摘要:

AbstractSerum proteins of pregnant rats were analyzed by paper electrophoresis following administration of the teratogenic disazo dyes trypan blue, Evans blue, Niagara blue 4B, Niagara sky blue 6B, Congo red, and Niagara blue 2B. Sera were obtained from blood taken by cardiac puncture just before dye injection, 48 hours after dye injection; and again at autopsy. All of the dyes tested caused a reduction in serum albumin and total protein concentration and an elevation in the concentration of beta or alpha‐2 globulins at some time during pregnancy. The remaining serum fractions reacted variably to the dye treatment. In spite of the rather consistent results presented in this paper, and similar findings reported for other teratogens, there is no direct proof that altered serum proteins, per se, are causally related to the production of malformation

ISSN:0040-3709    

DOI:10.1002/tera.1420020202

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThe uracil analogue 5‐fluorouracil (5‐FU) administered alone on day 9 of rat gestation was nonteratogenic at a dose of 10 mg/kg but highly teratogenic at 20 mg/kg. Simultaneous administration of the natural pyrimidine bases uracil (U) or thymine (Th) and the lower dose of 5‐FU was highly teratogenic and simultaneous administration of U or Th and the higher dose of 5‐FU was totally embryolethal, i.e., all litters resorbed before term. Uridine and thymidine given with 5‐FU had a similar effect but were less potent. The nucleotide thymidine monophosphate at greater than a molar equivalent dose failed to have this effect. The potentiative effect was reduced after a 1‐hour interval and virtually absent after a 3‐hour interval between injections of the analogue and natural base. When carbon tetrachloride was used to cause generalized damage to liver tissue a striking increase in teratogenic effect occurred, indicating that the intact liver tends to protect the embryo by catabolizing 5‐FU.Studies with14C‐labeled 5‐FU showed that a significantly greater amount of 5‐FU reached the embryo when the analogue plus U was administered than when the analogue was given alone. It is assumed that nonspecific pyrimidine‐degrading enzymes in maternal liver were temporarily saturated by the combined concentrations of 5‐FU and U, and hence the effect was tantamount either to increasing the dose of teratogen or decreasing liver function. This supposed action by hepatic enzymes is supported by data presented in the follow

ISSN:0040-3709    

DOI:10.1002/tera.1420020203

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThymine (Th), uracil (U), and the antimetabolite 5‐fluorouracil (5‐FU) are metabolized in vitro by rat liver enzyme systems present in the high‐speed supernatant soluble cell fraction. The data presented demonstrate that addition of either U or Th to such preparations or the use of livers from rats pretreated intraperitoneally with U or Th markedly decreases the ability of liver preparations to metabolize 5‐FU. These findings indicate that the decreased elimination from the body of a teratogenic dose of 5‐FU after treatment with an equimolar dose of U is due to the inhibition of metabolism of the antimetabolite in the maternal liver.The concomitant administration of the natural pyrimidines Th or U with 5‐FU resulted in prolonged high serum levels of the teratogen 5‐FU, which tended to enhance transfer to and uptake by the embryo. Since the embryo was unable to dispose of 5‐FU metabolically, prolonged high levels of 5‐FU would be expected to cause increased teratogenic effects. Studies with labeled 5‐FU revealed that most of the radioactivity found in the embryos was incorporated into RNA, with only about 30% in the TCA ex tract. Concomitant treatment of pregnant rats with 5‐FU and U had greater inhibitory effect on the incorporation of formate into the methyl group of DNA thymine in the embryo than treatment with 5‐FU alone. This treatment inhibited thymidylate synthetase more than an equimolar dose of 5‐FU alone. Neither treatment affected the high kina

ISSN:0040-3709    

DOI:10.1002/tera.1420020204

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractTo study directly the effects of hypoxia on the mammalian embryo, rat embryos at the 14‐, 22‐, and 35‐somite stages were explanted into the in vitro system of New. The initial heart rates in the three groups did not differ. With hypoxia the 22‐ and 35‐somite embryos responded with a prompt heart‐rate drop but no significant effect was found in the 14‐somite embryos. Irreversible sludging of yolksac circulation was associated with death in the

ISSN:0040-3709    

DOI:10.1002/tera.1420020205

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractAn aim of the present investigations was to use recently isolated strains of H‐1 and RV, which had been subjected to a minimum of laboratory passages, to induce transplacental infection orally in order to replicate natural infections in rats, the natural hosts, as well as in hamsters, which are subject to “spontaneous” infection with these agents. H‐1 virus had a remarkable ability to penetrate both the gut wall and placental barrier and infect fetuses within 24 hours of oral inoculation of pregnant hamsters, whereas such infections could be induced in rats only by parenteral inoculation. However, rats were susceptible to fetal infection with RV given orally. The pathogenesis of infection was somewhat different with the two viruses. RV, in contradistinction to H‐1, proliferated in maternal organs and possibly in the placenta for several days before invading the fetus. Both H‐1 and RV were alike in being transported in the blood in close association with erythrocytes. All fetuses invaded by either agent developed widespread infections prior to death as shown by the presence of intranuclear inclusions and cytolytic effects. Placentas remained intact and viable even after resorption of attached fetuses. The health of all mother animals was unaffected. One special strain — HHP — was the only RV strain to induce transplacental infection orally in hamsters. The various attributes of these parvoviruses that make them particularly favorable agents for the study of transplacental infection

ISSN:0040-3709    

DOI:10.1002/tera.1420020206

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420020207

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractAfter ascertaining that intrauterine growth and maturation continue when pregnancy is prolonged with progesterone in Sprague‐Dawley rats this technique was combined with the teratogens chlorcyclizine, vitamin A, and β‐aminopropionitrile (BAPN), to study the effects of 2 to 3 extra days of intrauterine growth on various abnormalities. Females were killed on day 21 or, if treated with progesterone, on day 24 of gestation. Untreated animals served as controls.In the day‐24 chlorcyclizine group, edema and hydronephrosis were either as severe as or more marked than in the day‐21 group and the testes remained near the kidneys rather than descending deep into the pelvis. Vertebral calcification, usually not present on day 21, had occurred by day 24. These findings suggest that edema, hydronephrosis, and undescended testes were probably permanent defects, whereas lack of calcification was due to delay in occurrence. The smaller dose of vitamin A produced facial abnormalities ranging from marked underdevelopment of the mandible to relative prognathism in day‐21 fetuses but mostly prognathism in day‐24 fetuses; whereas the higher dose produced severe underdevelopment of the jaws and decrease of skeletal calcification in young of both age groups. Severe limb malformations, noted in day‐21 fetuses after high doses of vitamin A, were not grossly altered by prolonging pregnancy. BAPN‐induced limb malformations and gibbus deformities noted on day 21 were still p

ISSN:0040-3709    

DOI:10.1002/tera.1420020208

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThe relation of alveolar clefts to morphogenesis of teeth in the line of the cleft was explored. The oral‐facial‐digital (OFD) syndrome is a unique experiment of nature wherein the position of the cleft is posterior to where it occurs in the more common types of cleft. In the latter the cleft occurs anterior to the maxillary canine and affects the number and form of the lateral incisor. In the OFD syndrome the cleft occurs posterior to the canine with duplicate canines, sometimes “T”‐shaped, occurring on either side of the alveolar cleft. These findings suggest a common timespace relation between alveolar clefting and tooth‐bud formation, probably occurring in the sixth week of emb

ISSN:0040-3709    

DOI:10.1002/tera.1420020209

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThe eyes of 17‐, 24‐, 28‐, and 31‐somite and 10‐ to 16‐day prenatal, newborn, and 6‐month‐old fidget (fi/fi) mice were studied. The present study showed that the eye abnormalities infi/fimice are due to growth retardation of the optic vesicle. Infi/fiembryos the volume of the optic vesicle and its mitotic index were considerably below normal. The reduced growth rate of the optic vesicle led to its delayed contact with the ectoderm and prevented normal lens induction. The lens often did not bud off from the surface ectoderm. In some cases the greatly reduced growth rate of the optic vesicle prevented its contact with the ectoderm and resulted in aphakia. Anophthalmia was also observed, which was caused by the arrest of eye development at the early optic‐vesicle stage. The mitotic index in the wall of myelencephalon and the ventral half of prosencephalon wall was considerably lower than normal. This suggests that the anomalies of the eye and the labyrinth infi/fimice are evidently due to an antecedent developmental abnorma

ISSN:0040-3709    

DOI:10.1002/tera.1420020210

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY

摘要:

AbstractThe lateral motor columns of a recently metamorphosed frog (Rana pipiens) that had three functional forelimbs on the left side were analyzed for differences on the two sides of the spinal cord. It was found that there was no gross hyperplasia on the left side, nor were there significant differences between the mean nuclear areas of the cells of the two sides. Significant differences did occur, however, in the distribution of nuclear sizes of the two sides. A greater proportion of the cells of the left side had large nuclear areas than did those of the right side. This points to a response of the lateral motor column to an increased periphery by increasing sizes of certain cells rather than by increasing cell numbers.

ISSN:0040-3709    

DOI:10.1002/tera.1420020211

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1969

数据来源: WILEY