Agonist-induced phosphorylation of the angiotensin AT1a receptor is localized to a serine/threonine-rich region of its cytoplasmic tail

Autosomal recessive juvenile parkinsonism (AR-JP) is a distinct clinical and genetic entity characterized by selective degeneration of nigral dopaminergic neurons and young-onset parkinsonism with remarkable response to levodopa. Recently, we mapped the gene locus for AR-JP to chromosome 6q25.2-q27 by linkage analysis and we identified a novel large gene, Parkin, consisting of 12 exons from this region; mutations of this gene were found to be the cause of AR-JP in two families. Now we report results of extensive molecular analysis on 34 affected individuals from 18 unrelated families with AR-JP. We found four different homozygous intragenic deletional mutations, involving exons 3 to 4, exon 3, exon 4, and exon 5 in 10 families (17 affected individuals). In addition to the exonic deletions, we identified a novel one-base deletion involving exon 5 in two families (2 affected individuals). All mutations so far found were deletional types in which large exonic deletion accounted for 50% (17 of 34) and the one-base deletion accounted for 6% (2/34); in the remaining, no homozygous mutations were found in the coding regions. Our findings indicate that loss of function of the Parkin protein results in the clinical phenotype of AR-JP and that subregions between introns 2 and 5 of the Parkin gene are mutational hot spots.     

In utero diagnosis of intrapericardial teratoma: a case for in utero open fetal surgery

We present a case of intrapericardial teratoma diagnosed by ultrasound at 26 weeks of gestation presenting as a large tumour mass and rapid development of hydrops fetalis. The fetus died in utero one day before scheduled open fetal surgery.     

Nutritional intervention and growth in children with chronic renal failure

During fifties there were at most few tens of persons in this country who believed in the future of computers and cybernetics. One group of such enthusiasts, headed by Antonín Svoboda, was working at a construction of the first Czech computer SAPO. The other group tried to analyse, anticipate, and prepare in advance various applications for the new systemic conceptions and for the information processing machines. Members of both groups met for discussions which opened prospects to the future and influenced many of other activities for a long time. At the early sixties, the Czechoslovak Cybernetic Society was established at the Czechoslovak Academy of Sciences and in 1962 the Main Problem Committee for the Medical Cybernetics was founded at the Department of Health. It coordinated majority of the research programmes in the medical cybernetics and informatics. In 1967-1969 the Committee prepared an extensive project of a medical information system (ZIS), but its accomplishment was finally blocked by the then authorities. However, interests for that topics kept growing and the new working places equipped with available computer technology were formed at the health and clinical centres. The first tentative lectures in medical cybernetics and biocybernetics at our faculty were introduced into the students curricula in the late sixties. Thematically, medical cybernetics subsequently differentiated into the medical informatics, simulations of biological and medical systems, and the biosignal analysis. The growing interest enabled to hold conferences since the middle of seventies, some of which were held periodically, sometimes with international participation. It is not possible in brevity to include the whole spectrum to those goal-directed activities nor to appraise adequately their future significance.     

Isolation of a novel mycobacterium from an adolescent with cervical lymphadenitis

A slow-growing mycobacterium was isolated from a cervical lymph node of an adolescent male. This isolate produced small, smooth, scotochromogenic colonies after 6 weeks of incubation at 25 degrees C and 30 degrees C (but not at 37 degrees C or 43 degrees C). The results of 16S-rRNA gene sequencing and high-performance liquid chromatography suggest that this isolate belongs to a hitherto unrecognised pathogenic species.     

Structure-based design of cathepsin K inhibitors containing a benzyloxy-substituted benzoyl peptidomimetic

Peptidomimetic cathepsin K inhibitors have been designed using binding models which were based on the X-ray crystal structure of an amino acid-based, active site-spanning inhibitor complexed with cathepsin K. These inhibitors, which contain a benzyloxybenzoyl group in place of a Cbz-leucine moiety, maintained good inhibitory potency relative to the amino acid-based inhibitor, and the binding models were found to be very predictive of relative inhibitor potency. The binding mode of one of the inhibitors was confirmed by X-ray crystallography, and the crystallographically determined structure is in close qualitative agreement with the initial binding model. These results strengthen the validity of a strategy involving iterative cycles of structure-based design, inhibitor synthesis and evaluation, and crystallographic structure determination for the discovery of peptidomimetic inhibitors.     

Microjet impingement followed by scanning electron microscopy as a qualitative technique to compare cellular adhesion to various biomaterials

Adhesion of cells to biomaterial surfaces is one of the major factors which mediates their biocompatibility. Quantitative or qualitative cell adhesion measurements would be useful for screening new implant materials. Microjet impingement has been evaluated by scanning electron microscopy, to determine to what extent it measures cell adhesion. The shear forces of the impingement, on the materials tested here, are seen to be greater than the cohesive strength of the cells in the impinged area, causing their rupture. The cell bodies are removed during impingement, leaving the sites of adhesion and other cellular material behind. Thus the method is shown not to provide quantification of cell adhesion forces for the metals and culture plastic tested. It is suggested that with highly adherent biomaterials, the distribution and patterns of these adhesion sites could be used for qualitative comparisons for screening of implant surfaces.     

Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.     

Abattoir survey of sheep and goats in The Gambia

An abattoir survey of sheep and goats was carried out in The Gambia for one year. A total of 1248 goats and 438 sheep, predominantly young females, were slaughtered and sampled. Sixty per cent of the females of both species were pregnant. There were no significant differences between the dressing percentages of different breeds and age groups. Sex and stage of pregnancy had a significant influence on carcase yields in both species. In goats the highest carcase yields were obtained during the early dry season. Most of the animals were clinically healthy and there were few pathological findings postmortem. In both species, there was a seasonal fluctuation of packed cell volume (PCV), with a minimum during the rains, and although the prevalence of trypanosomiasis was low it reduced the PCV. Faecal egg counts of Trichostrongylidae were highest during the rainy season and goats had higher faecal egg and coccidial oocyst counts than sheep. In sheep, a breed difference was observed for PCV and an age difference for egg excretion. The peak or higher rates of egg excretion occurred during the rains in both species. The immune status against peste des petits ruminants was significantly lower in goats (39 per cent) than in sheep (49.5 per cent). Antibodies against bluetongue virus were found in 62.6 per cent of goats and 55.8 per cent of sheep.