bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitotic index in mouse embryos with 6‐aminonicotinamide‐induced and inherited cleft lip
Authors: Trasler Daphne G. , Leong Susanna 
Published: June 2005

AbstractThree types of cleft lip were studied histologically before and during lip formation in mouse embryos. C57BL/6 embryos observed near term following treatment with 6‐aminonicotinamide (6AN) at gestation D9/12 (vp day = day 0) had 18% median cleft lip. Treated embryos observed at D10 and D11 showed retarded somite and nasal placode development. Sections at lip closure time showed marked reduction of medial and some reduction of lateral nasal processes, and the mitotic index was significantly reduced in the nasal area on D10 and D11 but less consistently in the neural area. 6AN‐treatment on D10/8, caused 22% lateral cleft lip. Treated embryos showed initial retardation of somite and nasal placode development that became normal by D11/14. Sections showed reduction of the medial and lateral nasal processes, and less organized denser nasal ectoderm. The mitotic index was significantly reduced in the nasal and neural areas on D10 and D11. In crosses having the major gene mutation dancer (Dc) 20% of embryos had lateral cleft lip and potential cleft lip mutant embryos showed reduced lateral and medial nasal processes. Mitotic index was not reduced in the nasal area but it was in the neural area. The CL/Fr strain, with a predisposing face shape in which 26% of the embryos have cleft lip of multifactorial origin, had a mitotic index similar to that of C57BL/6 (0% cleft lip) at lip closure time, D11/14, and prominent medial nasal processes. It is postulated that 6AN‐induced median cleft lip is due to reduced cell proliferation in and size of the medial nasal processes; 6AN‐induced lateral cleft lip to reduced cell proliferation and reduced medial and lateral nasal processes and dancer lateral cleft lip to reduction of the medial nasals.
Conjoined Twins in the United States, 1970–1977
Authors: Edmonds Larry D. , Layde Peter M. 
Published: June 2005

AbstractThe descriptive epidemiology of conjoined twinning in the United States was investigated using data from the Birth Defects Monitoring Program (BDMP), a nationwide congenital malformations surveillance system that monitors discharge diagnoses associated with a third of the births in the United States. This is the largest recorded series concerning conjoined twins; data were analyzed on 7,903,000 births monitored by the BDMP in the period 1970–1977. The analysis identified 81 sets of conjoined twins, for a crude incidence of 10.25 per million births. The most common types of conjoined twins were thoracoomphalopagus (28%), thoracopagus (18%), omphalopagus (10%), parasitic twins (10%), and craniopagus (6%). Conjoined twins are more common among females than males, and in nonwhites than whites. No maternal age effect was found. There was no evidence of seasonal or temporal clustering of the cases. The large number of conjoined twins who had birth defects that are not obviously linked to the conjoining (particularly neural tube defects and orofacial clefts) may provide insights into the pathogenesis of birth defects resulting from disordered embryonic migration and fusion.
Sauna and congenital defects
Authors: Saxén Lauri , Holmberg Peter C. , Nurminen Markku , Kuosma Eeva 
Published: June 2005

AbstractTo test a recent hypothesis on the causal relationship between sauna‐induced hyperthermia and congenital defects, 100 consecutive cases of defects of the central nervous system and 202 cases of orofacial clefts were singled out from the Finnish Registry of Malformations. The mothers and their time‐area‐matched referents were interviewed for their sauna habits. Almost every pregnant mother (98.5%) had visited the sauna regularly, and yet, the incidence of the CNS defects in Finland is among the lowest ever reported. No differences in the sauna habits were observed between the case and referent mothers. It is concluded that the relatively mild, temporal hyperthermia caused by the sauna should not be considered hazardous for the developing embryo.
Inhibition of β‐aminopropionitrile (βAPN)‐induced skeletal teratogenesis by the flavonoid β‐hydroxyethylrutosides (HR) in hamster fetuses
Authors: Joneja M. G. , Wiley M. J. 
Published: June 2005

AbstractSince biochemical studies have shown that flavonoids such as β‐hydroxyethylrutosides (HR) protect against the damage to collagen induced by lathyrogens in adult rats, this compound was given to pregnant hamsters in order to determine its effects on the teratogenicity induced by β‐aminopropionitrile (βAPN). A dose of 2,500 mg/kg of βAPN alone given by gavage on day 11 produced a high frequency (69.5%) of skeletal anomalies in the offspring of hamsters. Administration of HR immediately following βAPN to pregnant animals resulted in a significantly decreased teratogenic response (P < 0.05). These data provide evidence to support the view that the primary mechanism for the βAPN‐induced skeletal dysmorphogenesis is the inhibition of cross linking during the maturation of collagen fibers.
Developmental abnormalities of the olfactory bulb: A comparative teratological and experimental study of the pig and chick embryo
Authors: Venneman W. , Van Nie C. J. , Tibboel D. 
Published: June 2005

AbstractWe collected newborn pigs with facial dysmorphy. In ten animals complete unilateral or bilateral hare lip was found to be associated with agenesis, aplasia, or hypoplasia of the olfactory bulbs. In order to get insight into a possible pathomorphogenetic relation between these types of clefts, malformations of the olfactory bulbs, and the role of the derivatives of the olfactory placode, the right olfactory placode was extirpated in 180 chick embryos at stage 17–18 according to Hamburger and Hamilton. Forty of the 78 surviving embryos showed shortening and deviation of the upper bill to the right, absence of the right nasal ostium, and agenesis of the right olfactory bulb. These results provide experimental evidence that the olfactory placode induces the outgrowth of the olfactory bulb. They further suggest an involvement of the olfactory placode in the normal development of the face.
Cyclopia: An anatomic and histologic study of two specimens
Authors: Kokich Vincent G. , Ngim Chun‐Han , Siebert Joseph R. , Clarren Sterling K. , Cohen M. Michael 
Published: June 2005

AbstractThe craniofacial complex of two neonatal, human, cyclopic specimens was studied in detail. Both specimens exhibited a single ocular opening and one had a prominent proboscis positioned in the midline directly superior to the ocular aperture. No external nasal development was noted in the other specimen. The most remarkable finding was the lack of development of all skeletal derivatives of the ethmoidal cartilage (cribriform plate, perpendicular plate, superior and middle nasal conchae, medial orbital walls, and nasal septal cartilage) in both specimens. Since these bones normally form the medial, lateral, and superior walls of the nasal passage, this cavity was also absent. The two posterior halves of the maxillae were directed superiorly, medially, and with the vomer merged in the midline as a thick mass of bone. As a result the right and left alveolar portions of the maxillae were joined superiorly in the midline. With the absence of the nasal cavity, the right and left medial pterygoid plates merged medially with the palatal and pyramidal processes of the palatine bone to obstruct the junction between the oropharynx and nasopharynx (choanal atresia). The role of the skeletal parts of the ethmoid during maxillofacial growth and development is discussed.
Teratogenesis and low copper status resulting from D‐penicillamine in rats
Authors: Keen Carl L. , Mark‐Savage Pamela , Lönnerdal Bo , Hurley Lucille S. 
Published: June 2005

AbstractThe teratogenicity of D‐penicillamine was studied using the Sprague‐Dawley rat. Fetuses from rats fed diets containing 0.83% D‐penicillamine during pregnancy had a high incidence of malformations. Maternal and fetal tissue copper levels were significantly lower in the D‐penicillamine group than in controls, suggesting that the teratogenicity of the drug may be due in part to the induction of copper deficiency by its chelating properties.
Effects of environmentally differential rearing upon maze performance in prenatally irradiated microcephalic rats
Authors: Seo Misako L. , Inouye Minoru , Kiyono Sigehiro , Shibagaki Masamitsu 
Published: June 2005

AbstractPregnant rats received 100 rads of X‐irradiation on day 17 of gestation. Control pregnant rats were sham‐irradiated on the same gestation day. The male offspring were reared under environmentally enriched, standard colony, and impoverished conditions for 30 days after weaning. Then the Hebb–Williams maze test was carried out. All the prenatally X‐irradiated rats were microcephalic: their mean cerebral wet weight was 15.5% less than controls. The effect of X‐irradiation was not significant in error scores and running times, whereas the effect of environment was significant in these items; initial and total error scores and running times were decreased in enriched groups compared to impoverished groups in controls as well as in X‐irradiated animals.
Teratogenic effects of lithium in mice
Authors: Smithberg Morris , Dixit Padmakar K. 
Published: June 2005

AbstractThe question of the teratogenicity of lithium carbonate was tested in two inbred strains of mice that are susceptible to teratogens. Strains 129 and A/J mice were treated with varying dosages of lithium carbonate on day 8, 9, or 10, and strain A/J mice were sequentially treated on days 11, 12, and 13 of gestation. Another group of mice of strain 129 were given lithium carbonate in drinking water throughout pregnancy. Levels of lithium were determined in mouse serum (and in brain) of mothers and their offspring with the purpose of comparing equivalent values in mice and in man. A baseline dosage of 0.8 mg of lithium carbonate was chosen, since this dose produced a serum lithium level of 0.8 meq/L, which is comparable to values of patients treated for manic‐depressive illness. This baseline dosage or 2 and 4 times this amount did not prove teratogenic in strain 129 mice. However, 5.0 mg (200 mg/kg), which is one‐half the LD50 value, caused 41% malformations. The baseline dosage did not cause malformations in strain A/J when given on day 11, 12, or 13 of gestation. Lithium carbonate given in the drinking water to strain 129 mice throughout pregnancy at a concentration that produces serum levels in mice consistent with human values was deleterious. The data suggest that whole or part of total litters were eliminated. The few survivors were apparently normal. Our results suggest that 6 times the therapeutic serum lithium level in humans is teratogenic in mice, as tested by acute experiments. Chronic treatment with a quantity of lithium that produces a serum level equivalent to that of human values is toxic to whole or part of the litters of mice.
A study of fetal growth retardation in teratological tests: Relationship between body weight and ossification of the skeleton in rat fetuses
Authors: Ariyuki Fumio , Ishihara Haruo , Higaki Koh , Yasuda Mineo 
Published: June 2005

AbstractThe normal development of preterm rat fetuses (day 19.0 to day 21.0) was investigated with respect to body weight and ossification of the sacrococcygeal vertebrae, supraoccipital bone, sternebrae, and proximal phalanges in the forepaw. Normal standard growth curves were established for these indexes in rat fetuses. A method was devised for the analysis of the relationship between low body weight and retarded ossification induced by teratogenic agents. In normal fetuses, mean body weight and number of ossified sacrococcygeal vertebrae and the ossification stage of the supraoccipital bone increased approximately linearly with advancing fetal age. The number of ossified sternebrae and proximal phalanges in the forepaw increased curvilinearly with advancing fetal age. By use of the standard curves, fetal growth retardation observed in teratological experiments may be expressed as retardation in relation to the standard in hours. The characteristic pattern of growth retardation induced by an agent may be evaluated by comparison of the degree of retardation expressed in a common “hour” scale among various growth indexes. This method was applied to experimental data of fetal growth retardation induced by maternal fasting. The degree of retardation was found to differ among growth indexes; body weight and ossification of the sacrococcygeal vertebrae were the most severely retarded; ossification of the supraoccipital bone and the sternebrae was moderately retarded; ossification of the proximal phalanges in the forepaw was least retarded.
Blood flow during pregnancy in the rat: I. Flow patterns to maternal organs
Authors: Buelke‐Sam J. , Nelson C. J. , Byrd R. A. , Holson J. F. 
Published: June 2005

AbstractNormal blood flow patterns to several maternal organs were characterized in individual CD rats, nonpregnant (NP) or on day 6, 7, 8, 10, 11, 12, 13, 16, 18, or 20 of gestation using the radioactive microsphere technique. Weights and flow values were determined for several uterine tissue samples as well as maternal organs. No significant changes were found in blood flow to the stomach, spleen, and urinary bladder of these animals. There also were no remarkable changes as pregnancy progressed in blood flow to the lungs, suggesting that no marked arterial‐venous shunting occurs in maternal placental tissues over gestation. Slight but consistent decreases in absolute (ml/min) and relative (ml/min/g tissue) blood flow to the brain were noted, and percent cardiac output (CO) was significantly decreased on all days of gestation except day 7. Complex changes were observed in blood flow to the kidneys, liver, adrenals, and heart. Absolute flow to the kidneys and liver reached maximum values on day 11, although percent CO delivered to both organs was consistently reduced throughout gestation. Absolute flow to the heart and adrenals peaked on day 13 and days 11–12, respectively. Absolute flow to the ovaries increased nearly 5‐fold from the NP state (0.36 ± 0.11) to day 20 of pregnancy (1.61 ± 0.33). Interlitter differences in ovarian blood flow during midgestation were found to be a result of differences in litter size and distribution of embryo/fetuses between the two uterine horns. The fact that the majority of changes observed in maternal organ flow coincide with placental development, rapid augmentation of total uterine flow, and/or maternal hormonal changes suggests that these patterns may be important indicators of the dynamic physiology of pregnancy.
Teratogenicity in vitro of 2‐acetylaminofluorene: Role of biotransformation in the rat
Authors: Faustman‐Watts E. , Greenaway J. C. , Namkung M. J. , Fantel A. G. , Juchau M. R. 
Published: June 2005

Abstract2‐Acetylaminofluorene (AAF), a highly effective mutagen and carcinogen, was tested as a direct‐acting teratogen in an embryo culture system. Concentrations of up to 75 μg/ml (336 μM) of AAF produced no detectable malformations and only minimal decreases in viability and growth of rat embryos explanted on day 10 (11th day of gestation; the day after fertilization was designated as day 0). Inclusion of a microsomal monooxygenase system (prepared from rat liver) in the culture medium, however, resulted in marked changes in viability and growth. All explanted embryos exposed to concentrations of AAF above 60 μg/ml (269 μM) plus the microsomal monooxygenase system exhibited readily observable malformations as well as significant decreases in size and macromolecular content. Two metabolites, N‐hydroxy‐2‐acetylaminofluorene (N‐OH‐AAF) and N‐acetoxy‐2‐acetylaminofluorene (AAAF), each produced malformations in the absence of a monooxygenase system. At concentrations of 25 μg/ml (105 and 88 μM) approximately 50% of the embryos exposed to these metabolites were malformed. The predominant malformations associated with the metabolites were ventrolateral protrusions and hypoplasia of the prosencephalic region, whereas AAF plus the monooxygenase system produced an interruption of neural tube closure. This suggested the possibility that other metabolites may participate in the AAF‐induced malformation syndrome. The addition of the monooxygenase system to cultures containing N‐OH‐AAF or AAAF increased the frequency of malformations without increasing lethality or decreasing growth.
Ionic effects on strain differences in hepatic cytosolic glucocorticoid receptor levels in mice
Authors: Harper Kenneth J. , Erickson Robert P. 
Published: June 2005

AbstractIonic conditions were varied during homogenization of adult livers and during incubation of hepatic cytosol with glucocorticoid, and the effects on the detection of differences between inbred strains of mice for receptor levels were studied. When homogenized directly in 0.01 M Tris or homogenized in distilled water and then buffered to either 0.05 M Tris or 0.01 M potassium phosphate, A/J glucocorticoid receptor levels were greater than those of B10.A. However, when homogenized directly in 0.05 M Tris or buffered to 0.05 M potassium phosphate after homogenization in distilled water, A/J and B10.A had similar receptor levels. When buffered to 0.01 M Tris after homogenization in distilled water, A/J receptor levels were greater than those of B10.A but not significantly so. In Tris buffers, glucocorticoid receptor levels were higher when livers were homogenized directly in buffer than when liver homogenates were buffered after homogenization. This concentration effect is apparently due to the more rapid decay of glucocorticoid receptor in the lower molarity buffer. A reducing agent, thioglycerol, did not appear to affect either the rate of decay of the receptors or the measured level of receptor for B10.A and A/J. C57BL/6J receptor levels were measured in Tris buffers and had a similar relationship to A/J as did B10.A.
Another specific effect of prenatal acetazolamide exposure in the mouse
Authors: Beck Sidney L. 
Published: June 2005

AbstractSubcutaneous injection of pregnant mice on day 8 of gestation with 1,000 mg/kg or 200 mg/kg of an aqueous solution of the sodium salt of acetazolamide, divided into three equal treatments at 8‐hour intervals, in two series of experiments performed 8 months apart on separately purchased random bred CD‐1 animals, resulted in the occurrence of a novel variant of the frontal bones of the skull when animals exposed in utero were examined at 62 ± 2 days postnatal.In its greatest manifestation this variation consisted of a 2–3 mm posteriad extension of the dorsomedial portion of the posterior margin of both bones, although all degrees of asymmetry and variations in the extent of involvement of the posterior margin of the bones were seen. This frontal extension variant was seen in 30.9 ± 4.7% and 53.1 ± 5.0% of the 97 and 98 specimens in the highdose groups, and in 8.1 ± 2.7% and 14.6 ± 3.7% of the 99 and 89 low‐dose specimens in the two series. It was not seen in untreated groups, or to any significant extent in vehicle‐treated groups, or in a treatment regime involving exposure during days 9–11 of gestation. It was also not seen in 2,110 specimens from four other series of experiments reported in detail involving the teratogens, trypan blue (two series), 5‐bromodeoxyuridine, or 2,4,5‐T, or in approximately 1,000 specimens from comparable experiments with a variety of pesticides (Maneb, Captan, Trifluralin, Decamethrin) or Thalidomide.In contrast, a morphologically analogous variant, accessory parietal, in which a suture in the anterodorsal surface of the parietal bones running posteromedial and seemingly delimiting a separate bone, is seen in all series. Although it looks as though frontal extension could be an accessory parietal fused with the frontal bone, observation of the specimens does not strongly support that relationship. Even if that were the case, it happens only in day‐8 acetazolamide exposure.From the rather extensive series of observations performed, it would appear that frontal extension is a specific response to in utero exposure to acetazolamide during the day 8 of gestation.
Peripheral nerves do not play a trophic role in limb skeletal morphogenesis
Authors: Strecker Teresa R. , Stephens Trent D. 
Published: June 2005

AbstractResearch was undertaken to test the hypothesis that thalidomide‐induced limb defects resulted from damage to the neural crest or peripheral nerves and that normal limb development depends upon either the quality (level specific) or quantity of peripheral nerves. Barriers which were placed into early chick embryos to block brachial plexus‐level neural crest cells from reaching the limb resulted in normal limb skeletons. These data agree with previous work in suggesting that skeletal morphology is independent of innervation.
Maternal exposure to exogenous sex hormones in relation to birth weight of offspring
Authors: Polednak Anthony P. , Janerich Dwight T. , Glebatis Donna M. 
Published: June 2005

AbstractBirth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (<25, 25–29, and 30–39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for “threatened abortion,” but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal growth.
Pharmacology of dextroamphetamine‐induced cardiovascular malformations in the chick embryo
Authors: Cameron Ray H. , Kolesari Gary L. , Kalbfleisch John H. 
Published: June 2005

AbstractWe have observed dextroamphetamine sulfate to cause cardiovascular malformations in the 4‐day‐old chick embryo. Essentially all malformations were of the heart and great vessels. About one‐half of these were the abnormal persistence of the left fourth aortic arch. Ventricular septal defects comprised the vast majority of the other malformations. Since d‐amphetamine has both a direct and, more importantly, an indirect mode of alpha and beta adrenergic stimulation, three drugs were used to try to inhibit malformation production: alpha‐methyl‐p‐tyrosine (AMT), a catecholamine synthesis inhibitor; metoprolol, a beta1 blocker; and phentolamine, an alpha blocker. When given with d‐amphetamine, all three drugs significantly reduced the malformation rate resulting from d‐amphetamine alone. We speculate that the embryonic chick is capable of responding to the alpha and/or beta properties of dextroamphetamine sulfate. These properties may be causally related to the malformations observed.