tbuckley/cabot-search huggingface dataset:
Dynamic regulation of MEK/Erks and Akt/GSK-3? in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism
Authors: H BABA, J STYPMANN, F GRABELLUS, P KIRCHHOF, A SOKOLL, M SCHAFERS, A TAKEDA, M WILHELM, H SCHELD, N TAKEDA
Journal: Cardiovascular Research (2003)

Objective: Left ventricular assist devices (LVAD) are used to 'bridge' patients with end-stage heart failure to transplantation. After long-term LVAD support, ventricular function may partially recover, a process called 'reverse remodeling'. As several kinase-mediated signal transduction pathways have been implicated in the development of cardiac hypertrophy and failure, we examined the activities of the Erks, MEKs, Akt, GSK-3β, p70S6K, JNKs and p38 under LVAD support as well as during single myocyte strain and whole heart stretch. Methods: Western blotting and immunohistochemistry were performed using phospho-specific antibodies in matched samples from ten patients with end-stage heart failure before and after LVAD. Cyclic strain was performed in rat neonatal cardiac myocytes, and tensile stretch applied to Langendorff-perfused mouse hearts via a left ventricular balloon. Results: The activity of Erks and Akt in failing hearts dramatically decreased after LVAD support, while that of GSK-3β increased. There was an endo/epicardial gradient for Erk activity which persisted after LVAD despite the reduction of total Erk activity. TUNEL-positivity and myocyte size decreased after LVAD, but independently of changes in kinase activity. In cardiomyocytes and Langendorff-perfused mouse hearts both strain/stretch and its relief regulated the activities of Erks, Akt, and GSK-3β. Conclusion: Erks and Akt/GSK-3β are highly responsive to myocyte stretch in vitro and in vivo, and may be sensitive molecular parameters of 'reverse remodeling' under LVAD support.
Effect of Personality on Alveolar Ventilation in Patients with Chronic Airways Obstruction
Authors: T. J. H. Clark, G. M. Cochrane
Journal: BMJ (1970)

A study has been made of the personality of 44 patients with chronic airways obstruction (using the Eysenck Personality Inventory), this being related to the difference between their observed Pvco(2) and that predicted from their F.E.V.(1). This was designed to test the hypothesis that those patients with a lower Pvco(2) than predicted were the more extravert.The results showed a significant correlation between extraversion and the departure of Pvco(2) from predicted Those patients having a lower Pvco(2) than predicted were more extravert than those with a Pvco(2) higher than predicted. There was no correlation between neuroticism and the Pvco(2).These results support the hypothesis that the personality of a patient may play an important part in determining the alveolar ventilation found in patients with chronic airways obstruction. Patients known as "pink puffers" could more appropriately be named "pugnacious pink puffers."
John Harwood Keen
Authors: R. J. P. R. D. H. Boyd
Journal: BMJ (2013)

After posts across the country and national service in Hong Kong, John Harwood Keen was appointed as consultant paediatrician at Booth Hall Children’s Hospital and North Manchester General Hospital, and honorary lecturer in paediatrics at the University of Manchester in 1968. Despite an onerous workload in general paediatrics and neonatology, and having to …
ST-segment elevation in the electrocardiogram: a sign of myocardial ischemia
Authors: A Kléber
Journal: Cardiovascular Research (2000)

In 1972 Kjekshus et al. published the seminal article 'Distribution of myocardial injury and its relations to epicardial ST-segment changes after coronary occlusion in the dog' in Cardiovascular Research. In this article it was shown that the ST-segment elevation occurring early after occlusion of the left descending coronary artery was closely related to the depletion of the necrotic cells from creatine kinase and to flow reduction at a later stage (24 h). This correlation was especially prominent if the infarction was transmural. Starting from these phenomenological relationships, this article briefly describes and summarizes the experimental research which was carried out in other laboratories after the publication of Kjekshus et al. Special emphasis is laid on the discussion of the main basic mechanisms which underly the clinically observed ST-segment elevation and its evolution after the acute stage of ischemia, i.e. the changes in the transmembrane action potential and the alteration in electrical cell-to-cell coupling.
Pulmonary Coccidioidomycosis with Peritoneal Involvement Mimicking Lung Cancer with Peritoneal Carcinomatosis
Authors: Chi Ryang Chung, Yong Chul Lee, Yang Keun Rhee, Myoung Ja Chung, Yun Kyung Hong, Eui Yong Kweon, Seoung Ju Park
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Phase II Study of G3139, a Bcl-2 Antisense Oligonucleotide, in Combination With Dexamethasone and Thalidomide in Relapsed Multiple Myeloma Patients
Authors: Ashraf Z. Badros, Olga Goloubeva, Aaron P. Rapoport, Bashi Ratterree, Natalie Gahres, Barry Meisenberg, Naoko Takebe, Meyer Heyman, James Zwiebel, Howard Streicher, Christopher D. Gocke, Dragana Tomic, Jodi A. Flaws, Bin Zhang, Robert G. Fenton
Journal: Journal of Clinical Oncology (2005)

Bcl-2 regulates the mitochondrial apoptosis pathway that promotes chemotherapy resistance. Bcl-2 antisense oligonucleotide, G3139, targets Bcl-2 mRNA.G3139 was administered (3 to 7 mg/kg/d for 7 days) by continuous intravenous infusion. On day 4, patients started thalidomide (100 to 400 mg as tolerated) and dexamethasone (40 mg daily for 4 days) on 21-day cycles for three cycles. Stable and responding patients continued on 35-day cycles for 2 years.Thirty-three patients (median age, 60 years; range, 28 to 76 years) received 220 cycles. Patients received a median of three prior regimens including thalidomide (n = 15) and stem-cell transplantation (n = 31). The regimen was well tolerated; the median number of cycles per patient was eight (range, one to 16+ cycles). Toxicities included reversible increase in creatinine, thrombocytopenia, neutropenia, fatigue, anorexia, constipation, fever, neuropathy, edema, electrolyte disturbances, and hyperglycemia. Fifty-five percent of patients had objective responses, including two complete responses (CRs), four near CRs (positive immunofixation), and 12 partial responses; six patients had minimal responses (MRs). Of patients who received prior thalidomide, seven had objective responses, and three had MRs. The median duration of response was 13 months, and estimated progression-free and overall survival times were 12 and 17.4 months, respectively. Responding patients had significant increase in polyclonal immunoglobulin M (P = .005), indicating innate immune system activation. Western blot analysis of Bcl-2 protein isolated from myeloma cells before and after G3139 demonstrated a decrease of Bcl-2 levels in three of seven patients compared with six of nine patients using reverse transcriptase polymerase chain reaction.G3139, dexamethasone, and thalidomide are well tolerated and result in encouraging clinical responses in relapsed multiple myeloma patients.
Carcinoembryonic antigen and related antigens expressed on keratinocytes in inflammatory dermatoses
Authors: K. EGAWA, Y. HONDA, M. KUROKI, Y. INABA, T. ONO
Journal: British Journal of Dermatology (1996)

Carcinoembryonic antigen (CEA) is recognized as being important not only as a tumour marker, but also as a cell adhesion molecule in the metastasis of malignant tumour cells, and in the development of inflammatory disorders in some organs. However, the role played by this antigen in inflammatory dermatoses has not been studied previously. To investigate the expression of CEA in inflamed skin, we performed immunohistochemical studies to detect the antigen in both frozen and formalin-fixed, paraffin-embedded biopsy specimens of inflammatory dermatoses, using five different monoclonal antibodies and one polyclonal antibody against human CEA or CEA-related molecules. CEA and CEA-related antigens were expressed by epidermal keratinocytes and by some infiltrating inflammatory cells in inflamed skin. The expression was observed primarily in the upper part of the malpighian layers of the epidermis. On the basis of the distribution of this expression, we suggest an additional role for CEA-related molecules, differing from their roles as tumour markers and adhesion molecules, namely that these molecules may be associated with the state of differentiation of epidermal keratinocytes. Unexpected expression of CEA-related antigens was seen on normal follicular keratinocytes. Thus, it is conceivable that CEA-related antigen may also play a role in the biology of hair follicles.
Authors' Reply: Don't Let the Hypothesis Slip
Authors: Ben A Lopman, Geoff P Garnett, Simon Gregson, Simon Gregson, Peter R Mason
Journal: PLoS Medicine (2005)

I previously criticised the effective "statute of limitations" in several leading general medical journals "whereby authors of papers are immune to disclosure of methodological weaknesses once some arbitrary (short) period has elapsed" [2].Such a time limit discourages post-publication peer review, with potential correspondents deterred by the short and unambiguous deadline.I suggested that journals with such a policy should reconsider.The word limit on that article precluded additional adverse comments on journals' word limits for letters, although they were presented in Table 2 of that article [2].Subsequently, three of the six journals did revise their instructions [3-5], but each imposed tougher restrictions on letters, reducing either the maximum time limit, the maximum length, or both.The strictest current requirements are a two-week limit by The Lancet and a 175-word limit by the New England Journal of Medicine.Editors are seemingly falling over themselves to speed up and shorten letters, but this behaviour is inappropriate for a scientifi c journal.The key characteristic of science is not its infallibility, a quality it clearly does not and cannot have, but its self-correcting ability.The decision by medical editors to stifl e debate is misguided [2,6].A time limit, especially a very short one, signals that speed is more important than content, that convenience takes precedence over science.While it is reasonable to encourage early comments, there should be no time limit on comments aimed at clarifying or criticising study methodology.Likewise, it will often be impossible to explain the subtleties of methodological problems in 400 words, and impossible in only 175.Additional restrictions on the number of authors and references are also questionable.I am disappointed that PLoS Medicine has imposed a time limit of four weeks on correspondence.As explained above, I believe that such a limit is mistaken.
Diaphragm paralysis after nephrectomy
Authors: A Chetta
Journal: Thorax (2006)

We read with interest the case report by Moore et al 1 on the diaphragm weakness of two patients after anatomically distant surgery.

We are currently following a patient who had bilateral paralysis of the diaphragm after a nephrectomy for renal cancer. The patient, a 60 year old male non-smoker without any concomitant cardiac or lung disease, underwent surgery in August 2004 and immediately after the operation he complained of orthopnoea. Chest radiographs showed the elevation of both hemidiaphragms, which was not present preoperatively, along …
Augmentation of late sodium current unmasks the proarrhythmic effects of amiodarone
Authors: L. Wu, S. Rajamani, J. C. Shryock, H. Li, J. Ruskin, C. Antzelevitch, L. Belardinelli
Journal: Cardiovascular Research (2007)

AimClinical use of amiodarone is associated with occasional development of torsade de pointes (TdP). However, preclinical models have failed to demonstrate the proarrhythmic potential of amiodarone. The objective of this study was to reveal and explain the pro- and anti-arrhythmic effects of acute exposure to amiodarone in an animal model.
Therapeutic Targeting of Anaplastic Lymphoma Kinase in Lung Cancer: A Paradigm for Precision Cancer Medicine
Authors: Ryohei Katayama, Christine M. Lovly, Alice T. Shaw
Journal: Clinical Cancer Research (2015)

The anaplastic lymphoma kinase (ALK) receptor tyrosine kinase was initially discovered as a component of the fusion protein nucleophosmin (NPM)-ALK in anaplastic large-cell lymphoma (ALCL). Genomic alterations in ALK, including rearrangements, point mutations, and genomic amplification, have now been identified in several malignancies, including lymphoma, non-small cell lung cancer (NSCLC), neuroblastoma, inflammatory myofibroblastic tumor, and others. Importantly, ALK serves as a validated therapeutic target in these diseases. Several ALK tyrosine kinase inhibitors (TKI), including crizotinib, ceritinib, and alectinib, have been developed, and some of them have already been approved for clinical use. These ALK inhibitors have all shown remarkable clinical outcomes in ALK-rearranged NSCLC. Unfortunately, as is the case for other kinase inhibitors in clinical use, sensitive tumors inevitably relapse due to acquired resistance. This review focuses on the discovery, function, and therapeutic targeting of ALK, with a particular focus on ALK-rearranged NSCLC.
Flow-mediated dilatation of the basilar artery in vivo.
Authors: K Fujii, D D Heistad, F M Faraci
Journal: Circulation Research (1991)

Flow-mediated dilatation has been described mainly in peripheral conduit arteries. The goal of this study was to examine mechanisms and functional implications of flow-mediated dilatation in large cerebral arteries in vivo. Vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in 45 anesthetized rats. Mean blood flow velocity through the basilar artery increased by 94 +/- 8% during unilateral common carotid artery occlusion and 203 +/- 13% during bilateral occlusion. Diameter of the basilar artery increased by 10 +/- 1% during unilateral common carotid artery occlusion and 29 +/- 2% during bilateral occlusion from control diameter of 275 +/- 8 microns. Vasodilatation appeared with a delay of 13 +/- 1 seconds after the onset of the increase in flow velocity. With systemic arterial pressure maintained at baseline levels, pressure in the basilar artery (servonull) decreased initially during carotid occlusion, and during dilatation of the basilar artery, pressure was restored partially toward normal. Indomethacin (10 mg/kg i.v.), topical application of tetrodotoxin (10(-6) M), NG-monomethyl L-arginine (5 x 10(-6) M), tetraethylammonium chloride (10(-2) M), glibenclamide (10(-5) M), SKF 525A (3 x 10(-5) M), and ouabain (10(-5) M) had no effect on flow-mediated dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
Behavioral Symptoms in Patients With Breast Cancer and Survivors
Authors: Julienne E. Bower
Journal: Journal of Clinical Oncology (2008)

Behavioral symptoms are a common adverse effect of breast cancer diagnosis and treatment and include disturbances in energy, sleep, mood, and cognition. These symptoms cause serious disruption in patients' quality of life and may persist for years after treatment. Patients need accurate information about the occurrence of these adverse effects as well as assistance with symptom management. This review considers four of the most common behavioral sequelae of breast cancer, namely fatigue, sleep disturbance, depression, and cognitive impairment. Research on the prevalence, mechanisms, and treatment of each symptom is described, concluding with recommendations for future studies.
Expression of CD4 on human peripheral blood neutrophils
Authors: Priscilla Biswas, Barbara Mantelli, Antonio Sica, Mauro Malnati, Carla Panzeri, Alessandra Saccani, Hamid Hasson, Andrea Vecchi, Abby Saniabadi, Paolo Lusso, Adriano Lazzarin, Alberto Beretta
Journal: Blood (2003)
Reassessment of Antithyroid Drug Therapy of Graves' Disease
Authors: U Feldt-Rasmussen, D Glinoer, J Orgiazzi
Journal: Annual Review of Medicine (1993)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Interleukin-1 modulates myocardial contraction via dexamethasone sensitive production of nitric oxide
Authors: H. G Evans, M. J Lewis, A. M Shah
Journal: Cardiovascular Research (1993)

Journal Article Interleukin-1β modulates myocardial contraction via dexamethasone sensitive production of nitric oxide Get access Huw G Evans, Huw G Evans Cardiovascular Sciences Research Group, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom—Department of Pharmacology and Therapeutics: H G Evans, M J Lewis; Department of Cardiology: A M Shah. Correspondence to Dr Shah. Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm J Lewis, Malcolm J Lewis Cardiovascular Sciences Research Group, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom—Department of Pharmacology and Therapeutics: H G Evans, M J Lewis; Department of Cardiology: A M Shah. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ajay M Shah Ajay M Shah Cardiovascular Sciences Research Group, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom—Department of Pharmacology and Therapeutics: H G Evans, M J Lewis; Department of Cardiology: A M Shah. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 8, August 1993, Pages 1486–1490, https://doi.org/10.1093/cvr/27.8.1486 Published: 01 August 1993 Article history Received: 17 December 1992 Accepted: 30 March 1993 Published: 01 August 1993
Letter to the editor: Hypoplastic anemia in a hemophiliac first infused with a solvent/detergent treated factor VIII concentrate: The role of human B19 parvovirus
Authors: M. Morfini, G. Longo, P. Rossi Ferrini, A. Azzi, C. Zakrewska, S. Ciappi, P. Kolumban
Journal: American Journal of Hematology (1992)
Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K <sup>+</sup> Current ( <b> <i>I</i> </b> <sub>K,ACh</sub> ) in Chronic Human Atrial Fibrillation
Authors: D. Dobrev, E. Graf, E. Wettwer, H.M. Himmel, O. Hála, C. Doerfel, T. Christ, S. Schüler, U. Ravens
Journal: Circulation (2001)

Background Clinical and experimental evidence suggest that the parasympathetic nervous system is involved in the pathogenesis of atrial fibrillation (AF). However, it is unclear whether changes in G-protein-coupled inward rectifying K + current ( I K,ACh ) contribute to chronic AF. Methods and Results In the present study, we used electrophysiological recordings and competitive reverse-transcription polymerase chain reaction to study changes in I K,ACh and the level of the I K,ACh GIRK4 subunit in isolated human atrial myocytes and the atrial tissue of 39 patients with sinus rhythm and 24 patients with chronic AF. The density of I K,ACh was ≈50% smaller in myocytes from patients with AF compared with those in sinus rhythm, and this was accompanied by decreased levels of GIRK4 mRNA. The current density of the inward rectifying K + current ( I K1 ) was 2-fold larger during AF than in sinus rhythm, in correspondence with an increase in Kir2.1 mRNA. The larger I K1 in AF is consistent with more negative membrane potentials in right atrial trabeculae from AF patients. Moreover, action potential duration was reduced in AF, and the action potential shortening produced by muscarinic receptor stimulation was attenuated, indicating that the changes of I K1 and I K,ACh were functionally relevant. Conclusions Chronic human AF induces transcriptionally mediated upregulation of I K1 but downregulation of I K,ACh and attenuates the muscarinic receptor–mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I K,ACh to counteract the shortening of the atrial effective refractory period due to electrical remodeling.
Role of small calibre chest tube drainage for iatrogenic pneumothorax.
Authors: M Laub, N Milman, D Muller, E Struve-Christensen
Journal: Thorax (1990)

A 2 mm Teflon catheter was used as a chest tube in 28 patients with iatrogenic pneumothorax. Frequent aspirations through the catheter were performed in 16 of the patients. In the remaining 12 patients the catheter was connected to a one way flutter valve. The treatment was successful in 27 of the 28 patients--one patient required a large calibre chest tube. The mean drainage time was 48 hours. The small catheter technique is superior to the use of a large intercostal drain as it is much less traumatic and troublesome. The small calibre chest tube with a one way valve is recommended as a safe and easy technique.
Comparative Analysis of Amino Acid Usage and Protein Length Distribution Between Alternatively and Non-alternatively Spliced Genes Across Six Eukaryotic Genomes
Authors: Y. Zhuang
Journal: Molecular Biology and Evolution (2003)

Alternative splicing has been discovered in nearly all metazoan organisms as a mechanism to increase the diversity of gene products. However, the origin and evolution of alternatively spliced genes are still poorly understood. To understand the mechanisms for the evolution of alternatively spliced genes, it may be important to study the differences between alternatively and non-alternatively spliced genes. The aim of this research was to compare amino acid usage and protein length distribution between alternatively and non-alternatively spliced genes across six nearly complete eukaryotic genomes, including those of human (Homo sapiens), mouse (Mus musculus), rat (Rattus norvegicus), fruit fly (Drosophila melanogaster), Caenorhabditis elegans, and bovine (Bos taurus). Our results have suggested the following: (1) across the six species, alternatively and non-alternatively spliced genes have very similar tendency for amino acids usage for not only the overall scale but also those highly expressed genes, with all of the highly expressed genes having preferred amino acids including A, E, G, K, L, P, S, V, R, T, and D. (2) For not only the overall genes but also those highly expressed ones, the average length of the protein products of alternatively spliced genes is significantly greater than that of non-alternatively spliced ones. In contrast, distributions of protein lengths for the two groups of genes are very similar among all six species. Based on these results, we propose that alternatively spliced genes may have originated from non-alternatively spliced ones through events such as DNA mutations or gene fusion.
Citius and longius (faster and longer) with no α-actinin-3 in skeletal muscles?
Authors: Alejandro Lucia, Jesús Oliván, Félix Gómez-Gallego, Catalina Santiago, Marta Montil, Carl Foster
Journal: British Journal of Sports Medicine (2007)

The muscle protein α-actinin-3 (ACTN3) is normally thought to be expressed in type II muscle fibres and to be necessary for high-power, high-velocity muscle contractions, such as those typically seen in speed/power athletes. The authors report the case of a Spanish elite long jumper (two times Olympian, personal best of 8.26 m) whose genotype for the ACTN3 gene is 577XX (ACTN3 deficient). These data suggest that there might be notable exceptions to the concept that ACTN3 is the “gene for speed”.