tbuckley/cabot-search huggingface dataset:
Effects of endothelins on collagen turnover in cardiac fibroblasts
Authors: E. Guarda, L. C Katwa, P. R Myers, S. C Tyagi, K. T Weber
Journal: Cardiovascular Research (1993)

Objectives: Endothelins (ET-1 and ET-3) may be promoters of tissue remodelling, including fibrillar collagen accumulation. The hypothesis that ET-1 and ET-3 each modify cardiac fibroblast collagen turnover was tested. Methods: Confluent adult rat cardiac fibroblasts were maintained for 24 hours in medium with 0.4% fetal call serum, and varying concentrations of ET-1 or ET-3. Collagen synthesis was measured by 3H-proline incorporation. The synthesis of type I and III collagens was measured by enzyme linked immunosorbent assay (ELISA). The effects of endothelins on collagenase activity were estimated by zymography. Results: ET-1 and ET-3 increased collagen synthesis in a concentration-dependent manner with a maximal 1.7-fold increase (p < 0.001 v control cells). The effects of ET-1 or ET-3 on collagen synthesis were not blocked by PED-3512-PI (10−6 M). an ETA receptor antagonist. ET-1 and ET-3 each significantly (p < 0.01) increased the synthesis of both type I and III collagens. ET-1 caused a 5.8-fold decrease in collagenase activity (p<0.01 v control), and this effect was blocked by PED-3512-PI (10−6 M). ET-3 did not alter collagenase activity. Conclusion: ET-1 and ET-3 increased the synthesis of type I and III collagens, whereas ET-1. but not ET-3, reduced collagenase activity. The effects of endothelins on collagen synthesis in cardiac fibroblasts seem to be mediated through ETA and ETB receptors, whereas their effects on collagenase seem to be mediated by ETA receptors. Cardiovascular Research 1993: 27: 2130-2134
Year in review in intensive care medicine: 2003. II. Brain injury, hemodynamics, gastrointestinal tract, renal failure, metabolism, trauma, and postoperative
Authors: Edward Abraham, Peter Andrews, Massimo Antonelli, Laurent Brochard, Christian Brun-Buisson, Geoffrey Dobb, Jean-Yves Fagon, Johan Groeneveld, Jordi Mancebo, Philipp Metnitz, Stefano Nava, Michael Pinsky, Peter Radermacher, Marco Ranieri, Christian Richard, Robert Tasker, Benoit Vallet
Journal: Intensive Care Medicine (2004)
Renal findings in rheumatoid arthritis: clinical aspects of 132 necropsies.
Authors: M Boers, A M Croonen, B A Dijkmans, F C Breedveld, F Eulderink, A Cats, J J Weening
Journal: Annals of the Rheumatic Diseases (1987)

Renal abnormalities in 132 necropsied patients with rheumatoid arthritis were studied. Clinical findings before death included extra-articular manifestations of the disease (86% of patients), systemic vasculitis (6%), and uraemia (23%). Necropsy findings included nephrosclerosis (90%), systemic vasculitis (14%) with kidney involvement in 8%, amyloidosis (11%), membranous glomerulopathy (8%), and focal glomerular disease (8%). Association with clinical data suggests that both rheumatoid and non-rheumatoid disease may play a part in the cause of these abnormalities.
Nerve growth factor release with mast‐cell‐derived mediators in a patient with systemic mastocytosis after middle‐wave ultraviolet irradiation
Authors: M. Kurosawa, H. Inamura, H. Amano, N. Kanbe, H. Nagata, H. Nagai, S. Furukawa, Y. Miyachi
Journal: Allergy (1999)

Background: The symptoms of a 56‐year‐old man with systemic mastocytosis became worse with exposure to sunlight. We evaluated mast‐cell‐derived mediators and cytokines before and after exposure to ultraviolet light in the patient. Methods: The patient was irradiated with middle‐wave ultraviolet light, so‐called ultraviolet light B, and the levels of mediators and cytokines were measured serially. The point mutation Asp816Val in c‐ kit was investigated by analyzing polymerase chain reaction products from the complementary DNA of peripheral blood mononuclear cells. Results: Before irradiation, the levels of mast‐cell‐derived mediators and metabolites were elevated. Among various cytokines measured, including soluble c‐ kit and stem cell factor, only the level of nerve growth factor was elevated. After irradiation, the nerve growth factor level was further increased along with the levels of mast‐cell‐derived mediators and metabolites. The point mutation Asp816Val in c‐ kit was not detected in peripheral blood mononuclear cells. Conclusions: Middle‐wave ultraviolet light may activate mast cells to release nerve growth factor and mediators in systemic mastocytosis.
The Toll-like Receptor 3 L412F Polymorphism and Disease Progression in Idiopathic Pulmonary Fibrosis
Authors: David N. O’Dwyer, Michelle E. Armstrong, Glenda Trujillo, Gordon Cooke, Michael P. Keane, Padraic G. Fallon, A. John Simpson, Ann B. Millar, Emmet E. McGrath, Moira K. Whyte, Nik Hirani, Cory M. Hogaboam, Seamas C. Donnelly
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive interstitial pneumonia. The innate immune system provides a crucial function in the recognition of tissue injury and infection. Toll-like receptor 3 (TLR3) is an innate immune system receptor. We investigated the role of a functional TLR3 single-nucleotide polymorphism in IPF.To characterize the effects of the TLR3 Leu412Phe polymorphism in primary pulmonary fibroblasts from patients with IPF and disease progression in two independent IPF patient cohorts. To investigate the role of TLR3 in a murine model of pulmonary fibrosis.TLR3-mediated cytokine, type 1 IFN, and fibroproliferative responses were examined in TLR3 wild-type (Leu/Leu), heterozygote (Leu/Phe), and homozygote (Phe/Phe) primary IPF pulmonary fibroblasts by ELISA, real-time polymerase chain reaction, and proliferation assays. A murine model of bleomycin-induced pulmonary fibrosis was used in TLR3 wild-type (tlr3(+/+)) and TLR3 knockout mice (tlr3(-/-)). A genotyping approach was used to investigate the role of the TLR3 L412F polymorphism in disease progression in IPF using survival analysis and longitudinal decline in FVC.Activation of TLR3 in primary lung fibroblasts from TLR3 L412F-variant patients with IPF resulted in defective cytokine, type I IFN, and fibroproliferative responses. We demonstrate increased collagen and profibrotic cytokines in TLR3 knockout mice (tlr3(-/-)) compared with wild-type mice (tlr3(+/+)). TLR3 L412F was also associated with a significantly greater risk of mortality and an accelerated decline in FVC in patients with IPF.This study reveals the crucial role of defective TLR3 function in promoting progressive IPF.
Neurologic Manifestations of Infection with Human Immunodeficiency Virus
Authors: DANA H. GABUZDA
Journal: Annals of Internal Medicine (1987)

Subacute encephalitis caused by human immunodeficiency virus (HIV) infection of the central nervous system is the most frequent cause of neurologic dysfunction in patients with the acquired immunodeficiency syndrome (AIDS). This disorder results in progressive cognitive, motor, and behavioral abnormalities in at least two thirds of patients with AIDS. Pathologic evidence of subacute encephalitis is found in 90% of these patients at autopsy. Human immunodeficiency virus is also the etiologic agent in aseptic meningitis, a disease that can occur at the time of seroconversion. Other neurologic disorders frequently associated with HIV include peripheral neuropathies and vacuolar myelopathy. Thus, HIV is neurotropic and may enter the central nervous system early in the course of infection. Neurologic disease may be the only clinical manifestation of HIV infection. Although mechanisms of pathogenesis are unclear, cells of monocyte-macrophage lineage may be important in viral spread to and within the central nervous system. Effective antiviral therapy will probably require penetration of drugs across the bloodbrain barrier.
EXPERIMENTAL FIBROUS OSTEODYSTROPHY (OSTITIS FIBROSA) IN HYPERPARATHYROID DOGS
Authors: Henry L. Jaffe, Aaron Bodansky
Journal: The Journal of Experimental Medicine (1930)

These experiments have shown that parathyroid extract (parathormone Collip) can be injected into puppies in increasing amounts for long periods without fatal results. Thus time is allowed for bone changes to develop. Long continued injection leads to progressive decalcification and resorption of the existing bone, to fibrous replacement of the marrow, and to the production of the other features characteristic of ostitis fibrosa. Deformities eventually appear. It is safe to assume that the bone changes produced by hyperparathyroidization have the same pathogenesis as those observed in clinical cases believed to be instances of hyperparathyroidism—that is, cases with a negative mineral balance and decalcification of the skeleton.
Consumer Choices and the American Health Care System
Authors: James G. Kahn
Journal: JAMA (1992)

<h3>To the Editor.</h3> —Dr Reiser<sup>1</sup>bases his advocacy for a system of health insurance vouchers on the notion of consumer autonomy. While we agree that consumer autonomy is paramount in health care financing reform, his proposal reflects a fundamental misunderstanding of the kind of autonomy for which consumers yearn. His voucher system aspires to promote autonomy in the selection of health plans with different bundles of benefits; what consumers really want is the freedom to choose their own health care provider and to participate in the management of their own health care, unencumbered by health insurance restrictions. Reiser's faith that vouchers would facilitate optimal choice of health insurance is misplaced. Consumers are knowledgeable about their own health values, but few can untangle health plans that confound even insurance specialists. Furthermore, it is untenable to expect health care professionals to effectively counsel consumers, as Reiser suggests. Physicians, in particular, have
Abstract 4417: Uptake of the new paclitaxel-derivative (ANG1005) by the low-density lipoprotein receptor-related protein1 (LRP1) is related to the aggressive phenotype of glioblastoma cells
Authors: Yanick Bertrand, Jean-Christophe Currie, Michel Demeule, Anthony Régina, Danica Stanimirovic, Jean-Paul Castaigne, Richard Béliveau
Journal: Cancer Research (2010)

Abstract The most common primary brain tumour is glioblastoma multiforme (GBM). Despite latest cancer researches to improve the outcome of patients with GBM, this highly aggressive tumour remains one of the most difficult tumors to treat. Angiochem's Engineered Peptide Compounds (EPiC) provides a non-invasive and flexible platform for small and large molecules to treat brain diseases. Based on these properties, we have created a portfolio of new drug entities composed of siRNA, peptides and mAbs, The most advanced, ANG1005, is a new taxane derivative currently completing two Phase ½ clinical trials for the treatment of primary and secondary brain tumors. This EPiC drug is comprised of one Angiopep-2 peptide conjugated to three molecules of paclitaxel. Recently, Angiopep-2 has been shown to use the low-density lipoprotein related protein 1 (LRP1) has a gateway across the blood-brain barrier. Interestingly, LRP1 seems to be required in many tumours for the aggressive behaviour and is overexpressed in GBM. Here, we show an increase uptake of Angiopep-2 in implanted brain tumour using in vivo imaging when compared to the contralateral normal brain region. In these tumors, ANG1005 could be detected by LC/MS/MS analysis and immunohistochemistry. We next characterized Angiopep-2 and ANG1005 uptake in human U87 glioblastoma cell line. The transfection of U87 cells with siRNA LRP1 decreased the uptake of both Angiopep-2 and ANG1005 indicating that LRP1 is involved in their internalization in glioblastoma cells. Furthermore, we measured an increase in the uptake of both Angiopep-2 and ANG1005 in glioblastoma (U87) cells under three experimental conditions that mimic the aggressive cancer cell microenvironment: acidic pH, serum deprivation and hypoxia. Interestingly, under these conditions LRP1 expression was also increased. The increase of ANG1005 uptake and LRP1 expression indicates that the aggressive cancer microenvironment phenotype favors the entry of this anticancer drug into glioblastoma cells. Overall these results demonstrate that the EPiC drug ANG1005 can be an effective therapeutic strategy to target brain cancer cells and aggressive tumors such as GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4417.
Combination of pegylated IFN-α2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
Authors: Bengt Simonsson, Tobias Gedde-Dahl, Berit Markevärn, Kari Remes, Jesper Stentoft, Anders Almqvist, Mats Björeman, Max Flogegård, Perttu Koskenvesa, Anders Lindblom, Claes Malm, Satu Mustjoki, Kristina Myhr-Eriksson, Lotta Ohm, Anu Räsänen, Marjatta Sinisalo, Anders Själander, Ulla Strömberg, Ole Weiss Bjerrum, Hans Ehrencrona, Franz Gruber, Veli Kairisto, Karin Olsson, Fredrik Sandin, Arnon Nagler, Johan Lanng Nielsen, Henrik Hjorth-Hansen, Kimmo Porkka
Journal: Blood (2011)
KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells
Authors: Juan Xu, Bo Yu, Christine Hong, Cun-Yu Wang
Journal: International Journal of Oral Science (2013)

Mesenchymal stem cells (MSCs) have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B (also known as JMJD3) was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate (ALP) activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 (osterix, OSX), as well as extracellular matrix genes BGLAP (osteoclacin, OCN) and SPP1 (osteopontin, OPN), was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 (BMP2) promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.
Abstract 978: Synergistic activity of EP-100 and chemotherapies in cancer cell lines.
Authors: Carola Leuschner, Shashi Gavini, Hector W. Alila
Journal: Cancer Research (2013)

Abstract EP-100, a targeted anti-cancer drug comprised of a lytic peptide fused to Luteinizing Hormone Releasing Hormone (LHRH), is in Phase 2 clinical trial in tumors that over-express LHRH receptors in combination with paclitaxel. It kills cancer cells by membrane disruption. EP-100 was tested in combination with paclitaxel, vinorelbine, doxorubicin, cisplatinum, vincristine and 5 fluorouracil (5FU) in vitro. The sequence of adding EP-100 to the chemotherapeutics was tested in consideration of their half-lives (hours) than EP-100 (minutes). EP-100 was added to the cells before or after treatment with the chemotherapeutics to determine the order of treatment for maximum synergy. Cells were cultured in the presence of each single agent and in combination with EP-100 for 72h. Data were analyzed as IC50 values for each single drug and the combination with EP-100. Combination indices (CI) on interaction of EP-100 and each chemotherapeutic were determined. EP-100 alone was cytotoxic at low uM concentrations in LHRH receptor (+), multi-drug resistant human uterine sarcoma cell line MES-SA-Dx5 and a human breast cancer cell line MDA-MB-231 after 72 h incubation. Both cell lines were resistant to paclitaxel, vinorelbine, vincristine, 5-FU and cisplatinum. MES-SA-Dx5 cells were resistant to doxorubicin. Addition of EP-100 to each of the chemotherapeutics increased sensitivity to all of the drugs except 5-FU (Table 1). Combinations of EP-100 with paclitaxel, vincristine, vinorelbine, doxorubicin and cisplatinum resulted in potentiation of activity in a synergistic manner for both uterine sarcoma and breast cancer cell lines. The combination effects were synergistic with CIs of 0.2. The sequence of exposure was most potent when EP-100 was given first followed by incubation with paclitaxel, doxorubicin or vinorelbine. Table 1 In vitro activities (IC50 - nM) MES-SA-Dx5 Combination Index Potentiation MDA-MB-231 Combination Index Potentiation EP-100 Alone 3044 ± 558 1400 ± 300 Paclitaxel 33.7 ± 2.2 86.2 ± 5.9 EP100+Paclitaxel 0.014 ± 0.002 0.001 6000 15.9 ± 0.8 0.22 5.7 Vincristine 124.7 ± 16.3 26.3 ± 4.1 EP-100+Vincristine 5.7 ± 0.9 0.02 21.7 1.8 ± 0.1 0.09 15 Doxorubicin 32.6 ± 4.3 1.26 ± 0.4 EP-100+Doxorubicin 3.3 ± 0.6 0.09 9.6 1.1 ± 0.04 NA 1 Vinorelbine 63.22 ± 15.9 23.7 ± 3.4 EP-100+Vinorelbine 6.0 ± 1.6 0.06 10.5 3.1 ± 0.9 0.1 7.6 CDDP 54.5 ± 5.8 19.9 ± 6.2 EP-100 + CDDP 8.0 ± 2.6 0.2 6.8 8.1 ± 1.9 0.1 2.5 These results indicate that EP-100 synergizes with paclitaxel, doxorubicin, vinorelbine, vincristine and cisplatinum but not 5-FU in drug resistant human uterine sarcoma and breast cancer cells. Citation Format: Carola Leuschner, Shashi Gavini, Hector W. Alila. Synergistic activity of EP-100 and chemotherapies in cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 978. doi:10.1158/1538-7445.AM2013-978
Review of fungus-induced asthmatic reactions.
Authors: H F Kauffman, J F Tomee, T S van der Werf, J G de Monchy, G K Koëter
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Fungus-induced obstructive airway disease in atopic individuals can be differentiated into two categories: first, uncomplicated asthmatic reactions due to high but transient exposure to fungal spores (fungal asthma), resulting in a TH2-type response with immunoglobulin E-mediated reactions and eosinophilic inflammation; and second, a more complex asthmatic reaction due to colonization of the mucus-epithelial surface by virulent protease-producing fungi. The latter condition stimulates as exaggerated immunological response including all subclasses of antibodies directed against the microorganism and an intense eosinophilic infiltrate of the airways. The authors propose that the exaggerated inflammatory response in allergic bronchopulmonary fungosis damages epithelial cells and underlying tissue cells, resulting in inefficient elimination of the microorganisms and damage to matrix proteins of the lung tissue by proteases released by both the fungi and degranulating eosinophils. The positive effects of corticosteroids in the treatment of allergic bronchopulmonary aspergillosis probably results from the dampening of the inflammatory response and an increase of the efficiency of killing the fungi. Sensitization to fungi is high in childhood and declines rapidly with age, suggesting that younger children may be less proficient in clearing fungi from the airways. We propose that insufficient treatment of fungal asthma may result in damage to the bronchial mucosa and formation of bronchiectasis.
Th17 Cells Induce Ectopic Lymphoid Follicles in Central Nervous System Tissue Inflammation
Authors: Anneli Peters, Lisa A. Pitcher, Jenna M. Sullivan, Meike Mitsdoerffer, Sophie E. Acton, Bettina Franz, Kai Wucherpfennig, Shannon Turley, Michael C. Carroll, Raymond A. Sobel, Estelle Bettelli, Vijay K. Kuchroo
Journal: Immunity (2011)
Measuring Potential Dermal Transfer of a Pesticide to Children in a Child Care Center
Authors: Elaine A. Cohen Hubal, Peter P. Egeghy, Kelly W. Leovic, Gerry G. Akland
Journal: Environmental Health Perspectives (2005)

Currently, the major determinants of children's exposure to pesticides are not fully understood, and approaches for measuring and assessing dermal exposure in a residential setting have not been sufficiently evaluated. In one approach, dermal exposure is estimated using empirically derived transfer coefficients. To assess the feasibility of using this approach for assessing children's exposure to pesticides, we conducted a study was conducted in a child care center that had a preexisting contract with a pest control service for regular monthly pesticide applications. Children in the selected child care center were monitored using full-body cotton garments to measure dermal loading. Pesticide residues on classroom surfaces were measured in the areas where the children spent time. Measured surface-wipe loadings ranged from 0.47 to 120 ng/cm2, and total garment loadings ranged from 0.5 to 660 pg/cm2. The garment and surface loading measurements were used to calculate dermal-transfer coefficients for use in assessing children's residential exposure to pesticides. Dermal-transfer coefficients calculated using these data range from approximately 10 to 6,000 cm2/hr. The wide range in these values demonstrates the importance of developing standard surface-measurement protocols if this approach is to be used to assess dermal exposure in a residential environment. The upper-range values resulting from this study were found to be similar to the default value used by the U.S. Environmental Protection Agency to assess children's dermal exposures resulting from contact with indoor surfaces.
A study of instruments in preparation for a blood pressure survey of children.
Authors: L S Webber, A W Voors, T A Foster, G S Berenson
Journal: Circulation (1977)

In preparation for the measurement of blood pressure in children of a total geographic community, several preliminary studies of the validity and reliability of various methods and instruments for indirect blood pressure measurements were performed. These studies included Graeco-Latin Square designs, examination of children in a field setting, and assessments of the replicability of reading automatically recorded blood pressures. Each of the studies was designed to monitor the validity and replicability of instruments, methods, and observers. Controlling for subject, we compute biases due to instrument, method and observer and, where possible, eliminated them in the enusing studies. One automatic instrument, the Physiometrics recorder, was selected and used in conducting epidemiologic studies where it complements the measurements by the mercury sphygmomanometer.