[Survey on the status of chronic rheumatoid arthritis. 1) Osaka city].
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Biomedical subjects
Publications and source records attributed to M Tsujimoto.
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Addition of a lauroyl, stearoyl or docosanoyl group to the primary hydroxy group at the C-6 position of N-acetylmuramyl-L-alanyl-D-isoglutamine gave lipophilic derivatives that had definite adjuvancies in induction of delayed-type hypersensitivity and enhancement of antibody production against a test protein antigen, ovalbumin, when administered to guinea pigs as liposomes, that is without mineral oil. When administered as mineral oil-in-water emulsion, including Ribitype emulsions, rather than as water-in-mineral oil emulsions, N-acetylmuramyl-L-alanyl-D-isoglutamine and its 6-O-acyl derivatives showed only weak immunoadjuvancies.
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Bile duct cancers are still difficult to cure, and even if curatively resected locoregional recurrences are frequent. Biologic proliferative activity of the cancer may influence postoperative recurrence and the prognosis. A retrospective study was performed with the medical records of 44 consecutive patients who underwent surgery for histologically extrahepatic bile duct cancer (stage 3 or 4) at Osaka Police Hospital during the period 1980 to 1992. Univariate analysis suggested that the stage according to the UICC classification, curability, DNA ploidy, proliferating cell nuclear antigen (PCNA), S-phase and G2M-phase fractions, and histologic differentiation were significant prognostic factors. The Cox's proportional hazard model indicated that PCNA and histologic differentiation were independent prognostic factors for crude and cause-specific survival. When PCNA was omitted from the analysis, DNA ploidy and histologic differentiation were independent prognostic factors for both crude and cause-specific survival. These results suggested that proliferative activity influenced the postoperative prognosis of extrahepatic bile duct cancer.
The electron-microscopic features of a thyroid follicular adenoma with clear cell change is described. The tumor was 7 mm in size and located in the upper portion of the left lobe of the thyroid of a 29-year-old Japanese female. Its cut surface was pale brown in color and well demarcated. The lesion consisted of solid nests with pinpoint lumina. The cytoplasm of the tumor cells was completely clear, but slightly vesicular without oncocytic change. Electron-microscopic examination revealed that the cytoplasm of the tumor cells was filled with numerous empty vacuoles. The vacuoles consisted of dilated membranous structures, indicating that they had been formed from rough endoplasmic reticulum and Golgi apparatus. There was no accumulation of glycogen, mucin, or lipid. The dilated membranous structures in the cytoplasm may be related to the increased thyroglobulin synthesis by the tumor.
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Previous studies have demonstrated an elevated level of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA in hepatocarcinogenesis in a rodent model and of its protein as well as mRNA in human hepatocellular carcinoma (HCC). In order to elucidate the clinical significance of HB-EGF in human HCC, we immunohistochemically investigated its expression in 100 HCC cases with different characteristics. HB-EGF was not or only faintly expressed in non-cancerous hepatocytes. On the other hand, 59% of the HCC cases were classified as positive for HB-EGF, and its expression was more frequently observed in cases with low proliferating activity, at an early stage, of small size, without portal invasion, low alpha-fetoprotein level, without satellite nodules (borderline significance), and well or moderate differentiation. Furthermore, HB-EGF expression showed prognostic significance in both univariate and multivariate analyses and can be regarded as an independent prognostic factor of disease-free survival. These results strongly suggest the involvement of HB-EGF in early stage of HCC.
Expression of cell cycle modulators at the G1-S boundary, the retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1 as well as Ki-67 was investigated with 39 extrahepatic bile duct carcinomas (BDC). The Ki-67 labeling index (LI) was higher in cases with poor differentiation, lymph node metastasis and stage III or IV. Cyclin D1 overexpression was seen in 14 cases (35.8%). This phenomenon could be observed more frequently in cases of hilar carcinoma and with poor differentiation, perineural invasion, lymphatic invasion and lymph node metastasis. Furthermore, Ki-67 LI was higher in cyclin D1 overexpressing cases. p27 expression showed inverse relationships with Ki-67 LI, lymph node metastasis and aberrant p53 expression. Although p16 and p21 expression significantly correlated with lymph node metastasis and cyclin D1 overexpression, respectively, they were not related to Ki-67 LI. pRb expression was observed in all cases. Although the LI was lower in carcinoma of upper and middle bile ducts, no correlation was established between pRb expression and other clinicopathological parameters including Ki-67 LI. Aberrant p53 expression was observed in 13 cases (33.3%) and Ki-67 LI was significantly higher in these cases. These findings suggest that p27 and cyclin D1 strongly correlate with BDC proliferation and reflect the biological aggressiveness of this carcinoma.
Fas and Fas ligand expression were immunohistochemically investigated in 34 extrahepatic bile duct carcinomas (BDC) and nine ampulla carcinomas (AC). Fas expression was regarded as positive in 22 BDC cases (64.7%). The absence or decreased expression of Fas was frequently observed in cases with high biological aggressiveness such as advanced stage, moderate or poor differentiation, lymph node metastasis, aberrant p53 expression and high Ki-67 labeling index. A similar tendency was observed in AC where two cases without Fas expression were poorly differentiated with a high Ki-67 labeling index. Fas ligand expression in infiltrating mononuclear cells adjacent to the carcinoma nests was observed in only four BDC (11.1%) and in none of the AC examined. Fas ligand expression in carcinoma cells was observed in only one BDC, which showed Fas ligand expression also in mononuclear cells and not in any AC case. These results suggest that, although BDC and AC very frequently express Fas, Fas-mediated apoptosis is only occasionally induced in carcinoma cells because of the lack of Fas ligand expression in infiltrating mononuclear cells in these carcinomas.
bcl-2 expression in 38 extrahepatic bile duct carcinomas was immunohistochemically investigated in order to clarify its clinical significance in this carcinoma. bcl-2 was expressed in 17 cases (44.7%), in which more than 10% of the carcinoma cells were positive for bcl-2. bcl-2 expression was more frequently absent in cases with advanced stages (p = 0.0642), lymph node metastasis (p = 0.0009), perineural invasion (p = 0.0647) and aberrant p53 expression (p = 0.0181). Furthermore, bcl-2 expression was inversely related to the incidence of apoptosis (p = 0.0002) and proliferating activity of the cells (p < 0.0001). These results suggest that bcl-2 plays a role in negatively regulating apoptosis and its loss can be significantly linked to the biological aggressiveness of this carcinoma.
BACKGROUND: Cyclin D3, one of the D type cyclins, has been known as a cell cycle modulator at the G1-S phase. In the present study, we investigated its expression in pancreatic adenocarcinoma in order to elucidate its clinical role. MATERIALS AND METHODS: We examined cyclin D3 as well as, cyclin D1 overexpression in 60 pancreatic adenocarcinoma by means of immunohistochemistry. RESULTS: Cyclin D3 overexpression was found in 33.3% (20 cases) of the cases, being more frequently seen in cases showing high Ki-67 labeling index, stage IV, moderate- or poor-differentiation, lymph node metastasis and large size and cyclin D1 overexpression. Multivariate logistic analysis independently linked cyclin D3 overexpression to tumor size (p = 0.0392) and stage (p = 0.0312). Cyclin D1 overexpression was observed in 41.7% (25 cases) and was related to Ki-67 labeling index, cyclin A overexpression, stage, carcinoma differentiation, lymph node metastasis, tumor size, lymphatic invasion, perineural invasion and retropancreatic invasion. It was independently linked to carcinoma differentiation (p = 0.0081), lymph node metastasis (p = 0.0426) and lymphatic invasion (p = 0.0269). CONCLUSION: These results suggest that cyclin D3, as well as cyclin D1, plays a role in the progression, including cell proliferating activity, of pancreatic adenocarcinoma.