Functional studies on c.1347C>T,a polymorphism modulating phenotypic outcome in X-linked adrenoleukodystrophy

Tijdschrift voor Kindergeneeskunde -     

Characteristics of the sequence effect in Parkinson's disease

The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer‐based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo‐controlled, four‐way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.     

Malignant transformatin of human bronchial epithelial cells by radon-simulated {alpha}-particles

Epidemiological studies have shown that inhalation of radonis associated with an increased risk for bronchogenic carcinomain uranium miners. These     

The role of the duodenal microflora as a determinant of persistent diarrhoea

It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two often bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model.     

Rat CYP1B1: an adrenal cytochrome P450 that exhibits sex-dependent expression in livers and kidneys of TCDD-treated animals

The broad spectrum of biological responses associated with exposureto 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is believedto be due to the alteration in expression of TCDD-induciblegenes. The aim of this study was to investigate the effectsof TCDD on the in vivo tissue-specific expression of the recentlyidentified TCDD-inducible cytochrome P450 CYP1B1 [Sutter etal. (1994) J. Biol. Chem., 269, 13092–13099] in Sprague-Dawleyrats. We cloned the 5.0 kb rat homolog of CYP1B1 from a TCDD-treatedrat liver cDNA library and showed that the rat and human CYP1B1predicted amino acid sequences are 80% identical. RNA hybridizationanalysis snowed that CYP1B1 is constitutively expressed in theadrenal glands and also in the testes of untreated rats. Thistissue distribution suggests that CYP1B1 may be a physiologicalsteroid hydroxylase. Seventy-two hours post-administration of25 µg/kg body wt TCDD by gavage, steady-state levels ofthe 5.1 kb CYP1B1 RNA were increased > 50-fold in liver,and to a lesser extent in kidneys, lung, heart and ovaries.Average CYP1B1 RNA levels were significantly higher in the kidneysand livers of TCDD-treated females than in those from similarlytreated males. In contrast, no significant sex-difference wasobserved in the levels of CYP1A1 in these tissues in TCDD-treatedanimals. In Sprague-Dawley rats, TCDD is a more potent hepatocarcinogenin females than in males. The induction of CYP1B1 in TCDD ratliver may be a contributing factor to the carcinogenic actionof this persistent environmental pollutant.     

The interpretation of multifocal binary kernels

The interpretation of binary kernels derived by means of the mulifocal ERG has frequently been the source of confusion and controversy. The aim of this paper is to provide an intuitive understanding of the concept of kernels and to demonstrate with models and examples, the relationship between the kernels and individual responses. The sample data used to illustrate the various aspects of the technique were derived and analyzed by means of the multifocal VERIS^TM instrument using bipolar Burian-Allen contact lens electrodes. From the kernel data, response waveforms are synthesized that can be readily compared with those obtained with conventional flash, double flash and multi-flash ERG techniques. From the kernels of a single multifocal record, waveforms are synthesized that describe responses at various times after a preceding focal flash. It is shown that the observed adaptive changes in the waveforms depend not only on the flash interval but also on retinal eccentricity. Features on the response waveform exhibit independent adaptive behavior suggesting that they originate from different retinal sources. On one hand, the examples presented here illustrate the rich information on retinal dynamics contained in the kernels. On the other hand, they demonstrate how the interpretation of multifocal data can be facilitated when the kernel series is transformed into representations with more direct physiological appeal. This revised version was published online in July 2006 with corrections to the Cover Date.