tbuckley/cabot-search huggingface dataset:
The Effect of Corticosteroid Treatment on Pulmonary Function in Sarcoidosis
Authors: H. Smellie, G. H. Apthorp, R. Marshall
Journal: Thorax (1961)

Previous studies have shown that pulmonary function in sarcoidosis may be impaired in various ways.The vital capacity and lung volume may be reduced (Bruce and Wassen, 1940; Austrian, McClement, Renzetti, Donald, Riley, and Cournand, 1951), an emphysema pattern with increased residual volume and impaired mixing may be demonstrated (Stone,
Pure Natural Orifice Translumenal Endoscopic Surgery (NOTES) Transvaginal Nephrectomy
Authors: Jihad H. Kaouk, Georges-Pascal Haber, Raj K. Goel, Sebastien Crouzet, Stacy Brethauer, Farzeen Firoozi, Howard B. Goldman, Wesley M. White
Journal: European Urology (2009)
Regulation of capacitative calcium influx in cultured human mesangial cells
Authors: P Menè, F Pugliese, G A Cinotti
Journal: Journal of the American Society of Nephrology (1996)

Sustained Ca2+ influx follows discharge of intracellularly stored Ca2+ in a variety of cell types previously equilibrated in Ca(2+)-free media, including cultured human mesangial cells. This Ca2+ influx pathway has been referred to as capacitative Ca2+ entry or Ca2+ release-activated Ca2+ influx (iCRAC). This study investigated two cellular mechanisms potentially controlling iCRAC in human mesangial cells, protein kinase C (PKC), a key signalling kinase activated by vasoconstrictors that release Ca2+ from internal stores, and calmodulin, a Ca(2+)-binding protein that may couple Ca2+ release to the putative channel(s). The PKC activator phorbol myristate acetate (PMA) dose-dependently inhibited both Ca2+ influx in resting cells and iCRAC, assessed by microfluorometry in fura-2-loaded monolayers, when added before or after 1 uM angiotensin II (AngII) (Ca2+ influx at 1 mM (Ca2+)e +278 +/- 56%/+80 +/- 8%, at 10 mM + 473 +/- 59%/+250 +/- 24% (Ca2+)e, -/+ PMA, respectively, P < 0.05). PMA did not affect 5 uM ionomycin-induced iCRAC, possibly because it downregulated Ca2+ release by AngII but not by ionomycin, suggesting a key role of released Ca2+ in triggering subsequent Ca2+ influx. This was confirmed by buffering the (Ca2+)i elevation induced by AngII with intracellularly trapped 1,2-bis-(0-Aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA), which abolished any subsequent iCRAC. Moreover, the calmodulin inhibitors calmidazolium (10 uM), trifluoperazine (0.1 mM), or W-7 (0.1 mM) significantly inhibited AngII- or ionomycin-activated iCRAC (+106 +/- 38/229 +/- 53, +58 +/- 9/195 +/- 29, +161 +/- 38/180 +/- 40% at 1/10 mM (Ca2+)e, all P < 0.05), but did not affect basal Ca2+ entry, consistent with a direct role of cytoplasmic Ca2+ in the regulation of ion gating. These results indicate that iCRAC is under the control of both PKC and calmodulin, and that the site of regulation is distal to the emptying of Ca2+ stores. iCRAC may represent a key mechanism for the control of Ca(2+)-regulated mesangial functions.
Mutations defining functional regions of the superantigen staphylococcal enterotoxin B.
Authors: J W Kappler, A Herman, J Clements, P Marrack
Journal: The Journal of Experimental Medicine (1992)

Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a superantigen, SEB can bind to major histocompatibility complex (MHC) class II molecules to form a ligand for alpha/beta T cell receptors bearing particular V beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading to death. We show here that both of these functions map to the NH2-terminal portion of the toxin. Three regions were identified: one important in MHC class II binding, one in T cell recognition, and one in both functions. These results support the conclusion that the toxicity of SEB is related to massive T cell stimulation and release of cytokine mediators and show that the residues interacting with MHC and the T cell receptor are intertwined.
Reduced dose and duration of peginterferon alfa-2b and weight-based ribavirin in patients with genotype 2 and 3 chronic hepatitis C
Authors: Michael Manns, Stefan Zeuzem, Ajit Sood, Yoav Lurie, Markus Cornberg, Hartwig Klinker, Peter Buggisch, Martin Rössle, Holger Hinrichsen, Ismail Merican, Yaron Ilan, Stefan Mauss, Saif Abu-Mouch, Andryes Horban, Thomas H. Müller, Christoph Welsch, Rongdean Chen, Rab Faruqi, Lisa D. Pedicone, Heiner Wedemeyer
Journal: Journal of Hepatology (2011)
Does the use of per cent of predicted have any evidence base?
Authors: Martin R. Miller
Journal: European Respiratory Journal (2015)

Over 20 years ago there was a move to require an evidence base for the practice of medicine [1]. It is easy to understand that any new treatment or management strategy should have a firm evidence base to support its proposed use. However, implicit in a move to evidence-based practice is that one should repeatedly question all aspects of current practice to be sure, firstly, that they ever had an evidence base and, secondly, that they continue to do so. Researchers and journals need to apply more scrutiny to the use of % predicted <http://ow.ly/EVNvQ>
Meta-Analysis of Efficacy of Interventions for Elevated Depressive Symptoms in Adults Diagnosed With Cancer
Authors: Stacey L. Hart, Michael A. Hoyt, Michael Diefenbach, Derek R. Anderson, Kristin M. Kilbourn, Lynette L. Craft, Jennifer L. Steel, Pim Cuijpers, David C. Mohr, Mark Berendsen, Bonnie Spring, Annette L. Stanton
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundCancer patients are at increased risk for depression compared with individuals with no cancer diagnosis, yet few interventions target depressed cancer patients.
Stimulation of insulin secretion by medium-chain triglycerides in patients with cirrhosis
Authors: F. S. McCullough, M. Tzagournis, N. J. Greenberger, W. G. Linscheer
Journal: Gut (1971)

Oral medium-chain triglycerides were given to 10 normal volunteers, 12 cirrhotics (group I) without and 28 cirrhotics (group II) with abnormal portal systemic communications (ascites, splenomegaly, oesophageal varices, or surgically-created portacaval shunts). After 30 ml of medium-chain triglyceride oil there was no appreciable change in serum glucose levels in any of the three groups nor in serum insulin levels in the normals and in cirrhotics in group I. However, there was a significant increase in serum insulin levels in the cirrhotic patients in group II. It is suggested that the rise in serum insulin levels after medium-chain triglycerides noted in the cirrhotics with shunts is due to shunting of insulin-containing portal blood around the liver (anatomical shunts) and to a diminished hepatic cell mass capable of extracting insulin (functional shunt). This differential response of serum insulin levels to medium-chain triglycerides may prove to be of value in detecting the presence of abnormal portal systemic communications in cirrhotic patients.
Symptomatic zinc deficiency in breast-fed premature infants
Authors: C.S. MUNRO, CAMILLE LAZARO, C.M. LAWRENCE
Journal: British Journal of Dermatology (1989)

Journal Article Symptomatic zinc deficiency in breast‐fed premature infants Get access C.S. MUNRO, C.S. MUNRO Departments of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Dr C.S.Munro, Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, Tyne and Wear NE1 4LP, U.K. Search for other works by this author on: Oxford Academic Google Scholar CAMILLE LAZARO, CAMILLE LAZARO Departments of Paediatrics, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar C.M. LAWRENCE C.M. LAWRENCE Departments of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 121, Issue 6, 1 December 1989, Pages 773–778, https://doi.org/10.1111/j.1365-2133.1989.tb08221.x Published: 01 December 1989
P335Sudden unexplained death in Catalonia: comprehensive genetic analysis in post-mortem samples
Authors: OE Sanchez-Molero, O Campuzano, C Allegue, E Selga, I Mademont, M Coll, J Mates, A Iglesias, J Medallo, R Brugada
Journal: Cardiovascular Research (2014)

Purpose: Cardiovascular pathologies are the main cause of sudden death in developed countries. In population older than 50 years old, most deaths are due to coronary disease alterations, in the young deaths may be caused by "monogenetic disorders", channelopathies, or cardiomyopathies. Genetic analysis is not routinely performed in autopsy protocol when a cause of death is not identified in the young. In recent years the development of next generation sequencing (NGS) technology allows the investigation of high number of genes in a short period of time at low cost. We launched the MOSCAT project, a prospective post-mortem study that aims to identify the genetic cause of death in cases that remains without a conclusive diagnosis after a complete autopsy. Methods: Our cohort included a total of 88 cases: <50 years old, and no-conclusive cause of death after complete autopsy investigation. We divided the cohort into two groups, depending on DNA quality for NGS analysis. The first group included 59 samples with low quality. The main seven arrhythmogenic genes (KCNQ1, KCNH2, KCNE1, KCNE2, KCNE3, RYR2 and SCN5A) were analyzed using Sanger method. The second group included 43 samples analyzed by NGS, a total of 55 genes associated with SCD were analyzed. Potentially pathogenic role was determined when minor allele frequency (MAF) was less than 1% and at least one in silico prediction. A total of 14 samples were analyzed using both methods as internal control. Results: Our cohort of 88 samples showed a gender ratio of 2:1 (men: women respectively). In group 1 (sanger, 59 samples) we identified 30% arrythmogenic mutation carriers. In group 2 (NGS, 43 samples) we identified 15% arrythmogenic mutations and 85% associated with structural cardiomyopathies. Acording to age in group 1 we identified 27% mutations in patients younger than 35 and 34% in older than 35. By NGS we identified 50% arrythmogenic mutations and 50% structural mutations in less than 35 and 40% arrythmogenic mutations and 60% structural mutations in older than 35. Conclusions: In patients younger than 50, we identified arrythmogenic mutations in 25% and structural mutations in 70% of cases studied. Nearly 30% of post-mortem cases minor than 50 years with a no-conclusive cause of death carry a potential pathogenic variation that could explain the death. NGS technology adds additional information and may be useful in the identification of genetic causality. We believe that genetic analysis should be included in routine forensic guidelines when a no-conclusive cause of death arises, especially in cases under 35 years old.
Molecular regulation of pancreatic stellate cell function.
Authors: Robert Jaster
Journal: Molecular Cancer (2004)

Until now, no specific therapies are available to inhibit pancreatic fibrosis, a constant pathological feature of chronic pancreatitis and pancreatic cancer. One major reason is the incomplete knowledge of the molecular principles underlying fibrogenesis in the pancreas. In the past few years, evidence has been accumulated that activated pancreatic stellate cells (PSCs) are the predominant source of extracellular matrix (ECM) proteins in the diseased organ. PSCs are vitamin A-storing, fibroblast-like cells with close morphological and biochemical similarities to hepatic stellate cells (also known as Ito-cells). In response to profibrogenic mediators such as various cytokines, PSCs undergo an activation process that involves proliferation, exhibition of a myofibroblastic phenotype and enhanced production of ECM proteins. The intracellular mediators of activation signals, and their antagonists, are only partially known so far. Recent data suggest an important role of enzymes of the mitogen-activated protein kinase family in PSC activation. On the other hand, ligands of the nuclear receptor PPARγ (peroxisome proliferator-activated receptor γ) stimulate maintenance of a quiescent PSC phenotype. In the future, targeting regulators of the PSC activation process might become a promising approach for the treatment of pancreatic fibrosis.
Pathobiology of cast nephropathy from human Bence Jones proteins.
Authors: P W Sanders, B B Booker
Journal: Journal of Clinical Investigation (1992)

Renal failure is a common accompaniment of multiple myeloma and is usually due to cast nephropathy, or "myeloma kidney." To understand this lesion, four human Bence Jones proteins (BJP) were purified from the urine of volunteers who had either no evidence of renal dysfunction (BJP1) or renal failure from cast nephropathy (BJP2, BJP3, BJP4). When infused directly into the rat nephron in vivo, BJP2, BJP3, and BJP4 produced intraluminal obstruction by precipitating in the distal nephron; protein casts were never identified before the tip of the loop of Henle. Obstruction was related to the concentration of BJP in the perfusate. Addition of furosemide to the perfusate augmented obstruction in a concentration-dependent fashion. Pretreatment of rats with colchicine completely prevented obstruction and cast formation of perfused nephrons; beta-lumicolchicine did not prevent obstruction. Tamm-Horsfall glycoprotein purified from beta-lumicolchicine-treated and untreated rats coaggregated with BJP3 in vitro. Tamm-Horsfall glycoprotein from colchicine-treated rats did not contain sialic acid and did not aggregate with BJP3 in vitro. Thus, cast-forming human BJP coaggregated with Tamm-Horsfall glycoprotein and obstructed the rat distal nephron. Intranephronal obstruction was aggravated by decreasing extracellular fluid volume or adding furosemide. Finally, by decreasing secretion and altering the carbohydrate moiety of Tamm-Horsfall glycoprotein, colchicine prevented intraluminal cast formation and obstruction of the rat nephron.
Relation of disease activity during chronic hepatitis C infection to complexity of hypervariable region 1 quasispecies
Authors: N Yuki, N Hayashi, T Moribe, Y Matsushita, T Tabata, T Inoue, Y Kanazawa, K Ohkawa, A Kasahara, H Fusamoto, T Kamada
Journal: Hepatology (1997)

ABSTRACT We studied the heterogeneity in the E2/NS1 hypervariable region 1 of the hepatitis C virus (HCV) genome in relation to the natural course after infection. The subjects were composed of 38 chronic hepatitis C carriers who had been followed for 9 to 218 months after the onset of non–A, non–B (type C) hepatitis, being tested monthly for serum alanine aminotransferase levels. The complexity of the sequence heterogeneity was assessed by single–strand conformation polymorphism analysis. The quasispecies complexity had no relation to the route of infection, the time from infection and the duration of aminotransferase elevation after the onset. However, it had a significant relationship with the degree of aminotransferase elevation in the course of the disease. The quasispecies complexity was directly correlated with the first peak of serum aminotransferase at the onset ( r = .48, P &lt; .01) and the mean aminotransferase levels during the period of persistent aminotransferase elevation ( r = .58, P &lt; .01). Twenty–three of the 38 patients were further followed for 24 months with biweekly alanine transaminase (ALT) tests. Their aminotransferase levels remained within the normal range during follow–up, and no significant change was seen in the quasispecies complexity after this asymptomatic period. However among the 23 patients, the quasispecies complexity increased in six cases (26%) and decreased in five (22%). A significant direct relation was seen between changes in the quasispecies complexity and the mean aminotransferase levels during the asymptomatic period ( r = .55, P = .01). These findings suggest that the development of the HCV quasispecies nature may be related to the severity of the hepatitis in the course of infection.
Electrical activity of the external anal sphincter at different ages in childhood.
Authors: M L Molander, B Frenckner
Journal: Gut (1983)

In EMG recordings of the external anal sphincter there is a brief contraction in response to rapid rectal distension, and a preserved or increased activity during a prolonged substantial rectal distension in healthy adults. In order to determine if this activity develops during childhood 30 healthy children, aged 2 months to 15 years, were examined with their parents9 consent. EMG of the external anal sphincter during rest and during rectal distension was performed. All those children who had gained voluntary anal control showed an EMG recording similar to the adults. The 10 youngest children who had not gained voluntary control showed another EMG pattern. Instead of a brief contraction they had a brief loss of activity in response to rectal distension. During a prolonged rectal distension the external sphincter activity decreased and finally ceased. An intermediate state was found in the two youngest children who had gained voluntary control. The EMG pattern showed a good correlation with the maturation and gain of voluntary control of defaecation.
More than a context for learning? The epistemic triangle and the dialogic mind
Authors: Charles Fernyhough
Journal: Behavioral and Brain Sciences (2004)

Theory-of-mind (TOM) competence is under-specified in Carpendale &amp; Lewis's (C&amp;L's) account. In the neo-Vygotskian alternative outlined below, TOM development is driven by the internalisation of dialogic exchanges which preserve the triadic intentional relations of interactions within the epistemic triangle. On this view, TOM competence stems from children's ability to operate flexibly with the multiple perspectives manifested in internalised dialogue.
Membrane Cofactor Protein (MCP or CD46): Newest Member of the Regulators of Complement Activation Gene Cluster
Authors: M K Liszewski, T W Post, J P Atkinson
Journal: Annual Review of Immunology (1991)

Membrane cofactor protein (MCP; CD46) is a widely distributed C3b/C4b-binding cell surface glycoprotein which serves as an inhibitor of complement activation on host cells. The protein has been purified, multiple cDNAs cloned and sequenced, and the genomic organization determined. MCP belongs to a family known as the regulators of complement activation (RCA) gene cluster. The RCA members are related structurally [possess approximately 60 amino acid repeating motifs termed short consensus repeats (SCR)], functionally (bind C3b/C4b), and genetically (genes are tightly clustered on chromosome 1 at q3.2). Beginning at its amino-terminus, MCP is composed of four SCRs, a ser/thr/pro-enriched region, an area of undefined function, a transmembrane hydrophobic domain, a cytoplasmic anchor and cytoplasmic tail. On SDS-PAGE, MCP migrates as two broad forms with Mrs of 59,000-68,000 and 51,000-58,000. The quantity of each form expressed is inherited in an autosomal codominant fashion. This structural heterogeneity is partly explained by the expression of multiple cDNA/protein isoforms that arise by alternative splicing of ser/thr/pro-rich exons (sites of heavy O-glycosylation) and of cytoplasmic tails. This protein is of interest to immunologists and clinicians because of its role in regulation of the complement pathways and, therefore, inflammation in immune complex-mediated syndromes; to reproductive immunologists on account of its expression on sperm and at the maternal-fetal interface; and to tumor immunologists because of its high expression on malignant cells. The availability of monoclonal and polyclonal antibodies and molecular probes will be helpful in addressing questions about the biology of MCP in these and other areas.
Reduced Functional Expression and Molecular Synthesis of Inducible Nitric Oxide Synthase in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats
Authors: Julie Y.H. Chan, Ling-Lin Wang, Kay L.H. Wu, Samuel H.H. Chan
Journal: Circulation (2001)

Background We demonstrated recently that the prevalence of neuronal (nNOS) over inducible (iNOS) nitric oxide synthase activity at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone, and the associated dominance of sympathoexcitation over sympathoinhibition underlie the maintenance of sympathetic vasomotor outflow by the endogenous NO. Here, we evaluated the hypothesis that a significant downregulation of iNOS at the RVLM may play a crucial role in the genesis of augmented sympathetic vasomotor tone during hypertension. Methods and Results Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized with propofol were used. Compared with SHR, the hypotension, bradycardia, or depression in sympathetic vasomotor tone induced by bilateral microinjection of lipopolysaccharide (5 or 10 ng) into the RVLM of WKY rats exhibited significantly shorter-onset latency, appreciably steeper slope, and a greater incidence of mortality. All these effects of lipopolysaccharide (10 ng) were significantly blunted by coadministration of the selective iNOS inhibitor S -methylisothiourea (250 pmol). Reverse transcription-polymerase chain reaction and Western blot analyses further revealed significantly lower iNOS mRNA and protein levels at the ventrolateral medulla in SHR under basal conditions or on activation by lipopolysaccharide (10 ng). Conversely, nNOS mRNA and protein levels remained constant in the RVLM and were comparable in both strains of rats. Conclusions We conclude that a significant downregulation in both functional expression and molecular synthesis of iNOS at the RVLM may underlie the augmented sympathetic vasomotor tone during hypertension.
Impact of Oral Antihyperglycemic Therapy on All-Cause Mortality Among Patients With Diabetes in the Veterans Health Administration
Authors: Kristijan H. Kahler, Mangala Rajan, George G. Rhoads, Monika M. Safford, Kitaw Demissie, Shou-En Lu, Leonard M. Pogach
Journal: Diabetes Care (2007)

The objective of this analysis was to evaluate the impact of several classes of oral antihyperglycemic therapy relative to sulfonylurea monotherapy on all-cause mortality among a cohort of patients with diabetes from the Veterans Health Administration (VHA).A retrospective cohort study using data obtained from the VHA Diabetes Epidemiology Cohort was used. Users of oral antihyperglycemic therapy were classified into the following cohorts: sulfonylurea monotherapy, metformin monotherapy, metformin plus sulfonylurea, thiazolidinedione (TZD) use alone or in combination with other oral agents (TZD users), and no drug therapy. All-cause mortality was the outcome of interest. Multivariate mixed models incorporating a propensity score to account for imbalance among cohorts were used to estimate drug effects on mortality with associated 95% CIs.A total of 39,721 patients with diabetes were included in the study. Adjusted odds ratios and 95% CIs for all-cause mortality were 0.87 (0.68-1.10) for metformin monotherapy users, 0.92 (0.82-1.05) for metformin plus sulfonylurea users, and 1.04 (0.75-1.46) for TZD users, relative to sulfonylurea monotherapy users.We did not find any significant drug effect on all-cause mortality for any oral treatment cohorts relative to sulfonylurea oral monotherapy.