tbuckley/cabot-search huggingface dataset:
Phenotypic Heterogeneity of Genomic Disorders and Rare Copy-Number Variants
Authors: Santhosh Girirajan, Jill A. Rosenfeld, Bradley P. Coe, Sumit Parikh, Neil Friedman, Amy Goldstein, Robyn A. Filipink, Juliann S. McConnell, Brad Angle, Wendy S. Meschino, Marjan M. Nezarati, Alexander Asamoah, Kelly E. Jackson, Gordon C. Gowans, Judith A. Martin, Erin P. Carmany, David W. Stockton, Rhonda E. Schnur, Lynette S. Penney, Donna M. Martin, Salmo Raskin, Kathleen Leppig, Heidi Thiese, Rosemarie Smith, Erika Aberg, Dmitriy M. Niyazov, Luis F. Escobar, Dima El-Khechen, Kisha D. Johnson, Robert R. Lebel, Kiana Siefkas, Susie Ball, Natasha Shur, Marianne McGuire, Campbell K. Brasington, J. Edward Spence, Laura S. Martin, Carol Clericuzio, Blake C. Ballif, Lisa G. Shaffer, Evan E. Eichler
Journal: New England Journal of Medicine (2012)

Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management.We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization.Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P=2.11×10(-38)). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P=0.02).Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.).
Food Asphyxiation in Hospitalized Patients
Authors: Richard S. Irwin
Journal: JAMA (1977)

During a five-year period, food asphyxiation caused 1.3% of all deaths of patients who came to autopsy at a hospital for chronic diseases. Patients died suddendly, during or shortly after meals. Acute myocardial infarction was mistakenly diagnosed in eight of the 14 patients until autopsy was performed. Sedation, old age, and poor dentition predisposed to aspiration. Food asphyxiation is a common problem whenever and wherever people eat. To minimize its occurrence in hospitalized patients, sedatives should be prescribed judiciously, and diets ordered appropriately. Physicians should learn the simple methods of extracting inhaled food.
Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency
Authors: Simon T. MacDonald, Simon D. Bamforth, Chiann-Mun Chen, Cassandra R. Farthing, Angela Franklyn, Carol Broadbent, Jürgen E. Schneider, Yumiko Saga, Mark Lewandoski, Shoumo Bhattacharya
Journal: Cardiovascular Research (2008)

Deletion of the transcription factor Cited2 causes penetrant and phenotypically heterogenous cardiovascular and laterality defects and adrenal agenesis. Heterozygous human CITED2 mutation is associated with congenital heart disease, suggesting haploinsufficiency. Cited2 functions partly via a Nodal→Pitx2c pathway controlling left–right patterning. In this present study we investigated the primary site of Cited2 function and mechanisms of haploinsufficiency. A Cited2 conditional allele enabled its deletion in particular cell lineages in mouse development. A lacZ reporter cassette allowed indication of deletion. Congenic Cited2 heterozygous mice were used to investigate haploinsufficiency. Embryos were examined by magnetic resonance imaging, by sectioning and by quantitative real-time polymerase chain reaction (qRT-PCR). Epiblast-specific deletion of Cited2 using Sox2Cre recapitulated penetrant and phenotypically heterogenous cardiovascular and laterality defects. Neural crest-specific deletion using Wnt1Cre affected cranial ganglia but not cardiac development. Mesodermal deletion with Mesp1Cre resulted in low penetrance of septal defect. Mesodermal deletion with T-Cre resulted in adrenal agenesis, but infrequent cardiac septal and laterality defects. β-Galatactosidase staining and qRT-PCR demonstrated the efficiency and location of Cited2 deletion. Murine Cited2 heterozygosity is itself associated with cardiac malformation, with three of 45 embryos showing ventricular septal defect. Cited2 gene expression in E13.5 hearts was reduced 2.13-fold in Cited2+/− compared with wild-type (P = 2.62 × 10−6). The Cited2 target gene Pitx2c was reduced 1.5-fold in Cited2+/− (P = 0.038) hearts compared with wild-type, and reduced 4.9-fold in Cited2−/− hearts (P = 0.00031). Pitx2c levels were reduced two-fold (P = 0.009) in Cited2+/− embryos, in comparison with wild-type. Cited2 and Pitx2c expression were strongly correlated in wild-type and Cited2+/− hearts (Pearson rank correlation = 0.68, P = 0.0009). Cited2 expression was reduced 7474-fold in Sox2Cre deleted hearts compared with controls (P = 0.00017) and Pitx2c was reduced 3.1-fold (P = 0.013). Deletion of Cited2 with Mesp1Cre resulted in a 130-fold reduction in cardiac Cited2 expression compared with control (P = 0.0002), but Pitx2c expression was not affected. These results indicate that phenotypically heterogenous and penetrant cardiac malformations in Cited2 deficiency arise from a primary requirement in epiblast derivatives for left–right patterning, with a secondary cell-autonomous role in the mesoderm. Cardiac malformation associated with Cited2 haploinsufficiency may occur by reducing expression of key Cited2 targets such as Pitx2c.
The Influence of Pregnancy on IDDM Complications
Authors: Anusha Hemachandra, Demetrius Ellis, Cathy E Lloyd, Trevor J Orchard
Journal: Diabetes Care (1995)

OBJECTIVE Although pregnancy has been associated with an increased progression of certain insulin-dependent diabetes mellitus (IDDM) complications, particularly retinopathy, both the short- and long-term relationships between pregnancy and both neuropathy and macrovascular disease are poorly documented. This study was conducted to comprehensively examine the influence of pregnancy on the development and progression of IDDM complications. RESEARCH DESIGN AND METHODS Using the Pittsburgh Epidemiology of Diabetes Complications Study population (childhood-onset IDDM), two nested, pair-matched case-control studies were conducted. Women who had completed at least one successful pregnancy (n = 80) were matched to women with no history of pregnancy by age, duration of IDDM, race, and marital history. The first nested study (study 1) compared the prevalences of five IDDM complications between case and control groups. The second nested study (study 2) compared the incidences of the same five complications over an approximate 2-year interval during which the case subjects (n = 30) completed a successful pregnancy. RESULTS There were no significant differences in the prevalence rates of coronary heart disease, neuropathy, proliferative retinopathy, lower extremity arterial disease, and overt nephropathy by case-control status, while parity did not predict any complication in multiple logistic analysis (study 1). In study 2, there were small but nonsignificant differences in incidence rates of overt nephropathy and lower extremity arterial disease between the groups, whereas case subjects had almost 3 times the incidence rate of proliferative retinopathy (P = 0.58) and 10 times the incidence rate of neuropathy (P &amp;lt; 0.001) as did other matched control subjects. In multivariate analysis, parity predicted neuropathy incidence but did not predict the incidence of any other complication, including proliferative retinopathy. CONCLUSIONS Women with IDDM who experience a pregnancy may not be at an increased risk of diabetes complications later in life. However, in the short term, pregnancy may accelerate the development of some complications, such as neuropathy.
Intracardiac Pressure-Flow Dynamics in Isolated Ventricular Septal Defects
Authors: AARON R. LEVIN, MADISON S. SPACH, RAMON V. CANENT, JOHN P. BOINEAU, M. PAUL CAPP, VISHNU JAIN, ROGER C. BARR
Journal: Circulation (1967)

This study was conducted to determine the nature of intracardiac shunting in 50 patients between the ages of 3 and 15 years with isolated ventricular septal defects. Simultaneous right and left ventricular pressures and biplane cineangiocardiography were utilized to study the timing and the direction of flow across the defect. Patients with low to moderately elevated right ventricular pressures demonstrated left-to-right shunting across the defect throughout the cardiac cycle. When pressure in the right ventricle approximated that of the left, right-to-left shunting occurred across the defect into the left ventricle during isovolumic relaxation. All patients shared in common the following: (1) a predominant left-to-right gradient and shunt across the defect into the body of the right ventricle during diastole; and, (2) augmentation of the left-to-right gradient with resultant increase of the shunt into the right ventricle during isovolumic contraction immediately preceding opening of the aortic valve. In comparing patients with and without pulmonary hypertension, the major variations in the cardiac cycle occurred during the periods of ventricular ejection and isovolumic relaxation. These two periods are primarily affected by the changing relationships of the size of the defect, ratio of pulmonary to systemic resistance, and magnitude of net shunts.
THE REVISION OF THE PHARMACOPEIA.
Authors: A. L. BENEDICT
Journal: JAMA (1899)

It is none too early for the medical profession to begin to discuss the revision of the "U. S. Pharmacopeia," which is to take place next year. While the actual appointment of delegates to the pharmacopeial convention rests with medical and pharmacal colleges, state societies and the three Government medical services, the revision should represent the opinion of the profession at large. This opinion can be expressed only by free discussion in print and in various medical meetings. Within the last few decades a problem has arisen which successive pharmacopeial conventions have managed to ignore, but which must be faced in the near future. Up to 1860 or 1870, almost all drugs were either standard inorganic chemicals or vegetable substances which could be gathered by anyone with a working knowledge of botany, and which could be prepared for dispensing by very simple means. At present we are departing more and
Paralysis Following Poisoning by a New Organic Phosphorus Insecticide (Mipafox)
Authors: P. L. Bidstrup, J. A. Bonnell, A. G. Beckett
Journal: BMJ (1953)

EPIDEMIC HAEMORRHAGIC FEVER CBJouThe disease resembles a non-icteric form -of Weil's disease and may prove to be caused by a leptospire.Its prevalence along river banks and estuaries in North Korea during autumn months, the presence of a suitable rodent carrier in vast numbers, and its general clinical course, with special emphasis upon renal involvement, are all sugges- tive of such an infection despite the absence of positive proof by laboratory demonstration.Weil's disease has a case mortality of 3% for the age group 16-30 (Broom, 1951), our mortality was 1 in 40 (2.5%), but diagnosis was possibly made more often in milder cases owing to its epidemic quality.All agglutination tests for leptospirosis were negative.As renal failure in this disease follows a period of hypotension it may be due to anoxia, which Darmady and his colleagues (1944) suggest is the causative mechanism in Weil's disease; the pathological picture of the kidney is one of cortical pallor and medullary hyper- aemia, suggesting an alteration in the distribution of blood flow in the kidney which may short-circuit the glomeruli, as has been shown in rabbits by Trueta et al. (1947).Paralysis of the sympathetic nerves by high spinal anaesthesia was not attempted in our cases.The hypothalamic and pituitary lesions possibly have far-reaching effects upon the hormonal control of urinary secretion and upon the autonomic control of the vascular system, and may be responsible in part for the tendency to inversion of sleep rhythm noted in some of our cases.Adrenal cortical damage may be responsible for the pros- tration and electrolyte imbalance seen early in the disease and for the delayed water excretion and apparent lack of concentrating power of the kidneys in the later phases. SummaryAn epidemic disease broke out among our troops stationed in Korea during the autumn months of 1951; a summary of its characteristic features as seen in 40 cases treated at the British Commonwealth General Hospital, Kure, Japan, has been presented, together with some of its complications.Its aetiology remains obscure ; its similarity to anicteric forms of Weil's disease is noted.Chemotherapeutic and antibiotic agents have been proved of doubtful value in treatment.
Diet and Weight Loss
Authors: Theodore B. Van Itallie, Mei-Uih Yang
Journal: New England Journal of Medicine (1977)

Body weight is the most important index of nutritional status that is readily available to the physician; however, the ease and simplicity of the weighing procedure have tended to obscure the complexity of the physiologic processes that underlie weight change. Weight loss reflects a deficit of one or more body substances sufficient to produce a net decrease in body mass. For practical purposes, the constituents that can contribute appreciably to weight loss over the short term are water, fat, protein and glycogen. In much longer-term situations, deficits of minerals (from both bone and soft tissues) also make a small contribution . . .
Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated hepatic parenchymal cell injury during endotoxemia: importance of an intracellular oxidant stress
Authors: Hartmut Jaeschke, Ye-Shih Ho, Michael A. Fisher, Judy A. Lawson, Anwar Farhood
Journal: Hepatology (1999)

Neutrophils contribute to hepatocellular injury in a number of acuteinflammatory reactions. However, the molecular mechanism of parenchymal cell injury remains controversial. To address the issue of whether or not reactive oxygen species (ROS) are important in the injury process, we used the galactosamine/endotoxin (Gal/ET) model of acute liver failure, which involves a neutrophil–mediated parenchymal cell injury. In C3Heb/FeJ mice, Gal/ET induced a significant increase of hepatic and plasma levels of glutathione disulfide (GSSG), an indicator of oxidant stress, selectively during the neutrophil–mediated injury phase. In glutathione peroxidase-deficient mice ( Gpx1-/- ), Gal/ET or Gal/tumor necrosis factor α (TNF–α) caused more severe neutrophil–mediated liver injury compared with wild–type animals. However, there was no significant difference in other critical parameters, e.g. , activation of the transcription factor, nuclear factor–κB (NF–κB), and soluble intercellular adhesion molecule–1 (sICAM–1), parenchymal cell apoptosis, and neutrophil sequestration in the liver. Our results suggest that neutrophil–derived ROS are responsible for an intracellular oxidant stress in hepatocytes after Gal/ET treatment. Because of the higher susceptibility of Gpx1-/- mice to a neutrophil–mediated injury, we conclude that peroxides generated by neutrophils diffused into hepatocytes and contributed to parenchymal cell death in vivo . Thus, strengthening defense mechanisms against ROS in target cells can attenuate excessive inflammatory injury without affecting host defense reactions
The Use of Drugs in the Treatment of Early Phthisis
Authors: J. C. Thorowgood
Journal: BMJ (1891)

<h3>AIM</h3> To determine the frequency of GB virus C (GBV-C)/hepatitis G virus (HGV) infection before and after switch to the use of virus inactivated concentrates in haemophiliac patients infected with human immunodeficiency virus (HIV). <h3>PATIENTS AND METHODS</h3> Initial and follow up sera from 49 children with haemophilia were analysed for the presence of GBV-C/HGV RNA and antibodies to HGV (anti-HGV). All patients had been infected with HIV while receiving concentrates without virus inactivation before 1984 and were subsequently treated with virus inactivated concentrates. <h3>RESULTS</h3> In the first available serum sample (1987 or later), two of 49 patients were GBV-C/HGV RNA positive and two further patients were anti-HGV positive. During follow up (mean, 6 years), 14 patients developed markers of GBV-C/HGV infection. Eleven of these had received no blood products except clotting factor concentrates that had been prepared with virus inactivation. <h3>CONCLUSIONS</h3> Despite being treated with virus inactivated clotting factor concentrates, HIV positive patients with haemophilia are at an increased risk of manifesting GBV-C/HGV infection. We hypothesise that GBV-C/HGV is transmitted by these clotting factor concentrates. However, we cannot rule out the emergence of markers of GBV-C/HGV infection as a result of the progression of immune impairment in the course of HIV infection.
Treatment for Patients at Intermediate Risk of a Common Duct Stone—Reply
Authors: Pouya Iranmanesh, Jean-Louis Frossard, Christian Toso
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MicroRNA-486 regulates normal erythropoiesis and enhances growth and modulates drug response in CML progenitors
Authors: Li-Sheng Wang, Ling Li, Liang Li, Su Chu, Keh-Dong Shiang, Min Li, Hui-Yan Sun, Jun Xu, Feng-Jun Xiao, Guihua Sun, John J. Rossi, YinWei Ho, Ravi Bhatia
Journal: Blood (2014)
Multicolour spectral karyotyping of mouse chromosomes
Authors: Marek Liyanage, Allen Coleman, Stan du Manoir, Tim Veldman, Stephen McCormack, Robert B. Dickson, Carrolee Barlow, Anthony Wynshaw-Boris, Siegfried Janz, Johannes Wienberg, Malcolm A. Ferguson-Smith, Evelin Schröck, Thomas Ried
Journal: Nature Genetics (1996)
The surgical anatomy of the conduction tissues.
Authors: R H Anderson, S Y Ho, A E Becker
Journal: Thorax (1983)

On the basis of our collective experience we have reviewed the disposition of the cardiac conduction tissues as they might be observed by the surgeon in both normal and abnormal hearts. The sinus node lies subepicardially in the terminal sulcus; because of its variable blood supply the entire superior cavoatrial junction is a potential danger area. There are no morphologically discrete tracts extending through the atrial tissues between sinus and atrioventricular nodes. The atrioventricular node, the atrial extent of the atrioventricular conduction axis, is contained exclusively within the triangle of Koch. The axis penetrates through the central fibrous body and branches on the muscular ventricular septum immediately beneath the interventricular component of the membranous septum. The landmarks to these structures are described as they might be seen through the right atrium, left atrium, and aorta. Consideration is then given to the surgical anatomy of the abnormal muscular atrioventricular connections that underscore the ventricular pre-excitation syndromes. Finally, rules are developed whereby the disposition of the conduction tissues can be predicted with accuracy in congenitally malformed hearts, in the settings of both normal and abnormal chamber connections. The most important variables in this respect are alignment between the atrial and ventricular septal structures and the pattern of ventricular architecture present.
A CASE OF ECTOPIA VISCERUM
Authors: P. R. Cooper
Journal: BMJ (1917)

1917J-PNHiJMOTHOR.AX WITH HERNIA INTO PLEURAL CAVITY. [N A& 68f depthfs^f thie crypts, and surface applications could not be expected to reaclh them.Living cultures of Staphylococcus pyogenes albus lhad also been employed as sprays over thie tonsils in the hope of outgrowing the diphtheria bacillus, and it was usually found that swabs taklen next day were negative for Klebs- Loeffler organisms, but were loaded with staplhylococci.The bacilli, however, reappeared in large numbers within a day or two.The probable e-xplanation is that the large number of staplhylococci collected on the first swabs had outgrown tlle bacilli on the media.If, lhowever, the staphylococci outgrew tlle bacilli on the tonsils, tlhen fresh organisms were soon resupplied from the tonsillar crypts.CONCLUSIONS.1. TThat in apparently normal individuals the Bacillus diphtheriae may be harboured in the depths of the tonsillar crypts.-2.That complete enucleation of the tonsils seems to be a successful means for eliminating, diphltheria organisms from carriers, although it appears too drastic a measure for routine adoption.
Activation of Endothelial Ras Signaling Bypasses Senescence and Causes Abnormal Vascular Morphogenesis
Authors: Anshika Bajaj, Qingxia Zheng, Alejandro Adam, Peter Vincent, Kevin Pumiglia
Journal: Cancer Research (2010)

Angiogenesis is crucial for embryogenesis, reproduction, and wound healing and is a critical determinant of tumor growth and metastasis. The multifunctional signal transducer Ras is a proto-oncogene and frequently becomes mutated in a variety of human cancers, including angiosarcomas. Regulation of Ras is important for endothelial cell function and angiogenesis. Hyperactivation of Ras is linked with oncogene-induced senescence in many cell types. Given links between vascular malformations and angiosarcoma with activated Ras signaling, we sought to determine the consequence of sustained Ras activation on endothelial cell function. We find that sustained Ras activation in primary endothelial cells leads to prolonged activation of progrowth signaling, accompanied by a senescence bypass, enhanced proliferation, autonomous growth, and increased survival. Moreover, Ras severely compromises the ability of these cells to organize into vascular structures, instead promoting formation of planar endothelial sheets. This abnormal phenotype is regulated by phosphoinositide 3-kinase signaling, highlighting the therapeutic potential of agents targeting this axis in dealing with vascular morphogenic disorders and vascular normalization of tumors.