T-Cell receptor and autoimmune disease

Since the genes encoding the TCR have been cloned, their structure, organization, pattern of rearrangement, diversification and expression in ontogeny have been classified. However, there are still many important questions to be addressed, such as the nature of thymic education, tolerance, the mechanism of MHC-restricted antigen recognition and the relation between TCR repertoire and autoimmunity. In the future, new approaches to study these issues, such as transgenic mice, X-ray crystallography, and severe combined immune deficiency mice reconstituted with human hematopoietic cells will lead to a more profound understanding of these questions. This will hopefully allow us to manipulate the immune response in different and more effective ways than are currently available.     

Effect of acetylation of biodegradable polyrotaxanes on its supramolecular dissociation via terminal ester hydrolysis

Acetylation of biodegradable polyrotaxanes was examined to estimate the effect on its supramolecular dissociation via terminal ester hydrolysis. The biodegradable polyrotaxanes, in which many alpha-cyclodextrins (alpha-CD) are threaded onto a poly(ethylene glycol) chain capped with L-phenylalanine via ester linkages, were acetylated using acetic anhydride; alpha-CD release behavior was then characterized by in vitro hydrolysis. The degree of acetylation was changed by the concentration of acetic anhydride and the reaction time. The results of the in vitro hydrolysis indicate that the critical degree of acetylation to prolong supramolecular dissociation lies at around 30%. The terminal hydrolysis proceeded completely even with 100% of acetylation. These findings suggest that the hydrophobization of alpha-CDs in the polyrotaxane makes it possible to delay the time to complete the supramolecular dissociation. The hydrophobization of the polyrotaxane is of great importance for designing implantable materials that maintain their supramolecular structure until tissue regeneration with complete terminal hydrolysis.     

Hydrothermal modification of titanium surface in calcium solutions

Hydrothermal modification of a titanium surface in calcium solutions was performed. The apatite precipitation on the modified surface in Hanks' solution, as a simulated body fluid, was evaluated and the surface microstructure changes after the modification were characterized by thin-film X-ray diffractometry (TF-XRD) and X-ray photoelectron spectroscopy (XPS). Hydrothermal modification in CaO solution enhanced the precipitation of apatite on the titanium surface. High pH, high pressure and high temperature of the CaO solution increased the thickness of the surface-modified layer and enhanced the synthesis of calcium titanate which possibly promoted the precipitation of apatite in Hanks' solution. Hydrothermal modification in CaCl2 solution, on the other hand, showed reverse effects. The modification of titanium in CaO solution with hydrothermal treatment is expected to result in excellent osteointegration and can be easily performed by using an autoclave, a clinical apparatus widely used.     

Predictors of improvement in low back pain after lumbar decompression surgery: Prospective study of 140 patients

Background

Lumbar decompression surgery is often used to treat neurological symptoms of the lower extremity as a result of lumbar disease. However, this method also leads to the improvement of the accompanying low back pain (LBP). We studied the extent of LBP improvement after lumbar decompression surgery without fusion and the associated preoperative factors.

C1 lateral mass screw insertion caudally from C2 nerve root – An alternate method for insertion of C1 screws: A technical note and preliminary clinical results

Background

C1 lateral mass screw was widely used for fixation of the upper cervical spine. However, massive bleeding from the C1–2 venous plexus is sometimes encountered. In this study, we proposed an alternate method for C1 lateral mass screw insertion, which involves insertion of the screws caudally from the C2 nerve root to reduce bleeding from C1–2 venous plexus.

A novel preoperative predictor of pancreatic fistula using computed tomography after distal pancreatectomy with staple closure

Purpose

A thick pancreas has proven to be a conspicuous predictor of pancreatic fistula (PF) following distal pancreatectomy (DP) using staples. Other predictors for this serious surgical complication currently remain obscure. This study sought to identify novel predictors of PF following DP.

Methods

One hundred and twenty-two patients were retrospectively assessed to determine the correlation between PF occurrence and the clinicopathological findings and radiologic data from preoperative computed tomography (CT). CT assessments included the thickness of the pancreas (TP) and pancreatic CT number (pancreatic index; PI), calculated by dividing the pancreatic CT by the splenic CT density.

Results

Twenty-four patients (19.7%) developed a clinically relevant PF. TP was identified as an independent risk factor for PF in multivariate analyses (odds ratio 1.17; P?=?0.0095). In subgroup analyses, a lower PI in a thick pancreas was a significant predictor of PF (P?=?0.032). The combination of these two prediction parameters, known as the TP-to-PI ratio (TPIR), showed a significantly better prediction ability than TP alone (area under the receiver operating characteristic curve for the incidence of PF, TPIR 0.80 vs. TP 0.69; P?=?0.037).

Conclusion

Combining the CT number with TP substantially improves the prediction ability for the incidence of PF following DP with staple use.

     

Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide

We previously evaluated Wilms’ tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA‐A*24:02 restricted, 9‐mer WT1‐235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1‐235‐specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1‐235 peptide (WT1‐235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1‐235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1‐235 IgG antibody subclass was Th1‐type, IgG₁ and IgG₃. WT1‐235 IgG antibody production was significantly and positively correlated with both progression‐free survival (PFS) and overall survival (OS). Importantly, the combination of WT1‐235 IgG antibody production and positive delayed type‐hypersensitivity (DTH) to the WT1‐235 peptide was a better prognostic marker for long‐term OS than either parameter alone. These results suggested that WT1‐235 peptide vaccination induces not only WT1‐235‐specific CTLs as previously described but also WT1‐235‐specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine‐treated patients.     

Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells

Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury, when injected in high concentration. In the present study, we investigated the mechanisms for the cytotoxicity of GM on porcine aorta endothelial cells (PAECs). GM (0.5 - 5.0 mM) decreased cell viability in a dose-dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another serine protease inhibitor, or mesilate itself had no effect on cell viability. zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA fragmentation were also not observed after GM treatment. Moreover, Ca(2+) chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical scavengers had no effect on the GM-induced cell injury. On the other hand, cellular ATP content was decreased in the GM (2.0 mM)-treated cells. Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium iodine. These findings suggest that GM induces necrotic cell death via injury of the cell membrane.