bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11
Authors: WONG S , MOORE S , ORISIO S , MILLWARD A , DEMAINE A G 
Published: July 2010

SUMMARYType I diabetes is associated with the DQ loci of the MHC and to a lesser extent with the T cell antigen receptor (TcR) beta chain genes. The non-obese diabetic (NOD) mouse is an animal model of human diabetes, in which up to 90% of female mice develop overt insulin-dependent diabetes. Genetic studies in the NOD mouse suggest that there are at least three diabetogenic genes; one that maps to the MHC, another that may map to the mouse Thy-I locus, and a third that has still to be identified. We have investigated loci in the vicinity of the human Thy-I locus on chromosome 1 Iq23 and report here the results of restriction fragment length polymorphism (RFLP) analysis of the CD3 epsilon locus of 168 Caucasoid patients with type I diabetes. While no association was found between this locus and type I diabetes, a significant difference in the frequency of the CD3 epsilon 8-kb allelc was found between male and female patients (0.268 versus 0.430; p &lt; 0.0025, Pc= 002) and between female patients and healthy female controls (0.430 versus 0.267; P &lt; 0.015). These results suggest that a gene residing on chromosome 1 Iq23 may confer susceptibility to type 1 diabetes in women.
Triggered human mucosal T cells release tumour necrosis factor-alpha and interferon-gamma which kill human colonic epithelial cells
Authors: DEEM R L , SHANAHAN F , TARGAN S R 
Published: July 2010

SUMMARYT cell activation can lead to local tissue injury in organ culture studies of human fetal jejunum, either directly through cytotoxicity or indirectly by the release of cytotoxic cytokines. The goal of this study was to establish in vitro whether cylotoxic cytokines can be released by isolated colonic T cells and what cytokine interactions arc required for killing of human colonic epithelial cells. Cytokine-containing supernatants were induced by incubating unscparated lamina propria lymphocytes (LPL) or mucosal T cell subpopulations (separated by indirect panning) with anti-CD3 and/or K562 target cells for 18h at 37°C. Cytokines were measured by cytotoxicity assays using L929(murine fibroblast) and HT-29 (human colonic tumour) lines as target cells in combination with blocking anti-cytokine antibodies. Supernatanis derived from unseparaled, CD4+ (&gt;95% pure) and CD8+ (&gt;90% pure) LPL were cytotoxic to L929 targets (350 U/ml, 230 U/ml and 100 U/ml tumour necrosis factor-alpha, respectively). All or nearly all of the eylotoxicity was due to the presence of tumour necrosis factor-alpha (little or no tumour necrosis factor-beta was delected). These same supernatanis were cytoloxic (up to 32% lysis at 1/4 dilution) to HT-29 targets in a 48-h 111In release assay. Recombinant tumour necrosis factor-alpha and interferon-gamma alone produced minimal killing of HT-29, but together killed the HT-29 target celts. Anti-tumour necrosis factor-alpha or anti-interferon-gamma alone blocked killing of HT-29 target cells by LPL-derived supernatants, although anti-tumour necrosis factor-beta had no effect upon killing of HT-29. These results demonstrate that human LPL T cells, triggered by addition of anti-CD3 and target cells, produce tumour necrosis factor-alpha and interferon-gamma, both of which are required for optimal killing of HT-29. Simultaneous release of these cytokines in the vicinity of epithelial cells during immune responses could play an important role in the mucosal damage in chronic inflammatory states such as inflammatory bowel disease.
Natural autoantibodies may play a role in ineffective erythropoiesis during megaloblastic haemopoiesis
Authors: WIENER E , WICKRAMASINGHE S N 
Published: July 2010

SUMMARY
Marrow aspirates from 11 patients with megaloblastic haemopoiesis and from 14 healthy individuals with normoblustic haemopoiesis were studied for antibodies associated with polychromatic/orthochromatic erythroblasts, using an 125I-labelled anti-human immunoglobulin reagent and autoradiography. In addition, the expression on these cells of receptors for FcIgG (FcR) and of the type I receptor for fragments of the third complement component (CR1) were investigated with receptor-specific monoclonal antibodies. 125I-labelled anti-mouse immunoglobulin and autoradiography. The percentages of immunoglobulin-positive erythroblasts were significantly greater in the megaloblastic than in the normoblastic marrows. Abnormally high percentages of labelled erythroblasts were present in patients without any manifestations of an autoimmune disorder. The percentage of labelled erythroblasts in the marrows of the patients correlated well with the degree of anaemia. FcR were absent on the majority of megaloblasts or normoblasts while the expression of CRI was similar in both types of cell. The difference between the percentage labelling of megaloblasts and normoblasts was therefore unlikely to be due to greater binding of immune complexes with or without associated complement to mcgaloblasts than normoblasts. The megaloblast-hound immunoglobulin is, therefore, likely to have recognized abnormally expressed epitopes on the surface of megaloblasts. The results suggest that natural autoantibodies play a role in the destruction of erythroblasts during megaloblastic haemopoiesis.
Formation of subepithelial dense deposits in rats induced by a monoclonal antibody against the glomerular cell surface antigen
Authors: NISHIKAWA K , FUKATSU A , TAMAI H , SUZUKI N , ITO Y , SAKAMOTO N , MATSUO S 
Published: July 2010

SUMMARYWe developed a monoclonal antibody, H5H3, of IgG1 subclass by hybridization technique using spleen cells of mice immunized with plasma membrane fraction of isolated rat glomeruli. H5H3 recognized main bands at about 220 kD by immuno-overlay technique and bound to the glomerulus as well as brush border of proximal tubules by indirect immunofluorescenec (IF) microscopy on normal rat kidney frozen sections. By immunoelectron microscopy (IEM) it bound to the surface of mainly glomerular epithelial cell and weakly to the endothelial cell. After injection to Wistar rats it remained granularly in the glomerulus for more than 2 weeks seen by IF. When rats were pre-immunized with murine IgG 4 days before the injection of H5H3, mouse IgG, rat IgG and C3 were strongly visible granularly in the glomerulus in 14 days by IF. Numerous dense deposits were formed at subepithelial area seen by transmission electron microscopy. Perfusion experiment of H5H3 into rat left kidney showed granular distribution of mouse IgG in 48 h. indicating that the reaction occurred in situ. H5H3 bound diffusely in tine granular pattern on the surface of cultured glomerular epithelial cells (GEC) studied by IF and IEM. Antigenic redistribution occurred on GEC after incubation of H5H3 at 37°C. These results suggested the required conditions to form subepithetial immune dense deposits, namely that H5H3 after reaction with antigen could stay for long time in the glomerulus: that H5H3 became an antigen in autologous phase to induce large immune complexes: and H5H3 could induce antigenic modulation.
Both IgA subclasses are reduced in parotid saliva from patients with AIDS
Authors: MÜLLER F , FRØLAND S S , HVATUM M , RADL J , BRANDTZAEG P 
Published: July 2010

SUMMARYSecretory IgA (SIgA), the isotypes IgA1 and IgA2, and IgM were measured by ELISA in stimulated parotid saliva from patients with AIDS (n= 16), subjects with asymptomatic HIV infection (n= 28), and HIV-seronegative healthy controls (n= 19), SIgA was significantly reduced in the AIDS group (10.4 μg/ml) compared with the asymptomatic HIV-infected subjects (17.1 μg/ml) and the controls (23.0 μg/ml). This decrease comprised both IgA1 and IgA2 to a similar extent on a relative basis. The SIgA decrease in AIDS patients was in striking contrast to their serum IgA level, which was significantly increased (6.9 g/I) compared with the asymptomatic HIV-infected subjects (2.9 g/I) as well as the controls (2.8 g/I). Low parotid output of SIgA in patients with HIV infection was associated with low numbers of CD4+ lymphocytes in peripheral blood as well as the presence of oral infections. The parotid output of IgM was similar in all groups. A low level of SIgA in the external secretions of patients with AIDS may well contribute to their frequent mucosal infections of opportunistic microorganisms.
Antibodies to pneumococcal polysaccharides in pneumonia and response to pneumococcal vaccination in young children in Papua New Guinea
Authors: WITT C S , POMAT W , LEHMANN D , ALPERS M P 
Published: July 2010

SUMMARY
Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean children with pneumonia aged 0–14 months, in age-matched healthy Papua New Guinean controls and in healthy expatriate children living in Papua New Guinea. At 0–5 months of age, the IgG antibody titres against six of the eight polysaccharides measured were significantly lower in pneumonia patients than in both control groups. Antibody titres in 6–14-month-old Papua New Guinean controls were significantly lower than in control Papua New Guineans aged 0–5 months for five of the eight polysaccharides tested. In the 6–14-months age group the antibody titre was significantly lower in pneumonia patients than in controls for only one polysaccharide. For seven of the eight serotypes tested, antibody levels in expatriate controls did not decline with age. Antibody responses of Papua New Guinean children aged 6–18 months to a 23-valent pneumococcal vaccine were serotype dependent. Fold increases in response to the vaccine were greatest for the IgA isotype. IgG antibody responses were greater than three fold to four of the eight serotypes tested.
Porphyromonas gingivalis-specific serum IgG and IgA antibodies originate from immunoglobulin-secreting cells in inflamed gingiva
Authors: OGAWA T , KONO Y , MCGHEE M L , MCGHEE J R , ROBERTS J E , HAMADA S , KIYONO H 
Published: July 2010

SUMMARYPatients with adult periodontitis (AP) exhibit elevated serum antibody levels to Porphyromonas (Bacteroides) gingivalis; however, it is not known whether these antibodies originate from plasma cells in the local disease site or From peripheral lymphoid tissues. We studied the isotype and subclass levels and origin of antibodies to P. gingivalis fimbriae, since elevated serum anti-fimbriae responses were seen when compared with sera of healthy controls. IgG unti-fimbriae litres were dominant and the subclass response was IgG3 ≫ IgG1 &gt; IgG2 ≫ IgG4; however, some IgA anti-fimbriae antibodies were also seen. The IgA subclass fimbriae-specific response was mainly IgA1; however, significant IgA2 anti-fimbrae antibodies were seen. We also assessed numbers of anti-fimbriae antibody producing cells from peripheral blood mononuclear cells (PMBC) and from either healthy or inflamed gingiva of AP subjects. Gingival mononuclear cells (GMC) of AP patients exhibited high numbers of immunoglobulin-producing (spot-forming) cells (SFC) including fimbriae-specific antibody secreting cells in a pattern of IgG &gt; IgA &gt; &gt; &gt; IgM. However, low numbers of SFC were seen in GMC from healthy gingiva; further, no anti-timbriac SFC responses were noted in healthy GMC. Although no fimbriae-specific immunoglobulin-producing cells were seen in PBMC. low numbers of antigen-specific SFC were found in pokeweed mitogen-triggercd PBMC from AP subjects. Treatment of AP patients for plaque and surgical removal of inflamed gingiva resulted in significant reductions in serum anti-fimbriac responses. These studies show that AP patients exhibit brisk serum IgG and IgA subclass anti-fimbriac antibodies, whose origin appear to be the plasma cells present in the localized inflamed tissues.
Detection of human and murine common idiotypes of DNA antibodies in tissues and sera of patients with autoimmune diseases
Authors: WATTS R A , RAVIRAJAN C T , WILKINSON L S , WILLIAMS W , GRIFFITHS M , BUTCHER D , HORSFALL A T , STAINES N A , ISENBERG D A 
Published: July 2010

SUMMARYThe expression in tissue and serum of a panel of murine and human common DNA antibody idiotypes (Ids) (BEG 2. PR4, F-423, I-402, II-28. IV-228. V-88) has been investigated. The murine V-88 Id was detected in eight out of 10 and the human BEG 2 Id in five out of 10 labial biopsies from patients with Sjögren's syndrome. The murine F-423, I-402 and IV-228 Ids were identified in one out of 10 biopsies. In each case the pattern of staining was similar with staining of the acinar basement membrane and a cell population. Using double-labelling immunohistochemistry this cell population were identified as plasma cells. No staining was seen in Four normal labial biopsies. The V-88 Id was detected on the epithelial aspect of the thickened basement membrane in three out of nine renal biopsies from patients with systemic lupus erythematosus (SLE). None of the other Ids (BEG2, PR4, IV-228. F-423 or I-402) could be detected in renal tissue. None of the Ids were found in skin biopsies from SLE patients. Id V-88 may, like the 16/6 Id to which it is phenotypically related, play a role in the pathogenesis of renal lesions in SLE. The BEG 2 Id could be detected in the serum of patients with rheumatoid arthritis (RA) and active untreated tuberculosis. Ids II-28, V-88 and I-402 were elevated in serum from patients with Sjogren's syndrome and II-28 Id in serum from patients with myositis and RA. None of the Ids were elevated in serum from patients with SLE. Apart from the BEG 2 Id, none of the Ids were elevated in serum from patients with tuberculosis or Gram-negative infections. The presence of murine Ids in human tissue and serum suggests that they arc cross-species idiotypes and have been conserved through evolution.
Detection of interleukin-6 and interleukin-1 production in human thyroid epithelial cells by non-radioactivein situhybridization and immunohistochemical methods
Authors: ZHENG R Q H , ABNEY E , CHU C Q , FIELD M , GRUBECK-LOEBENSTEIN B , MAINI R N , FELDMANN M 
Published: July 2010

SUMMARYHuman endocrine thyroid epithelial cells have been described to produce cytokines in vitro. In order to determine whether they do so in vivo during thyroiditis. parallel studies on mRNA expression with a non-radioactive in situ hybridization technique and immunohislochemical detection for the protein were performed on frozen sections of thyroid samples from autoimmune thyroiditis (Graves' disease and Hashimoto's thyroiditis), non-toxic goitre and normal thyroid tissue. cDNA probes were sulphonated and their hybridization with mRN A was detected with a sulphonyl-specific monoclonal antibody. This signal was amplified and visualized with the alkaline phosphatase anti-alkaline phosphatase (APAAP) system. The protein products were detected with immuno-purified rabbit F(ab′)2 antibody fragments recognizing recombinant human cytokines, visualized by the immuno-peroxidase technique. Each sample was studied at the two levels. Both interleukin-6 mRNA and protein were found in the endocrine cells. There was no obvious difference between autoimmune thyroiditis and non-toxic goitre. However, normal thyroid epithelial cells produced less interleukin-6. Interleukin-1α mRNA and its protein were found in epithelial cells from Hashimoto's thyroiditis samples, but not in the others, except one Graves' disease sample, in which only mRNA was detected. Interleukin- 1β was not detected in these cells, its mRNA was only found in one of the Graves' disease samples. These cytokines were also detected in some infiltrating cells.
Serum immunomodulatory factors in gastrointestinal diseases. A 30-50-kD serum fraction in Crohn's disease capable of modulating lymphocyte activation
Authors: BIANCONE L , BOIRIVANT M , FAIS S , RICCI G L , PAGANELLI R , PALLONE F 
Published: July 2010

SUMMARYWe tested the hypothesis that serum factors present in Crohn's disease interfere with the process of lymphocyte activation. The mitogen-induced proliferation and the expression of early activation antigens by normal lymphocytes cultured in the presence of either Crohn's disease sera or sera from different controls were evaluated. The mitogen-induced proliferation was significantly impaired in the presence of Crohn's disease sera. These sera markedly inhibited the mitogen-induced interleukin-2 receptor (IL-2R) expression (48% inhibition), while the effect of sera on the expression of the transferrin receptor and the 4F2 antigen was much less pronounced. Diafiltration experiments showed that the inhibitory effect was confined to a 30–50-kD serum fraction. Such a serum property was not related to the patients' disease activity and disappeared after surgical removal of the affected bowel. The capability of inhibiting the mitogen-induced IL-2R expression was not restricted to Crohn's disease and was observed with sera from other inflammatory and neoplastic gastrointestinal disorders. This study indicates that a marked inhibition of the IL-2R is a mechanism underlying the immunosuppressive property of the serum in Crohn's disease and in other gastrointestinal conditions.
Clonotypic analysis of human antibodies specific forNeisseria meningitidispolysaccharides A and C in adults
Authors: LE MOLI S , MATRICARDI P M , QUINTI I , STROFFOLINI T , AMELIO R D 
Published: July 2010

SUMMARYSerum antibodies to the capsular polysaccharides A and C (PSA and PSC) of N. meningitidis in healthy adults before and after vaccination with the sole polysaccharides were analysed by isoelectric focusing (IEF). Before vaccination, 49% and 28% had naturally acquired antibodies against PSA and PSC, respectively, whereas 18 days after vaccine administration 84% and 91%, respectively, showed a detectable spectrotypic pattern. Oligoclonality appeared to be the main feature of naturally acquired and vaccine-induced antibodies for both polysaccharides. In all subjects the anti-PSA response, showing dominant bands at the same pH position, was more homogeneous than anti-PSC one. Most subjects with naturally acquired antibodies (25 out of 38 for PSA and 20 out of 22 for PSC) showed a spectrotypic pattern after vaccination, similar to that observed before vaccination (any differences were just related to band intensity), suggesting that PSA and PSC are able to recruit the same B cell clones previously primed with a T-dependent form of the antigen, i.e. the whole bacterium. However, in one-third of subjects with naturally acquired anti-PSA antibodies, the appearance of new alkaline bands after vaccination was observed. Furthermore, in subjects with absence of detectable natural antibodies, the vaccine-induced antibody response started in correspondence of alkaline pH areas, subsequently extending to neutral and acidic areas. Therefore, it may be hypothesized that alkaline antibody-secreting B cell clones are the first to be recruited. The final spectrotype in these subjects was similar to that observed in subjects with naturally acquired antibodies. This observation, together with the above reported data, allow us to conclude that natural (T-dependent pathway) and vaccine (T-independenl pathway) immunization induce the expression of the same antibody repertoire, for both meningococcal PSA and PSC.
Effect of recombinant human erythropoietin on human IgE productionin vitro
Authors: KIMATA H , YOSHIDA A , ISHIOKA C , MIKAWA H 
Published: July 2010

SUMMARYRecombinant human erythropoietin enhanced spontaneous IgE production 200–300% enhance ment) in cultures of peripheral blood mononuclear cells (MNC) from atopic patients. In contrast, IgG and IgA production were only slightly enhanced (30–50% enhancement), and IgM production was not affected by erythropoietin. The enhancement of IgE production by erythropoietin was indirect since it required T cells and monocytes. However, erythropoietin effect was specific since enhancement was blocked by anti-erythropoietin antibody but not by control antibody. Interleukin-4 (IL-4) also enhanced spontaneous IgE production from atopic MNC. However, the enhancing effect by erythropoietin is different from that by IL-4, since the erythropoietin effect was not blocked by anti-IL-4 antibody, and conversely IL-4 effect was not blocked by anti-erythropoietin antibody. In contrast to the enhancing effect on atopic MNC, erythropoietin failed to induce IgE production in cultures of MNC from normal donors while IL-4 induced IgE production from normal MNC. However, when normal MNC were pre-incubated with IL-4. erythropoietin enhanced IgE production from IL-4-pre-incubated MNC. Moreover. B cells separated from IL-4-pre-incubated MNC produced IgE which was enhanced by erythropoietin. However, this effect required T cells and monocytes. These results indicate that erythropoietin could regulate ongoing IgE production in vitro by T cell- and monocyte-dependent mechanisms.
Human T cell responses to β-galactosidase
Authors: OXLEY J D , BROOKES R H , RAYFIELD L S , SHEPHERD P S 
Published: July 2010

SUMMARYThe peripheral blood of most normal individuals has been shown to contain T cells that respond to β-galactosidase (β-Gal), presumably as a result of natural priming. Three T cell clones (clones 1,2,4) specific for β-Gal were isolated from peripheral blood mononuclear cells (PBMC) after pretreatment with leucine methyl ester (LeuOMe); a fourth clone from the same individual was isolated from untreated cells. All four clones were CD4+ CD8- aβTcR+ and clone 1 was additionally shown to be cytotoxic. Epstein-Barr virus (EBV) transformed B cell lines were derived from LeuOMe-treated or untreated PBMC and used to study the efficiency of presentation of β-Gal to one of the clones. The results indicated that B cells transformed after LeuOMe treatment presented β-Gal at lower concentrations than untreated controls. β-Gal would therefore appear to be a highly suitable model antigen for studies of immunoregulation in humans.
Japanese encephalitis virus latency in peripheral blood lymphocytes and recurrence of infection in children
Authors: SHARMA S , MATHUR A , PRAKASH V , KULSHRESHTHA R , KUMAR R , CHATURVEDI U C 
Published: July 2010

SUMMARYIn a study group of 40 children who had been admitted to hospital with acute encephalitis, the disease was due to infection with Japanese encephalitis virus (JEV). Three children developed recurrence of disease 8-9 months later. No virus had been isolated from these three patients during the acute stage of their illness, but virus was recovered from all during the recurrence phase by co-cultivation of their peripheral blood mononuclear cells in primary mouse embryo fibroblast cultures. Virus was also recovered by co-cultivation of peripheral blood mononuclear cells collected 8 months after their acute disease from three out of eight randomly selected asymptomatic children within the study group but not from similar cultures set up from JEV-seronegative children used as controls. Virus was also isolated by co-cultivation of T lymphocytes of asymptomatic children as detected by indirect immunofluorescence or by inoculation in mice.