bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferating cell nuclear antigen (PCNA) expression as a prognostic indicator for renal cell carcinoma: Comparison with tumour grade, mitotic index, and silver‐staining nucleolar organizer region numbers
Authors: Delahunt Brett , Bethwaite Peter B. , Nacey John N. , Ribas Jorge L. 
Published: June 2005

AbstractProliferating cell nuclear antigen (PCNA) expression in renal cell carcinoma (RCC) was determined by immunohistochemical staining using the PC10 clone. PCNA indices ranged from 2.4 to 53.1 per cent with mean indices of 12.6, 19.0, and 31.6 per cent for grades 1 to 3 RCC and 31.9 per cent for sarcomatoid RCC. There was a significant difference between the indices of grades 1 and 3 and grades 2 and 3 tumours and between grades 1 and 2 RCC and sarcomatoid RCC. AgNOR scores and mitotic indices were determined for each tumour and comparison of PCNA indices with mean AgNOR scores and mitotic indices showed only a weak correlation (PCNA/AGNORr= 0.406, PCNA/mitotic indexr= 0.315). Tumours were divided according to PCNA index (≤18 per cent and > 18 per cent) and there was a significant difference in survival between the two groups, for all cases, and for each of the Robson stages. Multivariate analysis using Cox's proportional hazard model showed PCNA index, tumour stage, and mean AgNOR score to be independent predictors of survival, while tumour grade and mitotic index were found to be dependent variables.
Quantitation of the renal arterial tree by fractal analysis
Authors: Cross Simon S. , Start Roger D. , Silcocks Paul B. , Bull Andrew D. , Cotton Dennis W. K. , Underwood James C. E. 
Published: June 2005

AbstractTo determine whether the renal arterial system has a fractal structure, the fractal dimension of renal angiograms from 52 necropsy cases was measured using an implementation of the box‐counting method on an image analysis system. The method was validated using objects with known fractal dimensions. The method was accurate with errors of less than 1.5 per cent and reproducible with initial values within 1.2 per cent of the mean of ten sets of measurements (reliability coefficient 0.968, 95 per cent confidence limits 0.911.0.984). In the 36 satisfactory angiograms the mean fractal dimension was 1.61 (SD 0.06), which was significantly greater than the topological dimension of 1 (P<0.0001), indicating that the renal arterial tree has a fractal structure. There was no significant relationship between age (P=0.494), sex (P=0.136), or systolic (P=0.069) or diastolic (P=0.990) blood pressure, but two congenitally abnormal kidneys (hypoplastic dysplasia and renal artery stenosis) had fractal dimensions at the lower end of the normal range (third percentile). Since the renal arterial tree has a fractal structure, Euclidean geometric measurements, such as area and boundary length, are invalid outside precisely defined conditions of magnification and resolution.
The earliest histopathological response to hypobaric hypoxia in rabbits in the rifugio torino (3370 M) on Monte Bianco
Authors: Smith P. , Heath D. , Williams D. , Bencini C, , Pulera N. , Giuntini C. 
Published: June 2005

AbstractTwelve Dutch rabbits were kept on Monte Bianco at an altitude of 3370 m. Half of the animals were killed after 3 months, the remainder after 6 months, and a further six animals maintained at sea‐level acted as controls. The carotid bodies of all the rabbits were processed for light and electron microscopy and examined qualitatively and quantitatively. The lungs were processed for light microscopical assessment of small pulmonary arterial vessels; the thickness of the pulmonary trunks and aortas were measured; and the hearts were dissected to obtain ratios of the ventricular weight. There was a slight increase in the right ventricular weight in the hypoxic rabbits but no change in the thickness of the pulmonary trunk compared with that of the aorta. In particular, there was no hypoxic remodelling of the pulmonary vasculature such as muscularization of pulmonary arterioles or intimal longitudinal muscie in pulmonary arteries. The earliest histopathological response to hypoxia occurred in the carotid bodies in the form of an increase in the count of the dark variant of chief cell after 3 months which returned to normal after 6 months. It is concluded that the carotid body of the rabbit responds with a change in its population of dark chief cells to a level of hypoxia which is insufficient to affect the pulmonary arterioles. Changes in the cardiopulmonary system can no longer be considered to be the earliest histopathological response to hypobaric hypoxia.
Patterns of CEA‐related antigenex pression in invasive squamous carcinoma of the cervix
Authors: Sanders D. S. A. , Ferryman S. R. , Bryant F. J. , Rollason T. P. 
Published: June 2005

AbstractThe recognition of an adhesive role for the CEA‐related antigens emphasizes the need for clear demonstration of the changes in CEA expression and subcellular localization between normal and neoplastic tissues. Using a panel of monoclonal and polyclonal antibodies, membranous and cytoplasmic CEA expression was seen in 50 invasive cervical squamous carcinomas in four distinct patterns dependent on tumour type and differentiation. Membranous CEA expression is a marker of differentiation in squamous carcinomas and may influence tumour behaviour and hence patient survival. Strong CEA positivity was seen on the endothelium of vessels containing tumour in ten cases where vascular metastases were prominent. Staining of these ten cases revealed concomitant sialated Lewis X positivity in tumour cells with weak endothelial positivity in three cases; cervical squamous tumour cells may localize to vascular endothelium, and hence disseminate, through specific binding of CEA and/or sialated Lewis X.
Proliferative state of the urothelium with benign and atypical changes. Correlation with transferrin and epidermal growth factor receptors and blood group antigens
Authors: Limas Catherine 
Published: June 2005

AbstractWe attempted to investigate how the proliferative state of the urothelium correlates with the reactivity for transferrin (Tf) and epidermal grown factor (EGF) receptors and the blood group (BG) antigen. We examined morphologically normal urothelium (34 cases), benign inflammatory and reactive conditions (24 cases), and atypical changes (20 cases) without exophytic or invasive neoplasia. The Ki67 nuclear antigen was used as the proliferation index and was complemented with the in vitro BrdU incorporation assay in 32 cases. The immunohistochemical reactions for Tf and EGF receptors and for the appropriate BG antigen were scored semi‐quantitatively on frozen sections. We found that normal urothelium has very low Ki67 and BrdU indices as well as low reactivity for the two receptors and is almost invariably positive for the BG antigen. Benign conditions such as inflammation and metaplasia significantly augment the proliferation indices and the Tf receptor with little change in the EGF receptor and no significant effect on the BG antigen. Moderate atypia includes biologically heterogeneous cases which vary widely in proliferation and receptor expression. Severe atypia‐carcinoma in situ is consistently associated with markedly elevated proliferation indices, strong Tf receptor reactivity, and depressed BG antigen. The reactivity for EGF receptor is less consistently increased. Cases with a combination of strong EGF receptor reactions and absence of the expected BG antigen have a poor prognosis with progression to invasive cancer.
Ultrastructural heterogeneity in undifferentiated bronchial carcinoma
Authors: Carter Naomi , Nelson Fiona , Gosney John R. 
Published: June 2005

AbstractElectron microscopy is often suggested as a useful aid to the classification of light microscopically undifferentiated bronchial malignancies, features such as dense‐core vesicles, desmosomes or tonofilaments, and microacini, allowing their designation as endocrine, squamous, or adenocarcinomas respectively. However, there is no reason to suppose that the heterogeneity of malignant bronchial tumours so often apparent by light microscopy or on immunolabelling might not occur at the ultrastructural level too. Extensive sampling of all deposits from eight subjects coming to necropsy with undifferentiated bronchial carcinoma revealed ultrastructural features of glandular and squamous differentiation to be widespread and often to occur together, although dense‐core vesicles were not seen in any of the tumours studied. Heterogeneity was present within individual tumour deposits and particularly between different deposits of those tumours which had disseminated, such that any ultrastructural diagnosis would have been significantly influenced by sampling. Such variation should be borne in mind when ultrastructural features are used to classify bronchial malignancies.
Electron microscopic study of the attachment and penetration of rabbit intestinal epithelium by Providencia alcalifaciens
Authors: Mathan Minnie M. , Mathan Vadakenadayil I. , Albert M. John 
Published: June 2005

AbstractIlea of adult rabbits with removable ileal ties (RITARD model) that developed diarrhoea and ileal loops of adult rabbits after inoculation with Providencia alcalifaciens, isolated from two patients with diarrhoea, were studied by transmission electron microscopy for enterocyte‐bacterial interactions. Two modes of entry of bacteria into epithelial cells were seen: one directly by endocytosis associated with polymerization of cytoskeletal components and the other by disruption of tight junctions with entry into and proliferation in intercellular spaces.
Antigen unmasking on formalin‐fixed, paraffin‐embedded tissue sections
Authors: Cattoretti Giorgio , Pileri Stefano , Parravicini Carlo , Becker Michael H. G. , Poggi Simonetta , Bifulco Carlo , Key Göran , D'Amato Lucia , Sabattini Elena , Feudale Elisa , Reynolds Fred , Gerdes Johannes , Rilke Franco 
Published: June 2005

AbstractEnzymatic and non‐enzymatic treatments for antigen unmasking on formalin‐fixed, paraffin‐embedded, dewaxed sections were optimized and compared by the use of a panel of antibodies of diagnostic relevance (anti‐cytokeratins, vimentin. S‐100. T‐ and B‐cell receptors, Ki‐67/MIB 1, muscle actin). Non‐enzymatic unmasking was obtained by boiling the slides in a microwave oven in 0.01 M salt solution (pH 6) or in 6 M urea. Trypsin or pronase digestion was used for comparison and found to be necessary for some of the reagents. The investigation was then extended to 256 antibodies; the epitopic amino acid sequence was known for 48 of them. We found that enzymatic and non‐enzymatic antigen unmasking are not dependent on the epitope sequence, but some antigens benefit selectively from one treatment but not from the other. Denaturation of proteins is the likely mechanism which leads to immunodetection on microwave oven‐boiled slides; this suggestion is supported by the use of denaturating solutions and by the observation that endogenous enzymes were inactivated and a few antigens were no longer immunodetectable after boiling. Non‐enzymatic methods for antigen unmasking are a powerful new tool for broadening the use of antibodies for immunostaining formalin‐fixed, paraffin‐embedded sections and should be used in parallel with the traditional enzymatic methods.
Genetic alterations of the TP53 gene, p53 protein expression and hpv infection in primary cervical carcinomas
Authors: Helland Åslaug , Holm Ruth , Kristensen Gunnar , Kaern Janne , Karlsen Frank , Trope Claes , Nesland Jahn M. , Børresen Anne‐Lise 
Published: June 2005

AbstractPrimary cervical carcinomas from 92 patients were investigated for genetic alterations in the tumour suppressor gene TP53. Studies of allelic imbalance (AI) were performed by Southern blot analysis and by using two PCR (polymerase chain reaction) polymorphisms within the TP53 gene. AI in the tumour was observed in 22 per cent (11 of 52 informative patients) and was significantly associated with recurrence both in a univariate (P=0.013) and in a multivariate (P=0.045) analysis. The DNA samples were subjected to mutation analysis of four of the conserved domains in the TP53 gene, using PCR followed by constant denaturant gel electrophoresis (CDGE). Mutations were observed in 2 of 92 tumours (2 per cent), of which one was a silent mutation and the other a frameshift. Overexpression of the p53 protein was found by immunostaining of sections from formalin‐fixed, paraffin‐embedded material in 55 per cent (51/92) of the tumours. In 88 per cent (45/51) of these, overexpression was present in less than 5 per cent of the tumour cells. Overexpression was significantly associated with relapse‐free survival only in a univariate analysis (P=0.045). AI of the TP53 locus did not correlate with p53 expression or mutation. The important gene on 17p, responsible for the shorter disease‐free survival for patients with AI of TP53, may therefore be another gene closely linked to TP53. In addition, the 92 tumour samples were tested for the presence of human papillomavirus (HPV) types 16 and 18. Fifty‐four per cent (50/92) of the samples were positive for HPV 16 usingin situhybridization, and 93 per cent (86/92) using the PCR technique. The numbers for HPV 18 were 15 per cent (14/92) and 23 per cent (21/92), respectively. Twenty‐one per cent (19/92) were positive for both HPV 16 and HPV 18, while 4 per cent (4/92) were negative for both HPV 16 and 18. The tumour with the frameshift TP53 mutation was HPV 16‐positive, and the four samples negative for HPV 16 and 18 did not contain TP53 mutations within the conserved domains but had elevated p53 protein expression.
Immunohistochemical evidence for the expression of proliferating cell nuclear antigen (PCNA) by non‐proliferating hepatocytes adjacent to metastatic tumours and in inflammatory conditions
Authors: Harrison Rebecca F. , Reynolds Gary M. , Rowlands David C. 
Published: June 2005

AbstractThe possibility that proliferating cell nuclear antigen (PCNA) is expressed by non‐proliferating liver cells was investigated. Liver biopsies from 107 patients were investigated, which included histologically normal liver, metastatic tumour, and inflammatory lesions. PCNA was detected using immunohistochemical staining with the monoclonal antibody PC10. This was compared with the proportion of proliferating cells as assessed by immunostaining for the Ki‐67 antigen using the monoclonal antibody MIB 1. Most cases of histologically normal liver showed few PC10‐positive cells. PCNA‐positive hepatocytes far outnumbered those positive with MIB 1 in specimens showing metastatic tumour or an inflammatory cell infiltrate. There was no relation between the degree of PCNA overexpression and the type of tumour present or the nature of the inflammatory lesion. Other cell types, including the biliary epithelium, did not show this large difference between the proportions of PC10‐ and MIB 1‐positive cells. It is concluded that non‐proliferating hepatocytes increase their levels of PCNA in a wide variety of pathological conditions. This may be mediated by cytokines released by tumour cells or inflammatory cells.
Vascular activation in the histopathogenesis of Hodgkin's disease: Potential role of endothelial tissue factor in intravascular thrombosis and necrosis
Authors: Ruco Luigi P. , Pittiglio Marco , Dejana Elisabetta , Baroni Carlo D. 
Published: June 2005

AbstractEndothelial cell activation and alterations of intravascular coagulation were investigated in 27 cases of Hodgkin's disease (HD), in five cases of anaplastic large cell lymphoma (ALCL), and in ten reactive lymph nodes. Lymph node sections were immunostained for E‐selectin, a molecule present on cytokine‐activated endothelial cells; for tissue factor (TF), a cellular initiator of the coagulation cascade; for glycoprotein (gp) II/III, a platelet‐specific antigen; and for fibrin. In HD, vascular activation was particularly prominent in the nodular sclerosis subtype, as indicated by a larger number of E‐selectin‐positive blood vessels (72 ± 49) compared with mixed cellularity (22 ± 37). High expression of E‐selectin was associated with alterations of intravascular coagulation, as indicated by immunostaining of some vascular endothelial cells for TF, by a higher incidence of intravascular thrombi, and by the extensive presence of areas of fibrin exudation and necrosis. In ALCL, the levels of endothelial cell activation and intravascular coagulation were comparable to those of HD nodular sclerosis. In reactive nodes, some E‐selectinpositive blood vessels were observed only in 3/10 cases; immunostaining for TF was not detected on endothelial cells; and alterations of intravascular coagulation were rarely observed.
Glomerular dimensions in children under 16 years of age
Authors: Moore Lynette , Williams Ruth , Staples Alan 
Published: June 2005

AbstractGlomerular area, perimeter, and mean maximum glomerular diameter were assessed in post‐mortem kidney tissue from 114 children who died suddenly in accidents and who were considered to have been previously healthy. One hundred glomeruli were measured from each case using a computer‐based measurement system. Regression analysis was used to analyse glomerular size with respect to age, body weight, height, and body mass index. The estimated mean glomerular area for newborns was 7934 μm2 (SE 314), increasing 8 per cent per year to 18 219 μm2 at 15 years of age. The estimated mean maximum glomerular diameter increased from 112 μm (SE 1.9μm) for newborns, approximately 3.6μm per year to reach 167 μm at age 15. Glomerular size correlated better with age than with height, weight, or body mass index, and glomeruli in the inner cortex were significantly larger than those in the middle and outer cortex. Glomerular size was significantly greater in female children than in the male children over the age range examined.
Identification of numerical chromosome aberrations in archival tumours by in situ hybridization to routine paraffin sections: Evaluation of 23 phaeochromocytomas
Authors: Van Dekken H. , Bosman F. T. , Teijgeman R. , Vissers C. J. , Tersteeg T. A. , Kerstens H. M. J. , Vooijs G. P. , Verhofstad A. A. J. 
Published: June 2005

AbstractWe have applied non‐isotopic in situ hybridization (ISH) to interphase cell nuclei of 23 phaeochromocytomas (18 primary and 5 metastatic tumours) within routine paraffin‐embedded tissue sections. Each tumour was screened for numerical aberrations with a defined alphoid repetitive DNA probe set containing DNA probes specific for chromosomes 1, 7, 15, and Y. Normal adrenal medullas and other normal human cell types served as cytogenetic controls. Preservation of tissue morphology enabled targeted analysis of tumour cells. The presence of numerical chromosome changes in the tumour cells could easily be evaluated by comparing the ISH results of the DNA probes. Numerical abnormalities not previously reported in this neoplasm included overrepresentation of chromosomes 1 and 7, loss of chromosome 15, and both gain and loss of chromosome Y (P values <0.01). The percentage of aneuploid cell nuclei in a tumour correlated well with the percentage of cells in the 4C peak of flow cytometric DNA histograms from these neoplasms. We conclude that interphase ISH can be used for the identification of new and reported cytogenetic changes in tumour cell nuclei within archival tissue sections. This novel procedure also allows for retrospective analysis of previously not karyotyped material.
Loss of α6 and β4 integrin subunits coincides with loss of basement membrane components in oral squamous cell carcinomas
Authors: Downer Caroline S. , Watt Fiona M. , Speight Paul M. 
Published: June 2005

AbstractIn oral squamous cell carcinomas, focal or extensive loss of basement membrane components and of integrins has been reported. The purpose of this study was to investigate whether those regions of the tumour‐connective tissue interface which lack laminin and type IV collagen coincide with areas of loss of the α6 and β4 integrin subunits on basal keratinocytes. Out of a total of 15 poor and moderately or well differentiated squamous cell carcinomas, all showed some loss or fragmentation of basement membrane proteins and in 12 the loss was coincident with loss of α6 and/or β4. In three cases, there was loss of basal integrin expression in areas where the basement membrane remained intact. These results provide further evidence that loss of integrins may play an important role in tumour progression and prompt us to speculate about the sequence of events leading to tumour invasion.
TGF‐βS and TGF‐β type II receptor in human epidermis: Differential expression in acute and chronic skin wounds
Authors: Schmid Peter , Cox David , Bilbe Graeme , McMaster Gary , Morrison Chris , Stähelin Hannes , Lüscher Nicholas , Seiler Walter 
Published: June 2005

AbstractExogenously applied transforming growth factor‐beta (TGF‐β) isoforms enhance wound healing processes in animal models;1 however, little is known about the expression of endogenous TGF‐βs and TGF‐β receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF‐β3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds—a pattern of expression closely mirrored by the TGF‐β type II receptor. Although not detected in intact skin, TGF‐β mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF‐β2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF‐β3 is important for maintenance of epidermal differentiation and that an induction of TGF‐β1 expression is essential for re‐epithelialization of human skin wounds. Lack of TGF‐β1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.
The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis
Authors: Davies Michael J. , Gordon J. L. , Gearing A. J. H. , Pigott R. , Woolf Neville , Katz David , Kyriakopoulos A. 
Published: June 2005

AbstractThe expression of PECAM, ICAM‐1, VCAM‐1, and E‐selectin was studied in 64 samples of human coronary arteries taken from 15 explanted hearts obtained within 5 min of transplantation. Normal artery (n=12), predominantly fibrous plaques (n=23), and plaques containing extracellular lipid (n=26) and three segments showing recanalization channels were studied. All endothelial cells strongly and equally expressed PECAM; positive staining was used to check that artefactual denudation of the endothelial surface had not occurred. PECAM was also present in some lipid‐filled macrophages. Normal arteries showed no VCAM‐1 staining but focal segments of the endothelium were positive for ICAM‐1 and E‐selectin. ICAM‐1 was strongly and constantly expressed by the endothelium over all types of plaques and in macrophages. E‐selectin expression was confined to endothelial cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of lipid‐containing plaques. VCAM‐1 staining of surface endothelium occurred in 39 per cent of fibrous and 20 per cent of lipid‐containing plaques. A population of spindle‐shaped cells of macrophage type (positive for EMB11 antigen) expressed VCAM‐1 in lipid‐containing plaques. Adventitial vessels adjacent to plaques showed endothelial expression of ICAM‐1 and E‐selectin. VCAM‐1 staining of adventitial vessel endothelium was associated with local lymphoid aggregation. In conclusion, the expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from advential vessels and the arterial lumen.