In order to definitively ascertain the functional contribution of lymphotoxin (LT) expressed by B cells, we produced mice with the LTbeta gene deleted from B cells (B-LTbeta KO mice). In contrast to systemic LTbeta deletion, in B-LTbeta KO mice only splenic microarchitecture was affected, while lymph nodes and Peyer's patches (PP) were normal, except for PP's reduced size. Even though B-LTbeta KO spleens retained a small number of follicular dendritic cells (FDC) which appeared to be dependent on LTbeta produced by T cells, IgG responses to sheep red blood cells were markedly reduced. Thus, the organogenic function of B-LTbeta is almost entirely restricted to spleen, where it supports the correct lymphoid architecture that is critical for an effective humoral immune response.

The gene expression patterns of primordial germ cells (PGCs) and embryonic stem cells were analyzed by a modified serial analysis of gene expression. During the process, we cloned a novel gene, PGC7, which was preferentially expressed in PGCs. Immunohistochemical analysis revealed that PGC7 was specifically expressed in early pre-implantation embryos, PGCs and oocytes. These results suggest that PGC7 might play an important role in the development of PGCs and oocytes.

The aim of this study was to investigate the effects of the pointspread function (PSF) and time-of-flight (TOF) on improving 18 F-FDG PET/CT images in relation to reconstruction parameters and noise-equivalent counts (NEC). Methods: This study consisted of a phantom study and a retrospective analysis of 39 consecutive patients who underwent clinical 18 F-FDG PET/CT. The body phantom of the National Electrical Manufacturers Association and International Electrotechnical Commission with a 10-mm-diameter sphere was filled with an 18 F-FDG solution with a 4:1 radioactivity ratio compared with the background. The PET data were reconstructed with the baseline orderedsubsets expectation maximization (OSEM) algorithm, with the OSEM1PSF model, with the OSEM1TOF model, and with the OSEM1PSF1TOF model. We evaluated image quality by visual assessment, the signal-to-noise ratio of the 10-mm sphere (SNR 10 mm ), the contrast of the 10-mm sphere, and the coefficient of variance in the phantom study and then determined the optimal reconstruction parameters. We also examined the effects of PSF and TOF on the quality of clinical images using the signal-to-noise ratio in the liver (SNR liver ) in relation to the NEC in the liver (NEC liver ). Results: In the phantom study, the SNR 10 mm was the highest for the OSEM1PSF1TOF model, and the highest value was obtained at iteration 2 for algorithms with the TOF and at iteration 3 for those without the TOF. In terms of a postsmoothing filter full width at half maximum (FWHM), the high SNR 10 mm was obtained with no filtering or was smaller than 2 mm for algorithms with PSF and was 4-6 mm for those without PSF. The balance between the contrast recovery and noise is different for algorithms with either PSF or TOF. A combination of PSF and TOF improved SNR 10 mm , contrast, and coefficient of variance, especially with a small-FWHM gaussian filter. In the clinical study, the SNR liver of the low-NEC liver group in the OSEM1PSF1TOF model was compared with that of the high-NEC liver group in conventional OSEM. The PSF1TOF improved the SNR liver by about 24.9% 6 9.81%. Conclusion: A combination of PSF and TOF clearly improves image quality, whereas optimization of the reconstruction parameters is necessary to obtain the best performance for PSF or TOF. Furthermore, this combination has the potential to provide good image quality with either lower activity or shorter acquisition time, thus improving patient comfort and reducing the radiation burden. PET/ CT with 18 F-FDG is useful for the detection and staging of various malignant tumors, monitoring of their response to therapy, and prognostic stratification (1-6). High image quality is required for an accurate diagnosis, although the spatial resolution of PET is relatively low in comparison to other imaging modalities (7). Recently, the information provided by the point-spread function (PSF) and time-of-flight (TOF) has been expected to improve the spatial resolution and signal-to-noise ratio (SNR), respectively, of PET images (8-10).A PET sca...

Objective To determine whether intervertebral disc (IVD) cells express β-catenin and to assess the role of the WNT/β-catenin signaling pathway in cellular senescence and aggrecan synthesis. Methods The expression of β-catenin messenger RNA (mRNA) and protein in rat IVD cells was assessed by using several real-time reverse transcription–polymerase chain reaction, Western blot, immunohistochemical, and immunofluorescence analyses. The effect of WNT/β-catenin on nucleus pulposus (NP) cells was examined by transfection experiments, an MTT assay, senescence-associated β-galactosidase staining, a cell cycle analysis, and a transforming growth factor (TGFβ)/bone morphogenetic protein (BMP) pathway–focused microarray analysis. Results We found that β-catenin mRNA and protein were expressed in discs in vivo and that rat NP cells exhibited increased β-catenin mRNA and protein upon stimulation with lithium chloride, a known activator of WNT signaling. LiCl treatment inhibited the proliferation of NP cells in a time- and dose-dependent manner. In addition, there was an increased level of cellular senescence in LiCl-treated cells. Long-term treatment with LiCl induced cell cycle arrest and promoted subsequent apoptosis in NP cells. Activation of WNT/β-catenin signaling also regulated the expression of aggrecan. We also demonstrated that WNT/β-catenin signaling induced the expression of matrix metalloproteinases (MMPs) and TGFβ in NP cells. Conclusion The activation of WNT/β-catenin signaling promotes cellular senescence and may modulate MMP and TGFβ signaling in NP cells. We hypothesize that the activation of WNT/β-catenin signaling may lead to an increased breakdown of the matrix, thereby promoting IVD degeneration.

Objective. It is difficult to identify a single causative factor for inflammatory arthritis because of the multifactorial nature of the disease. This study was undertaken to dissect the molecular complexity of systemic inflammatory disease, utilizing a combined approach of mutagenesis and systematic phenotype screening in a murine model.Methods. In a large-scale N-ethyl-N-nitrosourea mutagenesis project, the Ali14 mutant mouse strain was established because of dominant inheritance of spontaneous swelling and inflammation of the hind paws. Genetic mapping and subsequent candidate gene sequencing were conducted to find the causative gene, and systematic phenotyping of Ali14/؉ mice was performed in the German Mouse Clinic. Results.A novel missense mutation in the phospholipase C␥2 gene (Plcg2) was identified in Ali14/؉ mice. Because of the hyperreactive external entry of calcium observed in cultured B cells and other in vitro experiments, the Ali14 mutation is thought to be a novel gain-of-function allele of Plcg2. Findings from systematic screening of Ali14/؉ mice demonstrated various phenotypic changes: an abnormally high T cell:B cell