A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway

BACKGROUND: Intestinal atresia represents a significant surgically correctable cause of intestinal obstruction in neonates. Intestinal development proceeds as a tube-like structure with differentiation along its axis. As the intestine differentiates, the cecum develops at the transition from small to large intestine. Fgf10 is known to serve a key role in budding morphogenesis; however, little is known about its role in the development of this transitional structure. Here we evaluate the effect of Fgf10/Fgfr2b invalidation on the developing cecum. MATERIALS AND METHODS: Wild-type C57Bl/6, Fgf10(-/-), and Fgfr2b(-/-) embryos harvested from timed pregnant mothers were analyzed for cecal phenotype, Fgf10 expression, and differentiation of smooth muscle actin. RESULTS: Wt cecal development is first evident at E11.5. FGF10 is discreetly expressed in the area of the developing cecum at early stages of development. One hundred percent of Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with absence of epithelial and muscular layers. The development of neighboring anatomical structures such as the ileocecal valve is not affected by Fgf10/Fgfr2b invalidation. CONCLUSIONS: FGF10 expression is localized to the cecum early in the normal development of the cecum. Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with complete penetrance. Epithelial and muscular layers of the cecum are not present in the atretic cecum. The Fgf10(-/-) and Fgfr2b(-/-) mutants represent a genetically reproducible animal model of autosomal recessive intestinal atresia.     

Occlusion of the abdominal aorta caused by enlargement of the false lumen after graft replacement for a DeBakey type IIIb dissecting aneurysm: Report of a case

(Received for publication on July 10, 1997; accepted on Mar. 10, 1998)     

毛裂蜂斗菜中的1个新的倍半萜化合物

目的 研究菊科蜂斗菜属植物毛裂蜂斗菜Petasites tricholobus全草中倍半萜类化学成分。方法 采用正相硅胶、反相硅胶、葡聚糖凝胶、微孔树脂等多种柱色谱填料进行分离纯化,并运用MS、NMR、UV、IR等现代波谱分析技术对化合物结构进行鉴定。结果 从毛裂蜂斗菜50%乙醇提取物中分离得到5个倍半萜类化合物,分别鉴定为1α-(cismethylthioacryloyloxy)-8α-angeloyloxy-3β,4β-epoxy-bisabola-7(14),10-diene(1)、bakkenolide IIIb(2)、monoketone(3)、japonipene C(4)和petatewalide A(5)。结论 化合物1为新化合物,命名为毛裂蜂斗菜素;化合物2～5均为首次从毛裂蜂斗菜中分离得到。     

中西医结合治疗IIIb型前列腺炎及护理

目的：评价中西医结合治疗IIIb型前列腺炎的疗效。方法：对90例IIIb型前列腺炎患者进行4周的观察。中药灌肠2次/d;普适泰片2次/d,2粒/次。结果：治疗4周后总有效率93.7%,全组病例观察过程中未发现任何药物不良反应。结论：中西医结合治疗IIIb型前列腺炎的疗效确切,耐受性良好。     

FGFR2IIIb signaling regulates thymic epithelial differentiation.

Heterogeneous epithelial populations comprising the thymic environment influence early and late stages of T-cell development. The processes that regulate the differentiation of thymic epithelium and that are responsible for this heterogeneity are not well understood, although mesenchymal/epithelial interactions are clearly involved. Here, we show that targeted expression by thymocytes of an fibroblast growth factor receptor-2IIIb (FGFR2IIIb) ligand, FGF10, profoundly alters the differentiation and function of thymic epithelium (TE). Reconstitution of irradiated lckFGF10 mice with normal bone marrow restores normal thymic organization and function, while wild-type mice reconstituted with lckFGF10 bone marrow recapitulates some of the thymic alterations seen in lckFGF10 mice. We also demonstrate that interference with FGFR2IIIb signaling in the thymus with a soluble FGFR2IIIb dominant-negative fusion protein leads to precocious reductions in thymic size and cellularity that resemble age-related thymic involution. These findings indicate that TE compartments are dynamically maintained and that FGF signals are involved in this process.     

Inhibition of fibroblast growth factor receptor 2 attenuates proliferation and invasion of pancreatic cancer

The alternative splicing of the extracellular domain of fibroblast growth factor receptor (FGFR)‐2 generates the IIIb and IIIc isoforms. Expression of FGFR‐2 IIIb correlates with vascular endothelial growth factor‐A (VEGF‐A) expression and venous invasion of pancreatic ductal adenocarcinoma (PDAC). By contrast, FGFR‐2 IIIc expression correlates with faster development of liver metastasis after surgery, and increased proliferation rates and invasion of the cancer. In this study, we analyzed the expression and roles of total FGFR‐2 (both isoforms) to determine the effectiveness of FGFR‐2‐targeting therapy for PDAC. Immunohistochemically, FGFR‐2 was highly expressed in 25/48 (52.1%) PDAC cases, and correlated with advanced stage cancer. In FISH analysis, FGFR2 was amplified in 3/7 PDAC cell lines. We stably transfected an FGFR‐2 shRNA targeting the IIIb and IIIc isoforms into FGFR2‐amplified PDAC cells. The proliferation rates, migration, and invasion of FGFR‐2‐shRNA‐transfected cells were lower than those of control cells in vitro. In response to FGF‐2, FGFR‐2‐shRNA‐transfected cells showed decreased phosphorylation of ERK compared with control cells. The FGFR‐2‐shRNA‐transfected cells also expressed lower levels of vascular endothelial growth factor‐A than control cells, and formed smaller s.c. tumors in nude mice. These findings suggest that FGFR‐2 is a therapeutic target for inhibition in PDAC.     

Retrospective Study of Intentional Replantation for Type IIIb Dens Invaginatus with Periapical Lesions

IntroductionIn recent years, intentional replantation (IR) has received more attention for its high tooth survival rate and wide range of indications. Type IIIb dens invaginatus (DI) is 1 of the most serious types of tooth malformation and is very challenging to treat. When root end surgery is not feasible, IR may be considered as an alternative to extraction. However, there is little information available on the use of IR for type IIIb DI. Therefore, this study investigated the treatment outcomes and clinical procedures used for the treatment of type IIIb DI with IR.MethodsIR was performed to treat 10 patients with type IIIb DI with periapical lesions. Each tooth was examined clinically and radiologically. IR was selected by these patients as their treatment plan after treatment procedures were discussed. An experienced endodontist and an experienced surgeon performed all treatments using the same protocol and surgical technique. Postoperative assessments were composed of clinical and radiographic examinations, tooth survival, and functional status.ResultsThe follow-up period ranged from 4–39 months. After IR, 8 teeth were functioning properly with no clinical or radiologic signs of pathology. The other 2 teeth had complications after IR comprising the recurrence of periapical radiolucency and sinus tract formation in 1 patient and the development of a mucosal fenestration in another. Both of these patients received additional surgery and showed marked improvements.ConclusionsOur study evaluated the most clinical data to date and showed that IR may be a reliable alternative for type IIIb DI with a periapical lesion.