tbuckley/cabot-search huggingface dataset:
Physical factors in the stimulation of calonic peristalsis
Authors: J. D. Hardcastle, C. V. Mann
Journal: Gut (1970)

The effect of colonic distension and changes in intraluminal <i>p</i>H and osmolality have been investigated in patients with well established colostomies. Small volumes of acidic buffer (<i>p</i>H4) and hypertonic saline (4%) were found to be only a very weak peristaltic stimulus. Strong hypertonic solutions (glycerine BP) induced a poorly sustained peristaltic response in the majority of cases. Distension of the inactive colon did not stimulate peristalsis. Distension of a colon previously stimulated to peristaltic activity caused fresh waves of contraction. This study appears to show that by themselves physical factors play an unimportant role in initiating peristaltic activity in the colon.
Skeletal muscle satellite cell transplantation
Authors: P MENASCHE
Journal: Cardiovascular Research (2003)

Cell transplantation is currently gaining a growing interest as a potential new means of improving the prognosis of patients with cardiac failure. The basic assumption is that left ventricular dysfunction is primarily caused by the loss of a critical number of cardiomyocytes and that their replacement by new contractile cells could functionally 'regenerate' postinfarction scars in which these cells are implanted. Primarily for practical reasons, autologous skeletal myoblasts have been the first to undergo clinical trials but other cell types are also considered, particularly bone marrow stem cells which are attractive because of their autologous origin and their purported cardiomyocyte/endothelial transdifferentiation potential in response to cues present in the target organ. However, several key issues still need to be addressed including (1) the optimal type of donor cells, (2) the mechanism by which cell engraftment improves cardiac function, (3) the optimization of cell survival, and (4) the potential benefits of cell transplantation in nonischemic dilated cardiomyopathies. In parallel to the experimental studies designed to address these issues, clinical trials are underway and their results should hopefully allow the assessment of to what extent cellular therapy may improve the outcome of patients with heart failure.
Preventing blindness worldwide
Authors: A R Potter
Journal: BMJ (1994)

pain after the original insult has gone; they can also spread so that pain may be perceived as coming from a much wider area.Increased sensitisation of the dorsal horn may account for hyperpathia and allodynia.These changes could be responsible for the widespread sensitivity of the back and lower limbs to pressure commonly described by patients with chronic back pain.Descending impulses from the brain can also activate the sensitised dorsal horn so that a potential mechanism exists for integrating psychological distress and pain perception."2Patients who are given centrally acting analgesics before operation complain of less severe postoperative pain and wound hyperalgesia.'3The possibility of reducing this central sensitisation has implications for treating back pain.Ultimately the study of any pain must focus on the brain.
Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP
Authors: M Alexander
Journal: Cardiovascular Research (2000)

Objective: Previous studies from our group have shown a deficit in nitric oxide (NO) bioavailability and an excess production of the superoxide anion (O2−) in the stroke prone spontaneously hypertensive rat (SHRSP) compared to the normotensive Wistar Kyoto (WKY) strain. This present study has investigated whether adenoviral-mediated gene transfer of human eNOS or Cu/ZnSOD can alter the NO/O2− balance, thereby improving endothelial function. Methods: A recombinant adenovirus, Ad/Hu/eNOS, containing the human eNOS cDNA fragment was generated by homologous recombination in 293 cells. Ad/Hu/eNOS or Ad/Cu/ZnSOD was delivered into SHRSP carotid arteries in vivo, using a titre of 2×109–2×1010 plaque forming units (pfu)/ml, and the effect on gene expression was observed 24 h later. Results: Western blotting confirmed increased enzyme levels of eNOS and Cu/ZnSOD in the viral-infused vessels. Ex vivo, the pressor response to phenylephrine (PE) in the presence of l-NAME was increased in the eNOS-infused arteries relative to the contralateral controls, indicating restoration of basal NO availability to that observed in untreated control WKY rats. Infusion of the SOD virus produced a statistically insignificant increase in NO bioavailability. Conclusions: Our results support our previous findings obtained using a bovine eNOS recombinant adenovirus, that recombinant adenoviral gene transfer of human eNOS has a significant effect on NO bioavailability. In contrast, AdCu/ZnSOD gene transfer does not elicit an effect in our model. These results indicate that short-term overexpression of a recombinant eNOS, but not Cu/ZnSOD gene, in carotid arteries of the SHRSP is an effective means of locally increasing NO bioavailability to improve endothelial function.
Altered Signaling and Regulatory Mechanisms of Apoptosis in Focal and Segmental Glomerulosclerosis
Authors: WANSHENG WANG, ALEX TZANIDIS, MAJA DIVJAK, NAPIER MAURICE THOMSON, ALICIA NOEMI STEIN-OAKLEY
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The purpose of this study was to investigate signaling and regulatory mechanisms of apoptosis in a model of focal and segmental glomerulosclerosis. Sprague-Dawley rats received two doses of puromycin aminonucleoside (PAN) (day 0 and week 3) and a uninephrectomy (PAN model). Apoptosis was detected with the use of the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling technique. Bax, Bcl-2, Fas , and Fas ligand expression was analyzed by competitive reverse transcription-PCR. Bax, Bcl-2 , and Fas mRNA were localized by in situ hybridization. Renal function was transiently impaired after the first PAN dose. After the second PAN dose, further progressive renal impairment, tubular atrophy, interstitial fibrosis, and glomerulosclerosis were evident. Eighteen percent of PAN samples demonstrated up to 4 apoptotic cells/50 glomeruli, compared with 7% of sham controls (not significant). No consistent significant change in glomerular Bax, Bcl-2, Fas , and Fas ligand mRNA was evident by reverse transcription-PCR, although focal increases in glomerular Bcl-2 mRNA were demonstrated by in situ hybridization. In the tubulointerstitium, apoptosis was increased from weeks 1 to 12 ( P &lt; 0.01 PAN versus sham), correlated to renal function and tubulointerstitial injury ( P &lt; 0.01). Total renal Bax, Fas , and Fas ligand mRNA were upregulated in the PAN model, peaking at week 17 ( P &lt; 0.01 versus sham), whereas Bcl-2 mRNA was not significantly different in PAN versus sham controls. In situ hybridization in the PAN model demonstrated prominent Bax mRNA in dilated tubules and infiltrating leukocytes. Fas mRNA signal was localized to tubular epithelial cells and leukocytes. The results suggest that altered apoptotic signaling and regulatory mechanisms contribute to the tubulointerstitial injury in this model.
Preventing Cervical Cancer Globally by Acting Locally: If Not Now, When?
Authors: Julia C. Gage, Philip E. Castle
Journal: JNCI Journal of the National Cancer Institute (2010)

Invasive cervical cancer remains an important public health problem as a leading cause of cancer-related death in women in many developing countries (1) (http://globocan.iarc.fr/). Despite the promise of a highly efficacious prophylactic human papillomavirus (HPV) vaccine (2–4), HPV vaccination will not prevent approximately 30% of invasive cervical cancer nor does it treat preexisting infections and precancerous lesions, and it requires cold chain delivery and is expensive to administer. Even if vaccines were made available at a greatly reduced cost and widespread vaccination could be rapidly implemented globally (which is not possible in the near-to-mid term), the primary prevention of invasive cervical cancer by prophylactic HPV vaccination would not be realized for another 30 or more years, during which time an estimated 20 million additional cervical cancers will occur in less developed countries (1) (http://globocan.iarc.fr/). Therefore, secondary prevention, that is, screening and treatment of precancerous lesions, will be needed for a long time to come.
THE SUCTORIAL BULB IN "CULEX."
Authors: G. T. Collingwood
Journal: BMJ (1902)

siderable extent to make room for a railway and other build- ings in connection with a route to the gold fields, 25 people, Creoles and others, who had been living here for periods of two to ten years, on examination all gave negative results.As already stated by Daniels, negroes and others after living in appropriate parts of the interior are quite liable to infection, and this was confirmed by the fact of 3 out of 5 pure-blooded negroes who lived in the forest of the Pomeroon river being infected.St. Vincent.-Theconditions and prevalence of the parasite here resemble that in St. Lucia, cases not being found in people living permanently in Kingstown, the chief town of the island, but only in some country villages and districts.In Calliaqua, a village situated on the coast on sandy soil, with swampy ground between it and the sea, scrubby bush and swamps at its sides, and a background of rising hills, 8 out of 30 people, or 26.6 per cent., were found to be infected.
The acid-sensitive potassium channel TASK-1 in rat cardiac muscle
Authors: C PUTZKE, K WEMHONER, F SACHSE, S RINNE, G SCHLICHTHORL, X LI, L JAE, I ECKHARDT, E WISCHMEYER, H WULF
Journal: Cardiovascular Research (2007)

The outward current flowing through the two-pore domain acid-sensitive potassium channel TASK-1 (I(TASK)) and its inhibition via alpha1-adrenergic receptors was studied in rat ventricular cardiomyocytes.Quantitative RT-PCR experiments were carried out with mRNA from rat heart. Patch-clamp recordings were performed in isolated rat cardiomyocytes. TASK-1 and other K+ channels were expressed in Xenopus oocytes to study the pharmacological properties of a new TASK-1 channel blocker, A293.TASK-1 channels were found to be strongly expressed in rat heart. Analysis of the sensitivity of various K+ channels to A293 in Xenopus oocytes showed that at low concentrations A293 was a selective blocker of TASK-1 channels. I(TASK) in rat cardiomyocytes was dissected by application of A293 and by extracellular acidification to pH 6.0; it had an amplitude of approximately 0.30 pA/pF at +30 mV. Application of 200 nM A293 increased action potential duration (APD(50)) by 31+/-3% at a stimulation rate of 4 Hz. The plausibility of the effects of A293 on APD50 was checked with a mathematical action potential model. Application of the alpha1-adrenergic agonist methoxamine inhibited I(TASK) in Xenopus oocytes co-injected with cRNA for TASK-1 and alpha1A-receptors. In cardiomyocytes, methoxamine inhibited an outward current with characteristics similar to I(TASK). This effect was abolished in the presence of the alpha1A-antagonist 5-methyl-urapidil.Our results suggest that in rat cardiomyocytes I(TASK) makes a substantial contribution to the outward current flowing in the plateau range of potentials and that this current component can be inhibited via alpha1A-adrenergic receptors.
Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial
Authors: A Michael Lincoff, Roxana Mehran, Thomas J Povsic, Steven L Zelenkofske, Zhen Huang, Paul W Armstrong, P Gabriel Steg, Christoph Bode, Mauricio G Cohen, Christopher Buller, Peep Laanmets, Marco Valgimigli, Toomas Marandi, Viliam Fridrich, Warren J Cantor, Bela Merkely, Jose Lopez-Sendon, Jan H Cornel, Jaroslaw D Kasprzak, Michael Aschermann, Victor Guetta, Joao Morais, Peter R Sinnaeve, Kurt Huber, Rod Stables, Mary Ann Sellers, Marilyn Borgman, Lauren Glenn, Arnold I Levinson, Renato D Lopes, Vic Hasselblad, Richard C Becker, John H Alexander
Journal: The Lancet (2015)
Development of Neuropathy in Patients With Myeloma Treated With Thalidomide: Patterns of Occurrence and the Role of Electrophysiologic Monitoring
Authors: Linda Mileshkin, Richard Stark, Bruce Day, John F. Seymour, Jerome B. Zeldis, H. Miles Prince
Journal: Journal of Clinical Oncology (2006)

Purpose Peripheral neuropathy frequently limits the duration of treatment with thalidomide for patients with multiple myeloma. We assessed the time course of occurrence, possible predictive factors, and the utility of serial nerve electrophysiological studies (NES) for detecting onset of neuropathy. Patients and Methods Seventy-five patients with relapsed/refractory myeloma were enrolled onto a multicenter trial of dose-escalating thalidomide with or without interferon. Patients underwent clinical assessment plus NES at baseline and every 3 months. Time to development of neuropathy according to clinical or NES criteria was compared. Patient and treatment-related factors were compared as predictors of neuropathy. Results Thirty-nine percent had some NES abnormalities at baseline. Patients received thalidomide at a median dose-intensity of 373 mg/d. Thirty-one of 75 patients (41%) developed neuropathy during thalidomide treatment; 11 patients (15%) discontinued treatment with thalidomide due to neuropathy. The actuarial incidence of neuropathy increased from 38% at 6 months to 73% at 12 months, with 81% of responding patients developing this complication. Serial NES did not reliably predict the imminent development of clinical neuropathy requiring thalidomide cessation, nor were patient age, sex, or prior therapy predictive. Patients who developed neuropathy had a longer duration of thalidomide exposure (median, 268 v 89 days; P = .0001). Cumulative dose or dose-intensity received was not predictive. Conclusion The majority of patients will develop peripheral neuropathy given sufficient length of treatment with thalidomide. To minimize the risk of neurotoxicity, therapy should be limited to less than 6 months. Electrophysiologic monitoring provides no clear benefit versus careful clinical evaluation for the development of clinically significant neuropathy.
A 76-year-old lady with chronic cough and a discharging chest wall sinus
Authors: M. Deshpande, A. Kamath, K. Allinson, D. Peat, W. Parry
Journal: Thorax (2011)

A 76-year-old lady was referred to the respiratory clinic with a 6-month history of a discharging left chest wall sinus. She also had a 6-month history of dry cough, left chest wall pain and breathlessness. There was no history of fever, haemoptysis, weight loss or night sweats. She was a lifelong non-smoker and there was no history of asbestos exposure.

Investigations showed elevated white blood cell count of 14.5×109/l (neutrophil count 11×109/l) and C reactive protein 87 mg/L; renal and liver function tests were normal. Sputum cultures were negative.

She had a laparoscopic Nissen fundoplication 12 years earlier, complicated by perforation of the oesophagus. Subsequently, 6 years later, she developed dyspnoea; a chest x-ray at this time revealed a left-sided pleural-based abnormality. A thoracoscopic biopsy suggested benign pleural thickening/fibrosis. After thoracoscopy, she developed a discharging sinus around the access port site, which was excised.

The patient then relocated to the region and presented with a persistent discharge from the original chest wall sinus. Oral penicillin was …
Distribution of Ions and Water between Tissue Compartments in the Perfused Left Ventricle of the Rat Heart
Authors: ERNEST PAGE, EVA Gross PAGE
Journal: Circulation Research (1968)

Left ventricles from rat hearts were perfused through the coronary blood vessels for periods up to 90 minutes with solution containing radioactively labeled sulfate, sucrose, urea, glycerol, or chloride. Urea and glycerol equilibrate with all of tissue water. By contrast, 35 SO 4 and sucrose- 14 C equilibrate very rapidly with 40% of total water and slowly with an additional 20%; they are excluded from 40% of the tissue water. The two "cellular" compartments (C 2 , which equilibrates slowly with SO 4 and sucrose, and C 3 , from which SO 4 and sucrose are excluded) both lose water when hearts are perfused with a solution made hypertonic with NaCl. Chemical analyses for K, Na, and Cl, and measurements of the rate of equilibration of 36 C1 show that C 2 has low contents of Cl and Na. Experiments in which extracellular NaCl was replaced osmole for osmole by KCl according to the method of Boyle and Conway suggest that the boundaries of C 2 and C 3 may have different ionic permeabilities. These observations indicate that the division of mammalian heart muscle into tissue compartments is more complex than conventionally assumed, a conclusion reached by Bozler for frog heart muscle. They are inconsistent with the usual assumption that cardiac cellular water is homogeneous.
Bilirubin
Authors: Robert Öllinger, Martin Bilban, Anna Erat, Alberto Froio, James McDaid, Shivraj Tyagi, Eva Csizmadia, Aurelio V. Graça-Souza, Angela Liloia, Miguel P. Soares, Leo E. Otterbein, Anny Usheva, Kenichiro Yamashita, Fritz H. Bach
Journal: Circulation (2005)

Bilirubin, a natural product of heme catabolism by heme oxygenases, was considered a toxic waste product until 1987, when its antioxidant potential was recognized. On the basis of observations that oxidative stress is a potent trigger in vascular proliferative responses, that heme oxygenase-1 is antiatherogenic, and that several studies now show that individuals with high-normal or supranormal levels of plasma bilirubin have a lesser incidence of atherosclerosis-related diseases, we hypothesized that bilirubin would have salutary effects on preventing intimal hyperplasia after balloon injury.We found less balloon injury-induced neointima formation in hyperbilirubinemic Gunn rats and in wild-type rats treated with biliverdin, the precursor of bilirubin, than in controls. In vitro, bilirubin and biliverdin inhibited serum-driven smooth muscle cell cycle progression at the G1 phase via inhibition of the mitogen-activated protein kinase signal transduction pathways and inhibition of phosphorylation of the retinoblastoma tumor suppressor protein.Bilirubin and biliverdin might be potential therapeutics in vascular proliferative disorders.
The Evolution of Thrombospondins and Their Ligand-Binding Activities
Authors: A. A. Bentley, J. C. Adams
Journal: Molecular Biology and Evolution (2010)

The extracellular matrix (ECM) is a complex, multiprotein network that has essential roles in tissue integrity and intercellular signaling in the metazoa. Thrombospondins (TSPs) are extracellular, calcium-binding glycoproteins that have biologically important roles in mammals in angiogenesis, vascular biology, connective tissues, immune response, and synaptogenesis. The evolution of these complex functional properties is poorly understood. We report here on the evolution of TSPs and their ligand-binding capacities, from comparative genomics of species representing the major phyla of metazoa and experimental analyses of the oligomerization properties of noncanonical TSPs of basal deuterostomes. Monomeric, dimeric, trimeric, and pentameric TSPs have arisen through separate evolutionary events involving gain, loss, or modification of a coiled-coil domain or distinct domains at the amino-terminus. The relative transience of monomeric forms under evolution implicates a biological importance for multivalency of the C-terminal region of TSPs. Most protostomes have a single TSP gene encoding a pentameric TSP. The pentameric form is also present in deuterostomes, and gene duplications at the origin of deuterostomes and gene loss and further gene duplication events in the vertebrate lineage gave rise to distinct forms and novel domain architectures. Parallel analysis of the major ligands of mammalian TSPs revealed that many binding activities are neofunctions representing either coevolutionary innovations in the deuterostome lineage or neofunctions of ancient molecules such as CD36. Contrasting widely conserved capacities include binding to heparan glycosaminoglycans, fibrillar collagen, or RGD-dependent integrins. These findings identify TSPs as fundamental components of the extracellular interaction systems of metazoa and thus impact understanding of the evolution of ECM networks. The widely conserved activities of TSPs in binding to ECM components or PS2 clade integrins will be relevant to use of TSPs in synthetic extracellular matrices or tissue engineering. In contrast, the neofunctions of vertebrate TSPs likely include interactions suitable for therapeutic targeting without general disruption of ECM.
Therapeutic Targeting of B Cells for Rheumatic Autoimmune Diseases
Authors: Pablo Engel, José A. Gómez-Puerta, Manuel Ramos-Casals, Francisco Lozano, Xavier Bosch
Journal: Pharmacological Reviews (2011)

Autoreactive B cells are characterized by their ability to secrete autoantibodies directed against self-peptides. During the last decade, it has become increasingly apparent that B lymphocytes not only produce autoantibodies but also exert important regulatory roles independent of their function as antibody-producing cells. This is especially relevant in the context of autoimmunity, because autoreactive B cells have been shown to possess the ability to activate pathogenic T cells, to produce pro-inflammatory cytokines, and to promote the formation of tertiary lymphoid tissue in target organs. The production of monoclonal antibodies against B-cell-surface molecules has facilitated the characterization of several distinct B lymphocyte subsets. These cell-surface molecules have not only served as useful cell differentiation markers but have also helped to unravel the important biological functions of these cells. Some of these molecules, all of which are expressed on the cell surface, have proven to be effective therapeutic targets. In both animal models and in clinical assays, the efficient elimination of B lymphocytes has been shown to be useful in the treatment of rheumatoid arthritis and other autoimmune diseases. The treatment of most rheumatic autoimmune diseases relies mainly on the use of cytotoxic immunosuppressants and corticosteroids. Although this has resulted in improved disease survival, patients may nonetheless suffer severe adverse events and, in some cases, their relapse rate remains high. The increasing need for safer and more effective drugs along with burgeoning new insights into the pathogenesis of these disorders has fueled interest in biological agents; clinical trials involving the B-cell depletion agent rituximab have been especially promising. This article reviews the current knowledge of B-cell biology and pathogenesis as well as the modern therapeutic approaches for rheumatic autoimmune diseases focusing in particular on the targeting of B-cell-specific surface molecules and on the blocking of B-cell activation and survival.
Diverse Distribution of Red Cells and Albumin in the Dog Kidney
Authors: LAWRENCE S. LILIENFIELD, JOHN C. ROSE, NIELS A. LASSEN
Journal: Circulation Research (1958)

Cr 31 labeled red cells and I 131 human serum albumin were injected intravenously into 8 mongrel dogs. After 1 hour kidneys were removed and frozen rapidly with dry ice. Sections of outer cortex, inner cortex, outer medulla, inner medulla, outer papilla and inner papilla were removed and analyzed for Cr 51 and I 131 radioactivity. Tissue radioactivity was compared with that of arterial blood and concentrations of labeled red cells and albumin were calculated. No significant difference was found in relative red cell and albumin content between outer and inner cortex. The magnitude of the I 131 albumin content in the cortex is interpreted to indicate a sizeable extnivascular exchangeable albumin pool. The renal papillae were extraordinarily deficient in red cells, but contained per 100 Gm., albumin equivalent to that of 39 ml. of plasma.