bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant myopericytoma: expanding the spectrum of tumours with myopericytic differentiation
Authors: McMenamin M E , Fletcher C D M 
Published: March 2003

Aims:  The spectrum of tumours showing myopericytic differentiation is increasingly being defined and includes lesions such as myofibroma and infantile haemangiopericytoma. Here we seek to describe for the first time and clinicopathologically characterize examples of malignant myopericytoma.Methods and results:  Five cases of malignant myopericytoma were identified in the authors' consultation files. Immunostains were performed and clinical information was obtained. Tumours arose in three females and two males (median age 67 years, range 19–81 years) on the neck, arm, thigh and foot. One patient presented with disseminated metastases. One patient had a prior history of multiple benign myopericytomas in the same location. Four patients developed metastases and three died within 1 year. Tumours were composed of highly mitotic myoid‐appearing ovoid‐to‐spindle cells showing at least focally striking perivascular orientation resembling that seen in benign myopericytoma; three cases were focally fascicular and three showed thin‐walled branching vessels. All tumours showed at least focally prominent positivity for smooth muscle actin. One case showed dot‐like desmin positivity.Conclusions:  In reporting examples of malignant myopericytoma, we further characterize and broaden the morphological spectrum of myopericytic neoplasms. Available data indicate that malignant myopericytomas are associated with aggressive clinical behaviour.
Changes in cellular response to mycobacterial antigens and cytokine production patterns in leprosy patients during multiple drug therapy
Authors: Trao V. T. , Huong P. L. T. , Thuan A. T. , Anh D. D. , Trach D. D. , Rook G. A. W. , Wright E. P. 
Published: March 2003

Changes inMycobacterium leprae‐induced lymphoproliferative responses and mediator release by leprosy patients’ lymphocytes were followed during multiple drug therapy (MDT). At the time of diagnosis, multibacillary (MB) patients who did not develop reactions responded to both sonicatedM. lepraeand synthetic disaccharide coupled to bovine serum albumin (ND‐BSA) antigens, but those who would later develop reactions did not respond, even in the presence of added cytokines. The paucibacillary (PB) group initially had high responses to sonicatedM. lepraebut no response to ND‐BSA, even in the presence of added cytokines. In the first year of treatment, the supernatants of PB patients’ cell cultures contained factors that enhanced the phytohaemagglutinin (PHA) response of normal cells. In contrast, those MB patients who did not develop reactions at a later stage produced culture supernatants that were inhibitory. Interestingly, the MB patients who later developed reactions during treatment, and did not initially respond toM. leprae, produced supernatants containing enhancing factors, like those of the PB group. Later on in the treatment, all patients had the same patterns: when response toM. lepraedecreased from its highest level, inhibitory factors were produced. Further studies revealed that the supernatants which inhibited the PHA response of normal cells contained the active form of transforming growth factor‐β1(TGF‐β1), whatever the disease type or treatment status of the donor. These TGF‐β1levels correlated directly with the degree of inhibition. Similarly, supernatants that neither inhibited nor enhanced PHA responses contained the highest levels of interleukin‐10 (IL‐10), while those from treated patients that enhanced contained the lowest levels of interleukin‐4 (IL‐4) and interferon‐γ (IFN‐γ). These cytokine correlations transcended the conventional disease classification, and imply that all patients pass through a sequence of patterns of immune response during treatment. These treatment‐induced changes may explain occasional reports of response patterns at variance with the ‘immunological spectrum’ of leprosy.BB, borderlineBL, borderline lepromatousBT, borderline tuberculoidIFN‐γ, interferon gammaIL‐4, interleukin‐4IL‐10, interleukin‐10MB, multibacillaryPB, paucibacillaryRT–PCR, reverse transcriptase–polymerase chain reactionLL, polar lepromatousTGF‐β1, transforming growth factor‐β1TT, tuberculoid.
Anterior chamber‐associated immune deviation‐inducing cells activate T cells, and rescue them from antigen‐induced apoptosis
Authors: Takeuchi M. , Alard P. , Verbik D. , Ksander B. , Streilein J. W. 
Published: March 2003

SummaryImmune responses to antigens injected into the anterior chamber of the eye are devoid of T helper 1 (Th1)‐type responses of the delayed hypersensitivity type, which has been termed anterior chamber‐associated immune deviation (ACAID). Recently, it has been found that peritoneal exudate cells (PEC) from normal mice can be made to acquire the capacity to induce ACAID in vivo when the cells are pulsed with antigen in vitro in the presence of transforming growth factor‐β2 (TGF‐β2), a major cytokine in the ocular microenvironment. We now report that when ovalbumin (OVA)‐specific T cells from DO11.10 transgenic mice, or from OVA‐primed normal mice, were activated in vitro by normal (untreated) PEC pulsed with OVA, the responding T cells were induced to undergo apoptosis. However, when PEC were first treated with TGF‐β2 and then used to stimulate DO11.10 T cells in the presence of OVA, T‐cell proliferation occurred without evidence of increased apoptosis. The ability of TGF‐β2 to rescue responding T cells from apoptosis rested with the capacity of this cytokine to inhibit interleukin‐12 (IL‐12) production by PEC. Untreated PEC produced large amounts of IL‐12 upon interaction with responding T cells. Under these conditions, tumour necrosis factor‐α (TNF‐α) production was up‐regulated, and this cytokine, in turn, triggered apoptosis among T cells stimulated with OVA‐pulsed PEC. From these results, we conclude that TGF‐β2‐treated APC promote ACAID by rescuing antigen‐activated T cells from apoptosis, and by conferring upon these cells the capacity to down‐regulate delayed hypersensitivity.
Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat
Authors: Kenny E. , Mason D. , Pombo A. , Ramírez F. 
Published: March 2003

SummaryAmong peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8β chain, the remaining cells expressed the CD8α chain alone. Double positive cells were blast‐like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a hapten‐carrier complex increased the ratio of CD8αα : αβ expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells.
Mapping of the chicken immunoglobulin heavy‐chain constant region gene locus reveals an inverted α gene upstream of a condensed υ gene
Authors: Zhao Y. , Rabbani H. , Shimizu A. , Hammarström L. 
Published: March 2003

SummaryChicken antibodies are increasingly being used as diagnostic and therapeutic tools. As only the genomic organization of the µ encoding gene was previously known, we analysed the chicken immunoglobulin Y (IgY) and IgA (υ and α chain) immunoglobulin heavy‐chain constant region (IGHC) genes and the organization of the chicken IGHC locus. The α gene is encoded by four separate exons, whereas, surprisingly, there is no intervening DNA sequence between the CH1 and CH2 domains of the IgY heavy chain, which is thus encoded by three exons separated by two introns. DNA sequence analysis shows that the exon boundaries of the chicken IGHC genes are not consistent with published domain borders. Furthermore, differences in DNA sequence confirm the existence of IgY, IgA and IgM allotypes in chickens. Finally, our results show that the IGHC genes of chicken (IgY, IgA and IgM) are all colocated on chromosome E18C15W15, where the α gene is located upstream of the υ gene in an inverted transcriptional orientation. The distances between the µ and α genes and the α and υ genes are about 18 and 15 kilobases, respectively, and thus, the size of the whole chicken IGHC locus is approximately 67 kilobases.
Recombinant adenovirus vectors expressing interleukin‐5 and ‐6 specifically enhance mucosal immunoglobulin A responses in the lung
Authors: Braciak T. A. , Gallichan W. S. , Graham F. L. , Richards C. D. , Ramsay A. J. , Rosenthal K. L. , Gauldie J. 
Published: March 2003

SummaryIn this study, we have examined the in vivo effects of interleukin‐5 (IL‐5) and IL‐6 over‐expression on systemic and mucosal immune responses using recombinant human type 5 adenoviruses capable of expressing these cytokines upon infection. A recombinant adenovirus containing the murine IL‐5 gene within the E3 region was constructed and found to express high levels of IL‐5 protein both in vitro and in vivo. Intranasal inoculation of mice with this vector or a vector expressing murine IL‐6 increased adenovirus‐specific immunoglobulin A (IgA) titres in lung lavage fluid threefold compared with those elicited by control virus. The simultaneous expression of both cytokines by co‐inoculation altered the kinetics of the mucosal anti‐adenovirus IgA response and resulted in a more than additive increase in antibody titres. The co‐expression effect on IgA synthesis was not due to an increase in numbers of antigen‐specific resident lung tissue lymphocytes. When mucosal IgG responses were examined, IL‐6 expression had the largest impact on anti‐adenovirus levels, whereas co‐expression produced an intermediate response. Systemic immune responses were also affected by IL‐6 expression as a twofold increase in serum IgG anti‐adenovirus titres was observed after a secondary challenge with wild‐type adenovirus. These results demonstrate a relevant role for IL‐5 and IL‐6 in the development of mucosal immune responses in vivo and suggest that the incorporation of either IL‐5 and/or IL‐6 into recombinant adenovirus vectors may be a useful tool in the development of mucosal vaccines.
Inhibition of immunoglobulin E response to Japanese cedar pollen allergen (Cry j 1) in mice by DNA immunization: different outcomes dependent on the plasmid DNA inoculation method
Authors: Toda M. , Sato H. , Takebe Y. , Taniguchi Y. , Saito S. , Inouye S. , Takemori T. , Sakaguchi M. 
Published: March 2003

SummaryTo develop a new immunotherapy for Japanese cedar (Cryptomeria japonica; CJ) pollinosis, we evaluated the use of DNA immunization by inoculating mice with plasmid DNA encoding Cry j 1 as a CJ pollen major allergen (pCACJ1). Repeated intramuscular (i.m.) inoculation of BALB/c mice with pCACJ1 produced anti‐Cry j 1 antibody responses, which were predominately of the immunoglobulin G2a (IgG2a) type. Furthermore, this inoculation suppressed immunoglobulin E (IgE) and IgG1 antibody responses to subsequent alum‐precipitated Cry j 1 injections. Splenic T cells isolated from mice inoculated with pCACJ1 i.m. secreted interferon‐γ (IFN‐γ), but not interleukin (IL)‐4, in vitro upon stimulation with Cry j 1 as well as with p277–288, a peptide corresponding to the T‐cell epitope of Cry j 1. In contrast, inoculation of BALB/c mice with pCACJ1 by gene gun injection caused response predominantly of the IgG1 type, and enhanced production of anti‐Cry j 1 IgE antibodies to subsequent alum‐precipitated Cry j 1 injections. Splenic T cells isolated from pCACJ1‐innoculated mice by gene gun injection secreted both IFN‐γ and IL‐4 in vitro, upon stimulation with Cry j 1 as well as with p277–288. These findings suggest that i.m. inoculation with pCACJ1 effectively elicits Cry j 1‐specific T helper 1 (Th1)‐type immune responses, resulting in inhibition of the IgE response to Cry j 1.
Constitutive activation of Lck and Fyn tyrosine kinases in large granular lymphocytes infected with the γ‐herpesvirus agents of malignant catarrhal fever
Authors: Swa S. , Wright H. , Thomson J. , Reid H. , Haig D. 
Published: March 2003

SummaryLarge granular lymphocytes (LGL) with a T or natural killer (NK) lymphoblast morphology and indiscriminate (non‐major histocompatibility complex‐linked) cytotoxicity for a variety of target cells can be derived in culture from the tissues of animals infected with either alcelaphine herpesvirus‐1 (AlHV‐1) or ovine herpesvirus‐2 (OvHV‐2). In this study, LGL survival in the absence of exogenous interleukin‐2 was inhibited by the protein kinase inhibitor genestein, but not the p70 s6 kinase inhibitor rapamycin. Constitutive activation of the src kinases Lck and Fyn was demonstrated in a bovine LGL line infected with OvHV‐2 and in two rabbit LGL lines infected with AlHV‐1. The p44 erk1 and p42 erk2 mitogen‐activated protein kinases (MAPK) were also constitutively activated in the LGLs but not control T cells. Lck and Fyn kinase activity in the LGLs did not increase after mitogen (concanavalin A or concanavalin A plus phorbol ester) stimulation of the cells, in contrast to control T cells. Control T cells, but not the LGLs, proliferated after mitogen stimulation. An analysis of tyrosine phosphorylated proteins in the cells indicated that the LGLs exhibited some similarities and differences to activated control T cells. The results demonstrate that the activated phenotype of the LGLs, associated with malignant catarrhal fever virus infection and in the absence of exogenous interleukin‐2, involves constitutively activated Lck and Fyn kinases. These are normally crucial for the initial activation of T cells via several cell‐surface receptors (e.g. the T‐cell receptor and CD2). The inability of the LGLs to proliferate in response to mitogen may be due to an inability of Lck and Fyn to become further activated after mitogen stimulation.
Molecular structure of eight human autoreactive monoclonal antibodies
Authors: Aguilera I. , Melero J. , Nuñez‐Roldan A. , Sanchez B. 
Published: March 2003

SummaryThe heavy (H) and light (L) chain V‐region sequences of eight human autoreactive immunoglobulin M (IgM) monoclonal antibodies (mAbs: BY‐4, BY‐7, BY‐12, IRM‐3, IRM‐7, IRM‐8, IRM‐10 and CDC‐1) were determined at the cDNA level. All VH and VL families were identified. Four different VH families were represented, VH3 being the most common as five of the mAbs (BY‐7, BY‐12, IRM‐3, IRM‐8 and CDC‐1) used genetic elements of this family, whereas VH1, VH2 and VH4 were only present in IRM‐7, BY‐4 and IRM‐10, respectively. BY‐4, BY‐7, BY‐12, IRM‐7 and IRM‐10 reacted with a variety of self as well as non‐self antigens, thus exhibiting polyreactive behaviour. Comparison of the gene segments utilized by these mAbs with their germline counterparts revealed that the gene segments were close to germline configuration. The length of H‐CDR3 was found to be relatively long (27–60 nucleotides) among the polyreactive mAbs and the presence of Tyr and Trp residues in this region seems to be of vital importance for polyreactivity. We have analysed the utilization of gene elements and the presence of amino acid residues in regions particularly important for antigen binding, such as CDR. Common molecular features relating to the function of the mAbs are discussed.
Efficacy of cytokine gene transfection may differ for autologous and allogeneic tumour cell vaccines
Authors: Todryk S. M. , Birchall L. J. , Erlich R. , Halanek N. , Orleans‐Lindsay J. K. , Dalgleish A. G. 
Published: March 2003

SummaryWhole tumour cells are a logical basis for generating immunity against the cancers they comprise or represent. A number of human trials have been initiated using cytokine‐transfected whole tumour cells of autologous (patient‐derived) or allogeneic [major histocompatibility complex (MHC)‐disparate] origin as vaccines. Although precedent exists for the efficacy of autologous‐transfected cell vaccines in animal models, little preclinical evidence confirms that these findings will extrapolate to allogeneic‐transfected cell vaccines. In order to address this issue a murine melanoma cell line (K1735) was transfected to secrete interleukin (IL)‐2, IL‐4, IL‐7 or granulocyte–macrophage colony‐stimulating factor (GM‐CSF); cytokines currently in use in trials. The efficacy of these cells as irradiated vaccines was tested head‐to‐head in syngeneic (C3H) mice and in MHC‐disparate (C57BL/6) mice, the former being subsequently challenged with K1735 cells and the latter with naturally cross‐reactive B16‐F10 melanoma cells. Whilst the GM‐CSF‐secreting vaccine was the most effective at generating protection in C3H mice, little enhancement in protection above the wild‐type vaccine was seen with any of the transfections for the allogeneic vaccines, even though the wild‐type vaccine was more effective than the autologous B16‐F10 vaccine. Anti‐tumour cytotoxic T‐lymphocyte (CTL) activity was detected in both models but did not correlate well with protection, whilst in vitro anti‐tumour interferon‐γ (IFN‐γ) secretion tended to be higher following the GM‐CSF‐secreting vaccine. Cytokine transfection of vaccines generally increased anti‐tumour CTL activity and IFN‐γ secretion (T helper type 1 response). Further studies in other model systems are required to confirm this apparent lack of benefit of cytokine transduction over wild‐type allogeneic vaccines, and to determine which in vitro assays will correlate best with protection in vivo.
The developing human immune system: T‐cell receptor repertoire of children and young adults shows a wide discrepancy in the frequency of persistent oligoclonal T‐cell expansions
Authors: Wedderburn L. R. , Patel A. , Varsani H. , Woo P. 
Published: March 2003

SummaryWhile the T‐cell receptor (TCR) repertoire of the newborn is highly diverse, a gradual alteration in diversity of the expressed TCR repertoire, in particular the oligoclonality of CD8+ T cells, occurs with increasing age. The timing of the initiation of this process is unknown. These changes are associated with an accumulation of T‐cell expansions, thought to be in response to chronic antigen stimulation, frequently by persistent viruses such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV). Using reverse transcription–polymerase chain reaction heteroduplex analysis we have characterized the TCR expression of CD4 and CD8 cells from healthy young children and adults in order to delineate the age range at which these oligoclonal populations appear. We demonstrate that considerable oligoclonality can occur, even in healthy young children, and also that these expanded clonotypes persist. These are shown by heteroduplex to be exclusively within the CD28− subpopulation. The presence of such oligoclonal expansions correlates closely with the percentage of CD8+ cells that have the CD28− phenotype. However, we also show that control of chronic infection with EBV or CMV may coexist with a highly diverse, polyclonal TCR repertoire well into adulthood. These studies suggest that many factors affect the overall regulation of clone size in response to chronic antigens during the development of the immune system.
Major histocompatibility complex class II invariant chain expression in non‐antigen‐presenting cells
Authors: Veenstra Hanne , Ferris William F. , Bouic Patrick J. D. 
Published: March 2003

SummaryIn contrast to the generally accepted belief, the major histocompatibility complex (MHC) class II invariant chain (Ii) is commonly expressed intracellularly in cells that do not present exogenous antigens. Such cells include resting peripheral blood T cells and natural killer (NK) cells. In T cells, the Ii is associated with a 77 000 molecular‐weight molecule (p77) that has yet to be identified. This molecule is co‐precipitated with the anti‐Ii monoclonal antibody (mAb) VCD‐1, but not with mAb BU‐45. This suggests that in the p77–Ii complex, the extracellular epitope of Ii recognized by BU‐45 is hidden, whereas the Ii epitope for VCD‐1 remains exposed. In antigen‐presenting cells (APCs), p77 association with the Ii was minimal, if detectable. The p77–Ii association in non‐professional APCs suggests that the Ii may have another, more general, function other than the one accepted in antigen presentation.
Role of chemokines and chemokine receptors in the gastrointestinal tract
Authors: Ajuebor Maureen N. , Swain Mark G. 
Published: March 2003

SummaryThe pathological association between leucocytes and gastrointestinal diseases has long been recognized. Chemokines are a large family of chemotactic cytokines whose fundamental role is the recruitment of leucocytes to tissues. Although chemokines and their receptors are considered to be mediators of inflammation and tissue injury in several inflammatory diseases, their precise role in the pathophysiology of gastrointestinal diseases remains incompletely understood. Nonetheless, by virtue of their expression and localization at sites of gastrointestinal tissue injury and inflammation, a number of investigators have suggested a vital role for chemokines and their receptors in the pathophysiology of gastrointestinal diseases. This short review examines the role of chemokines and their receptors in the gastrointestinal tract with an emphasis on their involvement in the regulation of intestinal and hepatic inflammation.
Interleukin‐7 inhibits pre‐T‐cell differentiation induced by the pre‐T‐cell receptor signal and the effect is mimicked by hGM‐CSF in hGM‐CSF receptor transgenic mice
Authors: Yasuda Yuko , Kaneko Azusa , Nishijima Ichiko , Miyatake Shoichiro , Arai Ken‐ichi 
Published: March 2003

SummaryWe have previously reported that human granulocyte–macrophage colony‐stimulating factor (hGM‐CSF) causes a stage‐specific inhibition of T‐cell receptor (TCR) αβ cell development in the thymus of transgenic mice constitutively expressing the hGM‐CSF receptor. Since it has been reported that the addition of interleukin‐7 (IL‐7) to fetal thymic organ culture (FTOC) has similar effects, we compared the effects of IL‐7 and hGM‐CSF on TCRαβ cell development in hGM‐CSF receptor transgenic mice. We reconstituted fetal lobes with sorted pre‐T, or post pre‐T CD4−CD8− precursor cells. The addition of either IL‐7 or hGM‐CSF to these cultures suppressed further differentiation of pre‐T cells but not post pre‐T cells. At the same time, the cell number was increased, suggesting that pre‐T‐cell proliferation is stimulated by these cytokines. Furthermore, the differentiation of recombination‐activating gene‐1 (RAG‐1)‐deficient pre‐T cells in response to anti‐CD3 antibody stimulation was suppressed by either IL‐7 or hGM‐CSF, suggesting that these cytokines inhibit the pre‐T‐cell receptor (pre‐TCR) signal. This inhibition is unexpected because the pre‐TCR signal and the IL‐7 signal have previously been considered to be co‐operative. Recent analysis of the downstream events of IL‐7 receptor and GM‐CSF receptor revealed that they share common signal transduction molecules. Our results show that IL‐7 is able to promote pre‐T cell proliferation and to suppress differentiation induced by the pre‐TCR signal. GM‐CSF can mimic these biological activities of IL‐7 when the pre‐T cells express GM‐CSF receptors. Our data suggest that both timing and level of activation of the IL‐7 signalling pathway must be precisely regulated to facilitate the differentiation of thymocytes.