bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenic effect of platelet-derived growth factor in human glomerular mesangial cells: modulation and/or suppression by inflammatory cytokines
Authors: FLOEGE J , TOPLEY N , HOPPE I , BARRETT T B , RESCH K 
Published: July 2010

SUMMARYGlomerular mesangial cell proliferation constitutes a frequent pathological alteration in glomerulonephritis. In addition to platelet-derived growth factor (PDGK) inflammatory cytokines such as IL-1. IL-6 or tumour necrosis factor-alpha (TNF-α) have been proposed to have mitogenic activity for mesangial cells. A model was therefore established in which human mesangial cells (HMC) could be reversibly growth-arrested for prolonged times in serum-free medium without suffering irreversible functional or morphological changes. In this model 24 h stimulation with rhPDGF-BB induced an increase of the 3H-thymidine incorporation of 1190.280 (50 ng/ml) %± s.e.m. of medium control. Less growth induction was noted after stimulation with 50 ng ml rhPDGF-AB (925± I26) or rhPDGF-AA (575 ± 24%). Northern analysis confirmed the presence of both α and β-PDGF receptor subunit mRNA in growth-arrested HMCs. rhlL-lα, rhlL-1β, rhTNF-α or rhIL-6 at various doses and times, despite increasing cellular PGE2-release, did not induce significant proliferation in HMCs. Inhibition of PGE2-release did not change the lack ol mitogenicity of lL-l, TNF-α or lL-6. IL-6 did not alter the mitogenic response of the cells towards PDGF. In contrast, both IL-lα and lL-lβ (5 ng/ml) induced a delay but not augmentation of the PDGF growth response. This delay could be reversed by the concomitant addition or recombinant IL-6 or of anti-lL-1 antibody but not by inhibition of prostaglandin synthesis. High doses of TNF-α suppressed PDGF-induced proliferation. These data suggest that in growth-arrested HMCs inflammatory cytokines have a growth-modulating or -suppressive rather than (co-)mitogenic effect while PDGF-BB and-AB and to a lesser degree PDGF-AA are potent mitogens. The findings support the notion that the control of HMC proliferation in pathological situations depends on a complex network of interacting stimuli.
Ontogenesis of the secretory immune system and innate defence factors in human parotid glands
Authors: THRANE P S , ROGNUM T O , BRANDTZAEG P 
Published: July 2010

SUMMARYImmunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands, (1) Fetal specimens. Occasional IgM- and IgA- But no IgD-, IgG- or IgE-producing cells were seen (ratios, IgM:IgA:IgD:lgG:IgE–4:1:0:0:0). The IgA1 subclass dominated (median 90%, range 50–95%) and these cells were mostly J-chain-positive (median 97%, range 94 98%). Only few lgA2-producing cells were seen (median 10%, range 5–50%) and they were also mostly J-chain-positive (median 99%, range 98–100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (lgA:IgM:IgD:IgG:lgE–4:2:1 : 1:0). The IgA1 subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10–50%). Most IgA1 (median 97%, range 67–100%) and IgA2 (median 94%, range 75–100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.
COMPLEMENT ACTIVATION AND BIOINCOMPATIBIUTY
Authors: Mollnes T E , Videm V , Riesenfeld J , Garred P , Svennevig J L , Fosse E , Hogasen K , Harboe M 
Published: July 2010

AbstractThe degree of biocompatibility of biomaterials can be evaluated using various assay systems detecting activation of the blood cascade systems, leukocytes or platelets. Activation of complement is one mechanism associated with adverse effects observed when bioincompatible materials are used. We present data showing that the terminal complement compiex, an indicator of terminal pathway activation, is suitable for evaluation of biocompatibility of biomaterials such as cardiopulmonary bypass devices. Furthermore, our results suggest that bioincompatibility is improved when artificial surfaces are modified with end point attached functionally active heparin.
Beneficial effect of human therapeutic intravenous immunoglobulins (IVIg) in mercuric-chloride-induced autoimmune disease of Brown-Norway rats
Authors: ROSSI F , BELLON B , VIAL M C , DRUET P , KAZATCHKINE M D 
Published: July 2010

SUMMARYAdministration of HgCl2 to the susceptible Brown–Norway (BN) strain of rats induces an autoimmune disease characterized by polyclonal B cell activation, increased serum levels of IgE and the occurrence of anti-glomerular basement membrane antibody-mediated glomerulonephritis. We have observed that the simultaneous administration to BN rats of normal human polyspeciric immunoglobulins for therapeutic use (IVIg) with HgCl2 significantly decreased the occurrence and severity of proteinuria, and reduced serum IgE levels in diseased animals. Hypergammaglobulinaemia was potentiated in animals receiving HgCl2 and IVIg, compared with animals receiving HgCl2 alone. In vitro experiments indicated that F(ab')2 fragments from IVIg inhibited the binding to laminin of pathogenic anti-laminin antibodies from diseased rats, as did antibodies from the resistant Lewis strain of rats but not antibodies from susceptible BN rats. These observations suggest that IVIg may interfere with the immune regulatory mechanisms involved in mercury-induced autoimmune disease in an analogous fashion to the ability of IVIg to suppress the expression of certain pathological autoimmune responses in humans.
Human immune response to rabies nucleocapsid and glycoprotein antigens
Authors: KASEMPIMOLPORN S , HEMACHUDHA T , KHAWPLOD P , MANATSATHIT S 
Published: July 2010

SUMMARYAntibodies to two components of rabies virus, nucleocapsid (N) and glycoprotein (G), were compared in 11 rabies patients with those in nine recipients of Vero cell rabies vaccine. All rabies vaccinees had antibodies to N and G components by day 10 after the first vaccine injection. A similar but not identical response was observed in three out of 11 rabies patients. Serum antibodies appeared in rabies patients as early as 3 days after onset of the first symptoms of the disease. In these antibody-positive rabies patients, levels of both antibodies, but particularly of anti-N antibody, were lower than in the vaccinated group. Our results suggest that the process of immune recognition and of antibody development in human rabies is more likely to occur early in the pre-clinical phase, and that reactivity to N protein may be crucial for elicitation of neutralizing antibody.
Killing ofMycobacterium tuberculosiswithin human monocytes: activation by cytokines and calcitriol
Authors: DENIS M 
Published: July 2010

SUMMARYHuman monocytes were isolated and their ability to harbour growth of virulent tubercle bacilli was assessed, in the presence or absence of various immunomodulators. Calcitriol (1,25 (OH2), vitamin D3) alone, at doses of 10-7 -10-9 m endowed human monocytes with a significant ability to restrict intracellular growth of the tubercle bacilli. Crude immune lymphokines as well as recombinant interferon-gamma (IFN-γ) endowed monocytes with no tuberoulostatic activity. Similarly, other recombinant cytokines tested, notably colony-stimulating factor-1 (CSF-1), interleukin-1 (IL-1), interleukin-3 (IL-3) and interleukin-6 (IL-6) all failed to stimulate anti-tuberculous properties, and even increased growth of the tubercle bacilli in monocytes, in the case of CSF-1. Conversely, incubation of crude lymphokines in combination with calcitriol led to total stasis of the growth of M. tuberculosis. Experiments with recombinant cytokines and immunologically active vitamins showed that a combination of IFN-γ tumour necrosis factor-alpha and calcitriol induced a significant amount of intramonocyte killing of M. tuberculosis. Addition of this cocktail of factors to already infected monocytes fed to substantial killing of tubercle bacilli. These sets of experiments establish clearly that combinations of recombinant cytokines and vitamins may induce substantial intramonocyte killing of M. tuberculosis. The mechanism involved in this killing activity was not clarified.
A 19-year-old man with leucocyte adhesion deficiency.In vitroandin vivostudies of leucocyte function
Authors: DAVIES K A , TOOTHILL V J , SAVILL J , HOTCHIN N , PETERS A M , PEARSON J D , HASLETT C , BURKE M , LAW S K A , MERCER N F G , WALPORT M J , WEBSTER A D B 
Published: July 2010

SUMMARYWe describe a male patient with leucocyte adhesion molecule deficiency (LAD) or moderate phenotype. Although diagnosis was made only 2 years before his death, the patient survived until 19 yean of age. This enabled us to perform a number of novel investigations, both in vivo and in vitro, relating to his leucocyte biology. Monocytes cultured in vitro matured into morphologically normal, phagocytically capable macrophages, which were able to recognize aged‘apoptotic’neutrophils. By injection of radiolabelled autologous neutrophils we demonstrated a prolonged nculrophil half-life, but normal margination, de-margination on exercise, and splenic pooling. Neutrophil adherence in vitro to vascular cndotnclium was normal. Histological examination of the patient’s lungs at postmortem showed intravascular aggregation of polymorphonuclear leucocytes but a paucity of cells in the interstitium and alveolar spaces. These findings indicate that the peripheral blood leucocytosis commonly observed in these patients may be due to prolonged intravascular neutrophil survival, and suggest that CD11/18 molecules have an important role in facilitating neutrophil emigration from blood vessels at sites of inflammation.
Detection of anti-myeloperoxidase and anti-elastase antibodies in vasculitides and infections
Authors: GALLICCHIO M C , SAVIGE J A 
Published: July 2010

SUMMARY
Autoantibodies that produce a perinuclear pattern on indirect immunofluorescent examination of ethanol-fixed neutrophils (pANCA) are found in about half of all cases of microscopic polyarteritis. These antibodies are often directed against myeloperoxidase or elastase and we have developed sensitive reproducible ELISAs for their detection and study. Seven sera from 19 patients with microscopic polyarteritis or segmental necrotizing glomerulonephritis contained anti-myeloperoxidase or anti-elastase antibodies or both. In contrast, only one of 18 sera from patients with Wegener’s granulomatosis, where the pattern of immunofluorescence is predominantly cytoplasmic, had anti-myeloperoxidase antibodies and no anti-elastase antibodies were detected. Using sera from patients with microscopic polyarteritis, both anti-myeloperoxidase and anti-elastase antibodies were demonstrated to be of high affinity. There was no immunoglobulin class, subclass or light chain restriction noted. Anti-myeloperoxidase and anti-elastase antibodies were also found occasionally in anti-glomerular basement membrane disease, mixed connective tissue disease, systemic lupus erythematosus, post-streptococcal glomerulonephritis and atypical pneumonia. In further studies these antibodies were not associated with other lung infections, although anti-elastase antibodies were noted in one of 14 sera positive for ASOT that were tested. Anti-myeloperoxidase antibodies were found more frequently than anti-elastase antibodies and these antibodies were occasionally present together. In addition some sera with pANCA had neither anti-myeloperoxidase nor anti-elastase antibodies. The target molecules in these cases remain unclear.
UCHL1+ (CD45RO+)‘memory’T cells predominate in the CD4+ cellular infiltrate associated with allergen-induced late-phase skin reactions in atopic subjects
Authors: FREW A J , KAY A B 
Published: July 2010

SUMMARYWe have previously shown that CD4+ T lymphocytes accumulated at the site of allergen-induced late-phase reactions (LPR) in the skin of atopic subjects. In order to determine whether these were predominantly‘memory’or‘naive’cells, monoclonal antibodies recognizing isoforms of the CD45 common leucocyte antigen and immunocytochemical methods were used to study the composition of the T cell infiltrate. Allergen-induced late-phase skin reactions were biopsied6, 24 or 48 h after allergen challenge. Memory (CD45RO+/UCH L1+) T cells predominated and few naive (CD45RA/Leu 18+) cells were identified. Double immunofluorescence was used lo confirm that the UCHLI+ and Leu 18+ cells were CD4+ T lymphocytes. The selective recruitment of memory T cells to LPR sites is consistent with the active involvement of T lymphocytes in alopic allergic inflammation. A possible alternative explanation for apparently selective recruitment is the differential expression of endothelial adhesion molecules on memory and naive T lymphocytes.
Changes in leucocyte populations following murine bifunctional antibody infusion in colon cancer patients
Authors: GRIDLEV D S , STICKNEY D R 
Published: July 2010

SUMMARYThis study was undertaken to determine whether infusion of a unique ZCE/CHA bifunctional antibody (BFA, 5–40 mg) could alter the composition and functions of peripheral blood leucocytes in 18 patients with colon cancer. The BFA is made by combining chemically the Fab’fragments of two murine monoclonal antibodies. One fragment (ZCE 025) binds to the carcino-embryonic antigen (CEA) and the other (CHA 255) to an epitope, present on an In -benzyl EDTA analog of bleomycin (BLEDTA IV) and on 111In-hydroxy-ethyl-thiourca benzyl EDTA (EOTUBE). The radiolabelled epitope (111ln-BLEDTA IV or 111In-EOTUBE) was given 4 days after pre-localization with BFA. Peripheral blood samples were tested before BFA infusion, at the end of infusion (1 h later), and at 4 and 7 days post-infusion. A 50% or greater suppression in lymphocyte responsiveness to phytohaemagglutinin (PHA) and concanavalin A (Con A) was seen in 13 out of 18 and 12 out of 18 subjects, respectively, at some time after BFA infusion; this was especially evident in those patients with prc-infusion stimulation indices of &gt; 50 (PHA) and/or &gt; 10 (Con A). In contrast, natural killer (NIC) cell cytotoxicity and oxygen radical production increased in five out of 15 and in seven out of 18 subjects, respectively. Little or no change was observed in CD3, CD4, CDS. CD16, and CD19 markers on lymphocyte subpopulations as determined by flow cytometry. These data suggest that significant changes in mitogen-induced lymphoproliferation. NK cell cytotoxicity. and oxygen radical production can occur in a substantial proportion of cancer patients after infusion of the ZCE/ CH A bifunctional antibody system. The immunomodulation was unrelated to initial BFA dose, dose of BFA as a carrier, or to subsequent infusion of either form of the 111In cpilope. The clinical significance of these phenomena, if any, remains to be determined.
Studies in vivo and in vitro of serum amyloid P component in normals and in a patient with AA amyloidosis
Authors: HAWKINS P N , TENNENT G A , WOO P , PEPYS M B 
Published: July 2010

SUMMARY
Pure serum amyloid P component (SAP) was isolated from a normal donor pool, from individuals with the different genotypes of an MspI restriction fragment length polymorphism (RFLP) linked to the SAP gene, and from a patient with AA amyloidosis. The SAP preparations were all identical and all behaved as a single homogeneous species in polyacrylamide gel electrophoresis, isoelectric focussing, reverse-phase chromatography, binding in vitro to phosphoethanolamine-Sepharose (binding constant 2.4× 107l/mol) and AL amyloid fibrils (1.6 × 108l/mol), and binding to amyloid deposits in vivo in mice with casein-induced amyloidosis. The in vivo metabolism of 125I-SAP from a single donor was normal and identical in three healthy individuals representing the three different MspI RFLP genotypes. There is thus no frequent polymorphism of SAP in normal subjects, and SAP altered with respect to the characteristics studied here is not a necessary condition for pathogenesis of systemic AA amyloidosis.
Expression of the fibronectin receptor VLA-5 is regulated during human B cell differentiation and activation
Authors: BALLARD L L , BROWN E J , HOLERS V M 
Published: July 2010

SUMMARYWe examined the expression of VLA-5, a libronectin receptor, during human B cell development and activation. VLA-5 is a member of the integrin supergene family; VLAs arc heterodimers of at least six unique a chains sharing a common (i chain; most arc involved in cell attachment to extracellular matrix (ECM). A hypothesis of haematopoietic development is lhat maturing cells leave the bone marrow because of the loss of VLA-5 during differentiation. However, mature B ceils are not primarily circulating cells, and the role of ECM receptors in homing to peripheral lymphoid tissue and inflammatory sites is unknown. To examine the expression of VLA-5 during B cell development, cell lines blocked at specific stages of differentiation were evaluated for their synthesis and surface expression of VLA-5 using VLA-5-specific antibody and cDNA probes. VLA-5 mRNA and surface expression were found in the pre-B cell lines, REH and Nall 1, but not in more differentiated Raji cells or in several EBV-transformed peripheral B cell lines. Circulating peripheral B lymphocytes and resting tonsillar and splenic B lymphocytes expressed no VLA-5 by FACS analysis. Interestingly, mRNA and surface expression of VLA-5 were found in SKW. a highly differentiated, IgM-secreting line. In addition, low levels of staining for VLA-5 expression could be demonstrated when tonsillar or peripheral blood B lymphocytes were stimulated by Staphylococcus aureus Cowan (SAC). All cell lines expressed VLA-3 and VLA-4. two other receptors reported to mediate fibronectin binding in some cell types. Thus, our studies provided no evidence for developmental or inflammatory regulation of these receptors. Binding studies, however, demonstrated that adherence of both pre-B REH cells and SKW cells to fibronectin was almost completely inhibited by a monoclonal antibody to VLA-5o. In addition, Raji cells, which lack VLA-5 but express VLA-3 and VLA-4. showed very low level binding to Hbronectin. This demonstrates that for some B lymphocytes VLA-5, rather than other possible fibronectin receptors, primarily mediates attachment to fibronectin. These data also suggest that human VLA-5 expression is regulated during B cell development, with expression at a very early stage and then again after activation. This pattern of loss and reacquisition of an ECM receptor may be relevant to normal B cell maturation and to function during immunologic injury.
Identification of a myeloperoxidase inhibitor from normal human serum
Authors: YEA C M , DULARAY B , ELSON C J 
Published: July 2010

SUMMARYAn inhibitor of myeloperoxidase (MPO) has been identified in normal human serum. Initial experiments confirmed that high levels of MPO inhibitory activity are present in sera and that the inhibitor did not act by interfering with the assay. Purification of the inhibitor activity by salt precipitation followed by ton exchange and affinity chromatography revealed the presence of a protein of 150 kD. The purified inhibitory activity displayed dose and lime dependency and was not associated with IgG or IgA. It is considered that human serum contains an inhibitor of extracellular MPO capable of protecting against hypohalous acid release in host tissues and that if inhibitor levels are reduced such protection may fail.
Cord blood contains cells secreting antibodies to nervous system components
Authors: FREDRIKSON S , SUN J , XIAO B-G , LINK H 
Published: July 2010

SUMMARYUmbilical cord blood of newborns and peripheral blood or healthy adults were investigated by an immunospot assay for cells secreting IgG, IgA and IgM antibodies against myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG) which represent putative antigens for an autoimmune attack in multiple sclerosis (MS) and against acetylcholine receptor (AChR) which is considered an important autoantigen in myasthenia gravis. Cells secreting antibodies against one or more of these autoantigens were detected in 18 out of 24 newborns, and in eight out of 20 adults. Eight of the cord blood samples contained cells secreting antibodies of IgG, IgA and/or IgM isotypes to one antigen, five to two antigens, two to three antigens, two to four antigens, and one to five antigens. Most prominent were anti-MBP IgG antibody secreting cells which were detected in 13 newborns at a mean number of 1/20000 cord blood cells, and in six adults at a mean number of l/105 peripheral blood cells. Anti-AChR IgG antibody secreting cells were detected in four out of 12 newborns versus four out of 14 peripheral blood specimens, at mean values of 1/105 cells in both instances. Cells secreting autoantibodies of IgA and IgM isotypes were less frequent both in cord blood and peripheral blood. The occurrence of nervous tissue autoantibody secreting cells in newborns must be related to a possible primary role of such autoantibodies in MS and myasthenia gravis.
Substance P-induced granulocyte infiltration in mouse skin: the mast cell-dependent granulocyte infiltration by the N-terminal peptide is enhanced by the activation of vascular endothelial cells by the C-terminal peptide
Authors: IWAMOTO I , TOMOE S , TOMIOKA H , YOSHIDA S 
Published: July 2010

SUMMARYPrevious studies have shown that substance P induces granulocyte infiltration in mouse skin, which is mediated through mast cell degranulation. However, it is not yet known whether the direct effect of substance P on vascular endothclial cells is involved in the granulocyte infiltration in the skin. To solve this issue, we used the N-terminal peptide substance P1–9 (SP1–9), which is active for mast cells but inactive for vascular endolhelial cells, and the c-terminal peptide SP6–11, which is active for vascular endothelial cells but inactive for mast cells, since substance P activates both mast cells and vascular endothelial cells. The subcutaneous administration of substance P (10−7−10−5 m) caused granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice 6 h after the injection. SP1–9 (10−5–10−4 m) also caused granulocyte infiltration of mouse skin which was associated with mast cell degranulation. In contrast. SP6–11 (10−7-10−4 M), which was found to increase the vascular permeability of endothelial cells in mouse skin, induced no significant granulocyte infiltration nor mast cell degranulation. However, SP6–11 (10−5 10−4 m) enhanced SP1–9 -induced granulocyte infiltration in the skin without any significant increase in mast cell degranulation. We conclude that substance P causes granulocyte infiltration in mouse skin through both mast cell degranulation induced by the N-lerminal peptide of substance P and the activation of vascular endothelial cells induced by the c-terminal peptide of substance P.