Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) in middle-aged populations; however, it is unclear whether these SNPs are associated with body fatness in elderly people. We examined the association between genetic risk score (GRS) from BMI-associated SNPs and body fatness in elderly Japanese men. We also examined the contribution of GRS, dietary macronutrient intake, and physical activity to body fatness by different age groups. GRS was calculated from 10 BMI-associated SNPs in 84 middle-aged (30–64 years) and 97 elderly (65–79 years) Japanese men; subjects were divided into low, middle, and high GRS groups. Dietary macronutrient intake was assessed using a questionnaire, and physical activity was evaluated using both a questionnaire and an accelerometer. The middle-aged individuals with a high GRS had greater BMI; waist circumference; and total abdominal fat, visceral fat, and subcutaneous fat areas than the middle-aged individuals with low GRS, whereas the indicators were not different between the GRS groups in elderly individuals. Multiple linear regression analysis showed that GRS was the strongest predictor of BMI, total abdominal fat, and visceral fat in the middle-aged group, whereas fat, alcohol, and protein intakes or vigorous-intensity physical activity were more strongly associated with these indicators than was GRS in the elderly group. These results suggest that GRS from BMI-associated SNPs is not predictive of body fatness in elderly Japanese men. The stronger contribution of dietary macronutrient intake and physical activity to body fatness may attenuate the genetic predisposition in elderly men.     

Bronchioalveolar morphogenesis of human bronchial epithelial cells depending upon hepatocyte growth factor

Lung alveolar regeneration occurs in adult human lungs as a result of proliferation, differentiation and alveolar morphogenesis of stem cells. It is increasingly being believed that bronchial epithelial cells (BECs) have a potential as stem cells, because they are potent to differentiate into multiple central and peripheral lung cell types in three‐dimensional (3D) cultures, and they develop multiple foci with well‐differentiated histogenesis after transformed into neoplastic cells. In this study, we investigated morphogenic abilities of HBE135 human BECs immortalized by E6/E7 oncogene in 3D cultures. When HBE135 cells were cultured alone or co‐cultured with endothelial cells, the cells formed spherical colonies without branching. However, in co‐culture with lung fibroblast MRC‐9 cells, HBE135 cells formed colonies with bronchioalveolar‐like complex branching, suggesting that MRC‐9‐derived soluble factor(s) are responsible for the branching formation. MRC‐9 cells, not endothelial cells, were found to highly express hepatocyte growth factor (HGF), a soluble molecule involved in liver and kidney regeneration. An anti‐HGF neutralizing antibody severely suppressed the complex branching formation, but addition of HGF could not sufficiently compensate the morphogenic effects of MRC‐9 cells, suggesting that MCR‐9‐derived HGF was necessary but insufficient for the bronchioalveolar structure formation. Immunohistochemistry revealed that Met, a cognate receptor for HGF, was highly expressed and phosphorylated in neoplastic BECs from lung adenocarcinomas with well‐differentiated, not poorly differentiated, histogenesis. These results are consistent with the notion that BECs have an aspect of stem cells. This aspect appears to become manifest through HGF–Met signalling pathway activation.     

A novel mutation of the doublecortin gene in Japanese patients with X-linked lissencephaly and subcortical band heterotopia

The doublecortin (DCX) gene was recently found to be involved in patients with X-linked lissencephaly and subcortical band heterotopia or double cortex syndrome. We have studied the coding regions of the DCX gene in 11 Japanese patients with cortical dysplasia and have identified three different mutations (R186C in exon 3, R272X and R303X in exon 5) in four sporadic female cases. R272X, which has been detected in two unrelated cases, is a novel mutation. Although the number of cases studied remains limited, exon 5 may be a common mutational site in Japanese patients in contrast to many previus reports concerning exons 2 and 3. Received: 28 October 1998 / Accepted: 26 February 1999     

Vitamin B12 deficiency-induced increase of osteoclastic bone resorption caused by abnormal renal resorption of inorganic phosphorus via Napi2a

Vitamin B₁₂ deficiency is a risk factor for bone disorders via mechanisms not fully understood. In this study, an increase in serum inorganic phosphorus (Pi) concentrations was associated with a vitamin B₁₂ deficiency. Napi2a, a renal cotransporter for Pi reabsorption, accumulated on plasma membranes in a vitamin B₁₂ deficiency suggests that vitamin B₁₂ plays an important role in Pi homeostasis.     

Brief measure for screening complicated grief: reliability and discriminant validity

Background

Complicated grief, which is often under-recognized and under-treated, can lead to substantial impairment in functioning. The Brief Grief Questionnaire (BGQ) is a 5-item self-report or interview instrument for screening complicated grief. Although investigations with help-seeking samples suggest that the BGQ is valid and reliable, it has not been validated in a broader population.

Methodology/Principal Findings

A questionnaire was mailed to a randomly selected sample (n = 5000) residing in one of 4 areas of Japan. The BCQ was examined for responders who were bereaved more than 6 months and less than 10 years (n = 915). Non-specific psychological distress was assessed with the K6 screening scale. Multiple group confirmatory factor analysis supported a uni-dimensional factor structure and the invariance of parameters across gender and age. Cronbach''s alpha was sufficiently high (alpha = .75) to confirm internal consistency. Average Variance Extracted (0.39) was higher than the shared covariance (0.14) between BGQ and K6, suggesting discriminant validity.

Conclusions

The results of this study support the reliability and validity of the BGQ in the Japanese population. Future studies should examine predictive validity by using structured interviews or more detailed scales for complicated grief.     

The critical role of the universally conserved A2602 of 23S ribosomal RNA in the release of the nascent peptide during translation termination

The ribosomal peptidyl transferase center is responsible for two fundamental reactions, peptide bond formation and nascent peptide release, during the elongation and termination phases of protein synthesis, respectively. We used in vitro genetics to investigate the functional importance of conserved 23S rRNA nucleotides located in the peptidyl transferase active site for transpeptidation and peptidyl-tRNA hydrolysis. While mutations at A2451, U2585, and C2063 (E. coli numbering) did not significantly affect either of the reactions, substitution of A2602 with C or its deletion abolished the ribosome ability to promote peptide release but had little effect on transpeptidation. This indicates that the mechanism of peptide release is distinct from that of peptide bond formation, with A2602 playing a critical role in peptide release during translation termination.     

The isolation and culture of lily pollen protoplasts

Methods for the enzymatic isolation of lily protoplasts and their successful culture are described. When pre-anthesis binucleate pollen (immature pollen grains) was treated in enzyme solution containing macerozyme and cellulase, up to 80% lost their exine and gave rise to intact protoplasts within 1 h. These pollen protoplasts were uniform in size and densely cytoplasmic with two prominent generative and vegetative nuclei. The isolated pollen protoplasts regenerated a cell wall within 1 day of culture and produced a structure resembling a pollen tube after 10–12 days of culture. During this culture period, dividing generative nuclei or 2 sperm nuclei were observed in many protoplasts with regenerated cell walls.     

Design,synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

A series of novel 6-desfluoro [des-F(6)] and 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methoxyquinolones bearing 3-(1-aminocycloalkyl)pyrrolidin-1-yl substituents at the C-7 position (1–6) was synthesized to obtain potent drugs for nosocomial infections caused by Gram-positive pathogens. The des-F(6) compounds 4–6 exhibited at least four times more potent activity against representative Gram-positive bacteria than ciprofloxacin or moxifloxacin. Among the derivatives, 7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl] derivative 4, which showed favorable profiles in preliminary toxicological and non-clinical pharmacokinetic studies, exhibited potent antibacterial activity against clinically isolated Gram-positive pathogens that had become resistant to one or more antibiotics.