tbuckley/cabot-search huggingface dataset:
Short-Term Administration of a Cell-Permeable Caveolin-1 Peptide Prevents the Development of Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy
Authors: Jean-François Jasmin, Isabelle Mercier, Jocelyn Dupuis, Herbert B. Tanowitz, Michael P. Lisanti
Journal: Circulation (2006)

Caveolins (Cavs), the principal structural proteins of caveolar microdomains, have been implicated in the development of pulmonary hypertension (PH). Mice with homozygous deletion of the Cav-1 gene develop PH and right ventricular hypertrophy (RVH). Reductions in pulmonary Cav-1 expression have been shown in several animal models of PH and in patients with severe PH. Whether in vivo modulation of Cav-1 expression could affect the development of PH and RVH remains unknown. Therefore, we investigated the effect of in vivo administration of a Cav-1 mimetic peptide on the development of monocrotaline (MCT)-induced PH.Thirty minutes after injection of saline or 60 mg/kg MCT, rats were assigned to receive a daily injection of saline, a peptide corresponding to the homeodomain of the Drosophila transcription factor antennapedia (AP; 2.5 mg x kg(-1) x d(-1)), or a peptide consisting of the Cav-1-scaffolding domain coupled to AP (AP-Cav; 2.5 mg x kg(-1) x d(-1)) for 2 weeks. MCT and MCT+AP rats developed PH with respective right ventricular systolic pressures of 40.2 +/- 1.5 and 39.6 +/- 1.5 mm Hg. Administration of AP-Cav to MCT rats significantly reduced the right ventricular systolic pressure to 30.1 +/- 1.3 mm Hg. MCT and MCT+AP rats also developed pulmonary artery medial hypertrophy and RVH, which was normalized by administration of AP-Cav. Mechanistically, the development of PH was associated with reduced expression of pulmonary Cav-1 and Cav-2, hyperactivation of the STAT3 signaling cascade, and upregulation of cyclin D1 and D3 protein levels, all of which were prevented by administration of AP-Cav.Short-term administration of a Cav-based cell-permeable peptide to MCT rats prevents the development of pulmonary artery medial hypertrophy, PH, and RVH.
SDF-1 Genotype Influences Insulin-Dependent Mobilization of Adult Progenitor Cells in Type 2 Diabetes
Authors: Per M. Humpert, Renate Neuwirth, Marco J. Battista, Olga Voronko, Maximilian von Eynatten, Ilze Konrade, Gottfried Rudofsky, Thoralf Wendt, Andreas Hamann, Michael Morcos, Peter P. Nawroth, Angelika Bierhaus
Journal: Diabetes Care (2005)

CD34+/CD133+ circulating adult progenitor cells (PCs) play an important role in tissue repair in metabolic disease. PCs have a certain plasticity to differentiate into cells with tissue-specific phenotypes (1–3). In diabetic mice, therapeutic use of PCs in models of hindlimb ischemia and wound healing was particularly effective, suggesting a diabetes-dependent defect in PC function (4,5). Accordingly, in vitro outgrowth and angiogenic function of endothelial PCs differentiating from PCs (1) is diminished in patients with cardiovascular risk factors and in type 1 and type 2 diabetes (6–8). From clinical studies it is evident that insulin therapy is a factor determining cardiovascular complications and mortality in diabetes (9,10). It can therefore be speculated that insulin might influence mobilization of PCs in type 2 diabetes. In view of the strong genetic background for the development of late diabetes complications, we asked whether the SDF1-3′A/G genotype known to enhance PC mobilization (11) might be of influence.

In the pilot study presented here, we quantified the number of PCs by flourescence-activated cell sorter (FACS) analysis in 23 patients with poorly controlled type 2 diabetes (HbA1c 10.6 ± 1.6%, fasting glucose 15.9 ± 4.5 mmol/l) and 10 age-matched control subjects (59 ± 14 vs. 58 ± 10 years) without history of diabetes (HbA1c 5.4 ± 0.5%). After 5.4 ± 1.6 weeks of treatment with (additional) insulin, 11 patients from this cohort had a follow-up measurement of PCs. Adequate insulin supplementation was documented by a lowering of HbA …
Host ER–parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in <i>Toxoplasma gondii</i>–infected dendritic cells
Authors: Romina S. Goldszmid, Isabelle Coppens, Avital Lev, Pat Caspar, Ira Mellman, Alan Sher
Journal: The Journal of Experimental Medicine (2009)

Toxoplasma gondii tachyzoites infect host cells by an active invasion process leading to the formation of a specialized compartment, the parasitophorous vacuole (PV). PVs resist fusion with host cell endosomes and lysosomes and are thus distinct from phagosomes. Because the parasite remains sequestered within the PV, it is unclear how T. gondii-derived antigens (Ag's) access the major histocompatibility complex (MHC) class I pathway for presentation to CD8(+) T cells. We demonstrate that recruitment of host endoplasmic reticulum (hER) to the PV in T. gondii-infected dendritic cells (DCs) directly correlates with cross-priming of CD8(+) T cells. Furthermore, we document by immunoelectron microscopy the transfer of hER components into the PV, a process indicative of direct fusion between the two compartments. In strong contrast, no association between hER and phagosomes or Ag presentation activity was observed in DCs containing phagocytosed live or dead parasites. Importantly, cross-presentation of parasite-derived Ag in actively infected cells was blocked when hER retrotranslocation was inhibited, indicating that the hER serves as a conduit for the transport of Ag between the PV and host cytosol. Collectively, these findings demonstrate that pathogen-driven hER-PV interaction can serve as an important mechanism for Ag entry into the MHC class I pathway and CD8(+) T cell cross-priming.
TRANSCRIPTIONAL REGULATION DURING B CELL DEVELOPMENT
Authors: Andrew Henderson, Kathryn Calame
Journal: Annual Review of Immunology (1998)

▪ Abstract Information is increasingly available concerning the molecular events that occur during primary and antigen-dependent stages of B cell development. In this review the roles of transcription factors and coactivators are discussed with respect to changes in expression patterns of various genes during B cell development. Transcriptional regulation is also discussed in the context of developmentally regulated immunoglobulin gene V(D)J recombination, somatic hypermutation, and isotype switch recombination.
TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies
Authors: Stefanie J Klug, Meike Ressing, Jochem Koenig, Martin C Abba, Theodoros Agorastos, Sylvia MF Brenna, Marco Ciotti, BR Das, Annarosa Del Mistro, Aleksandra Dybikowska, Anna R Giuliano, Zivile Gudleviciene, Ulf Gyllensten, Andrea LF Haws, Aslaug Helland, C Simon Herrington, Alan Hildesheim, Olivier Humbey, Sun H Jee, Jae Weon Kim, Margaret M Madeleine, Joseph Menczer, Hextan YS Ngan, Akira Nishikawa, Yoshimitsu Niwa, Rosemary Pegoraro, MR Pillai, Gulielmina Ranzani, Giovanni Rezza, Adam N Rosenthal, Susanta Roychoudhury, Dhananjaya Saranath, Virginia M Schmitt, Sharmila Sengupta, Wannapa Settheetham-Ishida, Hiroshi Shirasawa, Peter JF Snijders, Mark H Stoler, Angel E Suárez-Rincón, Krisztina Szarka, Ruth Tachezy, Masatsugu Ueda, Ate GJ van der Zee, Magnus von Knebel Doeberitz, Ming-Tsang Wu, Tsuyoshi Yamashita, Ingeborg Zehbe, Maria Blettner
Journal: The Lancet Oncology (2009)
Late Onset Invasive Pneumococcal Disease in a Patient with IRAK4 Deficiency
Authors: Michael David O'Sullivan, Catherine Stroud, Mario Abinun, Rainer Doffinger, Steven O'Reilly, Marzena Ciechomska, Dawn Barge, Rebecca Treacy, Stephen Owens, Terry Flood, Andrew Gennery, Sophie Hambleton
Journal: Journal of Allergy and Clinical Immunology (2013)
Patients with acute on chronic liver failure display ‘sepsis-like’ immune paralysis
Authors: Hermann E. Wasmuth, Dagmar Kunz, Eray Yagmur, Annette Timmer-Stranghöner, Daniel Vidacek, Elmar Siewert, Jens Bach, Andreas Geier, Edmund A. Purucker, Axel M. Gressner, Siegfried Matern, Frank Lammert
Journal: Journal of Hepatology (2004)
Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes
Authors: Marica Bordicchia, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Paolo Dessì-Fulgheri, Chaoying Zhang, Nobuyuki Takahashi, Riccardo Sarzani, Sheila Collins
Journal: Journal of Clinical Investigation (2012)

The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C(-/-) mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology.
Lung function, CT-scan and X-ray in upper airway obstruction due to thyroid goitre
Authors: CF Melissant, SJ Smith, R Perlberger, J Verschakelen, JW Lammers, M Demedts
Journal: European Respiratory Journal (1994)

The purpose of this study was to assess the clinical reliability and to compare routine lung function tests (maximal flows and resistance) and radiological images (computed tomography (CT)-scan and X-ray) in upper airway obstruction. We, therefore, performed these examinations prospectively in 28 female patients (aged 68 +/- 13 yrs) with a goitre and without pulmonary disorders. Lung function measurements consisted of maximum expiratory and inspiratory flow-volume curves and of airway resistance. CT-scans and X-rays were performed during apnoea at functional residual capacity (FRC). Peak expiratory flow was 3.6 +/- 1.3 l.s-1 (i.e. 62 +/- 21% predicted); airway resistance was 0.38 +/- 0.14 kPa (i.e. 149 +/- 58% pred); and specific conductance was 1.0 +/- 0.3 kPa (i.e. 70 +/- 24% pred). Almost all lung function tests were significantly correlated with each other. On CT-scan the tracheal cross-sectional area at the zone of tracheal narrowing could be evaluated in 26 patients and was 58 +/- 17% (CT1/2) of the control area 2 cm above the carina (CT2). On X-ray the sagittal and coronal tracheal diameters at the zone of narrowing could only be measured in 16 subjects and were 60 +/- 17% (X-dia1/2) of the diameter at the control level. CT1/2 and X-dia1/2 were significantly correlated to each other. No correlation was found between the lung function tests and the radiological indices except airway resistance and CT2. Routine lung function and CT-scan do not provide comparable information on the degree of airway obstruction due to a goitre.(ABSTRACT TRUNCATED AT 250 WORDS)
Suppression of inflammation in ulcerative colitis by interferon- -1a is accompanied by inhibition of IL-13 production
Authors: P. J. Mannon, R. L. Hornung, Z. Yang, C. Yi, C. Groden, J. Friend, M. Yao, W. Strober, I. J. Fuss
Journal: Gut (2010)

<h3>Objective</h3> Ulcerative colitis is associated with increased interleukin 13 (IL-13) production by natural killer T cells. Taking advantage of the inhibitory actions of interferon β on IL-13 expression, this proof-of-concept study aimed to show that decreasing IL-13 production is associated with clinical improvement of ulcerative colitis symptoms. <h3>Design</h3> Open-label interventional drug trial. <h3>Setting</h3> Outpatient clinical research hospital. <h3>Patients</h3> Adult patients with active ulcerative colitis (Short Clinical Colitis Activity Index (SCCAI)≥5). <h3>Interventions</h3> Treatment with 30 μg IM interferon-β-1a (Avonex) weekly for 12 weeks with 6 month follow-up. <h3>Main outcome measures</h3> Clinical response was defined as ≥3 point drop in the SCCAI for at least two consecutive monitoring visits, and cytokine production was measured in cultured peripheral blood and lamina propria mononuclear cells (LPMC) before and after treatment. <h3>Results</h3> 11 of 16 patients were clinical responders, and 4 were in remission (SCCAI ≤ 2) at the end of treatment. Rectal bleeding subscores improved dramatically by week 4 (38% with frank bleeding vs 87% pretreatment). Increased IL-13 production by LPMC T cells fell significantly in clinical responders (690±99 vs 297±58 pg/ml p=0.015) but was unchanged in non-responders (542±83 vs 510±39 pg/ml). In addition, non-responders had significantly higher production of IL-17 and IL-6 pre-treatment compared to responders. <h3>Conclusions</h3> Interferon-β-1a induces clinical response and remission in a large subset of patients with ulcerative colitis that is associated with significant inhibition of IL-13 production. In addition, increased IL-17 and IL-6 production is associated with no response to interferon-β. These data provide a proof-of-concept that IL-13 is an effector cytokine in ulcerative colitis and should be a target for novel therapies.
Functional analysis of<i>ABCB4</i>mutations relates clinical outcomes of progressive familial intrahepatic cholestasis type 3 to the degree of MDR3 floppase activity
Authors: Raquel Gordo-Gilart, Sara Andueza, Loreto Hierro, Pilar Martínez-Fernández, Daniel D'Agostino, Paloma Jara, Luis Alvarez
Journal: Gut (2014)

<h3>Objective</h3> Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a potentially lethal autosomal recessive liver disease associated with mutations in <i>ABCB4</i>, the gene encoding the canalicular translocator of phosphatidylcholine MDR3. While some affected children benefit from ursodeoxycholic acid (UDCA) therapy, others evolve to end-stage liver disease. We aimed to evaluate whether these different outcomes are related to the impact of <i>ABCB4</i> mutations. <h3>Design</h3> Six children with PFIC3 were investigated by sequencing of <i>ABCB4</i> exons and flanking intron-exon boundaries and by immunohistochemistry. <i>ABCB4</i> missense mutations were phenotyped in vitro by assessing their effects on MDR3 expression, subcellular localisation, and phosphatidylcholine-translocating activity. The resulting data were contrasted with the clinical outcomes. <h3>Results</h3> Eight distinct <i>ABCB4</i> mutations were identified: one nonsense, one splicing and six missense mutations, four of which (G68R, T201M, P479L, D459H) affected MDR3 expression level. G68R and D459H also led to retention of the protein in endoplasmic reticulum. Phosphatidylcholine efflux assays indicated that T201M, P479L, S978P and E1118K mutations impaired MDR3 activity to variable degrees. Three children with mutations that caused a total loss of MDR3 expression/function manifested progressive liver disease refractory to UDCA treatment. This was also the case in a patient carrying two different mutations that, in combination, resulted in a 90% reduction in total MDR3 activity. A favourable response to UDCA was achieved in two patients with estimated MDR3 activities of 50% and 33%, respectively. <h3>Conclusions</h3> These data provide experimental evidence of the correlation between the degree of MDR3 floppase activity and the clinical outcomes of PFIC3.
Clinical characteristics of type 1 diabetic patients with and without severe hypoglycemia.
Authors: E W ter Braak, A M Appelman, M van de Laak, R P Stolk, T W van Haeften, D W Erkelens
Journal: Diabetes Care (2000)

To investigate the frequency of severe hypoglycemia (SH) and hypoglycemic coma and to identify clinical and behavioral risk indicators in a nonselected population of type 1 diabetic patients.This study involved a retrospective clinical survey of 195 consecutive patients using a questionnaire addressing the frequency of SH (i.e., help from others required) and hypoglycemic coma during the previous year, general characteristics, behavior, hypoglycemia awareness, and the Hypoglycemia Fear Survey Data regarding diabetes, treatment, long-term complications, comorbidity, and comedication were obtained from the patients' medical records.A total of 82% of subjects were receiving intensive insulin treatment, and mean +/- SD HbA(1c) was 7.8 +/- 1.2%. Mean duration of diabetes was 20 +/- 12 years. The occurrence of SH (including hypoglycemic coma) was 150 episodes/100 patient-years and affected 40.5% of the population. Hypoglycemic coma occurred in 19% of subjects (40 episodes/100 patient-years). SH without coma was independently related to nephropathy (odds ratio [OR] 4.8 [95% CI 1.5-15.1]), a threshold for hypoglycemic symptoms of <3 mmol/l (4.8 [1.8-12.0]), and a daily insulin dose 0.1 U/kg higher (1.3 [1.0-1.6]) (all ORs were adjusted for diabetes duration and use of comedication). Hypoglycemic coma was independently related to neuropathy (3.9 [1.5-10.4]), (nonselective) beta-blocking agents (14.9 [2.1-107.4]), and alcohol use (3.5 [1.3-9.1]) (all ORs were adjusted for diabetes duration).SH and hypoglycemic coma are common in a nonselected population with type 1 diabetes. The presence of long-term complications, a threshold for symptoms of <3 mmo/l, alcohol use, and (nonselective) beta-blockers were associated with SH during the previous year. If prospectively confirmed, these results may have consequences for clinical practice.
Dilutions of corticosteroids
Authors: P. M. Gaylarde
Journal: British Journal of Dermatology (1980)

Journal Article Dilutions of corticosteroids Get access P. M. Gaylarde P. M. Gaylarde Royal Free Hospital, Pond Street, London NW3 2QG Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 103, Issue 1, 1 July 1980, Pages 119–120, https://doi.org/10.1111/j.1365-2133.1980.tb15852.x Published: 01 July 1980
HEAVY CHAIN SUBCLASSES OF HUMAN γG-GLOBULIN
Authors: G. M. Bernier, R. E. Ballieux, K. T. Tominaga, F. W. Putnam
Journal: The Journal of Experimental Medicine (1967)

Two antigenic types of naturally occurring proteins related to the papain produced F(c) fragment of gammaG-globulin have been studied. Most normal and myeloma gammaG-globulins are related to one or the other of these proteins, based on antigenic and structural characteristics of their heavy chain. Molecules bearing the determinant "Cr" are approximately 10 times as abundant as those bearing the determinant termed "Zu" in pools of normal gammaG-globulin and among a large group of gammaG-myeloma globulins. Both populations have properties of typical gammaG-globulin antibodies. Splenic cells, stained for these two populations with specific fluorescent antibody preparations, are found to contain one or the other of the two populations of gammaG-globulin, but not both. Approximately 10 times as many cells contain the Cr determinant as contain the Zu determinant.
Advances in Targeting Src in the Treatment of Breast Cancer and Other Solid Malignancies
Authors: Erica L. Mayer, Ian E. Krop
Journal: Clinical Cancer Research (2010)

Src, a membrane-associated nonreceptor tyrosine kinase, plays a crucial role in the coordination and facilitation of cell-signaling pathways controlling a wide range of cellular functions, including growth, survival, invasion, adhesion, and migration. Deregulation and increased activity of Src has been observed in multiple human malignancies, prompting the development of specific inhibitors of Src. In preclinical studies, Src inhibitors show antitumor effects in multiple solid tumor types. Recently completed early-phase trials using the inhibitors dasatinib and bosutinib have suggested modest activity as monotherapy in breast and prostate cancer, with potentially greater activity in combination regimens. Given the interaction between Src and the estrogen receptor, ongoing trials are exploring combinations with endocrine therapy. The relationship between Src and the vascular endothelial growth factor receptor also justifies investigation of combinations with angiogenesis inhibitors. Future trials will continue to explore the contribution of Src inhibition with both chemotherapy and targeted agents.
Obama signs health bill to insure four million more children
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Earlier this week President Barack Obama signed the state children’s health insurance programme bill, to extend healthcare insurance to about four million US children. Around 10 million children under the age of 18 years currently lack healthcare insurance.

The bill was passed quickly by both the House of Representatives and the Senate after President Obama took office. A commentary published in the New England Journal of Medicine (doi:10.1056/NEJMp0900461) said, “The rapid action underscored Democrats’ intention to reverse or amend many health policies put in place during the Bush administration.”

President George W Bush had twice vetoed previous …
Concordance Between the 2005 International Diabetes Federation Definition for Diagnosing Metabolic Syndrome With the National Cholesterol Education Program Adult Treatment Panel III and the World Health Organization Definitions
Authors: Fernando Guerrero-Romero, Martha Rodr&ıacute;guez-Morán
Journal: Diabetes Care (2005)

Recently, the International Diabetes Federation (IDF) consensus (1) proposed a new definition for diagnosing metabolic syndrome. The new IDF definition includes a lower waist circumference than the National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria (2) for diagnosing abdominal obesity.

Since the most frequently used definitions for metabolic syndrome involve different criteria for diagnosis of obesity, and because differences in the prevalence of metabolic syndrome seem to reproduce differences in the prevalence of adiposity (3), we determined the concordance between the 2005 IDF definition for metabolic syndrome with the ATP III and World Health Organization (WHO) (4) definitions in a …