Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRalpha-/-xAIM-/- mice

BACKGROUND: Chronic colitis-harboring TCRalpha(- / - ) x AIM(- / - ) mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRalpha(- / - ) x AIM(- / - ) mice. METHODS: Thirteen female TCRalpha(- / - ) x AIM(- / - ) mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out. RESULTS: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation. CONCLUSIONS: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRalpha(- / - ) x AIM(- / - ) mice.     

The dominant negative effect of a kinase-defective insulin receptor on insulin-like growth factor-I-stimulated signaling in Rat-1 fibroblasts

To study the interaction between insulin receptor (IR) and insulin-like growth factor-I (IGF-I) receptor (IGF-IR) tyrosine kinases, we examined IGF-I action in Rat-1 cells expressing a naturally occurring tyrosine kinase-deficient mutant IR (Asp 1048 IR). IGF-I normally stimulated receptor autophosphorylation, IRS-I phosphorylation, and glycogen synthesis in cells expressing Asp 1048 IR. However, the Asp 1048 IR inhibited IGF-I-stimulated thymidine uptake by 45% to 52% and amino acid uptake (aminoisobutyric acid [AIB]) by 58% in Asp 1048 IR cells. Furthermore, IGF-I-stimulated tyrosine kinase activity toward synthetic polymers, Shc phosphorylation, and mitogen-activated protein (MAP) kinase activity was inhibited. The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild-type IGF-IR in Asp 1048 IR cells. These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF-IR in transmitting signals to Shc and MAP kinase activation, which leads to decreased IGF-I-stimulated DNA synthesis, and that the kinase-defective insulin receptor does not affect IGF-I-stimulated IRS-I phosphorylation, which leads to the normal IGF-I-stimulated glycogen synthesis.     

A high incidence of WT1 abnormality in bilateral Wilms tumours in Japan,and the penetrance rates in children with WT1 germline mutation

Background:

Bilateral Wilms tumours (BWTs) occur by germline mutation of various predisposing genes; one of which is WT1 whose abnormality was reported in 17–38% of BWTs in Caucasians, whereas no such studies have been conducted in East-Asians. Carriers with WT1 mutations are increasing because of improved survival.

Methods:

Statuses of WT1 and IGF2 were examined in 45 BWTs from 31 patients with WT1 sequencing and SNP array-based genomic analyses. The penetrance rates were estimated in WT1-mutant familial Wilms tumours collected from the present and previous studies.

Results:

We detected WT1 abnormalities in 25 (81%) of 31 patients and two families, which were included in the penetrance rate analysis of familial Wilms tumour. Of 35 BWTs from the 25 patients, 31 had small homozygous WT1 mutations and uniparental disomy of IGF2, while 4 had large 11p13 deletions with the retention of 11p heterozygosity. The penetrance rate was 100% if children inherited small WT1 mutations from their fathers, and 67% if inherited the mutations from their mothers, or inherited or had de novo 11p13 deletions irrespective of parental origin (P=0.057).

Conclusions:

The high incidence of WT1 abnormalities in Japanese BWTs sharply contrasts with the lower incidence in Caucasian counterparts, and the penetrance rates should be clarified for genetic counselling of survivors with WT1 mutations.     

Laparoscopic distal gastrectomy in a patient with gastric cancer complicated by eventration of the diaphragm: A case report

Diaphragmatic eventration refers to an abnormal elevation of the diaphragm. Here, we report the case of a patient with gastric cancer who underwent successful laparoscopic distal gastrectomy despite the presence of diaphragmatic eventration. The patient was a 72-year-old man diagnosed with early gastric cancer in the antrum, as detected by upper gastrointestinal endoscopy. Preoperative imaging revealed an elevation of the left side of the diaphragm, which was diagnosed as diaphragmatic eventration. Laparoscopic surgery is beneficial for obtaining an optimal field of view. However, there are critical points that must be considered when laparoscopic distal gastrectomy is performed in patients with gastric cancer complicated by diaphragmatic eventration. There were difficulties that affected manipulation because the elevated diaphragm drew the intraperitoneal organs into the thoracic cavity, causing displacement of the normal anatomical position. We found it beneficial to secure the lesser curvature of the stomach given the possible effects of gastric deformation.     

A case of anorexia nervosa with disseminated intravascular coagulation syndrome

A 36-year-old Japanese woman with anorexia nervosa (AN) was admitted to our department because of severe emaciation. Although we were thorough in her clinical management and were careful to avoid precipitating refeeding syndrome, disseminated intravascular coagulation (DIC) developed 3 weeks after hospitalization. We treated her for DIC with sepsis using anticoagulants, protease inhibitors, antithrombin, and platelet concentrate transfusion. To treat her bacterial infection, we administered antimicrobial drugs and immunoglobulin. We began probiotic and prebiotic (synbiotics) treatment for bacterial translocation. We think that the prevention of sepsis via bacterial translocation is an important aspect of care for patients with severe AN in addition to the prevention of refeeding syndrome.     

Intrahepatic biliary epithelial cell damage and inflammation in portal tract in association with chronic colitis-harboring TCRalpha(-/-) mice.

BACKGROUND: Intrahepatic bile ducts are the target for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The mechanisms of biliary epithelial cell damage in both diseases are not clearly understood. Ulcerative colitis (UC) is one of the known complications in PSC. In this study, we assessed the possible influence of apoptosis inhibitor expressed by macrophages (AIM) on intrahepatic bile ducts in the chronic colitis-harboring condition by generating T cell receptor alpha-deficient (TCRalpha(-/-))xAIM-deficient (AIM(-/-)) double-knockout mice. METHODS: TCRalpha(-/-)xAIM(-/-) mice were generated by crossbreeding TCRalpha(-/-) mice with AIM(-/-) mice. At 24 weeks of age, mice were sacrificed to obtain liver tissues for pathological examinations, and blood was collected to study the serum levels of IgG, IgM and IgA. RESULTS: In female TCRalpha(-/-)xAIM(-/-) mouse livers, mixed cellular infiltration in the portal area and epithelial cell damage in bile ducts were observed, when compared with female TCRalpha(-/-)xAIM(+/-) and male TCRalpha(-/-)xAIM(-/-) mice. Inflammation in hepatic parenchyma was mild to none in all mice. In the female mouse group, the serum IgA level was relatively increased in TCRalpha(-/-)xAIM(-/-) mice compared to TCRalpha(-/-)xAIM(+/-) mice. CONCLUSION: The defect of AIM might be involved not only in colonic mucosal inflammation but also in portal inflammation, as well as in biliary epithelial cell damage in the livers of female TCRalpha(-/-)xAIM(-/-) mice.     

A case of retropharyngeal abscess caused by penicillin-resistant Streptococcus pneumoniae

We report here a case of a 1-year-old girl with retropharyngeal abscess caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Computed tomography disclosed a retropharyngeal mass lesion (4 cm x 3 cm in diameter), and the diagnosis was confirmed by needle aspiration of the retropharyngeal space, which yielded PRSP. To our knowledge, this is the first report of a young subject in whom retropharyngeal abscess was caused by this organism. Retropharyngeal abscess is most common in children younger than 3 or 4 years of age, during which period a high carriage rate of PRSP is also shown. This patient was successfully treated with panipenem/betamipron.