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151.
MP Duyao AB Auerbach A Ryan F Persichetti GT Barnes SM McNeil P Ge JP Vonsattel JF Gusella AL Joyner 《Canadian Metallurgical Quarterly》1995,269(5222):407-410
Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function. 相似文献
152.
EJ Pappert CG Goetz F Niederman ZD Ling GT Stebbins PM Carvey 《Canadian Metallurgical Quarterly》1996,47(6):1493-1495
We performed the first double-blind, crossover comparison between levodopa/carbidopa (LD/CD) in optimized liquid versus tablet doses to measure plasma LD levels and relative effects on disabilities (motor function, fluctuations, and dyskinesias) in patients with Parkinson's disease. Twenty-three subjects with motor fluctuations were optimized with open-label LD/CD tablets and liquid. In a double-dummy design, patients randomly received 2 weeks of liquid and 2 weeks of tablet LD/CD. Twice during each arm, we evaluated patients hourly 9 AM to 4 PM with the use of plasma LD levels, the Unified Parkinson's Disease Rating Scale, a dyskinesia rating scale, and "on-off" ratings. Patients receiving liquid LD/CD ingested significantly higher doses and had significantly improved motor function and total "on" time, without an increase in dyskinesia severity. The number of motor fluctuations in the two phases was not significantly different. LD levels and variability were also equivalent with the two formulations. At optimized dosing, liquid LD/CD offers a means to significantly improve motor disability in patients with Parkinson's disease without exacerbating dyskinesia. 相似文献
153.
The effects of glutamate (Glu) and ATP on interleukin-6 (IL-6) production from cultured neonatal rat astrocyte were studied. Glu (100-200 mumol.L-1) strongly increased, IL-6 production at 16 h in a dose-dependent manner and ATP (50-100 mumol.L-1) induced a inhibition effect. The results suggest that Glu stimulted IL-6 release may be one of mechanisms of astrocyte "neuroprotective" function in ischmia/reperfusion. 相似文献
154.
A comparison of the areas under the plasma concentration-time curves after intravenous and oral administration of meperidine in 4 normal subjects indicated that 48% to 56% of the oral dose avoided "first-pass" metabolism and was systemically available. Similar estimates were obtained by applying the Loo-Riegelman method for calculating drug absorption viz, 47% to 60%. Oral availability predicted from a knowledge of drug clearance (blood) after intravenouration-time curves after oral administration exhibited irregularities and double peaks possibly indicative of the action of meperidine on the gut or a recycling process. 相似文献
155.
This study quantitatively characterizes the development of the major morphological features of the organ of Corti during the first 2 weeks postnatal, the period when the cat auditory system makes the transition from being essentially non-functional to having nearly adult-like responses. Four groups of kittens (n = 3) were studied at one day postnatal (P1), P5, P10, P15, and compared to adults. Measurements were made of the organ of Corti at 3 cochlear locations: 20%, 60% and 85% of basilar membrane length from the base cochlear locations which in the adult correspond to best frequencies of approximately 20 kHz, 2 kHz and 500 Hz, respectively. In addition, measurements of basilar membrane length and opening of the tunnel of Corti were made in 20 cochlear specimens from kittens aged P0-P6. Results indicate that: (i) at P0 the basilar membrane has attained adult length, and the tunnel of Corti is open over approximately the basal one-half of the cochlea; (ii) the initial opening of the tunnel of Corti occurs at a site about 4 mm from the cochlear base (best frequency of approximately 25 kHz in the adult cochlea); (iii) the thickness of the tympanic cell layer decreases markedly at the basal 20-kHz location; (iv) the areas of the tunnel of Corti and space of Nuel and the angulation of the inner hair cells (IHC) relative to the basilar membrane all show marked postnatal increases at both the middle and apical locations; (v) IHC are nearly adult-like in length and shape at birth, whereas the OHC (at 2-kHz and 500-Hz locations) undergo marked postnatal changes; (vi) disappearance of the marginal pillars and maturation of the supporting cells are not yet complete by P15. 相似文献
156.
JB Seward AJ Tajik DJ Hagler ER Giuliani GT Gau DG Ritter 《Canadian Metallurgical Quarterly》1977,39(2):217-225
Common ventricle is a rare congenital anomaly in which the ventricular chamber receives blood from two separate atrioventricular (A-V) valves or a common A-V valve. Diagnosis of common ventricle was established in 55 patients aged 3 months to 33 years (mean 10 years) at cardiac catheterization in all 55 and at operation or autopsy in 24. In common ventricle with two angiographically demonstrable A-V valves (47 patients), the echocardiographic features included: (1) simultaneous recording (in the same sonic beam with the transducer held stationary) of the echoes of an anterior and a posterior A-V valve without an intervening septal echo (45 of 47 patients); (2) absence, on a base to apex scan, of the ventricular septal echo in the usual position separating the A-V valves (47 of 47 patients); (3) recording, in patients with common ventricle and outflow chamber, of this small outflow chamber anterior to the A-V valves (20 of 23 patients); and (4) recording of echographic continuity of the posterior A-V valve and great artery (27 of 31 patients). In common ventricle with a common A-V valve (8 patients), the echocardiographic features included: (1) a single demonstrable A-V valve, located posteriorly in the ventricle, which showed a large amplitude of excursion during diastole; and (2) absence of a second A-V valve echo or ventricular septal echo. Eight patients were studied postoperatively after surgical correction by ventricular septation. Echographic features included visualization of a prosthetic septum that produced a dense echo and divided the common ventricle into "right" and "left" ventricular chambers. This septum had a large excursion anteriorly during systole. Because common ventricle is now amenable to surgical correction, echocardiography should play an important role in assessment of ventricular anatomy in this complex congenital cardiac defect. 相似文献
157.
158.
MS Hasson A Muscate GT Henehan PF Guidinger GA Petsko D Ringe GL Kenyon 《Canadian Metallurgical Quarterly》1995,4(5):955-959
A new large-scale purification method for benzoylformate decarboxylase from Pseudomonas putida has allowed us to undertake an X-ray crystallographic study of the enzyme. The previously observed instability of the enzyme was overcome by addition of 100 microM thiamine pyrophosphate to buffers used in the purification. The final enzyme preparation was more than 97% pure, as determined by denaturing gel electrophoresis and densitometry. The mobility of the enzyme on a gel filtration column indicates that it is a tetramer of 57-kDa subunits. Large, single crystals of benzoylformate decarboxylase were grown from solutions of buffered polyethylene glycol 400, pH 8.5. The crystals diffract to beyond 1.6 A resolution and are stable for days to X-ray radiation. Analysis of X-ray data from the crystals, along with the newly determined quaternary structure, identifies the space group as I222. The unit cell dimensions are a = 82 A, b = 97 A, c = 138 A. An average Vm value for the crystals is consistent with one subunit per asymmetric unit. The subunits of the tetramer must be arranged with tetrahedral 222 symmetry. 相似文献
159.
YP Talmi GT Wolf R Esclamado WR Carroll AM Sassler 《Canadian Metallurgical Quarterly》1993,103(9):1048-1051
Thyroid function may be reduced after treatment of cancer of the head and neck, and hypothyroidism is much more common after combination therapy. Whether hypoparathyroidism and subsequent hypocalcemia also occur after such treatment is unknown. Few related studies have been published in which changes in total serum calcium have been studied after cancer treatment with radioactive iodine or external radiation. Twenty-two disease-free head and neck cancer patients were studied, 1 to 3 years after multimodal treatment, to determine if changes in serum ionized calcium levels or thyroid function were present. Our results suggest that parathyroid function, as represented by ionized calcium levels remains normal after multimodality (surgery, radiation and/or chemotherapy) combined treatment. 相似文献
160.