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Biomedical subjects

W J Scott

Publications and source records attributed to W J Scott.

At least 127 records · Page 7Linked to original sources
PubMed1981

Carbonic anhydrase distribution in rodent embryos and its relationship to acetazolamide teratogenesis.

The carbonic anhydrase inhibitor, acetazolamide, leads to a unique distal postaxial right forelimb deformity in rats and CBA/J mice, but SWV mice are completely resistant. Using Hansson's histochemical method, the distribution of carbonic anhydrase and its inhibition by acetazolamide in rat, CBA/J mouse, and SWV mouse embryos were compared. Carbonic anhydrase activity was demonstrable in many tissues of sensitive rat and CBA/J mouse embryos and in resistant SWV mouse embryos. The forelimb buds of resistant and sensitive embryos possess carbonic anhydrase activity in the area between the ectoderm and adjacent mesenchyma with no localization of enzyme activity corresponding to the malformation seen in acetazolamide teratogenesis. This suggests that carbonic anhydrase in the forelimbs is not the primary site of action for acetazolamide. A distinctive staining pattern of nucleated erythrocytes in resistant embryos indicated the presence of a low activity form of carbonic anhydrase in nearly half of the erythrocytes. A five-to tenfold greater amount of acetazolamide was needed to completely inhibit carbonic anhydrase activity in nucleated erythrocytes from resistant embryos than in those from sensitive embryos. The existence of a low activity form of carbonic anhydrase in SWV embryo erythrocytes may be the basis of resistance to acetazolamide teratogenesis.

Abnormalities, Drug-Induced↗
PubMed1981

A dynamic analysis of migration: an assessment of the effects of age, family and career variables.

This paper examines the utility of viewing migration in the context of work careers and family life cycles. We do this by studying migration as a discrete state, continuous time process. We find that the inverse relationship between age and migration is due almost completely to the effects of family life cycle and work career variables. Further, we find that job- or location-specific resources, prestige and wage deter migration.

Adolescent↗
PubMed1980

A metabolite of a structural analog of thalidomide lacks teratogenic effect in pregnant rhesus monkeys.

A metabolite of CG 3033, a structural analog of thalidomide, was examined for teratogenic potential in rhesus monkeys. The metabolite EM 240 is produced in man by hydrolysis of the parent compound but the pathway is absent in nonhuman primates. Fifteen mg/kg administered orally throughout organogenesis to pregnant rhesus monkeys produced no evidence of embryotoxicity, including malformation.

Abnormalities, Drug-Induced↗
PubMed1980

Effect of 5-fluoro-2'-deoxyuridine on deoxyribonucleotide pools in vivo.

5-Fluoro-2'-deoxyuridine (FdUrd) lowered the dTTP levels in rapidly frozen 12-day W rat embryos and in a human neuroblastoma grown in nude N:NIH(S) mice to about 20% of control values. This effect was associated with greatly increased dCTP levels and reduction of dGTP levels essentially to zero. Elimination of the dGTP pool correlated temporally with the cytotoxicity of FdUrd. Extremely rapid fixation of tissue was required to avoid artifactually high deoxyribonucleoside triphosphate values.

Animals↗
PubMed1977

Non-confirmation of thalidomide induced teratogenesis in rats and mice.

It has been reported that thalidomide, dissolved in a 1:3 mixture of Tween 20 and physiological saline and administered intraperitoneally to pregnant mice and rats induces a variety of malformations, including limb deformaties, characteristic of the primate syndrome. The studies reported herein attempted to confirm these findings without success although the rodent strains used were not the same. A low level of non-specific malformations was observed in the fetuses of both species at dose levels reported to cause a 47 percent and 92 percent rate of malformation in mice and rats respectively. One possible source of difference was Tween 20 which was toxic to the point of lethality in these studies at dose levels reported to be non-toxic in the earlier studies.

Abnormalities, Drug-Induced↗
PubMed1977

The effects of thalidomide and two analogues on the regenerating forelimb of the newt.

Oral administration (3 mg/day) of thalidomide during the dedifferentiation and early limb-bud stages of newt forelimb regeneration produced a variety of specific limb deformities. Proximal and preaxial skeletal elements were the most severely malformed, e.g. preaxial hemimelia, severe proximal deformities, and preaxial polydactyly. Likewise, oral, daily doses (3 mg) of the teratogenic analogue, EM12, on days 7 and 8 following bilateral amputation caused the same incidence and type of forelimb abnormalities as did thalidomide. Conversely, the non-teratogenic analogue, EM87, when orally administered (3 mg/day) on days 7 and 8 post-amputation resulted in a low rate of limb deformities, similar in type to those seen in control regenerates. The type of limb deformities observed in the regenerating newt forelimb following thalidomide treatment nearly mimic those seen in the human and monkey syndromes. Therefore, the newt represents a possible model for investigating some of the problems associated with thalidomide teratogenesis.

Amputation, Surgical↗
PubMed1977

Weight differences in rat embryos prior to sexual differentiation.

Sex of day-12 rat embryos was determined using Barr body counts made on spreads of amniotic membranes examined histologically. Embryonic weight, protein content and rate of thymidine incorporation were compared in male and female embryos. Male embryos were found to be heavier and accordingly to contain more protein on absolute but not on per unit weight basis. The rate of thymidine incorporation did not differ in the two sexes. Since gonadogenesis in day-12 rat embryos is rudimentary, with gonadal differentiation of sex not yet apparent, the increased weight suggests that sex-linked genes exist which influence body growth prior to gonadal endocrine activity.

Animals↗
PubMed1976

Reduced interlitter variability in rats resulting from a restricted mating period, and reassessment of the ""litter effect''.

Rats were mated for two or 15 hours and variability of day-12-embryos in weight, protein content, and [3H]thymidine incorporation was compared in the long mating period (LMP) and short mating period (SMP) groups by a 2-level nested analysis of variance. Variability in day-20 fetal weight was similarly compared. In both groups day-12 embryonic weight was relatively more variable than day-20 fetal weight, and variability was less in SMP than LMP animals for each comparison made, although statistical significance was attained only for thymidine incorporation. ""Litter effects'' were noted but not of the magnitude reported by other investigators. It was concluded that inappropriate statistical methods have encouraged the belief that among-litter variability usually exceeds within-litter fetal weight variability. The teratological implications of reduced development variability and the ""litter effect'' are discussed.

Abnormalities, Drug-Induced↗
PubMed1975

Comparative distribution and embryotoxicity of hydroxyurea in pregnant rats and rhesus monkeys.

Hydroxyurea was given to pregnant rhesus monkeys and pregnant rats in regimens adjusted to produce similar degrees of teratogenicity, for the purpose of comparing the distribution of the drug in the females and their embryos. According, in rats 137 mg/kg/day ip on days 9-12 resulted in a drug half-life in maternal plasma of about 15 min and in embryos about 85 min, after the last injection; and in monkeys 100 mg/kg/days iv on days 23-32 resulted in drug half-life in maternal plasma estimated to be 120 min and in embryos 265 min, after the last injection. Using as a baseline of biological effects the minimal concentration known to inhibit DNA synthesis in rat embryos and cancer cells, namely 10(-4) M, it was calculated that the rat embryos in the present study were exposed to this level or more for approximately 12 h whereas the monkey embryos were exposed for approximately 100 h. Although the teratogenic effects were not identical in the two species, these data are interpreted to mean that rat embryos are teratogenically much more sensitive to hydroxyurea than monkey embryos. These observations have important implications in the selection of appropriate species for tests to estimate human teratogenic risks. The rat, which is currently the most widely used animal for such tests, displays sizeable differences from rhesue monkeys, which is one of the animals thought to be most like man in teratogenic susceptibility.

Amniotic Fluid↗
PubMed1975

Inhibition of ATP synthesis associated with 6-aminonicotinamide (6-AN) teratogenesis in rat embryos.

Pregnant rats were injected ip with 6 mg/kg 6-aminonicotinamide (6-AN) at day 12 of gestation. Embryos removed between 1 and 48 h later had reduced adenosine triphosphate (ATP) concentrations, of about 50% of control values. All fetuses examined near term were malformed. Nicotinamide (NAM, 100 mg/kg) given ip 1 h after 6-AN afforded protection: malformations occurred in only 15% of the survivors; and there was minimal ATP reduction, 15% below control values. NAM given 2 and 4 h after 6-AN produced intermediate ATP concentrations and malformation frequencies. Thus, there was a relation between the embryotoxic and ATP-depressant actions of 6-AN in day 12 rat embryos.

6-Aminonicotinamide↗