bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclophosphamide treatment antagonizes thein vitrodevelopment ofMycobacterium lepraemurium-induced suppressor cell precursors
Authors: GOSSELIN D , TURCOTTE R , LEMIEUX S 
Published: August 2010

SUMMARYThe in vitro-inducible maturation of splenic suppressor cell precursors detected during the early phase of Mycobacterium lepraemurium infection can be abrogated when a high dose of cyclophosphamide (Cy) is inoculated to infected mice 2 days before assay. The drug does not act directly on adherent suppressor cell precursors, but rather inhibits their activation by a non-adherent cell subset whose phenotype has not yet been elucidated. It was established by flow cytometry analyses, that despite a marked increase in the total number of splenic non-adherent cells following M. lepraemurium infection, the effect of Cy on Ia+, Thy-1+, CD4+ and CD8+ cells in infected mice was comparable to that observed in normal controls. It was not possible to determine the duration of the inhibiting effect of Cy on non-adherent regulatory cells, because the drug was itself inducing suppressor cells from 7 days after inoculation. By the time spleen cell suspensions were totally free of Cy-induced suppressor cells, infection-dependent suppressor cell precursors were once again detected, indicating that Cy treatment did not prevent their in vivo accumulation. Therefore, even though M, lepraemurium induced adherent suppressor cell precursors are themselves fully resistant to Cy, their development is transiently abrogated by the drug, most probably through the impairment of a non-adherent cell subset regulating their maturation.
T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis
Authors: PANDOLFI F , TRENTIN L , MARTIN J E SAN , WONG J T , KURNICK J T , MOSCICKI R A 
Published: August 2010

SUMMARYT lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the β chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.
Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features
Authors: AUKRUST P , FRØLAND S S , MÜLLER F 
Published: August 2010

SUMMARY
Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P &lt; 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs=– 0.61, P &lt; 0.005 and rs=– 0.83, P &lt; 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs=– 0.58, P &lt; 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.
Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating γδ+ T cells is correlated with disease activity
Authors: LAMOUR A , JOUEN-BEADES F , LEES O , GILBERT D , LE LOET X , TRON F 
Published: August 2010

SUMMARYThe phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on γδ+ T cells and CD4−CD8−αβ+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages or CD4−CD8−αβ+ T cells in patients and controls; (ii) a significant decrease of the γδ+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating γδ+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/γδ+ T cells was significantly higher in patients with active disease. HLA-DR+/γδ+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated γδ+ T cells were predominantly Vδ1. Taken together, these data support the involvement of γδ+ T cells in the pathogenesis of RA.
Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta
Authors: COOPER W O , FAVA R A , GATES C A , CREMER M A , TOWNES A S 
Published: August 2010

SUMMARYWe examined whether tumour necrosis factor (TNF) or transforming growth factor-beta 1 (TGF-β1) could alter the course of collagen-induced arthritis (CIA). Injection of 100 ng TNF or 500 ng TGF-β1 into ankle joints of normal rats induced a very limited inflammatory response, observable only upon histological analysis. However, when injected into ankle joints of rats 9 days after immunization with bovine type II collagen (CII), identical doses of TNF or TGF-β1 induced a sustained, clinically obvious inflammation and oedema that began within 8 h on average, as compared to 90 h in CII-inimunized control rats given no injections or intra-arlicular injections of buffer. The incidence of arthritis at 2 weeks post-immunization was 100% for TNF-injected hindpaws, compared with 55% for the control groups, a statistically significant difference. In rats passively immunized with a subarthritic dose of affinity purified antibody to rat-CII, intra-articular injection of 100 ng TNF or 500ng of TGF-β1 also induced intense, though transient arthritis. The rapid proinflammatory effects in CIA described in this study and the synergy demonstrated between anti-CII IgG and either cytokine, suggest that these cytokines can participate locally in the pathogenesis of arthritis.
Interferon-gamma (IFN-γ) and macrophage inflammatory proteins (MIP)-1 and -2 are involved in the regulation of the T cell-dependent chronic peritoneal neutrophilia of mice infected with mycobacteria
Authors: APPELBERG R 
Published: August 2010

SUMMARYIn mycobacterial infections of mice there is a chronic, immune-mediated mobilization of neutrophils to the infectious site. In this study we evaluated the role played by cytokines in the chronic peritoneal neutrophilia which occurs in mice intraperitoneally infected with Mycobacterium bovis BCG or M. avium. Antibodies to IFN-γ and to MIP-1 and -2 were effective in reducing peritoneal neutrophilia when given during the infection. Whereas the former antibody was only effective when given early, the latter two were effective when administered late in infection, suggesting the MIPs were direct mediators of neutrophil recruitment. Recombinant IFN-γ given intraperitoneally induced the accumulation of neutrophils and primed the peritoneal cells for an enhanced recruitment of neutrophils. Our data show that chronic neutrophilia during mycobacterial infection is regulated by different cytokines acting at different stages and levels of neutrophil recruitment.
Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase
Authors: FALK R J , BECKER M , TERRELL R , JENNETTE J C 
Published: August 2010

SUMMARY
We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in patients with systemic vasculitis react with a conformational epitope or epitopes on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a monoclonal anti-MPO antibodies were reacted with MPO in native and denatured states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and a 120-kD band representing the MPO hologenzyme, but not with denatured MPO fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity with native and denatured MPO in dot blot and Western blot analyses. Both polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not. These data suggest that (i) MPO-ANCA interact with a conformational epitope on the MPO molecule; and (ii) MPO-ANCA from different patients have similar reactivity with native versus denatured MPO.
Severe malaria in Gambian children is not due to lack of previous exposure to malaria
Authors: ERUNKULU O A , HILL A V S , KWIATKOWSKI D P , TODD J E , IQBAL J , BERZINS K , RILEY E M , GREENWOOD B M 
Published: August 2010

SUMMARY
The reasons why only a small proportion of African children infected with Plasmodium falciparum develop severe or fatal malaria are not known. One possible reason is that children who develop severe disease have had less previous exposure to malaria infection, and hence have less acquired immunity, than children who develop a mild clinical attack. To investigate this possibility we have measured titres of a wide range of anti-P. falciparum antibodies in plasma samples obtained from children with severe malaria, children with mild malaria and from children with other illnesses. Mean antibody levels in patients with malaria were higher than those in patients with other conditions but. with only one exception, there were no significant differences in antibody litres between cases of severe or mild malaria. A parasitized-erythrocyte agglutination assay was used to estimate the diversity of parasite isolates to which children had been exposed; plasma samples obtained from children with cerebral malaria recognized as many isolates as did samples obtained from children with mild disease. Our findings do not provide any support for the view that the development of severe malaria in a small proportion of African children infected with P. falciparum is due to lack of previous exposure lo the infection.
Potentiation of a weakly active ricin A chain immunotoxin recognizing the neural cell adhesion molecule
Authors: DERBYSHIRE E J , STAHEL R A , WAWRZYNCZAK E J 
Published: August 2010

SUMMARY
A ricin A chain immunotoxin, SEN36-ricin A chain, directed against the neural cell adhesion molecule (N-CAM) had no selective cytotoxic activity against three different small cell lung cancer (SCLC) cell lines in tissue culture despite expression of the target antigen on more than 98% of cells in each line detected by indirect immunofluorescence. Treatment of the SW2 SCLC cell line with suramin and interferons alpha and gamma increased the level of N-CAM expression only slightly and had no significant effect on the cytotoxic activity of the SEN36 immunotoxin. In the presence of the carboxylic ionophore monensin at a concentration of 0·1 μM, the toxicity of SEN36-ricin A chain to the SW2 cell line was enhanced by 12 000-fold. In contrast, lysosomotropic amines showed little or no potentiation of activity, suggesting that lysosomal degradation was not the major factor limiting the action of the anti-N-CAM immunotoxin. The findings of this study indicate that ricin A chain immunotoxins directed against N-CAM on SCLC are unlikely to have sufficient activity to be useful therapeutic agents in the absence of potentiating agents such as monensin, which can interfere with the normal intracellular pathways of antigen routing.
Mononuclear cells from HIV-infected patients produce factors which enhance functional activity of polymorphonuclear neutrophils from healthy subjects
Authors: GABRILOVICH D I , SHEPELEVA G K , SEREBROVSKAYA L V , AVDEEVA L A , SUVOROVA Z K , ROSLY I M , OGANEZOV V K , SAIDOV M Z , PANYUTICH A V , POKROVSKY V V 
Published: August 2010

SUMMARYThe influence of mononuclear cell supernatants (MNCS) from nine healthy donors and 35 HIV-infected patients (17 with lymphoadenopathy syndrome (LAS), 15 with ARC and three with AIDS) on functional activity of polymorphonuclear neutrophils (PMN) from healthy donors was investigated. MNC after short-term cultivation (24 h) produced factors which enhanced chemiluminescence (CL) and chemotaxis of PMN. This augmentation did not depend on stimulation of MNC by mitogens (lipopolysaccharide Escherichia coli (LPS) and concanavalin A (Con A)) or on activation of PMN by FMLP. After 48 h of cultivation only MNC stimulated by LPS produced these factors. MNCS from HIV-infected patients provoked a more pronounced augmentation of PMN CL compared with MNCS from healthy subjects. This enhancement was observed in patients at all stages of infection, but was more pronounced in patients with LAS, MNCS impact on PMN CL was not connected with proliferative activity of MNC but was correlated with the level of CD4 cells. It was shown that removal of adherent cells from MNC fraction resulted in decreased MNCS impact. Treatment of MNCS by antibody to IL-1β, IL-8, interferon-alpha (IFN-α) and tumour necrosis factor-alpha (TNF-ş) did not decrease MNCS impact on PMN CL.
Predictors of infection in chronic lymphocytic leukaemia (CLL)
Authors: GRIFFITHS H , LEA J , BUNCH C , LEE M , CHAPEL H 
Published: August 2010

SUMMARY
A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P=8·8 × 10−11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P=4·9 × 10−4). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P= &lt;0·00001).
The macrophage response to bacteria. Modulation of macrophage functional activity by peptidoglycan fromMoraxella (Branhamella) catarrhalis
Authors: KELLER R , GUSTAFSON J E , KEIST R 
Published: August 2010

SUMMARYMoraxella (Branhamella) catarrhalis organisms have been shown to be particularly efficient in inducing in a pure population of bone marrow-derived mononuclear phagocytes secretory and cellular activities. In the present study, the ability of peptidoglycan from this Gram-negative organism to trigger a macrophage response was compared with that elicited by peptidoglycan from Staphylococcus aureus and Bacillus subtilis. The results show that the three peptidoglycans were similarly active in triggering the secretion of tumour necrosis factor and tumouricidal activity but differed considerably in their ability to induce the generation of nitrite in macrophages; in this respect, peptidoglycan from M. catarrhalis was particularly potent. The impressive capacity of M. catarrhalis peptidoglycan to induce in low concentration the secretion of tumour necrosis factor and nitrite and tumouricidal activity may, in addition to its lipopolysaccharide, contribute to the extraordinary potential of this organism to trigger the functional activities of macrophages.
Characterization of B cell epitopes on the 16K antigen ofMycobacterium tuberculosis
Authors: VERBON A , HARTSKEERL R A , MORENO C , KOLK A H J 
Published: August 2010

SUMMARYTo characterize the antigenic parts of the 16K protein of Mycobacterium tuberculosis, overlapping peptides according to the amino acid sequence of the 16K protein were synthesized. In total, 14 peptides of 20 amino acids in length with an overlap of 10 amino acids and two additional decapeptides (amino acids 31–40 and 61–70) were tested with eight anti-16K MoAbs and human sera. The common recognition site of MoAbs F67-8and F67-16 was LRPTFDTRLM (amino acids 31–40) and of MoAbs F159-1 and F159-11 DPDKDVDIM V (amino acids 61-70). However, for binding of the MoAbs to these peptides additional amino acids were required at either the N- or C-terminus, suggesting that some kind of conformation is required. The recognition sites of the MoAbs F23-41, F23-49, F24-2 and TB68 could not be identified using the peptides, indicating that the MoAbs only bound to conformational epitopes and not to peptides which may contain parts of these epitopes. The MoAbs bound to β-galactosidase fusion proteins comprising parts of the 16K protein, indicating that some kind of native conformation is present on the recombinant proteins. Sera from 14 of 19 patients with tuberculosis and none from 19 controls reacted with the purified 16K protein. Sera from four of these 14 patients reacted with two overlapping peptides (amino acids 71–100). Apparently, antibodies in patients' sera against the 16K protein are predominantly directed against conformational epitopes.
Hepatitis C: a possible etiology for cryoglobulinaemia type II
Authors: PECHÈRE-BERTSCHI A , PERRIN L , de SAUSSURE P , WIDMANN J J , GIOSTRA E , SCHIFFERLI J A 
Published: August 2010

SUMMARYOut of 15 successive patients with mixed essential cryoglobulinaemia type II (monoclonal IgM kappa /IgG), 13 had serological evidence for hepatitis C infection as shown by specific enzyme immunoassays and immunoblot. RNA was purified from the serum of seven patients and hepatitis C sequences were identified in five following reverse transcription and DNA amplification. The liver histology showed chronic active hepatitis with or without cirrhosis in the 12 patients with hepatitis C who had a liver biopsy. The two patients without serological evidence of hepatitis C suffered from haematological malignancies. Hepatitis C may be a major etiological agent of cryoglobulinaemia type II.
Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus
Authors: BANSAL A , ROBERTS T , HAY E M , KAY R , PUMPHREY R S H , WILSON P B 
Published: August 2010

SUMMARYThe low affinity IgE receptor FcɛRII (CD23) is important in several aspects of T and B cell function. In this study serum levels of soluble CD23 (sCD23) were measured in three groups: 26 female patients with systemic lupus erythematosus (SLE), 21 females with primary Sjögren's syndrome (pSS) and 25 normal healthy females. The concentration of sCD23 was determined using an enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased levels of sCD23 were observed in pSS and in SLE patients compared with controls (median 23·0 versus 8·6, P &lt;0·0002 and 18·1 versus 8·6, P &lt;0·002 respectively). While the median level of sCD23 was found to be higher in pSS than in SLE the difference was not statistically significant. Patients with SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23 than patients not on this treatment (median 28·9 versus 14·4, P &lt;0·05). Amongst the control patients sCD23 was inexplicably lower in the female members relative to the males (median 8·5 versus 12·3, P &lt;0·05). Although serum IgG and IgA levels were significantly elevated in pSS and SLE patients relative to controls there was no direct correlation between sCD23 and the serum levels of these immunoglobulins. We conclude that B cell hyperactivity which occurs in both pSS and SLE is associated with raised levels of sCD23.
T cell responses to synthetic TSH receptor peptides in Graves' disease
Authors: TANDON N , FREEMAN M A , WEETMAN A P 
Published: August 2010

SUMMARY
Twenty-eight peptides, representing the entire extracellular domain of the TSH receptor, were synthesised to investigate which parts of this autoantigen may be targets for the T cell response in Graves' disease (GD). T cells from 11 of 21 controls and 26 of 36 newly diagnosed GD patients proliferated in response to one or more peptides with a stimulation index (SI) of &gt; 2·0 (χ2 = 2·31, P &gt; 0·1). The response of patients and controls to any of the individual peptides was also not statistically different. However, individual patients gave high SIs with certain peptides to which controls either gave an absent or very weak response. HLA-DR3 was not associated with any particular response to TSHR peptides. Three out of seven GD patients whose T cells were evaluated before and after treatment showed a response of this kind only early in the course of their disease. Intrathyroidal T cells from four GD patients did not give a consistent proliferative response to pools of five peptides, and depleting peripheral blood T cells of their CD8+ population did not affect the proliferative response. These results indicate that the T cell response to the TSH receptor in GD does not seem to be directed against any one particular epitope on the peptides we have tested which cover the extracellular domain.