bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteopontin, a Protein with Cytokine‐like Properties, is Associated with Inflammation in Crohn's Disease
Authors: Agnholt J. , Kelsen J. , Schack L. , Hvas C. L. , Dahlerup J. F. , Sørensen E. S. 
Published: May 2007

AbstractIn Crohn's disease (CD) mucosal T‐cells produce increased interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) levels and TNF‐α antibody treatment [Infliximab (Ifx)] is effective. Osteopontin (OPN), a glycoprotein stimulating activated T‐lymphocytes, may be involved in the disturbed immune‐regulation but also in normal immune‐homeostasis and mucosal repair, since it is expressed in many tissues and present in human milk. This study investigates plasma‐OPN levels in CD patients during Ifx treatment and the in vitro effect of OPN on intestinal T cells. Thirty‐seven CD patients received three Ifx doses at week 0, 2 and 6. Blood samples, colonic biopsies and clinical scores were obtained before treatment and at week 8, 26 and 52. In‐vivo activated T‐cell cultures were established from colonic biopsies in the presence of interleukin (IL)‐2 and IL‐4. The in vitro effect of OPN stimulation on T‐cell IFN‐γ, TNF‐α, and IL‐10 production was measured. Plasma‐OPN was increased in active CD (increased CRP‐level) compared with quiescent disease (P = 0.02) and declined after three Ifx doses (P = 0.04). It was inversely correlated with in vitro T‐cell IL‐10 production. OPN increased CD69 and CD25 expression and enhanced T‐cell IFN‐γ and TNF‐α production in a dose‐dependent fashion with higher levels in CD than in healthy controls (HC), but induced a concomitant higher IL‐10 production in HC than CD. In conclusion, plasma‐OPN levels are related to CD inflammation. In vitro, OPN‐stimulated IL‐10 production increases less in T‐cell cultures from CD patients than from HC, indicating that IL‐10 deficiency may be involved in the defect immune‐regulation in CD, even after OPN stimulation.
Passive Transfer of Experimental Autoimmune Neuritis by IL‐12 and IL‐18 Synergistically Potentiated Lymphoid Cells is Regulated by NKR‐P1+ Cells
Authors: Sun B. , Li H.‐L. , Wang J.‐H. , Wang G.‐Y. , Zhao R. , Mu L.‐L. , Jin L.‐H. 
Published: May 2007

AbstractThe aim of this study was to investigate the roles and mechanism of interleukin‐12 (IL‐12) and interleukin‐18 (IL‐18) in potentiating the autoreactivity of lymphoid cells specific for P2 53–78 peptide. P2 53–78‐specific lymphoid cells in the presence of IL‐12 or IL‐18 alone passive transferred only moderate experimental autoimmune neuritis (EAN) into a low percentage of recipients. However, lymphoid cells co‐cultured with both cytokines transferred aggressive clinical and histological EAN into all recipients. NKR‐P1+ cells (including NK and NKT cells) played an immunosuppressive function in passive transfer EAN and depletion of NKR‐P1+ cells by anti‐NKR‐P1 Ab and complement induced a more serious form of EAN. Nevertheless, lymphoid cells co‐cultured with both IL‐12 and IL‐18 induced high levels of interferon‐γ (IFN‐γ) and promoted Th1 differentiation partially through NKR‐P1+ cells and to some extent, NKR‐P1+ cell depletion inhibited the auto‐reactivity of lymphoid cells treated with IL‐12 and IL‐18.
Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets
Authors: Fritsch Fredin M. , Elgbratt K. , Svensson D. , Jansson L. , Melgar S. , Hultgren Hörnquist E. 
Published: May 2007

AbstractOne of the most widely used animal models for inflammatory bowel disease (IBD) is the dextran sulfate sodium (DSS)‐induced colitis. We have previously reported that 5 days administration of DSS in C57Bl/6J mice induces a colonic inflammation that progresses into chronicity after DSS removal, whereas in BALB/cJ mice the inflammation resolves within 4 weeks post‐DSS. Here we show that both thymic size and thymocyte numbers dramatically decreased in the acute phase of inflammation in C57Bl/6 mice, 7 days after DSS withdrawal. Mature, CD4+ and CD8+ single positive (SP) CD69lo CD62Lhi thymocytes were enriched in these mice, accompanied by a major decrease in the number of immature double positive (DP) thymocytes. However, the different maturation stages within the DP thymocyte subset were unchanged between healthy and inflamed C57Bl/6J mice. Interestingly, as the inflammation progressed into the chronic phase, the thymus recovered and 2 weeks after the acute inflammatory phase all the thymic parameters investigated in this study were restored to normal. In contrast, BALB/cJ mice only develop mild thymic alterations. Nevertheless, we found that within the double negative (DN) thymocytes an increased frequency and also total numbers of CD44+ CD25− (DN1) cells correlated with the severety of colitis, and that the frequency of CD44− CD25− (DN4) thymocytes decreased proportionally in the acute phase in BALB/cJ mice. Our observations suggest that the thymic effects are intimately connected to the intestinal inflammatory response in colitis regardless of the inflammatory stimuli.
A Novel Mannose‐binding Lectin‐associated Serine Protease 1/3 Gene Variant
Authors: Weiss G. , Madsen H. O. , Garred P. 
Published: May 2007

AbstractThe ficolins and mannose‐binding lectin (MBL) create complexes with three different serine proteases (MASP‐1, MASP‐2 and MASP‐3) and a truncated non‐enzymatic form of MASP‐2 (sMAP). MASP‐2 is able to activate complement by cleavage of C4 and C2, while the physiological functions of MASP‐1, MASP‐3 and sMAP still are debated. MASP‐1 and MASP‐3 are alternative spliced forms of the same MASP gene. To gain insight in the molecular variation in the MASP‐1/3 gene, we undertook a systematic study of the protein coding sequences of the MASP‐1/3 gene. The coding regions of the MASP‐1/3 gene were sequenced in 92 healthy Caucasian donors. A total of six nucleotide substitutions were detected. Five were detected only once. One polymorphism identified in exon 10 at position +50074 (rs 38343199) relative to the transcription start site resulting in the amino acid substitution of a glycine (GGG) with a glutamic acid residue (GAG) in the second complement control protein domain was observed. The frequency of this allele in 305 blood donors, 90 patients with systemic lupus erythematosus and 234 patients with the systemic inflammatory response syndrome (SIRS) and/or sepsis was 0.03, 0.017 and 0.03 respectively. No significant differences in genotype frequencies between the groups were observed (P > 0.45). However, the SIRS/sepsis group deviated from the Hardy–Weinberg expectations due to one variant allele homozygote (P = 0.07), which was not observed in the other groups. In conclusion, the MASP1/3 gene harbours a low‐frequent polymorphic site resulting in an amino acid substitution, which may influence the function of the gene product.
Activation of toll‐like receptors 2 and 4 by gram‐negative periodontal bacteria
Authors: Kikkert R. , Laine M. L. , Aarden L. A. , Van Winkelhoff A. J. 
Published: May 2007

Background/aims:  Periodontitis is a chronic infectious disease associated with a gram‐negative subgingival microflora. Bacterial components stimulate, among other receptors, Toll‐like receptor (TLR) 2 and/or TLR4. Accumulating evidence indicates that both qualitatively and quantitatively distinct immune responses result from the triggering of TLR2 as compared to TLR4 triggering. The aim was to study the interaction of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Prevotella intermedia, Prevotella nigrescens, Fusobacterium nucleatum and Veillonella parvula with TLR2 and TLR4. We investigated all known serotypes (K−, K1–K6) of P. gingivalis and A. actinomycetemcomitans serotype a–e strains for their potency to stimulate cytokine production.Methods:  Human embryonic kidney (HEK) cells, stably transfected with CD14, CD14‐TLR2, or CD14‐TLR4 and whole blood were stimulated with bacterial sonicates. Cytokine production (interleukin‐6, ‐8, ‐10 and ‐12) was measured in the supernatant by enzyme‐linked immunosorbent assay.Results:  All test bacteria stimulated HEK‐CD14‐TLR2, but only A. actinomycetemcomitans and V. parvula stimulated HEK‐CD14‐TLR4. No differences were found in the activation of HEK‐CD14‐TLR2/4, or cytokine production in whole blood between serotypes of P. gingivalis and A. actinomycetemcomitans.Conclusion:  Gram‐negative periodontal bacteria predominantly stimulated TLR2, which may be of importance for the Th1/Th2 cell orientation of the immune response in periodontitis.
An in vitro biofilm model of subgingival plaque
Authors: Walker C. , Sedlacek M. J. 
Published: May 2007

Introduction:  Numerous biofilm models have been described for the study of bacteria associated with the supragingival plaque. However, there are fewer models available for the study of subgingival plaque. The purpose of this study was to develop and validate a model that closely mimicked the composition of the subgingival flora.Methods:  The model was developed as follows: calcium hydroxyapatite disks were coated overnight with 10% sterile saliva, placed in flat‐bottomed tissue culture plates containing trypticase‐soy broth, directly inoculated with a small aliquot of dispersed subgingival plaque, incubated anaerobically, and transferred to fresh medium at 48‐h intervals until climax (steady‐state) biofilms were formed (∼10 days).Results:  The model, based on samples from eight periodontitis patients and eight healthy subjects, yielded a multi‐species, heterogeneous biofilm, consisting of both gram‐positive and gram‐negative species, and comprising 15–20 cultivable species associated with the subgingival flora. The species present and their proportions were reflective of the initial cultivable subgingival flora. Comparisons of the initial plaque samples from healthy subjects and the mature biofilms showed 81% similarity in species and 70% similarity in the proportions present. Biofilms formed from samples obtained from periodontally diseased subjects were 69% similar in species and 57% similar in the proportions present.Conclusions:  The biofilm model described here closely reproduces the composition of the cultivable subgingival plaque both in the species present and in their relative proportions. Differences existed between biofilms grown from diseased and non‐diseased sites with the former being characterized by the presence of periodontal pathogens at microbially significant levels.
Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis
Authors: Page R. C. , Lantz M. S. , Darveau R. , Jeffcoat M. , Mancl L. , Houston L. , Braham P. , Persson G. R. 
Published: May 2007

Introduction:  Periodontitis is a common infectious disease to which Porphyromonas gingivalis has been closely linked, in which the attachment tissues of the teeth and their alveolar bone housing are destroyed. We conducted a study to determine if immunization using a purified antigen could alter the onset and progression of the disease.Methods:  Using the ligature‐induced model of periodontitis in Macaca fascicularis, we immunized five animals with cysteine protease purified from P. gingivalis and used an additional five animals as controls. Alveolar bone loss was measured by digital subtraction radiography.Results:  Immunization induced high titers of specific immunoglobuin G serum antibodies that were opsonic. Total bacterial load, levels of P. gingivalis in subgingival plaque and levels of prostaglandin E2 in gingival crevicular fluid were significantly reduced. Onset and progression of alveolar bone loss was inhibited by approximately 50%. No manifestations of toxicity were observed.Conclusions:  Immunization using a purified protein antigen from P. gingivalis inhibits alveolar bone destruction in a ligature‐induced periodontitis model in M. fascicularis.
Effects of prolonged exposure to alkaline pH on Enterococcus faecalis survival and specific gene transcripts
Authors: Appelbe O. K. , Sedgley C. M. 
Published: May 2007

Introduction:  The persistence of Enterococcus faecalis in treated root canals has been attributed to its resistance to the high pH of antimicrobial agents used during treatment, but the specific mechanisms are not clear. We investigated the survival and gene expression of E. faecalis maintained in alkaline media.Methods:  E. faecalis JH2‐2 was maintained in media at pH 7, 10, 11 and 12 at either 25°C or 37°C for 1 week (168 h). At 24, 48, 72, 120 and 168 h, cell viability was determined in parallel with real‐time quantitative polymerase chain reaction analyses of stress response genes (dnaK, fba, ftsZ, GroEL, napA, pbp5, tsf and tuf).Results:  After 1 week the E. faecalis showed survival levels of 100% in pH 7, 1% in pH 10, 0.001% in pH 11 and 0.00001% in pH 12 media. At 37°C increased levels of gene transcripts occurred between 72 and 120 h in pH 7 media for ftsZ and dnaK, and in pH 10 media for ftsZ, pbp5, dnaK, napA, tsf, fba and GroEL. No increase in transcripts was observed at 37°C in media at pH 11 or pH 12, nor at 25°C in any media.Conclusion:  Transcripts of ftsZ, a gene involved in cell division, increased by 37‐fold after 120 h at pH 10 at 37°C. Overall, the greatest increase in levels of gene transcripts occurred in cultures maintained in pH 10 media at 37°C. These data may assist in understanding the survival strategies of E. faecalis following prolonged exposure to alkaline pH levels.
The microbiological profiles of saliva, supragingival and subgingival plaque and dental caries in adults with and without type 2 diabetes mellitus
Authors: Hintao J. , Teanpaisan R. , Chongsuvivatwong V. , Ratarasan C. , Dahlen G. 
Published: May 2007

Introduction:  The relationships between suspected bacteria in saliva, yeasts in oral rinse, and supragingival and subgingival plaque versus root surface and coronal caries in adults with type 2 diabetes mellitus and a non‐diabetic group were explored.Methods:  One‐hundred and five patients with type 2 diabetes and 103 non‐diabetic subjects were recruited; their periodontal status, plaque index and magnitude of root surface and coronal caries were assessed. Saliva and an oral rinse were cultured for mutans streptococci, lactobacilli and yeasts. Toothbrush samples of supragingival plaque and curette samples of subgingival plaque were assessed for 17 bacterial species using the checkerboard DNA–DNA hybridization method.Results:  Type 2 diabetes patients had significantly more severe periodontitis, a higher plaque index and a higher prevalence and magnitude of root surface caries than non‐diabetic subjects. Significantly more diabetic subjects had higher levels of Treponema denticola, Prevotella nigrescens, Streptococcus sanguinis, Streptococcus oralis and Streptococcus intermedius in their supragingival plaque than non‐diabetic subjects. No significant difference was found for the organisms in saliva, oral rinse and subgingival plaque between the two groups. After adjustment for diabetic status, root surface caries was associated with an increased count of mutans streptococci, lactobacilli and yeasts in saliva and of Streptococcus mutans in supragingival plaque samples. Coronal caries was only associated with lactobacilli and yeasts in saliva.Conclusion:  The number of cariogenic organisms in saliva and oral rinse estimated by culture demonstrated a stronger association with both root surface and coronal caries compared to those 17 species assessed with the checkerboard method in supragingival and subgingival plaque.
Oral epithelium–Candida glabrata interactions in vitro
Authors: Li L. , Dongari‐Bagtzoglou A. 
Published: May 2007

Background:  Oropharyngeal candidiasis is a common opportunistic infection and Candida glabrata is the second or third most frequently isolated species from oropharyngeal candidiasis lesions, after Candida albicans. The aim of this study was to study the cytokine‐inducing and cell‐damaging potential of C. glabrata in oral epithelial cells and compare this to C. albicans.Methods:  Oral epithelial cell lines and primary gingival epithelial cells were cocultured with C. glabrata strains GDH2269 and 94‐11 or C. albicans strains SC5314 and ATCC28366. Supernatants were analysed for the presence of interleukin‐1α (IL‐1α), IL‐8 and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) by enzyme‐linked immunosorbent assay. The cytotoxity of different strains was determined using the CytoTox‐96 assay.Results:  Compared to C. albicans, C. glabrata induced different proinflammatory cytokine responses in oral epithelial cells; a high level of GM‐CSF induction was only detected in C. glabrata‐infected cells and not in C. albicans‐infected cells, regardless of the origin of these cells (cell lines or primary cells) or the strain used. Like C. albicans, C. glabrata induced an IL‐1α response by oral epithelial cells, but this response was both strain‐dependent and epithelial cell origin‐dependent. Unlike C. albicans, C. glabrata failed to induce a strong IL‐8 response in any of the cell systems studied. Finally, in these studies C. glabrata showed lower cytotoxicity than C. albicans.Conclusions:  C. glabrata is less cytotoxic than C. albicans and induces different proinflammatory cytokine responses in oral epithelial cells.
Characterization of Candida albicans infection of an in vitro oral epithelial model using confocal laser scanning microscopy
Authors: Malic S. , Hill K. E. , Ralphs J. R. , Hayes A. , Thomas D. W. , Potts A. J. , Williams D. W. 
Published: May 2007

Introduction:  Oral candidosis presents as several distinct forms and one of these, chronic hyperplastic candidosis, is distinguished by penetration of the epithelium by Candida. The aim of this study was to use confocal laser scanning microscopy to examine invasion of the oral epithelium by Candida albicans from different oral conditions and to determine whether inherent strain differences exist that could relate to infection type. Reverse transcription–polymerase chain reaction was also used to detect products from virulence gene families.Methods:  C. albicans (n = 19) was used to infect reconstituted human oral epithelium, which was incubated for 12 h. One half of the reconstituted human oral epithelium was then fixed and stained with concanavalin A–Alexa 594, pan‐cytokeratin antibody–Alexa 488 and Hoechst nucleic acid dye. RNA was extracted from the remaining tissue for reverse transcription–polymerase chain reaction targeting secreted aspartyl proteinase, phospholipase and agglutinin‐like sequence genes of C. albicans.Results:  Confocal laser scanning microscopy revealed strain‐dependent tissue invasion, with differences evident in surface colonization, C. albicans morphology and the extent and pattern of tissue penetration. Hyphae were seen to directly penetrate epithelial cells and migrate between keratinocytes with yeast budding also evident in the reconstituted human oral epithelium. A relationship between ‘high tissue invasion’ and expression of secreted aspartyl proteinase genes 4–6 was noted. Interestingly, four of the five ‘high invaders’ originated from chronic hyperplastic candidosis.Conclusions:  Confocal laser scanning microscopy permitted high resolution analysis of reconstituted human oral epithelium invasion by C. albicans and identified strain differences in the invasion process. Association between extensive hyphal morphology, direct epithelial penetration and high surface colonization were made with the ‘highly invasive’ strains.
Cross‐reactive adaptive immune response to oral commensal bacteria results in an induction of receptor activator of nuclear factor‐κB ligand (RANKL)‐dependent periodontal bone resorption in a mouse model
Authors: Kawai T. , Paster B. J. , Komatsuzawa H. , Ernst C. W. O. , Goncalves R. B. , Sasaki H. , Ouhara K. , Stashenko P. P. , Sugai M. , Taubman M. A. 
Published: May 2007

Introduction:  The present study examined whether induction of an adaptive immune response to orally colonizing non‐pathogenic Pasteurella pneumotropica by immunization with the phylogenetically closely related bacterium, Actinobacillus actinomycetemcomitans, can result in periodontal bone loss in mice.Methods:  BALB/c mice harboring P. pneumotropica (P. pneumotropica+ mice) in the oral cavity or control P. pneumotropica‐free mice were immunized with fixed A. actinomycetemcomitans. The animals were sacrificed on day 30, and the following measurements were carried out: (i) serum immunoglobulin G and gingival T‐cell responses to A. actinomycetemcomitans and P. pneumotropica; (ii) periodontal bone loss; and (iii) identification of receptor activator of nuclear factor‐κB ligand (RANKL) ‐positive T cells in gingival tissue.Results:  Immunization with A. actinomycetemcomitans induced a significantly elevated serum immunoglobulin G response to the 29‐kDa A. actinomycetemcomitans outer membrane protein (Omp29), which showed strong cross‐reactivity with P. pneumotropica OmpA compared to results in the control non‐immunized mice. The A. actinomycetemcomitans‐immunized P. pneumotropica+ mice developed remarkable periodontal bone loss in a RANKL‐dependent manner, as determined by the abrogation of bone loss by treatment with osteoprotegerin‐Fc. The T cells isolated from the gingival tissue of A. actinomycetemcomitans‐immunized P. pneumotropica+ mice showed an in vitro proliferative response to both A. actinomycetemcomitans and P. pneumotropica antigen presentation, as well as production of soluble(s)RANKL in the culture supernatant. Double‐color confocal microscopy demonstrated that the frequency of RANKL+ T cells in the gingival tissue of A. actinomycetemcomitans‐immunized P. pneumotropica+ mice was remarkably elevated compared to control mice.Conclusion:  The induction of an adaptive immune response to orally colonizing non‐pathogenic P. pneumotropica results in RANKL‐dependent periodontal bone loss in mice.
Regional and Cyclic Variations in the Ultrastructural Features of Secretory Cells in the Oviductal Epithelium of the Chinese Meishan Pig
Authors: Abe H , Hoshi H 
Published: May 2007

ContentsThe Chinese Meishan pig is prolific breed and it is considered that this pig has a capacity with higher rates of embryonic survival. The oviductal secretory cells may affect the embryonic development and survival. The aim of the present study was to investigate the ultrastructural features of secretory cells in the various regions of the Chinese Meishan pig oviduct during the follicular and luteal phases of the oestrous cycle. In the ampullar secretory cells, numerous secretory granules with moderately electron‐dense matrices were present in the supranuclear cytoplasm and exocytosis of secretory granules was observed. The number of secretory granules was dramatically reduced in the ampullar secretory cells in the luteal phase. During the follicular phase in the fimbrial epithelium, the secretory cells contained rough endoplasmic reticulum and Golgi apparatus, but most cells had few small granules. In the luteal phase, the secretory cells in the ampullar and fimbrial epithelia extended beyond the luminal border of the ciliated cells. In the isthmus, many granules were present in the cytoplasm of secretory cells throughout the oestrous cycle, but the number of secretory granules was reduced in the luteal phase. The cytomorphometric data revealed that the height of ciliated cells decreased substantially in the fimbriae and ampulla at the luteal phase, while that of non‐ciliated cells was less affected. These results suggest that the drastic reduction of cell height of ciliated cells cause the extrusion of most secretory cells beyond the ciliated cells in the fimbriae and ampulla during the luteal phase. In summary, our ultrastructural observations of Chinese Meishan pig oviduct revealed marked cyclic changes in the ultrastructural features of secretory cells. In particular, the ultrastructural features and the numbers of secretory granules were distinctive for each particular segment. These findings should provide insight into the regional and cellular differences in functions of secretory cells of the Chinese Meishan pig oviduct.