Biomedical subjects
Publications and source records attributed to Y Kamibayashi.
This report describes two cases of congenital ectopic nail with bone deformity. Histologically, the squamous epithelium of the nail matrix lacked a definite granular layer. Resected nail tissue was connected with the periosteum of the tip of the ungual phalanx, which suggested that the contact of the ectopic nail matrix with the periosteum could impede intramembranous ossification and deform the bone shape.
We previously reported that LEC rats, which show a spontaneous occurrence of liver injury and hepatocellular carcinoma (HCC), are highly susceptible to chemical carcinogens such as diethylnitrosamine (DEN). Since abnormal copper accumulation in the liver of LEC rats was found to be a cause of liver injury, it is necessary to elucidate whether the carcinogen susceptibility of LEC rats is related to the accumulation of copper in the liver. In this study we have examined the relationship between the susceptibility of FI [LEC x LEA or LEC x Fischer 344 (F344)] and FI backcross rats to DEN and hepatic copper concentration, as copper accumulation has been demonstrated to be inherited as an autosomal recessive trait. The groups of F1 and F1 backcross rats were given a single intraperitoneal injection of DEN (20 mg/kg wt) and subjected to a modified Solt-Farber protocol for assaying glutathione S-transferase placental form (GST-P)-positive foci. The hepatic copper concentration was examined by atomic absorption. Although no F1 rats showed a high copper concentration in the liver, the numbers of foci were as high as those in LEC rats which accumulate copper. Backcross rats separated into high and low copper concentration groups at an almost 1:1 ratio, but there was no significant difference in the mean numbers of foci between these two groups. The results clearly indicate that the high susceptibility of LEC rats to DEN is genetically independent of copper accumulation in the liver. A possible dominant inheritance of this high carcinogen susceptibility was suggested. Biochemical measurement of cytochromes P450 and b5 in the liver of F1 rats indicated that alterations in drug metabolizing enzymes may be partially responsible for the high carcinogen susceptibility of LEC rats.
To elucidate what changes in the expression of gap junction proteins (connexins) occur at what stages during multistage mouse skin carcinogenesis in vivo, we immunohistochemically and morphometrically analyzed the expression of connexin 26 (Cx26) and connexin 43 (Cx43) in papillomas, well-, moderately- and poorly-differentiated squamous cell carcinomas, as well as in squamous cell carcinomas at invasion sites and those metastasized into lymph nodes in female CD-1 mice as a result of treatment with dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. In papillomas, no clear reduction of the two connexins was observed; however, Cx26 and Cx43 were frequently co-localized in the same gap junction plaques, whereas the two kinds of Cxs were differentially expressed in normal and surrounding non-tumorous epidermis. In squamous cell carcinomas, the expression of both Cx26 and Cx43 significantly decreased compared with surrounding non-tumorous epidermis and papillomas. The Western blot analysis confirmed that both Cx26 and Cx43 proteins were reduced in squamous cell carcinomas compared with papillomas. Furthermore, the expression of Cx26 was reduced as cancer cells became morphologically less differentiated, while that of Cx43 did not change. Squamous cell carcinomas at invasive sites showed clear reduction of Cx26 and Cx43. In squamous cell carcinomas metastasized into lymph nodes, Cx26 was expressed, but few carcinoma cells expressed Cx43. The localization of E-cadherin on the plasma membrane between cancer cells was maintained even at invasive and metastatic sites. Our data suggest that quantitative and qualitative changes in connexin expression are associated with tumor progression, including the loss of differentiation, and invasion and metastasis, during multistage mouse skin carcinogenesis.
We examined the expression of the gap junction proteins connexin 26 (Cx26), 32 (Cx32), and 43 (Cx43) in keratinocytes of newborn mouse epidermis to elucidate which connexins are expressed in keratinocytes in intact skin of newborn mice, and whether the expression of connexins is modulated during terminal differentiation of keratinocytes. Immunofluorescent staining using antibodies against Cx26, Cx32, and Cx43 combined with type-specific anti-keratin immunohistochemistry showed that Cx26 was expressed in keratinocytes in the granular layer and in the upper part of the squamous layer, whereas Cx43 was localized in keratinocytes in the basal layer and in the lower part of the squamous layer. No specific staining of Cx32 was found in mouse epidermis. Double staining of Cx26 and Cx43 revealed that some keratinocytes in the squamous layer expressed both connexins, but that in most cases localization of the two kinds of connexins was different, i.e., Cx26 was localized on the upper surface, whereas Cx43 was present on the lower surface of the plasma membrane of keratinocytes. Northern and Western blot analyses confirmed that Cx26 and Cx43, but not Cx32, were expressed at mRNA and protein levels in newborn mouse skin. These results suggest that the modulation of connexin expression from Cx43 to Cx26 takes place during terminal differentiation of keratinocytes in mouse epidermis.
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