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101.
Charbel Issa P Groppe M MacLaren RE 《Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft》2012,109(2):121-128
Genetic mutations are the cause of inherited retinal dystrophies. The underlying genetic basis of these diseases suggests that a gene therapy approach is logical either to replace or reduce the expression of defective genes. The first proof-of-concept clinical studies in patients with Leber's congenital amaurosis have suggested that retinal gene therapy is safe and potentially effective, at least for specific disease entities. In contrast to pharmacological treatment gene therapy has the advantage of being able to express a protein within specific cell populations and is a potentially definitive therapy. Besides replacing deficient genes in inherited diseases, additional strategies that might broaden the application of retinal gene therapy are also being developed. These include the permanent expression of neuroprotective substances or photosensitive molecules (so-called optogenetics). This overview discusses the current clinical strategies and potential problems of retinal gene therapy. 相似文献
102.
Advax™ adjuvant is derived from inulin, a natural plant-derived polysaccharide that when crystallized in the delta polymorphic form, becomes immunologically active. This study was performed to assess the ability of Advax™ adjuvant to enhance influenza vaccine immunogenicity and protection. Mice were immunized with influenza vaccine alone or combined with Advax™ adjuvant. Immuno-phenotyping of the anti-influenza response was performed including antibody isotypes, B-cell ELISPOT, CD4 and CD8 T-cell proliferation, influenza-stimulated cytokine secretion, DTH skin tests and challenge with live influenza virus. Advax™ adjuvant increased neutralizing antibody and memory B-cell responses to influenza. It similarly enhanced CD4 and CD8 T-cell proliferation and increased influenza-stimulated IL-2, IFN-γ, IL-5, IL-6, and GM-CSF responses. This translated into enhanced protection against mortality and morbidity in mice. Advax™ adjuvant provided significant antigen dose-sparing compared to influenza antigen alone. Protection could be transferred from mice that had received Advax™-adjuvanted vaccine to naïve mice by immune serum. Enhanced humoral and T-cell responses induced by Advax™-formulated vaccine were sustained 12 months post-immunization. Advax™ adjuvant had low reactogenicity and no adverse events were identified. This suggests Advax™ adjuvant could be a useful influenza vaccine adjuvant. 相似文献
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104.
Chalfoun CT McConnell MP Wirth GA Brenner KA Evans GR Kobayashi M 《Journal of reconstructive microsurgery》2012,28(3):211-219
Extensive abdominal wall defects may result from tumor extirpation, traumatic injury, or soft tissue infections. Extensive traumatic injuries can often disrupt the soft tissue content of the abdomen as well as the bony support provided by the pelvis. Reconstruction of the lower abdomen should aim to recreate dynamic stability. Five patients with extensive lower abdominal wall disruption following traumatic injuries or infection were treated using a novel flap for functional reconstruction. We devised a free neurotized osteomyocutaneous tensor fasciae latae (TFL) flap that would restore bony continuity by providing a vascularized bone graft and simultaneously maintain the integrity of the attachment of the tensor fascia latae muscle to the iliac crest, reestablishing musculofascial continuity. A branch of the superior gluteal nerve was harvested with this composite flap and coapted to an intercostal nerve for reinnervation, thereby creating a dynamic muscle in these patients. All patients underwent successful free tissue reconstruction with 100% flap survival. The lower abdominal wall and bony integrity of the pelvis were successfully reconstructed. Reinnervation has shown clinical signs of maintained dynamic stability. The innervated TFL osteomyocutaneous flap is an ideal option for lower abdominal reconstruction in patients with complex abdominoperineal defects with loss of bony integrity. 相似文献
105.
Charbel Al Bayssari Seydina M. Diene Lotfi Loucif Sushim Kumar Gupta Fouad Dabboussi Hassan Mallat Monzer Hamze Jean-Marc Rolain 《Antimicrobial agents and chemotherapy》2014,58(8):4966-4970
We report here the emergence of VIM-2 and IMP-15 carbapenemases in a series of clinical isolates of carbapenem-resistant Pseudomonas aeruginosa in Lebanon. We also describe the disruption of the oprD gene by either mutations or insertion sequence (IS) elements ISPa1328 and ISPre2 isoform. Our study reemphasizes a rapid dissemination of the VIM-2 carbapenemase-encoding gene in clinical isolates of P. aeruginosa in the Mediterranean basin. 相似文献
106.
107.
Alphonse Charbel Luca Tavernar Thomas Albrecht Fritz Brinkmann Joanne Verheij Eva Roos Monika Nadja Vogel Bruno Khler Christoph Springfeld Alexander Brobeil Peter Schirmacher Stephan Singer Arianeb Mehrabi Stephanie Roessler Benjamin Goeppert 《British journal of cancer》2022,127(9):1603
Background Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well‐defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions.Methods Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC. The spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis was comprehensively analysed using triplet sample sets of non-neoplastic epithelium, precursor lesion and invasive BTC. Immune-cell dynamics during IPN- and BilIN-associated carcinogenesis were subsequently compared.Results Stromal CD3+ (P = 0.002), CD4+ (P = 0.007) and CD8+ (P < 0.001) T cells, CD20+ B cells (P = 0.008), MUM1+ plasma cells (P = 0.012) and CD163+ M2-like macrophages (P = 0.008) significantly decreased in IPN compared to non-tumorous biliary epithelium. Upon transition from IPN to invasive BTC, stromal CD68+ (P = 0.001) and CD163+ (P < 0.001) macrophages significantly increased. In contrast, BilIN-driven carcinogenesis was characterised by significant reduction of intraepithelial CD8+ T-lymphocytic infiltration from non-tumorous epithelium via BilIN (P = 0.008) to BTC (P = 0.004).Conclusion IPN and BilIN are immunologically distinct entities that undergo different immune-cell variations during biliary carcinogenesis. Intraepithelial CD8+ T-lymphocytic infiltration of biliary tissue decreased already at the IPN-precursor stage, whereas BilIN-associated carcinogenesis showed a slowly progressing reduction towards invasive carcinoma.Subject terms: Cancer microenvironment, Immunoediting, Biliary tract cancer 相似文献
108.
109.
C T Fittkow S Q Shi E Bytautiene G Olson G R Saade R E Garfield 《Journal of perinatal medicine》2001,29(6):535-543
Light-induced fluorescence (LIF) of collagen was used to investigate in vivo changes in cervical collagen in guinea pigs during gestation and following sodium nitroprusside treatment. Natural fluorescence of collagen is due to collagen cross-linking molecules that connect single collagen fibers and therefore provide rigidity of the cervical stroma. LIF of cervical collagen was measured from the surface of the exocervix in anesthetized nonpregnant and timed pregnant guinea pigs at different times of gestation with an instrument designed in our lab (Collascope). Measurements were also performed in guinea pigs at midgestation before and 8 hours after intracervical treatment with sodium nitroprusside. Collagen fluorescence decreased significantly as pregnancy progressed, reached lowest values at delivery, and increased gradually postpartum. Treatment with sodium nitroprusside, but not with the vehicle, caused a significant decrease in LIF (p = 0.007). We conclude, that LIF changes in the cervix reflect the gradual cervical softening (ripening) during pregnancy and the return to the rigid state of the cervix postpartum. Cervical softening during pregnancy, and after sodium nitroprusside treatment, is associated with a decrease in collagen cross-links. Measurements of LIF can be used to investigate cervical softening in vivo. 相似文献
110.
G Saade R Homsi M Seoud 《European journal of obstetrics, gynecology, and reproductive biology》1991,40(2):149-152
Bernard-Soulier Syndrome is a rare autosomal recessive bleeding disorder characterized by a normal or low platelets count, the presence of giant platelets, and a prolonged bleeding time. Only five pregnant patients with this disease have been previously reported. Most of the complications seem to occur in the intrapartum or postpartum period. In some patients the disease can go unrecognized until the third or fourth decade. Our patient had two uneventful pregnancies, one pregnancy with early postpartum hemorrhage, and another pregnancy with intrapartum and late postpartum bleeding. Although the optimum mode of delivery is not clear yet, the vaginal route should be considered unless otherwise obstetrically indicated. Management of active bleeding episodes is also debatable; it includes platelets transfusions, desmopressin (DDAVP), antifibrinolytic therapy, and ecbolic agents for postpartum hemorrhage. 相似文献