[Show abstract][Hide abstract] ABSTRACT: Porphyromonas gingivalis was recently shown to cause intimal hyperplasia in a mouse model by a novel cholesterol-independent mechanism, suggesting to be a pathogen-specific feature of cardiovascular diseases. The aim of this study was to characterize the clinical and histopathological features of aortic aneurysms in cardiovascular disease patients harboring oral P. gingivalis.
Aortic aneurysm specimens were collected from 76 Japanese patients who underwent surgery, of whom dental plaque specimens were also collected from 31 patients. Bacterial DNA was extracted from each specimen to detect P. gingivalis by polymerase chain reaction. Histopathological analyses of the aortic aneurysm specimens, including immunohistochemical staining for embryonic myosin heavy chain isoform (SMemb) and S100 calcium-binding protein A9 (S100A9), were also performed.
The number of aneurysms occurring in the distal aorta was significantly higher in subjects positive for P. gingivalis in dental plaque compared with those who were negative. The expressions of S100A9 and SMemb were also significantly greater in the subjects positive for P. gingivalis in dental plaque. On the other hand, there were no significant differences in adipocellular accumulation between the groups.
These results suggest that aortic aneurysms in patients harboring oral P. gingivalis have greater expression of S100A9 and proliferative smooth muscle cells, which was different from the present patients without oral P. gingivalis.
[Show abstract][Hide abstract] ABSTRACT: We describe our experienced with a case of acute encephalopathy fugax associated with intra-arterial infusion chemotherapy for tongue cancer, which seemed to be reversible posterior leukoencephalopathy possibly related to cisplatin. A 58-year-old man was treated by intra-arterial infusion chemotherapy with cisplatin plus oral TS-1 for tongue cancer. Immediately after the 10th intra-arterial injection of cisplatin, the patient had acute encephalopathy associated with right motor paralysis of the right limbs, aphasia, disorientation, cortical blindness,and tonic convulsions. The next day, all symptoms improved. It is rare that acute encephalopathy occurs, but the risk should be considered in patients given chemotherapy.
Nippon Koku Geka Gakkai zasshi 01/2010; 56(4):271-275. DOI:10.5794/jjoms.56.271
[Show abstract][Hide abstract] ABSTRACT: Actinomycosis is a specific inflammatory disease involving mixed infection that chiefly shows trismus, board-like swelling, and multiple abscess; however, it has recently become difficult to diagnose actinomycosis bacteriologically and rare for patients to show typical symptoms because of the frequent use of antibiotics. We report a case of maxillary sequestration involving Actinomyces infection after loss of a tooth.The patient, a 54-year-old man, visited our hospital because of continuous oozing, swelling, and pain in the maxillary gingiva persisting for 9 months after loss of the right maxillary second premolar. X-ray examination revealed a radiopaque image with an irregular margin in the alveolar bone. The hard tissue in the socket removed surgically for a tentative diagnosis of the maxillary osteomyelitis was diagnosed histologically as maxillary sequestration with Actinomyces infection. Symptoms such as exudates, swelling, and pain in the maxillary gingiva resolved completely after surgery. Currently, 3 years after surgery, the patient has made favorable progress.
Nippon Koku Geka Gakkai zasshi 01/2010; 56(7):428-431. DOI:10.5794/jjoms.56.428
[Show abstract][Hide abstract] ABSTRACT: Porphyromonas gingivalis infection is thought to be a significant etiological factor in the development of cardiovascular diseases. However, scant definitive evidence has been presented concerning the pathological molecular mechanisms of these disorders. In the present study, we performed a molecular analysis of the developmental mechanisms of aortic intimal hyperplasia induced by P. gingivalis.
The effects of P. gingivalis-induced bacteremia on intimal hyperplasia were evaluated using a mouse model of aortic hyperplasia created by photochemical-induced endothelial cell injury. Alterations of gene expression profiles in injured blood vessels of the mice were extensively analyzed using DNA microarray assays to identify the key molecules involved in P. gingivalis-induced hyperplasia. In addition, human aneurismal specimens from patients with or without P. gingivalis infection were analyzed histochemically.
Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model. Concomitantly, S100 calcium-binding protein A9 (S100A9) and embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients.
We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.
Journal of Periodontal Research 11/2009; 45(3):337-44. DOI:10.1111/j.1600-0765.2009.01242.x · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A clonal cell line named RMD-1 was established from the skeletal muscle of a 20-day fetal rat. RMD-1 represents a morphologically homogeneous population of undifferentiated mesenchymal cells, expressing alpha-smooth muscle actin and type I collagen, but no cartilage-associated genes. When cultured in agarose gel containing 100 ng/ml of recombinant human bone morphogenetic protein 2 (rhBMP-2; BMP-2), RMD-1 cells formed colonies and showed chondrocyte-like features as assessed by their ultrastructure, metachromatic staining with toluidine blue, and the production of large hydrodynamic-size proteoglycans. RMD-1 cells also differentiated into chondrocytes when the cells were plated at high density (over 2.5 x 10(5) cells/cm2) on type I collagen and incubated in medium containing 0.5% fetal bovine serum and 100 ng/ml of BMP-2. This chondrogenic differentiation was evidenced by a distinct morphological change into spherical cells, an increase in the levels of sulfated glycosaminoglycans, a decrease in type I collagen mRNA and the expression of cartilage-associated genes, including type II collagen, type IX collagen, aggrecan and alkaline phosphatase. In the presence of ascorbic acid and 10% serum, RMD-1 cells increased in size and expressed type X collagen as well as high alkaline phosphatase activity, then induced matrix mineralization. Thus, RMD-1 is a unique cell line that can differentiate from undifferentiated mesenchymal cells into hypertrophic chondrocytes.
Journal of Bone and Mineral Research 04/2009; 11(4):544-53. DOI:10.1002/jbmr.5650110416 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Oral bacteria, including cariogenic and periodontal pathogens, are thought to be etiological factors in the development of cardiovascular diseases. To define this relationship, we analyzed the distribution of oral bacterial species in cardiovascular specimens.
Following acceptance into the study, 203 consecutive patients were analyzed, from whom 82 aortic valve specimens, 35 mitral valve specimens, and 86 aortic aneurysmal wall specimens, of which 16 contained aneurysmal thrombus tissues, were obtained. In addition, a total of 58 dental plaque specimens were collected from the same group of patients who underwent heart valve replacement or removal of aortic aneurysms. Bacterial DNA was extracted from both cardiovascular tissues and dental plaque in those cases and then species-specific polymerase chain reaction assays were used to analyze the occurrences of six oral streptococcal and six periodontal bacterial species.
Streptococcus mutans was the most frequently detected species in the cardiovascular specimens, followed by Aggregatibacter actinomycetemcomitans. As for dental plaque specimens from patients who underwent cardiovascular operations, most of the tested periodontitis-related species as well as oral streptococci were detected at high frequencies. Furthermore, the positive rate of S. mutans in cardiovascular specimens from patients whose dental plaque specimens were also positive for S. mutans was 78%, which was significantly higher than any other tested species when the same analysis was performed.
Our results suggest that specific oral bacterial species, such as S. mutans and A. actinomycetemcomitans, are related to bacteremia and may be etiologic factors for the development of cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect of a periodontal pathogen, Porphyromonas gingivalis, on human aortic smooth muscle cell (hAOSMC) proliferation as mechanisms of atherosclerosis. Cultured hAOSMCs exposed to the supernatant of plasma incubated with P. gingivalis showed a marked transformation from a contractile to proliferative phenotype, resulting in enhancement of cell growth. DNA microarray analysis revealed a P. gingivalis-dependent upregulation of S100A9 in hAOSMCs. Small interference-RNA for S100A9 dramatically attenuated the effect of P. gingivalis on transformation and proliferation of hAOSMCs. Our data suggested that upregulation of S100A9 mediated by P. gingivalis is an important event in the development of aortic intimal hyperplasia.
[Show abstract][Hide abstract] ABSTRACT: Porphyromonas gingivalis, a major periodontal pathogen, is gaining increasing attention for its possible association with cardiovascular diseases. Its fimbriae are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. In this study, fimA genotypic distribution was analyzed in P. gingivalis-infected cardiovascular specimens.
A total of 112 heart valves and 80 atheromatous plaque specimens were collected from patients undergoing cardiovascular surgery, as well as 56 dental plaque specimens. Bacterial DNA was extracted from each, and polymerase chain reaction analysis was carried out with a P. gingivalis-specific set of primers. P. gingivalis-positive specimens were further analyzed to discriminate the fimA genotype using polymerase chain reaction with fimA type-specific primer sets.
P. gingivalis was detected in 10.4% of the cardiovascular specimens and 50.0% of the dental plaque samples. In the latter, type II was most frequently detected (35.7%), followed by types I (28.6%) and IV (21.4%), while types IV and II were detected with considerable frequencies of 45.0% and 30.0%, respectively, in the cardiovascular specimens. In contrast, the occurrence of type I was limited (5.0%) in the cardiovascular specimens.
These results suggest that specific fimA genotypic clones, which are reportedly associated with periodontitis, are also frequently harbored in cardiovascular specimens, indicating the possible involvement of type II and IV clones in the initiation and progression of cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: Actinobacillus actinomycetemcomitans, an important pathogen in periodontitis, has also been detected in cardiovascular tissues. Sixty heart valves were collected during valve replacement surgery from 60 patients (one from each), 10 were from patients with infective endocarditis (IE group) and 50 were from patients with other valvular diseases (non-IE group). In addition, 46 samples of aneurysmal tissue were taken from 46 patients with a thoracic or abdominal aneurysm (Aneurysm group, one from each). Dental plaque samples were taken from 54 of the patients, 31 in the IE and non-IE groups and 23 in the aneurysm group. First, the distribution of A. actinomycetemcomitans in all specimens was analysed using a polymerase chain reaction method, which resulted in a positive reaction in 33 (31.1%) of the cardiovascular specimens and 25 (46.3%) of the dental plaque samples. Next, using serotype-specific sets of primers, the serotype distribution of A. actinomycetemcomitans in the cardiovascular specimens and dental plaque samples was found to be significantly different compared to dental plaque samples from Japanese subjects reported previously.
[Show abstract][Hide abstract] ABSTRACT: The involvement of oral bacteria in the pathogenesis of cardiovascular disease has been studied, with Streptococcus mutans, a pathogen of dental caries, detected in cardiovascular lesions at a high frequency. However, no information is available regarding the properties of S. mutans detected in those lesions. Heart valve specimens were collected from 52 patients and atheromatous plaque specimens from 50 patients, all of whom underwent cardiovascular operations, and dental plaque specimens were taken from 41 of those subjects prior to surgery. Furthermore, saliva samples were taken from 73 sets of healthy mothers (n=73) and their healthy children (n=78). Bacterial DNA was extracted from all specimens, then analysed by PCR with S. mutans-specific and serotype-specific primer sets. The detection rates of S. mutans in the heart valve and atheromatous plaque specimens were 63 and 64 %, respectively. Non-c serotypes were identified with a significantly higher frequency in both cardiovascular and dental plaque samples from the subjects who underwent surgery as compared to serotype c, which was detected in 70-75 % of the samples from the healthy subjects. The serotype distribution in cardiovascular patients was significantly different from that in healthy subjects, suggesting that S. mutans serotype may be related to cardiovascular disease.
Journal of Medical Microbiology 05/2007; 56(Pt 4):551-6. DOI:10.1099/jmm.0.47051-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The involvement of oral bacteria in the pathogenesis of cardiovascular diseases has been the focus of attention in many studies,
and several periodontal pathogens have been detected in diseased cardiovascular lesions, suggesting relationships between
oral microorganisms and cardiovascular diseases. However, no information is available regarding the involvement of cariogenic
pathogens such as Streptococcus mutans. The presence of oral streptococcal species and periodontitis-related bacteria in 35 heart valve and 27 atheromatous plaque
clinical specimens, as well as 32 dental plaque specimens from the same subjects, was analyzed using a PCR method. Furthermore,
broad-range PCR with DNA sequencing analysis was employed to identify the bacterial species in those samples. Streptococcus mutans was frequently detected in the heart valve (69%) and atheromatous plaque (74%) specimens, while other bacterial species,
including those related to periodontitis, were detected with much lower frequencies. The bacterial composition in cardiovascular
tissues was found to be markedly distinct from that in dental plaque, with only a limited number of species, including S. mutans, in the cardiovascular regions shown to have possibly originated from the oral cavity. Semiquantitative assay results revealed
that S. mutans was detected in significant quantities in the heart valve (40%) and atheromatous plaque (48%) specimens, whereas the quantities
of all other tested bacterial species, including several related to periodontitis, were negligible in the cardiovascular samples.
These results indicate that S. mutans is a possible causative agent of cardiovascular disease.
[Show abstract][Hide abstract] ABSTRACT: Streptococcus mutans, known to be an aetiologic agent of dental caries, also causes infective endocarditis (IE), although a comparison of isolates from the oral cavity and infected heart valve of the same patient has not been reported. In the present study, infected heart valve and dental plaque samples from a patient with IE were analysed. Broad-range PCR with DNA sequencing revealed that 50 clones from the dental plaque isolates were composed of oral streptococci and periodontopathic bacteria, whereas only Streptococcus mutans was detected in 50 clones from the heart valve. Eighteen strains of Streptococcus mutans were isolated from dental plaque and seven from the heart valve, and the biochemical properties of each were in accordance with those of Streptococcus mutans. DNA fingerprinting analysis revealed that all the oral isolates of Streptococcus mutans had similar patterns, which were different from those of the isolates from the infected heart valve. Western blotting using glucosyltransferase (GTF)-specific antiserum showed that the seven strains from the heart valve lacked the three types of intact GTF. In addition, the sucrose-dependent adhesion rates of these isolates were significantly lower than those of the oral isolates (P<0.001). Furthermore, the isolates from the heart valve were less susceptible to erythromycin and kanamycin. These results indicate that the properties of the Streptococcus mutans strains isolated from the infected valve were different from those of typical oral strains, which may be related to the effects of IE.
Journal of Medical Microbiology 08/2006; 55(Pt 8):1135-40. DOI:10.1099/jmm.0.46609-0 · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A close relationship between diabetes and chronic periodontitis has been demonstrated. We previously found that Porphyromonas gingivalis with the type II fimA gene is an infectious factor closely associated with the deterioration seen in diabetic periodontitis patients. In the present study, we examined whether other biomarkers are related to the development and deterioration of periodontitis often seen in type 2 diabetic individuals.
A total of 97 type 2 diabetes patients with and without periodontitis were recruited, and their periodontal and diabetic conditions were analyzed. The ratio (%) of teeth with an attachment loss >5 mm among all teeth in each subject was used as an index of periodontal deterioration. Peripheral blood was tested for levels of glycated hemoglobin (HbA1c), advanced glycation end products (AGEs), C-reactive protein (CRP), and cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-1beta). Subgingival plaque samples were also examined for the occurrences of Actinobacillus actinomycetemcomitans, Tannerella forsythensis, Treponema denticola, and Prevotella intermedia.
Serum AGEs were significantly associated with deterioration of periodontitis, whereas no other serum biochemical marker or bacterial occurrence showed a clear relationship with that condition.
AGEs may be factors associated with diabetic periodontitis and may be useful as biomarkers that reflect such deterioration.
Journal of Periodontology 02/2006; 77(1):15-20. DOI:10.1902/jop.2006.77.1.15 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of dedifferentiated adenoid cystic carcinoma (ACC) of the submaxillary gland. A 70 year-old female was referred with rapidly growing tumor at the left cervical region. Tumor resection associated with radical neck dissection was performed. Subsequently, the patient underwent chemoradiation therapy using cisplatin (CDDP) and 5-fluorouracil (5-FU), following the administration of S-1, a novel oral derivative of 5-FU. The tumor was composed of aggregates of eosinophilic hyalinized globules and undifferentiated carcinoma. The hyalinized globules showed the immunoreactivity for laminin and type IV collagen. At present, no tumor relapse and metastasis are observed.
Oral Oncology Extra 05/2005; 41(5):84-88. DOI:10.1016/j.ooe.2005.01.005