bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection, epitope‐mapping and function of anti‐Fas autoantibody in patients with silicosis
Authors: Takata‐Tomokuni Akiko , Ueki Ayako , Shiwa Mieko , Isozaki Yumika , Hatayama Tamayo , Katsuyama Hironobu , Hyodoh Fuminori , Fujimoto Wataru , Ueki Hiroaki , Kusaka Masayasu , Arikuni Hisashi , Otsuki Takemi 
Published: August 2005

SummaryDysregulation of apoptosis through the Fas–Fas ligand pathway is associated with the onset of autoimmune disease. Since autoantibodies directed against unknown antigens are present in the sera of these patients, sera samples were examined for the presence of autoantibodies directed against the Fas molecule. Using Western blotting and a ProteinChip analysis, autoantibodies against Fas were detected in patients with silicosis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and weakly detected in healthy individuals. Using epitope mapping employing 12‐amino‐acid polypeptides with the SPOTs system, a minimum of four epitopes and a maximum of 10 epitopes were found. Several amino acid residues involved in binding FasL, such as C66, R87, L90, E93 and H126, were presented within the epitopes. Serum containing a large amount of anti‐Fas autoantibody from silicosis patients inhibited the growth of a Fas‐expressing human cell line, but did not inhibit the growth of a low Fas‐expresser nor a Fas‐expresser in which the Fas gene had been silenced by small interference RNA. All epitopes in the intracellular region of Fas were located in the death domain. The possible roles of anti‐Fas autoantibody detected in healthy volunteers and patients with silicosis or autoimmune diseases are discussed here.
Phenotypical and functional alterations during the expansion phase of invariant Vα14 natural killer T (Vα14i NKT) cells in mice primed with α‐galactosylceramide
Authors: Ikarashi Yoshinori , Iizuka Akira , Koshidaka Yumie , Heike Yuji , Takaue Yoichi , Yoshida Mitsuzi , Kronenberg Mitchell , Wakasugi Hiro 
Published: August 2005

SummaryInvariant Vα14 natural killer T (Vα14i NKT) cells are a unique immunoregulatory T‐cell population that is restricted by CD1d. The glycolipid α‐galactosylceramide (α‐GalCer) is presented by CD1d and causes robust Vα14i NKT‐cell activation. Three days after injection of α‐GalCer, Vα14i NKT cells vigorously increase in number and then gradually decrease to normal levels. In the present study, we found that the re‐administration of α‐GalCer into mice primed 3 days earlier causes a marked increase in serum interleukin‐4 and interferon‐γ. Intracellular staining revealed that the only expanded Vα14i NKT cells are responsible for the enhanced cytokine production. The enhanced cytokine production was correlated with an increased number of Vα14i NKT cells after priming. Additionally, primed Vα14i NKT cells produced larger amounts of cytokine as compared with naive Vα14i NKT cells when cultured with α‐GalCer‐pulsed dendritic cells. Thus, we considered that a subset of expanded Vα14i NKT cells acquired a strong ability to produce cytokines. In contrast to mice primed 3 days earlier, cytokine production is markedly diminished in mice primed 7 days earlier. The expanded Vα14i NKT cells altered the surface phenotype (NK1.1– CD69–) and contained intracellular interferon‐γ. Additionally, we found that primed Vα14i NKT cells did not disappear or down‐regulate surface TCR expression when re‐injected with α‐GalCer as compared with naive Vα14i NKT cells. These results demonstrate that the function and surface phenotype of Vα14i NKT cells is dramatically altered after α‐GalCer priming.
Characterization of the B‐cell immune response elicited in BALB/c mice challenged with Neospora caninum tachyzoites
Authors: Teixeira Luzia , Marques Andreia , Meireles Carla Sofia , Seabra Ana Rita , Rodrigues Diana , Madureira Pedro , Faustino Augusto M. R. , Silva Carolina , Ribeiro Adília , Ferreira Paula , Correia da Costa José Manuel , Canada Nuno , Vilanova Manuel 
Published: August 2005

SummaryActivation of B cells occurring in hosts infected with protozoan parasites has been implicated either in protective or parasite‐evasion immune‐mediated mechanisms. Intraperitoneal inoculation of Neospora caninum tachyzoites into BALB/c mice induces an acute response characterized by a rapid increase in the numbers of CD69‐expressing peritoneal and splenic B cells. This early B‐cell stimulatory effect preceded an increase in the numbers of total and immunoglobulin‐secreting splenic B cells and a rise in serum levels of N. caninum‐specific immunoglobulins, predominantly of the immunoglobulin G2a (IgG2a) and IgM isotypes. Increased numbers of B cells expressing the costimulatory molecules CD80 and CD86 were also observed in the N. caninum‐infected mice. The B‐cell stimulatory effect observed in mice challenged with N. caninum tachyzoites was reduced in mice challenged with γ‐irradiated parasites. Contrasting with the peripheral B‐cell expansion, a depletion of B‐lineage cells was observed in the bone‐marrow of the N. caninum‐infected mice. Intradermal immunization of BALB/c mice with diverse N. caninum antigenic preparations although inducing the production of parasite‐specific antibodies nevertheless impaired interferon‐γ (IFN‐γ) mRNA expression and caused lethal susceptibility to infection in mice inoculated with a non‐lethal parasitic inoculum. This increased susceptibility to N. caninum was not observed in naïve mice passively transferred with anti‐N. caninum antibodies. Taken together, these results show that N. caninum induces in BALB/c mice a parasite‐specific, non‐polyclonal, B‐cell response, reinforce previous observations made by others showing that immunization with N. caninum whole structural antigens increases susceptibility to murine neosporosis and further stress the role of IFN‐γ in the host protective immune mechanisms against this parasite.
Identification of specific autoantigens in Sjögren's syndrome by SEREX
Authors: Uchida Kazuo , Akita Yoichi , Matsuo Keitaro , Fujiwara Shigeyoshi , Nakagawa Atsuko , Kazaoka Yoshiaki , Hachiya Hiroshi , Naganawa Yoshiyuki , Oh‐iwa Ichiro , Ohura Kiyoshi , Saga Shinsuke , Kawai Tatsushi , Matsumoto Yoshinari , Shimozato Kazuo , Kozaki Ken‐ichi 
Published: August 2005

SummaryWe carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch‐like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti‐IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS‐B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno‐privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ‐specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti‐SS‐B/La autoantibodies.
Mechanism of up‐regulation of immunoglobulin A production in the intestine of mice unresponsive to lipopolysaccharide
Authors: Kaneko Masahiro , Akiyama Yoshiyuki , Takimoto Hiroaki , Kumazawa Yoshio 
Published: August 2005

SummaryThe mechanisms by which immunoglobulin A (IgA) production up‐regulates in the intestine of Toll‐like receptor‐4 (TLR4)‐mutated mice were investigated. When TLR4‐mutated, C3H/HeJ and BALB/lpsd mice received oral administration of cholera toxin (CT), not only CT‐specific IgA levels in the intestinal lavage but also the number of IgA‐producing cells in intestinal lamina propria (iLP) significantly increased compared with those of the wild‐type C3H/He and BALB/c mice. Interleukin (IL)‐5‐producing cells and CD86+ cells in iLP also significantly increased in C3H/HeJ mice. The expression of major histocompatibility complex class II and CD86 on cells present in Peyer's patches (PPs) of C3H/HeJ mice was higher than those of C3H/He mice. In non‐immunized C3H/HeJ mice, the expression of transforming growth factor‐β (TGF‐β) mRNA and the percentages of IL‐10‐producing cells in PPs but not in spleen increased when compared with those in C3H/He mice. The suppressor of cytokine signalling‐1 (SOCS‐1) was expressed in PPs of C3H/He mice but not C3H/HeJ mice. These results indicate that high IgA levels in the intestine of TLR4‐mutated mice are due to up‐regulation of TGF‐β and IL‐10 and the lack of regulation by SOCS‐1.
Formononetin, a phyto‐oestrogen, and its metabolites up‐regulate interleukin‐4 production in activated T cells via increased AP‐1 DNA binding activity
Authors: Park Jin , Kim Seung H. , Cho Daeho , Kim Tae S. 
Published: August 2005

SummaryPhyto‐oestrogens are polyphenolic non‐steroidal plant compounds with oestrogen‐like biological activity. Phyto‐oestrogens have many biological effects including oestrogen agonist/antagonist properties. However, the effect of phyto‐oestrogens on allergic responses remains unclear. In this study we investigated whether formononetin, a phyto‐oestrogen, and its metabolites, daidzein and equol, affect production of interleukin‐4 (IL‐4), a pro‐inflammatory cytokine closely associated with allergic immune response, in primary CD4+ T cells and EL4 T lymphoma cells. Formononetin, daidzein and equol significantly enhanced IL‐4 production from both CD4+ T cells and EL4 cells in a dose‐dependent manner. Formononetin, daidzein and equol also enhanced IL‐4 gene promoter activity in EL4 cells transiently transfected with IL‐4 gene promoter constructs, but this effect was impaired in EL4 cells transfected with an IL‐4 promoter construct deleted of P4 site carrying nuclear factor of activated T cells (NF‐AT) and activator protein‐1 (AP‐1) binding sites. In addition, formononetin, daidzein and equol increased AP‐1 DNA binding activities while did not affect NF‐AT DNA binding activities. The enhancing effects on IL‐4 production and AP‐1 DNA binding activities were abrogated by specific inhibitors for phosphatidylinositol‐3‐kinase (PI3K), protein kinase C (PKC) and p38 mitogen‐activated protein kinase (MAPK), indicating that formononetin, daidzein and equol might enhance IL‐4 production by increased activation of AP‐1 through the PI3‐K/PKC/p38 MAPK signalling pathway. These results suggest that phyto‐oestrogens and some of their metabolites may increase allergic responses via the enhancement of IL‐4 production in T cells.
Regulatory activity of human CD4+ CD25+ T cells depends on allergen concentration, type of allergen and atopy status of the donor
Authors: Bellinghausen Iris , König Bettina , Böttcher Ingo , Knop Jürgen , Saloga Joachim 
Published: August 2005

SummaryRegulatory CD4+ CD25+ FoxP3‐positive T cells (Treg) are functional in most atopic patients with allergic rhinitis and are able to inhibit T helper type 1 (Th1) and Th2 cytokine production of CD4+ CD25– T cells. This study was designed to analyse the following additional aspects: influence of allergen concentration, influence of the type of allergen, and influence of the atopy status of the donor on the strength of the regulatory activity. CD4+ CD25– T cells from healthy non‐atopic controls or from grass‐pollen‐allergic or wasp‐venom‐allergic donors were stimulated alone or in the presence of Treg with autologous mature monocyte‐derived dendritic cells which were pulsed with different concentrations of the respective allergens. Treg from grass‐pollen‐allergic donors failed to inhibit proliferation but not cytokine production of CD4+ CD25– T cells at high antigen doses while Treg from non‐atopic donors did not fail at these allergen concentrations. Proliferative responses and cytokine production of CD4+ CD25– T cells from most of the examined wasp‐venom‐allergic patients were not inhibited at any concentration of wasp venom. The use of wasp venom‐ or phospholipase A2‐pulsed dendritic cells for stimulation of CD4+ CD25– T cells from donors who were not allergic to wasp stings only resulted in an inhibited proliferation and Th2 cytokine production by Treg at 10‐fold lower than the optimal concentration, while interferon‐γ production was inhibited at all concentrations investigated. These data demonstrate that in allergic diseases the function of Treg is dependent on the concentration and the type of the respective allergen with different thresholds for individual allergens and patients.
Dysregulated luminal bacterial antigen‐specific T‐cell responses and antigen‐presenting cell function in HLA‐B27 transgenic rats with chronic colitis
Authors: Qian Bi‐Feng , Tonkonogy Susan L. , Hoentjen Frank , Dieleman Levinus A. , Sartor R. Balfour 
Published: August 2005

SummaryHLA‐B27/β2 microglobulin transgenic (TG) rats spontaneously develop T‐cell‐mediated colitis when colonized with normal commensal bacteria, but remain disease‐free under germ‐free conditions. We investigated regulation of in vitro T‐cell responses to enteric bacterial components. Bacterial lysates prepared from the caecal contents of specific pathogen‐free (SPF) rats stimulated interferon‐γ (IFN‐γ) production by TG but not non‐TG mesenteric lymph node (MLN) cells. In contrast, essentially equivalent amounts of interleukin‐10 (IL‐10) were produced by TG and non‐TG cells. However, when cells from MLNs of non‐TG rats were cocultured with TG MLN cells, no suppression of IFN‐γ production was noted. Both non‐TG and TG antigen‐presenting cells (APC) pulsed with caecal bacterial lysate were able to induce IFN‐γ production by TG CD4+ cells, although non‐TG APC were more efficient than TG APC. Interestingly, the addition of exogenous IL‐10 inhibited non‐TG APC but not TG APC stimulation of IFN‐γ production by cocultured TG CD4+ lymphocytes. Conversely, in the presence of exogenous IFN‐γ, production of IL‐10 was significantly lower in the supernatants of TG compared to non‐TG APC cultures. We conclude that commensal luminal bacterial components induce exaggerated in vitro IFN‐γ responses in HLA‐B27 TG T cells, which may in turn inhibit the production of regulatory molecules, such as IL‐10. Alterations in the production of IFN‐γ, and in responses to this cytokine, as well as possible resistance of TG cells to suppressive regulation could together contribute to the development of chronic colitis in TG rats.
Extending the evaluation of a computer system used as a microswitch for word utterances of persons with multiple disabilities
Authors: Lancioni G. E. , O'Reilly M. F. , Singh N. N. , Sigafoos J. , Oliva D. , Montironi G. , Savino M. , Bosco A. 
Published: August 2005

AbstractBackground  Microswitches can be vital tools to help individuals with extensive multiple disabilities acquire control of environmental stimulation. This study was aimed at extending the evaluation of a computer system used as a microswitch for word utterances with three participants with multiple disabilities.Method  Sets of 7 or 12 word utterances were used for the participants. The utterances were divided into three groups, which were exposed to intervention successively. During the intervention and a 2‐month post‐intervention check, the participants’ emission of the target utterances led the system to present favourite, matching stimuli (i.e. provided that it recognized the utterances).Results  Intervention data showed that (1) the participants increased the frequencies of the target utterances and (2) the computer system recognized approximately 80% of those utterances. These findings were maintained at the post‐intervention check. An analysis of the levels of occurrence of individual utterances showed statistically significant differences among them, in line with the notions of preference and choice.Conclusions  The computer system was useful as a microswitch to enable access to favourite stimuli. There is a need to improve the accuracy of the system with respect to its recognition of the participants’ utterances.
Adaptive functioning and behaviour problems in relation to level of education in children and adolescents with intellectual disability
Authors: De Bildt A. , Sytema S. , Kraijer D. , Sparrow S. , Minderaa R. 
Published: August 2005

AbstractBackground  The interrelationship between adaptive functioning, behaviour problems and level of special education was studied in 186 children with IQs ranging from 61 to 70. The objective was to increase the insight into the contribution of adaptive functioning and general and autistic behaviour problems to the level of education in children with intellectual disability (ID).Methods  Children from two levels of special education in the Netherlands were compared with respect to adaptive functioning [Vineland Adaptive Behavior Scales (VABS)], general behaviour problems [Child Behavior Checklist (CBCL)] and autistic behaviour problems [Autism Behavior Checklist (ABC)]. The effect of behaviour problems on adaptive functioning, and the causal relationships between behaviour problems, adaptive functioning and level of education were investigated.Results  Children in schools for mild learning problems had higher VABS scores, and lower CBCL and ABC scores. The ABC had a significant effect on the total age equivalent of the VABS in schools for severe learning problems, the CBCL in schools for mild learning problems. A direct effect of the ABC and CBCL total scores on the VABS age equivalent was found, together with a direct effect of the VABS age equivalent on level of education and therefore an indirect effect of ABC and CBCL on level of education.Conclusions  In the children with the highest level of mild ID, adaptive functioning seems to be the most important factor that directly influences the level of education that a child attends. Autistic and general behaviour problems directly influence the level of adaptive functioning. Especially, autistic problems seem to have such a restrictive effect on the level of adaptive functioning that children do not reach the level of education that would be expected based on IQ. Clinical implications are discussed.
Blink rate in boys with fragile X syndrome: preliminary evidence for altered dopamine function
Authors: Roberts J. E. , Symons F. J. , Johnson A.‐M. , Hatton D. D. , Boccia M. L. 
Published: August 2005

AbstractBackground  Dopamine, a neurotransmitter involved in motor and cognitive functioning, can be non‐invasively measured via observation of spontaneous blink rates. Blink rates have been studied in a number of clinical conditions including schizophrenia, autism, Parkinsons, and attention deficit/hyperactivity disorder with results implicating either hyper or hypo dopaminergic states.Methods  This study examined spontaneous blink rate in boys with fragile X syndrome (FXS). Blink rates of boys (4–8 years old) with FXS (n = 6) were compared with those of age‐matched typically developing boys (n = 6) during active and passive tasks. Blink rates (blinks per minute) for each task were compared between the two groups. Then, the relation between blink measures and core FXS‐related features [problem behaviours, arousal, fmr 1 protein (FMRP)] were examined within the group of boys with FXS.Results  Blink rate in boys with FXS was significantly higher than typically developing boys during passive tasks. Within the FXS group, there were significant correlations between blink rate and problem behaviours and physiological arousal (i.e. heart activity) but not with FMRP.Conclusions  Observed differences in spontaneous blink rate between boys with and without FXS and the relation between blink rate and physiological and behavioural measures in boys with FXS suggests that further work examining dopamine dysfunction as  a factor in the pathophysiology of FXS may be warranted.
Detecting past population bottlenecks using temporal genetic data
Authors: RAMAKRISHNAN UMA , HADLY ELIZABETH A. , MOUNTAIN JOANNA L. 
Published: August 2005

AbstractPopulation bottlenecks wield a powerful influence on the evolution of species and populations by reducing the repertoire of responses available for stochastic environmental events. Although modern contractions of wild populations due to human‐related impacts have been documented globally, discerning historic bottlenecks for all but the most recent and severe events remains a serious challenge. Genetic samples dating to different points in time may provide a solution in some cases. We conducted serial coalescent simulations to assess the extent to which temporal genetic data are informative regarding population bottlenecks. These simulations demonstrated that the power to reject a constant population size hypothesis using both ancient and modern genetic data is almost always higher than that based solely on modern data. The difference in power between the modern and temporal DNA approaches depends significantly on effective population size and bottleneck intensity and less significantly on sample size. The temporal approach provides more power in cases of genetic recovery (via migration) from a bottleneck than in cases of demographic recovery (via population growth). Choice of genetic region is critical, as mutation rate heavily influences the extent to which temporal sampling yields novel information regarding the demographic history of populations.
The inadvertent introduction into Australia of Trypanosoma nabiasi, the trypanosome of the European rabbit (Oryctolagus cuniculus), and its potential for biocontrol
Authors: HAMILTON P. B. , STEVENS J. R. , HOLZ P. , BOAG B. , COOKE B. , GIBSON W. C. 
Published: August 2005

AbstractWild rabbits (Oryctolagus cuniculus) in Australia are the descendents of 24 animals from England released in 1859. We surveyed rabbits and rabbit fleas (Spilopsyllus cuniculi) in Australia for the presence of trypanosomes using parasitological and PCR‐based methods. Trypanosomes were detected in blood from the European rabbits by microscopy, and PCR using trypanosome‐specific small subunit ribosomal RNA (SSU rRNA) gene primers and those in rabbit fleas by PCR. This is the first record of trypanosomes from rabbits in Australia. We identified these Australian rabbit trypanosomes as Trypanosoma nabiasi, the trypanosome of the European rabbit, by comparison of morphology and SSU rRNA gene sequences of Australian and European rabbit trypanosomes. Phylogenetic analysis places T. nabiasi in a clade with rodent trypanosomes in the subgenus Herpetosoma and their common link appears to be transmission by fleas. Despite the strict host specificity of trypanosomes in this clade, phylogenies presented here suggest that they have not strictly cospeciated with their vertebrate hosts. We suggest that T. nabiasi was inadvertently introduced into Australia in the 1960s in its flea vector Spilopsyllus cuniculi, which was deliberately introduced as a potential vector of the myxoma virus. In view of the environmental and economic damage caused by rabbits in Australia and other islands, the development of a virulent or genetically modified T. nabiasi should be considered to control rabbits.