Chemical determinants of the rat electro-olfactogram.

The chemical properties that determine the distribution of the electro-olfactogram were studied after exposure of a large area of the rat olfactory epithelium. Multiple electrodes were placed along the rostral border of endoturbinate IV on the midline of the nasal cavity. This array of electrodes spanned a region containing the four receptor gene expression zones described for the rat. The response to a series of odorants containing only carbon, hydrogen, and oxygen was strongly related to electrode position. For most hydrocarbons, the responses were progressively larger toward the ventral epithelium. The only exceptions were aromatic hydrocarbons, which evoked nearly equal response sizes across the epithelium. Ketones and aldehydes evoked relatively larger dorsal responses than did hydrocarbons with similar structures. Aromatic ketones and aldehydes evoked systematically larger responses from the dorsal part of the epithelium. The response profiles for most odorants were well described by a linear fit to the electrode position along the dorsal-ventral position on the epithelium. However, a few bicyclic odorants and carboxylic acids evoked significantly nonlinear profiles. It is concluded that there is a systematic distribution of odorant sensitivity across this part of the epithelium and that this sensitivity is related to general chemical properties. Other evidence suggests that these properties extend to other parts of the epithelium. This spatial sensitivity of the epithelium to odorants probably contributes to olfactory coding in parallel with the convergence of axons from olfactory sensory neurons expressing the same receptor type.

Vitamin D receptor as a candidate tumor-suppressor gene in severe hyperparathyroidism of uremia.

Most chronic renal failure patients with severe refractory hyperparathyroidism harbor at least one monoclonal parathyroid tumor, but the specific acquired genetic defects that confer this clonal selective advantage remain poorly understood. Somatic inactivation of the vitamin D receptor (VDR) gene could contribute to clonal outgrowth, because a parathyroid cell containing this lesion would have an impaired response to the antiproliferative influence of 1,25-dihydroxyvitamin D3. Furthermore, diminished expression of VDR protein has been described in uremia-associated parathyroid tumors. Therefore, to assess VDR gene inactivation's potential pathogenetic role in this disease, we rigorously analyzed the VDR gene in 59 parathyroid tumors surgically resected from uremic patients. First, Southern blotting and/or PCR analyses of 29 tumor samples from 14 genetically informative patients revealed no allelic losses at the VDR locus. Next, direct DNA sequencing of all VDR splice junctions, associated intronic sequences, and virtually the entire VDR-coding region for all 59 tumors revealed no acquired mutations. Last, 37 tumor DNA samples were subjected to comparative genomic hybridization, and no chromosomal losses in the VDR region (12cen-q12) were observed. These observations suggest that inactivating defects within the VDR gene do not commonly contribute to the primary pathogenesis of severe refractory hyperparathyroidism in uremia.

A functional map in rat olfactory epithelium.

Multiple (four or eight) electrode arrays were placed for simultaneous electro-olfactogram (EOG) recordings of responses to a series of odors applied directly to the olfactory epithelium. Three different surfaces of the epithelium were exposed in rats immediately after death by anesthetic overdose. We tested three terpene compounds (carvone, limonene and 1,8-cineole) across the epithelium along the medial surface of the endoturbinate bones. Carvone, a ketone, evoked larger responses dorsally on the epithelium. The largest responses to 1,8-cineole (an ether) were seen in an intermediate-ventral region. The responses to limonene (a hydrocarbon) did not vary greatly across the regions, although they were often larger ventrally. The response distributions deviated from this simple pattern on the caudal part of endoturbinate IV, where the carvone responses were small and the limonene responses were larger. These differences were evident across a substantial concentration range. Similar distributions were seen for these three odors in tests along the dorsal-to-ventral direction across the nasal septum and in the medial-to-lateral direction across the dorsal aspect of one of the endoturbinate bones reaching out into the lateral recess. We argue that the spatial distributions of responses are correlated with the olfactory receptor gene expression zones.

A hip wear simulator for the evaluation of biomaterials in hip arthroplasty components.

A multistation (8-station) hip simulator has been designed and tested that provides a practical imitation of the motions and loads seen by the hip joint during a typical walking cycle. A biaxial rocking motion of +/- 23 degrees is synchronized with the respective resultant forces of the extension-flexion (heel-strike to toe-off) movements of the leg. This particular simulator provides a practical engineering in vitro implementation of the walking cycle. It also provides a realistic and practical compromise between general wear screening devices (such as pin-on-disk systems) and the intensive research accomplished through full scale simulation (full 6 degree-of-freedom systems) and modeling. Evaluation of system performance shows that control of rpm (revolutions-per-minute) for the desired axial rotation of 1 Hz was kept to 60 cpm +/- 1 cpm for axial loads (per actuator) as high as 4500 Newtons. Although loading error was 2% in the peak load areas of interest (3000 Newton), station-to-station load control variability was less than .6%. Baseline wear studies with this simulator using ultra-high-molecular-weight polyethylene and Cobalt-Chromium (UHMWPE/CoCr) hip systems indicate an average specimen-to-specimen wear variability of less than 7% range after 5 million test cycles. Testing was performed in a calf serum environment at an equilibrium temperature of 33 degrees C.