bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical double‐staining for Ah receptor and ARNT in human embryonic palatal shelves
Authors: Abbott B. D. , Probst M. R. , Perdew G. H. 
Published: June 2005

AbstractThe aryl hydrocarbon receptor (AhR) and the AhR nuclear translocator protein (ARNT) are basic–helix–loop–helix‐PAS (HLH) proteins involved in transcriptional regulation. Polycyclic aromatic halogenated chemicals, of which 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is the most potent, bind to the AhR. In the cellular cytoplasm, the AhR exists as a complex with the heat shock protein HSP90 and other small peptides. This complex dissociates following ligand binding and then the ligand‐bound AhR binds ARNT. The ligand–AhR–ARNT complex interacts with a specific, nuclear DNA sequence, the dioxin response elements (DRE), altering transcription of a regulated gene. Studies in hepatoma cell lines indicate that both proteins are required for regulation of transcription. In this study, AhR and ARNT were localized immunohistochemically in human embryonic palatal cells and specific patterns of expression were seen for each protein. A double‐staining protocol revealed that epithelial cells expressed both AhR and ARNT, but in mesenchyme and nasal spine cartilege individual cells were identified which expressed either AhR or ARNT. This heterogeneous pattern may be a means of suppressing transcriptional regulation and also suggests the existence of other, unidentified basic–helix–loop–helix partner(s). The heterogeneous expression pattern may also reflect a complex role for these HLH proteins as transcriptional regulators of embryonic development. © 1994 Wiley‐Liss, Inc.
Early events following maternal exposure to 5‐fluorouracil lead to dysmorphology in cultured embryonic tissues
Authors: Shuey D. L. , Buckalew A. R. , Wilke T. S. , Rogers J. M. , Abbott B. D. 
Published: June 2005

AbstractThe chemotherapeutic agent 5‐fluorouracil (5‐FU) is teratogenic in a number of species, yet the mechanism(s) of its developmental toxicity are not fully understood. Administration of 5‐FU to the pregnant CD rat on day 14 of gestation results in dose‐dependent growth retardation and numerous malformations in near‐term fetuses, including hindlimb defects and cleft palate. Following treatment, a number of rapid biochemical and cellular alterations are detectable in embryonic hindlimbs, craniofacial and other tissues, which include thymidylate synthetase (TS) inhibition and altered cell cycle progression. In order to assess the importance of these early events in 5‐FU‐induced dysmorphogenesis, embryonic mid‐facial tissues and hindlimbs were dissected 3 or 6 hr after administration of 5‐FU to the dam and placed in explant culture. After 5 days in culture, craniofacial explants were evaluated morphologically for palatal closure and growth was assessed by measuring total protein and DNA content. Hindlimb explants were stained for cartilage using alcian blue to evaluate development of the digits. Craniofacial explants cultured at either 3 or 6 hr after exposure exhibited dose‐dependent growth retardation and defects of palatal fusion at the end of the culture period. Deficits in protein and DNA content were similar to those in craniofacial tissues that continued to develop in utero after treatment, although morphological defects in cultured explants did not correlate well with the incidence of cleft palate in vivo. Dose‐dependent deficits in metatarsal and phalanx development were observed in hindlimb explants dissected either 3 or 6 hr after maternal treatment. These results suggest that events sufficient to produce growth retardation and dysmorphogenesis occur within 3 hr of 5‐FU administration, and support the hypothesis that direct, rapid, and short‐lived biochemical and cellular changes in embryonic target tissues (i.e., TS inhibition, cell cycle alterations, and/or as yet unidentified events) are the critical mechanistic events in 5‐FU developmental toxicity. © Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Growth Profiles of human autosomal trisomies at midgestation
Authors: Barr Mason 
Published: June 2005

AbstractSomatic and visceral growth profiles of midgestation human fetuses with trisomy 21, 18, or 13 demonstrate that each disorder has a characteristic pattern of growth aberration. The most striking deviations are short limbs in trisomy 21, subnormal adrenal and lung weights in trisomy 18, and supranormal spleen and kidney weights in trisomy 13. © 1994 Wiley‐Liss, Inc.
Axial rotation in rat embryos: Morphological analysis and microsurgical study on the role of the allantois
Authors: Fujinaga Masahiko , Hoffman Brian B. , Baden Jeffrey M. 
Published: June 2005

AbstractIn mouse and rat embryos, the embryonic disc develops within a cup‐shaped “egg cylinder” and consists of an inner layer of ectoderm and an outer layer of endoderm. Because of this configuration, the embryo first develops in a dorsally flexed position and then undergoes “axial rotation” to a ventrally flexed position. In the present study, we first analyzed the morphological process of axial rotation in rat embryos using novel reference axes set in the egg cylinder that remained invariant during the process. Our new perspective allowed us to demonstrate that the process consists of three movement which start at different stages of development: twisting of the upper body at stage 12/s7–8, twisting of the middle body at stage 13/s11–12, and twisting of the lower body (so called “tail”) at stage 14/s15–16. Axial rotation is an interesting developmental event not only because it is such a dynamic process but also because it is one of the earliest morphological sings of body asymmetry. This asymmetry is strongly biased in that tail almost always finishes up on the right side of the embryo for reasons that are still unknown. In the second part of the study, we preformed microsurgical experiments to extend our previous finding that removal of the allantois results in random determination of tail sidedness. We demonstrated that an allantois transplanted from another embryo can prevent this abnormal sidedness in an embryos whose allantois had been removed and that transecting the allantois did not lead to abnormal tail sidedness. A possible explanation is that the allantois produces a chemical factorthat controls tail sidedness. © 1995 Wiley‐Liss, Inc.
Interactions of Wnt‐1 and Wnt‐3a are essential for neural tube patterning
Authors: Augustine Karen A. , Liu Edison T. , Sadler T. W. 
Published: June 2005

AbstractWnt‐1 and Wnt‐3a have been postulated to share functional redundancy in spinal cord morphogenesis due to their homologies in protein structure and overlapping expression patterns. In this study, antisense oligonucleotides and a murine whole embryoculture system were used to examine functional interactions of Wnt‐1 and Wnt‐3a in late gastrulation and neurulation. Early somite mouse embryos were injected with combinations of Wnt‐1 and Wnt‐3a antisense oligonucleotides and then grown in vitro for up to 48 hr. Simultaneous inhibition of Wnt‐1and Wnt‐3a expression resulted in pattern loss in the presumptive spinal cord, which was apparent within 4 hr following antisense treatment. The neural tube was wavy, there was a reduction in the number of nuclear layers in the walls of the neural tube, and evidence of decreased cell adhesion between neuroepithelial cells by 12 hr postinjection. In addition, notochord and primitive streak abnormalities accompanied neural tube abnormalities. The existence of regulatory interactions between Wnt‐1, Wnt‐3a, and engrailed genes was also examined in this study. Antisense inhibition of Wnt‐1 or Wnt‐3a expression resulted in reduction of engrailed protein levels in the brain, somites, and spinal cord. However, simultaneous inhibition of both Wnt genes resulted in more complete loss of engrailed protein in these regions. Herein, we present data suggesting functional redundancy of Wnt‐1 and Wnt‐3a in neural tube patterning and in regulation Of engrailed expression. © 1995 Wiley‐Liss, Inc.
Development of the olfactory nerve: Its relationship to the craniofacies
Authors: Braddock Stephen R. , Grafe Marjorie R. , Jones Kenneth L. 
Published: June 2005

AbstractAlthough absence of the olfactory bulbs is a relatively common occurrence seen in holoprosencephaly, in Kallman syndrome, and in a number of malformation syndromes, the extent to which it determines olfactory nerve development, as well as the part it plays in the morphogenesis of the nasal structures, is unknown. Cases of arhinencephaly ascertained at autopsy were studied in an effort to better understand the relationships between the olfactory nerve, bulb, and facies. Based on these studies, it is concluded that both olfactory receptor cells and olfactory nerves are present in arhinencephaly, that the olfactory nerves did not make contact with the brain in these cases, that the presence of olfactory nerves is independent of the severity of the central nervous system malformation, and that the shape of the nasal sturctures is not dependent on the presence of the olfactory nerve. © 1995 WiIey‐Liss, Inc. © 1995 Wiley‐Liss, Inc.
Cellular adaptation to chronic cadmium exposure: Intracellular localization of metallothionein protein in human trophoblast cells (JAr)
Authors: Breen John G. , Nelson Eric , Miller Richard K. 
Published: June 2005

AbstractTrophoblast cells are the first embryonic cells that modulate the transfer of a variety of compounds (oxygen, amino acids, xenobiotics, metals) from the maternal to the fetal circulation in the human placenta. Human placental exposure to the toxic metal, cadmium (Cd) results in a decrease in the production of human chorionic gonadotropin (hCG), a decrease in the maternal to fetal transport of zinc (Zn), and trophoblastic necrosis. Thus, the ability of trophoblast cells to adapt to exposure to the toxic metal Cd has been considered crucial. In this study, the expression and intracellular localization of metallothionein (MT), a small molecular weight, metal binding protein, was examined in trophoblast cells (JAr) grown in normal media and in cells exposed chronically (6 months) to 2 μM CdCl2. Conventional and confocal fluorescence microscopy were used to examine the intracellular localization of MT protein in control cells and cells grown chronically in Cd. In unexposed trophoblast cells, MT protein was primarily perinuclear with low level, punctate expression in the cytosol. Following both chronic and 24 hour exposure to Cd, MT protein levels were increased (at least 3‐fold in both chronic and acute exposures) and the protein was now concentrated inside the nucleus with a lacy, cytoskeletal pattern of expression in the cytosol. To determine if the nuclear accumulation of MT protein was dependent on new protein synthesis, control cells were exposed to CdCl2(2 μM) and cycloheximide (2 μg/ml) for 24 hours. Following this exposure to Cd and cycloheximide, MT protein was perinuclear, suggesting that it was high levels of newly synthesized MT protein that accumulated in the nucleus of Cd treated cells. Cd exposed cells were also treated with colchicine (10 μM) to disrupt the cytoskeleton. Cytosolic MT protein expression in these cells was different from cells treated with Cd alone, suggesting that MT protein is associated with elements of the cytoskeleton. Thus, human trophoblast cells (JAr) exposed chronically will modulate cellular defense mechanisms to adapt to Cd. The specific redistribution of MT protein to the nucleus and to the cytoskeleton of challenged cells may be an important mechanism for cell defense against Cd and other toxicants. © 1995 Wiley‐Liss, Inc.
Role of formate in methanol‐induced exencephaly in CD‐1 mice
Authors: Dorman David C. , Bolon Brad , Struve Melanie F. , LaPerle Krista M. D. , Wong Brian A. , Elswick Barbara , Welsch Frank 
Published: June 2005

AbstractMouse embryos develop exencephaly when dams are exposed by inhalation to high concentrations (⩾10,000 ppm) of methanol on gestational day 8 (GD8; copulation plug = GD0). The present study examined the role of formate, an oxidative metabolite of methanol, in the development of methanol‐induced exencephaly in CD‐1 mice and cultured mouse embryos. The pharmacokinetics and developmental toxicity of sodium formate (750 mg/kg by gavage), a 6‐hr methanol inhalation (10,000 or 15,000 ppm), or methanol gavage (1.5 g/kg) in pregnant CD‐1 mice on GD8 were determined. Gross morphological evaluations for neural tube closure status in embryos or exencephaly in near‐term fetuses were performed. Decidual swellings and maternal plasma were analyzed for methanol and formate. The mean (± S.E.M.) end‐of‐exposure plasma methanol concentration was 223 ± 23 mM following the 6‐hr, 15,000 ppm methanol inhalation. There were no changes in blood or decidual swelling formate concentrations under any of the methanol exposure conditions. Peak formate levels in plasma (1.05 ± 0.2 mM; control 0.5 ± 0.3 mM) and decidual swelling (2.0 ± 0.2 mM; control 1.1 ± 0.2 mM) from pregnant mice (GD8) given sodium formate (750 mg/kg, po) were similar to those observed following a 6‐hr methanol inhalation of 15,000 ppm (plasma = 0.75 ± 0.1 mM; decidual swelling = 2.2 ± 0.3 mM) but did not result in exencephaly. In cultures of neurulating mouse embryos explanted on GD 8, the incidence of cephalic dysraphism observed on GD 9 + 6 hr was significantly increased relative to appropriate controls after a 12‐hr exposure to 375 mM methanol or to formate concentrations (40 mM) that exceeded those observed in vivo. These results suggest that exencephaly is a direct result of the effects of the parent compound methanol, administered at high concentrations, rather than the accumulation of formate. © 1995 Wiley‐Liss, Inc.
Physiologically based pharmacokinetics of methoxyacetic acid: Dose–effect considerations in C57BL/6 mice
Authors: O'flaherty Ellen J. , Nau Heinz , McCandless David , Beliles Robert P. , Schreiner Claire M. , Scott William J. 
Published: June 2005

AbstractMethoxyacetic acid (MAA), a weak acid with a pKa of 3.57, was used to test the broad hypothesis that distribution of weak acids in maternal and fetal tissues is determined principally by the pKa of the acid and the pH values of tissue and fluid compartments and to examine tissue dose–teratogenesis relationships, as well as administered dose–teratogenesis relationships. Five related experimental studies were conducted in pregnant C57BL/6CrlBR mice: a conventional dose–response study of developmental toxicity and transplacental pharmacokinetics in mice, a second dose–response study in which reproductive outcomes in litters from individual dams were related to individual pharmacokinetic behavior, a protein‐binding experiment, an embryo tissue localization study, and determination of pH in maternal and embryonic compartments after exposure to MAA. MAA was administered intraperitoneally at 9:00 a.m. on day 10 of gestation, at doses ranging from 88 to 164 mg/kg. Localization within the forelimb bud of the embryo, an MAA target site, was determined by computerized image analysis of the distribution of radiolabeled MAA. The kinetic predictions of a physiologically based model incorporating tissue pH values and MAA pKa agreed well with observed concentrations at the lowest dose However, at intermediate and higher doses, concentrations in both maternal and embryonic tissues were consistently underestimated. MAA was bound neither to maternal plasma proteins nor to embryonic proteins. Intermediate and higher doses of MAA caused dose‐dependent transient depressions in tissue pH, but these were not of sufficient duration to bring predicted tissue concentrations into congruence with the concentrations observed. Distribution of MAA within the forelimb bud was broadly consistent with the pH hypothesis, but MAA concentration was not increased in the distal postaxial sector that is the site of the precursor cells of the missing digits. Internal exposure to MAA, defined as the area under the maternal plasma or embryo concentration curve (AUC), was not proportional to administered dose, but AUC‐response relationships generated by the group and individual dose–response studies were comparable. While AUC may be a useful measure of effective MAA dose, it cannot be accurately predicted at teratogenic doses of this agent by the model as it is presently structured. © 1995 Wiley‐Liss, Inc.
Does concurrent or prior nicotine exposure interact with neonatal hypoxia to produce cardiac cell damage?
Authors: Tolson C. M. , Seidler F. J. , McCook E. C. , Slotkin T. A. 
Published: June 2005

AbstractCigarette smoking during pregnancy exposes the fetus to both nicotine and hypoxia/ischemia; postnatal exposure to second‐hand smoke also involves substances that cause hypoxia (CO, HCN). Although developing cardiac cells are more resistant to hypoxia‐induced damage than are mature cells, we examined whether nicotine affects this resistance, either when exposure is concurrent with hypoxia, or when animals are exposed to nicotine prenatally and receive subsequent hypoxic exposure. One, 8‐, or 15‐day‐old rats exposed to 7% O2 for 2 hr all showed inhibition of cardiac DNA synthesis. By contrast, administration of nicotine at either low (0.3 mg/kg) or high (3 mg/kg) doses failed to alter DNA synthesis. To examine effects on cells that were not undergoing mitosis, we examined ornithine decarboxylase (ODC), an enzymatic marker for cell damage. One day old rats showed inhibition of ODC by hypoxia, a response that represents preservation of cell integrity; by 8 days of age, ODC was increased by hypoxia, evidence of cell damage. The high dose of nicotine evoked an increase in ODC at all ages and the low dose exacerbated the effects of hypoxia at 8 days of age. Prenatal nicotine exposure caused a transient inhibition of cardiac DNA synthesis but did not produce evidence of cell damage (ODC, protein synthesis markers) by itself, nor did it alter the effect of a subsequent postnatal exposure to hypoxia. These results suggest that cardiac cell damage could emerge as a consequence of concurrent, repeated exposures to nicotine and hypoxia. Such effects could contribute to the elevated incidence of perinatal morbidity/mortality and Sudden Infant Death Syndrome associated with smoking. © 1995 Wiley‐Liss, Inc.
Effect of treatment with phenobarbital and stiripentol on carbamazepine‐induced teratogenicity and reactive metabolite formation
Authors: Finnell Richard H. , Bennett Gregory D. , Slattery John T. , Amore Benny M. , Bajpai Manoj , Levy René H. 
Published: June 2005

AbstractA model using SWV mice was developed to investigate the mechanistic basis of carbamazepine (CBZ)‐related fetotoxicity. Drug administration was initiated prior to conception and continued until day 18 of gestation. The incidence of malformation was 33% following CBZ exposure (1,500 mg/kg/day), compared with a 5% incidence in pair‐fed control animals (P< 0.05). Coadministration of nonteratogenic doses of phenobarbital (PB; a cytochrome P‐450 inducer) (45 mg/kg/day) and CBZ (1,000 mg/kg/day) increased the frequency of malformation from 10% to 26% (P<0.05), compared with mice dosed with CBZ alone (1,000 mg/kg/day). Coadministration of stiripentol (STP; a cytochrome P‐450 inhibitor) (300 mg/kg/day) decreased the incidence of malformations produced by CBZ (1,500 mg/kg/day) from 33% to 16.7% (P<0.05). The effect of PB administration on the binding of 14C in maternal and fetal tissue was assessed in dams that received CBZ (1,000 mg/kg/day) with or without PB (45 mg/kg/day) or STP (300 mg/kg/day) chronically and a single i.p. dose of 14C‐CBZ on day 12 of gestation. In all instances, binding was greatest in maternal liver, then in the placenta, fetal head and body, and maternal thigh muscle. In all tissues, PB caused a two‐ to threefold increase in binding, compared with binding in mice exposed to CBZ alone. STP administration decreased protein adduct formation only in maternal liver. The binding of 14C was also assessed in hepatic microsomes prepared from female mice exposed to CBZ and PB or STP as in the in vivo study of 14C binding. The extent of irreversible binding was 67% greater in microsomes prepared from mice pretreated with PB and CBZ than with CBZ alone, while STP resulted in only 21% inhibition of 14C adduct formation (P<0.05). The results are consistent with the formation of a chemically reactive teratogenic metabolite of CBZ in mice by cytochrome(s) P‐450. © 1996 Wiley‐Liss, Inc.
Atypical aortic coarctation and innominate artery stenosis associated with clubfoot and lower leg ischemia in an infant
Authors: Smith J. Clinton , Joransen James A. , Heath Bobby , Allen Bret C. 
Published: June 2005

AbstractWe report findings in a male infant born with talipes equinovarus and ischemic necrosis of the left lower leg and foot associated with atypical coarctation of the ascending aorta and stenosis and hypoplasia of the proximal innominate artery. We hypothesize that a vasculopathy of unknown etiology occurred in utero that resulted in ascending aortic arch coarctation and innominate artery stenosis. The presence of a thrombus in the coarcted segment suggests that one or more emboli could have been resposible for vascular compromise and subsequent clubfoot deformity and lower leg ischemia. Alternatively, a vasculopathy similar to that hypothesized as occurring in the aorta might also have occurred in the left anterior tibial artery, causing structural deformity and soft tissue ischemia of the left lower leg and foot. We believe that this is the first report of this association of findings. © 1996 Wiley‐Liss, Inc.
A captive behavioral enrichment study with Asian small‐clawed river otters (Aonyx cinerea)
Authors: Foster‐Turley Pat , Markowitz Hal 
Published: June 2005

AbstractAsian small‐clawed river otters (Aonyx cinerea) were given the opportunity to hunt for and capture live crickets (Acheta domestica) in a public interactive display. The otters learned the experimental routine during the first day of exposure. Different response levels were recorded at each of three capture sites, A, B, and C. The animals showed continued motivation for hunting despite the fact that there was no deprivation and the crickets represented an insignificant part of the diet. Besides live crickets, other items—cat food, dead crickets, and gelatin capsules—were introduced for five days each. The otters made the most captures per opportunity for live crickets, followed, in order of preference, by dead crickets, cat food, and gelatin capsules. Although gelatin capsules were found to be the least motivating prey item, the otters hunted for them whenever they were offered. Thus, any active opportunity to produce a change in their environment was rewarding to the otters.
Observations on the behavior of captive sitatunga (Tragelaphus spekei)
Authors: Popp James W. 
Published: June 2005

AbstractLittle is known about the behavior of the sitatunga. In order to learn more about their behavior, a group of sitatunga was studied at the Audubon Park and Zoological Garden. Courtship in the sitatunga begins with a male pursuing the female. The female occasionally stops, allowing the male to approach in the “low stretch” posture. If the female does not move away the male rests his chin on the female's rump and then mounts her. Males commonly horn branches, sticks, and turf. The possible functions of horning are discussed. Males also engage in sparring or “play‐fighting.” Mutual grooming, vocalizations, and mother‐young interactions of the sitatunga are described. The behavior of sitatunga is compared to that of other Tragelaphines.