X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
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In unanesthetized spinal cats, injected with l-DOPA, intra-axonal recording was used to investigate the primary afferent depolarization (PAD) evoked in different species of afferents by volleys in the flexor reflex afferents (FRA). It was confirmed that a late PAD is evoked in la afferents and usually not in Ib or cutaneous afferents. Some late PAD was observed in a few group II muscle afferents. Intracellular recording from motoneurones revealed a considerable depression of the Ia EPSP during the late PAD evoked from the FRA after DOPA, but it was diffkult to attribute this entirely to the PAD in Ia afferents since there was also a late postsynaptic conductance increase in the motoneurones. A further analysis was made on acute spinal cats not injected with DOPA, in which a late P.4D sometimes is evoked by FR24 volleys, without the late postsynaptic soma effects in motoneurones. The marked depression of the Ia EPSP evoked from the FRA under these conditions has a longer duration than the PAD in la afferent terminals. It is postulated that two mechanisms contribute to the Ia EPSP depression, presynaptic inhibition and “remote inhibition”; the latter action persisting after the repolarization of Ia afferents. The results are discussed in relation to reflex regulation of stepping. 相似文献
During the six months from October 1985 through March 1986, blood samples from 306,061 civilian applicants for military service from the United States were tested for antibody to the human immunodeficiency virus (HIV). Four hundred sixty subjects were positive for the antibody as determined by Western (immune) blot reactivity. The mean prevalence of HIV infection in this population of teenagers and young adults was thus 1.50 per 1000. According to multivariate analysis, the following demographic factors were found to be significant independent predictors of a positive HIV-antibody test: age (adjusted odds ratio = 1.10 per year), black race (adjusted odds ratio = 2.04), male sex (adjusted odds ratio = 1.84), residence in a densely populated county (adjusted odds ratio = 1.05 per 1000 per square mile), and residence in a metropolitan area with a high incidence of the acquired immunodeficiency syndrome (adjusted odds ratio = 1.53). Antibody-positive applicants were identified in 43 of the 50 states. Counties with high prevalence rates for HIV (greater than 5 per 1000) were located in New York State (four counties), New Jersey (three counties), California (two counties), Maryland (two counties), and Texas, Colorado, and Washington, D.C. 相似文献
The MICs of 10 antimicrobial agents were determined for 1,000 clinical aerobic and facultatively anaerobic gram-negative bacilli by the 6-h AutoMicrobic system Gram-Negative General Susceptibility-Plus Card (GSC+) (Vitek Systems, Inc., Hazelwood, Mo.) and by an 18-h reference agar dilution method. Results obtained by both systems were evaluated for twofold dilution discrepancies and for interpretive category discrepancies. MICs that differed by more than one twofold dilution between the two test systems were considered to be discrepant. The overall twofold dilution agreement of the GSC+ MICs to agar dilution MICs was 94.0%. The agreement for each drug tested ranged from 91.7% (ampicillin and chloramphenicol) to 96.5% (carbenicillin). Interpretive categories were considered in agreement when the susceptibility interpretations obtained by the two systems were both very susceptible, moderately susceptible, or resistant. The overall interpretive category agreement was 80.5%. This agreement increased to 95.8% when all minor errors (moderately susceptible, one system; very susceptible, the other system) that would not affect therapy were omitted. The AutoMicrobic system GSC+ provides rapid and accurate susceptibility test results for clinical aerobic and facultatively anaerobic gram-negative bacilli. 相似文献
The cellular fatty acid composition of Brucella ovis and Brucella abortus strains was determined by gas-liquid chromatography. Both species were characterized by the presence of fatty acids 16:0, 17:0, 17:0 cyclopropane, 18:0, 18:1, and 19:0 cyclopropane; B. ovis also contained some 15:0. There were differences in the relative proportions of the fatty acids present, and it was possible to differentiate B. ovis from B. abortus on the basis of the absence of 15:0, lower concentrations of 17:0 and 18:1, and higher concentrations of 19:0 cyclopropane in B. abortus. The data indicate that analysis of cellular fatty acid composition by gas-liquid chromatography can be used for the identification of B. ovis and its differentiation from B. abortus. 相似文献
The activity patterns in self- and cross-reinnervated flexor digitorum longus (FDL) and soleus (SOL) muscles were examined during natural movements in awake, unrestrained cats in which electromyographic (EMG) electrodes, tendon-force gauges, and muscle-length gauges had been chronically implanted under anesthesia and aseptic conditions. Kinesiological data were recorded between 13 and 22 mo after nerve surgery. Self-reinnervated FDL and SOL muscles (i.e., FDL----FDL and SOL----SOL, respectively) exhibited locomotor activity patterns that were the same as observed in normal, unoperated FDL and SOL muscles (26). FDL----FDL muscles exhibited primarily brief bursts of activity in early swing, just after the toes had left the ground, whereas SOL----SOL muscles showed bursts of activity just before and during stance. In contrast, the cross-reinnervated muscles (both SOL----FDL and FDL----SOL) that had little or no unwanted self-reinnervation showed the patterns of activity that are associated with the innervating foreign motoneurons. That is, cross-reinnervated SOL----FDL muscles were intensely active in quadrupedal standing and, during the stance phase of stepping, producing large force transients while actively lengthening. Conversely, cross-reinnervated FDL----SOL muscles were active mainly in short bursts at the onset of the swing phase of stepping, just after the foot had left the ground. There was considerable modulation of EMG and peak force output in FDL----SOL muscles with changing speed of locomotion, whereas little modulation was evident in SOL----FDL muscles. The activity patterns in self- and cross-reinnervated FDL and SOL muscles were also recorded during scratch and paw-shaking reflexes. As in locomotion, the observed patterns were in all cases consistent with those expected for the innervating motor pool rather than the innervated muscle. Muscles that had been dually reinnervated by both the original and foreign motor pools displayed activity patterns that were a mixture of the FDL and SOL activity patterns described above. The present results demonstrate that motoneuron activation patterns remain qualitatively unaltered when their motor axons reinnervate foreign muscles. In addition, the observations permit some quantitative estimates of the degree to which cross-reinnervated muscles are subjected to patterns of motoneuron activity and to conditions of mechanical loading that are markedly different from those in the self-reinnervated or normal conditions. 相似文献
1. The neuronal membrane responses to long constant current pulses (essentially current steps) have been studied in cat triceps surae motoneurones identified as to the type of muscle fibres, fast twitch (type F) or slow twitch (type S), innervated by the cell being studied. For each motoneurone the membrane time constant, τM, and input resistance, RN, were determined from the response to a current step. In addition, shorter time constants (`equalizing time constants') resulting from current spread into the dendrites were estimated by graphical analysis.
2. The electrotonic length of the combined motoneurone soma and dendritic tree was estimated from the current step data using the neuronal equivalent cylinder model formulated by Rall (Rall, 1969). The mean electrotonic length of the motoneurone equivalent cylinder was approximately 1·5 in both type F and type S motoneurones. The mean membrane time constant of type F cells was 5·6 msec and that of type S motoneurones was 6·7 msec. This difference in mean τM values was of border line statistical significance.
3. The results indicate that the electrotonic length of the combined dendritic trees of both large type F and small type S motoneurones is essentially the same. The implication of this conclusion for interpretation of previous analyses of the monosynaptic EPSP is discussed.