Girdin (girders of actin filaments) is a novel actin-binding Akt substrate that plays an important role in actin organization and Akt-dependent cell motility in fibroblasts.

During development of the central and peripheral nervous systems, neurite extension mediated via glial-cell-line-derived neurotrophic factor (GDNF) and its receptor RET is critical for neuronal differentiation. In the present study, we investigated the role of the RET substrate Dok-4 in neurite outgrowth induced by the GDNF/RET signaling pathway. In TGW neuroblastoma cells, which endogenously express both RET and Dok-4, depletion of Dok-4 through treatment with small interfering RNA resulted in a marked decrease in GDNF-stimulated neurite outgrowth. By contrast, exogenous expression of wild-type Dok-4 induced sustained p44/42 mitogen-activated protein kinase (ERK1/2) activation and enhanced neurite outgrowth. Expression of Dok-4 mutants in which the tyrosine residues at codons 187, 220 and 270, conserved between Dok-4, -5, and -6, were each replaced with a phenylalanine inhibited sustained ERK1/2 activation and neurite outgrowth. We also found that Dok-4 induced a significant activation of the small G protein Rap1 and that expression of a dominant active Rap1 mutant restored neurite outgrowth in Dok-4-depleted cells. By contrast, expression of a dominant negative Rap1 mutant impaired GDNF-stimulated neurite outgrowth from TGW cells. Finally, we found that neurite formation in cultured rat hippocampal neurons was enhanced by the expression of Dok-4. Together, our results suggest that Dok-4, through activation of the Rap1-ERK1/2 pathway, regulates GDNF-mediated neurite outgrowth during neuronal development.

Perineal rectosigmoidectomy (Altemeier's procedure), as used for the surgical treatment of full-thickness rectal prolapse, has a long history. The physiological derangement in patients with rectal prolapse is complex, frequently showing impairment of the rectoanal inhibitory reflex, intermittent high-pressure rectal motor activity, disturbances in anorectal sampling and attendant pudendal neuropathy. There are currently few defined preoperative factors in patients presenting with rectal prolapse and fecal leakage which predict for the restoration of continence after surgery. This review describes our technique of Altemeier's procedure and analyzes the reported results of this operation, presenting those studies which assessed postoperative continence and prolapse recurrence in particular. The lack of prospective randomized data regarding this perineal approach makes clinical interpretation difficult at the present time.

A new robotic system named "Hyper Finger" for minimally invasive surgery in deep organs has been developed. The finger size of the latest version is 10 mm and the entire system is much smaller and lighter, and can be set up on a camera tripod. This is one ofthe smallest master-slave robots in medicine. Each finger has nine degrees of freedom and several unique mechanisms are employed to solve the fundammlal issues ofconventional wire drive manipulators. The new concept and system were verified successfully by in-vivo remote minimally invasive surgery. Further improvements of the system toward a clinical version are now underway.

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