bluuebunny/crossref_metadata_2025 huggingface dataset:
Staphylococcus aureus Cowan Strain 1 Activation of B‐Chronic Lymphocytic Leukaemia Cells Augments the Response to CD40 Stimulation
Authors: Söderberg  , Thunberg  , Weigelt  , Christiansen  , Tötterman  , Carlsson  , Sällström  , Nilsson
Published: March 2003

The signals involved in regulating the proliferation, differentiation and survival of B‐chronic lymphocytic leukemia (B‐CLL) cells are fully understood. B‐CLL cells have been found to respond poorly to various activation signals and only after successful Epstein–Barr virus (EBV) transformation has it been possible to maintain such cells in long‐term cultures. In this work we describe a new method to activate and induce proliferation in B‐CLL cells and to maintain such cells in long‐term culture for longer than 1 month. We used a combination of protocols in an attempt to mimic some of the signals of a thymus‐dependent immune response. The B‐CLL cells were first activated with Staphylococcus aureus Cowan strain 1 (SAC) particles plus thioredoxin (Trx), followed by stimulation with interleukin (IL)‐2 + Trx. This treatment primed the cells for further stimulation with anti‐CD40 monoclonal antibody (MoAb) presented on irradiated CD32L cells (the CD40‐system) or soluble CD40 Ligand, and a combination of Trx and cytokines (IL‐4 + IL‐10), which allowed the cells to be maintained for up to 1 month with preserved viability and a variable rate of proliferation. However, induced proliferation of the B‐CLL cells was limited to ≈ 1 month, suggesting that additional signals are required to facilitate further proliferation.
B‐Cell Depletion Fails to Abrogate the Induction of Oral Tolerance of Specific Th1 Immune Responses in Mice
Authors: Peng  , Chang  , Lee  , Kuo
Published: March 2003

Antigen presentation by resting B cells has been shown to induce peripheral tolerance to intravenous (i.v.) administered soluble protein antigens. We further examined the role of resting B cells in the induction of oral tolerance. Mice were treated continuously from birth with rabbit antimouse IgM serum for 5 weeks. Immunohistological studies revealed that anti‐IgM treatment depleted B cell‐aggregated follicles in intestinal Peyer's patches. At 4‐weeks‐old, B cell‐depleted mice were fed 25 mg ovalbumin or given 10% chicken egg white to drink for 5 days. Anti‐IgM treatment was stopped 2 days after the last feed. Ten weeks later, the mice were immunized with 100 μg ovalbumin emulsified with complete Frund's adjuvant. Their T helper 1 (Th1) cell‐regulated systemic delayed‐type hypersensitivity, IgG2a antibody responses and spleen cell production of interferon‐r and interleukin‐2 were suppressed by prior ovalbumin or egg white feeding during anti‐IgM treatment. Active suppression of Th1 immune responses was also demonstrated following adoptive transfer of egg white‐fed donor spleen cells collected during anti‐IgM treatment to naïve recipients. Although enormous small resting B cells are aggregated in the mantle zones of follicles of intestinal Peyer's patches, they are not the antigen‐presenting cells seen in the induction of oral tolerance.
Splenectomy and Adoptive Cell Transfer Reveal a Prominent Role for Splenic Memory Lymphocytes in the Development of Chronic Relapsing Experimental Autoimmune Encephalomyelitis
Authors: Yang J. , Kubera M. , Zelek‐Molik A. , Nalepa I. , Hukkanen V. , Lindsberg P. J. , Meri S. , Seljelid R.
Published: March 2003

We previously reported that acute experimental autoimmune encephalomyelitis (EAE), induced by active immunization of SJL mice, could be converted into chronic relapsing EAE (CR‐EAE) by a pretreatment with neuroantigen and killed mycobacteria 2 months earlier. This finding indicates that immune memory, established by the pretreatment, influences the subsequent EAE induction. The present study shows that splenectomy and lymphadenectomy, applied 1 week before the subsequent active immunization of the pretreated mice, efficiently abort the chronic nature of CR‐EAE. Furthermore, we have found that adoptive transfer of lymphocytes from the spleen (but not of those from the local draining lymph nodes) of the pretreated mice to naive syngeneic recipients 1 week before the acute EAE‐induction immunization results in the development of CR‐EAE. On the other hand, the transfer of lymphocytes from the local draining lymph nodes aggravates the acute disease. These data support a critical role for immune memory of the previous suboptimal challenge in the development of chronic relapsing demyelinating disease.
Distinct Tumour Specificity and IL‐7 Requirements of CD56−and CD56+ Subsets of Human γδ T Cells
Authors: Zheng B. , Lam C. , Im S. , Huang J. , Luk W. , Lau S. Y. , Yau K. S. , Wong C. K. , Yao K. , Ng M. H.
Published: March 2003

γδ T cells are believed to recognize tissue injury caused by infections, tumours, as well as chemical and physical agents. The present study was carried out to study the feasibility of the ex vivo expansion of γδ T cells from healthy individuals, and to determine their functional capacity against tumours. We selectively expanded the peripheral γδ T cells of five donors against a myeloma cell line, XG‐7. Under optimal conditions, the resulting bulk cultures comprised about 82% of the γδ T cells, more than 90% of which showed the T‐cell receptor (TCR)‐Vγ9δ2 rearrangement. These γδ T‐cell cultures exhibited TCR‐γδ dependent cytotoxicity against different tumour cell lines including Molt‐4, BJAB, Epstein–Barr virus (EBV) transformed lymphoid cell lines (LCL), and the nasopharyngeal carcinoma (NPC) cell lines, CNE2 and 915, in addition to the stimulator XG‐7. By competitive cytotoxicity assays, the γδ T cells demonstrated recognition of at least three distinct target specificities expressed by Molt‐4, CNE2 and LCL, respectively, which were related to that expressed by the stimulator XG‐7 cells. The recognition of the specificity expressed by XG‐7 and Molt‐4 was further shown to require the participation of heat shock protein (HSP). The specificity expressed by CNE2 and 915 was preferentially recognized by the CD56 subset of γδ T cells, which could be sustained in the presence of interleukin (IL)‐7. These results suggested that γδ T‐cell immunity against tumour cell lines may be acquired in response to other types of tissue injury and, hence, implicates a role for their use in the prevention and treatment of tumours.
Alteration in CD29high CD4+ Lymphocyte Subset is a Common Feature of Early HIV Disease and of Active Tuberculosis
Authors: Diagbouga S. , Chiron J.‐P. , Sanou O. , Ledru E.
Published: March 2003

Peripheral CD4 T‐cell depletion has been observed in human immunodeficiency virus (HIV)‐negative patients with pulmonary tuberculosis (TB). To investigate more accurately this alteration, we studied peripheral blood CD45RA+ and CD29high CD4 subsets in 79 TB patients with (HIV+TB+) or without (HIV−TB+) HIV infection, 85 HIV‐infected patients without TB (HIV+TB−), and 43 healthy controls, all living in West Africa. The high proportion of CD4+CD29high T cells observed in controls was dramatically decreased in CDC‐A stage HIV+TB− patients. CD45RA+ CD4+ T cells were depleted during the CDC‐B stage. Both the percentage and the absolute count of CD29highCD4+ T cells were decreased in HIV−TB+ and HIV+TB+ patients versus controls, but CD45RA+CD4+ T cells were not decreased in TB patients without HIV‐infection. Although distinct alterations in the CD4+ T‐cell homeostasis are involved in TB‐ versus HIV‐infected subjects, our data suggest that the CD29+CD4+ T‐cell depletion observed during the early HIV disease contributes to the risk of active TB, by reducing the pool of T cells able to relocalize to the sites of the M. tuberculosis multiplication.
Mercury Inhibition of Neutrophil Activity: Evidence of Aberrant Cellular Signalling and Incoherent Cellular Metabolism
Authors: Worth R. G. , Esper R. M. , Warra N. S. , Kindzelskii A. L. , Rosenspire A. J. , Todd R. F. , Petty H. R.
Published: March 2003

Exposure to environmental heavy metals has been reported to affect the immune system. Here, we tested the hypothesis that Hg+2, acting through membrane proteins, disrupts metabolic dynamics and downstream cell functions in human neutrophils. We found that HgCl2 inhibited: (1) polarization and (2) immunoglobulin (Ig)G‐mediated phagocytosis of sheep erythrocytes in a dose‐dependent manner from 2.5 to 10 µm. Because these activities have been linked with pro‐inflammatory signalling, we also studied the effects of HgCl2 on intracellular signalling by measuring protein tyrosine phosphorylation. HgCl2 at doses = 1 µm increased tyrosine phosphorylation. We also studied the effect of HgCl2 on neutrophil metabolism by measuring NAD(P)H autofluorescence as an indicator of intracellular NAD(P)H concentration. After HgCl2 treatment, we found that normal sinusoidal NAD(P)H oscillations became incoherent. We recently reported that the NAD(P)H oscillation frequency is affected by cell migration and activation, which can in turn be regulated by integrin‐mediated signalling. Therefore, we examined the effects of HgCl2 on cell surface distribution of membrane proteins. After exposure to environmentally relevant concentrations of HgCl2 we found that CR3, but not other membrane proteins (e.g. uPAR, FcγRIIA and the formyl peptide receptor), became clustered on cell surfaces. We suggest that HgCl2 disrupts integrin signalling/functional pathways in neutrophils.
Novel Monoclonal Antibodies against Major Antigens of Mycobacterium bovis
Authors: Lyashchenko K. P. , Wiker H. G. , Harboe M. , Mcnair J. , Komissarenko S. V. , Pollock J. M.
Published: March 2003

MPB70 and MPB83 are among the most characteristically exported proteins defining a strongly expressed phenotype of Mycobacterium bovis. These proteins are known to be homologous to osteoblast‐specific factor 2. By in vitro culture of mycobacteria they appear to have a limited species distribution and to be relatively specific for M. bovis. Virtually identical genes are however, present in Mycobacterium tuberculosis. In order to facilitate further research into the immunobiology of these proteins and their potential application for differential diagnosis of tuberculosis as a result of M. bovis, we describe the reactivities of 20 monoclonal antibodies (MoAbs) to these proteins. Immunizing with bovine PPD generated 10 MoAbs. These antibodies reacted preferentially with the soluble MPB70 antigen using reducing conditions in SDS‐PAGE with western blotting. Ten MoAbs were generated by immunizing mice with fractions derived from a whole cell sonic extract of M. bovis. These antibodies reacted preferentially with the surface exposed MPB83 lipoglycoprotein.
IL‐12: Keeping Cell‐Mediated Immunity Alive
Authors: Park A. Y. , Scott P.
Published: March 2003

Interleukin (IL)‐12 has dominated the field of cell‐mediated immunity since its discovery more than 10 years ago, and clearly plays an essential role in the development of Th1 cells under a variety of conditions. Recent studies now indicate that the importance of IL‐12 is not limited to initiating an immune response, but may contribute to maintaining immunity. Thus, Th1 responses rapidly wane in the absence of IL‐12, leading to a loss in protective immunity against intracellular pathogens, such as Leishmania and Toxoplasma. Determining how IL‐12 maintains Th1 cells, and consequently cell‐mediated immunity, will provide new insights useful in controlling the immune response, and may thus influence the design of new vaccines and immunotherapies.
On the Role of CD3δ Chains in TCRγδ/CD3 Complexes during Assembly and Membrane Expression
Authors: Alibaud L. , Arnaud J. , Llobera R. , Rubin B.
Published: March 2003

The present study was performed in order to analyze whether T‐cell receptor (TCR)/CD3 assembly, intracellular transport and surface expression are carried in a similar way in αβ‐and γδ‐T cells. By means of optimal immunoprecipitation conditions with 35S‐methionine/cysteine‐ or biotin‐labelled TCR/CD3 proteins from αβ‐ or γδ‐T‐lymphoma‐cell lines, as well as TCRγδ cDNA transfectants, it was found that CD3δ chains associate less strongly with TCRγδ heterodimers compared to TCRαβ heterodimers. This preferential reactivity of CD3δ chains appears to be structural and not owing to differences in γδ‐ versus αβ‐T‐cell intracellular environments. Our results are in accordance firstly, with data from CD3δ‐deficient mice, which have γδ‐T cells but no αβ‐T cells, secondly with the suggested role of CD3δ chains in the positive selection of αβ‐T cells, a process apparently not followed by γδ‐T cells, and lastly with the differential roles of CD3δ chains versus CD3γ chains, explaining the maintenance of two CD3δ and CD3γ genes after the duplication from a CD3δ/γ gene present in avians. The impaired reactivity of CD3δ chains with TCRγδ heterodimers seems to be owing to a less efficient association with TCRγ chains. In contrast, CD3δ chains interact as strongly with TCRδ chains as do CD3γ chains with both TCRγ and TCRδ chains. These data may explain, at the molecular levels, why surface TCR/CD3 expression levels are impaired in γδ‐T cells from CD3γ‐deficient mice but not from CD3δ‐deficient mice.
Effector Cytolotic Funtion but not IFN‐γ Production in Cytotoxic T Cells Triggered by Virus‐Infected Target Cells In vitro
Authors: Regner M. , Lobigs M. , Blanden R. V. , Müllbacher A.
Published: March 2003

Cytolysis and interferon(IFN)‐γ production are two independent effector functions of activated cytotoxic T (Tc) cells. We have used the Tc‐cell response against the flavivirus, Murray Valley encephalitis virus (MVE), to investigate the requirements for inducing these two functions with regard to antigen‐concentration and CD8 coreceptor involvement. Cognate peptide‐pulsed target cells triggered cytolysis by primary ex vivo MVE‐immune as well as in vitro peptide‐restimulated splenocytes at lower peptide concentrations than IFNγ‐production (100‐fold lower in the case of primary ex vivo effectors). Little difference was observed in CD8 dependency. Importantly, neither of the effector populations were triggered to produce IFN‐γ by virus‐infected target cells, although cytolysis occurred. This result raises the posibility that the levels of presentation of cognate antigen on virus‐infected cells in vivo may be below the threshold required for the IFN‐γ production.
Inhibitory Effects of MoAbs against a Surface Protein Antigen in Real‐Time Adherence In vitro and Recolonization In vivo of Streptococcus mutans
Authors: Senpuku H. , Matin K. , Abdus S. MD. , Kurauchi I. , Sakurai S. , Kawashima M. , Murata T. , Miyazaki H. , Hanada N.
Published: March 2003

A surface protein antigen (PAc) of Streptococcus mutans, particularly the A‐region of the molecule, has been reported to interact with salivary components on the tooth surface. It might be a candidate antigen inducing the production of antibodies against the adherence of S. mutans to the tooth surface. We investigated the effects of monoclonal antibodies (MoAbs) obtained by immunization of synthetic PAc peptides that completely correspond to the amino acid sequence of part of the A‐region. These MoAbs recognize several core B‐cell epitopes in the sequence. Two (KH5 and SH2) of these antibodies reacted with both S. mutans and Streptococcus sobrinus, but not with Streptococcus sanguis, Streptococcus salivarius, Porphyromonas gingivalis or Lactobacillus casei. They clearly inhibited the real‐time adherence of S. mutans to salivary components in a biosensor. KH5, which showed a real‐time inhibition (71%), also significantly prevented the recolonization of S. mutans on the tooth surface in rats. These results suggested that the core B‐cell epitope (‐Y‐‐‐L‐‐Y‐‐‐‐) recognized by KH5 was the essential sequence in the antigenic epitopes of PAc protein recognized specifically by the inhibitory antibody. Therefore, the amino acid residues were found to be important in the initial attachment of S. mutans to the tooth surface. These results provide for the mechanism of PAc molecule in the initial attachment of S. mutans on the tooth surface and more effective designs for the removal of S. mutans and S. sobrinus from the oral cavity.
Chemokines and Cell Trafficking in Sjögren's Syndrome
Authors: Amft N. , Bowman S. J.
Published: March 2003

Sjögren's syndrome is a chronic inflammatory condition affecting exocrine glands, manifested clinically as dry eyes and dry mouth. It arises secondary to systemic immune‐mediated diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma or ‘primary’ Sjögren's syndrome. Histologically it is characterized by peri‐ductal aggregates of CD4 T lymphocytes, the frequent occurrence of ectopic germinal centres and, in some patients, B‐cell infiltration of ductal epithelium (myoepithelial sialadenitis). This latter lesion is the precursor for the development of low grade (MALT) B‐cell lymphoma. The identification over recent years of chemokines and their receptors enables us to address the specific processes involved in the migration of inflammatory cells into exocrine glands, the development of their secondary structures and patterns of retention within the glands and potentially the subsequent transformation of B cells into mucosa associated lymphoid tissue (MALT) lymphoma.
Specific Proliferative and Antibody Responses of Premature Infants to Intestinal Colonization with Nonpathogenic Probiotic E. coli Strain Nissle 1917
Authors: Cukrowska B. , LodÍnová‐ŽádnÍková R. , Enders C. , Sonnenborn U. , Schulze J. , Tlaskalová‐Hogenová H.
Published: March 2003

The aim of this study was to analyze the influence of oral administration of E. coli Nissle 1917 on the systemic humoral and cellular immunity in premature infants. Thirty‐four premature infants were colonized with E. coli Nissle 1917 in a randomized, placebo‐controlled blinded clinical trial. Stool samples of infants were analyzed repeatedly for the presence of the administered strain. The proliferative response to bacterial antigens of E. coli origin was measured in whole blood of 34 colonized infants and 27 noncolonized controls. E. coli colonization induced a significant increase in the proliferation of blood cells cultivated with bacterial components of E. coli Nissle 1917 and another E. coli strain in colonized infants as compared with noncolonized controls. Significantly higher amounts of specific anti‐E. coli Nissle 1917 antibodies (Ab) of immunoglobulin (Ig)A isotype and nonspecific polyclonal IgM were found in the blood of colonized infants compared to noncolonized placebo controls. We concluded that the oral application of E. coli Nissle 1917 after birth significantly stimulates specific humoral and cellular responses and simultaneously induces nonspecific natural immunity.
The Effect of LPS on Neutrophils from Patients with High Risk of Type 1 Diabetes Mellitus in relation to IL‐8, IL‐10 and IL‐12 Production and Apoptosis In Vitro
Authors: Glowacka E. , Banasik M. , Lewkowicz P. , Tchorzewski H.
Published: March 2003

Innate immunity includes neutrophil inflammatory function, tissue destruction and regulatory cytokine production. Programmed cell death (apoptosis) is postulated to be a key mechanism for neutrophil elimination during inflammation. The aim of the present study was to evaluate the neutrophil apoptosis in relation to IL‐8, IL‐10 and IL‐12 production in vitro by neutrophils of patients suffering from diabetes mellitus (DM)1 and the first‐degree relatives of patients with DM1. The early stage of neutrophils apoptosis was assessed morphologically, and the later stage by DNA‐binding dye propidium iodide, both after treatment with lipopolysaccharide (LPS), insulin or anti‐CD95 antibody (Ab) as stimulators. CD16 (FcγRIII) receptor expression was also evaluated. Production of IL‐8, IL‐10, and IL‐12 cytokine was evaluated in supernatant after neutrophil incubation for 21 h in culture medium alone, in medium in the presence of LPS, insulin or anti‐CD95 antibody (Ab). Cytokine concentrations were measured by enzyme‐linked immunosorbent assay (ELISA) method using commercially available kits. Our study demonstrates that LPS inhibits the early stage of apoptosis (as evaluated morphologically) of healthy donors' neutrophils. The LPS‐dependent early apoptosis inhibition of neutrophil of patients with DM1 or in prediabetics was decreased in comparison with control. The later stage of apoptosis of neutrophils treated in vitro with anti‐CD95 Ab of patients suffering from DM1 was decreased in comparison with prediabetics and healthy donors (propidium iodide (PI) staining). LPS‐induced production of anti‐apoptotic cytokines IL‐8, IL‐10 by neutrophils of prediabetic and patients with DM1 was increased. The formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced proapoptotic reactive oxygen intermediates (ROI) production was significantly higher in DM1 patients. We have concluded that neutrophils from prediabetic and diabetic patients demonstrated the misbalance in anti‐apoptotic IL‐8 and IL‐10 cytokine and proapoptotic ROI production. LPS‐dependent IL‐12 overproduction by neutrophils is responsible for the switch in T helper Th1/Th2 balance to Th1 and in this way may participate in inflammation and autoimmune DM1 progression.
Development of Mixed Th1/Th2 Type Immune Response and Protection Against Mycobacterium tuberculosis After Rectal or Subcutaneous Immunization of Newborn and Adult Mice with Mycobacterium bovis BCG
Authors: Lagranderie M. , Balazuc A.‐M. , Abolhassani M. , Chavarot P. , Nahori M.‐A. , Thouron F. , Milon G. , Marchal G.
Published: March 2003

Cell‐mediated immunity plays a key role in containing the growth of Mycobacterium tuberculosis in the host. The induction of an antibody response or a mixed cell‐mediated and humoral response is frequently associated with tuberculosis disease or a decrease in the ability to control M. tuberculosis load. We recently reported the induction of similar immune responses and protection by rectal, subcutaneous (SC) or intradermal administration of Mycobacterium bovis BCG in adult mice, guinea pigs and macaques. The rectal immunization, which did not induce the side‐effects associated with parenteral routes (axillary adenitis) and which could be used to reduce the risks of viral transmission associated with unsafe injections in the developing world, was analysed and compared in newborn and adult BALB/c mice. The rectal and SC immunization induced, in mice immunized as newborns or as adults, a mixed T helper 1/T helper 2 (Th1/Th2) immune response; however, particularly in adult mice, after SC administration of BCG, the level of Th2 immune response is significantly higher than it is by the rectal route. Six months after immunization with BCG, rectal and SC delivery induced similar levels of protective immunity against a virulent challenge with M. tuberculosis strain (H37Rv) in mice immunized as adults, but the rectal BCG delivery triggered stronger protection than the SC delivery if mice were immunized as newborns.
Chlamydia pneumoniae Inhibits Apoptosis in Human Epithelial and Monocyte Cell Lines*
Authors: Airenne S. , Surcel H.‐M. , Tuukkanen J. , Leinonen M. , Saikku P.
Published: March 2003

Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937‐line) were resistant to staurosporine and tumour necrosis factor (TNF)‐α‐induced physiological apoptosis 48, 72 or 120 h post‐infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow‐up post‐infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.
Phenotypic Study of Peripheral Blood Leucocytes in HTLV‐I‐Infected Individuals from Minas Gerais, Brazil
Authors: Brito‐Melo G.E.A. , Martins‐Filho O.A. , Carneiro‐Proietti A.B.F. , Catalan‐Soares B. , Ribas J.G. , Thorum G.W. , Barbosa‐Stancioli E.F. , De Pesquisas Em Htlv Grupo Interdisciplinar
Published: March 2003

The human T‐cell lymphotropic virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) associated with the HTLV‐I is a well‐defined clinical–pathological entity in which the virus and host immune responses contribute to the pathological mechanism. In this study, flow cytometric analysis of whole peripheral blood leucocytes (PBL) was performed to evaluate the immunological status of HTLV‐I‐infected individuals in an effort to better understand the role of the immune system in the development of HAM/TSP. We have evaluated three groups of infected patients including asymptomatic (AS = 18), ambulatory/oligosymptomatic (AM = 14) and hospitalized HAM/TSP individuals (HO = 42). Noninfected healthy blood donors were used for the control group (NI = 32). Our results demonstrated that the HO group presents an increased percentage of circulating T cells and a decreased percentage of B and natural killer (NK) cells, leading to the highest T/B‐cell ratio in comparison with the other groups. Interestingly, while an increased percentage of activated CD4+HLA‐DR+ T lymphocytes was observed in both AM and HO, only HO presented higher percentage of activated CD8+HLA‐DR+ in combination with the highest CD18 surface expression. This was true for all cell populations analysed, including T lymphocytes, monocytes and neutrophils. Moreover, the HO group was distinguished by a dramatic decrease in the percentage of CD8+CD28+ lymphocytes. Taken together, these findings demonstrate a potent cellular immune activation response involving primarily CD8+ T cells that is concomitant with disease progression in HAM/TSP. We also show that an upregulation of CD18 expression, a hallmark for increased cell migratory potential, might play a critical role in the development/maintenance of HAM/TSP.
Sema7A is a Potent Monocyte Stimulator
Authors: HOLMES S. , DOWNS A.‐M. , FOSBERRY A. , HAYES P. D. , MICHALOVICH D. , MURDOCH P. , MOORES K. , FOX J. , DEEN K. , PETTMAN G. , WATTAM T. , LEWIS C.
Published: March 2003

Sema7A is a recently described member of the semaphorin family that is associated with the cell surface via a glycophosphatidylinositol linkage. This study examined the mRNA expression and biological properties of this protein. Although the expression of Sema7A was demonstrated in lymphoid and myeloid cells, no stimulation of cytokine production or proliferation was evident in B or T cells. In contrast, Sema7A is an extremely potent monocyte activator, stimulating chemotaxis at 0.1 pm and inflammatory cytokine production (interleukin‐1 (IL‐1β), tumour necrosis factor‐α (TNF‐α), IL‐6 and IL‐8) and superoxide release at 1–10 pm. Sema7A is less effective at stimulating neutrophils. Sema7A also significantly increases granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production from monocytes but has no consistent effect on IL‐10, IL‐12 or IL‐18. Sema7A can also induce monocytes toward a dendritic cell morphology. Sema7A is expressed in monocytes and probably released through proteolysis and acts as a very potent autocrine activator of these cells.
Thickening and/or thinning upward patterns in sequences of strata: tests of significance
Authors: HARPER CHARLES W.
Published: March 2003

Geologists commonly purport that successions of strata show one or more thickening and/or thinning upward trends, often prompting colleagues to argue that the `trends' are subjectively identified, unproven or nonexistent. Parametric and randomization tests are proposed to evaluate the null hypothesis of random succession against a variety of alternative postulates of trend. In place of test statistics in vogue that merely compare each bed thickness with that of the beds immediately above and below it, test statistics based on Kendall's S and Tau that make sequence‐wide (or subsequence‐wide) comparisons of bed thicknesses are advocated. The test statistic used and the exact form of the test depends on the alternative model considered: against the alternative of a single thickening (and/or thinning) upward trend, Kendall's S or equivalently Kendall's Tau are recommended. These statistics make pair‐wise comparisons of beds, comparing bed thicknesses with their positions in the vertical sequence. Against the alternative of trends in g subsequences recognized a‐priori, e.g. those separated by breaks such as thick sequences of hemipelagic shale, test statistics proposed include: the weighted sum of the g Tau coefficients calculated for the individual subsequences (if subsequences are alleged to be all thickening or all thinning upward), and the weighted sum of the absolute value, or square, of the Tau coefficients (if subsequences are alleged to include both thickening and thinning upward patterns). Tests can indicate that a sequence has one or more subsequences which are nonrandom, but it will not indicate which. To test each subsequence for significance, test each of g subsequences at a level of significance = α/g, thus achieving an overall, sequence‐wide, level of significance = α. Against the alternative g subsequences recognized post‐hoc, i.e. purely on the basis of observed thickness patterns, a family of test statistics are proposed, each equal to the maximum value of the appropriate test statistic (defined for subsequences recognized a‐priori) that is attainable by partitioning the total sequence of beds into 1, 2,…. up to g subsequences. Both same‐type and mixed subsequences alternatives arise. Each test proposed is applied to several different sequences, mostly turbidites.
Outcrop‐scale acoustic facies analysis and latest Quaternary development of Hueneme and Dume submarine fans, offshore California
Authors: Piper  , Hiscott  , Normark
Published: March 2003

The uppermost Quaternary deposits of the Hueneme and Dume submarine fans in the Santa Monica Basin have been investigated using a closed‐spaced grid of boomer seismic‐reflection profiles, which give vertical resolution of a few tens of centimetres with acoustic penetration to 50 m. Acoustic facies integrated with geometry define six architectural elements, some with discrete subelements that are of a scale that can be recognized in outcrops of ancient turbidite systems. In the Santa Monica Basin, the relationship of these elements to fan morphology, stratigraphy and sediment source is precisely known.

The width of upper Hueneme fan valley has been reduced from 5 km since the last glacial maximum to 1 km at present by construction of laterally confined sandy levees within the main valley. The middle fan comprises three main subelements: thick sand deposits at the termination of the fan valley, low‐gradient sandy lobes typically 5 km long and < 10 m thick, and scoured lobes formed of alternating sand and mud beds with many erosional depressions. The site of thickest lobe sediment accumulation shifts through time, with each sand bed deposited in a previous bathymetric low (i.e. compensation cycles). The lower fan and basin plain consists of sheet‐like alternations of sand and mud with shallow channels and lenses.

Variations in the rate of late Quaternary sea level rise initiated changes in sediment facies distribution. At lowstand, and during the approximately 11 ka stillstand in sea level, the Hueneme Fan was fed largely by hyperpycnal flow from the Santa Clara River delta, depositing high sediment waves on the right hand levee and thick sandy lobes on the middle fan. At highstand of sea level, most turbidity currents were generated by failure of silty prodelta muds. In contrast, the smaller Dume Fan was apparently always fed from littoral drift of sand through a single‐canyon point source.
Aeolian dune migration along the Ceará coast, north‐eastern Brazil
Authors: Jimenez Jose A. , Maia Luis P. , Serra Jordi , Morais Jader
Published: March 2003

Aeolian dune dimensions and migration rates are analysed along the Ceará coast, north‐east Brazil. Dunes that are currently mobile along the Ceará coast are composed of barchans and sand sheets. The results show that barchans maintain an equilibrium form, which can be characterized by values of dimensionless shape parameters H/W and W/L, where H is the dune height, W is the wing‐to‐wing width and L is the dune length. Dunes are highly mobile, with average migration rates of 17·5 m year−1 for barchans and 10 m year−1 for sand sheets. The calculated migration rates were found to depend strongly on dune dimensions for both barchans and sand sheets, i.e. the larger the dune is, the lower the migration rate will be. This size dependence was associated with the existence of a representative common transport rate along the dune fields, which induces a different dune migration rate dependent on dune size. Finally, from the observed dune evolution, an aggregated scale aeolian sediment transport was inferred. This bulk transport rate, of the order of 90–100 m3 m−1 year−1, is only valid for a timescale of years to decades, which is the timescale used in dune evolution analysis.
The effect of wind speed and bed slope on sand transport
Authors: Iversen James D. , Rasmussen Keld R.
Published: March 2003

This paper reports on a wind tunnel study of the effects of bed slope and wind speed on aeolian mass transport. The use of a sloping wind tunnel has enabled estimation of the friction angle α to be about 40° for saltating particles in the range 170–540 μm. A formula relating dimensionless mass transport to friction speed and bed slope is proposed, and mass transport data for five uniform sand samples and one non‐uniform sand sample are shown to fit the equation well. In particular, the relationship reveals an overshoot in mass transport slightly above threshold collisions, a feature also evident when previous experimental data is re‐examined. As the number of mid‐air collisions between the saltating particles increases greatly with wind speed, the overshoot may occur as a result of increasing energy losses resulting from the collisions. Finally, it is demonstrated that data for saltating snow shows a similar overshoot in the dimensionless transport rate.
Rapid facies changes in Holocene fissure ridge hot spring travertines, Rapolano Terme, Italy
Authors: Guo Li , Riding Robert
Published: March 2003

Holocene hot water travertine continues to form at Terme San Giovanni, near Rapolano Terme, central Italy, although artificial diversion of the water has reduced deposition. Mesothermal water (≈38–39 °C) emerging from fault‐controlled vents located on a hilltop has created a linear fissure ridge 240 m long and up to 10 m high. Active parts of the ridge crest are covered by small cones; inactive parts are locally neotectonically fissured and have small pools. Ridge deposits include crystalline crust, paper‐thin raft and shrub lithotypes. The ridge has both smooth and terraced marginal slopes, dominated by crystalline crusts with small shrubs in terrace pools. At the base of the ridge, there is a rapid transition to lateral flats and depressions, where water from the ridge collects and deposits shrub, irregular pisoid, reed, paper‐thin raft and fine‐grained and organic‐rich travertines. Water channelled to nearby valley sides deposits thick crystalline crusts on valley slopes and waterfall overhangs, locally with small pools filled by smooth spherical pisoids. On the valley floor, mixing of waters forms varied stream‐fill deposits that include micritic reed, paper‐thin raft and coated bubble travertines. The diversity of travertine facies observed results from the location of the Terme San Giovanni hot springs on a hill crest, thus providing a wide array of downslope locations for further deposition. The abrupt facies transitions observed are characteristic of hot spring carbonates and result from a combination of rapid decrease in precipitation away from vents, variations in local surface topography and the feedback effect of travertine deposition itself, which dams and diverts water flow.
Subaqueous mass flow origin for Lower Permian diamictites and associated facies of the Grant Group, Barbwire Terrace, Canning Basin, Western Australia
Authors: Eyles  , Eyles
Published: March 2003

The intracratonic Canning Basin is Western Australia’s largest sedimentary basin (>400 000 km2) and has experienced repeated episodes of Phanerozoic extension and subsidence, resulting in deposition of a number of first‐order ‘megasequences’. A major phase of basin extension and sedimentation (Grant Group) occurred in the Late Carboniferous/Early Permian when Australia lay at high palaeolatitudes. Facies analysis of 5000 m of drill core from 25 continuously cored wells in Grant Group strata on the fault‐bounded Barbwire Terrace in the northern Canning Basin identified three facies associations (FAs). These record the predominance of fault‐generated, subaqueous mass flow and sediment reworking. The lowest association (FA I; up to 355 m thick) rests unconformably on tilted older strata and consists of coarse‐grained, subaqueously deposited, sediment gravity flow facies. These include fault‐generated breccias, massive and graded sandstones and conglomerates deposited by turbidity currents and diamictites generated by mixing of different textural populations during downslope remobilization. FA I is overlain abruptly by relatively fine‐grained deposits of FA II (up to 140 m thick), which consist of laminated to thin‐bedded mudstone and sandstone turbidites, recording an abrupt increase in relative water depths. In turn, these facies coarsen upwards and are transitional into shallow‐water, swaley cross‐stratified and rippled sandstones of FA III (up to 125 m thick). The overall stratigraphic succession probably records an initial phase of faulting and accommodation of coarse sediment (FA I), a subsequent phase of rapid subsidence, increasing water depths and ‘sediment underfilling’ (FA II) and, finally, a regressive phase of shoreface progradation. The occurrence of rare striated clasts in FA I suggests reworking of glacial sediment, but no direct glacial influence on sedimentation can be identified.
Dolomitization of the Waulsortian Limestone (Lower Carboniferous) in the Irish Midlands
Authors: Gregg Jay M. , Shelton Kevin L. , Johnson Aaron W. , Somerville Ian D. , Wright Wayne R.
Published: March 2003

The Waulsortian Limestone (Lower Carboniferous) of the southern Irish Midlands is dolomitized pervasively over a much larger region than previous studies have documented. This study indicates a complex, multistage, multiple fluid history for regional dolomitization. Partially and completely dolomitized sections of Waulsortian Limestones are characterized by finely crystalline (0·01–0·3 mm) planar dolomite. Planar replacive dolomite is commonly followed by coarse (≥0·5 mm) nonplanar replacive dolomite, and pervasive void‐filling saddle dolomite cement is frequently associated with Zn–Pb mineralization. Planar dolomite has average δ18O and δ13C values (‰ PDB) of –4·8 and 3·9 respectively. These are lower oxygen and slightly higher carbon isotope values than averages for marine limestones in the Waulsortian (δ18O=–2·2, δ13C=3·7). Mean C and O isotope values of planar replacive dolomite are also distinct from those of nonplanar and saddle dolomite cement (–7·0 and 3·3; –7·4 and 2·4 respectively). Fluid inclusions indicate a complex history involving at least three chemically and thermally distinct fluids during dolomite cementation. The petrography and geochemistry of planar dolomites are consistent with an early diagenetic origin, possibly in equilibrium with modified Carboniferous sea water. Where the Waulsortian was exposed to hydrothermal fluids (70–280 °C), planar dolomite underwent a neomorphic recrystallization to a coarser crystalline, planar and nonplanar dolomite characterized by lower δ18O values. Void‐filling dolomite cement is isotopically similar to nonplanar, replacive dolomite and reflects a similar origin from hydrothermal fluids. This history of multiple stages of dolomitization is significantly more complex than earlier models proposed for the Irish Midlands and provides a framework upon which to test competing models of regional vs. localized fluid flow.
Anatomy, geometry and sequence stratigraphy of basin floor to slope turbidite systems, Tanqua Karoo, South Africa
Authors: Johnson Stephen David , Flint Stephen , Hinds David , De Ville Wickens H.
Published: March 2003

The Tanqua area of the Karoo basin, South Africa, contains five Permian deep‐water turbidite fan systems, almost completely exposed over some 640 km2. Reconstruction of the basin‐fill and fan distributions indicates a progradational trend in the 450 m+ thick succession, from distal basin floor (fan 1) through basin‐floor subenvironments (fans 2, 3 and 4) to a slope setting (fan 5). Fans are up to 65 m thick with gradational to sharp bases and tops. Facies associations include basin plain claystone and distal turbidite siltstone/claystone and a range of fine‐grained sandstone associations, including low‐ and high‐density turbidite current deposits and proportionally minor debris/slurry flows. Architectural elements include sheets of amalgamated and layered styles and channels of five types. Each fan is interpreted as a low‐frequency lowstand systems tract with the shaly interfan intervals representing transgressive and highstand systems tracts. All fans show complex internal facies distributions but exhibit a high‐frequency internal stratigraphy based on fan‐wide zones of relative sediment starvation. These zones are interpreted as transgressive and highstand systems tracts of higher order sequences. Sandy packages between these fine‐grained intervals are interpreted as high‐frequency lowstand systems tracts and exhibit dominantly progradational stacking patterns, resulting in subtle downdip clinoform geometries. Bases of fans and intrafan packages are interpreted as low‐ and high‐frequency sequence boundaries respectively. Facies juxtapositions across these sequence boundaries are variable and may be gradational, sharp or erosive. In all cases, criteria for a basinward shift of facies are met, but there is no standard ‘motif’ for sequence boundaries in this system. High‐frequency sequences represent the dominant mechanism of active fan growth in the Tanqua deep‐water system.
Primary and diagenetic isotopic signals in fossils and hemipelagic carbonates: the Lower Jurassic of northern Spain
Authors: Rosales Idoia , Quesada Santiago , Robles Sergio
Published: March 2003

Stable isotope and trace element analyses of 230 Jurassic (Pliensbachian–Toarcian) samples from northern Spain have been performed to test the use of geochemical variations in fossils (belemnites and brachiopods) and whole‐rock hemipelagic carbonates as palaeoceanographic indicators. Although the succession analysed (Reinosa area, westernmost Basque–Cantabrian Basin) has been subject to severe thermal alteration during burial diagenesis, the samples appear to be well preserved. The degree of diagenetic alteration of the samples has been assessed through the application of integrated petrographic, chemical and cathodoluminescence analyses. It is demonstrated that brachiopods and whole‐rock carbonates, although widely used for palaeoceanic studies, do not retain their primary marine geochemical composition after burial diagenesis. In contrast, there is strong evidence that belemnite rostra preserve original isotopic values despite pervasive diagenesis of the host rock. Well‐preserved belemnite shells (non‐luminescent to slightly luminescent) typically show stable isotope values of +4·3‰ to –0·7‰δ13C, +0·7‰ to –3·2‰δ18O, and trace element contents of <32 μg g–1Mn, <250 μg g–1Fe, >950 μg g–1Sr and Sr/Mn ratios >80. This study suggests that the degree to which diagenesis has affected the preservation of an original isotopic composition may differ for different low‐Mg calcite fossil shells and hemipelagic bulk carbonates, behaviour that should be considered when marine isotopic signatures from other ancient carbonate rocks are investigated. Multiple non‐luminescent contemporaneous belemnite samples passed the petrographic and geochemical tests to be considered as palaeoceanic recorders, yet their δ13C and δ18O values exhibited moderate scatter. Such variability is likely to be related to the palaeoecological behaviour of belemnites and/or high‐frequency secular variations in sea‐water chemistry superimposed on the long‐term isotopic trend. A pronounced positive carbon‐isotope excursion (up to +4·3‰) is documented in the early Toarcianserpentinusbiozone, which correlates with the Toarcian δ13C maximum reported in other European and Tethyan regions.
Preservation of aeolian genetic units by lava flows in the Lower Cretaceous of the Paraná Basin, southern Brazil
Authors: Scherer Claiton M. S.
Published: March 2003

The Lower Cretaceous geological record of the intracratonic Paraná Basin in southern Brazil comprises a thick succession of aeolian sandstones and volcanic rocks. The intercalation between aeolian sandstone and volcanic floods allowed the preservation of distinct aeolian genetic units. Each genetic unit represents an accumulation episode, bounded by supersurfaces, that coincides with the base of lava flood events. The entire package can be subdivided into a Lower Genetic Unit, which corresponds to aeolian sandstones preserved below the initial lava flows (Botucatu Formation), and an upper set of genetic units, which comprises interlayered aeolian deposits and lava floods (Serra Geral Formation). The Lower Genetic Unit is up to 100 m thick. Its base is composed of ephemeral stream and aeolian sand sheet deposits that are overlain by cross‐bedded sandstones whose origin is ascribed to simple, locally composite, crescentic and complex linear aeolian dunes. Aeolian accumulation of the lower unit was possible as a result of the existence of a wide topographic basin, which caused wind deceleration, and a large sand availability that promoted a positive net sediment flux. The Upper Genetic Units comprise isolated sand bodies that occur in two different styles: (1) thin lenses (<3 m thick) formed by aeolian sand sheets; and (2) thick sand lenses (3–15 m) comprising cross‐bedded cosets generated by migration and climbing of simple to locally composite crescentic aeolian dunes. Accumulation of the aeolian strata was associated with wind deceleration within depressions on the irregular upper surface of the lava floods. The interruption of sedimentation in the Lower and Upper Genetic Units, and related development of supersurfaces, occurred as a result of widespread effusions of basaltic lava. Preservation of both wind‐rippled topset deposits of the aeolian dunes and pahoehoe lava imprints indicates that lava floods covered active aeolian dunes and, hence, protected the aeolian deposits from erosion, thus preserving the genetic units.