bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue iron loading and histopathological changes in hypotransferrinaemic mice
Authors: Simpson Robert J. , Konijn Abraham M. , Lombard Martin , Raja Kishor B. , Salisbury Jonathan R. , Peters Timothy J. 
Published: June 2005

AbstractTissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One‐year‐old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron‐loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron‐free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild‐type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6–12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6–8 weeks of age. It was concluded that 1‐year‐old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
pS2 protein in gastric carcinoma and normal gastric mucosa: Association with clinicopathological parameters and patient survival
Authors: Müller Wolfram , Borchard Franz 
Published: June 2005

AbstractThe presence of pS2 protein (pS2) was studied in a total of 120 consecutive patients with gastric carcinomas. This immunohistochemical study found pS2 expression in 48 per cent (n=58) of carcinomas. pS2 expression was also detected in normal gastric mucosa in 95 per cent (n=102) of specimens in upper antral mucopeptic glands and deep foveolar cells of the gastric pits but not in intestinal metaplasia. There was a significant statistical correlation between pS2 expression and extent of tumour growth (pT state) and expression of pepsinogen II by the tumours. There was no statistical correlation with clinical features such as patient age or sex or other pathological parameters (tumour stage, size, grade, and localization or growth pattern according to histological classification). There were no statistically significant differences in survival times between patients with pS2‐positive and pS2‐negative tumours. In contrast to findings concerning breast cancer, pS2 expression in gastric carcinomas has no influence on the patient's prognosis. On the other hand, strong expression of pS2 by surface epithelium of normal gastric mucosa may indicate that pS2 might play a role in physiological cell renewal of normal gastric mucosa.
Expression of p53 in oligodendrogliomas
Authors: Kros Johan M. , Godschalk Josiane J. C. J. , Krishnadath Kausilia K. , Van Eden Corbert G. 
Published: June 2005

AbstractThe expression of the nuclear protein p53 in oligodendrogliomas was investigated by immunohistochemistry, using a monoclonal anti‐p53 antibody (DO‐7) on formalin‐fixed, paraffin‐embedded material in 84 histologically verified cases, and compared with the histopathological grade and survival. p53‐immunoreactive cells were found in 75 per cent of the samples acquired at the first biopsy. The p53 labelling index was not related to the degree of nuclear anaplasia. Tumour cases with more than 75 per cent p53 immunostained cells had a rapidly fatal clinical course. However, no significant correlation was found between p53 labelling index and tumour grade, mitotic index, or ploidy status. In most tumour recurrences (n=25), the p53 labelling index increased or remained at the level of the first biopsy. In five cases (6 per cent), p53 was absent in the first sample as well as in the recurrence. Irrespective of the underlying aberration of either the gene or the metabolic pathway of p53, it is concluded that a high percentage (i.e., more than 75 per cent) of p53‐immunolabelled cells is predictive of an unfavourable clinical course, while a percentage lower than 75 per cent immunoreactive cells does not exclude a rapid fatal outcome.
Cytotoxicity of oxidized low‐density lipoprotein to mouse peritoneal macrophages: An ultrastructural study
Authors: Reid Vanessa C. , Mitchinson Malcolm J. , Skepper Jeremy N. 
Published: June 2005

AbstractMouse peritoneal macrophages (MPM) were incubated in culture medium containing low‐density lipoprotein (LDL), oxidized LDL (oxLDL), or as controls, for 24 h. Scanning electron microscopy of MPM exposed to oxLDL showed loss of membrane ruffles and extensive plasmalemmal ‘blebbing’. Transmission electron microscopy showed changes in up to 50 per cent of the cells, including vacuolation of the rough endoplasmic reticulum and reorganization of heterochromatin in the nuclei, characteristic of apoptosis. These changes were not seen in controls, nor in macrophages exposed to native LDL. Electron‐dense crystals were found in the cytoplasm of 1 in 50 of cells exposed to oxLDL. These were found to have a high content of calcium and phosphorus. It is proposed that oxLDL is capable of inducing apoptosis, which might explain the origin of the necrotic base of advanced atherosclerotic plaques.
An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms
Authors: Baas Inge O. , Mulder Jan‐Willem R. , Offerhaus G. Johan A. , Vogelstein Bert , Hamilton Stanley R. 
Published: June 2005

AbstractImmunohistochemical detection of intranuclear p53 gene product may indicate mutation of the p53 suppressor gene on chromosome 17p. We used six commercially available antibodies for p53 immunohistochemistry on 19 archival colorectal neoplasms and compared the results with the mutation status of the p53 gene and 17p allelic deletion status. By Friedman's ranking analysis, use of mouse monoclonal antibody DO7 with Target Unmasking Fluid (TUF) for antigen retrieval was the most sensitive and specific procedure (P<0·0001). Six of 7 cases with high expression (p53 Labeling Index >30 per cent using a CAS 200 image analyser) had p53 mutation. Of seven tumours without expression (LI < 1 per cent), six had no mutation and one had a truncating mutation which prohibited nuclear localization of gene product. The low expression group (1 per cent < LI <30 per cent, n = 5) consisted of three tumours without and two tumours with mutation. The sensitivity of high expression with the DO7–TUF method for p53 gene mutation was 67 per cent with specificity of 90 per cent, predictive value of a positive of 86 per cent, predictive value of a negative of 75 per cent, and efficiency of 79 per cent. This study suggests that immunohistochemistry is valuable for assessing p53 gene mutations in colorectal neoplasms, but further study is needed to elucidate the precise link between immunohistochemistry and molecular genetic alterations.
Variations in immunohistochemical detection of p53 protein overexpression in cervical carcinomas with different antibodies and methods of detection
Authors: Lambkin Helen A. , Mothersill Carmel M. , Kelehan Peter 
Published: June 2005

AbstractImmunocytochemical detection of p53 protein products in paraffin sections is possible with a number of antisera, monoclonal and polyclonal. Few corroborative results amongst different laboratories have been published due to variations in the antibodies, the fixation protocols, and the immunocytochemical methods applied. Antigen unmasking methods employing microwaves or proteolytic enzymes add to the disparity in the percentage of positive cases reported. In this study, paraffin sections of 55 cases of cervical carcinoma were immunostained with monoclonal antibodies p53‐DO7 and p53‐1801 (a) without section pretreatment, (b) with pronase digestion, and (c) with microwave antigen retrieval in citric acid buffer. Specimens fixed in buffered formalin required antigen unmasking to show positive staining. Pronase digestion caused false‐negative immunostaining. Microwave pretreatment with p53‐DO7 yielded 100 per cent positivity for p53 proteins but only 7/55 cases with more than 50 per cent positive cells. Monoclonal antibody p53‐DO7 detected more positive cases than p53‐1801. Immunostaining with antibodies to p53 proteins must be interpreted cautiously as variations in fixation, antibodies, and section pretreatment will significantly affect results.
NDP‐K/nm23 expression in human breast cancer in relation to relapse, survival, and other prognostic factors: An immunohistochemical study
Authors: Sawan Ali , Lascu I. , Veron M. , Anderson J. J. , Wright C. , Horne C. H. W. , Angus B. 
Published: June 2005

AbstractThe nm23 gene was originally identified by Steeg et al. by screening of cDNA libraries from murine melanoma cell lines of varying metastatic potential. An inverse relationship between metastatic potential and nm23 RNA and/or protein was found in four different metastatic model systems. It was proposed that nm23 may function as a suppressor gene for tumour metastasis. It has recently been found that the sequence of nm23 and NDP‐kinase (NDP‐K) is identical. Using an immunohistochemical technique and employing a polyclonal antibody to purified NDP‐K A, we have determined NDP‐K expression in a series of 197 breast carcinomas. One hundred and sixty (81·2 per cent) of these tumours were scored positive for NDP‐K and 37 (18·8 per cent) scored negative. No relationship was found between NDP‐K/nm23 expression and patient relapse or survival. Furthermore, no relationship was found between NDP‐K/nm23 expression and a number of other prognostic factors including tumour grade, oestrogen receptor, progesterone receptor, and p53 expression. Our results contradict the hypothesis concerning the possible role of NDP‐K/nm23 as a metastatic suppressor gene in human breast cancer, but further studies using antibodies specific for NDP‐K/nm23 subtypes are clearly indicated.
Production of two novel monoclonal antibodies against human renal glomeruli and theri application to the immunohistochemical investigation of crescentic glomerulonephritis
Authors: Kohda Yukimasa , Takeya Motohiro , Arima Seiya , Arima Seiya , Nakayama Mahito , Sato Tatsuo , Takahashi Kiyoshi 
Published: June 2005

AbstractTwo monoclonal antiboides (MAbs) against human renal glomeruli, HEP1 and HBM1, were produced using isolated human glomeruli as an antigen. Immunohistochemical and immunoelectron microscopic analyses revealed that the recognition site of HEP1 is the cell surface of the visceral glomerularepithelial cells. HEP1 showed no reaction in the renal interstitium or in other tissues. HBM1 recognized an antigen present in the basal lamina of the renal glomeruli, Bowman's capsule, and partly in the basement membrane of renal tubules, but it was not reactive with the mesangial matrix or renal interstitium. The isotype of both MAbs was IgG1, k. The molecular weights of their corresponding antigens were 127–177 and 220kD, respectively. Besides human tissues, HEP1 also showed cross‐reactions with antigens in the visceral glomerular epithelial cells of various animals other than mice. HBM1 recognized human antigen only. Using both MAbs, eight cases of crescentic glomerulonephritis were examined immunohistochemically. As a result, it was demonstrated that the crescents may not be formed by visceral glomerular epithelial cells. From this study, these two MAbs appear to be userful markers for the evaluation of renal glomerular disorders.
Ubiquitin profile in inflammatory leukocytes and binding of ubiquitin to murine AA amyloid: Immunocytochemical and immunogold electron microscopic studies
Authors: Alizadeh‐Khiavi K. , Li W. , Chronopoulos S. , Ali‐Khan Z. 
Published: June 2005

AbstractLysosomes in activated murine monocytoid cells have been implicated in AA amyloid formation. The pathophysiology of this process is not well understood. Previous studies into the nature of the relationship between ubiquitin (UB), possessing intrinsic amyloid enhancing factor (AEF) activity; serum amyloid A (SAA), the precursor protein of AA amyloid; and activated monocytoid cells have indicated a temporal and spatial relationship between these proteins and tissue AA amyloid deposits. To extend these findings, we have examined murine peritoneal leukocytes and splenic tissues during the early amyloid deposition phase by immunocytochemical and immunogold electron microscopic methods using monospecific anti‐ubiquitin and anti‐mouse AA amyloid antibodies. We show here enrichment of endosome–lysosome‐like (EL) vesicles in the activated monocytoid cells with UB and SAA, and the presence of UB‐bound AA amyloid fibrils in the EL vesicles, perikarya, and interstitial spaces. The importance of these findings is emphasized by the fact that activated monocytoid cells, containing UB in the EL vesicles, sequester and eventually localize SAA in their EL vesicles, and that UB binds to the EL‐contained AA amyloid fibrils. These findings may also have functional consequences for studies on the role of EL and UB in amyloidogenesis.
A time sequence of vessel wall changes in an experimental model of angioplasty
Authors: More Ranjit S. , Rutty Guy , Underwood Malcolm J. , Brack Michael J. , Gershlick Anthony H. 
Published: June 2005

AbstractA detailed temporal sequence of vessel wall changes in a rabbit model of balloon angioplasty, to the iliac arteries, at 30 min, 2h, day 1, day 3, day 7, day 14, 1 month, and 3 months was established using light microscopy, immunostaining for proliferating cell nuclear antigen, and electron microscopy. Complete endothelial denudation with extensive platelet and fibrin deposition was evident early. Intimal thickening, characterized by myointimal hyperplasia, was observed at day 7 and reached a maximum at 1 month. Re‐endothelization was complete by day 14. Cellular proliferation, seen early at day 1, reached a maximum at day 7 for the media and day 14 for the intima before returning to baseline levels by 1 month. This simple model of angioplasty with its reproducible myointimal hyperplasia should prove useful for assessing any potential agents for inhibiting this process.
Fractal geometric analysis of colorectal polyps
Authors: Cross Simon S. , Bury Jonathan P. , Silcocks Paul B. , Stephenson Timothy J. , Cotton Dennis W. K. 
Published: June 2005

AbstractColorectal polyps have a subjectively self‐similar structure which suggests that these structures may have fractal elements and that the fractal dimension may be a useful morphometric discriminant. The fractal dimensions of images from haematoxylin and eosin‐stained sections of 359 colorectal polyps (214 tubulovillous adenomas, 41 ‘pure’ tubular adenomas, 29 ‘pure’ villous adenomas, 68 metaplastic polyps, and 7 inflammatory polyps) were measured using a box‐counting method implemented on a microcomputer‐based image analysis system. Results were assessed using polychotomous logistic regression, confusion matrices, and kappa statistics. All examined polyps were shown to have a fractal structure in the range of scales examined. The fractal dimension was significantly different between different diagnostic categories (P<0·0001) and was a useful discriminant between these categories (kappa statistic 0·60 for the confusion matrix with size as the other variable). The fractal dimension did not shown any significant correlation with the grade of epithelial dysplasia (P>0·05). This study shows that colorectal polyps have a fractal structure over a defined range of magnification and Euclidean morphometric measurements will be invalid outside precisely defined conditions of resolution and magnification. The fractal dimension is a better way of quantitating the polyp shape and is a useful morphometric discriminant between diagnostic categories.
Bcl‐2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland
Authors: Pilotti Silvana , Collini Paola , Rilke Franco , Cattoretti Giorgio , Del Bo Romualdo , Pierotti Marco A. 
Published: June 2005

AbstractThe bcl‐2 product has been related to the block of programmed cell death (apoptosis) both in lymphoid and in epithelial cells. The pathological expression of bcl‐2 has been investigated mainly in haematological malignancies. Here we have investigated bcl‐2 expression in a model of epithelial tumours represented by the spectrum of carcinomas arising from the follicular epithelium of the human thyroid gland. The analysis was carried out by immunocytochemistry on archival material using monoclonal antibodies against bcl‐2 and thyroglobulin (Tg) on consecutive sections of 94 well‐differentiated carcinomas (WDCs), 19 poorly differentiated carcinomas (PDCs), and 22 undifferentiated carcinomas (UCs) of the thyroid gland. In a subset of 5 cases of UC showing a differentiated component (UC‐D), the expression of p53 protein was also investigated. As controls, fetal and adult normal thyroid glands and adenomas were analysed. bcl‐2 expression was detected in 74 of 94 cases (78·7 per cent) of WDC, 16 of 19 cases (84·2 per cent) of PDC, and 3 of 22 cases (13·6 per cent) of UC. Simultaneous expression of bcl‐2 protein and Tg was observed in 74 of 94 cases (78·7 per cent) of WDC, 13 of 19 cases (68·4 per cent) of PDC, and in no case of UC. bcl‐2 and Tg immunostaining was detected in all fetal and normal thyroid glands as well as in the adenoma specimens examined. In the subset of UC‐D, mutual exclusion of bcl‐2 and p53 expression was observed in the undifferentiated and differentiated components (p53 but not bcl‐2 expressed in the former). Our data indicate that within the spectrum of thyroid carcinomas bcl‐2 expression, similarly to Tg, is strictly correlated with cell differentiation and that its abrogation is restricted to UCs, in which alterations of the p53 gene represent a late genetic event related to tumour progression.
Classification of CEA‐related positivity in primary and metastatic malignant melanoma
Authors: Sanders D. S. A. , Evans A. T. , Allen C. A. , Bryant F. J. , Johnson G. D. , Hopkins J. , Stocks S. C. , Marsden J. R. , Kerr M. A. 
Published: June 2005

AbstractUsing a panel of antibodies to carcinoembryonic antigen (CEA), in paraffin‐processed biopsy material patchy, predominantly membranous positivity was seen on tumour cells in 70 per cent of cases of superficial spreading melanoma, 60 per cent of nodular melanomas, and 75 per cent of secondary deposits studied with unabsorbed polyclonal anti‐CEA only. No staining was seen using monoclonal anti‐CEAs. Localization of CEA to the cell membrane was confirmed with confocal microscopy. Immunoblotting of fresh frozen material detected CEA of around 180 kD in both primary and metastatic melanomas migrating with an apparent molecular weight of between 150 and 200 kD, indicating variable glycosylation of the protein. Recognition of an adhesive role for CEA with roles in immunolocalization and immunotherapy emphasizes the importance of more precise classification of CEA‐related positivity in human tumours.
Ki‐S1 and PCNA expression in erythroid precursors and megakaryocytes—A comparative study on proliferative and endoreduplicative activity in reactive and neoplastic bone marrow lesions
Authors: Thiele Juergen , Bertsch Hans Peter , Kracht Lutz Walter , Anwander Thomas , Zimmer Joerg Detlef , Kreipe Hans , Fischer Robert 
Published: June 2005

AbstractThe monoclonal antibody Ki‐S1 reacts with a cell proliferation‐associated nuclear antigen which is expressed in the G1 through G2/M phases of the cell cycle and is resistant to formalin fixation. We have studied Ki‐S1 and PCNA (PC10) immunostaining of erythroid precursors (proliferative activity) and megakaryocytes (endoreduplicative activity) in bone marrow trephine biopsies in a variety of reactive and neoplastic lesions using double immunohis‐tochemistry to identify both cell lineages. A significant increase in Ki‐S1 labelling compared with PCNA positivity was found in all conditions studied. In particular, specimens derived from secondary polycythaemia (SP), polycythaemia vera (P. vera), and primary osteomyelofibrosis (OMF), and from splenic tissue with myeloid metaplasia (MM), revealed a disproportionally high labelling index of erythropoiesis, which was not present in chronic myelogenous leukaemia (CML), AIDS, and autoimmune (idiopathic) thrombocytopenia (ITP). Enhancement of Ki‐S1 (PCNA) staining in SP and P. vera is in keeping with the relevant increase in erythroid precursor proliferation, but in OMF and MM there is overexpression of both proliferation markers, possibly due to secondary folic acid deficiency, which is known to cause a block in the S‐phase of the cell cycle. A significant correlation was observed between the sizes of megakaryocytes and their nuclei with Ki‐S1 (and also PCNA) staining. Ki‐S1 (and PCNA) labelling of predominantly smaller elements of this lineage supports a hypothesis that the phases of the cell cycle have different durations in the various steps of polyploidization, with a prolongation of G1/G2 at higher ploidy levels. A considerable number of large to giant (hyperpolyploid) megakaryocytes may have reached the end stage of endoreduplicative activity (Ki‐S1‐/PCNA‐negative GO phase). A comparative evaluation of these two proliferation markers adds significantly to our understanding of cell kinetics in erythro‐ and megakaryo‐poiesis, and sheds some light on the biological behaviour of these cell lineages in various disorders.
Cell proliferation correlates with prognosis in acinic cell carcinomas of salivary gland origin. Immunohistochemical study of 30 cases using the MIB 1 antibody in formalin‐fixed paraffin sections
Authors: Skalova Alena , Leivo Ilmo , Von Boguslawsky Kristina , Saksela Eero 
Published: June 2005

AbstractImmunohistochemical staining with the MIB 1 antibody was used to assess cell proliferation in 30 cases of acinic cell carcinoma of salivary glands. Until now, no prognostic factors have been available for these rare tumours. The MIB 1 monoclonal antibody recognizes the Ki‐67 antigen in formalin‐fixed, paraffin‐embedded tissues. A MIB 1 index was developed as a means of expressing the percentage of MIB 1‐positive tumour cell nuclei, and the tumours were scored without prior information of clinical behaviour. The staining results were then compared with the clinical outcome of the patients. All eight patients who developed tumour recurrences had MIB 1 indices higher than 5 per cent. Tumour recurrences could be predicted even in cases of bland morphology and low mitotic rate. Three patients died of their recurrent tumours, and had MIB 1 indices of 56.2, 12.7, 7.8 per cent in their primary tumours. Five of seven patients with MIB 1 indices higher than 10 per cent had unfavourable outcomes. None of the 17 patients with MIB 1 indices lower than 5 per cent developed recurrences during follow‐up periods up to 30 years. The present results indicate that MIB 1 staining appears to be a significant prognostic factor in acinic cell carcinomas of salivary gland origin.