Posttranslational regulation of sucrase-isomaltase expression in intestinal crypt and villus cells

Expression and synthesis of sucrase-isomaltase (SI) were studied in human jejunum and in the colon tumor cell lines Caco-2 and HT-29. Twelve monoclonal antibodies produced against the adult human intestinal enzyme were shown to recognize specifically SI by immunoprecipitation of 14C-labeled membrane proteins, analysis of enzyme activities in the immunoprecipitates, and immunoblotting. These antibodies produced markedly different patterns of immunofluorescent staining of the intestinal mucosa. Three of them were specific for the absorptive villus cells, while the other nine also stained the luminal membrane of the proliferative crypt cells, with different intensities which paralleled their ability to recognize SI in immunoblots. Sequential immunoprecipitation of SI solubilized from purified brush borders or entire jejunum with four selected antibodies demonstrated the presence of different forms of the enzyme, expressed by either villus or crypt cells. Two immunologically distinct forms of high mannose precursor (hmP1 and hmP2) were also identified in both jejunal mucosa and colon tumor cells. They were present as monomers and their immunological differences were preserved under various ionic and pH conditions. Pulse-chase studies indicated that, in Caco-2 cells, hmP1 is converted into hmP2 within 30 min of chase, and hmP2 is then processed into the complex-glycosylated precursor destined for the brush border membrane. hmP1 was immunologically related to the mature SI present in crypt cells and lacked the epitopes specific for mature SI expressed by villus cells. These results demonstrated that sucrase-isomaltase is synthesized by both crypt and villus cells, but processing of the cotranslationally glycosylated high mannose precursor is dependent on the state of differentiation of the enterocytes. This may represent a general mechanism for the regulation of expression of differentiated cell products at the post-translational level.     

Pollen-based biome reconstruction for southern Europe and Africa 18,000 yr bp

Pollen data from 18,000 ¹⁴C yr bp were compiled in order to reconstruct biome distributions at the last glacial maximum in southern Europe and Africa. Biome reconstructions were made using the objective biomization method applied to pollen counts using a complete list of dryland taxa wherever possible. Consistent and major differences from present‐day biomes are shown. Forest and xerophytic woods/scrub were replaced by steppe, both in the Mediterranean region and in southern Africa, except in south‐western Cape Province where fynbos (xerophytic scrub) persisted. Sites in the tropical highlands, characterized today by evergreen forest, were dominated by steppe and/or xerophytic vegetation (cf. today’s Ericaceous belt and Afroalpine grassland) at the last glacial maximum. Available data from the tropical lowlands are sparse but suggest that the modern tropical rain forest was largely replaced by tropical seasonal forest while the modern seasonal or dry forests were encroached on by savanna or steppe. Montane forest elements descended to lower elevations than today.     

Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications

Based on immunomodulatory, osteogenic, and pro-angiogenic properties of adipose-derived stem cells (ASCs), this study aims to assess the safety and efficacy of ASC-derived cell therapies for clinical indications. Two autologous ASC-derived products were proposed to 17 patients who had not experienced any success with conventional therapies: (1) a scaffold-free osteogenic three-dimensional graft for the treatment of bone non-union and (2) a biological dressing for dermal reconstruction of non-healing chronic wounds. Safety was studied using the quality control of the final product (genetic stability, microbiological/mycoplasma/endotoxin contamination) and the in vivo evaluation of adverse events after transplantation. Feasibility was assessed by the ability to reproducibly obtain the final ASC-based product with specific characteristics, the time necessary for graft manufacturing, the capacity to produce enough material to treat the lesion, the surgical handling of the graft, and the ability to manufacture the graft in line with hospital exemption regulations. For 16 patients (one patient did not undergo grafting because of spontaneous bone healing), in-process controls found no microbiological/mycoplasma/endotoxin contamination, no obvious deleterious genomic anomalies, and optimal ASC purity. Each type of graft was reproducibly obtained without significant delay for implantation and surgical handling was always according to the surgical procedure and the implantation site. No serious adverse events were noted for up to 54 months. We demonstrated that autologous ASC transplantation can be considered a safe and feasible therapy tool for extreme clinical indications of ASC properties and physiopathology of disease.     

ABCG transporters export cutin precursors for the formation of the plant cuticle

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The Effects of CAMPATH-1H on Cell Viability Do Not Correlate to the CD52 Density on the Cell Surface

Graft versus host disease (GvHD) is one of the main complications after hematological stem cell transplantation (HSCT). CAMPATH-1H is used in the pre-transplant conditioning regimen to effectively reduce GvHD by targeting CD52 antigens on T cells resulting in their depletion. Information regarding CD52 expression and the effects of CAMPATH-1H on immune cells is scant and limited to peripheral blood (PB) T and B cells. To date, the effects of CAMPATH-1H on cord blood (CB) cells has not been studied. Here we aimed to analyze CD52 expression and the effects of CAMPATH-1H on fresh or frozen, resting or activated, PB mononuclear cells (PBMC) and CB mononuclear cells (CBMC). In resting state, CD52 expression was higher in CB than PB T cell subsets (653.66±26.68 vs 453.32±19.2) and B cells (622.2±20.65 vs 612.0±9.101) except for natural killer (NK) cells where CD52 levels were higher in PB (421.0±9.857) than CB (334.3±9.559). In contrast, CD52 levels were comparable across all cell types after activation. CAMPATH-1H depleted resting cells more effectively than activated cells with approximately 80–95% of apoptosis observed with low levels of necrosis. There was no direct correlation between cell surface CD52 density and depleting effects of CAMPATH-1H. In addition, no difference in cell viability was noted when different concentrations of CAMPATH-1H were used. CD52 was not expressed on HSC but began to be expressed as the cells differentiate, implying that CAMPATH-1H could potentially affect HSC differentiation and proliferation. Our study provides insightful information, which contributes to the better understanding in the use of CAMPATH-1H as part of the conditioning regime in HSCT.     

Le traitement chirurgical des tumeurs endocrines digestives

Surgery is the only curative treatment for localized gastrointestinal endocrine tumors. It plays a major role in therapeutic strategy. It meets the oncological principles of treatment. It must take into consideration the site of the tumor, its extension and its secretory nature. In well-differentiated endocrine tumors according to WHO classification, surgery must be indicated, not only for the primary tumor but also for the metastasis, particularly liver metastasis. The primary gastrointestinal endocrine tumors (functional or non functional) are mainly pancreatic in origin but also can be situated in small bowel, appendix, colon, or rectum. Surgery is part of a comprehensive approach discussed in multidisciplinary meeting.