tbuckley/cabot-search huggingface dataset:
Short- and Long-Term Effects of Amiodarone on the Two Components of Cardiac Delayed Rectifier K <sup>+</sup> Current
Authors: Kaichiro Kamiya, Atsushi Nishiyama, Kenji Yasui, Mayumi Hojo, Michael C. Sanguinetti, Itsuo Kodama
Journal: Circulation (2001)

Background —Amiodarone is the most promising drug for the treatment of life-threatening tachyarrhythmias in patients with structural heart disease. The pharmacological effects of amiodarone on cardiac ion channels are complex and may differ for short-term and long-term administration. Methods and Results —The delayed rectifier K + current (I K ) of ventricular myocytes isolated from rabbit hearts was recorded with the whole-cell voltage-clamp technique. I K was separated into 2 components by use of specific blockers for either I Ks (chromanol 293B, 30 μmol/L) or I Kr (E-4031, 10 μmol/L). Short-term application of amiodarone caused a concentration-dependent decrease in I Kr with an IC 50 of 2.8 μmol/L (n=8) but only a minimal reduction in I Ks . The short-term effects of amiodarone were also determined in Xenopus oocytes expressing the cloned human channels that conduct I Kr and I Ks (HERG and KvLQT1/minK). HERG current in oocytes was reduced by amiodarone (IC 50 =38 μmol/L), whereas KvLQT1/minK current was unaffected by 300 μmol/L amiodarone. To study the effects of long-term drug administration, rabbits were treated for 4 weeks with oral amiodarone (100 mg · kg −1 · d −1 ) before cell isolation. Long-term administration of amiodarone decreased I K to 55% (n=10) in control rabbits and altered the relative density of I Kr and I Ks . The majority (92%) of current was I Kr . mRNA levels of rabbit ERG , KVLQT1 , and minK in left ventricular myocardium did not differ between control and long-term amiodarone. Conclusions —Amiodarone has differential effects on the 2 components of I K , depending on the application period; short-term treatment inhibits primarily I Kr , whereas long-term treatment reduces I Ks .
CpG Mutation Rates in the Human Genome Are Highly Dependent on Local GC Content
Authors: Karl J. Fryxell, Won-Jong Moon
Journal: Molecular Biology and Evolution (2004)

CpG dinucleotides mutate at a high rate because cytosine is vulnerable to deamination, cytosines in CpG dinucleotides are often methylated, and deamination of 5-methylcytosine (5mC) produces thymidine. Previous experiments have shown that DNA melting is the rate-limiting step in cytosine deamination. Here we show, through the analysis of human single-nucleotide polymorphisms (SNPs), that the mutation rate produced by 5mC deamination is highly dependent on local GC content. In fact, linear regression analysis showed that the log10 of the 5mC mutation rates (inferred from SNP frequencies) had slopes of −3 when graphed with respect to the GC content of neighboring sequences. This is the ideal slope that would be expected if the correlation between CpG underrepresentation and GC content had been solely caused by DNA melting. Moreover, this same result was obtained regardless of the SNP locations (all SNPs versus only SNPs in noncoding intergenic regions, excluding CpG islands) and regardless of the lengths over which GC content was calculated (SNP sequences with a modal length of 564 bp versus genomic contigs with a modal length of 163 kb). Several alternative interpretations are discussed.
Discontinuation of immunosuppression for prevention of kidney graft rejection after receiving a bone marrow transplant from the same HLA identical sibling donor
Authors: James L. Gajewski, Cindy Ippoliti, Yan Ma, Richard Champlin
Journal: American Journal of Hematology (2002)

Abstract Induction of tolerance in solid organ transplant recipients has been a long sought goal so that patients will not need lifelong immunosuppression. In this case report we review a patient who received a kidney transplant from an HLA matched related sibling and developed acute leukemia as a consequence of her immunosuppression. The patient was then treated with an allogeneic bone marrow transplant from her kidney donor. After the bone marrow transplant, all immunosuppression therapy for graft rejection and graft versus host disease was stopped. Six months after the bone marrow transplant, the patient's kidney function had no deterioration as a consequence of stopping immunosuppression. This illustrated that a combined solid organ/bone marrow transplant can help to induce tolerance. In fact, the tolerance to the bone marrow transplant for prevention of graft versus host disease may have been accomplished by the prior kidney transplant. Am. J. Hematol. 71:311–313, 2002. © 2002 Wiley‐Liss, Inc.
Necrosis of the skin induced by coumarin.
Authors: M. Chambers, R. D. Thornes, M. McKernan
Journal: BMJ (1989)

the morning immediately after night duty, rather than later in the afternoon after 31 continuous hours on duty, as we did.This is surely where the moral lies when it comes to considering the implications of our study for clinical practice.It is the long hours of continuous work rather than sleep loss that is the main culprit.
Matched Ventilation-perfusion Defect From A Pleural Effusion
Authors: Mark Tulchinsky, Lucas M. DeJohn
Journal: Clinical Nuclear Medicine (2008)

Pleural effusions in patients suspected of pulmonary thromboembolism can result in abnormalities on ventilation-perfusion scintigraphy. Often the cause of ventilation-perfusion scintigraphy abnormality is attenuation of lung activity by the effusion, which causes matched defects. Imaging in the prone position can move a free-flowing effusion, exposing true underlying perfusion. This useful maneuver has been reported previously to convert “indeterminate probability” to “low probability” scan. This report offers a more detailed description of the prone maneuver in a case where repositioning revealed underlying normal perfusion in an area with a previous matched defect—improving clinical usefulness of the scan.
Pain in the face.
Authors: A. S. Shalom
Journal: BMJ (1968)

psychosomatic diseases " have emotional sensitivity as their common property, and determinable specific sensitivities are found in most of them.The environment does the rest.-Iam, etc., RANYARD WEST.Church Stretton, Salop.Side-effects of Vinca Alkaloids SIR,-The findings by Dr. A. Vladutiu (22 June, p. 764) of acute dilatation of the gut in guinea-pigs receiving intraperitoneal injections of vinblastine is similar to the ex- perience of others working with this drug.Constipation, abdominal distension, and pain, sometimes sufficient to precipitate laparo- tomy, as well as acute urinary retention and loss of salivation, occasionally occur in patients receiving vinblastine,' 2 though the incidence of these complications is far greater in patients receiving the closely related alka- loid, vincristine.'' Prophylactic bulk laxa- tives and other aperients are recommended routinely for patients receiving vincristine.'Smith' found similar acute dilatation of the gut in mice treated with intraperitoneal injections of vinblastine, and moreover demonstrated degenerative changes in the myenteric plexus of the gut both in man and the mouse.This finding is in keeping with the known neurotoxicity of vinblastine, but more particularly of vincristine.'Almost certainly direct damage to the myenteric plexus causes paralysis of the gut.There is no evidence for the true ganglion-blocking action of vinblastine suggested by Dr.
Abstract 1494: Characterization of a novel pro-tumorigenic TGF-β RII mutation from oral squamous cell carcinoma
Authors: Hwakyung Son, Iha Park, Z.M. Che, J Kim
Journal: Cancer Research (2010)

Abstract TGF-β signaling plays various roles in tumor progression. Tumor suppressive TGF- β signaling is involved in early steps of carcinogenesis through loss of function which leads to deregulated proliferation. On the contrary, TGF- β signaling could be pro-tumorigenic in later stages of carcinogenesis by promoting epithelial-mesenchymal transition (EMT). Most of the reported TGF- β receptor-II mutations were loss of tumor suppressor function mutations and no pro-tumorigenic TGF- β receptor-II mutation has been identified in human tumors. This study aimed to analyze a novel mutation of TGF- β receptor-II found in metastatic lymph node of oral squamous cell carcinoma. This mutant converts amino acid 227 from I to T and amino acid 236 from N to D of TGF- β receptor-II. Promoter assay using 3TP-lux reporter showed that 227/236 double mutation significantly increased both basal and TGF- β-induced luciferase activity as compared to wild type in DR-26, TGF- β receptor-II-defective mink lung epithelial cells. Stable expression of 227/236 mutant enhanced migration and invasion as well as cell growth of HSC-2 cells, human oral squamous cancer cell line whose TGF- β signaling is not growth inhibitory. In 227/236 mutant transfectant, E-cadherin expression is reduced whereas snail expression has not been changed significantly. In orthotopic xenograft model to monitor the tumor growth, 227/236 mutant transfectant formed significantly larger tumors as compared to wild type transfectant. But, unexpectedly, there was no difference in the expression pattern of involucrin and E-cadherin in these tumor tissues, suggesting that this mutation did not affect EMT in vivo model system. In the study we present a novel gain-of-function mutation of TGF- β receptor II, which increased TGF- β signaling and thereby induced tumor growth without affecting EMT in HSC-2 oral squamous cancer cells. This work was supported by a grant from the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic research promotion fund KRF-2005-005-J05901). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1494.
Glycemic Exposure Is Associated With Reduced Pulmonary Function in Type 2 Diabetes
Authors: Wendy A. Davis, Matthew Knuiman, Peter Kendall, Valerie Grange, Timothy M.E. Davis
Journal: Diabetes Care (2004)

OBJECTIVE—To examine prospectively the relationship between diabetes, glycemic control, and spirometric measures. RESEARCH DESIGN AND METHODS—From a community-based cohort, 495 Europid (i.e., of European descent) patients with type 2 diabetes who had no history of pulmonary disease underwent baseline spirometry between 1993 and 1994. A subset of 125 patients was restudied a mean of 7.0 years later. The main outcome measures included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC), and peak expiratory flow (PEF) corrected for body temperature, air pressure, and water saturation and were expressed either in absolute terms or as percentage-predicted value for age, sex, and height. RESULTS—Mean percentage-predicted values of each spirometric measure were decreased &amp;gt;10% in the whole cohort at baseline and absolute measures continued to decline at an annual rate of 68, 71, and 84 ml/year and 17 l/min for FVC, FEV1, VC, and PEF, respectively, in the 125 prospectively studied patients. Declining lung function measures were consistently predicted by poor glycemic control in the form of a higher updated mean HbA1c, follow-up HbA1c, or follow-up fasting plasma glucose. In a Cox proportional hazards model, decreased FEV1 percentage-predicted value was an independent predictor of all-cause mortality. CONCLUSIONS—Reduced lung volumes and airflow limitation are likely to be chronic complications of type 2 diabetes, the severity of which relates to glycemic exposure. Airflow limitation is a predictor of death in type 2 diabetes after adjusting for other recognized risk factors.
Failure of the Eddyites in Arkansas.
Authors: Cheves Bevill
Journal: JAMA (1903)

Winfield, Ark., May 12, 1903. <h3>To the Editor:</h3> —I see inThe Journal, May 9, that the Eddyites failed to receive a charter in Philadelphia. At the past session of the Arkansas legislature these people got a bill through the senate to exempt them from Section 13 of the recent medical act of the state, but in the house we managed to put an amendment on the bill "providing that they receive no pay for their practice." The senate never concurred in the amendment, so they are out here.
Metallic mercury poisoning.
Authors: G. F. Birdwood, A. I. Ray
Journal: BMJ (1967)

Propranolol-induced Depression SIR,-Therapeutic indications for the beta- receptor adrenergic blocking agent propranolol, of which we have experience, include angina, cardiac arrythmias, and hypertension' ; and there are reports of its value in phaeochromocytoma not amenable to surgery,' hypertrophic obstructive cardio- myopathy,3 even Parkinsonian tremor,4 anxiety,' the sympathetic side-effects of thyrotoxicosis, and cyanotic attacks in Fallot's tetralogy.'It is likely, therefore, that
Ancient Whole Genome Enrichment Using Baits Built from Modern DNA
Authors: Jacob M. Enk, Alison M. Devault, Melanie Kuch, Yusuf E. Murgha, Jean-Marie Rouillard, Hendrik N. Poinar
Journal: Molecular Biology and Evolution (2014)

We report metrics from complete genome capture of nuclear DNA from extinct mammoths using biotinylated RNAs transcribed from an Asian elephant DNA extract. Enrichment of the nuclear genome ranged from 1.06- to 18.65-fold, to an apparent maximum threshold of ∼80% on-target. This projects an order of magnitude less costly complete genome sequencing from long-dead organisms, even when a reference genome is unavailable for bait design.
THE RELATION OF CIRCULATING ANTIBODIES TO SERUM DISEASE
Authors: Warfield T. Longcope, Francis M. Rackemann
Journal: The Journal of Experimental Medicine (1918)

1. The injection of horse serum either in small or in large amounts in human beings is always followed sooner or later by the development of hypersensitiveness of the skin to subsequent injections of horse serum. For the development of this reaction serum disease is not essential. 2. The blood serum of most patients who suffer from an attack of serum disease following injections of horse serum shows anaphylactin and precipitin for horse serum. 3. Anaphylactin and precipitin cannot be demonstrated in the blood serum of patients treated with horse serum who do not later present symptoms of serum sickness. 4. The appearance of anaphylactin and precipitin precedes shortly recovery from the disease. 5. With the appearance in the serum of antibodies to horse serum in great concentration, the antigen rapidly diminishes or disappears. 6. It is probable that the extrusion of these antibodies into the circulation is the result and not the cause of serum sickness. Their presence serves to neutralize or destroy the antigen and thus determines the recovery from serum sickness.
Atlas of Diabetes
Authors: John A. Colwell
Journal: JAMA (2012)

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
Analysis of Shock
Authors: V. H. Moon
Journal: BMJ (1944)

During a period of 40 years shock has been the subject of extensive and intensive study, both clinical and experi- mental.This has resulted in a mass of well-attested factual evidence, but agreement on the pathophysiological mechanisms has not been reached.Writers differ widely in their views, and readers are bewildered by the evidence set forth in support of the conflicting opinions.It appears that a logical correlation of the known facts is needed now rather than a search for new facts.A realistic examination of the causes for disagreement may be illuminating.What is Shock?The broad and indefinite use of this term is not the least among several causes for disagreement.Shock has been applied to a number of unrelated conditions.Many regard it as a state of acute circulatory failure characterized clinically by prostration, apathy or stupor, tachycardia, feeble regular pulse, and diminished
Serum IgD as a discriminator between the two periodic febrile syndromes hyper- immunoglobulinaemia D syndrome and Behcet's disease
Authors: N. BREZNIAK, S. SHTRASBURG, P. LANGEVITZ, A. LIVNEH, J. P H DRENTH, S. SHTRASBURG, P. LANGEVITZ, A. LIVNEH
Journal: Annals of the Rheumatic Diseases (1998)

The hyperimmunoglobulinaemia D (IgD) syndrome (HIDS) is a recently described periodic disease, manifested by febrile episodes, lasting several days and accompanied by abdominal pain, symmetrical oligoarthritis, cervical lymphadenopathy, skin lesions, and constantly increased serum IgD concentrations (>100 units/ml).1 HIDS shares its episodic febrile nature and many painful manifestations with several other clinical conditions, including familial Mediterranean fever, familial Hibernian fever, and Behcet’s disease (BD). Indeed, in a leading textbook of rheumatology, these entities were recently grouped in one chapter, entitled Intermittent and Periodic Arthritic Syndromes.2 Manifestations, distinguishing …
Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients.
Authors: P E Parsons, M Moss, J L Vannice, E E Moore, F A Moore, J E Repine
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Although numerous cytokines, including interleukin (IL)-1, IL-8, and tumor necrosis factor, circulate in critically ill patients at risk for acute respiratory distress syndrome (ARDS), none clearly predict the development of the syndrome. We hypothesized that cytokines, such as IL-1ra, IL-10, and IL-4, which modulate inflammation, might contribute to or reflect the development of acute lung injury. Accordingly, serial levels of IL-1ra and IL-10 were measured in 77 patients who were identifed as being at risk for the development of ARDS. Initial IL-1ra levels were significantly higher (p < 0.0001) in the patients (7.82 [2.29-38.01] ng/ml) than in normal control subjects (0.24 [0.24-0.34] ng/ml) but did not predict the development of ARDS. Initial IL-1ra levels, however, were greater (p = 0.038) in the patients who died (31.95 [3.02-65.06] ng/ml) compared with survivors (6.61 [1.86-29.33] ng/ml). Similarly, IL-10 levels were increased in patients (155 [53.75-318.75] ng/ml) compared with normal control subjects (0 ng/ml) but did not predict the development of ARDS. Like IL-1ra levels, initial IL-10 levels were significantly higher (p = 0.005) in patients who died compared with survivors. IL-4 was not detectable in any of the patient plasma samples measured. Thus, modulators of inflammation are increased in patients at risk for ARDS who die, but do not predict the development of the syndrome.
Quality of joint replacements not so bad?
Authors: P. E L Evans
Journal: BMJ (2009)

Some of the facts in Nick Clarke’s review of Panorama’s recent programme on independent sector treatment centres (ISTCs) cannot go unchallenged.1

He refers to a recent study about poor clinical results of joint replacement operations at the Weston NHS Treatment Centre in Somerset.2 Patients who had hip and knee replacements there had a significantly higher early reoperation rate than would …
Hazards of compression treatment of the leg: an estimate from Scottish surgeons.
Authors: M J Callam, C V Ruckley, J J Dale, D R Harper
Journal: BMJ (1987)

<h3>Abstract</h3> Hsp110s are well recognized nucleotide exchange factors (NEFs) of Hsp70s, in addition they are implicated in various aspects of cellular proteostasis as discrete chaperones with yet enigmatic molecular mechanism. Stark similarity in domain organization and structure between Hsp110s and Hsp70s, is easily discernible although the nature of domain communication and domain functions of Hsp110s are still puzzling. Here, we report atypical domain communication of yeast Hsp110, Sse1 using single molecule FRET, small angle X-ray scattering measurements (SAXS) and Molecular Dynamic simulations. Our data show that Sse1 lacks typical domain movements as exhibited by Hsp70s, albeit it undergoes unique structural alteration upon nucleotide and substrate binding. Hsp70-like domain-movements can be artificially salvaged in chimeric constructs of Hsp110-Hsp70 although such salvaging proves detrimental for the NEF activity of the protein. Furthermore, we show that substrate binding domain (SBD) of Hsp110, chaperones self, as well as foreign nucleotide binding domains (NBD). Interestingly, the substrate binding specificity of Hsp110 is largely determined by its NBD rather than SBD, the latter being the foremost substrate binding region for Hsp70s.