bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of p53 protein in normal, dysplastic, and neoplastic Barrett's oesophagus
Authors: Krishnadath Kausilia K. , Tilanus Hugo W. , van Blankenstein Mark , Bosman Fre T. , Mulder Andries H. 
Published: June 2005

AbstractAccumulation of p53 protein was determined by immunohistochemisty in archival material of biopsy specimens from 102 patients with Barrett's oesophagus with different grades of dysplasia, in 24 oesophageal adenocarcinomas associated with Barrett's oesophagus, and in 23 cases of metaplatic epithelium adjacent to these carcinomas. Immunostaining for the p53 protein was found in 23/102 (23 per cent) cases of the Barrett's oesophagus biopsies and in 12/23 (52 per cent) cases of Barrett's oesophagus adjacent to adenocarcinoma. Significant correlations were found between the grade of dysplasia and p53 immunoreactivity in both Barrett's biopsies without adenocarcinoma (P<0.001) and Barrett's oesophagus adjacent to adenocarcinoma (P<0.05). In the adenocarcinomas, intense nuclear immunohistochemical staining for p53 was diffusely or focally present in 20/24 (83 per cent) of the specimens. In Barrett's oesophagus, p53 is a progression marker with high expression in high‐grade dysplasia (89 per cent) and adenocarcinoma (83 per cent).
p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors
Authors: Nadal Alfons , Campo Elías , Pinto José , Mallofré Carme , Palacín Antonio , Arias Carlos , Traserra José , Cardesa Antonio 
Published: June 2005

Abstractp53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non‐invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S‐phase of the tumours, disease‐free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53‐positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low‐grade dysplasias and 5 of 10 (50 per cent) high‐grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease‐free nor overall survival showed differences between p53‐positive and p53‐negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progression of the tumours.
PCR‐mismatch analysis of p53 gene mutation in Hodgkin's disease
Authors: Xerri Luc , Parc Patricia , Bouabdallah Reda , Camerlo Jacques , Hassoun Jacques 
Published: June 2005

AbstractExpression of the p53 protein can be detected by immunohistochemistry in Reed‐Sternberg (RS) cells, the presumed neoplastic component of Hodgkin's disease (HD) lesions. At present, there is no clear molecular evidence that p53 positive immunostaining in HD correlates with the presence of mutations or other structural alterations of the p53 gene. To address this question, 49 cases of HD have been investigated for p53 expression by immuno‐histochemistry, using the DO1 monoclonal antibody on paraffin sections. Thirty‐seven out of 49 cases (75 per cent) exhibited positive immunostainining restricted to RS cells and variants. Among these 37 positive cases, ten cases were selected on the basis of a rich content of RS cells showing virtually 100 per cent DO1 positivity. A PCR‐mismatch strategy was chosen for the detection of p53 mutations. The threshold level of sensitivity was assessed on positive cell‐line controls. A proportion of 10–15 per cent p53 mutated cells mixed in a normal population could be identified. Total genomic DNA was extracted from the ten selected HD cases and PCR amplification of exons 5–8 of the p53 gene was performed. Heteroduplex mismatch analysis revealed no structural alterations of the p53 gene in any case. In view of these findings, it appears unlikely that the sensitivity of the method by itself can fully explain the negative results, although this possibility cannot be completely ruled out. Thus, it is conceivable that p53 positive immunostaining in HD may not necessarily imply genomic alterations in the classic ‘hot spot’ regions and may be related to another mechanism of p53 protein stabilization.
Loss of heterozygosity in ductal carcinoma in situ of the breast
Authors: Stratton Michael R. , Collins Nadine , Lakhani Sunil R. , Sloane John P. 
Published: June 2005

AbstractLoss of heterozygosity (LOH) at loci reported to show allele loss in invasive breast cancers was examined in ductal in situ carcinomas of the breast using polymorphic short tandem repeats and the polymerase chain reaction (PCR). LOH was detected at all loci examined in at least 11 per cent of the samples examined. The proportion of cases of in situ carcinoma showing LOH at these loci was similar to that previously reported in invasive cancers. Cases of pure in situ cancer without an invasive component exhibited an overall lower frequency of allele loss. LOH at more than one locus was observed in some intraductal cancers. In a small number of cases, LOH was present in the invasive but not in the intraductal component of the tumour, suggesting that mutation at the locus concerned was associated with development of invasive behaviour.
Expression of c‐myc protein is related to cell proliferation and expression of growth factor receptors in transitional cell bladder cancer
Authors: Lipponen Pertti K. 
Published: June 2005

AbstractArchival biopsy specimens from transitional cell bladder tumours (n=185) were analysed immunohistochemically for expression of c‐myc protein. The results were compared with compared with histopathological and clinical parameters and survival. Forty‐three per cent of the tumours were negative for c‐myc protein and weak, moderate, or strong cytoplasmic expression was found in 34, 14, and 9 per cent of cases, respectively. Nuclear positivity for c‐myc protein was detected in 35 per cent of tumours and nuclear opositivity was related to overexpression of c‐erb B‐2 (P=0.01) and a high proportion of nuclei were also positive for p53 oncoprotein (p<0.05). Cytoplasmic expression of c‐myc protein was related to histological grade (P=0.005), papillary status (P=0.007), the S‐phase fraction (P=0.008), the mitotic index (P=0.021), overexpression of epidermal growth factor receptor (P=0.045), and c‐erb B‐2 (P=0.17). Expression of c‐myc protein was not significantly related to the progression of tumours and it had no prognostic value in survival analysis. Independent predictors were the T‐category (P<0.001), papillary status. (P=0.001), and S‐phase fraction (P=0.061). The results show that while c‐myc gene product participates in growth regulation of human bladder cancer cells, it has no independent prognostic significance.
MDM2 and CDK4 gene amplification in Ewing's sarcoma
Authors: Ladanyi Marc , Lewis Ronald , Jhanwar Suresh C. , Gerald William , Huvos Andrew G. , Healey John H. 
Published: June 2005

AbstractAmplification of the MDM2 gene, which maps to chromosome band 12q13 and encodes a p53‐binding protein, may result in functional inactivation of p53 and has been observed in various bone and soft tissue sarcomas. Published studies have included few cases of Ewing's sarcoma (ES) or peripheral neuroectodermal tumour (PNET), a tumour group in which alterations of the p53 pathway have so far not been extensively studied. We examined two ES cell lines, RD‐ES and SK‐ES‐1, and 30 specimens from 27 patients (24 ES, 6 PNET; 19 primary, 4 local recurrence, 7 metastasis) for MDM2 gene amplification by Southern blot analysis. All 30 clinical specimens had been confirmed to contain sufficient ES/PNET DNA by the demonstration of a rearrangement of the t(11;22)‐associated EWS gene using an EWS cDNA probe on the same blots. MDM2 gene amplification was detected in 3 of 30 specimens (10 per cent), including two ES and one PNET, but in neither of the cell lines. The three cases with amplification were morphologically typical primary tumours. Two of the three cases also showed co‐amplification of the CDK4 gene, which endoces a cyclin‐dependent kinase and also maps to band 12q13. Clinically, all three cases had metastatic disease at diagnosis, compared with only 1 of 15 MDM2‐negative cases where the primary tumour was studied. The difference was statistically significant (P=0.005), suggesting an association of MDM2 amplification with advanced stage. Further accural and multivariate analysis of ES/PNET cases with MDM2 gene amplification will be necessary to confirm the clinical significance of these findings. The results suggest that the prevalence of MDM2 gene amplification in ES/PNET is comparable to other sarcomas, and implicate dysfunction of the p53 pathway in a subset of ES/PNET. The biological significance of CDK4 co‐amplification remains to be determined.
Epstein‐Barr virus in B‐cell non‐Hodgkin's lymphomas: Unexpected infection patterns and different infection incidence in low‐ and high‐grade types
Authors: Hummel Michael , Anagnostopoulos Ioannis , Korbjuhn Petra , Stein Harald 
Published: June 2005

AbstractTwo hundred and eight cases of B‐cell non‐Hodgkin's lymphoma (B‐NHL) occurring in Europeans without any signs of HIV infection were investigated for their association with an Epstein‐Barr virus (EBV) infection. The polymerase chain reaction (PCR) was applied for EBV‐DNA detection, in situ hybridization (ISH) for the cellular localization of EBV‐encoded small nuclear RNAs (EBER) and immediate‐early RNAs (BHLF), and immunohistology (IH) for the detection of EBV‐encoded latent membrane protein (LMP) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER‐ISH produced congruent results in those cases with amplifiable DNA. EBV was present overall in 26 per cent (54/208) of the B‐NHL cases. Through EBER‐ISH, the virus could be localized merely in rare non‐neoplastic bystander lymphocytes in 27 and additionally in tumour cells of 27 cases. Unexpectedly, the proportion of EBV‐infected tumour cells present in the different cases varied between 1 and 100 per cent. All but three of the cases with infected tumour cells were of high‐grade malignancy. Correlation with the morphological and immunological tumour phenotype revealed that all cases with more than 80 per cent EBER‐positive tumour cells were either B‐anaplastic large cell lymphomas (B‐ALCL), sporadic Burkitt's lymphomas, or B‐NHLs with partial or full plasmacellular differentiation. LMP was consistently absent from Burkitt's lymphomas and constantly expressed in B‐ALCLs with EBER‐positive tumour cells, while in all other instances it varied greatly and was rarer than EBER expression. The above findings suggest that in cases where EBV is present in 80–100 per cent of tumour cells, EBV infection takes place before malignant transformation and thus may have contributed to the malignant phenotype, whereas in the other cases with only a smaller number of infected tumour and single bystander cells, EBV infection may have occurred following malignant transformation. In these cases, infection would appear to be of little or no significance in tumourigenesis.
Identification of tumour‐specific translocations in archival material
Authors: Williams G. H. , Williams E. D. 
Published: June 2005

AbstractA reverse transcriptase nested polymerase reaction (RT‐nPCR) method has been developed to detect the presence of a tumour‐specific translocation in archival formalin‐fixed, paraffin‐embedded tissue. This technique can be applied to the large numbers of tumours in pathology departments' archives, allowing correlation of translocations with morphological diagnosis, response to therapy, and survival.
Immunohistochemical analysis of adhesion molecules in the micro‐environment of portal tracts in relation to aberrant expression of PDC‐E2 and HLA‐DR on the bile ducts in primary biliary cirrhosis
Authors: Yasoshima Mitsue , Nakanuma Yasuni , Tsuneyama Kouichi , van de Water Judy , Eric Gershwin M. 
Published: June 2005

AbstractWe have examined immunohistochemically the expression of adhesion molecules in the micro‐environment of portal tracts and their relationship to the expression of the pyruvate dehydrogenase E2 complex (PDC‐E2) and HLA‐DR in liver biopsy specimens.Ten cases of primary biliary cirrhosis (PBC) and 19 controls were examined, including four cases of extrahepatic biliary obstruction, six of chronic viral hepatitis, and nine normal livers. In PBC, the damaged small bile ducts demonstrated an increased expression of PDC‐E2 and an aberrant expression of HLA‐DR; about half of these damaged bile ducts also expressed intercellular adhesion molecules (ICAM)‐1 and a few expressed vascular adhesion molecule (VCAM)‐1. In addition, lymphocyte function‐associated antigen (LFA)‐1 and very late antigen (VLA)‐4 were expressed on infiltrating lymphocytes around these bile ducts. In contrst, in control livers, these alterations in antigen expression on the bile ducts were either not observed or were only focal and weak, when present. These findings suggest that ICAM‐1/LFA‐1 and also VCAM‐1/VLA‐4 linkages between the damaged bile ducts and lymphocytes may facilitate antigen‐specific reactions such as the presentation of antigens, possibly PDC‐E2, to the periductal lymphocytes in PBC. ICAM‐1, VCAM‐1, and E‐selectin were strongly expressed on the endothelial cells of some vessels in the portal tracts in PBC, suggesting the facilitation of the recruitment of lymphocytes around the of some vessels in the portal tracts in PBC, suggesting the facilitation of the recruitment of lymphocytes around the bile ducts of PBC. VCAM‐1, a member of the immunoglobulin superfamily, has not hitherto been reported on bile ducts.
In vitro effects of interleukins on human mesangial cells: Implications for glomerulonephritis
Authors: Chen W.‐P. , Chen A. , Lin C.‐Y. 
Published: June 2005

AbstractIntrinsic glomerular cells, especially mesangial cells, are considered to be actively involved in the pathogenesis of glomerulonephritis (GN), but the precise mechanism(s) remains elusive. We have previously demonstrated that nephritogenic IgA immune complex can stimulate human mesangial cells (HMCs) to increase their production of interleukin‐1 (IL‐1) and interleukin‐6 (IL‐6). In order to evaluate the roles of cytokines such as IL‐1 and/or IL‐6 and mesangial cells as mediators of renal injury in GN, we have now examined the changes of HMCs and their secreted products in vitro, after stimulation with various concentrations of IL‐1 and IL‐6. Cytokine‐activated HMCs showed the following changes: (1) increased cell size, with intracytoplasmic vaculoes, dilated endoplasmic reticulum, increased free ribosomes and polysomes, and mitochondrial swelling; (2) increased cell proliferation, reflected in thymidine incorporation and an increased proportion of S and G2/M phase cells by cell cycle analysis; (3) enhancement of IL‐6 mRNA expression in HMCs with stimulation of IL‐6 alone or IL‐1 plus IL‐6; and (4) release of large amounts of platelet activating factor (PAF), thromboxane B2 (TxB2), and superoxide anion. Taken together, these results strongly suggest that mesangial cell proliferation and increased production of immune/chemical mediators and superoxide anion can be directly induced by IL‐1 plus IL‐6. These changes may lead to ongoing renal injury.
Interphase cytogenetic analysis of distinct X‐chromosomal translocation breakpoints in synovial sarcoma
Authors: Janz Martin , de Leeuw Bertie , Weghuis Danielle Olde , Werner Martin , Nolte Martina , van Kessel Ad Geurts , Nordheim Alfred , Hipskind Robert A. 
Published: June 2005

AbstractSynovial sarcomas show a specific translocation involving chromosomes X and 18, t(X;18)(p11.2;q11.2). Two distinct X‐chromosomal breakpoints occur in different synovial sarcoma tumour samples. These breakpoints are located within two related genomic regions containing ornithine aminotransferase‐like sequences, termed OATAL1 and OATL2. Preliminary observations indicated the potential correlation of OATL1‐associated breakpoints with biphasic tumours and OATL2‐associated breakpoints with monophasic fibrous tumours. The present study uses interphase cytogenetics to investigate the nature of chromosomal aberrations in frozen synovial sarcoma tissue samples. Two‐colour fluorescence in situ hybridization (FISH) was performed using probes specific for the centromeres of chromosome X or 18, along with yeast artificial chromosome probes corresponding to the distinct breakpoint regions on Xp. One monophasic epithelial and two monophasic fibrous synovial sarcomas showed an OATL2‐associated breakpoint, while a biphasic tumour revealed a hybridization pattern indicating a breakpoint within the OATL1 region. These results confirm our previous suggestion of a relationship between alternative breakpoints in Xp11.2 and different histological phenotypes observed in synovial sarcomas. They also demonstrate the utility of the two‐colour hybridization approach for the identification of chromosomal changes in interphase nuclei isolated from frozen tissues.
Experimental ulceration leads to sequential expression of spasmolytic polypeptide, intestinal trefoil factor, epidermal growth factor and transforming growth factor alpha mRNAs in rat stomach
Authors: Alison Malcolm R. , Chinery Rebecca , Poulsom Richard , Ashwood Paul , Longcroft Janet M. , Wright Nicholas A. 
Published: June 2005

AbstractA model of gastric ulceration in the rat has been used to determine the expression of four messenger RNAs (mRNAs) encoding peptides considered to play active parts in the healing response. The trefoil peptides, rat spasmolytic polypeptide (rSP) and rat intestinal trefoil factor (rITF), along with epidermal growth factor (EFG) and transforming growth factor alpha (TGFα) were the molecules studied. Ulceration was caused under anaesthesia by brief application of a liquid nitrogen‐filled cryoprobe to the gastric serosal surface and RNA expression was monitored over the next 10 days. Each mRNA was quantified by ribonuclease protection assay, and mRNAs encoding rSP and rITF were localized within tissue sections by hybridization in situ with 35S antisense riboprobes. Ulceration induced the very rapid expression of first rSP and then rITF mRNA, whereas the mRNAs encoding EGF and TGFα increased at later times, with maxima recorded at 3 and 6 days, respectively. Hybridization in situ detected extensive rSP mRNA expression in the regenerative epithelia. The pronounced, but temporally different patterns of mRNA induction after ulceration suggest that the trefoil peptides may fulfil different and more ummediate roles than the more ‘traditional’ healing proteins EGF and TGAα.
Tenascin immunoreactivity in cryptogenic fibrosing alveolitis
Authors: Wallace W. A. H. , Howie S. E. M. , Lamb D. , Salter D. M. 
Published: June 2005

AbstractTenascin is a hexameric extracellular matrix (ECM) glycoprotein which has been demonstrated to have a temporal relationship with active scar formation in adult tissues. We hypothesized that this ECM protein might therefore serve to identify areas of active scarring in lung biopsies from patients with cryptogenic fibrosing alveolitis (CFA). The distribution of tenascin was examined in open lung biopsies from ten patients with CFA, six patients with sarcoidosis, and six pulmonary resection specimens from patients with no evidence of interstitial lung disease, using an immunohistochemical technique. Immunoreactive tenascin was not identified in histologically normal control lung parenchyma and was only focally found around large aggregates of granulomas in sarcoidosis. In the CFA, tenascin production was demonstrated in minimally damaged alveolar walls and areas of active disease but not in end‐stage scarred lung. There was considerable local heterogeneity of staining within cases, which did not appear to relate to the density of the local inflammatory infiltrate. Large plaques of tenascin were noted to be particularly associated with hyperplastic type II alveolar epithelial lining cells, which are recognized to produce fibrogenic cytokines. The examination of tenascin expression in open lung biopsies from patients with CFA may be useful in assessing fibrogenic activity and may thus provide additional prognostic information.
Standardized staining and analysis of argyrophilic nucleolar organizer region associated proteins (AgNORs) in radically resected colorectal adenocarcinoma—correlation with tumour stage and long‐term survival
Authors: Öfner Dietmar , Riedmann Bernhard , Maier Hans , Hittmair Anton , Rumer Astrid , Tötsch Martin , Spechtenhauser Bernhard , Böcker Werner , Schmid Kurt W. 
Published: June 2005

AbstractQuantification of silver‐stained nucleolar organizer region associated proteins (AgNORs) was introduced in histopathology as a marker of cellular and nucleolar activity. However, due to the poor staining quality obtained on routinely processed archival material, the method yielded controversial and sometimes non‐reproducible results. The recent introduction of wet autoclave pretreatment has reliably improved AgNOR staining quality on routinely formalin‐fixed and paraffin‐embedded tissues. In the present study, 92 routinely processed colorectal carcinomas were investigated, applying this novel staining technique. Subsequent standardized morphometric analysis revealed, irrespective of common tumour staging or grading classifications, a statistically highly significant correlation between AgNOR parameters and clinical course. The usefulness of standardized AgNOR parameters for the independent prediction of patient survival was proven by uni‐ and multivariate analysis.
The pathogenesis of fat embolism
Authors: Hulman Geoffrey 
Published: June 2005

AbstractFat embolism is a common autopsy finding in patients with or without a history of trauma. There are two basic mechanisms causing fat to embolize. Depot‐derived fat embolism arises by disruption of depot fat, usually as a result of trauma, allowing direct entry into the bloodstream. Plasma‐derived fat embolism is caused by agglutination of endogenous or infused exogenous fat such as Intralipid, with consequent embolism. Chylomicrons and Intralipid liposomes are known to undergo calcium‐dependent agglutination by C‐reactive protein (CRP), and this may play a role in vivo in this type of fat embolism.
Demonstration of DNA damage/repair in individual cells using in situ end labelling: Association of p53 with sites of DNA damage
Authors: Coates Philip J. , Save Vicki , Ansari Bijan , Hall Peter A. 
Published: June 2005

AbstractWe describe the development and application of in situ end labelling (ISEL) to identity sites of damaged DNA in the nuclei of individual cells. In cell culture, exposure to a variety of genotoxic agents induced a dose and time‐dependent increase in nuclear labelling. In addition, examination of histological sections of human skin exposed to solar‐simulated UV light showed ISEL in both keratinocytes and superficial dermal cells, with the same spatial and temporal distribution as that of a marker of DNA repair, PCNA (proliferating cell nuclear antigen). Using co‐localization techniques and confocal microscopy, we found increased levels of p53 in many ISEL‐positive cells in vitro, with a similar distribution of labelling in the nucleus. This observation provides further evidence for a direct role of p53 in the recognition of damaged DNA. Thus, ISEL should prove a convenient method for demonstrating genotoxic insult in individual cells and in histological material, and may have value in toxicological screening. This high‐resolution microscopy technique can also be used to compare the spatial distribution of various proteins implicated in the response to DNA damage with the sites of the lesion.