Waardenburg-Syndrom

BACKGROUND: Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. PATIENTS AND METHODS: Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. RESULTS AND CONCLUSION: In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.     

Application of a novel Active Allothetic Place Avoidance task (AAPA) in testing a pharmacological model of psychosis in rats: comparison with the Morris Water Maze

Administration of a non-competitive NMDA antagonist dizocilpine (MK-801) was proposed to be an animal model of psychosis. NMDA-receptor blockade is accompanied by increased locomotion, behavioral deficits, and other changes resembling psychotic symptoms. However, the role of NMDA-receptors in organizing brain representations is not understood yet. We tested the effect of NMDA-receptor blockade by systemic administration of dizocilpine at two different doses (0.1 or 0.2 mg/kg) in a recently designed Active Allothetic Place Avoidance (AAPA), a task which requires rats to separate spatial stimuli from two continuously dissociated subsets. The effect of dizocilpine on learning in the AAPA task was compared with its effect on acquisition of the reference memory version of the Morris Water Maze task. Both doses impaired performance in the Morris Water Maze task, whereas only the higher dose impaired performance in the AAPA task. The Morris Water Maze appears to be more sensitive to dizocilpine-induced behavioral deficit than the AAPA task. These findings support the notion that these two tasks are differentially dependent on the NMDA-receptor function.     

Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics

The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.     

Hypothesis of regulation of hip joint cartilage activity by mechanical loading

Hypothesis of regulation of proteosynthetic activity of chondrocytes is suggested. A deformation of the cartilage caused by contact hip joint stress and consequent deformation of the chondrocytes are considered as main factors that could influence the metabolism of the cartilage.     

Focal sarcoid-like change of the thyroid gland. A possible consequence of aspiration cytology?

An unusual case of focal accumulation of sarcoid-like granulomas occurring within the thyroid gland of a 43-year-old female patient is reported. The granulomas were found solely at the site of previous fine needle aspiration biopsy. The follow-up did not show any symptoms of systemic granulomatous disease. The pathogenesis of this lesion is discussed.     

Psychiatric disturbances and psychotropic drugs in tinnitus patients

At the ear, nose, and throat clinic of the Third Medical Faculty at Charles University and at the Psychiatry Department of the Institute for Further Education of Physicians in Prague, we examined 25 patients with tinnitus accompanied by psychiatric disturbances and followed them up for at least 6 months. Psychological changes in tinnitus patients occur in a characteristic chronological succession and manifest in three stages: defense, the search for adaptive mechanism, and relative recovery or a development of psychiatric disturbance (or both). Some psychotropic drugs probably diminish tinnitus by the mechanism of improving general psychiatric comfort and direct central influence. Subjective heaviness of tinnitus is defined by the authors as all the difficulties that exist along with tinnitus. It encompasses subjective evaluation of tinnitus loudness, frequency of tinnitus episodes, and psychiatric disturbances arising from the individual discomfort caused by tinnitus. The authors selected the visual analog scale as an easily used instrument appropriate for the complex evaluation of subjective heaviness of tinnitus.     

The regional oxygen saturation of pituitary adenomas is lower than that of the pituitary gland: microspectrophotometric study with potential clinical implications

OBJECTIVE: To study the regional oxygen saturation (rSO(2)) of pituitary adenomas, in comparison with that of the pituitary gland. METHODS: Microspectrophotometric (MSP) measurements of rSO(2) in adenomas and pituitary tissue were performed for a series of patients undergoing first-time transsphenoidal pituitary adenoma surgery, in a standardized anesthesia setting. The areas of measured tissue were sampled for histopathological and immunohistochemical (CD34 and CD45) assessments. The results of MSP measurements were compared with the results of the histopathological and immunohistochemical assessments. RESULTS: Thirty-six MSP measurements and tissue samples were obtained among 22 patients with pituitary macroadenomas, including 14 from adenoma tissue, 17 from the anterior pituitary lobe, and 5 from the posterior pituitary lobe. The rSO(2) of adenoma tissue (mean +/- standard deviation, 43.3 +/- 23.2%) was statistically significantly (P = 0.001) lower than the values for the anterior pituitary lobe (mean +/- standard deviation, 71.8 +/- 18.3%) and posterior pituitary lobe (mean +/- standard deviation, 74.9 +/- 4.8%). The difference between the rSO(2) values for the anterior pituitary lobe and posterior pituitary lobe was not significant. There were no statistically significant differences in microvessel density (as assessed with CD34 staining) or lymphocyte density (as assessed with CD45 staining) among the three tissue types. CONCLUSION: As assessed with MSP measurements, the rSO(2) of adenoma tissue was significantly lower than that of the pituitary gland, indicating differences in their blood supply and/or metabolism in pituitary macroadenomas. Further studies are needed to determine whether MSP measurements can reliably facilitate intraoperative delineation of adenoma and pituitary tissue, in the effort to achieve complete tumor removal with minimal injury to pituitary tissue.     

Activation of B cell apoptotic pathways in the course of Francisella tularensis infection

Francisella tularensis is a facultative intracellular, gram-negative bacterium that induces apoptosis in macrophages and B cells. Here we show apoptotic pathways that are activated in the Ramos human B cell line in the course of F. tularensis infection. Live bacteria F. tularensis FSC200 activate caspases 8, 9 and 3, as well as Bid; release cytochrome c and apoptosis-inducing factor from mitochondria; and induce depolarization of mitochondrial membrane potential in the Ramos cell line, thus leading these cells to apoptosis. Unlike live bacteria, killed F. tularensis FSC200 bacteria activated only caspase 3, and did not cause apoptosis of Ramos cells as measured by annexin V. Killed bacteria also caused accumulation of anti-apoptotic protein Bclx_L in mitochondrial membranes. Thus, live F. tularensis activates both caspase pathways (receptor-mediated and intrinsic) as well as caspase-independent mitochondrial death.     

The effect of short-range spatial variability on soil sampling uncertainty.

This paper aims to quantify the soil sampling uncertainty arising from the short-range spatial variability of elemental concentrations in the topsoils of agricultural, semi-natural, and contaminated environments. For the agricultural site, the relative standard sampling uncertainty ranges between 1% and 5.5%. For the semi-natural area, the sampling uncertainties are 2-4 times larger than in the agricultural area. The contaminated site exhibited significant short-range spatial variability in elemental composition, which resulted in sampling uncertainties of 20-30%.