Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis.

AIMS: To test the hypothesis that cyclooxygenase (COX)-1 or COX-2 expression is defective in lungs in idiopathic pulmonary fibrosis (IPF) and to characterize the cellular distribution. IPF is a progressive inflammatory lung disorder with an adverse prognosis. Previous work has shown that prostaglandin E2 (PGE2) regulates collagen deposition and fibroblast proliferation and a defect in COX regulation may contribute to the fibrosis that occurs in IPF. METHODS: Immunohistochemistry was utilized to determine COX immunoreactivity in lung sections from 25 IPF, six sarcoidosis and 14 control subjects. RESULTS: COX-1 and COX-2 expression in bronchiolar epithelial cells was significantly lower in IPF and sarcoidosis than in controls. No significant difference was found in COX-2 expression between macrophages in IPF and control sections, but COX-2 was reduced in macrophages in sarcoidosis compared with controls. CONCLUSIONS: These studies confirm COX-2 loss in bronchial epithelial cells but not macrophages in IPF, and show for the first time reduced constitutive COX-1 expression in epithelial cells and macrophages. Similar abnormalities were observed in sarcoidosis.

fas-fas-ligand antigen expression and its relationship to increased apoptosis in acute renal transplant rejection.

BACKGROUND: To examine the role of fas-fas-ligand interaction and apoptosis in acute transplant rejection. METHODS: Pre- and posttransplant renal allograft biopsies were stained by in situ 3-end labeling of DNA for detection of apoptotic cells (TUNEL) and immunohistochemistry techniques were used for demonstration of fas and fas-ligand antigen expression. RESULTS: Posttransplantation apoptosis was significantly increased in acute rejection and acute tubular necrosis (P<0.0001) compared to preimplantation biopsies and biopsies taken from grafts showing dysfunction not attributed to rejection. Fas and fas-ligand expression was demonstrated predominantly in the tubular epithelium. In preimplant biopsies fas was expressed in 11% (4/37) of cases; posttransplantation expression increased to: 44% (8/18) acute rejection, 63% (5/8) acute tubular necrosis, and 38% (5/13) dysfunction without evidence of rejection. Fas-ligand was expressed by 30% (11/37) of preimplant biopsies, posttransplantation expression was reduced in all groups: 17% (3/18) acute rejection, 13% (1/8) acute tubular necrosis, delayed xenograft rejection and 15% (2/13) dysfunction without evidence of rejection. A correlation with fas-1 expression preimplantation and a subsequent absence of acute rejection post transplant was noted (P<0.001). CONCLUSIONS: Apoptosis is a feature of acute rejection and acute tubular necrosis. Fas expression is uncommon preimplantation and increases non-specifically post transplant. Fas-1 was expressed by a third of preimplantation biopsies and expression was lost non-specifically post transplant. The expression of fas-ligand preimplantation correlated with an absence of acute rejection episodes posttransplant, suggesting some degree of immune privilege. These data suggest that the fas-fas-1 mediated pathway does not play a specific role in apoptosis during acute rejection. We were unable to find any evidence that the fas-fas-1-mediated pathway has a role in the increased apoptosis seen during acute rejection.

Use of tumour marker immunoreactivity to identify primary site of metastatic cancer.

OBJECTIVES: To determine whether variations in the expression of tumour related antigens can predict the origin of tumours. DESIGN: Immunohistological study of tumour marker expression in primary adenocarcinomas and respective metastatic deposits. Antibodies to the following tumour markers were used: polymorphic epithelial mucin (NCRC-11 and SM3), carcinoembryonic antigen, carcinoembryonic antigen with non-specific antigen co-specificity, CA125, CA19.9, prostate specific antigens, and thyroglobulin. SETTING: Histopathology department of teaching hospital. SUBJECTS: 100 pathology sections of metastatic adenocarcinoma and their related primary tumours. MAIN OUTCOME MEASURES: Concordance of reactivity between primary and metastatic tumours. Reactivity profiles of tumour sites. RESULTS: The correct primary site of origin was predicted in 70% (33/47) of tumours in men and 54% (27/43) tumours in women with antibodies SM3, 288, CA19.9, CA125, and PSA (men only). Specificities ranged from 68% for breast tumour to 98% for prostate tumour. CONCLUSION: Use of tumour markers in patients presenting with metastatic adenocarcinoma of unknown origin can help localise the probable primary sites and reduce the need for extensive and expensive imaging techniques.

Immunocytochemical investigation of intermediate filament proteins and epithelial membrane antigen in spindle cell tumours of the breast.

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.

The site of renin in the human uterus.

Renin has been known to be present in the human uterus for many years. The study reported in this paper deals with the identification of the site of renin in the human uterus by the peroxidase-antiperoxidase technique, using anti-human renin. Cells containing renin granules have been demonstrated only in patients complaining of menorrhagia. The cells occur singly and in clusters in the interarteriolar connective tissue within myometrium adjacent to the endometrium. The cells bear a striking resemblance to those of the juxta-glomerular apparatus of the kidney.