Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells.

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line.     

Peritoneal morphology in children treated by continuous ambulatory peritoneal dialysis

Fifty peritoneal biopsies (PB) from 35 patients with end-stage renal disease, treated by continuous ambulatory peritoneal dialysis (CAPD) and aged 2 months to 18 years, were examined by light microscopy (n=50) and/or scanning electron microscopy. PB were performed during surgical procedures immediately before the start of, during, or after the cessation of CAPD treatment. PB from 15 children without renal disease undergoing laparatomy were examined similarly. Before the start of CAPD, a scarcity and shortening of the mesothelial microvilli was observed by scanning electron microscopy. During and after CAPD, variable alterations of mesothelium, interstitium and capillaries were found. The mesothelial layer was absent in all 5 PB obtained during episodes of active peritonitis. In patients treated by CAPD for longer than 6 months, mesothelial denudation was observed more frequently (6/11) than in children treated for shorter periods (1/7) (P<0.08). Fibrosis of the peritoneal membrane was present in about 50% of patients during or after the cessation of CAPD without impairment of peritoneal function. No correlation was found between the presence of fibrosis and the frequency of peritonitis or the duration of CAPD treatment.     

Isolated and combined effects of prolonged exposures to noise and whole-body vibration on hearing,vision and strain

Summary This study was carried out in order: (1) to examine the effects of isolated and combined prolonged exposures to noise and whole-body vibration on hearing, vision and subjectively experienced strain, and (2) to check the combined effects with repeated exposures. Six male subjects were exposed twice to noise (N) at 92 dBA, whole-body vibration (V) in the Z-axis at 4 Hz and 1.0 ms^–2 rms, and noise and vibration (NV) for 90 min with each condition. Temporary threshold shifts of hearing (TTS) and their integrals (ITTS) were measured at 4, 6, 10, and 12 kHz. Visual acuity was examined by means of a very sensitive test. Cross-modality matching (CMM) of the handgrip force was used to judge the subjectively experienced strain. NV induced a clear tendency of higher TTS and ITTS than N, with several significant differences most pronounced at 10 kHz. With repeated exposures, the effect of NV decreased, while the reactions to N and V remained unchanged. The individual reactions to NV differed. The influence of the duration of exposures on vision depended on the condition; N caused time-dependent changes, whereas V did not. CMM-data increased with the duration of the exposure during V and NV. N was generally judged to be more straining than V; NV caused higher strain than V during the first 30 min of exposure only. Correlations between different effects suggest certain links between them. Additionally, less motivation — daily obtained by a questionnaire — often correlated with higher ITTS during N and NV. The results also illustrate the combined effects on the individual susceptibility, repetition of exposure, the kind of response, and, possibly, the actual psychic state.Abbreviations CMM cross-modality matching - MVC maximum voluntary contraction force - N exposure condition: noise level 92dBA, no whole-body vibration - NV exposure condition: combined exposure to noise with a level of 92 dBA and wholebody vibration with 4 Hz, 1 ms^–2 rms - V exposure condition: whole-body vibration with 4 Hz, 1 ms^–2 rms - TTS temporary threshold shift - ITTS integral of temporary threshold shift - WBV whole-body vibration in the common sense This work was done in the Temporary International Research Team on Combined Effects of Noise and Vibration of the Council of Mutual Economic Assistance of the Socialist Countries. The authors gratefully acknowledge the help and assistance of L.-M. Brumm, Y. Bening, M. Godau, G. Weber, and R. Vizcaino.     

The Mother-Observer Relationship: An Examination of the Participant Role of the Observer in Mother-Infant Observation

SUMMARY. The relationship between mother and observer in mother-infant observation as described by Esther Bick is examined. Specifically, the question as to whether this relationship influences what is being observed is considered.
The author gives an account of her own relationship as an observer with a mother. The mother was an epileptic and fell with her baby (then six weeks old) causing the baby to suffer a broken skull. Exploration of events during the period of observation leads to the conclusion that the relationship between the mother and the observer was one of transference. Within this transference the observer seemed to be the mother of the one observed. This together with the effects on the observed mother's unconscious conflict with her own mother due to epilepsy is described.
Given transference in the mother-observer relationship doubts are raised as to the tenability of the attitude of distance and non-interference prescribed for the observer. The conclusion is drawn that, in any case, the role of the observer is a participant role, which poses the epistemological problem of the interference of the observer with the observed.     

Prevalence study of primary dystonia in Iceland.

In Iceland, the crude prevalence for all types of primary dystonia was 37.1/10(5) (confidence interval, 30.4-44.9). Focal dystonia had the highest prevalence (31.2/10(5)), followed by segmental (3.1/10(5)), multifocal (2.4/10(5)) and generalized dystonia (0.3/10(5)). Cervical dystonia was the most common focal dystonia (11.5/10(5)), followed by limb dystonia (8.0/10(5)), laryngeal dystonia (5.9/10(5)), blepharospasm (3.1/10(5)), and oromandibular dystonia (2.8/10(5)). The male:female ratio for all patients was 1:1.9 (P=0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3-82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar.     

Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users.

BACKGROUND: Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. METHODS: Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. RESULTS: A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. CONCLUSIONS: Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.     

Bronchopulmonary foregut malformations with communication to the esophagus

Congenital abnormal communications between separated pulmonary tissue and the oesophagus are rarities. Only about 50 cases have been reported in the literature. For all different forms the term of bronchopulmonary foregut malformation (BPFM) was first applied by Gerle and his coworkers in 1968. Major symptoms of this condition involved respiratory distress, cough, dyspnea, vomiting and repeated pneumonia. This paper presents reports of two own patients. In both cases was confirmed a bronchopulmonary foregut malformation in the lower right thorax with ectopic main bronchus communicating into the distal oesophagus. According to the literature we describe our own experience and discuss embryologic pathogenesis and surgical consequences for children.