A genetic factor associated with low final bone mineral density in children after a long-term glucocorticoids treatment.

Treatment with glucocorticoids is associated with lower bone mineral density (BMD). We performed a genome-wide association study to analyze interactive effects between genotypes and cumulative dose of prednisone (PD) over 4.3 years of follow-up period on the final BMD Z-scores in 461 white children from the Childhood Asthma Management Program. No variants met the conventional criteria for genome-wide significance, and thus we looked for evidence of replication. The top 100-ranked single-nucleotide polymorphisms (SNPs) were then carried forward replication in 59 children with acute lymphoblastic leukemia (ALL) exposed to large fixed doses of PD as part of their chemotherapeutic regimen. Among them, rs6461639 (interaction P=1.88 × 10-5 in the CAMP population) showed a significant association with the final BMD Z-scores in the ALL population (P=0.016). The association of the ALL population was only present after correction for the anti-metabolite treatment arm (high vs low dose). We have identified a novel SNP, rs6461639, showing a significant effect on the final BMD Z-scores in two independent pediatric populations after long-term high-dose PD treatment.

Risk assessment of human exposure to cypermethrin during treatment of mandarin fields.

The potential dermal and respiratory exposure assessment and risk assessment for applicator were performed with cypermethrin EC. The pesticide was applied on a mandarin field using a power sprayer. Gloves were used for the hand exposure assessment, mask for face, and dermal patches for the other parts of the body. Personal air monitor equipped with a XAD-2 resin was used for the respiratory exposure assessment. During the application of cypermethrin in the field, the rate of potential dermal exposure ranged from 28.1 to 58.8 mg/h. The major exposure parts were upper-arms (22.1-24.6%) and legs (thigh and shin, 28.3-29.2%) for females and thigh (21.0-46.9%) and hand (14.9-19.3%) for males. Females were exposed more than males. No exposure was detected from the respiratory monitoring. For risk assessment, the potential dermal exposure (PDE), the absorbable quantity of exposure (AQE), and the margin of safety (MOS) were calculated. Among those four risk assessments, MOS was < 1 in only trial I, which indicated any possibility of risk. However, in the others, the possibility of risk was little. Moreover, the safe work time ranged from 3.61 h to 9.69 h.

Discovery of genes for ginsenoside biosynthesis by analysis of ginseng expressed sequence tags.

Expressed sequence tags (ESTs) provide a valuable tool that can be used to identify genes in secondary metabolite biosynthesis. Ginseng (Panax ginseng C.A Meyer) is a medicinal plant that accumulates ginsenosides in roots. We sequenced 11,636 ESTs from five ginseng libraries in order to create a gene resource for biosynthesis of ginsenosides, which are thought to be the major active component in roots. Only 59% of the ginseng ESTs exhibited significant homology to previously known polypeptide sequences. Stress- and pathogen-response proteins were most abundant in 4-year-old ginseng roots. ESTs involved in ginsenoside biosynthesis were identified by a keyword search of BLASTX results and a domain search of ginseng ESTs. We identified 4 oxidosqualene cyclase candidates involved in the cyclization reaction of 2,3-oxidosqualene, 9 nine cytochrome P450 and 12 glycosyltransferse candidates, which may be involved in modification of the triterpene backbone.

Structural analysis of glyceraldehyde 3-phosphate dehydrogenase from Escherichia coli: direct evidence of substrate binding and cofactor-induced conformational changes.

The crystal structures of gyceraldehyde 3-phosphate dehydrogenase (GAPDH) from Escherichia coli have been determined in three different enzymatic states, NAD(+)-free, NAD(+)-bound, and hemiacetal intermediate. The NAD(+)-free structure reported here has been determined from monoclinic and tetragonal crystal forms. The conformational changes in GAPDH induced by cofactor binding are limited to the residues that bind the adenine moiety of NAD(+). Glyceraldehyde 3-phosphate (GAP), the substrate of GAPDH, binds to the enzyme with its C3 phosphate in a hydrophilic pocket, called the "new P(i)" site, which is different from the originally proposed binding site for inorganic phosphate. This observed location of the C3 phosphate is consistent with the flip-flop model proposed for the enzyme mechanism [Skarzynski, T., Moody, P. C., and Wonacott, A. J. (1987) J. Mol. Biol. 193, 171-187]. Via incorporation of the new P(i) site in this model, it is now proposed that the C3 phosphate of GAP initially binds at the new P(i) site and then flips to the P(s) site before hydride transfer. A superposition of NAD(+)-bound and hemiacetal intermediate structures reveals an interaction between the hydroxyl oxygen at the hemiacetal C1 of GAP and the nicotinamide ring. This finding suggests that the cofactor NAD(+) may stabilize the transition state oxyanion of the hemiacetal intermediate in support of the flip-flop model for GAP binding.

[The early medical textbooks in Korea: medical textbooks published at Je Joong Won-Severance Hospital Medical School].

Kwang Hye Won(Je Joong Won), the first western hospital in Korea, was founded in 1885. The first western Medical School in Korea was open in 1886 under the hospital management. Dr. O. R. Avison, who came to Korea in 1893, resumed the medical education there, which was interrupted for some time before his arrival in Korea. He inaugurated translating and publishing medical textbooks with the help of Kim Pil Soon who later became one of the first seven graduates in Severance Hospital Medical School. The first western medical textbook translated into Korean was Henry Gray's Anatomy. However, these twice-translated manuscripts were never to be published on account of being lost and burnt down. The existing early anatomy textbooks, the editions of 1906 and 1909, are not the translation of Gray's Anatomy, but that of Japanese anatomy textbook of Gonda. The remaining oldest medical textbook in Korean is Inorganic Materia Medica published in 1905. This book is unique among its kind that O. R. Avison is the only translator of the book and it contains the prefaces of O. R. Avison and Kim Pil Soon. The publication of medical textbook was animated by the participation of other medical students, such as Hong Suk Hoo and Hong Jong Eun. The list of medical textbooks published includes almost all the field of medicine. The medical textbooks in actual existence are as follows: Inorganic Materia Medica (1905), Inorganic Chemistry (1906), Anatomy I (1906), Physiology (1906), Diagnostics I (1906), Diagnostics II (1907), Obstetrics (1908), Organic Chemistry (1909), Anatomy (1909), and Surgery (1910).

Induction of thermotolerance in early postimplantation rat embryos is associated with increased resistance to hyperthermia-induced apoptosis.

Previously we reported that hyperthermia (43 degrees C) induces cell death in neurulation stage rat embryos as part of the pathogenesis culminating in abnormal growth and development. We now show that hyperthermia-induced cell death occurs by a process termed apoptosis. DNA fragmentation, a hallmark of apoptosis, was noted as early as 2.5 hr after embryos were exposed to 43 degrees C. A smaller but significant increase in DNA fragmentation was also observed in embryos exposed to 42 degrees C, but only at the 5 hr time point. In control embryos, TUNEL-positive apoptotic bodies were consistently observed in the neuroepithelium at the point of neural tube closure and in the optic stalk. In embryos exposed to 43 degrees C, the number of TUNEL-positive apoptotic bodies was significantly increased. Using both gel electrophoresis and TUNEL, we also show that the induction of thermotolerance is associated with a significant reduction in DNA fragmentation. Together our results show that specific programmed cell death and hyperthermia-induced cell death correlate with internucleosomal DNA fragmentation characteristic of apoptosis. Finally, we show that the induction of thermotolerance in rat embryos is associated with a significant reduction in internucleosomal DNA fragmentation and associated apoptosis.

[An aspect of Buddhistic medicine in ancient Korea: Wonhyo and medicine].

Lack of historical records causes some difficulties in the historical studies of ancient Korea. It is the same case as that of the history of medicine. We imagine what the situation of medicine was like in ancient Korea with a bit of historical records. In ancient times, medicine had very close relation with religions. In ancient Korea, it had very close relation with Buddhism. According to Sam Kuk Sa Ki and Sam Kuk Yu Sa buddhist monks treated patients with the religious rituals. In this article, the authors would like to present a record which had been unnoticed until now. It is the commentary of Wonhyo on a certain Buddhistic cannon called Kum Kwang Myung Kyung. A chapter (Je Byung Poom) of this cannon is on the theory of medicine, causes of diseases and treatments. We can presume Wonhyo's knowledge of medicine at that time through his commentary on this chapter.

Neural plate microvillus lengthening in rat embryos grown in various concentrations of glucose and further studies of the mechanism.

Glucose is an important cellular nutrient, and in the early embryo, which is dependent mostly on anaerobic glycolysis, it is even more essential. Based on tissue culture cells in which glucose utilization has become membrane-limited, a concept has been developed that the tip of the microvilli is the entrance compartment for glucose and that the shaft sets up a diffusion barrier. An increase in length of the microvillus is associated with decreased entry of phosphorylated hexose into the cells. Our previous findings of lengthening of the microvilli of the neural plate cells after 40 min exposure to glucose at room temperature have been extended to a 17 hr whole embryo culture system. In cultures where the final concentration of glucose was 20 and 24 mg/dl there was embryonic death. In those cultures ending with 29-137 mg/dl of glucose the embryos developed normally. Those grown in dialyzed serum supplemented with B vitamins and glucose grew equally as well as those in whole rat serum. Somite numbers attained did not change with increasing glucose concentration but a modest increase in micromoles of glucose used per embryo was found, suggesting the presence of another source of energy at lower glucose concentrations. The average glucose utilization per gram of protein per hour was 844 mumol in these day 9.5-10 embryos and this compares to 733 mumol previously found using uniformly labeled 14C glucose on day 10.3. Lactate production averaged 85% of the glucose utilized. Pyruvate did not support growth in the absence of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)