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61.
Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins in healthy and bacteremic baboon 总被引:1,自引:0,他引:1
Solorzano Carmen C.; Kaibara Atsushi; Hess Phillip J.; Edwards Paul D.; Ksontini Riadh; Abouhamze Amer; McDaniel Sherry; Frazier Janet; Trujillo Deborah; Kieft Gary; Seely James; Kohno Tadahiko; Cosenza Mary Ellen; Clare-Salzler Michael; MacKay Sally L.D.; Martin Steven W.; Moldawer Lyle L.; Edwards Carl K. III 《Journal of applied physiology》1998,84(4):1119-1130
Immunogenicity, pharmacokinetics, and therapeutic efficacy ofthree novel dimeric soluble tumor necrosis factor (TNF)-receptor Iconstructs [TNF-binding protein (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were challenged with a lethal Escherichia coli bacteremia. The threeconstructs differed only in the number of extracellular domains of theTNF receptor I and were dimerized with polyethylene glycol. Althoughall three constructs had generally similar pharmacokinetics whenadministered to a naive animal, they differed quantitatively in theirimmunogenicity. Antibodies were detected more frequently, and titerswere significantly higher (P < 0.05)in both healthy and septic baboons that received the 4.0-domain TNF-bpconstruct, compared with animals receiving the 2.6-domain construct.When the TNF-bp constructs were administered a second time (21 dayslater), the half-lives of the three constructs were significantlyshorter in animals that had an antibody response after the firstinjection. In contrast, all three TNF-bp constructs were equallyeffective at improving outcome, blocking a systemic TNF- response,and attenuating the cytokine responses when administered at a dose of1.0 mg/kg body wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicityof TNF-bp constructs can be altered by changing the number offunctional domains, without affecting their capacity to neutralizeTNF- and to abrogate TNF-mediated pathology. 相似文献
62.
Vincent Timmerman Ann Löfgren Eric Le Guern Ping Liang Peter De Jonghe Jean-Jacques Martin Damienne Verhalle Wim Robberecht Riadh Gouider Alexis Brice Christine Van Broeckhoven 《Human genetics》1996,97(1):26-34
Hereditary neuropathy with liability to pressure palsies (HNPP) is in most cases associated with an interstitial deletion of the same 1.5-Mb region at 17p11.2 that is duplicated in Charcot-Marie-Tooth type 1A (CMT1A) patients. Unequal crossing-over following misalignment at flanking repeat sequences (CMT1A-REP), either leads to tandem duplication in CMT1A patients or deletion in HNPP patients. With the use of polymorphic DNA markers located within the CMT1A/HNPP duplication/deletion region we detected the HNPP deletion in 16 unrelated HNPP patients, 11 of Belgian and 5 of French origin. In all cases, the 1.5-Mb size of the HNPP deletion was confirmed by EcoRI dosage analysis using a CMT1A-REP probe. In the 16 HNPP patients, the same 370/320-kb EagI deletion-junction fragments were detected with pulsed field gel electrophoresis (PFGE), while in CMT1A patients, a 150-kb EagI duplication-junction fragment was seen. Thus, PFGE analysis of EagI-digested DNA with a CMT1A-REP probe allows direct detection of the HNPP deletion or the CMT1A duplication for DNA diagnostic purposes. 相似文献
63.
The consequences of direct iron deficiency and iron resupply were evaluated during development stages of two Tunisian chickpea varieties (INRAT88 and Chetoui) cultivated in continuously aerated solution with or without 20 muM Fe. The chlorosis score was estimated during culture. Growth parameters, chlorophyll concentration, acidification capacity and Fe concentration were measured every three days during the 21-day treatment. After three weeks of treatment, the chlorosis index was 3-fold higher in Chetoui than in INRAT88, and a considerable decrease of chlorophyll concentration was observed in Chetoui plants since the 6th day of -Fe deprivation. Iron deficiency significantly inhibited whole-plant biomass deposition in both varieties. However, the growth reduction appeared earlier, and was more pronounced in Chetoui than in INRAT88. The whole-plant Fe content decreased dramatically under deficient conditions, and we note an Fe enrichment in shoots at the expense of roots. The sensitivity of Chetoui as compared to INRAT88 was confirmed by the behaviour of resupplied (-Fe/+Fe) plants. In fact, the addition of iron to deficient plants had no significant effect in Chetoui, whereas it led to a total recovery in INRAT88. The capacity of INRAT88 to maintain plant growth and to preserve adequate chlorophyll synthesis under limited iron conditions is related to its better Fe-use efficiency, in addition to its capacity to rapidly recover from this stress. 相似文献
64.
Baklouti Emna Beulé Thierry Nasri Ameni Ben Romdhane Amal Drira Riadh Doulbeau Sylvie Rival Alain Drira Noureddine Fki Lotfi 《Plant Cell, Tissue and Organ Culture》2022,150(1):191-205
Plant Cell, Tissue and Organ Culture (PCTOC) - The present study is a part of a program designed at improving the date palm, Phoenix dactylifera L. cv. Barhee, through induced somaclonal variation.... 相似文献
65.
66.
Idrissa Samandoulgou Riadh Hammami Rocio Morales Rayas Ismail Fliss Julie Jean 《Applied and environmental microbiology》2015,81(22):7680-7686
Loss of ordered molecular structure in proteins is known to increase their adhesion to surfaces. The aim of this work was to study the stability of norovirus secondary and tertiary structures and its implications for viral adhesion to fresh foods and agrifood surfaces. The pH, ionic strength, and temperature conditions studied correspond to those prevalent in the principal vehicles of viral transmission (vomit and feces) and in the food processing and handling environment (pasteurization and refrigeration). The structures of virus-like particles representing GI.1, GII.4, and feline calicivirus (FCV) were studied using circular dichroism and intrinsic UV fluorescence. The particles were remarkably stable under most of the conditions. However, heating to 65°C caused losses of β-strand structure, notably in GI.1 and FCV, while at 75°C the α-helix content of GII.4 and FCV decreased and tertiary structures unfolded in all three cases. Combining temperature with pH or ionic strength caused variable losses of structure depending on the particle type. Regardless of pH, heating to pasteurization temperatures or higher would be required to increase GII.4 and FCV adhesion, while either low or high temperatures would favor GI.1 adhesion. Regardless of temperature, increased ionic strength would increase GII.4 adhesion but would decrease GI.1 adhesion. FCV adsorption would be greater at refrigeration, pasteurization, or high temperature combined with a low salt concentration or at a higher NaCl concentration regardless of temperature. Norovirus adhesion mediated by hydrophobic interaction may depend on hydrophobic residues normally exposed on the capsid surface at pH 3, pH 8, physiological ionic strength, and low temperature, while at pasteurization temperatures it may rely more on buried hydrophobic residues exposed upon structural rearrangement. 相似文献
67.
Mounira Hmani-Aifa Salma Ben Salem Zeineb Benzina Walid Bouassida Riadh Messaoud Khalil Turki Moncef Khairallah Ahmed Rebaï Faïza Fakhfekh Peter Söderkvist Hammadi Ayadi 《Human genetics》2009,126(4):575-587
Posterior microphthalmia (PM) is a relatively rare autosomal recessive condition with normal anterior segment and small posterior segment resulting in high hyperopia and retinal folding. It is an uncommon subtype of microphthalmia that has been mostly reported to coexist with several other ophthalmic conditions and to occur in sporadic cases. The membrane-type frizzled-related protein (MFRP) is the only gene so far reported implicated in autosomal recessive, non-syndromic and syndromic forms of PM. Here, we performed a clinical and genetic analysis using six consanguineous families ascertained from different regions of Tunisia and affected with non-syndromic PM that segregates as an autosomal recessive trait. To identify the disease-causing defect in these families, we first analysed MFRP gene, then some candidate genes (CHX10, OPA1, MITF, SOX2, CRYBB1-3 and CRYBA4) and loci (MCOP1, NNO1 and NNO2) previously implicated in different forms of microphthalmia. After exclusion of these genes and loci, we performed a genome-wide scan using a high density single nucleotide polymorphism (SNP) array 50 K in a large consanguineous pedigree. SNP genotyping revealed eight homozygous candidate regions on chromosomes 1, 2, 3, 6, 15, 17 and 21. Linkage analysis with additional microsatellite markers only retained the 2q37.1 region with a maximum LOD score of 8.85 obtained for D2S2344 at θ = 0.00. Further investigations are compatible for linkage of four more families to this region with a refined critical interval of 2.35 Mb. The screening of five candidate genes SAG, PDE6D, CHRND, CHRNG and IRK13 did not reveal any disease-causing mutation. 相似文献
68.
Mohd Saeed Munazzah Tasleem Ambreen Shoib Mohd Adnan Kausar Abdel Moneim E. Sulieman Nadiyah M. Alabdallah Zeina El Asmar Abdelmuhsin Abdelgadir Asma Al-Shammary Md Jahoor Alam Riadh Badroui Maryam Zahin 《Current issues in molecular biology》2022,44(7):2825
Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBEDB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors. 相似文献
69.
Nciri Riadh Mohamed Salah Allagui Ezzedine Bourogaa Christian Vincent Françoise Croute Abdelfattah Elfeki 《Biometals》2011,24(4):747-757
Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal
effects. The last decade has witnessed the following discoveries about its neuroprotective and neurotrophic properties, yet
the therapeutic mechanisms at the cellular level remain not-fully defined. We have undertaken the present study to determine
if chronic lithium treatment, at therapeutically relevant concentrations, exerts neurotrophic/neuroprotective effects in the
mouse brain in vivo. For this purpose, 10 months aged mice were fed for 3 months on food pellets contained 1 g (L1 group)
or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.4 and 0.8 mM, respectively. The evaluation
of lipid peroxidation level and the activities of catalase, superoxide-dismutase and glutathione-peroxidase showed that chronic
Li administration, at therapeutic doses doesn’t induce oxidative stress in brain tissue. No changes in the expression levels
of molecular chaperones, namely, the HSP70, and HSP90 heat shock proteins and the GRP94 glucose-regulated protein were detected.
Moreover, this treatment has caused (1) an increase in the relative brain weight (2) a delay in the age induced cerebral glucose
impairment (3) an enhancement of the neurogenesis in hippocampus and enthorinal cortex highlighted by silver impregnation.
Under these experimental conditions, no modifications were observed in expression levels of GSK3 and of its downstream target
β-catenin proteins. These results suggested that chronic Li administration, at therapeutic doses, has a neuroprotective/neurotrophic
properties and its therapeutic mechanism doesn’t implicate GSK3 inactivation. 相似文献
70.
Imène Ben Salah Héla Mahmoudi Margaret Gruber Tarek Slatni Mondher Boulaaba Mhemmed Gandour Dorsaf Messedi Karim Ben Hamed Riadh Ksouri Abdelali Hannoufa Chedly Abdelly 《Biologia》2011,66(5):813-820
The objective of this study was to determine more indepth physiological and antioxidant responses in two Medicago ciliaris lines (a salt-tolerant line TNC 1.8 and a salt-sensitive line TNC 11.9) with contrasting responses to 100 mM NaCl. Under salt stress, both lines showed a decrease in total biomass and in the growth rate for roots, but TNC 1.8 was less affected by salt than TNC 11.9 in that it maintained leaf growth even in the presence of added salt. In both lines, salt stress mainly affected micronutrient status (Fe, Mn, Cu and Zn) rather than K nutrition, but the tolerant line TNC 1.8 accumulated more Na in leaves and less in roots compared with TNC 11.9. Salt stress decreased total soluble sugars (TSS) in all organs of the sensitive line TNC 11.9, whereas TSS was only reduced in roots of the tolerant line. The salt-induced drop in growth was linked to an increase in lipid peroxidation in roots of both lines and in leaves of the sensitive line. The salt-tolerant line TNC 1.8 was more efficient at managing salt-induced oxidative damage in leaves and to a lesser extent in roots than the salt-sensitive line TNC 11.9, by preserving higher phenolic compound and superoxide dismutase levels in both organs. 相似文献