bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA-B27 subtypes in the spondarthropathies
Authors: MACLEAN I L , IQBALL S , WOO P , KEAT A C S , HUGHES R A , KINGSLEYJ G H , KNIGHT S C 
Published: July 2010

SUMMARYThe spondartliropathy (Sp)-associated HLA-B27 antigen includes al least seven subtypes. B*2701–07, of which 01, 02, 05 and 07 occur in Caucasians. This study examined the B27 subtype distribution in British patients with Sp. The 133 HLA-B27+ subjecis comprised 94 European Caucasian Sp (58 ankylosing spondylitis (AS), 22 reactive arlhrilis (ReA: 11 sexually acquired (SARA). 11 enteric (EReA)). eight undifferentiated Sp (USp). and six pauciarticular juvenile-onset chronic arthritis (pJCA)) patients, antl 34 healthy Caucasian controls, together with four Asian Indian and one Chinese. 35S-labelled B27 was immunoprecipitated with anti-B27 MoAbs. and subtyped according to isoelectric point (pi) following isoelectric focussing. The use of B27 MoAb permitted subtype assignment without full class 1 HLA lyping. The vast majority (95%) were B*27O5 (Caucasian controls 31/34; AS 55/58; ReA 21/22; USp 8/8. and pJCA 6/6; Indian control 1/1 and AS 2/3: Chinese pJCA I/I), and the remainder B*2702. No B*270l or 07 subjects were identified. AS occurs in both B*2702 and 05 subjects, and we extend this observation to small numbers of ReA and of Indian AS subjects. This implicates molecular features shared between B27 subtypes, rather than subtype-determining regions of the antigen, in Sp palhogenesis.
Augmented lymphocyte binding to cultured endothelium in psoriasis
Authors: LEE M L , TO S S T , COOPER A , JONES M , SCHRIEBER L 
Published: July 2010

SUMMARYLymphocyte binding to cultured human umbilical vein endothelial cells was evaluated using a modified centrifugation binding assay in 15 patients with psoriasis and compared with three patients with atopic dermatitis, 11 patients with rheumatoid arthritis and 28 normal controls. Patients with psoriasis demonstrated 61% augmented lymphocyte binding compared with normal controls (P&lt;0.0001), which was not explained by differences in age and sex or an effect of psoriatic sera. In serial studies of six patients, this difference was found to be reversible with treatment and clinical improvement. Lymphocytes from patients with atopic dermatitis demonstrated decreased binding to endothelium (P&lt;0.005), while those from patients with rheumatoid arthritis were not different from normal controls. This is the first skin disease described in which augmented lymphocyte binding to endothelium occurs, and may represent a mechanism by which lymphocytes are targeted to psoriatic skin.
Early time course of recruitment of immune surveillance in human skin after chemical provocation
Authors: FRIEDMANN P S , STRICKLAND I , MEMON A A , JOHNSON P M 
Published: July 2010

SUMMARYAs part of the defence function of skin it seems probable that mechanisms exist for the rapid recruitment of immune surveillance to ‘inspect’ any foreign substance that penetrates the skin. In the present study, evidence of such mechanisms was sought by following the time course of early changes in distribution of immune cells, expression of cell adhesion molecules and cytokines after epicutaneous challenge with provoking chemicals to which subjects were known to be either specifically ‘sensitive’ or ‘non-sensitive’; anthralin, an irritant chemical, was used as control. Fiftyseven individuals were studied and there were at least five biopsy samples at each lime point. Regardless of whether individuals were sensitive or not, or of the type of chemical, dermal microvascular endothelial cells showed increased expression of the adhesion molecules ELAM-1 and VCAM-1 within 2 h. and ICAM-I within 8 h. The intensity of immunohistochemical staining increased progressively up to 24 h. More vessels stained for ICAM-1 than for VCAM-1 or ELAM-1. implying that not every vessel expressed all three cell adhesion molecules. Another early change, observed 2 h after irritant challenge, was a significant increase in numbers of CD la+ dendritic cells in the superficial dermis from a median of 3/high power field (hpf) to 9.5/hpf (P&lt;0.03). This was not observed with ‘weak’ provoking substances, such as nickel, but did occur with the potent provoking agent dinitrochlorobenzene (DNCB). Thus, as little as 2 h after contact with provoking chemicals, the skin activates cellular mechanisms to increase T cell infiltration for the presumed purpose of immune surveillance. These mechanisms are not dependent upon specific immune sensitivity and reflect a capacity of skin cells to respond to chemical provocation.
Local immunosuppressive therapy with monoclonal anti-T cell antibody on renal allograft survival in the rat
Authors: LEE C J , YOSHIMURA N , SHIHO O , KITA M , OKA T 
Published: July 2010

SUMMARYConsiderable interest in the experimental and clinical use of MoAbs as potential therapeutic agents in allograft rejection has been generated by the recent reports of striking prolongation. In this study we investigated the efficacy of the local administration of MoAb OX-19 which is directed to the rat CD5 equivalent, through the renal artery using a rat kidney transplant model, in order to develop a potent method for modifying rejection while minimizing the systemic side effects. Untreated Lewis rats (LEW, RT-11) rejected Brown-Norway rat (BN, RT-1n) kidney at 7·8±0·2 days (n=10). Mean survival time (MST) of recipients treated with OX-19 (75 μg/kg per day) as single bolus injections via the dorsal penile vein for 7 days was 7·0 ± 0·2 days (n= 5, NS). LEW hosts receiving OX-19 (75 μg/kg per day) continuously for 7 days via a femoral vein by using an osmotic minipump (IV-treated group) showed a slight prolongation of graft survival (MST=8·8±0·9 days, n= 5), but this was not statistically significant. On the other hand, local continuous intrarenal arterial infusion of OX-19 (75 μg/kg per day) for 7 days (RA-treated group) significantly prolonged the graft survivals (MST =16·8± 1·3 days, n= 8, P&lt;0·01). Histological examination of MoAb-treated LEW hosts on day 6 post-grafting revealed that kidney grafts from RA-treated hosts showed a slight tubular necrosis, but reduced mononuclear cell infiltration, whereas kidney grafts from IV-treated hosts displayed a severe mononuclear cell infiltration around the artery with interstitial oedema. Moreover, the local intrarenal administration of OX-19, even when the dose is delayed until day 4 after renal grafting, has a therapeutic effect for on-going acute allograft rejection (MST= 11·4 ± 0·8 days, n= 8) compared with administration of OX-19 intravenously from day 4 after grafting (MST= 7·6 ±0·2 days, n= 5,P&lt;0·01) or with no treatment (MST = 7·8±0·2 days, P&lt;0·01). The phenotype of graft infiltrating cells (GIC) was investigated on day 6 post-grafting. There was a significantly lower percentage of cells positive for OX-19, OX-8, OX-26 (transferrin receptor), and OX-39 (1L-2 receptor) in the RA group than in the IV group. These results indicate that local administration of OX-19 via the renal artery is a more efficacious treatment than systemic i.v. injection, and suggests that it may provide a localized immunosuppression of allografts, with reduction of morbidity in clinical transplant recipients.
T lymphocytes in giant cell arteritic lesions are polyclonal cells expressing αβ type antigen receptors and VLA-1 integrin receptors
Authors: SCHAUFELBERGER C , STEMME S , ANDERSSON R , HANSSON G K 
Published: July 2010

SUMMARYGiant cell arteritis (GCA) is a common disease in the elderly. It is characterized by focal inflammatory lesions dominated by T lymphocytes and macrophages. The etiology of GCA is, however, still unknown. The aim of the present study was to determine whether lesional T cells represent clonal proliferations, and to characterize adhesion receptors that could be important for recruitment of T cells and antigen receptors involved in their activation. Temporal artery biopsies were obtained from 13 patients presenting with clinical signs of GCA. Immunohistochemistry was used to characterize cell surface receptors on CD3+ T cells in situ in the lesions of eight patients with biopsy-verified GCA. The overwhelming majority of T cells in GCA lesions expressed the TCRγδ receptors. In sections from three of eight patients, a small proportion of cells expressing TCRγδ was also seen. Almost all T cells expressed the integrin receptors, LFA-1 and VLA-1, as determined by double-staining. To characterize the clonal composition of the lesional T cell population, cells were isolated by collagenase digestion of two lesions and T cells cloned by limiting dilution in the presence of mitogenic antibodies, IL-2 and autologous feeder cells. Rearrangements of the T cell receptor (TCR) genes of the clones were analysed by Southern hybridization using probes for TCRγ and β genes. T cell clones established from GCA lesions exhibited heterogeneous rearrangement patterns, indicating a polyclonal origin of the cells. We conclude that GCA lesions contain T lymphocytes that are of polyclonal origin and express integrin-type adhesion receptors. This supports the hypothesis that GCA involves an inflammatory response during which polyclonal T cells adhere to arterial tissue components and accumulate in the developing lesions.
Calreticulin synthetic peptide analogues: anti-peptide antibodies in autoimmune rheumatic diseases
Authors: ROUTSIAS J G , TZIOUFAS A G , SAKARELLOS-DAITSIOTIS M , SAKARELLOS C , MOUTSOPOULOS H M 
Published: July 2010

SUMMARYAutoantibodies in sera from patients with systemic lupus erythemalosus (SLE) and onchocerciasis recognize calreticulin (CaR). a calcium-binding protein, as antigen. In this study we present the immunological properties of two synthetic peptides prepared to correspond to the 1–24 and 7–24 amino acid sequence of CaR. In contrast to information previously reported for the recombinant protein, the CaR-peptide analogues appeared immunoreactive to anti-Ro/SSA autoimmune sera. Human sera from patients with SLE, Sjogren's syndrome (SS), rheumatoid arthritis (RA), as well as mixed connective tissue disease (MCTD), demonstrated a positive autoimmune response (binding of antibodies), to the CaR-peptide analogues. These findings suggest that anti-calreticulin autoantibodies are not restricted to any disease specificity.
An improved enrichment method for functionally competent, highly purified peripheral blood dendritic cells and its application to HIV-infected blood samples
Authors: KARHUMAKI E , VILJANEN M E , COTTLER-FOX M , RANKI A , FOX C H , KROHN K J E 
Published: July 2010

SUMMARY
Dendritic cells (DC) were purified from human peripheral blood using a rapid and simple method based on magnetic depletion of phagocytes with carbonyl iron, followed by centrifugation of non-phagocytic cells on a Percoll density gradient and depletion of lymphocytes and macrophages/ monocytes with a panel of MoAbs and immunomagnetic beads. Enriched DC were obtained with &gt;99% purity as judged by non-specific esterase (NSE) staining. After isolation, these cells, representing 0.4% of the starting mononuclear cell population, still function as potent antigen-presenting cells for purified T lymphocytes. The present results confirm the ability of human peripheral blood DC to present soluble antigens to T cells including microbial antigens and show, further, that DC arc more potent soluble antigen-presenting cells than monocytes. The method was successfully applied to the purification of DC from the blood of HIV-infected individuals. We could not detect decreased numbers of DC in four individuals with early HIV infection and no replicating HIV was detected by in situ hybridization in the DC.
Human recombinant IL-1 receptor antagonist (IL-IRa) inhibits leukotriene B4 generation from human monocyte suspensions stimulated by lipopolysaccharide (LPS)
Authors: CONTI P , PANARA M R , BARBACANE R C , BONGRAZIO M , DEMPSEY R A , REALE M 
Published: July 2010

SUMMARYThe effect of human recombinant IL-1 receptor antagonist (hrIL-1Ra) on leukotriene B4 (LTB4) release was investigated in activated human monocyte cultures. To stimulate LTB4 generation, LPS was used as an agonist. Detection was performed with the highly sensitive radioimmunoassay method. The cells were treated with scalar concentrations using LPS at 1–1000 ng/ml for different periods of time. The greater LTB4 stimulation was found at LPS 100 ng/ml for 18 h incubation time. Preincubation of monocytes with cytochalasin B (CB) (5 μg/ml) for 15 min augmented the release of LTB4 when LPS was used. A dose-dependent inhibition was found when human monocytes were pretreated for 10 min with hrlL-l Ra at different concentrations (0·25–250 ng/ml) and then treated with LPS 100 ng/ml for 18 h. Maximum inhibition was observed at the highest concentration of hrlL-1 Ra (250 ng/ml). Macrophages treated with a non-selective 5-lipoxygcnasc inhibitor, nordihydro-guaiaretic acid (NDGA), used at 10 μm, added 15 min before LPS 100 ng/ml, produce a dose-dependent inhibition of LTB4. Cells pretreated with arachidonic acid, at various concentrations (10−9− 10−5 m) for 10 min and then treated with LPS 100 ng/ml for 18 h, were also inhibited in a dose-dependent manner by hrIL-1 Ra in their production of LTB4. The inhibition of LTB4 release by hrlL-I Ra, in LPS-stimulated human monocytes, may suggest an important modulatory role for this new cytokine (monokine) in inflammation and immunity and may hold future therapeutic implications for diseases involving LTB4 as a mediator.
Polymorphic MHC ancestral haplotypes affect the activity of tumour necrosis factor-alpha
Authors: ABRAHAM L J , FRENCH M A H , DAWKINS R L 
Published: July 2010

SUMMARYIt remains unclear which MHC loci are involved in susceptibility to autoimmune diseases and immune deficiencies. We have chosen to evaluate whether different alleles of tumour necrosis factor-alpha (TNF-α) are important, as TNF has been implicated in the etiology of many immunological disorders. We have shown previously that a restriction fragment length polymorphism in the TNF region correlates with MHC ancestral haplotypes. We therefore examined the effect of ancestral haplotype on the activity of TNF-α in culture supernatants of lymphoblastoid cell lines. The results demonstrate that TNF-α activity in supernatants of 8.1 (A1, B8, DR3) cell lines was higher than that present in the supernatants from cells homozygous for eight different MHC ancestral haplotypes, and indicate that polymorphisms in TNF-α, or in other MHC genes that regulate TNF, may be responsible for the 8.1 phenotype.
Increased spontaneous secretion of rheumatoid factor by intestinal lamina propria mononuclear cells from Crohn's disease but not ulcerative colitis patients
Authors: MacDERMOTT R P , SCHREIBER S , NASH G S , KOOPMAN W J 
Published: July 2010

SUMMARYIncreased levels of rheumatoid factors (RF) have been observed in the scrum of Crohn's disease but not ulcerative colitis patients, and have been proposed to relate to an increased state of intestinal lymphocyte activation. We have therefore examined the spontaneous in vitro secretion of RF by intestinal lamina propria mononuclear cells (MNC) isolated from specimens from control and inflammatory bowel disease (Crohn's disease, ulcerative colitis) patients. Normal intestinal lamina propria MNC spontaneously secrete rheumatoid factors of different isotypes during 14 days of in vitro culture (9·7 ng/ml IgA RF, 11·6 ng/ml IgM RF and 64·6 ng/ml IgA anti-Fc (IgG)). In matched studies intestinal MNC isolated from normal large bowel exhibited significantly greater levels of RF synthesis and secretion in vitro than normal small bowel intestinal MNC. A large increase in spontaneous RF secretion was observed from Crohn's disease intestinal MNC (21·4 ng/ml IgA RF, 21·4 ng/ml IgM RF, and 108·15 ng/ml IgA anti-Fc (IgG)), when compared with normal controls. The amount of RF secreted was dependent on the amount of inflammatory activity of the bowel specimens, from which the MNC were isolated (198·3 ng/ml of IgA anti-Fc(IgG) from involved versus 50·0 ng/ml from matched non-involved tissue). Ulcerative colitis MNC released decreased amounts of RF(7I ng/ml IgA RF, 6·2 ng/ml IgM RF, and 42·3 ng/ml IgA anti-Fc (IgG)). These observations using isolated intestinal MNC may explain the findings of RF changes in the sera of inflammatory bowel disease patients. Our observations support the hypothesis of a heightened stale of activation in normal intestinal lamina propria MNC, which is further increased in active Crohn's disease. The dissimilarities observed between Crohn's disease and ulcerative colitis may indicate fundamental differences in disease pathophysiology and will lead to further studies exploring intestinal immunoregulatory properties of RF.
The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells
Authors: SHINGU M , NAGAI Y , ISAYAMA T , NAONO T , NOBUNAGA M , NAGAI Y 
Published: July 2010

SUMMARY
It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase, and that such degradation is regulated by metalloproteinase inhibitors (TIMP). Therefore, the balance between collagenase and TIMP is an important factor for tissue destruction in inflammatory joints. In the present study the effects of cytokines on collagenase and TIMP production in chondrocytes as welt as the effects of cytokines on TIMP production in connective tissue cells were studied. IL-Iβ inhibited TIMP production in endothelial cells while enhancing TIMP production in synovial cells and chondrocytes. In addition, tumour necrosis factor-alpha (TNF-α) significantly inhibited and IL-6 significantly enhanced TIMP production in endothelial cells, synovial cells and chondrocytes. In the chondrocyte supernatant, collagenase activity/TIMP ratio was significantly elevated by the addition of either IL-lβ or TNF-α to the cells, whereas the ratio was significantly decreased by IL-6. These results suggest that the cytokine effects on TIMP production are different among the different cell types, and that either IL-lβ or TNF-α induce cartilage matrix degradation by disrupting the collagenase/TIMP balance, while, on the other hand, IL-6 protects the tissue through an opposite effect.
Enhand secretion of tumour necrosis factor-alpha, IL-6, and IL-1β by isolated lamina ropria monouclear cells from patients with ulcretive cilitis and Crohn's disease
Authors: REINECKER H-C , STEFFEN M , WITTHOEFT T , PFLUEGER I , SCHREIBER S , MacDERMOTT R P , RAEDLER A 
Published: July 2010

SUMMARYThe perpetuation of inflammation in ulcerative colitis and Crohn's disease may be regulated in part by an increased secretion of proinflammatory cytokines due to either an appropriate response to initial stimulating agents, and/or due to an impaired down-regulalion of cylokine secretion. The aim of this study was to determine the secretion patterns of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-α), IL-6 and IL-1β, from isolated lamina propria mononuclear cells (LPMNC) isolated from colonic biopsies from patients with untreated ulcerative colitis or Crohn's disease. LPMNC isoiated from involved inflammatory bowel disease (lBD) mucosa spontaneously produced increased amounts of TNF-α, IL-6, and IL-1β. The TNF-α secretion from IBD LPMNC could be further enhanced by pokeweed mitogen stimulation. The secretion patterns of TNF-α and IL-1β by LPMNC from patients with either uicerative colitis or Crohn's disease demonstrated a close correlation with the degree of tissue involvement and mucosal inflammation. LPMNC from noninvolved ulcerative colitis mucosa secreted markedly increased leveis of IL-6 compared with noninvolved Crohn's disease mucosa or control mucosa. The heightened lL-6 secretion from LPMNC from non-involved ulcerative colitis mucosa without visible or microscopic signs of inflammation indicates that the pathophysiologie mechanisms involved in the initiation of inflammation may differ between ulceralive colitis and Crohn's disease. The determination of proinflammatory cytokine secretion by isolated LPMNC from colonoseopic biopsies may be a sensitive method for monitoring the severity of mucosal inflammation in IBD patients.
B cell activation in clinically quiescent systemic lupus erythematosus (SLE) is related to immunoglobulin levels, but not to levels of anti-dsDNA, nor to concurrent T cell activation
Authors: SPRONK P E , v.d. GUN B T F , LIMBURG P C , KALLENBERG C G M 
Published: July 2010

SUMMARYIn clinically quiescent SLE hypergammaglobulinaemia, presence of autoantibodies, and increased soluble IL-2 receptors (sIL-2R) have been reported, suggesting persistent B as well as T cell activation. In contrast, the primary immune response lo test antigens is markedly decreased. To analyse these phenomena at a cellular level, we undertook a cross-sectional study on 13 non-active SLE patients and 15 controls. We determined the composition of lymphocyte subsets with special attention to activation markers (CD25, HLA-DR, CD38) and the presence of naive T cells (CD45RO-), and related those findings to serological parameters. In non-active SLE patients the expression of activation markers on B cells and T cells was higher than in normal controls (P≤ 0·02), but was not interrelated. Percentages of activated B cells in SLB were related lo levels of total IgG (P &lt; 0·02)and IgM (P &lt; 0·02) but not to anti-dsDNA, suggesting a disordered immune system also in clinically quiescent SLE. Numbers of CD4+ cells (P &lt; 0·001) and CD4+CD45RO- cells (P &lt; 0·05) were decreased. The latter finding might explain the anergy to primary test antigens in clinically quiescent SLE.
Immunological responses of Gambians in relation to clinical stage of HIV-2 disease
Authors: WHITTLE H , EGBOGA A , TODD J , MORGAN G , ROLFE M , SABALLY S , WILKINS A , CORRAH T 
Published: July 2010

SUMMARYThis study describes a broad spectrum of cellular and antibody-mediated immune responses found in 28 asymptomatic and 37 symptomatic Gambian patients with HIV-2 infection. It shows that these responses vary according to the stage of infection as described by three clinical staging systems. The first system was a local one based on the signs used for the WHO Bangui clinical definition of AIDS, the second, suggested by WHO, was based on a performance scale, and the third was that used by the Centre for Disease Control. Asymptomatic patients had significantly lower mean CD4 counts, lymphoproliferative and interferon-gamma (IFN-γ) responses and lower IgG and IgM antibody responses to keyhole limpet haemocyanin (KLH) than controls. These measurements and the size of the skin test reaction to purified protein derivative (PPD) or Candida antigen declined significantly according to the stage of infection. Mean values of the serological markers β2-microglobulin and neopterin and antibody titres to Epstein-Barr virus capsid antigen (EBVCA) rose significantly according to severity of disease. The Gambian or WHO clinical staging systems, which are easy and cheap to apply, may serve as an alternative to sophisticated and expensive immunological measurements when trying to stage disease and predict prognosis.