No abstract

MethodsAnimals. Lewis rats (7-10 weeks old) and C57BL/6 (B6) mice (7-10 weeks old) were purchased from Charles River Japan (Kanagawa, Japan) and used as donors and recipients, respectively. Jα281-deficient (Vα14 NKT cell-deficient [KO]) mice with a B6 background (22) were also used as recipients. In Vα14 NKT-KO mice, other lymphoid populations, such as T, B, and NK cells, remain intact (22). Vα14 NKT mice (RAG1 -/-, Vα14 Tg, and Vβ8.2 Tg) with a B6 background were also used (22). This mouse line expresses only transgenic Vα14

Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1+CD11b+ cells generated by transplantation and their IFN-γ production triggered by Vα14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Vα14 NKT cell–deficient (Jα281−/−) mice failed to produce IFN-γ, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of α-galactosylceramide, a specific ligand for Vα14 NKT cells, resulting in dramatically reduced IFN-γ production by Gr-1+CD11b+ cells, as well as Vα14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-γ they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Vα14 NKT cell function.

Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists in a precursor form in plasma and can be converted to the active form by trypsin and presumable trypsin-like enzymes. The trypsin-generated active form can not only cleave a small synthetic substrate, hippuryl-L-arginine, but can remove terminal arginine from bradykinin.

Considering the survival results according to specific lymph nodes involved, we concluded that the Japanese classification of lymph nodes, particularly hepatoduodenal ligament lymph nodes, should be reexamined, while another procedure to remove such lymph nodes completely should be developed.

Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Gastrointestinal T cell lymphoma (TCL) is a rare subset of peripheral TCL, presenting with or without cytotoxic phenotype, a history of coeliac disease (CD) and enteropathy. However, CD is rare in Japan. Here, we describe the clinicopathological features of 18 Japanese cases. Lesions were found in the small intestine (n=13), stomach (n=3) and colon (n=2). Seven patients presented with enteropathy but none had a history of CD. Lymphomas appeared as ulceration (n=11), tumour formation (n=6), or polypoid growth (n=1). Histologically (REAL classification), neoplastic lesions were composed of intestinal type T cell lymphoma (ITCL, n=13, including one case with NK type), anaplastic large cell (ALCL, n=2), adult T cell leukaemia/lymphoma (ATLL, n=2), and lymphoblastic type (n=1). Epstein Barr virus infection was detected by EBER-1 in situ hybridization in 6 of 11 cases with ITCL but not in the other types. ALCL expressed CD30. CD56 was expressed in 3 of 11 cases of ITCL but not in other types. Among the 10 examined cases, 8 were alphabeta T cell type [CD2+, CD3+, T cell receptor (TCR)delta-1-, betaF1+], one was gammadelta T cell type [CD2+, CD3+, TCRdelta-1+, betaF1-], and the remaining case expressed natural killer (NK) cell type [CD2+, CD3-, CD56+, TCRdelta-1-, betaF1-]. Among the 8 examined cases, 3 expressed CD103 molecule, which was associated with extrathymic T cells of intraepithelial lymphocytes. All cases except ATLL expressed the cytotoxicity-associated molecule of TIA-1, and 11 of 14 TIA-1 positive cases expressed activated cytotoxic molecules of perforin, granzyme B, and/or Fas ligand. Despite the morphological, genetic and phenotypic heterogeneity, prognosis was poor, and 11 of 13 patients with small intestinal lesions died albeit appropriate treatment, but 3 of 4 patients with gastric or colonic lesions were still alive. The main cause of death was intestinal perforation. The latter might be due to the site specificity of small intestine and tumour cytotoxicity.

Endoscopic sphincterotomy was performed in 469 patients for the treatment of biliary calculi, with procedure-related morbidity of 6.3% and mortality of 0.4%. Long-term follow-up to 10.5 years (mean 3.7 years) was completed in all of 408 patients at least six months postsphincterotomy. Recurrent stones developed in 21 patients (5.8%) after a mean of 2.4 years (range 4 months to 7 years); in 6 after 3 years. Eight patients reformed stones more than twice at a mean interval of 1.8 years (range, 5 months to 3.5 years). In the 122 patients with gallbladders in situ, acute cholecystitis occurred in 5 of 31 with gallstones (16%), but in none of the 91 without gallstones. In the 237 patients who had undergone cholecystectomy, 4 late deaths occurred secondary to recurrent choledocholithiasis and cholangitis. In the 49 patients with primary intrahepatic stones, 3 late deaths occurred secondary to hepatic abscess. These results suggest that (a) endoscopic sphincterotomy is a very effective procedure in long-term follow-up, (b) cholangiography should be done at the appearance of slight abdominal symptoms even after 3 years, (c) patients who have ever reformed stones should undergo cholangiography yearly for at least 4 years, and (d) cholecystectomy is recommended for patients with gallbladders after sphincterotomy, only if gallstones are present.