutations conferred an advantage in the early stage of tumor growth. The mutant cybrids also increased faster than wild type in culture. To complement the mtDNA mutations, we transfected a wild-type nuclear version of MTATP, whose codons were converted to the universal genetic codes containing a mitochondrial target sequence, into the nucleus of cybrids carrying mutant MTATP6. The restoration of MTATP slowed down the growth of tumor in transplantation. Conversely, expression of a mutant nuclear version of MTATP6 in the wild-type cybrids declined respiration and accelerated the tumor growth. These findings showed that the advantage in tumor growth depended upon the MTATP6 function but was not due to secondary nuclear mutations caused by the mutant mitochondria. Because apoptosis occurred less frequently in the mutant versus wild-type cybrids in cultures and tumors, the pathogenic mtDNA mutations seem to promote tumors by preventing apoptosis.
BMPR2 is required for postimplantation uterine function and pregnancy maintenance
Authors: Takashi Nagashima, Qinglei Li, Caterina Clementi, John P. Lydon, Francesco J. DeMayo, Martin M. Matzuk
Journal: Journal of Clinical Investigation (2013)

Abnormalities in cell-cell communication and growth factor signaling pathways can lead to defects in maternal-fetal interactions during pregnancy, including immunologic rejection of the fetal/placental unit. In this study, we discovered that bone morphogenetic protein receptor type 2 (BMPR2) is essential for postimplantation physiology and fertility. Despite normal implantation and early placental/fetal development, deletion of Bmpr2 in the uterine deciduae of mice triggered midgestation abnormalities in decidualization that resulted in abnormal vascular development, trophoblast defects, and a deficiency of uterine natural killer cells. Absence of BMPR2 signaling in the uterine decidua consequently suppressed IL-15, VEGF, angiopoietin, and corin signaling. Disruption of these pathways collectively lead to placental abruption, fetal demise, and female sterility, thereby placing BMPR2 at a central point in the regulation of several physiologic signaling pathways and events at the maternal-fetal interface. Since trophoblast invasion and uterine vascular modification are implicated in normal placentation and fetal growth in humans, our findings suggest that abnormalities in uterine BMPR2-mediated signaling pathways can have catastrophic consequences in women for the maintenance of pregnancy.
Guidelines for topical photodynamic therapy: update
Authors: C.A. Morton, K.E. McKenna, L.E. Rhodes
Journal: British Journal of Dermatology (2008)

Multicentre randomized controlled studies now demonstrate high efficacy of topical photodynamic therapy (PDT) for actinic keratoses, Bowen's disease (BD) and superficial basal cell carcinoma (BCC), and efficacy in thin nodular BCC, while confirming the superiority of cosmetic outcome over standard therapies. Long-term follow-up studies are also now available, indicating that PDT has recurrence rates equivalent to other standard therapies in BD and superficial BCC, but with lower sustained efficacy than surgery in nodular BCC. In contrast, current evidence does not support the use of topical PDT for squamous cell carcinoma. PDT can reduce the number of new lesions developing in patients at high risk of skin cancer and may have a role as a preventive therapy. Case reports and small series attest to the potential of PDT in a wide range of inflammatory/infective dermatoses, although recent studies indicate insufficient evidence to support its use in psoriasis. There is an accumulating evidence base for the use of PDT in acne, while detailed study of an optimized protocol is still required. In addition to high-quality treatment site cosmesis, several studies observe improvements in aspects of photoageing. Management of treatment-related pain/discomfort is a challenge in a minority of patients, and the modality is otherwise well tolerated. Long-term studies provide reassurance over the safety of repeated use of PDT.
AACR Special Conference on Epithelial-Mesenchymal Transition and Cancer Progression and Treatment
Authors: Evanthia T. Roussos, Zuzana Keckesova, John D. Haley, David M. Epstein, Robert A. Weinberg, John S. Condeelis
Journal: Cancer Research (2010)

Abstract Epithelial-mesenchymal transition (EMT) is a developmental program implicated in cancer progression and was the subject of the 2010 AACR meeting on the topic of EMT and Cancer Progression and Treatment held on February 28 to March 2 in Arlington, Virginia. A review of the involvement of EMT in gastrulation, organogenesis, carcinogenesis, and metastatic progression elucidated the overlap of EMT in these physiologic and pathologic conditions. Both novel and traditional markers of cells undergoing EMT were discussed and compared with features used to define cancer stem cells. Importantly, these defining characteristics of cells undergoing EMT were discussed in the context of therapeutic and prognostic developments. Cancer Res; 70(19); 7360–4. ©2010 AACR.
Mapping the new frontier: complex genetic disorders
Authors: R. Mayeux
Journal: Journal of Clinical Investigation (2005)

The remarkable achievements in human genetics over the years have been due to technological advances in gene mapping and in statistical methods that relate genetic variants to disease. Nearly every Mendelian genetic disorder has now been mapped to a specific gene or set of genes, but these discoveries have been limited to high-risk, variant alleles that segregate in rare families. With a working draft of the human genome now in hand, the availability of high-throughput genotyping, a plethora of genetic markers, and the development of new analytical methods, scientists are now turning their attention to common complex disorders such as diabetes, obesity, hypertension, and Alzheimer disease. In this issue, the JCI provides readers with a series dedicated to complex genetic disorders, offering a view of genetic medicine in the 21st century.
Pulmonary Edema Complicating Continuous Intravenous Prostacyclin in Pulmonary Capillary Hemangiomatosis
Authors: MARC HUMBERT, SOPHIE MAÎ TRE, FRÉDÉRIQUE CAPRON, BERNADETTE RAIN, DOMINIQUE MUSSET, GÉRALD SIMONNEAU
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Continuous intravenous epoprostenol (prostacyclin) produces hemodynamic and symptomatic responses and improves survival in patients with severe primary pulmonary hypertension refractory to conventional medical therapy. However, it has been recently shown that short-term infusion of epoprostenol can produce pulmonary edema in pulmonary veno-occlusive disease, presumably because of increased pulmonary perfusion in the presence of downstream vascular obstruction. We describe two additional cases of pulmonary edema complicating continuous intravenous epoprostenol in patients displaying severe pulmonary hypertension and pulmonary capillary hemangiomatosis, a rare condition characterized by the proliferation of thin-walled microvessels in the alveolar walls. This report indicates that epoprostenol therapy should not be used in patients with severe pulmonary hypertension secondary to pulmonary capillary hemangiomatosis.
What factors increase the risk of concussion in elite youth ice hockey players?
Authors: Tracy A Blake, Jian Kang, Willem H Meeuwisse, Nicole Lemke, Kathryn J Schneider, Kirsten A Taylor, Carolyn A Emery
Journal: British Journal of Sports Medicine (2013)

Objective To examine the risk of concussion amongst elite youth male and female ice hockey players. Design Prospective cohort study. Setting Community ice rinks and sport medicine clinics. Participants 764 Bantam (12–14 years) and Midget (15–17 years) ice hockey players. Assessment of Risk Factors: 743 players completed baseline SCAT2 testing (2011/2012 season). Age group, sex, previous concussion history, Total Symptoms Score (TSS), Balance Error Score (BES), Standardised Assessment of Concussion (SAC) Score and SCAT2 Total Score at baseline were evaluated as potential risk factors. Higher scores indicate greater impairment or symptoms. Main Outcome Measurements Players with a suspected concussion were assessed by a team therapist and referred to a sport medicine physician. Results Multivariate Poisson Regression analyses, adjusted for cluster by team, were used to estimate concussion risk ratios (RR). The RR for Bantam players with previous concussion history was 1.15 (95% CI 0.69 to 1.90) and for Midget players with previous concussion history was 2.83 (95% CI 1.69 to 4.72) compared to players in the same age group with no previous concussion history. The RR for players with baseline TSS and SCAT2 Total Score in the lowest 25%ile were 1.54 (95% CI 1.07 to 2.20) and 1.40 (95% CI 1.03 to 1.90), respectively, compared to those in the upper 75%ile. Sex, BES and SAC score were not predictive of concussion. Conclusions There is a greater risk of concussion in elite ice hockey players 15–17 years old with a previous history of concussion. Baseline TSS and SCAT2 Total Score in the lowest 25%ile are also predictive of concussion. Acknowledgements The University of Calgary Sport Injury Prevention Research Centre is one of the International Research Centres for Prevention of Injury and Protection of Athlete Health supported by the International Olympic Committee. We also acknowledge the support of Alberta Innovates Health Solutions, the Alberta Children's Hospital Institute for Child and Maternal Health (Alberta Children's Hospital Foundation) and Talisman Energy for their generous support.
Mothers, Babies, and Disease in Later Life
Authors: M. W Gillman
Journal: BMJ (1995)

D J P Barker BMJ Publishing Group, £29.95, pp 180 ISBN 0 7279 0835 9

Before the early part of this century, clinical coronary heart disease was a rarity. By the 1950s, however, the developed countries of the Western world were experiencing an epidemic. Initially this epidemic spawned population based studies, such as the Framingham study, aimed at identifying risk factors for coronary heart disease that are amenable to prevention strategies among susceptible adults. In the past couple of decades, however, it has become apparent that prevention of heart disease might be more effective if started in childhood and adolescence, when the precursors of adult hypertension and atherosclerosis are apparent and lifestyle habits are formed. Now comes a new paradigm: the precursors of coronary heart disease and of other adult chronic diseases, and thus the potential …
Bile Pigments in Health and Disease
Authors: Lawrence C. Parish
Journal: JAMA (1962)

An interesting monograph has appeared in which the various aspects of bile pigment are discussed in regard to their clinical applications. As part of the "Living Chemistry Series," this volume stresses the close relationship between chemistry and medicine so that a better understanding of heme breakdown can be achieved. Sections under discussion include the chemistry of the bile pigments with emphasis on the chemical makeup, classification, the bilatrienes, the biladienes, the bilenes, the bilanes, oxidation products, reactions, potical activity, prototopy, and nomenclature. Other chapters are centered around hemoglobin breakdown, urobilinoid pigments, bile pigment in the blood and the van den Bergh reaction, bile pigments in the body fluids and tissues, biosynthesis, conjugates, clinical jaundice including retention jaundice, regurgitation jaundice, jaundice in infancy, and hemolytic disease of the newborn, and lastly, clinical methods and interpretation. I was particularly interested in learning that Virchow in 1847 first noted the relationship between the
Prognostic Significance of Tumor Size in Patients with Stage III Non–Small-Cell Lung Cancer: A Surveillance, Epidemiology, and End Results (SEER) Survey from 1998 to 2003
Authors: Daniel Morgensztern, Saiama Waqar, Janakiraman Subramanian, Feng Gao, Kathryn Trinkaus, Ramaswamy Govindan
Journal: Journal of Thoracic Oncology (2012)
The Person: His Development Throughout the Life Cycle
Authors: John Romano
Journal: JAMA (1969)

This is an excellent book. It will be read with interest, profit, and excitement by medical students who are the principal audience the author has in mind. Others too—psychologists, nurses, social workers, and counselors from various disciplines—will find in it a clear exposition of human development and personality. The author writes extremely well, and his chapters capture not only his discriminating scholarship and his remarkably rich treasury of clinical experience but his essential warmth and genuine engagement with the events of human interaction. His pervasive humanity is clearly evident in the introductory remarks which clearly define the unique task of the physician. Equally impressive is the author's success in avoiding the pitfalls of allegiance to single idealogies, and to closedcircuit thinking. While he presents a dynamic view of personality functioning, his inferences are tempered by empirical data and clinical experience beyond the immediate realm of psychoanalysis. This balance, clear throughout,