bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atopic eczema is associated with delayed maturation of the antibody response to Pneumococcal vaccine
Authors: Arkwright P D , Patel L , Moran A , Haeney M R , Ewing C I , David T J 
Published: March 2003

SUMMARYThe aim of this study was to investigate a previously undocumented observation, that children with atopic eczema under 9 years of age tended to have a poor antibody response to Pneumococcal vaccination. Thirty-five children (mean age 8·8 years, range 3–16 years) with moderate to severe atopic eczema but no history of systemic infection were studied retrospectively. Pneumococcal antibody responses after immunization with Pneumovax II were compared with a hospital control group consisting of 36 children (mean age 6·0 years, range 3–16 years) with recurrent upper respiratory tract infections. Only 17% of children with atopic eczema aged 3–8 years responded to Pneumovax. This response was significantly poorer than that of the controls (57%) (odds ratio 0·20, 95% confidence interval (CI) 0·05–0·84, P = 0·03). There were no significant differences in the levels of total IgG2, the component of IgG associated with protective antibody responses to Pneumococcus between the two groups. Delay in maturation of the total IgG and IgG2 antibody response to Pneumococcus is a feature in this group of children with moderately severe atopic eczema.
Cardiolipin on the surface of apoptotic cells as a possible trigger for antiphospholipid antibodies
Authors: Sorice M , Circella A , Misasi R , Pittoni V , Garofalo T , Cirelli A , Pavan A , Pontieri G M , Valesini G 
Published: March 2003

SUMMARYThis study provides evidence that cardiolipin (CL) molecules are expressed on the surface of apoptotic cells and are recognized by antiphospholipid antibodies, purified from patients with the antiphospholipid antibody syndrome (APS). CL expression on cell surface was demonstrated by high performance thin layer chromatography analysis of phospholipids from plasma membrane purified fractions and by the positive staining with the CL-specific dye nonyl-acridine orange. This finding was complemented with the observation that aCL IgG purified from patients with APS bind to the surface of apoptotic cells. This staining shows a clustered distribution mostly localized on surface blebs. Interestingly, CL exposure on the cell surface preceded the DNA fragmentation, as shown by cytofluorimetric analysis. These findings demonstrate that exposure of CL molecules on the cell plasma membrane is an early event of the apoptotic cellular program that may represent an in vivo trigger for the generation of aCL.
Enhanced production of IL-8 in chronic but not in early ileal lesions of Crohn's disease (CD)
Authors: Brandt E , Colombel J-F , Ectors N , Gambiez L , Emilie D , Geboes K , Capron M , Desreumaux P 
Published: March 2003

SUMMARYDistinct Th1/Th2 patterns have been observed during the evolution of CD. The aim of this study was to compare neutrophil involvement and IL-8 mRNA and protein expression during early recurrent lesions and chronic phases of CD. Twenty-nine patients with CD having ileocolonic resection with anastomosis were studied. Biopsies were obtained during surgery from the non-inflamed ileal mucosa and from chronic ileal lesions. Endoscopic ileal biopsies were also taken from early recurrent ileal lesions occurring 3 months after surgery. Neutrophil counts were performed and mucosal IL-8 levels were evaluated by competitive reverse transcriptase-polymerase chain reaction and immunohistochemistry. Early recurrent ileal lesions were characterized by low neutrophil counts and IL-8 production at the mRNA and protein levels compared with the ileal chronic lesions. The main cellular sources of IL-8 in the early recurrent lesions were neutrophils, while in chronic lesions the majority of IL-8-stained cells were CD3+ T cells and macrophages. These results confirmed that the nature of the inflammatory infiltrate and the expression of cytokine profiles may differ between the acute and chronic phases of CD.
Blood fetal microchimerism in primary biliary cirrhosis
Authors: Invernizzi P , De Andreis C , Sirchia S M , Battezzati P M , Zuin M , Rossella F , Perego F , Bignotto M , Simoni G , Podda M 
Published: March 2003

SUMMARY
The autoimmune nature of primary biliary cirrhosis (PBC) is well established. We tested the hypothesis that fetal microchimerism indicated by the persistence of circulating fetal cells in women years after pregnancy might contribute to the aetiopathogenesis of PBC through a graft-versus-host-like response. We extracted DNA from the peripheral blood cells of 36 women carefully selected from 173 consecutive PBC patients, who were matched with 36 healthy women by age, age of last son, and number of children. Both patients and controls had to have male offspring, and no history of miscarriages or blood transfusions; they could not be twins. We tested all of the samples for the presence of two specific Y-chromosome sequences (SY154 and SRY) by amplifying DNA in a nested polymerase chain reaction. Y-chromosome-specific DNA was detected in the peripheral blood cell DNA of 13 (36%) of the 36 women with PBC and in 11 (31%) of the 36 healthy controls. The two groups of PBC patients with and without male DNA sequences were similar in terms of their clinical, biochemical, and serological features. Y-chromosome sequences were found in three of the four PBC women with associated systemic sclerosis. All of the 24 Y-positive samples contained SY154 sequences, but only three PBC patients and six controls showed the presence of both SY154 and SRY sequences. This discrepancy may suggest that not only fetal cells but also fragments of fetal DNA are present in maternal circulation. Overall, our data do not support the hypothesis that fetal microchimerism plays a significant role in the onset or progression of PBC.
Early decrease in surface expression of HLA-DQ predicts the development of infection in trauma patients
Authors: Taylor J V , Gordon L E , Polk H C 
Published: March 2003

SUMMARYThe behaviour of human leucocyte antigen-DR (HLA-DR) following injury has been extensively studied. However, the behaviour of other class II antigens following trauma has not been characterized as well, despite evidence that HLA-DQ genotype influences the response to several bacterial antigens. Our study attempts to characterize and analyse the behaviour of HLA-DQ after trauma in patients with and without infection. Twenty-five patients were studied following major injury. Fifteen of the 25 patients developed infection (men = 11, women = 4); 10 patients developed no infection (men = 9, women = 1). The mean age was 34 ± 12 years for patients with no infection and 52 ± 20 years for those with infection. Monocyte HLA-DQ surface expression was determined using FITC-labelled antibodies and flow cytometry. Expression was compared with a control population of 11 healthy volunteers. The percentage of monocytes expressing HLA-DQ following trauma was reduced in patients with infection and in those without infection, but returned to normal (days 8–14) only in those patients who did not develop infection. Monocyte HLA-DQ mean channel fluorescence was reduced on day 1, but quickly returned to normal in those patients who subsequently developed infection. Stimulated with lipopolysaccharide, the initial samples of 13 patients who developed infection showed that surface expression on these monocytes could be elevated into the normal range. We conclude that HLA-DQ is an additional early marker of outcome that may not function merely as an immune suppressor. The maintained ability of HLA-DQ to present self-antigens may be important in the initial stages of the host response to injury.
IL-1β- and IL-4-induced down-regulation of autotaxin mRNA and PC-1 in fibroblast-like synoviocytes of patients with rheumatoid arthritis (RA)
Authors: Kehlen A , Lauterbach R , Santos A N , Thiele K , Kabisch U , Weber E , Riemann D , Langner J 
Published: March 2003

SUMMARY
Autotaxin (ATX) is a 125-kD ectonucleotide pyrophosphate/phosphodiesterase, which was initially isolated and cloned from human melanoma cells as a potent stimulator of tumour cell motility. ATX shows 44% identity to the plasma cell membrane marker PC-1. Recently, we described the decreased expression of ATX mRNA in cultured fibroblast-like synoviocytes (SFC) of patients with RA by interferon-gamma. In this study using a competitive reverse transcriptase-polymerase chain reaction, we show an increased ATX mRNA expression in SFC from patients with RA in comparison with synoviocytes from non-RA patients. The median ATX mRNA amount in SFC of RA patients (440 pg/μg total RNA) was five-fold higher than the expression in synoviocytes from non-RA patients (80 pg/μg total RNA) or foreskin fibroblasts (MRHF cells, 90 pg/μg total RNA). In contrast to the elevated ATX mRNA expression in SFC of patients with RA, we did not measure increased mRNA amounts of PC-1 in these cells. Both the ATX mRNA amount and the 5′-nucleotide phosphodiesterase (PDE) activity of SFC lysate were reduced after treatment of SFC with the cytokines IL-1β or IL-4. IL-1β and IL-4 induced a down-regulation of PC-1 mRNA and protein expression in SFC. In SFC treated with transforming growth factor-beta the expression of PC-1 mRNA and protein was increased, whereas no significant effect on ATX mRNA expression was detectable. Pharmacological drugs used in therapy for RA, such as dexamethasone, cyclosporin, methotrexate and indomethacin, did not show a statistically significant effect on either ATX mRNA or PC-1 mRNA expression. Only pentoxifylline suppressed ATX mRNA as well as PC-1 mRNA expression. In conclusion, we show a tight regulation of ATX and PC-1 gene expression by cytokines detectable in the inflamed tissue of RA. Further investigations will deal with the regulation of ATX protein expression as well as with the function of ATX in RA.
Activation of signal-transducer and activator of transcription 1 (STAT1) in pouchitis
Authors: Kühbacher T , Gionchetti P , Hampe J , Helwig U , Rosenstiel P , Campieri M , Buhr H J , Schreiber S 
Published: March 2003

Summary
Activation of signal transducer and activator of transcription 1 (STAT1) is a hallmark of IFN-γ receptor signal transduction but is also part of the signalling pathway of other cytokines/growth factor receptors. In ulcerative colitis, high levels of activation and expression of STAT1 have been observed in comparison with both Crohn's Disease and normal controls. Pouchitis develops in some patients after Ileal-Pouch-Anal-Anastomosis (IPAA). The pathophysiology and aetiology of pouchitis is still unclear. Recent studies have shown an increased production of proinflammatory cytokines including IFN-γ. To investigate the expression and activation of STAT1 in pouchitis and the influence of treatment, patients were followed longitudinally from pouch operation. Diagnosis of pouchitis was made by clinical, endoscopic and histological criteria. Biopsies were obtained during routine endoscopy and snap frozen in liquid nitrogen. Nuclear and cytosolic extracts were prepared and the expression and activation of specific transcription factors were assessed by Western blot, electrophoretic mobility shift assay and immunofluorescence. Patients who develop pouchitis show highly increased levels of STAT1α as well as STAT1β expression and activation in comparison with both normal pouch and normal ileal mucosa. Improvement of pouchitis during antibiotic therapy relates to a normalization of STAT1 expression and activation. We conclude that activation of STAT1 correlates to clinical disease activity and therefore STAT1 could play an important role in the pathophysiology of pouchitis. Similarities in the pattern of activation of STAT1 in pouchitis and ulcerative colitis may suggest a common pathway in the immunopathophysiology of both diseases.
Inhibition of HIV-1-mediated syncytium formation and virus replication by the lipophosphoglycan fromLeishmania donovaniis due to an effect on early events in the virus life cycle
Authors: Genois N , Barbeau B , Olivier M , Tremblay M J 
Published: March 2003

SUMMARYPrevious findings have indicated that the major surface molecule of Leishmania, lipophosphoglycan (LPG), could abrogate HIV-1-induced syncytium formation and virus replication. In the present work, we were interested in characterizing this inhibitory process. Data from a new luciferase-based semiquantitative assay for syncytium formation, relying on the coincubation of a T-cell line containing an HIV-1 LTR-driven luciferase construct with a cell line chronically infected with HIV-1, confirmed that LPG was indeed a strong inhibitor of HIV-1-dependent syncytium formation and that this inhibition was dose-dependent. As determined by flow cytometric analyses, this inhibition was not apparently due to downregulation of CD4, CXCR4 or LFA-1, three distinct surface glycoproteins known to be important in HIV-1 mediated syncytium formation. Furthermore, LPG did not seem to affect signal transduction pathways in T cells as judged by measurement of HIV-1 LTR-driven reporter gene activity upon treatment with different stimuli. However, pretreatment of either of the cell lines used in the assay with LPG led to a significant decrease of virus-mediated syncytium formation, which was further accentuated when both cell lines were pretreated. LPG inhibition of HIV-1 replication was next assessed. When measuring either infection with luciferase-encoding recombinant HIV-1 particles or multinucleated giant cell formation following an acute virus infection, we again observed that LPG was efficient at blocking HIV-1 replication. Specific assays probing different steps of viral entry demonstrated that attachment was not hindered by LPG but that viral entry was modulated, suggesting that LPG targets a postbinding step. Hence, incorporation of LPG into a target cell membrane could influence its fluidity and diminish both the virus-cell and cell-to-cell fusion processes initiated by HIV-1.
Activation of human monocytes/macrophages by hypo-osmotic shock
Authors: Frenkel O , Shani E , Ben-Bassat I , Brok-Simoni F , Shinar E , Danon D 
Published: March 2003

SUMMARYPhagocytosis and secretion of interleukins and growth factors put the macrophage in the centre of the wound healing process. For the last four years over 400 human ulcers have been treated in elderly and paraplegic patients by local application of monocytes prepared from a blood unit, in a unique, closed, sterile system. The process of preparation includes a step of hypo-osmotic shock, which induces monocyte/macrophage activation. This is different from any other known method of activation. In the present study we evaluated the efficacy of the hypo-osmotic shock. We found enhanced levels of IL-1 (P = 0·004) and IL-6 (P = 0·001) in the incubation medium (100% autologous serum) of the activated cells, as compared with controls, prepared in the same system. The IL-1 reached a plateau after 6 and 12 h incubation at 37°C, in both experimental and control incubation medium. The level of IL-6 was further elevated after 12 and 24 h incubation in experimental and control incubation mediums (P = 0·001). The phagocytosis of fluorescent beads was markedly enhanced after hypo-osmotic shock (P = 0·005).The osmotic shock induced macrophages were compared to those stimulated with LPS, and osmotic shock was proved to be at least as efficient method of stimulation as LPS.
Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis
Authors: Nishitani Y , Kubo A , Iwano M , Minamino N , Hamano K , Fujimoto T , Nishino T , Shiiki H , Yonemasu K , Dohi K 
Published: March 2003

SUMMARYIn this study, we measured the mRNA levels of adrenomedullin (AM), C-type natriuretic peptide, vascular endothelial growth factor, interleukin-1β (IL-1β) and interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive) and 30 healthy volunteers. mRNA levels were measured using a real-time quantitative PCR method. Compared with healthy volunteers, IL-6 mRNA levels were elevated in LN patients (P &lt; 0.005), while AM mRNA levels were decreased (P &lt; 0.05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in active LN patients compared with inactive LN patients. In addition, IL-6 mRNA levels positively correlated and AM mRNA levels negatively correlated with SLE disease activity index and laboratory findings, such as blood urea nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary excretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negatively correlated with AM mRNA levels within the same LN patients. With regard to pathological findings, our results showed that IL-6 mRNA levels were higher, and AM mRNA levels significantly lower in patients with a high activity index compared to those with a low activity index. Following treatment with prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRNA levels increased to levels comparable to those in inactive LN and healthy volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA levels in active LN patient PBMC were suppressed by the addition of adrenomedullin. Our results suggest that an imbalance between IL-6 and AM levels may play an important role in the progression of SLE, and that the mRNA levels of these genes in PBMC may be used as a disease activity index for SLE.
Escherichia coli-induced expression of IL-1α, IL-1β, IL-6 and IL-8 in normal human renal tubular epithelial cells
Authors: Brauner A , Söderhäll M , Jacobson S H , Lundahl J , Andersson U , Andersson J 
Published: March 2003

SUMMARYThe aim of the present study was to investigate whether the IL-1 family cytokines, in addition to IL-6 and IL-8, could be induced in normal human cortical epithelial cells in response to bacterial stimuli. Human renal tissue was obtained from 9 patients undergoing elective tumour nephrectomy. Renal cortical epithelial cells of tubular origin were prepared from the unaffected tissue. The proximal tubular cells were stimulated for 2, 6 and 24 h with a heat-inactivated pyelonephritogenic Escherichia coli strain DS-17. Cultured unstimulated tubular cells served as controls. IL-1α, IL-1β, IL-1 receptor antagonist, IL-6, IL-8, IL-10, TNF-α, G-CSF and GM-CSF were analysed using immunohistochemistry at the single cell level. The nonstimulated cells were found to express low levels of IL-6 and IL-8 (mean value &lt; 3% of total cells). In contrast, E. coli exposure resulted in significantly increased incidences of IL-6 and IL-8 expressing cells (mean values ≈18% of total cells) peaking within two hours of stimulation (P &lt; 0·008 and P &lt; 0·02 versus non-stimulated cells, respectively). A gradual decrease was thereafter observed at 6 and 24 h, respectively, although persistently higher compared to controls. A different kinetic response was found for IL-1α, IL-1β and IL-1 receptor antagonist-expressing cells, which peaked 24 h after E. coli stimulation (mean values 3–10%) (P &lt; 0·008, P &lt; 0·02, P &lt; 0·02 versus non-stimulated cells, respectively). Low levels of TNF-α and GM-CSF were found in 3 of the 9 donated epithelial cells, peaking at 2 h, and IL-10 and G-CSF producing cells in 1 patient each. In conclusion we found that heat-inactivated pyelonephritic E. coli induced a proinflammatory cytokine response in the normal human proximal tubular cells including the IL-1 family, IL-6 and IL-8.
Activation of HIV-1-specific immune responses to an HIV-1 vaccine constructed from a replication-defective adenovirus vector using various combinations of immunization protocols
Authors: Yoshida T , Okuda K , Xin K-Q , Tadokoro K , Fukushima J , Toda S , Hagiwara E , Hamajima K , Koshino T , Saito T 
Published: March 2003

SUMMARYWe constructed a recombinant replication defective adenovirus vector containing the env gene (Ad-Bal) derived from macrophage-trophic HIV-1 (HIV-1 Bal). We then immunized mice with this vector using several administration routes and protocols, and examined the immune response. When the Ad-Bal viral vector (over 1 × 107 pfu) was injected subcutaneously, both humoral and cell-mediated immunities were induced. However, immune response induced by the Ad-Bal vector alone was weaker than that induced by the recombinant vaccinia viral vector. We then employed the following three immunization protocols: (l) DNA vaccination followed by immunization with the Ad-Bal; (2) vaccination using the Ad-Bal vector followed by DNA vaccination; and (3) DNA vaccination followed by Ad-Bal infection and passive transfer of dendritic cells (DCs) infected with the Ad-Bal. Among the three protocols, the last gave the strongest humoral and cell-mediated immunity. These results suggest that the combination of DNA vaccination, Ad-Bal vector infection and passive transfer of Ad-Bal-infected DCs can induce strong immunity against HIV-1 Bal.
Colonic epithelial cells induce endothelial cell expression of ICAM-1 and VCAM-1 by a NF-κB-dependent mechanism
Authors: Maaser C , Schoeppner S , Kucharzik T , Kraft M , Schoenherr E , Domschke W , Luegering N 
Published: March 2003

SUMMARYEpithelial cells are positioned in close proximity to endothelial cells. A non-contact coculture system was used to investigate whether colonic epithelial cells activated with various cytokines are able to provide signals that can modulate ICAM-1 and VCAM-1 expression on endothelial cells. Coculture of human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1) with TNF-α/IFN-γ-stimulated human colon epithelial cell lines led to a significant up-regulation of endothelial ICAM-1 and VCAM-1 expression. Increased ICAM-1 and VCAM-1 expression by endothelial cells was accompanied by an increase in endothelial cell NF-κB p65 and NF-κB-DNA-binding activity. Inhibition of endothelial NF-κB activation using the proteosome inhibitors MG-132 and BAY 11–7082 resulted in a significant decrease of ICAM-1 expression, indicating an important role for NF-κB in this response. This cross-talk may represent a biological mechanism for the gut epithelium to control the colonic inflammatory response and the subsequent immune cell recruitment during inflammation.
Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis
Authors: Kumar R , Pai K , Sundar S 
Published: March 2003

SUMMARYReactive oxygen intermediates (ROI), nitrite and interferon-gamma (IFN-γ) production were investigated at different times during treatment in 10 patients with visceral leishmaniasis (VL). Hydrogen peroxide (H2O2), superoxide (O2−) and IFN-γ production by cultured monocytes from patients with active VL were significantly lower compared with the healthy controls. In contrast, nitrite levels in the supernatants from monocyte cultures of VL patients were comparable to healthy controls and increased significantly during antileishmanial therapy. On day 20 of treatment, a significant increase in the release of H2O2, O2− and IFN-γ was observed. However, at follow-up, 4 months after the end of treatment, the production of H2O2, O2−, IFN-γ and nitrite had declined significantly. Thus, the impairment in hydrogen peroxide and superoxide production suggests that down-regulation of these mediators may be involved in the reduced killing of parasites by monocytes of active VL patients. Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy.