Migration of Tumor Antigen-Pulsed Dendritic Cells After Mucosal Administration in the Human Upper Respiratory Tract

Tumor-specific peptide-pulsed dendritic cells (DC) were administered via different routes to a group of patients with head and neck cancers. The migration and homing patterns of such antigen-stimulated cells was carefully studied employing single photon emission computed tomography (SPECT). The DC administered directly into the nasal submucosa quickly migrated very rapidly to the regional neck lymph nodes in the neck. However, after inoculation of the cells into the palatine tonsils, the DCs remained close to the site of administration and did not migrate to the regional lymph nodes or to other mucosal regions. After nasal submucosal administration of the DC, tumor-antigen-specific cytotoxic T cells were detected in the ipsilaterals but not in the contra lateral lymph nodes. These results suggest that after antigen processing, the regional lymph nodes serve as inductive sites for development of mucosal immune responses and for induction of memory cells during the local immunological responses in the nasopharyngeal-associated lymphoid tissue in man.     

Segmental and complementary expression of L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase and neutral amino acid transporter ASCT1 in the mouse kidney

3-Phosphoglycerate dehydrogenase (Phgdh) is the initial step enzyme in the phosphorylated pathway of L-serine biosynthesis. We have previously revealed in the brain that Phgdh is preferentially expressed in glial cells, but not in neurons, and that glia-borne L-serine exerts strong neurotrophic actions to neuronal survive, differentiation, and development. To investigate whether such an L-serine-meditated intercellular relationship is constructed in peripheral organs and tissues, we examined the kidney, which is one of the organs with the highest expression of Phgdh mRNA in the body. We found that Phgdh was distributed highly in the renal papilla and inner layer of the outer zone and moderately in the cortex, whereas it was almost negative in the outer layer of the outer zone. This heterogeneous distribution was due to selective expression in distinct tubular segments, i.e., the Bowman's capsule, proximal tubule, and thin limbs of the Henle's loop. Interestingly, neutral amino acid transporter ASCT1, which preferentially transports alanine, serine, cysteine, and threonine, was selectively expressed in Phgdh-negative tubular segments, i.e., the distal tubule and collecting duct. Therefore, either Phgdh or ASCT1 is provided to each segment of renal tubules, suggesting that metabolic interplay mediated by L-serine biosynthesis and supply may exist in the kidney too.     

Study of quantification of oxidative stresses caused by lifestyle habits

It is now clear that oxidative stresses caused by reactive oxygen species, free radicals originating in them, and lipid peroxides can be factors to cause over 90% of lifestyle-related diseases including cancer, heart diseases, cerebrovascular diseases, arteriosclerosis, hypertension, and diabetes mellitus. In the present study, health conditions, nutrition intake, bodily activities, smoking/non-smoking, and sleep hours among other factors were surveyed with youths around twenty years old of age as subjects, and those results and the results of measurement of speed for the generation of 8-OHdG (8-Hydroxy-2'-Deoxyguanosine) as oxidative stress biomarker were compared for consideration. As a result, there were correlations detected as to exercise habits, cholesterol values, and smoking habits. It was also clarified that oxidative stresses decrease by continuing taking constant aerobic exercises or by quitting smoking or reducing the numbers of cigarettes to smoke. Thereby, it was suggested that the measurement of speed for the generation of 8-OHdG can provide an indicator that is useful as an integrated evaluation to improve lifestyle habits that are to be understood to induce lifestyle-related diseases.