Estrogen uncouples beta-adrenergic receptor from the stimulatory guanine nucleotide-binding protein in female rat hypothalamus.

The responsiveness of adenylyl cyclase to beta-adrenergic receptor stimulation was investigated in membranes prepared from hypothalamus-preoptic area and cortex of ovariectomized female rats injected with oil vehicle or estradiol benzoate 24 or 48 h before death. Membranes from the hypothalamus-preoptic area of ovariectomized animals displayed a concentration-dependent stimulation of adenylyl cyclase when incubated with the beta-adrenergic receptor agonist, isoproterenol (10(-7)-10(-5) M). This response was suppressed in membranes from estrogen-treated animals. The effect of estrogen was observed 48 h, but not 24 h, after hormone administration. In addition, estrogen had no measurable effect on hypothalamic adenylyl cyclase activation by either GTP (10(-8)-10(-5) M) or forskolin (10(-8)-10(-6) M), on beta-adrenergic receptor density, or on antagonist binding affinity measured with the beta-adrenergic antagonist [125I]iodocyanopindolol. Analysis of isoproterenol displacement of iodocyanopindolol binding revealed that estrogen reduced agonist binding affinity in hypothalamus-preoptic area membranes. In membranes from ovariectomized controls, high affinity agonist binding to the beta-adrenergic receptor was apparent and was abolished by guanine nucleotides. However, membranes from estradiol-treated rats demonstrated only low affinity agonist binding that was unaffected by guanine nucleotides. Estradiol did not detectably alter concentrations of either cholera or pertussis toxin substrates in hypothalamus-preoptic area membranes. These data indicate that estrogen promotes a stable time-dependent desensitization of beta-adrenergic receptor activation of adenylyl cyclase in hypothalamus and preoptic area by uncoupling the receptor from the guanine nucleotide-binding protein, G8.

Moral panic versus the risk society: the implications of the changing sites of social anxiety.

This paper compares moral panic with the potential political catastrophes of a risk society. The aim of the comparison is threefold: 1. to establish the position of risk society threats alongside more conventional moral panics; 2. to examine the conceptual shifts that accompany the new types of threats; and 3. to outline the changing research agenda. The paper suggests that as new sites of social anxiety have emerged around environmental, nuclear, chemical and medical threats, the questions motivating moral panic research have lost much of their utility. Conceptually, it examines how the roulette dynamics of the risk society accidents expose hidden institutional violations that redound into 'hot potatoes' that are passed among and fumbled by various actors. Changing conceptions of folk devils, claims making activities, and of a safety are also discussed.

Tinea capitis in a newborn caused by two organisms.

Tinea capitis is a common infection of childhood. There have been several reports of tinea capitis in newborns. Our patient presented at 19 days of age to the emergency room with a scalp lesion of 5 days duration. The fungal culture grew both Trichophyton rubrum and Trichophyton mentagrophytes. The patient was successfully treated with oral griseofulvin.

Mental rotation of a tactile layout by young visually impaired children.

Mental rotation tasks have been used to probe the mental imagery both of sighted and of visually impaired people. People who have been blind since birth display a response pattern which is qualitatively similar to that of sighted people but tend to respond more slowly or with a higher error rate. It has been suggested that visually impaired people code the stimulus and its (or their own) motion in a different way from sighted people-in particular, congenitally blind people may ignore the external reference framework provided by the stimulus and surrounding objects, and instead use body-centred or movement-based coding systems. What has not been considered before is the relationship between different strategies for tactually exploring the stimulus and the response pattern of congenitally blind participants. Congenitally blind and partially sighted children were tested for their ability to learn and recall a layout of tactile symbols. Children explored layouts of one, three, or five shapes which they then attempted to reproduce. On half the trials there was a short pause between exploring and reproducing the layouts. In an aligned condition children reproduced the array from the same position at which they had explored it; in a rotated condition children were asked to move 90 degrees round the table between exploring and reproducing the layout. Both congenitally blind and partially sighted children were less accurate in the rotated condition than in the aligned condition. Five distinct strategies used by the children in learning the layout were identified. These strategies interacted with both visual status and age. We suggest that the use of strategies, rather than visual status or chronological age, accounts for differences in performances between children.

Phylogenetic relationships among genera of Massonieae (Hyacinthaceae) inferred from plastid DNA and seed morphology.

The tribe Massonieae Baker (Hyacinthaceae-Hyacinthoideae) presently consists of about 19 genera and 230 species distributed from Africa (south of the Sahara) to Madagascar and India. Based on atpB and trnL-F DNA sequences the tribe is monophyletic only when the genus Pseudoprospero is excluded from Massonieae. In most trnL-F trees, this genus occupies a basal position within subfamily Hyacinthoideae and is sister to the rest of the subfamily. Molecular data suggest that the remaining genera of Massonieae do not share common ancestry with the Eurasian/North-African tribe Hyacintheae Dumort. ( Scilla, Hyacinthus and allies), and thus a narrow concept of the essentially Eurasian genus Scilla is supported. Members of well-supported clades in Massonieae usually show similarities in seed characteristics as determined by scanning electron microscopy. Phylogenetic position and seed morphology indicate that Massonia angustifolia and M. zeyheri do not belong to the genus Massonia but fall into a clade together with Daubenya, Androsiphon and Amphisiphon. The genus Whiteheadia appears paraphyletic in the 50% majority rule trnL-F tree and occupies a basal position next to Massonia. However, in the strict consensus tree neither monophyly nor polyphyly can be excluded for this genus. Seed appendages are documented for members of the genera Ledebouria and Lachenalia. Within the genera of Massonieae there is a tendency towards bending of the seed axis. This phenomenon is most obvious within the genus Lachenalia. Delimitation of genera based on seed morphology largely agrees with the results of molecular studies. Correlation between number, size and color of seeds, geographical distribution and phylogenetic position of the genera are discussed.

Asbestos induction of extended lifespan in normal human mesothelial cells: interindividual susceptibility and SV40 T antigen.

Normal human mesothelial cells from individual donors were studied for susceptibility to asbestos-induction of apoptosis and generation of an extended lifespan population. Such populations were generated after death of the majority of cells and arose from a subset of mesothelial cultures (4/16) whereas fibroblastic cells (5/5) did not develop extended lifespan populations after asbestos exposure. All mesothelial cultures were examined for the presence of SV40 T antigen to obtain information on (i) the presence of SV40 T antigen expression in normal human mesothelial cells and (ii) the relationship between generation of an extended lifespan population and expression of SV40 T antigen. Immunostaining for SV40 T antigen was positive in 2/38 normal human mesothelial cultures. These cultures also had elevated p53 expression. However, the two isolates expressing SV40 T antigen did not exhibit enhanced proliferative potential or develop an extended lifespan population. Asbestos-generated extended lifespan populations were specifically resistant to asbestos-mediated but not to alpha-Fas-induced apoptosis. Deletion of p16Ink4a was shown in 70% of tumor samples. All mesothelioma cell lines examined showed homozygous deletion of this locus which extended to exon 1beta. Extended lifespan cultures were examined for expression of p16Ink4a to establish whether deletion was an early response to asbestos exposure. During their rapid growth phase, extended lifespan cultures showed decreased expression of p16Ink4a relative to untreated cultures, but methylation was not observed, and p16Ink4a expression became elevated when cells entered culture crisis. These data extend the earlier observation that asbestos can generate extended lifespan populations, providing data on frequency and cell type specificity. In addition, this report shows that generation of such populations does not require expression of SV40 T antigen. Extended lifespan cells could represent a population expressing early changes critical for mesothelioma development. Further study of these populations could identify such changes.

High levels of MDM2 are not correlated with the presence of wild-type p53 in human malignant mesothelioma cell lines.

Prior analysis of 20 human mesothelioma cell lines for p53 status revealed only two mutations and one p53 null cell line, although p53 expression was detected in most cell lines. In addition, mRNA and protein expression of the retinoblastoma gene product in human mesothelioma cell lines is similar to normal controls. We have tested for p53 induction after exposure to ionising radiation and demonstrate this induction and, to a lesser extent, p21(WAF1) induction, in both normal mesothelial cells and p53-positive mesothelioma cell lines. We postulated that high levels of MDM2 might alter p53 and retinoblastoma tumour-suppressor function in mesothelioma. However, Southern blot analysis for mdm2 indicated that no amplification had occurred in 18 mesothelioma cell lines tested. Steady-state mRNA and protein levels also did not indicate overexpression. These results indicate that high levels of MDM2 are not responsible for inactivating the functions of wild-type p53 or the retinoblastoma gene product during the pathogenesis of malignant mesothelioma.