bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the ret proto‐oncogene product in human normal and neoplastic tissues of neural crest origin
Authors: Nakamura Takuro , Ishizaka Yukihito , Nagao Minako , Hara Mitsuru , Ishikawa Takatoshi 
Published: June 2005

AbstractThe histological localization of the ret proto‐oncogene (proto‐ret) product was examined in neural crest‐derived and neuronal tissues together with their neoplastic counterparts by immunohistochemistry using a polyclonal antibody. Schwann cells, neurons, sympathetic ganglia, and cells of the adrenal medulla were positive for the proto‐ret product, whereas melanocytes were negative. Positive results were obtained from neural crest‐derived tumours such as schwannoma (69 per cent, 11/16), neurofibroma (59 per cent, 13/22), neuroblastoma (80 per cent, 4/5), phaeochromocytoma (100 per cent, 3/3) and medullary thyroid carcinoma (100 per cent, 3/3). The antibody reacted with all of the 22 astrocytomas examined. With negative proto‐ret expression in melanocytic tumours, proto‐ret expression was considered to correlate with the differentiation of some lineages of neural crest‐derived cells.
Microvascular lesions in reflux oesophagitis and Barrett's oesophagus
Authors: Sbarbati Andrea , Ricci Francesco , Inaspettato Giorgio , Lazzara Giuseppe , Cordiano Claudio , Osculati Francesco 
Published: June 2005

AbstractIn 30 patients with reflux oesophagitis, the mucosal microvessels have been studied by transmission electron microscopy. The aim of the study was to test the hypothesis that a microvascular injury is involved in reflux oesophagitis, and to clarify if the epithelial metaplasia is correlated with a contemporaneous modification of the microvasculature in Barrett's oesophagus. In squamous epithelium‐lined mucosa, signs of microangiopathy were found in all patients and capillaries regularly showed an interrupted, duplicated, or thickened basal lamina. In areas of columnar metaplasia, capillaries showed an ectatic lumen and a thin basal lamina without duplications or interruptions; endothelial cells had a thin rim of cytoplasm with many fenestrations. These findings demonstrate that microangiopathy is associated with epithelial damage in reflux oesophagitis.
Integrin expression in squamous neoplasia of the cervix
Authors: Hughes D. E. , Rebello G. , Al‐Nafussi A. 
Published: June 2005

AbstractEpithelial cell‐basement membrane interactions are important in maintaining tissue architecture and function, and the anatomical and functional relationships between epithelial cells and their basement membranes are clearly altered in malignancy. These interactions are thought to be largely mediated by the integrins, a family of heterodimeric transmembrane glycoproteins, each consisting of an α and a β chain. Epithelial integrins mainly belong to the β1 (VLA) subfamily, which forms receptors for matrix macromolecules such as fibronectin, laminin, and collagen. There is evidence that integrin expression changes in some epithelial malignancies, possibly in relation to invasive potential. Integrin expression in cervical neoplasia was studied by immunohistochemical examination of prospectively collected colposcopic biopsies. Well‐characterized monoclonal antibodies against β1–4, αl–6, and αV integrins were used to examine normal, koilocytic, and dysplastic cervical squamous epithelium, and invasive squamous carcinoma. β1, β4, α2, α3, α6, and αV were expressed by the basal layer of normal cervical squamous epithelium and by dysplastic cells in CIN (cervical intraepithelial neoplasia) 1 and 2, with none being lost and no new chains acquired. In CIN3, these integrins were either expressed throughout the ectocervical epithelium or restricted to the basal layer. In the latter cases, integrin expression was retained to a greater degree by dysplastic squamous epithelium within endocervical glands. These patterns could not be correlated with age or smear history in the cases examined. Patterns of integrin expression in neoplastic cervical epithelium therefore differ from those of normal cervical epithelium. It is possible that these changes may be related to changes in cellular function occurring during neoplastic progression.
Nuclear quantitative grading by discriminant analysis of renal cell carcinoma samples. A patient survival evaluation
Authors: Artacho‐Pérula Emilio , Roldán‐Villalobos Rafael , Martínez‐Cuevas Juan F. , López‐Rubio Fernando 
Published: June 2005

AbstractSpecimens from 60 cases of renal cell carcinoma (RCC) were graded employing quantitative nuclear data combined with multivariate discriminant analysis. Evaluation of patient survival was analysed with respect to quantitative microscopic and qualitative features. Both morphometric and stereological estimators were used to establish the nuclear size and form pattern of the RCC specimens. Tumoural dedifferentiation paralleled progressive increases in nuclear elongation and in two‐ and, especially, three‐dimensional—mean nuclear volume (MNV)—size parameters. Using stepwise discriminant analysis, 85‐0 per cent of the specimens were correctly classified when differentiating grade 2 and 3 tumours. It is concluded that simple and realistic estimates of MNV are the best discriminator for objective grading in patients with RCC. Univariate survival analysis demonstrated the important significance of several features such as MNV, clinical stage, and nuclear discriminant and histopathological tumour grades. Nuclear form factor PE, area, and perimeter were also significant. A prognosis study based on the Cox model using a stepwise selection of parameters showed that only MNV has an independent prognostic role when examining all investigated quantitative parameters. The clinical stage was the best prognostic feature when all quantitative and qualitative characteristics were included in the analysis.
Transformation from SAA2‐fibrils to AA‐fibrils in amyloid fibrillogenesis: In vivo observations in murine spleen using anti‐SAA and anti‐AA antibodies
Authors: Arai Kazumori , Miura Katsutoshi , Baba Satoshi , Shirasawa Haruyuki 
Published: June 2005

AbstractEarly amyloid fibrillogenesis from serum amyloid A protein (SAA) has been observed in the murine spleen after an injection of casein‐Freund's complete adjuvant in the presence of amyloid enhancing factor, using anti‐SAA C‐terminal (anti‐SAA) and anti‐amyloid A (AA) antibodies. In Western immunoblotting of sera, both SAA1 and SAA2 reached a maximum after 24 h and began to decrease after 48 h. In spleen extracts, SAA2, but not SAA1 or AA, was found from 48 h, when amyloid was first deposited in the marginal zone. Electron microscopic immunohistochemistry of this stage showed reaction products from SAA in the marginal zone as fine granules along the cell membrane of mononuclear cells and focal intercellular aggregates, which contained fine fibrils originating from the cell membrane. Amyloid nodules, surrounded by mononuclear cells, developed from this stage. In the nodules, fibrils were positive for anti‐SAA only in the vicinity of the cell membrane, while anti‐AA stained fibrils throughout. Our hypothesis for fibrillogenesis is thus as follows: Serum SAA2 is specifically deposited on mononuclear cells in the marginal zone and polymerized extracellularly into fibrils, retaining its antigenicity (SAA2 amyloid fibrils); these fibrils are then processed to AA amyloid fibrils in situ by cleavage of the C‐terminal portion of SAA2.
Apoptosis in bladder cancer as related to standard prognostic factors and prognosis
Authors: Lipponen P. K. , Aaltomaa S. 
Published: June 2005

AbstractFour hundred cases of transitional cell bladder cancer were reviewed by light microscopy for the presence of apoptotic cells in the primary tumour biopsy specimens. The number of apoptotic cells/mm2of neoplastic epithelium (apoptotic index, AI) was related to various histological features and prognosis. AI was related significantly to high T‐category, high grade, DNA aneuploidy, large nuclear morphometric variable values, and high proliferation rate of cancer cells. Tumours showing overexpression of p53 oncoprotein in over 10 per cent of the nuclei had significantly higher AI values than p53‐negative tumours. Multivariate regression analysis showed that AI was independently predicted by mitotic index, mean nuclear area, and papillary status. Progression, recurrence‐free survival, and survival of superficial tumours were all related significantly to AI. In multivariate survival analysis, T‐category, papillary status, grade, and mitotic index had independent prognostic value, while the recurrence‐free survival of Ta‐T1 tumours was related independently to AI. The results show that AI is related particularly to mitotic activity in transitional cell bladder tumours, while AI as assessed by light microscopy hardly has any independent prognostic significance.
Immunolocalization of serum amyloid A and AA amyloid in lysosomes in murine monocytoid cells: Confocal and immunogold electron microscopic studies
Authors: Chronopoulos S. , Laird D. W. , Ali‐Khan Z. 
Published: June 2005

AbstractMurine AA amyloid (AA) protein represents the amino‐terminal two‐third portion of SAA2, one of the isoforms of serum amyloid A. Whether plasma membrane‐bound or lysosomal enzymes in activated murine monocytoid cells degrade SAA2 to generate amyloidogenic AA‐like peptides is not clearly understood, although AA has been localized in the lysosomes. Here we show, using confocal and immunogold microscopy (IEM), that both SAA and AA localize in lysosomes of activated monocytoid cells from amyloidotic mice. Rabbit anti‐mouse AA IgG (RAA) and two monoclonal antibodies against murine lysosome‐associated membrane proteins (LAMP‐1 and LAMP‐2) were used to immunolocalize SAA/AA and lysosomes, respectively. Confocal analysis co‐localized both anti‐RAA and anti‐LAMP‐1/LAMP‐2 reactivities in the perikaryal organelles which by IEM proved to be electron‐dense lysosomes. LAMP‐1/LAMP‐2‐specific gold particles were also localized on lysosomal and perikaryal AA. The results suggest sequestration of SAA into the lysosomes. Since monocytoid cells are not known to phagocytose native amyloid fibrils, our results implicate lysosomes in AA formation.
CD4‐positive cells from patients with IgA nephropathy demonstrate increased mRNA of cytokines that induce the IgA switch and differentiation
Authors: Lai Kar Neng , Lui Siu Fai , Li Philip K. T. , Ho Rainbow T. H. , Leung Joseph C. K. , Chui Y. L. , Lim P. L. 
Published: June 2005

AbstractIgA nephropathy (IgAN) is characterized by raised serum IgA1 deposits. We have previously shown increased T‐cell activation in IgAN. Recently, transforming growth factor‐β (TGF‐β) has been shown to induce IgA isotype switch at a clonal level and interleukin 5 (IL5) promotes differentiation into IgA‐bearing B cells. In the present study we have examined the TGF‐β and IL5 mRNA expression by mitogen‐activated CD4‐positive T cells from patients with IgAN (n=25), patients with other primary nephritides (CGN) (n=24), and healthy control subjects (n=25). The cytokine genes were analysed by reverse transcription (RT)‐polymerase chain reaction (PCR) and were semi‐quantitated by normalizing the differences occurring during RT and PCR using a housekeeping gene, β‐actin. CD4‐positive T cells from IgA nephritic patients expressed a higher level of IL5 mRNA than healthy controls (P<0.01) and patients with CGN (P<0.005). CD4‐positive T cells from IgA nephritic patients expressed a higher level of TGF‐β mRNA than healthy controls (P<0.01) but no difference was demonstrated on comparison with CGN patients. Elevated TGF‐β mRNA expression in patients with CGN probably reflects its other important function as a (sclerogenic) factor involved in the glomerulosclerosis found in these nephritides. Our data suggest that there is increased expression of cytokine genes which induce the IgA isotype switch and differentiation; these immunological abnormalities may be important in the pathogenesis of IgAN.
The expression of alpha B‐crystallin in epithelial tumours: A useful tumour marker?
Authors: Pinder S. E. , Balsitis M. , Ellis I. O. , Landon M. , Mayer R. J. , Lowe J. 
Published: June 2005

AbstractAlpha B‐crystallin is a lens protein showing homology with small heat‐shock proteins. We have previously demonstrated its expression in non‐lenticular normal and diseased human tissues by immunostaining with a polyclonal antibody. In view of the expression seen in normal renal tubular epithelium, we have assessed the immunoreactivity of a variety of epithelial tumours, to determine the usefulness of alpha B‐crystallin as a specific renal tumour marker. Carcinomas arising from tissues which normally express alpha B‐crystallin, such as colo‐rectal and thyroid carcinomas, showed a varying pattern and degree of immunoreactivity. The most consistently positive tumours, however, with typically strong cytoplasmic and cell membrane staining, were renal cell carcinomas, 90 per cent of which showed positive immunoreactivity. This pattern of staining, while not absolutely specific, is a useful aid to the diagnosis of renal carcinoma. When a metastic deposit or a small biopsy is being assessed, anti‐alpha B‐crystallin may be included in a panel of antibodies, the pattern of staining of which may direct the search for the primary site of the tumour.
Recombination pattern of the TCR γ locus in human peripheral T‐cell lymphomas
Authors: Theodorou Joannis , Raphaël Martine , Bigorgne Claude , Fourcade Christine , Lahet Chantal , Cochet Gilles , Lefranc Marie‐Paule , Gaulard Philippe , Farcet Jean‐Pierre 
Published: June 2005

AbstractThe recombination events of the γ and β T‐cell receptor (TCR) loci were analysed in a series of 39 peripheral T‐cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ‐gene rearrangement while only 18/23 showed a concomitant β‐gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ‐ and β‐gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ‐rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ‐locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.
The expression pattern of contractile and intermediate filament proteins in developing skeletal muscle and rhabdomyosarcoma of childhood: Diagnostic and prognostic utility
Authors: Wijnaendts Liliane C. D. , Van Der Linden Johannes C. , Van Unnik Adriaan J. M. , Delemarre Jan F. M. , Voute Paul A. , Meijer Chris J. L. M. 
Published: June 2005

AbstractIn order to investigate whether rhabdomyosarcoma (RMS) can be related to equivalent stages of skeletal muscle development, muscle tissue of 21 human foetuses and 112 primary RMSs were characterized immunohistochemically using antibodies directed against vimentin, desmin, muscle‐specific actin (HHF35), sarcomeric actin (sr‐actin), smooth muscle actin (sm‐actin), and troponin‐T. During fetal skeletal muscle development, all myotubes/fibres of the first and second generations expressed desmin, HHF35, and sr‐actin. Vimentin was almost exclusively present in immature primary and secondary myotubes/fibres. Troponin‐T was expressed in immature myotubes/fibres of the first and second generations as well as mature fibres of the second generation. Sm‐actin was never expressed. Vimentin was expressed in 96 per cent of primary and 98 per cent of relapsed RMS; HHF35 in 96 and 98 per cent, respectively; desmin in 95 and 100 per cent; troponin‐T in 82 and 75 per cent; sr‐actin in 71 and 86 per cent; and sm‐actin in 13 and 17 per cent. The proportion of RMS cells reacting with vimentin, HHF35, and desmin was consistently higher than those expressing sr‐actin and troponin‐T. Neither the shape nor size of neoplastic RMS cells nor the histopathological types were related to the expression pattern of the investigated markers. RMS with aberrant expression of two or more markers predicted a worse prognosis than RMS in which at most one marker was aberrantly expressed (25 per cent and 54 per cent 10‐year survival, P=0·01). These results demonstrate that HHF35, desmin, sr‐actin, and troponin‐T have the potential to confirm the commitment of the tumours to the myogenic pathway which supports the diagnosis of RMS. However, it was impossible to relate RMS to equivalent stages of skeletal muscle development. Aberrant marker expression by RMS cells correlated significantly with patients' survival.
Expression of mdr1/P‐glycoprotein and p110 in neuroblastoma
Authors: Ramani Pramila , Dewchand Hamlata 
Published: June 2005

AbstractOverexpression of the multidrug resistance gene, mdr1, and its product, P‐glycoprotein (Pgp), has been associated with cross‐resistance to structurally unrelated compounds in cell lines and tumours. Recently, a non‐Pgp‐mediated form of drug resistance has been described, due to the overexpression of p110, a transport protein. Thirty formalin‐fixed, paraffin‐embedded neuroblastoma samples from 21 cases were examined for overexpression of mdr1 and Pgp using newly established non‐radioactive in situ hybridization and sensitive immunocytochemical techniques. Tumours were examined from patients with all the stages of disease and from primary and metastatic sites. Paired tumour samples (pre‐chemotherapy and post‐chemotherapy) were available from cases with stage 2 (n=1) and stage 4 disease (n=8). Immunoreactivity to p110 was also tested on all the samples. Mdr1 mRNA was expressed in 16/21 cases and in all the stages. Pgp immunoreactivity was detected in all the cases. Weak cytoplasmic immunoreactivity to p110 was seen in the ganglion cells in 12/21 cases. The expression of mdr1, Pgp, and p110 showed a statistically significant (two‐sided Fisher exact test, P=0.04, 0.03, 0.04, respectively) correlation with differentiation (Beckwith and Martin grading) but there was no correlation with survival. Pgp immunoreactivity also showed a significant correlation with favourable clinical variables: age less than 1 year at diagnosis and stages 1, 2, and 4 s (two‐sided Fisher exact test, P=0.01, 0.05, respectively).
Disruption of cell adhesion in renal epithelium without cadherin loss
Authors: O'Donnell Marie , Fleming Stewart 
Published: June 2005

AbstractLoss of cell adhesion is a critical event in the development of tumour invasiveness and metastases. Although loss of cadherin expression has been demonstrated to be associated with increased invasiveness and metastatic potential in some tumours, others, including renal carcinoma, show no such correlation. The aim of this study was to demonstrate that cell adhesion could be lost in phorbol ester‐treated renal epithelial cells and renal tumour cells without loss of A‐CAM expression. The model used has been shown previously to mimic changes that occur in the progression of renal carcinoma. We found that A‐CAM expression persists on the lateral surfaces of phorbol ester‐treated cells even though these cells lose cell‐cell adhesion. Similar findings were seen in renal carcinoma cells in culture. We conclude that loss of cell adhesion between tumour cells may occur either by loss of cadherins or as a result of loss cadherin function occurring as a consequence of cell transformation.
Components of the plasminogen activation system in uveal melanoma—a clinico‐pathological study
Authors: de Vries Teunis J. , Mooy Cornelia M. , van Balken Michael R. , Luyten Gregorius P. M. , Quax Paul H. A. , Verspaget Hein W. , Weidle Ulrich H. , Ruiter Dirk J. , van Muijen Goos N. P. 
Published: June 2005

AbstractIn tumour development, proteases such as plasminogen activators (PAs) play a role in degradation of the extracellular matrix and other tissue barriers. Recently, we demonstrated that plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of cutaneous melanocytic tumour progression. In this study we investigated the expression and distribution of the various components of the PA system and the presence of PA enzyme activity in 45 freshly frozen primary uveal melanomas with known follow‐up (14 spindle and 31 non‐spindle type) and in metastases (n=5). Tissue‐type PA (t‐PA) was found in endothelium of blood vessels and in tumour cells in almost all leisons, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour‐related death could be established. Urokinase PA (u‐PA) was expressed focally, by only five non‐spindle cell melanomas but in all metastases. u‐PA expression correlated with occurence of metastasis. u‐PA receptor (u‐PAR) was present in one‐third of all the tumours examined. Plasminogen activator inhibitors (PAI‐1 and PAI‐2) were found only focally in approximately 10 per cent of the lesions. Staining of t‐PA, u‐PA, and PAI was observed in all the metastases. We conclude that in uveal melanoma, u‐PA expression may be associated with metastatic disease and accordingly with a poor prognosis. Further research on a larger group of tumours with known follow‐up is needed to establish whether u‐PA positivity is of additional prognostic value in uveal melanoma.
Detection of numerical chromosomal aberrations in paraffin‐embedded malignant pleural mesothelioma by non‐isotopic in situ hybridization
Authors: Segers Kurt , Ramael Marc , Singh Samir Kumar , van Daele André , Weyler Joost , van Marck Eric 
Published: June 2005

AbstractAn in situ hybridization (ISH) study on paraffin sections of 13 malignant mesotheliomas was performed to detect numerical chromosomal aberrations with biotin‐labelled DNA probes specific for the centromeric regions of chromosomes 1, 3, 6, 7, 11, and 17. All chromosomes contributed to numerical changes, which can be summarized as follows: first, a monosomy for chromosome 6 was found in one case; second, in five cases a trisomy for at least one chromosome was detected; and third, in seven cases a pentasomy or a higher polysomy was found for at least one chromosome. Although these data have to be confirmed on a larger group of patients, survival analysis of this group showed no significant difference between the first and second groups taken together and the third group. In this study no specific numerical chromosomal aberrations were identified. Nevertheless, numerical gains appear to be more frequent than has previously been shown by karyotype analysis.