bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryonic development in vitro following short‐duration exposure to heat
Authors: Kimmel G. L. , Cuff J. M. , Kimmel C. A. , Heredia D. J. , Tudor N. , Silverman P. M. 
Published: June 2005

AbstractGestation day (GD) 10 rat embryos (10–12 somites) were exposed in vitro for 10 to 25 minutes at 42 or 43°C and evaluated 24 hrs later for alterations in growth and specific morphological parameters, using a modified Brown‐Fabro (Brown and Fabro: Teratology, 24:65–78, '81) scoring system that allowed evaluation of development relative to gestational age. At 42°C, crownrump length appeared to be particularly sensitive, responding to only 10 mins exposure. A 15‐min exposure resulted in decreased total protein, somite number and morphological score. No system was uniquely sensitive, since all parameters demonstrated some degree of response. Rather, systems affected were those that would be developing most rapidly at this time in gestation. At 43°C, all of the parameters measured were affected by a 10‐min exposure. These results demonstrate alterations in vitro after much shorter exposure periods than previously reported on GD10, which may be due, in part, to the use of a modified scoring system that permitted the evaluation of graded individual end point changes relative to gestational age. The response patterns demonstrated a clear temperature‐ and exposure duration‐dependency, with a shift from a more shallow duration‐response curve to a more dramatic inhibition of development as temperature increased from 42°C to 43°C. © 1993 Wiley‐Liss, Inc.
Statistical model for fetal death, fetal weight, and malformation in developmental toxicity studies
Authors: Catalano Paul J. , Scharfstein Daniel O. , Ryan Louise M. , Kimmel Carole A. , Kimmel Gary L. 
Published: June 2005

AbstractThe purpose of this paper is to present a statistical model for analyzing the joint effects of exposure on fetal death, fetal weight, and malformation in a developmental toxicity study. In addition to allowing for the usual litter effect, the model allows for correlations between different outcomes measured on the same fetus. Fitting the model requires first focusing on non‐live outcomes by modeling the probability of fetal death or resorption as a function of dose. Then outcomes among live fetuses are modeled using a two‐stage regression approach. The first stage models fetal weight as a function of dose and the second stage models fetal malformation as a function of dose, as well as residuals from the weight model. The regression coefficients from the malformation model have intuitive interpretations in terms of correlations between littermates and between different outcomes measured within the same fetus. Not only does the approach provide a useful way to investigate the relationship between adverse fetal outcomes, it also yields a natural framework for conducting quantitative risk assessment. A procedure is proposed for quantifying overall risk by incorporating the three outcomes in order to estimate safe dose levels and corresponding lower confidence limits. The method is illustrated using data from an experiment in mice conducted through the National Toxicology Program. © 1993 Wiley‐Liss, Inc.
Mouse placenta: Hemodynamics in the main maternal vessel and histopathologic changes induced by 2‐methoxyethanol and 2‐methoxyacetic acid following maternal dosing
Authors: Khera K. S. 
Published: June 2005

AbstractThe two main maternal vessels that are a major, if not the entire, source of maternal blood for the mouse placenta are unique in possessing intraluminal valvular projections. The morphologic configuration of these projections suggests their potential to converge, diverge, and rotate blood currents flowing under systolic pressure. The intravascular occurrence of circular fibrin bodies composed of concentric fibrin strands coagulated from the plasma and almost no blood cellular elements in these strands lends credence to this concept. Histopathologic changes in the extraembryonic and embryonic tissues induced by an intraperitoneal injection of 250 or 500 mg/kg of 2‐methoxyethanol, or its metabolite, 2‐methoxyacetic acid, via oral gavage were determined 48 hr after dosing CD‐1 mice on day 11 of pregnancy. Both compounds caused 1) marked congestion and dilatation, associated with or without fibrinous occlusions, of the main maternal vessel of the placenta, 2) serosanguinous exudation and maternal hemorrhages from the placental periphery, 3) necrosis and desquamation involving the mesometrial surface or peripheral edge of the placenta, 4) translabyrinthine embryonic hemorrhage into the maternal circulation, and 5) embryonic hemorrhages into the exocoelomic, amniotic, and pericardial cavities. These lesions signify a disordered maternal circulation in the placenta suggestive of potentially serious pathologic effects. These lesions may play a role in the resorption, reduction in fetal body weight, and syndactyly or oligodactyly attributed to 2‐methoxyethanol and 2‐methoxyacetic acid. © 1993 Wiley‐Liss, Inc.
Genetic analysis of the maternal factors controlling the survival of trisomy 16 mouse fetuses
Authors: Demczuk Suzanne , Vekemans Michel 
Published: June 2005

AbstractThe B × H recombinant inbred strains of mice were used to undertake a genetic analysis of the maternal factors controlling the survival of trisomy 16 fetuses. The data presented indicate that the prevalence of trisomic fetuses on day 15 of gestation varies significantly with the genetic background of the mother. The strain difference in the frequency of trisomy appears to be the result of selective elimination of trisomic fetuses. Various statistical methods employed to elucidate the genetic architecture of the trait from the recombinant inbred strains data indicate that the number of loci involved in the selection process ranges from one to five. Linkage association with two loci has been found; however, with a low probability level (P= 0.292). © 1993 Wiley‐Liss, Inc.
Microsurgical study on the mechanisms determining sidedness of axial rotation in rat embryos
Authors: Fujinaga Masahiko , Baden Jeffrey M. 
Published: June 2005

AbstractSidedness of left/right asymmetric body structures is strongly biased in most animals by mechanisms that are not well understood. In rat embryos, axial rotation starts at the 9–10 somite stage and is almost completed at the 17–18 somite stage. As a result, the ventrally flexed tail (caudal part of the body) and chorioallantoic placenta on the yolk sac take up their position normally on the right side of the embryo. Because the tail and chorion become connected via the allantois around the time when axial rotation takes place, we hypothesized that the allantois and possibly its connection to the chorion is important in determining sidedness of the tail. In the present study, we tested this hypothesis by surgically removing either the allantois or chorion before axial rotation started. Embryos were explanted at 8 am on Day 9 of gestation (presomite stage), and either the allantois or chorion was removed using microforceps. Embryos were then cultured in rotating bottles, and sidedness of the tail, chorioallantoic placenta, and bulboventricular loop (heart) was determined after 50 hours (∼25–26 somite stage). Removal of the allantois (n = 55) resulted in absence of the umbilical cord and a 49.1% incidence of inverted tail; a chorioallantoic placenta‐like structure developed on the yolk sac in the normal position. Removal of the chorion (n = 114) resulted in absence of the chorioallantoic placenta and a 20.2% incidence of inverted tail; the allantois either floated in the extraembryonic coelomic cavity or reached the yolk sac but did not form a chorioallantoic placenta‐like structure. Sidedness of the heart was not affected in either group. These results indicate that removal of the allantois results in complete loss of control of tail sidedness, whereas removal of the chorion results in only a partial loss of control. An incidental finding was that an avascular area developed on the yolk sac around the chorioallantoic placenta. This area became larger when the allantois was removed but disappeared when the chorion was removed. © 1993 Wiley‐Liss, Inc.
Hydantoin syndrome with holoprosencephaly: A possible rare teratogenic effect
Authors: Kotzot Dieter , Weigl Josef , Huk Walter , Rott Hans‐Dieter 
Published: June 2005

AbstractWe report on a newborn girl with lobar holoprosencephaly and clinical signs of hydantoin syndrome. During pregnancy the mother was treated with diphenylhydantoin and primidon for psychomotor and petit mal seizures. The possible relationship between hydantoin syndrome, holoprosencephaly, and maternal intake of anticonvulsants during pregnancy is discussed. © 1993 Wiley‐Liss, Inc.
Potentiation of triamcinolone‐induced cleft palate in mice by maternal high dietary fat
Authors: Zhou Mian , Walker Bruce E. 
Published: June 2005

AbstractThis study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD‐1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate‐producing effects of triamcinolone in mice. © 1993 Wiley‐Liss, Inc.
Utility of the murine erythroleukemic cell (MELC) in assessing mechanisms of action of DNA‐active developmental toxicants: Application to 5‐fluorouracil
Authors: Elstein Kenneth H. , Zucker Robert M. , Shuey Dana L. , Lau Christopher , Chernoff Neil , Rogers John M. 
Published: June 2005

AbstractMurine erythroleukemic cells (MELC) exposed to 2′‐deoxy‐5‐azacytidine (D‐AZA) or to the active cyclophosphamide (CP) metabolites phosphoramide mustard (PAM) and 4‐hydroxycyclophosphamide (OHCP) exhibit cell‐cycle perturbations similar to those seen in limb bud nuclei of gestational day (GD) 10 CD‐1 mouse embryos exposed in utero to D‐AZA or CP, respectively. The similarities in response suggest MELC may be a useful model for determining mechanisms of action of DNA‐active developmental toxicants. As such, we used the MELC model to investigate the mechanism of action of 5‐fluorouracil (5‐FU), an antimetabolite that induced in GD 14 rat fetuses an apparent S‐phase accumulation in limb cells 8 hr after in utero exposure, but S‐phase depletion in liver cells 24 hr postexposure. MELC timed‐recovery and synchronization studies suggest that in proliferative tissues, 5‐FU induces an early S‐phase accumulation, followed by a synchronous, concentration‐dependent delay in progression through the cell cycle. Consequently, it is the tissuespecific rate of delay, rather than different mechanisms of action, that results in apparent tissue‐specific perturbations. Moreover, growth and cell‐cycle data suggest that cells entering S phase (when TS activity is greatest) are the most sensitive to 5‐FU toxicity. Assays of the TS activity of recovering MELC reveal that although the initial extent of TS inhibition does not appear to be concentration‐dependent, the time to recovery is, suggesting that the rate of S‐phase progression is closely associated with TS activity. Together, the induction of similar cell‐cycle perturbations in embryonic/fetal tissues and MELC following exposure to CP (or CP metabolites), D‐AZA, or 5‐FU, as well as the adaptability of MELC to a variety of kinetic assays suggests that, for those developmental toxicants suspected of inducing cell‐cycle perturbations in embryonic/fetal tissues, MELC may prove useful for elucidating mechanisms of action. © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Reporting of malformations in routine health registers
Authors: Hemminki Elina , Meriläinen Jouni , Teperi Juha 
Published: June 2005

AbstractThe utility of three national registers—the malformation, birth, and hospital in‐patient discharge registers—in identification of malformations among 60,255 children born in 1987 in Finland was compared. Information in the malformation register is collected by specific reporting of physicians; information on the malformed children in the other two registers in 1987, through 1990 was routinely collected and identified by ICD 9‐codes (740‐759, 7886A). From October 1990 on, the ICD‐9 codes were omitted from the birth register and malformation data were asked only in a yes‐no question. In 1987, the malformation register included 1,032, the birth register 3,084 and the inpatient register 2,003 malformed infants identified up to the age of 1 year. There was underrepresentation of almost all malformation diagnoses in the malformation register. Individual linkage of the three registers showed that the malformation register revealed very few cases not recorded in the birth and the in‐patient registers. With the adoption of the new recording method in the birth register beginning in October 1990, reports of malformation declined by 75%. Our analyses showed that data sources based on diagnoses collected routinely and not requiring an explicit decision on whether or not a problem is a malformation, can be more useful for routine surveillance of occurrence of malformations. © 1993 Wiley‐Liss, Inc.
Evaluation of the effectiveness of a teratogen information service: A survey of patient and professional satisfaction
Authors: Ludowese C. J. , Marini T. , Laxova R. , Pauli R. M. 
Published: June 2005

AbstractWe have evaluated the effectiveness of the Wisconsin Teratogen Project (WTP), a teratogen information service, using two retrospective surveys. We surveyed medical professionals who utilized the WTP and patients who had received teratogen counseling in a clinic setting. The results from the medical professional survey indicated that medical professionals rely on the WTP for accurate and convenient teratogen information. A tendency to rely on the Physician's Desk Reference as an alternative resource was noted, reinforcing the need to encourage professionals to use teratogen information service projects. Major findings and conclusions from the patient survey included: patients found counseling to be most helpful if, whenever possible, numeric risks were provided; recommendations made in the absence of known risk were not considered by patients to be helpful for providing reassurance; overall compliance with recommendations was high but behavioral recommendations seemed to reduce reassurance and increase dissatisfaction with the service for some patients; and pregnant women exposed to low‐dose ionizing radiation were more likely to have considered termination of pregnancy prior to referral but were not more likely to terminate following counseling.Our findings suggest that although the WTP is considered an effective service overall, teratogen counselors should give special consideration to patient and counseling characteristics as these can significantly influence the perception of the risk counseling provided. Particular attention should be given to patients with low‐dose ionizing radiation exposure, since misperception of its teratogenic risk is extremely common. © 1993 Wiley‐Liss, Inc.
Relationship between abnormal somite development and axial skeletal defects in rats following heat exposure
Authors: Cuff Joyce M. , Kimmel Gary L. , Kimmel Carole A. , Heredia Dinorah J. , Tudor Natalie , Chen Judy 
Published: June 2005

AbstractThe effects of in vivo heat exposure on gestation day (GD) 10 rat embryos were evaluated on GD 11 to determine the relationships between morphological sequelae following in vivo and in vitro exposures and between effects detected on GD 11 and those observed in postnatal day (PND) 3 pups. Anesthetized rats were exposed to 42°C in a warm air incubator until their rectal temperatures reached 41°C or until a rectal temperature of 42–42.5°C had been maintained for 5 minutes. Heat‐exposed embryos exhibited a significant decrease in growth parameters including head length, somite number, and protein content/embryo versus controls. These changes correlated well with in vitro effects from an earlier study (G.L. Kimmel et al., '93). Among the morphological endpoints which were slightly delayed in development were the caudal neural tube, branchial bars, forelimb and hindlimb. The only effect on the embryos that could not be explained as a transient delay in development induced by heat was the induction of unsegmented somites. Additional embryos were exposed to 42°C for 15–20 min in vitro and examined specifically for unsegmented somites, which were observed in 47% of embryos exposed to 42°C in vivo or in vitro. This phenomenon was observed in somites 9–20, i.e., those that give rise to cervical and thoracic vertebrae and ribs. These results correlated well with the axial skeletal malformations observed in PND 3 pups exposed to the same heat treatment (C.A. Kimmel et al., '93). © 1993 Wiley‐Liss, Inc.This article is a US Government work and, as such, is in the public domain in the United States of America.
Glucose and scyllo‐inositol impair phosphoinositide hydrolysis in the 10.5‐day cultured rat conceptus: A role in dysmorphogenesis?
Authors: Strieleman P. J. , Metzger B. E. 
Published: June 2005

AbstractCulture of the postimplantation rat conceptus from gestational day 9.5–10.5 in media supplemented with d‐glucose or scyllo‐inositol decreases tissue myo‐inositol and phosphoinositides with a concomitant increase in dysmorphogenesis. A number of mitogenic agents initiate cellular proliferation and differentiation through receptors coupled to phosphoinositide hydrolysis. To test whether the decrease in conceptus phosphoinositides is associated with a reduced phosphoinositide hydrolytic response, we developed a protocol to stimulate phosphoinositide hydrolysis. Phosphoinositide hydrolysis was monitored by measurement of [3H]inositol phosphates after preincubation in serum free media. We examined the ability of serum, platelet‐derived growth factor (PDGF), epidermal‐derived growth factor (EGF), insulin‐like growth factor 1 (IGF‐1), insulin like growth factor 2 (IGF‐2), endothelin‐1 (ET‐1), and endothelin‐2 (ET‐2), to stimulate phosphoinositide hydrolysis. As measured by [3H]inositol monophosphate ([3H]InsP1) accumulation, normal rat serum, ET‐1, and ET‐2 stimulated phosphoinositide hydrolysis 47%, 420%, and 154% above the basal rate observed in serum free controls. EGF stimulated a statistically insignificant 15% increase while PDGF, IGF‐1, or IGF‐2 were without effect. We further characterized ET‐1 stimulated phosphoinositide hydrolysis. Dose‐response studies disclosed that incremental increases in [3H]InsP1 (129–420%) are observed over a concentration range of 10–1,000 nM. Maximal stimulation was not reached even at 1,000 nM. Temporally [3H]InsP1 and [3H]InsP3 levels increased linearly during incubation periods of 15‐60 min. We further analyzed ET‐1 stimulated phosphoinositide hydrolysis in 10.5‐day conceptuses cultured for 24 hr in media containing high concentrations of glucose (23.3‐56.6 mM) or scyllo‐inositol (0.55, 5.5 mM). Under these dysmorphogenic conditions that concomitantly decrease the phosphoinositide precursor pool the response to ET‐1 was blunted 28–76% for glucose and 29–65% for scyllo‐inositol. This suggests that the effect of glucose and scyllo‐inositol on lowering phosphoinositide precursor pools also results in a decrease in the response to agonists using the inositol/lipid intracellular pathway. This impaired signaling response may contribute to initiating dysmorphogenic events in diabetic embryopathy. © 1993 Wiley‐Liss, Inc.
Developmental changes in the optic nerve related to ethanol consumption in pregnant rats: Analysis of the ethanol‐exposed optic nerve
Authors: Pinazo‐Duran Maria Dolores , Renau‐Piqueras Jaime , Guerri Consuelo 
Published: June 2005

AbstractVisual impairment is one of the most common ophthalmic abnormalities in fetal alcohol syndrome. Pathologic changes in optic nerve development related to alcohol consumption could be involved in this dysfunction. In order to assess the consequences of pre‐ and postnatal exposure to alcohol on the developing optic nerve, we administered an ethanol‐containing liquid diet (5% w/v) before and during gestation and throughout lactation to rats and their offspring. A group of control animals were kept on a pair‐fed isocaloric diet. The optic nerves were obtained at key stages from fetuses (21 days of gestation) and pups (4, 7, 14, 21 and 28 postnatal days). Samples of the optic nerve cross‐section, behind the eyeball, were processed for analysis of gliogenesis, myelinogenesis, axonal growth, and remodelling events, using light and electron microscopy. Qualitative, morphometric, and immunocytochemical analyses, alternatively using anti‐GFAP and anti‐MBP antibodies, were carried out. Optic nerve cross‐sections from prenatal and postnatal alcohol‐exposed rats showed a decrease in size. Ultrastructural alterations and retarded development in macroglial cells, optic axons, and myelin sheath were also observed. The most prominent abnormalities were: damage of cytoplasmic organelles and disorganization of cytoskeleton in astrocytes; a decrease in free ribosome density and nuclear membrane inclusions in oligodendrocytes; and fragmentation of lamellae, aberrant myelin sheaths and intralamellar inclusions in myelin. These findings suggest that alcohol abuse during pregnancy is teratogenic to the optic nerve and closely related to the altered visual function. © 1993 Wiley‐Liss, Inc.