CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics.

The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR.     

Menstrual Perceptions and Preparation Among Female Adolescents

Seventy-four 8th- and 10th-grade students attending a private girls' school in Hawaii were queried about their perceptions of and preparation for menstruation using a questionnaire administered in a health education class. Eighty percent had already started menstruating. The most frequently cited perceptions by the respondents referred to both the inconveniences and the normalcy of menstruation. Many were first informed about menstruation by their mothers and stated that they also first informed their mothers when they started menstruating. Surprise, fear, and embarrassment were common initial reactions, while strong negative or positive emotions were more rare. Only 35% wanted boys and girls together during class discussion, but 89% stated that boys needed to be informed about menstruation. The most frequent reasons cited for noncoed settings were the girls' concern about their comfort in openly discussing menstruation. Thirty-eight percent thought parents should inform other siblings when they started menstruation, although almost half gave specific conditions the parents should consider. The majority thought the fifth to sixth grades were the best times to introduce menstruation content.     

Tooth movement and cytokines in gingival crevicular fluid and whole blood in growing and adult subjects.

INTRODUCTION: Tooth movement has been studied largely with respect to the force required for tipping when pressure distribution varies along the length of the periodontal ligament. But important factors for effective canine translation include the nature and magnitude of applied stress and the patient's cell biology. The purpose of this research was to test 3 hypotheses: (1) the velocity of tooth translation (v(t)) is related to applied stress and growth status, (2) a threshold of stress accounts for the lag phase, and (3) v(t) is correlated with the ratio (AI) of 2 cytokines (IL-1beta, IL-1RA) measured in gingival crevicular fluid (GCF) and stimulated whole blood (SWB). METHODS: Continuous maxillary canine retraction stresses of 13 kPa and 4, 26, or 52 kPa were applied bilaterally in 6 growing and 4 adult subjects for 84 days. Dental models and GCF samples were collected at 1- to 14-day intervals. Cytokines were measured in GCF and SWB cell cultures. RESULTS: V(t) was positively related to stress and was higher in growing subjects (P = .001). It was also related to AI(GCF) in growers (R2= 0.56) and nongrowers (R2= 0.72). Canines moved with 52 kPa showed a lag phase, and postlag phase AI(GCF) was twice that of lag phase AI(GCF). Mean v(t) and associated AI(GCF) during the postlag phase were nearly double the values for canines moved with 13 and 26 kPa. SWB production of cytokines was dose-dependent. For growing subjects, SWB IL-1RA was correlated with v(t) (R = 0.70-0.72), and AI(SWB) and IL-1beta concentrations were correlated with AI(GCF) (R = 0.73-0.78). CONCLUSIONS: V(t) varied with growth status and stresses < or = 52 kPa; stresses of < 52 kPa showed no lag phase; and equivalent stresses yielded subject-dependent differences in v(t), which correlated with cytokines in GCF and SWB.     

Comparison of two in vitro methods of bone lead analysis and the implications for in vivo measurements

Atomic absorption spectrometry and x-ray fluorescence have been used to determine the lead content of metatarsal and tibia bone samples. For a range of bone lead levels from 6.5 to 83 micrograms g-1 of ashed bone there is no evidence of a systematic difference between the two techniques of more than 1 microgram g-1. There is, however, some evidence that random differences between the two in vitro analyses applied to the same bone sample are larger than can be accounted for by known measurement uncertainties. Variations in bone composition could account for these differences. Because the x-ray fluorescence technique is applied in an identical way to in vivo analysis, it is concluded that the uncertainties in in vivo measurements are small.     

A radiological evaluation of phosphogypsum.

Phosphogypsum is the by-product resulting from phosphoric acid or phosphate fertilizer production. The phosphate are used in these chemical processes contains the naturally occurring radioactive material U and all its subsequent decay products. During processing, the U generally remains in the phosphoric acid product, while the daughter, 226Ra, tends to be concentrated in the phosphogypsum. Phosphogypsum has physical properties that make it useful as a sub-base for roadways, parking lots, and similar construction. A radiological evaluation, to determine exposures to workers mixing this material with a stabilizing agent (portland cement), was performed at a South Louisiana phosphoric acid chemical plant. Measurements of the 226Ra content of the phosphogypsum showed an average of 1.1 +/- 0.3 Bq g-1 (0.7-1.7 Bq g-1). The average measured gross gamma exposure rate on the phosphogypsum pile corresponded to a dose equivalent rate of 0.368 +/- 0.006 mu Sv h-1 (0.32-0.42 mu Sv h-1). Radon daughter concentrations measured on top of the phosphogypsum pile ranged from 0.0006 to 0.001 working levels. An analysis of the airborne 226Ra concentrations showed only background levels.