Cdc42 Facilitates Invasion but Not the Actin-Based Motility of Shigella

The enteric pathogen Shigella utilizes host-encoded proteins to invade the gastrointestinal tract. Efficient invasion of host cells requires the stimulation of Rho-family GTPases and cytoskeletal alterations by Shigella-encoded IpaC [1]. Following invasion and lysis of the phagosome, Shigella exploits the host's actin-based polymerization machinery to assemble an actin tail that serves as the propulsive force required for spreading within and between cells [2, 3]. The Shigella surface protein IcsA stimulates actin-tail formation by recruiting host-encoded N-WASP to drive Arp2/3-mediated actin assembly [4–7]. N-WASP is absolutely required for Shigella motility, but not for Shigella invasion [4, 6]. Although Rho-family GTPases have been implicated in both the invasion and motility of Shigella, the role of Cdc42, an N-WASP activator, in this process has been controversial [8, 9]. In these studies, we have examined the role of Cdc42 in Shigella invasion and actin-based motility using Cdc42-deficient cells. We demonstrate that Cdc42 is required for efficient Shigella invasion but reveal a minor Cdc42-independent pathway that can permit Shigella invasion. However, the actin-based motility of Shigella, as well as vaccinia, proceeds unperturbed in the absence of Cdc42. These data further support the involvement of distinct host-encoded proteins in the steps regulating invasion and intercellular spread of Shigella

The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells

The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4+CD25+Foxp3+ naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development/function of nTreg cells. We show that WKO mice have decreased numbers of CD4+CD25+Foxp3+ nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RBhi T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor–mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor–mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency

Response to Urinary Trypsin Inhibitor Therapy in Ulcerative Colitis is Associated With a Decrease in Mast Cell Count in the Colonic Mucosa

BACKGROUND: Urinary trypsin inhibitor (UTI, ulinastatin (R)) inhibits proteinases and has been used for the treatment of ulcerative colitis (UC). We investigated the therapeutic effect of UTI in patients with UC and correlated this effect to mast cell (MC) and macrophages (M) counts in the colonic mucosal wall. DESIGN: Patients with UC resistant to corticosteroids (n=16) and normal control subjects (n=10) were included in this study. Biopsy specimens obtained from the sigmoid colon of patients before and after UTI therapy were immunostained with antibodies to tryptase (AA1, MC) and CD68 (M). The number of MC and M in the lamina propria (LP) was determined and expressed per mm2 of LP. RESULTS: Nine patients with UC responded to UTI treatment. The mean number of MC in the upper part of LP in responders(440ﾂｱ51/mm2)was higher than nonresponders (312ﾂｱ76/mm2)and normal controls(200ﾂｱ47/mm2). MC counts in the lower part of the LP were not different in responders and nonresponders, although the counts in both groups were significantly higher than control. The number of M in the lower part of LP was similar in responders and nonresponders, but were higher than control subjects. M counts in the upper part of LP were similar in both groups of patients and control. Effective treatment with UTI in responders was associated with a significant fall in the number of MC in the upper layer of LP but not in M. CONCLUSION. Our results showed that UTI is an effective therapy in steroid-resistant UC. Our results also showed effective therapy with UTI was associated with a reduction in MC counts in the colonic mucosa, suggesting that the control of these cells may mediate, at least in part, the therapeutic effects of UTI in UC

Retention of Capsule Endoscopy at the Site of NSAIDs-induced Intestinal Ulcer ―Lessons to Learn―

A 77-year-old man with a history of non-steroidal anti-inflammatory drugs (NSAID) use was admitted to our hospital due to anemia and hypoalbuminemia. Radioisotope scintigraphy indicated protein loss from the small intestine. The patient underwent capsule endoscopy, which was later found to be retained in the ileum. Double-balloon endoscopy showed multiple strictures with ulcers in the small intestine. The capsule was found in proximal to one of the stenosis, and was removed by doubleballoon enteroscopy. Based on endoscopic findings, NSAID-induced enteritis was diagnosed. Although anemia and hypoalbuminemia improved after discontinuing NSAID, the patient developed ileus and underwent partial resection of the ileum. Multiple diaphragm-like strictures were present in the resected intestine. The current case highlights the importance of screening for intestinal strictures when NSAID ulcer is suspected

Spontaneous Regression of Colonic Lesions in Adult T-cell Leukemia

A 74-year-old man was admitted to our hospital because of diarrhea. Serum anti-HTLV-1 antibody was positive without abnormal lymphocytes. Colonoscopy demonstrated a edematous and congested mucosa with erosions, and ulcers in the region extending from the cecum to rectum. Biopsy specimens showed diffuse infiltration of abnormal lymphocytes positive for T-cell markers in the lamina propria. Conservative therapy was provided but no chemotherapy because of improvement of diarrhea within two weeks. A repeat colonoscopy 6 months later revealed scars without erosions or ulcers. Eight months after first admission, the patient was readmitted to our hospital because of acute ATL crisis, and died of hepatic involvement 7 days later. Colonic lesions associated with ATLS may show spontaneous regression and recurrence

Effects of psychotherapy for middle-aged individuals with anxiety disorders in a general medicine practice

Background: Anxiety disorders are mental disorders that cause somatic symptoms for which patients may seek care from generalmedicine departments. We focused on anxiety disorders in middle-aged patients and examined the effect of a psychotherapeuticintervention.Materials and Methods: The participants were 14 middle-aged patients diagnosed with an anxiety disorder. Patients receivedpretreatment assessments and were randomly assigned to a pharmacotherapy group (n = 8) or a pharmacotherapy and psychotherapygroup (n = 6). The duration of the study was three months. Pre-and post-treatment, the Medical Outcomes Study 36-ItemShort-Form Health Survey (SF-36), State-Trait Anxiety Inventory (STAI), and a visual analog scale (VAS) were administered. Inthe pharmacotherapy and psychotherapy group, salivary cortisol was collected pre- and post-psychotherapy at the first and finalpsychotherapy sessions.Result: Four patients in the pharmacotherapy group withdrew from the study. There were no significant differences in the totalscores of the SF-36 or STAI between groups. Improvement was seen in the pharmacotherapy and psychotherapy group pre- andpost- treatment. SF-36 subscales of bodily pain (p = 0.02) and mental health (p = 0.04) were significantly higher than posttreatment.The state anxiety score on the STAI improved post-treatment (p = 0.03). On the VAS, the pharmacotherapy and psychotherapygroup’s symptoms were significantly improved (p = 0.02).Conclusion: This suggests that psychotherapy for middle-aged individuals contributes to the improvement of anxiety states andHRQoL in general medicine departments. It promotes the recognition of curative effects and prevents doctor shopping

Significance of Background Coloration in Endoscopic Detection of Early Esophageal Squamous Cell Carcinoma

Endoscopic diagnostics of early squamous cell carcinoma (SCC) in the laryngo-esophageal region have dramatically improved together with development of less invasive endoscopic treatment. It is essential for gastrointestinal endoscopists to detect lesions when they are still endoscopically treatable, especially in this region since surgical approach can still be extremely invasive. Pioneers have found some notable fundamental alterations in early SCC and created several classifications. Inoue [Dig Endosc 2001;13(suppl): 40-41] proposed the intrapapillary capillary (IPCL) classification, which focused on the microvascular change of the mucosal surface. One of the significances of this classification is that it clearly distinguished the lesions that require further pathological evaluation by categorizing the diameter change of the IPCLs. On the other hand, Arima et al. [Esophagus 2005;2:191-197] advocated the alteration of microvessels as well as change of the vascular arrangement in the area. Most recently, the Japan Esophageal Society constructed a new classification uniting these two exemplary classifications as the \u27Japanese Classification of Magnifying Endoscopy for Early Squamous Cell Carcinoma\u27. This classification was intended to be simple and easily applicable in general clinical practice. Brownish color change between the IPCLs has reported to be one of the useful findings in distinguishing early SCC from benign changes such as inflammatory change and low-grade intraepithelial neoplasia. Nevertheless, the exact cause of this phenomenon remains unclear. We recently examined the association of color change with hemoglobin (Hb) in cancer tissue, since NBI exclusively detects the wavelength of Hb in superficial vessels in the gastrointestinal tract. This review article also describes our examination of a distinct finding in esophageal cancer, namely, \u27background coloration\u27

Adenocarcinoma of the Colon Presenting as Intussusception In Adult: Report of Two Cases

We present two adult cases of intussusception caused by adenocarcinoma of the colon. These cases represent typical cases of adult intussusception, a rare disease characterized by insidious onset, vague abdominal symptoms, and elusive diagnosis. On physical examination, the masses were palpable in the right hypochondrium. Colonic intussusception were diagnosed by characteristic finding on ultrasonography (US) and computer tomography (CT). Endoscopic examination showed pedunculated tumors with central ulceration, in the cecum, which caused colonic intussusception, and endoscopic biopsies showed adenocarcinoma of the colon. US and CT are useful non-invasive diagnostic tools that allow early detection of intussusception. Colonoscopy is recommended for differential diagnosis and possibly a direct reduction of intussusception

Polyglycolic Acid Felt Sealing Method for Prevention of Bleeding Related to Endoscopic Submucosal Dissection in Patients Taking Antithrombotic Agents

Background and Study Aims. When performing endoscopic submucosal dissection (ESD) for patients on antithrombotic agents, the frequency of delayed bleeding is expected to increase. The endoscopic polyglycolic acid (PGA) felt and fibrin glue sealing method could be a new method for prevention of delayed bleeding. Patients and Methods. The safety and efficacy of the endoscopic tissue sealing method with PGA sheets and fibrin glue for the prevention of post-ESD bleeding were examined in 104 patients taking antithrombotic agents. During the study period, 70 patients taking antithrombotic agents did not undergo the sealing method, 36 patients discontinued antithrombotic agents, and 724 patients had not received antithrombotic therapy. Results. Delayed bleeding rates were 3.8% (4/104) in the sealing group, 12.9% (9/70) in the nonsealing group, 8.3% (3/36) in the discontinuation group, and 4.6% (33/724) in the nonantithrombotic therapy group. Thus, the delayed bleeding rate was significantly lower in the sealing group than in the nonsealing group and comparable to that in the nonantithrombotic therapy group. Conclusions. This PGA felt and fibrin glue sealing method might become a promising post-ESD bleeding prevention method in patients taking antithrombotic agents (UMIN000013990, UMIN000013993)