bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathogenetic Roles of Angiogenic Factors in Pyogenic Granulornas in Pregnancy Are Modulated by Female Sex Hormones
Authors: Yuan Kuo , Wing Lih‐Yuh C. , Lin Ming T.
Published: February 2005

Background: An abundance of microvessels is the major phenotype of pyogenic granuloma, which has been considered a hormone‐related lesion based on clinical observations. Although angiogenic factors and inflammatory cytokines have been implied to play roles in the pathogenesis of pyogenic granuloma, their links to female steroid hormones still remain to be elucidated. Since apoptosis is important in limiting inflammation, we also investigated whether steroid hormones could protect granuloma cells from apoptosis and, therefore, lead to over‐reactive inflammatory response.

Methods: We employed immunoassays in a series of experiments, including human pyogenic granuloma in pregnancy, mouse air pouch granuloma and U937 (monoblastoid) cells in culture to clarify the relationship among vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐ 1 beta and female steroid hormones in granuloma formation. The apoptotic rates were analyzed in vivo and in vitro by terminal deoxynucleotidyl transferase‐mediated deoxyuridine 5‐triphosphate nick end labeling. (TUNEL) and flow cytometry, respectively.

Results: Both in human and animal studies, the immunoassays (enzyme‐linked immunoabsorbent assay [ELISA] and irnmunohistochemistry) detected significantly more VEGF and bFGF and less TNF‐α in hormones than the control group, while TUNEL assay revealed less apoptotic cells in groups with pregnancy levels of hormones. In vitro, progesterone enhanced the expression of VEGF in LPS‐treated U937 cells. Both estrogen and progesterone inhibited the apoptosis of U937 cells triggered by exogenous TNF‐α

Conclusions: Female steroid hormones may have dual effects on the pathogenesis of pyogenic granuloma in pregnancy. The hormones not only enhance the expression of angiogenic factors in inflamed tissue, but also decrease apoptosis of granuloma cells to extend angiogenic effect. J Periodontol 2002;73:701‐708.
Function of Laminins and Laminin‐Binding Integrins In Gingival Epithelial Cell Adhesion
Authors: Pakkala Tuomas , Virtanen lsmo , Oksanen Jaana , Jones Jonathan C.R. , Hormia Marketta
Published: February 2005

Background: In human gingiva, epithelial cells attach to their adjacent tissues by means of specialized molecular adhesion complexes and a basement membrane. Little is known about the synthesis of adhesion proteins by gingival keratinocytes; we, therefore, studied how cultured immortalized gingival epithelial cells produce laminins and express laminin‐binding integrins. We presumed that different laminins and integrins would be involved in the adhesion of gingival epithelial cells.

Methods: We cultured gingival keratinocytes and studied their production of laminins and expression of integrins using immunofluorescence microscopy, immunoprecipitation, and immunoblotting methods and by quantitative cell adhesion experiments. We also studied how gingival tissue expresses these adhesion proteins in vivo by using immunofluorescence microscopy.

Results: In immunofluorescence microscopy, the cells were seen to organize chains of laminin‐5 (α3β3γ2) to extracellular patches, whereas the α5 chain of laminin‐10 (α5βlγl) could only be seen intracellularly. Of the laminin‐binding integrin subunits, integrin α6 subunit was organized to dotted arrays, typical of prehemidesmosomal adhesions, whereas integrin α3 subunit was located at cell‐cell junctions, in prehemidesmosomal structures, and at some locations also in small focal‐contact like patches. lntegrin β1 subunit was found at cell‐cell junctions and in focal contacts. lmmunoprecipitation experiments showed that the cells synthesize and secrete chains of laminin‐5 and laminin‐ 10. In quantitative cell adhesion experiments, the cells adhered efficiently to these laminins by using cooperatively integrin α3β1 and α6β1 integrin complexes. None of the other known laminin‐binding integrin subunits appeared to be significantly involved in cell adhesion to these laminin isoforms.

Conclusions: Our results provide new information on gingival epithelial cell adhesion and extracellular matrix production and may thus aid in the understanding of periodontal physiology. J Periodontol 2002;73:709‐719.
The Role of Soluble Interleukin (IL)‐6 Receptor in Mediating the effects of IL‐6 on Matrix Metalloproteinase‐1 and Tissue Inhibitor of Metalloproteinase‐1 Expression by Gingival Fibroblasts
Authors: Irwin Chris R. , Myrillas Theofilos T. , Traynor Patrick , Leadbetter Nicola , Cawston Timothy E.
Published: February 2005

Background: Interleukin‐6 (IL‐6) is a multifunctional cytokine thought to play a role in the tissue destruction that characterizes periodontal disease. IL‐6 exerts its cellular effects through a cell‐surface receptor which also exists in a soluble from (sIL‐6r). This study investigated the effects of IL‐6 on matrix metalloproteinase (MMP)‐1 activity in gingival fibroblast cultures, specifically determining the role of the sIL‐6r in mediating these actions.

Methods: Fibroblasts were grown to confluence, washed in Hank's balanced saline solution (HBSS), and then cultured for 72 hours in serum‐free medium supplemented with 0.2% bovine serum albumin, 1 µg/ml Escherichia coli LPS and containing various combinations of IL‐6 and its soluble receptor over the concentration range 0 to 1,000 ng/ml. MMP‐1 and tissue inhibitor of MMP (TIMP)‐1 protein levels in the conditioned medium were assessed by enzyme‐linked immunosorbent assay (ELISA) and collagenolytic activity determined using a 3H‐acetylated type 1 collagen degradation assay.

Results: Results indicated that the addition of IL‐6 alone to cultures, over the concentration range 0 to 1,000 ng/ml, had no significant effect on MMP‐1 protein expression. However, addition of IL‐6 in combination with its soluble receptor resulted in a statistically significant, dose‐dependent upregulation in MMP‐1 expression. The IL‐6/slL‐6r combination also induced a significant increase in collagenolytic activity in cultures. IL‐6 and slL‐6r, either alone or in combination, had no marked effect on TlMP expression or cell growth.

Conclusions: These data strongly suggest that future clinical studies investigating the role of IL‐6 in periodontal disease must also determine the levels of slL‐6r within the periodontal tissues. J Periodontol 2002;73:741‐747.
Vascular Endothelial Growth Factor and Transforming Growth Factor‐α and ‐β1 Are Released From Human Cultured Gingival Epithelial Sheets
Authors: Momose Manabu , Murata Masashi , Kato Yumi , Yamazaki Kazushisa , Shinohara Chikara , Yoshie Hiromasa
Published: February 2005

Background: It has been demonstrated that human cultured epithelial sheets prepared by tissue engineering techniques provide useful graft material for wound healing and tissue regeneration. However, limited information is available with regard to biological effects such as release of growth factors from human cultured gingival epithelial sheets (HCGES). The purpose of this study was to measure the levels of growth factors released from HCGES into culture medium

Methods: Twenty patients aged 44 to 71 years with generalized chronic periodontitis were recruited, and their gingival tissues obtained during periodontal flap surgery. The levels of vascular endothelial growth factor (VEGF), transforming growth factor‐α and ‐βl (TGF‐α and ‐βl), and epidermal growth factor (EGF) released into the culture medium were determined using enzyme‐linked immunosorbent assay at the just confluent (Tl) and the adequate stratification (T2) culture stages. The medium without cells was collected as a control (TO) statistical tests were performed by analysis of variance and sheffé multiple range test among TO, T1, and T2.

Results: Significantly higher levels of VEGF and TGF‐α were observed at T1 and T2 compared to To (P<0.001). In addition, there was a significant difference in the TGF‐α levels between T2 and T1 (P<0.001). TGF‐βl at T1 was significantly higher in comparison to T0 (P<0.0l). EGF had been released only in a small amount at T2.

Conclusion: This study indicates that meaningful amounts of VEGF and TGF‐α and ‐βl are released from HCGES, which suggests potential for promoting wound healing and tissue regeneration after grafting. J Periodontol 2002;73:748‐753.
Comparative Study of Buccal Dehiscence Defects in Immediate, Delayed, and Late Maxillary Implant Placement With Collagen Membranes: Clinical Healing Between Placement and Second‐Stage Surgery
Authors: Nemcovsky Carlos E. , Artzi Zvi
Published: February 2005

Background: Implants can be placed at the time of tooth extraction (immediate), after several weeks (delayed), or after complete healing (late). The purpose of this study was to evaluate clinical bone healing of buccal dehiscence‐type defects around maxillary implants placed together with bioabsorbable collagen barrier membranes and bone graft at the 3 time points.

Methods: Three implant placement protocols were compared: immediate procedures primarily closed by a rotated split palatal flap (19 patients, 23 implants; group 1); delayed sites closed by a rotated (full‐thickness) palatal flap at the time of tooth extraction (25 patients, 39 implants; group 2); and late implantation (22 patients, 40 implants; group 3). One to 3 proximal implants were simultaneously placed. Defect height and width were measured at the time of implant placement and at second‐stage surgery. Surface area was calculated as half ellipses.

Results: The best results were obtained with delayed implantation. The mean percentage of the reduced defect height for groups 1, 2, and 3 was 77.4% ± 16.92%, 88.8% ± 15.29%. and 75.2% ± 17.99%, respectively, and the mean percentage area of the reduced defect was 90.2% ± 9.1 5%, 95.6% ± 8.73%, and 87.6% ± 11.48%, respectively. Differences between groups were statistically significant. The mean percentage of the reduced defect height and area was significantly smaller when there was spontaneous implant cover screw exposure. Single rather than multiple implant placement led to significantly better results.

Conclusions: Timing of placement, number of simultaneously placed implants, and spontaneous implant exposure significantly influence clinical bone healing around maxillary implants placed together with augmentation procedures. J Periodontol 2002;73:754‐761.
Permeability of Streptococcus mutans and Actinobacillus actinomycetemcomitans Through Guided Tissue Regeneration Membranes and Their Effects on Attachment of Periodontal Ligament Cells
Authors: Hung Shan‐Ling , Lin Yi‐Wen , Wang Yi‐Hui , Chen Yen‐Ting , Su Cheng‐Yao , Ling Li‐Jane
Published: February 2005

Background: Microbial colonization on barrier materials used in guided tissue regeneration (GTR) may adversely affect treatment outcomes. The purposes of this study were: 1) to compare the invasion of Streptococcus mutans and Actinobacillus actinomycetemcomitans through 3 GTR membranes, composed of expanded polytetrafluoroethylene (ePTFE; non‐resorbable), a glycolide fiber composite, and type I collagen (both bioabsorbable), and 2) to explore the effects of bacteria on the attachment of periodontal ligament (PDL) fibroblasts onto these membranes.

Methods: Bacterial permeability was analyzed using a tube capped with a GTR membrane as a septum and filled with media. The tube was then placed in a bigger tube inoculated with S. mutans or A. actinomycetemcomitans. The passage of bacteria through the membranes into the inner tube was monitored. For cellular attachment experiments, primary human PDL cells were placed onto the GTR membranes with or without bacteria. Attached cells were analyzed by scanning electron microscopy (SEM) analysis.

Results: The ePTFE membrane had the best barrier effects followed by the collagen membrane and then the glycolide fiber composite membrane. Moreover, S. mutans passed through these membranes faster than A. actinomycetemcomitans. The attachment of PDL cells on the 3 membranes was also varied. The ePTFE membrane was the worst substrate for PDL fibroblast attachment. Moreover, both bacteria influenced the cellular attachment on the GTR membranes.

Conclusions: Differences in the behavior of 3 GTR membranes penetrated by S. mutans and A. actinomycetemcomitans were demonstrated. The results suggest that attachment of PDL cells was affected on bacterial‐contaminated GTR membranes, which may alter healing following membrane exposure. J Periodontol 2002;73:843‐851.
A Study of the Initial Attachment and Subsequent Behavior of Rat Oral Epithelial Cells Cultured on Titanium
Authors: Shiraiwa Masaru , Goto Tetsuya , Yoshinari Masao , Koyano Kiyoshi , Tanaka Teruo
Published: February 2005

Background: The seal between an implant and the oral epithelium is an important factor for successful implant therapy. The purpose of this study was to evaluate the initial attachment and subsequent behavior of rat oral epithelial (OE) cells on pure titanium (Ti) used for dental implants.

Methods: OE cells derived from 4‐day‐old rats were cultured on Ti, polystyrene culture dishes, and glass coverslips. The number of attached cells, cell areas, number of colonies, and proliferation rates were measured. Additionally, immunostaining of vinculin and laminin‐5 (LN5) was performed, and LN5‐immunoreactive areas were measured.

Results: After 24 hours of culture, there were fewer cells attached to the Ti than to the polystyrene dishes or glass coverslips, and the area of cells was greater on the polystyrene than on the Ti or glass. OE cells reached their maximum proliferation rate after 48 hours of culture on the polystyrene and glass, and after 72 hours on Ti. LN5 was deposited behind cells as they migrated, and the LN5‐immunoreactive area was smaller on Ti than on polystyrene after 96 hours of culture.

Conclusions: The initial attachment of OE cells to Ti was inferior to that on polystyrene or glass, and the OE cell migration area indicated by the deposition of LN5 was smaller on Ti than on the other materials. Therefore, this study suggests that further improvement of Ti surface properties is needed for rapid attachment and spreading of oral epithelium to dental implants. J Periodontol 2002;73:852‐860.
Detection of Porphyromonas gingivalis DNA in Aortic Tissue by PCR
Authors: Stelzel Michael , Conrads Georg , Pankuweit Sabine , Maisch Bernhard , Vogt Sebastian , Moosdorf Rainer , Flores‐de‐Jacoby Lavin
Published: February 2005

Background: Periodontopathogens may play a role in the etiology of cardiovascular disease. The aim of the present study was to investigate biopsies of aortic tissue for the presence of periodontopathogens.

Methods: Samples taken from the aortas of 26 patients connected to a heart‐lung machine during open‐heart surgery were analyzed in a gene‐diagnostics laboratory by polymerase chain reaction. Immediately after biopsy, the samples were transferred into liquid nitrogen and stored at −80°C. 16S rRNA gene‐directed primers were used for general detection of bacterial cells, and specific primers for detection of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Questionable amplificons were verified by Southern hybridization using DNA probes.

Results: Bacterial DNA was found in 23 of 26 (88.5%) samples, in most cases only in concentrations around the detection limit. Four samples were clearly positive for P. gingivalis; A. actinomycetemcomitans was not detected.

Conclusion: These results might indicate a link between periodontopathogens entering the cardiovascular system and cardiovascular disease. J Periodontol 2002;73:868‐870.
Eikenella corrodens in Subgingival Plaque: Relationship to Age and Periodontal Condition
Authors: Suda Reiko , Lai Chern‐Hsiung , Yang Hui‐Wen , Hasegawa Kohji
Published: February 2005

Background: The purpose of this study was to determine the prevalence and distribution of Eikenella corrodens (E. corrodens) in subgingival plaque in different age and periodontitis groups and to examine whether its presence is related to periodontal diseases.

Methods: A total of 273 subgingival plaque samples from 213 periodontitis patients and 60 healthy subjects were assessed. Smears from each plaque sample were made and E. corrodens was detected by means of indirect immunofluorescent technique. Mean percentage of E. corrodens per total bacteria (distribution) was calculated in each sample. The prevalence (% of positive samples) and distribution of E. corrodens were statistically analyzed based on age or diagnosis by means of Fisher's exact test and analysis of variance (ANOVA).

Results: Prevalence of E. corrodens decreased by age in the healthy control group; however, prevalence did not change in periodontitis groups. Distribution of E. corrodens was highest in juvenile periodontitis (JP) (2.3 ± 1.5%) followed by post‐JP (1.7 ± 2.1%), prepubertal periodontitis (1.4 ± 1.1%), rapidly progressive periodontitis (0.8 ± 0.7%), adult periodontitis (0.7 ± 0.6%), and healthy subjects (0.3 ± 0.3%) (ANOVA, P <0.0001). The <20‐year‐old age group with periodontitis showed the highest distribution of E. corrodens (2.2 ± 1.6%) compared to the older age groups who were either healthy or had periodontitis (ANOVA, P <0.0001).

Conclusions: Since the distribution of E. corrodens is significantly higher in JP, post‐JP, and PP, E. corrodens might play an important role in the occurrence or progression of periodontitis in young patients. J Periodontol 2002;73:886‐891.
Immunohistochemical Analysis of Lymphocyte Subpopulations in Cyclosporin A‐Induced Gingival Overgrowth
Authors: Bulut Sule , Alaaddinoglu Emine E. , Bilezikç Banui , Demirhan Beyhan , Moray Gokhan
Published: February 2005

Background: Cyclosporin A (CsA) is an immunosuppressive agent that is known to induce gingival overgrowth (GO). Pharmacological, genetic, immunologic, and inflammatory factors seem to be involved in the complex pathogenesis of drug‐induced GO. Lymphocyte subpopulations in human gingival connective tissue have been implicated in the pathogenesis of inflammatory periodontal diseases. One purpose of this study was to quantify CD4, CD8‐, CD57‐, and epithelial membrane antigen (EMA)‐positive cells in the gingiva of renal transplant recipients treated with CsA, and compare them to findings in healthy controls. A second aim was to correlate cell numbers with clinical findings.

Methods: The study included 19 kidney recipients who were taking CsA and had significant GO (CsAGO+), 13 recipients who were taking CsA but showed no GO (CsAGO−), and 14 systemically healthy individuals with gingivitis (C). Sections from gingival biopsies were incubated with monoclonal antibodies for CD4, CD8, EMA, and CD57, and then analyzed using the avidin‐biotin complex method. In each specimen, the mononuclear cell types were quantified and their distribution was evaluated in 3 separate tissue zones: S = subepithelial connective tissue beneath the sulcular epithelium; O = subepithelial connective tissue beneath the oral epithelium; and M = middle connective tissue.

Results: There were no significant differences among the groups with respect to the numbers of CD4+ and CD8+ cells in each of the 3 zones (P >0.05). In zone S, the CsAGO+ group had significantly more EMA‐positive cells than either the C or CsAGO− groups (P <0.05). There were significant differences among the groups regarding numbers of CD57+ (natural killer) cells in zone M, with the lowest cell numbers in the CsAGO+ patients (P <0.05).

Conclusions: The results showed that low numbers of natural killer cells are important in the expression of plaque‐induced inflammatory changes in CsA‐associated GO. It appears that these cells may influence the drug's ability to induce proliferative activity. J Periodontol 2002;73:892‐899.
Factors That Modulate the Effects of Bone Morphogenetic Protein‐Induced Periodontal Regeneration: A Critical Review
Authors: King Gaston N. , Cochrant David L.
Published: February 2005

The healing process initiated by a single molecular species of bone morphogenetic protein (BMP) such as BMP‐2 or BMP‐7 sets in motion a cascade of cellular events resulting in differentiation of progenitor cells into phenotypes involved in periodontal regeneration. For example, animal studies show that a single dose of recombinant human (rh) BMP‐2 increases the rate of normal intramembranous bone formation and enhanced cementum formation during periodontal wound healing. However, the optimal effects of BMPs are modulated by a range of factors that need careful evaluation in clinical studies. These factors include the influence of root conditioning, occlusal loading, BMP dose, and the release characteristics of the carrier as well as the suitability of the model to evaluate the efficacy of BMPs. Each of these factors may affect the rate of BMP‐induced osteogenesis and cementogenesis and subsequent periodontal ligament (PDL) formation during the early and late stages of periodontal wound healing. Although BMP‐2 initiates stem cells along an osteogenic pathway, the dose may have to be of sufficient concentration to ensure other growth and differentiation factors do not redirect or retard the osteogenic potential of the cell. Understanding when to manipulate the cell's differentiation pathway with the application of single or multiple doses of BMPs at the appropriate concentration is required to optimize the effect of BMPs in periodontal wound healing. Therefore, different release profiles from the same carrier may be particularly important in tissues with mixed cell populations such as in the periodontium, where similar tissues like bone and cementum grow at different rates. Furthermore, treatment of intrabony defects with BMPs are likely to not only require appropriate temporal release of the BMP(s), but also a carrier that can serve as a template for new tissue formation providing space maintenance and supporting the mucoperiosteal flap. Many of these issues have not been adequately addressed from a periodontal standpoint; therefore the purpose of this review is to clarify our current understanding of the factors that are likely to modulate the effects of BMP‐induced periodontal regeneration. Moreover, assessing the importance of these factors is essential prior to conducting expensive human clinical trials. J Periodontol 2002;73:925‐936.
A Retrospective Case Series Comparing the Use of Demineralized Freeze‐Dried Bone Allograft and Freeze‐Dried Bone Allograft Combined With Enamel Matrix Derivative for the Treatment of Advanced Osseous Lesions
Authors: Rosen Paul S. , Reynolds Mark A.
Published: February 2005

Background: Combined regeneratbe approaches have been used for treating advanced osseous lesions around teeth. The aim of combining treatments is to enhance both clinical predictability and regeneratbe outcome compared to a monotherapeutic approach. This case series from a prioate practice reports on the clinical efficacy of an enamel matrix derioatioe (EMD) combined with either demineralized freeze‐dried bone allograft (DFDBA) or freeze‐dried bone allograft (FDBA) in the treatment of adoanced infrabony lesions. The aduanced lesions were veneered by a rapidly formed absorbable polymer barrier of poly (DL‐lactide) to enhance graft containment.

Methods: A total of 22 consecutiue patients, each contributing one infrabony lesion, are reported. After patients completed presurgical preparation, the infrabony lesions were surgically treated with a combined approach that included root surface treatment with citric acid. The two groups differed in their composite graft; one receiued DFDBA‐EMD (n = 10) and the other received FDBA‐EMD n = 12). Patients followed a stringent postoperatioe protocol and were eoaluated 6 months postsurgery. Clinical outcomes were assessed by changes in clinical attachment leoel (CAL) and probing depth (PO) from pretreatment. Surgical re‐entry of seoeral sites was possible in each group.

Results: CAL at pretreatment measured 9.2 ± 1.3 mm and 9.1 ± 1.9 mm for DFDBA‐EMD and FDBAEMD groups, respectiuely, with corresponding PD of 8.4 ± 1.6 mm and 8.9 ± 2.0 mm for each group. At 6 months post‐treatment, CALs were reduced to 4.7 ± 1.3 mm and 3.8 ± 1 .O mm for DFDBA‐EMD and FDBAEMD groups, respectiuely; with corresponding PD decreased to 3.0 ± 0.8 mm and 3.2 ± 1.0 mm. Relative improoements in CAL for the DFDBA‐EMD and DFDBA‐EMD groups were 49.1 % ± 11.O% and 57.3% ± 9.4%, respectioely (P <0.07).

Conclusions: This case series demonstrates the clinical benefits of using a combined therapeutic approach in which a biologic mediator (EMD) was combined with either DmBA or FDBA. In this limited case series, a trend was obseroed towards greater improoement in clinical attachment leoel gain in adoanced infrabony defects when EMD was combined with FDBA as compared to DFDBA. Larger prospective controlled clinical trials are needed to determine if differences exist in the relative efficacy of DFDBA uersus FDBA in combination with EMD. J Periodontol 2002;73:942‐949.
Bone Repair Following Recombinant Human Bone Morphogenetic Protein‐2 Stimulated Periodontal Regeneration
Authors: Selvig Knut A. , Sorensen Rachel G. , Wozney John M. , Wikesjö Ulf M.E.
Published: February 2005

Background: Recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in an absorbable sponge (ACS) carrier is currently being evaluated as candidate therapy for periodontal regeneration. The objective of this study was to characterize, in some detail, tissue reactions following surgical implantation of rhBMP‐2/ACS into periodontal defects.

Methods: Four young adult, male beagle dogs with surgically induced, bilateral, critical size, supraalveolar, mandibular premolar defects sequentially received rhBMP‐2/ACS (rhBMP‐2 at 0.2 mg/ml) in right and left jaw quadrants. After 4 or 8 weeks of healing, experimental teeth with surrounding tissues were harvested and processed for light and transmission electron microscopy.

Results: Surgical implantation of rhBMP‐2/ACS into large supraalveolar periodontal defects resulted in a variable tissue response without marked difference between 4‐ and 8‐week observations. New bone, exceeding the volume of the normal alveolar process, had formed within 4 weeks. The regenerated bone tissue consisted of finely trabeculated woven bone. Marrow spaces exhibited a continuous lining of osteoblasts, osteoclasts, and resting cells. The marrow spaces contained numerous large, thin‐walled vessels but were almost devoid of collagen fibrils or fibroblasts. Large voids (seromas) encountered in the newly formed bone were free of structured elements except for occasional aggregates of effete erythrocytes. A variety of tissue reactions were observed along the root surface including areas of resorption, areas of hard tissue deposition, and areas without resorptive or appositional activity. Ankylosis was a frequent observation, although areas showing characteristics of a periodontal ligament with a fine layer of acellular fiber cementum and occasional inserting Sharpey's fibers were also observed. Osteoblasts facing the root surface often appeared to be in a highly active state judged by their cuboidal shape, well‐developed endoplasmic reticulum and numerous mitochondria, and the presence of an adjacent layer of preosteoblasts. Conspicuous bundles of wide collagen fibrils near the dentin surface as well as within the marrow spaces were considered to represent remnants of the ACS. These fibrils were associated with areas of mineralization as verified by examination of undecalcified specimens.

Conclusions: rhBMP‐2/ACS elicits a rapid osteoinductive process throughout the implant as well as along and onto the instrumented adjacent root surface. Lamellated trabecular bone was the predominant regenerated tissue. A typical cementum‐periodontal ligament‐alveolar bone relationship was a rare observation. The great variability in histological tissue response along the instrumented root surface indicates that the stimulus to hard tissue formation resided primarily in the rhBMP‐2/ACS implant rather than in the root surface. J Periodontol 2002;73:1020‐1029.
Comparison Between Patient Expectation Before and Satisfaction After Periodontal Surgical Treatment
Authors: Lee Jae‐Mok , Song Keun Bae , Sohn Hee Yong , Jeong Seong Hwa , Kwon Ho Kwen
Published: February 2005

Background: The purposes of this study were to compare patient expectation before periodontal surgical treatment with their level of satisfaction afterward on the basis of a self‐reported questionnaire, and to analyze the relationship between various satisfaction factors and periodontal surgical treatment.

Methods: Information was obtained from 33 patients initially diagnosed with chronic periodontitis. The survey was completed twice by each patient, once before and once after modified Widman flap surgery.

Results: The satisfaction scores of items related to patient expectation of treatment outcome decreased significantly following surgery. The patients also expressed great dissatisfaction with items regarding disease prevention such as “desire for knowledge of periodontal disease prevention” and “desire for knowledge of recurrence control methods.” However, some items such as ”dental pain during treatment,” “dental fear of treatment,” and ”cost of treatment” increased significantly after treatment. The total mean score of general satisfaction before treatment was 2.65, decreasing to 2.60 after treatment.

Conclusions: Among the 5 subscales, any increase in patient satisfaction related to the treatment factors is difficult to achieve, but we should be able to raise the satisfaction level of our patients through improvement of the preventive measure factors. J Periodontol 2002;73:1037‐1042.
An Update on HIV and Periodontal Disease
Authors: Ryder Mark I.
Published: February 2005

With the advent of newer pharmacological approaches to the treatment of human immunodeficiency virus (HIV) infection, the incidence and progression of both atypical and conventional periodontal diseases are changing. The incidence of necrotizing periodontitis and gingival diseases of fungal origin appears to be on the decline as a result of these therapies that have led to increased life spans for HIV patients. However, in cases where these therapies lose their effectiveness and HIV patients relapse into an immunosuppressed state, these conditions may recur. Recent evidence has shown that HIV patients with more conventional periodontal diseases such as chronic periodontitis may have increased attachment loss and gingival recession when compared to their HIV‐negative counterparts. This pattern of loss of periodontal support may be due in part to a diffuse invasion of opportunistic bacterial infections, viruses, and fungi into the gingival tissue, leading to a more elevated and more diffuse destructive inflammatory response in the periodontal soft and hard tissues. While the accepted approaches to treating the spectrum of periodontal diseases in HIV patients remain essentially unchanged over the past 15 years, the impact of newer systemic therapies on patient immunocompetence may influence treatment decisions. J Periodontol 2002;73:1071‐1078.
Peripheral Odontogenic Keratocyst: A Report of 2 Cases
Authors: Ide Fumio , Shimoyama Tetsuo , Horie Norio
Published: February 2005

Background: Occurrence of a gingival cyst in adults that exhibits the histopathologic hallmarks of an odontogenic keratocyst (OKC) is rare.

Methods: Two cases of primary soft tissue OKC in an adult female are described. Both presented as an asymptomatic small nodule on the buccal gingiva of the anterior mandible.

Results: After simple excision, no recurrence was observed.

Conclusions: All available data indicate that, irrespective of the nomenclature, peripheral OKC should be included under the histopathological spectrum of gingival cysts in the adult. J Periodontol 2002;73:1079‐1081.
Intermittent Cigarette Smoke Inhalation May Affect Bone Volume Around Titanium Implants in Rats
Authors: Nociti Francisco Humberto , Neto João Batista César , Carvalho Marcelo , Sallum Enilson Antonio , Sallum Antonio Wilson
Published: February 2005

Background: A negative influence of smoking on implant outcomes has been reported. This animal study investigated the influence of cigarette smoke on osseointegration and newly formed bone within implant threads.

Methods: Male Wistar rats were included in the study. After anesthesia, the tibiae surface was exposed and a screw‐shaped titanium implant (4.0 mm in length; 2.2 mm in diameter) was placed bilaterally. The animals were randomly assigned to group 1, control, or group 2, intermittent cigarette smoke inhalation. The animals were sacrificed after 60 days and undecalcified sections obtained. The degree of bone‐to‐implant contact (BIC) and the bone area (BA) within the implant threads were measured in the cortical (zone A) and cancellous bone (zone B) areas.

Results: A slight difference in the BIC was noted between the groups, but this was not statistically significant either in zone A or in zone B (Mann‐Whitney test, P >0.05). In contrast, the BA close to the implant significantly decreased in both zones for group 2 (84.73% ± 4.77 versus 79.85% ± 6.17, zone A in groups 1 and 2, respectively, and 32.01% ± 6.62 versus 20.71% ± 8.57, zone B in groups 1 and 2, respectively, P <0.05).

Conclusion: Within the limits of the present study, intermittent cigarette smoke inhalation may result in a poor bone quality around titanium implants inserted in rats. J Periodontol 2002;73:982‐987.
Resolution of Crevicular Fluid Leukocyte Activity in Patients Treated for Aggressive Periodontal Disease
Authors: Buchmann Rainer , Hasilik Andrej , Van Dyke Thomas E. , Lange Dieter E.
Published: February 2005

Background: Enhanced neutrophil responses play a critical role in the activation of the innate immune system and causation of aggressive periodontitis (AgP). The hypothesis that comprehensive periodontal treatment expedites resolution of amplified leukocyte activity and facilitates the reconstitution of periodontal health was tested.

Methods: Four different gingival crevicular fluid (GCF) markers from 14 patients were characterized prior to and at 3, 6, 12, 24, and 36 months after periodontal therapy. GCF myeloperoxidase (MPO), beta‐N‐acetyl‐hexosaminidase (beta‐NAH), and beta‐glucuronidase (beta‐G) were determined spectrophotometrically, and cathepsin D (CD) by liquid scintillation counting using [14C] hemoglobin as substrate. The primary outcome was long‐term stability of periodontal health.

Results: In untreated AgP, GCF markers were significantly amplified (MPO: 1.9‐fold; beta‐NAH: 1.3‐fold; beta‐G: 1.7‐fold; CD: 4.7‐fold). Following periodontal therapy, the leukocyte activity was significantly dampened (0.3‐ to 0.5‐fold), and paralleled with a sustained improvement of periodontal health (P <0.05). Thereafter and at 3 years, GCF leukocyte responses remained on a physiologic low level compatible to normal immune function.

Conclusions: Comprehensive treatment of AP induces a downregulation of amplified crevicular neutrophil activity. The release of the innate immune system from exacerbating damage elicits a successful reconstitution of long‐term periodontal health with no setbacks seen after 3 years. J Periodontol 2002;73:995‐1002.
The Role of Gingipains in the Pathogenesis of Periodontal Disease
Authors: Imamura Takahisa
Published: February 2005

Gingipains are trypsin‐like cysteine proteinases produced by Porphyromonas gingivalis, a major causative bacterium of adult periodontitis. HRgpA (95 kDa) and RgpB (50 kDa), products of 2 distinct but related genes, rgpA and rgpB, respectively, are specific for Arg‐Xaa peptide bonds. Kgp, a product of the kgp gene, is specific for Lys‐Xaa bonds. HRgpA and Kgp are non‐covalent complexes containing separate catalytic and adhesion/hemagglutinin domains, while RgpB has only a catalytic domain with a primary structure essentially identical to that of the catalytic subunit of HRgp. HRgpA and RgpB induce vascular permeability enhancement through activation of the kallikrein/kinin pathway and activate the blood coagulation system, which, respectively, are potentially associated with gingival crevicular fluid production and progression of inflammation leading to alveolar bone loss in the periodontitis site. Kgp is the most potent fibrinogen/fibrin degrading enzyme of the 3 gingipains in human plasma and is involved in the bleeding tendency at the diseased gingiva. HRgpA activates coagulation factors and degrades fi‐brinogen/fibrin more efficiently than RgpB due to the adhesion/hemagglutinin domains, which have affinity for phospholipids and fibrinogen. Gingipains degrade macrophage CD14, thus inhibiting activation of the leukocytes through the lipopolysaccharide (LPS) receptor, and thereby facilitating sustained colonization of P. gingivalis. Gingipains play a role in bacterial housekeeping and infection, including amino acid uptake from host proteins and fimbriae maturation. Based on the important activities of gingipains in the bacterial infection and the pathogenesis of periodontitis, the bacterial proteinases can be targets for periodontal disease therapy. Immunization with RgpB, HRgpA, or a portion of HRgpA catalytic domain attenuated P. gingivalis induced disorders in mice. In addition, a trypsin‐like proteinase inhibitor retarded P. gingivalis growth specifically. Gingipains are potent virulence factors of P. gingivalis, and are likely to be associated with the development of periodontitis. It is, therefore, suggested that gingipain inhibition by vaccination and gingipain‐specific inhibitors is a useful therapy for adult periodontitis caused by P. gingivalis infection. J Periodontol 2003;74:111‐118.
Clinical and Microbiologic Study of Periodontitis Associated With Kindler Syndrome
Authors: Wiebe Colin B. , Penagos Homero , Luong Nancy , Slots J⊘rgen , Epstein Ervin , Siegel Dawn , Häkkinen Lari , Putnins Edward E. , Larjava Hannu S.
Published: February 2005

Background: Little is known about the onset and prevalence of periodontal disease in patients with the rare Kindler syndrome, genodermatological disorder. This study investigated the level of clinical periodontal attachment in relation to age and presence of putative periodontopathogenic bacteria in individuals with Kindler syndrome.

Methods: Eighteen individuals diagnosed with Kindler syndrome and 13 control subjects, aged 4 to 37 years, from rural Panama received a limited clinical periodontal examination. Subgingival samples were collected for identification of putative periodontal pathogens by polymerase chain reaction.

Results: Mild to severe gingivitis was a common finding in all adults of the study population. Seventy‐two percent (13/18) of the Kindler patients and 46% (6/13) of the control subjects showed mild to severe periodontal disease (P = 0.001, chi‐square test). The onset of periodontitis was earlier and the progression occurred at a faster rate in the Kindler group. There was a strong correlation (r = 0.83) between the level of attachment loss and age in the Kindler group and a weaker correlation (r = 0.66) in the control group. The appearance of gingival tissues suggested atypical periodontitis with spontaneous bleeding and fragile, often desquamative, gingiva. In periodontitis patients, Porphyromonas gingivalis and Dialister pneumosintes tended to occur more frequently in control individuals compared to those with Kindler syndrome.

Conclusions: In the Kindler group, periodontitis had an onset in early teenage years and progressed more rapidly compared to non‐Kindler individuals of the same geographic and ethnic group. Clinical and microbiological findings suggest atypical periodontitis in Kindler patients. We propose to include Kindler syndrome in the category of medical disorders predisposing to destructive periodontal disease. J Periodontol 2003;74:25‐31.
The Relationship Between Volatile Sulfur Compounds and Major Halitosis‐Inducing Factors
Authors: Lee Chae‐Hoon , Kho Hong‐Seop , Chung Sung‐Chang , Lee Sung‐Woo , Kim Young‐Ku
Published: February 2005

Background: Although tongue coating and periodontal conditions have been reported to be major halitosis‐inducing factors, the relationship between volatile sulfur compounds (VSC) and these 2 major factors is not yet fully understood. The aim of this study was to investigate the relationship of VSC concentrations to tongue coating and periodontal health.

Methods: Forty subjects (mean age 33.3 years, range 14 to 64 years) were enrolled in this study. Gas chromatography was performed to analyze each VSC component from the mouth air sampled prior to tongue scraping, after tongue scraping, and after a subsequent prophylaxis on the interdental spaces.

Results: CH3SH was the most malodorous component among the 3 major VSC from the mouth air. The high CH3SH group showed a significantly higher organoleptic rating (P <0.01), gingival index (P <0.01), bleeding index (P <0.01), probing depth (P <0.05), and VSC concentrations prior to tongue scraping (P <0.01), except for the amount of tongue coating, compared to the low CH3SH group. All VSC concentrations were vastly reduced by tongue scraping in both groups, and the remaining contents were nearly all removed by the subsequent prophylaxis. The VSC contents produced by the tongue coating played a major role [H2S: 76%; CH3SH: 52%; (CH3)2S: 55%] in the low CH3SH group. In the high CH3SH group which had poor periodontal health, the tongue coating still played a major role [H2S: 67%; CH3SH: 59%; (CH3)2S: 48%], but the interdental spaces also contributed to VSC production [H2S: 26%; CH3SH: 32%; (CH3)2S; 36%].

Conclusions: The tongue coating was demonstrated to be a primary halitosis‐inducing factor. Periodontal health was also shown to contribute to VSC production. J Periodontol 2003;74:32‐37.
Human Monoclonal Antibody Inhibits Porphyromonas gingivalis Hemagglutinin Activity
Authors: Kaizuka Kouji , Hosogi Yumiko , Hayakawa Mitsuo , Shibata Yasuko , Abiko Yoshimitsu
Published: February 2005

Background: Porphyromonas gingivalis has been implicated as an important pathogen in the development of chronic periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. One potential virulence factor, hemagglutinin, may mediate bacteria attachment onto and penetration into host cells, as well as agglutinate and lyse erythrocytes to intake heme, an absolute requirement for growth. We previously cloned the gene encoding the 130 kDa hemagglutinin domain (130k HMGD) and identified its functional domain. The construction of a human monoclonal antibody that is capable of inhibiting the hemagglutinating ability is significant and important toward the development of passive immunotherapy.

Methods: Human lymphocytes isolated from a donor, who had high antibody titer against the recombinant 130k HMGD (r130k HMGD), were immortalized by Epstein‐Barr virus, and specific antibody‐producing B cells were established by panning using the r130k HMGD.

Results: The constructed HuMAb‐HMGD1, IgG subclass, recognized the r130k HMGD as well as the 43 and 49 kDa major bands in P. gingivalis cells and vesicles. The HuMAb‐HMGD1 significantly inhibited hemagglutinating activity of P. gingivalis vesicles in a dose‐dependent manner. Furthermore, the HuMAb‐HMGD1 recognized the synthetic peptide, EGSNEFAPVQNLTGSSVG, which contains the functional domain of 130k HMGD.

Conclusion: The newly constructed HuMAb‐HMGD1 may prove to be useful for the development of passive immunization against periodontal diseases caused by P. gingivalis infection, pending the results of fertility study in disease mode. J Periodontol 2003;74:38‐43.
The Influence of Alendronate on Bone Formation and Resorption in a Rat Ectopic Bone Development Model
Authors: Yaffe Avinoam , Kollerman Ron , Bahar Hila , Binderman Itzhak
Published: February 2005

Background: Most bone grafting techniques that include bone marrow, alloplastic materials, and extracellular bone matrix produce new bone mass, filling bone defects unpredictably. In most cases, the new bone undergoes resorption due to low local strains, resulting in significant bone loss. Recently, it was shown that alendronate and other bisphosphonates reduce bone loss when administered systemically or locally. The aim of this study was to investigate whether alendronate is effective on bone formation or bone resorption.

Methods: A total of 64 rats were divided into 2 main groups. In all the rats, fresh bone marrow removed from DA young rats was placed into demineralized rat femur cylinders (DBMC) and implanted into subcutaneous sites of host DA rats, to form new bone. Group A served as an alendronate treatment group, and group B served as a non‐treated control. Group A received 100 µl of 1.5 mg/ml alendronate solution at 1, 2, and 3 weeks (group A1) and at 3, 4, and 5 weeks (group A2). At designated times, the rats were sacrificed, and the implanted DBMC was dissected out of the thorax and processed for histological and microradiography image analysis.

Results: Alendronate given at 1, 2, and 3 weeks (during the bone formation phase) did not increase the amount of bone or the visual bone density in comparison to the time‐matched control, after 4 and 8 weeks. When alendronate was injected at 3, 4, and 5 weeks, the bone mass increased by 70% and by 166% after 6 and 10 weeks, respectively, in comparison to the untreated control. The visual bone density in group A2 was maintained at the level of 140 ± 15 at 6 weeks and 152 ± 15 at 10 weeks. The matched, non‐treated control group B2 was signifi‐cantly lower, 106 ± 20 and 108 ± 15, respectively. The histological sections showed that alendronate treatment at 3, 4, and 5 weeks maintained the normal appearance of the ossicle at 6 and 10 weeks in comparison to the osteopenic bone appearance in the matched controls.

Conclusions: This study suggests that alendronate is effective in inhibiting bone loss, but ineffective during the bone formation phase. We suggest, therefore, that alendronate should be administered in procedures where bone resorption is expected. J Periodontol 2003;74:44‐50.
Periodontal Disease and Diabetes Mellitus: The Role of Tumor Necrosis Factor‐α in a 2‐Way Relationship
Authors: Nishimura Fusanori , Iwamoto Yoshihiro , Mineshiba Junji , Shimizu Akemi , Soga Yoshihiko , Murayama Yoji
Published: February 2005

It is generally accepted that obesity is associated with many other multiple‐risk factor syndromes such as hypertension, hyperlipidemia, type 2 diabetes mellitus, and periodontal disease. The number of obese people is increasing rapidly in both western and eastern countries. Adipocytes in the adipose tissues of obese people produce large quantities of biologically active molecules such as leptin, an important molecule regulating energy expenditure and body weight. Therefore, adipocyte‐derived active molecules, named adipocytokines, are candidate molecules accounting for the close association between obesity and other multiple‐risk factor syndromes. The proinflammatory cytokine tumor necrosis factor‐α (TNF‐α) is produced by adipocytes, and its blood concentration is elevated in obese patients and declines with weight loss. Studies have demonstrated that TNF‐α suppresses insulin action via its specific receptor; hence, it exacerbates insulin resistance. In addition to adipocytes, monocytes/macrophages produce large quantities of TNF‐α. Thus, TNF‐α, produced from monocytic cells due to inflammatory diseases, may have an additive influence on insulin sensitivity to adipocyte‐derived TNF‐α. Here, we hypothesized that 1) TNF‐α produced by the adipose tissues of obese patients acts as a risk factor for periodontal inflammation, and 2) TNF‐α produced due to periodontal inflammation may be an additional important factor influencing insulin sensitivity in both obese and type 2 diabetic patients. We believe that this interaction is a possible mechanism accounting for a 2‐way relationship between type 2 diabetes and periodontal disease. J Periodontol 2003;74:97‐102