DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins

The present study assessed whether prenatal androgen and estrogen exposure affected adult spatial learning and hippocampal morphology. Water maze performance, the CA1 and CA3 pyramidal cell field, and the dentate gyrus-granule cell layer (DG-GCL) morphology were assessed at adulthood (70+ days of age) in males, females, androgen-treated (testosterone propionate, TP, or dihydrotestosterone propionate, DHTP) females (2-4 mg/day), estradiol benzoate (EB)-treated females (100 microgram/day), and males treated with the antiandrogen flutamide (8 mg/day). Pregnant rats were injected daily (sc) between Embryonic Day 16 and birth; all pups were delivered by cesarean section. Flutamide-treated males were castrated upon delivery, and adult castrates were used to control for activational effects. Steroid-sensitive sex differences were observed in water maze performance in favor of males. Males had larger CA1 and CA3 pyramidal cell field volumes and soma sizes than females, which were feminized with flutamide treatment. TP and EB, but not DHTP, masculinized CA1 pyramidal cell field volume and neuronal soma size; CA3 was masculinized in both TP- and DHTP-treated females, while EB was ineffective. No effects were observed in cell density, number, or DG-GCL volume or due to adult hormone levels. Thus, prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on CA1 and CA3 pyramidal cell morphology. Hence, in addition to the previously reported postnatal component, there is also a prenatal component to the critical period in which gonadal steroids organize the neural mechanisms underlying sex differences in adult spatial ability.     

Degradation and repair of elastic fibers in rat lung interstitial fibroblast cultures

The results from previous studies have provided evidence to support the hypothesised association between intrauterine oestrogen exposure and subsequent risk of breast cancer. Information has not been available to study this relationship for several perinatal factors thought to be related to pregnancy oestrogen levels. Data collected from the mothers of women in two population-based case-control studies of breast cancer in women under the age of 45 years (510 case mothers, 436 control mothers) who were diagnosed between 1983 and 1992 in three western Washington counties were used to investigate further the relationship between intrauterine oestrogen exposure and risk of breast cancer. A pregnancy weight gain of 25-34 pounds was associated with breast cancer risk (odds ratio [OR] = 1.5; 95% confidence interval [CI] 1.1, 2.0); however, women whose mothers gained 35 pounds or more were not at increased risk. Use of antiemetic medication in women with any nausea and vomiting (OR = 2.9; 95% CI 1.1, 8.1) and use of diethylstilboestrol (DES) (OR = 2.3; 95% CI 0.8, 6.4) appeared to be positively associated with breast cancer risk. The results from this study provide limited support for the hypothesis that in utero oestrogen exposure may be related to subsequent breast cancer risk among young women.     

Alzheimer brain proteins investigated by two-dimensional gel electrophoresis with immobilized pH gradients in the first dimension

Two-dimensional (2-D) gel electrophoresis with immobilized pH gradient 4-8 in the first dimension was applied in the analysis of Alzheimer's disease brain proteins. The silver-stained 2-D maps of extracts from the frontal cerebral cortex were examined. About 800 and 550 protein spots could be observed on the electrophoretograms from the total and buffer-soluble fractions, respectively. In comparing the gels, four protein spots could now be detected which had either been hitherto undetectable (one spot) or which were weaker (two spots) or stronger (one spot) in density (in the controls) [corrected].     

Inter- and intra-limb coordination in arm tremor

Inter- and intra-limb coordination in arm tremor was examined in adult subjects under vision and no vision conditions using accelerometery techniques. The accelerometer data were analyzed using standard time and frequency domain analyses and the regularity of the acceleration time series was determined using an approximate entropy (Ap En) measure. The data analysis was structured to examine the hypothesis that there is a functional compensatory relation between the motion (tremor) of the limb segments in the arm coordination postural pointing task. The results showed that the level of acceleration increased in a proximal to distal direction within a single arm and was symmetrical across homologous arm segments. The frequency analysis showed the established power spectral profiles for each limb segment in postural tremor tasks, but the finger motion included (beyond the normal 8-12 Hz and 20 Hz tremor) a third slower peak at around 2-3 Hz, due possibly to the reactive forces of the other arm links. There was no effect of vision on the level or frequency patterns of accleration in the limb segments. The coordination analysis showed that there was no linkage between the arms in either the time or frequency domain in the execution of this postural task. This result would tend to suggest that the neuronal commands underlying normal tremor are not derived from a common central oscillator within the central nervous system but are organized in a parallel fashion. The strength of the coupling of intra-limb coordination varied according to the particular adjacent limb links. There were significant correlations in the time domain and coherence in the frequency domain in the acceleration signals between upper arm and forearm, and between hand and finger. The phase lag of the arm units within each of these respective segment pairs was close to in phase or 0 deg. Significant coherence in the frequency domain was also evident between upper arm and hand motion, with the phase lag between these segments being close to 180 deg out of phase. The Ap En analysis of the acceleration signals revealed that there was more regularity to the upper arm and hand accelerometer signals than the forearm and finger signals. The findings show that the intra-limb coordination of the arm links in a two-limb postural pointing task is effected by a compensatory synergy organized about the action of the wrist and shoulder joints. This compensatory synergy reduces the coordination of the 4 within-limb degrees of freedom (arm links) to, in effect, a single degree of freedom arm control task that is not coupled in organization to the motion of the other limb or the torso. It is proposed that this coordination solution reduces the degrees of freedom independently regulated for realization of the task goal but preserves independent body segment control in critical degrees of freedom for potential adaptation to postural perturbations.     

Conversion of normal human oral keratinocytes to tumorigenic cells is associated with the acquisition of resistance to TGF-beta

Normal human epithelial cells cannot proliferate and undergo apoptosis in the presence of transforming growth factor-beta (TGF-beta) in vitro, but many human epidermoid cancer cells are resistant to TGF-beta. Resistance to TGF-beta may thus, in part, be responsible for uncontrolled proliferation of cancer cells. Though detailed mechanisms for the resistance of cancer cells to TGF-beta remain unknown, resistance may be due to decreased expression of TGF-beta receptors from cancer cells. To investigate this possibility, we determined the expression of TGF-beta and type II TGF-beta receptor in primary normal human oral keratinocytes (NHOK), human papillomavirus-immortalized human oral keratinocytes (HOK-16B) and two tumor cell lines derived from HOK-16B (CTHOK-16B-BaP and CTHOK-16B-DMBA). Our results show that (1) the cellular and secretory TGF-beta levels in immortalized and tumor cells were notably lower than in NHOK and (2) the level of type II TGF-beta receptor of the tested cells was similar to each other. Taken together, the conversion of NHOK to tumorigenic cells may, in part, be due to the acquisition of NHOK resistance to TGF-beta through underexpression of this cytokine.     

Validity of universal wedge equation over the range of 60Cobalt to 25 MV photon beam energies

PURPOSE: Evaluating the validity of the universal wedge equation over the range of 60Cobalt (60CO) to 25 MV photon beam energies. METHODS AND MATERIALS: The universal wedge equation relates the beam weight of the wedged field to the effective wedge angle produced by combining the wedged field to the nonwedged field and is expressed as tan (theta) = B tan (theta w), where B is the normalized weight imposed on the wedged field, theta w is the maximum wedge angle of the wedge filter, and theta is the effective wedge angle. The isodose distributions from 60Co to 25 MV photon beam energies were used. For each photon energy, the isodose distributions of wedged and nonwedged fields were combined in different proportions. The effective wedge angle was determined from each resultant isodose distribution. RESULTS: The relationship between the weight of wedged field and the effective wedge angle was found to be nonlinear for wedge filters with maximum wedge angle greater than 30 degrees. The universal wedge equation predicts the effective wedge angle to within 2 degrees compared to the measured value.     

Electrosurgery for routine pediatric penile procedures

PURPOSE: Traditional teaching in urology has been to avoid electrosurgical devices in penile surgical procedures. In the last several years cutting current has been routinely used on the penis for making skin incisions, degloving, creating Byars flaps and destroying skin bridges. The purpose of this study was to determine the complications and final outcomes of electro-surgery. MATERIALS AND METHODS: A 5-year retrospective chart review was done to determine the complications and final outcomes of exclusively using electrical current to perform pediatric penile procedures. RESULTS: Electrosurgery was used to perform the entire surgical dissection in 346 patients, including circumcision in 124, repeat circumcision in 68, penoscrotal fusion/chordee repair in 127 and skin bridge procedures in 27. All patients had a satisfactory cosmetic result. After correction of penoscrotal fusion, separation at the scrotal suture line in 2 patients healed secondarily without sequelae. There was no hematoma, tissue necrosis or skin sloughing and all surgery was performed on an outpatient basis. CONCLUSIONS: Electrosurgery can be used safely and effectively for routine penile procedures, providing a bloodless operative field and excellent cosmetic results.