bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of lymphocytic infiltration on the blood-retinal barrier in experimental autoimmune uveoretinitis
Authors: LIGHTMAN S , GREENWOOD J 
Published: July 2010

SUMMARYUsing an experimental model of autoimmune uveoretinitis, we have examined the relationship of T cell infiltration in the retina to blood-retinal barrier (BRB) breakdown. Sensitive quantitative in vivo techniques were used to examine BRB permeability to sucrose, a low mol. wt non-transported solute. Electron microscopy was also used to localize extravasated horseradish peroxidase, a macromolecular visual tracer, from the retinal vasculature and to identify the route by which any leakage was occurring. No increase in BRB permeability was found prior to lymphocytic infiltration. By day 10 of the disease inflammatory cells could be seen within the structurally intact retina, which was shortly followed by an increase in the permeability of the BRB to sucrose. Only later in the disease process, when damage to the photoreceptor layer became apparent, did extravasation of the macromolecule HRP occur. At no stage of the disease process was there any detectable damage to inter-endothelial tight junctions. The size-dependency of tracer extravasation in the initial stages of the disease is indicative of a paracellular route being responsible for the increase in BRB permeability. In later stages of the disease some evidence of horseradish peroxidase filled ‘vesicle-like’ profiles was observed. We suggest that the devastating complication of BRB breakdown in ocular inflammation is a direct consequence of lymphocytic infiltration.
Monoclonal antibody epitopes of mycobacterial 65-kD heat-shock protein defined by epitope scanning
Authors: HAJEER A H , WORTHINGTON J , MORGAN K , BERNSTEIN R M 
Published: July 2010

SUMMARYThe binding sites for MoAbs to the 65-kD heat-shock protein (hsp65) of mycobacteria have been investigated by epitope scanning. Five hundred and twenty-six 8-mer peptides representing the complete sequence of Mycobacterium tuberculosis hsp65 were synthesised in duplicate using the Epitope Scanning Kit (CRB Ltd.). The epitopes of six MoAbs raised to the hsp65 of M. tuberculosis or M. leprae were investigated. We have identified the epitope of a new MoAb (DC 16); this epitope is continuous, hydrophilic in nature and 11 amino acids long. We have also confirmed the location of the epitopes of three MoAbs (IIH9, ML30 and IIC8). Thus the epitope scanning technique has proved suitable for the detection of continuous epitopes of hsp65.
Suppression of autoimmune thyroid disease by FK 506: influence on thyroid-infiltrating cells, adhesion molecule expression and anti-thyroglobulin antibody production
Authors: TAMURA K , WOO J , MURASE N , CARRIERI G , NALESNIK M A , THOMSON A W 
Published: July 2010

SUMMARYAutoimmune thyroid disease was induced in female PVG/c rats by neonatal thymectomy, followed by sublelhal, whole body x-irradiation. Disease development, assessed by histological evidence of lymphocytic thyroiditis and circulating levels of anti-thyroglobulin antibodies, was reduced significantly by a 3-week course of FK 506 (0.5 or 1.5 mg/kg per day) commencing after the detection of autoantibody production. Thyroid-infiltrating mononuclcar cells (MNC) in untreated rats stained predominantly for CD4+ and MHC class II antigen which was expressed widely on dendritic cells. Fewer infiltrating cells expressed TCR α/β, CD5, CD8 or LFA- 1β. Intercellular adhesion molecule-1 (ICAM-1) was observed on MNC, vascular endothelial cells and a minoritiy of residual thyroid epithelial cells. FK 506 administration reduced markedly the incidence of infiltrating TCRα/β+, CD5+, CD4+, CD8+, and LFA-1β+ cells and the expression both of MHC class II antigens and ICAM-I on MNC, endothelial cells and thyrocytes. Compared with normal PVG/c rats, there were reduced incidences of CD4+ CD8− and CD4− CD8+ lymphocytes and an elevation in the CD4+/ CD8+ cell ratio in the spleens of animals with autoimmune thyroiditis. These changes were partially reversed by FK 506. Systemic drug levels estimated by enzyme immunosorbent assay were in excess of those known to blockade cytokine production by CD4+ T lymphocytes in vitro and some evidence of minor renal dysfunction was observed. The results are consistent with a therapeutic effect of FK 506 mediated via interference with CD4+ T lymphocyte function and adhesion molecule-dependent cytotoxic effector mechanisms.
Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat
Authors: JUNG S , TOYKA K V , HARTUNG H-P 
Published: July 2010

SUMMARYThe influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG) on macro-phages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen- or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG, Like activation-induced T cell proliferation, IL-2-dependent growth of CD4+ T line cells was not affected by DSG, Preincubation of CD4+ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T eel) receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.
Uveitis and anti-neutrophil cytoplasmic antibodies
Authors: HAGEN E C , VAN DE VIJVER-REENALDA H , DE KEIZER R J W , KULSTRA A , VAN ES L A , DAHA M R , VAN DER WOUDE F J 
Published: July 2010

SUMMARY
Serum samples of 485 uveitis patients were screened for the presence of anti-neutrophil cytoplasmic antibodies using a standardized immunofluorescence test (IIF) on neutrophil granulocytes. Seventeen of these sera contained cytoplasmic (C)-ANCA antibodies, while two of the sera contained perinuclear (P)-ANCA antibodies (both antinuclear antibody (ANA)-positive, one anti-myeloperoxidase (MPO)-positive). None of the C-ANCA-positive sera reacted with proteinase-3 in ELISA using a highly purified proteinase-3 preparation. Four C-ANCA and one P-ANCA-positive serum reacted with MPO. The majority of the sera did react with azurophilic granules in ELISA. The implication of these results is that in patients with uveitis a positive C-ANCA test is not diagnostic for Wegener's granulomatosis, but is most probably caused by the presence of autoantibodies against as yet unknown constituents of azurophilic granules.
Enrichment and characterization of dendritic cells from human bronchoalveolar lavages
Authors: HAVENITH C E G , VAN HAARST J M W , BREEDIJK A J , BETJES M G H , HOOGSTEDEN H C , BEELEN R H J , HOEFSMIT E C M 
Published: July 2010

SUMMARYIn the present study about 0·3% to 1·6% of human bronchoalveolar lavage (BAL) cells were identified as typical dendritic cells (DC), having an irregular outline, lobulated nucleus, and clear distinguishable acid phosphatase activity or EBM11 (anti-CD68) reactivity in a spot near the nucleus. After DC enrichment, using transient adherence to plastic, FcR-panning, and a density metrizamide gradient, a population containing 7–8% typical DC was obtained. This DC-enriched low density fraction, containing the highest percentages of DC, very strongly induced T cell proliferation in an allogeneic mixed leucocyte reaction (MLR), which was significantly higher than that induced by other partly (un)fractionated BAL cells. These data indicate that DC seem to be the major accessory cells in the BAL fluid, and therefore may be important in the regulation of T cell immune responses in the lung.
Susceptibility to adjuvant arthritis: relative importance of adrenal activity and bacterial flora
Authors: VAN DE LANGERIJT A G M , VAN LENT P L E M , HERMUS A R M M , SWEEP C G J , COOLS A R , VAN DEN BERG W B 
Published: July 2010

SUMMARY
Previous studies on the regulation of bacterial-induced arthritis in rats have focused on endocrine aspects as well as differences in T cell immunity against bacterial epitopes. We analysed the role of both adrenal activity and bacterial flora in determining susceptibility to bacterial-induced arthritis. Outbred Wistar rats show a low incidence of adjuvant arthritis. Moderate sensitivity to adjuvant arthritis was found in a selected., stress-resist ant line of the Wistar rat, whereas no arthritis was found in a stress-susceptible Wistar line. Plasma corticosterone responses after IL-1α exposure were, however, identical in these two lines, excluding a direct correlation between susceptibility and corticosterone levels. In line with previous findings in germ-free (GF) F344 rats, GE Wistars also appeared highly susceptible to arthritis. We further analysed the corticosterone responses in GE and conventional (CV) rats. Administration of IL-1α induced identical corticosterone responses in both CV and GF E344 rats. In addition, plasma corticosterone levels were measured around the time of onset of arthritis. Whereas no rise was seen in the arthritis-resistant CV rats, a significant increase was observed from day 14 in GE rats, at the moment of onset of arthritis. Although this corticosterone response was insufficient to prevent arthritis, it may have ameliorated disease expression in the GK F344 rats. Our data indicate that the bacterial flora, and therefore T cell tolerance, is of prime importance in determining susceptibility, whereas the activity of the hypothalamus-pituitary-adrenal (HPA) axis may modulate disease severity.
Autoantibodies to cerebroside sulphate (sulphatide) in leprosy
Authors: WHEELER P R , RAYNES J G , MCADAM K P W J 
Published: July 2010

SUMMARYSera from 40 leprosy patients were screened for autoantibodies to cerebroside sulphate (sulphatide). Anti-sulphatide IgM in groups of patients with lepromatous (LL) and borderline (BL + BB + BT), but not with tuberculoid (TT) disease, were significantly elevated above the levels found in endemic control subjects. Eight-six percent (18 out of 21; mean 1·59 OD units) of LL, 33% (four out of 12; mean 1·08OD units) of borderline and 13% (one out of eight; mean 0·69 OD units) of tuberculoid patients had anti-sulphatide IgM in their sera above a cut-off value of 2 s.d. above the mean value (0·66 OD units) for control sera. Elevated anti-sulphatide IgG was detected in only one patient's serum, an individual with LL disease. The level of anti-sulphatide IgM was strongly correlated to expression of the TH3 idiotype, an idiotype previously defined by a human MoAb that bound Mycobacterium leprae phenolic glycolipid, Klebsiella capsular polysaccharide, polynucleotides and human tissues. The purified, TH3 MoAb was found in this study to bind sulphatide, but not cholesterol-3-sulphate or cerebroside. It is suggested that antisulphatide IgM is elevated in leprosy, in relation lo the bacterial load. Anti-sulphatide IgM fell at the onset of erythema nodosom leprosum (ENL) reaction, consistent with the deposition of serum antibodies, and thus may play a part in pathology during periods of inflammation, particularly in multibacillary patients.
Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections
Authors: Franchini M , Walker C , Henrard D R , Suter-Gut D , Braun P , Villiger B , Suter M 
Published: July 2010

SUMMARYThe lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into ‘lung symptomatic’ or ‘lung asymptomatic’ patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease.
Significance of extractable nuclear antigens in childhood autoimmune liver disease
Authors: Gregorio G V , Davies E T , Mieli-Vergani G , Vergani D 
Published: July 2010

SUMMARY
Antinuclear antibody (ANA) is found in connective tissue disorders and in autoimmune disease. While ANA-positive connective tissue disorders are subdivided according to possession of specific antibodies to extractable nuclear antigens (ENA) (anti-ribonucleoprotein (anti-RNP), anti-Smith (anti-Sm), anti-Ro, anti-La), little is known about the presence and significance of ENA in autoimmune liver disease. To investigate this, we have tested 35 children with autoimmune hepatitis (AIH) (19 ANA and/or smooth muscle antibody-positive (ANA/SMA +ve); 16 liver kidney microsomal 1-positive (LKM-1 +ve)) and 14 with ANA/SMA +ve autoimmune sclerosing cholangitis (ASC), using both double dimension immunodiffusion and ELISAs. Eighty children with non-autoimmune liver disease (20α1-antitrypsin deficiency, 20 Wilson's disease. 20 Alagille's syndrome and 20 chronic hepatitis B virus infection) and 20 healthy controls were also tested. ENA were detected in seven (20%) patients with AIH: two ANA-positive, one SMA-positive and four LKM-1-positive. Three were positive for anti-Sm, two for anti-La, one for anti-Sm/anti-La and one for anti-Sm/anti-La/anti-Ro. ENA-positive had more severe liver disease than ENA-negative patients (P &lt; 0·03). ENA were not detected in ASC, non-autoimmune liver diseases and controls. Our results indicate that ENA reactivity, including anti-Sm and anti-La, characteristic of systemic lupus erythematosus and Sjögren's syndrome, respectively, are present in some patients with AIH even in the absence of ANA, and may characterize a particularly severe form of the disease.
Anti-V3 antibody reactivity correlates with clinical stage of HIV-1 infection and with serum neutralizing activity
Authors: Fenouillet E , Blanes N , Benjouad A , Gluckman J C 
Published: July 2010

SUMMARYDuring HIV-1 infection, the current tenet is that only anti-gag antibodies decline, while those directed at env remain stable. Among the latter antibodies, those directed to the V3 domain of gpl20 are assumed to play a role in the immune surveillance against HIV-1. We investigated the correlation between anti-V3 antibody levels and the clinical stage of infection and the ability to neutralize syncytium formation. Using a V3-specific antigen-limited ELISA, we analysed the antibody levels of a panel of 93 HIV-1+ sera to V3 peptides derived from different HIV-1 strains and from the North American/European consensus sequence V3(Cs). Sera preferentially recognized V3 peptides from the representative V3(MN) strain and V3(Cs). Antibody reactivity to V3(MN) or V3(Cs) actually declined in relation with progression to AIDS, while antibodies against whole recombinant gpt60 or gp41 immunodominant epitope remained stable. There was a strong correlation (P &lt; 00001) between anti-V3 (Cs)/V3(MN) antibody levels and serum titres that neutralized HIV-1MN-mediated syncytia. Serology based on V3-specific antigen-limited ELISA indicates that anti-V3 antibody reactivity may decline during the course of HIV infection.
Redimune® NF Liquid, a ready-to-use, high-concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions
Authors:   the study investigators, Piguet D , Tosi C , Lüthi J-M , Andresen I , Juge O 
Published: July 2010

Summary
In clinical practice, intravenous immunoglobulin therapy (IVIG) is used in the management of a wide variety of medical conditions. Observational studies examining IVIG use in routine clinical practice are therefore an important means of validating findings from more strictly randomized controlled trials of patients with specific conditions. In this observational study, we examined the tolerability of a high-concentration (12%) ready-to-use liquid IVIG (Redimune® NF Liquid) when used in the standard management of a diverse range of conditions (including primary immunodeficiency diseases, neurology conditions, oncology conditions and immune thrombocytopaenic purpura). IVIG regimen and dose were selected by the physician based on the summary of product characteristics. During the study, 193 infusions were administered to 51 patients in 153 infusion cycles (per infusion cycle: one to five infusions; mean dose, 347·6 mg/kg; mean duration, 202·4 min). The mean maximum infusion rate per cycle was 2·9 mg/kg/min, demonstrating that the infusion rate was often higher than that recommended in the summary of product characteristics. Redimune® NF Liquid was well tolerated: there were 36 adverse reactions (at least probably associated with IVIG) in 10 patients (19·6% of sample, 0·24 per infusion cycle, 0·19 per infusion). The most common adverse reaction was headache (50% of reactions), followed by chills (13·8%). Most reactions (69%) were mild and there were no serious or unexpected reactions. In conclusion, in routine clinical practice involving patients with many different conditions, Redimune® NF Liquid was well tolerated by the majority of patients.
Association of intracellular pro- and anti-inflammatory cytokines in peripheral blood with the clinical or ultrasound indications for carotid endarterectomy in patients with carotid atherosclerosis
Authors: Profumo E , Buttari B , Tosti M E , Siracusano A , Ortona E , Margutti P , Capoano R , Salvati B , Riganò R 
Published: July 2010

Summary
Early non-invasive diagnostic information would be useful in identifying patients at risk of progressive carotid atherosclerosis, despite an apparently harmless plaque on ultrasound imaging. In this study, we assessed the possible association of intracellular cytokines in peripheral blood with the ultrasound (stenosis ≥ 70%) and clinical indications (transient ischaemic attack, amaurosis fugax or stroke) for carotid endarterectomy (CEA) in patients. Intracellular cytokine expression was determined in 106 patients (67 undergoing and 39 not undergoing CEA). Cells primed for the proinflammatory cytokines tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8 and the anti-inflammatory cytokines IL-4 and IL-10 were found in significantly higher percentages in patients undergoing CEA than in patients who were not (P &lt; 0·05). Intracellular cytokine expression was significantly higher in patients undergoing CEA who had stenosis ≥ 70% (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10), with previous stroke (IFN-γ, IL-1β, IL-6, IL-8, IL-4 and IL-10) and with amaurosis fugax (IFN-γ, IL-6, IL-4 and IL-10) than in patients not undergoing CEA. Increased intracellular cytokines in patients' peripheral blood might be a warning signal indicating progressive atherosclerosis. If so, intracellular cytokine monitoring could help in selecting patients at high risk of future clinical cardiovascular events and therefore most likely to benefit from CEA or adjustment of pharmacological therapy.
Study of Toll-like receptor gene loci in sarcoidosis
Authors: Schürmann M , Kwiatkowski R , Albrecht M , Fischer A , Hampe J , Müller-Quernheim J , Schwinger E , Schreiber S 
Published: July 2010

Summary
Sarcoidosis is a multi-factorial systemic disease of granulomatous inflammation. Current concepts of the aetiology include interactions of unknown environmental triggers with an inherited susceptibility. Toll-like receptors (TLRs) are main components of innate immunity and therefore TLR genes are candidate susceptibility genes in sarcoidosis. Ten members of the human TLR gene family have been identified and mapped to seven chromosomal segments. The aim of this study was to investigate all known TLR gene loci for genetic linkage with sarcoidosis and to follow positive signals with different methods. We analysed linkage of TLR gene loci to sarcoidosis by use of closely flanking microsatellite markers in 83 families with 180 affected siblings. We found significant linkage between sarcoidosis and markers of the TLR4 gene locus on chromosome 9q (non-parametric linkage score 2·63, P = 0·0043). No linkage was found for the remaining TLR gene loci. We subsequently genotyped 1203 sarcoidosis patients from 997 families, 1084 relatives and 537 control subjects for four single nucleotide polymorphisms of TLR4, including Asp299Gly and Thr399Ile. This genotype data set was studied by case–control comparisons and transmission disequilibrium tests, but showed no significant results. In summary, TLR4 − w ith significant genetic linkage results − appears to be the most promising member of the TLR gene family for further investigation in sarcoidosis. However, our results do not confirm the TLR4 polymorphisms Asp299Gly and Thr399Ile as susceptibility markers. Our results rather point to another as yet unidentified variant within or close to TLR4 that might confer susceptibility to sarcoidosis.
Evaluation of some non‐meat proteins for use in sausage
Authors: THOMAS M. A. , BAUMGARTNER P. A. , BOARD P. W. , GIPPS P. G. 
Published: July 2010

SummaryFresh sausages were made having 0, 20, 40, or 60% of the meat protein replaced with milk co‐precipitates, soy protein preparations, or sodium caseinate, in order to determine the effect of the protein additives on the physical properties of the sausage emulsions and on their sensory qualities. Two milk co‐precipitates at 40% substitution gave sausages that were not significantly different from the controls in general acceptability. The other protein preparations gave sausages of poorer sensory quality as did all the additives at the 20% level of substitution. Cooked luncheon sausages with 20% substituted protein were similar in general acceptability to the control. No relation was found between the physical properties of the emulsions and the sensory properties of the sausages.