Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloidderived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PDL1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Background: It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. Methods: A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a salinetreated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control).In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. Results: Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. Conclusions Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

Background: It is known that some analgesics as well as pain can affect the immune system. The aim of this study was to investigate the analgesic effect and immunomodulation of pregabalin (PGB) in a mouse incisional pain model. Methods: A postoperative pain model was induced by hind paw plantar incision in male BALB/c mice. Mice were randomly divided into four groups (n = 8): a salinetreated incision (incision), PGB-treated incision (PGB-incision), sham controls without incision or drug treatment (control), and a PGB-treated control (PGB-control).In the PGB treated groups, PGB was administered intraperitoneally (IP) 30 minutes before and 1 hour after the plantar incision. Changes of the mechanical nociceptive thresholds following incision were investigated. Mice were euthanized for spleen harvesting 12 hours after the plantar incision, and natural killer (NK) cytotoxicity to YAC 1 cells and lymphocyte proliferation responses to phytohemagglutinin were compared among these four groups. Results: Mechanical nociceptive thresholds were decreased after plantar incision and IP PGB administration recovered these decreased mechanical nociceptive thresholds (P < 0.001). NK activity was increased by foot incision, but NK activity in the PGB-incision group was significantly lower than that in the Incision group (P < 0.001). Incisional pain increased splenic lymphocyte proliferation, but PGB did not alter this response. Conclusions Incisional pain alters cell immunity of the spleen in BALB/c mice. PGB showed antinocieptive effect on mouse incisional pain and attenuates the activation of NK cells in this painful condition. These results suggest that PGB treatment prevents increases in pain induced NK cell activity.

Objective: : High precision and accuracy are expected in gamma knife radiosurgery treatment. Because of the requirement of clinically applying complex radiation and dose gradients together with a rapid radiation decline, a dedicated quality assurance program is required to maintain the radiation dosimetry and geometric accuracy and to reduce all associated risk factors. This study investigates the validity of Leksell Gamma plan (LGP)10.1.1 system of 5th generation Gamma Knife Perfexion as modified variable ellipsoid modeling technique (VEMT) method. Methods: : To verify LGP10.1.1 system, we compare the treatment plan program system of the Gamma Knife Perfexion, that is, the LGP, with the calculated value of the proposed modified VEMT program. To verify a modified VEMT method, we compare the distributions of the dose of Gamma Knife Perfexion measured by Gafchromic EBT3 and EBT-XD films. For verification, the center of an 80 mm radius solid water phantom is placed in the center of all sectors positioned at 16 mm, 4 mm and 8 mm; that is, the dose distribution is similar to the method used in the x, y, and z directions by the VEMT. The dose distribution in the axial direction is compared and analyzed based on Full-Width-of-Half-Maximum (FWHM) evaluation. Results: : The dose profile distribution was evaluated by FWHM, and it showed an average difference of 0.104 mm for the LGP value and 0.130 mm for the EBT-XD film. Conclusion : The modified VEMT yielded consistent results in the two processes. The use of the modified VEMT as a verification tool can enable the system to stably test and operate the Gamma Knife Perfexion treatment planning system.

Distraction osteogenesis is a biologic process of new bone formation between the surfaces of bone segments that are gradually separated by incremental traction. Distraction osteogenesis is clinically applied as a new treatment modality of mandibular hypoplasia or bony defect area in maxillofacial area by many studies of distraction devices and method. But disadvantage of distraction osteogenesis shows unfavorably long consolidation period and relapse tendency. Therefore. this experiment was designed to investigate the effectiveness of combined application of distraction and compression force for improving of bone quality and shortening of treatment period during distraction osteogenesis. Twenty-one Sprague-Dawley rats with 300-350gm were used. These were divided into two group as distraction group and combination group was applied with compression force in the consolidation period. The rat were sacrificed for gross finding, radiographic and histologic findings. at 2, 4 weeks after distraction. The result were follow : 1. On radiographic finding, all experimental groups appeared more radiopacity than control groups both at 2, 4 weeks after distraction. 2. On histologic finding, trabeculae of bone and mature lamellar bone were showed increasingly in experimental group. Ossification occured rapidly. From this study, we may suggest that compression force application in consolidation period during distraction osteogenesis can be useful method improve bone quality and to shorten the treatment period. But more experimental and clinical studis are necessitated on effects of compression force application during distraction osteogenesis.
Animals ; Mandible* ; Osteogenesis ; Osteogenesis, Distraction* ; Rats* ; Rats, Sprague-Dawley ; Recurrence ; Traction

The Reconstructive techniques of palatal defect are palatal island flap, palatal mucoperiosteal expansion, buccal flap, tongue flap, pushback palatoplasty, free flap and so on. We report a reconstruction of palatal defect using palatal flap. Excellent results were obtained by palatal connective tissue island flap and split thickness pedicle flap. Healing of defect occured rapidly. There were no postoperative complications except dull pain.
Connective Tissue ; Free Tissue Flaps ; Postoperative Complications ; Tongue

OBJECTIVES: The purpose of this study was to investigate the effects of cognitive differentation training of Integrated Psychological Therapy(a training program of executive function,concept formation,language,and abstraction) on micro-level cognitive function such as attention,memory and reaction time in patients with schizophrenia. METHODS: Twenty-four inpatients diagnosed as schizophrenia using DSM-lV were randomly assigned to 2 group. The training group went through a total of 12 sessions of cognitive differentiation training for 4 weeks. The control group received psychoeducation Timer of Vienna Test System were administered to all patients, both before and after the training program. RESULTS: 1) In the attention and concentration scores of Wechsler Memory Scale-Revised, between group, within group and interaction effects of training were not significant. 2) In the short-term memory scores of Wechsler Memory Scale-Revised, within group effect of training was significant(F(1,24)=15.09,p<0.05), but the between group and interaction effects did not reach significance. 3) In the long-term memory scores of Wechsler Memory Scale-Revised, within group effect of training was significant(F(1,24)=15.09,p<0.05), but the between group and interaction effects did not reach significance. 4) In the reaction time scores of Decision-Reaction Timer,interaction effect of training was significant(F(1,24)=5.18,p<0.05). 5) In the motor time scores of Decision-Reaction Timer,between group,within group and interaction effects of training were not significant. 6) In the decision time scores of Decision-Reaction Timer,interaction effect of training was significant(F(1,24)=6.00,p<0.05). CONCLUSION: Our findings suggest that cognitive differentiation training of Integrated Psychological Therapy is partly effective on improving micro-level cognitive functions such as reaction time(especially,decision time)in patients with schizophrenia.
Education ; Humans ; Inpatients ; Memory ; Memory, Long-Term ; Memory, Short-Term ; Reaction Time ; Schizophrenia

OBJECTIVES: Memory deficits in patients with schizophrenia have been well established, but it is still unclear how memory performance changes during verbal learning tasks. This study was designed to assess the pattem of verbal learning and memory performance to test the inefficiency of encoding processes in learning of schizophrenia. METHOD: Subjects consisted of 26 patients with schizophrenia who were unmedicated for atleast seven days and 22 normal controls who were matched for age,sex,and education. Verbal memory and learning were evaluated with computerized tasks composed of three consecutive immediate recall trials, a yes/no recognition test, and a delayed recall trial of a word list. RESULTS: Thepatients with schizophrenia showed significant learning deficits characterized by impaired immediate recall performance and poor learning of a word list. However, both verbal recognition performance and forgetting were comparable in both groups. Word clustering correlated significantly with recall performance. Clustering of patients decreased significantly over immediate and delay recall tasks and showed poor increase during consecutive recall tasks. CONCLUSION: Thest findings indicate that verbal learning and mnemonic strategy are impaired but learned information appears to be preserved in patients with schizophrenia. The results are consistent with the notion that a learning deficit is closely related with impaired encoding precesses in schizophrenia.
Education ; Humans ; Learning ; Memory Disorders ; Memory* ; Memory, Short-Term ; Schizophrenia* ; Verbal Learning