bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findings
Authors: Mooney E E , Nogales F F , Bergeron C , Tavassoli F A 
Published: March 2003

Retiform Sertoli–Leydig cell tumours: clinical, morphological and immunohistochemical findingsAims:  To determine the morphological and immunohistochemical profile of retiform Sertoli–Leydig cell tumours and to compare the observed profile with that of adult rete ovarii.Methods and results:  Nineteen retiform Sertoli–Leydig cell tumours were studied, eight by immunohistochemistry, and five examples of rete ovarii from adult females were also evaluated immunohistochemically. The patients ranged in age from 3 to 74 years with a mean age of 31 years. Four patients were virilized and had an abdominal mass; two were virilized with amenorrhoea and two had amenorrhoea alone. Eight presented with an abdominal mass and one patient was pregnant. Two tumours were incidental findings. Information on stage was available in 16 patients: 14 tumours were stage 1, one was stage 2, and one was stage 3. Fifteen tumours were of intermediate differentiation and four were poorly differentiated. Papillary structures were evident grossly in four cases. Microscopically, all cases had a retiform pattern in addition to varying quantities of sex cord, gonadal stromal and heterologous elements. Heterologous elements were present in 13 cases andconsisted of hepatocytes (n = 7), mucinous epithelium (n = 7) and skeletal muscle (n = 2). Immunohistochemical evaluation of eight tumours showed a more intense positivity for keratin in the retiform areas, whereas the gonadal stromal component had a more intense expression of inhibin. Inhibin stains Leydig cells strongly and hepatocytes moderately. Rete ovarii epithelium was positive for keratin and vimentin in the five cases studied, and for inhibin in one case. Follow‐up was available on 13 patients. Three tumours behaved in a malignant fashion: one each was stage 1, 2, and 3 at diagnosis.Conclusions:  Immunohistochemistry is useful in distinguishing retiform Sertoli–Leydig cell tumours from other tumours that they may resemble. Inclusion of inhibin is essential in a panel of antibodies to evaluate these tumours. The clinical behaviour of these neoplasms cannot always be predicted from their morphology or clinical stage.
High molecular weight cytokeratin antibody (clone 34βE12): a sensitive marker for differentiation of high‐grade invasive urothelial carcinoma from prostate cancer
Authors: Varma M , Morgan M , Amin M B , Wozniak S , Jasani B 
Published: March 2003

Aims:  There is no well‐established positive immunomarker for urothelial carcinoma. We evaluated the diagnostic utility of high molecular weight cytokeratin (HMWCK) antibody clone 34βE12 in differentiating high‐grade invasive urothelial carcinoma from prostate cancer.Methods and results:  Formalin‐fixed paraffin‐embedded sections from 28 cases of high‐grade invasive urothelial carcinoma (20 not otherwise specified (UC‐NOS), eight with glandular differentiation) and 20 cases of poorly differentiated prostate carcinoma were immunostained with a monoclonal antibody to carcinoembryonic antigen (CEA), clone 85A12 and with HMWCK antibody clone 34βE12 after microwave pretreatment or protease 24 predigestion. All cases of UC‐NOS expressed HMWCK on 34βE12 immunostaining after microwaving or enzyme predigestion. Immunoreactivity was intense and diffuse in all the cases after microwave pretreatment, whilst with enzyme predigestion immunoreactivity was sometimes patchy with <50% tumour cells positive in 20% of cases. In comparison with 34βE12, 85A12 was insensitive with 15% of UC‐NOS cases totally CEA‐negative and <50% tumour cell immunoreactivity in 60% of cases. Rare positive cells were present in two (10%) cases of prostate cancer with monoclonal anti‐CEA and 34βE12 on microwaved sections, but all the cases were HMWCK‐negative using 34βE12 on sections pretreated by enzyme digestion.Conclusions:  HMWCK antibody clone 34βE12, particularly when used with microwave heat retrieval, is a very sensitive positive marker for high‐grade invasive urothelial carcinoma.
Interaction of CTLA‐4 (CD152) with CD80 or CD86 inhibits human T‐cell activation
Authors: Vandenborre K. , Van Gool S. W. , Kasran A. , Ceuppens J. L. , Boogaerts M. A. , Vandenberghe P. 
Published: March 2003

SummaryOccupancy of CTLA‐4 (cytotoxic T‐lymphocyte antigen‐4 or CD152) negatively regulates the activation of mouse T lymphocytes, as indicated by the fate of CTLA‐4‐deficient mice, by the impact of anti‐CTLA‐4 monoclonal antibodies (mAbs) on mouse T‐cell activation in vitro and by the impact of CTLA‐4 blockade on the course of experimental tumoral, autoimmune, alloimmune or infectious disease in this animal. The function of human CTLA‐4, however, remains less clear. The expression and function of human CTLA‐4 were further explored. CTLA‐4 was expressed under mitogenic conditions only, its expression being, at least partially, dependent on the secretion of interleukin‐2. Memory T cells expressed CTLA‐4 with faster kinetics than naive T cells. The functional role of human CTLA‐4 was assessed utilizing a panel of four anti‐CTLA‐4 mAbs that blocked the interaction between CTLA‐4 and its ligands. These mAbs, in immobilized form, profoundly inhibited the activation of T cells by immobilized anti‐CD3 mAb in the absence of anti‐CD28 mAb, but co‐stimulated T‐cell activation in the presence of anti‐CD28 mAb. Finally, and importantly, blockade of the interaction of CTLA‐4 with its ligands using soluble anti‐CTLA‐4 mAbs, in intact form or as Fab fragments, enhanced T‐cell activation in several polyclonal or alloantigen‐specific CD80‐ or CD80/CD86‐dependent assays, as measured by cytokine production, cellular proliferation or cytotoxic responses. It is concluded that interaction of CTLA‐4 with its functional ligands, CD80 or CD86, can down‐regulate human T‐cell responses, probably by intracellular signalling events and independent of CD28 occupancy.
Elevated apoptosis of peripheral T lymphocytes in diabetic BB rats
Authors: Jung C.‐G. , Kamiyama T. , Agui T. 
Published: March 2003

SummaryThymocytes and peripheral lymphocytes of BioBreeding (BB) diabetes‐prone (BBDP) and diabetes‐resistant (BBDR) rat were analysed by fluorescence‐activated cell sorter (FACS). The number of CD4– CD8–, CD4+ CD8–, CD4– CD8+ and CD4+ CD8+ subsets was not different between BBDP and BBDR rat thymocytes, whereas spleen and lymph nodes in BBDP rats undergo severe T‐cell lymphopenia. Notably, mature CD4– CD8+[T‐cell receptor (TCR)‐αβ+ and CD5+] cells are certainly present in the BBDP rat thymus, unlike some previous reports, suggesting that the differentiation of CD4– CD8+ from CD4+ CD8+ cells occurs normally in the BBDP rat thymus. As a cause of peripheral T‐cell lymphopenia we suspected apoptosis of recent thymic emigrants. By FACS analysis with fluorescein isothiocyanate‐labelled annexin V, elevated apoptosis was evident in BBDP rat peripheral lymphocytes. Furthermore, terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling (TUNEL) staining in BBDP rat splenic sections revealed that a number of TUNEL‐positive cells were observed in the T‐lymphocyte‐rich area. From these results, we postulate that an abnormally elevated apoptosis of peripheral T lymphocytes, but not impaired thymocyte differentiation, is a cause of the peripheral T‐cell lymphopenia in BBDP rats.
Deficiency of the macrophage migration inhibitory factor gene has no significant effect on endotoxaemia
Authors: Honma N. , Koseki H. , Akasaka T. , Nakayama T. , Taniguchi M. , Serizawa I. , Akahori H. , Osawa M. , Mikayama T. 
Published: March 2003

SummaryBy targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mφ) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF‐deficient mice (maintained under specific pathogen‐free conditions) caused shock. No significant difference was detected between the MIF‐deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor‐α (TNF‐α) formation upon LPS injection. Peritoneal Mφ from the two strains produced TNF‐α in response to LPS with similar dose responses. Dexamethasone suppressed the LPS‐induced TNF‐α response of Mφ, but no difference was detected between the Mφ from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS‐induced TNF‐α production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS‐induced immune responses leading to shock.
Interferon‐γ up‐regulates intercellular adhesion molecule‐1 and vascular cell adhesion molecule‐1 and recruits lymphocytes into the vagina of immune mice challenged with herpes simplex virus‐2
Authors: Parr M. B. , Parr E. L. 
Published: March 2003

SummaryLymphocyte recruitment into tissues involves interactions between adhesion molecules on vascular endothelial cells and corresponding ligands on the lymphocyte surface. In the present study we investigated the expression of four endothelial addressins in the vagina and their possible up‐regulation by interferon‐γ (IFN‐γ) in immune mice after vaginal challenge with herpes simplex virus type 2. The adhesion molecules intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 (VCAM‐1) were minimally expressed in the vagina of non‐immune mice with or without vaginal challenge and in immune mice before challenge, but both were up‐regulated by IFN‐γ, directly or indirectly, in immune mice after challenge. Mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) was detected in most vaginas but was not up‐regulated by IFN‐γ in immune mice after virus challenge. E‐selectin was not detected in any vaginas. The results suggest that ICAM‐1 and VCAM‐1 may be involved in rapid, IFN‐γ‐mediated recruitment of lymphocytes to the vaginal mucosal of immune mice after local virus challenge.
Introducing endogenous antigens into the major histocompatibility complex (MHC) class II presentation pathway. Both Ii mediated inhibition and enhancement of endogenous peptide/MHC class II presentation require the same Ii domains
Authors: Frauwirth K. , Shastri N. 
Published: March 2003

SummaryThe invariant chain (Ii) plays a key role in regulating the antigen presentation function of major histocompatibility complex (MHC) class II molecules. Ii also influences the presentation of usually excluded endogenously synthesized proteins into the MHC class II presentation pathway. To evaluate the role of Ii in the generation of peptide–MHC class II complexes derived from endogenously synthesized proteins, we tested mutant Ii constructs in two model systems. Co‐expression of wild‐type Ii inhibits the presentation of hen‐egg lysozyme (HEL) 35–45/Ak complex, but enhances the presentation of ovalbumin (OVA) 247–265/Ak complex from endogenously synthesized HEL or OVA precursors. The differential sensitivity of these antigens to chloroquine was consistent with their being processed in distinct compartments. Nevertheless, with a panel of Ii deletion constructs we show here that both the Ii‐mediated inhibition and enhancement functions require the endosomal targeting and CLIP residues. Surprisingly, the Ii mutant lacking the endoplasmic reticulum lumenal residues 126–215, despite apparently lower expression, was at least as effective as full‐length Ii in antigen presentation assays. Thus, alternative pathways exist for processing endogenously expressed antigens, and Ii‐mediated inhibition and enhancement of peptide/MHC class II expression depend upon the same regions, with neither requiring the 89 C‐terminal, lumenal Ii residues.
The use of human CD68 transcriptional regulatory sequences to direct high‐level expression of class A scavenger receptor in macrophages in vitro and in vivo
Authors: Gough Peter J. , Gordon Siamon , Greaves David R. 
Published: March 2003

SummaryMacrophages (Mφ) play a key role in innate and acquired immunity. The study of Mφ biology has been hampered by the absence of suitable gene regulatory sequences for the overexpression of heterologous genes in Mφ. The human CD68 gene encodes a glycoprotein that is expressed in monocytes and Mφ, and therefore represents an attractive candidate gene for the generation of a Mφ‐specific gene‐targeting vector. A transgene expression cassette that combines 2·9 kb of CD68 5′ flanking sequence with the 83‐bp first intron (IVS‐1) of the CD68 gene, directed high‐level, long‐lasting expression of class A human scavenger receptor (hSR‐A) isoforms in the murine Mφ cell line, RAW‐264. By using this CD68 expression cassette to generate Mφ cell lines that overexpress a soluble secreted form of the extracellular portion of type I human SR‐A, we were able to purify significant quantities of this protein and show its ability to inhibit SR‐A‐mediated endocytosis. Analysis of two independent lines of transgenic mice that expressed type III human SR‐A under the control of the CD68 gene sequences revealed transgene mRNA expression in elicited Mφ populations and in mouse tissues in a pattern that was consistent with Mφ‐specific gene targeting. These data show that CD68 transcriptional regulatory sequences can be used to direct high‐level transgene expression in Mφin vitro and in vivo.
The genetic and immunopathological processes underlying collagen‐induced arthritis
Authors: Luross JEFF A. , Williams NEIL A. 
Published: March 2003

SummaryAnimal models of rheumatoid arthritis (RA) have provided substantial insights into basic pathogenic mechanisms of chronic inflammatory arthritis and autoimmune disease in general. Of the variety of models reported, collagen‐induced arthritis (CIA) has been the most characterized in terms of both its pathogenesis and its underlying immunological basis. Collagen‐induced arthritis has also been the model of choice in terms of testing potential new therapeutic agents for the treatment of human RA. Nevertheless, the complex nature of the balance between T‐cell cytokines and the chronic inflammatory processes is only recently becoming clear. This review focuses on these developments, highlighting their implications for our understanding of RA and for the use of CIA as a suitable animal model.
γδ T cells are critical for the induction of anterior chamber‐associated immune deviation
Authors: Xu Yijun , Kapp Judith A. 
Published: March 2003

SummaryAnterior chamber‐associated immune deviation (ACAID) is a systemic form of tolerance that is elicited by introducing antigens into the anterior chamber of the eye. ACAID is characterized by deficiencies in delayed‐type hypersensitivity and complement‐fixing antibodies upon subsequent challenge with antigen. The mechanisms responsible for the generation of this form of tolerance are not yet completely clear. Here we asked whether γδ T cells, which are critical in the induction of oral tolerance and nasal tolerance, play a role in ACAID. The percentage of splenic γδ T cells was higher in mice that received antigen via the anterior chamber compared to untreated mice. In addition, CD44 was up‐regulated on some splenic γδ and αβ T cells after the intraocular injection of antigen. Moreover, administration of antigen into the anterior chamber did not induce ACAID in the C57BL/6 mice pretreated with anti‐mouse δ‐chain monoclonal antibody or in the γδ T‐cell‐receptor‐deficient (δ−/−) mice. γδ T cells from wild‐type mice reconstituted ACAID when transferred into the δ−/− mice before injection of antigen, verifying that the deficiency in δ−/− mice results from the lack of γδ T cells rather than from an inadvertent change caused by deletion of the δ‐chain. These findings indicate that γδ T cells play a very important role in ocular tolerance.
Tissue distribution of products of the mouse decay‐accelerating factor (DAF) genes. Exploitation of a Daf1 knock‐out mouse and site‐specific monoclonal antibodies
Authors: Lin Feng , Fukuoka Yoshihiro , Spicer Andrew , Ohta Rieko , Okada Noriko , Harris Claire L. , Emancipator Steven N. , Medof M. Edward 
Published: March 2003

SummaryDecay‐accelerating factor (DAF) is a membrane regulator of C3 activation that protects self cells from autologous complement attack. In humans, DAF is uniformly expressed as a glycosylphosphatidylinositol (GPI)‐anchored molecule. In mice, both GPI‐anchored and transmembrane‐anchored DAF proteins are produced, each of which can be derived from two different genes (Daf1 and Daf2). In this report, we describe a Daf1 gene knock‐out mouse arising as the first product of a strategy for targeting one or both Daf genes. As part of the work, we characterize recently described monoclonal antibodies against murine DAF protein using deletion mutants synthesized in yeast, and then employ the monoclonal antibodies in conjunction with wild‐type and the Daf1 knock‐out mice to determine the tissue distribution of the mouse Daf1 and Daf2 gene products. To enhance the immunohistochemical detection of murine DAF protein, we utilized the sensitive tyramide fluorescence method. In wild‐type mice, we found strong DAF labelling of glomeruli, airway and gut epithelium, the spleen, vascular endothelium throughout all tissues, and seminiferous tubules of the testis. In Daf1 knock‐out mice, DAF labelling was ablated in most tissues, but strong labelling of the testis and splenic dendritic cells remained. In both sites, reverse transcription‐polymerase chain reaction analyses identified both GPI and transmembrane forms of Daf2 gene‐derived protein. The results have relevance for studies of in vivo murine DAF function and of murine DAF structure.
Herpes simplex virus 1 infected neuronal and skin cells differ in their susceptibility to complement attack
Authors: Rautemaa Riina , Helander Tuula , Meri Seppo 
Published: March 2003

SummaryHerpes simplex virus type 1 (HSV‐1) infection in neurons is lifelong and generally asymptomatic. Reactivation of this latent infection results in skin blistering whereas the respective peripheral neurons are rarely affected. Why the neuronal cells are spared while the skin cells are sacrificed is not well understood. In the present study our aim was to study whether neuronal and skin cells differ in their ability to control complement attack during HSV‐1 infection. Human embryonal skin (HES) cells and neuronal Paju cells were infected by HSV‐1 in vitro. Both types of infected cells activated complement but were initially resistant to membrane attack complex (MAC) deposition. During the first hours of infection the expression of the endogenous complement regulators decay accelerating factor (DAF) and CD59 increased on both HES and Paju cells. By 12 hr the infected HES cells had lost their ability to control complement attack. The expression of DAF and CD59 decreased and the cells became targets for MAC attack. In contrast, complement regulator expression on the Paju cells did not decrease below the initial level and complement C5b‐9 deposition was found only on 10% of the Paju cells at 12 hr. The results suggest that HSV‐infected neuronal cells are better than skin cells in protecting themselves against complement attack. This may contribute to the persistence of a latent HSV‐1 infection in neuronal cells for prolonged periods.
Stimulation of naïve T‐cell adhesion and immunological synapse formation by chemokine‐dependent and ‐independent mechanisms
Authors: Bromley Shannon K. , Dustin Michael L. 
Published: March 2003

SummaryChemokines adsorbed to the cell surface play an important role in the initial interactions of T cells with endothelial cells, and may also have a role in T‐cell interactions with dendritic cells. Therefore, we examined the effect of surface‐adsorbed chemokines on the interaction of naïve murine splenic T cells with supported bilayers containing intercellular adhesion molecule (ICAM)‐1, or with bone marrow‐derived cultured dendritic cells in the presence and absence of relevant MHC–peptide complexes. Naïve T cells formed immunological synapses, defined as a ring of lymphocyte function associated (LFA)‐1–ICAM‐1 interactions surrounding a central cluster of MHC–peptide complexes, on supported planar bilayers containing ICAM‐1 and relevant MHC–peptide complexes. Chemokines stimulated an increase in the percentage of naïve cells that adhered to ICAM‐1, but did not increase the average number of LFA‐1–ICAM‐1 interactions in the contact area. In contrast, relevant MHC–peptide complexes resulted in a small increase in the proportion of interacting T cells, but stimulated an 8‐fold increase in the number of LFA‐1–ICAM‐1 interactions in each contact formed. Naïve T cells displayed a significant basal adhesion to bone marrow dendritic cells that was further increased when relevant chemokines were adsorbed to the dendritic cell surface. However, basal and antigen‐stimulated T‐cell adhesion to dendritic cells was not sensitive to pertussis toxin. Thus, there are chemokine‐independent mechanisms that initiate adhesion between T cells and dendritic cells.
Role of stromal‐cell derived factor‐1 in the development of autoimmune diseases in non‐obese diabetic mice
Authors: Matin Khairul , Salam M. Abdus , Akhter Joynab , Hanada Nobuhiro , Senpuku Hidenobu 
Published: March 2003

SummaryThe chemokine stromal‐cell derived factor‐1 (SDF‐1) controls maturation, trafficking, and homing of certain subsets, lymphoid cells including immunogenic B and T cells, as a ligand of the CXCR4 chemokine receptor. Insulin‐dependent diabetes mellitus (IDDM) and Sjögren's syndrome (SS), both highly regulated autoimmune diseases, develop spontaneously in non‐obese diabetic (NOD) mice. To investigate the role of SDF‐1 in the development of autoimmune diseases, we injected groups of NOD female mice with antibodies to SDF‐1 (anti‐SDF‐1), which resulted in a 30% reduction of diabetes up to 30 weeks of age, delayed average diabetes onset by 10 weeks, and suppressed insulitis. Autoimmune sialoadenitis was evident in anti‐SDF‐1‐injected mice (SDF‐1‐Ig group) at the same level as in all groups of mice, whether injected with non‐specific antibodies or not. In addition, in the SDF‐1‐Ig group, a greater number of immunoglobulin M (IgM)− IgD− B220low CD38+ CD43+ CD23− progenitor B cells and IgM+ IgD+ B220high CD43− CD38+ CD24+ CD23+ mature B cells remained in the bone marrow, whereas infiltration of mature IgM+ B cells was less extensive in peripheral tissues. Our results suggested that anti‐SDF‐1 antibodies injection was effective in inhibiting diabetes and insulitis without affecting autoimmune sialoadenitis or SS in NOD mice. SDF‐1 may be an essential chemokine for trafficking and migration of autoreactive B cells in the development of diabetes.
Cytotoxic T lymphocyte‐associated antigen‐4 inhibits integrin‐mediated stimulation
Authors: Gatta Lucia , Calviello Gabriella , Di Nicuolo Fiorella , Pace Luigia , Ubaldi Vanessa , Doria Gino , Pioli Claudio 
Published: March 2003

SummaryThe negative role exerted by cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4) in the regulation of T‐cell activity, as induced by T‐cell receptor (TCR)/CD3 and CD28 costimulation, has been widely described. In the present work we investigated the role of CTLA‐4 in the control of cell activation, as induced by costimulation of the adhesion molecule lymphocyte function‐associated antigen‐1 (LFA‐1) in murine CD4+ T cells. Results show that CTLA‐4 engagement inhibits interleukin‐2 (IL‐2) production, not only when induced by CD3/CD28 costimulation, but also when CD4+ T cells are costimulated by anti‐CD3 and anti‐LFA‐1 monoclonal antibodies (mAbs). LFA‐1 has been described to induce Ca2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA‐4 engagement negatively affects Ca2+ mobilization and NF‐AT activation, as induced by LFA‐1 engagement alone. PLCγ1 phosphorylation was also dampened within minutes after CTLA‐4 engagement. Altogether these data indicate that through the control of signals induced by different receptors, CTLA‐4 could be a global attenuator of T‐cell activation.