PKR protection against intranasal vesicular stomatitis virus infection is mouse strain dependent.

The interferon-induced antiviral state is mediated by interferon-stimulated genes that are upregulated in concert after stimulation by type I interferons. Because so many viruses encode strategies to inactivate the interferon-inducible double-stranded RNA (dsRNA)-dependent protein kinase PKR, this protein is likely to be a major player in antiviral defense. Here we demonstrate the increased susceptibility of PKR-/- animals to vesicular stomatitis virus (VSV) by the intranasal route, but also demonstrate that the protective effects of PKR are mouse strain dependent. We have found the difference between wild-type-BALB/c and 129SvEv animals to be on the order of 5 logs, with high levels of virus present in the lungs of BALB/c but not 129SvEv animals. To evaluate the sensitivity of PKR-/- mice to VSV clearly, the PKR mutation was bred onto the resistant 129SvEv background. The increased sensitivity of PKR-/- mice, compared to PKR+/+ strain-matched controls, is on the order of 10-fold as measured by median lethal dose (LD50). PKR-/- 129 mice support VSV replication in the lung unlike controls. While this result clearly demonstrates an important role for PKR in protection against VSV infection of the lung, it also underlines the importance of other host factors in containing a viral infection.

Imagined body orientation and perception of the visual vertical.

The existence of body orientation mental imagery was tested by examining whether self roll tilt imagery affects the subjective visual vertical (SVV). Twenty healthy subjects judged the orientation of a dim luminous bar with respect to gravitational vertical, while normally seated in complete darkness with their head firmly restrained earth vertically. SVV was measured in three conditions: a reference condition with no imagery, and a left and a right imagery condition, during which the bar orientation was to be judged while the subjects imagine themselves roll-tilted towards left or right, respectively. The imagined roll tilts were of the same magnitude as roll tilts which generally induce an E-effect, i.e., an SVV lean toward the side opposite to those of body tilt. If imagery and perception of self roll tilt share common processes, self roll tilt imagery should induce an E-like effect. Results show an imagery-induced E-like effect, which strongly supports the idea that humans can perform mental imagery of body orientation about gravity.

Evidence of imagined passive self-motion through imagery-perception interaction.

The existence of whole-body passive self-motion mental imagery was investigated by examining whether the perception of passive body accelerations can be affected by passive self-motion imagery. Twenty healthy subjects recognised target passive body acceleration. This recognition task was performed under three conditions: (1) a baseline condition without imagery; (2) a compatible imagery condition during which subjects imagined themselves passively moving in the same direction as the target acceleration; (3) a non-compatible imagery condition during which subjects imagined themselves passively moving in the direction opposite to that of the target acceleration. The recognition of the target acceleration was improved under compatible and degraded under non-compatible imagery. This interaction implies that perception and imaginary share common representations, and supports the existence of passive self-motion imagery.

Vestibular sensitivity and vection chronometry along the spinal axis in erect man.

A study is reported of the relations between vestibular sensitivity and vection chronometry in healthy human adults. Twenty-three subjects were examined. For both vestibular and vection investigations, the subjects were seated in an armchair with the spinal axis aligned with the earth vertical and the head normally erect. The subjects' vestibular thresholds for detection of vertical upward accelerations were assessed by a double-staircase psychophysical method. The subjects' vection onset latencies were measured for both upward and downward directions. Since the vection onset latencies are presumed to be shortened by the decrease of the conflict between visual and vestibular afferents, the less-vestibular-sensitive subjects were hypothesised to have shorter vection onset latencies than the more-vestibular-sensitive ones. As expected, the results indicate a negative correlation between vestibular thresholds and vection onset latencies: the higher the vestibular thresholds, the lower the vection onset latencies.

Tracer technique to measure in vivo chemical transport rates within an implantable cell transplantation device.

An in vivo tracer technique that uses radiolabeled insulin as the tracer molecule has been developed to assess the rate of chemical transport between the cell transplantation chamber of an implantable bioartificial device and the host's circulatory system. The device considered here employs site-directed neovascularization of a porous matrix to induce capillary growth adjacent to an immunoisolated cell implantation chamber. This device design is being investigated as a vehicle for therapeutic cell transplantation, with the advantages that it allows the cells to perform their therapeutic function without the danger of immune rejection and it avoids damaging contact of blood flow with artificial surfaces. A pharmacokinetic model of the mass transport between the implantation chamber, the vascularized matrix, and the body has been devised to allow proper analysis and understanding of the experimental tracer results. Experiments performed in this study have been principally directed at evaluation of the tracer model parameters, but results also provide a quantitative measure of the progression of capillary growth into a porous matrix. Measured plasma tracer levels demonstrate that chemical transport rates within the implanted device increase with the progression of matrix vascular ingrowth. Agreement between the fitted model curves and the corresponding measured concentrations at different levels of capillary ingrowth demonstrate that the model provides a realistic representation of the actual capillary-mediated transport phenomena occurring within the device.

Somatostatin analog: effects on hypergastrinemia and hypercalcitoninemia.

A somatostatin analog (SMS 201-995) was used to treat symptomatic patients with a residual tumor burden of gastrinoma or medullary thyroid carcinoma and pathologic elevations of circulating marker peptides associated with these neuroendocrine tumors. Possible inhibitory effects of the analog on marker peptides, patients' symptoms, or tumor progression were studied in a dose-response protocol and during several months of self-injection of SMS 201-995. Both patients reported remarkable relief of secretory diarrhea and other symptoms, and serum gastrin was successfully suppressed by increasing doses of the analog. However, no effect was seen in reduction of hypercalcitoninemia. Morphologic imaging of residual tumor showed no progression of medullary thyroid carcinoma during treatment and, in the case of hepatic gastrinoma metastases, remarkable tumor regression was confirmed. No toxicity or glucose intolerance was experienced. Somatostatin analog shows promise for palliative management of endocrinologic symptoms due to neuroendocrine tumors, and an inhibitory effect can be measured in some but not all peptide markers. Further evidence of its negative trophic effect on tumor blood flow may suggest an antineoplastic potential, as well as palliative use of this new treatment.

The Computerized Notation System (CNS). A microcomputer system for rapid entry of notes by physicians and nurses.

A computerized notation system has been developed to produce a digital medical data base. Use of a separate physical record for every 1-4 patients allows several years of accumulated data to be easily accessible for patient "summaries" or admission "histories and physicals." To facilitate entry of data in the system, the physician is provided with a portable, complete computer system (HP-85, or Epson HX-20), a user-defined two-letter dictionary, and a program that produces all elements of the manual paper charting system. "Overview" and research data bases are developed from the digital medical data base records. In this paper, we report the efficiency of use of this computerized notation system in private outpatient and inpatient practice.

The computerized notation system: a portable, self-contained system for entry of physicians' and nurses' notes.

The Computerized Notation System (CNS) is a portable microprocessor system designed for use in outpatient clinics, hospital wards, and intensive care units. It can produce essentially all written communications required of both physicians and nurses, with printout at the bedside or in the clinic examining room. It is designed to ameliorate several problems which have limited direct computer entry by physicians and nurses (keyboard and processor access, marginal typing skills, lack of immediate printout, and logical restriction of menu choices). The system encourages and simplifies use of the problem-oriented approach to the patient, by producing organized, legible daily notes and patient summaries. Printouts of the system are compatible with the present hospital and clinic "paper charts." Clinical trials have confirmed the applicability, variability, and acceptability of the CNS in both hospital and outpatient practice.

Depolarization of the Electrogenic Transmembrane Electropotential of Zea mays L. by Bipolaris (Helminthosporium) maydis Race T Toxin, Azide, Cyanide, Dodecyl Succinic Acid, or Cold Temperature.

The transmembrane electrical potential of root cells of Zea mays L. cv. W64A in a modified 1x Higinbotham solution was partially depolarized by semipurified toxin obtained from Bipolaris (Helminthosporium) maydis race T. At a given toxin concentration depolarization of Texas cytoplasm cells was much greater than for normal cytoplasm cells. This observation correlated directly to the differential host susceptibility to the fungus. The time course and magnitude of depolarization were dependent on toxin concentration; at high concentration the electropotential difference change was rapid. Cortex cells depolarized more slowly than epidermal cells indicating that the toxin slowly permeated intercellular regions. Toxin concentrations which affected electropotential difference were of the same magnitude as those required to inhibit root growth, ion uptake, and mitochondrial processes.Azide, cyanide, and cold temperature (5 C) gave the same partial depolarization as did the toxin. Dodecyl succinic acid caused complete depolarization. These and other data indicate that one of the primary actions of the toxin is to inhibit electrogenic ion pumps in the plasmalemma.

Selective Inhibition of K, Na, Cl, and PO(4) Uptake in Zea mays L. by Bipolaris (Helminthosporium) maydis Race T Pathotoxin: Evidence for a Plasmalemma Target Site?

Pathotoxin preparations were obtained from either axenic culture filtrate of race T of Bipolaris maydis (Nisikado) Shoemaker (new culture media and toxin purification procedures are described) or extracts of maize leaves infected with the fungus. The toxins (10(-6) to 10(-8)m) caused inhibition of [(86)Rb]K(+) uptake in leaf discs and apical root segments of Zea mays L. cv W64A Texas (Tcms) and normal (N) cytoplasms. Significant inhibition was measurable as early as 5 min after adding toxin. In Tcms per cent inhibition was increased by increasing toxin concentration and time in toxin, by using solution at pH 5 rather than pH 7, by decreasing external KCl concentration over the range 50 to 0.1 mm (in the presence of 0.5 mm CaSO(4)), or by exposing leaf discs to light rather than dark during the uptake period in toxin. Root uptake of (22)Na(+) and (36)Cl(-) was inhibited to a lesser extent than K(+). Inhibition of (32)PO(4) (3-) uptake occurred after 40 min when cyclosis had ceased.When combined with data in the literature, our data indicate that the plasmalemma is the probable primary site of toxin action in N and Tcms maize. Comparison of the effects of toxin on K(+) uptake in N and Tcms maize suggests the existence of more than one mode of toxin action: a weak disruptive effect in N and Tcms, and in addition, specific membrane sites in Tcms involved in monovalent ion uptake.Six genotypes in N or Tcms cytoplasm which exhibited different degrees of disease susceptibility in the field showed a corresponding gradation of susceptibility to the toxin when a K(+) uptake bioassay was used. This correlation is strong evidence that the sites of toxin action affecting K(+) transport have characteristics closely related to cellular factors regulating susceptibility to fungal attack.

Transmembrane electropotential in barley roots as related to cell type, cell location, and cutting and aging effects.

Transmembrane electropotential difference (PD) was measured in whole roots of barley (Hordeum vulgare L. cvs. Compana and Himalaya). Seedlings were grown 4 to 5 days in aerated 0.5 mm CaSO(4) or a nutrient solution. Measurements of PD were made with roots bathed in CaSO(4), KCl + CaSO(4), or the nutrient solution. The following results were found. (a) There was a radial PD gradient with epidermal cells being 10 to 58 millivolts less negative than cells in the third layer of the cortex (outside to inside). There was no longitudinal PD gradient in the region 0.5 to 4 cm from the root tip, nor was there any difference between the PD of young root hairs and other epidermal cells. (b) Cell PD in excised whole roots was not detectably different from that found in roots attached to the shoot, and was unchanged for 2 hours from excision. (c) In 1-centimeter sections of root, cell PD at the freshly cut surface was depolarized by 90 millivolts from that in the intact root; cells farther than 1 millimeter from the cut surface were not depolarized. The PD of cells at the cut surface became more negative upon aging the segment in 0.5 mm CaSO(4), eventually becoming greater by -25 millivolts than that in cells of intact roots. Cells in segments to which the root tips were attached had less negative PDs after aging than those in subapical segments, indicating a possible hormonal effect. PDs in aged, excised segments are not equivalent to those in intact roots. (d) Creeping of cytoplasm over electrode tips inserted into the vacuole gave measurements of vacuole-to-cytoplasm PD of + 9 millivolts in 0.5 mm CaSO(4) and + 35 millivolts in 1 mm KCl + 0.5 mm CaSO(4). Most of the cell PD was across the plasmalemma. (e) The reducing sugar content of roots in CaSO(4) solution was greater than that of roots in the nutrient solution in which ion uptake, particularly K(+) occurred.

Inhibition of ion accumulation in maize roots by abscisic acid.

An inhibition of root growth, a decrease in the amount of potassium (as (86)Rb) and phosphate ((32)P) accumulation by the root, and a partial depolarization of transmembrane electropotential were observed to develop with a similar time course and to a similar extent when intact maize (Zea mays L.) roots were treated with 10(-5) M abscisic acid (ABA). Potassium uptake was inhibited by ABA when excised, low-salt roots were bathed in KCl, KH2PO4, or K2SO4. ABA did not affect the ATP content of the tissues, the activity of isolated mitochondria, nor the activity of microsomal K(+)-stimulated ATPases.