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Biomedical subjects

S L Beck

Publications and source records attributed to S L Beck.

At least 37 records · Page 2Linked to original sources
PubMed1990

Prenatal and postnatal assessment of Maneb-exposed CD-1 mice.

Skeletons of CD-1 mice exposed in utero during days 6 to 15 of gestation by gavage of their dams with 1200 mg/kg/day of Maneb in 1.0% carboxymethylcellulose (CMC), were examined between 60 and 65 days postnatal (DPN) for the 88 variants of the skeletal variant assay system (SVAS). Of the 58 variants that appeared, 13 differed (P less than 0.01) from untreated (UNTD), and 15 from vehicle-treated (VEH), despite absence of malformations at birth, weaning, or time of sacrifice. Major changes in frequencies of Parted Frontals, Abnormal Metoptic Roots, Reduced Articular Processes of the Thoracic (Th) Vertebrae, and Carpal Fusions occurred. Several variants affecting the Spinous Process of Th2 occurred in significant proportions as an unusual effect of this compound. In a series of 20 Maneb-treated litters dissected at 18 days post coitus (DPC), of 168 live fetuses, 9 had minor abnormalities, one was exencephalic, and 14 showed growth retardation. Prenatal mortality (20%) was higher than in UNTD (7.5%); litter size and litter weight were not significantly reduced. Ossification of cervical vertebral centra, and caudal vertebrae were significantly reduced, sternebra and limb ossification were not. Occurrence of 14-Ribs was increased. Although maternal mortality complicates interpretation, both traditional prenatal and postnatal examination focusing primarily on the skeleton revealed effects of exposure in the absence of frank malformations.

Abnormalities, Drug-Induced↗
PubMed1990

Use of the PDQ system in a clinical setting.

This pilot study examined the use of PDQ (Physician Data Query)--a user-friendly, full-text, cancer database--as a clinical information resource on an oncology unit. The twenty-nine participants included faculty, hematology-oncology fellows, residents, interns, medical students, pharmacists, and nursing staff. During the one-month study, PDQ was available twenty-four hours a day at the nursing station via a microcomputer. Participants were trained to use PDQ and allowed to search the database as prompted by clinical situations. The project evaluated the use of PDQ, as well as clinicians' perceptions of its usefulness. Results indicate that access to PDQ on an oncology unit provides an excellent educational and clinical resource. Fifty-one percent of the participants used PDQ an average of 2.4 times each. Heaviest users were medical trainees (78%), although 39% of nurses became users. Over half of the PDQ users reported that use of the database affected clinical care.

Hospitals, University↗
PubMed1989

Prenatal ossification as an indicator of exposure to toxic agents.

Following exposure to bromodeoxyuridine (BUDR), acetazolamide (ACZM), trypan blue (TRBL), cortisone (CORT), or diphenylhydantoin (DPH), alizarin-stained, cleared fetuses were examined at 18 days postcoitus for unossified cervical vertebral centra; number of ossified caudal vertebrae; number of ribs; and ossification of sternebrae, metatarsals, metacarpals, and phalangeal rows. At all teratogenic doses, in no vehicle-treated groups, and rarely in lower-dose groups, there were significant increases in frequency of unossified cervical centra, the first vertebra (C1) being most often affected, and C7 least often affected. In the high-dose CORT group, there was a significant correlation between unossified C1 and cleft palate. No association between abnormality and reduced ossification of cervical vertebrae was seen in other series examined, nor was there any correlation between litter size and abnormality. With minor complications, the number of ossified caudal vertebrae was significantly reduced after exposure at teratogenic dose levels to all compounds except DPH. Although caudal and cervical ossification were correlated with each other in those series examined, neither was correlated with abnormality. Frequency of 14 ribs was increased in BUDR, ACZM, and TRBL but not CORT or DPH. Other parameters were essentially unaffected. Significantly increased frequency of abnormality, when contrasted with untreated or vehicle-treated groups, was seen at high-dose levels in all but DPH treatments, and mortality was increased in ACZM D9-11, TRBL, and CORT. These studies show that reduced ossification of cervical centra is an excellent indicator of prenatal exposure to noxious substances, and caudal vertebrae appear to be useful as well. Increased frequency of 14 ribs occurred for all strong teratogens utilized if they were administered on day 7 or day 8 postcoitus.

Acetazolamide↗
PubMed1983

Assessment of adult skeletons to detect prenatal exposure to acetazolamide in mice.

A skeletal variant assay system (SVAS) consisting of a group of 88 spontaneously occurring qualitative variations of the adult mouse skeleton was applied to CD-1 animals that had been exposed in utero to 0, 200, or 1,000 mg/kg/day of the sodium salt of acetazolamide dissolved in distilled water, presented by SC injection of the dam during day 8 or days 9-11 of gestation. Two separate series of experiments were performed, and skeletons were examined at postnatal 62 +/- 2 days. Variation occurred in 62 and 67 characters in the two series. Frequencies of occurrence differed from untreated (UNTD) and vehicle-treated (VEH) values of substantial numbers of variants in a dose related manner for both series in both treatment regimes as did the number of variants which showed significantly different frequencies (P less than .01) in comparisons of experimental with either UNTD or VEH. At the high doses 12 and 16 variants occurred with significantly different frequencies from UNTD in day 8 treatments in the two series, and 15 and 19 variants differed in the days 9-11 treated group. Contrasting high-dose animals with appropriate vehicle controls revealed differences in 13 and 12 variants in day 8 treatment groups and in 18 and 15 variants in days 9-11 groups. Agreement between the two series was good, especially in the D9-11 treatments. Several variants differed significantly from both UNTD and VEH in both series of experiments. Among these were a number which appeared more or less specific to acetazolamide exposure. They include: day 8 treatments--accessory parietal, frontal extension, and 27 presacral vertebrae; day 9-11 treatments--sacral fusions in dorsal processes and vertebral bodies, and caudal fusions and malformations; both sets of treatments--lumbar fusions, and fusions of the transverse processes of the sacral vertebrae. Other importantly affected variants, also seen in exposure to other compounds include: day 8 treatments--abnormal metoptic roots; day 9-11 treatments--accessory mental foramen, foramina transversaria imperfecta of the atlas, arch foramen of the fifth cervical (C) vertebra, malformed sternebrae, fossa olecrani perforata, and fewer than 30 caudal vertebrae; both treatment regimes--parted frontals, accessory transverse foramina in C3-C6, reduced articular processes on the thoracic vertebrae, and 14 ribs. By all criteria applied, the SVAS is able to detect prenatal exposure to acetazolamide in adult skeletons even in the absence of any gross morphological abnormalities.

Acetazolamide↗
PubMed1983

Assessment of adult skeletons to detect prenatal exposure to trypan blue in mice.

A Skeletal Variant Assay System (SVAS) consisting of a group of 88 spontaneously occurring qualitative variations of the adult mouse skeleton was studied in CD-1 mice which had been exposed in utero by way of three daily ip injections of their dams on days 7-9 of gestation with trypan blue. Treatment groups received daily doses of 0.25 cc of 0, .037, .075, .15, or .30% trypan blue dissolved in 0.9% NaCl. Two separate series of experiments were performed, and skeletons were examined at 62 +/- 2 days postnatal. Sixty-six and 58 of the variants occurred in the two series, respectively. Frequencies of occurrence of substantial numbers of variants differed from Untreated (UNTD) and Vehicle-Treated (VEH) values in a dose-related manner for both series. At the high dose 18 and 22 variants occurred with significantly different (P less than .01) frequencies from UNTD in the two series. Contrasting high-dose animals with vehicle controls revealed significant differences in 24 and 17 variants. There were 13 and 14 variants in the two series, respectively, which differed from both UNTD and VEH. If one considers differences at P less than .01 in one comparison and P less than .05 in the other, then 22 and 18 variants qualify as being significantly different from both controls in the two series. Agreement between the two series was excellent regarding which variants were affected. Several differed significantly from both UNTD and VEH in both series of experiments. Among these were a number which appeared more or less specific to trypan blue exposure. They include Dyssymphysis of the Atlas, Carpal Fusions, and Tarsal Fusions. Although increased frequency of an Interfrontal bone is seen with several treatments, the magnitude of the response and the low doses at which it is elicited are unique to trypan blue exposure. Numerous low-dose effects are striking in this set of experiments, making the SVAS a very sensitive indicator of trypan blue exposure. In addition to the variants mentioned, a large cluster of cervical (C) vertebrae variants, including dyssymphyses, fusions, imperfect transverse foramina of C1 and C2, and accessory transverse foramina of C3-C6, as well as vertebral fusions at various levels (especially cervical, sacral, and caudal), appear to be the principal effects of exposure to this compound. In addition, rib malformations at the high dose level, and increased frequency of occurrence of 27-presacral vertebrae at all dose levels, were important effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗
PubMed1981

Assessment of adult skeletons to detect prenatal exposure to 2,4,5-T or Trifluralin in mice.

A group of 88 spontaneously occurring variations of the skeleton were studies in adult CD-1 mice which had been exposed in utero to the herbicides 2,4,5-T or Trifluralin, administered to their dams by gavage, in an attempt to detect subtle biological effects of these compounds even in the absence of gross malformations. Sixty-seven characters showed variation in this population. Of these, 19 were significantly different in frequency from untreated controls in mice having receiving a teratogenic dose of 2,4,5-T, with an average difference of 23.7%. Seventeen of them were increased in frequency. By contrast, only three traits differed from untreated among mice receiving a no-effect dose of 2,4,5-T. Twelve traits differed significantly from untreated in the Trifluralin-treated group; the average difference was 18.8%, with 10 of the traits being increased in frequency. Two clusters of affected variants specific to the 2,4,5-T high dose group included frontal bone variants in the skull (presence of an interfrontal bone and fusion of the frontals) and variants in the cervical vertebrae (imperfect foramina in the first and second cervicals, dyssymphysis of the second cervical, and a shift of the arch foramen from the fourth to the fifth cervical). Two other effects peculiar to the 2,4,5-T-treated specimens were a loss of the prominent dorsal spine of the second thoracic vertebra and a reduction in the number of caudal vertebrae. The most obvious effects specific to the Trifluralin treatment were an increase in occurrence of 14 ribs, an undoubled foramen ovale, and the occurrence of accessory foramina in the cervical vertebrae. A striking increase in frequency of parted frontals was seen in both 2,4,5-T high dose and Trifluralin-treated groups. The skeletal variant assay system may be used as a postnatal screen for detecting prenatal exposure to potentially noxious substances.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1976

Suceptibility of mice to audiogenic seizures is increased by handling their dams during gestation.

Fetal mice treated on days 10, 11, and 12 of gestation by injecting the mothers with (i) 50 milligrams of beta-2-thienylalanine, (ii) solvent, or (iii) sham injection had identical frequencies of audiogenic seizures when tested 23 days after birth; these frequencies were significantly higher than those of an unhandled control group. Results of the sham treatment suggest that maternal stress induced by handling, rather than the nature of the substance injected, increased the susceptibility of the offspring to seizures.

Alanine↗
PubMedDate not supplied

Using the journal club as a component of the research utilization process.

Although journal clubs are recommended for research utilization, the various ways in which journal clubs are conducted do not always lead to research utilization. Major institutional changes in practice must be preceded by a comprehensive literature search and a complete review. An example is provided of how a series of journal clubs using the comprehensive search approach led to research utilization.

Clinical Nursing Research↗
PubMedDate not supplied

Does genomic imprinting contribute to valproic acid teratogenicity?

Reciprocal outcrosses and backcrosses were made between strains of mice with different susceptibilities to valproic acid (VPA) teratogenicity. Relatively resistant C57BL/6J (C) and more susceptible SWV (S) strains of mice produced F1 hybrids in which the female parent was C and the male parent was S (CS-F1) as well as the reciprocal with S dams and C sires (SC-F1). Each was backcrossed to each strain, producing 8 types of backcross matings: CS x C, SC x C, CS x S, SC x S; C x CS, C x SC, S x CS, S x SC (for all matings dams are listed first). At 8d:12 +/- 5h of gestation, a teratogenic dose, 600 mg/kg, of aqueous VPA was injected ip into the dams. Fetuses were examined on gestation day (gd) 18 for abnormality, mortality, litter size, and weight. Genomic imprinting (imprinting) is a phenomenon at least in part involving hyper- or hypomethylation of bases in DNA, which is believed to determine whether or not the imprinted gene will be expressed. Imprinting has been reported to occur differentially in the male and female for a number of gene loci. Thus, in crosses between strains with differing susceptibility to VPA, if imprinting is occurring, the susceptibility of a fetus might be predicted to be disproportionately influenced by susceptibility of its grandparents. Significant differences in frequency (%) of occurrence of exencephaly in progeny of all backcrosses with F1 dams consistent with those expected for imprinting were found in the present study (CS-F1x C = 21.8 +/- 3.9%, SC-F1x C = 10.8 +/- 3.2%, P < 0.03; CS-F1x S = 14.8 +/- 3.1%, SC-F1x S = 6.3 +/- 2.3%, P < 0.03). SWV dams revealed the same pattern (S x SC-F1 = 50.0 +/- 8.3%, S x CS-F1 = 37.1 +/- 4.7%, P < 0.04). Differences in prenatal mortality also consistent with genomic imprinting occurred in backcrosses with pure-line SWV dams (S x SC = 64.4 +/- 8.0%, S x CS = 30.5 +/- 4.5%, P < 0.001). Fetal weight was reduced in a manner consistent with imprinting in backcrosses involving SWV (S x SC = 0.50 +/- 0.18 g, S x CS = 0.96 +/- 0.05, P < 0.01). Three of four of the parameters investigated showed differences in some of the backcrosses of reciprocal F1's consistent with those expected if genomic imprinting were occurring.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Contributions of dam and conceptus to differences in sensitivity to valproic acid among C57 black and SWV mice.

To ascertain the relative contributions of genotypes of conceptus and dam to developmental toxicity occasioned by valproic acid (VPA), crosses were established between resistant C57BL/6JBk (C, C57) and susceptible SWV/Bk (S, SWV) strains of mice. These included matings of pure lines, reciprocal outcrosses, and reciprocal backcrosses with F1 hybrids. At 8 d:12 h +/- 5 h, for each mating, 0, 500, or 600 mg/kg aqueous VPA was injected ip. Fetuses were examined on gestation day (gd) 18 for exencephaly (the paradigmatic anomaly), other abnormalities, mortality, litter size, and fetal weight. At 600 mg/kg, sensitivity to exencephaly induction in all cases was that of the dam, regardless of sire. Thus exencephaly here seems to be largely a function of the uterine environment produced by the maternal genotype. This inference is confirmed in backcrosses where F1-dams x S-sires and F1-dams x C-sires produced-identical outcomes, and S-dams x F1-sires produced much higher frequencies of exencephaly than C-dams x F1-sires. For prenatal mortality, the genotypes of both dam and conceptus appear to be important determinants. Fetal contribution is inferred from the observations that S-dam x S-sire matings produced a much higher frequency of mortality than S-dams x C-sires, and C-dams x C-sires produced higher mortality than C-dams x S-sires. Therefore, heterozygosity of the conceptus was protective. Among backcrosses, fetal determination of sensitivity to mortality is also seen by the observation that F1-dams x C-sires produces the same fetal mortality as C-dams x F1-sires. The contribution of uterine environment is seen in the observation that matings of S-dams x C-sires resulted in higher fetal mortality than did those with C-dams x S-sires. Therefore, identical conceptuses in different dams showed different levels of fetal loss. Thus exencephaly response appears to be largely controlled by genes active in the dam, and mortality as a result of a multigenic outcome with contributing genes active in both conceptus and dam. The data also suggest that SWV pure-line dams make a contribution to prenatal mortality not seen in C57 or F1 dams. Mean litter size among VPA-exposed litters showed high variability in pure lines and outcrosses. In backcrosses, F1 dams produced larger litters than pure line dams, arguing for heterosis as a contributor to this parameter. Reduction in litter size occasioned by VPA exposure was great in pure line dams and nonexistent in F1 dams. The SWV dams crossed with F1 sires were the only group among the backcrosses to show reduction of litter size, providing further confirmation of the increased sensitivity of pure-line (i.e., homozygous) SWV dams to VPA exposure. Fetal weight seems to be a function of uterine environment because female SWV produced conceptuses with lower fetal weight in all crosses, and produced a greater reduction in fetal weight attributable to VPA exposure than C57 or F1 dams. Fetal weight did not correlate closely with litter size, suggesting that a lower fetal weight may be a strain characteristic, as are exencephaly induction and prenatal mortality in response to VPA. Differences in sensitivity to VPA insult are seen for all parameters investigated with SWV dams being the most sensitive, but mechanisms seem to differ for a number of the endpoints.

Abnormalities, Drug-Induced↗