The cotton rat model for adenovirus ocular infection: antiviral activity of cidofovir

To determine the antiviral effects of compounds against ocular adenovirus (AdV) infection, we established an animal model of AdV infection in cotton rat eyes. Cotton rat eyes were inoculated intrastromally and topically with four AdV serotypes 4, 5, 8, and 37, and treated topically with 1% HPMPC (cidofovir) eye drops twice a day. The infected corneas were extracted and homogenized, and virus titers in the cornea specimens were determined by a plaque assay. The virus titer in AdV type 5-inoculated eyes peaked on days 0 through 3 after inoculation and virus shedding was detected for 18.0+/-2.8 days. AdV 5 antigen in the infected corneas was demonstrated in the corneal epithelial cells by immunofluorescence stain. However, for AdV serotypes 4, 8, and 37, no evidence of continued virus replication in cotton rat eyes was noted. Specimens from cidofovir-treated eyes infected with AdV 5 demonstrated a statistically significant reduction in the mean virus titer (days 3-15) (P=0.028) and virus shedding duration (P=0.0014), as compared with those of the control group.     

Radial dependence of lineal energy distribution of 290-MeV/u carbon and 500-MeV/u iron ion beams using a wall-less tissue-equivalent proportional counter

Using a wall-less tissue-equivalent proportional counter for a 0.72-μm site in tissue, we measured the radial dependence of the lineal energy distribution, yf(y), of 290-MeV/u carbon ions and 500-MeV/u iron ion beams. The measured yf(y) distributions and the dose-mean of y, y¯D, were compared with calculations performed with the track structure simulation code TRACION and the microdosimetric function of the Particle and Heavy Ion Transport code System (PHITS). The values of the measured y¯D were consistent with calculated results within an error of 2%, but differences in the shape of yf(y) were observed for iron ion irradiation. This result indicates that further improvement of the calculation model for yf(y) distribution in PHITS is needed for the analytical function that describes energy deposition by delta rays, particularly for primary ions having linear energy transfer in excess of a few hundred keV μm⁻¹.     

Molecular and epidemiological trend of rotavirus infection among infants and children in Japan

This study investigated the prevalence of group A, B, and C rotavirus (RAV, RBV, RCV) and adenovirus (AdV) infections in infants and children with acute gastroenteritis in Japan from July 2006 to June 2007. A total of 628 fecal specimens collected from infants and children with acute gastroenteritis in five different places (Maizuru, Tokyo, Sapporo, Saga and Osaka) in Japan during the period of July 2006–June 2007 were examined for RAV, RBV, RCV and AdV by RT-multiplex PCR. RAV was further characterized to G-typing and P-typing by RT-multiplex PCR and sequencing method. It was found that 123 (19.6%) fecal specimens were positive for RAV followed by AdV of 4.5%. RBV and RCV could not be detected in this study. Serotype G1 (58.5%) was identified at high levels followed by G9 (20.3%), G2 (11.4%), and G3 (7.3%). P genotyping revealed P[8] as predominant (84.6%) followed by P[4] (13.8%) and P[6] (1.6%). During the 2006/2007 rotavirus season, G1P[8] strains were most common with G9P[8], G2P[4], G3P[8], G1P[4] and G9P[6] also detected. It is clear from this study that RAV is still the cause of diseases in Japan. To our knowledge, this is the first report of RV P[6] strain in humans in Japan.     

Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.     

Surgical outcomes of vitrectomy for breakthrough vitreous hemorrhage in eyes with exudative age-related macular degeneration

Purpose

To report the outcomes of pars plana vitrectomy in cases with breakthrough vitreous hemorrhage (VH) secondary to exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy. We also investigated the relationship between the preoperative b-mode ultrasonographic findings and the postoperative visual acuity to determine if the ultrasonographic findings can predict the surgical outcome after pars plana vitrectomy.

Methods

This was a retrospective, interventional, case series. Twenty eyes of 20 patients were studied. The associations between the pre- and intraoperative factors and the final best-corrected visual acuity (BCVA) were determined. Recombinant tissue-plasminogen activator (tPA) was used in cases with massive hemorrhagic retinal detachment.

Results

Ten eyes with polypoidal choroidal vasculopathy (PCV), two eyes with choroidal neovascularization (CNV), and eight eyes with an unknown type of AMD were studied. The mean BCVA was 0.73?±?0.57 logarithm of the minimum angle of resolution (logMAR) units before developing the VH, 2.25?±?0.45 logMAR units before the surgery, and 1.52?±?0.87 logMAR units after the surgery. The BCVA improved significantly after the surgery (P?=?0.004) but was significantly worse than that before developing the VH (P?=?0.012). The cases of PCV had better final BCVA than cases of CNV (P?=?0.043, Mann–Whitney test). The preoperative presence of a subretinal elevation at the macula detected by ultrasonography was significantly associated with a poorer final BCVA (P?=?0.031).

Conclusions

Vitrectomy significantly improved visual function in the eyes with VH associated with exudative AMD. The eyes with PCV and no macular subretinal elevation on ultrasonography had a better visual prognosis.

     

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

For patients with relapsed acute promyelocytic leukemia (APL), all‐trans retinoic acid‐based salvage regimens can achieve second complete remission (CR2), but the optimal post‐remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)‐HSCT, 21 received allogeneic (allo)‐HSCT, and 30 received various regimens other than HSCT. The 5‐year event‐free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non‐HSCT group, 41.7%, 83.3% and 58.3% in the auto‐HSCT group and 71.1%, 76.2% and 9.8% in the allo‐HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo‐HSCT group than in other groups. Allo‐HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation‐related mortality (19%). Among older patients (age ≥40 years), the 5‐year OS was significantly better in the non‐HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.     

Tumor‐suppressive microRNA‐143/145 cluster targets hexokinase‐2 in renal cell carcinoma

Our recent studies of microRNA (miRNA) expression signatures have indicated that the miR‐143/145 cluster is significantly downregulated in several types of cancer and represents a putative tumor‐suppressive miRNA in human cancers. The aim of this study was to investigate the functional significance of the miR‐143/145 cluster in cancer cells and to identify novel molecular targets of the miR‐143/145 cluster in renal cell carcinoma (RCC). The expression levels of miR‐143 and miR‐145 were significantly downregulated in RCC tissues compared with adjacent non‐cancerous tissues. A significant positive correlation was recognized between miR‐143 and miR‐145 expression. Restoration of mature miR‐143 or miR‐145 in 786‐O and A498 RCC cells revealed that both mature miRNAs significantly inhibited cancer cell proliferation and invasion, suggesting that the miR‐143/145 cluster functioned as a tumor suppressor in RCC. Gene expression data and in silico database analysis showed that the hexokinase‐2 (HK2) gene, which encodes a glycolytic enzyme crucial for the Warburg effect in cancer cells, was a candidate target of the miR‐143/145 cluster. Luciferase reporter assays showed that both miR‐143 and miR‐145 directly regulated HK2. In RCC clinical specimens, the expression of HK2 was significantly higher in cancer tissues than in non‐cancerous tissues. Silencing HK2 suppressed RCC cell proliferation and invasion, suggesting that HK2 has oncogenic functions in RCC. Thus, our data showed that loss of the tumor‐suppressive miR‐143/145 cluster enhanced RCC cell proliferation and invasion through targeting HK2.