BackgroundSome Hirschsprung’s disease (HSCR) patients showed persistent bowel symptoms following an appropriately performed pull-through procedure. The mechanism is presumed to be down-regulated small-conductance calcium-activated potassium channel 3 (SK3) expression in the HSCR ganglionic intestines. We aimed to investigate the SK3 expression’s impact in HSCR patients after a properly performed pull-through surgery in an Indonesian population, a genetically distinct group within Asia.MethodsWe assessed SK3 gene expression in both the ganglionic and aganglionic colon of HSCR patients and controls colon by quantitative real-time polymerase chain reaction (RT-PCR).ResultsWe ascertained fourteen sporadic HSCR patients and six anorectal malformation patients as controls. Quantitative RT-PCR showed that the SK3 expression was significantly lower (23-fold) in the ganglionic colon group compared to the control group (9.9 ± 4.6 vs. 5.4 ± 3.4; p = 0.044). The expression of SK3 in the aganglionic colon group was also significantly lower (43-fold) compared to the control group (10.8 ± 4.4 vs. 5.4 ± 3.4; p = 0.015).ConclusionOur study shows that the down-regulated SK3 expression in ganglionic intestines might contribute to the persistent bowel symptoms following a properly performed pull-through surgery in Indonesian HSCR patients. Furthermore, this study is the first report of SK3 expression in a sample population of Asian ancestry.
The GDNF Family Ligands (GFLs) regulate neural development and kidney organogenesis by activating the RET receptor tyrosine kinase. Many RET‐dependent developmental processes involve long‐distance cell‐cell communications or cell polarity, which includes cell migration and axon guidance. This suggests that spatiotemporally regulated subcellular localization of RET protein and appropriate propagation of RET signaling in cells are essential for the physiological function of the GFLs. Little is known, however, about the dynamics of RET protein in cells. Addressing this issue requires development of a system that allows visualization of RET in living cells. In this study, we report generation of a novel knock‐in mouse line in which the RET‐EGFP chimeric receptor is expressed under the Ret promoter. Unlike Ret‐deficient mice that die after birth due to the absence of the enteric nervous system (ENS) and kidneys, RetRET‐EGFP/RET‐EGFP mice were viable and grew to adulthood with no overt abnormality, which indicated that RET‐EGFP exerts function comparable to RET. In neurons and ENS progenitors, RET‐EGFP signals were detected both on the cell membrane and in the cytoplasm, the latter of which appeared as a punctate pattern. Time‐lapse imaging of cultured neural cells and embryos revealed active transport of RET‐EGFP puncta in neuronal axons and cell bodies. Immunohistochemical analyses detected RET‐EGFP signals in early and recycling endosomes, indicating that RET‐EGFP is trafficked via the endocytic pathway. RetRET‐EGFP/RET‐EGFP mice enable visualization of functional RET protein in vivo for the first time and provide a unique platform to examine the dynamics and physiology of RET trafficking.
Anal stenosis is a late hemorrhoidectomy complication. Sphincterotomy and various anoplasty techniques are used for treatment severe anal stenosis, such as the C flap, House flap, U flap, and rotational S flap, but no procedure is ideal for every patient. We review 2 cases of severe circular anal stenosis. Their complaints included narrow caliber of the stool and feeling unsatisfied defecation. Excision of scar tissue using the circular technique was followed by reconstruction using the bilateral rotational S flap procedure. At the 1-year follow-up, the patient had complaints about neither defecation nor pain, and no longer needed laxative agents. In conclusion, the bilateral rotational S flap technique should be considered as a viable treatment because it can also prevent the occurrence of restenosis, especially given the consideration of adequate blood supply.
The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic‐lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1‐deficient mice, with the numbers of neurons expressing somatostatin (Sst+) decreased in multiple gut regions. Notably, the decrease in Sst+ neurons was associated with the corresponding increase in calbindin+ neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1 and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes.This article is protected by copyright. All rights reserved.
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