tbuckley/cabot-search huggingface dataset:
Characterisation of the transient outward K+ current in rabbit sinoatrial node cells
Authors: M Lei
Journal: Cardiovascular Research (2000)

Objective: To (i) characterise the electrophysiological and pharmacological properties of the transient outward K+ current, Ito, (ii) determine the relationship between the density of Ito and cell size, and (iii) determine the role of Ito in electrical activity in rabbit sinoatrial node cells at 35°C. Methods: Rabbit sinoatrial node cells were studied using whole-cell voltage and current clamp techniques. Results:Ito showed half activation and inactivation at +11 and −49 mV, respectively. Ito was blocked by 4-aminopyridine (4-AP) as well as the class I agents, quinidine and flecainide, with EC50 values of 326, 21, and 19 μM, respectively. The densities of the transient and sustained components of 4-AP-sensitive current were significantly correlated with cell capacitance, a measure of cell size, and were greater in cells with a larger capacitance. Block of Ito by 4-AP affected both the action potential and pacemaker activity of sinoatrial node cells and the effects were greater in cells with a larger capacitance. Conclusions:Ito in sinoatrial node cells shows similar electrophysiological and pharmacological properties to Ito in atrial and ventricular cells. The expression of Ito in sinoatrial node cells is heterogeneous and differs in large and small cells (likely to be from the periphery and centre of the sinoatrial node, respectively). Ito plays an important role in action potential configuration and pacemaker activity in sinoatrial node cells, especially in larger cells.
Central Nervous System Image Correlation Multiple Cerebral Vascular Accidents in a Child with Cyanotic Heart Disease
Authors: JOHN R. STY, ROBERT J. STARSHAK, HERBERT W. OECHLER
Journal: Clinical Nuclear Medicine (1982)

STY, JOHN R. M.D.; STARSHAK, ROBERT J. M.D.; OECHLER, HERBERT W. M.D. Author Information
Role of Nitric Oxide in the Coronary Microvascular Responses to Adenosine and Increased Metabolic Demand
Authors: Christopher J. H. Jones, Lih Kuo, Michael J. Davis, David V. DeFily, William M. Chilian
Journal: Circulation (1995)

Background The purpose of this study was to test the hypothesis that endothelium-derived nitric oxide (NO) participates in coronary microvascular responses to adenosine and pacing-induced increases in metabolic demand by maintaining an optimal distribution of coronary resistance. Methods and Results Coronary microvascular diameters were measured by stroboscopic epi-illumination and intravital microscopy in open-chest dogs (n=20). Epicardial coronary blood velocity (CBV) was measured by Doppler flowmetry. Responses to adenosine (1 and 10 μg · kg −1 · min −1 IC) and left atrial pacing (180 beats per minute) were recorded before and after inhibition of NO synthesis by N G -nitro- l -arginine methyl ester (L-NAME, 30 μg · kg −1 · min −1 IC). At baseline, adenosine dilated arterioles (&lt;100 μm) (11±4% and 25±3% diameter changes, P &lt;.05) more than small arteries (&gt;100 μm) (−4±6% and 7±3%, P &lt;.05 for the higher dose) and increased CBV (43±31% and 118±25%, P &lt;.05). Left atrial pacing dilated arterioles (12±2%, P &lt;.05) and small arteries (8±3%, P &lt;.05) and also increased CBV (68±9%, P &lt;.05). L-NAME abolished CBV increases caused by acetylcholine (10 and 100 ng · kg −1 · min −1 IC; 53±33% and 168±82% versus −12±15% and −1±14%, P &lt;.05) but not papaverine. Small arteries were constricted by L-NAME (−8±2%, P &lt;.05), arterioles were dilated (10±4%, P &lt;.05), and CBV was unchanged. After L-NAME, adenosine failed to dilate arterioles further (3±3% and 2±2%; P &lt;.05 versus prior responses), and CBV changes were attenuated (14±16% and 8±13%; P &lt;.05 versus prior responses). Pacing also failed to dilate arterioles (−4±2%, P &lt;.05 versus prior response), resulting in an attenuated CBV change (34±13%, P &lt;.05 versus prior response). The possibility that adenosine stimulates NO release in canine coronary arterioles was investigated in isolated arterioles (diameters, 81±4 μm; n=8). Adenosine caused dose-dependent dilation to maximal diameter, which was unaffected by inhibition of NO synthesis by L-NAME. Conclusions Inhibition of NO synthesis attenuates coronary dilation during adenosine infusions and during pacing-induced increases in metabolic demand. Inhibition of NO synthesis may shift the major site of coronary resistance into small arteries through autoregulatory adjustments in arterioles. These data therefore suggest that NO, by dilating predominantly small coronary arteries, promotes metabolic coronary dilation by preserving the tone and vasodilator reserve of arterioles.
IMPACT OF PRETREATMENT ISCHEMIA ON THERAPEUTIC RISK REDUCTION AND LONG-TERM PROGNOSIS IN PATIENTS WITH STABLE ANGINA: RESULTS FROM COURAGE TRIAL
Authors: Leslee J. Shaw, Daniel S. Berman, David J. Maron, Rory Hachamovitch, Pamela M. Hartigan, James K. Min, Steven P. Sedlis, Marcin Dada, G.B. John Mancini, Robert A. O’Rourke, John A. Spertus, Bernard R. Chaitman, Eric R. Bates, Koon K. Teo, William E. Boden, William S. Weintraub
Journal: Journal of the American College of Cardiology (2010)
Three Adult Cases of Listeria monocytogenes Meningitis in Vietnam
Authors: Tran Thi Hong Chau, James I. Campbell, Constance Schultsz, Nguyen Van Vinh Chau, To Song Diep, Stephen Baker, Nguyen Tran Chinh, Jeremy J. Farrar, H. Rogier van Doorn
Journal: PLoS Medicine (2010)

Which Routine Test Results Are Now Helpful?In bacterial meningitis there is characteristically a peripheral leucocytosisThe Learning Forum discusses an important clinical problem of relevance to a general medical audience.
Oral Cholecystography in Gilbert's Syndrome and Diagnostics of Jaundice
Authors: Henry S. Bloch
Journal: JAMA (1971)

To the Editor.—  In the overtly jaundiced patient, the oral cholecystogram tends to be deemphasized as a means of elucidating the underlying disease, because jaundice is so often associated with hepatic dysfunction impeding excretion of contrast agents into the bile. 1 There are, however, diseases capable of producing severe jaundice due to an isolated and quite specific metabolic defect, such as diminished ability of the liver to convert bilirubin into bilirubin glucuronide, as in Gilbert's syndrome. 2 Becasue the hyperbilirubinemia of Gilbert's syndrome appears to be due to faulty bilirubin metabolism alone, one would expect to obtain a normal oral cholecystogram readily in a patient with this syndrome, even in the presence of marked icterus. This hypothesis was borne out in one patient.  Report of a Case.—  A 17-year-old man had had intermittent yellow discoloration of his sclerae and skin for several months, which was becoming more persistent and intense.
The development of dermatology in the Netherlands
Authors: J.R. PRAKKEN
Journal: British Journal of Dermatology (1974)

Journal Article The development of dermatology in the Netherlands Get access J.R. PRAKKEN J.R. PRAKKEN Formerly head of the Department of Dermatology, University of Amsterdam, The Netherlands Requests for reprints to Professor J.R. Prakken, Minervalaan 73 III, Amsterdam‐2, The Netherlands. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 2, 1 August 1974, Pages 225–233, https://doi.org/10.1111/j.1365-2133.1974.tb15870.x Published: 01 August 1974 Article history Accepted: 21 November 1973 Published: 01 August 1974
Defects in coding joint formation in vivo in developing ATM-deficient B and T lymphocytes
Authors: Ching-Yu Huang, Girdhar G. Sharma, Laura M. Walker, Craig H. Bassing, Tej K. Pandita, Barry P. Sleckman
Journal: The Journal of Experimental Medicine (2007)

Ataxia-telangiectasia mutated (ATM)–deficient lymphocytes exhibit defects in coding joint formation during V(D)J recombination in vitro. Similar defects in vivo should affect both T and B cell development, yet the lymphoid phenotypes of ATM deficiency are more pronounced in the T cell compartment. In this regard, ATM-deficient mice exhibit a preferential T lymphopenia and have an increased incidence of nontransformed and transformed T cells with T cell receptor α/δ locus translocations. We demonstrate that there is an increase in the accumulation of unrepaired coding ends during different steps of antigen receptor gene assembly at both the immunoglobulin and T cell receptor loci in developing ATM-deficient B and T lymphocytes. Furthermore, we show that the frequency of ATM-deficient αβ T cells with translocations involving the T cell receptor α/δ locus is directly related to the number of T cell receptor α rearrangements that these cells can make during development. Collectively, these findings demonstrate that ATM deficiency leads to broad defects in coding joint formation in developing B and T lymphocytes in vivo, and they provide a potential molecular explanation as to why the developmental impact of these defects could be more pronounced in the T cell compartment.
Streptomycin in the Treatment of Bacterial Endocarditis
Authors: Norman L. Cressy, William J. Lahey, Paul Kunkel
Journal: New England Journal of Medicine (1948)

EXPERIENCE with streptomycin in the treatment of bacterial endocarditis is as yet limited. Hunter1 discussed 18 cases and suggested that streptomycin is the drug of choice in endocarditis caused by gram-negative bacilli and penicillin-resistant, gram-positive cocci, and in infections that fail to respond to maximal penicillin treatment.The case reports that follow present features of bacteriologic and therapeutic interest. The causative organism in the first case was a gram-negative, anaerobic, non-spore forming bacillus (bacteroides), and in the second, a highly resistant alpha-hemolytic streptococcus.Case 1. J. P., a 46-year-old man, entered the hospital in November, 1946, with a 2-month history . . .
<i>Galleries of the Stelvio–Lake Como</i>
Authors: Jeanette M. Smith
Journal: JAMA (2015)

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 Journals 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
Abstract LB-307: Giα proteins exhibit functional differences in activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells
Authors: Wen-Ming Chu
Journal: Cancer Research (2014)

Abstract Background In a classic model, Giα proteins, Gi1α, Gi2α and G3α, are important for transducing signals from Gi protein-coupled receptors (GPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Giα proteins are also important for activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of Giα proteins in activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether Giα proteins are also engaged in activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of Giα proteins in breast cancer remains to be elucidated. Results We found that Giα deficient MEFs showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Giα1/2/3 knockdown breast cancer cells exhibited a similar defect in this activation and a defect in in vitro growth and invasion. Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1's interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion. Citation Format: Wen-Ming Chu. Giα proteins exhibit functional differences in activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-307. doi:10.1158/1538-7445.AM2014-LB-307
Auer‐rod like inclusions in multiple myeloma
Authors: Abbas Hashim Abdulsalam, Barbara J. Bain
Journal: American Journal of Hematology (2013)

Auer-rod like inclusions in myeloma cells have been described in association with IgG, IgA, IgM and light chain only (kappa) myeloma2. They are generally2, but not invariably3, associated with paraproteins with kappa light chains and are more often associated with IgA myeloma. They do not represent immunoglobulin but rather are of lysosomal origin, being positive for alpha naphthyl acetate esterase, beta glucuronidase and acid phosphatase4. There is an association with adult Fanconi syndrome due to deposition of crystals in renal tubules2. Myeloma cells can also contain crystalline inclusions that do represent immunoglobulin but these differ from Auer-rod like inclusions in that they stain pale pink on Romanowsky stains, rather than being azurophilic.
Alcoholic ketoacidosis: an underdiagnosed condition?
Authors: C J Thompson, D G Johnston, P H Baylis, J Anderson
Journal: BMJ (1986)

The syndrome of alcoholic ketoacidosis has not been reported in Britain, whereas in-the United States it has been estimated to occur once for every four cases of diabetic ketoacidosis.I We describe two patients with alcoholic ketoacidosis who presented to this unit within one month and discuss the pathogenesis and features of the condition. CmlA 41 year old known alcoholic man presented to the casualty department after collapsing in the street.He had been drinking two bottles of whisky daily for three months and for 10 days had eaten little and suffered increasingly severe nausea and vomiting.He had longstanding asthma treated with salbutamol inhaler and prednisolone 10 mg daily.He was confused, icteric, and tachypnoeic with a ketotic odour to his breath.
P3 The national lung cancer awareness campaign: Evidence of a measurable impact in stage shift and eligibility for radical therapy
Authors: EM Hadley
Journal: Thorax (2013)

<h3>Rationale</h3> Lung cancer survival in North East London is consistently lower than expected. The incidence of late presentation with advanced, inoperable disease is significantly higher; our patients are also more likely to present via the emergency room than any other route. In the absence of an evidence based national screening programme for lung cancer in the UK, a National Lung Cancer Awareness Campaign was launched in 2012 for eight weeks with TV, radio and poster advertising. The campaign urged anyone who had been suffering with a cough for three weeks or more to see their general practitioner and ask for a chest X Ray. This study was designed to look at the impact of the national campaign on the local population in North East London. <h3>Method</h3> Every patient diagnosed with lung cancer in the 124 days leading up to the start of the campaign was compared with every patient diagnosed for 124 days from the start of the campaign. <h3>Results</h3> There was an 8% increase in the number of lung cancers diagnosed after the awareness campaign. The biggest increase was in squamous cell carcinoma. Overall, there was no stage shift seen. However the Trust serves two sites each with a specific catchment area. Patients on one site showed a significant stage shift. Stage 1a to 2b, 10.8% pre-campaign, 25% post-campaign (p &lt; 0.006) On the site where the significant stage shift was seen the rate of eligibility for radical therapy rose threefold from 10.5% to 33.3% (P &lt; 0.001). On both sites the rate of treatment with curative intent rose by 3.8% (NS). <h3>Conclusion</h3> The national awareness campaign has had a measurable effect on our lung cancer service. Overall we have seen an 8% increase in cancers diagnosed, but the key finding is that the patients from one site had a significant increase in early stage diagnosis and a threefold increase in eligibility for radical therapy. This is the first real evidence that a national campaign might have a measurable effect on lung cancer mortality.
A CASE OF LIGATION OF THE VERTEBRAL ARTERY TERY FOR AGGRAVATED EPILEPSY.
Authors: EDMUND ANDREWS
Journal: JAMA (1884)

Read to Section of Surgery and Anatomy of the American Medical Association, May, 1884. The proposition to ligate the vertebral artery for epilepsy has not met with great favor among surgeons, and the scanty literature upon the subject leaves its value a matter of uncertainty. I offer the following case, not as decisively proving the usefulness of the operation, but as a contribution toward the collection of facts necessary to the decision of the question. Mr.—, at the age of 17 received a very severe and afflicting mental shock, which was followed by epilepsy. The paroxysms increased in frequency until his mental powers were wrecked. He was in a state of thorough insanity, and from that cause added to the great frequency of the fits, had to be cared for in a state of virtual confinement. Five years later, at the age of twenty-two, he was brought to me in
Inhibition of tumour necrosis factor-? secretion from EpiDerm<sup>TM</sup>tissues by a novel small molecule, UTL-5d
Authors: J. Shaw, C. Liu, R. Martin, B. Chen, R. Holtz, W-H. Huang, A-R. Lee
Journal: British Journal of Dermatology (2007)

UTL-5d [N-(4-chlorophenyl)-3-carboxyamidyl-5-methylisoxazole] is a small-molecule tumour necrosis factor (TNF)-alpha modulator being investigated for its potential in several immune-mediated diseases, including psoriasis.We aimed to determine whether UTL-5d represents a potential antipsoriasis agent.Firstly, a keratinocyte cell-based study was used to study the inhibition of TNF-alpha and gene suppression by UTL-5d in vitro. Secondly, a multilayered human epidermis tissue model, consisting of normal human-derived epidermal keratinocytes, was used to study the dose-dependent reduction of TNF-alpha by UTL-5d as well as the feasibility of using UTL-5d in a lotion formulation.The cell-based study showed that UTL-5d significantly reduced TNF-alpha secretion from keratinocytes (68% reduction at 17 mug mL(-1)) and suppressed JAK3 and MAP3K2 genes by 70% and 40%, respectively. In the human epidermis tissue model, reduction of TNF-alpha by UTL-5d appeared to be dose dependent (8.35-33.4 microg mL(-1)); UTL-5d also reduced cell death induced by ultraviolet (UV) B. Tissues treated by UTL-5d in a preliminary lotion formulation showed significant reduction of TNF-alpha induced by UVB.Our results indicate that UTL-5d may be worthy of further investigation for its potential as a topical agent for psoriasis.
Age-Related Breast Cancer Therapy-Reply
Authors: Sheldon Greenfield
Journal: JAMA (1987)

<h3>In Reply.—</h3> We appreciate Dr Shocket's thoughtful questions. We cannot be sure of the patient or family role in rejecting appropriate management. However, this factor is unlikely to have played an important role in the treatment of these patients for two reasons. First, physicians in these hospitals occasionally indicated that patients had refused treatment. Most of these patients had high levels of comorbidity and were omitted because we were studying physician treatment. Second, the primary treatment for breast cancer is not very aggressive in terms of the toxic reactions and the burden to patients. We did not examine chemotherapy or treatment with extensive radiation. Therefore, we would not expect many patients to refuse this level of treatment. We think it is unlikely that patient refusal had any sizable impact on our conclusions. With respect to the definition of appropriate treatment, Dr Shocket focused on the appropriateness of axillary dissection. The
ME-14 * PRO-MIGRATORY AND -PROLIFERATIVE EFFECTS OF ASTROCYTES ON GBM CELLS
Authors: A. Mega, L. Sleire, D. Hagerstrand, P. O. Enger, M. Nister, A. Ostman
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is among the most lethal types of cancer. The pathological tissue contains different tumor-associated cell types, including astrocytes, which contribute to cancer biology. Our work aims at exploring the potential role(s) of crosstalk between astrocytes and malignant cells in GBM with regard to invasion, growth and drug response of the malignant cells. Studies are performed with the double intention of identifying the molecular details of such pathogenic paracrine cross-talk and to establish high-throughput assays for identification of novel candidate therapeutic agents. In order to look for astrocyte-dependent effects on glioblastoma cells proliferation and migration, we have performed co-culture experiments, including direct co-culture, transwell assays and conditioned medium assays. Interestingly, we identified consistent stimulatory effects of astrocytes on the migration and proliferation of glioblastoma cells. In a direct co-culture system where an initial amount of 1000 glioblastoma cells is seeded with or without astrocytes, glioblastoma cells grow much more in co-culture than monoculture. In a transwell assay some glioblastoma cells clearly increase their migration upon indirect contact with astrocytes (U87, A172, HF66), whereas others are minimally affected by the co-culture. A172 and HF66 increase their migration even more when cultured with astrocytes pre-stimulated with PDGF-BB. Preliminary results also indicate that the astrocyte-dependent stimulation of GBM proliferation is dependent on PDGFR-signaling in astrocytes and/or GBM cells. Additional studies are ongoing where a more in vivo-like assay - invasion of GBM cells into brain slices - is being applied. In this assay the role(s) of host factors is being explored by "priming" of brain slices with growth factors, such as TGF-beta and PDGF-BB, or inhibitors of these pathways. The co-culture- and brain slice-assays will also be used to explore if host cells, such as astrocytes, will modulate sensitivity to temozolomide which is the most commonly used drug for glioblastoma treatment.