tbuckley/cabot-search huggingface dataset:
Lack of chemokine receptor CCR1 enhances Th1 responses and glomerular injury during nephrotoxic nephritis
Authors: Peter S. Topham, Vilmos Csizmadia, Dulce Soler, Dawn Hines, Craig J. Gerard, David J. Salant, Wayne W. Hancock
Journal: Journal of Clinical Investigation (1999)

During the development of nephrotoxic nephritis (NTN) in the mouse, we find that a variety of chemokines and chemokine receptors are induced: CCR1 (RANTES, MIP-1α), CCR2 (MCP-1), CCR5 (RANTES, MIP-1α, MIP-1β), CXCR2 (MIP-2), and CXCR3 (IP-10). Their timing of expression indicated that CXCR2 and CCR1 are probably important in the neutrophil-dependent heterologous phase of the disease, whereas CCR1, CCR2, CCR5, and CXCR3 accompany the subsequent mononuclear cell infiltration characteristic of autologous disease. We therefore assessed the role of CCR1 in NTN using CCR1–/– mice. We found that neutrophil accumulation in CCR1–/– mice was comparable to that in wild-type animals but that renal recruitment of CD4+ and CD8+ T cells and macrophages increased significantly. Moreover, CCR1–/– mice developed more severe glomerulonephritis than did controls, with greater proteinuria and blood urea nitrogen, as well as a higher frequency of crescent formation. In addition, CCR1–/– mice showed enhanced Th1 immune responses, including titers of antigen-specific IgG2a antibody, delayed-type hypersensitivity responses, and production of IFN-γ and TNF-α. Lastly, using recombinant proteins and transfected cells that overexpressed CCR1, we demonstrated that MIP-1α, but not RANTES, bound CCR1 and induced cell chemotaxis. Thus, rather than simply promoting leukocyte recruitment during NTN, CCR1 expression profoundly alters the effector phase of glomerulonephritis. Therapeutic targeting of chemokine receptors may, on occasion, exacerbate underlying disease.
146. Development of Modified Adenovirus Vectors with Reduced Innate Immune Response
Authors: Hiroyuki Mizuguchi, Naoya Koizumi, Kenji Kawabata, Fuminori Sakurai, Takao Hayakawa
Journal: Molecular Therapy (2006)

Adenovirus (Ad) vectors derived from Ad type 5 are widely used in gene therapy and infect a broad range of cells. One of the limitations of Ad vector-mediated gene transfer is the innate immune response after systemic injection of the vector. Ad vectors induce the expression of numerous inflammatory cytokines and chemokines, such as interleukin 6 (IL-6), IL-12, tumor necrosis factor a (TNF-α), interferon-γ-inducible protein 10 (IP-10), RANTRS (regulation on activation, normal T cell expressed and secreted), monocyte chemoattractant protein 1 (MCP-1) et al. Ad particle or capsid proteins, not viral transcription products, trigger this immune response. The strategy to blunt (or reduce) this innate immune response or the development of Ad vectors with reduced innate immune response as well as the elucidation of mechanism of Ad vector-mediated innate immune response are required for safe gene therapy using Ad vectors. In the present study, we developed the modified Ad vectors with reduced innate immune response. First, we examined the organs responsible to secret cytokines after the systemic injection of Ad vectors into mouse. RT-PCR analysis showed that spleen, not liver, is the major site of cytokine (IL-6, IL-12, TNF-α) expression. Then, we examined the transgene expression in each organs, tissue distribution of Ad vector DNA, the serum cytokine levels, and serum ALT levels (as a marker of liver toxicity) after the injection of several types of capsid-modified Ad vectors in comparison with the conventional Ad vector. One of the modified Ad vectors showed higher transgene expression in each organs including liver than the conventional Ad vector. Interestingly, this Ad vector showed much reduced serum IL-6 and ALT levels, which were almost background levels. Quantitative PCR analysis to examine tissue distribution of Ad vector DNA showed that spleen distribution was reduced in this modified Ad vector, reflecting reduced IL-6 levels in serum. There was no difference of serum IL-12 levels between this modified Ad vector and the conventional Ad vector. Therefore, IL-6 and IL-12 would be expressed in different mechanism or different types of cells. We now examine the cell types responsible to secret cytokine expression in the spleen and other cytokines and chemokines expression in each organ by RT-PCR analysis.
Use of inoue balloon catheter to perform staged balloon inflations in combination with serial evaluation by color-flow Doppler minimizes mitral regurgitation as a complication of percutaneous mitral valvuloplasty
Authors: William A. Dietz, James B. Waters, K. Ramaswamy, John O. Pastore, Susan Flynn, Deborah A. Coletta, Donna Kenny, Jeffrey M. Isner
Journal: Journal of the American College of Cardiology (1991)
TRIPLE MAJOR AMPUTATION WITHOUT LIGATION OF THE BLOOD VESSELS.
Authors: WILLIAM B. PATTON
Journal: JAMA (1903)

The following unusual case has proved interesting to the local profession and may therefore be of general interest: M. B., aged 8, was run over by the steam cars, Sept. 16, 1903. He was taken to the Mitchell Thomas (City) Hospital, where Dr. F. P. Anzinger and I examined him. The right hand was crushed and the arm was hanging by the skin three inches above the wrist; the right foot was crushed to the ankle; the left foot was hanging by shreds three inches above the ankle. There was also a laceration of the scalp as well as a number of contusions on the back and thighs. There was no evidence of any considerable loss of blood and the boy suffered comparatively little from shock. Dr. Anzinger amputated the right leg while I removed the left. To secure sufficient flaps it was necessary to reamputate each limb far enough
Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary-care center
Authors: Xavier Forns, Sergi Ampurdanès, José Marı́a Sanchez-Tapias, Magda Guilera, Miquel Sans, Alberto Sánchez-Fueyo, Llorenç Quintó, Pedro Joya, Miquel Bruguera, Juan Rodés
Journal: Journal of Hepatology (2001)
Acute Esophageal Necrosis Associated with Alcoholic Hepatitis: Is It Black or Is It White?
Authors: A. Săftoiu, S. Cazacu, A. Kruse, C. Georgescu, V. Comănescu, T. Ciurea
Journal: Endoscopy (2005)

Acute esophageal necrosis is an uncommon condition diagnosed during endoscopy from the black appearance of the esophagus. We report three cases of acute esophageal necrosis, associated with severe alcoholic hepatitis. The pathogenesis was multifactorial in our patients, with gastroesophageal reflux combined with hypoperfusion probably being the key factor for the esophageal lesions. The patients presented a continuum of endoscopic appearances, ranging from the characteristic black esophageal mucosa with ulcerations to a thick white exudate that peeled away (pseudomembranes). However, esophageal biopsy specimens from all three patients had the same histological pattern of severe inflammation and necrosis. Thus, the possibility of acute esophageal necrosis should also be considered in patients with extensive necrosis covered by a white exudate, but without the characteristic pattern of a "black esophagus"; and the diagnosis should subsequently be confirmed by mucosal biopsies. Our report showed that ethanol-induced acute esophageal necrosis can appear in patients with a high alcohol intake, especially in immunosupressed patients with alcoholic hepatitis.
Septic Thrombophlebitis
Authors: Andrew M. Munster
Journal: JAMA (1974)

The presence of signs of systemic sepsis, positive blood cultures, and signs of local inflammation over a cannulated vein that fail to respond rapidly to removal of the cannula and appropriate antibiotic therapy should lead to a suspected diagnosis of septic thrombophlebitis. Surgical exploration and, if the diagnosis is proven, interruption or resection of such a vein should be undertaken to avoid potentially life-threatening complications. (<i>JAMA</i>230:1010-1011, 1974)
Glycosylated Hemoglobin in the Diagnosis of Non-insulin-dependent Diabetes Mellitus
Authors: Colin M Kesson, Richard E Young, Dinesh Talwar, James W Whitelaw, Donald A Robb
Journal: Diabetes Care (1982)

Fifty-one patients aged over 35 yr were referred because of glycosuria for a glucose tolerance test (GTT). In each patient hemoglobin A1 (HbA1) was estimated by a commercial minicolumn method and compared with hemoglobin A1c (HbA1c) determined by a modification of the method of Trivelli et al. Both HbA1 and HbA1c levels were normal in 96% of those patients with normal GTTs. In patients with diabetic GTTs, HbA1 was elevated in 90% but HbA1c was raised in only 43%. HbA1 estimation is a useful screening test for non-insulin-dependent diabetes and should be considered when criteria for diagnosis of diabetes mellitus are discussed.
Growth-Regulated Oncogene Is Pivotal in Thrombin-Induced Angiogenesis
Authors: Maresa Caunt, Liang Hu, Thomas Tang, Peter C. Brooks, Sherif Ibrahim, Simon Karpatkin
Journal: Cancer Research (2006)

Abstract The mechanism of thrombin-induced angiogenesis is poorly understood. Using a gene chip array to investigate the pro-malignant phenotype of thrombin-stimulated cells, we observed that thrombin markedly up-regulates growth-regulated oncogene-α (GRO-α) in several tumor cell lines as well as endothelial cells by mRNA and protein analysis. Thrombin enhanced the secretion of GRO-α from tumor cells 25- to 64-fold. GRO-α is a CXC chemokine with tumor-associated angiogenic as well as oncogenic activation following ligation of its CXCR2 receptor. GRO-α enhanced angiogenesis in the chick chorioallantoic membrane assay 2.2-fold, providing direct evidence for GRO-α as an angiogenic growth factor. Anti-GRO-α antibody completely inhibited the 2.7-fold thrombin-induced up-regulation of angiogenesis, as well as the 1.5-fold thrombin-induced up-regulation of both endothelial cell cord formation in Matrigel and growth in vitro. Thrombin as well as its PAR-1 receptor activation peptide [thrombin receptor activation peptide (TRAP)] as well as GRO-α all markedly increased vascular regulatory proteins and growth factors: matrix metalloproteinase (MMP)-1, MMP-2, vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), CD31, and receptors KDR and CXCR2 in human umbilical vein endothelial cells. All of the thrombin/TRAP gene up-regulations were completely inhibited by anti-GRO-α antibody and unaffected by irrelevant antibody. Similar inhibition of gene up-regulation as well as thrombin-induced chemotaxis was noted with small interfering RNA (shRNA) GRO-α KD 4T1 breast tumor and B16F10 melanoma cells. In vivo tumor growth studies in wild-type mice with shRNA GRO-α KD cells revealed 2- to 4-fold impaired tumor growth, metastasis, and angiogenesis, which was not affected by endogenous thrombin. Thus, thrombin-induced angiogenesis requires the up-regulation of GRO-α. Thrombin up-regulation of GRO-α in tumor cells as well as endothelial cells contributes to tumor angiogenesis. (Cancer Res 2006; 66(8): 4125-32)
Correlation of Corneal Complications with Eyelid Cicatricial Pathologies in Patients with Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Syndrome
Authors: M DIPASCUALE, E ESPANA, D LIU, T KAWAKITA, W LI, Y GAO, A BARADARANRAFII, A ELIZONDO, V RAJU, S TSENG
Journal: Ophthalmology (2005)
Abstract 3083: The RNA stability factor HuR promotes an angiogenic switch in colon cancer
Authors: Lisa E. Young, Dan A. Dixon
Journal: Cancer Research (2011)

Abstract The initiation and progression of colorectal tumorigenesis is characterized by alterations in gene expression that allow for the overexpression of oncogenic and tumor-promoting factors. In normal cells, the mRNA transcripts of these cancer-associated genes are targeted for rapid decay through AU-rich elements (ARE) present in the mRNA 3’ untranslated region (3′UTR). However, growing evidence reveals that the loss of ARE-mediated mRNA decay is a characteristic feature contributing to pathogenic gene expression in colorectal cancer. Our prior work identified enhanced expression of the RNA-binding protein HuR to occur during colon tumorigenesis and HuR overexpression is correlated with poor clinical prognosis. In this capacity, HuR promotes overexpression of many cancer-associated factors by binding to their ARE and interfering with subsequent rapid mRNA decay. To determine the functional significance of HuR overexpression in vivo, a tissue-specific HuR-transgenic mouse (HuR-Tg) was created that overexpresses HuR in the epithelium of the small intestine and colon. HuR-Tg mice displayed normal growth and did not reveal any morphological changes in the gastrointestinal tract. To test if HuR overexpression can impact tumorigenesis downstream a tumor initiating event, crosses between HuR-Tg mice and the APCMin/+ mouse, a genetic model of gastrointestinal tumorigenesis, were performed. As early as 12 weeks of age, HuR-Tg/APCMin/+ lines display a 2- to 4-fold increase in tumor burden and size in both the colon and small intestine compared to APCMin/+control mice. Based on HuR's ability to bind various ARE-containing mRNAs associated with angiogenesis, vascular density was assayed in tissue derived from HuR-Tg/APCMin/+ mice. Micro-vessel density was 2-fold greater in the tumors and surrounding tissue in APCMin/+ mice overexpressing HuR. Angiogenic mRNA array analysis of tumors derived from HuR-Tg/APCMin/+ mice showed enhanced expression of multiple ARE-containing angiogenic genes including the HuR target genes vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). Furthermore, dietary treatment of HuR-Tg/APCMin/+ mice with celecoxib attenuated HuR-dependent tumor formation and suppressed micro-vessel density and VEGF expression. These findings indicate that HuR functions during colon tumorigenesis downstream of a tumor-initiating event to stabilize ARE-containing mRNAs associated with tumor vascularization and identify this mRNA stability factor as a new molecular target for therapeutic intervention in controlling angiogenic gene expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3083. doi:10.1158/1538-7445.AM2011-3083
The Endothelium - An Introduction to Current Research.
Authors: C P Page
Journal: Cardiovascular Research (1992)

Journal Article The Endothelium – An Introduction to Current Research. Get access C P Page C P Page London, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 12, December 1992, Page 1227, https://doi.org/10.1093/cvr/26.12.1227 Published: 01 December 1992
Severe Congenital Tricuspid Incompetence in the Neonate
Authors: PETER A. BARR, JOHN M. CELERMAJER, J. DENBY BOWDLER, TIMOTHY B. CARTMILL
Journal: Circulation (1974)

Five neonates with congenital tricuspid incompetence due to severe tethering of the tricuspid valve to the right ventricle by abnormal chordal and papillary muscle attachments are described. The abnormality was called tricuspid valvular dysplasia (TVD) if the basal insertion of the valve was normal and the Ebstein malformation if it was displaced into the sinus portion of the ventricle. In the two infants with isolated TVD and severe tricuspid regurgitation the functional obstruction to right ventricular outflow (ORVO) produced by the high perinatal pulmonary vascular resistance (PVR) made the exclusion of pulmonary atresia difficult, despite selective right ventricular angiocardiography. In three infants the tricuspid valvular abnormality was associated with organic ORVO; pulmonary atresia in two and critical pulmonary valve stenosis in one. In the two infants with pulmonary atresia and intact ventricular septum (IVS) the severe tricuspid incompetence produced a clinical, radiological and hemodynamic profile which was clearly different from that usually seen in infants with pulmonary atresia and IVS and a normal right ventricular cavity (type 2 of Greenwold).
Variation in Treatment of Patients With Inflammatory Bowel Diseases at Major Referral Centers in the United States
Authors: Ashwin N. Ananthakrishnan, Jennifer Kwon, Laura Raffals, Bruce Sands, William F. Stenson, Dermot McGovern, John H. Kwon, Robert L. Rheaume, Robert S. Sandler
Journal: Clinical Gastroenterology and Hepatology (2014)
Andrew Shannon Ramsey
Authors: Elizabeth Ramsey
Journal: BMJ (2004)

Consultant physician Lisburn, Northern Ireland 1951-80 (b Belfast 1915; q Belfast 1939; MD, FRCP, FRCPI), died from cancer on 12 April 2004.

During the second world war he served with the Royal Army Medical Corps in north Africa and Italy. He was in command of a field ambulance, retiring with the rank of lieutenant colonel in 1947. He was awarded an MBE and was mentioned in dispatches. After obtaining further qualifications he was appointed the first consultant physician at the Lagan Valley Hospital. As well as establishing the medical unit there, he was instrumental in raising large sums to build the first coronary care unit in the area. Predeceased by his wife, he leaves two children and two grandchildren.
Characterization of Common Variable Immunodeficiency (CVID) Subgroups through Modulation of Their Interleukin-21 (aCD40/IL-4/IL-21) Pathway in Vitro
Authors: Marylin Desjardins, Marianne Beland, Jean-Philippe Drolet, Reza Alizadehfar, Bruce D. Mazer
Journal: Journal of Allergy and Clinical Immunology (2015)
Emergency services lack coordination, says healthcare watchdog
Authors: H. Adcock
Journal: BMJ (2008)

Urgent and emergency care services are performing well against individual targets, but the whole system is not working together as well as it could, says England’s healthcare watchdog. Patients are often left feeling confused and frustrated after having to repeat their details several times or are referred to services that don’t exist, the Healthcare Commission found.

The commission gathered data from out of hours GP services, emergency ambulance services, accident and emergency services, and urgent care centres serving the 152 primary care trusts in England. The areas were scored according to 36 indicators, including whether they were meeting the various national targets …
Effects of topical capsaicin in seasonal allergic rhinitis.
Authors: L Greiff, C Svensson, M Andersson, C G Persson
Journal: Thorax (1995)

BACKGROUND--Mucosal exudation (luminal entry) of bulk plasma is a key feature of airway defence and inflammation. In guinea pig and rat airways this response is readily produced by neurogenic irritants, notably capsaicin. Thus "neurogenic airway inflammation" has become an established concept. The present study examines whether capsaicin also produces mucosal exudation of plasma in human nasal airways both in health and disease (seasonal allergic rhinitis). METHODS--Pain-producing concentrations of capsaicin (30-300 ng/ml) were applied to the nasal mucosal surface both before and late into the pollen season. Levels of albumin in nasal lavage fluid were measured as an index of mucosal exudation of plasma. In a separate group of patients with seasonal allergic rhinitis nasal challenge with an exudative concentration of histamine was carried out before the birch pollen season and concentrations of albumin in lavage fluid were measured. RESULTS--Pollen counts and symptom scores revealed a mild pollen season. Capsaicin produced considerable nasal pain and this response was augmented late into the season when capsaicin also produced nasal blockage. However, capsaicin failed to produce any mucosal exudation of plasma either before or late into the pollen season. The exudative effect of histamine was confirmed. CONCLUSIONS--The augmented pain response to capsaicin suggests that a sensory nerve hyperresponsiveness may characterise allergic airways disease. In contrast to the effects on animal airways, capsaicin failed to produce mucosal exudation of plasma in the human nasal airway. The animal based neurogenic inflammation concept is therefore not valid for the human nasal airway, not even in inflamed airways when a neural hyperresponsiveness has developed.
Evolution of Class B Floral Homeotic Proteins: Obligate Heterodimerization Originated from Homodimerization
Authors: Kai-Uwe Winter, Christof Weiser, Kerstin Kaufmann, Arend Bohne, Charlotte Kirchner, Akira Kanno, Heinz Saedler, Günter Theißen
Journal: Molecular Biology and Evolution (2002)

The class B floral homeotic genes from the higher eudicot model systems Arabidopsis and Antirrhinum are involved in specifying the identity of petals and stamens during flower development. These genes exist in two different types termed DEF- and GLO-like genes. The proteins encoded by the class B genes are stable and functional in the cell only as heterodimeric complexes of a DEF- and a GLO-like protein. In line with this, heterodimerization is obligate for DNA binding in vitro. The genes whose products have to heterodimerize to be stable and functional are each other's closest relatives within their genomes. This suggests that the respective genes originated by gene duplication, and that heterodimerization is of relative recent origin and evolved from homodimerization. To test this hypothesis we have investigated the dimerization behavior of putative B proteins from phylogenetic informative taxa, employing electrophoretic mobility shift assays and the yeast two-hybrid system. We find that an ancestral B protein from the gymnosperm Gnetum gnemon binds DNA in a sequence-specific manner as a homodimer. Of the two types of B proteins from the monocot Lilium regale, the GLO-like protein is still able to homodimerize, whereas the DEF-like protein binds to DNA only as a heterodimeric complex with the GLO-like protein. These data suggest that heterodimerization evolved in two steps after a gene duplication that gave rise to DEF- and GLO-like genes. Heterodimerization may have originated after the gymnosperm-angiosperm split about 300 MYA but before the monocot-eudicot split 140-200 MYA. Heterodimerization may have become obligate for both types of flowering plant B proteins in the eudicot lineage after the monocot-eudicot split.
A Case of Retrosternal Diaphragmatic Hernia
Authors: R. Warwick-Brown
Journal: Thorax (1953)

<h3>Abstract</h3> <h3>Background</h3> Copy number alterations (CNAs), due to their large impact on the genome, have been an important contributing factor to oncogenesis and metastasis. Detecting genomic alterations from the shallow-sequencing data of a low-purity tumor sample remains a challenging task. <h3>Results</h3> We introduce Accucopy, a method to infer total copy numbers (TCNs) and allele-specific copy numbers (ASCNs) from challenging low-purity and low-coverage tumor samples. Accucopy adopts many robust statistical techniques such as kernel smoothing of coverage differentiation information to discern signals from noise and combines ideas from time-series analysis and the signal-processing field to derive a range of estimates for the period in a histogram of coverage differentiation information. Statistical learning models such as the tiered Gaussian mixture model, the Expectation-Maximization (EM) algorithm, and Sparse Bayesian Learning (SBL) were customized and built into the model. Accucopy is implemented in C++/Rust, packaged in a docker image, and supports non-human samples, more at http://www.yfish.org/software/. <h3>Conclusions</h3> We describe Accucopy, a method that can predict both TCNs and ASCNs from low-coverage low-purity tumor sequencing data. Through comparative analyses in both simulated and real-sequencing samples, we demonstrate that Accucopy is more accurate than Sclust, ABSOLUTE, and Sequenza.