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61.
62.
Yolanda K. Mueller Mathieu Bastard Patrick Nkemenang Eric Comte Geneviève Ehounou Sara Eyangoh Barbara Rusch Earnest Njih Tabah Laurence Toutous Trellu Jean-Francois Etard 《PLoS neglected tropical diseases》2016,10(4)
Background
Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis.Methododology/Principal Findings
Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0–98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2–84.7). Patients with intermediate BU probability needed to be tested by PCR.Conclusions/Significance
We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use. 相似文献63.
Biochemical and Immunological Properties of the Mouse Brain Enolases Purified by a Simple Method 总被引:6,自引:4,他引:2
Angelica Keller Hélène Scarna Anne Mermet Jean-Francois Pujol 《Journal of neurochemistry》1981,36(4):1389-1397
Abstract: A simple and rapid purification method is presented for the two mouse cerebral isozymes of enolase (EC 4.2.1.11), E1 and E3. The purity of the preparations was ascertained by electrophoresis under two different conditions. The biochemical and immunological properties of E1 and E3 were compared. The molecular weight of the cerebral enolases was analysed by column chromatography on Sephadex G 150 and by electrophoresis in the presence of SDS. Both E1 and E3 are homodimers with a subunit of molecular weight of 50,000. The procedure also yields a semi-purified fraction of E2. Conditions of in vitro formation of E2 from pure or semi-purified fractions of E1 and E3 show that it is likely to be a real hybrid, rather than an aggregate and that it is probably not an artefact formed during the purification. The Km values (Km= 3–4·10?5 M) for the substrate are not significantly different amongst the three forms. However, E1 and E2 but not E3 are inhibited by excess substrate. Antisera against E1 and E3 have been obtained from rabbit and goat, respectively. Antibodies against each protein do not show any cross-reactivity with each other. There is, however, a broad species cross-reactivity, showing conservation of each enolase form during evolution. Both anti-E1 and anti-E3 sera react with the E2 enolase fraction, in agreement with its hybrid structure. Anti-E3 serum does not react with extracts of other tested organs. Brain enolase 1 resembles liver enolase in its biochemical and immunological properties. A slight cross-reactivity of anti-E1 serum with muscle extracts is observed. Heterogeneity of brain enolase 1 is observed by both biochemical and immunological methods; the nature of this heterogeneity is discussed. 相似文献
64.
A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I. 总被引:5,自引:0,他引:5 下载免费PDF全文
P Lertrit A S Noer M J Jean-Francois R Kapsa X Dennett D Thyagarajan K Lethlean E Byrne S Marzuki 《American journal of human genetics》1992,51(3):457-468
The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A----G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA(Leu), was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A----G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A----G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation. 相似文献
65.
Daniele Bouhours Göran Larson Jean-Francois Bouhours Arne Lundblad Gunnar C Hansson 《Glycoconjugate journal》1987,4(1):59-71
Blood group A-active glycosphingolipids of the small intestine, A-6 and A-12, which have been characterized previously in the adult rat [Breimer ME, Hansson GC, Karlsson K-A, Leffler H (1982) J Biol Chem 257:906–12], were found to appear during postnatal development, using immunostaining on thin layer chromatograms with two monoclonal anti-A antibodies, A005 and A581. In this system, A005 was found to be specific for the A determinant based on the type 2 chain, while A581 reacted mainly with the A determinant based on the type 1 chain and only weakly with the A determinant based on the type 2 chain. A-6 Type 1 was detected first at 18 days after birth. Its concentration increased markedly during the fourth week. A-6 Type 2 was detected, at a very low level, in neonates. Its concentration increased between days 15 and 20 and then decreased almost to the neonate level by 28 days. Dodecaglycosylceramide A-12 followed the same pattern of reactivity as A-6 type 1 with A581, and remained strongly reactive with A005 after 20 days. Linear A-6 and branched A-12 appeared simultaneously. Antibodies directed against blood group H determinants based on the type 1 or type 2 chains did not detect any H structure which might have appeared as a precursor of either A-6 or A-12 at the early stages of postnatal development.Abbreviations A-6, A-12, H-5, H-10 etc
the glycolipids are abbreviated by giving blood group activity, and number of sugars (see also Fig. 1)
- GM3
GM3-ganglioside, H3NeuAc-LcCer
- PBS
phosphate-buffered saline 相似文献
66.
67.
J Bussenius CM Blazey N Aay NK Anand A Arcalas T Baik OJ Bowles CA Buhr S Costanzo JK Curtis SC Defina L Dubenko TS Heuer P Huang C Jaeger A Joshi AR Kennedy AI Kim K Lara J Lee J Li JC Lougheed S Ma S Malek JC Manalo JF Martini G McGrath M Nicoll JM Nuss M Pack CJ Peto TH Tsang L Wang SW Womble M Yakes W Zhang KD Rice 《Bioorganic & medicinal chemistry letters》2012,22(17):5396-5404
With structural guidance, tropane-derived HTS hits were modified to optimize for HSP90 inhibition and a desirable in vivo profile. Through an iterative SAR development process 12i (XL888) was discovered and shown to reduce HSP90 client protein content in PD studies. Furthermore, efficacy experiments performed in a NCI-N87 mouse xenograft model demonstrated tumor regression in some dosing regimens. 相似文献
68.
Sastry SK Rajfur Z Liu BP Cote JF Tremblay ML Burridge K 《The Journal of biological chemistry》2006,281(17):11627-11636
Cell motility is regulated by a balance between forward protrusion and tail retraction. These phenomena are controlled by a spatial asymmetry in signals at the front and the back of the cell. We show here that the protein-tyrosine phosphatase, PTP-PEST, is required for the coupling of protrusion and retraction during cell migration. PTP-PEST null fibroblasts, which are blocked in migration, exhibit exaggerated protrusions at the leading edge and long, unretracted tails in the rear. This altered morphology is accompanied by changes in the activity of Rho GTPases, Rac1 and RhoA, which mediate protrusion and retraction, respectively. PTP-PEST null cells exhibit enhanced Rac1 activity and decreased RhoA activity. We further show that PTP-PEST directly targets the upstream regulators of Rac1 and RhoA, VAV2 and p190RhoGAP. Moreover, we demonstrate that the activities of VAV2 and p190RhoGAP are regulated by PTP-PEST. Finally, we present evidence indicating the VAV2 can be regulated by integrin-mediated adhesion. These data suggest that PTP-PEST couples protrusion and retraction by acting on VAV2 and p190RhoGAP to reciprocally modulate the activity of Rac1 and RhoA. 相似文献
69.
The aryl hydrocarbon receptor activates the retinoic acid receptoralpha through SMRT antagonism 总被引:1,自引:0,他引:1
Aryl hydrocarbon receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or benzo(a)pyrene interfere with hormonal regulatory pathways, leading to endocrine disruption. Notably, the activated AhR exerts complex effects on estrogens and retinoids at both levels of their metabolism and regulation of cognate genes. Our current investigation of these AhR effects revealed the TCDD-dependent activation of a subset of retinoid-dependent genes (tissue-transglutaminase, IGF binding protein-3, AhR) in MCF-7 breast cancer cells. A collection of in vitro hormone-dependent reporter gene models showed that AhR activation by TCDD stimulated transactivation by several class I heteromeric receptors (retinoic and thyroid hormone receptors) while it antagonized homodimeric nuclear receptors (estrogen and progesterone receptors, ER and PR). TCDD exerted a dose-dependent effect on a retinoic acid-dependent reporter gene expressed in MCF-7 cells. AhR was shown to be involved in a mutual antagonism with RARalpha corepressor SMRT (silencing mediator of retinoid and thyroid receptors). This, and the documented physical interaction between AhR and SMRT suggested that SMRT sequestration by AhR might activate RARalpha in the absence of ligand. Immunocytochemical studies of AhR and SMRT strongly suggested they colocalized in nuclear bodies during this sequestration. Concurring with this interpretation, we observed an interaction in vitro between AhR and the PML protein, the core component of nuclear bodies. This ability of AhR to elicit spurious activation of retinoid receptors expands the scope of AhR ligands influence beyond ER antagonism and specific Dioxin-responsive genes. Unknown AhR endogenous ligands may also elicit gene transactivation by class I receptors, while being inactive on classic xenobiotic-responsive genes. 相似文献
70.
Rhea N. Coler Ajay Bhatia Jean-Francois Maisonneuve Peter Probst Brenda Barth Pamela Ovendale Hang Fang Mark Alderson Yves Lobet Joe Cohen Pascal Mettens & Steven G. Reed 《FEMS immunology and medical microbiology》2009,55(2):258-270
Chlamydia trachomatis infection is the most common sexually transmitted bacterial infection worldwide, with over 91 million cases estimated annually. An effective subunit vaccine against Chlamydia may require a multivalent subunit cocktail of antigens in a single formulation for broad coverage of a heterogeneous major histocompatibility complex population. Herein, we describe the identification of novel C. trachomatis antigens by CD4+ and CD8+ T-cell expression cloning, serological expression cloning, and an in silico analysis of the C. trachomatis genome. These antigens elicited human CD4+ T-cell responses, and a subset proved to be immunogenic and protective when administered as immunoprophylactic vaccines against C. trachomatis challenge. Candidate vaccines consisting of the prioritized C. trachomatis antigens adjuvanted in a GlaxoSmithKline proprietary AS01B adjuvant were prioritized based on induction of solid protection against challenge in C57BL/6 and BALB/c mice with C. trachomatis . Some of the vaccines prevented bacterial shedding and colonization of the upper genital tract to varying degrees by mechanisms that may include CD4+ T cells. 相似文献