tbuckley/cabot-search huggingface dataset:
Stimulation of arteriogenesis; a new concept for the treatment of arterial occlusive disease
Authors: N van Royen
Journal: Cardiovascular Research (2001)

After birth two forms of vessel growth can be observed; angiogenesis and arteriogenesis. Angiogenesis refers to the formation of capillary networks. Arteriogenesis refers to the growth of preexistent collateral arterioles leading to formation of large conductance arteries that are well capable to compensate for the loss of function of occluded arteries. The process of arteriogenesis is initiated when shear stresses increase in the preexistent collateral pathways upon narrowing of a main artery. The increased shear stress leads to an upregulation of cell adhesion molecules for circulating monocytes, which accumulate subsequently around the proliferating arteries and provide the several required cytokines and growth factors. Several strategies are currently tested for their potential to stimulate the process of arteriogenesis. These strategies focus either at shear stress, at direct stimulation of endothelial and smooth muscle cell growth or at the monocytic pathway and promising results were obtained from experimental studies. However, some important questions remain to be answered before arteriogenesis can be brought from bench to bedside.
1371 PROGRESS TOWARD THE CLINICAL APPLICATION OF AUTOLOGOUS INDUCED PLURIPOTENT STEM CELLS AND GENE REPAIR THERAPY FOR TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA
Authors: A. Bosman, B.E. Wildhaber, J. Birraux, C. Jond, M. Jaconi, O. Menzel
Journal: Journal of Hepatology (2011)
Cardiac Arrest
Authors: James R. Jude
Journal: JAMA (1961)

A new method of producing artificial circulation by external sternal compression without thoracotomy was evaluated in 138 episodes of cardiac arrest in 118 patients. Seventy-six arrests occurred outside the operating and recovery room areas. Seven out of every 10 were in asystole; the remainder were in ventricular fibrillation. Cardiac action was restored in 107 (78%) of the 138 cardiac arrests. In 84 (60%) of the 138, the prearrest status of the central nervous system and heart was regained. Twenty-eight (24%) of the 118 patients survived the arrest and inciting disease to leave the hospital. In patients with sudden cardiac arrest, rapid diagnosis followed by immediate artificial ventilation and circulation adequately protected the central nervous system. Cardiotonic drugs, electrocardiograms, ventricular defibrillation, and continued cardiovascular and pulmonary support were employed as needed.
Technical Refinement and Learning Curve for Attenuating Neurapraxia During Robotic-Assisted Radical Prostatectomy to Improve Sexual Function
Authors: Mehrdad Alemozaffar, Antoine Duclos, Nathanael D. Hevelone, Stuart R. Lipsitz, Tudor Borza, Hua-Yin Yu, Keith J. Kowalczyk, Jim C. Hu
Journal: European Urology (2012)
Acute Disseminated Histoplasmosis with a Report of a Case Occurring in England
Authors: F. C. Poles, J. D. OD. Lavertine
Journal: Thorax (1954)

Histoplasmosis, an acute, subacute, or chronic in- fection caused by the fungus Histoplasma capsulatum, is now known to occur sporadically in most countries of the world (Mochi and Edwards, 1952).It is endemic in a large area of North America, and to a lesser extent in Central and South America.The fungus may give rise to a variety of clinical syndromes (Beadenkopf and Loosli, 1951 ; Christie, 1951).Israel, De Lamater, Sones, Willis, and Mirmelstein (1952) distinguish four principal types of the disease.Active primary histoplasmosis, usually benign, is responsible for few symptoms, and is thus rarely diagnosed.Healed primary histoplasmosis is common in endemic areas and may be diagnosed by a positive nistoplasmin skin test; it is frequently accom- panied by radiological evidence of pulmonary calcification (Christie and Peterson, 1946; Furco- low, High, and Allen, 1946; Palmer, 1946; Prior and Allen, 1947; Bunnell and Furcolow, 1948).Acute disseminated histoplasmosis is often rapidly fatal with involvement of the tongue, larynx, reticulo-endothelial system, and adrenal glands as well as the lungs.This form is seen most com- monly in infants, in the aged, or in those debili- tated by tuberculosis or malignant disease.Finally, chronic disseminated histoplasmosis, commonly involving the skin, oropharynx, larynx, lungs, and lymph nodes, is in many cases ultimately fatal but arrest and recovery have been recorded in some instances. REVIEW OF THE LITERATUREAs the disease is endemic in the central and eastern parts of North America, most of the litera- ture has originated in the United States.Darling, in 1906, was the first to describe a fatal disease due to an organism producing pseudotubercles in the lungs, and focal necroses in the liver, spleen, and lymph nodes.At this time he considered that the organism was a protozoon, and proposed the name Histoplasma capsulatum.Interest was reawakened in 1934, when De
Selectin Inhibitor Bimosiamose Prolongs Survival of Kidney Allografts by Reduction in Intragraft Production of Cytokines and Chemokines
Authors: Robert Langer, Mouer Wang, Stanislaw M. Stepkowski, Wayne W. Hancock, Rongxiang Han, Ping Li, Lily Feng, Robert A. Kirken, Kurt L. Berens, Brian Dupre, Hemangshu Podder, Richard A.F. Dixon, Barry D. Kahan
Journal: Journal of the American Society of Nephrology (2004)

Binding of the P-, L-, and E-selectins to sialyl Lewis(x) (sLe(x)) retards circulating leukocytes, thereby facilitating their attachment to the blood vessels of allografts. Whether the selectin inhibitor bimosiamose (BIMO; C(46)H(54)O(16) . 0.25 H(2)O [867.4 molecular weight]) inhibits the rejection process of kidney allografts in a rat model was examined. Rat recipients acutely rejected kidney allografts at a mean survival time of 8.8 +/- 0.75 d. An intravenous 7-d infusion by osmotic pump of 2.5, 5, 10, or 20 mg/kg BIMO extended kidney allograft survival to 11.5 +/- 2.2 d (P < 0.03), 25.4 +/- 11.4 d (P < 0.006), 37.4 +/- 13.6 d (P < 0.001), and 39.8 +/- 34.5 d (P < 0.01), respectively. Combination of BIMO with cyclosporine produced synergistic interactions, as documented by the combination index (CI) values of 0.34 to 0.43 (CI <1 is synergistic; CI = 1 is additive; and CI >1 is antagonistic). Similarly, BIMO interacted synergistically with sirolimus (CI = 0.64) and FTY720 (CI = 0.22). While the mechanism of immunosuppression was being analyzed, decreased infiltration of CD4(+), CD8(+), and macrophages on day 7 after grafting was observed. Multiple cytokines were also expressed, including IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, IL-18, TNF-alpha, and IFN-gamma in kidney allografts on days 3, 5, and 7 after grafting, as measured by a ribonuclease protection assay. Furthermore, at similar time points, BIMO treatment reduced intragraft expression of P-selectin glycoprotein ligand-1, CX(3)CL1, CCL19, CCL20, and CCL2. Thus, BIMO blocks allograft rejection by reduction of intragraft expression of cytokines and chemokines.
Mite-related bacterial antigens stimulate inflammatory cells in rosacea
Authors: N. Lacey, S. Delaney, K. Kavanagh, F.C. Powell
Journal: British Journal of Dermatology (2007)

Journal Article Mite‐related bacterial antigens stimulate inflammatory cells in rosacea Get access N. Lacey, N. Lacey Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland *Regional Centre of Dermatology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland Search for other works by this author on: Oxford Academic Google Scholar S. Delaney, S. Delaney Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland *Regional Centre of Dermatology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland Search for other works by this author on: Oxford Academic Google Scholar K. Kavanagh, K. Kavanagh Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland *Regional Centre of Dermatology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland Search for other works by this author on: Oxford Academic Google Scholar F.C. Powell F.C. Powell Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland *Regional Centre of Dermatology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland Correspondence: Frank C. Powell. E‐mail: fpowell@eircom.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 3, 1 September 2007, Pages 474–481, https://doi.org/10.1111/j.1365-2133.2007.08028.x Published: 01 September 2007
Loss of red cell chemokine scavenging promotes transfusion-related lung inflammation
Authors: Nilam S. Mangalmurti, Zeyu Xiong, Mei Hulver, Mrunalini Ranganathan, Xiang Hong Liu, Timothy Oriss, Meghan Fitzpatrick, Marc Rubin, Darrell Triulzi, Augustine Choi, Janet S. Lee
Journal: Blood (2008)
(−)−Epigallocatechin Gallate Overcomes Resistance to Etoposide-Induced Cell Death by Targeting the Molecular Chaperone Glucose-Regulated Protein 78
Authors: Svetlana P. Ermakova, Bong Seok Kang, Bu Young Choi, Hong Seok Choi, Todd F. Schuster, Wei-Ya Ma, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2006)

Abstract Many beneficial properties have been attributed to (−)−epigallocatechin gallate (EGCG), including chemopreventive, anticarcinogenic, and antioxidant actions. In this study, we investigated the effects of EGCG on the function of glucose-regulated protein 78 (GRP78), which is associated with the multidrug resistance phenotype of many types of cancer cells. Our investigation was directed at elucidating the mechanism of the EGCG and GRP78 interaction and providing evidence about whether EGCG modulates the activity of anticancer drugs through the inhibition of GRP78 function. We found that EGCG directly interacted with GRP78 at the ATP-binding site of protein and regulated its function by competing with ATP binding, resulting in the inhibition of ATPase activity. EGCG binding caused the conversion of GRP78 from its active monomer to the inactive dimer and oligomer forms. Further, we showed that EGCG interfered with the formation of the antiapoptotic GRP78-caspase-7 complex, which resulted in an increased etoposide-induced apoptosis in cancer cells. We also showed that EGCG significantly suppressed the transformed phenotype of breast cancer cells treated with etoposide. Overall, these results strongly suggested that EGCG could prevent the antiapoptotic effect of GRP78, which usually suppresses the caspase-mediated cell death pathways in drug-treated cancer cells, contributing to the development of drug resistance. (Cancer Res 2006; 66(18): 9260-9) (Cancer Res 2006; 66(18): 9260-9)
Staphylococcus aureusgene expression in a rat model of infective endocarditis
Authors: Frank Hanses, Christelle Roux, Paul M Dunman, Bernd Salzberger, Jean C Lee
Journal: Genome Medicine (2014)

Diabetes mellitus is a frequent underlying comorbidity in patients with Staphylococcus aureus endocarditis, and it represents a risk factor for complications and a negative outcome. The pathogenesis of staphylococcal endocardial infections in diabetic hosts has been poorly characterized, and little is known about S. aureus gene expression in endocardial vegetations.We utilized a rat model of experimental S. aureus endocarditis to compare the pathogenesis of staphylococcal infection in diabetic and nondiabetic hosts and to study the global S. aureus transcriptome in endocardial vegetations in vivo.Diabetic rats had higher levels of bacteremia and larger endocardial vegetations than nondiabetic control animals. Microarray analyses revealed that 61 S. aureus genes were upregulated in diabetic rats, and the majority of these bacterial genes were involved in amino acid and carbohydrate metabolism. When bacterial gene expression in vivo (diabetic or nondiabetic endocardial vegetations) was compared to in vitro growth conditions, higher in vivo expression of genes encoding toxins and proteases was observed. Additionally, genes involved in the production of adhesins, capsular polysaccharide, and siderophores, as well as in amino acid and carbohydrate transport and metabolism, were upregulated in endocardial vegetations. To test the contribution of selected upregulated genes to the pathogenesis of staphylococcal endocarditis, isogenic deletion mutants were utilized. A mutant defective in production of the siderophore staphyloferrin B was attenuated in the endocarditis model, whereas the virulence of a surface adhesin (ΔsdrCDE) mutant was similar to that of the parental S. aureus strain.Our results emphasize the relevance of diabetes mellitus as a risk factor for infectious endocarditis and provide a basis for understanding gene expression during staphylococcal infections in vivo.
Development of Molecularly Targeted Therapies in Hepatocellular Carcinoma: Where Do We Go Now?
Authors: Richard S. Finn
Journal: Clinical Cancer Research (2010)

Abstract Hepatocellular carcinoma (HCC), once considered an orphan disease in the West, has become a global health concern. It is the third leading cause of cancer death worldwide, and its incidence continues to increase. Historically, the development of new systemic agents for advanced HCC has been lacking despite no clear benefit with traditional cytotoxic therapies. Although two randomized studies with sorafenib for the treatment of HCC patients have recently been completed, survival benefits have been modest and highlight the unmet medical need among patients with HCC. Given the clear need, clinical development of novel systemic agents in HCC has begun in earnest. These clinical studies are founded on a growing body of basic and translational science that has identified several potential molecular targets in HCC. The successful development of such targeted agents in the future will be linked to our ability to appropriately select patients for treatment based on their clinical stage (including extent of liver disease and extent of tumor) and on potential predictive markers of response. Here, we review these data in the context of rational drug development in HCC in the front-line setting and in previously treated patients. Clin Cancer Res; 16(2); 390–7.
Assertive screening: health checks prior to exercise programmes in older people
Authors: A J Campbell
Journal: British Journal of Sports Medicine (2008)

Assertive screening, as opposed to defensive screening, is done for the participant’s benefit not the provider’s protection. It is used to identify and manage chronic health conditions and functional limitation. It is neither risk averse nor protective but an “enabling, pre-exercise medical review that will facilitate safe and effective recreational participation”.1 Such screening asserts the right of older and functionally very limited people to participate in exercise programmes.

Unnecessary safety screening, medical clearance and detailed questionnaires may be a disincentive for an older person already ambivalent about commencing an exercise programme. Such screening may be an unjustified barrier to participation and presage an unwarranted encroachment of medical services into normal human activities. In a review of safety monitoring before an exercise programme in older persons, Gill and colleagues …
A recombinant 64 kilodalton protein of Mycobacterium bovis bacillus Calmette-Guerin specifically stimulates human T4 clones reactive to mycobacterial antigens.
Authors: F Emmrich, J Thole, J van Embden, S H Kaufmann
Journal: The Journal of Experimental Medicine (1986)

A recombinant 64 kD protein of Mycobacterium bovis bacillus Calmette-Guerin (BCG) (antigen A), which amounted to approximately 2% of an E. coli lysate, was tested for its capacity to stimulate human T4 clones reactive to mycobacterial proteins. Two out of four crossreactive clones, established from a patient with tuberculoid leprosy, which could be stimulated by protein preparations of M. leprae and M. tuberculosis, and by particulate M. bovis BCG were also reactive to antigen A without further enrichment from E. coli lysate. In addition, BCG-reactive T cell clones from two of three healthy PPD+ donors reacted with antigen A. This finding shows that human T cell clones may be useful for probing gene-cloned proteins of potential value for vaccination against diseases where protection is mediated exclusively by T cells.
Epigenetic interplay between mouse endogenous retroviruses and host genes
Authors: Rita Rebollo, Katharine Miceli-Royer, Ying Zhang, Sharareh Farivar, Liane Gagnier, Dixie L Mager
Journal: Genome biology (2012)

Transposable elements are often the targets of repressive epigenetic modifications such as DNA methylation that, in theory, have the potential to spread toward nearby genes and induce epigenetic silencing. To better understand the role of DNA methylation in the relationship between transposable elements and genes, we assessed the methylation state of mouse endogenous retroviruses (ERVs) located near genes. We found that ERVs of the ETn/MusD family show decreased DNA methylation when near transcription start sites in tissues where the nearby gene is expressed. ERVs belonging to the IAP family, however, are generally heavily methylated, regardless of the genomic environment and the tissue studied. Furthermore, we found full-length ETn and IAP copies that display differential DNA methylation between their two long terminal repeats (LTRs), suggesting that the environment surrounding gene promoters can prevent methylation of the nearby LTR. Spreading from methylated ERV copies to nearby genes was rarely observed, with the regions between the ERVs and genes apparently acting as a boundary, enriched in H3K4me3 and CTCF, which possibly protects the unmethylated gene promoter. Furthermore, the flanking regions of unmethylated ERV copies harbor H3K4me3, consistent with spreading of euchromatin from the host gene toward ERV insertions. We have shown that spreading of DNA methylation from ERV copies toward active gene promoters is rare. We provide evidence that genes can be protected from ERV-induced heterochromatin spreading by either blocking the invasion of repressive marks or by spreading euchromatin toward the ERV copy.
PAF, a potent proinflammatory mediator, looking for its role in the pathogenesis of joint damage
Authors: G HERRERO-BEAUMONT, J EGIDO
Journal: Annals of the Rheumatic Diseases (1997)

LeaderPAF, a potent proinflammatory mediator, looking for its role in the pathogenesis of joint damage Cell activation is accompanied by remodelling of its membrane components producing structurally diverse intracellular and extracellular lipids that seem to be essential in signal transduction, cell-cell communication, and as mediators in inflammation and pathophysiological mechanisms. 1 Phospholipases are pivotal enzymes in the generation of these lipids, including eicosanoids (mostly prostaglandins), platelet activating factor (PAF), diacylglycerides, and other newly discovered bioactive autacoids.PAF is a potent proinflammatory phospholipid mediator, involved in the pathogenesis of lung, liver, cardiovascular, renal, and other diseases. 2The gene coding for the human specific PAF receptor has recently been cloned from leucocytes showing homology to G protein coupled receptors. 3uring the inflammatory arthritic process there are basically tissue damage phenomena combined with reparative processes.In brief, endothelial damage is followed by inflammatory cell infiltration in the perivascular area and synovial membrane.Furthermore, hyperplasia of synovial cells and accumulation of fibronectin and other matrix proteins are also seen.These morphological changes result from cellular interactions caused by a large variety of soluble mediators.We present information suggesting that PAF may be one of the important agents participating in these processes.
Antibody to the murine type 3 complement receptor inhibits T lymphocyte-dependent recruitment of myelomonocytic cells in vivo.
Authors: H Rosen, G Milon, S Gordon
Journal: The Journal of Experimental Medicine (1989)

We have used the delayed-type hypersensitivity (DTH) response to SRBC or tuberculin to examine the role of the murine type 3 complement receptor in T lymphocyte-dependent inflammatory recruitment. Intravenous injection of 5C6, a CR3-specific rat mAb known to impair myelomonocytic adhesion, divided the DTH to SRBC in actively immunized mice into two phases. The early phase, which lasted 24 h, was characterized by maximal oedema and maximal inflammatory recruitment and was 5C6 inhibitable. The later phase was 5C6 resistant and reached a peak 48 h after antigenic challenge and was superimposable on the declining peak seen in control mice. Passive transfer of reactive T cells mixed with antigen was used to examine the myelomonocytic effector arm of the DTH alone. Both passive transfer of cutaneous DTH to SRBC and passive transfer of the largely monocytic T cell-dependent recruitment to tuberculin in the peritoneal cavity were completely abolished by systemic 5C6 treatment. Injection of 5C6-treated donor leukocytes at the site of passive transfer had no effect. Treatment of donor mice with 5C6 at the time of active immunization did not alter their ability to provide reactive T cells for passive transfer. The myelomonocyte-restricted rat mAb 7/4 and the rapidly cleared F(ab')2 fragment of 5C6 showed no inhibition of the DTH. In all cases, inhibition of footpad swelling correlated with histological evidence of inhibition of myelomonocytic cell recruitment. Peritoneal cell counts after local DTH to tuberculin showed complete inhibition of monocyte recruitment. We conclude that CR3 plays a quantitatively important role in T cell-dependent inflammatory recruitment. This is absolute in passive transfer experiments, but only partial after active immunization. Leukocyte CR3 plays a common role in both immunologically specific and nonspecific inflammatory recruitment and provides a target that could possibly be manipulated to therapeutic advantage.
Transforming growth factor signalling and matrix metalloproteinases in the mucosa overlying Crohn's disease strictures
Authors: A Di Sabatino, C L Jackson, K M Pickard, M Buckley, L Rovedatti, N A B Leakey, L Picariello, P Cazzola, G Monteleone, F Tonelli, G R Corazza, T T MacDonald, S L Pender
Journal: Gut (2009)

In addition to its crucial role in dampening tissue-damaging immune responses in the gut, transforming growth factor beta (TGFbeta) is a potent profibrogenic agent inducing collagen synthesis and regulating the balance between matrix-degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). TGFbeta signalling was investigated by analysis of Smad proteins and MMPs/TIMPs in the mucosa overlying strictures in patients with Crohn's disease (CD).Specimens were collected from macroscopically normal mucosa overlying strictured and non-strictured gut of patients with fibrostenosing CD. Isolated myofibroblasts were cultured with anti-TGFbeta blocking antibody or TGF beta 1. TGFbeta transcripts were analysed by quantitative reverse transcription-PCR (RT-PCR). Smad proteins and MMPs were determined by immunoblotting. MMP-12 activity was measured by a real-time MMP-12 activity assay. An in vitro wound-healing scratch assay was used to assess myofibroblast migration.TGFbeta transcripts, phosphorylated Smad2-Smad3 (pSmad2-3) and TIMP-1 proteins were higher in mucosa overlying strictures than in mucosa overlying non-strictured areas. In contrast, mucosa overlying strictured gut had lower expression of Smad7, MMP-12 and MMP-3. Myofibroblasts from mucosa overlying strictured gut showed higher TGFbeta transcripts, a greater pSmad2-3 response to TGFbeta, increased TIMP-1, lower Smad7, increased collagen production and reduced migration ability compared with myofibroblasts from mucosa overlying non-strictured gut. TGFbeta blockade increased myofibroblast MMP-12 production and migration, more obviously in myofibroblasts isolated from mucosa overlying non-strictured compared with strictured gut.Changes in TGF-beta signalling and MMP production were identified in the mucosa overlying strictures in CD which may give a window into the process of fibrosis.