tbuckley/cabot-search huggingface dataset:
The effect of octapressin on renal and intrarenal blood flow in cirrhosis of the liver
Authors: M. C. Kew, R. R. Varma, D. J. Sampson, S. Sherlock
Journal: Gut (1972)

The effect of octapressin (2-phenylalanine-8-lysine vasopressin) on renal and intrarenal blood flow was studied in 11 normotensive cirrhotic patients with abnormal renal perfusion. Renal haemodynamic changes were assessed with the <sup>133</sup>Xenon washout technique. Of the six patients given suppressor doses of octapressin intravenously renal blood flow improved in one only. A further three patients responded to the drug in a dose which increased the mean arterial pressure by 5 or more mm Hg. The increase in mean renal blood flow was accompanied by an improvement in renal cortical perfusion. In two patients renal blood flow decreased after the administration of octapressin. These findings, in conjunction with previous reports, suggest that octapressin will only consistently improve renal perfusion in cirrhotic subjects who are hypotensive and in whom the mean arterial blood pressure is raised by the drug, but do not exclude the possibility that octapressin may have a direct renal circulatory effect in some patients.
Galectin 1 is involved in vascular smooth muscle cell proliferation
Authors: E Moiseeva
Journal: Cardiovascular Research (2000)

Objective: Smooth muscle cell (SMC) migration and proliferation are the key steps in the development of atherosclerosis and restenosis. Matricellular proteins have been implicated in cell adhesion, migration and proliferation. Here we investigated the role of the matricellular protein galectin-1 (Gal-1), a β-galactoside-binding lectin, in SMC proliferation in atheroma and DNA synthesis in cell culture. Methods: Protein expression was visualised by tissue section immunostaining. RNA expression was analysed using Northern blot analysis. DNA synthesis of human vascular SMCs was determined by 3H-thymidine incorporation. Recombinant glutathione S-transferase–galectin-1 fusion protein (Gal FP) binding to extracellular matrix (ECM) proteins was measured by ELISA. Gal-1 binding to cells and ECM was estimated using 125I-labelled Gal FP. Results: Prominent Gal-1 staining coincided with SMC proliferation in human coronary endarterectomy samples in organoid culture. In cell culture, Gal-1 mRNA was upregulated in growing SMCs. Gal FP increased serum-induced DNA synthesis of human SMCs on plastic or endogenous ECM, but not of a rat PAC1 SM cell line. Also, Gal FP slightly increased SMC adhesion to ECM. SMCs exhibited a complex pattern of receptor-ligand interactions with Gal FP. The Gal-1 binding to SMCs was much stronger than to ECM, produced by these SMCs. We identified new ECM proteins: thrombospondin, vitronectin and osteopontin, which bound to Gal FP in a dose- and β-galactoside-dependent manner in ELISA. Conclusions: Gal-1 binding to SMCs was stronger than to ECM, although ECM of atherosclerotic blood vessels contained additional ECM proteins which bound to Gal-1. Gal-1 was upregulated during SMC growth and Gal FP enhanced serum-induced DNA synthesis in SMCs. Overall, Gal-1 upregulation is likely to provide a reinforcement of serum-induced events during vascular injury.
The design of orally bioavailable 2, 5‐diketopiperazine oxytocin antagonists: from concept to clinical candidate for premature labor
Authors: Alan D. Borthwick, John Liddle
Journal: Medicinal Research Reviews (2009)

A short, efficient and highly stereoselective synthesis has been developed for a series of 6-indanyl-3-alkyl-7-aryl/heterocyclic-(3R, 6R, 7R)-2, 5-diketopiperazine amides that are potent and selective oxytocin (OT) antagonists. Property-based design using an estimate of human oral absorption enabled focus to be directed to those templates with the greatest chance of delivering high bioavailability in humans. This led to the 2', 4'-difluorophenyl dimethylamide 40, a highly potent (pK(i) =9.2) and selective OT antagonist (>1,000-fold selectivity vs. the human vasopressin receptors V1a, V2, and V1b) with good oral bioavailability (>50%) in the rat and dog. Increased solubility and an improved Cyp450 profile was achieved with a range of 2'-substituted 7-(1',3'-oxazol-4'-yl)-(3R,6R,7R)-2,5-diketopiperazine amides and branching at the α-carbon of the 3-butyl group led to a superior rat pharmacokinetic profile that resulted in the discovery of the 2'-methyl-1',3'-oxazol-4'-yl morpholine amide derivative 74 GSK221149A (Retosiban), which had the best oral exposure and bioavailability in the rat. Retosiban has sub-nanomolar affinity (K(i) =0.65 nM) for the oxytocin receptor with >1400-fold selectivity over the closely related vasopressin receptors. It has good solubility, low protein binding and has a good Cyp450 profile with no significant inhibition IC(50) >100 µM. Retosiban is >15-fold more potent at the human oxytocin receptor than atosiban (a marketed i.v, peptide OT antagonist) and it has been shown to be an effective tocolytic by i.v. and by oral administration in rats, and was selected for progression as a potential clinical candidate for preterm labor.
P76 Investigating women's experiences of asthma care in pregnacy: a qualitative study
Authors: C Chamberlain, G R Williamson, B Knight, M Daley, DM Halpin
Journal: Thorax (2013)

<h3>Introduction and objectives</h3> Most asthmatic women have normal pregnancies and complications are infrequent when their asthma is controlled (BTS/SIGN 2012). Symptom control and medical treatment concern them, as does the impact of their illness and treatment on their unborn baby (Lim et al 2012). Few qualitative studies illustrate recently delivered asthmatic mothers’ feelings about their care, support and medication during their pregnancy. The aim of the study was to investigate in a qualitative study the thoughts and feelings of women’s experiences of asthma in pregnancy. <h3>Methods</h3> NHS IRAS ethical approval and trust research governance were obtained; women gave written informed consent subject to the usual ethical guarantees. Twenty-two women with asthma and a pregnancy within two years were invited to participate. Seven women were interviewed when data saturation was achieved. Data collection took place between March 2012 and September 2012. Interviews were transcribed and analysed using a phenomenological ‘Framework’ Method involving familiarisation; identifying a thematic framework; indexing; charting; mapping; interpretation. Data were independently analysed by two researchers and consensus reached concerning themes. <h3>Results</h3> Asthma and pregnancy Self-management including fears; lack of recognition of symptoms; poor knowledge of inhaled therapy Risk factors Anxieties including drugs, procedures, risks versus benefits General understanding of asthma Concealing symptoms <h3>Pregnancy and post-natal experiences</h3> Impact of exacerbations on baby; breastfeeding benefits; changes to asthma, post-natal experience <h3>Health professionals’</h3> Lack of regular contact; midwife support; interaction with healthcare professionals, education <h3>Conclusions</h3> These findings are globally relevant because maternal asthma is so prevalent. They illustrate participants’ experiences of their asthma care and their views on its improvement. Similar to the international literature (Lim et al 2012), pregnant asthmatic women have concerns about their care and treatment, which might be alleviated by outreach, joint working between respiratory nurse specialists, midwives and GP practice nurses. <h3>References</h3> British Thoracic Society (2012). British Guideline on the Management of Asthma. Available on-line at http://www.brit-thoracic.org.uk/Portals/0/Guidelines/AsthmaGuidelines/sign101%20Jan%202012.pdf Lim AS, Stewart K, Abramson MJ, Ryan K, George J (2012) Asthma during Pregnancy: The Experiences, Concerns and Views of Pregnant Women with Asthma. <i>J Asthma</i>. 49(5):474–9.
Human Experimentation by Industry: The Case of "Enzyme" Detergents
Authors: LAWARENCE M. LICHTENSTEIN
Journal: Annals of Internal Medicine (1971)

Editorial Notes1 December 1971Human Experimentation by Industry: The Case of "Enzyme" DetergentsLAWARENCE M. LICHTENSTEIN, M.D.LAWARENCE M. LICHTENSTEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-6-964 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwo recent reports inScienceare concerned with the toxicity of the "enzyme" additives used in a number of household detergent preparations (1, 2). These so-called "enzymes" are crude extracts derived from cultures ofBacillus subtilis; their exact composition is not defined, but clearly they contain many materials other than enzymes, and their toxicity and allergenicity persist after treatments that destroy enzymatic activity. One of the papers, by Professor René Dubos at Rockefeller University, reported that the enzyme additives were capable of causing both hemolysis and hemagglutination of sheep erythrocytes: in addition, several preparations had antibacterial activity against staphylococci, enterococci,...References1. DUBOS R: Toxic factors in enzymes used in laundry products. Science 173:259-260, 1971 CrossrefMedlineGoogle Scholar2. GOLDRINGRATNERGREENBURG IIL: Pulmonary hemorrhage in hamsters after exposure to proteolytic enzymes of Bacillus subtilis. Science 170:73-74, 1970 CrossrefMedlineGoogle Scholar3. FLINDT M: Pulmonary disease due to inhalation of derivatives of Bacillus subtilis containing proteolytic enzyme. Lancet 1:1177-1181, 1969 CrossrefMedlineGoogle Scholar4. NEWHOUSETAGGPOCOCK MBS: Epidemiological study of workers producing enzyme washing powders. Lancet 1:689-693, 1970 CrossrefMedlineGoogle Scholar5. FRANZMCMURRAINBERNSTEIN TKI: Reaginic allergy in workers exposed to B. subtilis enzyme (abstract). J Allergy 45:100, 1970 Google Scholar6. BELINFALSELHOBORN LEJ: Enzyme sensitization in consumers of enzyme-containing washing powders. Lancet 2: 1153-1157, 1970 MedlineGoogle Scholar7. BERNSTEIN I: Preliminary investigation of sensitization phenomena in populations not exposed to high concentrations of enzyme dust (abstract). J Allergy 47:97, 1971 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Johns Hopkins University, School of Medicine Baltimore, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByBiological effects of proteolytic enzyme detergents. 1 December 1971Volume 75, Issue 6Page: 964-965KeywordsAllergensBacillusEnzymesHemagglutinationToxicity Issue Published: 1 December 1971 PDF DownloadLoading ...
Independent midwifery care versus NHS care in the UK
Authors: A. Shorten, B. Shorten
Journal: BMJ (2009)

A need to balance risks, benefits, and choice

A commitment to quality and safety, together with choice and continuity of care, underpins current directions for the reform of maternity services in the United Kingdom and Australia.1 2 Recognition that midwifery-led care will be central to these changes, with options for women to give birth at home, has stimulated research about the safest and most effective models of care. Symon and colleagues (doi:10.1136/bmj.b2060) compare clinical outcomes between pregnant women accessing an independent midwife and women using the National Health Service (NHS).3 They found that obstetric risk factors were an important predictor of perinatal outcomes. Unwittingly the authors illustrate pitfalls involved in attempting to match disparate datasets. Nevertheless, they confirm some of what we already know about the benefits of continuity models of midwifery care and the important role of risk selection in achieving good perinatal outcomes.

Symon and colleagues attempted to match two groups of women, which is predictably problematic because women choosing independent midwifery care were a self selected group.3 Unfortunately, the matching process was largely unsuccessful, with numerous important differences remaining, including nutritional status, smoking status, alcohol consumption during pregnancy, geographic location of residence, obstetric risk from previous pregnancy, medical complications during current pregnancy, incidence of …
MALARIAL PIGMENT (SO-CALLED MELANIN): ITS NATURE AND MODE OF PRODUCTION
Authors: W. H. Brown
Journal: The Journal of Experimental Medicine (1911)

1. Two important methods for the study of malarial pigment are described. (a) A method for obtaining a solution of malarial pigment from fixed tissues without the removal of a trace of hemoglobin from the red blood corpuscles. (b) A method for obtaining an iron reaction in malarial pigment. 2. By comparing the bleach reactions and solubility of melanins and malarial pigment, the dissimilarity of the two classes of pigments has been demonstrated. 3. The spectroscopic examination of a solution of malarial pigment proves conclusively that the pigment is hematin. 4. It is suggested that the action of a proteolytic enzyme of the malarial parasite upon the hemoglobin of the red blood corpuscle is the most probable mode of elaboration of malarial pigment. 5. The difficulty with which the human organism disposes of malarial pigment indicates that the production of hematin cannot be considered as a normal intermediate process in the formation of bile pigments from hemoglobin.
China and Japan face epidemic of heart disease
Authors: Jane Parry
Journal: BMJ (2004)

China and Japan face epidemic of heart disease 15, 217, 163Asia is facing a cardiovascular disease epidemic as a result of increases in obesity, high blood pressure, and smoking, show data analysed in the Asia Pacific cohort studies collaboration.The findings are based on data from 600 000 people involved in 43 studies in nine places: China, Hong Kong, Thailand, Singapore, Australia, Japan, South Korea, Taiwan, and New Zealand.Whereas many western countries are grappling with rising obesity and have seen a peak in rates of smoking, in Asian countries-most notably China-several major risk factors are all rising."The pace of economic development in this part of the world is very fast, and smoking rates have increased rapidly too," said Professor
HEMOGLOBIN AND PLASMA PROTEIN
Authors: L. L. Miller, F. S. Robscheit-Robbins, G. H. Whipple
Journal: The Journal of Experimental Medicine (1945)

Hemoglobin (presumably its essential protein globin), given intraperitoneally to a protein-fasting dog, will be used effectively to supply the protein requirements of the body. Nitrogen balance may thus be maintained for 20 days under favorable conditions. New hemoglobin and plasma protein will be formed related to hemoglobin injections in depleted dogs where there is urgent need for these proteins (anemia and hypoproteinemia). Obviously this calls for supplementary amino acids which in globin are low and we assume these amino acids must be contributed from body protein stores. Plasma proteins (in plasma) tested in the same manner are completely utilized with no loss of nitrogen, positive nitrogen balance, weight balance, and no change in the albumin-globulin ratios. Hemoglobin (globin) is less effectively utilized as compared with plasma protein given parenterally and there is some increase in urinary nitrogen above control periods. The albumin-globulin ratio may be somewhat modified by hemoglobin injections intraperitoneally. Hemoglobin (globin) digests contribute effectively to body maintenance of nitrogen equilibrium. These digests are about as effective as whole hemoglobin in maintaining nitrogen balance but cause a rise in undetermined nitrogen not seen when hemoglobin alone is given intraperitoneally. Pigment radicles derived from hemoglobin given intraperitoneally are thrown away and appear as surplus bile pigment even when there is urgent need for all available nitrogenous material—given protein fasting, anemia, and hypoproteinemia in a bile fistula dog. The body evidently prefers to make rather than conserve the pyrrol aggregate (pigment radicle). We assume that the injected hemoglobin (globin) or hemoglobin digests contribute to the body protein pool and from this pool various proteins emerge to supply protein requirements of tissue or organ cells or to produce new hemoglobin or plasma protein if needed. We have no explanation as to what determines the pattern of this protein flow but new hemoglobin is very high on the priority list.
Increased expression of aquaporin-3 in the epidermis of DHCR24 knockout mice
Authors: R. Mirza, S. Hayasaka, F. Kambe, K. Maki, T. Kaji, Y. Murata, H. Seo
Journal: British Journal of Dermatology (2008)

Background The DHCR24 (3β‐hydroxysterol‐Δ24 reductase) gene encodes an enzyme catalysing conversion of desmosterol to cholesterol. Desmosterolosis is an autosomal recessive disease due to mutation in the DHCR24 gene, with low cholesterol and high desmosterol levels. To understand the pathophysiology of this disease, we utilized DHCR24 knockout mice and reported that DHCR24−/− mice die soon after birth. Their skin was less wrinkled, shiny, and revealed features of lethal restrictive dermopathy associated with severe defects in epidermal maturation and barrier function. Objectives Markedly increased transepidermal water loss in DHCR24−/− mice led us to examine the role of aquaporin‐3 (AQP3), because this is the only water/glycerol transporting channel protein expressed in the epidermis. Methods Expression of AQP3 was studied by Western blot analysis and immunohistochemistry in the epidermis of DHCR24−/− and wild‐type newborn mice. Glycerol uptake was determined in the isolated keratinocytes and glycerol content in the epidermis was analysed by an enzymatic method. Results In control mice, AQP3 was expressed only in cells of the stratum basale, indicating its expression in immature keratinocytes. In DHCR24−/− mice, AQP3 was expressed throughout the epidermis and colocalized with the immature keratinocytes (keratin 14‐positive cells). The increased AQP3 expression in the epidermis of DHCR24−/− mice was mirrored by a significantly higher glycerol uptake and glycerol content. This was associated with an increase in epidermal water content of DHCR24−/− mice. Conclusions This is the first demonstration that elevated AQP3 results in the retention of epidermal water, causing the taut, wrinkle‐free skin phenotype of the DHCR24−/− mice.
The Inflammasome — A Linebacker of Innate Defense
Authors: Joost P.H. Drenth, Jos W.M. van der Meer
Journal: New England Journal of Medicine (2006)

The cryopyrin gene, previously shown to be mutated in patients with periodic-fever syndrome, is critical in the innate immune response to some bacterial infections and to the inflammation that occurs after exposure to the crystalline material found in the joints of people with gout and pseudogout.
Effect Of Intravenous Immunoglobulin On Steroid-resistant Peripheral Neuropathy In Patients With Churg-Strauss Syndrome: A Double-blind, Placebo-controlled, Randomized Multicenter Trial
Authors: M. Taniguchi, T. Saito, G. Sobue, K. Akiyama
Journal: Journal of Allergy and Clinical Immunology (2011)
Mobile Chest Radiography Service for General Practitioners
Authors: L. B. P. Hartley, F. J. H. Walters
Journal: BMJ (1968)

In an eight-year period a mobile general practitioner chest x-ray referral service examined 100,000 patients referred by their family doctors. Of the patients examined, 8% were found to have previously undiagnosed significant thoracic disease. The incidence of pulmonary tuberculosis in need of treatment was 2.7 per thousand examinations (55% of them infectious). A total of 590 cases of primary cancer of lung were found. The incidence of this disease in men aged 45 and over was 19.4 per thousand examinations. A survey of general practitioners in the area concerned showed that they welcomed the service as a useful addition to their diagnostic facilities.
AGE DEPENDENT AND REGIONAL DIFFERENCE OF INFLAMMATORY RESPONSES IN THE DEVELOPMENT OF ATHEROSCLEROSIS IN APOLIPOPROTEIN E KNOCKOUT MICE
Authors: Sumiharu Sakamoto, Toshihiro Tsuruda, Kinta Hatakeyama, Yoko Sekita, Takuroh Imamura, Yujiro Asada, Kazuo Kitamura
Journal: Journal of the American College of Cardiology (2011)
Uptake and retention of hexakis (2-methoxyisobutyl isonitrile) technetium(I) in cultured chick myocardial cells. Mitochondrial and plasma membrane potential dependence.
Authors: D Piwnica-Worms, J F Kronauge, M L Chiu
Journal: Circulation (1990)

The fundamental myocellular uptake and retention mechanisms of hexakis (2-methoxyisobutyl isonitrile) technetium(I) (Tc-MIBI), a technetium-99m-based myocardial perfusion imaging agent, are unresolved. Because of the lipophilic cationic nature of Tc-MIBI, it may be distributed across biological membranes in response to transmembrane potential. To test this hypothesis, net uptake and retention of Tc-MIBI in cultured chick embryo ventricular myocytes were determined under conditions known to alter mitochondrial and plasma membrane potentials. Isovolumic depolarization of plasma membrane potentials in 130 mM extracellular K (Ko) 20 mM extracellular Cl buffer reduced net accumulation of Tc-MIBI from 171 +/- 16 (control) to 29 +/- 3.3 fmol intracellular Tc-MIBI/mg protein.nM extracellular Tc-MIBI. Unidirectional influx of Tc-MIBI in cells depolarized in 30 mM Ko buffer was also reduced; a resting plasma membrane potential of -87 +/- 6 mV was calculated from the Goldman flux equation using normal Ko/high Ko Tc-MIBI influx ratios. Addition of the potassium ionophore valinomycin to cells incubated in 130 mM Ko buffer to additionally depolarize mitochondrial membrane potentials further reduced net uptake of Tc-MIBI to levels comparable to that found in nonviable freeze-thawed preparations ([Tc-MIBI]i/[Tc-MIBI]o = 1). By depolarizing mitochondrial (and in part plasma membrane) potentials with the protonophores 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone (CCCP) Tc-MIBI was rapidly depleted from 181 +/- 16 (control) to 16 +/- 2.6 and 31 +/- 4.2 fmol/mg protein.nMo, respectively, with kinetics that did not correlate with loss of cellular ATP content. CCCP alone inhibited 90 +/- 3% of net accumulation or 66 +/- 3% of unidirectional influx of Tc-MIBI in a concentration-dependent manner. By hyperpolarizing mitochondrial membrane potentials with the K+/H+ ionophore nigericin or the ATP synthase inhibitor oligomycin, net uptake and retention of Tc-MIBI were increased by 60 +/- 9% and 375 +/- 20%, respectively. Caffeine, as well as the respiratory chain electron transport inhibitor rotenone, did not significantly alter net cell uptake (p greater than 0.2). These data indicate that the fundamental myocellular uptake mechanism of Tc-MIBI involves passive distribution across plasma and mitochondrial membranes and that at equilibrium Tc-MIBI is sequestered within mitochondria by the large negative transmembrane potentials.