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Biomedical subjects

S A Rice

Publications and source records attributed to S A Rice.

At least 73 records · Page 4Linked to original sources
PubMed1987

The behavioral effects of perinatal methimazole administration in Swiss Webster mice.

Methimazole was tested for use as a positive control agent in behavioral studies of mice. Continuous administration of the antithyroid agent via drinking water (0.1 mg/ml) from Day 16 of pregnancy through Day 10 postpartum produced developmental delays in mice offspring. Ten methimazole and 12 untreated litters were studied. Developmental milestones were unaltered; i.e., time of pinna detachment, incisor eruption, eye opening, vaginal patency, and testicular descent were not different between groups. Mean body weights of methimazole offspring were consistently reduced, but significant differences were isolated to a few days in the preweaning period and a few weeks during the postweaning period. There was no enduring effect. All preweaning tests showed some significant treatment-related changes; methimazole pups were developmentally delayed. Surface righting time was increased while time pivoting and the number of quadrants traveled were decreased in methimazole pups. Negative geotaxis showed significant treatment-related increases in the time to orient 180 degrees uphill, the percentage of pups orienting 180 degrees uphill, and the percentage of pups orienting less than 180 degrees. Ontogeny of swimming ability also showed significant delays. The only postweaning test evaluated, time on a rotating rod, showed no treatment-related effects. Brain weights Postnatal Day (PND) 120 were not different between groups. In this study, methimazole produced developmental delays in mice that were detectable by behavioral tests. Thus, methimazole has potential as a positive control agent for mice, not only to validate preweaning test sensitivity, but also to validate a laboratory's ability to perform preweaning behavioral studies.

Aging↗
PubMed1987

Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4.

The nuclear localization of the herpes simplex virus transcriptional activator protein ICP4 was studied by indirect immunofluorescence. At early times after viral infection, ICP4 quickly localized to a diffuse intranuclear distribution. ICP4 later concentrated in globular compartments within the nucleus. The redistribution to the compartments was dependent on viral DNA replication. Double staining for ICP4 and ICP8, the early major DNA-binding protein, revealed that both were found in the same intranuclear globular compartments at late times. These were previously named "replication compartments" (M. P. Quinlan, L. B. Chen, and D. M. Knipe, Cell 36:857-868, 1984). Because ICP4 and ICP8 are known to function in transcriptional activation and DNA replication, respectively, both DNA replication and late transcription may occur in these compartments. The association of ICP4 and ICP8 with the replication compartments appeared to be independent in that the retention of ICP8 in the compartments required ongoing viral DNA synthesis, while the association of ICP4 was independent of viral DNA synthesis once the compartments were formed. Because ICP4 shows a different distribution at early and late times, stimulation of transcription by ICP4 may involve different molecular events or contacts during these two periods of the replicative cycle.

Animals↗
PubMed1986

Reproductive and teratogenic effects of nitrous oxide, halothane, isoflurane, and enflurane in Sprague-Dawley rats.

A total of 305 timed-pregnant Sprague-Dawley rats were exposed for 6 h a day on each of three consecutive days in one of three periods, i.e., pregnancy days 14-16, 11-13, or 8-10, either to 0.55 times the minimum alveolar concentration (MAC) of nitrous oxide (75%) or to 0.75 MAC of halothane (0.8%), isoflurane (1.05%) or enflurane (1.65%); an additional 232 positive-control (retinoic acid) and air control rats were studied. Reproductive indices were determined, and the 5178 offspring delivered at cesarean section were examined for external, internal, and skeletal abnormalities. There were no major or minor teratologic effects in anesthetic treated groups, although several developmental variants were observed in halothane- and enflurane-treated groups. Nitrous oxide exposure on days 14-16 resulted in a three-fold increase in fetal resorptions. The results suggest that the volatile anesthetics are not teratogenic and confirm that nitrous oxide may be associated with increased reproductive loss.

Abnormalities, Drug-Induced↗
PubMed1986

Anesthetic metabolism and renal function in obese and nonobese Fischer 344 rats following enflurane or isoflurane anesthesia.

This study was designed to determine the nephrotoxic potential of prolonged anesthesia with enflurane or isoflurane in obese and nonobese Fischer 344 rats. Weight-paired rats received either a regular chow diet or Potter's high fat diet for 16 weeks. The chow-fed (nonobese) rats gained 20% in body weight compared with 45% for the Potter's-fed (obese) rats. Exposure of nine pairs of rats to 2.0% enflurane for 4 h resulted in significantly elevated peak serum F-levels (62 +/- 11 microM vs. 27 +/- 6 microM; P less than 0.001) in obese compared with nonobese rats and clinical signs of F(-)-induced nephrotoxicity (i.e., polyuria) confirmed by decreased creatinine and urea nitrogen clearances in the obese rats. Exposure of nine pairs of rats to 1.4% isoflurane for 4 h produced significantly elevated peak serum F-levels (27 +/- 8 microM vs. 9 +/- 0.4 microM; P less than 0.001) in obese compared with nonobese rats and subclinical nephrotoxicity in obese rats manifested by significantly decreased creatinine and urea nitrogen clearances, but without polyuria. This study suggest that obese patients may be at risk of developing F(-)-induced nephrotoxicity following prolonged enflurane anesthesia. Isoflurane may have significant potential for subclinical F(-)-induced nephrotoxicity in obese patients, to a degree that might affect renal clearance of some drugs in the postoperative period.

Alanine Transaminase↗
PubMed1986

Effect of diazepam treatment on hepatic microsomal anesthetic defluorinase activity.

Different dosing regimens with diazepam were evaluated in male Fischer 344 rats for their ability to enhance the metabolism of several inhalation anesthetics. In vitro metabolism was assessed by the rate of microsomal anesthetic defluorination as measured by the appearance of inorganic fluoride ion (i.e., defluorinase activity). Single daily doses of diazepam, 40 mg/kg, were delivered by gavage for either 7 or 14 days; more continuous dosing was achieved by administration of diazepam at 0.03% or 0.10% in food pellets. Hepatic microsomes isolated from treated rats showed significant dose-related elevations in methoxyflurane defluorinase activity, but not in enflurane or isoflurane defluorinase activities. The microsomal content of cytochromes P-450 and b5 and the NADPH-cytochrome-c-reductase activity was not significantly different among treated and untreated groups. Para-nitroanisole O-demethylase activity expressed per nmole cytochrome P-450 increased in the diazepam-treated groups. Extrapolation of these animal data to humans suggests that surgical patients treated chronically with diazepam are probably not at increased risk for inorganic fluoride-induced nephrotoxicity due to increased metabolism of the fluorinated inhalation anesthetics.

Anesthetics↗
PubMed1985

Fetal development in mice exposed to isoflurane.

The developmental toxicity of trace (0.006%), subanesthetic (0.06%), and light anesthetic (0.6%) exposure to isoflurane was examined in Swiss/Webster mice. No adverse effects were demonstrated following exposure of dams to 0.006% (n = 26) and 0.06% (n = 27) isoflurane for 4 hr daily on days 6-15 of pregnancy. Exposure to 0.6% isoflurane (n = 23) for the same period resulted in significantly decreased fetal weight, decreased skeletal ossification, minor hydronephrosis, and increased renal pelvic cavitation. The incidence of cleft palate also was significantly increased, abnormalities occurring in 12.1% of fetuses and affecting 11 of 23 litters. This incidence was considerably higher than that of the combined treatment and colony control groups (0.75%) and those that we have found in previous experiments with this mouse strain following exposure to halothane (1.2%) or enflurane (1.9%).

Abnormalities, Drug-Induced↗
PubMed1985

Halothane, isoflurane, and enflurane MAC in pregnant and nonpregnant female and male mice and rats.

The MAC of halothane, isoflurane, and enflurane was determined using the tail-clamp technique in pregnant female, nonpregnant female, and male Swiss Webster mice (n = 216) and Sprague-Dawley rats (n = 112). Mean MAC values (+/-SD) for halothane, isoflurane, and enflurane in mice were 0.95 +/- 0.07%, 1.34 +/- 0.10%, and 1.95 +/- 0.16%, respectively; values in rats were 1.03 +/- 0.04%, 1.46 +/- 0.06%, and 2.21 +/- 0.08%, respectively, all significantly higher than in mice. Neither the sex of the animals nor whether female animals were pregnant influenced the results.

Anesthesia, Inhalation↗
PubMed1985

Restricted changes in the adenovirus DNA-binding protein that lead to extended host range or temperature-sensitive phenotypes.

Human adenovirus fails to multiply efficiently in monkey cells owing to a block to late viral gene expression. Ad2hr400 through Ad2hr403 are a set of host range (hr) mutants which were selected for their ability to readily grow in these cells at 37 degrees C. The mutations responsible for this extended host range have previously been mapped to the 5' portion of the gene encoding the 72-kilodalton DNA-binding protein (DBP). DNA sequence analyses indicate that all four hr mutants contain the same alteration at coding triplet 130, which changes a histidine codon to a tyrosine codon. These results extend those of Anderson et al. (J. Virol. 48:31-39, 1983), which suggested that only this change in the DBP amino acid sequence can expand adenovirus host range to monkey cells. The hr phenotype does not appear to require phosphorylation of this tyrosine residue, since no phosphotyrosine was detected in DBP isolated from Ad2hr400-infected monkey cells. The hr mutants Ad2hr400 through Ad2hr403, however, are cold sensitive for growth in monkey cells. The mutant Ad2ts400, which was derived from Ad2hr400, represents a second class of hr mutants which can grow efficiently in monkey cells at 32.5 degrees C. The cold-resistant hr mutation of Ad2ts400 has previously been mapped to the 5' region of the DBP gene (map units 63.6 through 66). DNA sequence analysis of this region shows that this mutant contains the original hr alteration at coding triplet 130 as well as a second alteration at coding triplet 148, which changes an alanine codon to a valine codon. We suspect that the alterations at amino acids 130 and 148 change the structure of the amino-terminal domain of the DBP, allowing it to better interact with monkey cell components required for late viral gene expression. Ad2ts400 also contains a temperature-sensitive mutation which has previously been mapped to the 3' portion of the DBP gene (map units 61.3 through 63.6). Sequence analysis of this region indicates that the DBP coding triplet 413 has been altered. This change from a serine codon to a proline codon is the same alteration reported in the previously sequenced DBP mutants Ad5ts125 (W. Kruijer et al., Nucleic Acids Res. 9:4439-4457, 1981) and Ad5ts107 (W. Kruijer et al., Virology 124:425-433, 1983). Thus it appears that only a very limited number of changes in either the 5' or the 3' portion of the DBP gene can give rise to the hr or temperature-sensitive phenotypes, respectively.

Adenoviruses, Human↗
PubMed1985

Isolation and analysis of adenovirus type 5 mutants containing deletions in the gene encoding the DNA-binding protein.

A genetic system is described which allows the isolation and propagation of adenovirus mutants containing lesions in early region 2A (E2A), the gene encoding the multifunctional adenovirus DNA-binding protein (DBP). A cloned E2A gene was first mutagenized in vitro and then was introduced into the viral genome by in vivo recombination. The E2A mutants were propagated by growth in human cell lines which express an integrated copy of the DBP gene under the control of a dexamethasone-inducible promoter (D. F. Klessig, D. E. Brough, and V. Cleghon, Mol. Cell. Biol. 4:1354-1362, 1984). The protocol was used to construct five adenovirus mutants, Ad5d1801 through Ad5d1805, which contained deletions in E2A. One of the mutants, Ad5d1802, made no detectable DBP and thus represents the first DBP-negative adenovirus mutant, while the four other mutants made truncated DBP-related polypeptides. All five mutants were completely defective for growth and plaque formation on HeLa cell monolayers. Furthermore, the two mutants which were tested, Ad5d1801 and Ad5d1802, did not replicate their DNA in HeLa cells. The mutant Ad5d1804 encoded a truncated DBP-related protein which contained an entire amino-terminal domain derived from the host range mutant Ad5hr404, a variant of Ad5 which multiplies efficiently in monkey cells. While results of a previous study suggest that the amino-terminal domain of DBP could act independently of the carboxyl-terminal domain to enhance late gene expression in monkey cells, the Ad5d1804 polypeptide failed to relieve the block to late viral protein synthesis in monkey cells. The mutant Ad5d1802 was used to study the role of DBP in the regulation of early adenovirus gene expression in infected HeLa cells. These experiments show that E2A mRNA levels are consistently reduced approximately fivefold in Ad5d1802-infected cells, suggesting either a role for DBP in the expression of its own gene or a cis-acting defect caused by the E2A deletion. DBP does not appear to play a significant role in the regulation of adenovirus early regions 1A, 1B, 3, or 4 mRNA levels in infected HeLa cell monolayers since wild-type Ad5- and Ad5d1802-infected cells showed very little difference in the patterns of expression of these genes.

Adenoviruses, Human↗
PubMed1984

Reproduction and fetal development in rats exposed to nitrous oxide.

The effects of 24 hours of nitrous oxide exposure on reproductive indices and fetal development were examined in Sprague-Dawley rats. Four different experiments employing four concentrations of nitrous oxide--0.75%, 7.5%, 25% and 75%--established that the threshold of toxicity was greater than 25%. At 75% nitrous oxide there was a significant increase in early and late resorptions, and a consistent teratogenic effect (e.g., runts, ocular malformations, limb deformities). Neither the stress of shipping dams while pregnant nor the withholding of food during nitrous oxide exposure resulted in additional adverse effects. Exposure to 25% nitrous oxide was associated with increased deoxyuridine suppression values; however, adverse reproductive effects were not seen at this nitrous oxide concentration. The results of this and other studies which have examined the reproductive and teratogenic effects of nitrous oxide do not contraindicate its use in operating rooms nor, when necessary, as an anesthetic for pregnant surgical patients.

Abnormalities, Drug-Induced↗
PubMed1984

Liver function and anesthetic metabolism in rats with chronic renal impairment.

Patients and rats with chronic renal insufficiency (CRI) anesthetized with enflurane do not have significantly greater increases in postoperative serum inorganic fluoride levels when compared with subjects with normal renal function. The authors chose to investigate whether this observation is due to decreased anesthetic metabolism, secondary to the renal disease. Thus, male Fischer 344 rats with surgically induced CRI were studied to determine the effect of severe renal impairment: first, on in vivo hepatic function as measured by a serum liver enzyme profile, and second, on in vitro hepatic metabolism as indicated by microsomal anesthetic defluorination rates and cytochrome P-450 levels. Rats were operated on in two stages, 1 week apart, and assigned to one of three groups. Group 1 rats had a capsule stripping of each kidney. Group 2 rats had a capsule stripping of one kidney and then a nephrectomy of the other. Group 3 rats had the upper and lower poles of one kidney excised and then a nephrectomy of the other. There was no change in renal function in rats from Group 1 and 2. Chronic renal insufficiency in Group 3 rats was manifested by threefold elevations in serum creatinine and urea nitrogen levels and reciprocal decreases in clearances. After 89-98 days, blood was obtained for a serum liver enzyme profile and rats were killed for determination of in vitro hepatic metabolism. There were no changes suggestive of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The function(s) provided by the adenovirus-specified, DNA-binding protein required for viral late gene expression is independent of the role of the protein in viral DNA replication.

The adenovirus type 2 (Ad2) host range mutant Ad2hr400 grows efficiently in cultured monkey cells at 37 degrees C, but is cold sensitive for plaque formation and late gene expression at 32.5 degrees C. After nitrous acid mutagenesis of an Ad2hr400 stock, cold-resistant variants were selected in CV1 monkey cells at 32.5 degrees C. One such variant, Ad2ts400, was also temperature sensitive (ts) for growth in both CV1 and HeLa cells. Marker rescue analysis has been used to show that the two phenotypes, cold resistant and temperature sensitive, are due to two independent mutations, each of which resides in a different segment of the gene encoding the 72-kilodalton DNA binding protein (DBP). The cold-resistant mutation (map coordinates 63.6 to 66) is a host range alteration that enhances the ability of the virus to express late genes and grow productively in monkey cells at 32.5 degrees C. The temperature-sensitive mutation is in the same complementation group and maps to the same segment of the DBP gene (map coordinates 61.3 to 63.6) as the well-characterized DBP mutant Ad5ts125. Like Ad5ts125, Ad2ts400 is unable to replicate viral DNA or to properly shut off early mRNA expression at the nonpermissive temperature. Two sets of experiments with Ad2ts400 suggest that DBP contains separate functional domains. First, when CV1 cells are coinfected at the nonpermissive temperature with Ad2 plus Ad2ts400 (Ad2 allows DNA replication and entry into, but not completion of, the late phase of infection), normal late gene expression and productive growth occur. Second, temperature shift experiments show that, although DNA replication is severely restricted at the nonpermissive temperature in ts400-infected monkey cells, late gene expression occurs normally. These results indicate that the DBP activity required for normal late gene expression in monkey cells is functional even when the DBP's DNA replication activity is disrupted.

Adenoviridae↗
PubMed1983

Germ cell studies in mice after prolonged exposure to nitrous oxide.

Male and female Swiss Webster (SW) mice, age 13 to 14 weeks, were exposed by inhalation for 4 hr per day, 5 days per week, for 14 weeks, to either room air, 0.5% nitrous oxide, 5.0% nitrous oxide, or 50% nitrous oxide. Murine germ cells were examined for evidence of injury after this exposure. A group of male mice were treated with methyl methanesulfonate (MMS) as a positive control for sperm abnormalities while a group of female mice were treated with 3-methylcholanthrene (3-MC) as a positive control for oocyte destruction. There were no significant differences among the four inhalation exposure groups in testes weight, percentage of abnormally shaped sperm, sperm count, or histologic appearance of the testes; the mean percentage (+/- SE) of abnormal sperm ranged from 8.9 +/- 2.4 (5.0% nitrous oxide) to 13.5 +/- 0.5 (50% nitrous oxide) with a concurrent control value of 10.4 +/- 2.3%. In the positive control experiment, 25.2 +/- 4.1% of sperm from mice treated with MMS were abnormal compared with 2.5 +/- 0.3% of sperm from mice treated with saline (p less than 0.001), indicating that sperm of SW mice are sensitive to chemical damage. There was no significant difference between the mean number of oocytes in mice treated with 50% nitrous oxide (33.3 +/- 14.4) and in control mice (29.8 +/- 8.0). In the positive control experiment, mice treated with 3-MC had significantly fewer (p less than 0.001) primordial oocytes, 67.2 +/- 19.5 compared with control mice, 222.4 +/- 21.9, indicating that this strain is sensitive to chemical damage of the ovary. Thus, murine germ cells showed no evidence of toxic effects due to prolonged exposure to nitrous oxide.

Anesthesiology↗
PubMed1983

Metabolism by rat hepatic microsomes of fluorinated ether anesthetics following ethanol consumption.

The possibility that the metabolism of volatile inhalational anesthetics is altered following chronic ethanol consumption was investigated in male Fischer 344 rats. The hepatic microsomal defluorination rates of methoxyflurane, enflurane, and sevoflurane were determined for pair-fed rats receiving ethanol with normal caloric or with 50% of normal caloric intake. For comparison, the effects of phenobarbital treatment on anesthetic defluorination rates also were examined. Fourteen days of ad libitum consumption of 16% ethanol resulted in maximal defluorination rates of the above anesthetics. No overt signs of ethanol toxicity were observed. Ethanol-treated rats with a normal caloric intake had significantly increased microsomal defluorination rates per mg protein compared with pair-fed control rats as follows: methoxyflurane, 190% of control; enflurane, 298% of control; and sevoflurane, 301% of control. Ethanol-treated animals with 50% of normal caloric intake showed similar elevations in microsomal defluorination rates when compared with pair-fed controls. Phenobarbital treatment significantly increased the rate of methoxyflurane defluorination (673% of control), whereas the rates of sevoflurane defluorination (127% of control) and enflurane defluorination (86% of control) were not altered significantly. Phenobarbital treatment increased the microsomal content of cytochrome P-450, while ethanol treatment did not. This study demonstrated that regardless of total caloric intake, chronic ethanol consumption increases defluorination of inhalation anesthetics in Fischer 344 rats. It also illustrated that the two enzyme-inducing agents are unique with respect to the degree to which they enhance anesthetic defluorination.

Anesthetics↗
PubMed1983

Halothane inhibits metabolism of enflurane in Fischer 344 rats.

The authors investigated the effect of prior administration of halothane upon the metabolism of enflurane. Twenty-four, one-year-old male, Fischer 344 rats were assigned randomly to four anesthetic exposure groups. Groups 1 and 2 were controls exposed only to halothane and enflurane, respectively. Group 3 was exposed for 1 h to 0.3% halothane, followed by 2 h of 1% enflurane. Group 4 was exposed for 1 h to 1% halothane and then to 2 h of 1% enflurane. Blood samples were taken prior to, immediately following, and 1, 24, and 48 h after anesthetic exposure. Serum was assayed for inorganic fluoride (F-), SGOT and SGPT. Twenty-four-hour urinary collections were assayed for F excretion. Group 1 rats exposed to halothane alone had the lowest peak mean serum F- (5.0 microM). Group 2 rats exposed to enflurane alone had the highest serum F concentration 4 h after anesthesia (18.7 microM). Peak serum F in Group 3 rats (9.5 microM) was significantly lower than in Group 2 rats (enflurane control). In Group 4 rats, serum F- was not significantly different from Group 1 rats (halothane control) at any time. In the first 24 h after anesthetic exposure, urinary F- excretion in Groups 2 and 3 was significantly higher than in Groups 1 and 4. This study demonstrated that prior exposure to halothane reduced the metabolism of enflurane; previous work suggested that this was due to an interaction of halothane with hepatic cytochrome P-450.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Thymidine and methionine syntheses in pregnant rats exposed to nitrous oxide.

The dose-dependent effects of nitrous oxide on thymidine and methionine syntheses were investigated in pregnant rats. Female Sprague-Dawley rats were exposed on day 9 of gestation to 0.75%, 7.5%, or 75% nitrous oxide for 24 h. Immediately and 72 h after exposure, a deoxyuridine-suppression test was performed on maternal bone marrow and a methionine synthetase assay was performed on maternal liver to assess thymidine and methionine syntheses, respectively. Inhibition of thymidine synthesis was seen after exposure to 7.5% and 75%, but not after 0.75%, nitrous oxide. Recovery was complete 72 h after exposure. Methionine synthetase activity was abolished at all concentrations of nitrous oxide tested and did not return to control values 72 h after exposure. Fetal weight and gross appearance were not affected by exposure to nitrous oxide; however, the observed decrease in thymidine and methionine syntheses after nitrous oxide exposure may account for its teratogenic effects.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1982

Reproduction and fetal development in mice chronically exposed to nitrous oxide.

The effects of exposure to nitrous oxide on reproductive indices, fetal development, and male fertility were examined in Swiss/ICR mice. In experiment I, female mice were exposed for 4 hours per day on days 6-15 of pregnancy, to 0.5% (5,000 ppm), 5.0% (50,000 ppm), or 50% (500,000 ppm) nitrous oxide. Control mice were untreated, exposed to compressed air, or treated with retinoic acid on day 8 of gestation. In experiment II, male mice were treated, as above, for 9 weeks and then mated nightly for 7 nights to untreated, virgin females. In experiment I, 1,761 fetuses from 154 dams were examined and found to be without evidence of adverse nitrous oxide treatment effects. In experiment II there were no differences among the groups in the ability of males to impregnate females or in litter size, fetal wastage, or fetal size. When we compare nitrous oxide with other inhalation anesthetics we have studied employing a similar protocol, we find the order of reproductive toxicity to be: halothane greater than enflurane greater than methoxyflurane greater than nitrous oxide. None of the agents were toxic, however, at the trace concentrations usually found in operating rooms.

Abnormalities, Drug-Induced↗