bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteine protease of the nematodeNippostrongylus brasiliensispreferentially evokes an IgE/IgG1 antibody response in rats
Authors: Kamata I , Yamada M , Uchikawa R , Matsuda S , Arizono N 
Published: July 2010

SUMMARYSome cysteine proteases such as papain and those of mites and schistosomes have potent allergenic properties. To clarify the allergenicity of nematode cysteine proteases, the enzyme was purified from the intestinal nematode Nippostrongylus brasiliensis using cation exchange chromatography and gel filtration chromatography. The purified protease, of 16 kD and pi 8-5, showed maximum enzyme activity at pH 55 and substrate preference for Z-Phe-Arg-MCA. The specific inhibitors of cysteine protease leupeptin, iodoacetic acid, and E-64. completely suppressed the activity, indicating that the purified enzyme belongs to the cysteine protease family. Cysteine protease activity was found not only in somatic extract, but also in the excretory-secretory (ES) product of the nematode. When anti-cysteine protease immunoglobulin isotypes were examined in sera from rats infected with N. brasiliensis. a high level of IgG1 and a lower level of IgE antibody were detected. Depletion of IgG antibodies from the sera using protein G affinity columns resulted in a marked increase in reactivity of anti-cysteine protease IgE with the antigen, possibly due to the removal of competing IgG antibodies. In contrast to IgE and lgG1. production of anti-cysteine protease IgG2a was negligible. These results indicate that the nematode cysteine protease preferentially evokes an IgE/IgG1 antibody response.
Endothelial cells and renal epithelial cells do not express the Wegener's autoantigen, proteinase 3
Authors: King WJ , Adu. D , Daha MR , Brooks CJ , Radford DJ , Pall AA , Savage COS 
Published: July 2010

SUMMARYProteinase 3 (PR3) is the major antigen for autoantibodies (C-ANCA) against cytoplasmic components of neutrophils which are strongly associated with Wegener's granulomatosis (WG). Recent data that PR3 may be expressed by renal tubular epithelial cells and endothelial cells suggest potential for a direct pathogenic effect against these cells by C-ANCA or cytoxic T lymphocytes. Using a semi-quantitative polymerase chain reaction (PCR), ELISA and indirect immunofluorescence staining we studied endothelial and epithelial cell PR3 expression. By PCR, no PR3 expression was found in human umbilical vein endothelial cells (HUVEC) either untreated, or when treated with interferon-gamma (IFN-γ) (200 U/ml, 6h, 24h), IL-1 (20U/ml, 6h), tumour neurosis factor-alpha. (TNF-α) (200U/ml. 0. 1.2, 4, 6h) or IFN-γ+ TNF-a (6h); iliac vein and artery endothelial cells did not express PR3 either. In contrast. PR3 was detected in HL60 cells and neutrophils by PCR. expression being confirmed by sequence analysis. Three PR3 MoAbs showed no binding to unstimulated or TNF-α-stimulated HUVEC either by ELISA or by indirect immunofluorescence staining. The epithelial cell line A549 expressed PR3 when assayed by PCR. However, three renal epithelial cell lines (two tubular and one glomerular) showed little or no PR3 expression by PCR or ELISA. These studies fail to demonstrate evidence for PR3 expression by endothelial cells, even when using the highly sensitive PCR assay. Whilst PR3 expression by A549 cells is intriguing, the relevance of this in the pathology of WG is doubtful considering the negligible expression by renal epithelial cell lines.
Signalling via CD28 of human naive neonatal T lymphocytes
Authors: Hassan J , O'neill S , O'neill L A J , Pattison U , Reen D J 
Published: July 2010

SUMMARYAccessory molecules play a crucial role in the development of the T cell response to antigenic challenge. We have examined the role of CD28 in modulating the‘naive’ neonatal T cell response to anti-CD2-mediated activation. To compare the role of CD28, neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence or anti-CD28 MoAb. With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2, whereas adult T cells proliferated vigorously, with significant IL-2 production. Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells, whereas adult T cells showed only slight increases. Although IL-2 secretion was increased in the presence of anti-CD28 MoAb. neonatal T cell IL-2 production remained lower than in adults. In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels. Anti-CD28 MoAb costimulation increased NFkB levels in neonates, albeit to levels lower than that of adults. The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NFkB induction, reduced IL-2 mRNA expression and deficient IL-2 production. Although anti-CD28 MoAb costimulation enhances all of the above signals, NFkB and IL-2 levels remain lower than in adults, suggesting the need for further activation requirements in the neonate.
Glycosylphosphatidylinositol (GPI)-anchored surface antigens in the allogeneic activation of T cells
Authors: Schubert J , Stroehmann A , Scholz C , Schmidt R E 
Published: July 2010

SUMMARYGPI-linked surface molecules have recently been described as structures with an activation potential for human T lymphocytes. To study the role of these molecules in T cell activation we analysed GPI-deficient or normal T cells from patients with paroxysmal nocturnal haemoglobinuria (PNH). On activation with allogeneic Epstein-Barr virus (EBV)-transformed B cell lines GPI-deficient freshly separated T cells or continuously growing T cell lines exhibited a significantly lower proliferation or cytokine production compared with their normal counterparts. In contrast, stimulation via the T cell receptor-associated CD3 structure resulted in a comparable response. There was no difference in activation of normal T lymphocytes when GPI-deficient B cells were used as stimulators compared with normal B cells obtained from the same PNH patient. We conclude from these data that GPI deficiency in PNH leads to a functional deficiency of GPI-deficient T cells. In contrast, no difference in activation of T lymphocytes for GPI-deficient cells on the stimulator cell level was observed.
Delineation of producing ability of IgG and IgA subclasses by naive B cells in newborn infants and adult individuals
Authors: Yachie A , Konno A , Ohta K , Wada T , Seki H , Taniguchi N , Miyawaki T 
Published: July 2010

SUMMARYNeonatal B cells with the naive (sIgD+) phenotype are able to generate IgG- and IgA-producing cells as well as IgM production in the presence of memory CD4+ T cells expressing L-selectin (CD62L) in pokeweed mitogen-stimulated cultures. We used this system to examine comparatively the ability of naive B cells to produce IgG and IgA subclasses in newborn infants and adult individuals. Naive B cells were enriched from both donors on the basis of sIgD positivity, and memory (CD45RO+) CD4+ T cells with CD62L expression were isolated from adults. We here demonstrate some differences in profiles of IgG and IgA subclass production between neonatal and adult naive B cells. In neonatal B cells, IgG1 and IgG3 were predominantly produced, but IgG2 and IgG4 production was virtually absent. Similar to neonatal B cells, adult naive B cells produced mainly IgGq and IgG3, although memory (sIgD’) B cells from adults secreted all of the IgG subclasses. It should be noted that low but detectable levels of IgG2 and IgG4 were found in adults’naive B cell cultures. Although IgA produced by neonatal B cells was exclusively IgA1, IgA2-secreting cells were identifiable in adult naive B cells. The results suggest that further class switch of naive B cells to IgG2, IgG4 and IgA2 in addition to IgG1 and IgG3 may be controlled by their own age-dependent maturation process.
The acute phase protein response in patients receiving subcutaneous IL-6
Authors: Banks R E , Forbes M A , Storr M , Higginson J , Thompson D , Raynes J , Illingworth J M , Perren T J , Selby P J , Whicher J T 
Published: July 2010

SUMMARYIL-6, tumour necrosis factor-α (TNE-α) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based on in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of these cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an extensive range of positive and negative acute phase proteins. It was part of a larger investigation to assess the value of IL-6 in the management of chemotherapy-induced thrombocytopenia. IL-6 was administered by a daily subcutaneous injection for 7 days at a dose level of 1, 3. or 10 μg/kg/day. Increases in the positive acute phase proteins, serum amyloid A. C-reactive protein. α1-acid glycoprotein, α1-antichymotrypsin, haptoglobin, α1-antitrypsin, fibrinogen, complement component C3, and caeruloptasmin, were observed, with the greatest incremental changes and fastest responses being seen for C-reactive protein and serum amyloid A protein. The negative acute phase proteins transferrin, transthyretin and retinol binding protein all fell to a nadir within 48-96 h after the first IL-6 injection. Increases in complement component C4 were only found in two patients, which may be related to the increase in circulating TNF-α concentrations found only in these patients. This study has therefore shown that IL-6 is capable of causing changes in the majority of acute phase proteins in vivo. Although secondary induction of TNF-α was not observed in the majority of patients examined, it is still possible however that other cytokines involved in regulation of the acute phase response, such as IL-1, may have been induced and contributed to the overall response.
Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients
Authors: Ohkuma K , Sasaki T , Kamei S , Okuda S , Nakano H , Hamamoto T , Fujihara K , Nakashima I , Misu T , Itoyama Y 
Published: July 2010

SummaryIntravenous immunoglobulin (IVIg) preparations are reportedly effective in inhibiting the relapse of multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. In the system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of immunoglobulin G (IgG) on these antigen-presenting cells. Using monocytes derived from healthy volunteers, IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG enhanced the expression of CD83, a marker of mature DCs (mDCs). Furthermore, IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 α4-integrin], the adhesion molecule required for mDCs to cross the blood–brain barrier. We obtained similar results on all the aforementioned cell surface molecules investigated in both healthy controls and MS patients. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC differentiation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help to prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of immune cells into the central nervous system and affecting the cytokine profile.
Stimulation of monocytes is a pathway involved in systemic inflammatory response following haemorrhagic shock resuscitation: the effect of hypoxaemic resuscitation
Authors: Douzinas E E , Livaditi O , Tasoulis M-K , Pelekanou A , Giamarellos-Bourboulis E J 
Published: July 2010

SummaryThe present study was designed to investigate whether serum of animals subjected to hypoxaemic resuscitation from haemorrhagic shock may be a weak stimulant for monocytes or not. Twenty rabbits were subjected to haemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in eight rabbits under normoxaemic conditions (NormoxRes) and in 12 under hypoxaemic conditions (HypoxRes); seven rabbits were subjected to sham operation. Malondialdehyde (MDA) and tumour necrosis factor (TNF)-α were estimated in serum at serial time intervals; the serum was applied for stimulation of U937 monocytes with or without the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Expression of triggering receptor expressed on myeloid cells-1 (TREM-1) on U937 was also assessed by flow cytometric analysis. Death supervened in four animals of the NormoxRes (50%) and in one animal of the HypoxRes group (8·33%, P: 0·032). Serum levels of TNF-α and MDA were higher in NormoxRes compared to HypoxRes animals. Expression of TREM-1 on U937 monocytes was similar after stimulation with serum sampled from both groups. Concentrations of interleukin (IL)-1β, IL-6 and IL-8 of monocyte supernatants were higher after stimulation with serum of NormoxRes than HypoxRes rabbits. Production of cytokines after stimulation with serum was decreased significantly after addition of SB203580. It is concluded that stimulation of monocytes may contribute to the generation of the systemic inflammatory response during reperfusion after ischaemia. Lower stimulation of the p38 MAPK-mediated production of IL-1β, IL-6 and IL-8 by monocytes may be implicated as an explanation for the benefits shown for the host when resuscitation is performed under hypoxaemic conditions.
Systemic and local interferon-gamma production following Mycobacterium ulcerans infection
Authors: Schipper H S , Rutgers B , Huitema M G , Etuaful S N , Westenbrink B D , Limburg P C , Timens W , Van Der Werf T S 
Published: July 2010

Summary
Buruli ulcer disease (BUD) is an emerging predominantly tropical disease caused by Mycobacterium ulcerans. The initial pre-ulcerative skin lesion often breaks down into an ulcer with undermined edges. Healing is common but may require considerable time, and scarring often results in functional limitations. Considerable evidence has now emerged that patients with early BUD cannot mount a sufficient protective T helper 1 (Th1) cell response to M. ulcerans, but uncertainty remains as to whether immune protection is restored over time. This study investigates the Th1 cell response of patients with various stages of BUD on mycobacterial antigens. We measured interferon (IFN)-γ levels after ex vivo whole blood stimulation with tuberculin purified protein derivative (PPD), and compared the Th1 cell response of individuals with pre-ulcerative, ulcerative and healed BUD as well as healthy controls. Moreover, the systemic Th1 cell response was related to histopathological features in the various stages of surgically resected BUD lesions. We show that patients with ulcerative and healed BUD produce significantly higher IFN-γ levels after mycobacterial ex vivo whole blood stimulation than healthy controls, and that patients with a granulomatous tissue response produce higher IFN-γ levels than individuals without. We therefore suggest that the mounted Th1 cell response in ulcerative BUD patients might be related to their histopathological tissue response.
A comparison of ex vivo cytokine production in venous and capillary blood
Authors: Eriksson M , Sartono E , Martins C L , Balé C , Garly M-L , Whittle H , Aaby P , Pedersen B K , Yazdanbakhsh M , Erikstrup C , Benn C S 
Published: July 2010

Summary
We performed a randomized study of the immunological effects of an early measles vaccine given at 4·5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained. We analysed baseline samples from the first 50 children enrolled in the study to investigate the potential differences in ex vivo cytokine production between venous blood and capillary blood. We also obtained paired venous and capillary blood samples from 11 adult volunteers. Whole blood was stimulated with lipopolysaccharide (LPS) [a Toll-like receptor (TLR)-4 ligand], (S)-(2, 3-bis (palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, trihydrochloride (PAM3Cys) (a TLR-2 ligand), phytohaemagglutinin (PHA) or purified protein derivative (PPD). Cytokine concentrations in the supernatants were assessed by a multiplexed assay and were compared between venous and capillary samples in both infants and adults. The production of both the pro- and the anti-inflammatory cytokines, tumour necrosis factor (TNF)-α and interleukin (IL)-10, was higher in cultures of capillary blood compared with venous blood. This was found in non-stimulated control samples as well as in blood stimulated with PAM3Cys and PPD. Adults produced more IL-5 in venous blood than in capillary blood upon PHA stimulation. We found no other difference in the levels of IL-5 or IFN-γ between venous and capillary blood. In capillary blood we found sex differences in response to PHA but this was not the case in venous blood. We found significant differences in the production of cytokines between venous and capillary blood. Such differences should be taken into account when setting up immuno-epidemiological studies.
Exploring the feasibility of selective depletion of T lymphocyte subsets by whole blood immunoadsorption cytapheresis
Authors: Belak M , Valeri C R , Wright D G 
Published: July 2010

SummaryNormal turnover of T lymphocytes is slow relative to other blood cells. Consequently, the physical removal of circulating leucocytes by thoracic duct drainage, repeated leukapheresis or blood filtration results in T cell depletion and immunosuppression. However, clinical use of such procedures is impractical compared with immunosuppressive drugs or radiation. None the less, immunosuppression by physical depletion of T cells, avoiding the systemic toxicities of drugs and radiation, might have clinical advantages if immunophenotypically distinct T cell subsets could be depleted selectively. Recent advances in targeted plasma protein apheresis using adsorbent macrobead columns prompted us to determine whether analogous techniques might permit CD4+ T lymphocytes to be removed selectively from whole blood. To explore this possibility, we linked murine anti-human-CD4 and isotype-identical control monoclonal antibodies (mAbs) to agarose, polyacrylamide and polystyrene macrobeads (150–350 μm) and then evaluated the selectivity, specificity and efficiency of macrobead columns to remove CD4+ T cells from anti-coagulated whole blood at varying mAb densities and flow rates. We also examined saturation kinetics and Fc-oriention versus random coupling of mAbs to macrobeads. Sepharose 6MB macrobead (250–350 μm) columns proved to be most effective, selectively removing up to 98% of CD4+ T cells from whole blood. Moreover, depletion efficiency and selectivity were retained when these columns were reused after elution of adherent CD4+ cells. These studies indicate that selective depletion of T lymphocyte subsets by whole blood immunoadsorption apheresis using mAb-linked macrobead columns may be feasible on a clinical scale. It is possible that such apheresis techniques could achieve targeted forms of immunosuppression not possible with drugs or radiation.
A 10% ready-to-use intravenous human immunoglobulin offers potential economic advantages over a lyophilized product in the treatment of primary immunodeficiency
Authors: Kallenberg C G M 
Published: July 2010

Summary
Intravenous immunoglobulin (IVIg) replacement therapy is the standard of care for patients with primary humoral immunodeficiencies. This study evaluated differences in infusion time between a 10% IVIg ready-to-use solution and a 6% IVIg lyophilized product and addressed potential cost implications. After receiving in-hospital treatment with 6% IVIg lyophilized solution for at least 6 months, 14 patients with humoral immunodeficiency without anti-IgA antibodies received five successive infusions with 10% IVIg ready-to-use solution. Data on infusion times were collected during the last two infusions of each IVIg product when maximum infusion rates had been reached. The median infusion time was reduced from 104·4 min with the 6% IVIg lyophilized solution to 51·0 min with the 10% IVIg ready-to-use solution (51% reduction), with corresponding median maximum infusion rates of 4·1 ml/kg/h and 5·9 ml/kg/h, respectively. Median gammaglobulin (IgG) trough levels were 7·1 g/l for the 6% IVIg lyophilized solution and 7·9 g/l for the 10% IVIg ready-to-use solution. Fewer adverse events were observed after infusing with 10% IVIg ready-to-use solution compared with 6% IVIg lyophilized preparation. We conclude that the 10% IVIg ready-to-use solution was well tolerated by most patients and reduced the median infusion time by 51% compared with a 6% lyophilized preparation of IVIg. The reduced bed occupancy and nursing time associated with a reduced infusion time, together with the elimination of a reconstitution step, were estimated to provide a cost-saving of €59·42 per patient per infusion. Thus, this product has the potential to reduce overall costs of IVIg treatment. Reduced infusion time is also likely to improve patients' quality of life.
Selective expansion of T cell receptor (TCR) V beta 6 in tonsillar and peripheral blood T cells and its induction byin vitrostimulation withHaemophilus parainfluenzaein patients with IgA nephropathy
Authors: Nozawa H , Takahara M , Yoshizaki T , Goto T , Bandoh N , Harabuchi Y 
Published: July 2010

SummaryIgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been investigated fully. In this study, we compared the expression of T cell receptor (TCR) V beta families in tonsillar T cells of IgAN patients to those of non-IgAN patients. The reverse transcription–polymerase chain reaction (RT–PCR) and flow cytometric analyses showed that the TCR V beta 6 was used more frequently in tonsillar T cells of IgAN patients than in those of non-IgAN patients (P &lt; 0·01 each). Similarly, the proportions of TCR V beta 6-positive cells in peripheral blood T cells were significantly higher in IgAN patients than in non-IgAN patients (P &lt; 0·05). After tonsillectomy, the proportions decreased in IgAN patients (P &lt; 0·05), but did not in non-IgAN patients. Furthermore, in vitro stimulation with Haemophilus parainfluenzae antigen, which is reported to deposit in the glomerular mesangium of IgAN, enhanced expression of TCR V beta 6 in tonsillar T cells from both IgAN and non-IgAN patients. These results suggest that TCR V beta 6-positive tonsillar T cells might be activated by H. parainfluenzae, move into the kidney through blood circulation and induce glomerulonephritis.