bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low activity of the classical complement pathway predicts short survival of patients with chronic lymphocytic leukaemia
Authors: Varga L , Czink E , Miszlai ZS , PÁLÓCzi K , BÁNyai A , Szegedi G , FÜSt G 
Published: July 2010

SUMMARYThe activities of the classical (CP) and alternative (AP) complement pathways as well as the levels of some complement components and circulating immune complexes were measured in 43 patients with chronic lymphocytic leukaemia (CLL) between 1980 and 1984. Depressed C P activities were frequently found in these patients. Clinical course of the disease in the patients was followed until 1992, and compared with the initial complement values. During the follow-up period 36 patients died, death of 33 patients being related to the underlying disease. A strong positive correlation (P &lt; 0.01) was found between the length of survival of the patients and the initial CP values. Patients were divided into two groups: group A, short-term survivors, i.e patients who died in CLL-related complications within 3 years after the complement measurements; and group B, long-term survivors who died ≥ 4 years after the complement measurements due to any cause, or were alive at the end of the follow-up period. Average CP values in Group B were almost twice those in group A (P= 0.002), and a similar but less pronounced difference was found in C3 levels (P= 0.055). These differences were even more marked (P= 0 0006 and P= 0.0015, respectively) when only patients in Rai stage 2 and 3 were considered. Low classical pathway activities predicted short survival time: according to the logrank test, patients in Rai stage 2–3 with low (&lt; mean − 2 s.d. of the normal values), and normal CP levels survived for 2.0 ± 1.1, and 4.6 ± 3.0 years, respectively. All the nine and 11/13 patients with low CP and C4 levels, respectively, died within 3 years after the complement measurements were made. These findings indicate that complement measurements performed in CLL patients have a clinical value.
Effect of IL-4 and interferon-gamma (IFN-γ) on IL-3- and IL-5-induced eosinophil differentiation from human cord blood mononuclear cells
Authors: Ochiai K , Iwamoto I , Takahashi H , Yoshida S , Tomioka H , Yoshida S 
Published: July 2010

SUMMARYIL-4 and IFN-γ positively and negatively regulate allergic inflammation. To determine the regulatory mechanisms of eosinopoiesis by cytokines, we examined the effect of recombinant IL-4 and IFN-γ and of anti-IL-4 and anti-IFN-γ antibodies on IL-3- and IL-5-induced eosinophil differentiation from human umbilical cord blood mononuclear cells. rhIL-4 (10–300 U/ml) inhibited IL-3- and IL-5-induced eosinophil differentiation from cord blood mononuclear cells on day 28 of culture by 62–81% in a concentration-dependent manner. rhIFN-γ (5–500 U/ml) also inhibited IL-3- and IL-5-induced eosinophil differentiation by 80–99% in a concentration-dependent manner. The inhibitory effect of rhIL-4 and rhIFN-γ was observed only when rhIL-4 or rhIFN-γ were present in the culture from day 0 to day 14, but not from day 15 to day 28. Addition of anti-IL-4 antibody to the culture enhanced IL-3- and IL-5-induced eosinophil differentiation on day 28 of culture by 30%, whereas anti-IL-2 MoAb and anti-IFN-γ MoAb had no significant effect. These results indicate that IL-4 and IFN-γ have inhibitory effects on IL-3-and IL-5-induced eosinophil differentiation from its progenitor cells.
IL-4 induces neutrophilic maturation of HL-60 cells and activation of human peripheral blood neutrophils
Authors: Bober L A , Waters T A , Pugliese-Sivo C C , Sullivan L M , Narula S K , Grace M J 
Published: July 2010

SUMMARYIL-4 is a T-helper cell derived cytokine that has effects on myelomonocytic cell maturation and activation. We have studied the effect of IL-4 on neutrophilic maturation using the cell line HL-60 and found that it has a profound effect on the maturation and activation of the cell line. The treatment of HL-60 cells with recombinant hu IL-4 (0.15 to 15.0 ng/ml) induced a shift in the percentage of HL-60 cells staining positive for chloroacetate esterase enzyme activity (indicating commitment to the neutrophilic lineage). IL-4 increased surface expression of the neutrophil-lineage antigen WEM G11, the complement receptors CR3 (CD11b) and CR1 (CD35), but not for the monocyte differentiation antigen CD14. IL-4 treated HL-60 cells demonstrated enhanced Fc- and complement-mediated phagocytic capacity and increased hexose-monophosphate shunt activity. In addition, IL-4 was capable of sustaining the neutrophil maturation of HL-60 cells that had been pre-treated for 24h with DMSO. To investigate the effect of IL-4 on the mature neutrophil, we studied freshly isolated and rested human peripheral blood neutrophils. In the absence of other stimuli, neutrophils were induced by IL-4 to have significantly elevated phagocytic responses. The response was specific since treatment with anti-human IL-4 abolished phagocytic stimulation. Finally, IL-4 treatment also stimulated resting neutrophils to migrate toward zymosan-activated serum (ZAS) and human IL-5. The results demonstrate that IL-4 is a potent maturation factor for myelocytes to become neutrophils and that IL-4 can stimulate resting mature neutrophils.
Autoproliferation in HIV-1-infected patients undergoing active HIV-1-specific immunotherapy
Authors: TRAUGER R J , GIERMAKOWSKA W , WORMSLEY S , TURNER J , JENSEN F C , CARLO D J 
Published: July 2010

SUMMARYWe have observed a treatment-associated autoproliferative response in cultured peripheral blood mononuclear cells (PBMC) of asymptomatic HIV-1-infected subjects receiving a gp120-depleted, inactivated HIV-I antigen in incomplete Freund's adjuvant (IFA; HIV-I Immunogen). The frequency and magnitude of the autoproliferative response appeared to be dose-related (P&lt;0.05), and was not observed in subjects receiving IFA alone. Immunophenotyping of the proliferating cells demonstrated the presence of both CD4+ and CD8+ lymphocytes, with the CD4+ blasts almost exclusively expressing the CD45RO+ phenotype. A comparison of this response with the HIV-1-specific antigen stimulation responses in this cohort revealed a significant correlation between increases in HIV-1-specific cell-mediated immunity and autoproliferation (r2= 0.61, P &lt; 0.001). These findings suggest that immunization with the HIV-1 Immunogen induces an autoproliferative response that may reflect changes in HIV-1-specific cell-mediated immunity in infected individuals.
Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4
Authors: FRENCH M A H , DENIS K A , DAWKINS R , PETER J B 
Published: July 2010

SUMMARY
In order to define abnormalities of humoral immunity which determine susceptibility to respiratory tract infections in IgA-deficient adults, serum IgG subclass concentrations, and serum concentrations of pneumococcal antibodies and Haemophilus influenzae type B (Hib) antibodies sera from IgA-deficient adults with and without susceptibility to respiratory tract infections were compared. Infection susceptibility was not related to the degree of IgA deficiency, but was related to deficiency of IgG4 and, to a lesser extent, IgG2, as well as to low basal serum concentrations of pneumococcal polysaccharide antibodies. The combination of IgG2 and/or IgG4 deficiency and a non-protective basal serum concentration of antibody against two or more pneumococcal polysaccharides was present in the serum of six of 12 (50%) patients with severe infections, but only one of 44 (2%) patients without infections. Furthermore, the preservation of antibody responses against the most immunogenic pneumococcal polysaccharide type 3, but not against the less immunogenic types 7F, 9N and 14, in patients with severe infections suggested that abnormalities of pneumococcal polysaccharide antibody responses might include defects of affinity maturation.
Presentation of cartilage proteoglycan to a T cell hybridoma derived from a mouse with proteoglycan-induced arthritis
Authors: BRENNAN F R , NEGROIU G , BUZÁS E I , FÜLÖP C , HOLLÓ K , MIKECZ K , GLANT T T 
Published: July 2010

SUMMARYImmunization of BALB/c mice with human fetal cartilage proteoglycan (PG) produces progressive polyarthritis, and T ceils play key roles in the development of the disease. To gain an understanding of how PG is presented to autoreactive T cells by synovial antigen-presenting cells (APC), we examined the abilities of various syngeneic APC in presenting PG to a specific T ceil hybridoma 5/4E8, derived from a mouse with PG-induced arthritis. A20 B lymphoma cells and spleen cells were strong presenters of PG, but synoviocytes and P388D1 macrophages could only present PG effectively after stimulation with interferon-gamma (IFN-γ). The IFN-γ exerted its effect by up-regulating both MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression by these cells as neutralizing antibodies to Ia, LFA-1 and ICAM-1 inhibited presentation. Our studies also showed that synoviocytes and spleen cells took up and processed PG more rapidly than the cell lines. Cysteine and serine protease-dependent antigen presentation of PG was blocked at 4°C, 18°C and by chloroquine treatment, indicating that presentation required active uptake and processing in an acidic compartment, probably in lysosomes. Also, keratan sulphate-depleted and cyanogen bromide (CNBr) and 2-nitro-5-thiocyanobenzoic acid (NTCB)-cleaved PG elicited stronger T cell responses, as they were more easily processed than the native molecule. Furthermore, CNBr-generated peptides were presented by fixed APC, indicating that core protein fragments of cartilage PG can be presented directly by APC in context with MHC class II molecules.
Two phenotypically distinct B lymphocytes (IgMhighIgDlow and IgMlowIgDhigh) in chronic gastric ulcer in the rat
Authors: OHMIYA N , ITO M , OHBAYASHI M , ARISAWA T , GOTO H , TSUKAMOTO Y , HAYAKAWA T , ASAI J 
Published: July 2010

SUMMARY
We determined the kinetics and phenotypes of infiltrating B cells in gastric ulcer in the rat induced by gastric injection of acetic acid (day 0). Few B cells were found in the lesion in the early stages of ulceration. On day 40, two kinds of B cells with phenotypes of IgMhighIgDlowOX33 (CD45)+OX19 (CD5)- and IgMlowIgDhighOX33 (CD45)+ OX19(CD5)- were scattered in the granulation tissue of open ulcers, but not in the healed scar tissue. On day 180, those two kinds of B cells formed primary follicles in the granulation tissue of open ulcers, but were absent from the healed scar tissue. The IgMhighIgDlowOX33 (CD45)+OX19 (CD5)- B cell was considered to be identical to the marginal zone B cell of rat spleen. This phenotype of B cell might be associated with inflammatory process in chronic gastric ulcer.
Autoantigenic epitopes on eukaryotic L7
Authors: VON MIKECZ A H , HEMMERICH P H , PETER H-H , KRAWINKEL U 
Published: July 2010

SUMMARYRibosomal protein L7 has been established recently as a novel autoantigen representing a frequent target for autoantibodies from patients with systemic autoimmune diseases. Up to 75% of systemic lupus erythematosus (SLE) patients and 50% of mixed connective tissue disease (MCTD) and progressive systemic sclerosis (PSS) patients produce antibodies against in vitro translated L7 and form immunoprecipitable complexes. In this study the B cell response to protein L7 was investigated with respect to the immunogenic determinants recognized by autoantibodies. Eighteen truncated fragments of protein L7 were generated as recombinant fusions with glutathione-S-transferase and examined by immunoblotting for their reactivity with sera from patients suffering from systemic rheumatic diseases. Anti-L7 antibodies target three major non-overlapping autoepitopes. Two epitopes reside in the highly conserved C-terminal part of the protein, whereas the N-terminal autoepitope is not conserved during evolution. The N-terminal epitope comprises 24 amino acid residues. Ten amino acid resides of this epitope are shared with the BZIP-like RNA binding domain of protein L7. Autoantibodies recognizing this epitope cross-react with the corresponding region of a L7 homologue, namely ribosomal protein L7 (RPL7) from Dictyostelium discoideum. This indicates that amino acid residues 14VPE…KKR22, which are conserved between humans and fungi, contribute essentially to the formation of autoantibody-autoantigen complexes.
Detection of anti-topoisomerase I antibodies using a full length human topoisomerase I recombinant protein purified from a baculovirus expression system
Authors: WHYTE J , EARNSHAW W C , CHAMPOUX J J , PARKER L H , STEWART L , HALL N D , MCHUGH N J 
Published: July 2010

SUMMARYTopoisomerase I (topo I) is a major systemic sclerosis (SSc)-associated autoantigen. A cDNA construct encoding full length human topo I in a recombinant baculovirus transfer vector was used to infect insect cells in culture from which recombinant protein was purified. An ELISA using recombinant protein was evaluated in 340 sera including sera from 134 patients with SSc, of whom 33 had anti-topo I antibodies detected by immunodiffusion. A high yield of pure topo I of expected molecular mass and catalytic activity was obtained. The recombinant topo I ELISA was 92% sensitive and 98% specific in detecting anti-topo I antibodies which were present almost exclusively in patients with SSc. Therefore, the potential advantages of expressing human autoantigens in eukaryotic systems for diagnostic purposes were confirmed.
Increased expression of intercellular adhesion molecule-1 (ICAM-1) in a murine model of pulmonary eosinophilia and high IgE level
Authors: CHU H W , WANG J M , BOUTET M , BOULET L-P , LAVIOLETTE M 
Published: July 2010

SUMMARYT lymphocytes and eosinophils are probably involved in the pathogenesis of allergic broncho-pulmonary aspergillosis (ABPA), a disease characterized by pulmonary eosinophilia and high serum and lavage IgE levels. We recently developed a murine model of ABPA. To investigate the mechanisms of T lymphocyte and eosinophil recruitment to the lung in this disease, we examined the expression of ICAM-1 In the lung tissue of mouse challenged with Aspergillus fumigatus (Af) antigen. C57B1/6 mice were intranasally exposed to Af (Af group) or saline (control group) three times a week for 1, 2 or 3 weeks. On days 4, 7, 14 and 21, mice were killed and lung tissue was fixed in acetone and embedded in glycol methacrylate. Serial μm sections were stained with chromotrope 2R and MoAbs against ICAM-I. CD11a/CD18 (LFA-1) and CD3. Af-challenged mice presented significant increases in eosinophil, T lymphocyte and LFA-1-positive cell count and up-regulated expression of ICAM-1 in the lung tissue at all the time points examined. ICAM-1 expression intensity correlated with the number of T lymphocytes (r= 0·59, P &lt;0·01), LFA-1-positive cells (r= 0·68, P &lt; 0·001), but not of eosinophils (r=−0·24, P &gt; 0·05). These findings suggest that up-regulation of ICAM-1 expression is involved in the inflammatory process of this murine model of ABPA, and that this up-regulation may be more relevant to the T lymphocyte accumulation in the lung.
Antibodies to acetylcholinesterase cross-reacting with thyroglobulin in myasthenia gravis and Graves' disease
Authors: MAPPOURAS D G , PHILIPPOU G , HARALAMBOUS S , TZARTOS S J , BALAFAS A , SOUVATZOGLOU A , LYMBERI P 
Published: July 2010

SUMMARYIn the present study we analysed by ELISA the ability of sera from 50 patients with myasthenia gravis (MG), 20 with Hashimoto's thyroiditis (HT), 53 with Graves’ disease (GD) and 36 healthy controls (CR) to react with acetylcholinesterase (AChE) from Electrophorus electricus and human thyroglobulin (Tg). Significantly increased anti-AChE activity was exhibited by a high proportion of MG (IgG 36%) and GD (IgG 21%) sera, while increased anti-Tg activity was detected in all three patient groups (MG, IgG 26% and IgA 26%; HT, IgG 85% and IgA 40%; and GD, IgG 51%). Interestingly, a significant proportion of MG and GD sera exhibited both IgG anti-AChE and anti-Tg activities (MG, 18%; P&lt;0·001; and GD, 15%; P&lt;0·001, versus CR, 0%). This bi-reactivity was exhibited by anti-AChE antibodies cross-reacting with Tg (anti-AChE/Tg activity); (i) serum anti-AChE activity was effectively inhibited by soluble Tg, and (ii) affinity-purified anti-Tg antibodies cross-reacted with AChE. Cross-reactivity seems to be a property of pathological (auto) antibodies; induced (rabbit) antibodies to AChE or Tg were highly mono-specific. Analysis of clinical data showed that increased IgG anti-AChE/Tg activity was well associated with: (i) overlapping GD in MG (P&lt;0·02), and (ii) ophthalmopathy in GD (P&lt;0·01). In contrast, no correlation was noted in MG between anti-AChE activity units and anti-Tg activity units or acetylcholine receptor antibody titres. The clinical significance of anti-AChE/Tg antibodies remains to be elucidated.
The influence of allo-class II MHC-specific Th2 cells on the generation of CD4 and CD8 cytotoxic T cells to associated class I and class II MHC alloantigen
Authors: WOOD P J , COSSENS I A 
Published: July 2010

SUMMARYThere is considerable interest in whether CD4 T cell function can affect the outcome of allogeneic transplants. In mice tolerant to an isolated class II MHC disparity, the normal Th1 activity in vitro associated with graft rejection is switched to Th2 in tolerant animals. Because clinical transplants involve multiple class I and II MHC disparities we tested how the switch to Th2 activity of tolerant mice would affect the generation of CD4 and CD8 cytotoxic T cells (CTL) against MHC alloantigens to which the mice were not tolerant. A.TH mice (KkIsDd) were rendered neonatally tolerant of A.TL (KkIkDd) and the generation of CD4 or CD8 CTL measured in a mixed lymphocyte reaction (MLR) against (A.TLxB6)F1 stimulators. Normal mice generated CD4 CTL against both A.TL and B6 (KbIbDb), but tolerant mice were unable to generate cytotoxicity against either A.TL or B6. However, tolerant cells were able to generate CD8 CTL against B6. IL-4 inhibited the generation of CD4, but not CD8, CTL by normal cells and anti-IL-4 antibody was shown to increase the generation of CD4 CTL against B6 in F1 stimulated cultures. Overall the results showed that a Th2 response could inhibit the generation of CD4 CTL against concomitant alloantigen in a process at least partially involving IL-4, but that, conversely, tolerant Th2 cells could help in the generation of CD8 CTL. The results suggest that with whole MHC disparities a simple change of CD4 T cells to Th2 would not be enough to procure graft acceptance.
Two novel cationic staphylococcal proteins induce IL-2 secretion, proliferation and immunoglobulin synthesis in peripheral blood mononuclear cells (PBMC) of both healthy controls and patients with common variable immunodeficiency (CVID)
Authors: JAHREIS A , YOUSIF Y , RUMP J A , DRÄGER R , VOGT A , PETER H H , SCHLESIER M 
Published: July 2010

SUMMARYTwo cationic proteins, a neutral phosphatase (NP-tase) and a 70-kD protein (p70) were isolated from Staphylococcus aureus by ion exchange chromatography. We compared their properties to those of the well established B cell mitogen of whole, fixed Staph. aureus strain Cowan I cells (SAC). Both purified proteins were able to induce immunoglobulin synthesis in PBMC cultures of healthy donors. NP-tase and p70 also induced immunoglobulin synthesis of PBMC from those patienis with CVID who were also responsive to SAC plus IL-2 stimulation. Immunoglobulin synthesis in response to NP-tase and to p70 was time- and dose-dependent and could be inhibited by addition of specific antibodies against the proteins. In contrast to SAC, no addition of exogenous IL-2 was necessary to obtain maximal immunoglobulin synthesis induced by NP-tase or p70. However, neither protein was able to induce immunoglobulin synthesis in B cell-enriched cultures. High amounts of IL-2 were found in supernatants of PBMC from healthy donors following stimulation with low concentrations of NP-tase or p70, and this was associated with vigorous lymphocyte proliferation. Both proteins behave like typical antigens, and not like lectins or superantigens, since an NP-tase-stimulated T cell line showed an antigen-specific, MHC-restricted secondary response. In addition, no preferential T cell receptor Vβ chain usage was found with eight Vβ-specific MoAb. It is likely that the two proteins induce antigen-specific T cell activation, which is then followed by polyclonal activation of B cells via CD40 receptors and cytokine release
Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells from common variable immunodeficiency (CVI) patients
Authors: Ferrer J M , Iglesias J , HernÁNdez M , Matamoros N 
Published: July 2010

SUMMARYThe failure of B cells from CVI patients to secrete normal amounts of antibodies has been attributed either to an intrinsic B cell defect or to a lack of cooperation from T cells. In an attempt to improve the definition of the origin of this defect in one of the main cellular compartments, we studied the ability of helper CD4 cells and their CD4 CD45RO subpopulation from CVI patients to secrete interleukins (IL-2 and IL-4) in response to mitogen stimulation. We found that CD4 and CD4 CD45RO cells from some patients secrete abnormal amounts of interleukins (in general low levels of IL-2 and high levels of IL-4) upon stimulation with pokeweed mitogen (PWM). These irregularities may contribute to the defective differentiation of B cells in these patients.
Expression of vascular adhesion molecules on human endothelia in autoimmune thyroid disorders
Authors: Marazuela M , SÁNchez-Madrid F , Acevedo A , LarraÑAga E , De LandÁZuri M O 
Published: July 2010

SUMMARY
Cellular activation and expression of certain adhesion molecules within vascular endothelium is a critical event in leucocyte recruitment and emigration. A wide array of different adhesion receptors has been identified to mediate the interaction between endothelial cells (EC) and leucocyte subpopulations. In this study, the tissue expression of E-selectin, P-selectin, CD31, and endoglin endothelial cell adhesion molecules was studied on thyroid tissue from patients with Graves’ disease (GD) and Hashimoto's thyroiditis (HT), We found an up-regulated expression of E-selectin in EC in GD and HT thyroids, specifically in those areas more severely inflamed, with no reactivity in control thyroids, P-selectin was basally expressed in postcapillary venules in control glands, with an increased expression in HT and GD glands. On the other hand, increased CD31 expression was found on perifollicular, small and large venule EC from GD and HT glands, that correlated with the severity of mononuclear infiltration. In addition, CD31 expression was observed in some intrathyroidal macrophages and T cells in close proximity to CD31+ EC. Furthermore, a markedly enhanced expression of endoglin, a transforming growth factor-beta binding protein, was mainly located on perifollicular EC and EC from small venules as well as In adjacent macrophages from GD and HT thyroid glands. This enhanced expresion of E- and P-selectins, CD31 and endoglin by thyroid EC in GD and HT may reflect their ability to regulate leucocyte trafficking and activation.