tbuckley/cabot-search huggingface dataset:
Novel AE1 mutations in recessive distal renal tubular acidosis. Loss-of-function is rescued by glycophorin A.
Authors: V S Tanphaichitr, A Sumboonnanonda, H Ideguchi, C Shayakul, C Brugnara, M Takao, G Veerakul, S L Alper
Journal: Journal of Clinical Investigation (1998)

The AE1 gene encodes band 3 Cl-/HCO3- exchangers that are expressed both in the erythrocyte and in the acid-secreting, type A intercalated cells of the kidney. Kidney AE1 contributes to urinary acidification by providing the major exit route for HCO3- across the basolateral membrane. Several AE1 mutations cosegregate with dominantly transmitted nonsyndromic renal tubular acidosis (dRTA). However, the modest degree of in vitro hypofunction exhibited by these dRTA-associated mutations fails to explain the disease phenotype in light of the normal urinary acidification associated with the complete loss-of-function exhibited by AE1 mutations linked to dominant spherocytosis. We report here novel AE1 mutations linked to a recessive syndrome of dRTA and hemolytic anemia in which red cell anion transport is normal. Both affected individuals were triply homozygous for two benign mutations M31T and K56E and for the loss-of-function mutation, G701D. AE1 G701D loss-of-function was accompanied by impaired trafficking to the Xenopus oocyte surface. Coexpression with AE1 G701D of the erythroid AE1 chaperonin, glycophorin A, rescued both AE1-mediated Cl- transport and AE1 surface expression in oocytes. The genetic and functional data both suggest that the homozygous AE1 G701D mutation causes recessively transmitted dRTA in this kindred with apparently normal erythroid anion transport.
Abstract 3152: Sumoylation of eIF4E activates mRNA translation
Authors: Jing Hu, Xiang Xu, Jaya Vatsyayan, Chenxi Gao
Journal: Cancer Research (2010)

Abstract Eukaryotic translation initiation factor 4E (eIF4E) is the cap-binding protein that binds the 5’ cap structure of cellular mRNAs. Despite the obligatory role of eIF4E in cap-dependent mRNA translation, how the translation activity of eIF4E is controlled remains largely undefined. Here we report that mammalian eIF4E is regulated by SUMO-1 (small ubiquitin-related modifier-1) conjugation. eIF4E is sumoylated on lysines 36, 49, 162, 206 and 212. Using eIF4E sumo-deficient mutant as a tool, we find that eIF4E sumoylation disrupts the interaction of 4IF4E with its inhibitor 4E-BP1 (eIF4E-binding protein 1) and promotes the eIF4E/eIF4G association. Further, downregulation of eIF4E sumoylation inhibits eIF4E-dependent protein translation of a subset of genes that are critical for cell proliferation and preventing apoptosis, and abrogates the oncogenic and anti-apoptotic functions associated with eIF4E. These data indicates that sumoylation represents a novel fundamental regulation mechanism of protein synthesis. Our findings further suggest that eIF4E sumoylation may be important in promoting human cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3152.
Compliance, Caricature, and Culturally Aware Care
Authors: Debra Malina
Journal: New England Journal of Medicine (2005)

The referrals were always the same. Febrile seizures, noncompliant mother, noncompliant mother, noncompliant mother, noncompliant mother.So reports a California nurse who visited Lia Lee, the epileptic Hmong girl at the center of Anne Fadiman's 1997 book, The Spirit Catches You and You Fall Down. Most of Lia's U.S. health care providers attributed the worsening of her condition that culminated in brain death largely to parental noncompliance. As Fadiman reveals, Lia's immigrant parents, faced with a constantly changing regimen that was no match for the evil spirit they knew was causing Lia's fits, had neither the ability nor the . . .
Use of the Ultrasonic Doppler Method for Timing of Valvular Movement
Authors: JOHN B. KOSTIS, DIETRICH FLEISCHMANN, SAMUEL BELLET
Journal: Circulation (1969)

The ultrasonic Doppler method was employed to time the rapid movements (opening and closure) of the mitral and aortic valves. To exclude signals due to slowly moving structures (heart walls), the Doppler tracing was processed by a filter that eliminated low frequencies. Clear tracings containing two deflections, one due to the opening and the other to the closure of each valve, were obtained. The valvular origin of the deflections was verified by recordings simultaneous with intratardiac pressures in five dogs. The ultrasonic Doppler tracing was found to be a satisfactory aid in the differentiation of various extra heart sounds in 24 patients. Thus, the second heart sound precedes, the third heart sound follows, and the opening snap is simultaneous with the signal due to mitral opening. The fourth heart sound is simultaneous with the atrial component of the unfiltered Doppler signal. Ejection clicks and systolic clicks are simultaneous with or follow the signal due to aortic opening. Because of its simplicity and safety, this method used in conjunction with the phonocardiogram should prove helpful in distinguishing the opening snap, third and fourth heart sounds, and certain additional auscultatory phenomena.
Eosinophilia and gastrointestinal symptoms after ingestion of shiitake mushrooms☆☆☆★★★♢
Authors: Aaron M. Levy, Hirohito Kita, Sidney F. Phillips, Paul A. Schkade, Phillip D. Dyer, Gerald J. Gleich, Vincent A. Dubravec
Journal: Journal of Allergy and Clinical Immunology (1998)
Canine coronary vascular and cardiac responses to the prostaglandins
Authors: D. O. NUTTER, H. J. CRUMLY
Journal: Cardiovascular Research (1972)

Journal Article Canine coronary vascular and cardiac responses to the prostaglandins Get access DONALD O. NUTTER, DONALD O. NUTTER From the Cardiovascular Research Laboratory, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar HAROLD J. CRUMLY, JR. HAROLD J. CRUMLY, JR. From the Cardiovascular Research Laboratory, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 6, Issue 3, May 1972, Pages 217–225, https://doi.org/10.1093/cvr/6.3.217 Published: 01 May 1972
Drug Development, Regulation, and the Practice of Medicine
Authors: M. Nadasdi
Journal: JAMA (1975)

<h3>To the Editor.—</h3> In his article entitled "Drug Development, Regulation and the Practice of Medicine (229:1457, 1974), Wardell makes the following statement: Some of the most important decisions in drug therapeutics are no longer the prerogative of the medical profession but are now assumed by industry and by regulatory agencies. The medical profession has displayed little interest in these changes and, at least in the United States, has secured no right for itself to exert any influence on them. The thought-provoking words in this statement are "the medical profession." Medical doctors tend to regard their profession as a homogeneous group with the same moral standard, same aims, and same fulfillments. This feeling stems from the common ritual at the time of graduation: The Hippocratic Oath. Contrary to this contention, the medical profession is far from being homogeneous. The dean of a medical school, the editor of a medical journal, and
Ethical dilemma: Discontinuation of ventilation after brain stem death To whom is our duty of care? Policy should be balanced with concern for the family Brain stem death defines death in law
Authors: J M A Swinburn, S M Ali, D J Banerjee, Z P Khan, R. E Cranford, B. Jennett
Journal: BMJ (1999)

Ethical dilemma Discontinuation of ventilation after brain stem deathConfusion among the public over the difference between brain stem death and a persistent vegetative state can make it difficult to obtain consent to withdraw ventilation.Clinicians who have been faced with this dilemma outline their strategies for coping with such a situation, and a neurologist and a neurosurgeon offer their opinions.
Progeria: A Possible Therapeutic Approach
Authors: Samuel Ayres
Journal: JAMA (1974)

<h3>To the Editor.—</h3> An editorial by Samuel Vaisrub (226:1565, 1973) under the title "Nature's Experiment in Unnatural Aging," discussed the possibility of learning from one of nature's mistakes how to retard the aging process. He pointed out that progeria, a disease inherited as an autosomal recessive trait, is characterized by precocious senility, and that "the afflicted child with his wizened face, dwarfed stature, and the general appearance of senility usually dies of coronary heart disease during the first or second decade of life." Further evidence of senility has been established by finding deposits of lipofuscin, the "age pigment," in various cells of the body, and by the incidence of focal fibrosis of the myocardium. This pigment, according to Tappel<sup>1</sup>and other investigators, results from destructive autooxidation (lipid peroxidation) of the lipid portion of the biological membranes of cells and intracellular organelles. It is believed to represent an important factor
Ian Cunningham Sinclair Knight
Authors: Donald C MacPhail
Journal: BMJ (2004)

Former professor of urological surgery University of New Mexico Medical School, Albuquerque, New Mexico, United States (b 1923; q Edinburgh 1946; FRCS Ed), died from heart failure on 6 December 2003.

Ian served for three years in the Royal Air Force, returning to Edinburgh to complete his general surgical training. He became a consultant urologist in Doncaster, but in 1966, as he was plagued by respiratory problems, he decided to emigrate to New Mexico, with its pollution free dry climate. Following his tenure as professor of urology at the University of New Mexico Medical School, he was in private practice for 30 years. He leaves a wife, Ethel; three children; and two grandsons.
Abstract 3362: Diethylaminobenzaldehyde (DEAB) is not a specific inhibitor of ALDH1a1 isozyme
Authors: Jan S. Moreb, Lung-Ji Chang, Shuhong Han, Blanca Ostmark
Journal: Cancer Research (2010)

Abstract With the cancer stem cell theory, there has been an invigorated new interest in finding more markers for stem cells. Aldehdye dehydrogenase (ALDH) is one such marker that became popular since a flow cytometry based assay, Aldeflour staining, has become available. Diethylaminobenzaldehyde (DEAB), used in the Aldeflour assay, has been published many years ago as a specific inhibitor for ALDH1 isoform. The Aldeflour assay is promoted as testing the enzymatic activity of ALDH1. Therefore most researchers believe that the high ALDH activity detected in these early progenitors is mainly due to ALDH1. In this study, we explore the specificity of DEAB as an inhibitor of ALDH activity. We used two cancer cell lines known to have very low baseline ALDH activity, K562 leukemia and H1299 lung cancer cell lines. We prepared lentiviral vectors containing the full length of either ALDH2 or ALDH1a2 cDNA and used them to over express the enzymes in the two cell lines. Successful expression was measured by ALDH activity assay as well as by Western blot analysis and RT-PCR. Aldeflour staining assay was also used. The results show that we created 4 cell lines with successful high expression of each of the two enzymes as confirmed by multiple assays including the Aldeflour assay. In order to study the specificity of two known ALDH activity inhibitors, DEAB and tetraethylthiuram disulfide (disulfiram), we incubated each cell line with either inhibitor at 25 μM concentration for 48 hr and then measured the remaining ALDH enzymatic activity. Our results show that both inhibitors reduced ALDH activity of both overexpressed isozymes, ALDH2 and ALDH1a2, by 70-80%. These results suggest that DEAB is not a specific inhibitor for ALDH1a1 and that aldefluor assay is not specific assay for ALDH1a1 either. Therefore, investigators should be careful in their conclusions when using DEAB in studying candidate stem cells and that studies with more specific inhibitors, such as siRNA, are needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3362.
The anaemia of chronic disease
Authors: E J Fitzsimons
Journal: BMJ (2001)

Iron: such a remarkable remedy generally associated with strength and well being. Iron filings dissolved in vinegar were consumed by the ancient Greeks eager to acquire strength, and in 1600 iron was noted for its ability to restore “young girls when pallid, sickly and lacking colour to health and beauty.” Yet strangely it has no effective role in treating the most common type of anaemia to affect hospital inpatients.1 Recent developments have made the anaemia of chronic disease somewhat easier to diagnose, but it remains a puzzling condition.

Anaemia of chronic disease was established as a distinct entity in 1962 after studies on the anaemia associated with infection.2 All agree on the “big three” clinical causes: infection, inflammation (including connective tissue disorders), and neoplasia, which account for 75% of cases. Though the chronic disease that leads to the anaemia is usually easily identified, this is not always so, and occult disease must be considered in every case of unexplained anaemia.

One special case is the anaemia of chronic renal failure, which is thought to result from a combination of erythropoietin deficiency and anaemia of chronic disease. A further contribution may come from functional iron deficiency consequent on erythropoietin replacement for patients undergoing haemodialysis. In this setting and despite adequate …
Azathioprine maintenance therapy in IBD:medium term outcomes from a nurse-delivered IBD monitoring service at a district general hospital
Authors: H. E. Johnson, S. D. McLaughlin, S. A. Weaver
Journal: Gut (2011)

<h3>Introduction</h3> Azathioprine is widely acknowledged as the benchmark therapy for maintenance of remission in IBD. Published long term outcome data from the district general hospital setting are limited. <h3>Methods</h3> A prospective data base of IBD patients has been maintained at our unit since 2005. The authors reviewed the cases of all IBD patients commencing azathioprine treatment between June 2005 and December 2007 and followed up for at least 3 years. Thiopurine methyl transferase (TPMT) levels were checked on all patients. Azathioprine was prescribed at 2–2.5 mg/kg with dose reduction in patients with low TPMT. All patients complied with weekly blood monitoring for eight consecutive weeks. Clinical remission was defined as; a lack of symptoms in combination with Harvey Bradshaw Index (HBI) &lt;5 for Crohn9s disease (CD) or endoscopic remission for ulcerative colitis (UC). Abnormal liver function tests (LFTs) were defined as ALT 2× upper limit of normal (ULN). <h3>Results</h3> 120 patients were identified (75 CD, 45 UC). 57 (47.1%) were male; mean age was 45 years (range 17–83). 12 of the 120 (10%) patients moved and were lost to follow-up leaving 108 under continuing follow-up. 47 (43.5%) were still taking azathioprine and 44 (93.6%) of these were in a clinical remission at the time of the study. Of the 44 patients in remission 8 patients have had surgery but remain on azathioprine. Of the 61 patients who stopped azathioprine, median time to cessation 5 weeks (range 0.14–208). Reasons for stopping azathioprine were; Pancreatitis; 2 (3.3%), Low total white blood cell count; 4 (6.6%), Surgery; 9 (14.8%), Abnormal liver function tests (LFTs); 14 (23%), Side effects including myalgia, flu symptoms, rashes, nausea and vomiting and patient choice; 32 (26.7%). Treatment for the 61 patients stopping azathioprine were as follows: Mercaptopurine; 12 (19.7%), methotrexate; 4 (6.6%), Biologics; 6 (9.9%), 5-ASA; 28 (44.7%), Colectomy; 2 (3.3%), no treatment; 9 (14.8%). <h3>Conclusion</h3> These results demonstrate that in our unit more than half of patients failed to continue azathioprine in the medium term. This is higher than reported in tertiary centres. In those patients who continued azathioprine more than 90% were in a clinical remission at last follow-up. The majority of patients where treatment was stopped was because of side effects or abnormal LFTs. A recently published study has demonstrated that allopurinol in combination with low-dose azathioprine can bypass many adverse drug reactions and enable patients to continue azathioprine. The authors now routinely test 6-Thioguaine nucleotide levels and use allopurinol co-therapy in such patients. The authors aim to perform a further study to establish whether this treatment strategy will allow more of our patients to continue azathioprine.
An intravital fluorescence microscopic study of hepatic microvascular and cellular derangements in developing cirrhosis in rats
Authors: Brigitte Vollmar, Sören Siegmund, Michael D. Menger
Journal: Hepatology (1998)

Quantitative data defining the relationship between the hepatic microcirculation and the development of liver pathological changes could provide a basis for a better understanding of fibrogenic processes, such as cirrhosis. Therefore, we established the technique of intravital fluorescence microscopy and computer-assisted microcirculation analysis systems in developing cirrhosis in rats with the aim of quantitatively assessing the association of hepatic microvascular morphology with its disordered acinar architecture, and nonparenchymal cell transformation with collagen deposition, parenchymal cell loss, and liver dysfunction. In animals chronically exposed to carbon tetrachloride (CCl 4 ), the most significant microvascular changes progressively observed in vivo were the concomitant appearance of 1) sinusoid-free space around dilated postsinusoidal venules with 2) substituting occurrence of yellow-green autofluorescent collagen deposition, 3) reduction in sinusoidal density, but 4) increase of vascular lumen caused by the formation of shunting vessels bypassing the sinusoids. Present on-line analysis further indicated the local coincidence of changed spatial distribution of Ito cells (accumulation of vitamin A ultraviolet autofluorescence in zone 3) with fibrotic autofluorescent septa, causing significant collapse of parenchymal tissue (hepatocellular bis-benzamide fluorescence) and diminution of hepatocellular excretory function (bile flow). Regression analysis revealed strong correlations between loss of parenchymal tissue and both collagen deposition and sinusoidal rarefication, as well as between sinusoidal rarefication and collagen deposition. Thus, sequential in vivo analysis presented herein provides the new information on the concomitant onset of cellular, fibrotic, and microvascular changes in developing fibrosis/cirrhosis, excluding that distinct cellular or fibrotic alterations are a prerequisite for the manifestation of microcirculatory and vascular derangements or vice versa.
Individual-Based Model Framework to Assess Population Consequences of Polychlorinated Biphenyl Exposure in Bottlenose Dolphins
Authors: Ailsa J. Hall, Bernie J. McConnell, Teri K. Rowles, Alex Aguilar, Asuncion Borrell, Lori Schwacke, Peter J.H. Reijnders, Randall S. Wells
Journal: Environmental Health Perspectives (2005)

Marine mammals are susceptible to the effects of anthropogenic contaminants. Here we examine the effect of different polychlorinated biphenyl (PCB) accumulation scenarios on potential population growth rates using, as an example, data obtained for the population of bottlenose dolphins from Sarasota Bay, Florida. To achieve this goal, we developed an individual-based model framework that simulates the accumulation of PCBs in the population and modifies first-year calf survival based on maternal blubber PCB levels. In our example the current estimated annual PCB accumulation rate for the Sarasota Bay dolphin population might be depressing the potential population growth rate. However, our predictions are limited both by model naivety and parameter uncertainty. We emphasize the need for more data collection on the relationship between maternal blubber PCB levels and calf survivorship, the annual accumulation of PCBs in the blubber of females, and the transfer of PCBs to the calf through the placenta and during lactation. Such data require continued efforts directed toward long-term studies of known individuals in wild and semiwild populations.
Abstract 4848: Angintensin II Stimulates Microtubule Reorganization Mediated by SIRT2 in Endothelial Cells
Authors: Aiko H Komatsu, Tetsuaki Hirase, Machiko Asaka, Koichi Node
Journal: Circulation (2009)

Angiotensin II has been implicated in the pathophysiology of vascular remodeling. Microtubule composed of tubulins regulates cell shape, migration and survival. Tubulin acetylation plays an important role in the control of microtubule structure and microtubule-based cellular functions. We studied angiotensin II-induced changes in microtubules in endothelial cells. Immunofluorescence microscopy showed that acetylated tubulin was decreased in PECAM-1-positive cells in the intima of the aortic walls in mice loaded with angiotensin II, compared to mice loaded with control vehicle. In cultured human endothelial cells in quiescence, α -tubulin-positive microtubules were acetylated and showed radial layout from microtubule-organizing center to peripheral edge of cells. Angiotensin II induced disassembly and deacetylation of α -tubulin, which were blocked by pretreatment with losartan that is an angiotensin II type 1 receptor blocker, sirtinol that is an inhibitor for sirtuin class deacetylases, and depletion of a deacetylase SIRT2 by RNA interference. We investigated the involvement of SIRT2 in angiotensin II-induced endothelial cell migration using Boyden chamber method. Angiotensin II caused a significant increase in cell migration, which was blocked by pretreatment with sirtinol and SIRT2 depletion. It has been reported that angiotensin II is involeved in cytoskeletal reorganization stimulated by mechanical stretch in endothelial cells. To investigate the effects of mechanical stretch on microtubule reorganization, cultured endothelial cells were subjected to 10% uniaxial stretch and examnied by immunofluorescence. Mechanically stretched cells showed vertical alignment to tension direction and tubulin deacetylation in peripheral side of cells, compared to control static cells. Mechanical stretch-induced changes of microtubules were blocked by pretreatment with sirtinol and SIRT2 depletion. These data suggest that angiotensin II and mechanical stretch stimulate microtubule redistribution and deacetylation via SIRT2 in endothelial cells. Further studies are necessary to elucidate the roles of SIRT2-mediated microtubule reorganization in vascular remodeling.
Studies on 2', 3'-cyclic AMP 3'-phosphohydrolase in rabbit skin
Authors: MICHAEL MEZEI, CATHERINE MEZEI
Journal: British Journal of Dermatology (1979)

Previous studies indicated that 2', 3'-cyclic AMP 3'-phosphohydrolase, an enzyme which splits the 3'-phosphate bond of the 2', 3'-cyclic AMP, is primarily confined to nervous tissue. The physiological function of this enzyme is still unknown. In the present study this enzyme was found to be active in various organs of rabbit, i.e. liver, kidney, heart and skin, although to a much lesser extent than in brain and sciatic nerve. The finding of this enzyme in the skin generated further studies to measure the enzyme activity in normal and diseased skin. Chemically induced (surfactant-treated) skin disorder was used as a model for the present study. Topical application of Polysorbate 85 resulted in a two fold increase of the enzyme activity in rabbit skin. The results suggest that this enzyme may have some role in the repair mechanisms, particularly in the regeneration of damaged membranes.