bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of anti-IL-4, interferon-gamma and an antifungal triazole (SCH 42427) in paracoccidioidomycosis: correlation of IgE levels with outcome
Authors: HOSTETLER J S , BRUMMER E , COFFMAN R L , STEVENS D A 
Published: July 2010

SUMMARYParacoccidioidomycosis is characterized by depressed cellular but enhanced humoral immune responses, which suggests a Th2 type of response to infection. We investigated possible therapeutic roles for anti-IL-4, interferon-gamma (IFN-γ) and/or SCH 42427 (SCH), a new triazole antifungal agent, and their effect on serum IgE levels in a murine model of chronic Paracoccidioides brasiliensis infection. BALB/c mice infected by the pulmonary route were studied with three programmes. The subacute model and one acute model experiment investigated cytokine secretion by lymph node cells (LNC), and in a second acute experiment mice were given anti-IL-4, IFN-γ or nothing 24 h post infection, then killed at 4 weeks. In the chronic model, mice began treatment at 4 weeks post infection, receiving either SCH, IFN-γ alone, SCH + IFN-γ. or no treatment for 8 weeks. At 2-week intervals lung and spleen burdens of infection and serum polyclonal IgE levels were determined. In the subacute model (non-progressive infection), initially there was dual production of IL-4 and IFN-γ by antigen-stimulated LNC. In the acute progressive infection model IL-4, but not IFN-γ. was secreted. Anti-IL-4 treatment of the acute phase resulted in enhanced host resistance to infection, which correlated with decreased scrum IgE. The chronic model, in which the in vivo efficacy of SCH against P. brasiliensis was shown, suggests possible synergy between immunomodulation and antimicrobial chemotherapy (IFN-γ and SCH). Decreased organ burdens of infection in the chronic model after treatment with SCH, SCH plus IFN-γ, or anti-IL-4 correlated with decreased serum IgE. These promising novel approaches lo treatment of systemic fungal infections suggest a Th2 type of response to P. brasiliensis infection, which can be reversed with successful therapy.
In vitrocytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HIV
Authors: CARR A , TINDALL B , PENNY R , COOPER D A 
Published: July 2010

SUMMARYHypersensitivity to trimethoprim-sulphamethoxazole (TMP-SMX) in patients with HIV infection may be a result of either immune dysregulation, a direct cytotoxicity of the SMX-hydroxylamine metabolite (SMX-HA) (rather than SMX per se), or glutathione deficiency. We evaluated the in vitro cytotoxicity of SMX and SMX-HA to peripheral blood mononuclear cells (PBMC) of HIV-infected subjects to determine if the degree of in vitro cytotoxicity is associated with hypersensitivity, whether glutalhione inhibits cytotoxicity, and whether in vitro cytotoxicity is predictive for the development of hypersensitivity. Given that fever is often a prominent feature of hypersensitivity, we also assessed whether SMX or SMX-HA could induce the in vitro production of IL-lβ, IL-6 or tumour necrosis factor-alpha (TNF-α) by PBMC. Thecytotoxicitics of SMX and SMX-HA to PBMC were assessed in 45 HFV-infected patients with prior TMP-SMX therapy, and in eight HIV controls. Twelve HIV-infected subjects were studied prospectively before primary Pnvumocystis carinii pneumonia (PCP) therapy or reehallenge with TMP-SMX in previously hypersensitive subjects. Cylokine production was measured in four hypersensitive and two non-hypersensitive HlV-infccted subjects, and three HIV-uninfected controls. The cytotoxicity of SMX-HA to PBMC was significantly greater in the 22 HIV-infectcd patients with prior hypersensitiviiy than both the 23 HIV-infeeled paiients without hypersensitivity and the control group. Cytotoxicity was significantly reduced by glutalhione only in the hypersensitive group. SMX did not induce eylotoxicity in any group. In 12 subjects studied prospectively. SMX-HA cytotoxicity was also significantly greater in those with subsequent hypersensitivity. Exposure of PBMC to SMX-HA resulted in a modest increase in the production of IL-6, IL-1β and TNF-α, although no major difference was detected between subjects with or without hypersensitivity. These data suggest that SMX-HA and glutathione deficiency are involved in the pathogenesis of hypersensilivity to TMP-SMX in HIV-infected patients, and that in vit ro cytotoxicity could be useful in the diagnosis of hypersensilivity and predicting its likelihood.
Blockade of immunoregulatory Fc-signalling by HIV peptides: oligopeptides from HIV gpl20 and gp41 bind the Fc portion of IgG and increase thein vitroanti-ssDNA response
Authors: RAHIMPOUR R , ANDERSON C C , SINCLAIR N R StC 
Published: July 2010

SUMMARYConcomitant ligation of antigen receptors with Fc-receptors negatively signals B cells. Antibodies to the Fc portion of IgG prevent this negative Fc-signalling, provided that these antibodies do not emit Fc signals. Prevention of Fc signals leads to augmented antibody responses to self and foreign antigens, and reduces the requirement for T cells by 10- to 100-fold in T cell-dependent antibody responses. In EL1SA assays, peptides from conserved portions of the glycoproteins. H1V-I gp120 or gp41 from HIV-1 and HIV-2 bind to the Fc portion of IgG, but do not bind the F(ab′)2 portion of IgG. HIV-derivcd peptides. which bind to the Fc portion of IgG. augment the antibody-forming cell response to single-stranded (ss)DNA. The spontaneous response to ssDNA using spleen cells from young mice, and the response in the presence of exogenous DNA using spleen cells from old mice, are augmented to the greatest extent. These results demonstrate that HIV peptides bind to the Fc portion of IgG and augment immune responses to DNA; they suggest the possibility that blockade of the Fc portion of IgG antibodies is associated with a reduction in Fc-mediated regulation of anti-self responses. Blockade of regulatory Fc-signalling may account for increased circulating immune-globulins and autoantibodies in clinical AIDS.
Dendritic cells infected in vitro with human T cell leukaemia/lymphoma virus type-1 (HTLV-1); enhanced lymphocytic proliferation and tropical spastic paraparesis
Authors: ALI A , PATTERSON S , CRUICKSHANK K , RUDGE P , DALGLEISH A G , KNIGHT S C 
Published: July 2010

SUMMARY
Evidence supporting a role of the dendritic cell (DC) in stimulating autologous T cell activity in tropical spastic paraparesis (TSP) was sought by studies of cells taken from healthy volunteers and exposed Vo HTLV-1 in vitro. DC were co-cultured with an HTLV-1 -producing cell line (MT-2) at 1:1 or 10:1 ratios. These DC stimulated high levels of proliferation in autologousT cells. This was similar to that seen in an autologous mixed leucocyte reaction (AMLR) using cells from TSP patients. The requirement for both DC and virus was confirmed. since neither DC co-cultured with uninfected MT-2 cells nor addition of infected MT-2 cells directly to T cells caused significant stimulation. DC exposed to the highest dose of HTLV-1 (1:1) for 24 h before addition of T cells caused strong stimulation that increased after 8 h but almost disappeared by 72 h. In situ hybridization showed that approximately 25% of DC became infected in cultured cells after preincubation for 24 h, and over 50% were infected with a 72-h preincubation. We suggest that infection of DC by HTL V-l may be an initial step in altering the immune system in seronegative patients, and that persistent T cell stimulation in those with genetic susceptibility may underlie the produclion of neurological disease.
Selective impairment of T lymphocyte activation through the T cell receptor/CD3 complex after cytomegalovirus infection
Authors: TIMóN M , ARNAIZ-VILLENA A , RUIZ-CONTRERAS J , RAMOS-AMADOR J T , PACHECO A , REGUEIRO J R 
Published: July 2010

SUMMARYCytomegalovirus(CMV) infection is reported to cause transient immunosuppression in man. In this Study we have analysed ihe effect of CMV on T lymphocyte function in 29 children diagnosed for acute CMV infection. Peripheral blood mononuclear cells (PBMC) obtained from the palients showed a significant specific impairment in their proliferative response to enterotoxins A and C1. to coneanavalin A and to the anti-CD3 MoAb OKT3. The impaired responses were corrected with exogenous IL-2. In conlrast. slimulation using phytohaemagglutinin. as well as activation signals delivered through the surface molecules CD26 or CD28. elicited normal proliferalive responses in CMV PBMC. The results indicate that the T cell anergy associated with CMV infection is restricted to the T cell receptor/CD3 activation pathway.
Novel human immunoglobulin heavy chain constant region gene deletion haplotypes characterized by pulsed-field electrophoresis
Authors: OLSSON P G , RABBANI H , HAMMARSTRÖM L , SMITH C I E 
Published: July 2010

SUMMARYFifteen patients with selective IgG1 deficiency were screened for immunoglobulin H chain C region locus (IGHC) gene deletions and three deletion haplotypes were found: del Gl, delGI G4 and del G4. These haplotypes, together with four deletion haplotypes described by us previously (del G1 (NY), del G1 (VIT) del G1-G2 (NY) and del G2-G4 (HJE)). were further characterized using pulsed-field gel electrophoresis (PFGE) to determine the physical extent of the deletions. The MluI fragment sizes confirmed the deletions, although the deduced sizes of the most extensive deletions indicated that material had been inserted into the locus.
Bronchoalveolar lavage cell analysis and lung function impairment in patients with systemic lupus erythematosus (SLE)
Authors: GROEN H , ASLANDER M , BOOTSMA H , van der MARK Th W , KALLENBERG C G M , POSTMA D S 
Published: July 2010

SUMMARYWe examined the relationship between peripheral blood and bronchoalveolar lavage (BAL.) lymphocyte phenotypes and lung function in 19 patients with SLE. and evaluated their association with disease activity. Lung function assessment showed a mildly restrictive pattern with frequent impairment of transfer factor for carbon monoxide (TL,CO) and diffusing capacity of the alveolocapillary membrane (Dm), of late-expiratory airflow rales and with a high prevalence of increased airway resistance. TL,CO, KCO and Dm correlated inversely with the numbers of CD+ cells and CD56+/CD16+/CD3− (NK) cells in BAL. Oxygen radical production, both by stimulated and unslimulated BAL cells and blood polymorphonuclear leucocytes (PMN) was significantly increased in SLE. In comparison with healthy controls, patients with SLE had a lower percentage of CD19+ B cells in the BAL versus an increased percentage of these cells in peripheral blood. HLA-DR expression on CD4+ and CDS+ lung lymphocytes was markedly increased in SLE. Current SLE disease activity was not associated with changes in BAL or peripheral blood lymphocyte phenotypes. Our data suggest that an ongoing cell-mediated immune response is present in the lungs in SLE, particularly involving activated CD8+ T cells and CD56+/CD16+/CD3− NK cells. It is associated with up-regulated local production of oxygen radicals and with impaired pulmonary diffusing capacity. This inflammatory process seems to be independent of general SLE disease activity.
Triggering of respiratory burst by phagocytosis in monocytes of patients with systemic lupus erythematosus
Authors: GYIMESI E , KÁVAI M , KISS E , CSIPÖ I , SZÜCS G , SZEGEDI G Y 
Published: July 2010

SUMMARYThe triggering of the respiratory burst by phagocytosis via different receptors in monocytes of patients with systemic lupus erythematosus (SLE) was investigated. The superoxide anion synthesis was assayed by reduction of fcrricytochrome C that was inhibited by superoxide dismutase. The mononuclear cell suspensions were triggered by IgG-coated latex. C3 complement fragment-coated and uncoated yeast (Saccharomyces cerevisiae). Superoxide generation induced by phagocytosis via FcγR was decreased in monocytes of patients with SLE. On the other hand. MoAbs against FcγRI, FcγRII and especially CR3 could also induce superoxide anion synthesis. At the same time, superoxide generation induced by anti-CR3 could be inhibited with C3-coated yeast.
Effect of low-dose ultraviolet-B radiation on the function of human T lymphocytesin vitro
Authors: TEUNISSEN M B M , SYLVA-STEENLAND R M R , BOS J D 
Published: July 2010

SUMMARYPurified peripheral blood human T lymphocytes, derived from normal individuals, were assayed for their susceptibility to low doses of ultraviolet B (UVB) In vitro. Exposure of T cells to graded single doses (range 0–8 mJ/cm2) of UVB resulted in a dose-dependent reduction of viability. This phototoxic effect was not immediately apparent, however, but became manifest 48–72 h subsequent to irradiation. A dose as little as 0·5–1 mJ/cm2 was sufficient to cause 50% mortality. Irradiated T cells showed a reduced ability to proliferate, irrespective of the stimulus used, and a reduced ability to produce cytokines IL-2, IL-4, IL-5, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). This decreased ability was UVB-dose related and, remarkably, was exactly correlated to phototoxicity. UVB had no effect on CD4 and CD8 expression or their ratio, whereas the expression of IL-2R (CD25) was only slightly reduced. Our data suggest that UVB radiation neither selectively affects Th1 or Th2 nor CD4 or CD8 T cell subsets. The high susceptibility of T cells to UVB might explain, al least in part, the beneficial effect of phototherapy during treatment of certain immunodermatological diseases.
Transforming growth factor-beta (TGF-β) in human milk
Authors: SAITO S , YOSHIDA M , ICHIJO M , ISHIZAKA S , TSUJII T 
Published: July 2010

SUMMARYThe amount of TGF-β contained in human whey was studied by the colony formation of NRK47F cells. It was noted that a factor inducing colony formation did exist in human whey, and its action was neutralized when anti-TGF-β antibodies were introduced. This suggests that TGF-β does exist in human whey. In colostrum, the total amount of TGF-β was 1365·7 ± 242·9 ng /ml, of which the active form comprised 728·1 ± 248·7 ng/ml (n=21). In late milk, the total TGF-β was 952·5 ± 212·6 ng/ml, with an active form of 178·7 ± 157·3 ng/ml. Thus human milk contains a large amount of active TGF-β. Furthermore, it was revealed by the reverse transcriptase polymerase chain reaction that mRNAs coding TGF-β1 and TGF-β2 exist in human milk cells. These results suggest that both TGF-β1 and TGF-β2 exist in human milk.
IL-5 in post-traumatic eosinophilic pleural effusion
Authors: SCHANDENÉ L , NAMIAS B , CRUSIAUX A , LYBIN M , DEVOS R , VELU T , CAPEL P , BELLENS R , GOLDMAN M 
Published: July 2010

SUMMARYThoracic trauma or pneumothorax can result in pleural fluid eosinophilia. In this study we investigated the role of the eosinophilopoietic cytokine IL-5 in three cases of post-traumatic eosinophilic pleural effusions (EPE). Using a specific immunoenzymatic assay, significant levels of IL-5 were found in EPE (range 100–3000 pg/ml), while IL-5 was undetectable (&lt;25 pg/ml) in corresponding serum samples and in non-eosinophilic pleural fluids. IL-5 present in pleural fluids was found bioactive in a proiiferative assay using a mouse CTLL-2 cell line transfected with the cDNA corresponding to the a chain of the human IL-5 receptor. Using a reverse polymerase chain reaction (PCR) method, we found IL-5 mRNA expression within pleural mononuclear cells from patients with EPE, but not in corresponding peripheral blood mononuclear cells (PBMC), confirming that IL-5 is synthesized locally in the pleural cavity. In the two cases in which pleural CD4+ cells were purified, these cells were identified as the major source of IL-5. Taken together, these data indicate that the development of post-traumatic EPE is related to a local secretion of IL-5 by CD4+ cells present in the pleural cavity.
Limiting dilution analysis of the allo-MHC anti-paternal cytotoxic T cell response I: normal primigravid and multiparous pregnancies
Authors: MANYONDA I T , PEREIRA R S , PEARCE S M , SHARROCK C E M 
Published: July 2010

SUMMARYAnti-paternal cytotoxic T lymphocyte precursor frequencies (CTLpF) were determined by limiting dilution analysis (LDA) in the peripheral blood of eight primigravid and seven multiparous women during the three trimesters of pregnancy. In five of these women the responses to cord blood lymphocytes (CBL) and paternal lymphocytes were also determined at the time of delivery and at 6 weeks post delivery. As controls, CTLpF against unrelated third party donors were determined. A wide range of CTLpF against unrelated third groups of targets was found in both the primigravid and multiparous women, reflecting the wide range of frequencies found in random populations. These frequencies remained fairly constant during and 6 weeks after the pregnancy. Splitwell analysis demonstrated that the responses generated in our culture system were specific to the stimulator. The LDA data conform to single-hit kinetics, indicating that only cytotoxic T cells were limiting in the assay. Proliferative responses of maternal lymphocytes to paternal, cord blood and third party MHC antigens also remained unchanged as determined by time-course mixed lymphocyte reactions (MLR). Our data suggest that there is no significant allo-stimulation or suppression of the maternal immune system during normal pregnancy. The mother remains immunocompetent and is capable of both cytottjxic and proliferalive responses lo paternally-derived fetal MIC antigens. Our findings confirm that in normal pregnancy the trophoblast. which is devoid of classical MHC antigens, forms an effective immune barrier which prevents interaction of the maternal and fetal immune systems.
Studies on the mechanism of complement-mediated inhibition of antibody binding to HIV gp41
Authors: HIDVÉGI T , PROHÁSZKA Z , UJHELYI E , THIELENS N M , DIERICH M P , HAMPL H , ARLAUD G , NAGY K , FÜST G 
Published: July 2010

SUMMARYWe have previously demonstrated that HIV envelope gp41 binding to specific antibodies decreases after preincubation of fluid-phase gp41 in normal human serum. This inhibition is proven to be mediated by the classical complement pathway. In this study recombinant gp41 (rgp41) and/or synthetic peptides were preadsorbed to solid phase, and then complement (normal human serum heated human serum, purified Clq/heated Clq) and anti-gp41 antibodies were added either after each other or simultaneously, and the amounts of bound antibody, and deposited C3b, C4b and Clq were measured. Complement-dependent inhibition of antibody binding to solid-phase rgp41 was found, and Clq seems to be at least partially responsible for this phenomenon. Heating of Clq did not affect this process. Higher amounts of anti-gp41 antibodies significantly and dose-dependently enhanced C4b and C3b fixation to solid-phase rgp41. In the case of synthetic peptides corresponding to the immunodominant region of gp41, significant antibody binding to the solid-phase peptides was also detected, and pretreatment of peptides preadsorbed to solid phase with normal human serum almost totally abolished the antibody binding.
Variation in interferon-gamma responses toCoxiella burnetiiantigens with lymphocytes from vaccinated or naturally infected subjects
Authors: IZZO A A , MARMION B P 
Published: July 2010

SUMMARYPrevious work in our laboratory has shown that lymphocytes from persons vaccinated with a formalin-inactivated Phase I Q fever vaccine(Q-VaxCSL Ltd) show a mitogenic response to Coxiella burnetii antigens. The mitogenic response is the sum of that from various subsets of CD4+, T helper cells, CD8+ T cells and probably B cells. It does not distinguish between T helper cell responses leading to formation of interferon-gamma (IFN-γ)—a cytokine responsible for clearing intracellular infection with C. burnetii organisms—and responses of other T cell subsets which may produce disease-enhancing cytokines. The present study analyses (i) the capacity of Q-Vax to induce T cell sensitization which leads to IFN-γ responses on antigen stimulation, and (ii) the immunomodulatory, (down-regulatory) effects of the Phase I lipopolysaccharide (LPS) of the organism, which interacts with monocyte/macrophages to limit IL-2 production and production of IFN-γ by sensitized T lymphocytes.
Circulating adhesion molecules in tuberculosis
Authors: LAI C K W , WONG K C , CHAN C H S , HO S S , CHUNG S Y , HASKARD D O , LAI K N 
Published: July 2010

SUMMARYLeucocyte-endothelial adhesion molecules have been implicated in the pathogenesis of inflammatory diseases. To evaluate their role as markers of disease activity in tuberculosis, we have used an antigen capture ELISA to measure the serum concentrations of circulating intercellular adhesion molecule-1 (cICAM-1), E-selectin (cE-selectin) and vascular cell adhesion molecule-1 (cVCAM-1) in 34 patients with active tuberculosis (27 with pulmonary disease and seven with lymph node disease) before the commencement of standard chemotherapy, 15 subjects who had previously completed treatment for pulmonary tuberculosis, and 27 healthy volunteers. Circulating ICAM-1 and E-selectin levels were significantly elevated in patients with active tuberculosis when compared to those with treated disease (P⩽0.01), and healthy controls (P&lt; 0.02). Circulating VCAM-1 was raised in patients with active or old pulmonary tuberculosis (P&lt;0.02 versus healthy controls) but not in those with tuberculous lymphadenitis. Significant correlations were observed between the levels of cICAM-1 and cE-selectin (ρ= 0-63, P=0 0001), and between cICAM-1 and cVCAM-1 (ρ = 0.28, P=0.016). Taking the mean +2 s.d. of the serum level in healthy controls as the upper limit of normal range, circulating ICAM-1 had the best discriminative power in identifying active tuberculosis, being elevated in about 80% of patients but was raised in only 6.7% of subjects with treated disease and in 3.7% of normal subjects. Our data support the possibility that three adhesion molecules may be involved in the pathogenesis of tuberculosis and cICAM-1 may be a useful marker of disease activity.
Spontaneous cytotoxicity of intestinal intraepithelial lymphocytes: clues to the mechanism
Authors: ROBERTS A I , O'CONNELL S M , BIANCONE L , BROLIN R E , EBERT H C 
Published: July 2010

SUMMARYHuman intestinal intraepithelial lymphocytes (IEL) demonstrate target cell-restricted spontaneous cytotoxic (SC) activity that is due to CD2+CD3+CD8+CD16−CD56– effector eells: they kill epithelial cell (EC) tumours (such as DLD-1 colon cancer eells), but not natural killer (NK)-sensitive K-562 cells. The present study shows that the measured levels of SC activities by IEL correlated with those of autologous lamina propria lymphocytes (LPL), but not with those of peripheral blood lymphocytes (PBL). Also, the susceptibilities of DLD-1 cell clones to lysis by IEL and PBL effector cells did not correlate, suggesting different mechanisms of lysis. Antibody blocking experiments showed that the main surface molecules involved in lysis depended on the effector cell type: αEβt (HML-l) on IEL and CDI6 on PBL. No antibody-dependent cell-mediated cytotoxicity (ADCC) was demonstrated by IEL, even after stimulation with inerferon-gamma (IFN-γ). Few IEL expressed Fc receptors for IgG. This study describes further differences between the SC activities of IEL and PBL.