Objectively Measured Intensity-specific Physical Activity and Hippocampal Volume Among Community-dwelling Older Adults.

BACKGROUND: The hippocampus is a brain structure important for memory and cognitive function. Physical activity may help prevent hippocampal atrophy. However, few studies have measured sedentary behavior (SB) and intensity-specific physical activity using an accelerometer. This study aimed to examine the cross-sectional associations of objectively-determined SB, light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA) measured by an accelerometer with hippocampal volume among community-dwelling older adults using compositional data analysis (CoDa) approach. METHODS: This cross-sectional study was part of the Neuron to Environmental Impact across Generations (NEIGE) study. A randomly recruited sample of 485 Japanese older adults (47% male; aged 65-84 years) wore tri-axial accelerometers (Omron Healthcare) for 7 consecutive days in 2017. Hippocampal volume was measured with magnetic resonance imaging and the left and right hippocampal volumes were automatically segmented using FreeSurfer software. Associations of sedentary and physically active behaviors with hippocampal volume were examined with compositional linear regression analysis based on isometric log-ratio transformations of time use adjusted for potential confounding factors. RESULTS: The relative proportion of time spent in MVPA, compared to the other two activities, was significantly positively associated with right hippocampal volume (ß: 57.1, P-value = 0.027). However, no association existed between higher proportions of MVPA and left hippocampal volume, or between proportions of SB or LPA with either left or right hippocampal volumes. CONCLUSION: The proportion of time spent in MVPA, relative to the other two activities, was significantly positively associated with right hippocampal volume. MVPA may be beneficial for maintaining hippocampal volume.

Primary malignant lymphoma of the brain: frequent abnormalities and inactivation of p14 tumor suppressor gene.

Ten primary central nervous system lymphomas (PCNSL, brain lymphomas) were examined for p14 gene exon 1beta deletion, mutation and methylation by Southern blot analysis, nucleotide analysis of polymerase chain reaction clones and Southern blot-based methylation assay. In Southern blot analysis, from the signal densities of the hybridized bands and their similarities to those of exons 2 and 3 in our previous quantitative study, we found that exon 1beta was homozygously deleted in four cases, hemizygously deleted in five cases and not deleted in one case. Thus, the same deletion patterns covered the entire p14 gene for all cases except for one case, which suggested the hemizygous deletion of exons 1beta and 2 and homozygous deletion of exon 3. In addition, although exon 1beta mutation is rare in various tumors, we detected a missense mutation (L50R) in one case with a hemizygous deletion. Methylation of the 5'CpG island of the p14 gene was not suggested for any case without homozygous deletion. Our observation of frequent p14 gene abnormalities (90%) and inactivation (40-60%) was in striking contrast to the same pathological subtype of systemic lymphoma in which p14 gene abnormalities and inactivation were infrequent, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma.

Primary malignant lymphoma of the brain: mutation pattern of rearranged immunoglobulin heavy chain gene.

Using reverse transcription-polymerase chain reaction (RT-PCR), six primary brain lymphomas, pathologically diagnosed as diffuse large B-cell lymphoma, were examined for rearranged VH-D-JH sequences of the immunoglobulin heavy chain gene, focusing on somatic mutations and intraclonal heterogeneity. The reliability of the isolated PCR clones was confirmed by in situ hybridization (ISH) with complementarity-determining region (CDR) 3 oligonucleotide probes. Sequence analysis of the PCR clones revealed a high frequency of somatic mutation, ranging from 8.8 to 27.3% (mean 18.2%) in the VH gene segments in all the lymphomas. A significantly lower frequency of replacement (R) mutations than expected was also seen in their frameworks (FRs) in all cases. These findings suggested that the precursor cells were germinal center (GC)-related cells in these lymphomas. However, despite extensive cloning experiments, intraclonal heterogeneity was not detected in any case except for one in which it could not be ruled out. Thus, it seemed likely that all of our brain lymphomas were derived from GC-related cells and that at least most of them were from post-GC cells.