bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoblastoma (rb) gene product expression in lymphomas. Correlation with Ki67 growth fraction
Authors: Martínez Juan C. , Piris Miguel A. , Sánchez‐Beato Margarita , Villuendas Raquel , Orradre Juan L , Algara Patricia , Sánchez‐Verde Lidia , Martínez Pedro 
Published: June 2005

AbstractThe retinoblastoma susceptibility gene (Rb) has been characterized as a tumour suppressor gene. Rb protein is involved in cell‐cycle control, regulating gene transcription. The absence of Rb protein in inherited retinoblastoma has been proved to be the result of inactivation of both Rb alleles through mutation or deletion, according to the general model for suppressor genes. The frequent detection of Rb gene alterations in human tumours (retinoblastoma, osteosarcoma, bladder carcinoma, small‐cell lung carcinoma) and the correlation with clinical outcome found in some tumours prompted us to study Rb gene expression in lymphoid tumours in an attempt to determine whether Rb gene expression is related to histological type and degree of aggrcssivity in human lymphomas.To establish normal levels of Rb protein, its expression was analysed in vitro on cytospin preparations from normal and pokeweed mitogen (PWM) or phytohaemagglutinin (PHA)‐stimulated peripheral blood lymphocytes (PBLs), using a monoclonal antibody (PMG3‐245). Rb protein expression in vivo was quantified using a computer analysis system (CAS) on frozen sections from reactive and neoplastic lymphoid tissue. As a control of tissue preservation, and to compare Rb expression and growth fraction, the tumours and cells were labelled simultaneously with the Ki67 monoclonal antibody.Normal and stimulated lymphocytes showed a gradual increase of Rb protein during progression of the cell cycle, with a peak in the M phase. G0–G1 cells had no detectable levels of Rb protein, suggesting that the Rb gene may act as a ‘status quo’ cellular growth fraction control mechanism. In reactive lymphoid tissue, Rb protein was mainly expressed in germinal centres (lymph nodes, tonsils) and cortical thymocytes.There was a statistically significant correlation between Ki67 and Rb expression in non‐Hodgkin's lymphomas (NHLs), most low‐grade lymphomas having very weak or undetectable levels of Rb protein. The majority of high‐grade lymphomas have higher Rb protein levels. However, a group of ten lymphomas with no Rb protein was found, in spite of a Ki67 range similar to that found in the Rb‐positive lymphomas. This lack of Rb expression in a subset of high‐grade NHLs suggests that Rb deregulation, through deletion, mutation, or lack of transcription, may play a role in this group of tumours. Further studies should focus on Rb genetic alterations.
Malignant potential of aneuploid pancreatic endocrine tumours
Authors: Lee C. S. , Charlton I. G. , Williams R. A. , Dhillon A. P. , Rode J. 
Published: June 2005

AbstractEvaluation of the malignant potential of pancreatic endocrine tumours is difficult by histological criteria alone. Nuclear deoxyribonucleic acid (DNA) cytometric analysis can provide significant prognostic and biological information in a number of solid human tumours. Thus, the DNA profiles and nuclear parameters of 39 patients with pancreatic endocrine tumours diagnosed from 1969 to 1989 were studied, using computerized video image analysis. Of the 39 patients with tumours, 27 cases did not have evidence of metastatic disease at the time of investigation. The majority of these (N=21) showed a diploid profile. Five were aneuploid and one was tetraploid. In the 12 tumours that proved malignant, three had tissue of both the primary tumour and the metastases analysed; six had material only from the primary tumour, although metastatic disease was established clinically; and another three only had tissue from the secondary tumour studied. The majority of the malignant cases were aneupioid (N =7); three were dipioid; one showed a diploid primary but an aneuploid secondary; and one showed a hyperdiploid pattern. The percentage of nuclei with a DNA content greater than 5N (5CER) did not seem to contribute further to the assessment nor did the means of the nuclear areas and shape factors. It appears that ploidy studies may be useful in predicting malignant potential of pancreatic endocrine tumours. There is a high rate of immunostaining for insulin by benign pancreatic endocrine tumours and this may be a useful adjunct to distinguish them from their malignant counterparts. However, there is no statistically significant correlation between the expression of various hormones and the DNA ploidy of tumour cells.
Immunolocalization of heparinbinding growth factors (HBGF) types 1 and 2 in rat liver. Selective hyperexpression of HBGF‐2 in carbon tetrachloride‐induced fibrosis
Authors: Charlotte Frederic , Win Khin Maung , Preaux Anne‐Marie , Mavier Philippe , Dhumeaux Daniel , Zafrani Elie Serge , Rosenbaum Jean 
Published: June 2005

AbstractIto cells play a major role in liver fibrosis but the mechanisms controlling their activation in vivo are poorly understood. Heparin‐binding growth factors (H BGF) types 1 and 2 are mitogenic for cultured Ito cells. They have been found in liver extracts but their cellular localization is unknown. We have studied by immunohistochemistry KBGF‐1 and ‐2 expression in normal rat liver and in carbon tetrachloride (CCl4)‐induced fibrosis. In normal liver, HBGF‐1 was present only in sinusoidal cells whereas HBGF‐2 was also detected in endothelial cells lining major vessels. At the acute stage of CC14 intoxication, HBGF‐2 was expressed in centrilobular clusters of mononuclear phagocytes that were surrounded by many HBGF‐2‐negative Ito cells. In the later stages, HBGF‐2 was expressed by Ito cells within the fibrous bands. No modulation of HBGF‐1 expression was noted at any stage. These results suggest that (1) at the acute stage of CC14 intoxication, HBGF‐2 produced by mononuclear phagocytes could participate in the recruitment of Ito cells; and (2) during the CCl4‐induced fibrotic process, HBGF‐2 could contribute to Ito cell proliferation and the synthesis of fibrosis components. In this in vivo model of hepatic fibrosis, the hyperexpression of HBGF‐2 is a relatively specific event since the expression of a structurally related molecule, HBGF‐1 was not modulated.
Epstein‐Barr virus (EBV) in enteropathy‐associated T‐cell lymphoma (EATL)
Authors: Pan Langxing , Diss Tim C. , Peng Huaizheng , Lu Qilong , Wotherspoon Andrew C. , Thomas J. Alero , Isaacson Peter G. 
Published: June 2005

AbstractUsing Southern hybridization analysis, we have detected the Epstein‐Barr virus (EBV) genome in 36 per cent (4/11) of enteropathy‐associated T‐cell lymphoma (EATL), a frequency much higher than that seen in nodal T‐cell lymphomas in which we were able to show EBV DNA in only 3 per cent (1/30) of the cases examined. Using a terminal fragment probe, monoclonal proliferation of EBV in infected cells was demonstrated in three of the four EBV‐positive EATL cases (in one case, insufficient signal prevented the determination of EBV clonality). The EBV genome and an early transcript, EBER1, were identified in tumour cells by in situ hybridization. Expression of latent membrane protein (LMP) was detected in two EBV DNA/RNA‐positive EATL cases. In view of the known oncogenic properties of EBV and the putative central role of LMP in EBV‐induced cell immortalization, the results of this study suggest that the virus may play an aetiological role in the pathogenesis of EATL.
Participation of macrophages in segmental endocapillary proliferation preceding focal glomerular sclerosis
Authors: Saito Takao , Ootaka Tetsuya , Sato Hiroshi , Furuta Takashi , Sato Toshinobu , Soma Jun , Abe Keishi , Yoshinaga Kaoru 
Published: June 2005

AbstractWe studied infiltrating cells in the glomeruli of eight cases with focal segmental endocapillary proliferation (FSEP) using monoclonal antibodies to leukocyte common antigen, T cells, B cells, and monocytes/macrophages (Mo/Mφ). It was demonstrated by sequential biopsies performed in five cases that FSEP preceded focal glomerular sclerosis (FGS). Cell types in FSEP were compared with those in FGS from 17 patients with persistent nephrotic syndrome, ten non‐nephrotic patients, and eight patients with nephrotic syndrome which was initially responsive to steroid therapy but relapsed, as well as minimal change specimens from nine nephrotic patients. In the glomeruli, the mean total leukocyte counts increased significantly in the FSEP group (P < 0.01). The serial sections in FSEP revealed that Mo/Mφ were the predominant cells and were localized in areas of endocapillary proliferation. T‐cell or B‐cell infiltration was less marked. The extensive intracapillary distribution of p150,95 antigen belonging to the integrin family and acting as a C3bi receptor suggested that FSEP may be mediated by adhesion molecules expressed on Mo/Mφ. These findings indicate that Mo/Mφ may play a key role in FGS which shows endocapillary proliferation in the initial stage.
Study of renal tubular glycoconjugates in tubulointerstitial damage using conjugated lectins
Authors: Khan Tahir Naeem , Sinniah Raja 
Published: June 2005

AbstractChanges in the glycoconjugates of renal tubules associated with tubular damage were studied by lectin histo‐chemistry, and their possible significance was determined. The excretion of various saccharides in tubular casts may also serve as markers of renal tubular damage. Renal tissues from 55 cases with various glomerular diseases including ten controls were studied. The patients were divided into two groups: one with tubulointerstitial lesions (TILs) (30 cases), and the other without (15 cases). Our results showed a wide spectrum of changes, predominantly in the disease group with TILs. The brush border of the proximal tubules showed significantly increased staining with Triticum vulgaris (WGA) and decreased staining with Canavalia ensiformis (Con A) lectins in both disease groups. The distal tubules revealed a significant increase in the apical and a decrease in the basal staining with Arachis hypogaea (PNA) and WGA lectins, respectively, in cases with TILs. The significant decrease in the basal domain staining was also seen with WGA lectin in cortical ducts. The vulnerability of various segments of the tubules in the process of TILs was clearly demonstrable. It appeared that the distal tubules were the most vulnerable anatomical segments around which the TILs began and later spread to involve other segments of tubules.
Expression of the C‐erbB‐3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1
Authors: Rajkumar Thangarajan , Goden Calvin S. R. , Lemoine Nicholas R. , Gullick William J. 
Published: June 2005

AbstractWe have examined the expression of the c‐erbB‐3 protein in a wide range of tumours of the gastrointestinal (GI) tract using immunocytochemical staining. Two antibodies were employed, a polyclonal antibody, 49.3, and a new monoclonal antibody, RTJ1, both raised to a synthetic peptide from the cytoplasmic domain of the human c‐erbB‐3 protein. The antibodies recognize c‐erbB‐3 by immunoprecipitation and Western blotting of lysate prepared from a cell line engineered to overexpress the protein. Both antibodies also detect expression of the protein in formalin‐fixed, paraffin‐embedded human tissues. The RTJ1 monoclonal antibody gave superior staining, showing lower background and more pronounced cell surface immunoreactivity. The c‐erbB‐3 protein was found in normal epithelial cells throughout the GI tract, in squamous epithelium of the oropharanyx and oesophagus, in the parietal cells of the stomach, and in the surface enterocytes of the small and large bowel. Seventy‐six tumours arising at these sites were examined for c‐erbB‐3 protein expression. Widely varying levels of expression were seen, from absent to intense staining with cell membrane accentuation.
Trabecular bone does not have a fractal structure on light microscopic examination
Authors: Cross Simon S. , Rogers Suzanne , Silcocks Paul B. , Cotton Dennis W. K. 
Published: June 2005

AbstractThe fractal dimension of the boundary of trabecular bone in 62 biopsies was measured on histological sections using a box‐counting method implemented on a microcomputer image analysis system. The calculated fractal dimension had a mean value of 0.99 with a normal distribution. Since this value is not greater than the topological dimension (1), trabecular bone, when examined by light microscopy, does not have a fractal structure. Conventional Euclidean dimensions will continue to be the most useful measurements in bone histomorphometry.
Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours
Authors: Schadendorf Dirk , Gawlik Christian , Haney Uwe , Ostmeier Hermann , Suter Ludwig , Czarnetzki Beate M. 
Published: June 2005

AbstractIn order to evaluate the significance of adhesion molecules expressed on melanocytic tumours for progression and prognosis in vivo, we studied integrin expression (VLA‐1 to VLA‐6, CD18, CD51, CD61) on 10 naevi, 40 primary malignant melanomas, and 11 metastases by immunohistology using the APAAP technique. Evaluation was done by grouping the percentage of positive tumour cells in six categories. Statistical analysis (Wilcoxon rank test, Scheffe test) revealed significant differences in the expression of VLA‐1 (P <0.0001), VLA‐2 (P=0.0001), VLA‐5 (P=0.0093), VLA‐6 (P=0.0232), and CD61 (P0.0002) between naevi and primary melanomas. Comparing primary melanomas with metastases, a statistically significant decrease in the expression of VLA‐1, VLA‐2, and VLA‐6 was detectable, as well as a significant increase in VLA‐4 and VLA‐5. There was no correlation between integrin expression and tumour type (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma), regression and ulceration. Changes of VLA‐1, VLA‐4, and VLA‐6 expression correlated with the tumour thickness of the primary melanoma, but only VLA‐4 and VLA‐6 expression on primary melanomas correlated significantly with the development of metastases (P=0.024 and P=0.001). These changes of integrin expression during tumour progression particularly, the data showing an increase of VLA‐4, and a decrease of VLA‐6 expression support the concept that integrins are a new additional set of prognostic markers which indicate predisposition to the development of metastases.
Patterns of integrin common chain β1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size
Authors: Patriarca Carlo , Roncalli Massimo , Gambacorta Marcello , Cominotti Marzia , Coggi Guido , Viale Giuseppe 
Published: June 2005

AbstractThirty cases of hepatocellular carcinoma (HCC) were investigated immunocytochemically for expression of β1 integrin molecule and of collagen IV. Immunoreactivity was related to the tumour proliferation index, as detected by PCNA immunostaining, and to tumour size and grade. Membrane β1 integrin immunoreactivity was deteccted in the neoplasticc cells of all cases, though two different staining patterns were clearly recognized. In 14 cases, β1 integrin immunoreactivity was confined to the cell‐stroma interface, showing the same polarized pattern as the non‐neoplastic cell counterpart. This staining pattern was associated significantly (P 0.0001) with low PCNA labelling (i.e. less than 20 per cent of neoplastic cells showing nuclear immunostaining. Conversely, 16 cases showed non‐polarized pericellular β1 integrin immunostaining. This staining pattern was significantly associated (P < 0.0001)) with high PCNA labelling (more than 20 per cent of immunoreactive cells) and with tumour size greater than 4 cm in diameter (P < 0.0001). β1 Integrin, collagen IV, and PCNA immunoreactivities, however, did not correlate with the histological grade. The data emphasize that neoplastic progression of HCCs may be correlated with an aberrant expression of adhesion molecules and with a disruption of the collagen IV complement of basal membranes.
β1 and β4 integrin expression in methacarn and formalin‐fixed material from in situ ductal carcinoma of the breast
Authors: Hanby Andrew M. , Gillett Cheryl E. , Pignatelli Massimo , Stamp Gordon W. H. 
Published: June 2005

AbstractThe integrins are αβ heterodimeric transmembrane proteins mediating cell‐substratum as well as cell‐cell interactions. Previous distribution studies on integrin expression have been limited by the requirement for cryostat sectioned tissues, and consequent poor resolution. We have examined 40 examples of ductal carcinoma in situ (DCIS) for the expression of both β1 and β4 integrin chains. These showed strong polarized membrane staining of residual myoepithelial cells (correlating with expression of smooth muscle specific actin) and of the basement membrane region with β1 and β4 antibodies respectively. In 12 out of 40 cases, the DCIS was negative for the β1 chain and a variable pattern of reactivity was seen in the remaining cases. The β4 chain was detected focally and weakly in the tumour cells of 7/40 DCIS and strongly in one; all of these cases were also positive for the β1 chain. Of the 22 cases where co‐existent invasion was present, the infiltrating component showed either a similar degree or a diminution of the extent of immunostaining when compared with the in situ component; only one showed enhanced staining (β1 only). This study demonstrates that two of the main β chains, β1 and β4, can be effectively demonstrated on methacarn and cold (4°C) formalin‐fixed tissues by avidin‐biotin indirect immunoperoxidase staining and that the results are similar to those achieved using frozen tissue.
Induction of nitric oxide synthase in the neo‐vasculature of experimental tumours in mice
Authors: Buttery L. D. K. , Springall D. R. , Andrade S. P. , Riveros‐Moreno V. , Hart I. , Piper P. J. , Polak J. M. 
Published: June 2005

AbstractMaintenance of blood flow is an important factor in sustaining tumour growth. Functional studies have previously demonstrated a reduction in tumour blood flow with selective inhibitors of nitric oxide (NO) synthesis, L‐NAME (NG‐nitro‐L‐arginine‐methylester) and L‐NMMA (NG‐monomethyl‐L‐arginine), when administered locally to tumours derived from murine colon 26 adenocarcinoma and B16 melanoma cells. The type of NO synthase which might be responsible for this locally‐derived NO and the site of synthesis was not described. Here we have investigated the distribution of immunoreactivity and the biochemical characteristics of the enzymes synthesizing NO in the same murine model. Adenocarcinoma (colon 26) or melanoma (B16) cells were introduced into a sponge matrix implanted subcutaneously in mice. After 7, 12, and 14 days, the implants were removed and frozen sections were immunostained with rabbit antisera to constitutive and inducible isoforms of NO synthase. Immunoreactivity with antisera to inducible NO synthase was detected in the vasculature of neoplastic implants, with and without the sponge, at 12 and 14 days. The enzyme was not evident in 7‐day‐old tumours, in non‐neoplastic implants, in areas of tissue outside the tumour, or in adenocarcinoma or melanoma cells. Enzyme activity was measurable in homogenates of neoplastic implants removed at day 7 and was found to be Ca2+/calmodulin‐independent. Immunoreactivity with antisera to inducible NO synthase was seen principally in the endothelium of newly‐formed capillaries, identified by immunostaining for von Willebrand factor in serial sections. Immunoreactivity with antiserum to constitutive NO synthase was not evident in either neoplastic or non‐neoplastic implants. These results suggest that neoplasms can modulate the synthesis of NO in their vasculature by inducing the generation of NO synthase and hence the production of NO which could be very important in maintaining the tumour blood flow.
Distribution of the extracellular matrix components in human glomerular lesions
Authors: Büyükbabani Nesimi , Droz Dominique 
Published: June 2005

AbstractMost glomerular pathologies are associated with alterations of the matrix compartment. Using reagents directed against the α/α2 and α3 chains of type IV collagen [α1/α2(IV), α3(IV)], laminin, heparan sulphate proteoglycan (HPG), fibronectin, collagen I, and collagen III, we investigated the modifications of the glomerular matrix components in several human glomerular lesions compared with normal kidney. In type I membranous glomerulo‐nephritis (MGN) (nine cases), we did not observe alterations in the matrix component distribution. In MGN types II and III (five cases), the spikes and chainettes were made of the α3(IV) chain, laminin, and HPG, while the α1/α2(IV) chains were localized along the subendothelial side of the glomerular basement membrane (GBM). In focal and segmental glomerulosclerosis (six cases), fibronectin, α1/α2(IV) chains, laminin, and small amounts of interstitial collagens were detected within the collapsed capillary loops; the newly formed matrix material between the podocytes and the GBM contained the α1/α2(IV) chains, laminin, and HPG but not the α3(IV) chain. In crescentic glomerulo‐nephritis (six cases), fibronectin was the most abundant and, in purely cellular crescents, the unique component. A basement membrane‐like network containing laminin, HPG, α1/α2(IV) chains, and interstitial collagens developed in a second step between the crescent cells. Interstitial collagens were present in the crescent framework, even when the integrity of Bowman's capsule was preserved. In membranoproliferative glomerulonephritis (five cases), we observed strong accumulation of fibronectin in the thickened mesangial spaces together with accumulation of laminin, α1/α2(IV) chains, and HPG; type I collagen was also present in the central part of the mesangial areas. This study shows that each glomerular lesion is characterized by particular alterations of the matrix components.
Proliferation in malignant mesothelioma as determined by mitosis counts and immunoreactivity for proliferating cell nuclear antigen (PCNA)
Authors: Ramael Marc , Jacobs Werner , Weyler Joost , van Meerbeeck Jan , Białasiewicz Pjotr , van den Bossche Jan , Buysse Corinne , Vermeire Paul , Van Marck Eric 
Published: June 2005

AbstractIn order to assess its discriminating and prognostic value, we studied immunoreactivity for proliferating nuclear cell antigen (PCNA) in human malignant mesothelioma (31 cases) and in human non‐neoplastic mesothelium (33 cases with reactive mesothelium and 20 cases of normal mesothellum) using the murine monoclonal antibody PC 10. We also compared it with mitosis counts expressed as the mitotic volume index (MV index). There were differences between malignant mesothelioma, reactive mesothelium, and normal mesothelium for percentage of PCNA immunoreactive cells (mean ± SD; 27 ± 9, 9·5 ± 5·1, and 3·6 ± 1·6, respectively) and for their MV index (20·3 ± 4·5, 9·4 ± 2·1, and 3·6 ± 0·6, respectively). The median actuarial survival was 10·1 months for patients with less than 25 per cent PCNA immunoreactive cells, 9·4 months for patients with less than 20 mitoses per mm2 of tumoural tissue, 5·9 months for patients with more than 25 per cent PCNA immunoreactive cells, and 5·3 months for patients with more than 20 mitoses per mm2 of tumoural tissue. Our results suggest that PCNA immunoreactivity is useful in discriminating between neoplastic and non‐neoplastic mesothelium and that it may have prognostic value in malignant mesothelioma.