The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei

Trypanosoma brucei evades the immune system by switching between Variant Surface Glycoprotein (VSG) genes. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites (ESs). It has been postulated that ES polymorphism plays a role in host adaptation. To gain more insight into ES architecture, we have determined the complete sequence of Bacterial Artificial Chromosomes (BACs) containing DNA from three ESs and their flanking regions. There was variation in the order and number of ES-associated genes (ESAGs). ESAGs 6 and 7, encoding transferrin receptor subunits, are the only ESAGs with functional copies in every ES that has been sequenced until now. A BAC clone containing the VO2 ES sequences comprised approximately half of a 330 kb 'intermediate' chromosome. The extensive similarity between this intermediate chromosome and the left telomere of T. brucei 927 chromosome I, suggests that this previously uncharacterised intermediate size class of chromosomes could have arisen from breakage of megabase chromosomes. Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES.     

Developmental aspects of nevus spilus: review of the literature apropos of 7 cases

The nevus on nevus is a dischromic lesion with a double component made of a pigmented, pale-brown coloured spot, most often congenital punctuated by macular or discretely papular darker elements, with a usually later setting-up and conventionally characterized by an absence of evolutivity. A series of seven cases is reported of whom three present a very peculiar evolution: A 37 years old man is taking a medical advice for a nevus on a congenital nevus on the right buttock on which appeared later on a blue-coloured, lightly sensitive nodule which clinically calls to mind the diagnosis of a blue nevus: the surgical exeresis is refused by the patient. A little girl, born in 1972, has since her birth a nevus on nevus of her right fore-arm; in 1975 and 1976 appeared successively on this lesion three nodules evocative of Spitz melanoma (fig. 4), which are surgically removed; histologic examination confirms the clinical diagnosis (fig. 5). A woman, aged 38, presents a big nevus on congenital zosteriform nevus of the right lower limb; since 1982, one of the dark elements situated on the lower third of the leg is progressively spreading and becoming polychromic (fig. 6); the clinical suspicious of superficial spreading malignant melanoma is confirmed by the histologic examination. In the literature, the terminology aiming to call this kind of nevic pale brown spot recovered by darker macules is not quite clear, as it was already emphasized by Stewart in 1978 (27). Indeed, numerous different denomination are found in it: "nevus spilus", nevus on nevus", "spotty nevus" "speckled lentiginous nevus", "speckled nevus "spilus".(ABSTRACT TRUNCATED AT 250 WORDS)     

Pattern electroretinogram and visual evoked potential amplitudes are influenced by different stimulus field sizes and scotomata

The pattern electroretinogram and the visual evoked potential were recorded simultaneously with various stimulus fields and artificial scotomata of increasing sizes. In contrast to an earlier study, a smaller check size (20) and two stimulus field sizes (20° × 20° and 10° × 10°) for the scotomata were used. With a concentric decreasing stimulus field, a reduction of both the pattern electroretinogram and visual evoked potential was found. Both showed a simultaneous reduction of amplitudes, but, compared with the amplitude in the full field, the reduction was more extensive for the pattern electroretinogram at each test field size. This implies a greater contribution to the pattern electroretinogram from more eccentric retinal parts. An artificial central scotoma of increasing size in the 20° × 20° field had less influence on the pattern electroretinogram than on the visual evoked potential. The percentage amplitude loss of the visual evoked potential was more pronounced. The visual evoked potential was eventually abolished by a scotoma size from 10° × 10° upward, while the pattern electroretinogram was still registrable. When scotomata of similar size were introduced in a smaller (10° × 10°) field, percentage pattern electroretinogram and visual evoked potential amplitude losses were less separated than in a larger (20° × 20°) test field.     

Sympathoinhibition by rilmenidine in conscious rabbits: involvement of α2-adrenoceptors

Summary Cardiovascular and sympathetic nervous system effects of the mixed ₂-adrenoceptor and imidazoline receptor agonist rilmenidine were studied in conscious rabbits chronically instrumented for the recording of the firing rate of renal sympathetic fibers. Separate experiments were carried out on pithed rabbits with electrically stimulated (2 Hz) sympathetic outflow. Drugs were administered intravenously in a cumulative manner.In conscious rabbits, rilmenidine 0.1, 0.3 and 1.0 mg kg^–1 dose-dependently lowered blood pressure, renal sympathetic nerve activity, heart rate and the plasma concentration of noradrenaline and adrenaline. The effect on blood pressure and plasma catecholamines was maximal after 0.3 mg kg^–1 whereas heart rate and renal sympathetic nerve activity decreased further after rilmenidine 1.0 mg kg^–1. Yohimbine 0.1 and 0.5 mg kg^–1, when injected subsequently, attenuated and at the higher dose abolished all effects of rilmenidine. The effects of rilmenidine were also antagonized by the ₂-adrenoceptor antagonist 2-(2,3-dihydro-2-methoxy-1,4-benzodioxin-2-yl)-4,5-dihydro-1H-imidazole HCl (RX821002; 0.1 and 0.5 mg kg^–1). Yohimbine 0.1 and 0.5 mg kg^–1 did not attenuate or attenuated only slightly the decrease of heart rate and renal sympathetic nerve activity produced by infusion of vasopressin. In pithed rabbits with electrically-stimulated sympathetic outflow, yohimbine 0.1 submaximally and yohimbine 0.5 mg kg^–1 maximally increased the plasma noradrenaline concentration.The experiments show by direct measurement of sympathetic nerve firing and plasma catecholamines that rilmenidine causes sympathoinhibition in conscious rabbits, presumably through central sites of action. The antagonism by yohimbine, at doses which are selective for ₂-adrenoceptors (vs. imidazoline receptors), demonstrates the involvement of ₂-adrenoceptors in the sympatho-inhibition.Correspondence to: B. Szabo at the above address     

Inhibition of uptake1 by (+)-oxaprotiline reveals a differential central regulation of noradrenaline and adrenaline release

Summary Inhibition of uptake, in the central nervous system leads to a decrease of sympathetic outflow to many tissues; central a2-adrenoceptors are involved in this decrease. The aim of the present study was to compare the effects of the selective uptake, inhibitor (+)-oxaprotiline on the plasma kinetics of noradrenaline and adrenaline in anaesthetized and in conscious rabbits. [³H]Noradrenaline and [^3H]adrenaline were infused iv. The arterial plasma concentrations of endogenous and radiolabelled noradrenaline and adrenaline were measured, and the clearance from and spillover into the plasma of noradrenaline and adrenaline were calculated.Results obtained in conscious and anaesthetized rabbits were similar. (+)-Oxaprotiline 0.2, 0.6 and 1.8 mg kg^–1 iv. dose-dependently reduced the clearance of [³H]noradrenaline from the plasma. The clearance of [³H]adrenaline was reduced less. The spillover of endogenous noradrenaline was decreased by up to 35%. In contrast, the spillover of adrenaline tended to be enhanced. Prazosin 0.1 and 1 mg kg^–1 was injected iv. in a second part of each experiment. It lowered the blood pressure and caused a marked increase in noradrenaline spillover but no increase or even a decrease in adrenaline spillover.The results are compatible with the following hypothesis. The sympathetic outflow from the central nervous system is subject to a twofold a-adrenoceptor-mediated modulation: -adrenoceptor-mediated inhibition and ₁-adrenoceptor-mediated excitation. In the control of the sympathetic outflow to many extra-adrenal tissues, the ₂-adrenergic inhibition prevails. Uptake₁ inhibitors depress sympathetic outflow to such tissues by enhancing the ₂-adrenergic inhibition. In the regulation of the sympathetic outflow to the adrenal medulla, in contrast, ₂-adrenergic inhibition and ₁-adrenergic excitation have a similar impact. Uptake, inhibitors, hence, cause little change in adrenaline release: the two opposing influences cancel out. Prazosin produces an increase in noradrenaline but not adrenaline release because the loss of the central ₁ sympathoexcitation attenuates at best slightly the baroreflex to most extra-adrenal tissues but dampens markedly the baroreflex to the adrenal medulla. Correspondence to B. Szabo at the above address     

Cardiovascular effects of agmatine,a “clonidine-displacing substance”, in conscious rabbits

Agmatine has been identified as a clonidine-displacing substance in extracts from bovine brain. We studied its effect on cardiovascular regulation and the role played in this effect by ₂-adrenoceptors.In conscious rabbits, agmatine 10 g kg^–1 injected intracisternally (i.e.) caused no change, whereas agmatine 30, 100 and 300 g kg^–1 i.e. increased renal sympathetic nerve firing, the plasma concentration of noradrenaline and adrenaline and arterial blood pressure. Heart rate tended to be decreased. Yohimbine 1.5 g kg^–1 i.e. caused no change, whereas yohimbine 5, 15 and 50 g kg^–1 increased renal sympathetic nerve activity, the plasma concentration of noradrenaline and adrenaline, blood pressure and heart rate. In rabbit brain cortex slices preincubated with [³H]-noradrenaline, agmatine 1 to 100 M did not modify the electrically evoked overflow of tritium (either 4 pulses at 100 Hz or 36 pulses at 3 Hz). The evoked overflow was reduced by 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK 14304) 0.03 to 30 nM (4 pulses at 100 Hz), and this inhibition was not affected by agmatine 10 and 100 M. Agmatine did not change the basal efflux of tritium.The results show that agmatine, like yohimbine, causes central sympathoexcitation when given i.e., but agmatine differs from yohimbine in that it does not increase heart rate. Agmatine acts neither as an agonist nor as an antagonist at the ₂-autoreceptors in rabbit brain cortex. ₂-Adrenoceptors, therefore, are probably not involved in its cardiovascular effects. An action at imidazoline receptors in the medulla oblongata or some other hitherto unknown mechanism may be responsible for the sympathoexcitation.     

PRENATAL DETECTION OF THE DELTA F 508 MUTATION USING FLUORESCENT PCR AND COMPARISON OF THE RESULTS WITH CONVENTIONAL PCR

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasians. The most frequent mutation associated with cystic fibrosis has been identified as the 3 bp deletion Delta F 508. While existing polymerase chain reactions (PCR) (allele specific amplification) used to screen for CF are both sensitive and specific, we tested the prenatal application of fluorescent polymerase chain reaction and subsequent DNA fragment analysis that appears to be fast and sensitive. DNA samples (n=146) isolated from amniotic fluid (n=108), chorion villus biopsies (n=6), and human peripheral blood (n=32) were analyzed for the presence of Delta F 508 using the fluorescent method. Of these, 10 carriers of Delta F 508 mutation were detected. We achieved the same results with conventional PCR and fluorescent PCR.