bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma protein profiles in early asthmatic responses to inhalation allergen challenge
Authors: Rhim T. , Choi Y.‐S. , Nam B.‐Y. , Uh S. T. , Park J. S. , Kim Y.‐H. , Paik Y.‐K. , Park C.‐S. 
Published: December 2008

Although mediators, such as lipids, cytokines, and chemokines, are related to the appearance of an IPR, there has been no reliable indicator to predict conditions for the appearance of an IPR.In this study, we adopted a proteomic approach to investigate the pathogenesis at the level of the plasma proteins and to develop plasma markers to predict the appearance of an IPR following an inhalation challenge with Dermatophagoides pteronyssinus (D.p.). Sixteen mild asthmatics were recruited. Plasma was obtained before challenge and when a decline in forced expiratory volume in 1 s (FEV1) values greater than 20% from the phosphate‐buffered saline value was achieved during D.p. allergen challenge (positive responders), or at 60 min after the highest concentration of D.p. allergen was inhaled (negative responders). After comparing normalized volumes of the spots in the two groups, differentially expressed spots were identified using intra‐gel digestion and mass spectrometric analysis. Before D.p. antigen challenge, four spots of gamma fibrinogen and its isoforms were significantly decreased and two spots of complement C3 fragments were significantly increased in the positive responders compared to the negative responders. After D.p. antigen challenge, complement C3 fragment was persistently higher, while gamma fibrinogen was lower in the positive responders than in the negative responders. A validation study using Western blotting showed that gamma fibrinogen expression in the IPR‐positive asthmatics was significantly decreased compared to the average of the IPR‐negative asthmatic control group. These results indicate that alterations in the complement cascade and fibrinogen may predispose patients to the appearance of an immediate response to D.p. allergen challenge and may provide plasma markers to predict the appearance of an IPR.
Gene targeting demonstrates that inducible nitric oxide synthase is not essential for resistance to oral candidiasis in mice, or for killing of Candida albicans by macrophages in vitro
Authors: Farah C. S. , Saunus J. M. , Hu Y. , Kazoullis A. , Ashman R. B. 
Published: December 2008

Introduction:  Oral candidiasis is caused by opportunistic infections with the yeast Candida albicans. Previous studies have demonstrated important roles for innate immunity and T helper type 1‐mediated inflammatory reactions in recovery from infection, with macrophages and neutrophils as key effector cells. Both effector cell types use the inducible isoform of nitric oxide synthase (iNOS) to generate candidacidal molecules, but it is not clear whether nitric oxide (NO) is an absolute requirement for candidacidal effector activity.Methods:  In this study we directly investigated the role of iNOS‐derived NO in resistance to murine experimental oral candidiasis, using iNOS knockout mice.Results:  Knockout mice were no more susceptible to oral candidiasis than wild‐type controls. Bone marrow‐derived macrophages from the knockout mice killed C. albicans yeasts efficiently in vitro, and were still able to produce nitrites in an iNOS‐independent manner, albeit less efficiently than wild‐type controls. There were no significant differences in local mucosal production of interleukins 6, 12, 17A, or 23, interferon‐γ, or transforming growth factor‐β 24 h after oral challenge with C. albicans.Conclusion:  These data suggest that iNOS‐derived NO is not required for resistance to oral candidiasis in vivo, and that bone marrow‐derived macrophages may have iNOS‐independent means of generating reactive nitrogen species.
Evidence of the presence of T helper type 17 cells in chronic lesions of human periodontal disease
Authors: Cardoso C. R. , Garlet G. P. , Crippa G. E. , Rosa A. L. , Júnior W. M. , Rossi M. A. , Silva J. S. 
Published: December 2008

Introduction:  Periodontal disease is a chronic inflammation of the attachment structures of the teeth, triggered by potentially hazardous microorganisms and the consequent immune‐inflammatory responses. In humans, the T helper type 17 (Th17) lineage, characterized by interleukin‐17 (IL‐17) production, develops under transforming growth factor‐β (TGF‐β), IL‐1β, and IL‐6 signaling, while its pool is maintained by IL‐23. Although this subset of cells has been implicated in various autoimmune, inflammatory, and bone‐destructive conditions, the exact role of T lymphocytes in chronic periodontitis is still controversial. Therefore, in this study we investigated the presence of Th17 cells in human periodontal disease.Methods:  Gingival and alveolar bone samples from healthy patients and patients with chronic periodontitis were collected and used for the subsequent assays. The messenger RNA expression for the cytokines IL‐17, TGF‐β, IL‐1β, IL‐6, and IL‐23 in gingiva or IL‐17 and receptor activator for nuclear factor‐κB ligand in alveolar bone was evaluated by real‐time polymerase chain reaction. The production of IL‐17, TGF‐β, IL‐1β, IL‐6, and IL‐23 proteins was evaluated by immunohistochemistry and the presence of Th17 cells in the inflamed gingiva was confirmed by immunofluorescence confocal microscopy for CD4 and IL‐17 colocalization.Results:  Our data demonstrated elevated levels of IL‐17, TGF‐β, IL‐1β, IL‐6, and IL‐23 messenger RNA and protein in diseased tissues as well as the presence of Th17 cells in gingiva from patients with periodontitis. Moreover, IL‐17 and the bone resorption factor RANKL were abundantly expressed in the alveolar bone of diseased patients, in contrast to low detection in controls.Conclusion:  These results provided strong evidence for the presence of Th17 cells in the sites of chronic inflammation in human periodontal disease.
Cytokines in gingival crevicular fluid of adolescents and young adults
Authors: Kamma J. , Mombelli A. , Tsinidou K. , Vasdekis V. , Giannopoulou C. 
Published: December 2008

Background/aim:  The purpose of this study was to compare the levels of the cytokines interleukin‐1β (IL‐1β), IL‐4, and IL‐8 in the gingival crevicular fluid (GCF) of adolescents and young adults.Methods:  Twenty‐five adolescents aged between 14 and 16 years (Group A) and 20 periodontally healthy young adults aged between 25 and 35 years (Group B) were selected from two private dental clinics limited to pedodontics and periodontics respectively in Piraeus Greece. All subjects were systemically healthy. Clinical examination included probing pocket depth (PPD), presence or absence of plaque, and bleeding on probing (BOP). GCF was collected from four sites per subject. IL‐1β, IL‐4, and IL‐8, measured as total amounts (pg/30 s), were evaluated in 180 samples using a commercially available sandwich enzyme‐linked immunosorbent assay.Results:  IL‐1β mean levels of Groups A and B were adjusted for BOP and PPD. Differences of IL‐1β mean levels between the two age groups were statistically significant (F = 50.245, P < 0.001) in favour of Group A. Adolescents showed statistically significantly lower mean levels of IL‐4 than young adults in the presence of BOP (F = 10.690, P = 0.001). There was no statistically significant difference between adolescents and adults for the means of IL‐8 adjusted for BOP and plaque presence (F = 2.032, P = 0.161).Conclusions:  Within the limits of this study the differences reported in mean levels of IL‐1β and IL‐4 may be attributed to the different age status.
The host cytokine response to Porphyromonas gingivalis is modified by gingipains
Authors: Stathopoulou P. G. , Benakanakere M. R. , Galicia J. C. , Kinane D. F. 
Published: December 2008

Background/aims:  Clinical studies indicate that primary proinflammatory cytokines, such as interleukin‐1β (IL‐1β) are elevated in the gingival crevice around teeth with periodontitis but the secondary cytokines and chemokines, IL‐6 and IL‐8, are not. The human gingival epithelial cells (HGECs) lining the gingival sulcus respond to perturbation by microbes of dental plaque by releasing a wide range of cytokines. Porphyromonas gingivalis, a putative periodontal pathogen, possesses numerous virulence factors some of which directly impact on the host response. In the present study, we sought to determine how P. gingivalis influences the inflammatory cytokine responses.Methods:  HGECs were challenged with P. gingivalis and other putative periodontal pathogens, and the resultant production of IL‐1β, IL‐6, and IL‐8 was assayed by enzyme‐linked immunosorbent assay (ELISA). Culture supernatants and recombinant human cytokines were challenged with live P. gingivalis wild‐type and gingipain‐deficient strains and the resultant cytokine profile was assessed by ELISA and Western blot.Results:  We show here that primary HGECs challenged with live P. gingivalis result in high levels of IL‐1β but not the related secondary cytokines IL‐6 and IL‐8. We further demonstrate that cytokine response differences are the result of the action of P. gingivalis proteases, with lysine gingipain being the most effective.Conclusion:  We conclude that P. gingivalis, through lysine gingipain, can subvert the protective host proinflammatory response by direct cytokine degradation. Changes in the crevicular cytokine profile have consequences in periodontal disease pathogenesis that should be considered in the development of diagnostic and therapeutic modalities.
Multiple components contribute to ability of saliva to inhibit influenza viruses
Authors: White M. R. , Helmerhorst E. J. , Ligtenberg A. , Karpel M. , Tecle T. , Siqueira W. L. , Oppenheim F. G. , Hartshorn K. L. 
Published: December 2008

Introduction:  Saliva is a potentially important barrier against respiratory viral infection but its mechanism of action is not well studied.Methods:  We tested the antiviral activities of whole saliva, specific salivary gland secretions, and purified salivary proteins against strains of influenza A virus (IAV) in vitro.Results:  Whole saliva or parotid or submandibular/sublingual secretions from healthy donors inhibited IAV based on hemagglutination inhibition and neutralization assays. This differs from human immunodeficiency virus (HIV), for which only submandibular/sublingual secretions are reported to be inhibitory. Among purified salivary proteins, MUC5B, scavenger receptor cysteine‐rich glycoprotein 340 (salivary gp‐340), histatins, and human neutrophil defensins (HNPs) inhibited IAV at the concentrations present in whole saliva. In contrast, some abundant salivary proteins (acidic proline‐rich proteins and amylase) had no activity, nor did several other less abundant salivary proteins with known activity against HIV (e.g. thrombospondin or serum leukocyte protease inhibitor). Whole saliva and MUC5B did not inhibit neuraminidase activity of IAV and viral neutralizing and aggregating activity of MUC5B was potentiated by the neuraminidase inhibitor oseltamivir. Hence, MUC5B inhibits IAV by presenting a sialic acid ligand for the viral hemagglutinin. The mechanism of action of histatins requires further study.Conclusions:  These findings indicate that saliva represents an important initial barrier to IAV infection and underline the complexity of host defense activity of oral secretions. Of interest, antiviral activity of saliva against IAV and HIV differs in terms of specific glandular secretions and proteins that are inhibitory.
Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases
Authors: Fukada S. Y. , Silva T. A. , Garlet G. P. , Rosa A. L. , Da Silva J. S. , Cunha F. Q. 
Published: December 2008

Introduction:  Periapical chronic lesion formation involves activation of the immune response and alveolar bone resorption around the tooth apex. However, the overall roles of T helper type 1 (Th1), Th2, and T‐regulatory cell (Treg) responses and osteoclast regulatory factors in periapical cysts and granulomas have not been fully determined. This study aimed to investigate whether different forms of apical periodontitis, namely cysts and granulomas, show different balances of Th1, Th2 regulators, Treg markers, and factors involved in osteoclast chemotaxis and activation.Methods:  Gene expression of these factors was assessed using quantitative real‐time polymerase chain reaction, in samples obtained from healthy gingiva (n = 8), periapical granulomas (n = 20), and cysts (n = 10).Results:  Periapical cysts exhibited a greater expression of GATA‐3, while a greater expression of T‐bet, Foxp3, and interleukin‐10 (IL‐10) was seen in granulomas. The expression of interferon‐γ, IL‐4, and transforming growth factor‐β was similar in both lesions. Regarding osteoclastic factors, while the expression of SDF‐1α/CXCL12 and CCR1 was higher in cysts, the expression of RANKL was significantly higher in granulomas. Both lesions exhibited similar expression of CXCR4, CKβ8/CCL23, and osteoprotegerin, which were significantly higher than in control.Conclusion:  Our results showed a predominance of osteoclast activity in granulomas that was correlated with the Th1 response. The concomitant expression of Treg cell markers suggests a possible suppression of the Th1 response in granulomas. On the other hand, in cysts the Th2 activity is augmented. The mechanisms of periradicular lesion development are still not fully understood but the imbalance of immune and osteoclastic cell activity in cysts and granulomas seems to be critically regulated by Treg cells.
Association between Bifidobacteriaceae and the clinical severity of root caries lesions
Authors: Mantzourani M. , Fenlon M. , Beighton D. 
Published: December 2008

Background/aims:  The isolation of members of the family Bifidobacteriaceae (bifids) from oral samples has been sporadic and a recent cloning study has suggested that they are not detectable in root caries lesions.Methods:  To better understand the presence of bifids in root caries we obtained clinical samples (15 of each) from sound exposed root surfaces, leathery remineralizing root lesions, and soft active root lesions. We investigated each for the presence of bifids using a mupirocin‐containing selective medium and identified the isolates using 16S recombinant RNA sequencing.Results:  The proportion of bifids, as a percentage of the total anaerobic count, was significantly related to the clinical status of the sites sampled, being 7.88 ± 1.93 in the infected dentine from soft lesions, 1.61 ± 0.91 in leathery lesions, and 0.05 ± 0.39 in plaque from sound exposed root surfaces. Bifids were isolated from all soft lesions, 13 of 15 leathery lesions, and five of the plaque samples. Bifidobacterium dentium was isolated from four of the plaque samples, from 13 samples from leathery lesions, and from 12 of the 15 samples of infected dentine from the soft active lesions. Parascardovia denticolens and Scardovia genomospecies C1 were each isolated from samples associated with all three clinical conditions whereas Scardovia inopicata and Bifidobacterium subtile were both isolated from the infected dentine of the leathery and soft lesions. Bifidobacterium breve was isolated from the infected dentine of soft root caries lesions.Conclusion:  Bifids may be routinely isolated from root caries lesions using appropriate cultural methods.
Toll‐like receptors 2 and 5 in human gingival epithelial cells co‐operate with T‐cell cytokine interleukin‐17
Authors: Beklen A. , Sorsa T. , Konttinen Y. T. 
Published: December 2008

Background/aim:  Periodontitis begins as the result of perturbation of the gingival epithelial cells caused by subgingival bacteria interacting with the epithelial cells via pattern recognition receptors. Toll‐like receptors (TLRs) have been shown to play an important role in the recognition of periodontal pathogens so we have studied the interaction of TLR ligands with TLR2 and TLR5 for cytokine production in the cultures of gingival epithelial cells.Methods:  Immunohistochemistry was used for the localization of TLR2 and TLR5 in tissue specimens. Enzyme‐linked immunosorbent assays were performed to detect the levels of interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), released from gingival epithelial cell cultures following stimulation with TLR ligand alone or in combination with IL‐17.Results:  Both TLR2 and TLR5 were increased in periodontitis (2128 ± 159 vs. 449 ± 59 and 2456 ± 297 vs. 679 ± 103, respectively, P < 0.001) including gingival epithelial cells that stained strongly. Cultured gingival epithelial cells stimulated with their respective ligands (HKLM, a TLR2 ligand that is also found in Porphyromonas gingivalis, and flagellin, a TLR5 ligand that is also found in Treponema denticola) produced both IL‐1β and TNF‐α. To mimic T‐cell help, IL‐17 was added. This further greatly enhanced TLR ligand‐induced IL‐1β (P < 0.001) and TNF‐α (P < 0.01) production.Conclusions:  These findings show how pathogen‐associated molecular patterns, shared by many different periodontopathogenic bacteria, stimulate the resident gingival epithelial cells to inflammatory responses in a TLR‐dependent manner. This stimulation may be particularly strong in periodontitis and when T helper type 17 cells provide T‐cell help in intercellular cooperation.
Molecular analyses of bacterial DNA in extirpated heart valves from patients with infective endocarditis
Authors: Nomura R. , Nakano K. , Nemoto H. , Mukai T. , Hata H. , Toda K. , Yoshioka H. , Taniguchi K. , Amano A. , Ooshima T. 
Published: December 2008

Background/aims:  Infective endocarditis (IE) is caused by a microbial infection of the endothelial surface of the heart. Although blood culture examinations are commonly used to determine the associated bacterial species, molecular techniques, which enable rapid identification of targeted bacterial species, have recently been applied in clinical cases.Methods:  Nine heart valve specimens from IE patients (six subacute cases and three acute cases) were extirpated and collected, then bacterial DNA was extracted. Bacterial species in the specimens were determined by two different molecular methods and the results were compared with those from a conventional blood culture technique. In addition, a comparison between the two molecular methods was carried out using known numbers of six streptococcal species.Results:  The conventional blood culture method revealed the bacterial species in eight cases, while one was found to be negative. Multiple species were identified in most of the cases by both molecular methods; however, those specified by one method were not always consistent with those specified by the other. Furthermore, the species determined by the blood culture technique were not always identified by the molecular methods. We also found that the two molecular methods used in the present study were extremely sensitive to detect from 1 to 100 cells of individual oral streptococcal species.Conclusion:  Our results suggest that species specified by molecular methods may have disseminated incidentally into the bloodstream, so interpretation of such results should be carefully undertaken in clinical situations.
Zinc and copper play a role in coaggregation inhibiting action of Porphyromonas gingivalis
Authors: Tamura M. , Ochiai K. 
Published: December 2008

Background/aim:  We investigated the mechanisms of adherence of salivary and serum proteins, which mimic gingival crevicular fluid (GCF), to Porphyromonas gingivalis, and the effects of these adhered proteins on coaggregation and hemagglutination properties.Methods:  The amounts of salivary and serum proteins adhering to P. gingivalis were determined using 3H‐labeled and non‐labeled proteins. The coaggregation between P. gingivalis and Streptococcus oralis or Streptococcus gordonii was observed. Hemagglutination was evaluated using sheep erythrocytes. Proteins that interacted with zinc or copper in saliva and serum and on P. gingivalis were examined using sodium dodecyl sulfate–polyacrylamide gel electrophoresis.Results:  The amount of salivary or serum proteins that adhered to the surface of P. gingivalis strains was increased by cations, especially zinc and copper ions. The pretreatment of bacterial cells with salivary or serum proteins before the assay inhibited coaggregation with gram‐positive bacteria and hemagglutination. These phenomena were enhanced by the presence of zinc or copper ions during the pretreatment of P. gingivalis with proteins. We detected protein bands that were related to these cations in saliva and serum and on P. gingivalis.Conclusions:  Our findings suggest that zinc and copper ions markedly enhanced the adhesion and accumulation of salivary and serum proteins on cells of P. gingivalis and inhibited the coaggregation and hemagglutination of P. gingivalis. These cations might be useful for limiting the settlement of P. gingivalis in the gingival sulcus with the goal of preventing periodontal disease.
THE OXYGEN TENSION OF CEREBROSPINAL FLUID IN PATIENTS WITH BRAIN LESIONS
Authors: Rossanda M. , Gordon E. 
Published: December 2008

SUMMARYCerebrospinal‐fluid oxygen tension as a possible index of the oxygen supply to the brain was measured in 75 patients. The mean CSF p02 in comatose patients was significantly lower than in conscious patients, although arterial p02 was only moderately decreased. The cerebral venous p02 was slightly increased in coma. The calculated mean capillary p02 was approximately the same in comatose and conscious patients. The capillary‐CSF p02 difference was consequently greater in comatose than in conscious patients.These data suggest the presence of CBF maldistribution and possibly a hindrance to gas diffusion in the severely diseased brain.Artificial ventilation with high oxygen concentration and moderate hyperventilation is recommended for the treatment of these patients.ZUSAMMENFASSUNGBei 75 Patienten wurde die Sauerstoffspannung im Liquor cerebro spinalis als moglicher Gradmesser der Sauerstoffzufuhr zum Gehirn gemessen. Der mittlere CSF‐p02 war bei komatosen Patienten significant niedriger als bei wachen Patienten, wogegen der arterielle p02 nur massig vermindert war. Der Sauerstoflfdruck in den Gehirnvenen war im Koma leicht erhoht. Der errechnete mittlere Kapillar‐p02 war bei komatosen und wachen Patienten annfihernd gleich. Die SauerstofF‐Druckdifferenz zwischen Kapillarblut und Liquor war folglich bei den komatosen Patienten grosser als bei den wachen.Diese Befunde deuten auf eine Fehlverteilung des Liquors und auf ein mogliches Hindernis fur die Gasdiffusion im schwergeschadigten Gehirn hin.Kunstliche Beatmung mit hoher Sauerstoffkonzentration und massige Hyperventilation werden fiir die Behandlung dieser Patienten empfohlen.