bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell receptor haplotypes in families of patients with insulin-dependent diabetes mellitus
Authors: KELLY H , GARLEPP M J 
Published: July 2010

SUMMARY
The frequencies of Bgl 11 and BamH1 restriction fragment length polymorphisms (RFLP) of Cβ Vβ8, Vβ11 and Vβ7.2 have been defined in a healthy Australian population. Linkage disequilibrium between alleles of the T cell receptor (TCR) Vβ8 and Vβ11 gene segments has been confirmed. We have also confirmed the lack of linkage disequilibrium between either of these loci and alleles at Cβ or Vβ7.2. Using RFLPs at Vβ11 and Vβ8 loci TCR β haplotypes have been identified in five families in which the probands have insulin-dependent diabetes mellitus (IDDM). An extremely rare haplotype. marked by the higher molecular weight Bam H1 allele (H, H) at each of Vβ11 and Vβ8, was found in the DR4+ DR3− probands of two families (P= 0·004). In three families in which the probands had DR3. the more common TCR haplotype LH (Vβ11, Vβ8) was found. Taken together, these data confirm that linkage disequilibrium does exist in the TCR β locus, at least in some regions, and suggest that detailed analysis of the relationship between TCR Vβ haplotypes and HLA is warranted since these RFLPs may be markers for important allelic V gene sequence variations.
Identification and purification of a receptor on macrophages for the dengue virus-induced suppressor cytokine
Authors: MUKHERJEE R , CHATURVEDI P , CHATURVEDI U C 
Published: July 2010

SUMMARY
Dengue type 2 virus (DV)-induced suppressor cylokine (SF) binds to macrophages to transmit the suppressor signal to recruit the second subpopulation of suppressor T cells. The present study was undertaken to identify and purify the receptor for SF(SF-R) on macrophages. The binding of 125I-SF to macrophages was saturable and reversible. Scatchard analysis showed the presence of both high (54 000/cell) and low (178 × 106/cell) affinity receptor sites. The binding of 125I-SF to macrophages was inhibited by pretreatment of macrophages with anti-SF antiseruin but not by a heterologous antiserum. Normal mouse peritoneal macrophage membrane was solubilized with Triton-X-100 and the components separated by low pressure liquid chromatography (LPLC) to purify SF-R. The presence of SF binding moiety (SF-R) was screened at each step of purification. The purified SF-R resolved into two bands of 45–50 kD mol. wt on SDS-PAGE. 125I-SF + SF-R complex run on SDS-PAGE showed a single band at about 55–60 kD mol. wt by autoradiography. Anti-SF-R anti serum reacted with SF-R in a Western blot test; the reaction was abolished by pretreatment of the blots with proteinase K, but not by pretreatment with periodic acid. SF-R was composed of two polypeptide chains (α and β) which were obtained in pure form by high performance liquid chromatography (HPLC) of dithiothreitol- and iodoacetamide-treated SF-R. Only the β chain bound SF.
Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophiis in patients with myelodysplastic syndromes
Authors: OHSAKA A , KITAGAWA S , YUO A , MOTOYOSHI K , FURUSAWA S , MIURA Y , TAKAKU F , SAITO M 
Published: July 2010

SUMMARYThe superoxide (O2−-releasing capacity in response to N-fomiyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granuloeyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating faclor (rhGM-CSF) on FMLP-induced O2− release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O2− -releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutJ-ophils. the O2−-releasing capacity in MDS neutrophils was increased in 9/14 patients, nonnal in three patients and decreased in two patients. There was no close relationship between the O2−-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming eflect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 μg/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O2 release. These findings demonstrate that the neutrophil O2−-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.
Induction of mouse monocyte Ia expression by a mesangial cell-derived product
Authors: YAMASHITA W , LIU Y J , OOI B S 
Published: July 2010

SUMMARYPrevious studies in many laboratories have shown that macrophage hi expression is not constitutive but under regulation. We provide data which demonstrate that product(s) of mouse mesangial cell cultures Induce blood monocyte la expression as demonstrated by immunofluoresconce. This process is time-reialed and is also dependent on novel protein synthesis, being abrogated when themonocytes arepretreated with cycloheximidc. Preliminary characterization shows the mesangial cell product to be sensitive to healing at 100°C × 30 min, to be resistant to digestion by trypsin at a concentration of 4 × 10–6 M. and to have a molecular size of 10–100 kD as established by Amicon ultrafiltration. The substance is not interferon-gamma (IFN-γ) since cultured mesangial cells had no contaminating T cells, mesangial cell supernatant had no delectable levels of IFN-γ, and the Ia-inducing activity of the mesangial cell product was not abrogated by incubation of monoeytes with mesangial cell supernatant which had been immunoprecipitated with anti-IFN-γ. Similarly, experiments using anti-CSF-1 have excluded the possibility that the substance is CSF-1. The results of the study have relevance to the mechanisms by which inonocytes which take up residence in the glomerular mesangium acquire la positivity. and also provide a potentially novel pathway by which a tissue product may induce monocytes to express Ia.
Enhancement of IL-1, IL-2 production and IL-2 receptor generation in patients with acute rheumatic fever and active rheumatic heart disease; a prospective study
Authors: MORRIS K , MOHAN C , WAHI P L , ANAND I S , GANGULY N K 
Published: July 2010

SUMMARYIn a prospective study, patients with quiescent rheumatic heart disease (CRHD), streptococcal pharyngitis (SP) and healthy normal subjects produced comparable amounts of IL-1 and IL-2, but acute rheumatic fever (ARF) patients produced significantly elevated amounts of IL-1 and IL-2 at all intervals up to 48 weeks. In active rheumatic heart disease (ARHD), IL-1 activity returned to within normal range at 48 weeks, but IL-2 activity remained persistently elevated compared with CRHD, SP and healthy age- and sex-matched volunteers. CD4+ T lymphocytes were significantly increased in the peripheral blood of ARF and ARHD patients. The amount of IL-2 produced by ARF and ARHD patients correlated with the percentage of helper T lymphocytes (CD4+ cells) but not with the percentage of suppressor/cytotoxic T lymphocytes (CD8+ cells). Moreover, pre- and post-phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from ARF and ARHD patients contained higher proportions of IL-2R+ (CD25+) cells than those from patients with SP, CRHD and normal individuals, which persisted up to 48 weeks. The percentage of CD25+ cells in both types of PBMC cultures directly correlated with the percentage of CD4+ cells and not with CD8+ cells in active rheumatic patients only. These findings indicate that the immune response in ARF and ARHD patients is skewed to produce activated helper T cells that release IL-2 which drives the accumulation of more T helper cells. The result is an undamped helper T cell response in the peripheral blood of these patients.
Antigenic regions within the hepatitis C virus envelope 1 and non-structural proteins: identification of an IgG3-restricted recognition site within the envelope 1 protein
Authors: SALLBERG M , RUDÉN U , WAHREN B , MAGNIUS L O 
Published: July 2010

SUMMARYAntibody binding to antigenic regions of hepatitis C virus (HCV) envelope 1 (El; residues 183–380), E2/non-structural (NS) 1 (residues 380–437), NS1 (residues 643–690), and NS4(1684–1751) proteins were assayed for 50 sera with antibodies to HCV (anti-HCV) and for 46 sera without anti-HCV. Thirty-four peptides. 18 residues long with an eight-amino acid overIap within each HCV region, were synthesized and tested with all 96 sera. Within the E region 183–380, the major binding site was located to residues 203–220, and was recognized by eight sera. Within the E2/NS1 region 380–437, the peptide covering residues 410–427 was recognized by two sera, and within the NSl region 643–690, peptides covering residues 663–690 were recognized by four sera. Within the NS4 region 1684–1751, 27 sera were reactive to one or more of the NS4 peptides, and 21 out of these were reactive with peptide 1694–1711. One part of the major binding site could be located to residues 1701–1704, with the sequence Leu-Tyr-Arg-Glu. The IgGl, IgG3 and IgG4 subcIasses were reactive with the five antigenic regions of HCV core, residues 1–18, 11–28, 21–38, 51–68 and 101–118. Reactivity to the major envelope site consisted almost exclusively of IgG3, and reactivity to the major site of NS4 consisted only of IgG1. Thus, a non-restricted IgG response to linear HCV-encoded binding sites was found to the core protein, whereas IgG subcIass-restricted linear binding sites were found within the El protein, and within the NS4 protein.
Modulation of human mesangial cell behaviour by extracellular matrix components—the possible role of interstitial type III collagen
Authors: SAITO K , SHIMIZU P , SATO T , OITE T 
Published: July 2010

SUMMARY
We have investigated the effects of various extracellular matrix (ECM) components on the behaviour of human mesangial cells (HMC) in u gel culture system using a modified MTT assay method. When cultured on u reconstituted basement membrane. Matrigel (M gel), HMC aggregated and formed isolated colonies initially, then extended an array of cell processes to form a dendritic network structure and proliferated very slowly as the culture period progressed. On type I colIagen gel (Cl gel), however. HMC developed elongated bipoIar shapes, migrated into the gel. and showed rapid cell growth. Next, separate ECM components, such as type III and IV colIagens. Iaminin. heparm and heparan sulphate, were incorporated into CI gel and HMC proliferation was assessed. Although attachment of HMC to each gel did not differ significantly. HMC proliferation was inhibited markedly on gels containing type III colIagen, heparin and heparan sulphate: type IV colIagen suppressed HMC proliferation slightly; and Iaminin had no significant effect. These data suggest that interstitial type I and III colIagcns. which arc often observed in diseased glomcruli. as well as the basement membrane components, may pIay important roles in the reguIation of HMC proliferation under pathophysiological conditions in vivo. We conclude that HMC behaviour is affected by the surrounding ECM constituents, which appear to function as a refined moduIator.
Rheumatoid arthritis: how well do the theories fit the evidence?
Authors: McCULLOCH J , LYDYARD P M , ROOK G A W 
Published: July 2010

SUMMARYIn this brief review, inspired partly by a symposium at the autumn meeting of the British Society for Immunology, 1992, varying hypotheses concerning the etiopathogenesis of rheumatoid arthritis (RA) are explored and tested against current evidence. Immunogenetic considerations, whilst of interest, have not aided our understanding of the development of this disease. The association with restricted HLA-DR β chain hypervariable sequences does not hold true with all cases of RA (but may be related to disease severity) and studies of T cell receptor (TCR) β chain usage fail to show consistent oligoclonality of infiltrating T cells in the synovial compartment. Etiologies based on triggering by bacteria are also considered: homologies between the ‘shared epitope’ sequences of HLA-DR 1 and DR4 β chains, Escherichia coli dnaJ and Proteus haemolysin do not indicate any feasible mechanisms for the development of RA, and cannot explain the many cases in which such DR sequences do not occur, though new data from man and animals enhance interest in the role of bowel flora. Finally, the striking parallels between slow bacterial infections and RA, in terms of immunogenetics, pathology, IgG glycosylation abnormalities and autoimmune manifestations, are put forward as circumstantial evidence that such bacterial infections may underly, or trigger, this serious disease.
Local production and localization of transforming growth factor-beta in tuberculous pleurisy
Authors: MAEDA J , UEKI N , OHKAWA T , IWAHASHI N , NAKANO T , HADA T , HIGASHINO K 
Published: July 2010

SUMMARYTransforming growth factor-beta (TGF-β) is one of the cytokines which play an immunosuppressive role in an inflammatory process. To investigate the local production of TGF-β, we evaluated the levels of TGF-β in tuberculous pleural effusions (TBPE) and non-tuberculous benign pleural effusions (non-TBPE) by the growth inhibition assay with MvILu mink lung epithelial cells. The mean level of TGF-β in TBPE (46·1 ± 31·5 pM; mean ± s.d.) was higher than in non-TBPE (21·7 ± 12·3 pM) (P&lt;0.05). Although the level of interferon-gamma (IFN-γ) in TBPE measured by ELISA was significantly higher than in non-TBPE. there was no significant difference in the levels of tumour necrosis factor-alpha (TNF-α) measured by ELISA between these two groups. Moreover, to elucidate localization of TGF-β in tuberculous pleurisy, immunohistochemical studies of pleura, using the rabbit polyclonal antibody Ab39 against latent TGF-β1 binding protein (LTBP) were performed. Results revealed that LTBP was localized in immature fibrotic areas where infiltrations of T lymphocytes and macrophages were absent. Importantly, the major sources of LTBP in these areas were thought to be mesothelial cells and fibroblasts. LTBP was not found in granulomas and mature fibrotic areas. Our data suggest that TGF-β in tuberculous pleurisy may play important roles for regression of granulomatous inflammation and pleural fibrosis for tissue repair.
Production and analysis of IgG monoclonal anti-DNA antibodies from systemic lupus erythematosus (SLE) patients
Authors: EHRENSTEIN M , LONGHURST C , ISENBERG D A 
Published: July 2010

SUMMARY
This study compares recently devised methods for producing IgG anti-DNA MoAbs from patients with SLE and analyses the antibodies generated from one patient at different phases of disease. Lymphocytes from SLE patients were transformed with Epstein-Barr virus (EBV) and/or fused with a heteromyeloma cell line, CB-F7. Direct fusion with CB-F7 resulted in the highest proportion of IgG-secreting lines, whereas EBV transformation resulted in a high percentage of IgM-secreting lines. Using direct fusion, five IgM anti-DNA antibody-secreting hybridomas were generated using lymphocytes from a patient with relatively inactive SLE. Six months later when the disease was active, only IgG anti-DNA antibodies were produced. The antigen-binding patterns of the MoAbs were analysed. Only one of the IgM anti-DNA antibodies reacted with dsDNA by ELISA and none by Crithidia immunofluorescence, whereas two of the IgG antibodies reacted with dsDNA by ELISA and Crithidia but did not bind to ssDNA. Only the two IgG high affinity anti-dsDNA antibodies bound to histones, and this was enhanced by added DNA, whereas three IgM antibodies bound to cardiolipin. This study supports the notion that MoAbs derived from a patient with SLE represent those found in the serum of SLE patients at different stages of disease activity. The binding to histones by the two IgG anti-dsDNA antibodies supports the recently expressed view that antibodies binding DNA/histone may be important in the pathogenesis of SLE.
Similar frequency of autoantibodies against 70-kD class heat-shock proteins in healthy subjects and systemic lupus erythematosus patients
Authors: KINDAS-MÜGGE I , STEINER G , SMOLEN J S 
Published: July 2010

SUMMARYStress or heat-shock proteins may be involved in the initiation and perpetuation of autoimmune diseases. In order to investigate a possible role of autoantibodies against the 70-kD family of heat-shock proteins in systemic lupus erythematosus (SLE), sera of SLE patients and healthy subjects were tested for the presence of IgG and IgM antibodies to 70-kD class proteins. These proteins were purified by affinity chromatography on ATP-agarose and used in Western blotting studies. The data obtained revealed that antibodies to the 72-kD and the 73-kD heat-shock proteins occurred with similar frequencies both in healthy subjects and SLE patients. Thus, approximately 20% of the sera in each group contained IgG antibodies, and IgM antibodies were detected in about 30% of the sera tested. Moreover, in SLE patients no association between the occurrence and litre of these antibodies and disease activity was found. These data suggest that antibodies to the 70-kD class heat-shock proteins are naturally occurring and argue therefore against an involvement of these antibodies in the pathogenesis of SLE.
Differential induction of helper T cell subsets during blood-stagePlasmodium chabaudiAS infection in resistant and susceptible mice
Authors: STEVENSON M M , TAM M-F 
Published: July 2010

SUMMARYThe induction of T helper cell subsets during the course of non-lethal or lethal blood-stage Plasmodium chabaudi AS infection was investigated using inbred strains of mice which differ in the level of resistance to this intraerythrocytic parasite. Resistant C57B1/6 mice experience a non-lethal course of infection characterized by moderate levels of both parasitaemia and anaemia and resolution of primary acute infection by 4 weeks, while susceptible A/J mice experience lethal infection with fulminant parasitaemia and severe anaemia. T helper subset function was assessed during infection by determining the kinetics of spleen cell production in vitro of the Th1-derived cytokine, interferon-gamma (IFN-γ), and of the Th2-dcrived cytokine, IL-5, using sandwich ELISAs. Spleen cells from resistant C57B1/6 mice were found to produce high levels of IFN-γ within 1 week of infection in response to both the mitogen concanavalin A (Con A) and malaria antigen. Furthermore, CD4+ T cells were found to be the source of I FN-γ while both CD4+ and CD8+ T cells were found to produce IL-5. Decreased IFN-γ production after day 10 was concomitant with significant production of IL-5 between 2 and 3 weeks post infection. In contrast, spleen cells from susceptible A/J mice produced high levels of IL-5 within the first week of infection. In addition, these animals were found to have high serum levels of IL-5. These results, thus, confirm previous observations that resolution of primary blood-stage P. chabaudi infection occurs by sequential activation of Th1 CD4+ T cells followed by activation of the Th2 subset, and in addition, suggest that induction of a strong Th2 response early in infection may lead to a severe and lethal course of malaria.
Phenotypic characterization of CD8+ T cell populations in HIV disease and in anti-HIV immunity
Authors: WATRET K C , WHITELAW J A , FROEBEL K S , BIRD A G 
Published: July 2010

SUMMARYThe CD8+ T cell population is believed to play an important role in the control of viral infection, both for suppression of viral replication and for cytotoxic activity against viral infected cells. Elevated numbers of CD8+ T cells have been demonstrated in HIV infection, and CD8+ cytotoxic T cell (CTL) activity is associated with the early, asymptomatic stage of disease. We investigated the phenotypic characteristics of the CD8 population, in whole blood, in HIV disease and determined the predominant CD8+ subpopulation involved in anti-HIV CTL activity. We found that CD8+ T cells co-expressing markers of activation (HLA-DR), memory (CD45RO, CD29), and cytotoxic activity (S6F1) were significantly elevated in the early stages of disease, while the numbers of naive (CD45RA) cells remained unchanged. Progression to AIDS resulted in an overall loss of absolute CD8+ T cells, though the percentages of CD8+ HLA-DR+ and CD8+ S6F1+ remained elevated. In contrast to patients in the late stages of disease, anti-HIVgag CTL activity, following in vitro stimulation, was present in most HIV+ asymptomatic subjects and was associated with an expansion of CD8+ HLA-DR+ and CD8+ CD45RO+ cells. The absence of CTL activity was associated with a reduced ability of these populations to expand in vitro and with a significant loss of peripheral CD4+ T cells, independent of clinical stage. We suggest that CD8+ expressing HLA-DR+ CD45RO+ and S6F1+ play an important role in anti-HIV cytotoxicity.
Increased expression of interferon-gamma in hyperplastic lymph nodes from HIV-infected patients
Authors: BOYLE M J , BERGER M F , TSCHUCHNIGG M , VALENTINE J E , KENNEDY B G , DIVJAK M , COOPER D A , TURNER J J , PENNY R , SEWELL W A 
Published: July 2010

SUMMARYPolyclonal B cell activation is characteristic of HIV infection and occurs in the presence of severe CD4+ lymphocyte depletion. In contrast, CD4+ lymphocytes are the dominant T cell in the reactive lymphoid tissues of patients not infected with HIV. In this study, lymph node biopsies from eight HIV-infectcd patients with persistent generalized lymphadenopathy syndrome (PGL) were assessed for IL-lβ, IL-2, IL-4, IL-6, IL-10, interferon-gamma (IFN-γ) and tumour necrosis factor-beta (TNF-β) gene expression using the polymerase chain reaction (PCR). The cytokine gene expression of two cases of reactive adenopathy in patients not infected with HIV was assessed for comparison. IFN-γ was expressed much more strongly in the PGL samples than in control reactive lymphoid tissues, whereas the other cytokines were expressed to a similar extent in both types of tissues. IFN-γ may have an important role in maintaining the adenopalhy of HIV-infected patients. Expression of cytokines such as IL-2, IL-4 and IL-10 in HIV nodes may be adequate to allow the recruitment of naive B cells to the reactive process.
Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9
Authors: MILIS L , MORRIS C A , SHEEHAN M C , CHARLESWORTH J A , PUSSELL B A 
Published: July 2010

SUMMARYIn the activated complement system, vitronectin (complement S-protein) occupies the metaslable membrane binding site of the nascent precursor complex C5b-7, so that the newly formed SC5b-7 is unable to insert into cell membranes. Some evidence also indicates that vilronectin limits on-going membrane-associated pore formation by inhibiting C9 polymerization. It has been assumed that these two stages of terminal complement complex (TCC) inhibition take place through charge interactions between the heparin-binding region of vitronectin and homologous cysteine-rich sequences of the late complement proteins C6, C7, C8 and C9. We examined SC5b-7 formation and inhibition of C9 binding in the TCC using separate haemolytic assays. The mode of action of vitronectin in these assays was compared with two 15mer peptides which span residues 348–379 of the heparin-binding region, and a heparin-attinity polypeptide. protamine sulphate. The results showed that vitronectin acts predominantly through SC5b-7 production with a lesser effect on the inhibition of C9 lytic pore formation. In contrast, protamine sulphate did not prevent C5b-7 membrane attachment, but was a potent inhibitor of C9-mediated lysis. The peptides did not inhibit C5b-7 membrane insertion and only one affected C9 binding. These data suggest that the two stages of TCC inhibition involve separate binding sites on the vitronectin molecule. The site for association with nascent C5b-7 is unknown, whereas inhibition of C9 binding and pore formation lakes place through the heparin-binding region.