In the present study, weights of calves (14 days after birth) derived from embryos of a homogeneous line (Tajima line) of Japanese Black Cow, cultured in vitro under various oxygen conditions was ...examined. In vitro matured and fertilized oocytes were incubated for 48 h in modified synthetic oviduct fluid medium under 5% CO2 in air and embryos reaching at least the 5-cell stage were selected for further culture under various gas conditions (high oxygen tension: 5% CO, in air; low oxygen tension: 5% O2, 5% CO2, 90% N2) for 5 days. Embryos that developed to the blastocyst stage were transferred to Holstein cows or cryopreserved until transfer. When embryos were cultured under high oxygen tension and cryopreserved, the weights of male calves (at 14 days) were significantly heavier than in the other groups. However, there was no significant difference in gestation lengths of male calves. In female calves, no difference was observed in either the weight or gestation length of calves irrespective of oxygen tension during the culture period or embryo conditions (fresh or frozen). From the results of the present study, it is suggested that the oxygen concentration during culture and cryopreservation synergistically induced the production of overweight male calves without influencing gestation length.
To describe the eating habits and physical activity of Japanese children aged 10 y, and to investigate their relationship to lipids and body mass index (BMI); also to study the relationship between ...BMI and lipids in these children.
This was a cross-sectional study conducted at six schools in Shiratori, Japan during 1992-1994. Physical examinations and questionnaires were used to collect data from 457 fifth grade children, aged 10 y.
The diet of these children was mixed, with Japanese and Western foods almost equally reported. Boys were more active than girls. More active children had higher high density lipoprotein cholesterol (HDL-C), and children who ate a more Japanese diet had slightly lower HDL-C. BMI was positively related to cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides and inversely related to HDL-C. The amount of rice intake was positively associated with the BMI of these children.
In our study of Japanese children aged 10 y, their diets were fairly Westernized, and most children were fairly inactive based on our activity score. Although obesity is low in these young Japanese subjects (14.1%), children who were obese (BMI>20) had worse lipid profiles than those who were not obese. An exceptionally high rice intake was associated with obesity, and thus may be an early warning sign for future obesity.
Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date ...explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10−9). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
High-throughput assay of molecular markers enables to utilize large amounts of markers in linkage mapping. To incorporate numerous markers into a linkage map, the development of a highly efficient ...method for linkage mapping is indispensable. When the number of loci is large, locus ordering is a major difficulty in linkage mapping, since the number of possible orders becomes very large. To address this problem, we developed a new algorithm for locus ordering and used it in a newly developed computer program called AntMap. The algorithm is based on ant colony optimization, which is a set of metaheuristic algorithms inspired by the cooperative behavior of real ants in finding the shortest path from their nest to a food source. Using this algorithm, AntMap seeks the linear order of loci that minimizes the sum of adjacent recombination fractions or that maximizes the log likelihood of locus order. Analyses based on simulated data sets indicated that our algorithm displayed a high efficiency level. The high performance of the algorithm enabled to save time and labor, and also to validate an estimated order by bootstrap tests. Our algorithm and AntMap should enable to construct high-throughput systems for linkage mapping. AntMap is available under a GNU general public license at http://cse.naro.affrc.go.jp/iwatah/antmap/index.html. Source codes and executables of AntMap can be obtained there.
Trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in human epidermal ...growth factor receptor 2-positive metastatic breast cancer patients. This study evaluated the maximum tolerated dose, toxicity and pharmacokinetics of trastuzumab emtansine in Japanese breast cancer patients.
Inoperable advanced or recurrent human epidermal growth factor receptor 2-positive breast cancer patients were administered trastuzumab emtansine intravenously at a dose of 1.8, 2.4 or 3.6 mg/kg every 3 weeks. The maximum tolerated dose was estimated using the continual reassessment method.
This study enrolled 10 patients who were administered trastuzumab emtansine for a median of seven cycles. The dose-limiting toxicity was Grade 3 elevation of aspartate aminotransferase/alanine aminotransferase at the 2.4 mg/kg dose level. The maximum tolerated dose was estimated to be 3.6 mg/kg because at the point when dose-limiting toxicity was evaluable in 10 patients, the probability of dose-limiting toxicity estimated using the continual reassessment method was closest to 25% at a dose of 3.6 mg/kg and this was unchanged by the results for patients enrolled after that. The most frequent adverse events were nausea, arthralgia, fever, fatigue and decreased appetite. Adverse events were generally tolerable. The maximum concentration and area under the concentration-time curve increased linearly with the dose.
Trastuzumab emtansine up to 3.6 mg/kg was well tolerated by Japanese breast cancer patients. Although thrombocytopenia and hepatotoxicity tended to be more severe than was seen in Western patients in previous trastuzumab emtansine trials, those adverse events recovered without special supportive treatment.
The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome
P4501A (CYP1A) signaling pathway. By the ...cloning of 5′-flanking regions of CYP1A5 gene from common cormorant (
Phalacrocorax carbo) and chicken (
Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (
ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (
ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by
in vitro reporter gene assays revealed that two XREs at −613 bp and −1585 bp in
ccCYP1A5, and one XRE at −262 bp in
ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC
50 for the transcriptional activity in both cormorant AHR1- and AHR2-
ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-
ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC
50 for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species.
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