Plasma von Willebrand factor and thrombomodulin as markers of vascular disorders in patients undergoing regular hemodialysis therapy

Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are regarded as reflecting the release reaction by vascular endothelial cells and/or endothelial cell injury, and increased levels of thrombomodulin (TM) antigen as reflecting damage to endothelial cells. We investigated changes in plasma vWF:Ag and TM antigen levels during the course of regular hemodialysis treatment (RDT) in 14 patients undergoing RDT in order to evaluate the effect of hemodialysis (HD) on endothelial cells. vWF:Ag and TM were both measured by the sandwich EIA method. Predialysis levels of vWF:Ag and TM in RDT patients were both significantly higher than normal control values. Neither patient age nor blood pressure was not correlated with predialysis vWF:Ag and TM levels. Both vWF:Ag and TM levels significantly increased during a single HD session. There was a positive correlation between predialysis TM levels and duration of HD and an inverse correlation between the amount of vWF:Ag released during HD and duration of HD. It appears that HD procedures induce stimulation and damage of endothelial cells and that long-term, recurrent HD treatment may predispose to vascular disorders.     

Significance of α9β1 and αvβ6 integrin expression in breast carcinoma

Background  Both α9β1 and αvβ6 integrins have been newly identified from the tracheal epithelium of guinea pig. It has been pointed out that α9β1 functions as a receptor for tenascin-C and osteopontin. As for the ligands of αvβ6, fibronectin and tenascin-C have been identified. It has not been ascertained whether α9β1 and αvβ6 are expressed in normal breast tissue, benign breast lesion or breast carcinoma. Methods  Immunohistochemical staining for α9β1 and αvβ6 was performed in benign breast lesion and breast carcinoma specimens. Western blotting was carried out on 11 breast carcinoma cases. Results  α9β1 was expressed in the cytoplasm of carcinoma cells in 23 of 90 cases (26%) and αvβ6 in the membrane of carcinoma cells in 16 of 90 cases (18%). However, these findings of α9β1 and αvβ6 did not correlate with any clinicopathological factors including the patients’ age, tumor size, histological type of carcinoma, location of carcinoma cells and hormone receptor status. With regard to the histological grade of carcinoma, αvβ6 and α9β1 expression did not statistically correlate, although no expression of αvβ6 was observed in 14 cases of Grade I. On Western-blott analysis strong and weak bands consistent with αvβ6 were noted in the membrane fraction extracted from breast carcinoma cells. On the other hand weak bands consistent with α9 subunit were noted in the whole cell lysates of breast carcinoma cells and very weak or no bands consistent with α9 subunit were noted in the membrane fraction extracted from the breast carcinoma cells. Conclusions  Significance of α9β1 and αvβ6 integrins expression in breast carcinoma was still unknown on clinicopathological examination. The findings of Western blot analysis may indicate that the transportation system of glycoproteins such as integrins to the cell membrane of carcinoma cells is disturbed, although these integrins can be produced.     

Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach.

Gastric cancer is one of the most common malignancies worldwide. In this study, we screened for genes upregulated in gastric cancer by comparing gene expression profiles from serial analysis of gene expression and microarray and identified the palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) gene. Immunostaining for PLUNC in 140 gastric cancer cases revealed strong and extensive staining of PLUNC in hepatoid adenocarcinoma of the stomach, whereas 7% of conventional gastric cancer cases showed focal immunostaining of PLUNC. Gastric hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphologic similarities to hepatocellular carcinoma. To investigate the utility of PLUNC immunostaining in the diagnosis of gastric hepatoid adenocarcinoma, six cases of gastric hepatoid adenocarcinoma (six primary tumors and two associated liver metastases) were studied further. PLUNC staining was observed in all six primary hepatoid adenocarcinomas. PLUNC staining was observed in both the hepatoid adenocarcinoma and tubular/papillary adenocarcinoma components of primary tumors, although PLUNC staining was preferentially localized in tubular/papillary adenocarcinoma components. Staining of PLUNC was also detected in both liver metastases. PLUNC staining was not observed in 52 cases of primary hepatocellular carcinoma or in normal adult or fetal liver. These results indicate that PLUNC is a novel marker that distinguishes gastric hepatoid adenocarcinoma from primary hepatocellular carcinoma.     

Epithelial hyperplasia of the breast. Comparison of incidence between cases of breast carcinoma and control autopsy specimens with immunohistochemical observation of blood group antigens.

Epithelial hyperplasia in the duct, ductule or lobule of the breast is a very common lesion and has been considered to carry a risk of subsequent invasive carcinoma. However, it is not known whether epithelial hyperplasia can transform into carcinoma or whether malignant change occurs de novo. We analyzed the incidence of epithelial hyperplasia of the breast by making a comparison between cases of breast carcinoma and control autopsy specimens, and studied differences in the membrane antigens of the constituent cells using immunohistochemical staining of blood group antigens. It was found that the frequency of epithelial hyperplasia was higher in the cases of breast carcinoma. The lesions showed loss of A, B and H antigens at high frequency, and the proportion of lesions showing loss of these antigens became higher as the atypia of the lesion increased. On the other hand, expression of Lea antigen was observed more frequently in atypical epithelial hyperplasia or in situ carcinoma than in ordinary epithelial hyperplasia. These findings suggest possible transformation from epithelial hyperplasia to carcinoma, and indicate that atypical epithelial hyperplasia may be precancerous in nature.     

Long term administration of cyclophosphamide in MRL/1 mice. I. The effects on the development of immunological abnormalities and lupus nephritis

Weekly injection of cyclophosphamide (Cy) into MRL/Mp-lpr/lpr (MRL/l) mice, at a dose of 10-20 mg/kg, from 1 month of age prevented the development of generalized lymph node enlargement, decreased serum levels of anti-DNA antibodies and immune complexes, and markedly prolonged their life span. Cy effectively suppressed enhanced differentiation of B cells, as evidenced by decreased number of immunoglobulin secreting cells in the spleen. Cy was also shown to suppress abnormal expansion of Thy-1 positive cells in lymphoid organs of MRL/1 mice. These results suggested that Cy prevented the development of murine lupus like syndrome in MRL/1 mice through suppression of spontaneous polyclonal B cell activation and also by reducing the number of T cells to exert excessive helper activity on B cells.     

Comparison of thallium-201 and gallium-67 imaging in evaluation of head and neck tumors

PURPOSE: 201Tl imaging was compared with 67Ga imaging in the detection of malignant head and neck tumors. METHOD: Eighteen patients with tumors in the head and neck region underwent both planar and SPECT imaging using 201Tl-chloride and 67Ga-citrate. The detection of primary tumors and lymph node (LN) metastases by visual evaluation was compared between 201Tl and 67Ga imaging. Additionally, quantitative analysis of the SPECT images was performed in eight patients. RESULTS: On visual evaluation, primary tumor uptake was detectable in 100% on the 201Tl SPECT images compared with 44% on the 67Ga SPECT images. The sensitivity, specificity, and accuracy of 201Tl in detecting LN metastases were higher than those of 67Ga SPECT; however, there was no statistical difference between 201Tl and 67Ga. The tumor-to-background ratio was significantly higher on 201Tl SPECT than on 67Ga SPECT. CONCLUSION: This study suggested that 201Tl could be useful in the evaluation of malignant tumors in the head and neck region.     

Trends in Benign Breast Tumors in Japanese Women, 1973–1995: Experience of Hiroshima Tumor Tissue Registry

Although some benign breast lesions such as multiple intraductal papilloma have been pointed out as a risk factor for breast cancer, there is little documentation about trends in the incidence of benign tumors of the breast in Japanese women. The author conducted an epidemiological study using data abstracted from the Hiroshima Tumor Tissue Registry file, which includes cases of malignant and benign neoplasms in Hiroshima prefecture between 1973 and 1995. A total of 17 064 cases of female breast tumor were registered in the file between 1973 and 1995. The registration rate for fibroadenoma of the female breast was 19.5 among females and peaked during the 5-year period 1983–1987, while the fibroadenoma registration rate in Hiroshima gradually decreased between 1988 and 1995. The registration rate for intraductal papilloma has risen substantially in Hiroshima, with about a 5-fold increase among females between 1973 and 1995. The mean proportion of fibroadenoma cases accompanied by malignant tumors of the breast was 1.85%, and there was no significant change in the mean proportion between 1973 and 1995 (P=0.17). On the other hand, the mean proportion of intraductal papilloma cases accompanied by malignant tumors of the breast gradually rose with about a 14-fold increase among females between 1973 and 1995. The significance of intraductal papilloma as a risk factor for breast cancer may have increased.