Endoscopic titanium clip closure of gastric fistula after splenectomy: A case report.

This report describes a 52-year-old male patient with blunt abdominal traumatic rupture of the spleen due to injuries sustained in an automobile accident. Following splenectomy, the patient developed a gastric fistula. He underwent a long period of conservative treatment, including antibiotics and total parenteral nutrition, which was ineffective. The fistula could not be closed and titanium clip closure using a gastroscopy was then performed in order to close the fistula. After endoscopic therapy and clipping surgery, the patient's general condition improved significantly, and he had no post-procedural abdominal complications. On post-clipping day 6, the gastric fistula was completely closed as shown by X-ray examination of the upper digestive tract. The patient was discharged from hospital and no complications were observed during the six-month follow-up period. Our report suggests that titanium clip closure using endoscopy may be the choice of treatment in patients with a gastric fistula.

Ocular coloboma and dorsoventral neuroretinal patterning defects in Lrp6 mutant eyes.

Coloboma, an ocular birth defect seen in humans and other species, is caused by incomplete closure of the optic fissure. Here, we demonstrate that genetic deletion of Lrp6, a bottleneck coreceptor in the canonical Wnt signaling pathway, results in ocular coloboma and neuroretinal patterning defects in mice. The expression of ventral neuroretinal patterning gene Vax2 was conserved but with dorsally shifted expression domains; however, the dorsal neuroretinal patterning gene Tbx5 was lost in the Lrp6-mutant eyes at embryonic day 10.5. Both Bmp4 and phosphorylated Smad 1/5/8 were also significantly attenuated in the dorsal neuroretina. In addition, the retinoic acid synthesizing enzymes Raldh1 and Raldh3 were significantly changed in the mutant eyes. Our findings suggest that defective retinal patterning causes coloboma in the Lrp6-deficient mice, and that canonical Wnt signaling plays a primary role in dorsal neuroretinal patterning and related morphogenetic movements by regulation of both Bmp and retinoic acid signaling pathways.

Activation of the Wnt/beta-catenin signaling reporter in developing mouse olfactory nerve layer marks a specialized subgroup of olfactory ensheathing cells.

Wnt reporter TOPgal mice carry a beta-galactosidase (betagal) gene under the control of the Wnt/beta-catenin signaling responsive elements. We found that the intensely immunolabeled betagal+ cells were co-immunolabeled with Nestin and formed a tangentially oriented single-cell layer in the "connecting or docking zone" where the olfactory sensory axons attached to the brain surface during mid-gestation. During early postnatal development, betagal+ cells were located in the inner olfactory nerve layer (ONLi) and co-labeled with olfactory ensheathing cell (OEC) markers S100beta and NPY but not with lineage-specific markers for neurons, oligodendrocytes, astrocytes, and microglia, demonstrating that the TOPgal marked a subpopulation of OECs. By confocal microscopy, we found that TOPgal activated processes extended along the developing glomerulus and formed multiple tunnel-like structures that ensheathe and bridge olfactory sensory axonal bundles from ONLi to the glomerulus, which may play a key role in glomerulus formation and convergent sorting of the peripheral olfactory axons.

Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants.

Mice with mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein-6 (LRP6) have a smaller and severely disorganized dorsal thalamus and lack thalamocortical projections. Using molecular markers, we showed that most dorsal thalamic and epithalamic neurons were missing, and most of the major dorsal thalamic nuclei were not identifiable. However, the ventral thalamus was essentially unaffected, although the dorsal thalamic defect leads to rostral displacement of portions of the ventral thalamus. Analysis of younger embryos showed that epithalamic and dorsal thalamic neurons were not produced at early stages of development, whereas ventral thalamic neurons were still produced. These defects were accompanied by improper formation of the boundary between dorsal and ventral thalamus, the zona limitans interthalamica (ZLI). Furthermore, the expression of an early marker of posterior forebrain development that marks the compartment from the midbrain-hindbrain junction to the ZLI (including the future dorsal thalamus, pretectum, and midbrain) was disrupted, supporting the idea that diencephalic development is abnormal from very early in embryogenesis. This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway.

Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities.

LRP6 mutant mice have generalized defects in the Wnt/beta-catenin signaling pathway because of the crucial function of LRP6 as a Wnt signaling co-receptor (Pinson et al., 2000). We examined the hippocampal phenotype of single LRP6 mutant mice as well as LRP6/Lef1 double mutant mice. LRP6 mutants had reduced production of dentate granule neurons and abnormalities of the radial glial scaffolding in the forming dentate gyrus. These defects were more severe with the addition of a single Lef1 null allele to an LRP6 null background. Pyramidal cell fields were unaffected in the LRP6, Lef1, or double mutants. The dentate defects were accompanied by decreased numbers of mitotic precursors in the migratory pathway to the dentate and in the displaced proliferative zone in the dentate itself. At earlier gestational ages, there was a reduction in the number of dentate granule cell progenitors in the dentate ventricular zone before the emigration of the earliest differentiated granule neurons and precursors to form the dentate anlage.

Temporal and spatial profiles of ABCA2-expressing oligodendrocytes in the developing rat brain.

ABCA2 protein belongs to the ABCA subclass of ATP-binding cassette (ABC) transporters proposed to exert critical functions in transmembrane transport of endogenous lipids. In this study, we found by immunoblot analyses that approximately 260 kDa of ABCA2 protein is expressed predominantly in oligodendrocytes, and that the expression of the protein is upregulated in the brain during maturation, especially between postnatal days 6 and 19. Parallel to the changes in expression of ABCA2, immunohistochemical analyses showed rapid spatial spread of ABCA2-immunolabeled oligodendrocytes in the brain during this period. These temporal and spatial changes in ABCA2 expression were in good agreement with findings in myeloarchitectonics reported previously. Further, double immunolabeling with ABCA2 and a major structural protein of myelin, myelin basic protein, demonstrated that onset of ABCA2 expression in oligodendrocytes coincides with the appearance of thick myelin segments immunolabeled with myelin basic protein. Because ABCA2 was abundantly expressed in adult cortex in white matter and gray matter, coexpression of ABCA2 and a marker for the oligodendroglial progenitors NG2 or platelet-derived growth factor alpha receptor was investigated. No cells coexpressing ABCA2 and the marker were observed, suggesting that ABCA2 is expressed predominantly in myelin-forming oligodendrocytes distinct from the adult oligodendroglial progenitors tested. These results suggested a role for ABCA2 in membrane transport of substrates such as the lipids that are closely linked to myelination processes.

PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways.

Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from the ovine brain in 1989 as a novel hypothalamic hormone that potently activates adenylate cyclase to produce cyclic AMP in pituitary cells. This neuropeptide belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily, and exists in two amidated forms as PACAP38 (38-amino acid residues) and PACAP27 derived from the same precursor. The primary structure of PACAP has been remarkably conserved throughout evolution among tunicata, ichthyopsida, amphibia and mammalia, and a PACAP-like neuropeptide has also been determined in Drosophila. Both PACAP and its receptors are mainly distributed in the nervous and endocrine systems showing pleiotropic functions with high potency. There are three types of receptors with high PACAP-binding affinity and with different tissue-distribution patterns. All of them belong to G-protein-coupled receptor superfamily with seven transmembrane domains. PAC(1) is the PACAP-specific receptor and exists in at least eight splice variants which couple to different intracellular signal transduction pathways. VPAC(1) and VPAC(2) are the common receptors for both PACAP and VIP, which are coupled to adenylate cyclase. This review article presents and discusses an update on PACAP research and its pleiotropic physiological functions based on multiple receptor-mediated signaling mechanisms in both the central and peripheral nervous system, including the regulation of hypothalamic neurosecretion, homeostatic control of circadian clock and behavioral actions, involvement in learning and memory processes, neuroprotective effects such as anti-apoptosis and response to injury and inflammation, and neural ontogenetic functions on proliferation/differentiation processes from early stages.

ATP-binding cassette transporter ABCA2 (ABC2) expression in the developing spinal cord and PNS during myelination.

We examined developmental characteristics of the ATP-binding cassette transporter ABCA2 (or ABC2) -expressing cells in rat spinal cord and peripheral nerves. In adult spinal cord, ABCA2 immunoreactivity was detected in lysosome-like organelles of mature oligodendrocyte cell bodies, and a single specific band was detected by Western blot analysis. In postnatal developing spinal cord, ABCA2 immunolabeling was first detected in a small number of cells restricted to the ventral marginal area and the dorsal funiculus at birth (P0). ABCA2-positive cells were co-immunolabeled by O4, a marker for late progenitor and immature oligodendrocytes. At the same time, myelin basic protein was apparent in the same restricted regions. The number of ABCA2 and O4 co-immunolabeled cells increased quickly in both dorsal and ventral regions from P2 and reached a peak at P8. After transient expression from P0 to P8, O4 labeling in white matter tracts decreased and disappeared. In contrast, ABCA2-positive oligodendrocytes persisted in gray and white matter throughout the spinal cord into adulthood. These data suggest a role for the ABCA2 transporter in maturation of oligodendrocyte lineage cells and the onset of myelination in the central nervous system. In addition, ABCA2 immunoreactivity was detected in the ciliated region of the ependyma in the central canal from early postnatal development. ABCA2 immunoreactivity was also detected in the Schwann cell lineage in developing spinal nerves and in adult trigeminal and sciatic nerves. ABCA2 was also expressed in numerous undetermined cells distributed in para-nerve connective tissues and nerve sheaths throughout early postnatal development. These data indicate multiple levels of involvement for ABCA2 in nervous system development especially with strong evidence for a role in myelination.