tbuckley/cabot-search huggingface dataset:
Cognitive Deficits and Predictors 3 Years After Diagnosis of a Pilocytic Astrocytoma in Childhood
Authors: Femke K. Aarsen, Philippe F. Paquier, Willem-Frans Arts, Marie-Lise Van Veelen, Erna Michiels, Maarten Lequin, Coriene E. Catsman-Berrevoets
Journal: Journal of Clinical Oncology (2009)

Purpose To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). Patients and Methods Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. Conclusion Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).
Stem Cell Therapy for Heart Failure
Authors: Philippe Menasché
Journal: Circulation (2009)

So far, the major safety issue raised by the use of stem cells for cardiac repair has been the occurrence of ventricular arrhythmias, particularly after skeletal myoblast transplantation. Although one cannot refute a potential intrinsic arrhythmogenicity of stem cells, primarily related to their common lack of electromechanical integration into the recipient myocardium, it is also important to recognize that patients eligible for cell replacement therapy are prone to develop arrhythmias because of their underlying ischemic heart disease. Another confounding factor is the method used for the intramyocardial delivery of the cells, which can cause enough inflammatory tissue damage to further increase ventricular irritability on top of an already high baseline level. Thus any strategy designed to minimize the risk of stem cell–associated ventricular arrhythmias should take into account, besides the cell-specific ability to appropriately couple with host cardiomyocytes, the method of cell transfer and the nature of the myocardial environment targeted for cell engraftment. A more accurate characterization of the baseline risk of arrhythmias in these patients would thus be helpful for better assessing the respective contribution of the donor cells and the host myocardium to these complications. The risk-to-benefit ratio of stem cell therapy will finally have to be revisited in light of the fact that because this baseline risk is usually high, most of these patients will in any way be fitted with an implantable defibrillator.
Harnessing the Multifunctionality in Nature: A Bioactive Agent Release System with Self‐Antimicrobial and Immunomodulatory Properties
Authors: Hayriye Özçelik, Nihal Engin Vrana, Alexandru Gudima, Vladimir Riabov, Alexei Gratchev, Youssef Haikel, Marie‐Hélène Metz‐Boutigue, Adele Carradò, Jacques Faerber, Thierry Roland, Harald Klüter, Julia Kzhyshkowska, Pierre Schaaf, Philippe Lavalle
Journal: Advanced Healthcare Materials (2015)

Major problems with biomedical devices in particular implants located in nonsterile environments concern: (i) excessive immune response to the implant, (ii) development of bacterial biofilms, and (iii) yeast and fungi infections. An original multifunctional coating that addresses all these issues concomitantly is developed. A new exponentially growing polyelectrolyte multilayer film based on polyarginine (PAR) and hyaluronic acid (HA) is designed. The films have a strong inhibitory effect on the production of inflammatory cytokines released by human primary macrophage subpopulations. This could reduce potential chronic inflammatory reaction following implantation. Next, it is shown that PAR, due to its positive charges, has an antimicrobial activity in film format against Staphylococcus aureus for 24 h. In order to have a long‐term antimicrobial activity, a precursor nanoscale silver coating is deposited on the surface before adding the PAR/HA films. Moreover, the PAR/HA films can be easily further functionalized by embedding antimicrobial peptides, like catestatin (CAT), a natural host defense peptide. This PAR/HA+CAT film proves to be effective as an antimicrobial coating against yeast and fungi and its cytocompatibility is also assessed. Finally, this all‐in‐one system constitutes an original strategy to limit inflammation and prevents bacteria, yeast, and fungi infections.
Pharmacology and inotropic potential of forskolin in the human heart.
Authors: M R Bristow, R Ginsburg, A Strosberg, W Montgomery, W Minobe
Journal: Journal of Clinical Investigation (1984)

We evaluated the effects of the diterpene compound forskolin in human myocardial adenylate cyclase preparations, isolated trabeculae and papillary muscles derived from failing human hearts, and acutely instrumented dogs. Forskolin was a potent, powerful activator of human myocardial adenylate cyclase and produced maximal effects that were 4.82 (normally functioning left ventricle) and 6.13 (failing left ventricle) fold greater than isoproterenol. In contrast to isoproterenol, forskolin retained full activity in membrane preparations derived from failing hearts. In cyclase preparations, forskolin demonstrated unique substrate and Mg2+ kinetic properties that could be distinguished from hormone receptor-coupled agonists or fluoride ion. The adenylate cyclase stimulatory effect of forskolin was synergistic with isoproterenol, apparently due to the location of forskolin activation being beyond the level of hormone receptor-agonist in the receptor-cyclase complex. Forskolin was a potent positive inotrope in failing human myocardium, producing a stimulation of contraction that was similar to isoproterenol. Finally, in open chest dogs forskolin was a positive inotropic agent that reduced preload and afterload. We conclude that forskolin belongs to a class of agents that may have therapeutic potential in the treatment of congestive heart failure.
RECURRENT GENITAL AND ORAL ULCERATION WITH EOSINOPHILIA.
Authors: I. J. MERENLENDER, B. SCHWARTZ, J. L. STAFFORD
Journal: British Journal of Dermatology (1961)

Journal Article RECURRENT GENITAL AND ORAL ULCERATION WITH EOSINOPHILIA. Get access I. J. MERENLENDER, M.D. (Berlin), I. J. MERENLENDER, M.D. (Berlin) The Departments of Dermatology and Haematology, St. George's Hospital, London, S.W.1 Search for other works by this author on: Oxford Academic Google Scholar B. SCHWARTZ, M.D.(Lond.), D.P.H., B. SCHWARTZ, M.D.(Lond.), D.P.H. The Departments of Dermatology and Haematology, St. George's Hospital, London, S.W.1 Search for other works by this author on: Oxford Academic Google Scholar J. L. STAFFORD, M.B., Ch.B.(Birm.). J. L. STAFFORD, M.B., Ch.B.(Birm.). The Departments of Dermatology and Haematology, St. George's Hospital, London, S.W.1 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 7, 1 July 1961, Pages 273–277, https://doi.org/10.1111/j.1365-2133.1961.tb14444.x Published: 01 July 1961
Role of Adhesin Release for Mucosal Colonization by a Bacterial Pathogen
Authors: Loïc Coutte, Sylvie Alonso, Nathalie Reveneau, Eve Willery, Brigitte Quatannens, Camille Locht, Françoise Jacob-Dubuisson
Journal: The Journal of Experimental Medicine (2003)

Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract.
The effects of KH 1060, a potent 20-epi analogue of the vitamin D3 hormone, on hairless mouse skin in vivo
Authors: R. GNIADECKI, M. GNIADECKA, J. SERUP
Journal: British Journal of Dermatology (2010)

Dermal effects of KH 1060, a novel, highly potent 20‐epi analogue of 1α,25‐dihyroxyvitamin D3, were investigated in a hairless mouse model. During daily topical applications of a 0.4 μm solution of KH 1060 for 4 weeks, epidermal hyperplasia and an increase of dermal thickness and mass were observed. KH 1060 upregulated glycosaminoglycan and collagen synthesis in the skin, and increased glycosaminoglycan deposition in the subepidermal region. Reverse transcription‐polymerase chain reaction amplification of the transforming growth factor (TGF) β1‐specific mRNA revealed that KH 1060 stimulated expression of this growth factor in the epidermis, but not in the dermis. Changes observed after application of 1α, 25‐dihydroxyvitamin D3 were much less pronounced but qualitatively similar to the effects of KH 1060, whereas structurally related but receptor inactive compounds, vitamin D3 and 1β,25‐dihydroxyvitamin D3, did not produce any effects. Furthermore, we were unable to demonstrate the involvement of the non‐genomic, receptor‐independent vitamin D signalling in the skin, using a specific stimulator (Ro 24–2090) and a blocker (1β, 25‐dihydroxyvitamin D3) of this pathway. Our findings provide the first evidence that a strong vitamin D3 analogue triggers synthesis of skin connective tissue, possibly via vitamin D receptor activation and the paracrine action of epidermis‐derived TGF‐β1.
Sensitization to airborne allergens among adults and its impact on allergic symptoms: A population survey in northern Vietnam
Authors: Hoàng Thi Lâm, Linda Ekerljung, Anders Bjerg, Nguyên Van Tuòng, B. Lundback, Eva Ronmark
Journal: European Respiratory Journal (2014)

Background Allergic sensitization is associated with allergic diseases and asthma. These associations have not been studied on general population level among adults in Vietnam.

Aim To study the prevalence of allergic sensitization and its association with asthma and allergic rhinitis among adults in urban and rural Vietnam.

Methods From 5782 responders to a questionnaire survey in urban and rural northern Vietnam a random sample was invited to a clinical follow-up study, and 684 (46%) participated. The methods included a structured interview using a modified GA2LEN questionnaire on symptoms and possible determinants for disease. Skin prick test (SPT) with ten common airborne allergens, lung function test, and methacholine test was performed among subjects aged ≤60 years.

Results Allergic sensitization was most common to B tropicalis (23.8%), followed by D pteronyssinus (13.5%), cockroach (13.3%) and D farinae (10.5%). Altogether 33.8% had a positive SPT to at least one allergen. Sensitization to animals, pollen and moulds were low. No major difference by area was found. Sensitization to all major allergens was significantly more common among men. Allergic rhinitis was strongly associated with sensitization to mites, cockroach, cats and dogs. In contrast, sensitization was not associated with a report of asthma or symptoms common in asthma, although a significant association was found between the number of positive SPT reactions and bronchial hyper-reactivity defined as PC20 ≤2mg/ml.

Conclusion The storage mite B tropicalis was the most common sensitizer in northern Vietnam. Sensitization was associated with allergic rhinitis but less so with asthma.
Captopril Overdose Resulting in Hypotension
Authors: W. Lynn Augenstein
Journal: JAMA (1988)

We present a case in which a patient took an overdose of captopril (Capoten) and alprazolam (Xanax) in a suicide attempt. The patient presented with hypotension (systolic blood pressure of 80 mm Hg) and drowsiness. The hypotension initially responded to administration of intravenous fluids and dopamine; however, it recurred twice at 18.5 and 24.5 hours after ingestion. These episodes again responded to administration of fluids and dopamine. A plasma captopril level of 27,391.1 nmol/L (5982 ng/mL) was documented, as well as a depressed level of angiotensin converting enzyme. Captopril is an angiotensin converting enzyme inhibitor used in the management of hypertension and ventricular failure; to our knowledge, this is the first case of an acute captopril overdose reported in the English-language literature. The role of captopril in inducing hypotension is discussed herein.
Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation
Authors: H. Wang
Journal: Journal of Clinical Investigation (2006)

The CD18 hypomorphic (CD18hypo) PL/J mouse model clinically resembling human psoriasis is characterized by reduced expression of the common chain of beta2 integrins (CD11/CD18) to only 2-16% of WT levels. Previously we found that this chronic psoriasiform skin inflammation also depends on the presence of CD4+ T cells. Herein we investigated the role of macrophages in this CD18hypo mouse model. Activated macrophages were significantly increased in lesional skin as well as in inflamed skin draining lymph nodes (DLNs) of affected CD18hypo mice and were identified as being an important source of TNF-alpha in vivo. Both depletion of macrophages and neutralization of TNF-alpha resulted in a significant alleviation of psoriasiform skin inflammation. As monocyte chemotactic protein 1 was enhanced in lesional skin of affected CD18hypo mice, we intradermally injected recombinant murine monocyte chemotactic protein-1 (rJE/MCP-1) alone or in combination with rTNF-alpha into the skin of healthy CD18hypo mice. Only simultaneous injection of rJE/MCP-1 and rTNF-alpha, but neither substance alone, resulted in the induction of psoriasiform skin inflammation around the injection sites with recruitment and activation of macrophages. Collectively, our data suggest that maintenance of psoriasiform skin inflammation critically depends on efficient recruitment and activation of macrophages with sufficient release of TNF-alpha.
Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog.
Authors: R J Bache, R M Ball, F R Cobb, J C Rembert, J C Greenfield
Journal: Journal of Clinical Investigation (1975)

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.
Phase I, Dose-Escalation Trial of the Oral Cyclin-Dependent Kinase 4/6 Inhibitor PD 0332991, Administered Using a 21-Day Schedule in Patients with Advanced Cancer
Authors: Keith T. Flaherty, Patricia M. LoRusso, Angela DeMichele, Vandana G. Abramson, Rachel Courtney, Sophia S. Randolph, M. Naveed Shaik, Keith D. Wilner, Peter J. O'Dwyer, Gary K. Schwartz
Journal: Clinical Cancer Research (2011)

To identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the first-in-class, oral CDK4/6 inhibitor PD 0332991 administered once daily for 21 of 28 days (3/1 schedule) in patients with retinoblastoma protein (Rb)-positive advanced solid tumors and to describe pharmacokinetic-pharmacodynamic relationships relative to drug effects.This open-label phase I study (NCT00141297) enrolled patients who received PD 0332991 orally in six dose-escalation cohorts in a standard 3 + 3 design.Forty-one patients were enrolled. DLTs were observed in five patients (12%) overall; at the 75, 125, and 150 mg once daily dose levels. The MTD and recommended phase II dose of PD 0332991 was 125 mg once daily. Neutropenia was the only dose-limiting effect. After cycle 1, grade 3 neutropenia, anemia, and leukopenia occurred in five (12%), three (7%), and one (2%) patient(s), respectively. The most common non-hematologic adverse events included fatigue, nausea, and diarrhea. Thirty-seven patients were evaluable for tumor response; 10 (27%) had stable disease for ≥4 cycles of whom six derived prolonged benefit (≥10 cycles). PD 0332991 was slowly absorbed (median T(max), 5.5 hours), and slowly eliminated (mean half-life was 25.9 hours) with a large volume of distribution (mean, 2,793 L). The area under the concentration-time curve increased linearly with dose. Using an E(max) model, neutropenia was shown to be proportional to exposure.PD 0332991 warrants phase II testing at 125 mg once daily, at which dose neutropenia was the sole significant toxicity.
Tumor Immunobiological Differences in Prostate Cancer between African-American and European-American Men
Authors: Tiffany A. Wallace, Robyn L. Prueitt, Ming Yi, Tiffany M. Howe, John W. Gillespie, Harris G. Yfantis, Robert M. Stephens, Neil E. Caporaso, Christopher A. Loffredo, Stefan Ambs
Journal: Cancer Research (2008)

Abstract The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared with European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical variables. We also evaluated 18 nontumor prostate tissues from seven African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate of ≤5% to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Several known metastasis-promoting genes, including autocrine mobility factor receptor, chemokine (C-X-C motif) receptor 4, and matrix metalloproteinase 9, were more highly expressed in tumors from African-Americans than European-Americans. Furthermore, a two-gene tumor signature that accurately differentiated between African-American and European-American patients was identified. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. [Cancer Res 2008;68(3):927–36]
Cyclophosphamide Triggers Follicle Activation and “Burnout”; AS101 Prevents Follicle Loss and Preserves Fertility
Authors: Lital Kalich-Philosoph, Hadassa Roness, Alon Carmely, Michal Fishel-Bartal, Hagai Ligumsky, Shoshana Paglin, Ido Wolf, Hannah Kanety, Benjamin Sredni, Dror Meirow
Journal: Science Translational Medicine (2013)

Cyclophosphamide activates dormant follicle growth, leading to depletion of ovarian reserve, and AS101 prevents this activation, rescuing fertility in mice.
A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study
Authors: A.A. Lissoni, N. Colombo, A. Pellegrino, G. Parma, P. Zola, D. Katsaros, S. Chiari, A. Buda, F. Landoni, M. Peiretti, T. Dell’Anna, R. Fruscio, M. Signorelli, R. Grassi, I. Floriani, R. Fossati, V. Torri, E. Rulli
Journal: Annals of Oncology (2009)