Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

The cytokine interleukin-1 (IL-1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL-1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL-1 are involved in hippocampal-dependent memory and long-term potentiation (LTP). To examine this hypothesis, we studied IL-1 receptor type I knockout (IL-1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL-1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild-type controls. Furthermore, IL-1rKO exhibited diminished contextual fear conditioning. In contrast, IL-1rKO mice were similar to control animals in hippocampal-independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory-cued fear conditioning was normal. Electrophysiologically, anesthetized IL-1rKO mice exhibited enhanced paired-pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired-pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL-1rKO mice compared with WT controls. These results suggest that IL-1 contributes to the regulation of memory processes as well as short- and long-term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation.     

Reproducibility of visual activation in functional magnetic resonance imaging at very high field strength (4 Tesla)

PURPOSE: The reproducibility of functional magnetic resonance imaging (fMRI) has been studied on 1.5 Tesla (T) (high field strength) scanners. We report the reproducibility of visual activation in fMRI at 4 T (very high field strength). METHODS: Five healthy subjects were scanned twice in the same session with a 4 T scanner during binocular flashing visual stimulation. The activated areas during the first and second acquisition were compared.RESULTS: Activation of the visual cortex was observed in all subjects and activation of lateral geniculate nucleus was also detected in four subjects. The ratio of overlapping activated voxels in the first and second acquisition was 0.81 +/- 0.05. CONCLUSIONS: Reproducibility of visual activation using fMRI at 4 T was found to be acceptable, and the results from 4T scanners show a reliability similar to those at 1.5 T.     

Antimicrobial susceptibility of community-acquired uropathogens in northern Israel

In order to study the trends in resistance to first line antimicrobial agents, the susceptibility patterns of 8338 community urinary isolates collected during 1995 were compared with 6692 isolates from 1999. Our data shows that community-acquired Gram-negative uropathogens remained highly susceptible to ciprofloxacin, cefuroxime and amoxycillin/clavulanate with sensitivities of 94, 89 and 83% respectively. Nitrofurantoin was shown to be suitable (99% susceptibility rate) only for Escherichia coli urinary tract infections. Ampicillin, first generation cephalosporins and sulphamethoxazole/trimethoprim could no longer be considered first line drugs for empirical treatment of clinically evident urinary tract infection because of very high resistant rates. Ampicillin remained a good choice for urinary infections caused by enterococci, 98% of the strains being susceptible. It was found that 1.25% of the Gram-negative uropathogens isolated during 1999 were extended spectrum beta-lactamase producers which suggests that this plasmid-encoded trait is finding its way into the community.     

Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo

Considerable research effort is currently being directed towards understanding the mechanisms mediating the antiproliferative effects of non-steroidal anti-inflammatory drugs (NSAIDs) and, more recently, of cyclooxygenase (COX)-2 inhibitors as well. A key question is whether NSAIDs (excluding sulindac) exert their anticarcinogenic effects in vivo by a mechanism that is dependent on their capacity to inhibit COX activity. Some studies with cultured tumor cells in vitro have argued against such a linkage, showing that NSAIDs inhibit cell replication and/or augment apoptosis only at concentrations that exceed those required to inhibit COX activities 10- to 100-fold. The significance of these results for the observed anticarcinogenic effects of NSAIDs in vivo has not yet been evaluated. We addressed this question by comparing, for the same tumor cells, the effects of the NSAID indomethacin on cell growth parameters when the cells were grown in culture to the effects seen in the in vivo growing tumor in the mouse. Indomethacin added to cultured Lewis lung carcinoma cells exerted a potent antiproliferative effect ((3)H thymidine assay) and reduced cell viability (MTT[3-(4,5-dimethyl(thiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay) at low doses (10-20 microM) in parallel with its inhibitory effect on cellular cyclooxygenase. These effects of indomethacin appeared to arise from a clear antiproliferative shift in the profile of the cell cycle parameters towards a reduced percentage of cells at the S and G(2)/M phases, together with an increased percentage of cells at the G(1) phase. Significantly, similar results were seen when indomethacin was given in vivo at the low dose of 2 mg per kg/day, which blocked blood platelet COX activity and at the same time produced a delay in tumor growth initiation and attenuation of apparent primary tumor growth as well as growth of lung metastases. These results thus provide strong support for the notion that COX inhibition is a major determinant in the antitumorigenic effect of indomethacin in vivo.     

High-level handwashing compliance in a community teaching hospital: a challenge that can be met!

Handwashing is the most important and least expensive measure for preventing the transmission of hospital-acquired infection. Compliance, however, rarely exceeds 40%, even in intensive care units. The present study evaluated the effectiveness of the authors' infection control programme in relation to handwashing compliance of healthcare workers. Ten nursing students observed 300 uninformed staff members and recorded their handwashing practices throughout the working day. The observations were categorized by profession, gender, age, hospital unit and type of delivered care. In 1035 opportunities that required handwashing, the overall compliance was 76%. Healthcare workers washed hands before (68%) and after patient care (80%). Females complied more than males (69 vs. 80%, P<0.0001) and nurses more than physicians (81 vs. 69%, P<0.001). In intensive care units, overall compliance exceeded 97%, while in other wards and in the emergency departments, it approximated 61%. More handwashing was observed during the evening shift compared with the morning shift (P=0.02). Despite the high compliance, only 30% washed their hands for the required 10-20s. In conclusion, compliance with handwashing in the authors' institution is the highest reported to date, and reflects the intensive and incessant educational infection control programme.     

The cognitive correlates of white matter abnormalities in normal aging: a quantitative review

Cerebral white matter of asymptomatic people frequently exhibits circumscribed areas of hyperintensity on magnetic resonance (MR) images and hypodensity on computed tomography scans. However, behavioral implications of this phenomenon remain unclear. In this meta-analysis, the authors examine cumulative evidence regarding the cognitive sequelae of white matter abnormalities in adults without dementia. The influence of potential moderator variables, such as neuroimaging technique, location of the lesions, rating scale, and demographic characteristics of the sample on the association between the burden of white matter hyperintensities and cognitive performance was also examined. Results indicate that white matter abnormalities observed on MR images are associated with attenuated performance on tasks of processing speed, immediate and delayed memory, executive functions, and indices of global cognitive functioning. There was no significant link between the white matter hyperintensities and psychometric indices of intelligence or fine motor performance.     

Galectin-3 maintains the transformed phenotype of thyroid papillary carcinoma cells

Galectin-3, a beta-galactoside-binding protein, is highly expressed in thyroid papillary carcinomas, while functional relevance of galectin-3 overexpression to the malignant phenotype remains elusive. In the present study we transfected galectin-3 antisense cDNA into the human thyroid papillary carcinoma cell line NPA which expresses an innately high level of galectin-3, and examined the effect of antisense inhibition of galectin-3 expression on the transformed phenotype. There was no difference in anchorage-dependent growth between the antisense clones and either the control or parental clones. In contrast, anchorage-independent growth and saturation density of the antisense clones were significantly suppressed compared to those of either the control or parental clones. These results demonstrate that overexpression of galectin-3 in thyroid papillary carcinoma cells is necessary for the maintenance of transformed phenotype, and suggest galectin-3 as a potential target for therapeutic interventions in the future.