bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoradiographic localization of endothelin‐1 binding sites in human colonic cancer tissue
Authors: Inagaki Hiroshi , Bishop Anne E. , Eimoto Tadaaki , Polak Julia M. 
Published: June 2005

AbstractEndothelin‐1, a potent vasoconstrictor, has been reported to stimulate mitogenesis in various types of normal and neoplastic cells and to be involved in neurotransmission. Recently, many human cancer cell lines, including those from the human colon, have been shown to produce endothelin. In this study, the occurrence of endothelin‐1 binding sites was investigated in human colonic cancer tissues using in vitro autoradiography. Specific [125I]endothelin‐1 binding sites were identified over tumour vessels and stromal tissues surrounding cancer cell nests. The distribution was heterogeneous, and dense silver grains were localized, especially over clusters of fibroblasts adjacent to the cancer cell nests. Endothelin binding was minimal in the cancer cells, as in the normal crypt epithelium. Quantitative analysis of the autoradiographs demonstrated high affinity (Kd = 0·50 ± 0·06 nM; mean ± SEM) binding sites, with a maximum binding capacity (Bmax) of 40 ± 3·2 amol/mm2 in the cancer tissues. Our results provide evidence that specific endothelin‐1 binding sites are expressed in the stromal tissues including tumour vessels, fibroblasts, and nerve fibres. Endothelin‐1 may play a modulatory role in blood supply, mitogenesis, and neurotransmission in a paracrine fashion through the stromal components in human colonic cancers.
The erbB‐3 Gene in human pancreatic cancer
Authors: Lemoine Nicholas R. , Lobresco Maria , Leung Hing , Barton Claire , Hughes Christine M. , Prigent Sally A. , Gullick William J. , Klöppel Günter 
Published: June 2005

AbstractAbnormalities of the type 1 growth factor receptor family have been implicated in the pathogenesis of pancreatic cancer. There is evidence for a potential autocrine loop involving overexpression of the epidermal growth factor (EGF) receptor and its ligands, as well as overexpression of the erbB‐2 receptor. A third member of this receptor family, erbB‐3, has recently been recognized and found to be abnormally expressed in some types of human cancer. In this study we show that overexpression of the erbB‐3 protein occurs very frequently in carcinoma of the exocrine pancreas and also in chronic pancreatitis. We found no evidence of amplification or rearrangement of the erbB‐3 gene by Southern blot analysis of DNA from pancreatic cancer cells lines.
Production and characterization of a polyclonal antibody to the c‐erbB‐3 protein: Examination of c‐erbB‐3 protein expression in adenocarcinomas
Authors: Poller D. N. , Spendlove I. , Baker C. , Church R. , Ellis I. O. , Plowman G. D. , Mayer R. J. 
Published: June 2005

AbstractA polyclonal rabbit antibody was raised to the c‐erbB‐3 protein using a synthetic peptide corresponding to amino acids 1229–1241 of the predicted protein sequence of c‐erbB‐3. In Western blot analysis this antibody detects a single band at ˜165kD in a c‐erbB‐3 transfected (293/HER‐3) human cell line. c‐erbB‐3 protein expression was then examined in a variety of adenocarcinomas. Expression of c‐erbB‐3 protein was indicated by membrane and/or cyto‐plasmic tumour cell immunoreactivity in formalin‐fixed, paraffin‐embedded tissue sections. c‐erbB‐3 protein was detected in a series of 13 out of 14 primary breast carcinomas, 3 of 5 gastric adenocarcinomas, 8 of 9 colonic adenocarcinomas, 2 of 9 prostatic adenocarcinomas, 0 of 6 renal cell carcinomas, 1 of 4 primary lung adenocarcinomas, and 5 of 7 endometrial adenocarcinomas. Immunohistochemical expression of the c‐erbB‐3 protein appears to be a relatively common event in adenocarcinomas, and further studies are now warranted to establish the role of the c‐erbB‐3 protein in neoplasia.
Detection of capsid antigen of human papillomavirus (HPV) in benign lesions of female genital tract using anti‐HPV monoclonal antibody
Authors: Iwasaki Takuya , Sata Tetsutaro , Sugase Motoyasu , Sato Yuko , Kurata Takeshi , Suzuki Kenji , Ohmoto Hiroshi , Iwamoto Seiichi , Matsukura Toshihiko 
Published: June 2005

AbstractWe established a murine monoclonal antibody (K1H8) to human papillomavirus (HPV) using alkaline‐disrupted virions of HPV type 1 (HPV‐l) as the immunogen. K1H8 recognized a 57 kD capsid protein of HPV‐1 and detected the antigen in paraffin sections of formalin‐fixed tissue. With K1H8, we examined immunchistochemically 68 biopsy specimens obtained from the female genital tract. The specimens were histologically condyloma acuminatum or koilocytotic lesions with or without dysplasia and each specimen was found to harbour a single type of genital HPV, such as types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56, and 58, by Southern blot hybridization analysis. The antigen was localized in the nuclei and occasionally in the cytoplasm of squamous cells showing koilocytotic changes. Eighty‐four per cent of the specimens (57 cases) showed positivity for the antigen, indicating that K1H8 is a broadly‐reactive antibody to various genital HPVs. The results suggest that benign mucosal lesions of the female genital tract are more frequently associated with viral production and are a potential source of transmission.
High incidence of EBV genome in CD30‐positive non‐Hodgkin's lymphomas
Authors: Kanavaros P. , Jiwa N. M. , De Bruin P. C. , Valk P. Van Der , Noorduyn L. A. , Van Heerde P. , Gordijn R. , Horstman A. , Mullink R. , Willemze R. , Walboomers J. M. M. , Meijer C. J. L. M. 
Published: June 2005

AbstractIn Hodgkin's disease, Epstein–Barr virus (EBV) is found in CD30‐positive Reed–Sternberg cells. We therefore studied 60 CD30‐positive non‐Hodgkin's lymphomas (NHLs) for the presence of EBV by the polymerase chain reaction (PCR) and DNA in situ hybridization (DISH), and by immunohistochemistry for the latent EBV proteins LMP and EBNA‐2. CD30‐negative NHLs and reactive lymph nodes served as controls. The CD30‐positive cases comprised 17 anaplastic large cell lymphomas (ALCLs) (> 75 per cent CD30‐positive cells) and 43 non‐ALCLs (with 5–35 per cent CD30‐positive cells). By PCR, 40 of 60 CD30‐positive NHLs (67 per cent) were EBV‐positive; in CD30‐negative cases, 6/29 (21 per cent) were EBV‐positive, as were 12/50 (24 per cent) reactive lymph nodes. The DISH procedure demonstrated the EBV genome exclusively in the nuclei of tumour cells in 23 of the 37 PCR EBV‐positive cases that were tested. PCR‐negative cases were always DISH‐negative, as were the PCR‐positive reactive lymph nodes and CD30‐negative NHLs. Immunohistochemistry demonstrated LMP in neoplastic cells of 7/47 (15 per cent) CD30‐positive NHLs, both ALCL and non‐ALCL always in PCR EBV‐positive cases, but never in the two control groups. EBNA‐2 staining could not be detected. It is concluded that EBV is present (and transcriptionally active) in a sizeable number of NHLs and an association between the presence of the EBV genome and CD30 expression seems likely.
Changes in hepatic lymph vessels in endotoxaemia
Authors: Shibayama Yuro , Urano Toru , Nakata Katsuji 
Published: June 2005

AbstractThis study was undertaken into rats to investigate changes in the hepatic lymph vessels and the space of Disse in endotoxaemia and to examine their relationship with the development of endotoxin‐induced hepatic injury. Lymph stasis, namely dilatation of the lymph vessels and oedema, developed rapidly in the medium‐sized portal canals, the large portal canals, and the liver hilum after endotoxin injection, but not in the small portal canals. Such changes reached their maximum 4–8 h after endotoxin injection and had recovered markedly by 16 h after the injection. The space of Disse remained within normal limits during this period. These findings suggest that the intrahepatic lymph stasis in endotoxaemia may be caused by a reduction in the pumping activity of the extrahepatic and the intrahepatic large lymph vessels rather than by an increase of lymph formation in the liver lobules. There was no evidence suggesting a direct relationship between the disturbance of hepatic lymph flow and the development of hepatic injury in endotoxaemia.
Monoclonal antibodies against recombinant parts of the Ki‐67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave‐processed formalin‐fixed paraffin sections
Authors: Cattoretti Giorgio , Becker Michael H. G. , Key Göran , Duchrow Michael , Schlüuter Carsten , Galle Jürgen , Gerdes Johannes 
Published: June 2005

AbstractThe monoclonal antibody Ki‐67 reacts with a human nuclear cell proliferation‐associated antigen that is expressed in all active parts of the cell cycle. Recently we have raised monoclonal antibodies, MIB 1–3, against recombinant parts of the Ki‐67 antigen. These antibodies are true Ki‐67 equivalents, as demonstrated by immunostaining of fresh specimens, biochemistry, and molecular biological techniques. Formalin‐fixed, paraffin‐embedded sections routinely processed for immunohistochemistry failed to stain for Ki‐67 and MIB 2. Antibodies MIB 1 and MIB 3 labelled mitotic figures, while non‐mitotic proliferating cells were negative under these conditions. However, when dewaxed microwave oven‐ processed paraffin sections of formalin‐fixed tissues were used, MIB 1 and MIB 3 gave strong nuclear staining of those cells presumed to proliferate under a variety of normal and neoplastic conditions. Moreover, routine decalcification or depigmentation techniques did not alter the immunoreactivity of MIB I and MIB 3 with microwave‐processed paraffin sections. This method is highly reproducible, easy to perform at low cost, and no additional technical skill is needed because after microwave treatment just routine immunohistochemical methods are used. Since we have successfully applied this new method to sections obtained from paraffin blocks stored for a long time (in one case more than 60 years), the assessment of cell kinetics through the detection of Ki‐67 antigen is now possible on archival material collected in histopathology departments all over the world.
Epstein–Barr virus (EBV) and Hodgkin's disease in children: Incidence of EBV latent membrane protein in malignant cells
Authors: Weinreb M. , Day P. J. R. , Murray P. G. , Raafat F. , Crocker J. , Parkes S. E. , Coad N. A. G. , Jones J. T. , Mann J. R. 
Published: June 2005

AbstractPrevious studies have detected EBV DNA by Southern blotting or in situ hybridization in biopsy material from up to 30 per cent of adult cases of Hodgkin's disease. Here we have used monoclonal antibodies specific for the EBV latent membrane protein LMP1 to examine archival material from children with Hodgkin's disease. Material from 74 cases (54 males and 20 females) was examined and 37 (30 males and 7 females) were classified as LMPl‐positive in the malignant cells. LMP1 positivity was present in 4/13 (31 per cent) of lymphocyte predominant, 14/36 (39 per cent) of nodular sclerosis, 17/20 (85 per cent) of mixed celiularty, 1/2 (50 per cent) of lymphocyte depletion, and 1/3 (33 per cent) of unclassified subtypes. The positive cases by clinical stage were 19/22 (41 per cent), II 9/20 (45 per cent), III 11/24 (46 per cent), and IV 8/8 (100 percent). LMP1 positivity was present in 2/5 (40 percent) children aged less than 5 years, 12/ 27 (44 per cent) aged 5–10 years, and 23/42 (48 per cent) aged between 10 and 15 years. The association between EBV and Hodgkin's disease in children thus appeared to be more frequent in patients with mixed cellularity and advanced disease, but examples of EBV‐positive tumours were found in all histological subtypes, stages, and ages. Stepwise discriminant function analysis showed that clinical stage IV and mixed cellularity histology are independently associated with LMP1 positivity. These observations indicate that Hodgkin's disease in children is at least as strongly linked to EBV as is the disease in adults.
Immunoreactivity for p53 protein in malignant mesothelioma and non‐neoplastic mesothelium
Authors: Ramael Marc , Lemmens Greet , Eerdekens Christa , Buysse Corinne , Deblier Ivo , Jacobs Werner , Van Marck Eric 
Published: June 2005

AbstractThe presence of p53 protein in non‐neoplastic pleural mesothelium (40 cases) and in human malignant mesothelioma (36 cases) was assessed immunohistochemically using the antibodies DO7, CM‐1 and PAb240. In a quarter of the malignant mesotheliomas, there was nuclear immunoreactivity for p53 protein with both the DO7 and CM‐1 antibodies. There were no statistically significant differences between the various mesothelioma subtypes (P>0·05). No immunoreactivity was found with the PAb240 antibody, suggesting absence of mutant‐type p53 protein. Non‐ neoplastic mesothelium was not immunoreactive with any of the antibodies. We conclude that there is immunoreactivity for p53 protein in some mesotheliomas. p53 protein immunoreactivity could be used to discriminate between neoplastic and reactive mesothelium.
Dominantly inherited tubular aggregate myopathy
Authors: Cameron C. H. Stuart , Allen Ingrid V. , Patterson Victor , Avaria Maria A. 
Published: June 2005

AbstractWe report an unusual familial myopathy characterized morphologically by the presence of large tubular aggregates in all fibre types. Two patients, a father and daughter, presented with slowly progressive proximal weakness, limitation of eye movement, and Achilles tendon contractures. Serum creatine kinase was 5–10 times normal. Light microscopy revealed type I fibre predominance. Basophilic accumulations, which stained intensely with the NADH‐TR reaction, were present in both fibre types. Electron microscopy revealed that these consisted of tightly packed parallel tubular arrays. These varied somewhat in their ultrastructural appearance and were classified accordingly as type I, II, and III tubular structures. The tubular aggregates appear to be derived from the sarcoplasmic reticulum. This report further supports the evidence of a distinct clinico‐pathological entity of genetic origin.
Epstein–Barr virus in Reed–Sternberg G‐like cells in non Hodgkin's lymphomas
Authors: Khan G. , Norton A. J. , Slavin G. 
Published: June 2005

AbstractIn the course of our study on Hodgkin's disease (HD), ten cases of non‐Hodgkin's lymphomas (NHL) containing Hodgkin and Reed‐Sternberg‐like (MRS) cells were encountered. Many of these cases had initially been diagnosed as HD, but on careful review of the histology, with the aid of immunophenotyping studies, they were reclassified as NHL. The presence of Epstein–Barr virus (EBV) in these HRS‐like cells was investigated using a combination of EBER in situ hybridization (ISH) and immunostaining for the detection of EBV‐encoded latent membrane protein (LMP). HRS‐like cells in four cases (two lymphoplasmacytoid lymphomas, one Richter's transformation of lymphoplasmacytoid lymphoma, and one immunoblastic lymphoma of T‐cell type) were found to be EBV‐positive. In two of these cases, a second biopsy taken up to 10 years later also contained EBV in the HRS‐like cells. In three of the four cases, HRS‐like cells expressed the activation antigen CD30, but the expression of B‐ or T‐cell antigens was variable. All cases of T‐cell‐rich B‐cell lymphomas were negative for EBV. In conclusion, EBV may play a role in the development of HRS‐like cells i some cases of NHL. The relationship of HRS‐like cells to HRS cells of HD is discussed.
Immunohistochemical analysis of p53 protein overexpression in normal, premalignant, and malignant tissues of the cervix uteri
Authors: Holm Ruth , Skomedal Hanne , Helland åslaug , Kristensen Gunnar , Bøsrresen Anne‐Lise , Nesland Jahn M. 
Published: June 2005

AbstractTwo hundred and thirty‐eight cervical lesions ranging from normal to malignant were examined for overexpression of p53 protein. Whereas p53 protein was identified in 62 per cent of invasive squamous cell carcinomas, 11 per cent of invasive adenocarcinomas, and 7 per cent of squamous cell carcinomas in situ, no staining was found in adenocarcinoma in situ, dysplastic tissue, condyloma, and normal tissue. In 9 per cent of the positive cases of invasive squamous cell carcinomas. 5‐50 per cent of the tumour ceiis were immunoreactive for p53 protein, whereas the other positive specimens were characterized by only rare p53‐positive cells. We conclude that in invasive cervical carcinomas widespread overexpression of p53 protein is unusual, but occasional positive nuclei can be found frequently. Furthermore, our results indicate that altered expression of p53 protein may be involved in the progression of cervical carcinomas.
Immunocytochemical localization of c‐erbB‐2 protein in transitional cell carcinoma of the urinary bladder
Authors: Coombs L. M. , Oliver S. , Sweeney E. , Knowles M. 
Published: June 2005

AbstractThe level of expression and cellular localization of the c‐erbB‐2 gene product in transitional cell carcinoma of the urinary tract is controversial. Analysis of the c‐erbB‐2 gene structure and comparison of its expression in the same cells by Southern, Northern and immunoblotting, and by immunocytochemistry minimize the errors of interpretation inherent in one technique. Such a ‘correlative study’ has been performed on tumours from 82 patients, c‐erbB‐2 gene amplification was detected in 14 per cent of initial tumours and was associated with grade (.P< 0·001). Raised levels of mRNA were seen in those tumours with increased gene copy number and in 13 per cent of the remainder. Immunoblotting detected the expected 185 kD immunoreactive protein and a 155 kD piotein associated with high gene copy number. Immunocytochemistry localized c‐erbB‐2 immunoreactivity to the cell membrane and cytoplasm, and the latter predominated. Four antibodies to c‐erbB‐2 (AB‐3, 21N, pAb 1, and NCL CB11) were compared on contiguous sections of the same tumour and showed the same pattern of immunoreactivity. Similarly, analyses carried out in three independent laboratories identified the same cellular localization. Membrane and cytoplasmic immunoreactivity was demonstrated in all tumours with gene amplification or increased mRNA levels and in 40 per cent of the remaining tumours. We showed that immunocytochemistry requires careful standardization of techniques and quantitation between different groups. However, despite variations in the intensity of immunoreactivity, the total number of positive cells remained constant. Therefore quantitation must be based on the number of positive cells and, ideally, their immunoreactive content relative to normal and positive tissue controls.
Paraffin wax‐embedded material as a source of DNA for the detection of somatic genetic changes
Authors: Sundaresan V. , Ganly P. , Hasleton P. , Bleehen N. M. , Rabbitts P. 
Published: June 2005

AbstractLoss of genetic material, corresponding to chromosomal deletions, has been detected in a wide range of tumours and may indicate the position of a tumour suppressor gene. In order to identify the position of such a gene more precisely, many tumour samples must be studied until a minimum consensus deletion is characterized. This process is particularly necessary for lung tumours in which the deletion in chromosome 3, seen with such high frequencies in all histological subtypes, is almost always large. We have recently described the use of the polymerase chain reaction (PCR) for restriction fragment length polymorphism (RFLP) analysis of DNA isolated from small bronchial biopsies of lung tumours. In this study we adapted this technique to allow genotyping of DNA isolated from paraffin wax‐embedded material (PWEM) microdissected from glass slides. We have investigated 12 lung tumours at polymorphic loci on chromosome 3 and showed allelic loss in all samples. In adapting PCR–RFLP analysis for DNA isolated from PWEM, we have concentrated on those approaches which might be adaptable to routine clinical practice. Somatic genetic changes are now being identified in many tumour types, and this information is expected to be of diagnostic and prognostic significance.
Detection of calcitonin and calcitonin gene‐related peptide mRNA in human medullary thyroid carcinoma. A retrospective study
Authors: Denijn Maryléne , De Weger Roel A. , Van Unnik Jan A. M. , Otter Wim Den , Lips Cees J. M. 
Published: June 2005

AbstractIn Situ hybridization finds many applications in modern pathology. In many cases, special attention is paid to the processing of the tissues prior to in situ hybridization. In order to investigate the value of RNA in situ hybridization (RISH) in retrospective studies, we performed RISH for calcitonin and calcitonin gene‐related peptide (CGRP)‐I and HomRNA in eight medullary thyroid carcinomas processed in 1981–1983. RISH was successful with radioactive calcitonin and CGRP‐1 probes. With biotinylated probes, only calcitcnin‐specific probes gave adequate results. The concentrations of CGRP mRNA were probably too low to be detected by non‐radioactive RISH. The results of RISH were correlated with the immunohistochemical localization of the polypeptides. The results matched in all cases except one, where hybridization for calcitonin mRNA was found, but no immunoreactive calcitonin polypeptide. We con‐clude that RISH can be successfully used for retrospective analysis, even after long storage of tissue embedded in poraffin.
In situ correlation of synthesis and storage of parathormone in parathyroid gland disease
Authors: Kendall C. H. , Potter Linda , Brown R. , Jasani B. , Pringle J. H. , Lauder I. 
Published: June 2005

AbstractThe distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44–68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pauern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated ‘colloid’ in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.
Localization of plasminogen activator inhibitor‐1 production in inflamed appendix by in situ mRNA hybridization
Authors: Whawell Simon A. , Wang Yiming , Fleming Kenneth A. , Thompson Elizabeth M. , Thompson Jeremy N 
Published: June 2005

AbstractThe peritoneum has been shown to possess fibrinolytic activity which is thought to play a role in the prevention of intra‐abdominal adhesion formation. Recently inflamed peritoneal tissue has been shown to have reduced fibrinolytic activity secondary to increased levels of plasminogen activator inhibitor‐1 (PAI‐1). The aim of this study was to localize the production of PAI‐1 in appendix tissue using in situ mRNA hybridization. Sections of normal and inflamed appendix were hybridized with a digoxigenin‐labelled cDNA probe. PAI‐1 production was localized to both mcsothelium and serosal blood vessel endothelium in all inflamed appendix samples. Cell identities were confirmed using immunohistochemistry directed against mesothelial and endothlial cell markers. Staining was not seen on sections of normal appendix or on negative control slides of inflamed appendix (hybridization with plasmid DNA, PAI‐1 probe following ribonuclease digestion). The identification of the cells expressing the PAI‐1 gene in peritoneum increases our understanding of the pathophysiological changes in fibrinolytic activity which occur in inflammation and may lead to adhesion formation.