Xenopus Zic3, a primary regulator both in neural and neural crest development

Xenopus Zic3 is a Xenopus homologue of mouse Zic and Drosophila pair-rule gene, odd-paired. We show here that Zic3 has significant roles both in neural and neural crest development in Xenopus embryo. Expression of Zic3 is first detected in prospective neural plate region at gastrulation. Onset of the expression was earlier than most proneural genes and followed chordin expression. The expression was induced by blockade of BMP4 signal. Overexpression of Zic3 resulted in hyperplastic neural and neural crest derived tissue. In animal cap explant, the overexpression of Zic3 induced expression of all the proneural genes and neural crest marker genes. These findings suggest that Zic3 can determine the ectodermal cell fate and promote the earliest step of neural and neural crest development.     

Cartilage oligomeric matrix protein in serum and synovial fluid of rheumatoid arthritis: potential use as a marker for joint cartilage damage

This study examined the serum and synovial fluid concentrations of cartilage oligomeric matrix protein (COMP) in relation to the evolution of joint cartilage damage and the requirement for surgery in 125 patients with rheumatoid arthritis (RA). We compared the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and matrix metalloproteinase-3 (MMP-3) levels with COMP levels determined by specific enzyme-linked immunosorbent assay (ELISA). Patients were divided into three groups: (1) patients with least erosive disease (LES); (2) patients with more erosive disease (MES); and (3) patients with mutilating disease (MUD). In addition, synovial fluid samples were collected from patients undergoing arthroscopic synovectomy of the knee joint (ASS) and total knee arthroplasty (TKA). Serum COMP levels correlated with the ESR (P < 0.0001, r = 0.374, n = 125) and the CRP level (P = 0.0014, r = 0.281, n = 125). COMP levels did not correlate with the MMP-3 level (P = 0.182, r = 0.114, n = 125). The COMP levels of the LES group were significantly lower than those of the MES or MUD groups. Lastly, synovial fluid COMP levels in the TKA group were higher than in the ASS group. Therefore, these findings suggest that serum and synovial fluid COMP levels in patients with RA may reflect cartilage destruction and are correlated with the ESR and the CRP level, which are indicators of the acute-phase response.     

Appearance of specific mucins recognized by monoclonal antibodies in rat gastric mucosa healing from HCl-induced gastric mucosal damage

Background Mucus is an important factor in the physiological defense mechanism of the gastrointestinal tract. We have reported that two distinct antigenicities reacting with anti-mucin monoclonal antibodies (mAbs), HCM31 and RGM26, emerged in epithelial cells regenerating from acetic acid-induced gastric damage in the rat. Here, we examined whether the expression of specific mucins occurred during the healing stage of acute gastric mucosal lesions, and what was the principal alteration of the mucus in the regenerating process of gastric epithelia from slight mucosal lesions.Methods Eight-week-old male Wistar rats were used. The animals were administered 0.6N hydrochloric acid, or 0.5% carboxymethyl cellulose sodium salt into their stomachs. Twenty-four, 48, and 72h after the HCl administration, their stomachs were removed. Immunohistochemical observation was performed after staining with the mAbs, RGM21, RGM26, HIK1083, or HCM31.Results Twenty-four hours after the administration of HCl, mucous cells stained with RGM26 emerged in the deeper area of the surface epithelial cells in the damaged corpus mucosa. After 48h, HCM31-positive cells were noted in the epithelial cells where the mucosal damage reached more deeply.Conclusions The appearance of specific mucin species was observed in the regenerating epithelia of the rat during the healing process from acute gastric mucosal damage.     

Spraying of phenol red dye as a screening test for <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in surgically resected stomach specimens

Background Endoscopic spraying of phenol red dye and urea (phenol red test) has recently been used to assess the distribution of Helicobacter pylori in the gastric mucosa. We examined whether the phenol red test could be used to detect H. pylori in surgically resected stomachs.Methods A total of 82 surgically resected stomachs, obtained from 82 patients (mean age, 60.1 years; range, 33–84 years) with early gastric carcinomas were examined. Phenol red solution and urea were sprayed over the entire mucosa of each resected stomach. A color change from yellow to red was considered as a positive reaction for H. pylori. Gastric mucosal specimens taken from positively stained and negatively stained areas on the phenol red test were then examined immunohistochemically to determine the degree of H. pylori colonization.Results Diffusely positive reactions were seen in 16 resected stomachs (19%), and regionally positive reactions were seen in 36 (44%). The other 30 stomachs (37%) showed no color change (negative reaction). H. pylori was detected immunohistochemically significantly more frequently in positively stained than in negatively stained areas (P 0.0001). Specificity, sensitivity, and predictive values for positive and negative results of the phenol red test, determined on the basis of H. pylori immunostaining, were 100%, 74.3%, 100%, and 72.7%, respectively.Conclusions The phenol red test is a specific, relatively sensitive, rapid, easy-to-use, and repeatable method that can be used to diagnose H. pylori infection in surgically resected material. It enables pathologists as well as gastroenterologists with no microbiological expertise to easily diagnose H. pylori infection.     

Role of sodium channels in recovery of sciatic nerve‐stretch injury in rats

Introduction: To elucidate the mechanism of functional recovery after gradual nerve‐stretch injury, we used rats in which the femur length was increased by 15 mm at 1.5 mm/day. Methods: We performed electrophysiology, mRNA analysis of tetrodotoxin‐resistant voltage‐gated sodium channels (TTX‐R VGSCs) in dorsal root ganglia, and histology of unmyelinated sciatic nerve fibers and examined pain thresholds at 1, 10, 20, and 30 days after cessation of lengthening. Results: Electrophysiology revealed conduction block after cessation that recovered after 30 days. TTX‐R VGSC levels decreased immediately after cessation but were restored after 10 (Nav1.9) or 20 (Nav1.8) days. Histology revealed that injured unmyelinated nerve fibers regenerate 30 days after cessation. Pain threshold decreased gradually during lengthening but had not recovered to the control group level after 30 days. Conclusions: Early restoration of TTX‐R VGSC mRNA in dorsal root ganglia preceded functional recovery of stretched nerves before regeneration of injured unmyelinated nerve fibers. Muscle Nerve 50 : 425–430, 2014     

Protective effects of simultaneous splenectomy on small‐for‐size liver graft injury in rat liver transplantation

Splenectomy is an effective technique in living donor liver transplantation (LDLT) with small‐for‐size (SFS) liver grafts for overcoming SFS liver graft injury. However, the protective mechanism of splenectomy is still unclear. The aim of this study was to investigate how splenectomy could attenuate SFS graft injury through the measurement of biochemical factors, particularly the expression of endothelin (ET)‐1, which is a key molecule of microcirculatory disorders by mediating sinusoidal vasoconstriction. We performed rat orthotopic liver transplantation using SFS liver grafts with or without splenectomy. We investigated intragraft expression of ET‐1 mRNA and hepatic protein levels of ET‐1. In addition, portal pressure, hepatic injury and morphological changes, and survival rate were evaluated. In result, intragraft ET‐1 mRNA expression after SFS liver transplantation was significantly downregulated by splenectomy, and hepatic expression of ET‐1 in SFS grafts was rarely observed. Splenectomy inhibited the increase in portal pressure, ameliorated SFS liver graft injury and improved the graft survival rate after SFS liver transplantation. In conclusion, splenectomy improved the SFS liver injury and decreased the expression of ET‐1 by attenuating portal hypertension on SFS liver transplantation. Downregulation of intragraft ET‐1 expression plays important roles in the protective mechanism of splenectomy in SFS liver transplantation.     

Selective expansion of donor‐derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome

IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs.     

Long-term prognosis of Kawasaki disease patients with coronary artery obstruction

Summary The prognosis of coronary artery obstruction was studied in patients with Kawasaki disease. Between May 1973 and December 1987, coronary artery obstruction was diagnosed by coronary angiography in 30 patients (21 males, 9 females), of whom, only 8 (26.7%) had clinical symptoms. One patient died after 9 years of illness. Two complained of frequent chest pain, which disappeared after bypass surgery in one case and spontaneously in the other. Five had symptomatic myocardial infarction. Myocardial ischemia was diagnosed in 31.8% by treadmill stress testing, but was well demonstrated in 85.7% by thallium-201 myocardial tomography. Frequent ventricular premature beats, Wenckebachtype atrioventricular block, and ST-segment depression accompanied by chest pain were recognized by 24-h Holter monitoring. In the past, the methods used to determine the prognosis of Kawasaki disease patients with coronary artery obstruction were not adequate. However, the examinations used in this study revealed an improved ability to determine the prognosis in this disease. Myocardial tomography, in particular, provided a more accurate evaluation of myocardial damage. Ventricular arrhythmias seem to be a serious problem in these patients. Therefore, careful observation using these tests, especially myocardial tomography and Holter monitoring, should be done even if the patients are free of symptoms.