bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down-regulation of specific antigen-driven cytokine production in a population with endemicSchistosoma japonicuminfection
Authors: SHEN L , ZHANG Z S , WU H W , WEIR R E , XIE Z W , HU L S , CHEN S Z , JI M J , SU C , ZHANG Y , BICKLE Q D , COUSENS S N , TAYLOR M G , WU G L 
Published: March 2003

SUMMARYSchistosome antigen-driven cytokine responses and antischistosome antibody levels of residents of a Schistosoma japonicum endemic island in Poyang Lake, Jiangxi Province were studied before and 45 days after treatment with praziquantel. IL-4, IL-5, IL-10 and INF-γ were all detected in the supernatants of whole-blood cultures after stimulation with schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP). The percentages of subjects producing detectable amounts of each cytokine assayed were higher in the group who were negative by stool examination at the start of the study than in those who were initially stool positive. After praziquantel treatment the percentages of subjects producing both type I and type II cytokines increased. This suggests that the production of both types of cytokine was down-regulated in the presence of live, egg-laying S. japonicum adult worms but that this was reversible by treatment. In contrast, the antibody studies showed higher levels of SWAP and SEA-specific antibodies (IgE, total IgG, IgG4, IgM) in subjects who were originally stool-positive than in those who were stool-negative. After treatment specific IgE responses were elevated, but total IgG and IgG4 anti-SEA and IgM anti-SWAP antibody levels all fell significantly.
Interference of PR3-ANCA with the enzymatic activity of PR3: differences in patients during active disease or remission of Wegener's granulomatosis
Authors: VAN DER GELD Y M , TOOL A T J , VIDELER J , DE HAAS M , COHEN TERVAERT J W , STEGEMAN C A , LIMBURG P C , KALLENBERG C G M , ROOS D 
Published: March 2003

SUMMARY
Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. Levels of PR3-ANCA do not always correspond to clinical disease activity.
To investigate the relationship between functional effects of PR3-ANCA and disease activity, we tested the effect of IgG samples from sera of 43 WG patients, taken during active disease or remission, for their capacity to interfere with the proteolytic activity of PR3. Furthermore, longitudinal sera of seven WG patients were included. The enzymatic activity of PR3 was determined (1) with casein or with a small synthetic substrate and (2) by complexation of PR3 with α1-antitrypsin (α1-AT).
With a fixed concentration (100 μg/ml) of IgG, PR3-ANCA from patients during an active phase of WG had a higher inhibitory capacity towards the proteolytic activity of PR3 and complexation of PR3 with α1-AT than did PR3-ANCA from WG patients during remission. However, the number of PR3-ANCA units that gave 50% inhibition of the PR3 enzymatic activity and its complexation with α1-AT was lower for patients during remission than for patients during an active phase of WG, indicating a stronger inhibitory capacity at a molar base.
In conclusion, PR3-ANCA from patients during remission had a relatively higher inhibitory capacity towards the enzymatic activity of PR3 than PR3-ANCA from patients during an active phase. This may indicate that during active disease the ANCA titre is increased, but the number of active ANCA molecules that recognize the enzyme-inhibiting epitopes is not increased.
CD57+ T cells augment IFN-γproduction in a one-way mixed lymphocyte reaction and their expansion after stem cell transplantation in paediatric patients
Authors: KOIKE Y , SEKI S , OHKAWA T , KANEKO T , KOGAWA K , FUJITSUKA S , HIRAIDE H , SEKINE I 
Published: March 2003

SummaryTo clarify the immune response of CD57+ T cells (most of them are CD8+) in peripheral blood (PB) against alloantigens in order to elucidate the T helper 1 (Th 1) immune response, we assessed the role of CD57+ T cells in IFN-γ (one of the representative Th 1 cytokines) production in a one-way mixed lymphocyte reaction (MLR). In this study, we showed that CD57+ T cells in responder cells were essential for effective IFN-γ production in allogeneic MLR due partly to the augmentation of the alloresponse of regular T cells. Furthermore, IFN-γ production in MLR correlated with the proportions of CD57+ T cells in PB regardless of the responders’ age. We also showed that the extent of the expansion of CD57+ T cells in paediatric patients after haematopoietic stem cell transplantation (HSCT) was markedly lower than that in adult patients. In addition, CD57+ T cells purified and activated with a combination of cytokines showed a greater cytotoxicity than regular T cells against human umbilical vein endothelial cells. Because IFN-γ production in one-way MLR is a useful predictor of graft-versus-host disease (GVHD), especially in the acute phase that occurs after allogeneic HSCT, our findings suggested that CD57+ T cells play a role in the development of GVHD and thus may explain the reason as to why a higher donor age is associated with an increased risk of developing GVHD while, in addition, the incidence of severe GVHD in paediatric patients is lower than that in adult patients.
IL-10 induces mesangial cell proliferation via a PDGF-dependent mechanism
Authors: ROBERTSON T E , NIKOLIC-PATERSON D J , HURST L A , ATKINS R C , CHADBAN S J 
Published: March 2003

Summary
Interleukin-10 (IL-10) is a mesangial cell growth factor in vivo and in vitro. However, the mechanism by which IL-10 exerts its mitogenic activity is not known. The aim of this study was to determine whether IL-10 induces mesangial cell proliferation in a PDGF-dependent or independent fashion. A well-­characterized rat mesangial cell line (1097) was used in a series of cell proliferation experiments in which cells were serum-starved and then incubated with recombinant IL-10 in the presence or absence of STI 571 (a specific inhibitor of signalling via the PDGF-α and β receptors) or a neutralizing anti-PDGF-AB antibody. IL-10 induced significant mesangial cell proliferation at 24 and 48 h after cytokine addition. This response was inhibited totally by the addition of STI-571, demonstrating that IL-10 mitogenic activity has an absolute requirement for signalling through the PDGF receptor. In further studies, it was found that STI-571 could be added 24 h after IL-10 stimulation and still exert a profound inhibition of IL-10 mitogenic activity. The ability of a neutralizing anti-PDGF-AB antibody to inhibit completely IL-10-induced mesangial cell proliferation confirmed that IL-10 acts via induction of an autocrine PDGF response rather than the possibility that IL-10 may transactivate the PDGF receptor in a PDGF-independent fashion. In conclusion, this study has demonstrated that IL-10 induces mesangial cell proliferation via an autocrine PDGF-mediated mechanism. Thus, therapies which antagonize PDGF signalling will also inhibit any contribution of IL-10 to mesangial proliferation.
Direct modulatory effect of C-reactive protein on primary human monocyte adhesion to human endothelial cells
Authors: WOOLLARD K J , PHILLIPS D C , GRIFFITHS H R 
Published: March 2003

SummaryC-reactive protein (CRP) is the prototypic acute phase serum protein in humans. The effects of CRP on primary human monocyte adhesion molecule expression and interaction with the endothelium have not been studied. Herein, we describe an investigation into the phenotypic and functional consequences of CRP binding to peripheral blood monocytes ex vivo. Peripheral whole blood was collected from healthy, non-smoking males. Mononuclear cells (MNC) and monocytes were isolated by differential centrifugation using lymphoprep and Dynal negative isolation kit, respectively. Cells were exposed to CRP from 0 to 250 µg/ml for 0–60 min at 37°C and analysed for (a) CD11b, PECAM-1 (CD31) and CD32 expression by flow cytometry and (b) adhesion to LPS (1 µg/ml; 0–24 h) treated human umbilical vein endothelial cells (HUVEC). CD14+ monocyte expression of CD11b increased significantly up to twofold when exposed to CRP, compared to controls. There was no significant difference in CD32 expression, whereas CD31 expression decreased after exposure to CRP. CRP treatment of monocytes inhibited their adhesion to early LPS-activated HUVEC (0–5 h). However, the adhesion of CRP-treated monocytes to HUVEC was significantly greater to late activation antigens on HUVEC (24 h, LPS) compared to controls. We have shown that CRP can affect monocyte activation ex vivo and induce phenotypic changes that result in an altered recruitment to endothelial cells. This study provides the first evidence for a further role for C-reactive protein in both monocyte activation and adhesion, which may be of importance during an inflammatory event.
Adjuvant modulation of the immune responses and the outcome of infection withChlamydia pneumoniae
Authors: BANDHOLTZ L , KREUGER M R , SVANHOLM C , WIGZELL H , ROTTENGERG M E 
Published: March 2003

SummaryImmunization with different adjuvants resulted in antithetic outcomes of infection with Chlamydia pneumoniae. Immunization with the outer major protein-2 from C. pneumoniae (OMP-2) emulsified in Freund's complete adjuvant (FCA) thus increased the susceptibility of mice to infection with the bacteria. The detrimental effect was not observed upon inoculation of irrelevant antigens or major outer membrane protein (MOMP) in FCA, but was also observed after immunization with FCA–chlamydial heat shock protein-60 (HSP-60). The harmful effect of FCA-OMP-2 depended on the presence of both CD4+ and CD8+ cells and was mediated by IL-10, as shown using gene-ablated mice. The increased susceptibility to infection caused by FCA-OMP-2 immunization was long-lasting and observed in mice infected 4 months after the last dose of immunogen. In contrast, partial protection against C. pneumoniae was observed when FCA was replaced with oligodeoxynucleotides containing immunostimulatory CpG motifs mixed with Freund's incomplete adjuvant (FIA-IS-CpG). These polar outcomes of infection related to the cytokine pattern: antigen-stimulated spleen cells from FCA-OMP-2-immunized mice showed higher IL-10/IFN-γ ratios than FIA-IS-CpG-OMP-2-immunized animals. In agreement, sera from FCA-OMP-2 showed higher anti-OMP-2 IgG1/IgG2a ratios than FIA-IS-CpG-OMP-2-immunized animals. Finally, OMP-2 also generated a protective response when delivered by a eukaryotic expression vector in tandem with CTLA4, a procedure that targeted OMP-2 to antigen-presenting cells.
Involvement of CD27/CD70 interactions in antigen-specific cytotoxic T-lymphocyte (CTL) activity by perforin-mediated cytotoxicity
Authors: YAMADA S , SHINOZAKI K , AGEMATSU K 
Published: March 2003

SummaryCD27 molecules are shown to be essential in the regulation of the death, activation and differentiation of T and B cells. However, the influence of CD27 on cytotoxic T-cell function remains obscure. Autologous EBV transformed B-cell lines (LCL), which highly express CD27 ligand CD70, here stimulated T cells and induced the cytotoxic T-lymphocyte (CTL) activity via T-cell antigen receptors (TCR). The cytotoxicity against LCL was diminished when anti-CD70 blocking MoAb was added initially in the culture. Resting T cells killed more CD70-transfected P815 cells than wild type P815 cells in the presence of anti-CD3 MoAb as measured by a 4-h 51Cr release assay, and the cytotoxicity of both of the cell populations completely disappeared in the presence of concanamycin A (CMA). The expression of the perforin by the LCL-induced CTL in the presence of anti-CD70 blocking MoAb was diminished as compared with that without the blockage of CD27/CD70 interactions. The CTL induced by LCL did not kill Fas-transfected WR cells. CD27 signalling in the T cells did not affect Fas ligand (FasL) mRNA expression, LAK activity and IFN-γ synthesis in humans. Our data demonstrate that CD27/CD70 interactions enhance the cytotoxicity of CTL in the induction phase through enhancement of killing activity induced via the perforin-dependent mechanism, but not via the Fas/FasL system.
Reactive arthritis and serum levels of mannose binding lectin – lack of association
Authors: LOCHT H , CHRISTIANSEN M , LAURSEN I 
Published: March 2003

SUMMARY
The purpose was to evaluate the possible association of serum mannose binding lectin (s-MBL) levels on type of triggering microbe, duration of diarrhoea, incidence and course of reactive arthritis (ReA) caused by Salmonella, Yersinia and Campylobacter. Sixty patients with ReA of 1–228 months duration, 173 patients with ReA or uncomplicated enterocolitis caused by Campylobacter, 226 sera from patients with elevated antibody levels against Salmonella, Yersinia or Campylobacter, and 114 blood donors were tested for s-MBL using ELISA technique, both direct mannan binding assay and sandwich ELISA. s-MBL was compared with C-reactive protein (CRP) levels and with the ability of activating complement C4. Among the 114 donors 9% had s-MBL &lt;50 µg/l, 16% had from 50–500 µg/l and 75% had &gt;500 µg/l. The distribution of s-MBL levels in the three-patient groups did not differ significantly from the controls. There were no indications that low s-MBL was associated with prolonged duration of arthritis, diarrhoea or individual bacterial infections. The two MBL assays were comparable with respect to serum concentrations, indicating that the actual circulating MBL was also functionally active. s-MBL exhibited acute phase reactant behaviour and correlated to CRP level, but only in patients with s-MBL concentrations exceeding 1000 µg/l. MBL in 10 randomly selected ReA sera were tested for the ability to activate complement C4. The results did not differ from those of donor controls. This study demonstrates that the distributions of s-MBL levels in serum among patients with ReA are not different from donor controls. The course, outcome or triggering bacteria are not associated with a particular level of s-MBL.
Vaginal T lymphocyte population kinetics during experimental vaginal candidosis: evidence for a possible role of CD8+ T cells in protection against vaginal candidosis
Authors: GHALEB M , HAMAD M , ABU-ELTEEN K H 
Published: March 2003

SUMMARYVaginal candidosis represents a significant health problem to women of childbearing age worldwide. It has been postulated that localized T cells play a role in protection against vaginal candidosis. In an attempt to evaluate the role of vaginal T cells in protection against vaginal candidosis, T cell population kinetics was evaluated using an oestrogen-dependent vaginal candidosis murine model. Vaginal T lymphocytes were isolated at different time points post C. albicans inoculation, viable cells were enumerated, phenotypically analysed for the expression of CD3, CD4 and CD8 T cell markers and absolute numbers of T cell subsets were calculated. Oestrogen-induced persistence of vaginal candidosis resulted in a significant increase in the total number of vaginal lymphocytes within 24–48 h post infection; increased vaginal lymphocyte numbers persisted throughout the infection period. The number of CD3+ T cells dramatically increased following C. albicans administration and was maintained at high levels throughout the infection period. The majority of CD3+ T cells were of the CD8+ type; however, considerable numbers of both CD4+ T cells and CD4+CD8+ T cells were also observed throughout the infection period. The considerable and persistent increase in vaginal T cell numbers in general and that of CD8+ T cells in particular are evidence of the possible role played by localized T cells in protection against vaginal candidosis.
High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: evidence for serum factors interfering with the binding to gp130
Authors: PIGNATTI P , CIAPPONI L , GALLE P , HANSEN M B , MASSA M , MEAZZA C , PAONESSA G , NOVICK D , CILIBERTO G , MARTINI A , DE BENEDETTI F 
Published: March 2003

SUMMARYWe previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6.
High positive frequency of antibodies to metallothionein and heat shock protein 70 in sera of patients with metal allergy
Authors: JIN G-B , NAKAYAMA H , SHMYHLO M , INOUE S , KONDO M , IKEZAWA Z , OUCHI Y , CYONG J-C 
Published: March 2003

SUMMARY
Two principal types of stress protein, heat shock proteins (hsps) and metallothionein (MT), are induced in cells responding to a variety of stresses. They play an important role in protecting cells from these stresses. However, many reports indicate that antibodies to hsps are present in human serum and are associated with several autoimmunity diseases. Metals, which are commonly allergenic to humans, induce both MT and hsp70 (one of the hsps family). Until now, there has been no report of any antibody to MT in human serum. In the present study, serum samples from healthy controls (Group I), and patients suffering from atopic dermatitis without (Group II) or with (Group III) metal allergy, were measured for antibodies to MT and hsp70, using an enzyme-linked immunosorbent assay (ELISA). Metal allergy was confirmed by patch testing. We first found that antibody to MT exists in human serum. We also found a high positive frequency of antibody to MT (51·3%) and to hsp70 (43·6%) in the sera of Group III, compared to those of Group I (3·8% and 5·1%) or Group II (6·4% and 5·1%). Furthermore, there was a strong positive correlation between antibody to MT and antibody to hsp70 in Group III (P = 0·0013), but not in Group I and Group II. Our results indicate that antibody to MT exists in human serum, as do antibodies to hsps, and suggest that elevated levels of MT and hsp70 antibodies are associated with metal allergy in atopic patients.
A family with hereditary extra‐adrenal paragangliomas without evidence for mutations in the von Hippel‐Lindau disease or ret genes
Authors: Sköldberg  , Grimelius  , Woodward  , Rorsman  , Van Schothorst  , Winqvist  , Karlsson  , Åkerström  , Kämpe  , Husebye  
Published: March 2003

OBJECTIVESTo characterize a family with hereditary paraganglioma, and to search for germline mutations in the von Hippel‐Lindau disease (VHL) tumour suppressor gene and the ret proto‐oncogene.DESIGNPatient records and histopathological reports were reviewed. Available tumour samples were reinvestigated using immunohistochemical techniques. The VHL gene was investigated by single strand conformational polymorphism analysis of PCR products amplified from exons 1, 2 and 3 and the 3′ untranslated region. The ret gene was analysed by amplifying and sequencing exons 10, 11 and 16.PATIENTSA family with paragangliomas in three consecutive generations was investigated.RESULTSThe affected individuals were found to have multiple extra‐adrenal paragangliomas. All three affected individuals had retroperitoneal tumours, and two also had paraganglioma in the neck. No mutations of the VHL or ret genes were detected.CONCLUSIONSThe described family may represent a novel dominantly inherited neuroendocrine tumour syndrome.
Genotype‐phenotype analysis in late onset 21‐hydroxylase deficiency in comparison to the classical forms
Authors: Rumsby  , Avey  , Conway  , Honour  
Published: March 2003

OBJECTIVETo establish the type and frequency of mutations causing late onset 21‐hydroxylase deficiency and associated clinical and biochemical phenotypes and to compare these findings to those from heterozygotes and homozygotes for classical 21‐hydroxylase deficiency.DESIGNAnalysis of the 21‐hydroxylase genes by DNA amplification and mutation detection. Measurement of serum 17‐hydroxyprogesterone following stimulation with adrenocorticotrophic hormone.PATIENTSFifteen patients with late onset congenital adrenal hyperplasia, 18 obligate heterozygotes for classical congenital adrenal hyperplasia, 95 patients with classical 21‐hydroxylase deficiency.MEASUREMENTS17‐hydroxyprogesterone following adrenal stimulation with adrenocorticotrophic hormone; frequency of 10 common mutations in the 21‐hydroxylase gene.RESULTSOf alleles from patients with late onset CAH 46% carried V281L and 10% P30L mutations compared to 2.6% and 1.1% respectively of alleles from patients with the classical disease where the most common mutations are a splice site mutation in intron 2 (34%), deletions (25%) and I172N (15%). Serum 17‐hydroxyprogesterone following Synacthen stimulation reliably differentiated the late onset patients from carriers for the classical disease, whereas there was overlap of the basal 17‐hydroxyprogesterone concen_tration between these two conditions.CONCLUSIONSNormal basal serum 17‐hydroxyprogesterone levels cannot exclude late onset CAH, although response to adrenocorticotrophic stimulation clearly distinguished this disorder from carriers of the classical disease. The frequency of mutations causing less severe enzyme deficiency was higher in the late onset patients than in a group of classical patients, although other genes or environmental pressures may determine the age of onset of disease.