bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal study of the IgG antibody response to HIV-1 pl7gagprotein in HIV-1+ patients with haemophilia: titre and avidity
Authors: CHARGELEGUE D , O'TOOLE C M , COLVIN B T 
Published: October 2008

SUMMARYThe IgG response to HIV-1 p17 gag protein was studied for up to 6 years in 12 HIV-1-infected patients with haemophilia, who had seroconverted between 1982 and 1985. To assess any prognostic value, pl7 IgG titres were compared with p24 IgG titres. CD4 cell counts and p24 antigenacmia. p17 IgG avidity index was also examined. A strong similarity was found between the IgG titre to HIV-1 pl7 and that to p24. In patients who developed AIDS the decline in pl7 IgG titres could precede by several years the drop in CD4 cells to under 200 cells/μl; whereas some long-term asymptomatic patients (CDCII) had increasing p17 IgG titres and stable CD4 cell counts. Declining p17 and p24 IgG titres were not always associated with an increase in p24 antigenaemia. IgG titres were found to be better predictors of disease progression than CD4 cell counts or p24 antigenaemia. Patients who developed AIDS during the study were also characterized by a lower p17 IgG avidity than patients who remained asymptomatic This result suggests that IgG avidity could have prognostic relevance and be of importance for host resistance to AIDS onset.
Parainfluenza type 1 virus-infected cells are killed by both CD8+ and CD4+ cytotoxic T cell precursors
Authors: SLOBOD K S , ALLAN J E 
Published: October 2008

SUMMARYThe memory cytotoxic T lymphocyte (CTL) response to human parainfluenza type 1 virus (hPIV-1), a prominent cause ol'respiratory infection in young children, has been analysed for a panel of healthy adults. The CTL response to the parainfluenza viruses has not been investigated previously. Precursor CTL (CTLp) with activity against hPI V-1 -infected Epstein Barr virus (EBV)-transformed B lymphoblastoid target cells were found at a relatively high precursor frequency (approximately 1/ 2500–1/4700 CD8+ and CD4+ subsets respectively) in peripheral blood. Both CD4+ and CD8+ CTLp were delected by the analysis of individual microcultures set up under limiting dilution conditions from freshly isolated blood, the phenotype of the responder cell from individual wells being determined by flow cytometry. Further characterization of the CTL response demonstrated MHC restriction by the HLA-A2 glycoprotein in 3/4 HLA-A2+ donors. The presence of effective, hPIV-1-directed T cell memory may explain, in part, the protection observed in the adult population.
T cell memory specific for self and non-self antigens in rats persistently infected with Borna disease virus
Authors: ROTT O , HERZOG S , CASH E 
Published: October 2008

SUMMARYWe have studied CD4+ Thl T cell responses in Borna disease (BD). a virus-mediated immune disease of the central nervous system (CNS). and demonstrate the priming of virus-specific as well as autoreacti ve T cells specific for myelin antigens in the course of viral infection. The fate of these in vivo generated T cells was subsequently assessed by in vitro proliferation assays with lymphocytes from different lymphoid organs of diseased animals over a long period of time. Virus-specific T cell responses continuously decreased during the establishment of persistent infection and could no longer be detected after 5–6 months post infectionem, when inflammatory reactions in the brain had ceased. By contrast, autoantigen-specific T cells kept their ability to mount characteristic secondary responses—although at an overall rather low level—over long periods of time; these autoreactive T cells homed to a specific lymphoid organ, the perithymic lymph node. Our study thus describes for the first time a complete decline of virus-specific T cell memory in a persistent viral infection, and raises the question how long-lasting T cell aulorcaclivily is controlled.
Immunogenicity of the meningococcal stress protein MSP63 during natural infection
Authors: PANNEKOEK Y , SCHUURMAN I G A , DANKERT J , van PUTTEN J P M 
Published: October 2008

SUMMARYAcute- and convalesccnt-phasc sera from 40 patients with meningococcal disease were evaluated for immunorcactivity with the meningococcal member of the hsp60 stress protein family. The IgG response was measured by ELISA, using bacterial cell lysate of the corresponding patients' strain, and purified hsp60 proteins from Neisseria meningitldis (MSP63), Escherichia coli (GroEL) and Mycobacterium bemis BCG (65K) as antigens. Analysis of the antibody responses revealed that 24/35 patients (69%) with elevated anti-meningococcal titres. generated anti-MSP63 antibodies during the time course of infection. Twelve of these patients generated antibodies specific for MSP63. in six patients anti-MSP63 levels exceeded anli-GroEL/65K antibodies. In the remaining six patients, equal levels of anti-MSP63 and anti-GroEL/65K were measured. We conclude that MSP63 is expressed and immunogenic during natural meningococcal infection, and that individual subjects have a restricted response to the antigen, resulting in the recognition of Neisseria-sp hsp60 epitopes and/or cross-reactive hsp60 determinants.
Successful primate immunization with peptides conjugated to purified protein derivative or mycobacterial heat shock proteins in the absence of adjuvants
Authors: PERRAUT R , LUSSOW A R , GAVOILLE S , GARRAUD O , MATILE H , TOLGNE C , VAN EMBDEN J , VAN DER ZEE R , LAMBERT P-H , GYSIN J , DEL GIUDICE G 
Published: October 2008

SUMMARYWe have previously shown in mice that antibodies can be induced to synthetic malaria peptides conjugated to mycobacterial antigens, such as purilied protein derivative (PPD) or heal shock proteins (hsp), and given in the absence of adjuvants after a previous priming with bacille Calmette-Guerin (BCG). In the present study we investigated this model of immunization in the non-human primates. Saimiri sciureus monkeys. Monkeys primed with BCG subcutaneously and then immunized subcutaneously with the Plasmodium falciparum sporozoite (NANP)40, synthetic peptide conjugated to PPD or mycobacterial hsp of 65 or 70 kD. in the absence of adjuvants, produced anti-peptide and anti-sporozoite IgG anybodies. Interestingly, the carrier effect of the hsp of 70 kD for the induction of anti-(NANP)40 antibodies was also observed in the absence of a previous priming with BCG. These data suggest that such a vaccination strategy may be applied to humans.
Contrasting levels ofin vitrocytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration
Authors: YANNI G , WHELAN A , FEIGHERY C , QUINLAN W , SYMONS J , DUFF G , BRESNIHAN B 
Published: October 2008

SUMMARYSynovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0·25 g) were cultured for cytokine production. The highest levels of IL-1β and IL-6 were produced by group A tissues: 19·1 ± 19·6 ng/ml IL-1β (mean ± s.d.) and 264·4 ± 301·9 ng/ml IL-6, versus 3·8±6·6 ng/ml and 54·7±42·6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P=0·04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction.
Antibody penetration of viable human cells. II. Anti-RNP antibodies binding to RNP antigen expressed on cell surface, which may mediate the antibody internalization
Authors: MA J , KING N , CHEN S-L , PENNY R , BREIT S N 
Published: October 2008

SUMMARYAs U1 small nuclear ribonucleoprotein (U1 snRNP2) has a crucial role in pre-mRNP splicing, the interaction of anti-RNP antibody with snRNP within viable lymphocytes may profoundly influence cell functions. We have shown that antibody can penetrate viable human lymphocytes, and anti-RNP antibodies enter more cells than other anti-nuclear antibodies or control IgG. In order to study the in vitro interaction of anti-RNP antibodies with viable cells. T lymphocytes were metabolically labelled with 35S-methionine, then incubated with the antibodies and washed. A set of 35S-labelled cell-associated snRNP polypeptides A, B′/B, C and D were found to bind to both monospecific human polyclonal anti-RNP IgG (human anti-RNP IgG) and a mouse monoclonal anti-RNP antibody (2·73), indicating that anti-RNP antibodies interacted with RNP antigen inside or/and on the surface of viable cells. To investigate antibody binding to RNP antigen on the cell surface, the cell surface proteins were either iodinated with 125I or the cells processed for immunoelectron microscopic studices after incubation with MoAb. At least seven 125I-labelled polypeptides on the cell surface were found to be immunoprecipitated by the anti-RNP MoAb which have similar molecular weights to U snRNP polypeptidcs 70K, A, B, D, E, F, and G. The immunoelectron microscopic studies showed that the gold particles formed clustered patches on the cell membrane. Further studies suggested that RNP antigen bound to the cell surface, and the RNP binding structure was probably a heterodimer receptor. This study provides evidence to suggest that anti-RNP antibody entry into viable cells may be mediated by interaction with RNP antigen expressed on the cell surface.
Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-α1-antitrypsin complexation to disease activity in Wegener's granulomatosis
Authors: DOLMAN K M , STEGEMAN C A , van de WIEL B A , HACK C E , Kr von dem BORNE A E G , KALLENBERG C G M , GOLDSCHMEDING R 
Published: October 2008

SUMMARY
In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor, α1antitrypsin (α1AT). In the present study we investigated whether this inhibitory effect of C-ANCA on PR3-α1 AT complexation correlates with clinical activity of WG. Serial serum samples of eight consecutive patients with histologically proven relapses of WG were tested. At the moment of relapse all sera revealed inhibitory activity towards PR3-α-1 AT complexation (median 22%, range 10–59%). Disease activity score (r=0·87, P&lt;0·02) and C-rcactive protein (CRP) levels (r= 0·66. P&lt;0·1) correlated with C-ANCA inhibition of PR3-α1 AT complexation, while they did not correlate with the C-ANCA titre detected by indirect immunofluorcsccnce (IIF) nor with IgG anti-PR3 antibody level measured by ELISA. The inhibitory effect of C-ANCA on PR3-α1 AT complexation had risen significantly at the moment of relapse compared with values 3 months (P&lt;0·05) and 6 months (P&lt;0·01) before relapse. Eight patients with established WG and positive for C-ANCA but without clinical evidence of relapse served as controls. In this group no inhibitory effect of C-ANCA on PR3-α1AT complexation was observed in 7/8 patients sera. Sera of one control patient contained moderate C-ANCA inhibitory activity towards PR3-α1AT complexalion, which remained at a constant level during the 6 months period of observation. Thus, disease activity in WG appears to be more closely related to C-ANCA inhibitory activity towards PR3-α1AT complexation.
C3 and C4 gene expression and interferon-gamma-mediated regulation in human glomerular mesangial cells
Authors: SACKS S , ZHOU W , CAMPBELL R D , MARTIN J 
Published: October 2008

SUMMARYThe glomerular mesangial cell (GMC) plays a key role in the maintenance of glomerular structure and function and in the mediation of glomerular injury. To explore the potential of this cell to produce complement and react to local inflammatory signals, we studied the synthesis and regulation of the third and fourth components of complement in cultured human GMC. Using metabolic labelling and immunoprecipitation, we found that C3 and C4 polypeptide chains were synthesized and secreted by GMC. Interferon-gamma (IFN-γ) led to an increase in C4 protein synthesis, but not C3 synthesis. There was a corresponding increase in C4 mRNA in IFN-γ-activated cells, but no increase in C3 mRNA, as determined by semi-quantitative polymerase chain reaction (PCR) estimation. These results demonstrate that human GMC can synthesize C3 and C4 proteins, and that regulation of expression of the C4 gene is mediated by IFN-γ. We hypothesize that GMC production of complement could influence the clearance of immune aggregates by the kidney and the mediation of glomerular injury.
Serum glomerular binding activity is highly correlated with renal disease in MRL/lprmice
Authors: BERNSTEIN K A , BOLSHOUN D , LEFKOWITH J B 
Published: October 2008

SUMMARYThe pathogenesis of lupus nephritis is felt to be mediated by anti-DNA antibodies. However, the anti-DNA response and renal disease do not entirely correspond. We recently developed a new assay which detects immune elements based on their ability to bind glomeruli as an alternative approach to understanding the pathogenesis of this disorder. The glomerular binding activity (GBA) defined by this assay consists of immune elements containing IgG which interact specifically with renal (issue, the binding of which is DNase-inhibitable, but which do not bind to DNA directly. In the current study we assessed the relationship between GBA and renal disease in MRL/lpr mice (both untreated and cyclophosphamide-treated) and compared it with the anti-DNA assay. Both assays were highly correlated with renal disease in untreated mice in terms of proteinuria. In cyclophosphamide-treated mice, however, only a weak correlation between the anti-DNA assay and proteinuria was apparent. GBA. in contrast, was more strongly correlated with proteinuria in treated mice. This correlation improved substantially when the DNase-sensitive component of the GBA was used. GBA appeared related to, but not covariant with, the anti-DNA response. These results demonstrate that GBA is a better correlate of murine lupus nephritis than the anti-DNA assay, and suggest that the immune elements detected by this assay, the DNase-sensitive component in particular, may be pathogenically important.
The paraproteins in systemic capillary leak syndrome
Authors: ZHANG W , EWAN P W , LACHMANN P J 
Published: October 2008

SUMMARYSystemic capillary leak syndrome (SCLS) is a rare disease characterized by episodes of collapse due to rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. The pathogenesis of this disease is unknown. The diagnosis is made largely on clinical grounds, and investigations arc unhelpful. The only consistent abnormality is that an IgG paraprotein is found in most patients, raising the possibility that the paraprotein may be involved in the pathogencsis of the disease. Reduction of the paraprotein level in our patient was associated with remission. Blood samples from three SCLS patients and one probable SCLS have been studied. All patients had monoclonal IgG paraproteins. The purified paraproteins were all of IgG1 subclass and had k light chains. However, they differed in size and charge. Antibodies against each of the paraproteins were raised in rabbits. Affinity-purified anti-idiotypic antibodies were tested for cross-reactivity against the other paraproteins using immunoblotting and Ouchtcrlony assay. These assays showed that the anti-idiotypic antibodies reacted only with the immunizing paraprotein and not with any of the other paraproteins. i.e. that the paraproteins do not share a common idiotype. Paraproteins did not bind to cultured endothelial cells, either unaclivated or following activation with interferon-gamma (IFN-γ). IL-2 or IL-6. In addition, we were unable to demonstrate any cytotoxicity towards cultured human endothelial cells by paraprolein alone, or in the presence of neutrophils (pronounced neutrophilia being a feature of attacks). The relationship between the paraproteins and the disease remains unclear. It is likely that additional, as yet unidcntilied. factors arc required for the paraprotein to lead to capillary leak.
The presence of immunosuppressive ‘p15E-like’ factors in the serum and urine of patients suffering from malign and benign breast tumours
Authors: STÖGER H , WILDERS-TRUSCHNIG M , SAMONIGG H , SCHMID M , BAUERNHOFER T , TIRAN A , TAS M , DREXHAGE H A 
Published: October 2008

SUMMARYCertain types of tumours are capable of producing factors inhibiting mononuclear phagocyte chemotaxis which may contribute to defects in imtnunosurveillance. In head and neck cancer these factors are said to be related to the retroviral protein p15E. This study examines the presence of p15E-like factors in serum and urine of patients with malign and benign breast tumours. Thirty patients with breast cancer, 29 patients with benign breast masses, and 28 healthy controls were tested blindly with the monocyte polarization assay, using N-formyl-methionyl-leueylphenylalanine as chemoattractant. The low molecular weight fractions prepared of sera of the malign tumour patients inhibited the monocytc polarization significantly (mean inhibition 34%, s.d. = 12) compared with those of benign tumour patients (15%, s.d. = 7) and of controls (14%, s.d. = 6). The observed inhibitory effects on the monocyte polarization could be compensated by MoAbs reactive to p15E-related antigens. The mean difference between the polarization inhibition with and without anti-p15E adsorption (the ‘p15E-likc factor-induced inhibition’) was 25% (s.d. = 13) in the breast cancer group, compared with 7% (s.d. = 5) in the benign tumour patients and 5% (s.d. = 4) in the healthy control group. Surgical removal of the tumours resulted in a restoration of the monocytc polarization in 20/23 (87%) patients of the breast cancer group. Results testing preoperative urine samples correlated well with those of corresponding sera. These data give additional support to the concept that tumour-derived p15E-like factors are responsible for the inhibitory effect on monocytc chemolaxis in breast cancer patients, and that these factors can be found in serum as well as in urine.
IgG inhibits the increase of platelet-associated C3 stimulated by anti-platelet antibodies
Authors: NOMURA S , MIYAZAKI Y , MIYAKE T , YAMAGUCHI K , KIDO H , KAWAKATSU T , FUKUROI T , KAGAWA H , SUZUKI M , YANABU M , KOKAWA T 
Published: October 2008

SUMMARYWe investigated the increase of platelet-associated IgG and complement component 3 (C3) caused by the in vitro action of anti-platelet MoAbs, and the effect of mouse and human IgG on these events. Anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib MoAbs caused a slight increase of C3. but not of platelet-associated IgG. In contrast, anti-CD9and anti-Fcγ II receptor MoAbs caused an increase of both platelet-associated C3 and IgG. In particular, three MoAbs which activated the complement system caused a marked increase of C3. When platelet-rich plasma was treated with aspirin and prostaglandin E1 before incubation with antibodies, the increase of platelet-associated IgG was inhibited in all cases. In contrast, the increase of platelet-associated C3 was scarcely influenced. These results suggest that the binding to platelets of platelet-activating antibodies caused the increased expression of IgG molecules on the platelet surface and a possible increase of platelet-associated IgG. However, the increase of platelet-associated C3 appeared to depend on specific characteristics of the antibodies tested, such as a complement-activating effect. In addition, intact mouse or human IgG inhibited the increase of platelet-associated C3 caused by complement-activating antibodies, while F(ab′)2 mouse or human IgG had no such effect. This suggested that the Fc portion of IgG may block the increase of C3 mediated by anti-platelet antibodies.
A novel flow cytometric assay for the quantification of adhesion of subsets within a heterogeneous cell population; analysis of lymphocyte function-associated antigen-1 (LFA-l)-mediated binding of bone marrow-derived primary tumour cells of patients with multiple myeloma
Authors: AHSMANN E J M , BENSCHOP R J , de GRUYL T D , FABER J A J , LOKHORST H M , BLOEM A C 
Published: October 2008

SUMMARYIn a previous study the expression of the adhesion molecule LFA-1 on tumour cells in patients suffering from multiple myeloma (MM) was correlated with growth of the malignant plasma cells in vivo. Here we describe a novel in vitro flow cytometric adhesion assay (FCAA) which, based on scatter and fluorescence properties, was used to analyse the contribution of the LFA-1/intercellular adhesion molecule-1 (ICAM-1) adhesion pathway in the binding of bone marrow (BM)-dcrived LFA-1-positive primary tumour cells of patients with MM to interferon-gamma (IFN-γ)-activated, ICAM-1-positive, human venous umbilical endothclial cells (huVEC) in vitro. To validate the FCAA. cells from different myeloma cell lines were labelled with the fluorescent dye CFDA or stained for CD38 expression, and LFA-1-mediated adhesion to IFN-γ-activated endothclial cells was quantified. Results obtained with the FCAA were compared with a conventional adhesion assay employing 51Cr-labelled cells. Statistical analysis revealed that both assays gave similar results. This allowed analysis of the contribution of LFA-1 to the adhesive potential of malignant plasma cells in bone marrow mononuclcar cells (BMMC) from MM patients to IFN-γ-activated endothclial cells. The results prove that LFA-1 expressed on bone marrow-derived plasma cells from MM patients can be used for cellular adhesion to ICAM-1 expressed on adherent growing cells, and are suggestive fora role of the LFA-1/ICAM-1 adhesion pathway in the pathophysiology of MM. The FCAA described in this study is a generally applicable assay, allowing analysis of the interaction of distinct subpopulations with in vitro grown adherent cells of different origin.
IL-2 receptor gene expression and IL-2 production by human preterm newborns' cells
Authors: BESSLER H , SIROTA L , NOTTI I , MILO T , DJALDETTI M 
Published: October 2008

SUMMARYIL-2 receptor (IL-2R) gene expression in human umbilical cord blood mononuclear cells (CBMC) of preterm and term newborns was examined following stimulation for 18 h with phytohaemagglutinin (PHA) and compared with that of adult peripheral blood mononuclear cells (PBMC: mothers and control group). mRNA for IL-2R could not be detected in CBMC of preterm infants, whereas the mRNA levels for IL-2R found in full term neonales were similar to those observed in PBMC of adults. IL-2 activity in conditioned medium (CM) of mononuclear cells stimulated with either optimal or suboptimal PHA concentrations for 24 h and 48 h was also determined. At 24 h of stimulation, IL-2 activity found in CM obtained from CBMC of preterm and term newborns was significantly higher than that found in CM of adults' PBMC. A further enhancement of IL-2 activity (six to eight times) was observed in CM of preterm and term cells stimulated for 48 h. whereas no significant difference was found in IL-2 activity in CM from adult cells tested at the two incubation periods. The present findings may provide an additional explanation for the impaired function of the immune system, and the high susceptibility to infections observed in preterm newborns.