tbuckley/cabot-search huggingface dataset:
Ten Minutes for the Family: Systemic Interventions in Primary Care
Authors: Iona Heath
Journal: BMJ (2004)

Ten minutes seems a ridiculously short time in which to attempt to tackle the always complex health problems of a single individual. To use the same allotted time to take on the interacting and compounding problems of a whole family might seem absurdly ambitious. Yet any general practitioner knows the astonishing amount of suffering, endurance, and meaning that can be revealed and contained within a single consultation of this length. Three of the four authors of this book have substantial experience of working in UK general practice, where 10 minute appointments are standard. This deliberately pragmatic book is full of practical wisdom that can be taken straight …
Pulmonary Complications and Water Retention in Prolonged Mechanical Ventilation
Authors: Arnold Sladen, Myron B. Laver, Henning Pontoppidan
Journal: New England Journal of Medicine (1968)

In a retrospective study of 100 patients treated with prolonged mechanical ventilation, water retention without evidence of cardiac failure developed in 19. This was associated with radiologic evidence of pulmonary edema and with the following significant changes: a mean gain in weight of 2.6 kg; a mean increase in the alveolar-arterial oxygen tension gradient of 127 mm of mercury; a decrease in vital capacity of 29 per cent; a reduction in estimated compliance of 31 per cent; a fall in hematocrit of.13 percent; and a decrease in serum sodium of 5.80 mEq per liter. These changes were reversed after the institution of a negative water balance by restriction of water intake and by diuretic therapy. Radiologic improvement was usually prompt. The appearance of pulmonary edema may be related to a relative water overload, a rise in antidiuretic hormone production or subclinical cardiac failure.
Hla Class Ii Genes Determine the Natural Variance of Hepatitis C Viral Load
Authors: Liam J. Fanning, John Levis, Elizabeth Kenny-Walsh, Michael Whelton, Kathleen O'Sullivan, Fergus Shanahan
Journal: Hepatology (2001)

The aim of this study was to investigate the relationship between human leukocyte antigen (HLA) class II genes and the natural fluctuations in hepatitis C viral load in a homogeneous patient population. The study group consisted of 57 viremic (hepatitis C virus [HCV] 1b) women for whom HLA class II DRB1 and DQB1 haplotyping, virologic, histologic, and biochemical markers of disease activity were available. All patients were infected with HCV 1b from the same source of hepatitis C-contaminated anti-D immunoglobulin during the period from May 1977 to November 1978. The mean slope of change of viral load was 0.34 (SD +/- 0.73) log(10) viral copies/mL/year, which is significantly different from zero, P < 10(-9). Analysis of the relationship between the slope of change of viral load and HLA class II haplotype indicated a significantly different slope of change of viral load between the alleles of (1) DRB1(*)15 and DRB1(*)0701, and (2) DQB1(*)0602 and DQB1(*)0201, P(c) =.036 and P(c) =.026 after Bonferroni correction for multiple comparisons, respectively. Significant differences for grade and stage of disease at liver biopsy were observed for DQB1(*)0501 and DQB1(*)0201 alleles; P =.019, r(s) =.64, and P =.047, r(s) =.57, respectively. In addition, significant differences in stage of disease were found to exist between DRB1(*)13 and DRB1(*)0701, P =.031, r(s) = -.71. Our results define an association between the slope of change of viral load and HLA class II haplotype in patients infected with genotype 1b of HCV. This suggests a role for host immunogenetic factors in HCV infection in this homogeneous group.
Expression and role of p75 interleukin 2 receptor on human monocytes.
Authors: I Espinoza-Delgado, J R Ortaldo, R Winkler-Pickett, K Sugamura, L Varesio, D L Longo
Journal: The Journal of Experimental Medicine (1990)

We investigated the expression of IL-2R subunits in human monocytes using the TU27 mAb, which recognizes the p75 chain, and anti-Tac mAb, which recognizes the p55 moiety of the IL-2R. We found that p75 but not p55 is constitutively expressed in more than 90% of fresh human monocytes. Antibody to p75, but not to p55, inhibited the activation of monocytes to a cytotoxic stage induced by IL-2 but did not block IFN-gamma-induced cytotoxicity. Our data demonstrate that the p75 chain is expressed on human monocytes and is involved in the activation of monocytes by IL-2.
Up From Little Egypt
Authors: Lester S. King
Journal: JAMA (1969)

Percival Bailey is a distinguished investigator of the nervous system— in surgery, pathology, anatomy, physiology, psychiatry. In addition, he is one of the most colorful figures in American medicine. And in addition, he is an accomplished and skillful writer. We see all three of these facets in a new volume that brings together a series of autobiographical essays that Bailey had presented before the Chicago Literary Club. Like a probing searchlight, the essays brilliantly illuminate some aspects but leave others in obscurity. The book is a succession of vignettes, each of which presents sharply etched details, and in the aggregate they provide a broad autobiographical survey. Prefacing the essays is a short biographical sketch of the more conventional sort, written by Ruth Anderson Tooze, and there is a short foreword by Paul C. Bucy. Bailey was born in "downstate" southern Illinois, in 1892. Although raised in poverty, he was determined
Hyperosmolar Nonketotic Syndrome and Steroid Diabetes
Authors: John E. Woods
Journal: JAMA (1975)

So-called steroid (glucocorticoids) diabetes developed in 11 (5.5%) of 202 patients receiving 216 renal allografts between December 1963 and June 1974. In three of the 11 patients, hyperosmolar nonketotic syndrome was present at diagnosis; all of the three recovered. Eight of the 11 patients survived with functioning allografts, and only one of the eight requires insulin. Hyperglycemia has been detected in most transplant patients tested in the immediate postoperative period. Factors (including stress from surgery and treatment with drugs such as furosemide) predispose to this condition.
Cyclosporine A limits myocardial infarct size even when administered after onset of ischemia
Authors: Christof Weinbrenner, Guang S Liu, James M Downey, Michael V Cohen
Journal: Cardiovascular Research (1998)

Objective: The role of the immunosuppressant cyclosporine A as a preconditioning-mimetic in the rabbit heart was examined. Methods: Cyclosporine A, a potent protein 2B or calcium/calmodulin-dependent phosphatase (PP) inhibitor, was administered to isolated rabbit hearts starting either 15 min prior to or 10 or 20 min after the onset of a 30 min period of regional ischemia and continuing until the onset of reperfusion. The effect of pretreatment with a second PP2B antagonist, FK-506, was also examined. In an additional protocol L-NAME was perfused for 50 min starting 5 min before the 45-min infusion of cyclosporine A. After 2 h of reperfusion infarct size was measured with triphenyltetrazolium chloride. In a second study left ventricular biopsies of isolated rabbit hearts were obtained to measure the effect of cyclosporine A on dephosphorylation of phosphorylase kinase by calcium/calmodulin-dependent phosphatases. Results: Pretreatment with cyclosporine A resulted in only 10.0% infarction of the risk zone, significantly less than that in untreated control hearts (28.7%, p<0.001) but comparable to the extent of infarction in ischemically preconditioned hearts (10.0%, p<0.001 vs. control). Equivalent protection was also observed in hearts with treatment delayed for 10 min following the onset of ischemia (10.4% infarction, p<0.001 vs. control). However, protection waned when cyclosporine A was administered only during the last 10 min of the 30-min ischemic period (25.5% infarction, p=n.s. vs. control). Pretreatment with FK-506 also resulted in myocardial salvage (10.4% infarction, p<0.001 vs. control). When hearts were exposed to a co-infusion of L-NAME and cyclosporine A, protection was still evident (18.1% infarction, p<0.05 vs. L-NAME), although not as robust as that seen with the PP2B blocker alone. In hearts pretreated with cyclosporine A dephosphorylation of phosphorylase kinase by calcium/calmodulin-dependent phosphatases was inhibited by 67%. Conclusions: Cyclosporine A and FK-506, potent PP2B inhibitors, can protect the ischemic rabbit heart, and at least cyclosporine A continues to be effective when infusion is delayed until after the onset of ischemia. The mechanism of this protection may be related to inhibition of phosphatases and prolongation of the phosphorylation state of ischemic cells.
Rapid Communication: Effect of blood viscocity on arterial flow induced dilator response
Authors: A. M Melkumyants, S. A Balashov
Journal: Cardiovascular Research (1990)

Experiments were designed to determine whether blood viscocity affects flow induced dilator response in conduit arteries. Changes in diameter of the femoral artery of anaesthetised cats evoked by stepwise blood flow increases were recorded at normal blood viscocity, at haemodilution, and at haemoconcentration, under conditions of stabilised transmural pressure. Dilator responses caused by the same increments in flow rate increased at haemoconcentration and decreased at haemodilution, in parallel with the changes in blood viscocity. These data show that haemodilution attenuates and haemoconcentration augments flow induced dilatation, and they confirm the suggestion that flow induced arterial dilatation is due to endothelial sensitivity to shear stress.
Airways obstruction in rheumatoid arthritis.
Authors: D M Geddes, M Webley, P A Emerson
Journal: Annals of the Rheumatic Diseases (1979)

Owing to the report of an association between rheumatoid arthritis (RA) and obliterative bronchiolitis we have determined the prevalence of airflow obstruction in unselected patients with RA and normal chest radiographs. Spirometry was performed on 100 patients with rheumatoid arthritis and 84 control subjects matched for age, sex, and smoking habits. Patients with rheumatoid arthritis had significantly lower values for FEV1, FVC, FEV1/FVC, and MMEFR when compared with the controls: 39 patients had abnormal spirometry, and at least 32 showed airways obstruction. The prevalence of airflow obstruction is remarkably high, and we suggest that airway disease may be the commonest form of lung involvement in rheumatoid arthritis.
Chemokine Fractalkine Mediates Leukocyte Recruitment to Inflammatory Endothelial Cells in Flowing Whole Blood
Authors: Christian Schulz, Andreas Schäfer, Moritz Stolla, Sandra Kerstan, Michael Lorenz, Marie-Luise von Brühl, Matthias Schiemann, Johann Bauersachs, Torsten Gloe, Dirk H. Busch, Meinrad Gawaz, Steffen Massberg
Journal: Circulation (2007)

The membrane-bound chemokine fractalkine (CX3CL1) is expressed on various cell types such as activated endothelial cells and has been implicated in the inflammatory process of atherosclerosis. The aim of the present study was to dissect the role of fractalkine in leukocyte recruitment to inflamed endothelium under arterial shear forces.With the use of immunofluorescence and laminar flow assays, the present study shows that human umbilical vein endothelial cells stimulated with tumor necrosis factor-alpha and interferon-gamma abundantly express CX3CL1 and promote substantial leukocyte accumulation under arterial flow conditions. In the presence of high shear, firm adhesion of leukocytes to inflamed endothelial cells is reduced by approximately 40% by a function-blocking anti-fractalkine antibody or by an antibody directed against the fractalkine receptor (CX3CR1). With the use of intravital video-fluorescence microscopy we demonstrate that inhibition of fractalkine signaling attenuates leukocyte adhesion to the atherosclerotic carotid artery of apolipoprotein E-deficient mice, which suggests that the CX3CL1-CX3CR1 axis is critically involved in leukocyte adhesion to inflamed endothelial cells under high shear forces both in vitro and in vivo. Surprisingly, platelets were strictly required for fractalkine-induced leukocyte adhesion at high shear rates. Correspondingly, specific inhibition of platelet adhesion to inflamed endothelial cells also significantly reduced leukocyte accumulation. We show that both soluble and membrane-bound fractalkine induces platelet degranulation and subsequent surface expression of P-selectin, which thereby promotes direct platelet-leukocyte interaction.Fractalkine expressed by inflamed endothelial cells triggers P-selectin exposure on adherent platelets, which thereby initiates the local accumulation of leukocytes under arterial shear, an essential step in the development of atherosclerotic lesions.
Thiol-disulfide effects on hepatic glutathione transport. Studies in cultured rat hepatocytes and perfused livers.
Authors: S C Lu, J L Ge, H Y Huang, J Kuhlenkamp, N Kaplowitz
Journal: Journal of Clinical Investigation (1993)

In cultured rat hepatocytes, cystine led to an inhibition of GSH efflux by lowering the Vmax by approximately 35% without affecting the Km. The cystine-mediated inhibition of GSH efflux was rapid in onset (< 1 h), with near maximum effect at 0.1 mM. Inhibition was still observed when cystine uptake was prevented. Cystine and sulfobromophthalein-GSH, a selective inhibitor of sinusoidal transport of GSH, did not exhibit additive inhibitory effects on GSH efflux. Depletion of ATP or membrane depolarization after cystine treatment were excluded as potential mechanisms. DTT not only reversed the cystine-mediated inhibition of GSH efflux, it stimulated GSH efflux up to 400-500%. The DTT effect was immediate in onset, reaching maximum after 30 min, and was partially reversed by cystine, suggesting that the two share a common site(s) of action. DTT treatment did not alter cellular ATP levels or change the membrane potential. In cultured hepatocytes, DTT treatment increased the Vmax of GSH efflux by approximately 500% without affecting the Km. Inhibition of microtubular function and vesicular acidification did not affect basal or DTT stimulated efflux. Both cystine and DTT effects on sinusoidal GSH efflux were confirmed in perfused livers. In summary, the capacity of the sinusoidal GSH transporter is markedly influenced by thiol-disulfide status.
Dual Modes of Natural Selection on Upstream Open Reading Frames
Authors: D. E. Neafsey, J. E. Galagan
Journal: Molecular Biology and Evolution (2007)

Upstream open reading frames (uORFs) are common features of eukaryotic genes, occurring in 10%–25% of 5′ leader sequences. Upstream ORFs that have been subjected to experimental analysis have been generally found to decrease translational efficiency of the downstream coding sequence. Previous investigations of uORFs in mammals and yeast have detected uORFs conserved over long evolutionary distances, prompting speculation about the nature and cause of the natural selection underlying such conservation. We have analyzed uORFs in the basidiomycetous fungal pathogen Cryptococcus neoformans to discern the properties of this purifying selection. We find that uORFs in the Cryptococcus species complex are conserved at twice the expected rate, and we report 122 uORFs that are conserved among all four sequenced Cryptococcus strains. A significantly greater proportion of uORF losses occur via direct mutation to the uORF start codon than expected. This observation suggests that mutational disruption of a uORF that leaves the start codon intact may be selectively disadvantageous, perhaps because of the risk of premature translation initiation. Accounting for this constrained mode of loss and comparing the relative conservation of uORFs between the 5′ leader and control sequences enables us to calculate that at least a third of uORFs may be conserved for their effects on translational efficiency. The remaining fraction may be conserved either by chance or as a result of selective pressure to prevent premature translation initiation from the uORF start codon. We find that the majority of conserved uORFs do not exhibit codon usage bias or conservation at the amino acid level, and therefore they do not likely encode bioactive peptides. Our analysis suggests that uORFs are an important and underappreciated mechanism of post-transcriptional gene regulation in eukaryotes.
OPENING DISCUSSION ON "MILITARY DENTAL PRACTICE—ITS MODIFICATIONS AND LIMITATIONS."
Authors: JOHN S. MARSHALL
Journal: JAMA (1901)

The passage of the Army Reorganization Bill with its section creating a Corps of Dental Surgeons for the U. S. Army, makes an epoch in the history of modern dental surgery; an epoch which has never had its counterpart before in the history of the world, the influence of which is destined to be far-reaching in its beneficent results, and of great importance in the elevation of our educational and professional standards. When we take into consideration the fact that modern dentistry covers, in its growth and development, a period less than the lifetime of many individuals, we have good reason to be proud of its achievements. Sixty years ago there was no such thing in existence as a dental college; a dental journal had not been thought of, or a scientific dental society organized. The practice of dentistry at this time was, with few exceptions, in the hands of
Hepatocyte growth factor/<i>c-met</i>signaling is required for stem-cell-mediated liver regeneration in mice
Authors: Tsuyoshi Ishikawa, Valentina M. Factor, Jens U. Marquardt, Chiara Raggi, Daekwan Seo, Mitsuteru Kitade, Elizabeth A. Conner, Snorri S. Thorgeirsson
Journal: Hepatology (2011)

Hepatocyte growth factor (HGF)/c-Met supports a pleiotrophic signal transduction pathway that controls stem cell homeostasis. Here, we directly addressed the role of c-Met in stem-cell-mediated liver regeneration by utilizing mice harboring c-met floxed alleles and Alb-Cre or Mx1-Cre transgenes. To activate oval cells, the hepatic stem cell (HSC) progeny, we used a model of liver injury induced by diet containing the porphyrinogenic agent, 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC). Deletion of c-met in oval cells was confirmed in both models by polymerase chain reaction analysis of fluorescence-activated cell-sorted epithelial cell adhesion molecule (EpCam)-positive cells. Loss of c-Met receptor decreased the sphere-forming capacity of oval cells in vitro as well as reduced oval cell pool, impaired migration, and decreased hepatocytic differentiation in vivo, as demonstrated by double immunofluorescence using oval- (A6 and EpCam) and hepatocyte-specific (i.e. hepatocyte nuclear factor 4-alpha) antibodies. Furthermore, lack of c-Met had a profound effect on tissue remodeling and overall composition of HSC niche, which was associated with greatly reduced matrix metalloproteinase (MMP)9 activity and decreased expression of stromal-cell-derived factor 1. Using a combination of double immunofluorescence of cell-type-specific markers with MMP9 and gelatin zymography on the isolated cell populations, we identified macrophages as a major source of MMP9 in DDC-treated livers. The Mx1-Cre-driven c-met deletion caused the greatest phenotypic impact on HSCs response, as compared to the selective inactivation in the epithelial cell lineages achieved in c-Met(fl/fl); Alb-Cre(+/-) mice. However, in both models, genetic loss of c-met triggered a similar cascade of events, leading to the failure of HSC mobilization and death of the mice.
Trends in Serum Cholesterol Levels from 1980 to 1987
Authors: Gregory L. Burke, J. Michael Sprafka, Aaron R. Folsom, Lorraine P. Hahn, Russell V. Luepker, Henry Blackburn
Journal: New England Journal of Medicine (1991)

We assessed community trends in the awareness, treatment, and control of hypercholesterolemia (defined as a serum cholesterol level ≥6.21 mmol per liter [240 mg per deciliter]) during the 1980s in the Minneapolis—St. Paul (Twin Cities) metropolitan area. Twin Cities residents 25 to 74 years old participated in independent, cross-sectional, population-based surveys of risk factors for cardiovascular disease in 1980–1982 (n = 3365) and 1985–1987 (n = 4545).
Juvenile onset inflammatory bowel disease: height and body mass index in adult life
Authors: A Ferguson, D M Sedgwick
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To establish the frequency of permanent growth failure in juvenile onset inflammatory bowel disease. <b>Design</b> : Measurement of height and weight in a geographically based cohort at a mean of 14 (range 5.2-29.5) years after diagnosis. Comparison with data from surveys of British adults in 1980 and 1987. <b>Setting</b> : NHS hospitals throughout Scotland. Subjects - 105 Children admitted to hospital during 1968-83 who fulfilled diagnostic criteria for Crohn9s disease or ulcerative colitis and lived in specified regions. 87 were aged over 18 and living in Britain at follow up. <b>Main outcome measures</b> : Height, weight, body mass index, and sexual maturity. <b>Results</b> : All patients were sexually mature. 67 of the 70 patients examined were of normal height, and three women with Crohn9s disease were abnormally short. Weight and body mass index were normal in all patients with ulcerative colitis. Patients with Crohn9s disease had significantly lower weight than those with ulcerative colitis (men 66.8 (9.5) kg v 78.4 (13.8) kg, P=0.04; women 51.5 (8.2) kg v 63.0 (12.1) kg, P&lt;0.02) irrespective of disease activity. Body mass index was also significantly lower than the normal distribution (P&lt;0.01). Growth retardation was not mentioned as a problem for any of the 17 patients interviewed only by telephone. <b>Conclusions</b> : Despite growth retardation in the teenage years most young people with inflammatory bowel disease will eventually achieve normal height. Reasons for lower weight in patients with Crohn9s disease remain to be established.
Post-natal endothelial progenitor cells for neovascularization in tissue regeneration
Authors: H Masuda
Journal: Cardiovascular Research (2003)

The isolation of endothelial progenitor cells (EPCs) derived from bone marrow (BM) was an outstanding event in the recognition of 'de novo vessel formation' in adults occurring as physiological and pathological responses. The finding that EPCs home to sites of neovascularization and differentiate into endothelial cells (ECs) in situ is consistent with 'vasculogenesis', a critical paradigm well described for embryonic neovascularization, but proposed recently in adults in which a reservoir of stem or progenitor cells contributes to vascular organogenesis. EPCs have also been considered as therapeutic agents to supply the potent origin of neovascularization under pathological conditions. This review provides an update of EPC biology as well as highlighting their potential use for therapeutic regeneration.
The Whole Internist Catalog. A Compendium of Clues to Diagnosis and Management.
Authors: Milton J. Chatton
Journal: Annals of Internal Medicine (1981)

This book is the product of the work of five authors who are associated with the University of New York Upstate Medical Center and Veterans Administration Medical Center, Syracuse, NY.  The authors indicate that the book is not meant to be a comprehensive manual of procedures, therapeutic methods, and laboratory medicine, but is an attempt to present answers to some common, practical problems. A broad range of selected topics in internal medicine is generously interspersed with lists, tables, aphorisms, mnemonics, shortcuts, word derivations, and diagnostic and therapeutic pearls. Brief discussions of medicolegal considerations, human sexuality, cost containment, and other special aspects of patient management are included. There are supporting references for each section.  The subject matter of The Whole Internist Catalog is presented in an entertaining but rather unorthodox manner. Reader interest is supposedly enhanced with eye-catching subject titles, eg, Z-Z-Z-Z-Z-Z (for snoring); It's a Gas (for flatulence); Cooked Goose