bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of Fcγ receptors on human endothelial cells stimulated with cytokines tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)
Authors: Pan L-F , Kreisle R A , Shi Y-D 
Published: March 2003

SUMMARYThis investigation was conducted to detect Fcγ receptors (FcγR) on cytokine-stimulated human endothelial cells (EC) by measuring anti-FcγR MoAb binding with an ELISA. TNF-α and IFN-γ significantly increased the expression of FcγR type II (FcγRII) and type III (FcγRIII) on aortic EC. Simultaneous treatment with both cytokines had a synergistic effect and pretreatment of EC with IFN-γ augmented the effect of TNF-α. The greatest effect was the increase (up to four-to-six-fold) in expression of FcγRII found by the simultaneous treatment of aortic EC with both cytokines. The receptors were expressed on the cell surface and showed receptor capping after incubation at 37°C. This study showed that the inflammatory cytokines TNF-α and IFN-γ enhanced low-affinity FcγR expression on human EC in vitro. The expression of FcγR may contribute to the specific localization of circulating immune complexes on blood vessels in areas of vasculitis.
T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission
Authors: King W J , Brooks C J , Holder R , Hughes P , Adu D , Savage C O S 
Published: March 2003

SUMMARYANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are present in patients with systemic vasculitis. The aim of this work was to determine whether such patients have T cell responses to these antigens and whether these responses are related to disease activity. Peripheral blood lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3, native (non-HI) PR3, HI whole α-granules, and 25 overlapping peptides covering the entire PR3 sequence. Significant responses to both whole PR3 preparations were seen from patient and control groups, and to the α-granules from the patient group. Patients responded at all stages of disease: active, remitting, treated or untreated. Only two patients responded significantly to MPO. Responses were significantly higher with the patient group than the control group to all four whole ANCA antigens. Responses to those PR3 peptides containing epitopes known to be recognized by ANCA were detected from one patient. Thus, these studies demonstrate that T cells from vasculitis patients can proliferate to PR3 and occasionally to associated ANCA antigens. Further, responses may persist even after disease remission has been achieved.
Reduced IL-1 production in adolescents with mite antigen asthma in remission
Authors: Noma T , Ichikawa K , Yoshizawa I , Aoki K , Kawano Y , Baba M 
Published: March 2003

AbstractTo determine the immunological mechanisms associated with outgrowing mite antigen-induced bronchial asthma during adolescence, we studied the relationship between clinical status and Dermatophagoides farinae (Df) antigen-induced peripheral cell activation by measuring IL-1α and IL-lβ production in patients with bronchial asthma. After antigen-driven restimulation in vitro, there was increased IL-1α, IL-1β production by peripheral blood mononuclear cells (PBMC) from patients with active bronchial asthma, while cellular IL-1α, IL-1β production was reduced in patients with asthma in remission. IL-1α and IL-1β production by PBMC (possibly reflecting airway inflammation) after exposure to Df antigen might be down-regulated in patients outgrowing mite antigen-induced asthma, because lipopolysaccharide-induced IL-1α, IL-1β production (seen in both normal individuals and patients with active asthma) was also reduced when patients were in remission.
Interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) are necessary in the early stages of induction of CD4 and CD8 cytotoxic T cells byMycobacterium lepraeheat shock protein (hsp) 65 kD
Authors: Del C Sasiain M , DE LA Barrera S , Fink S , Finiasz M , Alemán M , Fariña M H , Pizzariello G , Valdez R 
Published: March 2003

SUMMARYCytotoxic T cells (CTL) may play an important role in host defence against mycobacterial infections. CD4 CTL are preferentially induced by mycobacteria, but both CD4 and CD8 CTL may be necessary components of a protective immune response. The 65-kD mycobacterium heat shock protein (hsp65) is a poor inducer of CTL in multibacillary leprosy (MB) patients. In this study we evaluate the possible role of cytokines in modulating the cytotoxic activity of CTL from leprosy patients and normal individuals (N) against autologous macrophages presenting Mycobacterium leprae hsp65. Our results show that hsp65-specific CTL were generated from both CD4 and CD8 lymphocytes. In N, individual cytokines as well as the combination of them were able to modify the hsp65-induced cytotoxic activity. The effect of cytokines on leprosy patients' lymphocytes was different in MB and paucibacillary (PB) patients. Thus, IL-6, IL-2, IFN-γ or TNF-α did not modify the generation of hsp65-CTL from either MB (with or without an erythema nodosum episode (ENL)) or PB. In all the patients the simultaneous addition of two cytokines was required in order to increase CTL generation. In MB, IL-6 plus IFN-γ or IL-2 increased both CD4 and CD8 CTL, while TNF-α plus IFN-γ up-regulated only CD4 CTL. In PB, CD8 CTL were prominent with IL-6 plus IFN-γ, while the increase was significant in CD4 CTL with IL-6 plus IL-2. Down-regulation of CTL was observed by addition of IL-4, IL-10, anti-IFN-γ or anti-TNF-α in N controls. Our data demonstrate that IFN-γ and TNF-α must be present for at least the first 60 h of the induction stage in order to generate full hsp65 CTL. Hence, IFN-γ and TNF-α would be key factors in the generation of hsp65 CTL.
Endotoxin release and cytokine production in acute and chronic meningococcaemia
Authors: Prins J M , Lauw F N , Derkx B H F , Speelman P , Kuijper E J , Dankert J , Van Deventer S J H 
Published: March 2003

SUMMARY
Chronic meningococcaemia is a relatively benign manifestation of meningococcal disease. Whether bacterial virulence factors are responsible for this benign course has not been studied. We compared the in vitro endotoxin-liberating ability and cytokine-inducing potential of 31 Neisseria meningitidis isolates obtained from children with acute septic shock with that of nine isolates obtained from patients with chronic meningococcaemia and 12 isolates obtained from carriers with respiratory symptoms. The median endotoxin level released in vitro after 3 h of incubation was significantly higher for isolates causing septic shock compared with isolates from the other two groups (P = 0.01 and 0.02, Mann–Whitney test). This was not explained by differences in bacterial growth rate in vitro. The median IL-6 levels in whole blood ex vivo after 4 h of incubation were also significantly lower for isolates causing chronic meningococcaemia (P = 0.04, Mann–Whitney test). The endotoxin and cytokine levels measured on admission in the 31 children with acute meningococcal septic shock showed a 1000-fold variation. No relationship was established between the amount of endotoxin released by the causative microorganisms in vitro and the endotoxin or cytokine levels in the corresponding 31 children. These results suggest a diminished bacterial virulence for isolates causing chronic meningococcaemia. However, other factors than the endotoxin-releasing potential of the microorganism involved are responsible for the wide variation in endotoxin and therefore cytokine levels in patients with acute meningococcal septic shock.
IgG-mediated anaphylaxis via Fcγ receptor in CD40-deficient mice
Authors: Wakayama H , Hasegawa Y , Kawabe T , Saito H , Kikutani H , Shimokata K 
Published: March 2003

SUMMARYAnaphylaxis denotes an immediate hypersensitivity reaction to allergen, exclusively mediated by IgE antibodies. However, IgE antibodies do not explain all the syndromes that are encountered. We investigated potent IgG-mediated anaphylaxis in CD40-deficient mice that lack the immunoglobulin class switching for T cell-dependent antigens. Immunization with ovalbumin did not induce either humoral responses of IgG, IgA, and IgE, or systemic anaphylaxis in CD40-deficient mice. Although systemic anaphylaxis by active immunization was not observed in CD40-deficient mice, both passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis assessed by mouse blood pressure monitoring with cervical artery catheterization did take place when antigen-specific IgG was transferred and then antigen challenge given. Further, to investigate the inflammatory pathway of IgG-mediated immediate hypersensitivity reactions, we focused on the Fcγ receptor (FcγR) function. Pretreatment of the mice with the anti-FcγRII/FcγRIII MoAb clearly blocked the response of PCA and passive systemic anaphylaxis, suggesting that they were initiated through FcγR. In conclusion, we directly demonstrate the IgG-mediated anaphylaxis and its triggering mechanism through FcγR in in vivo conditions. In addition to IgE-mediated anaphylaxis, IgG-mediated anaphylaxis should be considered and the blocking of FcγR would provide one of the therapeutic targets for the control of IgG-mediated hypersensitivity diseases.
Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines
Authors: Dieleman L A , Palmen M J H J , Akol H , Bloemena E , PEña A S , Meuwissen S G M , Van Rees E P 
Published: March 2003

SUMMARYOral administration of DSS has been reported to induce an acute and chronic colitis in mice. The aim of our study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a Th1/Th2 response and how this would relate to mucosal regeneration. Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2–5 weeks consumption of water. Control mice received only water. The animals were killed at 3 and 6 weeks after induction. Their colons were isolated for histology and immunohistochemistry, using specific MoAbs for T and B cells, macrophages, interferon-gamma (IFN-γ), IL-4 and IL-5. Colons were scored for inflammation, damage and regeneration. Two weeks after stopping DSS the colonic epithelium had only partially healed. Total colitis scores were still increased, especially in the distal colon, which was due to more inflammation, damage and less regeneration. In areas of incomplete colonic healing the basal parts of the lamina propria contained macrophages and CD4+ T cells. These CD4+ T cells showed a focal increase of IFN-γ and IL-4 staining compared with control animals. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Th1 as well as Th2 cytokine profile. We postulate that chronic immune activation mediated by both populations of Th cells can interfere with colonic healing and can play a role in the pathogenesis of chronic colitis.
In vitroproduction of IgG4 by peripheral blood mononuclear cells (PBMC): the contribution of committed B cells
Authors: DE Boer B A , Kruize Y C M , Yazdanbakhsh M 
Published: March 2003

SUMMARYIgG4 and IgE isotypes contribute marginally to the pool of circulating antibodies in healthy individuals, but are elevated during atopic diseases and particularly upon helminth infections. To examine whether the high levels of these isotypes in circulation are reflected in a higher capacity of PBMC to produce IgG4 and IgE, we examined cells from patients infected with filarial nematodes that exhibit high levels of IgG4 and IgE. Indeed, IgG4 production by PBMC correlated strongly with plasma levels of IgG4 (r = 0.534, P = 0.002), but such correlation was not found for IgE. The replacement of CD19+ cells from PBMC by IgD+ cells abrogated the high capacity of PBMC to make IgG4. This indicates that an altered B cell compartment accounts for the high IgG4-producing capacity of the PBMC. The high production of IgG4 in vitro was not dependent on IL-4 and IL-13, as neutralizing antibodies to these cytokines did not inhibit IgG4. However, IgE release by PBMC was dependent on IL-4 and IL-13. Anti-filarial IgG4 was detected in culture supernatants from filarial patients and its production was independent of IL-4 and IL-13. These results demonstrate that in individuals with elevated IgG4, the B cell compartment in PBMC carries cells that are already committed to IgG4 production and are independent of IL-4 and IL-13.
C7 deficiency in an Irish family: a deletion defect which is predominant in the Irish
Authors: O'hara A M , Fernie B A , Moran A P , Williams Y E , Connaughton J J , Orren A , Hobart M J 
Published: March 2003

SUMMARYHuman deficiencies of terminal complement components are known to be associated with increased susceptibility to Neisseria meningitidis infection. Polymorphic DNA marker studies in complement deficient investigations allow identification of haplotypes associated with the deficiency and enable the possible identification of heterozygote carriers of the defect. We report studies of an Irish family in which the index case had suffered recurrent meningococcal disease and was found to be deficient in the seventh component of complement (C7). The availability of all family members enabled us to determine the segregating haplotypes. The defects in the family segregated with two very closely related C6 and C7 DNA haplotypes, one of which is known to be associated with the large Irish C7 DNA deletion defect. The index case and two C7 deficient siblings were found to be homozygous for this defect, a deletion that spans approx. 6.8 kbp and encompasses exons 7 and 8. The deletion defect of exons 7 and 8 of C7 has been found in homozygous form in another C7 deficient Irish individual, and is present in heterozygous form in C7 deficient members of a third Irish family. Therefore, this deletion defect occurs in five of the six deficient chromosomes of these three unrelated Irish families, raising the interesting question of how prevalent this defect may be within the Irish community.
Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine
Authors: Fijen C A P , Kuijper E J , Drogari-Apiranthitou M , Van Leeuwen Y , Daha M R , Dankert J 
Published: March 2003

SUMMARY
Individuals with properdin, C3 or late complement component deficiency (LCCD) frequently develop meningococcal disease. Vaccination of these persons has been recommended, although reports on efficacy are scarce and not conclusive. We immunized 53 complement-deficient persons, of whom 19 had properdin deficiency, seven a C3 deficiency syndrome and 27 had LCCD with the tetravalent (ACYW) meningococcal capsular polysaccharide vaccine. Serological studies were performed in 43 of them. As controls 25 non-complement-deficient relatives of the complement-deficient vaccinees and 21 healthy non-related controls were vaccinated. Post-vaccination, complement-deficient individuals and controls developed a significant immunoglobulin-specific antibody response to capsular polysaccharides group A, C, Y, W135, but a great individual variation was noticed. Also, the proportion of vaccinees of the various vaccinated groups with a significant increase in bactericidal titre (assayed with heterologous complement) was similar. Opsonization of meningococci A and W135 with sera of the 20 LCCD individuals yielded in 11 (55%) and eight (40%) sera a significant increase of phagocytic activity after vaccination, respectively. Despite vaccination, four complement-deficient patients experienced six episodes of meningococcal disease in the 6 years post-vaccination. Four episodes were due to serogroup B, not included in the vaccine. Despite good response to serogroup Y upon vaccination, disease due to serogroup Y occurred in two C8β-deficient patients, 3.5 and 5 years post-vaccination. These results support the recommendation to vaccinate complement-deficient individuals and to revaccinate them every 3 years.
Autoantibodies to human melanocyte-specific protein Pmel17 in the sera of vitiligo patients: a sensitive and quantitative radioimmunoassay (RIA)
Authors: Kemp E H , Gawkrodger D J , Watson P F , Weetman A P 
Published: March 2003

SUMMARY
In the present study we describe the in vitro transcription-translation of human melanocyte-specific protein Pmel17 cDNA and subsequent use of the resulting 35S-labelled Pmel17 in an RIA to analyse vitiligo sera for the presence of Pmel17 antibodies. Of 53 vitiligo sera examined in the assay, three (5.9%) were found to be positive for Pmel17 antibodies. In contrast, sera from 20 healthy controls, 10 patients with Hashimoto's thyroiditis and 10 patients with Graves' disease (GD) were all negative for Pmel17 antibodies. All three patients positive for Pmel17 antibodies (aged 50–63 years) had had vitiligo of the symmetrical type for &gt; 1 year and all of them also had an associated autoimmune disorder: GD in one and autoimmune hypothyroidism in two. In addition, all three patients had antibodies to the melanogenic enzymes tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) in their serum. Absorption studies indicated that preincubation with COS-7 cell extract containing expressed Pmel17 absorbed out the immunoreactivity of the three sera positive in the RIA, confirming the anti-Pmel17 reactivity of the sera from these patients. In contrast, COS-7 cell extracts containing either expressed tyrosinase, TRP-1 or TRP-2 did not remove the anti-Pmel17 reactivity of the three sera in the RIA. This lack of cross-reactivity suggests that the humoral response to Pmel17 in these patients is specific and independent of the antibody reactivity to tyrosinase, TRP-1 and TRP-2.
Systemic immune response after intravesical instillation of bacille Calmette–Guérin (BCG) for superficial bladder cancer
Authors: TANIGUCHI K , KOGA S , NISHIKIDO M , YAMASHITA S , SAKURAGI T , KANETAKE H , SAITO Y 
Published: March 2003

SUMMARY
The mechanism of anti-tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL-1β, IL-2, IL-6, tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and macrophage colony-stimulating factor (M-CSF) after BCG instillation. Levels of IL-2 and IFN-γ in the serum also increased after BCG instillation, but IL-1β, IL-6, TNF-α and M-CSF were not detectable. Maximal levels of IL-2 and IFN-γ in the urine or serum were shown after the fourth instillation. BCG-induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour-free patients produced higher BCG-induced killer cell activity than tumour recurrence patients. BCG-induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.
Successful immunomodulating in AIDS patients with ursodeoxycholic acid—a pilot study
Authors: KURKTSCHIEV D , TEMELKOVA-KURKTSCHIEV T , HORN K , SCHENTKE K-U 
Published: March 2003

SUMMARYBased on the positive therapeutic results with ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis, in whom we observed a clinical improvement in conjunction with the normalization of the low pretreatment dipeptidyl peptidase (DPIV, CD26) expression of peripheral blood lymphocytes (PBL), we hypothesized that the very low DPIV expression in AIDS patients could be positively influenced by UDCA. Four young male AIDS patients were therefore treated with 750 mg of UDCA for 4 months. The low CD26 expression (2–8% of the PBL versus 18–28% in healthy controls) at the beginning of the study rose to 10–16% after UDCA therapy. Simultaneously we observed a two-to-three-fold elevation of the absolute number of lymphocytes as well as a slight increase of CD4+ cells. These effects were similar in all examined patients. Further investigations should be conducted on this potentially beneficial effect of UDCA.
Quantitative and qualitative differences in bronchoalveolar inflammatory cells inPseudomonas aeruginosa-resistant and -susceptible mice
Authors: SAPRU K , STOTLAND P K , STEVENSON M M 
Published: March 2003

SUMMARYThe difference in severity of Pseudomonas aeruginosa-induced chronic lung infection may be determined by differences in host inflammatory responses. In the present study we investigate this possibility using BALB/c and C57Bl/6 mice, resistant and susceptible, respectively, to chronic lung infection with P. aeruginosa. Following intratracheal inoculation of P. aeruginosa-impregnated agar beads, C57Bl/6 mice mounted a stronger inflammatory response with significantly higher total cell numbers in the bronchoalveolar lavage fluid compared with BALB/c mice. While polymorphonuclear leucocytes were the predominant cell in C57Bl/6 mice, macrophages constituted the majority in BALB/c mice at day 7 post-infection. Alveolar macrophages from C57Bl/6 mice showed significantly higher spontaneous production of nitric oxide (NO) at day 7 post-infection compared with BALB/c mice. Following in vitro stimulation with heat-killed Pseudomonas antigen, these cells produced significantly higher NO compared with cells from BALB/c mice at day 21 post-infection. Production of tumour necrosis factor-alpha (TNF-α) by alveolar macrophages was significantly higher at day 7 in BALB/c mice compared with C57Bl/6 mice, which showed significantly higher levels at day 28 post-infection. Taken together, these results suggest that defects in the host inflammatory process contribute to the variable outcome of chronic lung infection with P. aeruginosa. An exaggerated inflammatory response dominated by polymorphonuclear cells correlates with susceptibility to infection, whilst a modest inflammatory response dominated by macrophages correlates with resistance. Moreover, the quantity and timing of production of NO and TNF-α by alveolar macrophages may modulate the course and outcome of infection.
A novel mutant γc chain from a patient with typical phenotype of X-linked severe combined immunodeficiency (SCID) has partial signalling function for mediating IL-2 and IL-4 receptor action
Authors: KUMAKI S , OCHS H D , KUROPATWINSKI K K , KONNO T , TIMOUR M S , COSMAN D , BAUMANN H 
Published: March 2003

SUMMARY
Mutations of the common γ (γc) chain result in X-linked SCID (X-SCID), which is characterized by the reduction in number or absence of peripheral blood T cells and natural killer (NK) cells, with retention of normal numbers of B cells. In the present study we describe a novel mutant γc chain of an X-SCID patient with a typical X-SCID phenotype. This mutant receptor subunit is able to associate with Jak3 to transduce a weak signal. The Jak3-specific action is demonstrated by the induction of gene expression through the haematopoietin receptor response element (HRRE) by IL-2 and IL-4 in the experimental model of transiently transfected hepatoma cells over-expressing Jak3. This result suggests that a threshold in the γc–Jak3 interaction determines the X-SCID phenotype.