Endomorphin-2 modulates productions of TNF-alpha,IL-1beta,IL-10, and IL-12, and alters functions related to innate immune of macrophages

We evaluate immunological effects of opioid peptide endomorphin-2 on the production of cytokines related to inflammation and Th1/Th2 balance, and functions related to innate immune of rat peritoneal macrophages. Endomorphin-2 inhibited TNF-, IL-10, and IL-12 productions, but potentiated IL-1 production by macrophages. Moreover, endomorphin-2 potentiated macrophage adhesion to fibronectin, and the expression of adhesion molecule Mac-1 on macrophages. In contrast, endomorphin-2 suppressed phagocytosis of opsonized E. coli by macrophages, without affecting phagocytosis of non-opsonized E. coli. In addition, endomorphin-2 inhibited macrophage chemotaxis, and the production of superoxide anion by macrophages. These results suggest that endomorphin-2 may alter macrophage functions such as cytokine productions and functions related to innate immune.     

CEROID-LIKE HISTIOCYTIC GRANULOMA OF GALL-BLADDER — A PREVIOUSLY UNDESCRIBED LESION —

In the present study, 13 cases of a peculiar gall-bladder granuloma characterized by marked proliferation of ceroid-fllled brown histiocytes were pathomorphologically, histochemically and ultrastructurally examined to define the pathologic features of such a lesion previously undescribed in the literature. The lesion grossly showed a granulomatous appearance of yellow brown to dark brown color developing in the wall of gall-bladder. Histologically, there was proliferation of histiocytes containing abundant brown pigment granules In their cytoplasm. The pigment granules proved to have staining characteristics closely resembling those of lipogenic ceroid-like pigment. Ultrastructurally, these granules showed membrane-bound, pleomorphic osmiophilic inclusions of heterogenous materials. With regard to the pathogenesis of this granuloma, it may be suggested that lipid components of bile juice, particularly unsaturated fatty acids and phospholipids, play an Important role as a source of ceroidogenesis In the proliferating histiocytes.     

Expression of CD10 by stromal cells during colorectal tumor development

CD10 is a cell surface metalloprotease expressed by a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes, and some epithelial cells. We noticed that stromal cells of some cancers are positive for CD10. In this study, we investigated the role of CD10 produced by the stromal cells of colorectal neoplasms in the progression of colorectal neoplasms. Immunohistochemical examination of CD10 and p53 was performed in 169 colorectal epithelial neoplasms representing various stages of carcinogenesis. The results were correlated with the morphologic characteristics of the neoplasms. There was no expression of CD10 in the stromal cells of normal colorectal tissue. CD10-positive stromal cells were present adjacent to the tumor cells in 16 of 73 adenomas with mild or moderate dysplasia. More frequent expression of CD10 by the stromal cells was detected in adenomas with severe dysplasia (12 of 17), intramucosal carcinomas (10 of 16), and invasive carcinomas (50 of 63) than in adenomas with mild or moderate dysplasia (P < 0.0001). Expression of CD10 by > 10% of the stromal cells was detected only within the area of the invasive growth front of invasive carcinomas, not in adenomas and in only 1 of the intramucosal carcinomas. The difference between invasive and non invasive tumors was significant (P < 0.0001). The stromal expression of CD10 was significantly associated with the accumulation of p53 and a larger tumor size. These results indicate that CD10 expression is an integral part of colorectal carcinogenesis. CD10 expression seems to contribute to the invasion and thus probably facilitates metastasis.     

Functional mapping of the activity of the R region in the human T-cell leukemia virus type I long terminal repeat to increase gene expression

We previously demonstrated the activity of the R fragment in the long terminal repeat of human T-cell leukemia virus type I for elevation of the level of gene expression. In this study, the fragment was deleted with BAL31 nuclease to determine its functional domain. Series of the shortened R fragments were linked to the simian virus 40 promoter unit, which regulated expression of a reporter gene. Examination with the R fragments deleted from the 5 and 3 ends showed that borders of the functional domain were mapped within nucleotide positions 458 to 473 for the 5 end and nucleotide positions 559 to 594 for the 3 end, respectively. Thus we conclude that a 136-base-pair fragment corresponding to the second half of the R region was sufficient to allow elevation of the level of gene expression.     

A medaka gene map: the trace of ancestral vertebrate proto-chromosomes revealed by comparative gene mapping

The mapping of Hox clusters and many duplicated genes in zebrafish indicated an extra whole-genome duplication in ray-fined fish. However, to reconstruct the preduplication chromosomes (proto-chromosomes), the comparative genomic studies of more distantly related teleosts are essential. Medaka and zebrafish are ideal for this purpose, because their lineages separated from their last common ancestor approximately 140 million years ago. To reconstruct ancient vertebrate chromosomes, including the chromosomes of the vertebrate ancestor of humans from 450 million years ago, we mapped 818 genes and expressed sequence tags (ESTs) on a single meiotic backcross panel obtained from inbred strains of the medaka, Oryzias latipes. Comparisons of linkage relationships of orthologous genes among three species of vertebrates (medaka, zebrafish, and human) indicate the number and content of the chromosomes of the last common ancestor of ray-fined fish and lobe-fined fish (including humans), and the extra whole genome duplication event in the ray-fin lineage occurred in the common ancestor of perhaps all teleosts.     

Clinical features of oral allergy syndrome to plant foods allergens in Kanto regions]

BACKGROUND: Recently, it is recognized that the patients of oral allergy syndrome (OAS) to fruits are increasing. However, there are little knowledges of the background, character, and seriousness about these patients in Kanto regions. OBJECTIVE: We aimed to investigate the clinical features of OAS patients to plant origin foods in Kanto regions. METHODS: The patient, who visited Sagamihara National Hospital from 2000 to 2005 and developed some allergic symptoms to plant origin foods, were studied by a questionary survey. RESULTS: As for the 42 subjects, average age are 36 years old, male:female=8:34, merger of other allergic disease is 35 allergic rhinitis of 42 subjects (83%), 34 of asthma (81%), 14 of atopic dermatitis (33%). The causes of OAS symptoms are 32 rose-family fruits, 34 non-rose family fruits, 14 vegetables, 11 nuts, 2 grains subjects. As for the symptom, only in the oral and pharynx symptoms are found in 12, the systemic symptoms is 29, anaphylaxis is 11 subjects. Allergic rhinitis preceded on the 90% subjects with pollinosis, very high rate. On the other hand, the 20% of all subjects have no symptoms of allergic rhinitis. CONCLUSION: A nasal catarrh symptoms went ahead in most of the OAS subjects in Kanto regions. In addition, considering from some patients have no black alder pollinosis and/or are allergic to many non-rose-family fruits at high frequency, there might be a broad cross-reactivity between many pollens other than alder and plant origin foods.     

Nuclear accumulation of beta-catenin in intestinal-type gastric carcinoma: correlation with early tumor invasion

Mutation of the adenomatous polyposis coli gene, which is known to be an early event in the carcinogenesis of intestinal-type gastric carcinoma, leads to accumulation of beta-catenin. In addition, beta-catenin has been found to activate down stream signaling molecules in the wingless/Wnt pathway. In this study, the clinical significance of nuclear accumulation of beta-catenin was evaluated in gastric carcinoma. Immunohistochemical staining showed nuclear localization in 16 (12%) of 139 (94 intestinal-type and 45 diffuse-type) gastric carcinomas, and all 16 lesions with nuclear staining were intestinal-type adenocarcinomas. Of the 16 cases, 15 were in the early clinical stage. In the remaining case, the lesion had invaded the subserosal layer and showed strong nuclear staining at the invasive front. In 14 of the 16 cases with nuclear localization, there were no abnormal mobility shifts detected using polymerase chain reaction-single strand conformational polymorphism analysis. This was confirmed using direct sequencing analysis, which revealed the wild-type sequence in the 12 cases tested. Nuclear accumulation of beta-catenin did not correlate with lymph node metastasis or 5-year survival. These findings suggest that high intranuclear levels of beta-catenin protein play an important role in early tumor growth and may function in initiation of invasive processes in intestinal-type gastric carcinoma.     

HLA-B40, B18, B27, and B37 allele discrimination using group-specific amplification and SSCP method

We developed a system for discriminating HLA-B40, B18, B27, and B37 alleles using a two-step PCR method followed by SSCP analysis. Fragments (0.8 kb) including exon 2, intron 2, and exon 3 were amplified in the first PCR. We used two sets of primers, one specific for HLA-B60-related alleles and the other specific for HLA-B6l-related, B18, B27, and B37 alleles. No amplifications of other class I genes or pseudogenes were observed. In the second PCR, exon 2 and exon 3 were amplified separately, using diluents of the first PCR products as templates. HLA-B6l-related, B18, B27, B37, and B60-related alleles were clearly discriminated in the SSCP analysis of the second PCR products. In a population study in which B6l alleles were analyzed, B^*4003 was detected in two Japanese individuals in addition to two B6l alleles previously reported to occur in Japanese, B^*4002 and B^*4006. The relative frequencies of B^*4002, B^*4006, and B^*4003 in Japanese were 58, 35, and 6%, respectively. The individuals having B^*4003 are the first non-South Americans in whom this allele has been detected. The SSCP banding patterns of 18 HLA-B60-positive Japanese population samples were identical to those of a B^*40012 sample for both exon 2 and exon 3. We also demonstrated that the B37 allele occurring in some Japanese is B^*3701.     

Immunolocalization of aromatase in human minor salivary glands of the lower lip with primary Sjogren's syndrome

The enzyme aromatase Is Involved In the conversion of androgens to estrogens and in the modulation of various androgenlc and estrogenlc actions. Abnormalities of estrogen metabolism have been postulated to play roles in the development and/or pathophyslology of Sjdgren's syndrome. In the present study, aromatase was immunolocal-ized In 75 cases of Inflammatory disorders of human minor salivary glands of the lower lip. These included cases of primary Sjögren's syndrome (19 cases), of chronic slaladenitis (34 cases) and of mucous extravasation cysts (22 cases), in order to clarify the possible involvement of in situ estrogen production in primary Sjögren's syndrome. Aromatase Immunoreactlvlty was detected In myoepithelial cells of acini and in interstitial cells adjacent to acini and ducts In 13/19 (68%) cases of primary Sjögren's syndrome. In contrast, aromatase expression was detected In only six of 34 (18%) cases of chronic sialadenttis and in seven of 22 (32%) cases of mucous extravasation cyst. These results suggest that Increased aromatase expression in minor salivary glands with primary Sjogren's syndrome in premenopausal women may be involved in the biological features of primary Sjogren's syndrome through the production of estrogens in situ and possibly through the aggravation of the inflammatory reaction.