To gain insight into the interactions between transcriptional factor proteins and DNA, the DNA-reactive drugs (+)-CC-1065 and pluramycin were used to target specific protein-DNA complexes. The structural features of the complex between the transcriptional activator Sp1 and the 21-base-pair repeat of the early promoter region of SV40 DNA were examined using hydroxyl-radical footprinting; (+)-CC-1065, a sequence-specific minor groove bending probe; and circularization experiments. The results show that the 21-base-pair repeat region has an intrinsically in-phase bent structure that is stabilized upon saturation Sp1 binding by protein-DNA and protein-protein interactions to produce a looping structure. The intercalating drug pluramycin was used to probe the structural details of the interaction between the TATA binding protein (TBP) and the TATA box DNA sequence. TBP, which directs initiation of RNA transcription, exhibits two-fold symmetry and apparently interacts with the TATA box in a symmetrical fashion. However, the interaction results in an asymmetric effect, in that transcription is initiated only in the downstream direction. Using pluramycin as a probe, it was determined that TBP binding to the human myoglobin TATA sequences enhances pluramycin reactivity at a site immediately downstream of the TATA box. The implications on transcriptional control of ternary complexes comprised of transcriptional factors, DNA, and DNA-reactive compounds will be presented.

Aminoglycosides↗

PubMedDate not supplied

Estrogens and benign prostatic hyperplasia: the basis for aromatase inhibitor therapy.

Benign prostatic hyperplasia is generally regarded as being a hormone-dependent disorder. The inductive action of stromal elements on the glandular epithelium and the demonstrable estrogen sensitivity of the stroma suggest that estrogens may play a role in the etiology of prostatic hyperplasia. This hypothesis forms the theoretical basis for the proposed use of aromatase inhibitors in treatment of this disorder.

Aromatase Inhibitors↗

PubMedDate not supplied

Descriptive analysis of multiple response topographies of challenging behavior across two settings.

Time-based lag sequential analyses were conducted on 23 topographies of challenging behavior shown by five young people with severe mental retardation across two settings. Potential behavioural functions were identified for 21 of the 23 behaviors. Responses classes, including two or more distinct behaviors, were identified for four of the five participants. Two participants showed evidence of two functionally distinct response classes; for one person each response class included both self-injurious and stereotypic behaviors. For 9 of the 11 behaviors for which data were available, the hypothesised function of behaviors was consistent across settings. For one person, data suggested that the function of one self-injurious behavior was contextually determined. Cross-validation with brief experimental analyses resulted in agreement on the general behavioral function for 12 of the 14 instances in which both approaches positively identified a potential function for a behavior. Implications for future research and practice are discussed.

Adolescent↗

PubMedDate not supplied

The quality and costs of residential services for adults with multiple disabilities: a comparative evaluation.

The costs and quality of four different service models for 40 adults with multiple disabilities were compared. The four service models were: specialised institution-based units; a specialised, campus-style, further education service; specialised community-based group homes; and "ordinary" community-based group homes. Some information was also available from five adults with multiple disabilities living in traditional institutions for people with mental retardation. On almost all measures of service outcome the specialised group-home model was the "preferred" service model, although this model was not associated with particularly high service costs. There was, however, considerable variation in quality within, as well as between, service models, with some residents in all service models experiencing levels of support and engagement similar to those found in traditional institutions. The results of the study are discussed in relation to notions of typical practice and normative standards. The implications of the findings are discussed.

Activities of Daily Living↗

PubMedDate not supplied

Comparison of psychophysical and evoked-potential tuning curves in the chinchilla.

Frequency selectivity was examined in normal-hearing chinchillas using psychophysical and evoked-potential tuning curves. The acoustic conditions and masking procedures used for the evoked-potential and psychophysical studies were nearly identical. Frequency selectivities as measured by psychophysical and physiologic techniques were quite similar across different probe frequencies. The results suggest that the relatively efficient evoked-potential procedure may be substituted for the time-consuming psychophysical paradigm. Furthermore, the results are consistent with the view that tuning takes place primarily at the auditory periphery.

Animals↗

PubMedDate not supplied

Intrahippocampal LPS injections reduce Abeta load in APP+PS1 transgenic mice.

Multiple lines of evidence indicate that inflammatory processes are involved in the pathogenesis of Alzheimer's disease. Lipopolysaccharide (LPS) is widely used to induce inflammation in experimental systems. Consequently we injected LPS or saline intrahippocampally in 11 and 16 months old APP+PS1 transgenic mice to induce brain inflammation, then used immunocytochemistry to examine amyloid pathology 7 days later. As expected, LPS activated microglia as indicated by a significant increase in the area covered by major histocompatibility complex-II (MHC-II) immunostaining in the mice injected with LPS compared to the saline injected. Simultaneously, Abeta immunostaining showed an unexpected reduction of the Abeta load in the mice injected with LPS compared to the saline injected. This effect of LPS on the Abeta load in APP+PS1 mice strengthens the hypothesis that moderate amounts of microglial activation may be beneficial in Alzheimer's disease, by increasing the clearance of Abeta.

Amyloid beta-Peptides↗

PubMedDate not supplied

African-American women who smoke crack cocaine: sexual trauma and the mother-daughter relationship.

This study evolved from previous writings that linked sexual abuse to the quality of the mother-daughter relationship. The purpose of this investigation was to examine the mother-daughter relationship among African-American women who abuse crack cocaine by comparing three different groups: women who have not experienced incest but have experienced sexual abuse; women who have experienced incest; and women who have not experienced sexual abuse. A convenience sample of 64 African-American women was used, 35 of whom were in drug abuse treatment and 29 of whom were abusing crack cocaine. Using analysis of variance studies, significant differences were found between the three groups in terms of the mother-daughter relationship. Differences were also found between the group that experienced incest and the group that experienced nonincestuous sexual abuse in terms of the amount of abuse and first age of abuse. This preliminary investigation indicates the need for further study of specific populations in this area--most notably, African-American women who abuse crack cocaine.

Adult↗

PubMedDate not supplied

Mother-daughter identification: Polish and Polish-American mothers and their adult daughters.

Toward the goal of furthering our understanding of the mother-daughter relationship, we investigated one aspect of the mother-daughter relationship, the mutual identification that occurs within it. Mutual identification was defined as the process by which a mother and her daughter internalize characteristics of each other. A convenience sample of 81 Polish and 81 Polish-American mother-daughter dyads was studied. Mother-daughter identification was measured using a semantic differential (SD) scale that included 12 concepts. Analyses using paired t tests revealed that there was no significant difference between the ratings of the Polish-American mothers and those of their daughters on 7 of the 12 concepts and no significant difference between the ratings of the Polish mothers and those of their daughters on 10 of the 12. There were, however, statistically significant differences between the Polish and Polish-American women's ratings of the concepts. These data are interpreted as support for the theory of mother-daughter identification.

Adult↗

PubMedDate not supplied

Neural correlates of sensorineural hearing loss.

Sensorineural hearing loss is characterized by a relatively well defined set of audiological signs and symptoms such as elevated thresholds, abnormally rapid loudness growth, subjective tinnitus, poor speech discrimination, and a reduction in temporal summation of acoustic energy. Knowledge of the underlying neural mechanisms responsible for some of these auditory distortions has progressed substantially within the past 10 yrs as a result of physiological studies on hearing-impaired animals. Some of the important neurophysiological changes relevant to sensorineural hearing loss are reviewed. One important effect associated with sensorineural hearing loss is the broadening of the cochlear filtering mechanism which may influence loudness growth and the perception of complex sounds. The neurophysiological results may also provide new insights in interpreting traditional audiological data and help in developing more refined tests for fitting hearing aids or differentiating patients with sensorineural hearing loss.

Animals↗