tbuckley/cabot-search huggingface dataset:
THE EFFECT OF INTRAVENOUSLY ADMINISTERED 6063, THE CARBONIC ANHYDRASE INHIBITOR, 2-ACETYLAMINO-1,3,4-THIADIAZOLE-5-SULFONAMIDE, ON FLUID AND ELECTROLYTES IN NORMAL SUBJECTS AND PATIENTS WITH CONGESTIVE HEART FAILURE
Authors: Charles K. Friedberg, Mark Halpern, Robert Taymor
Journal: Journal of Clinical Investigation (1952)

Many of the clinical features of congestive heart failure are determined by the abnormal accumulation of water in the extracellular space, an event largely dependent upon the abnormal renal retention of sodium. Although there is a lack of knowledge of the exact mechanism responsible for this abnormality in renal excretion, it is well known that agents that enhance the excretion of sodium are valuable in the treatment of heart failure. The normal kidney plays an important part in preventing the sodium depletion of body fluids and maintaining the normal range of pH of the blood. This is accomplished by the tubular reabsorption of almost all the sodium which is filtered through the glomerulus and the conversion of the alkaline glomerular filtrate into an acid urine (1). The enzyme, carbonic anhydrase, found to be present in the renal cortex as well as other tissues such as gastric mucosa and erythrocytes of mammals (2), is regarded as an important element in the mechanism for the acidification of the urine (3) and the reabsorption of sodium. The inhibition of carbonic anhydrase and the prevention of the formation of an acid urine may serve as a method for reducing the abnormal sodium retention which is a feature of congestive heart failure. Following the observation that sulfanilamide induced acidosis (4) with an alkaline urine (5) and an increased excretion of sodium and potassium (6, 7) and the demonstration that sulfonamide compounds were specific carbonic anhydrase inhibitors (8), Hober suggested that the alkalinization of the urine was due to the inhibition of carbonic anhydrase in the renal tubules (9). Subsequently, Pitts and Alexander showed that sulfanilamide reduced the capacity of the kidney to eliminate acid under maximal stimulation by a
Adverse Ventilatory Strategy Causes Pulmonary-to-Systemic Translocation of Endotoxin
Authors: DAMIAN B. MURPHY, NUALA CREGG, LORRAINE TREMBLAY, DOREEN ENGELBERTS, JOHN G. LAFFEY, ARTHUR S. SLUTSKY, ALEX ROMASCHIN, BRIAN P. KAVANAGH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Accumulating evidence strongly suggests that ventilatory strategy has an important impact on development of lung injury and patient outcome. Adverse ventilatory strategies have been shown to cause release of pulmonary-derived cytokines and may permit bacterial translocation from the lung to the systemic circulation. Because endotoxin is a potent and clinically important stimulant of cytokine-mediated systemic inflammatory responses that can lead to multiorgan failure, we investigated the effects of ventilatory strategy on lung-to-systemic translocation of endotoxin. We studied the effects of protective (tidal volume [VT] 5 ml. kg(-)(1), positive end-expiratory pressure [PEEP] 10 to 12.5 cm H(2)O) versus nonprotective (VT 12 ml. kg(-)(1), PEEP zero) ventilatory strategy on translocation of endotracheally instilled endotoxin. Anesthetized New Zealand White rabbits were subjected to saline lung lavage, and 32 were randomized to one of four groups: PS (protective ventilation + instilled saline); PE (protective ventilation + instilled endotoxin); NS (nonprotective ventilation + instilled saline); NE (nonprotective ventilation + instilled endotoxin), and ventilated for 3 h. Plasma endotoxin levels increased significantly in the NE group, and remained low and unchanged in the other groups. Peak levels of plasma tumor necrosis factor-alpha (TNF-alpha) were higher in NE versus other groups. Pa(O(2)) and mean arterial pressure (Pa) were lowest, and requirement for pressor and bicarbonate support greatest, in the NE group. Finally, plasma endotoxin levels were significantly greater in eventual nonsurvivors than survivors. These data provide convincing evidence for pulmonary translocation of lung-derived endotoxin. This translocation depends on ventilatory strategy, and suggests a pathophysiologic link between ventilatory strategy and outcome.
The Influence of the Airways Resistance and Alveolar Pressure on the Pulmonary Vascular Resistance in Chronic Bronchitis
Authors: P. Harris, N. Segel, I. Green, E. Housley
Journal: Cardiovascular Research (1968)

Journal Article The Influence of the Airways Resistance and Alveolar Pressure on the Pulmonary Vascular Resistance in Chronic Bronchitis Get access P. Harris, P. Harris * Department of Medicine, Queen Elizabeth Hospital, Birmingham * Present address: Institute of Cardiology, 35 Wimpole Street, London, W.1. Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Segel, N. Segel Department of Medicine, Queen Elizabeth Hospital, Birmingham Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Green, I. Green Department of Medicine, Queen Elizabeth Hospital, Birmingham Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Housley E. Housley Department of Medicine, Queen Elizabeth Hospital, Birmingham Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 2, Issue 1, January 1968, Pages 84–92, https://doi.org/10.1093/cvr/2.1.84 Published: 01 January 1968 Article history Received: 20 March 1967 Published: 01 January 1968
Evidence for an influence of mechanical restitution on beat-to-beat variations in haemodynamics during chronic atrial fibrillation in patients
Authors: S Hardman
Journal: Cardiovascular Research (1998)

We tested the hypothesis that beat-to-beat changes in haemodynamics during atrial fibrillation include an effect of each preceding R-R interval through the interval-strength relationship (mechanical restitution).The variation in stroke volume and pulse pressure characteristic of atrial fibrillation is usually ascribed to time dependent ventricular filling.We measured the maximum rate of rise of left ventricular pressure (LVdP/dtmax), and aortic blood velocity and its integral in patients with atrial fibrillation undergoing cardiac catheterisation. The contractile response of isometric human myocardial trabeculae to sequences of atrial fibrillation was also studied, using the recorded ECGs as stimuli. The trabeculae were obtained from the resected right ventricular outflow tracts of patients with Fallot's tetralogy undergoing operative correction.Beat-to-beat variations in contractile function during atrial fibrillation in the patients were recorded as LVdP/dtmax and left ventricular ejection (ascending aortic) velocity integral (proportional to stroke volume). Both these indices correlated well with the response to the same ECG (R wave) sequences in the isometric model measured as the maximum rate of rise of force, dF/dtmax, r = 0.72 to 0.81, p, 0.0001. When short pre-preceding intervals were excluded (minimizing the effect of post-extrasystolic potentiation), these variables showed a positive curvilinear relationship to preceding interval typical of mechanical restitution.Mechanical restitution, which causes beat-to-beat changes in inotropic state, accounts in part for the changes in stroke volume in atrial fibrillation.
Abstract 1153: Nanoparticle delivery of microRNA-107 reduces the tumorigenicity of head and neck squamous carcinoma (HNSCC)
Authors: Longzhu Piao, Manchao Zhang, Tizhi Su, Sanjay Bhave, Hong Li, Theodoros N. Teknos, Quintin Pan
Journal: Cancer Research (2011)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The 5-year survival rate of HNSCC has remained stagnant despite advances in the clinical management of this disease. Understanding the molecular pathways that lead to aggressive HNSCC is crucial to identify new “druggable” targets for anti-cancer drug development. Recently, our laboratory showed that miR-107 is significantly reduced in primary HNSCC tumors and HNSCC cell lines. Ectopic expression of miR-107 in CAL-27 HNSCC cells significantly inhibited cell proliferation, DNA replication, clonogenic survival, and tumor growth in nude mice. Our data demonstrate the potential application of miR-107 as a novel anti-cancer therapeutic for HNSCC. In this study, we determine the efficacy of miR-107 encapsulated nanoparticles (NP-miR-107) in a xenograft model of HNSCC. NP-miR-107 was successfully formulated by ethanol injection method. The particle size of NP-miR-107 was 47.8 ± 3.5 nm and zeta potential was +12.1 mV. NP-miR-107 significantly retarded (57.6% inhibition, p&amp;lt;0.02) tumor growth of CAL27 HNSCC tumors compared to NP-miR-control; tumor volume of 340.6 ± 51.6 mm3 and 804.1 ± 181.6 mm3 for the NP-miR-107 group and the NP-miR-control group, respectively. Moreover, Kaplan-Meir analysis showed a survival advantage for the NP-miR-107 treatment group (p=0.039). Our results demonstrate that our nanoparticles are an effective carrier approach to deliver therapeutic miRs to tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1153. doi:10.1158/1538-7445.AM2011-1153
Preserving fertility in children treated for cancer
Authors: D. M Green
Journal: BMJ (2001)

The survival rate for children and adolescents with cancer has improved dramatically in recent years, 1 2 so that increasing numbers of successfully treated children and adolescents are growing up into adults. One estimate is that they represented 1 in 900 people aged 15–44 in the United States in 2000.3 Among the many concerns of these young people as they grow up is their fertility.

Survivors of childhood and adolescent cancer are subfertile. A large study (the five centre study) of survivors treated between 1945 and 1975 showed an adjusted relative fertility in survivors of 0.85 (95% confidence interval 0.78 to 0.92) compared with that of their siblings.4 The adjusted relative fertility of male survivors (0.76, 0.68 to 0.86) was slightly lower than that of female survivors (0.93, 0.83 to 1.04). The most dramatic declines in relative fertility rates were in male survivors who …
Abstract P2-09-12: Withaferin A-mediated inhibition of breast carcinoma involves concomitant activation of CHOP and Elk1 via ERK/ribosomal S6 kinase (RSK) signaling axis regulating death receptor 5 expression
Authors: D Sharma, A Nagalingam, P Kuppusamy, N Saxena
Journal: Cancer Research (2013)

Abstract Introduction: Despite significant progress towards screening efforts and targeted therapies, breast cancer is still a leading cause of cancer-related mortality among women. Novel therapeutic strategies are clearly needed for effective targeting of breast cancer. Natural products continue to generate interest for identification of potential chemopreventive and therapeutic agents. Withaferin A (WFA) is a bioactive small molecule that has been proposed as a new-generation molecule capable of eliciting growth inhibitory effect on cancer cells. The molecular mechanisms by which WFA mediates inhibition of breast cancer remain elusive. The present study was designed to systematically elucidate the underlying mechanisms by which WFA inhibits growth and metastatic potential of breast cancer cells. Methods: Efficacy of WFA treatment on cell growth was evaluated by using clonogenicity, and anchorage–independent growth. Western blot and immunofluorescence analysis were used to examine activation of ERK/RSK (extracellular signal-regulated kinase/ ribosomal S6 kinase) and downstream signaling axes. Functional importance of ERK/RSK and CHOP (C/EBP homologous protein) in the biologic effects of WFA was examined by using overexpression, phospho-deficient constructs and specific inhibitors. Finally, mouse xenografts, immunohistochemical, RT-PCR and western blot analysis of tumors were used. Results: Analysis of the underlying molecular mechanisms revealed that WFA treatment induced phosphorylation of RSK2 in an ERK-dependent manner. Further, WFA-induced ERK/RSK signaling resulted in concomitant upregulation of CHOP and Elk-1(ETS-like transcription factor 1). By using ERK1/2 siRNA and FMK-MEA inhibitor, we found that ERK/RSK signaling axis is required for WFA-mediated modulation of CHOP and Elk-1. Intriguingly, we discovered that WFA triggers the nuclear translocation of CHOP and Elk1 resulting in transcriptional upregulation of Death Receptor protein (DR5). CHOP and Elk1 overexpression potentiated while phospho-deficient Elk-1 inhibited WFA-induced DR5 expression exhibiting that CHOP/Elk-1 cooperatively regulate DR5 expression. Furthermore, using nontoxic doses of WFA, we showed that WFA treatment effectively inhibited breast tumorigenesis in vivo. Analysis of WFA-treated breast tumors showed increased activation of ERK/RSK axis and DR5 along with higher nuclear accumulation of CHOP and Elk-1. Conclusion: These data provided first in vitro and in vivo evidence of the integral role of a previously unrecognized crosstalk between WFA and ERK/RSK and CHOP/Elk-1 axes in breast tumor growth inhibition. WFA treatment could potentially be a rational therapeutic strategy for breast carcinoma. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-12.
Department of Health issues new tariffs for NHS trusts
Authors: Andrew Cole
Journal: BMJ (2006)

The acting chief executive of the NHS, Ian Carruthers, last week ordered an immediate review of all aspects of the tariffs charged by NHS trusts under the “payment by results” system, after serious miscalculations that left primary care trusts in financial limbo.

Sir Ian also apologised on behalf of the Department of Health for the difficulties the mistakes had caused. The tariffs—a price structure itemising how much provider trusts can charge to primary care and other trusts for particular operations or treatments—have now been recalculated and made available to trusts.

But concern is growing among health managers that the delay in setting the prices could further …
Introduction of vascular smooth muscle cells expressing recombinant genes in vivo.
Authors: G Plautz, E G Nabel, G J Nabel
Journal: Circulation (1991)

Vascular smooth muscle cells contribute to the formation of atherosclerotic plaques by proliferating in response to vascular injury and releasing growth-promoting factors. Because their autocrine and paracrine effects are not fully understood, expression of such growth factor genes in specific cell types in vivo would help to determine their mechanism of action. We describe a method to transfer vascular smooth muscle cells expressing recombinant gene products to localized segments of the arterial wall. Vascular smooth muscle cells from the inbred Yucatan minipig were infected in vitro with an amphotropic, replication-defective retrovirus transducing the gene for Escherichia coli beta-galactosidase. Vascular smooth muscle cells expressing this recombinant gene were implanted, using a catheter, into denuded iliofemoral artery segments of pigs in vivo. These arteries subsequently demonstrated beta-galactosidase activity in cells of the intima and media. This method, which provides for the introduction of genetically modified smooth muscle cells, can be used to define the biological effects of recombinant genes in the vessel wall and potentially to provide alternative treatments of vascular diseases.
THE RIGHT TO PREVENTION OF INFECTIOUS DISEASE
Authors: Abraham Zingher
Journal: JAMA (1927)

<h3>To the Editor:</h3> —I was called in consultation by a physician to see a 3 year old child suffering from diphtheria. The physician himself had delivered the child and had taken care of it since birth. I saw the patient, noted the bull-shaped neck, the diphtheritic membrane appearing at the nostrils, covering the fauces, and making its way down to the larynx, and gave my opinion that it was too late. The child was sent to the Willard Parker Hospital and died the following day. The patient had received two days previously an insufficient dose of antitoxin, but evidently the disease had started at an earlier date than suspected as the hidden and most dangerous form of nasopharyngeal diphtheria—in the posterior nasopharyngeal fossa. A fatal dose of diphtheria toxin can easily be absorbed from this area before the physician may become aware with what he is dealing. I asked the
Interleukin-3 Stimulates Migration and Proliferation of Vascular Smooth Muscle Cells
Authors: Maria Felice Brizzi, Luisa Formato, Patrizia Dentelli, Arturo Rosso, Marzia Pavan, Giovanni Garbarino, Marco Pegoraro, Giovanni Camussi, Luigi Pegoraro
Journal: Circulation (2001)

Background —Cytokines released by activated T lymphocytes are key regulators of chronic inflammatory response, including atherosclerosis. The aim of this study was to investigate the presence of interleukin-3 (IL-3) in lymphocytes infiltrating the atherosclerotic plaque and the effect of this cytokine on primary vascular smooth muscle cells (SMCs). Methods and Results —Twenty atherosclerotic carotid arterial specimens and 5 early atherosclerotic lesions from the internal carotid were manually minced to fragments, and T lymphocytes infiltrating the atherosclerotic plaque were isolated on solid-phase anti-CD3 polystyrene plates. Southern blot analysis demonstrated that in all samples, lymphocytes expressed IL-3 and IL-2 receptor α-chain transcripts, indicating that in this context, the activated T lymphocytes may release IL-3. We further analyzed the expression of the IL-3 receptor and the biological effects exerted by the ligand on vascular SMCs. β-IL-3–transducing subunit was detected both on cultured SMCs and on endothelial cells and SMCs within atheroma. The analysis of the IL-3–induced biological effects demonstrated that it was able to trigger both mitogenic and motogenic signals. Moreover, we demonstrated that the addition of PD98059, a known inhibitor of the MAP–extracellular signaling-regulated/MAP kinase pathway, completely inhibited IL-3–mediated MAP kinase activation and IL-3–induced migration and proliferation. Finally, IL-3 was found to stimulate vascular endothelial growth factor (VEGF) gene transcription. Conclusions —IL-3, expressed by activated T lymphocytes infiltrating early and advanced atherosclerotic plaques, may sustain the atherosclerotic process either directly, by activating SMC migration and proliferation, or indirectly, via VEGF production.
Effect of Hypoglycemia on β-Adrenergic Sensitivity in Normal and Type 1 Diabetic Subjects
Authors: Andreas Fritsche, Michael Stumvoll, Matthias Grüb, Sonja Sieslack, Walter Renn, Reinhold-Michael Schmülling, Hans-Ulrich Häring, John E Gerich
Journal: Diabetes Care (1998)

OBJECTIVE The purpose of this study was to assess the potential role of reduced tissue sensitivity to catecholamines in the pathogenesis of hypoglycemia unawareness in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The effect of a single episode of hypoglycemia on β-adrenergic sensitivity was studied in 10 type 1 diabetic patients with apparently normal awareness of hypoglycemia (age 29 ± 5 years, diabetes duration 13 ± 8 years, HbA1c 7.3 ± 0.9%) and 10 age-matched healthy control subjects. β-adrenergic sensitivity was measured with the isoproterenol test after a hyperinsulinemic euglycemic clamp and after a hyperinsulinemic hypoglycemic clamp. β-adrenergic sensitivity was expressed as the dose of intravenous isoproterenol that increased the heart rate by 25 beats/min (IC25). RESULTS During hypoglycemia, diabetic subjects had an impaired plasma epinephrine response compared with that of the control subjects (16.7 ± 5.0 vs. 40.1 ± 6.8 ng/ml, P = 0.02). In control subjects, the IC25 was lower after hypoglycemia than after euglycemia (0.83 ± 0.22 vs. 1.13 ± 0.21 μg, P = 0.02) indicating an increase in β-adrenergic sensitivity. In diabetic subjects, on the other hand, the IC25 was greater after hypoglycemia than after euglycemia (1.00 ± 0.26 vs. 0.65 ± 0.14 μ, P = 0.04), indicating a decrease in β-adrenergic sensitivity. CONCLUSIONS In normal subjects, a single episode of hypoglycemia increases β-adrenergic sensitivity. In diabetic subjects, in contrast, hypoglycemia reduces β-adrenergic sensitivity. These results provide evidence that in type 1 diabetic patients, some maladaptation of tissue sensitivity to catecholamines contributes to the development of hypoglycemia unawareness. A unifying hypothesis is presented for the pathogenesis of hypoglycemia unawareness in type 1 diabetic patients incorporating the concepts of both a reduced catecholamine response and reduced adrenergic sensitivity.
Influence of preload and afterload on genioglossus muscle length in awake goats.
Authors: M J Brennick, R A Parisi, S J England
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The genioglossus is an upper airway dilator muscle, the length of which is directly related to patency in the oropharyngeal region. We hypothesized that genioglossal length (Lgg) is dynamically influenced by the afterload exerted by negative upper airway pressure during inspiration and by the intrinsic length-tension characteristics of the muscle (preload). Seven awake goats were chronically instrumented with electrodes for EMGgg and sonomicrometry for Lgg. We examined the Lgg-EMGgg relationship during hypercapnia and inspiratory resistive loading (18 cm H2O/L/s). The goats breathed through the upper airway (TC) or airflow was diverted through a tracheostomy (TO). We found that: (1) passive inspiratory lengthening was observed with negative upper airway pressure (UAP) but not when UAP = 0 (TO breathing), (2) Lgg shortening for a given EMGgg was significantly decreased with negative inspiratory UAP, and (3) phasic Lgg shortening per unit EMGgg was greatest when Lgg was near optimal length (Lo). We conclude that genioglossal length is substantially influenced by afterload exerted by negative UAP and that genioglossal active shortening may be limited if the muscle operates at a length significantly greater or less than the optimal length.
Structural and Immunologic Aspects of Vascular and Capsular Basement Membranes.
Authors: Nicholas A. Kefalides
Journal: Annals of Internal Medicine (1969)

s1 May 1969Structural and Immunologic Aspects of Vascular and Capsular Basement Membranes.Nicholas A. Kefalides, M.D., Berta Denduchis, Ph.D.Nicholas A. Kefalides, M.D.Search for more papers by this author, Berta Denduchis, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1088_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPrevious studies demonstrated the cross antigenicity between endothelial and epithelial basement membranes. In the present study we have isolated and characterized chemically and immunologically the antigenic components of basement membranes from the glomerulus, alveolus, and lens capsule. The basement membranes were solubilized by reduction and alkylation and antisera prepared in rabbits. On immunodiffusion two precipitin lines of identity form when antiserum to either reduced and alkylated glomerulus or lens-capsule basement membranes is reacted with both antigens. Reduced and alkylated alveolus basement membrane reacts similarly with both antisera. Upon fractionation of the basement membranes two antigenic components are obtained. One is... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Chicago, Illinois PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1088-1089KeywordsAntigensBasement membraneChemical fractionationRabbits Issue Published: 1 May 1969 PDF DownloadLoading ...