Pituitary adenylate cyclase-activating polypeptide (PACAP), a 38-amino acid neuropeptide belonging to the secretin-glucagon-vasoactive intestinal peptide (VIP) family, performs a variety of functions in both the nervous and immune systems. In this study, we examined the effects of PACAP on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. When administrated intraperitoneally every other day after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, PACAP ameliorated both the clinical and pathological manifestations of EAE Ex vivo examination revealed a significant inhibition of MOG35-55-specific Th1 response in mice treated with PACAP. In vitro analysis revealed that PACAP suppressed the production of inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-12, and expression of the costimulatory factor B7-2 on macrophage and microglia, which may function as antigen presenting cells (APC) in the CNS. While PACAP suppressed the differentiation of MOG35-55-specific T cells into Th1 effectors upon restimulation with MOG35-55-expressing APC, it did not affect interferon (IFN)-gamma production by MOG35-55-specific T cells stimulated with anti-CD3 and anti-CD28. These observations suggested that PACAP suppressed induction of EAE primarily via suppression of APC function and inflammatory cytokine production. PACAP may be useful in the future treatment of Th1-mediated autoimmune diseases, such as multiple sclerosis.

We previously described nine cases of angiocentric lymphoma of a possible natural killer (NK)-cell lineage with a surface CD3-CD56+ phenotype occurring in sites other than the upper and lower respiratory tract. This study was performed to investigate the association of Epstein-Barr virus (EBV) with these lymphomas, using the polymerase chain reaction (PCR) for the presence of EBV-DNA, in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs) and immunohistology for EBV-determined nuclear antigen-2 (EBNA-2) and latent membrane protein-1 (LMP-1) in paraffin sections. PCR and ISH produced almost identical results, and EBERs were identified in the nuclei of the lymphoma cells of three cases, two of which exhibited LMP-1 in the cytoplasm of tumour cells without EBNA-2 expression. Molecular genetic analysis revealed EBV to be incorporated into these three EBER-positive cases either clonally or biclonally. It was revealed by re-evaluation of their morphology with the established EBV status on each case that, in contrast to the rather variable and irregular cellular composition of the EBV-positive tumours, the EBV-negative tumours stood out because of their remarkably uniform 'blastoid' appearance, and could be grouped as blastic NK-cell lymphoma. The relationship of the EBV-positive cases with nasal NK-cell tumours has yet to be clarified.

In this study, we hypothesize that anti-cytokeratin 18 (CK18) antibody and CK18:anti-CK18 immune complex increase in sera in patients with idiopathic pulmonary fibrosis (IPF). To prove the existence of anti-CK18 antibodies in patients' sera, bovine CK18 was stained with patients' sera using a Western blotting. In patients with IPF, anti-CK18 antibodies were clearly demonstrated in sera by Western blotting. Then, we tried to establish an enzyme-linked immunosorbent assay (ELISA) to quantify anti-CK18 antibodies and CK18:anti-CK18 immune complexes in sera of patients with IPF. Levels of anti-human CK18 antibodies in sera of patients with IPF (0.81 +/- 0.31, mean +/- SD) measured by ELISA were significantly high compared with that of normal volunteers (0.45 +/- 0.06, p < 0.01). In addition, levels of CK18:anti-CK18 antibody complexes in patients' sera (0.64 +/- 0.35, man +/- SD) significantly increased compared with those of normal subjects (0.40 +/- 0.10, p < 0.01). These results suggest that anti-CK18 antibody and its immune complex may have played a role in the process of lung injury in IPF.

The amplification and/or rearrangement of the cyclin D1 gene, a positive regulatory element of the G1 to S phase of the cell cycle, has been reported in various human tumors, suggesting an oncogenic role of this gene. In this study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 patients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinct patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of only 2 of the 25 HCC patients (8%) examined and no particular clinicopathological characteristics were found in these patients. In contrast, the cytoplasmic staining pattern, without nuclear staining, was detected in 8 of the 25 patients with HCC (32%). A significant correlation was found between the expression of cytoplasmic cyclin D1 and patients with tumor thrombus in the portal vein (Vp), as well as those with intrahepatic metastasis (IM). These results indicate that the cytoplasmic cyclin D1 expression appears to be related to the prognosis of HCC. The Ag nucleolar organizer regions (NORs) counts in cyclin D1-positive and -negative patients were not significantly different, suggesting that immunostaining for cyclin D1 has the potential to be a unique prognostic marker in human HCC. Simultaneous immunohistochemical study with p53 antibody in the same series of HCC revealed that 88% of the patients positive for cyclin D1 also expressed p53 and that in 91% of the patients negative for p53, cyclin D1 was not expressed. These results suggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.

Background: The number of papers published by an institution is acknowledged as an easy-to-understand research outcome. However, the quantity as well as the quality of research papers needs to be assessed. Methods: To determine the relation between the number of published papers and paper quality, a survey was conducted to assess publications focusing on interventional clinical trials reported by 11 core clinical research hospitals. A score was calculated for each paper using Système d’interrogation, de gestionet d’analyse des publications scientifiques scoring system, allowing for a clinical paper quality assessment independent of the field. Paper quality was defined as the relative Journal impact factor (IF) total score/number of papers. Results: We surveyed 580 clinical trial papers. For each of the 11 medical institutions (a–k), respectively, the following was found: number of published papers: a:66, b:64, c:61, d:56, e:54, f:51, g:46, h:46, i:46, j:45, k:45 (median: 51, maximum: 66, minimum: 45); total Journal IF: a:204, b:252, c:207, d:225, e:257, f:164, g:216, h:190, i:156, j:179, k:219 (median: 207, maximum: 257, minimum: 156); relative Journal IF total score: a:244, b:272, c:260, d:299, e:268, f:215, g:225, h:208, i:189, j:223, k:218 (median: 225, maximum: 299, minimum: 189); and paper quality (relative Journal IF total score/number of papers): a:3.70, b:4.25, c:4.26, d:5.34, e:4.96, f:4.22, g:4.89, h:4.52, i:4.11, j:4.96, k:4.84 (median: 4.52, maximum: 5.34, minimum: 3.70). Additionally, no significant relation was found between the number of published papers and paper quality (correlation coefficient, −0.33, P = 0.32). Conclusions: The number of published papers does not correspond to paper quality. When assessing an institution’s ability to perform clinical research, an assessment of paper quality should be included along with the number of published papers.