bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the complement receptor 3 (CD11b/CD18) in human rectal epithelium
Authors: Hussain L A , Kelly C G , Rodin A , Jourdan M , Lehner T 
Published: July 2010

SUMMARYRectal and cervicovaginal mucosa are common routes of transmission of HIV, although the mechanism of transmission is unknown. We have investigated human rectal and cervicovaginal epithelia for the expression of complement receptors (CR) and cell adhesion molecules which may be involved in HIV and other infections. In rectal mucosa, CR3 was detected in the surface and crypt epithelial cells by immunohistology, using MoAbs to CD18 and CD11b in 10 out of 15 specimens. RNA transcripts encoding both CD11b and CD18 were also demonstrated in surface and crypt epithelial cells by in situ hybridization. Although CD11b was detected in the epithelial cells in three out of the 14 cervicovaginal specimens, we were unable to detect CD 18. We suggest that expression of the CD11b/CD18 heterodimer might facilitate transmission of HIV by enhancing binding of HIV–antibody complexes in seminal fluid to epithelial cells. Alternatively, since intercellular adhesion molecule-1 (ICAM-1) is a receptor for CD11b/CD18, this may promote adhesion between epithelial cells and HIV-infected mononuclear cells in seminal fluid.
Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease
Authors: Rowbotham D S , Howdle P D , Trejdosiewicz L K 
Published: July 2010

SUMMARY
A mycobacterial etiology has been proposed In Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycobacterium tuberculosis and Myco. paratuber culosis in patients with CD (n = 13), compared with ulcerative colitis (UC; n = 17) and controls (n = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates., column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25. CD69). coupled with blastogenesis assays (3H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculosis and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 0.95; P&lt;0.0001) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4± (T helper) subset. Although up to 15% of CD8± (suppressor/cytotoxic) cells also became activated, the CD8± cells did not proliferate subsequently. Cells expressing the alternate γω form of the T cell receptor (TCR γω±) did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specific increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not support a mycobacterial etiopathology of Crohn's disease.
'Split tolerance’ induction by intrathymic injection of acetylcholine receptor in a rat model of autoimmune myasthenia gravis; implications for the design of specific immunotherapies
Authors: Ohtsuru I , Matsuo H , Fukudome T , Suenaga A , Tsujihata M , Nagataki S 
Published: July 2010

SUMMARYExperimental autoimmune myasthenia gravis (EAMG) in the Lewis rat, induced by a single injection of acetylcholine receptor (AChR) protein, is a model used to study human myasthenia gravis (MG), The production of anti-AChR antibodies In the animal model and human MG is T cell-dependent, and AChR-specific T cells have been considered as a potential target for specific immunotherapy. Intrathymic injection of antigens induces antigen-specific tolerance in several T cell-mediated autoimmune models. We examined the effect of intrathymic injection of AChR on T cell responses and the production of antibodies to AChR in EAMG rats. Primed lymph node cells from rats receiving intrathymic injection of AChR exhibited reduced proliferation to AChR with marked suppression of interferon-gamma (IFN-γ) secretion in the antigen-stimulated culture, compared with those of rats injected with PBS. However, neither anti-Narke AChR nor anti-rat AChR antibody production was suppressed or enhanced in intrathymically AChR-injected animals compared with that of animals injected intrathymically with PBS or perithymically with AChR. This ‘split tolerance’ may be attributable to the suppression of type-1 T helper cells (Th1). Our results suggest that the suppression of Th1 function alone may not be sufficient for the prevention of antibody-mediated autoimmune diseases.
An immunosuppressive murine leukaemia virus induces a Th1 → Th2 switch and abrogates the IgM antibody response to sheep erythrocytes by suppressing the production of IL-2
Authors: Faxvaag A , Espevik T , Dalen A 
Published: July 2010

SUMMARYMany retroviruses have tropism for cells in the immune system and have a propensity to induce immunosuppression in the host. Some of the effects of retroviruses on immune cell function are thought to be mediated through cytokines. Friend ImmunoSuppressive virus-2 (FlS-2) is a low oneogenic murine leukaemia virus (MuLV) that induces lymphadenopathy and immunosuppression in NMRI mice. The role of T cell cytokines during the generation of a primary antibody response in healthy and FIS-2-infected mice was studied following the antibody response to sheep erythrocytes by an in vitro immunization (IVI) technique. In cultures from FIS-2-infected mice, the antibody response was reduced compared with cultures from uninfected mice and the production of the Th2 cytokines IL-4 and IL-6 was elevated, whereas the Th1 cytokines IL-2, interferongamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) were reduced. The suppressed antisheep erythrocyte antibody response in cultures from mice infected with FIS-2 seemed to be caused by an insufficient production of IL-2, since addition of recombinant IL-2, stimulated the antibody response. This effect was also observed in cultures depleted of T cells, indicating a direct effect of IL-2 on B cells. A switch to a Th2 cell response and suppression of IL-2 production might play a central role in the immune cell dysfunction induced by FIS-2.
Immune responsiveness inMycobacterium avium-infected mice: changes in the proportion of T cell subsets and antibody production during the course of infection
Authors: Xu D L , Goto Y , Amoako K K , Nagatomo T , Uchida K , Shinjo T 
Published: July 2010

SUMMARYThe C57B1/6 susceptible (BegS) and its resistant (Begr) congenic mouse, previously developed by retrogressive backcrossing, were infected with 1 × 106 colony-forming units (CFU) of Mycobacterium avium and bacterial growth and their immune responses during the early and prolonged periods of infection were examined. There was a high proliferation in the liver and spleen of BegS mice, whereas no proliferation was observed in the Begr mice. Similarly, the sizes and weights of these organs were much higher than those of their Begr counterparts. The size and number of granulomas in Begr were also found to be higher than those of Begr. The CD3+ and CD4+ subsets increased dramatically in both mice during the early stage of infection. However, in the later phase of the infection, these populations decreased dramatically in Begr mice, but not in Begr mice, resulting in a depression in cell-mediated immune responses. No significant decrease in cellmediated immune responses was observed in Begr mice even after prolonged infection. ELISA was performed to determine the antibody levels in both mice, and it was found that serum IgG and IgM levels in Begs were comparatively higher than those in Begr mice throughout the period of infection. The Beg gene therefore may have an important role in the maintenance of resistance not only in the early phase but also in the later phase of Myco. avium infection.
Reactive arthritis-associated bacteria can stimulate lymphocyte proliferation in non-exposed individuals and newborns
Authors: Chieco-Bianchi F , Hedley K , Weissensteiner T , Panayi G S , Kingsley G H 
Published: July 2010

SUMMARYIn reactive arthritis (ReA) a specific T cell response to the triggering bacterial antigen is present in the synovial fluid, while in paired peripheral blood T cells the response is markedly reduced. The proliferative response to ReA-associated bacteria in the peripheral blood of ReA patients was compared with that seen in the blood of healthy adults, who denied exposure to these microbes. and in the umbilical cord blood of newborns, who have clearly not been exposed to bacterial antigen. Peripheral blood mononuelear cells (PBMC) from non-exposed adults and those from umbilical cord blood proliferated to ReA-associated bacteria, whilst little response was seen in ReA PBMC. The response was MHC class Il-restricted, required processing of the bacterial antigen, was seen in both CD45RO+ and CD45RA+ subsets, and was not oligoclonal. These T cell responses are similar to those previously demonstrated in non-exposed individuals to malaria, leishmania and trypanosoma antigen, and may reflect the existence of ‘natural’ T cell immunity to ReA-associated bacteria. The lack of such responses in ReA peripheral blood may suggest that such ‘natural’ responses may restrict the dissemination or progression of infection.
A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement
Authors: Ling M , Piddlesden S J , Morgan B P 
Published: July 2010

SUMMARYExtracts of the herb Ephedra sinica have long been used in traditional Chinese medicine for the treatment of, among other conditions, acute nephritis. In preliminary studies it was shown that extracts of ephedra caused inhibition of complement in vitro. We thus set out to isolate the active component(s) of this herb, to examine the complement-inhibiting capacity in sera from different species, and to characterize the mechanism(s) by which it inhibits complement. Aqueous extraction of the herb followed by fractionation using thin layer chromatography (TLC) demonstrated that complement-inhibiting activity resided within a single band, hereafter termed the complementinhibiting component (CIC). which represents an as yet uncharacterized polyantonic carbohydrate molecule, TLC-purified CIC inhibited the classical complement pathway in all species tested (human, pig, guinea pig, rat and rabbit). Using erythrocyte intermediates and sera specifically depleted of individual components it was apparent that CIC inhibited C2. This- finding was confirmed using purified human C2, CIC causing a dose-dependent loss of C2 haemolytic activity. At much higher doses, CIC also showed some inhibiting effect in the terminal pathway, and this was shown to be due to inhibition of C9. In the alternative pathway CIC also showed inhibitory activity, although its site of action in this pathway remains unresolved. In Chinese medicine the herb is taken orally, though no studies of complement levels in patients taking the herb have been reported. Preliminary data indicate that oral administration in rats causes a partial inhibition of serum complement activity. Given the current enthusiasm for complement inhibition as a therapy for inflammatory diseases, this non-toxic, naturally occurring agent might be of therapeutic value.
Cyclosporin A (CsA) modulates the glomerular production of inflammatory mediators and proteoglycans in experimental nephrosis
Authors: Bustos C , GonzÁLez-Cuadrado S , Ruiz-Ortega M , GÓMez-Guerrero C , GonzÁLez E , Plaza J J , Hgido J 
Published: July 2010

SUMMARYNephrosis is characterized by glomerular epithelial cell injury and a decrease in the glomerular basement membrane (GBM) proteoglycan content. Although CsA is a useful treatment for a group of patients with this disease, its mechanism of action is unclear. We have previously shown that in experimental nephrosis there is an increase in the glomerular production of tumour necrosis factor-alpha (TNF-α) and platelet-activating factor (PAF). Here we have studied the effect of CsA on kidney generation of TNF-α and PAF in puromycin aminonucleoside (PAN) nephrosis as well as on the synthesis of proteoglycans by cultured glomerular epithelial cells. Rats receiving CsA had. on day 8 of PAN injection, a significant reduction in proteinuria, blood cholesterol levels and in interstitial mononuclear cells. A diminution in glomerular production and urinary excretion of TNF-α and PAF was also noted. In in vitro studies, at 24 h of incubation PAF and TNF-a induced in glomerular epithelial cells a significant decrease in proteoglycan synthesis. Neither PA F nor TNF-α had any significant effect on glomerular epithelial cell proliferation. CsA alone induced a dose-response increase in proteoglycan synthesis and a slight decrease in cell proliferation, CsA also reversed the inhibitory effect of PAF and TNF-α on proteoglycan synthesis. However, CsA did not alter the pattern of proteoglycan prtxiuction, remaining around 50% chondroitinase ABC-, 15% heparitinase-sensitive. Our results indicate that PAF and TNF-α could be implicated in the pathogenesis of nephrosis through the inhibition of proteoglycan synthesis by glomerular epithelial cells. The beneficial effect of CsA in nephrosis may be due to the recovery of the GBM charge selectivity caused by the normalization of glomerular PAF and TNF-α synthesis and the increase in proteoglycan synthesis by glomerular epithelial cells.
Recombinant soluble FcγRII inhibits immune complex precipitation
Authors: Gavin A L , Wines B D , Powell M S , Hogarth P M 
Published: July 2010

SUMMARYControl of IgG immune complex formation and deposition is important in determining the nature and extent of subsequent immune effector responses, and appears to be aberrant in some autoimmune diseases. In this study we demonstrate that recombinant soluble FCγRII (rsFcγRII) is an effective modulator of immune complex formation, delaying immune precipitation in a manner which is dose-dependent, and can be specifically inhibited by anti-FcγRII MoAb Fab’ fragments. This inhibitory role in immune precipitation also provides a possible mechanist explanation for our previous demonstration of the efficacy or rsFcγRII as an inhibitor of immune complex-induced inflammation in the Arthus reaction in vivo. RSFcγRH inhibited immune complex precipitation in two different experimental systems. First, rsFc7RII inhibited the precipitation of 125I-bovine serum albumin (BSA)-anti-BSA complexes in a dose-dependent manner, while an irrelevant protein (soybean trypsin inhibitor) had no effect on the precipitation of the immune complexes. Moreover. RsFcγRII inhibited the precipitation of ovalbumin (OVA) anti-OVA complexes as determined by turbidimetric analysis, where the inhibition of immune complex precipitation by rsFc7RII was dose-dependent and was specifically blocked by prior ineubation with Fab’ fragments of a blocking MoAb to FcγRII. RSFcγRII could inhibit the precipitation of BSA anti-BSA complexes in the presence of excess bystander IgG and did not inhibit complement-mediated prevention of immune precipitation, demonstrating that rsFcγRII did not block C1 binding to the BSA anti-BSA complex. Unlike complement. RSFC7RIL could not cause re-solubilization of pre-formed precipitated BSA- anti-BSA complexes. Soluble FcγRS have been detected in biological fluids of normal and inflammatory disease patients., yet the role of SFcγR is still unclear. However, they now play a potential role in the modulation of immune complex solubility.
Mannose-binding protein in preterm infants: developmental profile and clinical significance
Authors: Lau Y L , Chan S Y , Turner M W , Fong J , Karlberg J 
Published: July 2010

SUMMARYThe aim of this study was to determine the developmental profile of mannose-binding protein (MBP) in preterm infants. MBP was measured in 885 longitudinally collected serum samples from 168 preterm infants, and 63 were genotyped with respect to the codon 54 mutation in the MBP gene. MBP level/codon 54 genotyping were also determined on the cord blood of 146/123 term infants and 138/123 adults, respectively. The best cut-off values of MBP for dividing preterm, term infants and adults into ‘low’ and ‘high’ M BP groups were 400 ng/ml (55 low, 113 high), 700 ng/ml (35 low, 111 high) and 750 ng/ml (33 low. 105 high), respectively, by achieving the least number of misclassifications according to the codon 54 mutation. The relative risk of the ‘low’ groups for presence of the codon 54 mutation compared with ‘high’ groups were 42 4, 67–9 and 22–9 for preterm, term infants and adults, respectively (P KO 00001). The gestational age and birth weight of the ‘low’(n = 55) and ‘high’(n= 113) MBP groups of the 168 preterm infants were 29.5 ± 2.8 weeks, 30.5±2.8 weeks (p=0.03) and 1230±317g, 1277±289g (p = 0.35). respectively. The mean MBP levels of these two groups of preterm infants were different (P&lt;0001) at all ages measured. As a whole group, the MBP level rose from a mean of 500 ng/ml at 25 weeks gestation to 1700ng/ml at 20 weeks post full-term. The mortality rates of ‘low’ and ‘high’ MBP groups of preterm infants were 22% and 12%, respectively (p-0.113). This difference in mortality was due to gestational age and birth weight standard deviation score (SDS) after adjusting for length of gestation and gender (p = 0.0001) rather than to low MBP levels (p = 0 65). MBP levels were not related to birthweight SDS score (P = 0 26). The mean ± sd. MBP levels for preterm, term infants and adults without the codon 54 mutation were 1225 ±701 ng/ml (n = 45), 2064 ± 829 ng/ml (n= 88) and 2473 ± 1395ng/ml (n = 95), respectively; the corresponding values for those with the codon 54 mutation were 130 ±275 ng/ml (n= 18), 533 ±665 ng/ml (n = 35)and 330±225ng/ ml (n= 28), respectively. Intra-uterine growth retardation in preterm infants does not influence MBP levels. For those without the codon 54 mutation, there is a significant difference in MBP level between the three age groups. For those with the codon 54 mutation, there is a significant difference between preterm and term infants, but not between term infants and adults. We conclude that there is a maturation in MBP levels for preterm infants, and that a moderately low MBP phenotype does not affect survival. We cannot exclude an effect of profoundly reduced MBP levels (characteristic of individuals homozygous for the codon 54 mutation), since no such preterm infant was identified in this study.
Acute phase proteins and recombinant IL-2 therapy: prediction of response and survival in patients with colorectal cancer
Authors: Simpson W G , Heys S D , Whiting P H , Eremin O , Broom J 
Published: July 2010

SUMMARYTwenty-four patients with metastatic colorectal cancer were treated with recombinant IL-2 (rIL-2) by continuous intravenous infusion for 5 days (18 · 106 U/m2 per 24 h), followed by three injections of 5-fluorouracil (600 mg/m2) and folinic acid (25mg/m2) at weekly intervals. The response to treatment was assessed using standard UICC criteria (partial or complete response, stasis or progression of disease). The serum concentrations of the acute phase proteins; C-reactive protein (CRP), retinol binding protein (RBP), α1-antitrypsin (α1-AT), transferrin (TF) and albumin were measured. A response to therapy occurred in the tumours of seven (29%) of the 24 patients (two complete and five partial responses). All patients who demonstrated a response to treatment had a serum albumin level of &gt; 37 g/l and a CRP level of · 10 mg/l. In contrast, of the 17 patients who did not respond to therapy, 12 (71%) had a serum albumin of less than 37 g/dl and a CRP of greater than 10 mg/l. Examination of the survival times of the 12 patients who had a pretreatment serum albumin level of less than 37 g/l revealed that all had died within 12 months of cessation of therapy. However, 58% of patients with pretreatment serum albumin levels of greater than 37 g/l survived for longer than 12 months. These results have shown that (i) patients who respond to rIL-2-based therapy and (ii) those patients who have prolonged survival times, can be identified by pretreatment measurement of serum levels of acute phase proteins.
Effects of anti-CD3 monoclonal antibodies on functional activity of lymphocytes: studiesin vivoandin vitro
Authors: Parlevliet KJ , Chamuleau M E D , Yong S-L , Raasveld M H M , Ten Berge I J M , Schellekens P TH A 
Published: July 2010

SUMMARYLymphocyte functional activity was tested in 38 renal transplant recipients receiving induction treatment with various anti-CD3 MoAbs, i.e. OKT3, T3.G2a (an IgG2a anti-CD3 MoAb) or T3.A (an IgA anti-CD3 MoAb of the same idiotype). During treatment with OKT3 and T3.G2a, lymphocyte response to phytohaemagglutinin-P (PHA), as determined with the use of a whole-blood lymphocyte culture technique, decreased significantly. However, during treatment with T3.A PHA response was not affected. Using a conventional lymphocyte culture technique, PHA response was unchanged during treatment with all three MoAbs, indicating that the immunosuppressive effect of OKT3 and T3.G2a is probably dependent upon the presence of MoAb in culture medium and is reversible. In addition, we tested in vitro inhibition of aspecific mitogen- or antigen-induced lymphocyte stimulation by OKT3, T3.A and T3.G2a. It appeared that at low concentrations (&lt; 25ng/ml) T3.G2a and OKT3 exerted a stronger immunosuppressive effect than T3.A. However, at higher concentrations T3.A, OKT3 and T3.G2a were equally immunosuppressive. We conclude that the immunosuppressive effect of T3.A is caused by blindfolding. At low concentrations T3.G2a exerts its immunosuppressive effect mainly through modulation of the CD3 and/or T cell receptor complex, as a result of interaction with Fc receptors on monocytes. At higher concentrations blindfolding of the CD3/T cell receptor complex may contribute to immunosuppression.
The affinity of IgG antibodies to gag p24 and p17 in HIV-1-infected patients correlates with disease progression
Authors: Chargelegue D , Stanley C M , O'toole C M , Colvin B T , Steward M W 
Published: July 2010

SUMMARYThe affinity of anti-gag antibody was studied for up to 9 years (1984–1993) in sera from 15 HIV-1+ patients with haemophilia. On the basis of their 1993 clinical status patients were divided into two groups: (i) patients who remained asymptomatic (n= 9); and (ii) those who progressed to AIDS between late 1987 and 1993. The affinity constants of antibody for p24 and p17 were determined by a double isotope fluid-phase radioimmunoassay; and the relationships between antibody affinity and titre, patient clinical course, CD4 cell counts and p24 antigenaemia were analysed. The affinity of p24- and p17-specilic antibody was up to 100 times greater in asymptomatic patients than in patients who progressed to AIDS. Patients who developed AIDS either lost or failed to develop high-affinity antibodies early in the infection. Asymptomatic patients maintained high-affinity antibodies for several years; however, in some of these patients the affinity of anti-p24 and p17 antibodies subsequently fell later in the study period. The presence of low-affinity antibody and progressive reduction in the titre of specific antibody were earlier predictors of disease onset than CD4 cell counts. The failure to either develop or maintain high affinity gag-specific antibody suggests an early impairment of T helper function in individuals who progressed to AIDS. The presence of antibody of high affinity could be essential in controlling virus replication and the onset of AIDS.