bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies to double-stranded (ds)DNA immunoprecipitate 18S ribosomal RNA by virtue of their interaction with ribosomal protein S1 and suppress in vitro protein synthesis
Authors: Tsuzaka K , Winkler T H , Kalden J R , Reichlin M 
Published: November 2003

Abstract
We report that four systemic lupus erythematosus (SLE) patient sera containing anti-dsDNA antibodies, three affinity-purified anti-dsDNA IgG, and a human anti-dsDNA MoAb (33.H11) immunoprecipitate 18S ribosomal RNA from DNase-treated 32P-labelled MOLT4 cell extract. This 18S RNA precipitation was inhibited completely by preincubating 33.H11 with calf thymus dsDNA or the recombinant human ribosomal protein S1, which was reported to cross-react with anti-dsDNA antibodies (J Immunol 1996; 156:1668–75). Whole IgG from three SLE sera with anti-dsDNA antibodies, 33.H11, and three affinity-purified anti-dsDNA IgG inhibited in vitro translation of globin mRNA (percent inhibition was 36–50%). This translation inhibition by anti-dsDNA antibodies was enhanced (67–79%) when the reticulocyte lysate was treated with DNase. Suppression of protein synthesis could be a pathogenic mechanism of anti-dsDNA antibodies, since it has also been shown that anti-dsDNA penetrates living cells (J Immunol 1995; 154:4857–64) in culture.
Respiratory syncytial virus-induced cytokine production by neonatal macrophages
Authors: Tsutsumi H , Matsuda K , Sone S , Takeuchi R , Chiba S 
Published: November 2003

Abstract
The induction of immunoregulatory cytokines IL-1β, IL-6, IL-12, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) was studied with neonatal (cord blood) monocyte-derived macrophages (MDM) after in vitro infection with respiratory syncytial virus (RSV). The expression of mRNAs for these cytokines in RSV-infected MDM was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The activities of these cytokines were assayed by ELISA. Significant increase of expression of mRNA for IL-6, IL-12, TNF-α and IFN-γ occurred within 2 h after infection and decreased within 6 h after infection. At 20 h after infection the MDM produced and secreted moderate levels of IL-6 and TNF-α; however, no IL-12 and IFN-γ activities were detected. Moderate IL-1β mRNA was expressed before RSV infection, and its expression increased at 2 h after infection. However, no detectable IL-1β was secreted in culture fluids. These observations suggest that RSV-infected neonatal macrophages produce and secrete IL-6 and TNF-α quickly during the eclipse phase of RSV infection and therefore may play a prominent role in the initiation of the immune response to RSV.
Expression of leucocyte–endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-α)
Authors: Vanhée D , Molet S , Gosset P , Tillie-Leblond I , Boitelle A , Wallaert B , Tonnel A-B 
Published: November 2003

Abstract
Coal workers' pneumoconiosis (CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in alveolar spaces. In this study, we investigated in CWP the implication of adhesion molecules such as E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) and the role of TNF-α which is one of the cytokines inducing their expression. Adhesion molecule expression was analysed by immunohistochemistry on lung biopsies from patients with CWP and from healthy subjects. In parallel, soluble adhesion molecules were detected in bronchoalveolar lavage fluids (BALF) from patients by specific ELISA. The involvement of TNF in the induction of these adhesion molecules was measured (i) by immunohistochemistry on sections from lung fragments, and (ii) by evaluating in vitro the expression of adhesion molecules on endothelial cells and on alveolar epithelial cells in the presence of alveolar macrophage supernatants. In control subjects, a weak staining of ICAM-1 was detected only in alveolar walls, while E-selectin and VCAM-1 were undetectable. In pneumoconiotic patients, ICAM-1 was expressed at a high level by endothelium, by alveolar and bronchial epithelial cells and by alveolar macrophages. E-selectin and VCAM-1 expression remained undetectable. Measurement of soluble adhesion molecule showed that only the concentration of sICAM-1 was significantly increased in BALF from patients with CWP compared with controls. The involvement of TNF in this ICAM-1 expression was shown by the in vitro effect of alveolar macrophage supernatants on adhesion molecule expresssion by endothelial cells and epithelial cells (this effect was neutralized by anti-TNF antibodies) and by the increased production of TNF in the lung of pneumoconiotic patients. These data provide evidence for the involvement of ICAM-1, induced at least in part by alveolar macrophage-derived TNF, in the development of the inflammatory reaction in CWP.
Characteristics of asymptomatic secondary immune responses to measles virus in late convalescent donors
Authors: HUISS S , DAMIEN B , SCHNEIDER F , MULLER C P 
Published: November 2003

SUMMARY
Among 44 fully protected, late convalescent adults re-exposed to measles, four developed an asymptomatic secondary immune response (SIR) with a significant increase in measles virus (MV)-specific IgG and low IgM. The boosted antibodies were mainly of the IgG1 subclass and reacted with the nucleoprotein and the haemagglutinin protein. About 30 weeks after re-exposure, antibody levels had decreased by 35–50%, suggesting that the booster effect may only be transient. SIR was only found in individuals with a pre-exposure IgG level below a well defined threshold. Antibody levels above this threshold fully protected against SIR. SIR seems to be an ‘all or none response’ where the magnitude of increase in specific IgG is independent of pre-exposure antibody levels as long as these are below the above threshold. In combination with pre-exposure neutralizing and haemagglutination inhibiting titres, a threshold was defined below which SIR is likely to occur. This may be useful to predict susceptibility to SIR in a given population, since individuals undergoing clinically inapparent SIR are among seropositive subjects, the most likely candidates to support transmission of virus.
Surface antigen expression in spleen cells of C57Bl/6 mice during ageing: influence of sex and parity
Authors: BARRAT F , LESOURD B M , LOUISE A , BOULOUIS H-J , VINCENT-NAULLEAU S , THIBAULT D , SANAA M , NEWAY T , PILET C H 
Published: November 2003

SUMMARY
So far all studies on the murine ageing process have been conducted on virgin mice. Immune ageing may be influenced by sex hormone differences related to sex or pregnancies. The aim of this study was to investigate whether pregnancies and gender influence the cell changes observed during ageing in a peripheral lymphoid compartment of C57Bl/6 mice. Using flow cytometry, changes in (Thy1.2+) T cell, (B220+) B cell and (CD11b/Mac-1) macrophage spleen populations were monitored in 2, 8 (3 months after last pregnancy) 15 and 23-month-old mice including males, virgin and multiparous females. The development of naive (CDCD44low), memory (CD44high), activated/memory (MEL-14, CD62L) cells were investigated in CD4+ and CE8+ T cell subsets. Both short term (at 8 months) and long term (at 15 and 23 months) effects of multiparity were obvious in the lymphocyte/macrophage population changes associated with the ageing process. Short-term effects included delayed appearance of CD4+CD44high memory lymphocytes and increased numbers of both CD4+MEL-14low activated/memory cells and Mac-1+ macrophages when compared with virgin control mice. Later effects of multiparity were increased CD8αdull populations and increased T/B cell ratios and the ratio of memory to naive CD4+ cells (CD44+high/CD44+low). A sex effect was noticed: males exhibited lower Mac-1+ levels and memory/naive ratio in CD4+ subset than virgin females throughout life. These results suggest that gender and/or pregnancies affect the age-related distribution of lymphoid and macrophage cell populations in the spleen of C57Bl/6 mice.
Characteristics of synovial fluid effusion in collagen-induced arthritis (CIA) in the DA rat; a comparison of histology and antibody reactivities in an experimental chronic arthritis model and rheumatoid arthritis (RA)
Authors: ERLANDSSON HARRIS H , LILJESTRÖM M , KLARESKOG L 
Published: November 2003

SUMMARY
We have characterized the cellular content and some antibody reactivities in synovial fluid (SF) from DA rats with CIA. Since CIA is widely used as a model for RA, in which many studies concerning immune responses are performed on SF samples, we considered it important to describe the local, disease-causing immune reactions in CIA. At the peak of disease (day 22 after immunization), the major cell population in CIA SF was granulocytes (72%), but macrophages (17·9%), plasma cells (2·6%) and lymphocytes (7·7%) were also present. The CIA synovial membrane (SM) obtained at the same time was mainly infiltrated by monocytes, with granulocytes, lymphocytes and plasma cells also present. Cell populations in blood did not differ between arthritic and normal DA rats. Equally, high anti-collagen type II (CII) and rheumatoid factor (RF) levels could be detected both in SF and in sera. Notably, RF levels were also increased in normal DA rats. Moderate levels of anti-heat shock protein 65 kD (hsp) antibodies were recorded systemically in both normal and diseased animals. In conclusion, the cellular composition in SF and in SM are similar in rat CIA and in RA. The morphological differences between SF and SM that are characteristic for RA could also be demonstrated in CIA. The antibody data indicate systemic production of anti-CII and anti-hsp antibodies as well as RF, but they give no support for local production of these antibodies in the joints, which is the case in RA.
Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay
Authors: MACANOVIC M , LACHMANN P J 
Published: November 2003

SUMMARY
A new radial enzyme diffusion (RED) method for the measurement of DNase activity in serum and urine is described. The sensitivity of the assay is in the range of 15.6–500 ng/ml. The assay is based on the hydrolysis of double-stranded (ds) DNA (or nucleosomes) in agarose. The specificity of the reaction for DNase I was established by showing that either EDTA in the reaction buffer or G-actin abolished DNase activity. Being a functional assay, RED has advantages over radioimmunoassay (RIA) or ELISA, since antigenic assays may also measure complexes of DNase with actin. This method was used to measure DNase activity in the sera and urine of lupus-prone mice (NZB/NZW F1 hybrids, aged 4–6 weeks). Serum DNase activity in these mice was significantly lower (mean 9 ng/ml) than in control, normal mice of the same age and sex (mean 37 ng/ml). Concentration of DNase in the urine of 4–6-week-old female NZB/NZW F1 hybrids (24 ng/ml) was significantly lower then in control mice (521 ng/ml). The RED method was used to measure the concentration of actin as the DNase inhibitor in serum. G-actin in the presence of ATP binds DNase and inhibits its nucleolytic activity. Since ATP is necessary for the actin inhibition of DNase I, this shows that there is actin as well as DNase I in the serum. Actin is not only ATP-dependent, but also heat-labile. Heating the sera for 10 min at 50°C increases DNase activity. This is an alternative method for measuring the concentration of actin in the serum. An almost identical estimate of actin concentration in sera of normal mice was found from the difference of DNase activity in the presence or absence of ATP (mean actin concentration = 21 ng/ml) or from the difference of DNase activity in heated and non-heated serum (mean actin concentration 18 ng/ml). We were not able to demonstrate DNase inhibitors in the urine of either control or NZB/W F1 hybrid mice.
Anti-ribosomal and ‘P-peptide’-specific autoantibodies bind to T lymphocytes
Authors: STAFFORD H A , CHEN A E , ANDERSON C J , PAUL A G A , WYATT E L , LEE L A , NEAS B R 
Published: November 2003

SUMMARY
Patients with systemic lupus erythematosus (SLE) frequently have anti-lymphocyte autoantibodies, some of which also bind to surfaces of neurons. Since anti-ribosomal P protein autoantibodies (anti-P) from SLE patients also bind to surfaces of neurons, we hypothesized that anti-P are anti-lymphocyte antibodies. A panel of human T lymphocytes was evaluated for anti-P binding by indirect immunofluorescence. Affinity-purified anti-ribosomal antibodies were used as a source of anti-P. These autoantibodies bound to the surfaces of all transformed T cell lines tested. This binding was not mediated by Fc receptors. It was inhibitable by ribosomes. Anti-P bound to circulating T lymphocytes from healthy adults and children. They also bound to thymocytes and cord blood T cells from normal neonates. Circulating T cells from SLE patients with anti-P bound less anti-P than cells from healthy controls. Two patients were studied on multiple occasions. The capacity of their T cells to bind anti-P correlated inversely with titres of anti-ribosomal antibodies. Anti-ribosomal antibodies, other than anti-P, also appear to bind to T cells. The surface of T cells contains a protein with the size and antigenicity of the ribosomal P protein, P0. We conclude that anti-ribosomal antibodies are a subset of anti-lymphocyte autoantibodies. Their possible role in the pathogenesis of lymphopenia or lymphocyte dysfunction in SLE has to be defined in further studies.
Heterozygous C8β complement deficiency does not predispose to meningococcal disease
Authors: PLATONOV A E , SHIPULIN G A , SHIPULINA O JU , VERSHININA I V , DENSEN P 
Published: November 2003

SUMMARY
We have identified 42 Russian patients with homozygous C8β complement component deficiency, all of whom had experienced at least one episode of systemic meningococcal disease. About 90% of these individuals have a C → T exchange in exon 9, leading to a premature stop codon. If, like the homozygous-deficient state, heterozygous C8β deficiency constitutes a risk factor for meningococcal disease, it would be expected to be detected with increased frequency among individuals suffering from this disease. Using allele-specific polymerase chain reaction (PCR)we studied 153 consecutive patients with meningococcal disease admitted to the Moscow Hospital for Infectious Diseases to determine the frequency of C8 null allele. No individuals with heterozygous C → T exchange were identified among these 153 patients, despite the fact that seven persons were detected who had homozygous C8β deficiency, caused by the same C → T exchange in exon 9, and one patient who had C7 component deficiency. Thus, heterozygous deficiency, although more frequent than homozygous deficiency in the general population, does not result in a substantial increase in susceptibility to meningococcal disease.
Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributory factor to the breach of tolerance to thyroid antigens?
Authors: SOSPEDRA M , TOLOSA E , ARMENGOL P , ASHHAB Y , URLINGER S , LUCAS-MARTIN A , FOZ-SALA M , JARAQUEMADA D , PUJOL-BORRELL R 
Published: November 2003

SUMMARY
According to the ‘aberrant HLA expression’ hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-γ) and to a lesser extent by IFN-α. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the ‘aberrant HLA expression’ hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of ‘autoimmunity by breach of peripheral tolerance’.
Non-restricted T cell receptor (TCR)-Vα and -Vβ gene usage in patients with pulmonary sarcoidosis
Authors: HOSHINO T , SUZUKI R , TSURUTA Y , MATSUTANI T , KIKUCHI M , KAWAMOTO M , GOUHARA R , SHIRAISHI T , MOCHIZUKI M , ITOH K , OIZUMI K 
Published: November 2003

SUMMARY
Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by the pronounced accumulation of CD4+ T cells and macrophages in the affected organs. TCR variable (V)α and Vβ gene usage in patients with sarcoidosis is still a matter of discussion. In this investigation, we analysed TCR-Vα and -Vβ gene usage in bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) of 30 patients with active pulmonary sarcoidosis using an adapter ligation method, reverse transcriptase-polymerase chain reaction (RT-PCR), and sequence-specific oligonucleotide probe (SSOP) analyses. There was no significant difference in TCR-Vα or -Vβ gene usage between BALF (n=12) or PBMC (n=27) of patients and PBMC of healthy subjects (n=10). Neither selective TCR-Vα nor -Vβ expansion was observed in the paired BALF and PBMC from seven of nine patients. However, selective expansions were observed in a few TCR-Vα or -Vβ subsets in the BALF or PBMC of some individuals. Although a modest increase in a few TCR-Vα or -Vβ subsets was observed in the BALF or PBMC of some individuals, the increased TCR-Vα or -Vβ subsets were not closely associated with the HLA-DRB1, DQA1, DQB1, and DPB1 alleles of these patients. These results suggest that TCR-Vα or -Vβ gene usage is not restricted in both lung and peripheral blood in the majority of patients with active pulmonary sarcoidosis.
A non-protective T helper 1 response against the intra-macrophage protozoan Theileria annulata
Authors: CAMPBELL J D M , BROWN D J , NICHANI A K , HOWIE S E M , SPOONER R L , GLASS E J 
Published: November 2003

SUMMARY
Theileria annulata is a protozoan parasite which infects and transforms bovine macrophages. Infected macrophages possess augmented antigen presentation capabilities, as they are able to activate the majority of T cells from unexposed animals. In vivo, T cells in the draining lymph node (principal site of parasite development) are activated ‘non-specifically’ by the parasite. This event is followed by failure of the immune response to control the infection. Protective immune responses against intra-macrophage protozoa are usually mediated by T helper 1 (Th1) T cell responses. Here we examine the cytokine responses made by T. annulata-activated T cells. We show that the outcome of in vitro activation of T cells by parasitized macrophages is a skewing of their cytokine responses towards preferential expression of interferon-gamma (IFN-γ) mRNA. The in vitro response is mirrored during in vivo infection, as greatly elevated amounts of IFN-γ protein are found in lymph efferent from infected lymph nodes, while expression of IL-4 mRNA within the node stops. IFN-γ production does not correlate with protection against the parasite, as infected cells flourish during peak IFN-γ production, and only very small amounts of IFN-γ are produced during the effective immune response of an immunized animal. Overproduction of IFN-γ and loss of IL-4 expression are also likely to account for the failure of B cells to reach the light zone of germinal centres, a developmental step which is tightly regulated by cytokines.
Cellular mRNA expression of interferon-gamma (IFN-γ), IL-4 and IL-10 relates to resistance to experimental autoimmune myasthenia gravis (EAMG) in young Lewis rats
Authors: SHI F-D , ZHANG G-X , BAI X-F , VAN DER MEIDE P-H , LINK H 
Published: November 2003

SUMMARY
Age-related alterations in the immune system, including changes in lymphocyte subset composition, result in changes of cytokine patterns and might thereby influence the incidence and severity of autoimmune diseases. To investigate the age-related resistance to EAMG, an animal model for human MG, young (4-week-old) and adult (8–10-week-old) female Lewis rats were immunized with Torpedo acetylcholine receptor (AChR) and Freund's complete adjuvant (FCA). Adult Lewis rats showed severe weight loss and progressive muscular weakness after immunization, while young rats developed minor clinical signs of EAMG after a prolonged interval post-immunization. By comparison with adult rats, the young had lower AChR-specific T and B cells responses, and less muscle AChR loss. In situ hybridization performed on mononuclear cells (MNC) from lymph nodes revealed that young rats had lower levels of AChR-specific IFN-γ, IL-4 and IL-10 mRNA-expressing cells compared with adult rats. Since IFN-γ, IL-4 and IL-10 promote the development of EAMG, the low expression of these cytokines might contribute to EAMG resistance in young Lewis rats.
Effect of body weight and caloric restriction on serum complement proteins, including Factor D/adipsin: studies in anorexia nervosa and obesity
Authors: POMEROY C , MITCHELL J , ECKERT E , RAYMOND N , CROSBY R , DALMASSO A P 
Published: November 2003

SUMMARY
Complement plays important roles in host immune defences, and recent studies suggest that adipose tissue is an important site of production for some complement proteins. Starvation has been associated with low complement levels, but studied populations have usually had concomitant opportunistic infections or other conditions which might affect complement levels. To determine the impact of body weight and changes in body weight on serum complement, we investigated levels of complement proteins in otherwise healthy patients with a wide range of body weights, including patients with anorexia nervosa before and after treatment, obese dieters before and after weight loss, and normal weight controls. We found that complement proteins of the alternative pathway (C3, B, and D), alternative pathway haemolytic activity (AP50) and the inhibitors H and I were low in starving anorectics and normalized with weight gain. C3a levels were comparable in anorectics at low weight and after weight gain, indicating that low serum complement levels were attributable to hypoproduction and not complement cascade activation with consumption. Further, levels of C3, B, AP50, H and I, but not D, were higher than controls in obese patients and decreased toward normal after weight loss. Overall, percentage of ideal body weight, changes in body weight, and serum transferrin were each highly correlated with serum levels of complement proteins. We conclude that levels of alternative pathway complement components are determined in part by factors that influence body weight and by weight changes, possibly due to changes in production in adipose tissue or at other sites.