bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of tissue markers p27kip1, MIB‐1, and CD44s for the pre‐operative prediction of tumour features in screen‐detected prostate cancer
Authors: Vis A. N. , van Rhijn B. W. G. , Noordzij M. A. , Schröder F. H. , van der Kwast Th. H. 
Published: October 2002

AbstractThe pre‐operative prediction of prognostic tumour features in the radical prostatectomy specimen using routine clinicopathological variables remains limited. The present study evaluated the predictive value of the cell‐cycle protein p27kip1, the proliferation marker MIB‐1, and the cell‐adhesion protein CD44s, determined on the diagnostic needle biopsy of asymptomatic men screened for prostate cancer. Of 81 screen‐detected prostate cancers, representative biopsy cores and matched radical prostatectomy specimens were immunohistochemically stained for these tissue markers. Conventional pre‐operative and post‐operative clinicopathological variables were assessed and cancers were divided according to a validated tumour classification model (potentially harmless, clinically significant). Low (<50%) p27kip1 expression, high (≥10%) MIB‐1 expression, and low (<25%) CD44s expression were considered adverse prognostic signs. Binary logistic regression analysis was performed to assess the most valuable predictors of clinically significant disease. An adverse prognostic immunostaining assessment on the biopsy was found in 10 (12.3%), 17 (21.0%), and 25 (30.9%) cases for p27kip1, MIB‐1, and CD44s, respectively. The concordance in tissue marker assessment between the biopsy specimen and matched radical prostatectomy specimens was low for all three. The positive predictive value (PPV) of p27kip1 was 90.0%, remarkably higher than that of MIB‐1 and CD44s (41.2% and 52.0%, respectively), indicating that a low radical prostatectomy p27kip1 score is expected if the biopsy p27kip1 score is low. Logistic regression analysis revealed that biopsy Gleason score (p<0.01) and p27kip1 assessment (p<0.01) remained the only significant predictors of clinically significant disease. All cases with low p27kip1 expression were found to have clinically significant disease after radical prostatectomy. The assessment of p27kip1 in the biopsy specimen might thus assist in distinguishing between potentially aggressive and potentially non‐aggressive disease in prostate cancer screening. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of histological features associated with metastatic potential in thin (<1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group
Authors: Cook Martin G. , Spatz Alain , Bröcker Eva‐Bettina , Ruiter Dirk J. 
Published: October 2002

Abstract An Erratum has been published for this article in The Journal of Pathology 197(5) 2002, 692.
Contrary to expectations, a small number of thin (<1 mm) melanomas do metastasize. This collaborative study was performed in an attempt to identify the morphological basis of such aggressive behaviour. Regression was expected to be the explanation for the lack of thickness in some cases. Whether a vertical growth phase (VGP) was present in the remainder was carefully assessed. A pilot study had identified two other patterns associated with metastasis in thin melanomas. These were termed ‘junctional expansion nodules’ and ‘melanomatous follicular invasion’. Both were seen in the absence of other dermal invasion. These two patterns were included in the study, which comprised 54 cases and 56 controls, which were thin melanomas which had not metastasized 5 years after excision. Regression was present in 50% of test cases (30.4% in controls, p=0.036) and VGP was present in 59.3% of cases and 48.2% of controls. The thinnest metastasizing melanoma without regression was 0.27 mm. Eight (14.8%) cases, however, had metastasized but showed neither regression nor VGP; seven of these showed a junctional expansion nodule, present in only three controls (p=0.016). Five of these seven also showed melanomatous follicular invasion. One of these five showed this follicular involvement without a junctional nodule. Melanomatous follicular invasion was not seen in the control cases (p=0.012). Mitoses were seen in the VGP of both test and control cases, but high counts (>3 per mm2) were much more common in the metastasizing lesions (p=0.007). These findings support the idea that in most cases, regression and/or a VGP are required for metastasis to occur. However, a small number of thin melanomas without these features, as conventionally described, still metastasize. This implies that VGP may require redefinition and that junctional expansion nodules and melanomatous follicular invasion may be variants of VGP. Copyright © 2002 John Wiley & Sons, Ltd.
Herpesviruses in brain and Alzheimer's disease
Authors: Lin Woan‐Ru , Wozniak Matthew A. , Cooper Robert J. , Wilcock Gordon K. , Itzhaki Ruth F. 
Published: October 2002

AbstractIt has been established, using polymerase chain reaction (PCR), that herpes simplex virus type 1 (HSV1) is present in a high proportion of brains of elderly normal subjects and Alzheimer's disease (AD) patients. It was subsequently discovered that the virus confers a strong risk of AD when in brain of carriers of the type 4 allele of the apolipoprotein E gene (apoE‐ε4). This study has now sought, using PCR, the presence of three other herpesviruses in brain: human herpesvirus 6 (HHV6)—types A and B, herpes simplex virus type 2 (HSV2) and cytomegalovirus (CMV). HHV6 is present in a much higher proportion of the AD than of age‐matched normal brains (70% vs. 40%, p=0.003) and there is extensive overlap with the presence of HSV1 in AD brains, but HHV6, unlike HSV1, is not directly associated in AD with apoE‐ε4. In 59% of the AD patients' brains harbouring HHV6, type B is present while 38% harbour both type A and type B, and 3% type A. HSV2 is present at relatively low frequency in brains of both AD patients and normals (13% and 20%), and CMV at rather higher frequencies in the two groups (36% and 35%); in neither case is the difference between the groups statistically significant. It is suggested that the striking difference in the proportion of elderly brains harbouring HSV1 and HSV2 might reflect the lower proportion of people infected with the latter, or the difference in susceptibility of the frontotemporal regions to the two viruses. In the case of HHV6, it is not possible to exclude its presence as an opportunist, but alternatively, it might enhance the damage caused by HSV1 and apoE‐ε4 in AD; in some viral diseases it is associated with characteristic brain lesions and it also augments the damage caused by certain viruses in cell culture and in animals. Copyright © 2002 John Wiley & Sons, Ltd.
Extranodal marginal zone B cell lymphomas of the uvea: an analysis of 13 cases
Authors: Coupland Sarah E. , Foss Hans‐Dieter , Hidayat Ahmed A. , Cockerham Glenn C. , Hummel Michael , Stein Harald 
Published: October 2002

AbstractThe majority of primary lymphoproliferative lesions of the uvea represent low‐grade B cell lymphomas and often display a prominent plasmacellular differentiation. The purpose of the current study was to classify the uveal lymphoproliferations according to the REAL classification; examine the immune profile of the plasmacellular differentiated tumour cells using the plasma cell‐related antigens multiple myeloma oncogene‐1‐protein (MUM1), Vs38c, CD38 and CD138; and to compare this profile with that of mature reactive plasma cells. Following fixation, 13 lymphoproliferative lesions of the uvea were categorized on the basis of their morphology and immunophenotype according to the REAL classification. Included in the immunohistochemistry were B cell‐specific activator protein (BSAP), MUM1, Vs38c, CD38 and CD138. Nested polymerase chain reaction (PCR) was also performed on DNA extracted from paraffin sections for the detection of gene rearrangements of the heavy immunoglobulin chain (IgH). All of the 13 uveal tract lymphoproliferative lesions represented malignant lymphoma of B cell non‐Hodgkin type and could be diagnosed as ‘extranodal marginal zone B cell lymphomas’ (EMZL). The degree of plasmacellular differentiation varied between the tumours. In contrast to their non‐plasmacytoid counterparts, the ‘plasmacytoid’ EMZL tumour cells were negative for the B cell markers CD20 and BSAP, and demonstrated heterogeneous positivity for the markers MUM1, Vs38c, CD38 and CD138. The most consistent marker was MUM1, being observed in all tumours. Co‐expression of all plasma cell markers was observed in four (31%) uveal EMZL. Loss of CD138 expression was observed in six (46%) tumours, of Vs38c expression in five (38%) and of CD38 in one (7%) tumour. Although the diagnosis of malignant lymphoma was unequivocally based on morphological and immunophenotypical features, the molecular analysis was able to demonstrate clonal B cell populations in only one uveal EMZL. All uveal lymphoid proliferations investigated represented EMZL, with the corresponding morphology and immunophenotype as seen in EMZL in other extranodal locations. MUM1, followed by CD38 expression, were the most constant plasma cell antigens in the plasmacytoid EMZL tumour cells, with both Vs38c and CD138 positivity being lost in many tumours. Aberrant immune profiles of plasma cell‐related antigens may be of help in the establishment of malignancy in uveal lymphoproliferative lesions, particularly where interpretation of light chain expression and/or PCR results is difficult. Copyright © 2002 John Wiley & Sons, Ltd.
Changes in myosin heavy chain and its localization in rat heart in association with hypobaric hypoxia‐induced pulmonary hypertension
Authors: Nakanishi Kuniaki , Nakata Yasuko , Kanazawa Fumiko , Imamura Shin‐ichiro , Matsuoka Rumiko , Osada Hiroshi , Kawai Toshiaki , Uenoyama Maki , Aurues Takashi , Ikeda Tomosumi 
Published: October 2002

AbstractExperimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodelling of the heart. In rat cardiac ventricles, pressure and volume overload are well known to be associated with changes in cardiac myosin heavy chain (MHC) isoforms. To study the effects of HHE on the MHC profile in the ventricles, 83 male Wistar rats were housed in a chamber at the equivalent of 5500 m altitude for 1–8 weeks. Pulmonary arterial pressure, right ventricular free wall (RVFW) weight, the ratio of RVFW weight over body weight (BW), the ratio of left ventricular free wall (LVFW) weight over BW, and myocyte diameter in both ventricles showed significant increases after 1 week, 2 weeks, 1 week, 6 weeks, and 4 weeks of HHE, respectively. Semi‐quantitative reverse transcriptase–polymerase chain reaction revealed that β‐MHC mRNA expression was increased significantly in both ventricles at 6 and 8 weeks of HHE, whereas α‐MHC mRNA expression was decreased significantly at 6 and 8 weeks of HHE in the right ventricle (RV) and at 6 weeks of HHE in the left ventricle (LV). The percentage of myosin containing the β‐MHC isoform was increased significantly at 4–8 weeks of HHE in RV and at 6 weeks of HHE in LV. In situ hybridization showed that the area of strong staining for β‐MHC mRNA was increased in both ventricles at 8 weeks of HHE, and showed a decrease from RVFW to cardiac septum, and from cardiac septum to LVFW. These results suggest that HHE has a significant effect on the expression of both MHC mRNA and protein in the heart, particularly in RV. These changes may reflect a role for cardiac MHC in the response to pulmonary hypertension in HHE. Copyright © 2002 John Wiley & Sons, Ltd.
Mucin gene expression in intraductal papillary‐mucinous pancreatic tumours and related lesions
Authors: Terris Benoît , Dubois Sylvie , Buisine Marie‐Pierre , Sauvanet Alain , Ruszniewski Philippe , Aubert Jean‐Pierre , Porchet Nicole , Couvelard Anne , Degott Claude , Fléjou Jean‐Francois 
Published: October 2002

AbstractIntraductal papillary‐mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas. Copyright © 2002 John Wiley & Sons, Ltd.
Lack of in vivo blockade of Fas‐ and TNFR1‐mediated hepatocyte apoptosis by the hepatitis C virus
Authors: Rubbia‐Brandt Laura , Taylor Sophia , Gindre Patrizia , Quadri Rafael , Abid Karim , Spahr Laurent , Negro Francesco 
Published: October 2002

AbstractIn vitro data have shown that the hepatitis C virus (HCV) core protein binds to protein members of the tumour necrosis factor receptor (TNFR) superfamily. Since this interaction could be relevant to HCV persistence and oncogenesis, this study assessed whether HCV may interfere with the apoptotic cascade in vivo. Apoptosis (by TUNEL) and Fas and TNFR1 expression (by immunohistochemistry) were scored in the liver of 60 chronic hepatitis C patients. Results were compared with the liver disease grading and staging scores and the HCV replication level in serum and liver. Apoptotic hepatocytes were stained in 29 cases. Fas was expressed in 35 cases and TNFR1 in 21, 15 patients (25%) being negative for both receptors. Overall, the numbers of TUNEL‐, Fas‐ and TNFR‐positive hepatocytes did not correlate with the extent of intrahepatic CD8+ T‐lymphocyte infiltration, the grading and staging of liver disease, or the serum or liver HCV RNA levels. Furthermore, when patients expressing either Fas or TNFR1 were stratified according to serum HCV RNA levels, cases with detectable hepatocyte apoptosis had higher HCV viraemias. In conclusion, an HCV‐mediated, in vivo blockade of hepatocyte apoptosis via the Fas‐ or TNFR1‐dependent pathways seems unlikely. Copyright © 2002 John Wiley & Sons, Ltd.
Functional allelic loss detected at the protein level in archival human tumours using allele‐specific E‐cadherin monoclonal antibodies
Authors: Becker Karl‐Friedrich , Kremmer Elisabeth , Eulitz Manfred , Schulz Stephan , Mages Jörg , Handschuh Gabriele , Wheelock Margaret J. , Cleton‐Jansen Anne‐Marie , Höfler Heinz , Becker Ingrid 
Published: October 2002

AbstractImmunohistochemical analysis has been used to show that expression of the homophilic cell‐to‐cell adhesion molecule, E‐cadherin, is frequently altered in human cancers, including gastric and breast carcinoma. Besides genetic down‐regulation, structural mutations such as in‐frame deletions of exon 8 and exon 9 were frequently found; these may affect the binding of monoclonal antibodies used for immunohistochemical analysis. In this study it was found that antibodies HECD‐1 and E9, two monoclonal antibodies often used in E‐cadherin immunoanalysis, react with epitopes present at least in part in exon 8 and exon 9, respectively. This study generated and characterized a mutation‐specific monoclonal antibody, E‐cad delta 8‐1, reacting with the mutant protein lacking exon 8 but not with the wild‐type molecule. By using E‐cad delta 8‐1 and HECD‐1, it was possible separately to analyse the immunoreactivity of mutant and normal E‐cadherin proteins, respectively, in an allele‐specific manner in archival material. A similar analysis was performed using E9 and the previously characterized mutation‐specific antibody E‐cad delta 9‐1. Typically, in gastric and breast cancer harbouring E‐cadherin splice site gene mutations, the mutant proteins were expressed but the wild‐type protein was not detected in malignant tissues. These results indicate that variant‐specific monoclonal antibodies can be used to identify differentially expressed E‐cadherin proteins. For immunohistochemical analysis of E‐cadherin, at least two different monoclonal antibodies should be used to exclude alterations of the epitopes resulting in failure to detect a mutant protein. Copyright © 2002 John Wiley & Sons, Ltd.
Different expression of hepatitis B surface antigen between hepatocellular carcinoma and its surrounding liver tissue, studied using a tissue microarray
Authors: Wang Yi , Wu Meng‐Chao , Sham Jonathan S. T. , Tai Lai‐Shan , Fang Yan , Wu Wei‐Qing , Xie Dan , Guan Xin‐Yuan 
Published: October 2002

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is highly associated with chronic liver disease, including hepatitis B viral infection. In order to study the association between hepatitis B virus (HBV) infection and HCC development, tissue microarrays were used to detect the expression of hepatitis B surface antigen (HBsAg) in 194 HCCs and their surrounding liver tissues, using anti‐HBsAg monoclonal antibody. The results showed that the expression of HBsAg is significantly lower in tumour tissue than in non‐tumour tissue. Among the 138 cases with positive serum HBsAg, expression of HBsAg was more frequently detected in non‐tumour tissue (103 cases, 75%) than in tumour tissue (11 cases, 8%). RT‐PCR and Southern blot analysis were performed to explore the mechanism of the decreased expression of HBsAg in tumour cells. The RT‐PCR results showed that absence or decreased expression of the HBV S gene was detected in 3/15 (20%) and 6/15 (40%) HCCs, respectively. Integration of HBV in 23 pairs of HCCs and their matched non‐tumour liver tissues was studied by Southern blot. The results showed that the integrated HBV S gene sequence was detected in 19/23 tumours (83%) and 1/23 non‐tumour tissues (4%), whereas the free replicative virus form was observed in 3/23 tumours (13%) and 14/23 non‐tumour tissues (61%). These findings suggest that HBsAg‐negative results in tumour tissues were directly related to HBV DNA insertion and provide new insights into the involvement of HBsAg in hepatocarcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Embryonic stem cells
Authors: Bishop Anne E. , Buttery Lee D. K. , Polak Julia M. 
Published: October 2002

AbstractThe capacity of embryonic stem cells for virtually unlimited self‐renewal and differentiation capacity has opened up the prospect of widespread applications in biomedical research and regenerative medicine. For the latter, the cells provide hope that it will be possible to overcome the problems of donor tissue shortage and also, by making the cells immunocompatible with the recipient, implant rejection. Four years after the first derivation of human pluripotent cell lines from pre‐implantation embryos, a great deal has been learnt about their biology and how differentiation can be encouraged towards particular cell lineages. However, considerable research is needed, not least into means to enrich and purify derivative cell lineages, before clinical trials can be considered. Copyright © 2002 John Wiley & Sons, Ltd.
Protection of the Peyer's patch‐associated crypt and villus epithelium against methotrexate‐induced damage is based on its distinct regulation of proliferation
Authors: Renes Ingrid B. , Verburg Melissa , Bulsing Nathalie P. , Ferdinandusse Sacha , Büller Hans A. , Dekker Jan , Einerhand Alexandra W. C. 
Published: October 2002

AbstractThe crypt and villus epithelium associated with Peyer's patches (PPs) is largely spared from methotrexate (MTX)‐induced damage, compared with the non‐patch (NP) epithelium. To assess the mechanism(s) preventing damage to the PP epithelium after MTX treatment, epithelial proliferation, apoptosis, and cell functions were studied in a rat‐MTX model. Small intestinal segments containing PPs were excised after MTX treatment. Epithelial proliferation and apoptosis were assessed by detection of incorporated BrdU and cleaved caspase‐3, respectively. Epithelial functions were determined by the expression of cell type‐specific gene products at mRNA and protein level. Before and after MTX treatment, the number of BrdU‐positive cells was higher in PP crypts than in NP crypts. BrdU incorporation was diminished in NP crypts, while in PP crypts incorporation was hardly affected. In PP and NP crypts, similar and increased levels of cleaved caspase‐3‐positive cells were observed after MTX. The enterocyte markers, sucrase‐isomaltase, sodium‐glucose co‐transporter 1, glucose transporters 2 and 5, and intestinal and liver fatty acid binding protein, were down‐regulated after MTX in NP epithelium but not in PP epithelium. In contrast, expression of the goblet cell markers, Muc2 and trefoil factor 3, and the Paneth cell marker, lysozyme, was maintained after MTX in both PP and NP epithelium. In conclusion, as MTX‐induced apoptosis was similar in PP and NP crypts, the protection of the PP epithelium seems to be based on differences in the regulation of epithelial proliferation. Enterocyte function in the PP epithelium was unaffected by MTX treatment. Goblet and Paneth cell function was maintained in both NP and PP epithelium. Copyright © 2002 John Wiley & Sons, Ltd.
Prostatic stem cells
Authors: Foster C. S. , Dodson A. , Karavana V. , Smith P. H. , Ke Y. 
Published: October 2002

AbstractMultipotent cells within the epithelial compartment, together with phenotypically ‘plastic’ mesenchyma cells (stromal stem cells), provide a repository of protected genetic information from which the structure, stability and functionality of the prostate gland can be maintained. However, mere preservation of cells in a non‐dividing state is insufficient to provide the necessary reservoir of information from which the structure and function of the prostate gland can be retained or recreated. Rather, there is a constant dynamic interaction, at the level of information exchange, between stem cells (whether epithelial or mesenchymal) and their surrounding environment (both humoral and physical). Thus, with respect to epithelial stem cells, these reside within environmental ‘niches’ which allow their controlled and limited proliferation while preserving genomic integrity. Similar ‘mesenchymal niches’ are also predicted to occur, although not yet identified, thus providing the multipotent source from which the full spectrum of stromal phenotypes might be regenerated. Recent data from studies of the haematopoietic and hepato‐biliary systems indicate that the potential scope of stem cells far exceeds the immediate phenotypic complement of those tissues within which they originate, being dependent upon their precise environment as well as their genomic integrity. Copyright © 2002 John Wiley & Sons, Ltd.