bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endometrial extramedullary haemopoiesis
Authors: Creagh Teresa M. , Bain Barbara J. , Evans David J. , Reid Cecil D. L. , Young Robert H. , Flanagan Adrienne M. 
Published: June 2005

AbstractFour cases of endometrial extramedullary haemopoiesis are reported, all with associated haematological disease. The diagnoses of a myeloproliferative disorder and thalassaemia trait were made as a consequence of the histological observations and subsequent haematological investigations in two cases. The third case occurred in a patient with an established diagnosis of chronic myeloid leukaemia. The diagnosis of extramedullary haemopoiesis in the final case was made on autopsy material from a patient with multiple myeloma. The endometrium from five other women with known myelofibrosis was examined but extramedullary haemopoiesis was not found. Endometrium from 32 fetuses did not contain haemopoietic elements, excluding the likelihood of the endometrium being a common site for extramedullary haemopoiesis in development. Endometrial extramedullary haemopoiesis is an uncommon finding, but it is worthy of note, as it may herald the presence of an underlying haematological abnormality.
Non‐isotopic in situ hybridization at the ultrastructural level
Authors: Morey Adrienne L. 
Published: June 2005

AbstractNon‐isotopic in situ hybridization techniques are becoming increasingly widely used at the ultrastructural level, permitting rapid localization of nucleic acid targets with a high degree of resolution. Technical considerations dictate that the great specificity of the method cannot be matched by a similar degree of sensitivity; the value of non‐isotopic ultrastructural in situ hybridization lies in its unique ability to localize nucleic acid targets in relation to submicroscopic cellular structures. This article presents an overview of non‐isotopic ultrastructural hybridization methods and applications.
The phenotypic changes in tumour infiltrating lymphocytes and tumour cells following intra‐arterial infusion of interleukin‐2 in patients with squamous cell carcinoma
Authors: Salter Janine , Maclennan Kenneth A. , Moore Jaqualyn , Dadian Grace , Riches Pamela G. , Gore Martin E. 
Published: June 2005

AbstractThis study evaluates the morphological and phenotypic changes that occur in squamous cell carcinoma of the head and neck when local infusions of interleukin‐2 (IL‐2) are given. Twelve patients were treated with a range of doses of IL‐2 (3 × 103 to 3 × 106 international units/day) by continuous intra‐arterial infusion for 10 days. Biopsies of the tumour were taken pre‐ and 48 h post‐therapy, snap‐frozen, cut, and examined histologically and immunocytochemically. Local infusions of IL‐2 increase the numbers of antigen‐presenting Langerhans cells (CDIa‐positive) and infiltrating lymphocytes, predominantly of the CD3 and CD4 (T‐helper) phenotypes. Locally infused IL‐2 results in the expression of MHC (major histocompatibility complex) class II antigens on the surface of the tumour cells, capillary and post‐capillary endothelial cells, and peri‐tumoural macrophages. Intratumoural NK (natural killer) cells and CD8‐positive (T‐cytotoxic) infiltrating lymphocytes were not increased by this therapy and CD25 (IL‐2 receptor) was only increased in those patients treated at the lower does levels. The system of intra‐arterial cytokine infusion into head and neck tumours developed in this study is a useful model to examine the biological effects of cytokines, since in vivo they are mainly produced and act locally, Furthermore, the infused tumours are easily accessible to biopsy. The results from studies such as this may influence the design of tumour‐targeted cytokine gene therapy programmes.
ICAM‐1 and VCAM‐1 expression in accelerated cardiac allograft arteriopathy and myocardial rejection are influenced differently by cyclosporine a and tumour necrosis factor‐α blockade
Authors: Molossi Silvana , Clausell Nadine , Sett Suvro , Rabinovitch Marlene 
Published: June 2005

AbstractExpression of the vascular cell adhesion molecules intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) occurs in allograft myocardium and in coronary arteries, promoting adhesion and transendothelial migration of inflammatory cells. We therefore investigated, in cholesterol‐fed rabbits 9–10 days following heterotopic cardiac transplantation, whether the reduction of both myocardial rejection and graft arteriopathy with cyclosporine A (CsA) or graft arteriopathy alone with tumour necrosis factor‐α soluble receptor (TNFsr) was associated with suppression of ICAM‐1 and VCAM‐1 expression. Host hearts showed negative immunostaining for these adhesion molecules, whereas donor specimens from untreated (control) rabbits showed moderate immunostaining for ICAM‐1 and weaker immunostaining for VCAM‐1 in the coronary arteries, myocardium (cardiac myocytes), and perivenular regions. The selective reduction of the coronary arteriopathy with TNFsr was associated with somewhat reduced expression of these adhesion molecules in the arteries, whereas CsA also suppressed myocardial rejection and markedly decreased both vascular and myocyte expression of ICAM‐1 and VCAM‐1.
Specific accumulation of exogenous fibronectin in experimental glomerulosclerosis
Authors: Bergijk Eline C. , Baelde Hans J. , De Heer Emile , Killen Paul D. , Bruijn Jan Anthonie 
Published: June 2005

AbstractThe prognosis of patients showing glomerulosclerosis as a complication of an immunologically mediated kidney disease is poor. To improve the diagnosis and treatment of these patients, it is important to understand the processes involved in the development of glomerulosclerosis. In this study, we investigated the molecular composition of experimental end‐stage glomerular sclerotic lesions and their pathogenesis in chronic graft‐versus‐host disease (GvHD) in the mouse and chronic serum sickness in the rat. Accumulation studies were performed to determine the degree of specific trapping of constituents from the circulation. Two different models were investigated to determine whether differences in disease initiation resulted in different compositions of the glomerulosclerotic lesions. In both models, glomeulosclerosis was preceded by expansion of the mesangial matrix and thickening of the glomerular basement membrane (GBM). The end‐stage sclerotic lesions consisted mainly of fibronectin, which appeared to displace the other extracellular matrix (ECM) components peripherally in the mesangial matrix and GBM. The abundance of fibronectin in the lesions was not reflected in the mRNA levels for this component. Indeed, antibodies directed against the cellular form of fibronectin did not stain positive in the end‐stage lesions. These findings, together with accumulation studies, suggest that specific accumulation rather than de novo synthesis of fibronectin plays a major role in the development of experimental glomerulosclerosis, which appears to be independent of the pathway of induction.
DNA content and expression of tumour markers in germ cells adjacent to germ cell tumours in childhood: Probably A different origin for infantile and adolescent germ cell tumours
Authors: Jørgensen Niels , Müller Jørn , Giwercman Aleksander , Visfeldt Jakob , Møller Henrik , Skakkebæk Niels E. 
Published: June 2005

AbstractThe origin of testicular germ cell tumours occurring during childhood is poorly understood. In adults, the classical seminomas and non‐seminomas originate from carcinoma in situ of the testis, which can usually also be detected in seminiferous tubules adjacent to the tumours. In order to contribute with information regarding a possible association between carcinoma in situ and the childhood group of germ cell tumours, we investigated seminiferous tubules adjacent to 13 infantile yolk sac tumours, five infantile teratomas, and six adolescent germ cell tumours of various types, using morphological evaluation, immunohistochemical staining with markers for carcinoma in situ cells, and densitometric DNA measurement of the germ cells. We detected clear differences between the germ cell populations adjacent to adolescent and infantile germ cell tumours. The former were associated with both normal germ cells and carcinoma in situ cells. The presence of carcinoma in situ cells strongly suggested that the adolescent tumours arose from carcinoma in situ cells, like germ cell tumours occurring in adult men. Although we were in doubt in two cases, the infantile germ cell tumours were in general not associated with carcinoma in situ cells. The aetiology of infantile yolk sac tumours and teratomas may therefore be fundamentally different from that of adolescent and adult germ cell tumours. The origin of yolk sac tumours and teratomas remains to be elucidated.
The effect of interleukin‐6 and soluble interleukin‐6 receptor protein on the bone resorptive activity of human osteoclasts generated in vitro
Authors: Flanagan Adrienne M. , Stow Mark D. , Williams Richard 
Published: June 2005

AbstractThe role of interleukin‐6 (IL‐6) in the regulation of bone resorption is and has not been studied using human tissue in vitro. This study exploits a recently described in vitro model, whereby osteoclasts, defined as cells that resorb bone, can be generated from human bone marrow, and investigated the effect of IL‐6 and its soluble receptor on bone resorption, in the presence of 1,25‐dihydroxyvitamin D3[1,25(OH)2 vitamin D3]. Human bone marrow was cultured to form a confluent stroma, sedimented onto devitalized bone slices, and recharged with non‐adherent bone marrow cells. 1,25(OH)2 vitamin D3 increased bone resorption, whereas IL‐6 failed to induce a similar stimulatory effect. Both IL‐6 at 100 ng/ml and soluble IL‐6 receptor protein in the absence of exogenous IL‐6 inhibited the stimulatory effect of 1,25(OH)2 vitamin D3. Bone resorption was never observed when non‐adherent haemopoietic cells were cultured in the absence of stroma but in the presence of IL‐6, which indicates that IL‐6 cannot replace the stromal factor(s) required for the formation of cells capable of resorbing bone. These results suggest that IL‐6 at high concentrations is not a critical cytokine in stimulating osteoclastic bone resorption.
Apoptosis in the human liver during allograft rejection and end‐stage liver disease
Authors: Afford Simon C. , Hubscher Stefan , Strain Alastair J. , Adams David H. , Neuberger James M. 
Published: June 2005

AbstractThe contribution of apoptosis (programmed cell death) to cellular damage in human liver disease is unknown. Using the in situ DNA end labelling method (ISEL), evidence was sought of programmed cell death (PCD) in liver tissue from patients with various liver diseases. In particular, the study aimed to determine whether PCD is involved in either the loss of interlobular bile ducts (vanishing bile duct syndrome—VBDS) or the perivenular hepatocyte drop‐out, both of which are characteristic of irreversible graft rejection. Large numbers of apoptotic hepatocytes were found in pervenular areas in tissues taken from patients with chronic graft rejection. Significant hepatocyte apoptosis, was not seen in long‐term stable allografts, primary biliary cirrhosis, cholestasis, paracetamol‐induced fulminant hepatic failure, or fulminant hepatic failure of indeterminate origin (non‐A, non‐B, non‐C hepatitis). Bile ducts rarely stained positively, but mononuclear cells present in the post‐transplant tissues were frequently positive, showing nuclear or cytoplasmic staining. The presence of cytoplasmic staining suggested that some mononuclear cells had ingested apoptotic DNA from other cellular sources. PCD may thus contribute to the perivenular hepatocyte loss in chronic rejection. The absence of ductular epithelial cell staining suggests that PCD is not involved significantly in the bile duct loss of VBDS. Furthermore, apoptosis of monomuclear cells implies that PCD may be involved in regulating the inflammatory cell infiltration of graft rejection.
Subcellular localization of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in human intrahepatic biliary epithelial cells
Authors: Joplin Ruth , Wallace Lorraine L. , Johnson Gerald D. , Lindsay J. Gordon , Yeaman Stephen J. , Palmer Jeremy M. , Strain Alastair J. , Neuberger James M. 
Published: June 2005

AbstractIn previous histological studies, biliary epithelial cells (BEC) in the liver of patients with primary biliary cirrhosis (PBC), but not controls, reacted strongly with antibodies specific for the major autoantigen associated with PBC, the E2 component of pyruvate dehydrogenase complex (PDC‐E2). In this study we have used transmission electron microscopy (TEM) to document the precise subscellular localization of PDC‐E2 in BEC. Two antibodies which recognize PDC‐E2 were used: affinity‐purified anti‐PDC‐E2 raised in rabbits; and human antibody from the serum of patients with PBC, affinity‐purified against human heart PDC. The intracellular localization of antibody binding was determined by laser scanning confocal microscopy and TEM. Both antibodies bound to the inner membrane of mitochondria in BEC isolated from both patients with PBC and controls, but binding to the external aspect of the plasma membrane was observed only in BEC from patients with PBC. Surface antigen expression in PBC may make BEC immunological targets.
The abnormal isoform of the prion protein accumulates in late‐endosome‐like organelles in scrapie‐infected mouse brain
Authors: Arnold Jane E. , Tipler Carron , Laszlo Lajos , Hope James , Landon Michael , Mayer R. John 
Published: June 2005

AbstractThe prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie‐infected mouse brain was used to show, both biochemically and by double‐labelled immunogold electron microscopy, that proteinase K‐resistant PrPsc is enriched in subcellular structures which contain the cation‐independent mannose 6‐phosphate receptor, ubiquitin‐protein conjugates, β‐glucuronidase, and cathepsin B, termed late endosome‐like organelles. The glycosylinositol phospholipid membrane‐anchored PrPc will enter such compartments for normal degradation and the organelles may therfore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.
Distribution of cyclooxygenase isoforms in murine chronic granulomatous inflammation. Implications for future anti‐inflammatory therapy
Authors: Appleton Ian , Tomlinson Annette , Mitchell Jane A. , Willoughby Derek A. 
Published: June 2005

AbstractInhibition of the enzyme cyclooxygenase (COX) is the basis for the mechanism of action of non‐steroidal anti‐inflammatory drugs (NSAIDs). COX exists as a constitutive (COX‐1) and a mitogen‐inducible (COX‐2) isoform. The relative contribution of COX‐1 and COX‐2 to inflammation is unknown. This study investigated COX activity and the distribution of COX‐1 and COX‐2 during the development of a murine air pouch model of chronic granulomatous inflammation. COX activity progressively rose and was maximal at day 14. Of the COX metabolites measured, PGE2 was the greatest >6‐keto PGF1α>TXB2>PGF2α. By day 7, COX‐2‐labelled fibroblast‐ and macrophage‐like cells were observed and their number and distribution increased with time. At all time points, endothelial cells of venules in the loose connective tissue of the dermis showed immunoreactivity for COX‐2. After day 14, labelling of capillaries in the granuloma was also observed. This study is the first to show that COX‐2 is the predominant COX isoform in all stages of the inflammatory response. These results suggest that selective inhibition of COX‐2 may prove more beneficial, with fewer gastric and renal side‐effects, than existing NSAID therapy for the treatment of chronic inflammatory diseases.
Analysis of the BCL‐6 gene configuration in diffuse B‐cell non‐Hodgkin's lymphomas and Hodgkin's disease
Authors: Pescarmona Edoardo , Lo Coco Francesco , Pacchiarotti Alberto , Rapanotti Maria Cristina , Cimino Giuseppe , Di Paolo Barbara , Baroni Carlo D. 
Published: June 2005

AbstractBCL‐6 is a novel proto‐oncogene that codes for a zinc‐finger protein sharing homologies with many transcription factors. It has recently been shown that BCL‐6 is involved in chromosome band 3q27 aberrations in non‐Hodgkin's lymphomas (NHLs) and BCL‐6 rearrangements have been detected in 34–45 per cent of diffuse large cell lymphomas with B immunophenotype. We have studied the BCL‐6 gene configuration by Southern blot analysis in 60 cases of B‐cell NHL and in 17 cases of Hodgkin's disease (HD). BCL‐6 was rearranged in 15/46 (32·6 per cent) diffuse B‐large cell lymphomas, mainly with centroblastic morphology, and in 2/11 (18·2 per cent) follicular (centroblastic‐centrocytic) lymphomas. Conversely, all cases of HD, including four cases of lymphocyte predominant, nodular type (nodular paragranuloma), had a germline configuration. These findings confirm that BCL‐6 is rearranged in a significant percentage of diffuse B‐large cell lymphomas, suggesting that this proto‐oncogene might have a pathogenetic role in this subset of NHLs, but our preliminary analysis suggests that BCL‐6 lesions are not involved in the pathogenesis of HD. However, further investigations using more sensitive techniques are required to confirm these findings.
MDM2 expression in lymphoid cells and reactive and neoplastic lymphoid tissue. Comparative study with p53 expression
Authors: Martinez Juan C. , Mateo Marisol , Sá;nchez‐Beato Margarita , Villuendas Raquel , Orradre Juan L. , Algara Patrocinio , Sáanchez‐Verde Lydia , García Pedro , López Carmen , Martínez Pedro , Piris Miguel A. 
Published: June 2005

AbstractMDM2 and p53 immunohistochemical protein expression was analysed in lymphocytes and in reactive and neoplastic lymphoid tissue. Phytohaemagglutinin (PHA)‐stimulated lymphocytes displayed MDM2 and p53 co‐expression. In 8 of 8 tonsils, 24 of 24 Hodgkin's disease (HD), and 10 of 24 high‐grade non‐Hodgkin's lymphoma (HG‐NHL) specimens, MDM2 paralleled p53 nuclear expression in non‐tumour and tumour cells. The number of positive cells was greater and the staining intensity was stronger for p53 than for MDM2. In another nine of the 24 HG‐NHL cases studied, dissociated expression was observed, with high p53 expression and very low or absent MDM2 expression. In five cases, both MDM2 and p53 were negative. The eight low‐grade NHL (LG‐NHL) cases were also MDM2‐ and p53‐negative. MDM2 and p53 expression in PHA‐activated lymphocytes and reactive lymphoid tissue is probably an expression of opposing biological signals regulating cell proliferation. Parallel MDM2 and p53 expression in all HD and in 10 out of 24 HG/NHL cases may indicate that this growth suppressive pathway is maintained in those cases. However, dissociated MDM2/p53 expression (nine cases) and the absence of expression of both proteins (five cases) may represent examples of deregulation of this growth control pathway. These findings are in agreement with previous in vitro studies in cell lines regarding the role of MDM2/p53 interaction in the regulation of growth control and extend this observation to normal lymphocytes and reactive lymphoid tissue, suggesting a possible role for MDM2 deregulation in lymphomagenesis.
CD25‐negative hairy cell leukaemia: Intracytoplasmic detection of Tac antigen and interferon‐induced surface expression
Authors: Tison Tiziana , Dazzi Francesco , Giacon Claudia , Vianello Fabrizio , Valente Maria Luisa , Radossi Paolo , Sgarabotto Dino , Girolami Antonio , Pennelli Natale , Poletti Alessandro 
Published: June 2005

AbstractHairy cell leukaemia (HCL) is a chronic lymphoproliferative disease of B‐cell lineage. One of the peculiar immunophenotypic markers is the strong expression of the p55 chain of the interleukin‐2 receptor (IL2R), recognized by anti‐CD25 (or anti‐Tac) monoclonal antibody. However, it is known that in rare cases CD25 may not be detectable, even when variant forms of HCL are excluded. The possibility has not been investigated that in these situations CD25 is present in the cytoplasm of the neoplastic cells. This paper describes a case in which the clinical, histological, and electron microscopic features were consistent with a typical HCL. Immunophenotype analysis showed the whole spectrum of markers of HCL, except for the expression of IL2R. The soluble form of the molecule was, however, increased in the patient's serum. Cytospin staining of the neoplastic B cells with anti‐CD25 clearly demonstrated the presence of IL2R in the cytoplasm of hairy cells. When the cells were cultivated in vitro in the presence of interferon‐α2b, CD25 was detectable at the membrane level. These findings suggest that at least some cases of CD25‐negative HCL may express cytoplasmic IL2R.
p53 immunoreactivity and mutation of the p53 gene in smooth muscle tumours of the uterine corpus
Authors: Jeffers Michael D. , Farquharson Maura A. , Richmond James A. , McNicol Ann Marie 
Published: June 2005

AbstractMutation and overexpression of p53 have been described in uterine malignant mixed Müllerian tumours and in endometrial adenocarcinoma, where it has been associated with a poor prognosis. This study examines p53 expression and mutation of the p53 gene in benign and malignant smooth muscle tumours of the uterine corpus. p53 expression was evaluated by immunohistochemistry in formalin‐fixed, paraffin‐embedded tissue from 23 leiomyo‐sarcomas, 10 tumours of uncertain malignant potential (TUMPs), and 18 leiomyomas. Single‐stranded conformational polymorphism, (SSCP) analysis of exons 5–8 of the p53 gene was performed on 13 leiomyosarcomas, nine TUMPs, and eight leiomyomas. With microwave antigen retrieval, p53 immunoreactivity was seen in 13/23 leiomyosarcomas, 6/10 TUMPs, and 1/18 leiomyomas. Normal myometrium was unstained. In the absence of microwave treatment, staining was abolished in three leiomyosarcomas, all immunoreactive TUMPs, and the single positive leiomyoma. SSCP analysis revealed mutation in three leiomyosarcomas. There was one mutation in exon 5 in a case with positive immunohistochemistry. Two cases with negative staining showed mutation, one in exon 7 and one in exon 8. Mutation was present in exon 7 in 4/9 and in exon 6 in 1/9 TUMPs. All of these cases showed positive immunohistochemistry. There was no significant difference in outcome between cases with and without positive immunohistochemistry. p53 expression is seen in a significant proportion of uterine leiomyosarcomas. Microwave antigen retrieval increases the proportion of positive cases and also results in positive staining in TUMPs. Mutation of the p53 gene occurs in only a minority of leiomyosarcomas and in a significant proportion of TUMPs. Positive immunohistochemistry does not, however, correlate with the presence of mutation and other factors may be responsible for p53 detection in many cases.