Synaptic modifications accompanying epileptogenesis in vitro: long-term depression of GABA-mediated inhibition

We used an in vitro model similar to kindling to examine the processes underlying epileptogenesis. A 60 Hz train was applied every 5–10 min to the Schaffer collateral pathways in guinea pig hippocampal slices until epileptiform bursting was elicited in the CA3 region. The resultant alterations in both spontaneous and evoked activities were studied using intracellular recordings from CA3 pyramidal cells. An attempt was made to elucidate the synaptic modifications responsible for the conversion to this state of enhanced excitability. Analyses revealed that the emergence of epileptiform discharge was accompanied by a long-term depression of evoked inhibitory conductances. This tetanus-induced reduction of inhibition involved both the early and late phases of the evoked hyperpolarization, suggesting modification of both the GABA_A and GABA_B receptor-mediated events. Previous studies have suggested that NMDA receptor activation plays an important role in the induction of epileptiform activity in this model. Our data, showing that depression of inhibition can be induced in the presence of CNQX, is consistent with this hypothesis. The parallel development of long-term depression of inhibition and epileptiform bursting following tetanic stimulation suggests that plasticity of the inhibitory transmission process is a potential source of vulnerability contributing to epileptogenesis.     

Thoracic outlet syndrome: a comprehensive evaluation

Using various modalities, 480 patients were evaluated for thoracic outlet compression syndrome. Of this group, 300 patients were eventually diagnosed as having thoracic outlet syndrome after extensive evaluation. Ninety of these patients underwent a total of 103 operative procedures for thoracic outlet decompression. Nerve conduction velocities and directional Doppler studies were the most useful adjuncts in making the diagnosis. Surgical therapy after proper selection yielded an 80.6 per cent long-term "good" operative result and an additional 6.9 per cent long-term "fair" operative result in follow-up to 12 years.     

dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina.

Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long-term cell survival of all retinal neurons. As diffusible factors, these molecules act non-cell-autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell-autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Muller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell-autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild-type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long-term dim-light vision. Taken together, our studies suggest a role for the dazed gene in rod and Muller cell development and overall retinal cell survival and maintenance.     

Assessment of HER-2/neu status in breast cancer. Automated Cellular Imaging System (ACIS)-assisted quantitation of immunohistochemical assay achieves high accuracy in comparison with fluorescence in situ hybridization assay as the standard

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.     

Interleukin 2 (IL2) is assigned to human chromosome 4

The human gene for interleukin 2 (IL2)was assigned to chromosome 4 using human-mouse somatic cell hybrids and Southern filter hybridization of cell hybrid DNA. To identify IL2,a recombinant DNA probe (pIL2-50A) was used which contained a human interleukin 2 cDNA insert which hybridized to a 3.5-kb fragment in human DNA when cleaved with the restriction enzyme EcoRL.     

Patient and partner perceptions about preventing genital herpes transmission

Research over the past decade has provided a new understanding of genital herpes transmission and measures that can reduce transmission risk. It is unclear, however, how those affected by genital herpes access and interpret this information to make decisions about risk behaviours. This study measured how people with genital herpes and their partners perceived prevention methods, barriers and facilitating factors, and information sources. Formative evaluation was conducted, and survey data were collected from visitors to four websites (n=1849). Results suggest that the prevention messages of refraining from sex during disease outbreaks and condom use have had the greatest reach. Misconceptions about the potential role of suppressive antiviral therapy for genital herpes prevention persist among a substantial percentage of respondents. Accurate information concerning transmission between outbreaks, the effectiveness of condoms and the role of antiviral medication is critical in preventing the spread of genital herpes.     

Human figure drawing ability and vestibular processing dysfunction in learning-disabled children

Explored the relationship between vestibular function as measured by duration of postrotary nystagmus and human figure drawing ability in 40 children labeled as learning disabled. Regression analysis revealed that the variable of chronological age shared the most variance with human figure drawing scores. Postrotary nystagmus durations also shared a significant amount of variance with human figure drawing scores, while the variables of IQ and sex were nonsignificant. The results provide additional support for the assertion that some learning-disabled children evidence deficits in vestibular processing ability and that these deficits may affect performance on cognitive-perceptual tasks.