bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular localisation of C‐myc product in human colorectal epithelial neoplasia
Authors: Royds Janice A. , Sharrard R. Michael , Wagner Bart , Polacarz Steven V. 
Published: June 2005

AbstractAberrant expression of c‐myc has been implicated in the development of colorectal carcinomas. We have used monoclonal antibodies 6E10 and 9E10, raised against mid‐sequence and C‐terminal peptides of the c‐myc protein, to study the distribution of myc protein in normal and diseased bowel at the light microscope and ultrastructural levels. Normal mucosa showed staining only of some nuclei in the proliferative zones of crypts. In adenomas, staining varied from predominantly nuclear to pancellular to focal or pancytoplasmic. Moderately well differentiated areas of carcinomas gave strong focal cytoplasmic staining, while in poorly differentiated tumours staining was pancytoplasmic. Electron microscopy with these antibodies detected myc protein associated with dense chromatin and, where cytoplasmic staining occurred, with polyribosomes. Tumours showed a reduced staining of nuclear pores compared with normal tissue. Comparison of staining patterns with 6E10 and 9E10 in normal tissue, adenomas, and tumours suggests that tumour progression is associated with an accumulation of cytoplasmic c‐myc protein, perhaps resulting from alterations to the C‐terminus which reduce the efficiency of nuclear targeting of the protein and thus disrupt the regulation of the cell cycle.
P53 protein expression in lymphomas and reactive lymphoid tissue
Authors: Villuendas Raquel , Piris Miguel A. , Orradre Juan L. , Mollejo Manuela , Algara Patrocinio , Sanchez Lydia , Martinez Juan C. , Martinez Pedro 
Published: June 2005

AbstractP53 is a tumour suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth, regulating the entry of the cell into the S‐phase. P53 mutations have been identified in a progressively increasing number of human malignancies. Nuclear p53 protein is usually present in non‐tumour cells in minute concentrations, due to its short half‐life. In contrast, tumours with p53 mRNA mutations show a higher nuclear protein concentration, detectable by immunohistological techniques, due to stabilization by complexing with other proteins such as heat‐shock protein or wild‐type p53 protein.Leveis of nuclear p53 protein detected by immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the aid of an image analysis system in 83 non‐Hodgkin's lymphomas (NHLs) and 13 cases of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils, and lymphadenitis. High levels of p53 protein (>5 per cent of the cells) were present only in high‐grade lymphomas (in the proportion 13/55), with a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (<5 per cent) of p53 protein were detected in low‐grade B‐ and T‐cell lymphomas, as well as in most of the cases of Hodgkin's disease, where p53 protein was selectively present in Hodgkin and Reed‐Sternberg cells. In 5/14 reactive tonsils or lymph nodes, occasional p53‐positive cells were identified.These results suggest a relationship between levels of p53 protein and the aggressiveness of NHL. The sporadic presence of p53‐positive cells in human reactive tissues suggests that its expression could depend not only on mutation, but also on stabilization of the protein through complexing with other nuclear proteins. It is not known if this mechanism is also responsible for the p53 nuclear accumulation in high‐grade lymphomas.
A tumour promoter induces alterations in vinculin and actin distribution in human renal epithelium
Authors: Rahilly Maeve A. , Fleming Stewart 
Published: June 2005

AbstractLoss of cell–substratum adhesion is an important factor during tumour progression. We have previously described reduced focal contact components and poorly organized cytoskeletal actin in renal cell carcinomas. In this study, we have used the potent tumour promoter TPA on cultured human renal epithelium to mimic neoplastic transformation. The morphological changes induced by TPA were examined by phase contrast and fluorescence microscopy. TPA treatment caused rounding up of cells and loss of adhesion to either fibronectin or laminin substrata. Cytoskeletal actin was redistributed from orientated stress fibre bundles to a perinuclear circumferential arrangement. This was accompanied by a progressive reduction in the number of vinculin‐containing contacts with accumulation of vinculin in punctate spots in the perinuclear region. These altered membrane‐cytoskeletal interactions induced by TPA are entirely reversible and mimic epigenetic changes which occur during tumour progression.
Apposition of fibroblasts to mast cells and lymphocytes in normal human lung and in cryptogenic fibrosing alveolitis. Ultrastructure and cell perimeter measurements
Authors: Heard Brian E. , Dewar Ann , Corrin Bryan 
Published: June 2005

AbstractThe perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (–19.6, 25.1); P = 0.65). The PPAF range overall was 3.8–94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung.The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung.
X‐ray microanalysis of bulk hydrated specimens of neoplastic and non‐neoplastic human urothelium
Authors: Hopkins Diane M. , Morris James A. , Oates Kenneth , Huddart Henry , Staff William G. 
Published: June 2005

AbstractSpecimens of neoplastic and non‐neoplastic human urothelium were rapidly frozen against a copper block immersed in liquid nitrogen, planed in a cryoultramicrotome and then examined by low‐temperature scanning electron microscopy (LTSEM) following coating by aluminium. Energy dispersive X‐ray microanalysis (XRMA) was performed on the superficial urothelial cells and on gelatin blocks mounted in parallel which had known concentrations of sodium, potassium, chloride, and phosphorus. The neoplastic urothelial cells had significantly less phosphorus (P <0.05) than non‐neoplastic cells and the ratios K+/P,K+/Na+, and K+/Cl− were significantly higher in neoplastic cells than in non‐neoplastic cells (P <0.00001). These results are consistent with those expected in cells with a sustained increase in intracellular pH caused by stimulation of Na+/H+ ion membrane exchange.
Macrophage and perisinusoidal cell kinetics in acute liver injury
Authors: Johnson Sarah J. , Hines Julie E. , Burt Alastair D. 
Published: June 2005

AbstractPerisinusoidal cells (PSCs) are currently regarded as the major source of extracellular matrix proteins during hepatic fibrogenesis in response to liver injury. However, the cellular mechanisms underlying their response to injury are not fully understood. One hypothesis is that the PSCs are stimulated by peptide growth factors produced by hepatic macrophages (Kupffer cells) in response to parenchymal cell damage. In this study we have investigated the kinetics of the PSC and macrophage populations in acute carbon tetrachloride‐induced hepatic injury in rats. PSCs were identified immunohistochemically by detection of cytoplasmic desmin; monocytes and macrophages were detected using the monoclonal antibodies ED1 and ED2; cells in S phase were identified by immunohistochemical detection of nuclear‐incorporated bromodeoxyuridine. The results showed an expansion of the desmin‐positive PSC population, predominantly within the damaged perivenular zones, which reached a peak on days 3 and 4 following administration of carbon tetrachloride; this was contributed to by local PSC proliferation. The PSC response was preceded by an expansion of the macrophage population resulting from both local macrophage proliferation and influx of blood monocytes. These results are in keeping with the hypothesis that the PSC response to acute liver injury is mediated, at least in part, by hepatic macrophages.
The distribution of LH39 basement membrane epitope in the tumour stroma of oral squmaous cell carcinomas
Authors: Almeida Bernice M. , Challacombe Stephen J. , Eveson John W. , Morgan Peter R. , Purkis Patricia E. , Leigh Irene M. 
Published: June 2005

AbstractLH39 monoclonal antibody detects a novel component of epithelial and endothelial basement membranes. The expression of LH39 antigen was investigated by immunohistochemistry in 55 oral squamous cell carcinomas and compared with 15 pyogenic granulomas of skin and oral mucosa, 20 non‐specific oral ulcers, and 20 specimens of normal oral mucosa. The distribution of this basement membrane epitope was compared with that of other basement membrane components, type IV collagen, and laminin. LH39 monoclonal antibody labelled basement membrane surrounding small blood vessels in normal human organs. In oral squamous cell carcinomas, in contrast to the other basement membrane antigens, the LH39 epitope was not detectable in vessels within histologically recognizable tumour stroma. Neovascularization is known to attend malignant neoplasms and this finding was interpreted as absence of LH39 antigen within newly formed vessels. In support of this hypothesis, LH39 immunoreactivity was absent in newly formed blood vessels within pyogenic granulomas and the granulation tissue within ulcers. As increasing neovascularization is reported to correlate with a rising rate of metastasis, assessment of tumour angiogenesis may be of value in selecting patients for initial aggressive therapy.
Optimization of non‐isotopic in situ hybridization on formalin‐fixed, paraffin‐embedded material using digoxigenin‐labelled probes and transgenic tissues
Authors: Fleming Kenneth A. , Evans Mark , Ryley K. Claire , Franklin David , Lovell‐badge Robin H. , Morey Adrienne L. 
Published: June 2005

AbstractThe sensitivity of non‐isotopic in situ hybridization (NISH), particularly on formalin‐fixed, paraffin‐embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human α‐1‐antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity—about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non‐specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform.
Reduction in apoptosis relative to mitosis in histologically normal epithelium accompanies fibrocystic change and carcinoma of the premenopausal human breast
Authors: Allan David J. , Howell Anthony , Roberts Stephen A. , Williams Gerrard T. , Watson Robert J. , Coyne John D. , Clarke Robert B. , Laidlaw Ian J. , Potten Christopher S. 
Published: June 2005

AbstractThe aims of this study in 227 premenopausal women were (a) to determine the mitotic index (MI), the thymidine labelling index (LI), and the apoptotic index (AI) within the epithelial cells of histologically ‘normal’ human breast biopsy material removed away from the site of either a fibroadenoma or a carcinoma; and (b) to relate differences in the kinetic indices of the ‘normal’ epithelium to the pathology in the same breast diagnosed as fibroadenoma alone (125 patients), fibroadenoma with accompanying mild fibrocystic change (79 patients), or carcinoma (23 patients). Ratios of the average indices (AI/MI, AI/LI, MI/LI) were also calculated to minimize uncertainties related to the total cell population counted, the denominator in the LI, MI, and AI All indices and ratios of indices were corrected for age, averaged over the cycle, and expressed as log‐transformed values for analysis. Significant (P<0.001) reductions in AI and in apoptosis relative to mitosis (reduced AI/MI) were found in ‘normal’ epithelium from breasts having fibrocystic change (AI = 0.17 ± 0.02; AI/MI = 1.01 ± 0.18) and carcinoma (AI = 0.19 ± 0.04; AI/MI=0.8 ± 0.29), compared with breast with fibroadenoma alone (AI = 0.27 ± 0.03; AI/MI = 1.29 ± 0.39). In the absence of significant differences in MI and LI between the ‘normal’ tissue groups, this finding raises the possibility that reduced epithelial cell apoptosis might be causally associated with the development of fibrocystic change and with an increased risk of development of carcinoma. Reduced apoptosis may lead to a shift in tissue kinetics towards expansion of cell numbers, and also to the preservation of genetically aberrant cells, favouring neoplastic development. The indices, however, are complex and must be interpreted with caution.
The effect of cyclosporin a on cationized bovine serum albumin‐induced nephropathy in NZW rabbits
Authors: Bass Paul S. , Wang Yiming , Nawab Mashal Al , Evans Beryl , Thomas Hywel , Davies David R. 
Published: June 2005

AbstractThe effect of cyclosporin A (CyA) was studied on the morphology and protein excretion of a rabbit chronic serum sickness nephritis using cationized bovine serum albumin (cBSA). One group of rabbits was given intravenous (i.v.) immunizing doses of cBSA and Escherichia coli endotoxin. One week later, these animals began a 6‐week i.v. injection schedule of cBSA only. A second group followed the same injection protocol, but was given intramuscular (i.m.) CyA for 3 days prior to the immunizing dose of cBSA/endotoxin and throughout the subsequent cBSA schedule. A third group was given i.m. CyA only. Regular blood samples for CyA levels were taken from animals given the drug. Two 24‐h urine samples were obtained from all animals in the study. Analysis of the blood samples showed that immunosuppressive levels of CyA were achieved after two i.m. doses of CyA. These levels were maintained during the course of the schedule. Morphologically, all rabbits completing the cBSA only injection schedule showed evidence of an immunemediated glomerulopathy with variably severe membranous and endocapillary proliferative change. Less than half the rabbits in the cBSA/CyA group showed any evidence of membranous change. The glomeruli of animals given CyA only were normal. No morphological evidence of CyA toxicity was seen in any animal given the drug. The proteinuria profiles, however, suggested that as well as reducing protein excretion in rabbits given cBSA, CyA may interact with the immunizing dose of cBSA to produce an early, reversible, nephrotoxic effect. These results show that (a) immunosuppressive levels of CyA can be efficiently obtained and maintained by the i.m. route, (b) commencing CyA treatment before initiating cBSA injections ameliorates cBSA glomerulopathy in the majority of rabbits tested, and (c) using this protocol, no significant CyA‐induced morphological effects are seen.
Diabetic glomerulosclerosis—immunogold ultrastructural studies on the glomerular distribution of type IV collagen and heparan sulphate proteoglycan
Authors: Woodrow David , Moss Jill , Shore Ian , Spiro Robert G. 
Published: June 2005

AbstractWe have undertaken an ultrastructural immunogold investigation of the distribution of type IV collagen and heparan sulphate proteoglycan (HSPG) in glomeruli from the kidneys of one normal control and three patients with diabetes mellitus and proteinuria. The sample included both diffuse and nodular diabetic glomerulosclerosis. In the control and diabetic kidneys, the type IV collagen was present predominantly on the endothelial aspect of the glomerular basement membrane (GBM), and by contrast the HSPG was found mainly on the epithelial side. In the mesangium in both control and diabetic glomeruli, type IV collagen was found predominantly in the central regions, while HSPG was mostly restricted to the region beneath the epithelial cells. Consequently, where there is a marked increase in mesangial matrix with nodule formation in diabetics there is a corresponding increase in the amount of type IV collagen but not of HSPG. Although the three diabetic patients were proteinuric, the HSPG was not decreased in the thickened GBMs.
The ultrastructure of pulmonary arteries and arterioles in emphysema
Authors: Smith Paul , Rodgers Brian , Heath Donald , Yacoub Magdi 
Published: June 2005

AbstractThe lungs from three cases of pulmonary emphysema obtained at heart‐lung transplantation were examined by electron microscopy to determine the origin of intimal longitudinal muscle and the formation of muscular tubes in small pulmonary arteries and arterioles. The earliest change consisted of migration of mature smooth muscle cells from the media of small pulmonary arteries, through gaps in the internal elastic lamina, into the subendothelial space. Most of these cells then adopted a longitudinal orientation, maintained a muscular phenotype, and became enmeshed in a web of elastic fibres. A small minority, immediately subjacent to the endothelium, were orientated circularly and, in some vessels, were enclosed by rudimentary internal and external elastic laminae to form early muscular tubes. Pulmonary arterioles, which are normally devoid of a media, contained several layers of circularly orientated smooth muscle cells, some of which also formed muscular tubes. It is postulated that the limited migration of mature smooth muscle cells seen in states of chronic hypoxia is mediated by a different stimulus from that causing the florid invasion of the intima by immature smooth muscle, with subsequent transformation into myofibroblasts, which characterize plexogenic pulmonary arteriopathy.
In situ detection of oxidative stress in rat hepatocytes
Authors: Mochida Satoshi , Masaki Naohiko , Ohta Yasuhiko , Matsui Atsushi , Ogata Itsuro , Fujiwara Kenji 
Published: June 2005

AbstractIn rat hepatocytes in primary culture incubated with nitro blue tetrazolium, formazan content was increased by addition of t‐butyl hydroperoxide, a potent oxidant, in a dose‐related manner, but not by addition of valinomycin, which kills hepatocytes through mitochondrial damage. This increment after t‐butyl hydroperoxide addition was not seen in hepatotyctes preincubated with deferoxamine mesylate, a ferric iron chelator which inhibits radical formation. Liver perfusion with nitro blue tetrazolium and t‐butyl hydroperoxide in rats produced formazan deposition faintly on the surface of hepatocytes throughout the liver and prominently in the cytoplasm of some hepatocytes, which was attenuated when performed following deferoxamine mesylate perfusion. When liver perfusion with nitro blue tetrazolium was performed in carbon tetrachloride‐intoxicated rats, formazan deposition appeared diffusely in hepatocytes in the centrilobular areas. Similar deposition was also observed on the surface and in the cytoplasm of hepatocytes in the periportal and mid‐zonal areas in rats undergoing post‐ischaemic reperfusion. Liver perfusion with nitro blue tetrazolium can detect in situ oxidative stress in hepatocytes and may be a useful tool for studying the role of lipid peroxidation in rat liver injury.
A study of adhesion molecules as markers of progression in malignant melanoma
Authors: Denton Karin J. , Stretch Jonathan R. , Gatter Kevin C. , Harris Adrian L. 
Published: June 2005

AbstractAdhesion molecules are substances which are involved in the interactions between cells, and between cells and the extracellular matrix in both benign and malignant tissues. Two members of this group—intercellular adhesion molecule‐1 (ICAM‐l) and MUC18—have previously been found to be expressed on melanoma; however, studies seeking a correlation between expression and metaslatic behaviour have yielded conflicting results. In this study we investigated the expression of these two antigens and that of a number of other adhesion molecules [VCAM‐1, ELAM, and the neural cell adhesion molecule (NCAM)] on a range of benign and malignant melanocytic lesions. Both ICAM‐1 and MUC18 were found on a high percentage of all melanocytic lesions including benign naevi. VCAM‐1 was found to be expressed on 79 per cent of benign naevi, 62 per cent of primary melanomas less than 1‐5 mm in depth, and 6 per cent of thick primaries. The antigen was present on 14 per cent of lymph node metastases and on no extranodal deposits. This suggests that loss of melanoma cell adhesion mediated by VCAM‐1 may be important in the development of metastatic melanoma.
Immunohistochemical studies on the innervation of human transplanted liver
Authors: Dhillon Amar P. , Sankey Elizabeth A. , Wang Jiahua H. , Wightman A. Kay , Mathur Sandip , Burroughs Andrew K. , Scheuer Peter J. 
Published: June 2005

AbstractThe changing pattern of innervation in the human transplanted liver was studied from the day of transplantation to 5 years later. Seven liver biopsies from non‐transplant controls, 37 liver biopsies from 22 transplant patients, and one of these biopsied livers removed at retransplantation, were available for the study. Sections were immunostained for protein gene product 9.5 (PGP 9.5), neurone‐specific enolase (NSE), S‐100 protein, and vasoactive intestinal poly‐peptide. NSE and PGP 9.5 demonstrated nerves most successfully in our tissues. Staining for most small nerves was reduced by day 5 post‐transplantation. Scanty fine nerves could be detected from day 13 to day 241 in occasional biopsies. Consistently identifiable immunostaining of PGP 9.5 and NSE nerve fibres was again apparent in portal areas after this time in all but one case. The findings indicate that in transplanted liver limited reinnervation can eventually take place. This could be due to either proliferation of intrinsic nerves, or regrowth of extrinsic nerves, or both.
Dermatopathological aspects of restrictive dermopathy
Authors: Piérard‐franchimont Claudine , Piérard GéRald E. , Estrada Trinh Hermanns‐Lě Jorge Arrese , Verloes Alain , Mulliez N. 
Published: June 2005

AbstractWe present an immunopathological and electronmicroscopic study of the skin of two newborns affected by restrictive dermopathy. Evidence of abnormal maturation was found in the epidermis, cutaneous appendages, dermis, and hypodermis. Our observations confirm two previous descriptions. We emphasize some unreported data concerning the L1 antigen and Factor XIIIa in the skin. The L1 antigen is expressed in the interadnexal epidermis, but not in hair follicles. This is the reverse pattern compared with normal skin. Factor XIIIa is poorly expressed in dermal dendrocytes, which appear rare compared with controls. The multiple defects in maturation found in all cutaneous tissues suggest a qualitative or quantitative aberration in control mechanisms of tissue interactions.