tbuckley/cabot-search huggingface dataset:
The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing
Authors: Soung-Hoon Lee, Mi-Yeon Kim, Hyun-Yi Kim, Young-Mi Lee, Heesu Kim, Kyoung Ae Nam, Mi Ryung Roh, Do Sik Min, Kee Yang Chung, Kang-Yell Choi
Journal: The Journal of Experimental Medicine (2015)

Wnt/β-catenin signaling plays important roles in cutaneous wound healing and dermal fibrosis. However, its regulatory mechanism has not been fully elucidated, and a commercially available wound-healing agent targeting this pathway is desirable but currently unavailable. We found that CXXC-type zinc finger protein 5 (CXXC5) serves as a negative feedback regulator of the Wnt/β-catenin pathway by interacting with the Dishevelled (Dvl) protein. In humans, CXXC5 protein levels were reduced in epidermal keratinocytes and dermal fibroblasts of acute wounds. A differential regulation of β-catenin, α-smooth muscle actin (α-SMA), and collagen I by overexpression and silencing of CXXC5 in vitro indicated a critical role for this factor in myofibroblast differentiation and collagen production. In addition, CXXC5−/− mice exhibited accelerated cutaneous wound healing, as well as enhanced keratin 14 and collagen synthesis. Protein transduction domain (PTD)–Dvl-binding motif (DBM), a competitor peptide blocking CXXC5-Dvl interactions, disrupted this negative feedback loop and activated β-catenin and collagen production in vitro. Co-treatment of skin wounds with PTD-DBM and valproic acid (VPA), a glycogen synthase kinase 3β (GSK3β) inhibitor which activates the Wnt/β-catenin pathway, synergistically accelerated cutaneous wound healing in mice. Together, these data suggest that CXXC5 would represent a potential target for future therapies aimed at improving wound healing.
Primary cutaneous non-Hodgkin’s lymphoma with aggressive histology: inferior outcome is associated with peripheral T-cell type and elevated lactate dehydrogenase, but not extent of cutaneous involvement
Authors: C. Visco, L.J. Medeiros, D. Jones, T. Smith, M.A. Rodriguez, P. McLaughlin, J. Romaguera, F. Cabanillas, A.H. Sarris
Journal: Annals of Oncology (2002)
Granulocyte Macrophage Colony-Stimulating Factor
Authors: Jonathan L. McQualter, Rima Darwiche, Christine Ewing, Manabu Onuki, Thomas W. Kay, John A. Hamilton, Hugh H. Reid, Claude C.A. Bernard
Journal: The Journal of Experimental Medicine (2001)

Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, can be induced by immunization with a number of myelin antigens. In particular, myelin oligodendrocyte glycoprotein, a central nervous system (CNS)-specific antigen expressed on the myelin surface, is able to induce a paralytic MS-like disease with extensive CNS inflammation and demyelination in several strains of animals. Although not well understood, the egress of immune cells into the CNS in EAE is governed by a complex interplay between pro and antiinflammatory cytokines and chemokines. The hematopoietic growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is considered to play a central role in maintaining chronic inflammation. The present study was designed to investigate the previously unexplored role of GM-CSF in autoimmune-mediated demyelination. GM-CSF−/− mice are resistant to EAE, display decreased antigen-specific proliferation of splenocytes, and fail to sustain immune cell infiltrates in the CNS, thus revealing key activities for GM-CSF in the development of inflammatory demyelinating lesions and control of migration and/or proliferation of leukocytes within the CNS. These results hold implications for the pathogenesis of inflammatory and demyelinating diseases and may provide the basis for more effective therapies for inflammatory diseases, and more specifically for multiple sclerosis.
Intestinal gas distribution determines abdominal symptoms
Authors: H Harder
Journal: Gut (2003)

<b>Background:</b> Patients with functional gut disorders manifest poor tolerance to intestinal gas loads but the mechanism of this dysfunction is unknown. <b>Aim:</b> Our aims were firstly, to explore the relative importance of the amount of intestinal gas versus its distribution on symptom production, and secondly, to correlate gut motility and perception of gas loads. <b>Subjects:</b> Fourteen healthy subjects with no gastrointestinal symptoms. <b>Methods:</b> In each subject a gas mixture was infused (12 ml/min) either into the jejunum or rectum for one hour during blocked rectal gas outflow, and subsequently gas clearance was measured over one hour of free rectal evacuation. We measured abdominal perception, distension, and gut tone by duodenal and rectal barostats. <b>Results:</b> Similar magnitude of gas retention (720 ml) produced significantly more abdominal symptoms with jejunal compared with rectal infusion (perception score 4.4 (0.4) <i>v </i>1.5 (0.5), respectively; p&lt;0.01) whereas abdominal distension was similar (15 (2) mm and 14 (1) mm girth increment, respectively). Jejunal gas loads were associated with proximal contraction (by 57 (5)%) and colonic loads with distal relaxation (by 99 (20)%). <b>Conclusion:</b> The volume of gas within the gut determines abdominal distension whereas symptom perception depends on intraluminal gas distribution and possibly also on the gut motor response to gas loads.
Association of Cancer Sites With Tobacco and Alcohol Consumption and Socioeconomic Status of Patients: Interview Study From the Third National Cancer Survey
Authors: Roger R. Williams, John W. Horm
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Association of Cancer Sites With Tobacco and Alcohol Consumption and Socioeconomic Status of Patients: Interview Study From the Third National Cancer Survey Get access Roger R. Williams, M.D., Roger R. Williams, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Horm, M.S. John W. Horm, M.S. 4 4Address reprint requests to Mr. Horm. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 3, March 1977, Pages 525–547, https://doi.org/10.1093/jnci/58.3.525 Published: 01 March 1977 Article history Received: 24 March 1976 Accepted: 26 July 1976 Published: 01 March 1977
Sequence and functional analyses of Haemophilus spp. genomic islands
Authors: Mario Juhas, Peter M Power, Rosalind M Harding, David JP Ferguson, Ioanna D Dimopoulou, Abdel RE Elamin, Zaini Mohd-Zain, Derek W Hood, Richard Adegbola, Alice Erwin, Arnold Smith, Robert S Munson, Alistair Harrison, Lucielle Mansfield, Stephen Bentley, Derrick W Crook
Journal: Genome biology (2007)

Abstract Background A major part of horizontal gene transfer that contributes to the diversification and adaptation of bacteria is facilitated by genomic islands. The evolution of these islands is poorly understood. Some progress was made with the identification of a set of phylogenetically related genomic islands among the Proteobacteria, recognized from the investigation of the evolutionary origins of a Haemophilus influenzae antibiotic resistance island, namely ICE Hin1056 . More clarity comes from this comparative analysis of seven complete sequences of the ICE Hin1056 genomic island subfamily. Results These genomic islands have core and accessory genes in approximately equal proportion, with none demonstrating recent acquisition from other islands. The number of variable sites within core genes is similar to that found in the host bacteria. Furthermore, the GC content of the core genes is similar to that of the host bacteria (38% to 40%). Most of the core gene content is formed by the syntenic type IV secretion system dependent conjugative module and replicative module. GC content and lack of variable sites indicate that the antibiotic resistance genes were acquired relatively recently. An analysis of conjugation efficiency and antibiotic susceptibility demonstrates that phenotypic expression of genomic island-borne genes differs between different hosts. Conclusion Genomic islands of the ICE Hin1056 subfamily have a longstanding relationship with H. influenzae and H. parainfluenzae and are co-evolving as semi-autonomous genomes within the 'supragenomes' of their host species. They have promoted bacterial diversity and adaptation through becoming efficient vectors of antibiotic resistance by the recent acquisition of antibiotic resistance transposons.
Exchange of Blood Between Pulmonary and Systemic Circulations via Bronchopulmonary Anastomoses
Authors: P. Aramendia, J. Martinez L. De Letona, D. M. Aviado
Journal: Circulation Research (1962)

In anesthetized dogs, the dye-dilution technique was applied to detect the transfer of blood between the bronchial and pulmonary vessels. The injection of Cardio-green into the pulmonary artery did not show a double peak in the dye-concentration curve of blood in the azygos vein. This does not exclude the possibility of a shunt from the pulmonary artery to the bronchial veins because the flow of the dye may take longer to reach the bronchial veins than does that from the bronchial artery. The injection of the dye into the left ventricle with sampling of the blood in the left atrium showed a double peak in the dyedilution curve. The latter is interpreted to indicate blood flow from the bronchial arteries to the pulmonary vessels via the bronchopulmonary anastomoses. In five dogs, the mean value for bronchopulmonary flow was 8 per cent of left ventricular output. The corresponding flow values were increased in three dogs with chronic ligation of the left pulmonary artery, not increased in four dogs with pulmonary embolization, and reduced in two dogs subjected to inhalation of heat. All these results suggest that previous estimates of 1 per cent for bronchial flow may be an underestimation, but the maximum value of 8 per cent in anesthetized dogs calculated by the dye-dilution technique will have to be reevaluated by other methods.
Antitumor Activity and Biomarker Analysis of Sunitinib in Patients With Bevacizumab-Refractory Metastatic Renal Cell Carcinoma
Authors: Brian I. Rini, M. Dror Michaelson, Jonathan E. Rosenberg, Ronald M. Bukowski, Jeffrey A. Sosman, Walter M. Stadler, Thomas E. Hutson, Kim Margolin, Charles S. Harmon, Samuel E. DePrimo, Sindy T. Kim, Isan Chen, Daniel J. George
Journal: Journal of Clinical Oncology (2008)

To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response.Patients with mRCC and disease progression after bevacizumab-based therapy received oral sunitinib 50 mg once daily in 6-week cycles on a 4/2 schedule (4 weeks with treatment followed by 2 weeks without treatment) in a phase II multicenter study. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), duration of response (DR), overall survival (OS), and safety. Plasma soluble proteins (vascular endothelial growth factor [VEGF]-A, VEGF-C, soluble VEGF receptor [sVEGFR]-3, and placental growth factor [PlGF]) levels were measured.Sixty-one patients were enrolled. The ORR was 23.0% (95% CI, 13.2% to 35.5%), median PFS was 30.4 weeks (95% CI, 18.3 to 36.7 weeks), median DR was 44.1 weeks (95% CI, 25.0 to 102.7 weeks), and median OS was 47.1 weeks (95% CI, 36.9 to 79.4 weeks). Mean plasma VEGF-A and PlGF levels significantly increased whereas VEGF-C and sVEGFR-3 levels decreased with sunitinib treatment. Lower baseline levels of sVEGFR-3 and VEGF-C were associated with longer PFS and ORR. Most treatment-related adverse events were of mild-to-moderate intensity and included fatigue, hypertension, and hand-foot syndrome.Sunitinib has substantial antitumor activity in patients with bevacizumab-refractory mRCC and modulates circulating VEGF pathway biomarkers. These data support the hypothesis that sunitinib inhibits signaling pathways involved in bevacizumab resistance. Baseline levels of sVEGFR-3 and VEGF-C may have potential utility as biomarkers of clinical efficacy in this setting.
Regulatory peptides of gut and brain
Authors: D. Wingate
Journal: Gut (1983)

structure and function and relation to the immune response.The liver is then considered as a whole in relation to its circulation and interaction with other organs.Finally, the major disease mechanisms, hepatocellular regeneration, cholestasis, fibro- genesis, neoplasia, and portal hypertension are considered.The practising hepatologist, gastroenterologist and even biochemist or pathologist will find this book hard to read.He (or she) must be encouraged to persevere, it represents the liver disease of tomorrow.It is fitting that this book is dedicated to Hans Popper, the founder of modern hepatology.He has himself contributed an excellent chapter on hepatocyte death.The book may seem costly, but it is a bargain for the material it contains.It is a must for hospital libraries.
Imaging Dopamine Transmission in Cocaine Dependence: Link Between Neurochemistry and Response to Treatment
Authors: Diana Martinez, Kenneth M. Carpenter, Fei Liu, Mark Slifstein, Allegra Broft, Alessandra Calvo Friedman, Dileep Kumar, Ronald Van Heertum, Herbert D. Kleber, Edward Nunes
Journal: American Journal of Psychiatry (2011)

Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, positron emission tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is linked to cocaine-seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. The authors hypothesized that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals.Prior to treatment, cocaine-dependent subjects underwent two PET scans using [(11)C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D(2/3) receptor binding and presynaptic dopamine release.Both of the outcome measures were lower in the volunteers who did not respond to treatment than in those who experienced a positive treatment response.These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.
Multicolor fate mapping of Langerhans cell homeostasis
Authors: Clément Ghigo, Isabelle Mondor, Audrey Jorquera, Jonathan Nowak, Stephan Wienert, Sonja P. Zahner, Björn E. Clausen, Hervé Luche, Bernard Malissen, Frederick Klauschen, Marc Bajénoff
Journal: The Journal of Experimental Medicine (2013)

Langerhans cells (LCs) constitute a network of immune sentinels in the skin epidermis that is seeded during embryogenesis. Whereas the development of LCs has been extensively studied, much less is known about the homeostatic renewal of adult LCs in "nonmanipulated" animals. Here, we present a new multicolor fluorescent fate mapping system and quantification approach to investigate adult LC homeostasis. This novel approach enables us to propose and provide evidence for a model in which the adult epidermal LC network is not formed by mature coequal LCs endowed with proliferative capabilities, but rather constituted by adjacent proliferative units composed of "dividing" LCs and their terminally differentiated daughter cells. Altogether, our results demonstrate the general utility of our novel fate-mapping system to follow cell population dynamics in vivo and to establish an alternative model for LC homeostasis.
<i>Staphylococcus aureus</i> Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with <scp>l</scp>-Lysine
Authors: Andreas Peschel, Ralph W. Jack, Michael Otto, L. Vincent Collins, Petra Staubitz, Graeme Nicholson, Hubert Kalbacher, Willem F. Nieuwenhuizen, Günther Jung, Andrej Tarkowski, Kok P.M. van Kessel, Jos A.G. van Strijp
Journal: The Journal of Experimental Medicine (2001)

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.
Hodgkin's disease in 35 patients with HIV infection: An experience with epirubicin, bleomycin, vinblastine and prednisone chemotherapy in combination with antiretroviral therapy and primary use of G-CSF
Authors: D. Errante, J. Gabarre, A.L. Ridolfo, G. Rossi, A.M. Nosari, C. Gisselbrecht, Y. Kerneis, F. Mazzetti, E. Vaccher, R. Talamini, A. Carbone, U. Tirelli
Journal: Annals of Oncology (1999)

The optimal therapeutic approach for patients with Hodgkin's disease and human immunodeficiency virus infection (HD-HIV) is unknown. In an attempt to improve the results previously obtained with EBV (epirubicin, bleomycin and vinblastine) without G-CSF (Cancer 1994; 73: 437-44), in January 1993 we started a trial using chemotherapy (CT) consisting of EBV plus prednisone (EBVP), concomitant antiretroviral therapy (zidovudine, AZT or dideoxinosyne, DDI), and G-CSF.Up to August, 1997, 35 (30 M/5 F) consecutive previously untreated patients (median age 34, range 21-53 years) with HD-HIV were enrolled in the European Intergroup Study HD-HIV. Their median performance status was 1 (range 1-3). At diagnosis of HD, 26% of the patients had AIDS, 90% had B symptoms at HD presentation and 83% had advanced-stage HD. Patients received E 70 mg/m2 i.v. on day 1, B 10 mg/m2 i.v. on day 1, V 6 mg/m2 i.v. on day 1 and P 40 mg/m2 p.o. from day 1 to day 5 (EBVP). Courses were repeated every 21 days for six cycles. AZT (250 mg x 2/day), or DDI (200 or 300 mg x 2/day) if AZT had been previously used, were given orally from the beginning of CT. G-CSF was given at the dose of 5 mcg/kg/day s.c. from day 6 to day 20 in all cycles.An overall response rate of 91% was observed. There were 74% complete responses (CR) and 17% partial responses (PR). Toxicity was moderate, with grade 3-4 leukopenia and thrombocytopenia in 10 (32%) and three (10%) patients, respectively. The median number of administered cycles was 6 (range 3-6). Twenty-three of 35 patients received AZT and nine patients received DDI. Three (8%) patients had opportunistic infections (OI) during or immediately after CT. The median CD4+ cell count was 219/mm3 (6-812) at HD diagnosis and 220/mm3 (2-619) after the end of combined therapy, and these numbers remained unchanged. Ten of 26 (38%) patients who achieved CR relapsed. Twenty-three patients died of HD progression alone or in association with OI, being the cause of death in 48% and 9% of patients respectively. The median survival was 16 months, with a survival rate of 32% and a disease-free survival of 53% at 36 months.The combined antineoplastic and antiretroviral treatment is feasible, but HD in HIV setting is associated with a more adverse prognosis than in the general population. Although the CR rate obtained was satisfactory, the relapse rate was high. Furthermore, comparison of the results of our two consecutive prospective studies demonstrated no overall improvement in the current trial with respect to the CR rate and survival.
Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon
Authors: Adrian M. Di Bisceglie, Anne M. Stoddard, Jules L. Dienstag, Mitchell L. Shiffman, Leonard B. Seeff, Herbert L. Bonkovsky, Chihiro Morishima, Elizabeth C. Wright, Kristin K. Snow, William M. Lee, Robert J. Fontana, Timothy R. Morgan, Marc G. Ghany
Journal: Hepatology (2011)

Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (HEPATOLOGY 2011;)