Hereditary multiple exostoses (EXT) is an autosomal dominant condition characterized by short stature and the development of bony protuberances at the ends of all the long bones. Three genetic locl have been identified by genetic linkage analysis at chromosomes 8q24.1, 11p11-13 and 19p. The EXT1 gene on chromosome 8 was recently identified and characterized. Here, we report the isolation and characterization of the EXT2 gene. This gene shows striking sequence similarity to the EXT1 gene, and we have identified a four base deletion segregating with the phenotype. Both EXT1 and EXT2 show significant homology with one additional expressed sequence tag, defining a new multigene family of proteins with potential tumour suppressor activity.
Cerebral blood flow (CBF) in humans was measured at rest and during dynamic exercise on a cycle ergometer corresponding to 56% (range 27-85) of maximal O2 uptake (VO2max). Exercise bouts were performed by 16 male and female subjects, lasted 15 min each, and were carried out in a semisupine position. CBF (133Xe clearance) was expressed as the initial slope index (ISI) and as the first compartment flow (F1). CBF at rest [ISI, 58 (range 45-73); F1, 76 (range 55-98) ml.100 g-1.min-1] increased during exercise [ISI to 79 (57-94) and F1 to 118 (75-164) ml.100 g-1.min-1, P less than 0.01]. CBF did not differ significantly between work loads from 32 (24-33) to 86% (74-96) of VO2max (n = 10). During exercise, mean arterial pressure increased from 84 (60-100) to 101 (78-124) Torr (P less than 0.01) and PCO2 remained unchanged [5.1 (4.6-5.6) vs. 5.4 (4.4-6.3) kPa, n = 6]. These results demonstrate a median increase of 31% (0-87) in CBF by ISI and a median increase of 58% (0-133) in CBF by F1 during dynamic exercise in humans.
SUMMARY1. In order to evaluate the importance of afferent neural feedback from the working muscles for cardiovascular and ventilatory responses to dynamic exercise, epidural anaesthesia was induced at L3-L4. Six healthy males cycled for 20 min at 57 % of maximum oxygen uptake and for 8-12 min at increasing work intensities until exhaustion at 238 + 30 W without as well as with epidural anaesthesia.2. Presence of afferent neural blockade was verified by cutaneous sensory analgesia below T10-T11 and attenuated post-exercise ischaemic pressor response (45 + 8-24 + 6 mmHg). Efferent sympathetic nerves appear to be intact since basal heart rate and blood pressure as well as the cardiovascular responses to a Valsalva manoeuvre and to a cold pressor test were unchanged.3. During dynamic exercise with epidural anaesthesia, blood pressure was lower than in control experiments; however, ventilation and heart rate were not affected.4. The results indicate that afferent neural activity from the working muscles is important for blood pressure regulation during dynamic exercise in man but may not be necessary for eliciting the ventilatory and heart rate responses.
The chromosome of Bacillus subtilis codes for seven extracytoplasmic function sigma factors the activity of which is modulated normally by a cognate anti-sigma factor. While inducing factors and genes for four of them (sigma(M), sigma(W), sigma(X), and sigma(Y)) have been identified, those of the remaining three sigma factors including sigma(V) remain elusive. The objective of the present study was the unequivocal identification of its anti-sigma factor and of genes controlled by sigma(V). In many cases reported so far the gene coding for the anti-sigma factor is located immediately downstream of the gene coding for the sigma factor, and both form a bicistronic operon. We could show by two different experimental approaches that this is also the case for sigV and rsiV. Under conditions of overproduction of sigma(V), 13 genes could be identified being induced several-fold by the DNA macroarray technique. Induction of three of them was confirmed by Northern blots, and the potential promoter of sigV was identified by primer extension. This led to the deduction of a consensus sequence recognized by sigma(V).
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