Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene

Glutamatergic synaptic potentials induced by micromolar concentrations of the potassium conductance blocker 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in the presence of 10 microM bicuculline (BIC). These synaptic potentials originate from neostriatal cortical and thalamic afferents and were completely blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric acid (2-APV). Their inter-event time intervals could be fitted to exponential distributions, suggesting that they are induced randomly. Their amplitude distributions had most counts around 1 mV and fewer counts with values up to 5 mV. Since input resistance of the recorded neurons is about 40 M omega, the amplitudes agree to quantal size measurements in mammalian central neurons. The action of a D2 agonist, quinpirole, was studied on the frequency of these events. Mean amplitude of synaptic potentials was preserved in the presence of 2-10 microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic potentials was reduced in 35% of cases. The effect was blocked by the D2 antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing threshold did not change during quinpirole effect, suggesting a presynaptic site of action for quinpirole in some but not all glutamatergic afferents that make contact on a single cell. The present experiments show that dopaminergic presynaptic modulation of glutamatergic transmission in the neostriatum does not affect all stimulated afferents, suggesting that it is selective towards some of them. This may control the quality and quantity of afferent flow upon neostriatal neurons.     

Children conceived by in vitro fertilisation after fresh embryo transfer

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.     

Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension

In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.     

Simple protocols to determine dust potentials from cattle feedlot soil and surface samples

Cattle feedlot dust is an annoyance and may be a route for nutrient transport, odor emission, and pathogen dispersion, but important environmental factors that contribute to dust emissions are poorly characterized. A general protocol was devised to test feedlot samples for their ability to produce dust under a variety of environmental conditions. A blender was modified to produce dust from a variety of dried feedlot surface and soil samples and collect airborne particles on glass fiber filters by vacuum collection. A general blending protocol optimized for sample volume (150-175 cm3), blending time (5 min of pre-blending), and dust collection time (15 s) provided consistent dust measurements for all samples tested. The procedure performed well on samples that varied in organic matter content, but was restricted to samples containing less than 200 to 700 g H2O kg(-1) dry matter (DM). When applied to field samples, the technique demonstrated considerable spatial variability between feedlot pen sites. Mechanistically, dust potential was related to moisture and organic matter content. An alternative protocol also demonstrated differences within pen sites in maximum dust potential and dust airborne residence time. The two protocols were not intended, nor are they suitable, for predicting actual particulate matter emissions from agricultural sources. Rather, the protocols rapidly and inexpensively compared the potential for dust emission from samples of differing composition under a variety of environmental conditions.     

Effects of sleeping in a chemical protective mask on sleep quality and cognitive performance

PURPOSE: We wanted to determine whether sleep is disrupted when soldiers sleep in a new chemical protective mask, the M40. Sleep quantity and quality, extent of protection provided by the mask during sleep, and next day performance were assessed. METHOD: After several days of training, 9 male soldiers slept with and without the M40 mask on four occasions. RESULTS: Soldiers were able to tolerate the mask for most or all of the night. However, sleep, as assessed by wrist-worn activity monitors, was significantly disturbed. Minutes (mean +/- SEM) of waking significantly increased, from 25 +/- 2.1 to 86 +/- 8.5 per night (p < 0.001), and number of awakenings rose from 8 +/- 0.6 to 20 +/- 0.9 (p < 0.0001). Soldiers reported that it took longer and was more difficult to fall asleep when wearing the mask. Errors on a choice reaction time task increased significantly and subjects reported greater fatigue and sleepiness the day after sleeping in the mask. Protection provided by the masks varied substantially among subjects and declined over the course of the study. Some soldiers were protected throughout the night but others were only protected intermittently. CONCLUSION: We conclude that sleeping in the chemical protective mask should only be done when necessary, given the adverse effects on sleep and daytime function, as well as the variability of protection, of the mask.