Vertical mother-to-infant transmission of herpes simplex virus 2 is correlated with tropism due to mutations in viral UL13.

Although neonates are commonly exposed to vaginal herpes simplex virus (HSV)-2, neonatal herpes is rare. Therefore, we analyzed paired infant and maternal HSV-2 isolates from two cases of mother-to-infant transmission to identify viral factors contributing to vertical transmission. Sixteen infant isolates with neonatal herpes and 27 genital isolates in their third trimester were included. The infant isolates were significantly more temperature-independent than the maternal isolates. Sequence comparison revealed viral UL13 protein kinase (UL13-PK) mutation in the infant isolates in both cases. In the expanded cohort, infant isolates (5/18) had significantly more UL13-PK mutations than genital isolates (1/29). Isolates within 8 days post-birth (3/4) had a significantly higher frequency of UL13-PK mutation than those after 9 days (2/14), suggesting a close association between UL13-PK mutations and vertical transmission. Elongation factor 1-delta was identified as a target of UL13-PK by proteomic analysis of UL13-PK-positive and -negative HepG2 cells. The mixed infant isolates with the intact and mutated UL13-PK conferred altered cell tropism, temperature independence adapting to fetal temperature, and better growth properties in Vero and hepatoblastoma HepG2 cells than in HSV-2 with intact and mutated UL13-PK alone, indicating that viral UL13-PK mutation is essential for vertical HSV-2 transmission.

The effects of a two-minute original exercise program supported by the workplace unit on the workers' work engagement: the "Bipoji" exercise.

[Purpose] This study examined whether workplace support of an exercise program would increase the workers' engagement. [Participants and Methods] Employees at two facilities of the Kyoto Industrial Health Association (the Uji branch and the headquarters) were recruited. A survey of 238 employees was conducted. A seminar was held, at the facilities, about the "Bipoji" exercise program and afterward the participants underwent different procedures. The Uji branch (the support group) supported the continuation of the program for two months. At the headquarters (the control group), the individual decided whether to continue the program. Data were collected at the time of the seminar (the baseline) and two months later. A questionnaire measured work engagement using the Utrecht Work Engagement Scale. [Results] At the follow-up, data were collected from 65 people (60.2%) from the support group and 97 people (74.6%) from the control group. The average change in the Utrecht Work Engagement Scale scores was 1.7 and -1.2, for the support group and the control group, respectively. When adjusted for background factors, the change was 1.6 and -1.2, for the support group and the control group, respectively. This indicates a significant increase in work engagement for the support group. [Conclusion] These results suggest that a workplace exercise program can improve work engagement.

Feasibility of cognitive remediation therapy for adults with autism spectrum disorders: a single-group pilot study.

BACKGROUND: Set-shifting (SS) difficulties and weak central coherence (CC) are commonly associated with autism spectrum disorders (ASD). Cognitive remediation therapy (CRT) aims to improve such cognitive processing; however, there are no reports on CRT for patients with ASD. This pilot study aimed to provide preliminary evidence to support the use of CRT for individuals with ASD and provide data to inform future studies. PARTICIPANTS AND METHODS: Nineteen individuals with ASD were recruited and administered a series of neuropsychological and questionnaire measures to examine cognitive function and clinical outcomes such as anxiety and depression. Participants received CRT, and cognitive function and clinical variables were re-evaluated at postintervention and after 3 months. RESULTS: The participants demonstrated significant improvement in CC and anxiety at postintervention, which was maintained at 3-month follow-up. Although SS scores had improved with a large effect size, this was not statistically significant. CONCLUSION: CRT improved CC and anxiety scores for individuals with ASD, suggesting that CRT is an effective treatment for individuals with ASD.

Profile of anti-herpetic action of ASP2151 (amenamevir) as a helicase-primase inhibitor.

The antiherpetic drugs acyclovir (ACV, valaciclovir) and penciclovir (famciclovir) are phosphorylated by viral thymidine kinase and terminate DNA synthesis. ASP2151 (amenamevir) and foscavir (PFA) directly inhibit viral helicase-primase and DNA polymerase, respectively, and inhibit replication of herpes simplex virus (HSV) and varicella-zoster virus. ACV, ASP2151, and PFA all inhibit HSV with a different mechanism of action and as a consequence, the kinetics of viral DNA accumulation and progeny virus production differ. This study focused on how viral DNA synthesis and its related events in the replication cycle would influence anti-HSV action of ACV, ASP2151, and PFA. ASP2151 suppressed HSV replication more efficiently than ACV at 10 × 50% effective concentration of plaque formation (EC50), when treatments were started 0-24 h after infection. ASP2151 and PFA were more potent than ACV in suppressing viral DNA synthesis and infectious virus production when they were added up to 3 h following infection. The virus replicated in the presence of ACV was compared for the ratios of HSV DNA copy number to infectivity with that without ACV and infectivity of ACV-treated virus was less efficient than that without ACV-treatment. The EC50 of infected cells in the time course after infection was preserved in PFA, limited in ASP2151, and much increased for ACV, indicating that viral DNA synthesis had little effect on antiviral action of PFA and ASP2151 but reduced the susceptibility of ACV. ASP2151 showed a preferable profile as an anti-herpetic agent with a better pharmacokinetic profile than ACV.

Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study.

A ferric citrate formulation for treating hyperphosphatemia is a new therapeutic that not only suppresses the accumulation of phosphorus in patients with chronic kidney disease-mineral bone disorders (CKD-MBD), but also ameliorates anemia caused by iron deficiency. In contrast, it has been demonstrated that intravenous iron injection markedly increases oxidative stress. This study was designed to investigate the effect of a ferric citrate formulation on oxidative stress in CKD-MBD patients receiving hemodialysis therapy. Fifteen CKD-MBD patients undergoing dialysis were enrolled in this study. The patients were orally administered a ferric citrate formulation for 6 months. Their plasma phosphorus concentrations remained unchanged with the switch from other phosphorus adsorbents to the ferric citrate formulation. In addition, the ferric citrate formulation generally allowed for dose reduction of an erythropoiesis stimulating agent with an increased hematopoietic effect. The average values of plasma ferritin level increased after the introduction of a ferric citrate formulation, but did not exceed 100 (ng/mL). Interestingly, oxidative stress markers did not increase significantly, and anti-oxidative capacity was not significantly decreased at 6 months after the drug administration. Similarly, no change was observed in any inflammation markers. The ferric citrate formulation induces negligible oxidative stress in CKD-MBD patients receiving dialysis under the present clinical condition.

Subclinical generation of acyclovir-resistant herpes simplex virus with mutation of homopolymeric guanosine strings during acyclovir therapy.

BACKGROUND: Suppressive therapy in patients with genital herpes has been used in Japan since 2006. Susceptibility and resistance of herpes simplex virus (HSV)-2 to acyclovir were examined in genital isolates from patients receiving suppressive therapy and compared with those from those naïve to acyclovir and receiving episodic treatment with acyclovir. OBJECTIVE: The aim of this study was to analyze the effect of acyclovir use on the susceptibility to acyclovir and analysis of the thymidine kinase gene by acyclovir treatment. METHODS: Genital HSV isolates were obtained from three patients groups. Susceptibility to acyclovir, the frequency of acyclovir-resistant clones and mutations in the thymidine kinase gene of acyclovir-resistant clones were determined. RESULTS: Susceptibility to ACV was significantly higher in isolates from patients receiving suppressive therapy than those naïve to acyclovir and receiving episodic treatment, but the frequencies of resistant clones were similar among the three groups. Mutation in guanosine homopolymeric strings (G-string mutation) was significantly more frequent in clones during episodic treatment and suppressive therapy than clones from patients naïve to ACV. The frequency of G-string mutation was significantly less frequent in isolates from patients naïve to ACV than those experienced ACV therapy. CONCLUSION: The frequency of acyclovir-resistant mutants was not increased by episodic and suppressive therapy, but exposure to acyclovir significantly generated G-string mutations, possibly induced by acyclovir. Acyclovir therapy had no substantial effects on the susceptibility of HSV-2 or frequency of resistant virus but did generate subclinical G-string mutants in patients' HSV-2.

Identification of ribonucleotide reductase mutation causing temperature-sensitivity of herpes simplex virus isolates from whitlow by deep sequencing.

Herpes simplex virus 2 caused a genital ulcer, and a secondary herpetic whitlow appeared during acyclovir therapy. The secondary and recurrent whitlow isolates were acyclovir-resistant and temperature-sensitive in contrast to a genital isolate. We identified the ribonucleotide reductase mutation responsible for temperature-sensitivity by deep-sequencing analysis.

Characterization of susceptibility variants of influenza virus grown in the presence of T-705.

T-705 (favipiravir) is a potent inhibitor of RNA polymerases of influenza viruses. Susceptibility variants were isolated during passages in the presence of T-705. Nine variants with 0.4 to 2.1 times the 50% inhibitory concentration for plaque formation of the parent A/PR/8/34 (H1N1) strain had amino acid variations in the PB1, PB2, and PA genes of the RNA polymerase complex. However, the variation patterns in the RNA polymerase complex indicated that T-705 does not work as a mutagen, and resistant mutants were not isolated, possibly because a mutation leading to resistance would be lethal to the RNA polymerase function.

Significant but weak spousal concordance of metabolic syndrome components in Japanese couples.

OBJECTIVE: This study was initiated to investigate if spousal concordance in metabolic syndrome (MS) components exist in Japan. METHODS: In all, 756 couples (mean age: 48.9 and 47.3 years for husbands and wives, respectively) were identified. Each subject was classified as an MS, MS reserves (MSRES) or no risk of MS (NonMS) case after Japanese Ministry of Health, Labour and Welfare (JMHLW) criteria. Criteria of the National Cholesterol Education Program and of the Joint Interim Statement were also applied. RESULTS: With Japanese Ministry of Health, Labor and Welfare (JMHLW) criteria, MS, MSRES and NonMS cases accounted for 11.9, 14.7 and 73.4 % in husbands and 1.6, 3.7 and 94.7 % in wives. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SBP) and hemoglobin A1c (HbA1c) showed significant correlation (p < 0.01). Correlation was also significant (p < 0.05) for mean blood pressure (MBP) and fasting plasma glucose (FPG). When adjusted for age, correlations were significant only for WC, BMI and HbA1c. Furthermore, none of the correlation coefficients were greater than 0.2. Logistic regression analyses did not suggest significant mutual influence in MS status between the couples. CONCLUSIONS: Spousal concordance in MS components was detected for WC, BMI, SBP, MBP, FPG and HbA1c, but the correlation was generally weak and modest in Japanese couples.

[Dose impact of a carbon fiber couch for stereotactic body radiation therapy of lung tumors].

The aim of this study was to measure the dose attenuation caused by a carbon fiber radiation therapy table (Imaging Couch Top; ICT, BrainLab) and to evaluate the dosimetric impact of ICT during stereotactic body radiation therapy (SBRT) in lung tumors. The dose attenuation of ICT was measured using an ionization chamber and modeled by means of a treatment planning system (TPS). SBRT was planned with and without ICT in a lung tumor phantom and ten cases of clinical lung tumors. The results were analyzed from isocenter doses and a dose-volume histogram (DVH): D95, Dmean, V20, V5, homogeneity index (HI), and conformity index (CI). The dose attenuation of the ICT modeled with TPS agreed to within ±1% of the actually measured values. The isocenter doses, D95 and Dmean with and without ICT showed differences of 4.1-5% for posterior single field and three fields in the phantom study, and differences of 0.6-2.4% for five fields and rotation in the phantom study and six fields in ten clinical cases. The dose impact of ICT was not significant for five or more fields in SBRT. It is thus possible to reduce the dose effect of ICT by modifying the beam angle and beam weight in the treatment plan.

Angular dependence correction of MatriXX and its application to composite dose verification.

We measured the angular dependence of central and off-axis detectors in a 2D ionization chamber array, MatriXX, and applied correction factors (CFs) to improve the accuracy of composite dose verification of IMRT and VMAT. The MatriXX doses were measured with a 10° step for gantry angles (θ) of 0°-180°, and a 1° step for lateral angles of 90°-110° in a phantom, with a 30 × 10 cm2 field for 6 MV and 10 MV photons. The MatriXX doses were also calculated under the same conditions by the Monte Carlo (MC) algorithm. The CFs for the angular dependence of MatriXX were obtained as a function of θ from the ratios of MatriXX-measured doses to MC-calculated doses, and normalized at θ = 0°. The corrected MatriXX were validated with different fields, various simple plans, and clinical treatment plans. The dose distributions were compared with those of MC calculations and film. The absolute doses were also compared with ionization chamber and MC-calculated doses. The angular dependence of MatriXX showed over-responses of up to 6% and 4% at θ = 90° and under-responses of up to 15% and 11% at 92°, and 8% and 5% at 180° for 6 MV and 10 MV photons, respectively. At 92°, the CFs for the off-axis detectors were larger by up to 7% and 6% than those for the central detectors for 6 MV and 10 MV photons, respectively, and were within 2.5% at other gantry angles. For simple plans, MatriXX doses with angular correction were within 2% of those measured with the ionization chamber at the central axis and off-axis. For clinical treatment plans, MatriXX with angular correction agreed well with dose distributions calculated by the treatment planning system (TPS) for gamma evaluation at 3% and 3 mm. The angular dependence corrections of MatriXX were useful in improving the measurement accuracy of composite dose verification of IMRT and VMAT.

Efficacy of ASP2151, a helicase-primase inhibitor, against thymidine kinase-deficient herpes simplex virus type 2 infection in vitro and in vivo.

ASP2151 was developed as a novel inhibitor of herpes simplex virus (HSV) and varicella-zoster virus helicase-primase. The anti-HSV activity of ASP2151 toward a clinical HSV isolate with acyclovir (ACV)-resistant/thymidine kinase (TK)-deficiency was characterized in vitro and in vivo using a plaque reduction assay and the ear pinna infection in mice. The IC(50) ranged from 0.018 to 0.024 µg/ml, indicating the susceptibility of TK-deficient HSV-2 was similar to that of wild-type HSV-2 strains. Anti-HSV activity of ASP2151 in vivo was evaluated in mice infected with wild-type HSV-2 and TK-deficient HSV-2. ASP2151 significantly reduced the copy numbers of wild-type HSV-2 and TK-deficient HSV-2 at the inoculation ear pinna, while valacyclovir significantly reduced the copy number of wild type HSV-2 but not that of TK-deficient HSV-2 in the inoculated ear pinna. Thus, ASP 2151 showed therapeutic efficacy in mice infected with both wild-type and TK-deficient HSV-2. In conclusion, ASP2151 is a promising novel herpes helicase-primase inhibitor that indicates the feasibility of ASP2151 for clinical application for the treatment of HSV infections, including ACV-resistant/TK-deficient HSV infection.

Characterization of a fully human monoclonal antibody against extracellular domain of matrix protein 2 of influenza A virus.

The extra-cellular domain of the influenza virus matrix protein 2 (M2e) is highly conserved between influenza A virus strains compared to hemagglutinin and neuraminidase, and has long been viewed as a potential and universal vaccine target. M2e induces no or only weak and transient immune responses following infection, making it difficult to detect M2e-specific antibodies producing B-cells in human peripheral blood lymphocytes. Recently, using a single-cell manipulation method, immunospot array assay on a chip (ISAAC), we obtained an M2e-specific human antibody (Ab1-10) from the peripheral blood of a healthy volunteer. In this report, we have demonstrate that Ab1-10 reacted not only to seasonal influenza A viruses, but also to pandemic (H1N1) 2009 virus (2009 H1N1) and highly pathogenic avian influenza A virus, and that the antibody-bound M2e of 2009 H1N1 inactivated the virus with high affinity (∼10(-10)M). More importantly, it inhibited 2009 H1N1 viral propagation in vitro. These results suggest that Ab1-10 might be a potential candidate for antibody therapeutics for a wide range of influenza A viruses.

Assessment of cerebral perfusion from bypass arteries using magnetic resonance regional perfusion imaging in patients with moyamoya disease.

PURPOSE: The purpose of this study was to evaluate whether cerebral perfusion from bypassed arteries can be demonstrated on regional perfusion imaging (RPI) using arterial spin labeling. We then compared cerebral perfusion on RPI and digital subtraction angiography (DSA) in moyamoya patients who underwent extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We performed RPI using a 3-T magnetic resonance scanner and DSA studies in 11 moyamoya patients treated by bypass surgery. For RPI we placed a selective labeling slab on the bypassed external carotid artery. Two neuroradiologists determined the extent and location of the cerebral perfusion from bypass arteries in the middle cerebral artery territories on RPI and DSA. Kappa analysis was used to assess the interobserver agreement with respect to the extent and location of the cerebral perfusion and to evaluate the intermodality agreement between RPI and DSA. RESULTS: Interobserver agreement for the extent of cerebral perfusion on RPI was very good (kappa=0.89), with excellent location (kappa=1.00). Intermodality agreement for the extent of perfusion was very good (kappa=0.89), with good location (kappa=0.74). CONCLUSION: RPI is useful for evaluating cerebral perfusion from bypass arteries in moyamoya patients.

Risk for non-obese Japanese workers to develop metabolic syndrome.

With regard to metabolic syndrome-related risks (MS risks), obese workers have been the focus of attention, and less attention has been paid to non-obese subjects as if they were free from the risks. The present analysis was initiated to know if no-obesity means no-MS risks. Participants of the study were 804 male workers, who showed no pathological findings in 12 MS-related and other health parameters in 2003, and had complete sets of data in 2008. They were classified by BMI in 2003 into lean (< 18.5), normal (> or = 18.5 to < 25) and obese groups (> or =25). Proportion of MS in 2008 was examined by use of the second phase of MS criteria. Proportions for the lean, normal and obese subjects who met MS criteria in 2008 were 3.2, 4.8 and 5.3%, respectively, with no significant difference in proportions among them. In the non-obese (i.e., lean+normal) group, age was not significantly influential to increase BMI. Thus, the MS risk exists even in non-obese young workers. Anti-MS effort should be directed not only to obese but to non-obese workers, and care should be extended irrespective of ages.

Design and synthesis of isonucleosides constructed on a 2-oxa-6-thiabicyclo[3.2.0]heptane scaffold.

A novel method for the design and synthesis of an isonucleoside containing a 2-oxa-6-thiobicyclo[3.2.0]heptane skeleton is described. 2,2-Dimethyl-1,3-dioxan-5-one 13 was converted into a dioxabicyclohexane derivative in six steps. After cleavage of the epoxide group with a thiol (thiophenol or PMB mercaptan), the resulting product was subjected to the Mitsunobu reaction in the presence of a nucleobase. The reaction proceeded via the migration of the thiosulfide groups and gave the desired isonucleoside derivatives. In the case of a phenyl sulfide derivative, radical desulfurization followed by deprotection gave 4'-substituted 2',3'-dideoxyisonucleosides. A PMB sulfide derivative, on the other hand, was converted into the corresponding dimesylate, which was then treated with mercury acetate and trifluoroacetic acid to remove the PMB group. The resulting thiol derivative was treated with DBU to give the desired isonucleoside constructed on a 2-oxa-6-thiobicyclo[3.2.0]heptane scaffold after deprotection. The optimized conformer of the isonucleoside was calculated using DFT at the B3LYP/6-31G** level and was compared with that of lamivudine using model compounds.

Grading astrocytic tumors by using apparent diffusion coefficient parameters: superiority of a one- versus two-parameter pilot method.

PURPOSE: To assess the utility of both minimum apparent diffusion coefficients (ADCs) and ADC difference values for grading astrocytic tumors at magnetic resonance imaging. MATERIALS AND METHODS: The hospital's institutional review board approved this retrospective study and waived informed consent. Fifty patients (23 male patients, 27 female patients; median age, 53 years) with newly diagnosed astrocytic tumors were evaluated. Two observers blinded to clinical information independently measured the ADCs by manually placing three to five regions of interest (40-60 mm(2)) within the solid tumor either with or without contrast material-enhanced components and calculated the average ADC. Minimum and maximum ADCs were selected, and the difference between them was recorded as the ADC difference value. These ADC values were used as the parameters for tumor grading and were compared by using the Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis. RESULTS: According to ROC analyses for distinguishing tumor grade, minimum ADCs showed the largest areas under the ROC curve. Minimum ADCs optimally helped distinguish grade 1 from higher-grade tumors at a cutoff value of 1.47 x 10(-3) mm(2)/sec and grade 4 from lower-grade tumors at a cutoff value of 1.01 x 10(-3) mm(2)/sec (P < .001 for both). ADC difference values helped distinguish grade 2 from grade 3 tumors at a cutoff value of 0.31 x 10(-3) mm(2)/sec (P < .001). When tumors were graded by using the combined minimum ADC and ADC difference cutoff values mentioned above (the two-parameter method), the following positive predictive values were obtained: grade 1 tumors, 73% (eight of 11); grade 2 tumors, 100% (five of five); grade 3 tumors, 67% (eight of 12); and grade 4 tumors, 91% (20 of 22). CONCLUSION: Using a combination of minimum ADCs and ADC difference values (the two-parameter method) facilitates the accurate grading of astrocytic tumors.

Differentiation of common large sellar-suprasellar masses effect of artificial neural network on radiologists' diagnosis performance.

RATIONALE AND OBJECTIVES: When pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst grow in the sellar and suprasellar region, it is often difficult to differentiate among these three lesions on magnetic resonance (MR) images. The purpose of this study was to apply an artificial neural network (ANN) for differential diagnosis among these three lesions with MR images and retrospectively evaluate the effect of ANN output on radiologists' performance. MATERIALS AND METHODS: Forty-three patients with sellar-suprasellar masses were studied. The ANN was designed to differentiate among pituitary adenoma, craniopharyngioma, and Rathke's cleft cyst by using patients' ages and nine MR image findings obtained by three neuroradiologists using a subjective rating scale. In the observer performance test, MR images were viewed by nine radiologists, including four neuroradiologists and five general radiologists, first without and then with ANN output. The radiologists' performance was evaluated using receiver-operating characteristic analysis with a continuous rating scale. RESULTS: The ANN showed high performance in differentiation among the three lesions (area under the receiver-operating characteristic curve, 0.990). The average area under the curve for all radiologists for differentiation among the three lesions increased significantly from 0.910 to 0.985 (P = .0024) when they used the computer output. Areas under the curves for the general radiologists and neuroradiologists increased from 0.876 to 0.983 (P = .0083) and from 0.952 to 0.989 (P = .038), respectively. CONCLUSION: In diagnostic performance for differentiation among pituitary macroadenoma, craniopharyngioma, and Rathke's cleft cyst with MR imaging, the ANN resulted in parity between neuroradiologists and general radiologists.

Human subthalamic nucleus: evaluation with high-resolution MR imaging at 3.0 T.

INTRODUCTION: The purpose of this study was to compare the visibility of the normal subthalamic nucleus (STN) between fast spin-echo T2-weighted (FSE T2-W) images and fast short inversion time inversion-recovery (FSTIR) images, and to assess the age-related changes of the STN at 3.0 T. METHODS: We evaluated high-resolution FSE T2-W and FSTIR images in 24 neurologically normal subjects. Using both sequences, we assessed the visibility of the margins of the STN, and calculated the difference in signal intensity between the STN and structures adjacent to the STN. Then, to assess the age-related changes of the STN, we calculated the contrast-to-noise ratio between the STN and the white matter, and measured the position, length, and height of the STN. All data were statistically evaluated. RESULTS: The visibility of the lower margin of the STN was significantly better on the FSTIR images than on the FSE T2-W images (P = 0.0001), while the visibility of other margins was significantly better on the FSE T2-W images than on the FSTIR mages (P = 0.002). The difference in signal intensity between the STN and substantia nigra was significantly greater on the FSTIR images than on the FSE T2-W images (P < 0.0001). The distance from the midline to the lateral border of the STN increased with age (FSE T2-W images: left r = 0.4916, P = 0.015; right r = 0.4442, P = 0.030). CONCLUSION: The combined reading of both FSE T2-W and FSTIR images at 3 T will improve the identification of the STN. The age-related positional change of the STN should be considered in target determination for deep brain stimulation procedures.

Treponema denticola induces interleukin-8 and macrophage chemoattractant protein 1 production in human umbilical vein epithelial cells.

Treponema denticola, a major pathogen of periodontitis, has also been detected in the lesions of atherosclerosis. The aim of this study was to investigate induction of chemokine production in human umbilical vein endothelial cells (HUVECs) by T. denticola and determine whether those chemokines were degraded by a protease, dentilisin. T. denticola ATCC35405 or dentilisin-deficient mutant K1 were added to HUVECs and levels of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in the culture supernatants were determined by enzyme-linked immunosorbent assay. T. denticola ATCC35405 induced production of IL-8 in a time-dependent manner, with both production of IL-8 and expression of IL-8 mRNA showing higher levels than with exposure to dentilisin-deficient mutant K1. Although exposure to ATCC35405 induced expression of MCP-1 mRNA in the HUVECs, MCP-1 levels were remained similar to that in unstimulated cells. IL-8 and MCP-1 showed partial hydrolysis with exposure to T. denticola ATCC35405, but not with T. denticola K1. These results suggest that T. denticola can evade host defense mechanisms by modulating production of IL-8 and MCP-1, and that this play a role in the development of chronic infections such as periodontitis. The association of T. denticola infection to atherosclerosis was also discussed based on the present study.