Septicemia from Lactobacillus rhamnosus GG,from a Probiotic Enriched Yogurt,in a Patient with Autologous Stem Cell Transplantation

Probiotics and Antimicrobial Proteins - Probiotic-rich foods are consumed without much restriction. We report here, a case of septic shock caused by yogurt derived Lactobacillus species in a...     

Clinical Report on the First Prototype of a Photoacoustic Tomography System with Dual Illumination for Breast Cancer Imaging

Photoacoustic tomography is a recently developed imaging modality that can provide high spatial-resolution images of hemoglobin distribution in tissues such as the breast. Because breast cancer is an angiogenesis-dependent type of malignancy, we evaluated the clinical acceptability of breast tissue images produced using our first prototype photoacoustic mammography (PAM) system in patients with known cancer. Post-excisionally, histological sections of the tumors were stained immunohistochemically (IHC) for CD31 (an endothelial marker) and carbonic anhydrase IX (CAIX) (a marker of hypoxia). Whole-slide scanning and image analyses were used to evaluate the tumor microvessel distribution pattern and to calculate the total vascular perimeter (TVP)/area for each lesion. In this clinical study, 42 lesions were primarily scanned using PAM preoperatively, three of which were reported to be benign and were excluded from statistical analysis. Images were produced for 29 out of 39 cancers (visibility rate = 74.4%) at the median depth of 26.5 (3.25–51.2) mm. Age, menopausal status, body mass index, history of neoadjuvant treatment, clinical stage and histological tumor angiogenesis markers did not seem to affect the visibility. The oxygen saturation level in all of the measured lesions was lower than in the subcutaneous counterpart vessels (Wilcoxon test, p value<0.001), as well as in the counterpart contralateral normal breast region of interest (ROI) (Wilcoxon test, p value = 0.001). Although the oxygen saturation level was not statistically significant between CAIX-positive vs. -negative cases, lesional TVP/area showed a positive correlation with the oxygen saturation level only in the group that had received therapy before PAM. In conclusion, the vascular and oxygenation data obtained by PAM have great potential for identifying functional features of breast tumors.     

The Hsp90 Inhibitor Geldanamycin Abrogates Colocalization of eIF4E and eIF4E-Transporter into Stress Granules and Association of eIF4E with eIF4G

The eukaryotic translation initiation factor eIF4E plays a critical role in the control of translation initiation through binding to the mRNA 5′ cap structure. eIF4E is also a component of processing bodies and stress granules, which are two types of cytoplasmic RNA granule in which translationally inactivated mRNAs accumulate. We found that treatment with the Hsp90 inhibitor geldanamycin leads to a substantial reduction in the number of HeLa cells that contain processing bodies. In contrast, stress granules are not disrupted but seem to be only partially affected by the inhibition of Hsp90. However, it is striking that eIF4E as well as its binding partner eIF4E transporter (4E-T), which mediates the import of eIF4E into the nucleus, are obviously lost from stress granules. Furthermore, the amount of eIF4G that is associated with the cap via eIF4E is reduced by geldanamycin treatment. Thus, the chaperone activity of Hsp90 probably contributes to the correct localization of eIF4E and 4E-T to stress granules and also to the interaction between eIF4E and eIF4G, both of which may be needed for eIF4E to acquire the physiological functionality that underlies the mechanism of translation initiation.     

Responses of coral reefs to increased amplitude of sea-level changes at the Mid-Pleistocene Climate Transition

We show responses of coral reefs to increased amplitude of sea-level changes at the Mid-Pleistocene Climate Transition (MPT) based on lithostratigraphic, sedimentologic and calcareous nannofossil biostratigraphic investigations on Pleistocene reef-complex deposits (Ryukyu Group) on the Motobu Peninsula, Okinawa-jima, Central Ryukyus. Our data show that reef growth started in earliest Quaternary time (1.45-1.65 Ma) and that extensive reef formation dates back to ∼ 0.8 Ma. The mode of Quaternary sedimentation changed at ∼ 0.8 Ma in the study area. Before this time, thick siliciclastics and mixed carbonate-siliciclastics accumulated, which were followed by the deposition of bioclastic sediments (detrital limestone). No indications have been found of episodic subaerial exposures in these deposits and no calcareous nannofossil biozones are lacking. Since the detrital limestone includes biogenic components characterizing fore-reef to shelf environments, the coastal areas of the northern Motobu Peninsula mostly lay in fore-reef to shelf environments for > 0.6 million years (between ∼ 0.8 Ma and 1.45-1.65 Ma), when the sediments had not been subaerially exposed due to sea-level changes characterized by relatively small amplitudes. Coral limestone that formed in the latest Early to Middle Pleistocene between 0.4 Ma and 0.8 Ma extends over the study area, ranging in elevation from 0 to 70 m. This coral limestone grades upward into fore-reef to shelf carbonates (rhodolith, Cycloclypeus-Operculina, and detrital limestones) which is in turn overlain by coral limestone. This succession, combined with configuration of the lithofacies and paleobathymetry inferred from lithology and biogenic components, implies that the reef-complex deposits formed responding to sea-level changes with amplitude of > 60 m. Consequently, we suggest that the change in the mode of sedimentation results from increased amplitude of sea-level fluctuations at ∼ 0.8 Ma. This timing corresponds roughly to the timing of the Mid-Pleistocene Climate Transition (MPT).     

Development of a novel fusogenic viral liposome system (HVJ-liposomes) and its applications to the treatment of acquired diseases

Toward human gene therapy and gene analysis in vivo, a novel hybrid vector based on liposome has been developed for more efficient gene delivery and gene expression. The liposome was decorated with HVJ (Sendai virus) envelope fusion proteins to introduce DNA directly into the cytoplasm, and contained DNA and DNA-binding nucelar protein to enhance expression of the gene. Recently, several types of HVJ-liposomes were developed by altering the lipid components of the liposomes. HVJ-cationic liposomes increased gene delivery 100 - 800 times more efficiently in vitro than the conventional HVJ-anionic liposomes. HVJ-cationic liposomes were also more useful for gene expression in restricted portions of organs and for gene therapy of disseminated cancers. It was further discovered that the use of anionic liposomes with a virus-mimicking lipid composition (HVJ-AVE liposomes) increased transfection efficiency by several fold in vivo, especially in liver and muscle. By coupling the Epstein-Barr (EB) virus replicon apparatus to HVJ-liposomes, transgene expression was sustained in vitro and in vivo. Most animal organs were found to be suitable targets for the fusigenicviral liposome system, and numerous gene therapy strategies using this system were successful in animals.     

Accuracy of specimen-specific nonlinear finite element analysis for evaluation of radial diaphysis strength in cadaver material

The feasibility of a user-specific finite element model for predicting the in situ strength of the radius after implantation of bone plates for open fracture reduction was established. The effect of metal artifact in CT imaging was characterized. The results were verified against biomechanical test data. Fourteen cadaveric radii were divided into two groups: (1) intact radii for evaluating the accuracy of radial diaphysis strength predictions with finite element analysis and (2) radii with a locking plate affixed for evaluating metal artifact. All bones were imaged with CT. In the plated group, radii were first imaged with the plates affixed (for simulating digital plate removal). They were then subsequently imaged with the locking plates and screws removed (actual plate removal). Fracture strength of the radius diaphysis under axial compression was predicted with a three-dimensional, specimen-specific, nonlinear finite element analysis for both the intact and plated bones (bones with and without the plate captured in the scan). Specimens were then loaded to failure using a universal testing machine to verify the actual fracture load. In the intact group, the physical and predicted fracture loads were strongly correlated. For radii with plates affixed, the physical and predicted (simulated plate removal and actual plate removal) fracture loads were strongly correlated. This study demonstrates that our specimen-specific finite element analysis can accurately predict the strength of the radial diaphysis. The metal artifact from CT imaging was shown to produce an overestimate of strength.     

Implications of Amino Acid Substitutions in GyrA at Position 83 in Terms of Oxolinic Acid Resistance in Field Isolates of Burkholderia glumae, a Causal Agent of Bacterial Seedling Rot and Grain Rot of Rice

Oxolinic acid (OA), a quinolone, inhibits the activity of DNA gyrase composed of GyrA and GyrB and shows antibacterial activity against Burkholderia glumae. Since B. glumae causes bacterial seedling rot and grain rot of rice, both of which are devastating diseases, the emergence of OA-resistant bacteria has important implications on rice cultivation in Japan. Based on the MIC of OA, 35 B. glumae field isolates isolated from rice seedlings grown from OA-treated seeds in Japan were divided into sensitive isolates (OSs; 0.5 μg/ml), moderately resistant isolates (MRs; 50 μg/ml), and highly resistant isolates (HRs; ≥100 μg/ml). Recombination with gyrA of an OS, Pg-10, led MRs and HRs to become OA susceptible, suggesting that gyrA mutations are involved in the OA resistance of field isolates. The amino acid at position 83 in the GyrA of all OSs was Ser, but in all MRs and HRs it was Arg and Ile, respectively. Ser83Arg and Ser83Ile substitutions in the GyrA of an OS, Pg-10, resulted in moderate and high OA resistance, respectively. Moreover, Arg83Ser and Ile83Ser substitutions in the GyrA of MRs and HRs, respectively, resulted in susceptibility to OA. These results suggest that Ser83Arg and Ser83Ile substitutions in GyrA are commonly responsible for resistance to OA in B. glumae field isolates.