A diffusion-based neurite length-sensing mechanism involved in neuronal symmetry breaking

Shootin1, one of the earliest markers of neuronal symmetry breaking, accumulates in the neurite tips of polarizing neurons in a neurite length-dependent manner. Thus, neurons sense their neurites' length and translate this spatial information into a molecular signal, shootin1 concentration.Quantitative live cell imaging of shootin1 dynamics combined with mathematical modeling analyses reveals that its anterograde transport and retrograde diffusion in neurite shafts account for the neurite length-dependent accumulation of shootin1.The neurite length-dependent shootin1 accumulation and shootin1-induced neurite outgrowth constitute a positive feedback loop that amplifies stochastic shootin1 signals in neurite tips.Quantitative mathematical modeling shows that the above positive feedback loop, together with shootin1 upregulation, constitutes a core mechanism for neuronal symmetry breaking

Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization

Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We describe a novel protein, named shootin1, that became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites. Eventually, shootin1 accumulated asymmetrically in a single neurite, which led to axon induction for polarization. Disturbing the asymmetric organization of shootin1 by excess shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited polarization. Overexpression and RNA interference data suggest that shootin1 is required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was transported anterogradely to the growth cones and diffused back to the soma; inhibiting this transport prevented its asymmetric accumulation in neurons. We propose that shootin1 is involved in the generation of internal asymmetric signals required for neuronal polarization

Clinical study of single-incision laparoscopic cholecystectomy

We experienced 63 patients with non-inflammatory disease who underwent single-incision laparoscopic cholecystectomy (TANKO-LC). Herein we report the procedure of operation and the short-term results. We compared 63 cases of TANKO-LC with 109 cases of non-inflammatory conventional laparoscopic cholecystectomy (S-LC) within the same period. At first, our standard procedure was to insert multiple trocars in the abdominal cavity through a single wound ; now, we insert only a single trocar all cases. In the 63 cases investigation, 3 cases required trocar addition and one case converted to open surgery. Intra and postoperative complications were recognized in 2 cases (port-site infection). No significant complications were recognized. In comparing the TANKO-LC group and the S-LC group, the operation time was intentionally longer in the TANKO-LC group (TANKO-LC group : 118 min, S-LC group : 90 min), but there were no differences in the blood loss, the rates of intra and postoperative complications and the conversion rate. Laparoscopic cholecystectomy is a standard operation for gallbladder removal, but single-incision laparoscopic cholecystectomy is considered a useful operation with the same low operative complication rate yet more satisfactory cosmetic results

Clinical study of the prognostic factors in colorectal cancer patients with synchronous liver metastasis

This study was aimed to clarify the prognostic factors in colorectal cancer patients with synchronous liver metastasis. Fifty-four patients were assessed to evaluate prognoses according to various clinico-pathological factors and therapeutic procedures. The patients' survival was significantly related to extrahepatic distant metastasis and therapeutic procedures. Regarding therapeutic procedures, the liver resection group showed significantly improved survival compared with the chemotherapy group, especially in liver metastasis Grade B. For colorectal liver metastases, it is clear that liver resection is the most effective treatment at present. Further improvement of patient prognoses is expected to be achieved by future research on combination chemotherapy

A case of transverse colon cancer with remarkable extramural invasion to stomach and jejunum

A 77-year-old woman was admitted to our hospital due to abdominal pain and body weight loss. A palpable mass the size of an infant's head was tender on palpation and identified as an epigastric lesion. Colonoscopic examination revealed stenosis of the transverse colon, although no intraluminal growth of the tumor was found. The histologic findings of the biopsy material were poorly differentiated and/or undifferentiated cells. Abdominal CT scan showed an irregular-shaped tumor with a diameter of 10cm invading the stomach and jejunum. We performed an operation under a diagnosis of extramurally growing cancer or malignant lymphoma of the colon. Partial resection of the transverse colon was done by distal gastrectomy and partial resection of the jejunum. Histologic examination of the operative specimens revealed moderately differentiated adenocarcinoma of the transverse colon, prominently proliferating into the surrounding tissues. The finding of a long stenotic lesion and extramural compression by colonography are characteristic of this tumor, based on a review of 43 literature reports in Japan

Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF

Insulin-like growth factor (IGF)-1 plays crucial roles in growth control and rearrangements of the cytoskeleton. IGF-1 binds to the IGF-1 receptor and thereby induces the autophosphorylation of this receptor at its tyrosine residues. The phosphorylation of the IGF-1 receptor is thought to initiate a cascade of events. Although various signaling molecules have been identified, they appear to interact with the tyrosine-phosphorylated IGF-1 receptor. Here, we identified leukemia-associated Rho guanine nucleotide exchange factor (GEF) (LARG), which contains the PSD-95/Dlg/ZO-1 (PDZ), regulator of G protein signaling (RGS), Dbl homology, and pleckstrin homology domains, as a nonphosphorylated IGF-1 receptor-interacting molecule. LARG formed a complex with the IGF-1 receptor in vivo, and the PDZ domain of LARG interacted directly with the COOH-terminal domain of IGF-1 receptor in vitro. LARG had an exchange activity for Rho in vitro and induced the formation of stress fibers in NIH 3T3 fibroblasts. When MDCKII epithelial cells were treated with IGF-1, Rho and its effector Rho-associated kinase (Rho-kinase) were activated and actin stress fibers were enhanced. Furthermore, the IGF-1–induced Rho-kinase activation and the enhancement of stress fibers were inhibited by ectopic expression of the PDZ and RGS domains of LARG. Taken together, these results indicate that IGF-1 activates the Rho/Rho-kinase pathway via a LARG/IGF-1 receptor complex and thereby regulates cytoskeletal rearrangements

Analysis of Surgical Outcomes of Diverticular Disease of the Colon

We analyzed retrospectively the surgical outcomes of diverticular diseases of the colon at the surgical division of Fukuyama Medical Center. Data were collected from 39 patients who underwent surgery for diverticular disease at Fukuyama Medical Center. Thirty-nine patients were admitted between 2005 and 2010. The mean age of the 39 patients was 63.6 years. The collected data included patient demographics, patient history, type of surgery and complications. Patients were divided into 2 groups, Elective vs. Emergent group, right vs. left colon group and laparotomy vs. laparoscopic approach. Multivariate analysis of the logistic model of morbidity revealed a significantly higher rate in the left colon and the Cox proportional hazards model clearly showed fewer postoperative hospital days with the laparoscopic approach. Surgical procedures should be decided in reference to the particular clinical and pathological features of diverticular disease to gain an acceptable morbidity and mortality rates