tbuckley/cabot-search huggingface dataset:
Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine.
Authors: S R Lentz, J E Sadler
Journal: Journal of Clinical Investigation (1991)

Elevated levels of plasma homocysteine are associated with both venous and arterial thrombosis. Homocysteine inhibits the function of thrombomodulin, an anticoagulant glycoprotein on the endothelial surface that serves as a cofactor for the activation of protein C by thrombin. The effects of homocysteine on thrombomodulin expression and protein C activation were investigated in cultured human umbilical vein endothelial cells and CV-1(18A) cells that express recombinant human thrombomodulin. Addition of 5 mM homocysteine to endothelial cells produced slight increases in thrombomodulin mRNA and thrombomodulin synthesis without affecting cell viability. In both cell types, thrombomodulin synthesized in the presence of homocysteine remained sensitive to digestion with endoglycosidase H and failed to appear on the cell surface, suggesting impaired transit along the secretory pathway. In a cell-free protein C activation assay, homocysteine irreversibly inactivated both thrombomodulin and protein C in a process that required free thiol groups and was inhibited by the oxidizing agents diamide or N-ethylmaleimide. By inhibiting both thrombomodulin surface expression and protein C activation, homocysteine may contribute to the development of thrombosis in patients with cystathionine beta-synthase deficiency.
Molecular Profiling of Synaptic Vesicle Docking Sites Reveals Novel Proteins but Few Differences between Glutamatergic and GABAergic Synapses
Authors: Janina Boyken, Mads Grønborg, Dietmar Riedel, Henning Urlaub, Reinhard Jahn, John Jia En Chua
Journal: Neuron (2013)
Mathematics Deficits in Adolescents With Bipolar I Disorder
Authors: Diane C. Lagace, Stanley P. Kutcher, Heather A. Robertson
Journal: American Journal of Psychiatry (2002)

This study examined mathematical ability in adolescents with bipolar I disorder, compared to adolescents with major depressive disorder and psychiatrically healthy comparison subjects.Participants (N=119) included adolescents in remission from bipolar disorder (N=44) or major depressive disorder (N=30), as well as comparison subjects (N=45) with no psychiatric history. Participants were assessed with the following measures: the Wide-Range Achievement Test, Revised 2 (WRAT-R2), Peabody Individual Achievement Test, Bay Area Functional Performance Evaluation Task-Oriented Assessment (functional mathematics subtest), Test of Nonverbal Intellegence-2, and a self-report of mathematics performance.WRAT-R2 and Peabody Individual Achievement Test scores for spelling, mathematics, and reading revealed that adolescents with bipolar disorder had significantly lower achievement in mathematics, compared to subjects with major depressive disorder and comparison subjects. Results for the Test of Nonverbal Intellegence-2 were not significantly different between groups. Adolescents with bipolar disorder took significantly longer to complete the Bay Area Functional Performance Evaluation mathematics task. Significantly fewer adolescents with bipolar disorder (9%) reported above-average mathematics performance, compared with the other groups.Adolescents with remitted bipolar disorder have a specific profile of mathematics difficulties that differentiates them from both adolescents with unipolar depression and psychiatrically healthy comparison subjects. These mathematics deficits may not derive simply from more global deficits in nonverbal intelligence or executive functioning, but may be associated with neuroanatomical abnormalities that result in cognitive deficits, including a slowed response time. These deficits suggest the need for specialized assessment of mathematics as part of a comprehensive clinical follow-up treatment plan.
ABCC6 Localizes to the Mitochondria-Associated Membrane
Authors: Lisa J. Martin, Edward Lau, Harpreet Singh, Laurent Vergnes, Elizabeth J. Tarling, Margarete Mehrabian, Imran Mungrue, Sheila Xiao, Diana Shih, Lawrence Castellani, Peipei Ping, Karen Reue, Enrico Stefani, Thomas A. Drake, Kristina Bostrom, Aldons J. Lusis
Journal: Circulation Research (2012)

Rationale: Mutations of the orphan transporter ABCC6 (ATP-binding cassette, subfamily C, member 6) cause the connective tissue disorder pseudoxanthoma elasticum. ABCC6 was thought to be located on the plasma membrane of liver and kidney cells. Objective: Mouse systems genetics and bioinformatics suggested that ABCC6 deficiency affects mitochondrial gene expression. We therefore tested whether ABCC6 associates with mitochondria. Methods and Results: We found ABCC6 in crude mitochondrial fractions and subsequently pinpointed its localization to the purified mitochondria-associated membrane fraction. Cell-surface biotinylation in hepatocytes confirmed that ABCC6 is intracellular. Abcc6-knockout mice demonstrated mitochondrial abnormalities and decreased respiration reserve capacity. Conclusions: Our finding that ABCC6 localizes to the mitochondria-associated membrane has implications for its mechanism of action in normal and diseased states.
A Common Variant of the Endothelial Nitric Oxide Synthase (Glu <sup>298</sup> →Asp) Is a Major Risk Factor for Coronary Artery Disease in the UK
Authors: Aroon D. Hingorani, Chia Fan Liang, Jenny Fatibene, Amelia Lyon, Sue Monteith, Ann Parsons, Stephen Haydock, Ruth V. Hopper, Nigel G. Stephens, Kevin M. O’Shaughnessy, Morris J. Brown
Journal: Circulation (1999)

Background —Endothelium-derived nitric oxide (NO) is synthesised from l -arginine by endothelial nitric oxide synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because reduced NO synthesis has been implicated in the development of coronary atherosclerosis, which has a heritable component, we hypothesised that polymorphisms of NOS 3 might be associated with increased susceptibility to this disorder. Methods and Results —Single-strand conformation polymorphism analysis of NOS 3 identified a G→T polymorphism in exon 7 of the gene which encodes a Glu→Asp amino acid substitution at residue 298 of eNOS. We investigated the relationship between this Glu 298 →Asp variant and atherosclerotic coronary artery disease (CAD) using 2 independent case-controlled studies. In the first study (CHAOS), cases consisted of 298 unrelated patients with positive coronary angiograms and controls were 138 unrelated healthy individuals ascertained through a population health screen. In the second study (CHAOS II), the cases were 249 patients with recent myocardial infarction (MI), and a further 183 unrelated controls. There was an excess of homozygotes for the Asp 298 variant among patients with angiographic CAD, and among patients with recent MI when compared with their respective controls (35.9% versus 10.2%, P &lt;0.0001 in CHAOS, and 18.1% versus 8.7%, P &lt;0.02 in CHAOS II). In comparison to Glu 298 homozygotes, homozygosity for Asp 298 was associated with an odds ratio of 4.2 (95% CI, 2.3 to 7.9) for angiographic CAD and 2.5 (95% CI, 1.3 to 4.2) for MI. Conclusions —Homozygosity for a common NOS 3 polymorphism (894 G→T) which encodes a Glu 298 →Asp amino acid substitution in eNOS is a risk factor for angiographic CAD and recent MI in this population.
Hepatitis B and C coinfections and persistent hepatitis B infections: Clinical outcome and liver pathology after transplantation
Authors: E J Huang, T L Wright, J R Lake, C Combs, L D Ferrell
Journal: Hepatology (1996)

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are common complications after orthotopic liver transplantation (OLT), but the liver pathology and clinical outcomes of HBV infection with HCV coinfection have not been thoroughly examined. In this study, we used the polymerase chain reaction (PCR) to detect HBV and HCV in pre- and post-OLT sera of 38 patients and correlated the findings with clinical outcome and liver pathology. Of 13 patients who were HBV and HCV negative before OLT, 9 acquired HBV infection, and 4 developed acquired HBV and HCV coinfections after OLT. Persistent HBV infections were present in 10 patients. Three patients with pre-OLT HBV infections developed persistent HBV and acquired HCV coinfections after OLT; 5 with pre-OLT HCV infections developed acquired HBV and persistent HCV coinfections after OLT, and 7 had persistent HBV and HCV coinfections before and after OLT. Portal/periportal inflammation was the same in all groups; however, lobular inflammation and fibrosis were more severe in patients with persistent HBV infections and in those with acquired HBV and HCV coinfections. Two major histopathological patterns were present in patients with HBV and HCV coinfections, one with predominant features of HCV infection, and the other with those of HBV infection. Patients with post-OLT HBV and HCV coinfections had survival rates similar to those with acquired HBV infection, whereas patients with persistent HBV infections experienced more allograft loss caused by chronic hepatitis or fibrosing cytolytic hepatitis, and had a more dire clinical outcome than the others. Although the limited numbers reported in this study prevent a definitive conclusion, our data suggest that in patients with HBV and HCV coinfections, the presence of HCV may improve the clinical outcome as compared with the expected outcome of persistent HBV infection alone.
The Asymptomatic Hernia
Authors: David R. Flum
Journal: JAMA (2006)

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
Progressive macular leucoderma in a patient with congenital ichthyosiform erythroderma
Authors: A. Torrelo, M.D. Marrero, I.G. Mediero, M.A. Martinez, A. Zambrano
Journal: British Journal of Dermatology (2001)

Sir, Autosomal recessive ichthyoses (ARI) are heterogeneous disorders, with diverse clinical presentations and course. We report a patient with ARI and a striking progressive macular leucoderma. A 1‐year‐old girl was first seen in our department in 1993 because of scaling erythroderma since birth. Her parents were not consanguineous, and another sibling was normal. She was born at term, and did not have a collodion baby phenotype. Examination showed diffuse erythroderma with extensive, fine scaling, and palmoplantar keratoderma. She also had severe ectropion and diffuse hair loss. The remainder of the general examination was normal, as well as thorough neurological and ophthalmological examinations. Full blood count and film, serum biochemistry, immunological profile, blood phytanic acid and very long chain fatty acid levels, biotinidase activity, and urinary excretion of oligosaccharides and amino acids were all normal. Direct light microscopy, polarized light microscopy and scanning electron microscopy of the hairs and eyebrows were repeatedly normal. Cysteic acid content of the hairs was not different from that in a normal control. Brain magnetic resonance imaging did not show any abnormality. Three skin biopsy specimens (two from the trunk and one from the thigh), taken at different times, showed similar results: intense hyperkeratosis with parakeratosis, follicular plugs, acanthosis, and elongation of rete ridges. The granular layer was almost absent. An intense vascular hyperplasia and dilatation was seen in the dermis. Electron microscopy showed striking lipid vacuoles in the stratum corneum cells.
UDDER INFECTION WITH STREPTOCOCCI OF THE SCARLET FEVER TYPE
Authors: F. S. Jones
Journal: The Journal of Experimental Medicine (1928)

The experiments indicate that milk filtered through a Berkefeld candle V or heated at 58 degrees C. for 20 minutes when added to blood agar plate cultures interferes with the development of colonies of the scarlet fever streptococcus. The observed inhibition is proportional to the amount of milk. When the approximate milk dilution in the Petri dish is 1:20 or 1:25 growth of the organisms is completely suppressed or only a small proportion of non-hemolytic colonies develop. As the amount of milk is decreased the colonies become larger and their hemolytic zones more pronounced, although even when the final dilution of milk reaches 1:100 or 1:125 only colonies easily mistaken for the narrow zoned bovine streptococci appear. The effects upon the surviving organisms would appear to be transient since both the non-hemolytic colonies and those with small zones manifest the original hemolytic properties when transferred to other media. When scarlet fever streptococci are added in small quantities to milk heated at 58 degrees C. for 20 minutes and incubated growth is inhibited. If the period is prolonged the streptococci are killed. On refrigeration of such mixtures some of the streptoccci are killed but others survive the test period.
Nail unit squamous cell carcinoma in people with immunosuppression
Authors: E. Ormerod, D. de Berker
Journal: British Journal of Dermatology (2015)

Nail unit squamous cell carcinoma (NUSCC) is uncommon and diagnosis is often initially incorrect or delayed. Immunosuppression appears important in the clinical behaviour of NUSCCs.To highlight the frequency and nature of immunosuppression in a case series of patients with NUSCC, and identify the distinguishing characteristics in this subgroup.Clinical, photographic and histological details were reviewed for all patients with NUSCC, over a 16-year period in a university dermatology department.Forty-three patients were identified and seven (16%) were immunosuppressed. Patients with immunosuppression presented at a younger age (mean 52 vs. 63 years, P = 0.08) and sooner (mean 9 vs. 65 months, P < 0.001) than immunocompetent patients, and had a higher frequency of polydactylous disease [four of seven (57%) vs. two of 36 (6%), P < 0.001], relapse at the same site [two of seven (29%) vs. 0], and recurrent disease at other sites [four of seven (57%) vs. 0].Immunosuppression plays a role in the development and clinical behaviour of NUSCCs. Clinicians should have a low threshold for early biopsy of nail dystrophies, particularly in those with immunosuppression. These patients are at higher risk of relapse and recurrent disease and therefore require prolonged follow-up.
TCT-112 Left Ventricular Ejection Fraction Improves Less after Trans-Apical Transcatheter Aortic Valve Replacement Compared to a Trans-Femoral Approach
Authors: William F. Fearon, Sammy Elmariah, Tom McAndrew, Gus J. Vlahakes, Michael Fischbein, David Liang, Susheel Kodali, Martin Leon, Lars Svensson, Philippe Pibarot, Pamela Douglas, Jonathan J. Passeri, Todd Dewey, Wilson Y. Szeto, Vasilis Babaliaros, Vinod Thourani, Mathew Williams, D. Craig Miller
Journal: Journal of the American College of Cardiology (2013)
<i>In vivo</i>diagnosis of allergic diseases-allergen provocation tests
Authors: I. Agache, M. Bilò, G.-J. Braunstahl, L. Delgado, P. Demoly, P. Eigenmann, P. Gevaert, E. Gomes, P. Hellings, F. Horak, A. Muraro, T. Werfel, M. Jutel
Journal: Allergy (2015)

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff.
Analysis of Chemotherapeutic Response in Ovarian Cancers Using Publicly Available High-Throughput Data
Authors: Jesus Gonzalez Bosquet, Douglas C. Marchion, HyeSook Chon, Johnathan M. Lancaster, Stephen Chanock
Journal: Cancer Research (2014)

A third of patients with epithelial ovarian cancer (OVCA) will not respond to standard treatment. The determination of a robust signature that predicts chemoresponse could lead to the identification of molecular markers for response as well as possible clinical implementation in the future to identify patients at risk of failing therapy. This pilot study was designed to identify biologic processes affecting candidate pathways associated with chemoresponse and to create a robust gene signature for follow-up studies. After identifying common pathways associated with chemoresponse in serous OVCA in three independent gene-expression experiments, we assessed the biologic processes associated with them using The Cancer Genome Atlas (TCGA) dataset for serous OVCA. We identified differential copy-number alterations (CNA), mutations, DNA methylation, and miRNA expression between patients that responded to standard treatment and those who did not or recurred prematurely. We correlated these significant parameters with gene expression to create a signature of 422 genes associated with chemoresponse. A consensus clustering of this signature identified two differentiated clusters with unique molecular patterns: cluster 1 was significant for cellular signaling and immune response (mainly cell-mediated); and cluster 2 was significant for pathways involving DNA-damage repair and replication, cell cycle, and apoptosis. Validation through consensus clustering was performed in five independent OVCA gene-expression experiments. Genes were located in the same cluster with consistent agreement in all five studies (κ coefficient ≥ 0.6 in 4). Integrating high-throughput biologic data have created a robust molecular signature that predicts chemoresponse in OVCA.
Impact of Distraction on the Driving Performance of Adolescents With and Without Attention-Deficit/Hyperactivity Disorder
Authors: Megan Narad, Annie A. Garner, Anne A. Brassell, Dyani Saxby, Tanya N. Antonini, Kathleen M. O’Brien, Leanne Tamm, Gerald Matthews, Jeffery N. Epstein
Journal: JAMA Pediatrics (2013)

<h3>Importance</h3> This study extends the literature regarding attention-deficit/hyperactivity disorder (ADHD)–related driving impairments to a newly licensed, adolescent population. <h3>Objective</h3> To investigate the combined risks of adolescence, ADHD, and distracted driving (cell phone conversation and text messaging) on driving performance. <h3>Design, Setting, and Participants</h3> Adolescents aged 16 to 17 years with (n = 28) and without (n = 33) ADHD engaged in a simulated drive under 3 conditions (no distraction, cell phone conversation, and texting). During each condition, one unexpected event (eg, another car suddenly merging into driver’s lane) was introduced. <h3>Interventions</h3> Cell phone conversation, texting, and no distraction while driving. <h3>Main Outcomes and Measures</h3> Self-report of driving history, average speed, standard deviation of speed, standard deviation of lateral position, and braking reaction time during driving simulation. <h3>Results</h3> Adolescents with ADHD reported fewer months of driving experience and a higher proportion of driving violations than control subjects. After controlling for months of driving history, adolescents with ADHD demonstrated more variability in speed and lane position than control subjects. There were no group differences for braking reaction time. Furthermore, texting negatively impacted the driving performance of all participants as evidenced by increased variability in speed and lane position. <h3>Conclusions</h3> To our knowledge, this study is one of the first to investigate distracted driving in adolescents with ADHD and adds to a growing body of literature documenting that individuals with ADHD are at increased risk for negative driving outcomes. Furthermore, texting significantly impairs the driving performance of all adolescents and increases existing driving-related impairment in adolescents with ADHD, highlighting the need for education and enforcement of regulations against texting for this age group.
A Prospective Randomized Trial Comparing the 1-Stage with the 2-Stage Implantation of a Pulse Generator in Patients with Pelvic Floor Dysfunction Selected for Sacral Nerve Stimulation
Authors: K. Everaert, W. Kerckhaert, H. Caluwaerts, M. Audenaert, H. Vereecke, G. De Cuypere, A. Boelaert, U. Van den Hombergh, W. Oosterlinck
Journal: European Urology (2003)
Decreased Splenic Perfusion Without Functional Asplenia
Authors: RICHARD P. SPENCER, JOHN J. SZIKLAS, KOLLI SURESH
Journal: Clinical Nuclear Medicine (1979)

Although functional asplenia may be associated with decreased splenic perfusion, two cases are presented which illustrate that the converse is not necessarily true. That is, two patients with markedly reduced splenic perfusion still showed splenic extraction of radiocolloid. These cases clearly demonstrate the dissociation of splenic blood flow and the radiocolloid extraction processes. Factors which might have contributed to the decreased perfusion are discussed.
Selective activation and accumulation of oligoclonal V beta-specific T cells in active pulmonary sarcoidosis.
Authors: J D Forman, J T Klein, R F Silver, M C Liu, B M Greenlee, D R Moller
Journal: Journal of Clinical Investigation (1994)

Sarcoidosis is a granulomatous disease in which activated T cells, responding to an unidentified stimulus, accumulate at sites of disease such as the lung. To evaluate the hypothesis that active sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR) specific T cells, we analyzed TCR V beta gene expression in lung and blood T cells of patients with active sarcoidosis and, for comparison, normal individuals using polymerase chain reaction amplification of 20 V beta gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR V beta distributions similar to that of normal blood, providing evidence for a lack of generalized skewing of the T cell repertoire in the normal, noninfected lung. Compared to normal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more V beta genes in either the lung or blood. Five V beta gene families (V beta 5, V beta 8, V beta 15, V beta 16, and V beta 18) were most frequently utilized in a biased fashion by sarcoid lung or blood T cells. Furthermore, dramatic skewing of the T cell repertoire was apparent when sarcoid lung and blood T cells were expanded by short-term culture with IL-2. Sequence analysis demonstrated a bias in V beta gene expression was usually due to expansion of select V beta-specific clones, some of which contained a similar V(D)J junctional region motif. These observations provide evidence for a selective activation and accumulation of antigen-specific V beta-expressing T cells in sarcoidosis.