Vanadate stimulates differentiation and neurite outgrowth in rat pheochromocytoma PC12 cells and neurite extension in human neuroblastoma SH-SY5Y cells.

We show here that a protein tyrosine phosphatase inhibitor, sodium orthovanadate, induces rat pheochromocytoma cells to express neurites, a prominent morphological marker of neuronal phenotype. Vanadate-induced differentiation and neurite outgrowth in pheochromocytoma cells was not as extensive as that induced by the positive control employed, nerve growth factor. However, neurite outgrowth responses were comparable between nerve growth factor-treated pheochromocytoma cells and cells primed and then restimulated with vanadate. In the human neuroblastoma cell line, SH-SY5Y, a single exposure to vanadate induced neurite extension in this cell line equal to that initiated by nerve growth factor. In both cell lines vanadate treatment resulted in tyrosine phosphorylation of several high-molecular-weight proteins and using anti-phosphotyrosine antibodies, intense fluorescence was observed in the cell body and neurites of pheochromocytoma cells exposed to vanadate. Vanadate mediated differentiation and neurite outgrowth in pheochromocytoma cells could be ablated by the tyrosine kinase inhibitor erbastatin, whereas nerve growth factor-induced neurite outgrowth was only partially inhibited. In SH-SY5Y cells, erbstatin mediated partial inhibition of both vanadate and nerve growth factor-induced neurite elongation with similar kinetics. In contrast, K252b, a trk tyrosine kinase inhibitor, exhibited only a 30% reduction of neurite outgrowth in vanadate treated pheochromocytoma cells but an 80% reduction in nerve growth factor-treated cells. In SH-SY5Y cells, K252a did not have a statistically significant effect on neurite elongation induced by vanadate in contrast to a 60% reduction in nerve growth factor-treated cells. The membrane impermeable analogue K252b, had no effect on neurite elongation induced with either vanadate or nerve growth factor in these cells. The effects of vanadate were not mimicked by ouabain (0.1-50 microM) indicating that vanadate does not induce differentiation and/or neurite extension by inhibiting ion channel Na,K-ATPase, which is one of its other well-characterised inhibitory activities. Evidence for the selective action of vanadate on some but not all neuronal cell lines comes from the fact that it did not induce neurite extension in the human neuroblastoma cell line SK-N-MC. These data imply that vanadate-induced neurite outgrowth responses in pheochromocytoma and SH-SY5Y cells can be induced by the inhibition of tyrosine phosphatases and appears not to simply mimic nerve growth factor signals. The target(s) of vanadate action in the two cell lines are currently being sought.

Electromagnetic implantable middle ear hearing device of the ossicular-stimulating type: principles, designs, and experiments.

This report analyzes the principles, describes designs, and discusses the advantages and disadvantages of different types of implantable middle ear hearing devices. Preliminary acute experiments using an electromagnetic transducer for an implantable hearing device of the ossicular-stimulating type were performed in cats. A miniature samarium cobalt rare earth magnet was cemented on the head of the stapes. An electromagnetic coil powered either by direct wiring or by telemetry was used to stimulate the stapes. The performance of the system was evaluated by electrophysiologic assessment of hearing (brain stem evoked response potentials). The findings showed that the device is functional with good "implant gain" (35 dB average) and consumes reasonably low current (0.6 mA) with telemetry. Further investigation is necessary in order to develop an implantable middle ear hearing device with successful clinical application.

Water vapour and temperature dynamics in the upper airways of normal and CF subjects.

Water vapour partial pressure (PH2O) and temperature (T) were measured together, continuously, at the airway opening (either lips or nares) and at the oropharynx of human subjects with normal lungs or with cystic fibrosis (CF). No apparent differences in PH2O or T were found between normal and CF groups breathing ambient air (22 +/- 2 degrees C). During inspiration the relative humidity at the pharynx for nose breathing (95%) was higher than for mouth breathing (75%). For hot air breathing (48 +/- 2 degrees C), the PH2O and relative humidity of inspired gas at the pharynx was lower for the CF group than for the normal group. Also, the CF group had a higher airway surface temperature at the airway openings on inspiration. These data suggest that when the rate of evaporation is sufficiently high, the rate-limiting step may be water transport through the mucosal tissue and/or secretions. At least for the upper airways, this rate limitation is more evident for CF patients than for normal subjects.

Etiology of ventriculomegaly in choroid plexus papilloma.

In order to test the hypothesis that overproduction of cerebrospinal fluid can cause the hydrocephalus seen in choroid plexus papillomas, adult mongrel dogs with and without hydrocephalus were subjected to high pressure intraventricular infusions of artificial cerebrospinal fluid (CSF). Pre- and postinfusion volumes were calculated, using a new method for on-line measurement of ventricular volume involving linear measurements from Conray ventriculograms. Ventricular volumes increased an average of 8% in 36 h. The dogs previously made hydrocephalic by the intracisternal injection of kaolin had a significant volume increase (34% in 36 h). Overproduction of CSF alone can produce hydrocephalus, but the presence of hydrocephalus in choroid plexus papillomas is more likely to be a result of the complex interaction of CSF overproduction and partial restriction of CSF flow.

Conditioning of inspired air by a hygroscopic condenser humidifier.

The heat and water content of inspired air is critical to the pulmonary viability of patients with artificial airways. By continuously measuring gas conditions in the ventilator circuits of 6 adult ICU patients, we studied the heat and water reclaimed from expired air by a hygroscopic condenser humidifier (HCH) in the circuit. Temperature, partial pressure of water vapor (PH2O) and relative humidity (RH) were determined at the tracheal outlet of the endotracheal tube. The HCH was 63% efficient; the end-inspiratory gas delivered to the patients averaged 30.9 degrees C with a PH2O of 32.5 mm Hg and an RH of 97.3% or, equivalently, an RH of 69.2% referenced to 37 degrees C. These values are lower than those reported in the literature for gas in the trachea during nose breathing of ambient air, but greater than the values reported for mouth breathing of ambient air.

Measurement system for respiratory water vapor and temperature dynamics.

An instrumentation system has been developed to simultaneously measure water vapor and temperature at the same point within respiratory airways during breathing. A mass spectrometer was used to analyze gas continuously sampled through a modified inlet catheter. At the tip of the catheter, gas temperature is sensed by a microbead thermistor. Adequate water vapor dynamics is achieved by a two-step procedure. First, the tip of the sampling catheter is constricted to reduce the catheter's internal pressure and thereby prevent condensation and evaporation. Second, the water vapor signal from the mass spectrometer is compensated electronically to improve its transient response. As part of the evaluation of the system, water vapor and gas temperature were measured in the oropharynx of human subjects.

Dynamic water vapor and temperature calibration system.

The objective evaluation of thermal and humidification processes in the pulmonary system requires accurate dynamic measurements of temperature and water vapor concentration of a flowing gas mixture. The adequacy of instruments used for such measurements can only be determined by dynamic calibration techniques. We have developed a method of producing step changes in temperature and water vapor content of a gas mixture undergoing controlled steady flow. The system consists of two reservoirs and a slide valve that switches a test section between them. The inlet (usually a probe or catheter tip) of the device to be calibrated is positioned in the test section. The flow rate through the test section is minimally changed during the transition between gas from one reservoir to that of the other. The system has been used to analyze the response of a thermistor and a respiratory mass spectrometer to changes in gas temperature and water vapor.

Prevalence of eggs of Baylisascaris procyonis (Nematoda:Ascaroidea) in raccoon scats from an urban and a rural community.

Twenty-six of 97 (27%) scats from raccoons (Procyon lotor) in an urban area and 37 of 121 (31%) scats from raccoons collected in a rural area of Indiana during October and November of 1980 contained eggs of Baylisascaris procyonis, an ascarid of animal health significance. Raccoons that were livetrapped from the same areas had similar prevalences of B. procyonis eggs in their feces. Therefore, monitoring the prevalence of B. procyonis in raccoon populations by analyzing scats appeared to be feasible.

Influence of the spatial periodicity of moving gratings on motion response.

The present experiments examine the suprathreshold response of the motion or direction-selective portion of the human visual system by means of the motion aftereffect (MAE). The MAE was measured as a function of the contrast and spatial frequency of moving sinusoidal gratings. For spatial frequencies less than 1 cy/deg, the MAE speed was found to increase linearly with log contrast up to 80%. For spatial frequencies greater than 1 cy/deg, the rate of increase of the MAE speed with log contrast was not found to be linear over the entire range of contrast. The nonlinearity was greatest for the 8 and 10 cy/deg gratings, which showed very little increase in MAE speed with contrast above 25%. We conclude that the direction-specific mechanisms in human vision show a more limited contrast response to the high spatial frequencies than does the visual system as a whole.