bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lupus Glomerulonephritis Revisited 2004: Autoimmunity and End‐Organ Damage
Authors: Bagavant H. , Deshmukh U. S. , Gaskin F. , Fu S. M. 
Published: July 2004

AbstractHistopathology of the kidney and clinical presentation are critical factors in the diagnosis of immune‐mediated glomerulonephritis (GN). The histological manifestations of glomerular injury are shared by multiple underlying mechanisms. Work from our laboratory and from other investigators shows that antinuclear, antihistone or anti‐dsDNA antibodies are neither required nor sufficient for development of lupus GN. In addition, antibody to dsDNA can be generated by mechanisms other than loss of tolerance to chromatin. Genetic analyses demonstrate that although there is some interaction between autoantibody production and renal disease, the phenotypes are regulated by distinct genetic intervals. Furthermore, renal failure is not an essential outcome of the immune‐complex deposition and proliferative lupus GN. These data are also supported by published studies from systemic lupus erythematosus (SLE) patients. The immune regulation of lupus GN is distinct from other organ‐specific diseases and not influenced by CD25+ or NK1.1+ regulatory T cells. Thus, fatal GN may depend upon a kidney‐reactive T‐cell response that, in turn, may be regulated by gender and intrinsic end‐organ factors. The data discussed in this review call for a re‐evaluation of the current paradigms for pathogenesis of SLE. An interactive model separating autoimmunity from end‐organ susceptibility for the pathogenesis of SLE is proposed.
CD28nullCD4+ T Cells – Characterization of an Effector Memory T‐Cell Population in Patients with Rheumatoid Arthritis
Authors: Fasth A. E. R. , Cao D. , Van Vollenhoven R. , Trollmo C. , Malmström V. 
Published: July 2004

Abstract.CD4+ T cells lacking the costimulatory molecule CD28 have been described both in elderly individuals and in chronic inflammatory disorders, one being rheumatoid arthritis (RA). We, in this study, provide a comprehensive characterization of cell surface markers on and function of such CD28nullCD4+ T cells, as well as correlations with clinical parameters. We conclude that of all surface markers associated with these cells, only CD57 and CD11b are expressed on the majority of them. This CD28null population occurred in one‐third of patients with RA and was independent of clinical characteristics. The population was persistent and expanded in peripheral blood, but was excluded from the joint in most patients. Functionally, CD28nullCD4+ T cells were potent effector memory cells with regard to their proliferation and cytokine‐secretion profiles. This capacity correlated with a hitherto unpublished surface phenotype, the cells being uniformly CCR7– and CD43high. Moreover, a new terminally differentiated CD45RA+CCR7– population of CD4+ T cells was identified. We would like to suggest that in the unbalanced immune system of patients with autoimmune disease and chronic infection an expanded CD28nullCD4+ T‐cell population able to secrete high levels of cytokines is likely to contribute to disease manifestations.
Mannan‐Binding Lectin and RSV Lower Respiratory Tract Infection Leading to Hospitalization in Children: A Case–Control Study from Soweto, South Africa
Authors: Kristensen I. A. , Thiel S. , Steffensen R. , Madhi S. , Sorour G. , Olsen J. 
Published: July 2004

AbstractRespiratory syncytial virus (RSV) is the most important microbiological cause of lower respiratory tract infection (LRTI) in infants. Mannan‐binding lectin (MBL) is believed to play a major protective role in the vulnerable period in infancy where the maternal antibodies have been catabolized, and the adaptive immune system has not yet matured. Mutations in the promoter region and in exon 1 of the gene‐encoding MBL result in low serum levels of MBL. MBL deficiency is the most common immunodeficiency on the African Continent with frequencies of the variant alleles up to 0.29. We investigated whether MBL deficiency has an impact on the hospitalization for LRTI caused by RSV in infants from Soweto, South Africa. The cases were ethnic black Africans identified through surveillance for RSV‐LRTI at Chris Hani Baragwanath Hospital, Soweto, and the controls were sampled from four immunization clinics in the area. Fifty‐five cases and 113 age‐ and sex‐matched controls were identified. Seventy‐six per cent were under 6 months of age, and 42% (n = 23) were under 3 months of age. No association was found between low levels of MBL or carriage of variant alleles and LRTI caused by RSV, odds ratio (OR) 1.00 (CI 0.99–1.03) and OR 1.24 (0.73–2.12). We did not find support for the hypothesis that MBL deficiency leads to the hospitalization for LRTI caused by RSV.
Immunoglobulin Heavy‐Chain Receptor Editing is Observed in the NOD/SCID Model of Human B‐Cell Development
Authors: Kolar G. R. , Capra J. D. 
Published: July 2004

AbstractReceptor editing and receptor revision are the two mechanisms of antibody diversity that result in either complete V‐gene replacement or the formation of hybrid V genes. We do not yet understand how this process unfolds, because they are rare and difficult to study in vivo. In this study, we describe a family of VH4‐34:VH4‐61 hybrids isolated from a human B‐cell chimeric non‐obese diabetic/severe combined immunodeficient mouse. The observation of hybrid immunoglobulin sequences in human B cells that developed in this model system makes it useful for the study of this mechanism of diversification and tolerance.
Release of DNA from Dead and Dying Lymphocyte and Monocyte Cell Lines In Vitro
Authors: Choi J.‐J. , Reich C. F. , Pisetsky D. S. 
Published: July 2004

AbstractDNA is a nuclear macromolecule that circulates in the blood where its levels can reflect the activity of inflammatory and malignant diseases. While dead and dying cells have usually been considered the source of blood DNA, the mechanisms for its release during apoptosis and necrosis are not well defined. To elucidate DNA release, an in vitro model system was used, assessing DNA in the media of living, apoptotic or necrotic Jurkat and U937 cells. Apoptosis was induced by etoposide, camptothecin or staurosporine, while necrosis was induced by heating at 56 °C. DNA release was measured by fluorometry with the dye PicoGreen while the extent of death was measured by fluorescence‐activated cell sorter analysis with propidium iodide and annexin. Apoptotic Jurkat cells released significantly more DNA in the media than untreated cells while necrotic cells did not show significant DNA release. U937 cells showed similar findings. Pretreatment of Jurkat cells with z‐VAD‐fmk, a caspase inhibitor, reduced both apoptosis and DNA release. By gel electrophoresis, extracellular DNA from apoptotic cells showed laddering with low molecular weight fragments. These studies suggest that extracellular release of DNA is a consequence of apoptosis and may account for some of the DNA in the blood.
Inhibition of the Proteasome Reduces Transfer‐Induced Diabetes in Nonobese Diabetic Mice
Authors: Petrovic J. , Hall H. , Mehr R. , Glas R. , Höglund P. 
Published: July 2004

AbstractInhibition of the 26S proteasome reduces the severity of several immune‐mediated diseases. Here, we report that the proteasome also regulates transfer‐induced diabetes in nonobese mice. Treatment of recipient mice with the proteasome inhibitor Nα‐benzyloxycarbonyl‐l‐leucyl‐l‐leucyl‐l‐leucinal (MG132) resulted in a 76% reduction in transfer‐induced diabetes. The closely related inhibitor carbobenzoxy‐l‐leucyl‐l‐leucinal that inhibits calpains but not the proteasome had no protective effect, suggesting that MG132 acted via inhibition of the proteasome. MG132 decreased proliferation of transferred T cells in the pancreatic lymph nodes in vivo and prevented their expansion in a dose‐dependent manner in vitro, consistent with a direct effect by MG132 on the T cells. MG132 did not prevent migration of transferred T cells into the islets but reduced the number of mice with severe infiltration. We suggest that MG132 prevents transfer‐induced diabetes by directly targeting the autoreactive T cells and lowering their diabetogenic potential.
Activation of Natural Killer Cells: Underlying Molecular Mechanisms Revealed
Authors: Backström E. , Kristensson K. , Ljunggren H.‐G. 
Published: July 2004

AbstractNatural killer (NK) cells, the third major lymphocyte population, are important effector cells against certain infections and tumours. They have also been implicated as a link between innate and adaptive immune responses. In recent years, much attention has been paid to the NK cell inhibitory receptors and their interaction with major histocompatibility complex class I molecules on target cells. This review summarizes recent findings on regulation of NK cell activity with an emphasis on NK cell stimulatory receptors. A particular emphasis is devoted to the receptor NKG2D that is expressed on all NK cells.
Antinucleosome Autoantibodies Bind Directly to Cell Lines In Vitro and via the FcγRIIB Receptor to B Lymphocytes In Vivo: A Role for Immune Complexes in Interactions between Antinucleosome IgG2a and B cells of BXSB Lupus Mice
Authors: Li X. , Egorina E. , Bertelsen E. L. , Dahlen H. , Hannestad K. 
Published: July 2004

AbstractThe initial novel observation of this study was that most B cells of male BXSB lupus mice bear surface IgG2ab of extrinsic origin. To define the surface antigen, we here examine three (NZBxBXSB)F1‐derived IgG2ab monoclonal antibodies (mAbs) selected for binding to cell surfaces. Surprisingly, all three mAbs bound the nucleosome (nuc) particle, the fundamental unit of chromatin and an early target of autoimmunity in systemic lupus erythematosus. Their tentative dissociation constant (Kd) for soluble nuc particles was approximately 7 × 10−10 m. The mAbs bound more weakly to both H2A–H2B‐DNA and H3–H4‐DNA complexes, and in immunoblot they stained all four core histones. The mAbs detected a surface antigen on all cell lines examined, present on viable cells. When stripped of nuc , and in the presence of DNase I, their binding to cell lines improved. Heparin displaced the antigen from the cell surface. In vivo, the three mAbs stained B cells of several BALB/c mice clearly stronger than the isotype control; this differential staining was significantly reduced in FcγRIIB‐deficient mice. The results indicate that the three mAbs recognize (a) planted antigen on viable cultured cells and (b) soluble autoantigen in vivo, leading to immune complexes that bind to FcγRIIB. Further experiments demonstrated that antinuc IgG2a could be eluted from splenocytes of a male BXSB lupus mouse. Hence, at least part of the extrinsic IgG2ab found on BXSB B cells may represent FcγRIIB‐bound nuc‐IgG2ab complexes.
Avian Helios and Evolution of the Ikaros Family
Authors: Kohonen P. , Nera K.‐P. , Lassila O. 
Published: July 2004

AbstractHelios (Znfn1a2) is an Ikaros‐related lymphoid regulatory protein with possible involvement in T‐cell development and function as well as in the early events of haematopoietic stem cell differentiation. To evaluate the role of Helios in avian haemato/lymphopoiesis, we have characterized the avian Helios gene. In contrast to studies in mouse and human, we have found that the highly conserved avian Helios encodes a novel exon and three isoforms. Furthermore, the avian Helios expression precedes Ikaros in the ontogeny, being present already on the first day of embryonic development. Additionally, expression in the bursa of Fabricius, germinal centres and B‐cell lines suggests a role for Helios also in the B‐cell lineage. Phylogenetic studies of the Ikaros family along with data on paralogous chromosome segments in the human genome connect the expansion of the Ikaros family and thus possibly the emergence of the adaptive immune system with the putative second round of genome duplications and indicate that the Ikaros gene family is linked with the Hox gene clusters.
Linear nevus comedonicus with epidermolytic hyperkeratosis
Authors: Schecter Amy K. , Lester Brian , Pan Teddy D. , Robinson‐Bostom Leslie 
Published: July 2004

Background:  Nevus comedonicus (NC) is rarely associated with the histopathologic pattern of follicular epidermolytic hyperkeratosis (EHK). We found eight cases reported. In one case, the condition was transmitted to the offspring in the form of generalized EHK.Methods:  We describe a case of linear NC with EHK in a 46‐year‐old woman.Results:  Histopathologic examination revealed the typical features of NC. Additionally, the follicular epithelial walls showed EHK with characteristic perinuclear vacuolization in the stratum spinosum and stratum granulosum and large, irregular keratohyalin granules in the granular cell layer.Conclusions:  The clinical and histopathologic features of this case are consistent with a diagnosis of linear NC with EHK. Lesions of NC suspected by clinical exam should be examined microscopically to look for features of EHK. If present, patients should be educated about the risk, albeit rare, of passing on a more severe form of the disorder to subsequent generations.
Matrilysin‐1 (MMP‐7) and MMP‐19 are expressed by Paget's cells in extramammary Paget's disease
Authors: Kuivanen Tiina , Tanskanen Maarit , Jahkola Tiina , Impola Ulla , Asko‐Seljavaara Sirpa , Saarialho‐Kere Ulpu 
Published: July 2004

Background:  Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer.Methods:  The expression of MMP‐1, MMP‐2, MMP‐3, MMP‐7, MMP‐9, MMP‐13, and MMP‐19 was analyzed by immuno‐ histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin‐5 (LN‐5) and tenascin‐C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry.Results:  MMP‐7 (matrilysin‐1) and MMP‐19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP‐2, MMP‐9, or MMP‐13, which is seen in many cancers, was not evident in EMPD. LN‐5 and tenascin‐C positivity did not correlate with the level of invasion. MMP‐7, MMP‐13, and MMP‐19 were detected abundantly in MMPD, while MMP‐9 was absent.Conclusions:  MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP‐7 and four samples positive for MMP‐19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin.
The geometric mean length, a new statistic to describe the distribution of character steps on a tree
Authors: Grandcolas Philippe , Robillard Tony , D'Haese Cyrille , Desutter‐Grandcolas Laure , Guilbert Eric , Murienne Jérôme 
Published: July 2004

AbstractThe geometric mean length (GML) is proposed as a new statistic aimed at describing the evenness of character changes on a tree for a given set of character optimizations. It is the geometric mean of the number of steps on each branch of the tree, varying between a maximum value when all branch lengths are equal, and a minimum value when all branches but one have only one character step. It can be scaled according to its theoretical maximum value, thus indicating a relative GML that allows a comparison of the evenness of character steps between different tree topologies.
Phylogenetic relationships of the genera of Theaceae based on morphology
Authors: Luna Isolda , Ochoterena Helga 
Published: July 2004

AbstractThis work represents the first phylogenetic analysis of all genera belonging to the plant family Theaceae (sensu lato). The study is based on 60 morphological characters derived from herbarium specimens and an extensive literature review of 37 genera (including the outgroup). In contrast to the results from molecular data, Theaceae is here found to consist of one clade in which the recognition of two families or subfamilies would leave Theaceae s.s. paraphyletic. Within that clade, Ternstroemiaceae is supported as monophyletic and includesAdinandra,Anneslea,Archboldiodendron,Balthasaria,Cleyera,Eurya,Euryodendron,Ficalhoa,Freziera,Symplococarpon,TernstroemiaandVisnea. The paraphyletic Theaceae s.s. includesApterosperma, Camellia, Dankia,Gordonia,Pyrenaria,Schima, andStewartia. Tetrameristaceae (PentameristaandTetramerista) are supported as a monophyletic family, with Pellicieraceae (Pelliciera) as sister group, and that clade is sister to the rest of the taxa. Bonnetiaceae (ArchytaeaandBonnetia) and Kielmeyeroideae of the Clusiaceae (Caraipa,Haploclathra,Kielmeyera,Mahurea,Marila, andNeotatea) are also supported as monophyletic. Given the differences between the results obtained from morphological and molecular data, we consider that there is still a need for further research, including combined analyses.
Phylogeny and the modalities of acoustic diversification in extant Eneopterinae (Insecta, Orthoptera, Grylloidea, Eneopteridae)
Authors: Robillard Tony , Desutter‐Grandcolas Laure 
Published: July 2004

AbstractCalling with a tegminal stridulatory apparatus is widespread in crickets. However, the evolution of cricket stridulums has been poorly studied and then only on the basis of prephylogenetic models, which are unable to account for the huge diversity recently documented for acoustic features in crickets. The present paper focuses on the evolution of acoustic devices in the subfamily Eneopterinae. This is the first attempt to reconstruct the phylogeny of a large and diverse cricket clade in order to analyze the evolution of emitting structures using precise homology statements. In the first step, we reconstruct the phylogeny of this clade using a morphological data set of 193 characters and 45 taxa. The resultant phylogeny supports the monophyly of the subfamily and that of the 13 genera represented by at least two species in our taxonomic sample. Phylogenetic relationships within the subfamily also support the definition of five tribes: Eurepini, Eneopterini, Nisitrini, Xenogryllini and Lebinthini. In the second step, the evolution of acoustic devices is studied by optimization of venation characters defined on precise homology statements. As hypothesized by previous authors, losses of acoustic communication occur independently in the course of eneopterine evolution; however, they happen abruptly with no intermediate state. Our results also document for the first time the modalities of forewing evolution: the diversification of male forewing venation originates from two processes, a continuous and regular modification process, responsible for slight venation change; and an irregular, more intense punctuated process, allowing the emergence of different venations. This diversification process with sudden changes could be related to the occurrence of acoustic novelties in advertisement calls.
Risks of interleukin‐1 genetic polymorphisms and Helicobacter pylori infection in the development of gastric cancer
Authors: Chen A. , Li C.‐N. , Hsu P.‐I. , Lai K.‐H. , Tseng H.‐H. , Hsu P.‐N. , Lo G.‐H. , Lo C.‐C. , Lin C.‐K. , Hwang I.‐R. , Yamaoka Y. , Chen H.‐C. 
Published: July 2004

SummaryBackground : The host genetic factors that determine the clinical outcomes of Helicobacter pylori‐infected individuals remain unclear.Aim : To elucidate the risks of host interleukin‐1 (IL‐1) genetic polymorphisms and H. pylori infection in the development of gastric cancer.Methods : In a case–control study of 164 controls and 142 patients with gastric cancer, the IL‐1B‐511 biallelic polymorphisms and the IL‐1RN penta‐allelic variable number of tandem repeats were genotyped.Results : The carriage of IL‐1RN*2, male gender, old age and H. pylori infection independently increased the risk of gastric cancer, with odds ratios of 3.3 [95% confidence interval (CI), 1.4–7.7], 2.1 (95% CI, 1.2–3.8), 5.3 (95% CI, 3.1–9.0) and 2.2 (95% CI, 1.3–3.8), respectively. H. pylori‐infected individuals who were carriers of IL‐1RN*2 showed increased risks of both intestinal and diffuse types of gastric cancer, with odds ratios of 11.0 and 8.7, respectively. In addition, these individuals also had a higher score of intestinal metaplasia in the corpus than did uninfected non‐carriers.Conclusions : This study is the first to verify IL‐1RN*2 as an independent factor governing the development of gastric cancer in Asian individuals. A combination of H. pylori testing and host genotyping may target the eradication of H. pylori to high‐risk individuals.
Hepatitis C virus‐related extra‐hepatic disease — aetiopathogenesis and management
Authors: Medina J. , García‐Buey L. , Moreno‐Otero R. 
Published: July 2004

SummaryHepatitis C virus infection is often associated with extra‐hepatic manifestations, secondary to the elicitation of autoimmune reactions, generalized deposition of immune complexes and lymphoproliferative disorders. The most clearly established associations are those linking chronic hepatitis C with mixed cryoglobulinaemia (and the related glomerulonephritis and cutaneous vasculitis), as well as with the presence of autoantibodies. Less well‐documented disorders include non‐Hodgkin's lymphoma, thrombocytopenia, sialadenitis, thyroid disease, lichen planus, porphyria cutanea tarda, rheumatoid disorders and neurological disorders. Extra‐hepatic manifestations are most frequent in patients of female sex, advanced age, long‐lasting infection and cirrhosis. Optimal treatment strategies should be based on the predominant manifestation of the disease. In the case of autoimmune disorders not clearly attributable to the viral infection, corticosteroids may be the most effective option. Interferon‐α alone or in combination with ribavirin may be indicated for those disorders related to immune complex deposition, such as mixed cryoglobulinaemia, although relapses of extra‐hepatic signs often occur on discontinuation of treatment. In some cases, interferon‐α may induce or exacerbate some extra‐hepatic manifestations.