Contribution of physical fitness component to health status in middle-aged and elderly females

This study determined the physical fitness component that contributes to improving and maintaining health status for each age group as well as quantifying the degree of the relationship between health status and physical fitness in middle-aged and elderly females. The participants were 2,371 females aged 30 to 69 years. Ten physical fitness tests and medical checkups were performed. The participants were divided into a healthy group and an unhealthy group according to health status. Multiple discriminant analysis was applied to the multivariate data. Correct discriminant probabilities of the multiple discriminant function to discriminate the healthy and unhealthy groups for females ranged from 63.0% to 77.5%. These results suggest that there is a relatively high relationship between health status and physical fitness level for middle-aged and elderly females. With each individual's discriminant score calculated by the obtained multiple discriminant function as the index of the degree of health, the Pearson's correlation coefficient of the discriminant score and the performance in each physical fitness test were calculated. The aging change from 30 to 69 years old was classified into four patterns according to the contribution. The result of this study is considered to be useful as objective data to prepare an exercise program considering the contribution of the physical fitness component of health status.     

Calcium-independent induction of cytocidal activity of polymorphonuclear leukocytes by phorbol myristate acetate-like tumor promoters

Tumor promoters were tested for the ability to induce cytocidal activity of polymorphonuclear leukocytes (PMNs), and the extracellular calcium-dependency of their PMN cytotoxicities were examined in comparison with that by some immunomodulators. Immunomodulators such as linear beta-1, 3-D-glucan (TAK) induced potent cytocidal activity of PMNs. The induction was dependent on extracellular Ca2+. Tumor promoters such as phorbol 12-myristate 13-acetate (PMA) and its derivatives, teleocidin which is structurally unrelated to PMA, and croton oil as an example of mixture also induced potent PMN cytotoxicities. In the latter cases, however, the induction was not dependent on extracellular Ca2+. The ability of these tumor promoters to induce PMN cytotoxicity correlated well with their skin-tumor promoting activities. These results indicate that inductions by PMA-like tumor promoters are distinguishable from those by TAK-like immunomodulators in not being Ca2+-dependent. The application of Ca2+-independent PMN cytotoxicity to detect PMA-like tumor promoters is discussed.     

Spread of X-chromosome inactivation into chromosome 15 is associated with Prader–Willi syndrome phenotype in a boy with a t(X;15)(p21.1;q11.2) translocation

X-chromosome inactivation (XCI) is an essential mechanism in females that compensates for the genome imbalance between females and males. It is known that XCI can spread into an autosome of patients with X;autosome translocations. The subject was a 5-year-old boy with Prader?CWilli syndrome (PWS)-like features including hypotonia, hypo-genitalism, hypo-pigmentation, and developmental delay. G-banding, fluorescent in situ hybridization, BrdU-incorporated replication, human androgen receptor gene locus assay, SNP microarrays, ChIP-on-chip assay, bisulfite sequencing, and real-time RT-PCR were performed. Cytogenetic analyses revealed that the karyotype was 46,XY,der(X)t(X;15)(p21.1;q11.2),?15. In the derivative chromosome, the X and half of the chromosome 15 segments showed late replication. The X segment was maternal, and the chromosome 15 region was paternal, indicating its post-zygotic origin. The two chromosome 15s had a biparental origin. The DNA methylation level was relatively high in the region proximal from the breakpoint, and the level decreased toward the middle of the chromosome 15 region; however, scattered areas of hypermethylation were found in the distal region. The promoter regions of the imprinted SNRPN and the non-imprinted OCA2 genes were completely and half methylated, respectively. However, no methylation was found in the adjacent imprinted gene UBE3A, which contained a lower density of LINE1 repeats. Our findings suggest that XCI spread into the paternal chromosome 15 led to the aberrant hypermethylation of SNRPN and OCA2 and their decreased expression, which contributes to the PWS-like features and hypo-pigmentation of the patient. To our knowledge, this is the first chromosome-wide methylation study in which the DNA methylation level is demonstrated in an autosome subject to XCI.     

Heart rate variability during long truck driving work

We recorded ambulatory electrocardiograms of 6 long distance truck drivers during their work period in order to observe the affect of autonomic nervous function and symptoms while doing their work. We also recorded their work patterns every minute. The RR50 value and the LFP/HFP ratio were calculated every two minutes based on R-R interval data. RR50 was significantly higher during taking naps than during other periods of work shifts, while, the LFP/HFP ratio showed significantly lower during taking naps than during other periods of work shifts. RR50 in the morning was significantly higher than that in the afternoon. On the contrary, the LFP/HFP ratio showed opposite tendency. Only on the times of driving, RR50 was significantly higher in the morning than that in the afternoon. On the other hand, the LFP/HFP ratio showed an opposite tendency. These results show that the parasympathetic nervous activities were more dominant than sympathetic nervous activities in the morning during the subjects were doing long distance truck driving including midnight work. Driving while in high parasympathetic nervous activity levels may add to cardiovascular stress and lead to drowsiness. And this may result in disrupted attention. It is necessary to decrease work time and improve working conditions of truck drivers working long-hour shifts.     

Early candidacy for differentiation into heterocysts in the filamentous cyanobacterium Anabaena sp. PCC 7120

The filamentous cyanobacterium Anabaena sp. PCC 7120 fixes dinitrogen facultatively. Upon depletion of combined nitrogen, about 10% of vegetative cells within the filaments differentiate terminally into nitrogen-fixing cells. The heterocyst has been studied as a model system of prokaryotic cell differentiation, with major focus on signal transduction and pattern formation. The fate of heterocyst differentiation is determined at about the eighth hour of induction (point of no return), well before conspicuous morphological or metabolic changes occur. However, little is known about how the initial heterocysts are selected after the induction by nitrogen deprivation. To address this question, we followed the fate of every cells on agar plates after nitrogen deprivation with an interval of 4 h. About 10% of heterocysts were formed without prior division after the start of nitrogen deprivation. The intensity of fluorescence of GFP in the transformants of hetR-gfp increased markedly in the future heterocysts at the fourth hour with respect to other cells. We also noted that the growing filaments consisted of clusters of four consecutive cells that we call quartets. About 75% of initial heterocysts originated from either of the two outer cells of quartets at the start of nitrogen deprivation. These results suggest that the future heterocysts are loosely selected at early times after the start of nitrogen deprivation, before the commitment. Such early candidacy could be explained by different properties of the outer and inner cells of a quartet, but the molecular nature of candidacy remains to be uncovered.     

Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 2: optimization of inhibitors of human thymidine phosphorylase and their selectivity with uridine phosphorylase

A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2'-deoxy-5-(trifluoromethyl)uridine (F(3)dThd) pharmacokinetics. As a result, TAS-102 (a combination of F(3)dThd and TPI) is currently in phase 1 clinical studies.     

Antimicrobial susceptibility and genetic relatedness of bovine Stenotrophomonas maltophilia isolates from a mastitis outbreak

Aims: To evaluate the antimicrobial susceptibility and genetic relatedness of 11 Stenotrophomonas maltophilia isolates from an outbreak of bovine clinical mastitis in one herd and two isolates from two separate mastitis cases in two other herds. Methods and Results: Thirteen S. maltophilia isolates were obtained from milk samples from 11 cows from three dairy herds in Japan during 2008. We tested their susceptibility to 14 antimicrobials by broth microdilution and identified their genotypes by enterobacterial repetitive intergenic consensus 2 (ERIC2)‐PCR. Every cow had acute mild mastitis (slightly watery foremilk with flakes) without systemic symptoms and all resolved within 3–5 weeks of diagnosis. Eleven of the 13 isolates derived from nine cows in one herd over a 7‐month period exhibited a closely related ERIC2 type (A). The remaining two isolates derived from two cows from two other herds exhibited two distinct ERIC2 types (B and C). Most of the 13 isolates exhibited susceptibility to trimethoprim‐sulfamethoxazole, chloramphenicol, minocycline and levofloxacin; however, they were resistant to four β‐lactams, kanamycin, gentamicin and oxytetracycline. They were intermediate to enrofloxacin. Conclusions: Eleven closely related S. maltophilia isolates were involved in a herd outbreak of mastitis to some extent. Bovine S. maltophilia isolates exhibited resistance to many classes of antimicrobials. Significance and impact of study: This is a rare report of a herd outbreak of bovine mastitis involving closely related S. maltophilia isolates.