Hyogo College of Medicine

About: Hyogo College of Medicine is a education organization based out in Nishinomiya, Hyôgo, Japan. It is known for research contribution in the topics: Cancer & Transplantation. The organization has 5030 authors who have published 10629 publications receiving 258734 citations. The organization is also known as: Hyōgo ika daigaku.

Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.

Abstract: Semaphorins and their receptors have diverse functions in axon guidance, organogenesis, vascularization and/or angiogenesis, oncogenesis and regulation of immune responses1,2,3,4,5,6,7,8,9,10,11. The primary receptors for semaphorins are members of the plexin family2,12,13,14. In particular, plexin-A1, together with ligand-binding neuropilins, transduces repulsive axon guidance signals for soluble class III semaphorins15, whereas plexin-A1 has multiple functions in chick cardiogenesis as a receptor for the transmembrane semaphorin, Sema6D, independent of neuropilins16. Additionally, plexin-A1 has been implicated in dendritic cell function in the immune system17. However, the role of plexin-A1 in vivo, and the mechanisms underlying its pleiotropic functions, remain unclear. Here, we generated plexin-A1-deficient (plexin-A1−/−) mice and identified its important roles, not only in immune responses, but also in bone homeostasis. Furthermore, we show that plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12. These findings reveal an unexpected role for plexin-A1 and present a novel signalling mechanism for exerting the pleiotropic functions of semaphorins.

Predictive factors for proximal junctional kyphosis in long fusions to the sacrum in adult spinal deformity

Abstract: STUDY DESIGN A retrospective study. OBJECTIVE To assess the mechanisms and the independent risk factors associated with proximal junctional kyphosis (PJK) in patients treated surgically for adult spinal deformity with long fusions to the sacrum. SUMMARY OF BACKGROUND DATA The occurrence of PJK may be related to preoperative and postoperative sagittal parameters. The mechanisms and risk factors for PJK in adults are not well defined. METHODS Consecutive patients who underwent long instrumented fusion surgery (≥6 vertebrae) to the sacrum with a minimum of 2 years of follow-up were retrospectively studied. Risk factors included patient factors, surgical factors, and radiographical parameters such as thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis, pelvic tilt, and pelvic incidence. RESULTS Ninety consecutive patients (mean age, 64.5 yr) met inclusion criteria. Radiographical PJK occurred in 37 of the 90 (41%) patients with a mean follow-up of 2.9 years. The most common mechanism of PJK was fracture at the upper instrumented vertebra (UIV) in 19 (51%) patients. Twelve (13%) patients with PJK were treated surgically with proximal extension of the instrumented fusion. Preoperative TK more than 30°, preoperative proximal junctional angle more than 10°, change in LL more than 30°, and pelvic incidence more than 55° were identified as predictors associated with PJK. Achievement of ideal global sagittal realignment (sagittal vertical axis <50 mm, pelvic tilt <20°, and pelvic incidence-LL <±10°) protected against the development of PJK (19% vs. 45%). A multivariate regression analysis revealed changes in LL more than 30°, and preoperative TK more than 30° were the independent risk factors associated with PJK. CONCLUSION Fracture at the UIV was the most common mechanism for PJK. Change in LL more than 30° and pre-existing TK more than 30° were identified as independent risk factors. Optimal postoperative alignment of the spine protects against the development of PJK. A surgical strategy to minimize PJK may include preoperative planning for reconstructions with a goal of optimal postoperative alignment. LEVEL OF EVIDENCE 3.

IFN-gamma-inducing factor/IL-18 administration mediates IFN-gamma- and IL-12-independent antitumor effects.

Abstract: We evaluated the mechanism of the antitumor effects of mouse rIFN-gamma-inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN-gamma levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN-gamma or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8+ T cells, but not CD4+ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells, but in IFN-gamma- and IL-12-independent pathways.