tbuckley/cabot-search huggingface dataset:
Benign intracranial hypertension during prednisolone treatment for inflammatory bowel disease.
Authors: M Newton, B T Cooper
Journal: Gut (1994)

Benign intracranial hypertension (BIH, pseudotumour cerebri) is a rare condition with unknown aetiology although hormonal influences have been implicated. It occurs spontaneously, particularly in young obese women, and is associated with several drug treatments including corticosteroids. Two young adult women are described in whom headache and papilloedema in association with raised intracranial pressure occurred during prednisolone treatment for inflammatory bowel disease. This provides further evidence of the risk of BIH during corticosteroid treatment and has not been described before in adults with this condition. Advice is given to gastroenterologists to use corticosteroids with caution in adults, particularly young, fertile female patients. The treatment of a severe relapse of colitis in a patient who has had one episode of steroid related BIH remains a dilemma.
Down-Regulation of CD9 Expression during Prostate Carcinoma Progression Is Associated with <i>CD9</i> mRNA Modifications
Authors: Jia-Chi Wang, Louis R. Bégin, Nathalie G. Bérubé, Simone Chevalier, Armen G. Aprikian, Henriette Gourdeau, Mario Chevrette
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cluster-of-differentiation antigen 9 (CD9) protein, a member of the tetraspanin family, has been implicated in carcinogenesis of various human tumors. Although decreased expression of the CD82 tetraspanin protein, a close CD9 relative, is associated with prostate cancer progression, CD9 expression has not been analyzed in this malignancy. Experimental Design: CD9 expression in human prostatic adenocarcinoma was analyzed by immunohistochemistry on 167 primary tumors and 88 lymph node or bone metastases. CD9 cDNA was sequenced from two human prostate cancer cell lines, prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (PIN), and normal prostatic tissues. Results: Although CD9 was detected in the epithelium of normal prostatic tissues, reduced or loss of CD9 expression within neoplastic cells was observed in 24% of 107 clinically localized primary adenocarcinomas, 85% of 60 clinically advanced primary adenocarcinomas, 85% of 65 lymph node metastases, and 65% of 23 bone metastases. Difference in CD9 expression between clinically localized and advanced diseases was highly significant (P &amp;lt; 1 × 10−7). Whereas there was no alteration of CD9 cDNA in normal tissues, all PC-3–derived cell lines, one PIN, and four prostatic adenocarcinomas harbored deletions in their CD9 cDNAs. Recurring CD9 point mutations were also found in PC-3M-LN4 cells, one PIN, and seven prostatic adenocarcinomas. Conclusions: CD9 expression is significantly reduced and even lost during prostate cancer progression. Moreover, deletions and mutations of the CD9 mRNA may be associated with loss of protein expression observed in tumor cells. Our data suggest that CD9 inactivation may play an important role in prostate cancer progression.
Dimethyl Sulfoxide Inhibits Tissue Factor Expression, Thrombus Formation, and Vascular Smooth Muscle Cell Activation
Authors: Giovanni G. Camici, Jan Steffel, Alexander Akhmedov, Nicola Schafer, Jeannette Baldinger, Urs Schulz, Kushiar Shojaati, Christian M. Matter, Zhihong Yang, Thomas F. Lüscher, Felix C. Tanner
Journal: Circulation (2006)

Subacute stent thrombosis is a major clinical concern, and the search for new molecules to cover stents remains important. Dimethyl sulfoxide (DMSO) is used for preservation of hematopoietic progenitor cells and is infused into patients undergoing bone marrow transplantation. Despite its intravenous application, the impact of DMSO on vascular cells has not been assessed.In human endothelial cells, monocytes, and vascular smooth muscle cells (VSMC), DMSO inhibited tissue factor (TF) expression and activity in response to tumor necrosis factor-alpha or thrombin in a concentration-dependent manner. DMSO did not exert any toxic effects as assessed by phase-contrast microscopy, trypan blue exclusion, and lactate dehydrogenase release. Real-time polymerase chain reaction revealed that inhibition of TF expression occurred at the mRNA level. This effect was mediated by reduced activation of the mitogen-activated protein kinases c-Jun terminal NH2 kinase (51+/-6%; P=0.0005) and p38 (50+/-3%; P<0.0001) but not p44/42 (P=NS). In contrast to TF, DMSO did not affect expression of TF pathway inhibitor or plasminogen activator inhibitor-1. In vivo, DMSO treatment suppressed TF activity (41%; P<0.002) and prevented thrombotic occlusion in a mouse carotid artery photochemical injury model. DMSO also inhibited VSMC proliferation (70%; P=0.005) and migration (77%; P=0.0001) in a concentration-dependent manner; moreover, it prevented rapamycin and paclitaxel-induced upregulation of TF expression.DMSO suppresses TF expression and activity, as well as thrombus formation; in addition, it inhibits VSMC proliferation and migration. Given its routine use in modern clinical practice, we propose DMSO as a novel strategy for coating drug-eluting stents and treating acute coronary syndromes.
A plague of deubiquitination
Authors: Kendall Powell
Journal: The Journal of Experimental Medicine (2005)

Antiinflammatory eggsProteins secreted by parasite eggs might hold the key to the next antiinflammatory therapy.On page 1319, Smith and colleagues describe the first chemokine binding protein (CKBP) produced by a human pathogen and show that it can suppress acute inflammation in disease models.The blood-dwelling worm Schistosoma mansoni takes advantage of the host's immune system in two ways.It subverts specific inflammatory cells to help move its eggs from the intestinal vasculature to the feces, where they can be shed.It also suppresses the immune response in order to establish chronic infections, in part as shown here by keeping other inflammatory cells away from the eggs.This selective cell recruitment was not due solely to cytokine modulation, a known schistosome ability.As viruses produce chemokine binding proteins to neutralize host chemokines, the authors investigated whether S. mansoni might also make a chemokine binding protein to mask the eggs from strong inflammation.Smith and colleagues now identify a novel CKBP (smCKBP) that is secreted from schistosome eggs.This protein bound to the chemokines CXCL8 and CCL3 and prevented them from binding to their receptors on immune cells.Injecting mice with recombinant smCKBP blocked chemokinemediated neutrophil infiltration in response to a variety of inflammatory stimuli.This treatment, however, had no effect on chronic inflammation disorders such as arthritis.The authors suggest that, in nature, the parasite eggs secrete smCKBP to keep neutrophils and macrophages out of the surrounding granuloma so as not to attract immune attention, but pinning this mechanism down will require further study.Already tolerated by infected humans, smCKBP holds great potential as a new therapy for acute inflammatory diseases, especially those caused by neutrophilia.
Endovascular versus Open Repair of Abdominal Aortic Aneurysm
Authors: Nora Toma
Journal: New England Journal of Medicine (2010)

Few data are available on the long-term outcome of endovascular repair of abdominal aortic aneurysm as compared with open repair.From 1999 through 2004 at 37 hospitals in the United Kingdom, we randomly assigned 1252 patients with large abdominal aortic aneurysms (> or = 5.5 cm in diameter) to undergo either endovascular or open repair; 626 patients were assigned to each group. Patients were followed for rates of death, graft-related complications, reinterventions, and resource use until the end of 2009. Logistic regression and Cox regression were used to compare outcomes in the two groups.The 30-day operative mortality was 1.8% in the endovascular-repair group and 4.3% in the open-repair group (adjusted odds ratio for endovascular repair as compared with open repair, 0.39; 95% confidence interval [CI], 0.18 to 0.87; P=0.02). The endovascular-repair group had an early benefit with respect to aneurysm-related mortality, but the benefit was lost by the end of the study, at least partially because of fatal endograft ruptures (adjusted hazard ratio, 0.92; 95% CI, 0.57 to 1.49; P=0.73). By the end of follow-up, there was no significant difference between the two groups in the rate of death from any cause (adjusted hazard ratio, 1.03; 95% CI, 0.86 to 1.23; P=0.72). The rates of graft-related complications and reinterventions were higher with endovascular repair, and new complications occurred up to 8 years after randomization, contributing to higher overall costs.In this large, randomized trial, endovascular repair of abdominal aortic aneurysm was associated with a significantly lower operative mortality than open surgical repair. However, no differences were seen in total mortality or aneurysm-related mortality in the long term. Endovascular repair was associated with increased rates of graft-related complications and reinterventions and was more costly. (Current Controlled Trials number, ISRCTN55703451.)
Spontaneous Tumor Lysis Syndrome Presenting As Acute Renal Failure in an Adult With De Novo Aleukemic T-ALL: Value of Renal Biopsy?
Authors: Konstantin Schlick, Gernot Schilcher, Peter Krisper, Peter Neumeister, Werner Linkesch, Christine Beham-Schmid, Ariane Aigelsreiter
Journal: Journal of Clinical Oncology (2011)
IMPACT OF BIVALIRUDIN ON ACCESS AND NON-ACCESS RELATED BLEEDING IN PATIENTS UNDERGOING BALLOON AORTIC VALVULOPLASTY: RESULTS FROM A 2-CENTER REGISTRY
Authors: Annapoorna Subhash Kini, Kleanthis Theodoropoulos, Jennifer Yu, Usman Baber, Samantha Sartori, Georgios Vlachojannis, Jason Kovacic, Mauricio Cohen, Robert Pyo, Brian O&apos;Neill, David Knopf, Claudia Martinez, Carlos Alfonso, Roxana Mehran, George Dangas, Samin Sharma
Journal: Journal of the American College of Cardiology (2012)
Type 2 Diabetes
Authors: R.J. MacIsaac, C. Tsalamandris, S. Panagiotopoulos, T.J. Smith, K.J. McNeill, G. Jerums
Journal: Journal of the American Society of Nephrology (2005)

Renal failure in type 2 diabetes is truly a medical catastrophe of worldwide dimension ([1][1]): In all countries of the western world, diabetes, mostly type 2, has become the most frequent comorbid condition in patients admitted for renal replacement therapy. It had long been recognized that the
Bacterial proteases in IBD and IBS
Authors: Natalie Steck, Kerstin Mueller, Michael Schemann, Dirk Haller
Journal: Gut (2011)

Proteases play a decisive role in health and disease. They fulfil diverse functions and have been associated with the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The current knowledge focuses on host-derived proteases including matrix metalloproteinases, various serine proteases and cathepsins. The possible contribution of bacterial proteases has been largely ignored in the pathogenesis of IBD and IBS, although there is increasing evidence, especially demonstrated for proteases from pathogenic bacteria. The underlying mechanisms extend to proteases from commensal bacteria which may be relevant for disease susceptibility. The intestinal microbiota and its proteolytic capacity exhibit the potential to contribute to the pathogenesis of IBD and IBS. This review highlights the relevance of host- and bacteria-derived proteases and their signalling mechanisms.
Iatrogenic Acute Cardiac Tamponade
Authors: Edwin J. Lilly
Journal: JAMA (1961)

In each of the 3 cases here described there was sudden collapse during surgical or diagnostic procedures within the thoracic cavity, and in each case the trouble was recognized as cardiac tamponade due to hemorrhage into the pericardium. Removal of the extravasated blood and rhythmic manual compression of the heart (RMC) were carried out in each case. This sufficed to restore a regular beat in the second patient; in the first it was also necessary to defibrillate electrically; and in the third calcium gluconate was given intravenously. All patients recovered without evidence of residual neurological damage. Acute cardiac tamponade can result from invasion of the thorax during surgical or diagnostic procedures. It appears without warning and demands immediate treatment, preferably by thoracotomy, with RMC if necessary.
Surgical preparation induces injury and promotes smooth muscle cell proliferation in a culture of human saphenous vein
Authors: A. A Soyombo, G. D Angelini, A. J Bryan, A. C Newby
Journal: Cardiovascular Research (1993)

Objective: The aim was to investigate the influence of vessel wall injury, incurred during routine vein preparation, on smooth muscle cell proliferation. Methods: A newly developed quantitative organ culture was used, in which segments of human saphenous vein were cultured in medium containing 30% fetal bovine serum and 1 μCi·ml−1 of [3H]thymidine for up to 14 d. Endothelial integrity was measured by scanning electron microscopy and medial cell viability by adenine nucleotide concentrations. Cell proliferation was measured by DNA concentration, global incorporation of [3H]thymidine, and by counting labelled cells in autoradiographs of transverse sections. Results: Surgical preparation led to endothelial injury and reduced adenine triphosphate concentration by 60%. Surgically prepared veins also suffered a significant decline in DNA concentration during culture, which implied that injury led to cell necrosis. Surgically prepared veins showed 2.1- and 2.7-fold greater global incorporation of [3H]thymidine than freshly isolated veins after 7 and 14 d in culture, respectively, which corresponded with a 23-fold and 11-fold greater abundance of thymidine labelled cells in the medial layer. Intimal thickening and the numbers of total and thymidine labelled cells in the intimal layer were similar. Conclusions: The data show that injury incurred during routine surgical preparation is associated with enhanced medial smooth muscle cell proliferation. The effect of injury was most probably to permit an increased response of medial smooth muscle cells to serum derived mitogens. Cardiovascular Research 1993;27:1961-1967
Molecular mechanism of mast cell–mediated innate defense against endothelin and snake venom sarafotoxin
Authors: Lars A. Schneider, Susan M. Schlenner, Thorsten B. Feyerabend, Markus Wunderlin, Hans-Reimer Rodewald
Journal: The Journal of Experimental Medicine (2007)

Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such “nicking” is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not “evade” Mc-cpa's substrate specificity without loss of toxicity.
Functional Selectivity at the μ-Opioid Receptor: Implications for Understanding Opioid Analgesia and Tolerance
Authors: Kirsten M. Raehal, Cullen L. Schmid, Chad E. Groer, Laura M. Bohn
Journal: Pharmacological Reviews (2011)

Opioids are the most effective analgesic drugs for the management of moderate or severe pain, yet their clinical use is often limited because of the onset of adverse side effects. Drugs in this class produce most of their physiological effects through activation of the μ opioid receptor; however, an increasing number of studies demonstrate that different opioids, while presumably acting at this single receptor, can activate distinct downstream responses, a phenomenon termed functional selectivity. Functional selectivity of receptor-mediated events can manifest as a function of the drug used, the cellular or neuronal environment examined, or the signaling or behavioral measure recorded. This review summarizes both in vitro and in vivo work demonstrating functional selectivity at the μ opioid receptor in terms of G protein coupling, receptor phosphorylation, interactions with β-arrestins, receptor desensitization, internalization and signaling, and details on how these differences may relate to the progression of analgesic tolerance after their extended use.
Success story: Clontarf Foundation promotes education, life-skills and employment prospects through Australian Rules Football
Authors: Gerard Neesham, Andrew P Garnham
Journal: British Journal of Sports Medicine (2012)

BJSM 's mandate is to contribute to health—health of individuals, groups and nations. BJSM 's specific niche is in innovation (research), education and knowledge translation—turning research into action. As a result, papers such as the call to the WHO to undertake ‘7 investments’ to prevent physical inactivity and thus, contribute to reducing non-communicable disease1 are central to BJSM 's mission. The BJSM has published papers on how ‘football’ (as it is known in most parts of the world), contributes to health and education.2 ,3 In this issue of BJSM , guest-edited by the Australasian College of Sports Physicians it is appropriate to highlight how Australian Rules Football and has been used to approach a similar problem. A philanthropic Foundation—the Clontarf Foundation—sees football (as a vehicle to improve the education, discipline, life skills, self-esteem and employment prospects of young Aboriginal men and by doing so equip them to participate meaningfully in society. Success stories are important in implementation and dissemination;4 the purpose of this and similar articles in BJSM are to draw attention to programmes that work so they can be adapted …
Adolf Meyer and the Development of American Psychiatry
Authors: THEODORE LIDZ
Journal: American Journal of Psychiatry (1966)

Adolf Meyer was a major force in molding psychiatry into its current form; his teachings are so solidly incorporated into American psychiatric theory and practice that the extent of his influence is often over-looked. He brought American psychiatry its pluralistic and instrumental orientation, its holistic approach, its psychobiological understanding that human behavior is integrated at a symbolic level, its conceptualization of psychiatric disorders as maladaptive reaction patterns rather than as discrete disease entities, its interest in the psychotherapy of the psychoses. He provided psychiatry with a fundamental scientific orientation that fitted into the remainder of science and also opened the way for the inclusion of data concerning human experience and biography in biological thinking.
Therapeutic Response in Feline Sandhoff Disease Despite Immunity to Intracranial Gene Therapy
Authors: Allison M Bradbury, J Nicholas Cochran, Victoria J McCurdy, Aime K Johnson, Brandon L Brunson, Heather Gray-Edwards, Stanley G Leroy, Misako Hwang, Ashley N Randle, Laura S Jackson, Nancy E Morrison, Rena C Baek, Thomas N Seyfried, Seng H Cheng, Nancy R Cox, Henry J Baker, M Begona Cachón-González, Timothy M Cox, Miguel Sena-Esteves, Douglas R Martin
Journal: Molecular Therapy (2013)

Salutary responses to adeno-associated viral (AAV) gene therapy have been reported in the mouse model of Sandhoff disease (SD), a neurodegenerative lysosomal storage disease caused by deficiency of β-N-acetylhexosaminidase (Hex). While untreated mice reach the humane endpoint by 4.1 months of age, mice treated by a single intracranial injection of vectors expressing human hexosaminidase may live a normal life span of 2 years. When treated with the same therapeutic vectors used in mice, two cats with SD lived to 7.0 and 8.2 months of age, compared with an untreated life span of 4.5 ± 0.5 months (n = 11). Because a pronounced humoral immune response to both the AAV1 vectors and human hexosaminidase was documented, feline cDNAs for the hexosaminidase α- and β-subunits were cloned into AAVrh8 vectors. Cats treated with vectors expressing feline hexosaminidase produced enzymatic activity >75-fold normal at the brain injection site with little evidence of an immune infiltrate. Affected cats treated with feline-specific vectors by bilateral injection of the thalamus lived to 10.4 ± 3.7 months of age (n = 3), or 2.3 times as long as untreated cats. These studies support the therapeutic potential of AAV vectors for SD and underscore the importance of species-specific cDNAs for translational research. Salutary responses to adeno-associated viral (AAV) gene therapy have been reported in the mouse model of Sandhoff disease (SD), a neurodegenerative lysosomal storage disease caused by deficiency of β-N-acetylhexosaminidase (Hex). While untreated mice reach the humane endpoint by 4.1 months of age, mice treated by a single intracranial injection of vectors expressing human hexosaminidase may live a normal life span of 2 years. When treated with the same therapeutic vectors used in mice, two cats with SD lived to 7.0 and 8.2 months of age, compared with an untreated life span of 4.5 ± 0.5 months (n = 11). Because a pronounced humoral immune response to both the AAV1 vectors and human hexosaminidase was documented, feline cDNAs for the hexosaminidase α- and β-subunits were cloned into AAVrh8 vectors. Cats treated with vectors expressing feline hexosaminidase produced enzymatic activity >75-fold normal at the brain injection site with little evidence of an immune infiltrate. Affected cats treated with feline-specific vectors by bilateral injection of the thalamus lived to 10.4 ± 3.7 months of age (n = 3), or 2.3 times as long as untreated cats. These studies support the therapeutic potential of AAV vectors for SD and underscore the importance of species-specific cDNAs for translational research.