Dimeric but not monomeric soluble CD40 prolongs allograft survival and generates regulatory T cells that inhibit CTL function

BACKGROUND: We previously reported that adenovirus mediated CD40Ig gene therapy (AdCD40Ig) induced long-term acceptance of fully allogeneic rat cardiac allografts, however, the underlying mechanism has not been fully clarified. To address this we have compared the ability of dimeric and monomeric soluble CD40 to prolong allograft survival in vivo and generate regulatory T cells in vitro. METHODS: The ability of CD40Ig (soluble dimmer, containing an Fc region) or CD40/Myc/His (soluble monomer, lacking an Fc region) therapy to generate CD4CD25 regulatory T cells in vitro and to prevent rejection of rat cardiac allografts (ACI to LEWIS) was compared. Immunoregulatory capacity of regulatory T cells generated was determined by suppression of alloantigen specific proliferation and cytotoxicity. RESULTS: Dimeric soluble CD40Ig did not inhibit CD4 T cell proliferation but rather promoted IL-2 production and the generation of CD4CD25 T cells, which regulated alloantigen-specific cytotoxic T lymphocyte activity. Treatment with either AdCD40Ig or purified soluble CD40Ig prolonged the survival of rat cardiac allografts. In contrast, although monomeric soluble CD40/Myc/His suppressed IL-12 production in a similar manner to that achieved by CD40Ig, it did not augment IL-2 production. Moreover, while CD40/Myc/His also generated CD4CD25 T cells, they did not exhibit regulatory activity and administration of soluble CD40/Myc/His failed to prolong cardiac allograft survival. CONCLUSIONS: These results suggest signaling through CD154 in addition to blocking of CD154-CD40 interaction is important for the immunomodulatory effects of soluble CD40Ig. Taken together, our results provide new insight into the mechanism of immunomodulation by soluble CD40 constructs.     

Assessment of the signal intensity distribution pattern within the unruptured cerebral aneurysms using color-coded 3D MR angiography

To evaluate the interaction between the MR signal intensity distribution pattern and bleb formation/ deformation of the aneurysmal dome, fifty cases of the unruptured cerebral aneurysms were investigated with the color-coded 3D MR angiography. Patterns were categorized into central-type, neck-type and peripheral-type according to the distribution of MR signals with low-, moderate- and high signal intensity areas. Imaging analysis revealed the significant relationship (P < 0.02) of the peripheral-type aneurysms to the bleb formation and deformation of the dome, compared with those of central- and neck-type. Additionally, peripheral-type signal intensity distribution pattern was shown with aneurysms harboring relatively large dome size and lateral-type growth including internal carotid aneurysms. Prospective analysis of intraaneurysmal flow pattern with the color-coded 3D MR angiography may provide patient-specific analysis of intraaneurysmal flow status in relation to the morphological change of the corresponding aneurysmal dome in the management of unruptured cerebral aneurysms.     

Treatment for Ewing's sarcoma family of tumors in children

The outcome of patients with Ewing Sarcoma Family of Tumors (ESFT) in our country is poor in comparison with American and European. We performed a review of the relevant data regarding the current status in the treatment of ESFT. The results of the major American and European cooperative groups were discussed, including the treatment strategies used and the prognostic factors identified for both localized and metastatic ESFT. We also discussed a new trial for the establishment of the standard treatment of ESFT in our country.     

Detection of single nucleotide polymorphism in the FUT2 gene by temperature gradient gel electrophoresis

A simple and rapid analysis system for single nucleotide polymorphisms (SNPs) was investigated for the FUT2 gene using the temperature gradient gel electrophoresis (TGGE) method. The 426-bp or 259-bp FUT2 fragments were amplified from heterozygous samples using primers, and the heteroduplex and homoduplex bands were detected by TGGE. The FUT2 fragments amplified from homozygous samples were denatured and re-annealed with a known sequence fragment, forming heteroduplex bands which were analyzed by TGGE. The fragment patterns of homoduplex and heteroduplex bands in TGGE were specific to the genotypes, and more specifically, the number of heteroduplex bands and the migration of the homoduplex bands corresponded to the number of nucleotide substitutions and the change in GC content due to the substitutions, respectively. Thus, the TGGE technique can act as a high-throughput method for the detection and the presumption of sequences of known and unknown SNPs in the FUT2 gene.     

Patient-controlled Dietary Schedule Improves Clinical Outcome after Gastrectomy for Gastric Cancer

Although studies have shown that early oral feeding after abdominal surgery is feasible, the optimal dietary schedule has not been established. This study was conducted prospectively to compare the clinical outcome of patient-controlled dietary schedule with that of conventional dietary schedule after gastric resection for early cancer. Patients in the patient-controlled diet (PC) group (n = 53) received a solid diet on demand; patients in the conventional regimen (CR) group (n = 50) received a solid diet from postoperative day (POD) 10. All patients underwent distal gastrectomy for early gastric cancer. A liquid diet was tolerated by the PC group on POD 2, and a solid diet was taken on POD 6 after gastrectomy, earlier than in the CR group. The postoperative hospital stay was 18.5 ± 5.9 days (10–40) in the PC group, versus 21.7 ± 8.8 days (14–57) in the CR group (p = 0.02). Patients in the PC group had a higher daily oral intake of calories on POD 10 than those in the CR group (p = 0.02). Changes in body weight and serum albumin during the postoperative period and after discharge, and the incidence of complications and variances from clinical pathways did not show significant differences between the two groups. The PC schedule was feasible after distal gastrectomy for early gastric cancer. It improved the clinical outcome, with a shorter postoperative hospital stay and a higher oral energy intake on early phase, compared with the CR schedule. Moreover, the PC approach was useful for establishing the optimal dietary schedule and improving the clinical pathway.     

Gastric cancer developing in the stomach after pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy: Case report and review of the literature

A 59-year-old woman underwent surgery for uterine corpus cancer in March 1998. She also underwent pylorus-preserving pancreaticoduodenectomy with pancreaticogastrostomy for common bile duct cancer in November 1998. She was followed up at our outpatient clinic after pylorus-preserving pancreaticoduodenectomy. In November 2002, her carcinoembryonic antigen level became elevated and abdominal ultrasound revealed a huge tumor. Gastroscopy showed a Borrmann type 3 tumor at the anastomosis of the pancreaticogastrostomy, and a biopsy revealed adenocarcinoma. With a diagnosis of advanced gastric cancer, she underwent total gastrectomy, splenectomy, and residual pancreatectomy in January 2003. The pathologic .ndings revealed that the gastric cancer was separated from the pancreas, suggesting that the cancer had developed from the stomach. The present report describes a rare case of gastric cancer that had developed at the anastomosis of a pancreaticogastrostomy.     

Unusual variant of the anterior cerebral artery

A rare abnormality of the A1 segment of the anterior cerebral artery (ACA) is reported. The right ACA bifurcated into two parts at the middle point of the A1 segment, and these segments did not rejoin. The superior right A1 segment connected with the left A1 and formed a single pericallosal artery. The inferior right A1, from which the right ophthalmic artery originated, had no connection with the left A1.