bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocellular carcinoma: an overview
Authors: Anthony P P 
Published: March 2003

Hepatocellular carcinoma: an overview Hepatocellular carcinoma remains widely prevalent in tropical Africa and south‐east Asia and is largely related to chronic hepatitis B virus (HBV) infection. Primary prevention by vaccination of infants at or near birth is effective but any reduction in tumour incidence cannot be expected for decades to come yet, even in those countries in which the necessary resources exist, as millions of adults remain chronically infected. Meanwhile, the incidence is rising in Japan, Mediterranean countries of Europe, Middle East and North Africa and in the USA, largely due to chronic hepatitis C virus (HCV) infection introduced by the indiscriminate use of unscreened blood and blood products in the recent past. Much has been learned from molecular biological studies on hepatocarcinogenesis incriminating the HBX gene of HBV, the core protein of HCV and a unique guanine to thymine transversion at codon 249 has been observed in cases due to aflatoxin exposure. The subject of precancerous lesions, notably adenomatous/dysplastic nodules and large‐cell/small‐cell change continues to be a source of much debate and the distinction of nodular lesions in cirrhosis from early carcinoma remains uncertain. Spontaneous regression of hepatocellular carcinoma is rare but it is probably immunologically mediated and treatment by activated T‐lymphocytes may reduce recurrence rates after surgery. The positive identification of hepatocellular carcinoma by a liver‐specific antibody has greatly facilitated the diagnosis in difficult cases.
Sclerosing haemangioma of the lung is positive for MIB‐1 in cell membrane and cytoplasmic staining pattern
Authors: Hattori H 
Published: March 2003

Sclerosing haemangioma of the lung is positive for MIB‐1 in cell membrane and cytoplasmic staining pattern Aims: MIB‐1 is a monoclonal antibody raised against the recombinant part of the Ki67 antigen, which is expressed in the nuclei of all the active part of the cell cycle. Recently, cell membrane and cytoplasmic pattern of staining with MIB‐1 in hyalinizing trabecular adenoma of the thyroid was reported. Sclerosing haemangioma of the lung is a tumour of uncertain histogenesis with a usually benign course. The tumour is mainly composed of cuboidal cells that line the papillary or tubular structure and pale cells that are found in the stroma. Methods and results: We examined a cell membrane and cytoplasmic immunoreactive pattern for MIB‐1 antibody in sclerosing haemangioma. In all of the five cases examined, distinct cell membrane and cytoplasmic MIB‐1 positivity mainly in the pale cells was noted. None of the carcinomas of the lung showed this type of staining with MIB‐1. Conclusion: This result shows that, although the staining may be a result of cross reaction, cell membrane and cytoplasmic MIB‐1 positivity is unique in that it could distinguish sclerosing haemangioma from other malignant epithelial tumours of the lung.
Biliary epithelial trefoil peptide expression is increased in biliary diseases
Authors: Srivatsa G , Giraud A S , Ulaganathan M , Yeomans N D , Dow C , Nicoll A J 
Published: March 2003

Biliary epithelial trefoil peptide expression is increased in biliary diseases Aims: Maintenance of the cellular integrity of the biliary epithelium may involve the production of mucins and mucin‐associated peptides. In the luminal gastrointestinal tract, mucins and the mucin‐associated trefoil peptides (TFF) are integral to cytoprotection and cellular repair of the mucosa. Methods and results: Samples of normal and diseased human liver tissue were examined using histological and immunohistochemical techniques, for the expression of TFF and mucins. Bile ducts were classified as small, medium or large depending upon the number of biliary epithelial cells. TFF expression was demonstrated in biliary epithelial cells of both normal and diseased liver tissue. TFF expression was greatest in the large bile ducts. In normal liver tissue, expression of at least one TFF was demonstrated in 2–7% of small bile ducts, 5–31% of medium bile ducts and 31–85% of large bile ducts. Seventy‐seven percent of large bile ducts secreted mucins and all three TFF concurrently, compared with 3% of medium bile ducts and no small bile ducts. Biliary disease resulted in an increased expression of TFF1 and TFF3 in the medium bile ducts. Conclusions: The biliary epithelial cells in normal and diseased human liver tissue express TFF, particularly in the larger bile ducts. TFF expression may be up‐regulated or induced in biliary diseases as a response to injury, as is seen in epithelial damage elsewhere in the gastrointestinal tract.
Primary monotypic epithelioid angiomyolipoma of bone
Authors: Insabato L , De Rosa G , Terracciano L M , Fazioli F , Di Santo F , Rosai J 
Published: March 2003

Primary monotypic epithelioid angiomyolipoma of bone Aims: Monotypic epithelioid angiomyolipoma is a distinct and definable variant of angiomyolipoma, composed of monomorphous epithelioid cells that show HMB45 immunoreactivity. Angiomyolipoma, including its morphological variants, belongs to the family of perivascular epithelioid cell tumour. Methods and results: The tumour was examined using immunohistochemical staining and by transmission electron microscopy. Neoplastic cells showed a cytoplasmic granular positivity for HMB45. Conclusions: Extrarenal angiomyolipomas are rare and, to the best of our knowledge, this is the first reported case of a primary monotypic epithelioid angiomyolipoma of bone in a patient without evidence of tuberous sclerosis.
Identifying BAC clones for diagnosis of conventional renal cell carcinoma by FISH
Authors: Heinze F , Kovacs G 
Published: March 2003

Aims: The new classification of renal cell tumours relies on tumour‐specific genetic alterations, which can be detected by different techniques. For diagnosis of conventional renal cell carcinoma by FISH we have isolated BAC clones from the chromosomal regions of interest.Methods and results: A BAC library was screened by microsatellites mapped to the smallest overlapping regions of loss of heterozygosity (LOH) at chromosomes 3p, 5q, 6q, 8p, 9p and 14q. Positive BACs were tested by carrying out FISH in normal cells for signal/noise ratio. Subsequently, 11 conventional and two papillary renal cell carcinomas were analysed by the new diagnostic BAC set and the results were compared with those obtained by microsatellite allelotyping. The diagnostic value of FISH was comparable to that of microsatellite analysis in nearly all tumours except those with extreme chromosomal polyploidization.Conclusions: We conclude that both FISH and microsatellite analyses are helpful to strengthen the diagnosis of conventional renal cell carcinoma. However, both techniques may have some disadvantage in a special setting.
Activation‐dependent expression of the insulin‐like growth factor binding protein‐2 in human lymphocytes
Authors: Föll J. L. , Dannecker L. , Zehrer C. , Hettmer S. , Berger J. , Elmlinger M. , Niethammer D. , Ranke M. B. , Dannecker G. E. 
Published: March 2003

The expression of the insulin‐like growth factor binding protein‐2 (IGFBP‐2) was assayed in mononuclear cells originating from different organs of the immune system. All mononuclear cells studied did express IGFBP‐2, but the expression level was found to be dependent on the cell type and origin of the cell. T cells showed a higher expression of IGFBP‐2 mRNA than did B cells, and CD34+stem cells expressed IGFBP‐2 mRNA at a high level. Expression was highest in bone marrow and thymus. Stimulation of peripheral mononuclear cells resulted in a marked increase of IGFBP‐2 mRNA and also intracellular IGFBP‐2, as analysed by fluorescence staining. This increase parallels the increase of other known T‐cell activation markers. Furthermore, the increase of intracellular IGFBP‐2 seems to precede T‐cell blast formation and all T cells in active phases of the cell cycle have high levels of IGFBP‐2. Our results provide a basis for further investigations on the contribution of the IGF‐system to the regulation of T‐cell proliferation and differentiation. IGFBP‐2, in particular, may have an important influence in the regulation of T‐cell activation and proliferation.A 23187, calcium ionophore IGF I/II, insulin‐like growth factor‐I/II IGFBPs, insulin‐like growth factor binding proteins PBMC, peripheral blood mononuclear cell MNC, mononuclear cell MACS, magnetic‐activated cell sorting GAPDH, glycerinaldehydphosphate RT‐PCR, reverse transcriptase–polymerase chain reaction.
Kinetics of interferon‐γ secretion and its regulatory factors in the early phase of acute graft‐versus‐host disease
Authors: Hu H. Z. , Li G. L. , Lim Y. K. , Chan S. H. , Yap E. H. 
Published: March 2003

SummaryIncreased serum levels of interferon‐γ (IFN‐γ) have been observed in acute graft‐versus‐host disease (GVHD). Recent in vitro studies have demonstrated that interleukin‐12 (IL‐12) and interleukin‐18 (IL‐18) synergistically up‐regulate IFN‐γ secretion. In this communication, we investigated the factors relevant to IFN‐γ secretion in acute GVHD. A murine model of acute GVHD was established by injecting donor spleen cells into severe combined immunodeficiency (SCID) mice. A series of specimens, including sera, livers and spleens derived from the GVHD mice, were investigated with histological examination, enzyme‐linked immunosorbent assay (ELISA), flow cytometry, and semiquantitative reverse transcription–polymerase chain reaction (RT–PCR). IFN‐γ secretion increased in serum 3 days after spleen cell transfer, peaked on day 7, and then gradually decreased close to the baseline level by day 35. A synchronized increase of activated T cells and mRNA expression of IL‐12, IL‐18 and their respective receptors was observed after spleen cell transfer. However, only the kinetic expression pattern of IL‐12 receptor (IL‐12R) β2 chains was closely correlated with that of IFN‐γ, while IL‐12 dropped to the baseline level earlier than IFN‐γ. Therefore, IFN‐γ expression in the early phase of acute GVHD is a mono‐peak and self‐restricted pattern. Its secretion is closely related with T‐cell activation, the presence of IL‐12, IL‐18 and their respective receptors. However, the limiting factors for IFN‐γ secretion seem to be IL‐12 and IL‐12R β2 chains.
Morphine‐induced macrophage apoptosis: the role of transforming growth factor‐β
Authors: Singhal P. C. , Kapasi A. A. , Franki N. , Reddy K. 
Published: March 2003

SummaryLaboratory and clinical reports indicate that opiate addicts are prone to infections. This effect of opiates is partly attributed to opiate‐induced macrophage (Mφ) apoptosis. In the present study, we evaluated the role of transforming growth factor‐β (TGF‐β) in morphine‐induced apoptosis of murine J774 cells and peritoneal Mφ. Mφ harvested from morphine‐treated mice showed greater (P < 0·0001) apoptosis when compared with control Mφ. Morphine also enhanced apoptosis of J774 cells and peritoneal Mφ. Anti‐TGF‐β antibody inhibited (P < 0·001) the morphine‐induced apoptosis in J774 cells (control 0·7 ± 0·4%; 10−6 m morphine 23·5 ± 0·7%; anti‐TGF‐β antibody (Ab) + 10−6 m morphine 8·1 ± 0·7%; apoptotic cells/field) and peritoneal Mφ (control 1·5 ± 0·9%; 10−6 m morphine 29·1 ± 1·4%; 10−6 m morphine + anti‐TGF‐β Ab 19·1 ± 1·8%; apoptotic cells/field). TGF‐β enhanced (P < 0·001) apoptosis of J774 cells and peritoneal Mφ. TGF‐β also promoted Mφ DNA fragmentation into integer multiples of 180 bp (ladder pattern). Immunocytochemical studies revealed that morphine enhanced the Mφ cytoplasmic content of TGF‐β. In addition, Western blotting showed increased production of TGF‐β by morphine‐treated J774 cells when compared with control cells. Morphine increased J774 cell expression of bax. Interestingly, morphine‐induced bax expression was inhibited by anti‐TGF‐β Ab. As both morphine‐induced J774 cell apoptosis and bax expression were inhibited by anti‐TGF‐β Ab, it appears that morphine‐induced J774 cell apoptosis may be mediated through the generation of TGF‐β.
Interleukin‐10 does not affect phagocytosis of particulate antigen by bonemarrow‐derived dendritic cells but does impair antigen presentation
Authors: Faulkner L. , Buchan G. , Baird M. 
Published: March 2003

SummaryDendritic cells (DC) are important initiators of an immune response so understanding the factors controlling antigen acquisition and presentation has important consequences for the use of these cells in vaccines and other forms of immunotherapy. We investigated the factors that influence phagocytosis by immature bone marrow‐derived DC (BMDC) and the effect of interleukin‐10 (IL‐10) on this process. Two sizes of fluorescent particles and recombinant bacillus Calmette–Guèrin expressing the green fluorescent protein (rBCG) were used as particulate antigens. The percentage of cells taking up the antigen was found to be dependent on the size and dose of the particles, and the length of exposure to them. BMDC exposed to IL‐10 at various concentrations for different periods exhibited no distinguishable change in antigen uptake. However, if BMDC treated with IL‐10 and rBCG were then exposed to a second dose of particulate antigen, uptake was increased compared with those BMDC not treated with IL‐10. The expression of major histocompatibility complex class II, CD80, CD86 and CD11c by BMDC after phagocytosing rBCG or inert beads, was inhibited when the BMDC were pretreated with IL‐10. In contrast, the expression of CD25 was increased. BMDC that had taken up BCG or purified protein derivative (PPD) were able to stimulate primed T‐cell proliferation but this was severely inhibited if the BMDC were cultured with IL‐10 before exposure to the antigen. This work suggests that although IL‐10 does not affect the phagocytic capacity of BMDC, it does inhibit maturation of the cells and consequently, T‐cell activation.
Common antigenicity between Japanese cedar (Cryptomeria japonica) pollen and Japanese cypress (Chamaecyparis obtusa) pollen, I. H‐2 complex affects cross responsiveness to Cry j 1 and Cha o 1 at the T‐ and B‐cell level in mice
Authors: Kingetsu I. , Ohno N. , Hayashi N. , Sakaguchi M. , Inouye S. , Saito S. 
Published: March 2003

SummaryCommon antigenicity among two purified Japanese cedar pollen allergens (Cry j 1 and Cry j 2) and one Japanese cypress pollen allergen (Cha o 1) was explored at the T‐cell and B‐cell level in mice of different H‐2 haplotypes. Cry j 2 did not show any common antigenicity with Cry j 1 or Cha o 1. B10.S (H‐2S) mice immunized with Cry j 1 or Cha o 1 generated T cells and antibodies reactive to both antigens, indicating the common antigenicity of these antigens. C57BL/6 (H‐2b) mice were non‐responders to Cry j 1. BALB/c (H‐2d) mice immunized with Cry j 1 or Cha o 1 and C57BL/6 mice immunized with Cha o 1 generated T cells that were only reactive with the respective immunogen, but produced antibody reactive to both Cry j 1 and Cha o 1, indicating that Cry j 1 and Cha o 1 share their B‐cell epitope but not their T‐cell epitope. This finding may provide a clue for the clarification of the T‐cell and B‐cell epitopes of Cry j 1 and Cha o 1, even though the data are influenced by H‐2 complex restriction in mice. Considering that H‐2 complex restriction affects cross responsiveness to Cry j 1 and Cha o 1 at the T‐ and B‐cell level in mice, we assessed the possible situation in humans exposed sequentially to Japanese cedar pollen and Japanese cypress pollen.
Immunoglobulin E antibodies of atopic individuals exhibit a broad usage of VH‐gene families
Authors: Eibensteiner P. , Spitzauer S. , Steinberger P. , Kraft D. , Valenta R. 
Published: March 2003

SummaryThe term ‘atopy’ describes the genetically determined tendency to mount immunoglobulin E (IgE) antibody responses against per se harmless antigens (allergens). In this study we investigated the usage of VH families in the formation of IgE antibodies in 10 patients suffering from mucosal and/or skin manifestations of atopy. IgE antibody reactivities to exogenous allergen sources as well as to autoallergens were determined and, by immunoabsorption, it was demonstrated that allergen‐specific IgE accounted for most of the total serum IgE levels in these patients. Using primers with specificity for the VH1–6 gene families and a primer specific for the first constant region of human IgE, cDNAs coding for IgE heavy chain fragments were amplified using the reverse transcription–polymerase chain reaction (RT–PCR) from peripheral blood lymphocytes of the 10 atopic individuals. Hybridization of the heavy chain‐encoding cDNAs with an IgE‐specific internal oligonucleotide probe revealed a broad usage of all VH‐gene families in the atopic individuals. The spectrum of VH families used in a given atopic individual was neither associated with the type or severity of clinical symptoms nor with the number of allergens recognized. The fact that allergen‐specific IgE antibodies in atopic individuals originate from a broad variety of B cells thus reflects the activation of multiple B‐cell clones during allergen sensitization. This finding should be borne in mind if therapeutic strategies for Type I allergy are considered that aim at a clonal elimination of allergen‐specific B cells.
Hydrogen peroxide augments eosinophil adhesion via β2 integrin
Authors: Nagata M. , Yamamoto H. , Shibasaki M. , Sakamoto Y. , Matsuo H. 
Published: March 2003

SummaryDuring eosinophil (EOS) accumulation at sites of allergic inflammation, an initial step is the binding of EOS to adhesion molecules expressed on vascular endothelial cells (EC). We have previously observed that adhesion of peripheral blood EOS to recombinant human vascular cell adhesion molecule‐1 (rh‐VCAM‐1) stimulates the respiratory burst of EOS. Although the biological consequence of this activation remains to be elucidated, reactive oxygen species such as hydrogen peroxide (H2O2) may modify the adhesive property of EOS. In the present study, we examined whether H2O2 modifies the adhesive property of EOS. EOS were isolated from the peripheral blood of healthy subjects. Adhesion of the EOS to paraformaldehyde‐fixed human umbilical vein EC (HUVEC), stimulated or not stimulated with tumour necrosis factor‐α (TNF‐α; 100 p
m for 24 hr), was examined in the presence or absence of H2O2. H2O2 significantly enhanced adhesion of EOS to both resting and TNF‐α‐stimulated fixed HUVEC (P < 0·01, respectively). Such enhancing effects were inhibited by anti‐β2 integrin antibody or anti‐CD11b antibody, but not by anti‐CD11a or anti‐α4 integrin antibody. H2O2 also enhanced EOS adhesion to rh‐intracellular cell adhesion molecule‐1 (ICAM‐1) but not to rh‐VCAM‐1. Finally, H2O2 enhanced the expression of both CD11b and CD18 on EOS. These results indicate that H2O2 directly augments the adhesive property of EOS through β2 integrin.
Disaccharides generated from heparan sulphate or heparin modulate chemokine‐induced T‐cell adhesion to extracellular matrix
Authors: Hershkoviz R. , Schor H. , Ariel A. , Hecht I. , Cohen I. R. , Lider O. , Cahalon L. 
Published: March 2003

SummaryWe have found previously that disaccharides (DS) enzymatically generated from heparin or heparan sulphate can modulate tumour necrosis factor‐α (TNF‐α) secretion from immune cells in vitro and cell‐mediated immune reactions in vivo. Here, we show that such DS can modulate the adhesion and migration of human T cells. We found that certain heparin‐ and heparan sulphate‐derived DS induced, in a dose‐dependent manner, the adhesion of human T cells to both extracellular matrix (ECM) and immobilized fibronectin (FN); maximal T‐cell adhesion occurred with 1 ng/ml of DS. The levels of T‐cell adhesion to ECM that were induced by the tested DS molecules resembled those induced by the prototypic chemokine, macrophage inflammatory protein 1β (MIP‐1β). However, the kinetics of DS‐induced T‐cell adhesion to FN resembled that induced by phorbol myristate acetate (PMA), but not that induced by MIP‐1β. This adhesion appeared to involve β1 integrin recognition and activation, and was associated with specific intracellular activation pathways. Although a first exposure of T cells to certain DS molecules appeared to result in cell adhesion, a subsequent exposure of T cells to pro‐adhesive chemokines, such as MIP‐1β or RANTES, but not to other pro‐adhesive stimuli, for example interleukin‐2 or CD3 cross‐linking, resulted in inhibition of T‐cell adhesion to and chemotactic migration through FN. Hence, we propose that the breakdown products of tissues generated by inflammatory enzymes are part of an intrinsic functional programme, and not necessarily molecular waste. Moreover, because the DS molecules exert their modulatory functions within a limited time, it appears that the historical encounters of the tissue‐invading cells with the constituents of inflamed loci may dictate the cells’ behaviour upon subsequent exposure to proinflammatory mediators.
Production and functional characterization of a soluble recombinant form ofmouse CD59
Authors: Rushmere N. K. , Van Den Berg C. W. , Morgan B. P. 
Published: March 2003

SummaryThis report describes the engineering, expression, purification and functional characterization of a soluble recombinant form of murine CD59 (srMoCD59). We report the expression in Chinese hamster ovary (CHO) cells of a modified mouse CD59 cDNA that had been truncated at D‐74, resulting in the loss of the glycosylphosphatidyl inositol (GPI) anchor, and containing six additional C‐terminal histidines. The expressed srMoCD59 was purified from tissue culture supernatant by means of its poly‐histidine tag using immobilized metal affinity chromatography. In comparison with CD59 on mouse erythrocytes, the srMoCD59 had a reduced molecular weight (18–20 000 as compared with 20–28 000 for GPI‐anchored srMoCD59). The terminal complement inhibitory capacity of this soluble recombinant protein was assessed using two methods: a cobra venom factor (CVF)‐triggered ‘reactive‐lysis’ system and a C5b‐7 site assay. In both assays, srMoCD59 inhibited lysis by the sera from all three species tested in the rank order mouse > rat >> human. The amount of srMoCD59 required to produce 50% inhibition of lysis in the C5b‐7 site assay, using purified terminal components to develop lysis, was 10‐fold less than that required in the same assay when EDTA serum was used as a source of C8 and C9, or in the CVF reactive lysis system. These data indicate that the presence of serum markedly interfered with the activity of srMoCD59 and have important implications for the use of recombinant soluble CD59 analogues as therapeutic agents in complement‐mediated diseases.