Head circumference of children with Williams-Beuren syndrome

Head circumference is considered an important parameter of brain growth and development. Syndrome-specific standards for head circumference in Williams-Beuren syndrome (WBS) are not available to date, although mental retardation is a leading manifestation in the syndrome. Therefore, we investigated head growth in 63 girls (251 measurements) and 88 boys (298 measurements) with WBS between birth and adulthood. Most measurements in both sexes were from the first 4 years of life (n = 162 in girls and n = 189 in boys). Mean (±SD) head circumference at birth was 33.39 ± 1.38 cm and 34.02 ± 1.44 cm for term girls and boys, respectively. Although head growth in WBS girls and boys was at a slower velocity, the pattern of head circumference was similar to that in the normal population. After the age of 3 months, head circumference started to fall below the normal mean in girls (0.5–2 cm). In boys, mean head circumference was below the normal mean already at 1 month of age (2 cm). The deficit increased to 3 cm from 6 months to 4 years. Adult OFC was 52.85 ± 1.75 cm (n = 16) compared to 55.70 ± 1.83 cm (n = 46; P < 0.00001) in WBS women and 55.51 ± 1.68 cm (n = 30) compared to 57.87 ± 1.29 cm (n = 31; P < 0.00001) in WBS men. During development, microcephaly is only seen in about one third of WBS patients. © 1994 Wiley-Liss, Inc.     

Suggestions for the assessment of the allergenic potential of genetically modified organisms

The prevalence of allergic diseases has been increasing continuously and, accordingly, there is a great desire to evaluate the allergenic potential of components in our daily environment (e.g., food). Although there is almost no scientific evidence that genetically modified organisms (GMOs) exhibit increased allergenicity compared with the corresponding wild type significant concerns have been raised regarding this matter. In principle, it is possible that the allergenic potential of GMOs may be increased due to the introduction of potential foreign allergens, to potentially upregulated expression of allergenic components caused by the modification of the wild type organism or to different means of exposure. According to the current practice, the proteins to be introduced into a GMO are evaluated for their physiochemical properties, sequence homology with known allergens and occasionally regarding their allergenic activity. We discuss why these current rules and procedures cannot predict or exclude the allergenicity of a given GMO with certainty. As an alternative we suggest to improve the current evaluation by an experimental comparison of the wild-type organism with the whole GMO regarding their potential to elicit reactions in allergic individuals and to induce de novo sensitizations. We also recommend that the suggested assessment procedures be equally applied to GMOs as well as to natural cultivars in order to establish effective measures for allergy prevention.     

Proton magnetic resonance spectroscopy in ecstasy (MDMA) users

The popular recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has well-recognized neurotoxic effects upon central serotonergic systems in animal studies. In humans, the use of MDMA has been linked to cognitive problems, particularly to deficits in long-term memory and learning. Recent studies with proton magnetic resonance spectroscopy (1H MRS) have reported relatively low levels of the neuronal marker N-acetylaspartate (NAA) in MDMA users, however, these results have been ambiguous. Moreover, the only available 1H MRS study of the hippocampus reported normal findings in a small sample of five MDMA users. In the present study, we compared 13 polyvalent ecstasy users with 13 matched controls. We found no differences between the NAA/creatine/phosphocreatine (Cr) ratios of users and controls in neocortical regions, and only a tendency towards lower NAA/Cr ratios in the left hippocampus of MDMA users. Thus, compared with cognitive deficits, 1H MRS appears to be a less sensitive marker of potential neurotoxic damage in ecstasy users.     

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na⁺/H⁺ antiport, amiloride (1 mM) and ethylisopro-pylamiloride (EIPA, 50 M), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na⁺]_e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 M). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloride-sensitive transport process, presumably the Na⁺/H⁺ exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.     

Neuronal Cell Death in Scrapie-Infected Mice Is Due to Apoptosis

Neuronal loss is a salient yet poorly understood feature in the pathology of transmissible spongiform encephalopathies (prion diseases). Cell culture experiments with neurotoxic prion protein fragments suggest that neuronal cell death in these diseases may be due to apoptosis. To test this hypothesis in vivo we used the in situ end-labeling (ISEL) technique and electron microscopy to study cell death in an experimental scrapie system in the mouse. ISEL, which relies on the incorporation of labeled nucleotides in fragmented DNA by terminal transferase, showed labeled nuclei in the brains and retinae of mice infected with the 79A strain of scrapie, whereas no labeling was observed in control animals. In the retina the highest numbers of labeled nuclei were found in the outer nuclear layer 120 days post infection followed by massive cell loss in this layer. In the brain, labeled nuclei were mainly found in the granular layer of the cerebellum of terminally ill mice. This corresponded to the presence of small dark nuclei with condensed and occasionally fragmented chromatin at the light and electron microscopical levels. Our results support the hypothesis that neuronal loss in spongiform encephalopathies is due to apoptosis. This may explain the almost complete absence of inflammatory response in prion diseases in the face of widespread neuronal cell death, and may also have therapeutic implications in the future.     

Renin gene and angiotensin II AT1 receptor gene expression in the kidneys of normal and of two-kidney/one-clip rats

This study aimed to investigate the inter-relation between the angiotensin II (ANG II) AT₁ receptor and renin gene expression in rat kidneys. To this end, renin mRNA levels and mRNA levels for AT_1a and AT_1b were assayed by RNase protection in the kidneys of normal rats, in animals treated with the AT₁ antagonist losartan and in rats bearing 0.2-mm left renal artery clips for 2 days. In normal rats, we found a negative correlation between renin mRNA levels and AT_1a receptor mRNA levels. Losartan led to a fourfold increase in renin mRNA levels without changing AT₁ receptor mRNA levels. Unilateral renal artery clipping increased renin mRNA levels fourfold in the clipped kidney and suppressed renin mRNA levels in the contralateral kidneys. AT₁ receptor mRNA levels were not changed in the contralateral intact kidneys, but were significantly decreased by 15–25% in the clipped kidneys. Renin mRNA levels were inversely correlated to AT_1a mRNA levels in the clipped, but not in the contralateral, kidneys. Our findings suggest that the systemic activity of the renin angiotensin system has no regulatory influence on renal AT₁ receptor gene expression. Renin mRNA levels in normal and in clipped kidneys appear to be negatively determined by the level of AT_1a receptor gene expression. Thus modulation of AT_1a receptor gene expression could be a pathway for indirect modulation of renin gene expression by ANG II. This conclusion is in agreement with the observation that AT₁ receptor antagonists are powerful stimulators of the renin system.