ISSN:0022-3417    

DOI:10.1002/path.1711680202

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractComparative analysis of expression levels of genes in benign and malignant tumours of the breast has been performed. Differential screening of cDNA libraries identified four genes of the mitochondrial genome as being expressed at different levels in the two tissues compared, but further investigations showed that only the gene encoding subunit 2 of cytochromecoxidase (COII) is expressed at significantly higher levels in carcinomas compared with fibroadenomas. The mitochondrial genes encoding subunits 2 and 4 of NADH dehydrogenase, and subunit 6 of F0F1ATPase, were not found to be differentially expressed in carcinomas and fibroadenomas. All four genes were expressed in the epithelium of human breast carcinomas, as shown byin situhybridization. The expression level of the COII gene is also correlated with carcinoma grade. No gross alterations to the mitochondrial DNA from these tumours could be detected. The possible implications of these results on the behavioural differences between fibroadenomas and carcinomas are discussed.

ISSN:0022-3417    

DOI:10.1002/path.1711680203

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractBrains from mice infected with either the 87V or the ME7 strains of mouse‐passaged sheep scrapie were taken at stages during the disease process and immunostained to show the localization of ubiquitin‐protein conjugates. In both models, conjugates were seen as fine, dot‐like structures; as coarser, granular lesions within or adjacent to neurones; and in areas surrounding plaques. The dot‐like structures were visible at 28 days post‐ME7 infection and at 55 days in 87V‐infected mice. In both models, the extent of immunoreactive changes increased as the disease progressed and terminal infection was as described earlier by us (Loweet al., J. Pathot1990;162: 61–66). The patterns of development of these features were distinctive in two ways: progression from region to region was observable and the density of the pathological lesions grew exponentially as the clinical symptoms appeared. The earliest pathological dot‐like structures corresponded temporally with the earliest detection of PrPscby Western blotting, and immunogold electron microscopic investigation of the dot‐like lesions indicated that they were the multi‐vesicular, lysosome‐related, dense bodies that we have described previously in terminal disease (Laszloet al., J Pathol1992;166: 333–341).Until now, ubiquitin–protein conjugates were seen mainly in inclusion bodies associated with the terminal stages of a range of human degenerative diseases. This study establishes that ubiquitin–protein conjugates accumulate in lysosome‐related bodies very early and appear to be intimately related to the pathological processes in the animal d

ISSN:0022-3417    

DOI:10.1002/path.1711680204

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractImmunohistochemical staining with a novel monoclonal antibody, KiSl, which recognizes a cell cycle‐associated antigen, was investigated in 142 cases of stage I and II invasive breast carcinoma. KiS 1 staining indices were compared with disease‐free interval, overall survival, and post‐relapse survival. Using a semi‐quantitative method of assessment, we found that tumours with a high level of staining (34/142,24 per cent) had a significantly worse prognosis than those with a low level of staining (108/142, 76 per cent). Significant correlations were found between KiS1 staining and disease‐free interval (P<0·001), overall survival (P<0·001), and post‐relapse survival (P=0·008). A more time‐consuming, quantitative method of assessment gave similar results. Cox multivariate analysis showed these results to be independent of nodal status, histological type, and grade of tumour (P=0·01). We conclude that KiS1 is a valuable new antibody which affords useful prognostic information in breast carcinoma. As it can be used in formalin‐fixed, paraffinembedded material, it may be of particular use in the study of small lesions such as those identified in the Breast Cancer

ISSN:0022-3417    

DOI:10.1002/path.1711680205

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractUsing spleen cells from athymic nude mice grafted with Ichikawa tumour, we have generated the monoclonal antibody IND.64, which detects a proliferation‐associated nuclear antigen. Immunoblotting analysis with IND.64 showed a double band with apparent molecular weights of 395 and 345 kD. In normal human tissues, the antigen detected by IND.64 was expressed only by the nuclei of proliferating cells, such as germinal centre cells of reactive lymph nodes, cortical thymocytes, the basal layer of the skin, and proiiferative compartments of the stomach, small intestine, and colon. IND.64 did not react with cells known to be non‐proliferative or to show only a low turnover, such as cells of the kidney, liver, smooth muscle, cardiac muscle, and brain. The expression of this antigen during the cell cycle was determined using two approaches: IND.64 immunostaining of synchronized adult bovine aortic endothelial cells and flow cytometric analysis of double‐labelled PHA‐stimulated peripheral mononuclear blood leucocytes with a DNA marker and IND.64. The antigen recognized by IND.64 was found to appear in the late G1 phase, and persisted in phases S, G2, and M, but was absent in the G0 and early Gl phases. IND.64 was further investigated in different tumour types to evaluate the correlation between the percentage of IND.64‐positive cells (IND.64 index) and the histological grade. In non‐Hodgkin's lymphomas, an excellent correlation was found between the percentage of IND.64‐positive cells and the cytomorphological grade. In nodular sclerosis and mixed cellularity Hodgkin's disease, a high number of Reed‐Sternberg cells were positive with IND.64. The non‐lymphoid neoplasms investigated showed a variable percentage of positive cells, IND.64 appears to be a promising tissue marker to complement the evaluation of prognosi

ISSN:0022-3417    

DOI:10.1002/path.1711680206

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe effect of delayed fixation on the immunoreactivity of proliferating cell nuclear antigen (PCNA) was investigated using eight breast carcinomas. Topologically shuffled samples of each tumour were immersed in fixative at times of 0·5. 1,2,4,6,18, and 24 h after surgical removal. In addition to a PCNA index (percentage of positive cells per 1200 tumour cells), a semi‐quantitive PCNA grading system was used, based on estimates of more than or less than 50 per cent of positive tumour cells at each time interval. The PCNA index of six tumours increased by a mean of 10 per cent with a fixation delay of 24 h. The PCNA grade of all eight tumours showed no change with delayed fixati

ISSN:0022-3417    

DOI:10.1002/path.1711680207

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMorphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow‐up data were available for these patients, which were drawn from a larger, previously reported series.1The morphometric data were compared with patient survival, clinico‐pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico‐pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P<0·01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico‐pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P<0·01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferat

ISSN:0022-3417    

DOI:10.1002/path.1711680208

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe distribution of cell adhesion molecules (CAMs) and matrix proteins in the normal synovium of four subjects was studied by immunohistology in order to determine the factors governing the cellular and tissue organization of the intimal and subintimal compartments. Basement membrane proteins, laminin, and collagen type IV, as well as vitronectin and fibronectin, were identified in the intima and there was corresponding expression of integrin and non‐integrin receptors (e.g., CD29, CD49b, CD49d, CD49e, CD49f, CD51, CD61, CD44) for these matrix proteins. There were notable differences in CAM expression between intimal, subintimal, and vascular compartments of the synovial membrane. Phenotypic heterogeneity for CAMs involved in cell–cell interactions, particularly CDlla, CD 11 b, ICAM‐1, and HLA‐DR, was also present. The range of CAMs expressed by synovial and endothelial cells not only indicates a structural role for these antigens, but also suggests that they may control leucocyie traffic into the membrane, including recruitment of cells into the synovial

ISSN:0022-3417    

DOI:10.1002/path.1711680209

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractWe have previously reported that heparin can enhance the removal of antigen from the glomeruli of rats with chronic serum sickness glomerulonephritis. We have performed two studies to investigate the relevance of anticoagulation to this effect. The first experiment was essentially a repeat of those described before, but instead of using heparin, anticoagulation was achieved using Ancrod, which causes depletion of fibrinogen. The amount of antigen in the glomeruli of these rats at the end of the experiment did not differ from controls. In the second experiment, both kidneys were excised from rats with glomerulonephritis induced by a radiolabelled cationic antigen. Of each pair of kidneys, one was perfused for 30 min at 5 ml/min with Hank's balanced salt solution (HBSS) at 37°C. The other was perfused with HBSS to which a total of 4500 units of heparin had been added. The antigen content of isolated glomeruli was subsequently measured. In every case, the kidney perfused with heparin had less antigen per glomerulus than the control contralateral kidney. The ability of heparin to enhance removal of glomerular immune complex deposits is therefore not mediated by anticoagulation

ISSN:0022-3417    

DOI:10.1002/path.1711680210

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractInjection of isologous monoclonal antibodies (SR2, SR3) caused anti‐glomerular basement membrane antibody‐induced glomerulonephritis (anti‐GBM nephritis) in WKY/NCrj rats. The antibodies were obtained from hybridoma cells derived from fusion of the spleen of a nephritic WKY/NCrj ral injected with rat solubilized renal basement membranes with adjuvant, and mouse SP2 myeloma cells. They belonged to the rat IgG2a subclass and bound to rat kidney in a linear pattern along the glomerular and tubular basement membranes. Histological changes in glomeruli were detected at day 1 after the injection; proteinuria with haematuria appeared on day 2; and proteinuria became severe and reached a plateau by day 5. These results demonstrate that anti‐GBM nephritis can even be induced by an isologous monoclonal antibody and that the rat IgG2a subclass is at least nephritogenic. The experimental model of anti‐GBM nephritis with isologous monoclonal antibodies makes it possible and easier to analyse further the mechanism of anti‐GB

ISSN:0022-3417    

DOI:10.1002/path.1711680211

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY