Salmonella typhimurium harboring plasmid expressing interleukin-12 induced attenuation of infection and protective immune responses

IL-12 is known to be an essential cytokine which appears to provide protective immunity against intracellular bacteria, such as Salmonella. In this study, we investigated the possibility of developing a vaccine using IL-12 against virulent Salmonella. We used the host defense system activated by cytokine IL-12. The highly virulent Salmonella strain (Salmonella typhimurium UK-1) was transformed with cytokine-expressing plasmids. These live, wild-type pathogens were used as vaccine strains without undergoing any other biological or genetic attenuating processes. The newly developed strains induced partial protection from infections (30-40%). Of note, the interleukin-12 transformed pathogen was safe upon immunization with low doses (103 CFU), induced IgG responses, and stimulated protective immune responses against Salmonella Typhimurium in mice (80-100%). These results suggest that IL-12 induced attenuation of wild-type Salmonella in the host infection stage and vaccine development using the wild-type strain harboring IL-12 secreting plasmids may be considered as an alternative process for intracellular bacterial vaccine development without the inconvenience of time-consuming attenuation processes

A Survey on the Impact of Operation Volume on Rectal Cancer Management

The rectal cancer management can be influenced by the surgeon's practice and the hospital. This study was to evaluate the differences according to the surgeon's operative volume and the level of the hospital. Questionnaires were sent out to the members of the 'Korean Society of Coloproctology', and the responses were evaluated according to the surgeon's operation volume, the surgeon's age, and the level of the hospital. Sixty responses were received during the three months' period (from August to October 2004). Thirty three respondents (55%) operated more than 50 cases of rectal cancer per year (high-volume surgeons), and 37 respondents (61%) worked at university hospitals or tertiary care facilities (high-level hospitals). The preoperative evaluation with endorectal ultrasonography (ERUS) was significantly different according to the surgeon's operation volume and the level of the hospital, whereas magnetic resonance imaging and positron emission tomography (PET) was significantly different only for the surgeon's operation volume. The preoperative radiation therapy was significantly different according to the surgeon's operation volume, the surgeon's age, and the level of the hospital. However, there was no significant difference found on the operative procedures or postoperative surveillance. The preoperative loco-regional evaluation and the preoperative radiation therapy could be considered as the factors that influence the volume-outcome relationship in rectal cancer treatment

Putative cell adhesion membrane protein Vstm5 regulates neuronal morphology and migration in the central nervous system

During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporationin utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics.SIGNIFICANCE STATEMENTNeuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development.</jats:p

Development of the MICROMEGAS Detector for Measuring the Energy Spectrum of Alpha Particles by using a 241-Am Source

We have developed MICROMEGAS (MICRO MEsh GASeous) detectors for detecting {\alpha} particles emitted from an 241-Am standard source. The voltage applied to the ionization region of the detector is optimized for stable operation at room temperature and atmospheric pressure. The energy of {\alpha} particles from the 241-Am source can be varied by changing the flight path of the {\alpha} particle from the 241 Am source. The channel numbers of the experimentally-measured pulse peak positions for different energies of the {\alpha} particles are associated with the energies deposited by the alpha particles in the ionization region of the detector as calculated by using GEANT4 simulations; thus, the energy calibration of the MICROMEGAS detector for {\alpha} particles is done. For the energy calibration, the thickness of the ionization region is adjusted so that {\alpha} particles may completely stop in the ionization region and their kinetic energies are fully deposited in the region. The efficiency of our MICROMEGAS detector for {\alpha} particles under the present conditions is found to be ~ 97.3 %

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

PURPOSE: Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer. MATERIALS AND METHODS: A total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls. RESULTS: Interpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma. CONCLUSION: Our study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.ope

An Annular Array MPT for Enhanced Generation of Omnidirectional SH Waves in a Plate

If guided wave transducers are fabricated in an annular array type, the excitation and measurement of target guided wave modes could be considerably enhanced (see, e.g., [1]). Accordingly, various annular array transducers have been developed, including those generating omnidirectional Lamb waves in a plate. Here, we newly consider an annular array type MPT (magnetostrictive patch transducer) to generate enhanced SH (shear-horizontal) waves in a plate. This annular array MPT is based on our earlier development of an omnidirectional SH wave MPT [2]. For wave field analysis by the annular array SH wave MPT, the strain response in a plate due to wave excitation by the MPT is calculated by using the Green’s function approach [3]. Using the analysis, an optimal configuration of the annular array MPT which can maximize the transducer output at the given frequency is determined. For the validation of numerical predictions, a series of experiments with varying frequencies were carried out and the numerical results were found to be in good agreement with the experimental results