Modulation of embryonic glutathione peroxidase activity and phenytoin teratogenicity by dietary deprivation of selenium in CD-1 mice

Selenium (Se)-dependent and -independent glutathione (GSH) peroxidases detoxify H2O2 and lipid hydroperoxides, which may mediate the teratogenicity of phenytoin and related xenobiotics. To test this hypothesis, CD-1 mice were placed on Se-deficient diets for 15, 25 or 40 days and bred so that the day of analysis corresponded to gestational day 11. In Se-replete control animals, embryonic peroxidase activities were only 5% of activities in maternal liver (P < .05). After 15 days of Se deprivation, maternal activities for H2O2 (reflecting Se-dependent peroxidase) and cumene hydroperoxide (CmOOH) (reflecting both Se-dependent and -independent peroxidases) were reduced to 20% (P < .05) and 35% of controls, respectively. At this time, the incidence of fetal cleft palates initiated by phenytoin (55 mg/kg intraperitoneally on gestational days 11, 12 and 13) was doubled, from 12% to 25% (P < .05). Selenite rescue (Na2SeO3, 350 micrograms/kg intraperitoneally on day 9) restored maternal and embryonic peroxidase activities and completely inhibited phenytoin-initiated postpartum lethality and fetal resorptions in animals that had been Se depleted for 15 days. After 40 days of Se deprivation, maternal and embryonic peroxidase/H2O2 activities were reduced to < 1% and 27% of Se-replete controls, respectively. In contrast, maternal peroxidase/CmOOH activity was increased to 70% of controls, reflecting induction of Se-independent peroxidase, compared with that with 15 days' depletion. Phenytoin-initiated cleft palates with 40 days' depletion appeared to be reduced (16%) compared with Se-replete controls (24%) (P < .07). In 40-day Se-depleted animals given selenite rescue, the 10% incidence of cleft palates was significantly lower than that in the 40-day Se-replete group (24%) but not the Se-depleted group (16%). This is the first demonstration of reduced Se-dependent GSH peroxidase activities in embryonic tissues with dietary Se-deprivation. The results implicate reactive oxygen species and lipid hydroperoxides in the mechanism of phenytoin teratogenicity and suggest that GSH peroxidases are important embryoprotective enzymes.     

Fine physical mapping of Ph1, a chromosome pairing regulator gene in polyploid wheat

The diploid-like chromosome pairing in polyploid wheat is controlled by the Ph1 (pairing homoeologous) gene that is located on chromosome arm 5BL. By using a combination of cytogenetic and molecular techniques, we report the physical location of the Ph1 gene to a submicroscopic chromosome region (Ph1 gene region) that is flanked by the breakpoints of two deletions (5BL-1 and ph1c) and is marked by a DNA probe (XksuS1). The Ph1 gene region is present distal to the breakpoint of deletion 5BL-1 but proximal to the C-band 5BL2.1. Two other DNA probes (Xpsr128 and Xksu75) flank the region-Xpsr128 being proximal and Xksu75 being distal. The estimated size of the region is less than 3 Mb. The chromosome region around the Ph1 gene is high in recombination as the genetic distance of the region between 5BL-1 breakpoint and C-band 5BL2.1 (not resolved by the microscope) is at least 9.3 cM.     

Comparative severity of respiratory lesions of sialodacryoadenitis virus and Sendai virus infections in LEW and F344 rats

In several chronic diseases, lesions are more severe in LEW rats than in F344 rats. To determine whether or not acute viral diseases also are more severe in LEW rats than in F344 rats, we inoculated 6-7-week-old LEW and F344 rats with 10(7.2) cell culture infective units of sialodacryoadenitis virus or 10(4.7) infective units of Sendai virus. Twenty-four rats of each strain were given each virus. Lesions in nasal passages, tracheas, intrapulmonary airways, and pulmonary alveoli in 6 or 12 rats inoculated with each virus were assessed by scoring 5, 10, and 14 days after inoculation. Both viruses caused typical patchy necrotizing rhinitis, tracheitis, bronchitis, and bronchiolitis, with multifocal pneumonitis, in rats of both strains. Mean lesion indices for LEW rats given sialodacryoadenitis virus were significantly different from those for F344 rats for nasal passages on days 10 (0.999 vs. 0.680) and 14 (0.736 vs. 0.278), bronchi on day 5 (0.479 vs. 0.361), and alveoli on day 5 (0.677 vs. 0.275). Lesion indices for LEW rats given Sendai virus were significantly different from those for F344 rats for nasal passages on days 10 (1.000 vs. 0.611) and 14 (0.778 vs. 0.583); trachea on day 10 (0.625 vs. 0.028); bronchi on days 5 (0.476 vs. 0.331), 10 (0.123 vs. 0.013), and 14 (0.038 vs. 0); and alveoli on days 5 (0.413 vs. 0.114) and 10 (0.185 vs. 0.020). Thus, at the tested doses, both viruses caused more severe respiratory tract lesions in LEW rats than in F344 rats.     

Site and parameters of microstimulation: evidence for independent effects on the properties of saccades evoked from the primate superior colliculus

1. Microstimulation is used to investigate how activity in the superior colliculus (SC) contributes to determining the properties of primate saccadic eye movements. The site of collicular stimulation, the duration of the stimulation train, and the frequency of the stimulation train are each varied to examine the relative contributions of the locus, duration, and level of collicular activity to determining saccade amplitude, direction, duration, and velocity. 2. For any given site of stimulation, a relationship between movement amplitude and train duration can be demonstrated. Movement amplitude is a monotonically increasing, but saturating, function of increasing train duration. The size of the largest movement is dictated by the site of stimulation. Within the range over which amplitude can be modulated, movement offset is linked to the offset of the stimulation train. As a result, each decrement or increment in train duration produces a corresponding decrement or increment in movement duration. 3. The peak velocity of an evoked movement is influenced by the frequency of stimulation; a higher frequency of stimulation produces a movement of higher velocity. 4. The effects of train duration and frequency can be traded to produce movements that have comparable amplitudes but different dynamic characteristics; high-velocity movements of short duration and low-velocity movements of long duration can be produced by stimulating with high-frequency, short-duration, and low-frequency, long-duration trains, respectively. Across stimulation frequencies, the amplitude of an evoked movement is best related to the total number of pulses in the stimulation train. 5. Because it is possible to compensate for reduced velocity by increasing the duration of the stimulation train, the same site-specific maximum amplitude can be attained with different frequencies of stimulation. 6. Small, but significant, changes in movement direction occur as a result of varying train duration or train frequency. 7. The latency to movement onset (i.e., interval from stimulation onset to movement onset) depends upon the frequency of stimulation. A higher frequency of stimulation produces a movement of shorter latency. 8. These data demonstrate that both the site of stimulation and the parameters of stimulation contribute to determining the properties of a movement evoked from the primate SC. In doing so, they contradict the results of early microstimulation studies that suggest that the properties of eye movements evoked from the primate SC are determined solely by the site of stimulation. The findings conflict with the traditional view of collicular function that suggests that the collicular motor representation is purely anatomic. Rather, these data support a revised view whereby the locus, duration, and level of collicular activity contribute to determining the properties of a primate saccadic eye movement. According to this view, independent information relating to desired displacement and saccade velocity are extracted from the spatiotemporal profile of collicular activity.