bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiopathic effects of dichloroacetate in the fetal long‐evans rat
Authors: Epstein D. L. , Nolen G. A. , Randall J. L. , Christ S. A. , Read E. J. , Stober J. A. , Smith M. K. 
Published: June 2005

AbstractDichloroacetic acid (DCA) is a by‐product of the chlorine disinfection of water and may occur in treated water at levels exceeding 100 μg/L. Previous studies revealed teratogenic effects, particularly heart malformations, at high doses (900–2,400 mg/kg given on days 6–15 of pregnancy). In a series of three studies, groups of 7–10 Long‐Evans rats were dosed with 1,900 mg/kg of DCA on days 6–8, 9–11, or 12–15; with 2,400 mg/kg on days 10, 11, 12, or 13; and with 3,500 mg/kg on days 9, 10, 11, 12, or 13, in an attempt to determine the most sensitive period and further characterize the heart defect. In a fourth study, six dams were treated with 1,900 mg/kg of DCA days 6–15 of pregnancy, and 56 fetuses were harvested for light microscopy of the heart. Eight control fetuses from four litters were also examined. No heart malformations were seen in the groups treated with 1,900 mg/kg DCA days 6–8 but were present in the group treated on days 9–11 and 12–15, with the higher incidence occurring on days 12–15. Single doses of 2,400 mg/kg DCA given on days 10, 11, 12, or 13 resulted in a much lower incidence of cardiac malformations, which occurred only on days 10 and 12. The high dose of DCA (3,500 mg/kg) did not increase the incidence of heart defects but showed that dosing on day 9 as well as on days 10 and 12 would produce the defect. The defects seen were characterized as high interventricular septal defects (H‐IVSD). Light microscopy showed that the defect was caudal to the semilunar valves, with the anterior right wall of the aorta communicating with the right ventricle. Another aspect of the defect is at the level of the semilunar valves, with the right cusp or sinus of Valsalva in communication with the right ventricle. The defects are discussed more fully and methods for further study suggested. © 1992 Wiley‐Liss, Inc.
Standardized residuals as a means for detection of growth alteration in the pathologic human fetus
Authors: Sherwood Richard J. , Robinson Haynes B. , May Richard L. , Meindl Richard S. 
Published: June 2005

AbstractThis paper introduces and discusses the use of standardized residuals as a technique for comparing the growth of normal and pathologic human fetuses. Anthropometric measures, radiographic measures, and organ weights were regressed on known gestational age of second‐ and third‐trimester fetuses. Standardized residuals were calculated for a group of potentially growth‐impaired fetuses. Use of residuals aids in identification of patterns of growth alteration in specific pathologies. Most important, studying the response of developing organ systems to a variety of insults may elucidate mechanisms of growth regulation in the fetus. We emphasize the special quality of the multivariate measures of the core sample of fetuses from the Akron Children's Hospital collection. © 1992 Wiley‐Liss, Inc.
Absence of limbs and gross body wall defects: An epidemiological study of related rare malformation conditions
Authors: Mastroiacovo Pierpaolo , Källén Bengt , Knudsen Lisbeth B. , Lancaster Paul A. L. , Castilla Eduardo E. , Mutchinick Osvaldo , Robert Elisabeth 
Published: June 2005

AbstractThe study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed. © 1992 Wiley‐Liss, Inc.
Association of paternal alcohol use with gestational age and birth weight
Authors: Savitz David A. , Zhang Jun , Schwingl Pamela , John Esther M. 
Published: June 2005

AbstractPaternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (<37 weeks completed gestation), moderately low birth weight (1,501–2,500 g), very low birth weight (≤1,500 g), small‐for‐gestational‐age (<10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose‐response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome. © 1992 Wiley‐Liss, Inc.
Omphalocele and gastroschisis: A collaborative study of five Italian congenital malformation registries
Authors: Calzolari E. , Volpato S. , Bianchi F. , Cianciulli D. , Tenconi R. , Clementi M. , Calabro A. , Lungarotti S. , Mastroiacovo P. P. , Botto L. , Spagnolo A. , Milan M. 
Published: June 2005

AbstractDuring 1984–1989, 116 cases of omphalocele and 42 cases of gastroschisis were detected among 736,760 consecutive births in the area covered by five Italian congenital malformation registries. The prevalence rate was 1.6 per 10,000 for omphalocele and 0.6 per 10,000 for gastroschisis. Three additional cases were detected among spontaneous abortions, giving a total of 117 cases of omphalocele and 44 of gastroschisis. No variations in prevalence rates were observed among registries. A cluster of omphalocele was found in 1989 in Firenze. All cases were sporadic except for one infant with two sibs with Beck‐with–Wiedemann syndrome. A predominance of male infants was observed for both defects. This study confirms the very young maternal age for isolated gastroschisis as compared to that for omphalocele and controls. Birth weight and the percentage of small‐for‐date is different among isolated gastroschisis, omphalocele and controls. Associated anomalies occurred in 45 cases of omphalocele and 11 cases of gastroschisis. Our data confirm the association of omphalocele with trisomies 13 and 18. Twelve cases of omphalocele and gastroschisis with associated limb defects were classified as limb body wall complex. The possible differences in etiopathology between omphalocele and gastroschisis, both isolated and associated, are discussed. © 1993 Wiley‐Liss, Inc.
Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): III. Developmental and hematologic studies
Authors: Tarantal A. F. , O'Brien W. D. , Hendrickx A. G. 
Published: June 2005

AbstractThe multiple applications of diagnostic ultrasound in obstetrics have resulted in a continued rise in the prenatal population exposed each year. Although human epidemiologic and experimental studies with various animal models have not consistently documented any significant, reproducible findings related to clinically relevant exposures, technologic changes in scanning equipment and gaps in our knowledge regarding the interaction(s) of ultrasound with tissues emphasize the need to pursue safety issues. Studies with nonhuman primates have provided information on the potential for pre and postnatal effects on offspring exposed repeatedly during gestation (ATL MK 600, 7.5 MHz, ISPTA = 27 m W/cm2; ISPPA = 85 W/cm2; Estimated power = 12 m W—scanned for 10 min 5 times weekly gestational day [GD] 20–35; 3 times weekly GD 36–60; once weekly for 20 min GD 60–150). These studies have indicated transient effects on body weight, white blood cell counts (WBCs), and muscle tone postnatally. In an effort to confirm these findings and focus on hematologic changes, a second series of studies was initiated using the same exposure conditions (N = 22; 11 exposed, 11 sham controls). Data derived from both studies were combined and confirmed transient reductions in body weights for infants up through 4 months of age (P ⩽ 0.03); no statistically significant differences in muscle tone were noted. Similar to the original findings, WBCs were transiently reduced on days 3 (P ⩽ 0.02) and 21 (P ⩽ 0.05); prenatal sampling indicated a significant difference between the groups on GD 140 (P ⩽ 0.04). No direct effects were evident in bone marrow aspirates collected on postnatal days 3, 9, and 21 ± 1. Although animals were able to compensate for these observed changes and remained unaffected by their occurrence, additional studies will be required to further our understanding of this phenomenon. © 1993 Wiley‐Liss, Inc.
Developmental toxicity of caffeine in the larvae of Xenopus laevis
Authors: Sakamoto Michiko K. , Mima Shin , Kihara Takahide , Matsuo Takuya , Yasuda Yoshiko , Tanimura Takashi 
Published: June 2005

AbstractTo examine the developmental toxicity of caffeine, Xenopus larvae just after hatching, were continuously exposed to 100–2,000 mg/L caffeine for 48 hours. Caffeine interfered with development of Xenopus larvae at a concentration of 100 mg/L and above in a concentration‐dependent manner. Characteristic external abnormalities, such as shortened body with wavy fins, were observed, the severity of which was clearly concentration dependent. These larvae were frequently accompanied by abnormal body flexure and edema in the fin. Light microscopy revealed that exposure to caffeine induced severe damage in the myotome and neural tube, and at higher concentrations, the epidermal tissue was also affected. Myoblasts showed wide intercellular spaces, and their cytoplasm lost uniform staining. Ultrastructural studies of myoblasts revealed distinct myofibril disorganization and degeneration, and mitochondrial alterations. In the neural tube, cells at the dorsal part of tube showed wide intercellular spaces and some of them were segregated to the peripheral region. Furthermore, vacuole‐like structures of various sizes appeared in the white matter. The outer layer of epithelial cells in the epidermis were vacuolated and swollen. With regard to the pathogenesis of myofibril damage, caffeine appeared to cause a disturbance of intracellular calcium regulation, by releasing calcium ions from the sarcoplasmic reticulum, and the mitochondrial changes observed in myotomal cells were considered to be reflective of this increased intracellular calcium ion levels. It is speculated that caffeine interferes with cell adhesion in the myotome and neural tube by affecting calcium ion regulation. © 1993 Wiley‐Liss, Inc.
Preovulatory administration of clomiphene citrate to mice causes fetal growth retardation and neural tube defects (exencephaly) by an indirect maternal effect
Authors: Dziadek Marie 
Published: June 2005

AbstractClomiphene citrate was administered to female mice at different doses and different times prior to ovulation, in the preimplantation period after ovulation, and after implantation. Pregnancy outcome was determined on day 15 of gestation, when the number of implantations and resorptions were calculated relative to the number of ovulations, and fetuses were assessed for size and stage of development and morphological abnormalities. Preovulatory administration of clomiphene citrate caused decreased implantation rates and growth retardation of surviving fetuses, the degree of the effect being dependent on the dose and the time of drug injection relative to ovulation. The implantation rate was lowest, and the degree of fetal growth retardation highest, when clomiphene citrate was administered immediately before ovulation. An increased incidence of exencephaly was found in the fetuses of females injected with clomiphene citrate prior to ovulation. Transfer of blastocysts from treated mice to untreated fosters showed the effect of clomiphene citrate on implantation and fetal growth to be predominantly mediated through the female reproductive tract, rather than a direct effect on the embryo itself. Administration of clomiphene citrate in the preimplantational period resulted in complete inhibition of implantation, while the only effect when administration was after implantation was a slight reduction in fetal weight. These results indicate that preovulatory clomiphene citrate impairs uterine function, which has an indirect effect on the growth and development of the postimplantation embryo. © 1993 Wiley‐Liss, Inc.
Dose‐response models for developmental malformations
Authors: Gaylor David W. , Chen James J. 
Published: June 2005

AbstractAn empirical dose‐response model can generally be found for bioassay data, which provides a mathematical relationship between the incidence of a developmental malformation and dose of a toxicant in the experimental dose range. If biological principles and data can be used in the formulation of the dose‐response model, the estimation of the incidence of malformations outside of the experimental dose range may be improved. In this paper, exponential growth of morphological structures in rodents during gestation is assumed. Further, it is assumed that some structural malformations are the result of reduced or delayed growth and the incidence of structurally normal fetuses is proportional to fetal weight raised to a power. When the exponential growth rate constant is reduced by dose raised to a power, a Weibull dose‐response function is obtained. When the exponential growth rate constant is modeled by a polynomial function of dose, a polynomial‐exponential dose‐response model is obtained. The Weibull and the polynomial‐exponential model, restricted to degrees from one up to the number of dosed groups, were fit to a database of bioassay data assembled from Teratology Vol. 1 (1968) to Vol. 42 (1990). In general the two models gave similar results and often gave exactly the same fit. The linear term appeared in the polynomial‐exponential model in about one‐fourth of the cases and was not related to the background incidence. Published 1993 by Wiley‐Liss, Inc.
Ataxia and a cerebellar defect in the exencephaly‐prone SELH/Bc mouse stock
Authors: Juriloff D. M. , Harris M. J. , Harrod M. L. , Gunn T. M. , Miller J. E. 
Published: June 2005

AbstractSELH/Bc inbred mice have an abnormal mechanism of anterior neural tube closure and 10–20% of embryos have a lethal neural tube closure defect, exencephaly. Our previous studies have focused on this multifactorial threshold trait. However, SELH mice are also characterized by another trait that also shows non‐Mendelian transmission ratios, an ataxia recognized in juvenile and adult mice. Here we report our first genetic and morphological studies of the ataxia trait. Recent pedigree records for the SELH colony showed that 7% of the 467 weaned progeny from normal breeding pairs were ataxic; 17 of the 20 pairs produced ataxic progeny. This result was statistically consistent with the hypothesis that all SELH mice have the ataxic genotype, which is expressed in only 7% of them. Genetic studies of an outcross to a normal strain and the subsequent F2 and testcross of the F2 were also done. The results were consistent with a one or two gene locus cause of liability to ataxia in SELH mice. The genetic correlation between exencephaly production and ataxia production for a sample of nine F2 males was 0.35, as expected if both traits are caused by the same genes, but was not statistically significant. In another approach, we examined the morphology of brains from normal and ataxic adult SELH mice. All 20 brains from non‐ataxic SELH mice were morphologically normal. In all 18 brains from ataxic SELH mice the cerebellum was abnormal, lacking the vermis, and characterized by a midline fissure. This phenotype in mice has previously been known in Mendelian mutants at the Wnt‐1 locus. Our observations in SELH mice suggest that these cerebellar defects can also show multifactorial threshold patterns of occurrence. Because the site of origin of the cerebellum is the site of maximal delay in neural tube closure in SELH mice, the exencephaly and ataxia may share a common genetic etiology. © 1993 Wiley‐Liss, Inc.
Effects of Retinoic acid on cartilage differentiation in a chondrogenic cell line
Authors: Lau W. F. , Tertinegg I. , Heersche J. N. M. 
Published: June 2005

AbstractPreviously we have isolated the monopotential chondrogenic cell line RCJ 3.1 C5.18 from the multipotential mesenchymal cell line RCJ 3.1 [Grigoriadis et al.: Endocrinology, 125:2103–2110, 1989]. When cultured for approximately 20 days under appropriate conditions, these cells form cartilage nodules. In the present investigation, we have used this cell line to study the effects of all‐trans retinoic acid (RA) on chondroblast differentiation, cartilage formation, and cartilage degradation. Continuous exposure of cultures to RA (0.01–100 nM) inhibited chondroblast differentiation and glycosaminoglycan (GAG) accumulation in a dose‐dependent manner, without comparable effects on cell growth. Pulse treatment with RA for various 4 day periods during a 17–24 day culture period established that RA inhibited differentiation of chondroprogenitors at all periods tested. These effects were reversible, except for part of the effect on early chondroprogenitors. Treatment with RA on days 13–17 in 17 day cultures not only resulted in cessation of cartilage formation, but also in disappearance of pre‐existing cartilage nodules. We demonstrated that this was associated with RA‐induced downregulation of GAG synthesis and increased degradation of cartilage proteoglycans. Hence, the inhibitory effects of RA on cartilage formation consist of inhibition of chondroblast differentiation, inhibition of GAG synthesis by differentiated chondroblasts, and stimulation of cartilage proteoglycan degradation by differentiated chondroblasts and/or chondrocytes. These results indicate that the clonal monopotential chondrogenic cell line RCJ 3.1 C5.18 forms a good model system to study the effects of retinoids on cartilage differentiation, formation, and degradation. © 1993 Wiley‐Liss, Inc.
Serotonin and cardiac morphogenesis in the mouse embryo
Authors: Yavarone M. S. , Shuey D. L. , Tamir H. , Sadler T. W. , Lauder J. M. 
Published: June 2005

AbstractThe possible involvement of the neurotransmitter serotonin (5‐HT) and its binding protein (SBP) in cardiac morphogenesis was studied using mouse whole embryo culture (together with immunocytochemistry or 3H‐thymidine autoradiography) and a cell migration assay. Embryos were cultured before and during the period of endocardial cushion formation, embryonic (E) days 9–12, in the presence of 5‐HT, the monoamine oxidase (MAO) inhibitor nialamide, or an uptake inhibitor (fluoxetine or sertraline). For the migration assay, cells from the outflow tracts of E12 embryos were dissociated and placed in a chemotaxis chamber together with different concentrations of 5‐HT. E9 embryos cultured in the presence of 10 μM 5‐HT and nialamide exhibited intense 5‐HT immunoreactivity (5‐HT IR) throughout the myocardium. This staining was greatly diminished by fluoxetine, sertraline, or the absence of nialamide. As morphogenesis proceeded, myocardial staining in embryos exposed to 5‐HT became restricted to developing endocardial cushion forming regions and was more completely blocked by uptake inhibitors. No evidence for 5‐HT synthesis by myocardium was found at any age studied using the precursor L‐tryptophan. SBP was present in endocardial cushions in cultured and uncultured embryos. 3H‐thymidine autoradiography demonstrated that both fluoxetine and sertraline inhibited proliferation of cardiac mesenchyme, endocardium, and myocardium. These effects were most pronounced when exposure began at E9 (prior to cushion formation). Dose‐dependent effects of 5‐HT on migration of outflow tract cells were also observed. Taken together, these results suggest that 5‐HT may play a role in cardiac morphogenesis during endocardial cushion formation. © 1993 Wiley‐Liss, Inc.
Embryonic development of the mammalian caudal Neural Tube
Authors: Nievelstein R. A. J. , Hartwig N. G. , Vermeij‐Keers C. , Valk J. 
Published: June 2005

AbstractIn the literature, some controversy still exists about the embryonic developmental processes involved in the formation of the caudal neural tube. Therefore, a three‐dimensional and histological study concerning the normal development of the caudal neural tube was performed on both mouse and human embryos. Three developmental processes can be distinguished in caudal neural tube development: caudal neuropore closure, secondary neurulation, and degeneration and differentiation of the secondary neural tube. Caudal neuropore closure occurs at the level of somite 32–34 in both species. Therefore, primary neurulation leads to the formation of all spinal cord segments and ganglia. Secondary neurulation involves cell deposition from a cluster of neurectodermal cells at the caudal end of the closed neural tube, directly around a lumen, the lumen always in contact with the lumen of the primary neural tube. This process leads only to the formation of the primordia of the filum terminale and ventriculus terminalis and, possibly, part of the conus medullaris. Secondary neurulation is followed by a period characterized by degeneration and differentiation of the secondary neural tube. Its lumen and neural tissue will disappear, whereas part of the secondary neurectodermal cells differentiate to a fibrous layer comparable and continuous with the marginal layer of the primary neural tube. This fibrous layer represents the future filum terminale. The embryological processes indicated above can be helpful in the interpretation of congenital anomalies affecting the caudal spinal cord and spine. © 1993 Wiley‐Liss, Inc.