tbuckley/cabot-search huggingface dataset:
Methyldibromoglutaronitrile in rinse-off products causes allergic contact dermatitis: an experimental study
Authors: C.D. Jensen, J.D. Johansen, T. Menne, K.E. Andersen
Journal: British Journal of Dermatology (2004)

Background The frequency of sensitivity to the cosmetic preservative methyldibromoglutaronitrile (MDBGN) has increased significantly in Europe. Most cases of allergic contact dermatitis from MDBGN are caused by leave‐on cosmetic products. The risk of developing allergic contact dermatitis from rinse‐off products has been less studied. Objectives To investigate the allergic response elicited in presensitized individuals from exposure to a rinse‐off product preserved with the maximum permitted level of MDBGN. Methods Nineteen contact allergic individuals and nine controls participated in a double‐blind, randomized repeated open application test (ROAT) using two coded liquid soaps with and without MDBGN. Areas of 50 cm2 on the lower arms were washed with the soaps twice a day for up to 28 days; two of the subjects continued for 34 days. The subjects were also patch tested with a dilution series of MDBGN to determine their patch test threshold values. Results Seven presensitized individuals (37%) developed allergic contact dermatitis from the soap containing MDBGN. The mean dose of MDBGN per application was 2·2 µg cm−2 and the reactions appeared between days 6 and 34. All nine controls had negative ROATs. The difference in reactivity between test subjects and controls was significant (one‐sided Fisher's exact test, P = 0·04). Patch test threshold values ranged from < 0·001% to 0·2% MDBGN in ethanol/water. Conclusions This study shows that the exposure to a rinse‐off product containing the maximum permitted level of MDBGN can easily elicit an allergic response in presensitized individuals. Along with reported cases of induction and elicitation caused by MDBGN in rinse‐off products the study indicates that the permitted level of MDBGN in rinse‐off products is too high. We recommend that this level should be re‐evaluated.
Demographic and Health Surveys: caesarean section rates in sub-Saharan Africa
Authors: P. Buekens
Journal: BMJ (2003)

It is well documented that caesarean section rates have increased in many Latin American and Asian countries, and that many of these interventions are unnecessary. 1 2Fewer data are available on trends in caesarean section rates in sub-Saharan Africa, where concern centres on lack of access to necessary interventions. 3
Rapamycin Prevents Seizures After Depletion of STRADA in a Rare Neurodevelopmental Disorder
Authors: Whitney E. Parker, Ksenia A. Orlova, William H. Parker, Jacqueline F. Birnbaum, Vera P. Krymskaya, Dmitry A. Goncharov, Marianna Baybis, Jelte Helfferich, Kei Okochi, Kevin A. Strauss, Peter B. Crino
Journal: Science Translational Medicine (2013)

Blocking mTORC1 rescues the neural progenitor cell migratory defect caused by depletion of the STRADA pseudokinase and reduces seizures in patients with a rare neurodevelopmental disorder.
Periodic fevers enter the era of molecular diagnosis
Authors: J. P H Drenth
Journal: BMJ (2000)

Periodic fever syndromes are a group of disorders characterised by attacks of fever separated by symptom free intervals. So far four types, all inherited, have been described. Familial Mediterranean fever and hyper-IgD and periodic fever syndrome (hyper-IgD syndrome) are transmitted as autosomal recessive traits while familial Hibernian fever and Muckle-Wells syndrome are autosomal dominant periodic fevers. Over the past decade the gene for Muckle-Wells syndrome has been localised and those for the other three disorders identified. This work has resulted in better means of diagnosing these rare conditions and has also thrown new light on the molecular basis of inflammation.

Familial Mediterranean fever is the commonest periodic fever disorder, occurring mainly in people originating from the Mediterranean basin.1 In Israel alone over 5000 people are estimated to suffer from this disorder. Attacks start before the age of 20 and are characterised by short (1-4 days) attacks of fever and serositis. Most patients have recurrent peritonitis, but pleuritis also occurs. Asymmetric monoarthritis of the large joints is common, while an erysipelas-like rash develops less often. Familial Mediterranean fever can be complicated by nephropathic amyloidosis of the AA type, but in most patients colchicine up …
STUDIES IN THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION
Authors: Abraham Penner, Alice Ida Bernheim
Journal: The Journal of Experimental Medicine (1960)

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion.
Induction of Transglutaminase 2 by a Liver X Receptor/Retinoic Acid Receptor α Pathway Increases the Clearance of Apoptotic Cells by Human Macrophages
Authors: Cédric Rébé, Magalie Raveneau, Angélique Chevriaux, Daniela Lakomy, Anne-Laure Sberna, Annie Costa, Ginette Bessède, Anne Athias, Eric Steinmetz, Jean Marc A. Lobaccaro, Georges Alves, Alexandre Menicacci, Sébastien Vachenc, Eric Solary, Philippe Gambert, David Masson
Journal: Circulation Research (2009)

Rationale: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are involved in the control of cholesterol homeostasis and inflammatory response. Human monocytes and macrophages express high levels of these receptors and are appropriate cells to study the response to LXR agonists. Objective: The purpose of this study was to identify new LXR targets in human primary monocytes and macrophages and the consequences of their activation. Methods and Results: We show that LXR agonists significantly increase the mRNA and protein levels of the retinoic acid receptor (RAR)α in primary monocytes and macrophages. LXR agonists promote RARα gene transcription through binding to a specific LXR response element on RARα gene promoter. Preincubation of monocytes or macrophages with LXR agonists before RARα agonist treatment enhances synergistically the expression of several RARα target genes. One of these genes encodes transglutaminase (TGM)2, a key factor required for macrophage phagocytosis. Accordingly, the combination of LXR and RARα agonists at concentrations found in human atherosclerotic plaques markedly enhances the capabilities of macrophages to engulf apoptotic cells in a TGM2-dependent manner. Conclusions: These results indicate an important role for LXRs in the control of phagocytosis through an RARα-TGM2–dependent mechanism. A combination of LXR/RARα agonists that may operate in atherosclerosis could also constitute a promising strategy to improve the clearance of apoptotic cells by macrophages in other pathological situations.
Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma
Authors: J. Lee, W.K. Kang, J.M. Kwon, S.Y. Oh, H.R. Lee, H.J. Kim, B.B. Park, H.Y. Lim, M.J. Han, J.O. Park, Y.S. Park
Journal: Annals of Oncology (2006)
Individual and combined actions of calcium, sodium, and potassium ions on baroreceptors in the rat.
Authors: M C Andresen, S Kuraoka, A M Brown
Journal: Circulation Research (1979)

We examined the effects of changes in the extracellular concentrations of Na, K, and Ca ions on the steady state pressure-discharge relationships of individual baroreceptors, using an in vitro aortic arch-aortic nerve preparation.We determined the concentration-response relationships for each of the three cations, as well as for the combined effects of changes in Ca 1+ -K + and Ca* + -Na + .The concentrations tested ranged from normal values to values well above and below normal.For each ion and each combination, effects on the pressure-discharge curves appeared as continuous functions of concentration.Lowering [Na + ]o or [K + ]« or increasing [Ca 1+ ]o shifted pressure-response curves to the right.Increasing [K + ] o or decreasing [Ca 1+ ] 0 shifted the curves to the left.The steady state effects of small increases in [Na*]o were inconsistent.Combinations of changes in ion concentration enhanced the effects in a way that was consistent with the results of individual changes, although quantitative comparisons were not made.Thus, the Ca 1+ curves for threshold pressure were shifted to the left by lowering [Na + ]o or to the right by increasing [K +]o-Measurements of static volume, diameter, and distensibility showed no significant changes in the vessel wall during these changes so that, for equivalent strains, nervous discharge was clearly altered.Hence, the main actions are likely to be on the receptor and its axon rather than on the smooth muscle of the vessel wall, although local mechanical effects cannot be excluded completely.The results were interpreted by applying the electrophyeiological theory of nerve membranes.These effects of extracellular ions on baroreceptors may have particular significance due to the special role of the baroreceptors in regulatory reflexes.
Molecular Phylogeny of the Helianthus Genus, Based on Nuclear Restriction-Fragment-Length Polymorphism (RFLP)
Authors: L Gentzbittel, A Perrault, P Nicolas
Journal: Molecular Biology and Evolution (1992)

The systematics of 44 species of the Helianthus genus were studied by digestion of total DNAs by three six-base restriction endonucleases (EgnI, EcoRV, and Hind111 ) and by probing with 10 nuclear probes, resulting in a mean number of 63 hybridization signals per sample. First, the number of substitutions, per nucleotide site, between each of the genomes was estimated on the basis of the distribution of 345 fragments between samples, according to the “fragment method” of Nei and Li. These pairwise distances were used to construct evolutionary trees by means of the unweighted pair grouping with arithmetic means and by the neighbor-joining method. The phylogenies produced by these two methods, where all the sections and series defined by morphological classification are separated, mirror the botanical classification of the genus. However, the integration of polyploid species (2n = 4x or 2n = 6x) leads to their artificial separation from the diploids. The separation of H. petiolaris and H. neglectus from the Helianthus section could provide evidence for two distinct lineages of annual species within the Helianthus genus. Second, varimax factor analysis, based on the F matrix, allows separation of species according to the similarity index and gives a plane representation that is close to the morphological classification given by the weighted pair grouping with arithmetic means. Third, the changes in the accuracy of distance estimates according to the number of probe-enzyme combinations used show that 30 combinations produce a general dispersion of ~5% on both sides of the mean value. Model fitting to the decreasing dispersion indicates that 60 probe-enzyme combinations would ensure a dispersion of distance estimation of < l%, even in the case of distantly related species.
Regression of glioma tumor growth in F98 and U87 rat glioma models by the Nitrone OKN-007
Authors: Rheal A. Towner, David L. Gillespie, Andrea Schwager, Debra G. Saunders, Nataliya Smith, Charity E. Njoku, Richard S. Krysiak, Chelsea Larabee, Henna Iqbal, Robert A. Floyd, David W. A. Bourne, Osama Abdullah, Edward W. Hsu, Randy L. Jensen
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme, a World Health Organization grade IV glioma, has a poor prognosis in humans despite current treatment options. Here, we present magnetic resonance imaging (MRI) data regarding the regression of aggressive rat F98 gliomas and human U87 glioma xenografts after treatment with the nitrone compound OKN-007, a disulfonyl derivative of α-phenyl-tert-butyl nitrone. MRI was used to assess tumor volumes in F98 and U87 gliomas, and bioluminescence imaging was used to measure tumor volumes in F98 gliomas encoded with the luciferase gene (F98luc). Immunohistochemistry was used to assess angiogenesis (vascular endothelial growth factor [VEGF] and microvessel density [MVD]), cell differentiation (carbonic anhydrase IX [CA-IX]), hypoxia (hypoxia-inducible factor-1α [HIF-1α]), cell proliferation (glucose transporter 1 [Glut-1] and MIB-1), proliferation index, and apoptosis (cleaved caspase 3) markers in F98 gliomas. VEGF, CA-IX, Glut-1, HIF-1α, and cleaved caspase 3 were assessed in U87 gliomas. Animal survival was found to be significantly increased (P < .001 for F98, P < .01 for U87) in the group that received OKN-007 treatment compared with the untreated groups. After MRI detection of F98 gliomas, OKN-007, administered orally, was found to decrease tumor growth (P < .05). U87 glioma volumes were found to significantly decrease (P < .05) after OKN-007 treatment, compared with untreated animals. OKN-007 administration resulted in significant decreases in tumor hypoxia (HIF-1α [P < .05] in both F98 and U87), angiogenesis (MVD [P < .05], but not VEGF, in F98 or U87), and cell proliferation (Glut-1 [P < .05 in F98, P < .01 in U87] and MIB-1 [P < .01] in F98) and caused a significant increase in apoptosis (cleaved caspase 3 [P < .001 in F98, P < .05 in U87]), compared with untreated animals. OKN-007 may be considered as a promising therapeutic addition or alternative for the treatment of aggressive human gliomas.
High-dose intravenous glucocorticoid therapy abrogates circulating dendritic cells
Authors: Takafumi Suda, Kingo Chida, Hiroyuki Matsuda, Hideo Hashizume, Kyotaro Ide, Koushi Yokomura, Kenichiro Suzuki, Hirofumi Kuwata, Seiichi Miwa, Hideki Nakano, Tomoyuki Fujisawa, Noriyuki Enomoto, Akio Matsushita, Hirotoshi Nakamura
Journal: Journal of Allergy and Clinical Immunology (2003)
Hereditary sideroblastic anemia with associated platelet abnormalities
Authors: Gerald Soslau, Isadora Brodsky
Journal: American Journal of Hematology (1989)

A 62 year old male (R.H.) presented with a mild anemia (Hb 11-12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40-50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11-12 gm%) with 40-50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non-classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.
Quadrilateral space syndrome: a case study and review of the literature: Table 1
Authors: W T Hoskins, H P Pollard, A J McDonald
Journal: British Journal of Sports Medicine (2005)

Quadrilateral space syndrome is an uncommon injury. The true prevalence is unknown because of a lack of literature and possible misdiagnosis. Prevalence may increase as knowledge of the syndrome increases. The case is presented of a recreational triathlete who had a spontaneous onset of quadrilateral space syndrome. The diagnosis was made by physical examination and confirmed with magnetic resonance imaging. A conservative, yet aggressive rehabilitation programme resulted in functional improvement within six weeks. Results have been maintained for eight weeks.
Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide.
Authors: I U Schraufstatter, D B Hinshaw, P A Hyslop, R G Spragg, C G Cochrane
Journal: Journal of Clinical Investigation (1986)

To determine the biochemical basis of the oxidant-induced injury of cells, we have studied early changes after exposure of P388D1 murine macrophages to hydrogen peroxide. Total intracellular NAD+ levels in P388D1 cells decreased with H2O2 concentrations of 40 microM or higher. Doses of H2O2 between 0.1 and 2.5 mM led to an 80% depletion of NAD within 20 min. With doses of H2O2 of 250 microM or lower, the fall in NAD and, as shown previously, ATP, was reversible. Higher doses of H2O2 that cause ultimate lysis of the cells, induced an irreversible depletion of NAD and ATP. Poly-ADP-ribose polymerase, a nuclear enzyme associated with DNA damage and repair, which catalyzes conversion of NAD to nicotinamide and protein-bound poly-ADP-ribose, was activated by exposure of the cells to concentrations of 40 microM H2O2 or higher. Activation of poly-ADP-ribose polymerase was also observed in peripheral lymphocytes incubated in the presence of phorbol myristate acetate-stimulated polymorphonuclear neutrophils. Examination of the possibility that DNA alteration was involved was performed by measurement of thymidine incorporation and determination of DNA single-strand breaks (SSB) in cells exposed to H2O2. H2O2 at 40 microM or higher inhibited DNA synthesis, and induced SSB within less than 30 s. These results suggest that DNA damage induced within seconds after addition of oxidant may lead to stimulation of poly-ADP-ribose polymerase, and a consequent fall in NAD. Excessive stimulation of poly-ADP-ribose polymerase leads to a fall in NAD sufficient to interfere with ATP synthesis.
Peripheral blood eosinophil counts and bronchial responsiveness.
Authors: K J Taylor, A R Luksza
Journal: Thorax (1987)

Bronchial responsiveness (histamine PC20) and peripheral blood eosinophil counts were measured in 23 asthmatic subjects, of whom 14 were atopic and nine non-atopic. In the group as a whole there was an inverse correlation between baseline eosinophil count and histamine PC20 (r = -0.71; p less than 0.001). For atopic subjects a relationship between eosinophil count and histamine PC20 was observed (r = -0.74; p less than 0.01), but there was no correlation between eosinophil count and baseline FEV1 or baseline FEV1 and histamine PC20. For the non-atopic subjects a similar relationship between eosinophil count and histamine PC20 was seen (r = -0.68; p less than 0.05) and a less significant inverse correlation between baseline eosinophil count and baseline FEV1 (r = -0.65; p less than 0.05). These results show a relationship between eosinophil count and non-specific bronchial responsiveness in both atopic and non-atopic asthma.
Contribution of the Endotracheal Tube and the Upper Airway to Breathing Workload
Authors: CHRISTIAN STRAUS, BRUNO LOUIS, DANIEL ISABEY, FRANÇOIS LEMAIRE, ALAIN HARF, LAURENT BROCHARD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The influence of the endotracheal tube (ETT) during a T-piece trial remains controversial. Our aim was to compare the work of breathing of 14 successfully extubated patients at the end of a 2-h trial (T) and after extubation (E) of the trachea, and to assess, using the acoustic reflection method, the resistance of the endotracheal tube and of the supraglottic airway as well as their related work. We found that the work of breathing of the patients was identical between T and E (1.72 +/- 0.59 versus 1.63 +/- 0.45 J/L; p = 0.50 and 23.5 +/- 10.6 versus 22.6 +/- 9.7 J/min; p = 0.70). There was no significant difference between the beginning and the end of the T-piece trial (1.57 +/- 0.53 versus 1.72 +/- 0.59 J/ L, p = 0.10). The work caused by the ETT amounted to 11.0 +/- 3.9% of the total work of breathing. The supraglottic airway resistance was in the normal range and was significantly smaller than the endotracheal tube resistance (0.79 +/- 0.4 versus 1.43 +/- 0.31 cm H2O x s/L; p = 0.008, flow = 0.25 L/s). We conclude that a 2-h trial of spontaneous breathing through an endotracheal tube well mimics the work of breathing performed after extubation, in patients who pass a weaning trial and do not require reintubation.
A8.5 Fibroblast Activation Protein Alpha in Inflammatory Bone Destruction
Authors: Christina Wunrau, Corinna Wehmeyer, Marianne Heitzmann, Thomas Pap, Berno Dankbar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Fibroblast Activation Protein alpha (FAPα) is an integral membrane serine protease that plays a major role in migration, wound healing, and metastasis. Based on recent studies that have implicated membrane-bound serine proteases in osteoclast migration, we studied the expression of FAPα in rheumatoid arthritis (RA) and analysed its role in osteoclast development under inflammatory conditions. <h3>Methods</h3> FAPα expression in vivo was determined by immunohistochemistry in human synovial tissues of patients with RA and osteoarthritis (OA) as well as in hind paws of tumour necrosis factor-alpha transgenic (hTNFtg) mice, which develop a RA-like destructive arthritis. In vitro expression and regulation of FAPα was analysed in differentiated osteoclasts cocultured with osteoblasts, RA or OA synovial fibroblasts (SF) by PCR. To scrutinise the role of FAPα in osteoclastogenesis, we analysed the in vitro differentiation of osteoclasts from wildtype (WT) and FAP<sup>-/-</sup> mice (Oncology Research, Boehringer Ingelheim RCV, Vienna) by TRAP staining. In order to assess the role of FAP in arthritis severity, we crossed FAP<sup>-/-</sup> and hTNFtg mice and performed TRAP staining. <h3>Results</h3> RA synovial tissues demonstrated a high expression of FAPα throughout the tissue whereas in OA samples FAPα was expressed only in the lining layer. In vitro, no expression of FAPα was found in differentiated preosteoclasts and osteoclasts, but coculture experiments showed that RASF, but not OASF or osteoblasts, induce the expression of FAPα in preosteoclasts and osteoclasts. Consistent with the selective induction of FAPα in osteoclasts by RASF, FAPα expression was detected in osteoclasts at the invasion front of the hyperplastic synovial tissues in joints of hTNFtg mice. FAP<sup>-/-</sup> mice show a severely diminished osteoclast formation compared to WT. We also found a lesser amount of osteoclasts in the hind paws of FAP<sup>-/-</sup>hTNFtg compared to hTNFtg. <h3>Conclusions</h3> The disease-dependent expression of FAPα by osteoclasts in human RA and hTNFtg mice suggests an important role of FAPα in joint destruction in RA. The selective induction of FAPα in preosteoclasts and osteoclasts by RASF indicate that FAPα may be regulated through the interaction with the pannus tissue. The fact, that under inflammatory conditions the loss of FAP led to a reduced number of osteoclasts in the hind paws and FAP deficient bone marrow derived macrophages showed a reduced osteoclast formation, suggest a role of this serine protease in macrophage/osteoclast precursor migration and differentiation.