Transplantation of Graft Anti-Host Cytotoxic T Lymphocytes Along with Allogeneic Bone Marrow Skips Macrophage-Induced Graft-Versus-Host Disease.

Graft-versus-host disease (GVHD) is a physiological response of the graft to allogeneic hosts. However, the effector cells, affected organ(s), and cytokines in the GVHD remain controversially discussed, without having determined a particular cytotoxic activity of the graft against the host. After i.v. injection of C57BL/6 (H-2b) spleen cells into irradiated BDF1 (H-2b/d) mice, the hosts developed interferon-gamma (IFN-γ)-dependent bone marrow (BM) GVHD on days 5-17. When H-2DdKd transgenic H-2b lymphoma cells were i.p. inoculated into irradiated, H-2b splenocyte-transplanted H-2b/d mice, the infiltration of macrophages cytotoxic against H-2DdKd transgenic H-2b mouse skin epithelia (a GVHD activity) into the peritoneal cavity preceded several days the infiltration of interleukin (IL)-2-dependent cytotoxic T lymphocytes (CTLs) to achieve a graft-versus-leukemia (GVL) effect. In contrast, allogeneic BM transplanted alone into the irradiated mice did not induce GVHD for 44 days, whereas i.v. injection of graft anti-host macrophages or graft anti-host CTLs along with allogeneic BM, respectively, induced GVHD or promoted the GVL effect in the absence of GVHD. These results revealed that macrophage-induced GVHD and the CTL-mediated GVL effect were a set (Th1: IFN-γ/IL-2) response of the graft to allogeneic hosts and leukemia cells, respectively, and that graft T cell activation rather than inhibition skipped GVHD after BM transplantation.

[Injection of High Concentration Glucose Solution for Pleural Coating Reduces Postoperative Recurrence of Spontaneous Pneumothorax;A Short-term Retrospective Study].

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is the standard treatment for patients with spontaneous pneumothorax (SP). However, postoperative recurrence is not infrequent even with an absorbable covering sheet used to reinforce the visceral pleura. Recent reports suggest that intraoperative injection of a highly concentrated glucose solution into the thoracic cavity provides effective prophylaxis against postoperative SP recurrence. Since September 2015, we have been injecting 50 ml of 50 % glucose solution intraoperatively for pleural coating (GPC) around an absorbable sheet to prevent postoperative SP recurrence. METHODS: We evaluated 340 patients who underwent VATS between February 2011 and June 2017(88 patients:GPC group, 252:non-GPC group), and we retrospectively analyzed the efficacy of GPC in preventing postoperative SP recurrence. RESULTS: One year postoperative recurrence rates of GPC and non-GPC groups were 9.0 and 17.9%,respectively. The log-rank test revealed GPC as a significant factor in preventing postoperative recurrence (p=0.020). No severe adverse events occurred in either group. Minor postoperative complications, viz., high blood sugar, high volume of chest tube drainage occurred in the GPC group. CONCLUSION: Application of GPC is beneficial in reducing postoperative recurrence of SP.

[Propensity-score-matched Comparison of Postoperative Pain Between Young and Elderly Patients Who Underwent Video-assisted Thoracoscopic Surgery for Spontaneous Pneumothorax].

Video-assisted thoracoscopic surgery (VATS) is the standard treatment for spontaneous pneumothorax(SP). Although VATS has decreased the postoperative pain in comparison with conventional thoracotomy, the procedure still often requires sufficient postoperative pain management especially for young patients, and the present study on the postoperative pain management focused on the age difference was designed. Using the numerical rating scale, we compared postoperative pain between the young group(36 patients) and the elderly group (36 patients) selected by propensity score matching in order to adjust for the patients' backgrounds. Although the young group had significantly stronger pain than the elderly group immediately after surgery(4.9±2.5 vs.3.2±2.4, p=0.002), it improved promptly. Moreover, the young group required significantly more frequent continuous infusions of opioids after surgery( p=0.001). In conclusion, it is considered that the postoperative pain management in the pneumothorax surgery should be customized according to the age.

Blood supply--susceptible formation of melanin pigment in hair bulb melanocytes of mice.

BACKGROUND: Allogeneic skin grafts onto C57BL/6 mice are rejected, and the rejected skin is replaced by surrounding skin with black hair. In contrast, syngeneic skin grafts are tolerated, and gray hair grows on the grafts. METHODS: To explore the mechanism of gray hair growing on the tolerated skin grafts, we prepared full-thickness skin (2-cm square) autografts, 2 (2 cm + 2 cm) horizontal or vertical parallel incisions, and U-shaped (2 cm × 2 cm × 2 cm) flaps with or without pedicle vessels. The grafts, incisions, and flaps were fixed by suturing with string and protected by a transparent bandage. On day 14 after the operation, the bandages were removed to observe the color of the hair growing on the skin. RESULTS: Skin autografts from wild-type or hepatocyte growth factor-transgenic (Tg) C57BL/6 mice survived with gray hair, whereas those from steel factor (Kitl)-Tg C57BL/6 mice survived with black hair. In addition, U-shaped flaps lacking both of the 2 main feeding vessels of wild-type mice had gray hair at the tip of the flaps. Light microscopy after staining with hematoxylin and eosin or dihydroxyphenylalanine showed that the formation of melanin pigment in the follicles, but not in the interadnexal skin, was susceptible to the blood supply. CONCLUSIONS: Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

Specific binding of HLA-B44 to human macrophage MHC receptor 1 on monocytes.

Allograft (H-2D(d)K(d))-induced macrophages (AIM) in C57BL/6 (H-2D(b)K(b)) mice exhibit major histocompatibility complex (MHC) haplotype-specific killing of allografts in a macrophage MHC receptor 1 (MMR1; for H-2D(d))- and MMR2 (for H-2K(d))-dependent manner. Recently, we showed HLA-B62 to be a ligand for the human homologue of mouse MMR2. In the present study, we isolated a cDNA encoding the human homologue of mouse MMR1 and found HLA-B44 to be the sole ligand specific for the human MMR1 by using beads that had been conjugated with 80 kinds of HLA proteins. Flow cytometric analyses revealed that HLA-B44-conjugated beads are specifically bound to HEK293T cells expressing human MMR1, that HLA-B44 tetramers are bound to the human MMR1-transfected HEK293T cells with a dissociation constant of 3.0×10(-9) M, and that the interaction was completely inhibited by the addition of R15 monoclonal antibody specific for mouse MMR1. The MMR1 cDNA (1537-bp) encoded a 473-amino acid polypeptide and was expressed at least in part in the brain and peripheral blood mononuclear cells (PBMCs) or monocytes, but not in granulocytes or lymphocytes. PBMCs from 7 non-H-2D(d) (non-self), but none from 5 H-2D(d) (self), in-bred mice expressed mouse MMR1 specific for H-2D(d). In contrast, PBMCs from none of the 16 human volunteers expressed HLA-B44; whereas those from only 3 of these 16 volunteers expressed human MMR1. These results reveal that human MMR1 on monocytes is a novel receptor specific for HLA-B44.

Resection margin with anatomic or nonanatomic hepatectomy for liver metastasis from colorectal cancer.

BACKGROUND: When hepatectomy is used as a primary treatment for liver metastasis from colorectal cancer (CRCLM), the balance between surgical curability and functional preservation of the remnant liver is of great importance. METHODS: A total of 108 patients who underwent initial hepatectomy for CRCLM were retrospectively analyzed with respect to tumor extent, operative method, and prognosis, including recurrence. RESULTS: The 1-, 2-, 3-, and 5-year overall survival rates (OS) for all patients were 90.5%, 77.8%, 63.2%, and 51.6%, respectively. Multivariate analysis indicated serum carbohydrate antigen 19-9 (CA 19-9) level after hepatectomy (<36 or ≥36 mAU/mL) and presence of recurrence as independent prognostic factors of OS (P = 0.0458 and 0.0249, respectively), and tumor depth of colorectal cancer (

Prognostic clinicopathological factors after curative resection of small bowel adenocarcinoma.

PURPOSE: Small bowel adenocarcinoma is a relatively uncommon neoplasm that accounts for approximately 0.3% to 2.4% of digestive cancers. In comparison with carcinomas of the other areas of the gastrointestinal tract, the prognosis for small bowel adenocarcinoma is generally worse. The prognostic factors of small bowel adenocarcinoma were analyzed retrospectively, and the significance of operative procedure, lymphadenectomy, and adjuvant chemotherapy was evaluated. METHODS: From 1990 to 2009, 30 patients with small bowel adenocarcinoma who underwent surgery at Osaka Medical College Hospital were analyzed with respect to tumor extent, operation method, and prognosis. RESULTS: Overall 5-year survival was 52.5%, and the median survival time was 27.0 months. On univariate and multivariate analyses, the location (duodenum vs. jejunum and ileum), size (greater or less than 70 mm), and tumor, nodes, and metastasis (TNM) stage (stage 0 + I + II vs. III + IV) of the tumor were the significant prognostic factors. No differences in survival and recurrence rates were observed between patients undergoing pancreaticoduodenectomy and those undergoing partial resection, between those undergoing mural lymphadenectomy and those undergoing extended lymphadenectomy, or between those with and without adjuvant chemotherapy. The combination of surgery and adjuvant chemotherapy did not control recurrence or improve the prognosis. CONCLUSIONS: In small bowel adenocarcinoma, location, size, and TNM stage of the tumors were the independent prognostic factors after curative resections. Partial resection with mural lymphadenectomy may be recommended as optimal surgery for small bowel adenocarcinoma.

Transgene number-dependent, gene expression rate-independent rejection of Dd -, Kd-, or Dd Kd -transgened mouse skin or tumor cells from C57BL/6 Db Kb mice.

Recipient cells migrating into the transplantation site of an allograft recognize histocompatibility antigens on the grafts and are cytotoxic against the grafts. Although the alloreactive immune response is predominantly directed at the major histocompatibility complex (major histocompatibility complex [MHC]; H-2 in mice) class I molecules, the basic mechanisms of allograft rejection (e.g., ligand-receptor interaction) remain unclear, because of the polymorphism and complexity of the MHC. To examine the role of MHC class I molecules in allograft rejection, D(d) , K(d) or D(d) K(d) -transgenic skin or tumor cells we established on a C57BL/6 (D(b) K(b) ) background and transplanted into C57BL/6 mice. Skin grafts from allogeneic (i.e., BALB/c, B10.D2, and BDF1) strains of mice were rejected from C57BL/6 mice on days 12-14 after grafting, whereas isografts were tolerated by these mice. Unexpectedly, skin grafts from D(d) -, K(d) -, and D(d) K(d) -transgenic C57BL/6 mice were rejected on days 12-14 in a transgene expression rate-independent manner from 9/19 (47%), 20/39 (51%), and 12/17 (71%) of C57BL/6 mice, respectively. Similarly, intradermally transplanted allogeneic (i.e., Meth A), but not syngeneic (i.e., EL-4), tumor cells were rejected from C57BL/6 mice; the growth of D(d) - or K(d) -transfected EL-4 cells was delayed by 10-13 days; and 4/10 (40%) of D(d) K(d) -transfected tumor cells were rejected from C57BL/6 mice. These results indicate that D(d) and K(d) genes are equivalent as allogeneic MHC class I genes and that C57BL/6 (D(b) K(b) ) mice reject D(d) -, K(d) -, or D(d) K(d) -transgened skin or tumor cells in a transgene number-dependent, gene expression rate-independent manner.