Hideo Yoshioka

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (16)42.18 Total impact

  • [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.
    Oral Diseases 10/2010; 17(4):370-8. · 2.38 Impact Factor
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    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. · 1.99 Impact Factor
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    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.
    Oral Microbiology and Immunology 03/2009; 24(1):43-9. · 2.81 Impact Factor
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    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.
    Oral Microbiology and Immunology 03/2009; 24(1):64-8. · 2.81 Impact Factor
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    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.
    FEBS letters 01/2009; 583(1):128-34. · 3.54 Impact Factor
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    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.
    Oral Microbiology and Immunology 05/2008; 23(2):170-2. · 2.81 Impact Factor
  • Journal of Medical Microbiology 11/2007; 56(Pt 10):1413-5. · 2.30 Impact Factor
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    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. · 2.30 Impact Factor
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    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.
    Oral Microbiology and Immunology 05/2007; 22(2):136-9. · 2.81 Impact Factor
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    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.
    Journal of Clinical Microbiology 10/2006; 44(9):3313-7. · 4.07 Impact Factor
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    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. · 2.30 Impact Factor
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    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. · 2.40 Impact Factor
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    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.
  • Diabetes Care 03/2005; 28(2):433-4. · 7.74 Impact Factor
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    ABSTRACT: The immunohistochemical localization of thrombospondin-1 (TSP-1) in human normal oral mucosa and oral squamous cell carcinoma (SCC) was examined. The immunostaining of TSP-1 was mainly localized in the connective tissues adjacent to the epithelium of oral mucosa, whereas epithelial cells showed negligible immunoreactivity for TSP-1. TSP-1 expression was striking in the stroma of SCC. TSP-1 synthesis by SCC cells and fibroblasts in culture was examined by immunoprecipitation with anti-TSP-1 antibody. Fibroblasts produced a large amount of TSP-1, whereas SCC cells secreted little amount of TSP-1. Treatment of fibroblasts by the conditioned medium of SCC cells led to an increase in TSP-1 synthesis. TSP-1 induced haptotactic migration and stimulated the production of matrix metalloproteinase-9 (MMP-9) in SCC cells. These results suggest that TSP-1 in the stroma of oral SCC might be synthesized by mesenchymal cells but not by epithelial cells, and that the synthesis of TSP-1 might be regulated by interaction with SCC cells. TSP-1 accumulated in the stroma might promote the progression of oral SCC by enhancing the motility and proteolytic activity in a paracrine manner.
    International Journal of Molecular Medicine 11/2003; 12(4):447-52. · 1.96 Impact Factor
  • Noriaki Tanaka, Munehiro Takeda, Hideo Yoshioka
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    ABSTRACT: A 64-year-old male with primary squamous cell carcinoma of the tongue (T3N0M0) was treated with the novel fluoropyrimidine oral anticancer drug TS-1 and selective intra-arterial infusion of CDDP. His past history revealed pulmonary emphysema as a complication. Since his pulmonary function was reduced and it would have been difficult to perform surgery under general anesthesia, we started administration of TS-1 (100 mg/day) first and added selective arterial infusion of CDDP (5 mg/day) after one week of TS-1. On day 8 of TS-1 administration (day 2 of arterial infusion), the tumor had shrunk considerably, and on day 15 of TS-1 administration (day 9 of arterial infusion) the tumor had almost completely disappeared. Nausea and vomiting developed as adverse effects on day 20 of TS-1 administration (day 14 of arterial infusion), and administration of the anticancer drugs was stopped. Nutrition management and an antiemetic agent were started by intravenous drip infusion, and the adverse effects improved one week after administration was stopped. By the 5th week after the start of treatment, the tumor had disappeared macroscopically, and a CR had been achieved. Interstitial radiotherapy was performed as supplemental therapy, and as of this writing, September 3, 2002, 16 months after the start of treatment, the patient is being followed on an outpatient basis. His course has been favorable and recurrence-free. Although there were some slight adverse reactions, they were relatively mild, and since sufficient efficacy was observed, oral TS-1 plus selective intra-arterial CDDP therapy was concluded to be an effective method of treatment for patients with a past medical history making their general condition unfavorable.
    Gan to kagaku ryoho. Cancer & chemotherapy 05/2003; 30(4):511-4.

Publication Stats

318 Citations
42.18 Total Impact Points


  • 2006–2010
    • Osaka City University
      • Department of Pharmacology
      Ōsaka, Ōsaka, Japan
  • 2003–2010
    • Osaka Rosai Hospital
      Ōsaka, Ōsaka, Japan
  • 2006–2009
    • Osaka University
      • Department of Oral Frontier Biology
      Suika, Ōsaka, Japan