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.

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.

[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.

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.

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.

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.

Quantitative analysis and effect of attenuation correction on lymph node staging of non-small cell lung cancer on SPECT and CT.

OBJECTIVE: The purpose of our study was to assess quantitative indexes and the effect of attenuation correction on the evaluation of lymph node metastasis in the staging of non-small cell lung cancer (NSCLC) using fused thallium-201 SPECT/CT images. MATERIALS AND METHODS: We evaluated 156 lymph nodes (66 metastatic, 90 nonmetastatic) from 29 patients with NSCLC. Using our combined SPECT/CT system, all patients underwent 201Tl SPECT and CT examinations immediately (early images) and 3 hr after (delayed images) the injection of 201Tl. SPECT images were reconstructed with and without attenuation correction. For the quantitative evaluation of lymph node metastasis, we calculated the early ratio, the delayed ratio, and the washout ratio for SPECT images and the short-axis diameter for CT images. Receiver operating characteristic (ROC) analysis was performed in each index for the differentiation between metastatic and nonmetastatic lymph nodes. Visual analysis was also performed by two experienced radiologists. RESULTS: The area under the ROC curve (A(z)) showed that early ratio and delayed ratio were superior to short-axis diameter for the assessment of lymph node metastasis. In addition, early and delayed ratios on attenuation-corrected images were superior to those ratios on images without attenuation correction. However, the A(z) value for washout ratio was smaller than that for short-axis diameter. Early ratio on attenuation-corrected images was the most useful index (A(z) = 0.94). The sensitivity, specificity, and accuracy for early ratio on attenuation-corrected images were 78.8%, 94.4%, and 87.8% for the diagnosis of lymph node metastasis and 84.6%, 100%, and 93.1% for clinical staging (N0-N1 vs N2-N3), respectively. Fused images showed significantly higher diagnostic accuracy than CT images on visual analysis. CONCLUSION: Quantitative assessment using fused SPECT/CT images is useful for the diagnosis of lymph node metastasis in patients with NSCLC.