bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and molecular diversity among Erwinia isolates from potato in Algeria
Authors: Yahiaoui‐Zaidi R. , Jouan B. , Andrivon D.
Published: March 2003

The variability within a collection of 100 isolates of Erwinia collected from various potato cultivars and locations in Algeria was studied using physiological, biochemical and molecular tests. The comparison of their biochemical characteristics with those of the type isolates CFBP 1526 (E. carotovora ssp. atroseptica), CFBP 2046 (E. carotovora ssp. carotovora) and CFBP 2048 (E. chrysanthemi) indicated that all the isolates collected in Algeria belonged to the species E. carotovora. They included 40 typical E. carotovora ssp. carotovora and 14 E. carotovora ssp. atroseptica; the remaining 46 isolates could not be classified as E. carotovora ssp. atroseptica or ssp. carotovora, even though they were true Erwinia. Amplification of total genomic DNA with the primers Y1 and Y2, specific for E. carotovora, yielded an amplified fragment of the expected size in 99 isolates. The primers Y45 and Y46 specifically amplified a 439‐bp DNA fragment in all E. carotovora ssp. atroseptica isolates tested, but not in isolates of the other E. carotovora subspecies or in atypical isolates, as expected from the characteristics of these primers. The digestion patterns of the 99 amplified products with the restriction enzymes AluI, HaeII, HpaII and Sau3AI yielded 12 RFLP groups, three of which were undescribed. The 14 isolates of E. carotovora ssp. atroseptica shared a single restriction pattern (RFLP group 1), while the typical isolates of E. carotovora ssp. carotovora and the atypical isolates composed the remaining groups (3, 4, 8–10, 12, 14, 22 and 25–27), reflecting the heterogeneity among these isolates.
Antibody‐Dependent Cell‐Mediated Cytotoxicity to Gliadin‐Coated Cells with Sera from Children with Coeliac Disease
Authors: Saalman  , Wold  , Dahlgren  , Fällström  , Hanson  , Ahlstedt
Published: March 2003

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) has been suggested as a contributing immunological mechanism in the disease process of coeliac disease. In the present study, sera from coeliac children were examined for their capacity to mediate ADCC against gliadin‐coated target cells. The ADCC‐mediating efficacy of sera were tested using monocytes from healthy adults as effector cells and gliadin‐coated erythrocytes from the same donor as targets. Using monocytes as effector cells, sera from children with active coeliac disease (untreated or challenged), demonstrated significantly higher ADCC‐mediating capacity than sera from healthy and disease references as well as children with treated coeliac disease. A positive correlation was found between the ADCC‐mediating capacity and serum IgG as well as IgA anti‐gliadin antibody levels. The results suggest that an antibody‐dependent monocyte/macrophage‐induced cytotoxic reaction might be involved in the disease process of coeliac disease.
Induction of Human Leukaemic Mast Cell Differentiation by Fibroblast Supernatants, but not by Stem Cell Factor
Authors: Grabbe  , Welker  , Grützkau  , Dippel  , Nürnberg  , Zuberbier  , Henz
Published: March 2003

In order to explore the potential existence of human mast cell growth factors other than stem cell factor (SCF), we have compared SCF to L‐cell fibroblast supernatants (LCS) during in vitro mast cell differentiation, using human leukaemic mast cells (HMC‐1 cells) which contain a gain‐of‐function mutated SCF receptor (c‐Kit) as model. At baseline, cells exhibited an immature phenotype, with <25% being metachromatic or chloroacetate esterase, tryptase and FcεRIα positive. Intracellular levels of histamine, tryptase, TNF‐α and chymase were low, whereas 83% of cells were c‐Kit positive. During a 10 day culture with 30% LCS, a significant, time‐dependent increase of all mast cell markers, except for chymase and c‐Kit, was observed at the protein and for tryptase and FcεRIα also at the mRNA level. Cytoplasmatic granulation and stimulated histamine and leukotriene C4 release were increased as well. In contrast to LCS, rhSCF induced none of these changes in HMC‐1 cells. On Sephadex G100 fractionation of LCS, HMC‐1 cells increased tryptase activity with fractions between 40 and 60, and below 10 kDa, away from the SCF peak. These data show that HMC‐1 cells fail to differentiate in response to SCF and that in additon to SCF, LCS contains other human mast cell growth factors.
The Simulation of Density‐Dependent Effects in the Recirculation of T Lymphocytes
Authors: Stekel
Published: March 2003

T‐lymphocyte recirculation appears to be slower in nude or irradiated rats as compared with normal rats. A mathematical model of T‐lymphocyte recirculation that incorporates interactions between T cells and dendritic cells in the lymphoid tissue is presented. It is shown that these interactions are able to explain the differences in recirculation times between normal and nude or irradiated rats, and also the time‐scales seen in long‐term thoracic duct cannulations.
Effect of Anti‐Neutrophil Cytoplasmic Antibodies on Proteinase 3‐Induced Apoptosis of Human Endothelial Cells
Authors: Taekema‐Roelvink  , Van Kooten  , Janssens  , Heemskerk  , Daha
Published: March 2003

Wegener's granulomatosis is characterized by crescentic necrotizing glomerulonephritis and systemic vasculitis. Both proteinase 3 (PR3) and anti‐neutrophil cytoplasmic antibodies (ANCA), directed against this enzyme, are thought to play a pathogenic role. PR3 has been shown to cause detachment and cytolysis of human umbilical vein endothelial cells (HUVEC) in vitro and to induce apoptosis of bovine pulmonary artery endothelial cells. In the present study we investigated the effect of PR3 and ANCA on the induction of apoptosis of human endothelial cells in vitro. HUVEC were cultured in the absence or presence of varying concentrations of PR3 for different time periods and apoptosis was assessed by three different methods. Staining of the cells with Hoechst 33258 and assessment of nuclear morphology by ultraviolet (UV) light microscopy revealed a dose‐dependent induction of apoptosis, as determined by cell counts. A concentration of 8 μg/ml PR3 was found to induce 16% apoptosis after 16 h incubation. Analysis of apoptosis by flow cytometry using the terminal deoxynucleotidyl transferase‐mediated dUTP‐fluorescein nick‐end labelling (TUNEL) method also demonstrated a dose‐dependent induction of apoptosis by PR3. DNA fragmentation was confirmed by agarose gel electrophoresis. To investigate the effect of ANCA on PR3‐mediated apoptosis, HUVEC were exposed to immunoglobulin G (IgG) from patients with Wegener's granulomatosis or systemic vasculitis, and from normal controls, in the presence or absence of PR3. Enhancement of PR3‐mediated apoptosis was found in two of 10 IgG samples with anti‐PR3 activity, whereas a reduction in apoptosis was observed in two others. Anti‐MPO (myeloperoxidase)‐positive IgG, six additional anti‐PR3 positive IgG samples and control IgG samples did not have any detectable effect on apoptosis. These studies suggest that ANCA may modulate the relative degree of injury in some cases of Wegener's granulomatosis.
Characterization of CD40‐Dependent Immunoglobulin Class Switching
Authors: Ström  , Laurencikiené  , Miskiniené  , Severinson
Published: March 2003

Previous studies have shown that signalling via CD40 together with cytokines stimulates immunoglobulin (Ig) class switching in B cells. This process includes induction of germline (GL) transcripts and switch recombination. Using an agonistic rat anti‐mouse CD40 monoclonal antibody (MoAb), we investigated the role of CD40 signalling in these molecular events. We found that stimulation of murine B cells induced high steady‐state levels of germline γ1, γ2b and low levels of ε transcripts. No detectable γ2a or αRNA were found and the level of γ3 transcripts was high both in stimulated and unstimulated cells. Although cells treated with anti‐CD40 MoAb had high levels of GL γ1 and γ3 transcripts, we failed to detect switching to IgG1 or IgG3. However, anti‐CD40 MoAb‐stimulated cells increased expression of IgG2b. Interestingly, anti‐CD40 plus interleukin (IL)‐5 induced switching to IgG1. Previous work has demonstrated that CD40 signalling, but not lipopolysaccharide (LPS), induces the γ1 promoter and that NF‐κB motifs are important. We show here that both LPS and anti‐CD40 activated NF‐κB proteins binding to the γ1 promoter. The bound NF‐κB complexes were different with regard to total concentration and subunit composition. In the light of our data, the mechanism of CD40‐mediated Ig class switching is discussed.
The Genetics of Systemic Lupus Erythematosus
Authors: Lindqvist  , Alarcón‐Riquelme
Published: March 2003

There is considerable evidence that the development of systemic lupus erythematosus (SLE) has a strong genetic basis. For more than 20 years, much effort has been made to understand the genetics of SLE. Association studies in humans suggest the existence of genetic effects by the alleles encoded in the HLA, deficiencies in the complement genes and the low‐affinity variants of Fcγ‐receptors. In mouse models of SLE at least 13 loci have been identified, including the MHC, linked to lupus‐related phenotypes such as nephritis and production of autoantibodies. Recently, linkage studies have been performed in human SLE; one investigating a candidate region based on synteny to a murine susceptibility locus and four genome‐wide linkage studies in various populations. Linkage was demonstrated to several chromosomal regions, some of which are syntenic to murine lupus susceptibility loci. Interestingly, many of the identified chromosomal regions co‐localise with loci implicated in other autoimmune diseases.
Effects of Ageing on Generation of ED2high Major Histocompatibility Complex Class II+ Macrophages During Cold Stress
Authors: Kizaki  , Ookawara  , Haga  , Matsuura  , Ohno
Published: March 2003

The effects of cold stress (5 °C, 24 h) were investigated on the function and surface phenotype of peritoneal cells in the monocyte/macrophage lineage from young (8–10‐week‐old) and old (22–24‐month‐old) rats. The role of glucocorticoid (GC) in the immunomodulation by cold stress was also examined. The proportion of cells with a high density of ED2 (ED2high cells), expressing major histocompatibility complex (MHC) class II molecules, was significantly increased in peritoneal cells during cold stress in young, but not in old, rats. Antigen‐presenting function was significantly higher in ED2high cells than in cells with a low density of ED2 (ED2low cells), thereby indicating that ED2high cells are at a functionally high level. While serum corticosterone concentration in old rats increased markedly after 3 h of cold stress, that in young rats did not vary substantially, and was followed by a significant decrease in both groups of rats after 24 h of cold stress. Administration of dexamethasone to young rats completely inhibited the increase of ED2high cells caused by cold stress. Meanwhile, the proportion of ED2high cells in young rats was significantly increased by adrenalectomy. Furthermore, nuclear translocation of a large amount of the GC receptor was observed in ED2low cells. These results suggest that cold stress enhances immune function in young rats, but not in old rats, and that the generation of ED2high cells are partly regulated by circulating GC level.
High Resolution Electroelution of Polyacrylamide Gels for the Purification of Single Proteins from Mycobacterium tuberculosis Culture Filtrate
Authors: Weldingh  , Hansen  , Jacobsen  , Andersen
Published: March 2003

Culture filtrate from Mycobacterium tuberculosis contains protective molecules which have been used successfully in experimental vaccines against tuberculosis. Despite an increasing number of mycobacterial proteins being characterised, a major effort is still needed to get an overview of the many potentially interesting molecules in culture filtrate. In this study we describe a high throughput method for purification and biological evaluation of protein components in complex protein mixtures. The method presents a new application of the recently developed Mini Whole Gel Eluter and employs this apparatus for the high resolution electroelution of selected molecular mass fractions of protein mixtures previously separated in large polyacrylamide gels. Two novel M. tuberculosis culture filtrate proteins (CspA and TB18.6) were purified by this method, their N‐terminal sequences were determined and the open reading frame encoding each of the proteins identified. The immunological recognition of the molecules were evaluated in tuberculosis infected mice and guinea pigs. Both proteins induced DTH responses in guinea pigs and IFN‐γ release from spleen lymphocytes isolated from infected mice.
Acute Phase Serum Amyloid A Protein Increases High Density Lipoprotein Binding to Human Peripheral Blood Mononuclear Cells and an Endothelial Cell Line
Authors: Hayat  , Raynes
Published: March 2003

Serum Amyloid A (SAA) is an acute‐phase protein secreted mainly by hepatocytes and is largely associated with high‐density lipoprotein (HDL) in plasma. It has been suggested that SAA alters HDL binding to the cell surface and that this in turn changes HDL‐mediated cholesterol delivery to cells. Incorporation of SAA into HDL at concentrations equivalent to those found physiologically in moderate inflammation mediated a 1.5‐fold increase in the binding of HDL to adherent peripheral blood mononuclear cells but had no effect on binding of the lipoprotein to the monocyte cell lines, U937 or THP‐1. SAA incorporation also increased binding to an endotheial cell line, EA.hy.926. Hepatoma cells (HuH‐7) showed no change in specific binding of the SAA‐enriched HDL particle compared to normal HDL. These results suggest that a specific receptor for HDL‐bound SAA is found on differentiated human macrophages and an endothelial cell line, which may have functional significance in lipid metabolism or other macrophage responses during inflammation.
Naive Monocytes Can Trigger Transendothelial Migration of Peripheral Blood Cells Through the Induction of Endothelial Tumour Necrosis Factor‐α
Authors: Eissner  , Lindner  , Konur  , Kreutz  , Andreesen  , Holler
Published: March 2003

In this manuscript we describe a potentially new mechanism by which unstimulated human monocytes activate endothelial cells (EC) through the secondary induction of endothelial tumour necrosis factor alpha (TNF‐α). Serum free supernatants (SN) of peripheral blood mononuclear cells (PBMC) strongly induce the expression of intercellular adhesion molecule 1 (ICAM‐1, CD54), vascular cell adhesion molecule 1 (VCAM‐1, CD106), and endothelial–leukocyte adhesion molecule 1 (ELAM‐1, CD62E) on human EC 24 and 4 h post treatment, respectively. Further characterization of the responsible subpopulation revealed the CD14+ monocytes and a monocytic cell line (MM6) to produce an endothelial activating factor (EAF). The EAF also triggers an adhesion and a transendothelial migration (TEM) of peripheral blood cells. Using neutralization with an anti TNF‐α MoAb MAK195, EAF is not identical with TNF‐α, but induces the expression of endothelial TNF‐α, since MAK195 blocked TEM only when coincubated with EC, not with monocytes. Furthermore, intracellular TNF‐α was significantly upregulated in EC after treatment with SN‐MM6. Another evidence for a secondary autocrine mechanism was provided by culturing the EC with a conditioned medium of SN‐MM6 treated EC. This conditioned medium induces an adhesion molecule expression and TEM in a similar way to SN‐MM6 and can completely be inactivated by anti TNF‐α. Taken together, these data may have an impact for, e.g. transplantational settings that donor monocytes may trigger an inflammatory response in the absence of further activation signals by eliciting an endogenous TNF‐α response in the host.
β2‐Microglobulin/CD8 ‐/‐  Mice Reveal Significant Role for CD8+ T Cells in Graft Rejection Responses in β2‐Microglobulin ‐/‐ Mice
Authors: Freland  , Ljunggren
Published: March 2003

β2‐microglobulin (β2m) ‐/‐ mice have often been used as a model to investigate host resistance to grafted tissues in the absence of CD8+ T cells. However, the realization that β2m ‐/‐ mice have a small pool of CD8+ T cells imply that these cells may take part in immune responses in vivo. To directly address the role of CD8+ T cell responses in β2m ‐/‐ mice, we introduced a CD8 null mutation into these mice. The β2m/CD8 ‐/‐ mice and the corresponding control mice were primed, and challenged with syngeneic tumour grafts. While β2m ‐/‐ mice readily cleared such tumour grafts, similar tumour grafts grew progressively in a dose dependent manner in the β2m/CD8 ‐/‐ mice. The present results imply that residual CD8+ T cells in β2m ‐/‐ mice may carry out significant biological functions, and suggest that studies using β2m ‐/‐ mice as a model for CD8+ T cell deficiency must be regarded with some caution.
Binding of Murine Antibodies Against Whole‐Cell Pertussis Vaccine or Filamentous Haemagglutinin by Bordetella pertussis from Patients with Whooping Cough
Authors: Van Den Berg  , Beekhuizen  , Van Furth  , Mooi
Published: March 2003

In 1996 an unexpected rise in the incidence of whooping cough occurred in the Netherlands, and antigenic divergence between vaccine strains and clinical isolates has been suggested as a cause for this phenomenon. To investigate this assumption, the binding of murine antibodies against the whole‐cell pertussis vaccine or filamentous haemagglutinin, an important protective antigen, to a limited number of Bordetella pertussis strains isolated during different time‐periods (1991–92, 1994 and 1996) was assessed. The results showed that all strains were recognized equally well by these antisera, indicating that filamentous haemagglutinin was unchanged during the time‐periods examined. Although over the years changes have occurred in at least two surface proteins of B. pertussis, these changes are too subtle to be recognized by the antibodies raised in mice. Further research is required to assess whether antigenic variation of B. pertussis has an effect on protective immunity.
The Enhancing Role of Complement in Human Immunodeficiency Virus Infection: Soluble Recombinant CR1 (CD35) Inhibits Complement‐Mediated Enhancement of Infection of a CD4‐positive T‐Cell Line with Human Immunodeficiency Virus‐1
Authors: Delibrias  , Fischer  , Kazatchkine
Published: March 2003

The present study investigated the effect of soluble recombinant CR1 (srCR1, sCD35) on complement‐dependent enhancement of human immunodeficiency virus‐1 (HIV‐1) infection in vitro. Cells of the human T‐cell line HPB‐ALL were infected with HIV‐1 that had been preopsonized with normal human HIV‐seronegative serum in the presence of srCR1. At nanomolar concentrations, srCR1 suppressed complement‐dependent enhancement of infection of HPB‐ALL cells in a dose‐dependent manner. Under these conditions, infection was decreased to levels similar to those observed in cells infected with unopsonized virus. These observations provide further evidence to support the role of complement‐dependent opsonization facilitating viral entry into target cells.
Migration of Mononuclear Cells in the Modified Boyden Chamber as Evaluated by DNA Quantification and Flow Cytometry
Authors: Ellingsen  , Storgaard  , MøLler  , Buus  , Andersen  , Obel  , Stengaard‐Pedersen
Published: March 2003

In vitro migration of mononuclear cells in the modified Boyden chamber was evaluated using flow cytometry and DNA quantification (Hoechst 33258) of all adherent and nonadherent cells. The effects of different membrane pore sizes, cell concentrations and incubation times were studied. Pore sizes of 3 and 5 μm resulted in a reduction in the number of nonadherent cells compared with a pore size of 8 μm. Reducing the incubation time from 60 to 40 and 20 min resulted in too few migrating monocytes for analysis by flow cytometry. Flow cytometry showed that both monocytes and lymphocytes migrated and adhered to the membrane when using peripheral blood mononuclear cells (PBMC) to study monocyte migration. Migration of lymphocytes under these conditions is a novel observation. A substantial number of migrated cells could be identified by flow cytometry and quantified by DNA measurement as nonadherent below the membrane. Samples of synovial fluid (n = 49) and plasma (n = 133) as chemoattractants analysed in triplicate resulted in mean coefficient of variation (CV) values of 11 and 9%, respectively. Variation from assay to assay on the same day, using N‐formyl‐methionyl‐leucyl‐phenylanine (fMLP) 10−7 m as chemoattractant resulted in a CV of 13%. Day‐to‐day variation, using fMLP 10−7 m as chemoattractant and the same well on three different days, resulted in a CV of 21%. These results were obtained using a pore size of 5 μm, a PBMC concentration of 3 × 106/ml and 60 min of incubation. The combination of DNA quantification and flow cytometry thus allowed characterization and quantification of subsets of migrating adherent as well as nonadherent mononuclear cells.
Dissection of the Role of CD3γ Chains in Profound but Reversible T‐Cell Receptor Down‐regulation
Authors: Rubin  , Llobera  , Gouaillard  , Alcover  , Arnaud
Published: March 2003

T‐lymphocyte activity in the immune system is regulated by the quantity of surface membrane T‐cell antigen receptors (TCR). The amount of surface‐bound TCR is dependent on the rate of [ 1] biosynthesis, assembly and intracellular transport of the individual chains composing the TCR/CD3 complex and [ 2] the internalization and recycling of the receptors. The TCR–ligand interaction augments receptor internalization. In the present paper, we have studied short‐ and long‐term down‐regulation of TCR/CD3 complexes with monoclonal anti‐TCR/CD3 antibodies, and attempted to determine which component(s) of the TCR/CD3 complex are responsible for these two phenomena. Our data indicate that short‐ and long‐term down‐regulation is mediated by different mechanisms, and that the extracellular and/or transmembrane regions of CD3γ molecules appear to play an important role in chronic TCR/CD3 down‐regulation and subsequent deficient re‐expression. These results may have important implications for the understanding of induction of T‐cell tolerance or anergy.
Mechanisms of Neonatal Tolerance Induced in an Animal Model for Primary Sjögren's Syndrome by Intravenous Administration of Autoantigen
Authors: Saegusa  , Ishimaru  , Haneji  , Yanagi  , Yoneda  , Saito  , Hayashi
Published: March 2003

Neonatal exposure to autoantigen is believed to induce effective antigen‐specific T‐cell tolerance in experimental models of autoimmunity. We have identified 120 kDa α‐fodrin autoantigen in an animal model for primary Sjögren's syndrome (SS), that has been determined as a candidate autoantigen in both an animal model and the patients with primary SS. We demonstrate here that neonatal injection of autoantigen induce relevant tolerance when treated with intravenous (i.v.) administration within 24 h after birth, but not with i.v. injection after the thymectomy or with intraperitoneal injection. Autoantigen‐specific T‐cell response was significantly reduced in mice induced neonatal tolerance, and the activation markers of splenic CD4+ T cells were down‐regulated in mice treated with neonatal administration. Because we detected that neonatal i.v. injection of autoantigen prevented Th1 response, it is possible that the autoantigen administration within 24 h after birth induce regulatory T cells that had a protective effect against Th1‐mediated autoimmune diseases. These results indicate that the prevention of the spontaneous anti‐120 kDa α‐fodrin response in vivo, by tolerization of the autoantigen‐reactive T cells, blocked the development of autoimmune lesions in an animal model for primary SS.
Polymeric IgA Binding to the Human pIgR Elicits Intracellular Signalling, but Fails to Stimulate pIgR‐Transcytosis
Authors: Giffroy D. , Courtoy P.‐J. , Vaerman J.‐P.
Published: March 2003

The intracellular pathway of polymeric immunoglobulin receptor (pIgR) is governed by multiple signals that lead to constitutive transcytosis. In addition, in transfected polarized MDCK cells, polymeric immunoglobulin A (pIgA) binding stimulates rabbit pIgR‐transcytosis, owing to phospholipase‐Cγ1 activation and increase of intracellular calcium. Transcytosis of rat pIgR across hepatocytes is similarly accelerated by pIgA injection. In contrast we show here that human Madrin‐Darby Canine Kidney (pIgR)‐transcytosis, in human Calu‐3 and human pIgR‐transfected MDCK cells, is not promoted by pIgA, as monitored by a continuous apical release of its secreted ectodomain. However, the incubation of cells expressing human or rabbit pIgR with pIgA induces a comparable IP3 production, and pIgR‐transcytosis of either species is accelerated by the protein kinase C (PKC)‐activator phorbol myristate acetate. Without pIgA, mimicking phospholipase‐C activation by combining low concentrations of phorbol myristate acetate with ionomycin, or high concentrations of ionomycin alone, stimulates the rabbit, but not the human, pIgR transcytosis. These data suggest that the species difference in pIgA‐induced pIgR‐transcytosis does not stem from the defective production of second messengers, but from a different sensitivity of pIgR to intracellular calcium. Our results outline the danger of extrapolating to humans the abundant data obtained from mucosal vaccination of laboratory animals.
Role of CD8+ Cell‐Produced Anti‐Viral Factors in Protective Immunity in HIV‐2‐Exposed but Seronegative Macaques Resistant to Intrarectal SIVsm Challenge
Authors: Ahmed R. K. S. , Nilsson C. , Biberfeld G. , Thorstensson R.
Published: March 2003

The cell‐mediated immune response is likely to be important in controlling HIV/SIV infection. There is evidence that β‐chemokines and other, as yet unknown, anti‐viral factors play a role in host defence against HIV infection. We reported previously that HIV‐2 exposed but seronegative cynomolgus macaques developed SIV‐specific cytotoxic T lymphocytes and were resistant to mucosal SIV challenge. The aim of this study was to examine CD8+ cell‐dependent production of β‐chemokines and other anti‐viral factors in these macaques. The animals, selected from among 17 monkeys enrolled in two separate experiments, were either treated with an anti‐viral drug or immunized passively with HIV‐2 antibody‐positive serum. Three of these monkeys were protected against repeated HIV‐2 challenge and were also able to control SIV infection 3 years later. Control samples were obtained from four macaques that became SIV infected and from 39 naïve animals. The three resistant monkeys showed significantly higher production of RANTES and MIP‐1α than the 39 naïve animals. In addition, SIV infection was suppressed by CD8+ cell culture supernatants of these monkeys. However, antibodies to chemokines only partially neutralized CD8+ cell‐mediated SIV suppression indicating that the anti‐viral activity observed in these monkeys was the result of combined action of several inhibitory factors.
Effects of Subcutaneous IL‐2 Therapy on Telomere Lengths in PBMC in HIV‐Infected Patients
Authors: Aladdin H. , Larsen C. S. , Schjerling P. , Møller B. K. , Buhl M. R. , Gerstoft J , Pedersen B. K. , Ullum H.
Published: March 2003

In this study we investigated the effect of interleukin‐2 (IL‐2) on mean terminal restriction fragment (TRF) lengths in peripheral blood mononuclear cells (PBMC). Ten human immunodeficiency virus (HIV)‐infected individuals were included and IL‐2 was administered subcutaneously with 3 × 106 IU three times a week for 24 weeks. Mean TRF length was decreased on average by 267 bp at week 4 (P = 0.03) and 286 bp at week 8 (P = 0.09). Individual TRF changes at weeks 12, 16, 20 and 24 were highly variable. However, in the 12 weeks following therapy, TRF lengths generally increased reaching baseline levels by the end of the study. At baseline, mean TRF lengths were positively correlated to the ratio of naïve and memory phenotype within both CD4+ and CD8+ cells. This study shows that IL‐2 treatment induces transient shortened mean TRF lengths in PBMC from HIV‐infected individuals, indicating that IL‐2 enhances the lymphocyte count by peripheral proliferation or recruitment of memory T cells into the blood.
Disturbances in the Peripheral T‐Cell Repertoire of Patients with Motor Neuron Disease: High Levels of Activation and Indirect Evidence of Superantigen
Authors: Katchar K. , Osorio L. , Conradi S. , Wigzell H. , Gigliotti D.
Published: March 2003

Our data on peripheral blood T cells from Motor neuron disease (MND) patients indicate major immunological disturbances linked to this disease. Both CD4+ and CD8+ T‐cell subsets display an increased fraction of cells showing activation markers compared to controls, indicating an unusually high level of activity in both populations. Likewise, an increased number of T‐cell expansions were noted in MND patients compared to controls, most dramatically observed in the CD4+ T‐cell subset, where 5/144 T‐cell V genes analyzed in eight subjects turned out to be expanded in the peripheral blood. In the CD8+ T‐cell subset, four out of eight MND patients had peripheral BV gene expansions, 9/144 V genes analyzed. However, the most interesting result was the observation that in three out eight MND patients, expansions concerning the same BV gene were present in both CD4+ and CD8+ subsets (BV8S1 in two and BV12S1 in one patient). Parallel expansions of BV‐gene restricted populations in both CD4+ and CD8+ subsets in the same individual, in an major histocompatibility complex (MHC)‐unrestricted manner, are normally limited to situations where superantigens are involved. No known superantigen has to date been described with the capacity to simultaneously stimulate both BV8S1 and BV12S1, suggesting that the postulated ‘MND‐associated’ superantigen is a hitherto undefined molecule.
Nasal Administration of Schistosoma mansoni Egg Antigen‐Cholera B Subunit Conjugate Suppresses Hepatic Granuloma Formation and Reduces Mortality in S. mansoni‐Infected Mice
Authors: Sun J.‐B. , Stadecker M. J. , Mielcarek N. , Lakew M. , Li B.‐L. , Hernandez H. J. , Czerkinsky C. , Holmgren J.
Published: March 2003

Granulomatous inflammation in schistosomiasis is a delayed‐type hypersensitivity reaction mediated by CD4+ T cells specific for parasite egg antigens (Ags). In an attempt to control T‐cell responses leading to excessive harmful inflammation and granuloma formation, especially in the liver, BALB/c mice were intranasally (i.n.) treated with soluble Schistosoma mansoni egg Ags (SEA) conjugated to cholera toxin B subunit (CTB), a mucosa‐binding protein with demonstrated capacity to suppress inflammatory T‐cell functions after mucosal administration. Treatment with CTB–SEA significantly conjugate a reduced liver granuloma formation in infected mice associated with decreased SEA specific Th1‐ and Th2‐type immune responses by liver leukocytes. Importantly, treatment with CTB–SEA conjugate also significantly reduced the mortality in chronically infected mice. In S. mansoni‐infected large‐granuloma forming CBA mice, i.n. treatment with purified Sm‐p40, the major egg antigen, conjugated to CTB likewise significantly inhibited hepatic egg granuloma formation. A reduction of SEA‐driven lymphoproliferation and of interferon (IFN)‐γ, interleukin (IL)‐4 and IL‐5 production, together with an increase in transforming growth factor (TGF)‐β1 production, were observed in splenic cells from CTB‐Sm‐p40‐treated SEA‐sensitized mice, as well as in liver leukocytes from CTB‐Sm‐p40‐treated schistosome‐infected mice. These results indicate that mucosal administration of SEA or purified Sm‐p40 antigen in conjunction with CTB is highly effective in curtailing immunopathologic manifestations of schistosomiasis in vivo in infected hosts.
Analysis of the Immune Status in Latvian Chernobyl Clean‐up Workers with Nononcological Thyroid Diseases
Authors: Kurjane N. , Bruvere R. , Shitova O. , Romanova T. , Jaunalksne I. , Kirschfink M. , Sochnevs A.
Published: March 2003

The aim of the present work was to characterize the immune status of 385 individuals who participated in the 1986–90 clean‐up work of the after effects of the Chernobyl nuclear power plant explosion. Fifty‐nine Chernobyl clean‐up workers developed the most common thyroid diseases; euthyroid nodular and diffuse goiter; 47 healthy blood donors were taken as controls. The levels of immunoglobulins (IgA, IgG and IgM), the numbers of peripheral blood leukocytes, lymphocytes, monocytes, T lymphocytes and their subpopulations (CD3+, CD4+, CD8+), B lymphocytes (CD19+), natural killer (NK) cells (CD16+), classical and alternative pathway activity of complement (CH50, APH50), the C3 split product C3d, and neutrophil phagocytosis were determined in the peripheral blood. We found a significantly decreased number of CD16+ cells (natural killer), of CD4+ and CD8+ T lymphocytes, a reduced neutrophil phagocytic activity as well as a significant complement activation in Chernobyl clean‐up workers with and without thyroid diseases when compared with normal levels and those in the control group. In addition, the number of CD3+ and CD4+ cells was significantly higher in patients with nodular goiter when compared with that in patients with diffuse goiter. Levels of IgG and numbers of monocytes were significantly decreased in persons who worked in Chernobyl in 1986 during the first 2 months after the accident (with maximal radiation exposure) but were without correlation to thyroid disorders. Our results clearly reflect an impaired immune system in the Chernobyl clean‐up workers even 10–14 years after the nuclear accident.
Retracted: Enhanced Inhibition of Tumour Growth and Metastasis, and Induction of Antitumour Immunity by IL‐2‐IgG2b Fusion Protein
Authors: Budagian V. , Nanni P. , Lollini P. L. , Musiani P. , Carlo E. DI , Bulanova E. , Paus R. , Bulfone‐Paus S.
Published: March 2003

Budagian V, Nanni P, Lollini PL, Musiani P, Di Carlo E, Bulanova E, Paus R, Bulfone‐Paus S. Enhanced Inhibition of Tumour Growth and Metastasis, and Induction of Antitumour Immunity by IL‐2‐IgG2b Fusion Protein. Scand J Immunol 2002;55:484–492

Cytokine‐immunoglobulin (Ig)‐fusion proteins have attracted increasing interest as antitumour agents. Here, we have investigated the antimetastatic and antitumour responses elicited in vivo by mammary adenocarcinoma cells (TS/A) engineered to secrete interleukin (IL)‐2‐IgG fusion proteins. TS/A cells were transfected with DNA coding for IL‐2‐IgG2b, IgG2b or IL‐2, and injected subcutaneously into syngeneic mice. Animals injected with TS/A‐IL‐2 or TS/A‐IL‐2‐IgG2b both efficiently rejected tumours, whereas treatment with parental cells or TS/A‐IgG2b was lethal. Interestingly, only mice vaccinated with IL‐2‐IgG2b fusion protein‐secreting cells showed a long‐lasting protective immunity against a later challenge with parental tumour cells. Moreover, the metastatic potential of TS/A‐IL‐2‐IgG2b‐transfected cells was dramatically decreased compared with TS/A‐IL‐2‐cells, with a virtual absence of lung metastases after intravenous injection. Adenocarcinomas secreting IL‐2‐IgG2b exhibited a more prominent, early and persistent infiltration of CD4+, CD8+ and natural killer (NK) cells than TS/A‐IL‐2 cells. Therefore, upon transfection into adenocarcinoma cells, the IgG2b part of IL‐2 fusion protein exerts intriguing added antitumour properties over IL‐2 alone, thus contributing to a long‐lasting tumour immunity, probably by the recruitment of specific immune effector cells. These findings suggest a promising new oncotherapeutic strategy for poorly immunogenic tumours: vaccination with tumour cells engineered to secrete IL‐2‐IgG2b fusion protein.
Mucosal Immunity Induced by Intramuscular Administration of Free Peptides In‐Line with PADRE: IgA Antibodies to the ELDKWA Epitope of HIV gp41
Authors: Decroix N. , Quan C. P. , Pamonsinlapatham P. , Bouvet J.‐P.
Published: March 2003

To improve the mucosal antibody response against a short amino acid (aa) sequence (ELDKWA) of HIV gp41, we have investigated a construction including this peptide in‐line with the Pan DR epitope (PADRE). ELDKWA is a conserved peptide playing a key role in the pathogenicity of HIV transmission. PADRE is a non‐natural peptide with multipotential immunogenic properties. The results show striking differences between mucosal and systemic immune systems, with a preferential response of the mucosal organs. In contrast with most mucosal immunizations, the intracellular response persists for over two months after the last injection. This strongly suggests that further investigations of conserved key epitopes from various pathogens may lead to safe and chemically defined mucosal vaccines with synthetic peptides. These candidate vaccines with free peptides may be suitable for mass campaigns even in developing countries.
Late Dinantian palaeokarst of England and Wales: implications for exposure surface development
Authors: Vanstone Simon D.
Published: March 2003

Palaeokarst is an important feature of late Dinantian exposure surfaces. Soil‐filled depressions are widely developed. These are comparable to modern day solution dolines and were probably interspersed by areas of relatively bare limestone pavement. The palaeokarst primarily exhibits a smooth, mamillated to potholed surface form, consistent with its formation beneath a soil cover. Areas between the depressions have been extensively stylolitised and would likely have originally been characterized by small‐scale fretted and sculpted karren forms typical of subaerial karstification. Palaeokarst pits making up the depressions are thought to have been initiated through stem‐flow drainage from trees. Rain water, intercepted by the crown of the tree, was concentrated at specific sites on the emergent surface and dissolution beneath the trunk produced cylindrical pits that propagated vertically downwards. Trees responsible for concentrating drainage may also have enhanced the acidic nature of the rain water through leaching of organic acids from foliar and woody tissues. Downward propagation of the pits was limited to the uppermost 1–2 m and enlargement primarily occurred through lateral amalgamation of adjacent pits. Once initiated, continued development of the depressions would have been self perpetuating; the preferential accumulation of volcanic ash and organic matter enhancing water retention and encouraging further vegetation growth. In contrast, intervening areas would have been characterized by slow vertical denudation only. Karstification likely took of the order of a few hundred years in the case of potholed palaeokarstic surfaces formed solely by stem‐flow drainage, to a few tens of thousands of years where the palaeokarst is more mature.
Diagenetic origin of Basal Anhydrite in the Cretaceous Maha Sarakham salt: Khorat Plateau, NE Thailand
Authors: Tabakh Mohamed El , Schreiber B. Charlotte , Utha‐Aroon Cherdsak , Coshell Lee , Warren John K.
Published: March 2003

Development of a diagenetic anhydrite bed at the base of the Cretaceous Maha Sarakham Saline Formation (the `Basal Anhydrite' member) of the Khorat Plateau in north‐eastern Thailand took place due to leaching and/or pressure dissolution of salt at the contact between an underlying active sandstone aquifer system and an overlying massive halite‐dominated evaporite sequence. Basal evaporites composed of halite with intercalated anhydrite of the latter sequence are undergoing dissolution as a result of subsurface flushing, with anhydrite produced as the insoluble residue. The result is a 1·1 m thick interval of nodular anhydrite displaying unique, basin‐wide continuity. Observed textures, petrographic features and chemical data from the anhydrite and associated authigenic minerals support the origin of the Basal Anhydrite Member as an accumulation residue from the dissolution of the Maha Sarakham salts. Petrographically, the anhydrite in this unit is made up of crystals that are blocky and recrystallized, sheared, generally elongated and broken, and is bounded at the bottom by organic‐rich stylolite surfaces. Authigenic and euhedral dolomite and calcite crystals are associated with the anhydrite. Traces of pyrite, galena and chalcopyrite are present along the stylolite surfaces suggesting supply of fresh water from the underlying sandstone at highly reducing conditions of burial. The δ34S of sulphate in the Basal Anhydrite averages 15 ‰ (CDT) and falls within the isotopic composition of the anhydrite in the Cretaceous Maha Sarakham Formation proper and the Cretaceous values of marine evaporites. Measured δ18O in dolomite range from −4·37 to −14·26‰ (PDB) suggesting a re‐equilibration of dolomite with basinal water depleted in 18O and possible recrystallization of dolomite under relatively elevated temperatures. The δ13C, however, varies from +1·57 to −2·53‰ (PDB) suggesting a contribution of carbon from oxidation of organic matter. This basal anhydrite bed, similar to basinwide beds found at the bottom of many giant evaporite sequences, has always been considered to be depositional. Here, at the base of the Maha Sarakham Formation, we demonstrate that the anhydrite is diagenetic in origin and was formed by accumulation of original anhydrite by dissolution of interbedded halite from waters circulating though the underlying aquifer: it represents an `upside‐down' caprock.
Deep‐sea volcaniclastic sedimentary systems: an example from La Fournaise volcano, Réunion Island, Indian Ocean
Authors: Ollier  , Cochonat  , Lénat  , Labazuy
Published: March 2003

A volcaniclastic sedimentary fan extending to water depths of 4000 m is characterized using gravity cores, camera surveys, high‐resolution sonar images, seismic records and bathymetry from the submarine portion of La Fournaise volcano, Réunion Island, a basaltic shield volcano in the SW Indian Ocean.

Three main areas are identified from the study: (1) the proximal fan extending from 500 m water depth down to 2000 m water depth; (2) the outer fan extending from 2000 m water depth down to 3600 m water depth; (3) the basin extending beyond 3600 m water depth. Within these three main areas, seven distinct submarine environments are defined: the proximal fan is characterized by volcanic basement outcrops, sedimentary slides, deep‐water deltas, debris‐avalanche deposits, and eroded floor in the valley outlets; the outer fan is characterized by a discontinuous fine‐grained sedimentary cover overlying coarse‐grained turbidites or undifferentiated volcanic basement; the basin is characterized by hemipelagic muds and fine‐grained turbidites interbedded with sandy and gravelly turbidite lobes.

The evolution of the deep‐sea volcaniclastic fan is strongly influenced by sector collapses, such as the one which occurred 0·0042 Ma ago. This collapse produced a minimum of 6 km3 of debris‐avalanche deposit in the proximal area. The feeding regime of the deep‐sea fan is ‘alluvial dominated’ before the occurrence of any sector collapse and ‘lava‐dominated’ after the occurrence of a sector collapse.

The main deep‐water lava‐fed delta is prograding among the blocks of the debris‐avalanche deposits as a result of turbidity flows occurring on the delta slope. These turbidity flows are triggered routinely by wave‐action, earthquakes and accumulation of new volcanic debris on top of the deltas.

Both turbidity currents triggered on the deep‐water delta slope, and those triggered by debris avalanche reworked volcaniclastic material as far as 100 km from the shore line.
Rapid development of gravelly high‐density turbidity currents in marine Gilbert‐type fan deltas, Loreto Basin, Baja California Sur, Mexico
Authors: Falk Peter D. , Dorsey Rebecca J.
Published: March 2003

The Pliocene Loreto basin is an asymmetrical half graben located on the eastern margin of Baja California Sur, Mexico, which formed by rapid subsidence along the dextral‐normal Loreto fault. The southern Loreto basin contains numerous, well exposed coarse‐grained Gilbert‐type fan deltas that were derived from the footwall of the Loreto fault. Detailed sedimentological study of individual foreset beds provides information about down‐slope flow transformations of cohesionless sediment gravity flows in shallow water. Deposits of Gilbert‐delta foresets consist of ungraded, normal‐graded, inverse‐ to normal‐graded, and bipartite conglomerate and sandstone. Lateral transitions in sorting, grading style and internal structure are commonly observed within individual beds, both across and down slope, suggesting heterogeneity within flows and a close relationship between high‐density turbidity currents and gravel traction carpets. A conceptual model for flow transformation and deposition of high‐density turbidity currents on Gilbert‐delta foreset slopes is developed for Pliocene strata in the Loreto basin. In this model, ungraded cohesionless debris flows evolved rapidly down‐slope into normal‐graded gravelly turbidity currents. With continued down‐slope transport, the gravel fraction collapses and becomes concentrated into a basal traction carpet undergoing laminar shear, and is over‐ridden by a sandy turbulent suspension. The short distances (10–20 m) over which lateral transitions within single beds are observed indicate very rapid flow transformations (10–20 s) and rapid deposition of gravel traction carpets by frictional freezing on and near the base of the foreset slope.
The sequence of events around the epicentre of the 1929 Grand Banks earthquake: initiation of debris flows and turbidity current inferred from sidescan sonar
Authors: Piper David J. W. , Cochonat Pierre , Morrison Martin L.
Published: March 2003

Continental slope sediment failures around the epicentre of the 1929 ‘Grand Banks’ earthquake have been imaged with the SAR (Système Acoustique Remorqué) high‐resolution, deep‐towed sidescan sonar and sub‐bottom profiler. The data are augmented by seismic reflection profiles, cores and observations from submersibles. Failure occurs only in water depths greater than about 650 m. Rotational, retrogressive slumps, on a variety of scales, appear to have been initiated on local steep areas of seabed above shallow (5–25 m) regional shear planes covering a large area of the failure zone. The slumps pass downslope into debris flows, which include blocky lemniscate bodies and intervening channels. Clear evidence of current erosion is found only in steep‐sided valleys: we infer that debris flows passed through hydraulic jumps on these steep slopes and were transformed into turbidity currents which then evolved ignitively. Delayed retrogressive failure and transformation of debris flows into turbidity currents through hydraulic jumps provide a mechanism to produce a turbidity current with sustained flow over many hours.