Subgenomic T cell receptor alpha and delta (TRA/TRD) loci in common carp.

In jawed vertebrates, the T cell receptor alpha (TRA) and delta (TRD) genes, which encode the TRα and TRδ chains, respectively, are located as a nested structure on a single chromosome. To date, no animal has been reported to harbor multiple TRA/TRD loci on different chromosomes. Therefore, herein, we describe the first full annotation of the TRA/TRD genomic regions of common carp, an allo-tetraploid fish species that experiences cyprinid-specific whole-genome duplication (WGD) in evolution. Fine genomic maps of TRA/TRD genomic regions 1 and 2, on LG30 and LG22, respectively, were constructed using the annotations of complete sets of TRA and TRD genes, including TRA/TRD variable (V), TRA junction (J), and constant (C), TRD diversity (D), and the J and C genes. The structure and synteny of the TRA/TRD genomic regions were highly conserved in zebrafish, indicating that these regions are on individual chromosomes. Furthermore, analysis of the variable regions of the TRA and TRD genes in a monoclonal T cell line revealed that both subgenomic regions 1 and 2 were indeed rearranged. Although carp TRAV and TRDV genes were phylogenetically divided into different lineages, they were mixed and organized into the TRA/TRD V gene clusters on the genome, similar to that in other vertebrates. Notably, 285 potential TRA/TRD V genes were detected in the TRA/TRD genomic regions, which is the most abundant number of genes in vertebrates and approximately two-fold that in zebrafish. The recombination signal sequences (RSSs) at the end of each V gene differed between TRAV and TRDV, suggesting that RSS variations might separate each V gene into a TRα or TRδ chain. This study is the first to describe subgenomic TRA/TRD loci in animals. Our findings provide fundamental insights to elucidate the impact of WGD on the evolution of immune repertoire.

Usefulness of PET-guided surgery with 64Cu-labeled cetuximab for resection of intrapancreatic residual tumors in a xenograft mouse model of resectable pancreatic cancer.

BACKGROUND: In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery. METHODS: A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations. RESULTS: Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group. CONCLUSIONS: OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.

Efficacy of Electroconvulsive Therapy for Neuropathic Pain Comorbid with Major Depression.

We report a case of a 41-year-old male with postinjury neuropathic pain comorbid with major depression in which electroconvulsive therapy (ECT) was effective in relieving both neuropathic pain and major depression. A total of 12 sessions of bilateral ECT were performed using a Thymatron® (Somatics LLC; Lake Bluff, IL). After ECT, the patient was subsequently maintained on paroxetine, eszopiclone (2 mg/day), and alprazolam. There was no relapse for at least one year after the last ECT. This case indicates that ECT might be an alternative treatment for major depression associated with chronic neuropathic pain after traumatic injury.