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.     

Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin

In vitro antigen stimulation of peripheral blood mononuclear cells (PBMCs) does not induce immunoglobulin (Ig) production. However, pretreatment of PBMCs with l-leucyl-l-leucine methyl ester (LLME) prior to in vitro stimulation removes the suppression of Ig production. In the present study, we attempted to identify the target cells of LLME and determine the mechanisms by which Ig production in PBMCs is suppressed. We found that CD14⁺ monocytes are involved in the suppression of Ig production in PBMCs. Furthermore, we confirmed that heavy-chain ferritin derived from CD14⁺ monocytes suppresses Ig production in PBMCs, possibly through iron sequestration.     

The scaffold protein JLP plays a key role in regulating ultraviolet B‐induced apoptosis in mice

The ultraviolet B (UVB) component of sunlight can cause severe damage to skin cells and even induce skin cancer. Growing evidence indicates that the UVB‐induced signaling network is complex and involves diverse cellular processes. In this study, we investigated the role of c‐Jun NH₂‐terminal kinase‐associated leucine zipper protein (JLP), a scaffold protein for mitogen‐activated protein kinase (MAPK) signaling cascades, in UVB‐induced apoptosis. We found that UVB‐induced skin epidermal apoptosis was prevented in Jlp knockout (KO) as well as in keratinocyte‐specific Jlp KO mice. Analysis of the repair of UVB‐induced DNA damage over time showed no evidence for the involvement of JLP in this process. In contrast, UVB‐stimulated p38 MAPK activation in the skin was impaired in both Jlp KO and keratinocyte‐specific Jlp KO mice. Moreover, topical treatment of UVB‐irradiated mouse skin with a p38 inhibitor significantly suppressed the epidermal apoptosis in wild‐type mice, but not in Jlp KO mice. Our findings suggest that JLP in skin basal keratinocytes plays an important role in UVB‐induced apoptosis by modulating p38 MAPK signaling pathways. This is the first study to show a critical role for JLP in an in vivo response to environmental stimulation.     

Primary orbital neuroblastoma in a 1‐month‐old boy

Neuroblastoma is a malignant tumor predominantly occurring in children and usually arising from the adrenal gland or sympathetic ganglia. We describe a neuroblastoma in a 1‐month‐old boy arising from his left orbital cavity. This tumor was refractory to chemotherapy or radiotherapy, requiring enucleation of the left eye for complete removal of the intraorbital tumor. Thereafter, he received high‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation, and has been in complete remission for 3 years. Unlike neuroblastomas arising from the adrenal gland or sympathetic ganglia, primary orbital neuroblastoma may be refractory even in early infancy.     

Brief Questioning by Nursing Staffs before Endoscopic Examination May Not Always Pick Up Clinical Symptoms of Endoscopic Reflux Esophagitis

The clinical features of patients reflux esophagitis without any symptoms have not been clearly demonstrated. This study evaluated the clinical features of patients with endoscopy-positive reflux esophagitis, who did not complain of symptoms, as detected by brief questioning by nursing staffs. Eight thousand and thirty-one patients not taking medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia and acid regurgitation by nursing staffs before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) patients were classified as positive for reflux esophagitis. The endoscope positive subjects who complain heartburn were 539/1199 (45.0%).The endoscope positive subjects who do not complain symptoms were 465 in 1199 positive reflux esophagitis (38.8%). We compared endoscopic positive subjects without any complain by brief question by nursing staffs to endoscopic positive subjects with heartburn. Male gender, no obesity, absence of hiatus hernia, and low-grade esophagitis were associated with endoscopy-positive patients who do not complain of symptoms. The results of this study indicated correct detection of clinical symptoms of reflux esophagitis might be not easy with brief questioning by nursing staffs before endoscopic examination.     

Induction of Extrahepatic Biliary Carcinoma by N-Nitrosobis(2-oxopropyl)amine in Hamsters Given Cholecystoduodenostomy with Dissection of the Common Duct

The methods we used to produce a carcinoma in the extrahepatic bile duct and gallbladder in hamsters are described along with the characteristics of the induced tumors. Female Syrian golden hamsters were first subjected to Cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (CDDB) and were, 4 weeks later, treated with weekly subcutaneous injections of N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 10 mg/kg body weight for 9 weeks. The animals were killed at the 12th, 16th and 20th week after the initiation of BOP treatment. Extrahepatic bile duct carcinoma developed in 16%, 24% and 41% and gallbladder carcinoma occurred in 58%, 81% and 82% of the hamsters, respectively, at the corresponding times of killing. The incidences were significantly higher than those in sham-operated controls ( P <0.01). The induced extrahepatic bile duct carcinomas were predominantly of the polypoid type and gallbladder carcinomas were of the papillary type in growth form, being morphologically similar to early stage biliary carcinoma in humans. Immunohistochemical staining using bromodeoxynridine and anti-bromo-deoxyuridine monoclonal antibody demonstrated that the CDDB procedure greatly accelerated the cell kinetic activity of the biliary epithelium, and this was considered to be a major factor promoting the development of biliary carcinomas in this hamster model. In conclusion, this new model provides a high incidence of tumor development at the extrahepatic biliary tract and is expected to be useful for clarifying the characteristics of this highly malignant tumor.     

Lymphokine-activated killer cell activity of peripheral blood,spleen, regional lymph node,and tumor infiltrating lymphocytes in gastric cancer patients

Lymphokine-activated killer (LAK) cell activity of peripheral blood mono-nuclear cells (PBM), spleen cells (SPC), regional lymph node cells (LNC), and tumor-infiltrating lymphocytes (TIL), induced by activation with in-terleukin 2 (IL 2) for 4 days, was evaluated in patients with gastric carcinoma. TIL exhibited the lowest LAK activity and the cytotoxicity of LNC was significantly lower than that of either PBM or SPC. There was no difference between PBM and SPC. Then, there were significant correlations of LAK activity among PBM, SPC, and LNC, whereas poor correlations were observed in the cytotoxicity between TIL and PBM, SPC, or LNC. Phenotypic analysis of each cell population was performed before and after activation with IL 2. Before culture, the cells mediating natural killer (NK) activity such as CD16⁺, CD56⁺, and CD57⁺ cells were few in LNC and TIL. However, CD56⁺ and CD57⁺ cells in TIL were increased after culture. Then, CD4⁺ Leu8⁺ and CD8⁺ CD11⁺ cells, which identify suppressor cell function, were not elevated in LNC or TIL, as compared to that in PBM or SPC. Further, the proportions of OKIa1⁺ and CD25⁺ cells expressing T-cell activation and IL 2 receptor were uniformly increased in all cell populations after culture. These results indicate the differential reactivity of each lymphocyte population to IL 2 and fundamental dysfunction of LNC and, especially TIL, suggesting the specific influence of the local tumor environment on the lymphocyte function in the area in patients with gastric carcinoma. © Wiley-Liss, Inc.     

CARCINOGENESIS: Bilioenterostomy enhances biliary carcinogenesis in hamsters

The aim of this study was to examine whether the type of bilioenterostomyenhances biliary carcinogenesis in the hamster model. Syrianhamsters were divided into the following groups; simple laparotomy(control group), cholecystoduodenostomy with dissection of theextrahepatic bile duct on the distal end of the common duct(CDDB group) and cholecystoileostomy with dissection of theextrahepatic bile duct on the distal end of the common duct(CIDB group). Following these procedures, all hamsters receivedN-nitrosobis(2-oxopropyl)amine. The diameter of the extrahepaticbile duct and plasma levels of cholecystokinin (CCK) were measuredand the number of neoplastic lesions was counted microscopically.Proliferative effect of the procedures on the biliary epitheliumwas examined by proliferative cell nuclear antigen. In the CDDBgroup the extrahepatic bile duct was significantly dilated andcarcinogenesis of the gall-bladder and extrahepatic bile ductswas enhanced. In the CIDB group the CCK bioactivity was stimulatedand intrahepatic biliary duct, but not gall bladder and extrahepaticbile duct, carcinogenesis was promoted more than that observedin the CDDB group. Proliferation of the biliary duct epitheliumwas enhanced in both the CDDB and CIDB groups. Cholecystoduodenostomyenhanced intra- and extrahepatic bile duct carcinoma, whereascholecystoileostomy promoted only intrahepatic bile duct carcinoma.Some factors in the intestinal juice seem to play a role inthe promotion of biliary tract carcinoma.