tbuckley/cabot-search huggingface dataset:
Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval
Authors: Reza Mazhari, H. Bradley Nuss, Antonis A. Armoundas, Raimond L. Winslow, Eduardo Marbán
Journal: Journal of Clinical Investigation (2002)

Regulatory subunit KCNE3 (E3) interacts with KCNQ1 (Q1) in epithelia, regulating its activation kinetics and augmenting current density. Since E3 is expressed weakly in the heart, we hypothesized that ectopic expression of E3 in cardiac myocytes might abbreviate action potential duration (APD) by interacting with Q1 and augmenting the delayed rectifier current (IK). Thus, we transiently coexpressed E3 with Q1 and KCNE1 (E1) in Chinese hamster ovary cells and found that E3 coexpression increased outward current at potentials by ≥ –80 mV and accelerated activation. We then examined the changes in cardiac electrophysiology following injection of adenovirus-expressed E3 into the left ventricular cavity of guinea pigs. After 72 hours, the corrected QT interval of the electrocardiogram was reduced by ∼10%. APD was reduced by >3-fold in E3-transduced cells relative to controls, while E-4031–insensitive IK and activation kinetics were significantly augmented. Based on quantitative modeling of a transmural cardiac segment, we demonstrate that the degree of QT interval abbreviation observed results from electrotonic interactions in the face of limited transduction efficiency and that heterogeneous transduction of E3 may actually potentiate arrhythmias. Provided that fairly homogeneous ectopic ventricular expression of regulatory subunits can be achieved, this approach may be useful in enhancing repolarization and in treating long QT syndrome.
Awakenings
Authors: Harold L. Klawans
Journal: JAMA (1988)

Christopher Columbus did not discover America. While that statement is undoubtedly true, it is historically irrelevant. In terms of the history of both Europe and the "New World," it was the journey of Columbus that began their interaction and brought to a definite end their independent existences. Oliver Sacks did not invent the concept of writing about his own clinical experiences with interesting and unusual patients for educated though medically unsophisticated readers. Physicians have undoubtedly been entertaining friends and acquaintances with such tales since Hippocrates or even earlier. Until 1973, Trevas and William Carlos Williams were probably the best-recognized practitioners of this subspecialty. No more. It is Oliver Sacks who has taken over the field, and for most readers he is the one physician who discovered the genre—the Christopher Columbus of medical writing. And this is the book that started the voyage. <i>Awakenings</i>was first published in 1973, but this
Addiction Medicine
Authors: John E. Franklin
Journal: JAMA (1994)

Debate has intensified this year in political, media, and scientific circles regarding the success or failure of the "War on Drugs." Surgeon General Elders' call to study the matter this year has met with swift response. Two recent opinion articles, from an addiction medicine perspective, highlight the pros and cons of changing existing drug use laws.<sup>1,2</sup> Recent optimism regarding decreasing drug use in high school students has been tempered by a closer examination of the data and recent trends. According to the American Drug and Alcohol Survey, after a 5-year drop in drug use by high school students, there are early indications of a rise in the percentage of eighth graders who have tried marijuana and inhalants.<sup>3</sup>This survey echoes the National Survey of Secondary School Students, which also found statistically significant increases in the use of drugs in eighth graders.<sup>4</sup>These statistics do not include the
Exhaust Emissions from Light- and Heavy-Duty Vehicles: Chemical Composition, Impact of Exhaust after Treatment, and Fuel Parameters
Authors: Roger Westerholm, Karl-Erik Egeback
Journal: Environmental Health Perspectives (1994)

This paper presents results from the characterization of vehicle exhaust that were obtained primarily within the Swedish Urban Air Project, "Tatortsprojektet."Exhaust emissions from both gasoline-and diesel-fueled vehicles have been investigated with respect to regulated pollutants (carbon monoxide [CO], hydrocarbon [HC], nitrogen oxides [NO ], and particulate), unregulated pollutants, and in bioassay tests (Ames test, TCDD receptor affinity tests).Unregulated pollutants present in both the particle-and the semi-volatile phases were characterized.Special interest was focused on the impact of fuel composition on heavy-duty diesel vehicle emissions.It was confirmed that there exists a quantifiable relationship between diesel-fuel variables of the fuel blends, the chemical composition of the emissions, and their biological effects.According to the results from the multivariate analysis, the most important fuel parameters are: polycyclic aromatic hydrocarbons (PAH) content, 90% distillation point, final boiling point, specific heat, aromatic content, density, and sulfur content.-
Unusual gas shadow in pelvis of asymptomatic patient
Authors: E. L. Lame
Journal: JAMA (1977)

<h3>History</h3> A 47-year-old patient had anteroposterior and lateral films of the pelvis taken because of a minor injury to the left hip and knee. <h3>Diagnosis</h3> Transsexual pelvis. <h3>Comment</h3> A 47-year-old patient, originally a male, had had a transsexual conversion some years ago at another hospital. The anteroposterior roentgenogram of the pelvis (Fig 1) shows a typical normal male bony contour and structure (heavy bones and small pelvic cavity), with what appears to be a semiopaque speculum or obturator in the midline. The lateral view (Fig 2) locates this shadow not in the rectum but in the vagina. The patient then indicated that the shadow was that of a vaginal dilator, used frequently and over long periods to maintain patency in the surgically produced vagina. The dilator is a standard product produced by dealers in gynecologic material and measures about 13.34 cm in length and about 3.18 cm in diameter (Fig
Hemiparesis in cervical spondylosis
Authors: E. M. Wallack
Journal: JAMA (1976)

Two patients with hemiparesis were thought to have intracranial sions. Cervical spondylosis was discovered, and the condition of both patients improved after laminectomy. Although it has been rarely emphasized in the past, cervical spondylosis should be considered in the differential diagnosis of hemiparesis. (<i>JAMA</i>236:2524-2525, 1976)
Susceptibility to autoimmune chronic active hepatitis: Human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors
Authors: P Donaldson
Journal: Hepatology (1991)

After nearly 18 years of research, the association between human leukocyte antigens A1-B8-DR3 and autoimmune chronic active hepatitis still provokes debate. The principal reasons for this are disease heterogeneity and racial variation in the distribution of human leukocyte antigens between populations. The aim of the present study was to reexamine the relationship between these antigens and autoimmune chronic active hepatitis in a well-characterized series of patients. Ninety-six outpatients with autoimmune chronic active hepatitis and an additional 14 referred for liver transplantation with end-stage autoimmune chronic active hepatitis were studied. Human leukocyte antigen frequencies were compared with those of 100 racially and geographically matched controls. The A1-B8-DR3 haplotype was present in 38% of patients compared with 11% of controls (x2 = 20.6, p < 0.0005). When all the DR3-positive patients were eliminated, there was a striking secondary association with DR4; 35 (80%) of 44 remaining patients were DR4 positive compared with 31 (39%) of 79 DR3-negative controls (Fisher's exact probability test p = 0.000031, pc = 0.0013). In addition patients with A1-B8-DR3 are seen at a significantly younger age than those without (39.75 yr vs. 48.21 yr, p < 0.025), relapse more frequently (52% of patients with A1-B8-DR3 relapsed on one or more occasions compared with 34% of patients without this haplotype) and are more frequently referred for liver transplantation. These data indicate for the first time that two genes within the major histocompatibility complex closely linked to the DR3 and DR4 genes independently confer susceptibility to autoimmune chronic active hepatitis. (HEPATOLOGY 1991;13:701–706.)
Coronary embolization with myocardial infarction. Late complication in a patient with a Starr-Edwards Mitral-Valve prosthesis
Authors: E. H. Lamkin
Journal: JAMA (1965)

CORONARY embolization is an infrequent cause of myocardial infarction. Oakley and his associates<sup>1</sup>were able to collect only 90 cases from the literature, to which they added five cases of their own. Wenger and Bauer<sup>2</sup>found 11 cases of coronaryartery embolism in 17,469 consecutive autopsy cases at Mount Sinai Hospital, New York, for a general necropsy incidence of 0.06%. The actual incidence of coronary occlusion due to embolism is unknown. Although 50% of cases of coronary embolism are associated with bacterial endocarditis, several other sources of emboli have been less commonly reported. In addition to paradoxical embolization, emboli may arise from any one of a number of sites in the left side of the heart and its immediate tributaries. The advent of open-heart surgery, and particularly valve prosthesis, has introduced a new source for thrombus formation and subsequent embolization, namely thrombosis on the prosthetic valve. This paper presents the
Early G2/M checkpoint failure as a molecular mechanism underlying etoposide-induced chromosomal aberrations
Authors: S. Nakada
Journal: Journal of Clinical Investigation (2005)

Topoisomerase II (Topo II) inhibitors are cell cycle–specific DNA-damaging agents and often correlate with secondary leukemia with chromosomal translocations involving the mixed-lineage leukemia/myeloid lymphoid leukemia (MLL) gene on chromosome 11 band q23 (11q23). In spite of the clinical importance, the molecular mechanism for this chromosomal translocation has yet to be elucidated. In this study, we employed 2-color FISH and detected intracellular chromosomal translocations induced by etoposide treatment. Cells such as ataxia-telangiectasia mutated–deficient fibroblasts and U2OS cells, in which the early G2/M checkpoint after treatment with low concentrations of etoposide has been lost, executed mitosis with etoposide-induced DNA double-strand breaks, and 2-color FISH signals located on either side of the MLL gene were segregated in the postmitotic G1 phase. Long-term culture of cells that had executed mitosis under etoposide treatment showed frequent structural abnormalities of chromosome 11. These findings provide convincing evidence for Topo II inhibitor–induced 11q23 translocation. Our study also suggests an important role of the early G2/M checkpoint in preventing fixation of chromosomal abnormalities and reveals environmental and genetic risk factors for the development of chromosome 11 translocations, namely, low concentrations of Topo II inhibitors and dysfunctional early G2/M checkpoint control.
ADDRESS.
Authors: A. J. VANCE
Journal: JAMA (1898)

Today treasure-laden memory brings before me as an ever-changing kaleidoscope the faces of the men who have stood as I stand today before this honorable body. Some are still with us giving their energies and intellects to the up-building of our profession. Others have crossed over and are resting from the toil and heat of the day. Not only the faces of the men who have preceded me for the fifteen years I have known this society, but many of their thoughts found an abiding place in my search for medical knowledge, that have often been of great benefit to me. It is not my object to speak today of the recent developments that have been made in the world of medical science. It has been a matter of great interest to know something of the foundation of medicine, and in my research I find that it is from the Egyptians
Decrease in hydroxyproline excretion in a patient with Marfan's syndrome after methandrostenolone therapy
Authors: C. R. Jones
Journal: JAMA (1969)

Long-term methandrostenolone therapy was associated with a markedly lowered hydroxyproline excretion and increased physical well-being in a 36-year-old patient with Marfan's syndrome. It is suggested that the anabolic steroid favorably affected collagen metabolism in this patient.
Association of the cannabinoid receptor 2 (CB2) Gln63Arg polymorphism with indices of liver damage in obese children: An alternative way to highlight the CB2 hepatoprotective properties
Authors: Sophie Lotersztajn, Fatima Teixeira-Clerc, Vanessa Deveaux, Sylvie Manin, Ariane Mallat
Journal: Hepatology (2011)

We thank Rossi and colleagues for their interest in our experimental findings delineating the impact of CB2 receptors in experimental models of liver injury. We reported recently that the hepatic cannabinoid receptor 2 (CB2) displays beneficial hepatoprotective and antifibrogenic properties.1, 2 However, as stressed by Rossi and colleagues, we also demonstrated that treatment of obese mice with the CB2-selective agonist JWH-133 enhances insulin resistance and steatosis.3 Deleterious effects of CB2 agonism in obese mice were attributed to a proinflammatory effect of adipose tissue CB2 receptors.3 However, our recent findings in a model of alcoholic liver injury indicate that stimulation of hepatic CB2 receptors reduces the development of fatty liver.4 Altogether, our experimental data demonstrate the protective effects of hepatic CB2 receptors against liver injury, steatosis, and fibrosis. In their cohort study of over 400 obese children, Rossi and colleagues show a positive correlation between the presence of a CB2 variant with reduced activity, as assessed in culture studies, and the degree of liver injury estimated by serum aminotransferase levels. These interesting findings constitute the first evidence supporting the clinical relevance of hepatoprotective effects of CB2 receptors. Further studies should be conducted to examine the impact of CB2 polymorphism on the severity of liver lesions (steatosis, necroinflammation, and fibrosis) in patients with nonalcoholic steatohepatitis. Sophie Lotersztajn* , Fatima Teixeira-Clerc*, Vanessa Deveaux*, Sylvie Manin*, Ariane Mallat* , * INSERM U955, Créteil France, Université Paris Est, Créteil France
Home Visit
Authors: Donna Pucciani
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
THE TREATMENT OF INTESTINAL INTOXICATION IN INFANTS
Journal: JAMA (1926)

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
A surrogate system for informed consent
Authors: H. C. Fost
Journal: JAMA (1975)

Since "informed consent" is frequently obtained in a clinical setting where the patient is anxious and overwhelmed with feelings, toward the physician, of awe, trust, and dependency, it is often of dubious value in protecting human subjects. We devised, as a possible alternative mechanism for uncovering patient views toward a specific research protocol, a surrogate system of consent. The surrogates' responses seemed more candid and diverse than the responses one usually hears in the "real" clinical setting. Potential applications of such a system lie in further study of the consent process, and as a means for individual investigators to better gauge consumer attitudes toward specific projects. (<i>JAMA</i>233:800-803, 1975)
Intravesical rad-IFNα/Syn3 for patients with high-grade, bacillus Calmette-Guérin (BCG) refractory or relapsed non-muscle invasive bladder cancer: A phase II randomized study.
Authors: Stephen A. Boorjian, Neal D. Shore, Daniel Canter, Kenneth Ogan, Lawrence Ivan Karsh, Tracy Downs, Leonard G. Gomella, Ashish M. Kamat, Yair Lotan, Robert S. Svatek, Trinity J. Bivalacqua, Robert Grubb, Tracey Krupski, Seth P. Lerner, Michael Woods, Brant Allen Inman, Matthew I. Milowsky, Nigel Parker, David Sawutz, Colin P.N. Dinney
Journal: Journal of Clinical Oncology (2017)

279 Background: While bacillus Calmette-Guérin (BCG) is the most effective intravesical treatment for reducing recurrence and progression for high-risk non-muscle invasive bladder cancer (NMIBC), many patients are either refractory to treatment or relapse. We assessed the efficacy and safety of rAd-IFNα/Syn 3 (Instiladrin, FKD Finland), a replication deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG refractory or relapsed NMIBC. Methods: In this open-label, US multicenter (n=13), parallel-arm Phase II study (NCT01687244), 43 patients with HG BCG refractory or relapsed NMIBC were randomized 1:1 to receive intravesical rAd-IFNα/Syn3 at 1x10 11 or 3x10 11 viral particles/mL. Patients responding at months 3, 6, and 9 were re-treated at months 4, 7, and 10. Most patients (n=21) had a primary tumor classification of carcinoma in situ (CIS); 9 had both CIS and Ta/T1 disease and 10 had Ta/T1 disease alone. The primary endpoint was 12-month HG recurrence-free survival (RFS). All patients receiving at least one dose were included in efficacy and safety analyses. Results: Forty patients received rAd-IFNα/Syn3 (1 x 10 11 vp/mL: n=21; 3 x 10 11 vp/mL: n=19) between November 2012 and April 2015. Fourteen patients (35.0%; 90% CI 22.6%, 49.2%) remained free of HG tumor recurrence 12 months after initial treatment. Comparable 12 month HG RFS was noted between dosage arms, as well as between patients with refractory and relapsed NMIBC. Interestingly, the 12 month HG recurrence-free survival for patients with Ta/T1-only disease was 50% (5/10). rAd-IFNα/Syn3 was well-tolerated, with no Grade 5 adverse events (AEs), one Grade 4 AE (COPD; unrelated to treatment), and no patient discontinuing treatment due to an adverse event. The most frequently reported AEs were micturition urgency (n=16), dysuria and pollakiuria (n=13 each), fatigue (n=9), and nocturia (n=10). Conclusions: rAd-IFNα/Syn3 was well tolerated and demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who are unable or unwilling to undergo radical cystectomy. A phase III trial utilizing this novel agent is ongoing. Clinical trial information: 01687244.
First Journal
Journal: JAMA (1996)

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
Vascular Endothelial Estrogen Receptor α Is Modulated by Estrogen Status and Related to Endothelial Function and Endothelial Nitric Oxide Synthase in Healthy Women
Authors: Kathleen M. Gavin, Douglas R. Seals, Annemarie E. Silver, Kerrie L. Moreau
Journal: Endocrine Reviews (2009)

ABSTRACT Context and Objective Estrogen receptor α (ERα), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ERα is influenced by estrogen status and is related to vascular endothelial function in healthy women. Methods ERα protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women. Results In premenopausal women (n = 10), ERα expression was 30% lower (P &amp;lt; 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ERα expression was 33% lower (P &amp;lt; 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ERα expression was strongly related (r = 0.67; P &amp;lt; 0.001) to EDD, which was reduced in postmenopausal women. ERα abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20). Conclusions These results provide the first evidence that expression of ERα in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ERα expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.