bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leishmanial Amastigote Antigen P‐2 Induces Major Histocompatibility Complex Class II‐Dependent Natural Killer‐Cell Reactivity in Cells from Healthy Donors
Authors: Nylén S. , Maasho K. , McMahon‐Pratt D. , Akuffo H. 
Published: March 2004

AbstractInnate mechanisms involving natural killer cells have been implied to play an important role in immunity against Leishmania infection. Previous studies have evaluated responses to three purified amastigote antigens, P‐2, P‐4 and P‐8, of Leishmania pifanoi. The P‐4 and P‐8 antigens have been demonstrated to induce protection in mouse models, as well as to induce cellular responses in American cutaneous leishmaniasis patients. Cells from Leishmania aethiopica‐infected leishmaniasis patients preferentially responded to P‐8 and, to a lesser extent, to the cysteine proteinase, P‐2. In this study, it is shown that cells from healthy donors, including cells from truly naïve donors (cord blood), could be stimulated to proliferation and cytokine production by P‐2. The main proliferating cell types in healthy adult donors were CD16/56+ and the CD8+ cells. Blocking of major histocompatibility complex (MHC) class II with α‐MHC class II antibodies markedly inhibited proliferation and interferon‐γ (IFN‐γ) production, whereas interleukin‐10 production was not affected. Experimental evidence indicates that CD4+ cells were not necessary for the proliferative and IFN‐γ responses; however, an adherent cell population was required. Furthermore, CD16/56+ cells expressing MHC class II were expanded following P‐2 stimulation. The responses to P‐2 show a striking similarity to responses induced by the vaccine candidate Leishmania homologue of receptors for activated C‐kinase (LACK) in healthy donors. The responses described here may not be desirable when aiming at inducing protective immune responses with a vaccine, and the implications of these results for the development of vaccines against leishmaniasis are discussed.
Serum‐Soluble Selectin Levels in Patients with Rheumatoid Arthritis and Systemic Sclerosis
Authors: Ateş A. , Kinikli G. , Turgay M. , Duman M. 
Published: March 2004

AbstractSoluble forms of selectins may play a regulatory role in inflammatory responses that are key to the pathophysiology of rheumatic diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). The aim of this study was to examine whether the elevated serum‐soluble (s) selectin levels are associated with RA or SSc. Serum sE‐, sL‐ and sP‐selectin levels were measured by sandwich enzyme‐linked immunosorbent assay in 34 RA patients, 30 SSc patients and 16 healthy subjects. The levels of sE‐selectin were significantly higher in RA and SSc patients than those in healthy subjects. The sL‐selectin level was significantly lower in RA patients compared to healthy subjects. Serum sP‐selectin levels were not significantly different among the study groups. The active RA patients had significantly higher serum sE‐ and sL‐selectin levels compared to inactive RA patients. Also, some correlations were observed between the serum selectin levels and measures of disease activity such as erythrocyte sedimentation rate and C‐reactive protein in RA patients. The higher levels of sE‐selectin were found in SSc patients with pulmonary fibrosis, and there was also a negative correlation between diffusion capacity for carbon monoxide and serum sE‐selectin. Serum levels of selectins may provide a useful additional marker for disease activity in RA patients and for disease severity in SSc patients.
Serum Mannose‐Binding Lectin Levels and mbl2 Gene Polymorphisms in Different Age and Gender Groups of Southern Chinese Adults
Authors: Ip W. K. , To Y. F. , Cheng S. K. , Lau Y. L. 
Published: March 2004

AbstractMannose‐binding lectin (MBL) is an acute‐phase serum protein, and its inherited deficiency has been shown to predispose to infections. The developmental profile of serum MBL in preterm infants has been demonstrated previously. To determine the profiles of serum MBL levels and mbl2 polymorphisms over age and genders in an adult population, samples from 689 southern Chinese (age range 16–57 years; 382 males and 307 females) were studied using enzyme‐linked immunosorbent assay and high‐throughput genotyping of mbl2. Serum MBL levels maintained within a narrow range from age groups of 16–20 years old to 31–40 years old (mean of 2050–2160 µg/l) and declined to a mean of 1466 µg/l in the last age group 41–57 years old. No significant differences were found in the distributions of mbl2 haplotypes (YA, XA and YB) among all these age groups. Between gender groups, no significant imbalance of MBL profile in terms of serum MBL levels and distribution of mbl2 haplotypes was found. Results suggest an important role of circulating MBL in first‐line host defence because MBL maintains at fairly constant levels after childhood and no gender influence on the MBL profile.
Antibodies Raised Against the Second Extracellular Loop of the Human Muscarinic M3 Receptor Mimic Functional Autoantibodies in Sjögren's Syndrome
Authors: Cavill D. , Waterman S. A. , Gordon T. P. 
Published: March 2004

AbstractFunctional antimuscarinic M3 receptor (M3R) autoantibodies have been shown to inhibit cholinergic neurotransmission at the postsynaptic level and appear to mediate parasympathetic dysfunction, including sicca symptoms in Sjögren's syndrome (SS). The precise epitope(s) involved in the inhibition of M3R‐mediated cholinergic neurotransmission has not been defined. In this study, an active immunization approach to raise antibodies with functional activity against the second extracellular loop of the M3R was used and their functional properties were compared with those of human autoantibodies. Peptides corresponding to the second extracellular loop of the M3R were used as immunogens in rabbits, and antisera were tested for inhibition of carbachol‐evoked colon smooth muscle contraction in parallel with immunoglobulin G from a patient with SS. Anti‐M3R antibodies were affinity purified on a peptide representing a dominant functional epitope at the COOH terminus of the second extracellular loop of the M3R and tested for concentration‐dependent inhibition. Experimentally raised anti‐M3R antibodies, like the human autoantibodies, showed concentration‐dependent and noncompetitive inhibition of carbachol‐evoked colon contractions. Inhibitory activity was detected by functional assays at concentrations as low as 3 ng/ml, which was below the threshold of detection of antibody by peptide enzyme‐linked immunosorbent assay. It is concluded that the experimentally raised anti‐M3R antibodies share the functional properties of autoantibodies in patients with SS.
Involvement of Interleukin‐1β in Systemic Morphine Effects on Paw Oedema in a Mouse Model of Acute Inflammation
Authors: Pourpak Z. , Ahmadiani A. , Alebouyeh M. 
Published: March 2004

AbstractRecent studies suggest that peripheral morphine may represent a valuable treatment in acute inflammatory painful diseases through peripheral or central mechanisms. In the present study, anti‐inflammatory effects of systemic morphine on carrageenan‐induced hind paw oedema were examined in a model of peripheral acute oedema in mice. Carrageenan induced a time‐dependent inflammation that was maximal 3 h after administration. While intraperitoneal administration of morphine sulfate at a low dose (1 mg/kg) increased carrageenan‐induced hind paw oedema, intraperitoneal injection of morphine sulfate at a high dose (7 mg/kg) resulted in significant anti‐inflammatory effects on carrageenan‐induced hind paw oedema. These anti‐inflammatory effects were blocked by pretreatment with naloxone. Measuring the serum levels of interleukin‐1β revealed that increases in serum levels of this cytokine were involved in morphine anti‐inflammatory effects. Pretreatment with naloxone decreased interleukin‐1β serum levels near to those of control group. In conclusion, these data demonstrate that morphine produced pro‐ or anti‐inflammatory effects in a dose‐dependent manner through peripheral or central mechanisms. The observed anti‐inflammatory effects may be due to an increase in the cytokine production and/or release by host immune systems.
Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡
Authors: Mota G. , Moldovan I. , Calugaru A. , Hirt M. , Kozma E. , Galatiuc C. , Brasoveanu L. , Boltz‐Nitulescu G. 
Published: March 2004

AbstractHuman natural killer (NK) cells express low‐affinity Fc immunoglobulin G (IgG) receptor (FcγRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab′)2 fragments of 3G8 anti‐CD16 monoclonal antibody (mAb) to FcγRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 °C, the FcγRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab′)2 fragments of 3G8 anti‐CD16 mAb. The calculated half‐time (T1/2) of in vitro mIgG dissociation from FcγRIIIA was 130 min. By cross‐linking the mIgG ligand with F(ab′)2 fragments of anti‐human IgG antibody, the T1/2 decreases to 85 min. In kinetics study, it has been shown that 125I‐mIgG bound to FcγRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcγRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross‐linking of mIgG‐FcγRIIIA complex, was observed on NK cells treated with RU36156. When the FcγRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcγRIIIA from cleavage, augments NK‐cell activation and may interfere in their killing capacity.
Blocking CC Chemokine Receptor (CCR) 1 and CCR5 During Herpes Simplex Virus Type 2 Infection In Vivo Impairs Host Defence and Perturbs the Cytokine Response
Authors: Sørensen L. N. , Paludan S. R. 
Published: March 2004

AbstractElimination of viral infections is dependent on rapid recruitment of leucocytes to infected areas. Chemokines constitute a class of cytokines that regulate migration of leucocytes to sites of infection. In this work, the expression and function of CC chemokine receptor (CCR)1 and CCR5 and their ligands during a generalized herpes simplex virus type 2 (HSV‐2) infection in mice were studied. Many CCR1 and CCR5 ligands were expressed in infected organs after intraperitoneal infection. In particular, CC chemokine expression in the liver preceded the expression of CCR1 and CCR5, suggesting recruitment of cells bearing these receptors, which correlated with a decrease in viral titres. Administration of Met‐RANTES, a CCR1 and CCR5 antagonist, led to impaired antiviral response with significantly higher viral titre in the liver on days 1 and 6 after infection. This observation was accompanied by a decreased and shortened recruitment of natural killer cells to the peritoneum of infected mice treated with the antagonist. Despite this reduced recruitment of antiviral leucocytes in mice receiving Met‐RANTES, peritoneal cells from these mice produced markedly enhanced levels of pro‐inflammatory cytokines. Altogether, the results suggest that CCR1 and/or CCR5 are important for both viral clearance and eventual control of the immune response.
Additive Effects of Leflunomide and Tacrolimus in Prevention of Islet Xenograft Rejection
Authors: Zhang L. , Qi Z. , Wu D. , Shan S. , Ekberg H. 
Published: March 2004

AbstractLeflunomide is a low molecular weight immunosuppressive drug which inhibits the enzymes dehydroorotate dehydrogenase and protein tyrosine kinase, both of which are important components in the immune response. As the mechanisms of action of leflunomide and tacrolimus are different, we postulated an additive or synergistic effect of the two drugs and investigated the effects of leflunomide alone, or in combination with a suboptimal dose of tacrolimus, on xenogeneic islet transplantation in a rat‐to‐mouse model. A total of 1200–1500 rat islets were transplanted under the left kidney capsule of streptozotocin‐induced diabetic BALB/c mice. The median survival time (MST) of the untreated group was 6 days. Leflunomide at 5, 10 and 20 mg/kg/d administrated for 10 days significantly prolonged MST to 10, 16 and 20 days. A dose of tacrolimus (2 mg/kg/d) was associated with a graft survival of 9 (range 6–12) days; most grafts rejected during ongoing therapy. When tacrolimus (2 mg/kg/d) was combined with leflunomide (10 mg/kg/d), the survival time of the islet xenografts was increased further to 22 days, significantly longer than with leflunomide or tacrolimus alone. In summary, our findings demonstrate that leflunomide prolonged xenogeneic islet graft survival, and that its immunosuppressive effect was improved when combined with tacrolimus.
Supporting community solutions to family violence
Authors: Taylor Judy , Cheers Brian , Weetra Colin , Gentle Ian 
Published: March 2004

Competing discourses have always figured prominently in policy debates about violence against women and children. Legislation and services to address it have largely been developed from theory and empirical knowledge of domestic violence occurring in intimate relationships. Knowledge from an Indigenous perspective about family violence, embedded in a context of colonisation and involving a broader range of relationships, has been less influential. One of the consequences of this is that when Indigenous communities identify solutions to address family violence holistically, these solutions are difficult to implement. Research with a remote South Australian Aboriginal community, looking for ways to reduce the level of family violence, resulted in new understandings of it. Linking issues of economic deprivation, dispossession and the breaking down of culture, the community devised a holistic community development approach to reduce family violence.This paper identifies the waves of understanding about family violence and argues that community‐initiated solutions must be supported by policy and funding options based on an Indigenous understanding of family violence.
Laminin‐2 stimulates the proliferation of epithelial cells in a conjunctival epithelial cell line
Authors: Dowgiert J. , Sosne G. , Kurpakus‐Wheater M. 
Published: March 2004

Abstract.  Laminin‐2 (LN‐2, α2β1γ1) is a basement membrane‐associated laminin isoform usually considered in the context of muscle and nerve tissues. To test the hypothesis that LN‐2 can additionally modulate epithelial cell biology, an analysis of the role of LN‐2 in cell adhesion, activation of signalling intermediates and proliferation was undertaken. A virally transformed human conjunctival epithelial cell line (HC0597) was utilized in this study. Adhesion assays using function‐inhibiting antibodies demonstrated that α3β1 integrin is essential for the rapid attachment of conjunctival epithelial cells to LN‐2. Bromodeoxyuridine (BrdU) incorporation analyses revealed that, compared with LN‐1 or LN‐10, LN‐2 significantly promotes epithelial proliferation. Phosphorylation of the signalling intermediates Erk1/2 and Akt‐1 was observed within 15 min of cell adhesion to LN‐2. Inhibiting α3β1 integrin function decreased total cellular phosphotyrosine levels, specifically inhibited phosphorylation of Erk1/2 and Akt‐1, and dampened the proliferation response of epithelial cells adherent to LN‐2. Inhibition of Erk or Akt activation inhibited cell proliferation in a dose‐dependent manner. However, the inhibition of Erk resulted in a stronger suppression of proliferation compared with Akt inhibition. From these results, it is concluded that human conjunctival epithelial cells adhere to immobilized LN‐2 using α3β1 integrin. α3β1 integrin/LN‐2 signalling, transduced primarily through an Erk pathway, enhances epithelial cell proliferation. These results demonstrate that LN‐2 can impact on epithelial cell biology in addition to nerve and muscle, and provide information regarding the role of this isoform in ocular surface epithelial cells.
Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers
Authors: He Z. P. , Tan W. Q. , Tang Y. F. , Zhang H. J. , Feng M. F. 
Published: March 2004

Abstract.  Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem‐like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV‐6, cytokeratin‐19 (CK‐19) and albumin. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis displayed that the freshly isolated cells co‐expressed albumin, cytokeratin‐7 (CK‐7) and CK‐19 mRNA, indicating that they were essentially bipotential hepatic stem‐like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK‐7 and CK‐19 in the cells derived from the expanding colonies at day 95 were confirmed by RT‐PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential nature of hepatic stem cells.
Cell cycle time and rate of entry of cells into mitosis in the small intestine of young rats
Authors: Wille A. C. M. , Oliveira F. A. , Soares M. A. M. , Gomes J. R. 
Published: March 2004

Abstract.  Cell cycle time (TC) and the rate of entry of cells into mitosis (rM) in the jejunum and duodenum of young rats were investigated using the stathmokinetic method. The cell cycle times in the jejunum were 24.3 and 28.3 h in light and dark periods, respectively. Cell cycle times in the duodenum were 17.1 and 21.5 h in light and dark periods, respectively. Rates of entry of cells into mitosis in the jejunum were 1.2 and 1.1 cells/cell/h in light and dark periods and rates of entry of cells into mitosis in the duodenum were 1.4 and 1.8 cells/cell/h in light and dark periods, respectively. Although these changes to cell cycle time values are not statistically significant, the variation between the two periods should be considered in relation to its possible biological effects.
Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent
Authors: AFUWAPE A O , TURNER M W , STROBEL S 
Published: March 2004

SUMMARYMost studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (β-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-β was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory outcome and this is also reflected by the systemic cytokine profile.
Inhibition of stem cell factor reduces pulmonary cytokine levels during allergic airway responses
Authors: BERLIN A A , LINCOLN P , TOMKINSON A , LUKACS N W 
Published: March 2004

SUMMARYStem cell factor (SCF) has a significant role in the inflammation and activation of allergic airway responses. When monoclonal anti-SCF was administered intratracheally during allergen challenge there was a significant alteration of eosinophil accumulation and airway hyperreactivity (AHR). Anti-SCF treatment also attenuated pulmonary cytokine and chemokine levels. In particular, there was an antibody dose-dependent decrease in interleukin (IL)-5 and tumour necrosis factor (TNF)-α. There was also a significant reduction of CCL2 and CCL5, which correlated with the reduction in AHR. Mice treated with anti-SCF demonstrated a significant decrease in pulmonary gob-5 gene expression, which has been shown to correlate to goblet cell hyperplasia/metaplasia relating to airway mucus production. Blocking SCF-mediated activation within the airway using a monoclonal antibody indicates that this cytokine may represent a viable target for therapeutic intervention that could affect multiple aspects of allergen-induced immunopathology.