bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysosomes as key organelles in the pathogenesis of prion encephalopathies
Authors: Laszlo Lajos , Lowe James , Self Tim , Kenward Nigel , Landon Michael , McBride Trisha , Farquhar Christine , McConnell Irene , Brown John , Hope James , Mayer R. John 
Published: June 2005

AbstractThe causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and β‐glucuronidase (markers of the lysosomal compartment) and prion protein(PrP) in both control and scrapie‐infected mouse brain.In scrapie‐infected brain, lysosomes and lysosome‐related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high numbers in neuronal cell processes. These structures contain PrP, together with the lysosomal markers ubiquitin conjugates, hsp 70, and β‐glucuronidase, which could also be identified spilling from tubulovesicular dense bodies into areas of early rarefaction in neuronal processes; we suggest that these areas of rarefaction are the precursor lesions of spongiform change.We advance the hypothesis that spongiform change is brought about by cytoskeletal disruption in neuronal processes caused by liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting as the bioreactor for processing of normal PrP to the abnormal isoform. The continuous production of increasing quantities of abnormal PrPsc in lysosome‐related bodies will eventually cause disruption of the lysosomal membrane with destruction of the neuronal cytoskeleton and the initiation of vacuolation. Later, death of the cell will be associated with release of the PrPsc isoform into the extracellular environment. Repeated rounds of phagocytosis, lysosomal biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and neuronal lysis will lead to an exponential increase in cell damage and cell death.The recognition of the central role played by lysosmes in the pathogenesis of this group of diseases opens new avenues for potential therapeutic intervention.
Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms
Authors: Barbareschi Mattia , Girlando Salvatore , Mauri Francesco A. , Arrigoni Gianluigi , Laurino Licia , Palma Paolo Dalla , Doglioni Claudio 
Published: June 2005

AbstractTypical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA‐labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi‐quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.
Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining
Authors: Koukoulis George , Rayner Anne , Tan Kai‐Chah , Williams Roger , Portmann Bernard 
Published: June 2005

AbstractLittle data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL‐PCNA (clone PC‐10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post‐mortem needle‐specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid‐lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immuno‐reactivity was higher in samples taken within 5–6 days than in those obtained at 9–11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar ‘nodules’ in cases with a map‐like distribution of collapsed and non‐collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA‐positive ovoid nuclei, forming periporal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled ‘oval cells’ described in animal studies.
Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value
Authors: Bryne Magne , Koppang Hanna S. , Lilleng Rune , Kjærheim Åsmund 
Published: June 2005

AbstractSeveral recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963–1972 (N= 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P<0.01). Inter‐observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Broders' grading of the whole biopsy had no prognostic value (P<0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis.
Assessment of p53 protein expression in normal, benign, and malignant oral mucosa
Authors: Ogden Graham R. , Kiddie Roy A. , Lunny Declan P. , Lane David P. 
Published: June 2005

AbstractRecent studies have shown the accumulation of high levels of p53 protein to be associated with malignant disease, within a range of tissues. This paper assesses p53 expression in oral mucosal disease. Biopsies were obtained from a range of oral disorders which included normal, benign, premalignant, and malignant oral tissue. In addition, oral smears were obtained from a limited number of patients with biopsy‐proven oral cancer. Expression of the p53 protein was assessed using the polyclonal antibody CM1, together with a standard immunoperoxidase technique. A total of 37 oral cancers were assessed, of which 20 were found to express the p53 protein (54 per cent of cases). The p53 protein was not identified in normal, benign, or premalignant oral mucosa (54 cases). The identification of p53 within biopsies of oral mucosal lesions would appear to correlate with oral malignancy.
Degranulation of cystic fibrosis nasal polyp mast cells
Authors: Henderson William R. , Chi Emil Y. 
Published: June 2005

AbstractThe ultrastructure of nasal polyps from cystic fibrosis (CF) patients was compared with non‐CF nasal polyps in this study. Morphometric analysis showed that CF nasal polyps contained greater numbers of mast cells, endothelial cells, lymphocytes, and plasma cells compared with the non‐CF specimens. Morphologic evidence of degranulation was seen in approximately 30 per cent of the CF mast cells but was not observed in the non‐CF mast cells. Increased numbers of small granules, vacuolated granules, and lipid bodies were noted in the CF compared with the non‐CF nasal polyp mast cells. Also observed was a decrease in collagen in the extracellular space of the CF nasal polyps compared with the non‐CF specimens. Although eosinophils were observed in the non‐CF nasal polyp tissue, these leukocytes were absent in the CF nasal polyps. These data indicate that striking morphologic differences exist between CF and non‐CF nasal polyps with mast cell degranulation, a salient feature of CF specimens.
Improve your hospital autopsy rate to 40–50 per cent, a tale of two towns
Authors: Champ Caroline , Tyler Xenia , Andrews Peter S. , Coghill Stuart B. 
Published: June 2005

AbstractIn the light of medical audit, all pathology departments are scrutinizing their hospital autopsy rate. In most countries, the rate has fallen over the last few decades to between 10 and 20 per cent. However, it is still possible to achieve a much higher rate.We compare two neighbouring District General Hospital (DGHs): Northampton, with the more usual autopsy rate of 11 per cent, and Kettering, with a higher rate of 40–50 per cent. These hospitals are comparable in almost every way except for the system used to request permission for an autopsy. These differences were evaluated and the following factors were found to be of importance in achieving a high rate:

centralization of death certificates within the mortuary and personal contact between the certifying doctor and the relatives within the bereavement room;
mortuary pathology technicians are designated as bereavement officers and act as coordinators between relatives, clinicians, and pathologists; and
regular clinico‐pathological meetings and a positive attitude to autopsies by clinicians.
The fractal dimension may be a useful morphometric discriminant in histopathology
Authors: Cross Simon S. , Cotton Dennis W. K. 
Published: June 2005

AbstractThe hypothesis is presented that fractal geometry, and the fractal dimension in particular, is likely to be a more useful method of image analysis in histopathology than the use of regular Euclidean geometry. The concept of the fractal dimension is described and it is suggested that many human tumours have a fractal structure over a wide range of scales. It is postulated that the fractal dimension will be useful in discriminating between different diagnostic categories and may also allow more precise prognostic stratification within single diagnostic groups.
Immunoreactivity for p‐170 glycoprotein in malignant mesothelioma and in non‐neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB‐1
Authors: Ramael Marc , Bossche Jan Van Den , Buysse Corinne , Van Meerbeeck Jan , Segers Kurt , Vermeire Paul , Van Marck Eric 
Published: June 2005

AbstractThe results of an immunohistochemical study of P‐170 glycoprotein immunoreactivity in human non‐neoplastic mesothelium (35 cases) and in malignantmesothelioma (33 cases) using the murine monoclonal antibody JSB‐1 are reported. The majority of malignant mesothelioma cases exhibited cytoplasmic and membrane immunoreactivity in neoplastic cells. These findings are highly significant when compared with the absence of immunoreactivity in normal mesothelium.
Immunoelectron microscopy of cationized bovine serum albumininduced glomerulonephritis in the rabbit
Authors: Al‐nawab M. D. , Bass P. S. , Das A. K. , Davies D. R. 
Published: June 2005

AbstractChronic immune complex glomerulonephritis was induced in a group of New Zealand white rabbits by daily intravenous injections of cationized bovine serum albumin (cBSA). The animals were serially killed and renal tissue was embedded in the hydrophilic resin Lowicryl K4M for immunoelectron microscopy. The results demonstrate the progressive deposition of rabbit IgG in the glomerular basement membrane in this model, with aggregation of immunoglobulins occurring only in the subepithelial space. Proteinuria developed concurrently with this event. Glomerular visceral epithelial cell (GVEC) endocytosis of immune material was observed at various stages of the disease process, suggesting that GVECs may be part of a clearance mechanism acting within the glomerulus.
Peripolar cells, granulated glomerular epithelial cells, and their relationship to the juxtaglomerular apparatus in malignant hypertension
Authors: Gardiner D. Stuart , Lindop George B. M. 
Published: June 2005

AbstractWe have examined 12 autopsy kidneys from cases of malignant hypertension and compared them with normal controls. Peripolar cells and other granulated glomerular epithelial cells were counted in serial paraffin sections, and renin‐containing cells were quantified using an immunoperoxidase technique and a human renin antiserum. There were significantly more peripolar cells and other granulated glomerular epithelial cells in the cases of malignant hypertension. Most granulated glomerular epithelial cells were podocytes, situated at the periphery of the tuft. Peripolar cells correlated in number with other granulated glomerular epithelial cells and they had a similar distribution within the renal cortex, but there was no correlation between either of these cells and the number of renin‐containing cells. There was hyperplasia of renin‐containing cells in some juxtaglomerular apparatuses (JGAs), although the proportion of renin‐positive JGAs was unaltered. These results suggest that peripolar cells and other glomerular epithelial cells react in a similar way in malignant hypertension, but they do not support the hypothesis that peripolar cells are part of the JGA.
The ultrastructure of oesophageal carcinomas: Multidirectional differentiation. A transmission electron microscopic study of 43 cases
Authors: Newman Joseph , Antonakopoulos George N. , Darnton S. Jane , Matthews Hugoe R. 
Published: June 2005

AbstractForty‐three oesophageal carcinomas, comprising 15 squamous cell carcinomas, 22 adenocarcinomas, 5 small cell carcinomas, and 1 adenosquamous carcinoma, were examined by transmission electron microscopy. The ultra‐structural features of each tumour type are detailed. Multi‐directional differentiation (heterogeneity) was observed in 11 cases: 5 squamous cell carcinomas with focal glandular features; 4 adenocarcinomas with focal squamous features; and 2 small cell carcinomas, one with glandular and the other with squamous features. Abnormal distributions of desmosomes in squamous cell carcinomas and of polarity of tumour cells in adenocarcinomas are described.
Diagnosis of the acute ischaemic heart by ion elution from myocardium
Authors: Reid W. A. , Brown D. , Purves D. , Barnes I. 
Published: June 2005

AbstractThe post‐mortem diagnosis of acute myocardial ischaemia may be difficult to establish in the absence of morphological changes in the myocardium or recent coronary thrombosis. Ischaemic cell injury leads to potassium (K) efflux and sodium (Na) influx and, if the blood is still circulating, the K : Na ratio of the tissue falls. In this study, the K : Na ratio was measured by eluting the ions from samples of myocardium and assaying the eluate. The method yields similar results to those obtained by a previous method, in which myocardial samples were homogenized. The K : Na ratios on samples of horizontal slices through the heart were plotted on maps of the slices. A low K : Na ratio corresponded to, but extended beyond, areas where there was morphological evidence of ischaemia. The method is simple and may be of use in routine practice.
Renal cell carcinoma: Comparison of morphological and flow cytometric parameters of primary tumour and invasive tumour lying within the renal vein
Authors: Novelli M. R. , Maciver A. G. 
Published: June 2005

AbstractHistological assessment and DNA flow cytometry have been performed on 15 kidneys containing primary adenocarcinomas which had invaded the renal vein. Comparison of morphological variables showed that samples of the intravenous tumour were more commonly composed of granular cells (53 per cent) than were samples from the main tumour mass (16 per cent), and were also of higher nuclear grade. In 7 of 14 kidneys, DNA studies showed either a higher S‐phase fraction (five cases) or DNA aneuploidy (two cases) in tumour cells lying within the renal vein. The mean S‐phase fraction was also shown to increase in higher nuclear grades. Thus, both morphological and biological differences exist between invasive tumour cells lying within the renal vein and those in the main tumour. This is a useful model for the investigation of venous invasion and may give a better prediction of the metastatic potential of renal cell carcinoma.
Myoendothelial contacts in arteriolosclerosis
Authors: Sosa‐melgarejo Jorge A. , Berry Colin L. 
Published: June 2005

AbstractHuman renal biopsies were examined electron microscopically to investigate close contacts between endothelial and smooth muscle cells in small arterioles. These myoendothelial contacts were seen in the form of cytoplasmic projections passing through fenestrae in the basal lamina. Most of these cell processes seem to arise from the endothelial cells. In the control vessels, the separation between the endothelial cells and smooth muscle cells of the tunica media is 0.09‐0.27 μm. With arteriolosclerosis there is an increasing separation between the elements of the intima and the media, from 1.0 to 2.42 μm. In spite of this increasing separation, myoendothelial contacts maintain an intercellular space of 10–15 nm, as observed in the control vessels. At 2.42 μm of separation, the amount of extracellular material accumulated is such that the cells can no longer keep in contact. Break up of the myoendothelial contacts may be responsible for impairment of communication between the tunica intima and media in the vessel wall in arteriolosclerosis.
Epstein—barr virus latent membrane protein expression by Hodgkin and Reed—Sternberg‐like cells in acute infectious mononucleosis
Authors: Isaacson Peter G. , Schmid Christina , Pan Langxing , Wotherspoon Andrew C. , Wright Dennis H. 
Published: June 2005

AbstractIn the light of reports of latent membrane protein (LMP) expression by Hodgkin and Reed—Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen (four cases) from 14 patients with acute infectious mononucleosis (IM) have been examined for the presence of HRS‐like cells and immunostained with an antibody to LMP. Sections of the tonsils and one lymph node were also stained with a panel of antibodies which characterize HRS cells of Hodgkin's disease. The tonsils contained abundant HRS‐like cells, mainly adjacent to the crypts, which were highlighted by strong LMP expression. The immunophenotype of these cells closely, but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph nodes and spleens showed the typical changes of acute IM but only few LMP‐positive HRS‐like cells were present in the cervical lymph nodes and hardly any were present in the inguinal nodes and spleen. These findings suggest that tonsillar crypt squamous epithelium may play a role in the formation of LMP‐positive HRS‐like cells; these cells could be progenitors of Hodgkin's disease HRS cells and, if so, this might explain the restricted sites of presentation of Hodgkin's disease.
Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell carcinomas
Authors: Kovacs Angela , Storkel Stephan , Thoenes Wolfgang , Kovacs Gyula 
Published: June 2005

AbstractRenal cell tumours are characterized by the loss of chromosome 3p and trisomy of 5q segments (common, nonpapillary renal cell carcinoma), or by trisomy of chromosomes 7 and 17 and loss of the Y chromosome (papillary renal cell carcinoma), or by random karyotype changes and mitochondrial DNA alterations (renal oncocytoma). We have studied by means of RFLP analysis the genomic and mitochondrial DNA in 11 chromophobe renal cell carcinomas, which have a unique morphology among kidney cancers. We found a loss of the constitutional heterozygosity at chromosomal regions 3p, 5q, 17p, and 17q, a combination of allclic losses that has not been found in other types of renal cell tumours. Three of the tumours showed a gross alteration in the restriction pattern of the mitochondrial DNA. A combined morphological and genetic analysis suggests that chromophobe renal cell carcinoma is a distinct entity.
A two‐colour technique for chromosome in situ hybridization in tissue sections
Authors: Lutz Steffi , Welter Cornelius , Zang Klaus D. , Seitz Gerhard , Blin Nikolaus , Urbschat Klaus 
Published: June 2005

AbstractBy extending non‐isotopic in situ hybridization of DNA probes (targeted to metaphase chromosomes or interphase nuclei) to hybridization using tissue sections, additional topological information on the DNA structure and specific alterations can be obtained. We have established a method for the application of two different, chromosome‐specific probes labelled with two colour dyes allowing simultaneous detection of two‐colour signals. This method was tested in and is applicable to tissue sections of various origins. To demonstrate its sensitivity, prostate carcinomas (either as cryosections or as sections from paraffin blocks) were investigated for the presence or absence of chromosomes 1 and Y. The technique presented here, comparable to immunohistochemical staining, is particularly useful for routine application in diagnostic laboratories and testing of fresh or archival material.
Seminal vesicle amyloid: The first example of exocrine cell origin of an amyloid fibril precursor
Authors: Cornwell Gibbons G. , Westermark Gunilla T. , Pitkanen Peter , Westermark Per 
Published: June 2005

AbstractAmyloid fibrils have been extracted from seminal vesicles, and a dominant 14 kD amyloid fibril protein has been identified. An antiserum to this protein reacted both with amyloid and with epithelial cells in some normal seminal vesicles. These reactions were blocked with seminal vesicle secretion and seminal vesicle amyloid fibril protein, but not by degraded amyloid fibrils or fibril protein from other types of amyloid. It is concluded that seminal vesicle amyloid is derived from secretory proteins of the seminal vesicles. As such, it is the first amyloid described which appears to be the product of an exocrine secretory cell.