Therapeutic effect of alpha-galactosylceramide-loaded dendritic cells genetically engineered to express SLC/CCL21 along with tumor antigen against peritoneally disseminated tumor cells

The close cooperation of both innate and acquired immunity is essential for the induction of truly effective antitumor immunity. We tested a strategy to enhance the cross-talk between NKT cells and conventional antigen-specific T cells with the use of alpha GalCer-loaded dendritic cells genetically engineered to express antigen plus chemokine, attracting both conventional T cells and NKT cells. DC genetically engineered to express a model antigen, OVA, along with SLC/CCL21 or monokine induced by IFN-gamma/CXCL9, had been generated using a method based on in vitro differentiation of DC from mouse ES cells. The ES-DC were loaded with alpha-GalCer and transferred to mice bearing MO4, an OVA-expressing melanoma, and their capacity to evoke antitumor immunity was evaluated. In vivo transfer of either OVA-expressing ES-DC, stimulating OVA-reactive T cells, or alpha-GalCer-loaded non-transfectant ES-DC, stimulating NKT cells, elicited a significant but limited degree of protection against the i.p. disseminated MO4. A more potent antitumor effect was observed when alpha-GalCer was loaded to ES-DC expressing OVA before in vivo transfer, and the effect was abrogated by the administration of anti-CD8, anti-NK1.1 or anti-asialo GM1 antibody. alpha-GalCer-loaded double transfectant ES-DC expressing SLC along with OVA induced the most potent antitumor immunity. Thus, alpha-GalCer-loaded ES-DC expressing tumor-associated antigen along with SLC can stimulate multiple subsets of effector cells to induce a potent therapeutic effect against peritoneally disseminated tumor cells. The present study suggests a novel way to use alpha-GalCer in immunotherapy for peritoneally     

Argyrophilic nucleolar organizer regions of breast tumors: Assessment of aspirated cytological materials

To investigate the correlation between argyrophilic nucleolar organizer regions (Ag-NORs)and the malignant potential of breast tumors, we analyzed Ag-NORs of cytological specimens obtained from 190 patients with various types of breast disease by preoperative aspiration biopsy. The average number of Ag-NORs per nucleus was defined as the Ag-NOR score. The Ag-NOR score was 5.7 +/- 1.7 in the group of women with breast carcinoma (n =70), 2.6= 0.4 in the group with fibroadenoma (n= 54) and 2.9= 0.6 in the group with mastopathy (n= 66). The level was significantly higher in breast carcinoma than in each benign disease(P < 0.001 in both cases). The score was 6.5 +/- 2.3 in the group with four or more metastatic lymph nodes (n = 21), 5.2+/- 1.2 in the group with one to three metastatic lymph node (n= 10) and 5.1+/- 1.1 in that with no metastatic lymph node (n = 39);the score was significantly (P < 0.05) higher in the groups with four or more metastatic lymph modes than in the other groups, respectively. Thus, a correlaton was observed between the Ag-NOR score and lymph node status. These data suggest that a higher Ag-NOR score reflects high-grade malignancy.     

Comparison of speedy PCR-ssp method and serological typing of HLA-A24 for Japanese cancer patients

Human leukocyte antigen (HLA) typing is essential to carry out HLA-class I restricted antigenic peptide-based cancer immunotherapy. To establish a one-step polymerase chain reaction-sequence-specific primer (PCR-SSP) method, we designed two novel HLA-A24-specific primer sets and determined the optimal conditions for specific amplification. Then, we performed HLA-A24 typing of two healthy donors' and 17 cancer patients' peripheral blood with serological typing and PCR-SSP typing. Eleven of the 19 cases were determined HLA-A24-positive by the PCR-SSP method precisely; however, five cases showed false positive with serological analysis. Thus, for HLA-A24 typing in the Japanese population, the PCR-SSP method is faster and more accurate than serological typing.     

Biological materials: a materials science approach

The approach used by Materials Science and Engineering is revealing new aspects in the structure and properties of biological materials. The integration of advanced characterization, mechanical testing, and modeling methods can rationalize heretofore unexplained aspects of these structures. As an illustration of the power of this methodology, we apply it to biomineralized shells, avian beaks and feathers, and fish scales. We also present a few selected bioinspired applications: Velcro, an Al2O3-PMMA composite inspired by the abalone shell, and synthetic attachment devices inspired by gecko.     

Spatial and topologic distribution of verapamil-sensitive atrial tachycardia originating from the vicinity of the atrioventricular node

BACKGROUND: Little information exists regarding the precise distribution of verapamil-sensitive atrial tachycardia originating from the vicinity of the atrioventricular node (V-AT). METHODS: In 12 patients with V-AT, we examined the spatial and topologic distribution of tachycardia origin relative to the His bundle (HB) site. The V-AT origin was divided into six areas: anterior (A-HB), posterior (P-HB), superior (S-HB), inferior (I-HB), lateral (L-HB), and septal (SP-HB) portion of HB catheter. Three dimensional distance between the distal pair of the electrodes of HB catheter and that of V-AT origin (DIS) was obtained by calculating the distances on the right and left anterior fluoroscopic images. Topologic distribution was expressed as the interval between the onset of the atrial electrogram of V-AT origin and that of HB catheter (INT). RESULTS: The tachycardia origin was observed at the P-HB in four, S-HB in two, I-HB in two, SP-HB in three, and L-HB in one patient. The tachycardia cycle length, DIS, and INT were 369 +/- 67 ms, 12 +/- 3 mm, and -12 +/- 8 ms, respectively. After successful ablation of initial V-AT (1st V-AT), V-AT with a different origin (2nd V-AT) was induced in five patients. The tachycardia origin, tachycardia cycle length, DIS, and INT of the 2nd V-AT (P-HB in three, S-HB in one, and SP-HB in one patient; 333 +/- 66 ms, 8 +/- 3 mm, and -11 +/- 4 ms, respectively) were not different from those of 1st V-AT. CONCLUSIONS: V-AT often shows a shift in tachycardia origin to another site where the spatial and topologic distributions are similar to those of 1st V-AT.     

Dampness,food habits,and sick building syndrome symptoms in elementary school pupils

Objectives  

We investigated dampness/mold in schools and dwellings, and food habits and subjective symptoms in elementary school pupils, in order to clarify the effect of dampness and food habits on subjective symptoms in elementary school pupils.