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Biomedical subjects

C Sang

Publications and source records attributed to C Sang.

7 recordsLinked to original sources

Transgenic mice with an expanded CAG repeat controlled by the human AR promoter show polyglutamine nuclear inclusions and neuronal dysfunction without neuronal cell death.

We generated transgenic mice that expressed a highly expanded 239 polyglutamine (polyQ) repeat under the control of the human androgen receptor promoter. These transgenic mice developed progressive neurological phenotypes of muscular weakness and ataxia, small body size and short life-span. PolyQ nuclear inclusions (NIs) were remarkable and widespread but found in selective regions of the central nervous system (CNS) such as the spinal cord, cerebrum and cerebellum as well as in selective peripheral visceral organs. This distribution pattern resembled that of spinal and bulbar muscular atrophy somewhat, but was more widespread. In neuronal tissues, NIs were present in astrocytes as well as neurons. Cytoplasmic and axonal inclusions were not observed. In the CNS regions with abundant NIs, neuronal populations were well-preserved, and neither neuronal cell death, reactive astrogliosis nor microglial invasions were detected. These findings suggest that polyQ alone can induce the neuronal dysfunction that precedes gross neuronal degeneration and provides a clue for investigating molecular mechanisms that underly the pathway to neuronal dysfunction from polyQ expansion.

Animals↗

The substance P receptor antagonist CP-99,994 reduces acute postoperative pain.

BACKGROUND: Animal studies suggest that substance P, a peptide that preferentially activates the neurokinin-1 (NK1) receptor, is involved in pain transmission, with particular importance in pain after inflammation. METHODS: The analgesic efficacy of CP-99,994, a NK1 receptor antagonist, was compared with ibuprofen and placebo in 78 subjects undergoing third molar extraction. The initial 60 subjects randomly received 1 of 3 possible treatments in a double-blind fashion before oral surgery: 750 microg/kg CP-99,994 infused intravenously over 5 hours on a tapering regimen starting 2 hours before surgery, 600 mg oral ibuprofen 30 minutes before surgery, or placebo. In a second study, 18 subjects were randomized to the same regimens starting 30 minutes before surgery to maximize the amount of CP-99,994 circulating during pain onset. RESULTS: In the first study, ibuprofen significantly reduced pain, as measured by visual analog scale, from 90 to 240 minutes postoperatively compared with placebo. CP-99,994 produced analgesia that was significant at 90 minutes (P < 0.01 compared with placebo), but not at subsequent time points. In the second study, ibuprofen and, to a lesser extent, CP-99,994 significantly suppressed pain in comparison to placebo at 60, 90, and 120 minutes (P < 0.05). The incidence of side effects was similar across groups. CONCLUSIONS: This replicate demonstration that a NK1 receptor blocker relieves clinical pain supports the hypothesis that substance P contributes to the generation of pain in humans. The reduction in postoperative pain at doses not producing side effects suggests that NK1 antagonists may be clinically useful.

Acute Disease↗

[The analysis of fatty acid composition in syncytiotrophoblast plasma membranes of human placenta].

The fatty acids were determined in syncytiotrophoblast plasma membranes of the eighteen human placenta from the normal pregnant women. With the method of Landon, the fat was purified in syncytiotrophoblast plasma membranes, which was extracted from the placenta by using the procedure of Whitsett. The methylated fatty acids were separated with gas chromatography in which a glass column packed with DEGS was used. In comparing the retention time of the sample with the standards and referring to the results of GC/MS, thirteen peaks were identified and quantified. The area normalization method was used to determine the distribution, the compositions and contents of fatty acids in syncytiotrophoblast plasma membranes. It is shown that the amount of identified fatty acids attains 74.1% of total peak area, in which the amount of saturated fatty acids was 30.64%, and the unsaturated was 43.46%.

Cell Membrane↗

A cochlear model using feed-forward outer-hair-cell forces.

A linear (frequency-domain) model of the cat cochlea (implemented in both 1- and 2-dimensional versions) has been developed which uses outer hair cell (OHC) forces in a geometry which includes the longitudinal (base-to-apex) tilt of the outer hair cells (OHCs). When positive (contractile) real OHC force-constants are used, very large (50 + dB) response peaks along with very rapidly accumulating phase lags (which can reach -50 pi radians) are obtained. The wider the longitudinal segmentation, the broader the peaks and the less the phase accumulation; 71-microns segmentation produced the most realistic responses. These large response peaks are achieved by a small zone of negative resistance (ca. 1 mm) just basal to the response peak and the virtual 'zeroing' of the basilar membrane's effective impedance over the entire peak region (ca. 2.5 mm). To produce these peaks, the OHCs generate about 25-times the incoming acoustic power. Inclusion of low-pass filtering in the model's OHC representation produces, by contrast, very unrealistic notch-and-peak displacement complexes accompanied by very large phase lags, for all segmentation widths used. However, when phase reversals of OHC forces are also added, achieved by imbedding a resonant system within the tectorial membrane, very realistic peaks and phase functions are produced. More power must, however, be generated by the OHCs (about 70-times the incoming). The end result is output which mimics quite closely the living basilar membrane's responses to low-intensity high-frequency tones.

Acoustic Stimulation↗

Doppler myocardial imaging: a new method of data acquisition for three-dimensional echocardiography.

The precise morphologic characteristics of any intracardiac tumor have important implications regarding surgical planning and operative repair. Three-dimensional echocardiography has proved to be a valuable clinical technique in this field. Current methods of three-dimensional reconstruction of two-dimensional images are based on the standard gray-scale imaging technique. However, precordial gray-scale data-set information is frequently of suboptimal quality because of data degradation caused by ultrasound attenuation by chest wall structures. This has limited the use of the transthoracic three-dimensional technique to "echogenic" patients. Doppler myocardial imaging (DMI), a new ultrasound technique based on the Doppler principle, is influenced less by chest wall attenuation and in addition offers a better boundary detection algorithm for the cardiac structures. To determine if there may be a potential benefit of DMI to acquire data for three-dimensional reconstruction, a 33-year-old woman with a large intracardiac mass was studied. In this case three-dimensional gray-scale and DMI data sets were compared and contrasted with pathologic information. DMI allowed both the qualification of mass volume and the correct definition of the morphology of the mass. It was also possible to identify the precise site of attachment of the mass to the mitral valve leaflets. The information thus obtained was correlated with both operative and pathologic findings.

Adult↗