bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological Alterations in Gestational Day 13 Rat Embryos from Albendazole‐Treated Dams
Authors: MANTOVANI Alberto , MACRÌ Caterina , RICCIARDI Claudio , STAZI Anna Velia 
Published: May 2008

AbstractGestational day (GD) 13 rat embryos from dams treated p. o. with albendazole (ABZ) on GD 10–12 were examined as an experimental model for the pathogenesis of embryotoxicity induced by benzimidazole compounds. Dosage levels were 0, 10, 20 and 30 mg/kg b. w. of ABZ. At 10 mg/kg b. w., most embryos appeared macroscopically normal. However, the histological examination of a representative sample showed subtle alterations including discrete necrotic foci in the lateral and rostral telencephalon, delayed differentiation of lens, increased wavyness of the notochord caudad to the forelimb bud and absent or poorly defined apical ectodermal ridge in the forelimb bud. At 20 and 30 mg/kg b. w. a sharp, dose‐related increase in embryolethality, developmental delays and macroscopic abnormalities were accompanied histologically by marked necrotic alterations of a number of embryonic tissues. The telencephalon and neural tube were severely affected, showing also a regeneration attempt through the disordered formation of tubules. Besides neuroectoderm, necrosis and tissue depletion were mostly evident in neural crest and mesoderm‐derived structures, such as branchial bars, limb buds and paraxial mesoderm. Lesions in the somites showed a head‐to‐tail increasing gradient; the sclerotomes were consistently more affected than the dermatomes. Wavyness of the notochord cephalad to the forelimb bud and fragmented/abnormal nuclei in the erythroblasts were also noted. Examination of embryos during in vivo organogenesis may be a useful tool for investigating the pathogenesis of embryotoxicity.
BUS/ldr, a Mutant Mouse Strain Exhibiting Abnormal Behaviors: Behavioral Similarities of BUS Mice and Chemically Labyrinthectomized Mice
Authors: HANAI Atsuko , TSUJI Keiichiro , OTANI Hiroki , MORIYAMA Kenji , SHOJI Ryujiro , YONEZAWA Satoshi 
Published: May 2008

AbstractThe behavioral abnormalities of homozygotes (bus/bus) of mutant bustling mice, BUS/ldr, were characterized in comparison with those of heterozygotes (+/bus) and of chemically labyrinthectomized mice. Homozygotes were 4‐fold more active than heterozygotes, as evaluated in an open field (11 × 17 cm) for 24 hr by means of Animex. Homozygotes revealed the lack of righting reflex and of head nystagmus on a rotating board, the frequent backward‐moving and the inability to swim, in addition to characteristic behaviors such as circling, head bobbing and head tossing. Bilaterally labyrinthectomized mice behaviorally mimicked BUS homozygotes: The behavioral patterns of operated animals were essentially the same as those of BUS homozygotes with respect to all reflex and locomotor indices employed, suggesting that some peripheral vestibular dysfunction, though unidentified yet, is attributed to abnormal behaviors of BUS mice. Unilaterally labyrinthectomized mice were not hyperactive, nor exhibited circling behavior.
Simple Methods for Objective Assessment of Sperm Viability and Motility with MTT Assay and Sperm Quality Analyzer (SQA) in Rats
Authors: HARA Hiroaki , TAKAI Ryou , TANAKA Naomi , MIZOGUCHI Keiji , TSUNO Tatsuya , IGARASHI Shin‐ichi , USAMI Masayoshi 
Published: May 2008

AbstractTo confirm the applicability of MTT assay and sperm quality analyzer (SQA) to the examination of sperm viability and motility in rats, epididymal spermatozoa derived from male rats (Slc:SD) treated with nitrobenzene at a dose of 60 mg/kg/day for 16 days were examined by these methods. Epididymal fluid was suspended in Dulbecco's modified Eagle's medium containing 25 mM fructose in ratio of 1:125. Sperm concentrations in the epididymal fluid were 2.48 ± 0.55 (× 106/μl, mean ± SD, n = 8) in the control and 2.20 ± 0.54 in the nitrobenzene group, and did not significantly differ between the groups. Both absorbance unit of the MTT assay (1.497 ± 0.406 vs. 1.084 ± 0.350) and SMI (sperm motility index) value of the SQA (204.0 ± 15.3 vs. 182.5 ± 21.6) were significantly decreased in nitrobenzene group. The results suggest that the examinations of sperm viability and motility with MTT assay and SQA are available for the reproductive toxicology in rats.
A Common Mutation in the Tyrosine Kinase Domain of the Fibroblast Growth Factor Receptor 3 Gene in Two Japanese Patients with Hypochondroplasia
Authors: KITOH Hiroshi , YAMADA Yasukazu , GOTO Haruko , OGASAWARA Nobuaki , NOGAMI Hiroshi 
Published: May 2008

AbstractWe examined two Japanese patients with hypochondroplasia (HCH) whether they had mutations in the gene (FGFR3) encoding the fibroblast growth factor receptor 3 using polymerase chain reaction (PCR) coupled with direct sequencing. In both of our patients, a C→A transversion was detected in nucleotide 1659, predicting a substitution of asparagine for lysine at position 540 of the mature protein which corresponds a part of the tyrosine kinase 1 (TK1) domain. Our results suggest that a common mutation specific for HCH in the TK1 domain of FGFR3 exists among Japanese patients with HCH.
Fetal Laser Surgery Exo Utero in Mice*
Authors: NARUSE Ichiro , KEINO Hiromi , TANIGUCHI Masahiko 
Published: May 2008

ABSTRACT  It has been very difficult to investigate mammalian embryogenesis. Whole‐embryo culture systems allow the observation of mammalian embryogenesis and enable the manipulation of the embryos, but it is almost impossible to culture fetuses at the late gestational period. The exo utero method does allow the manipulation of mammalian fetuses at the late gestational period. In this review, the detailed method of exo ufero surgery in mice is described, and the advantages and disadvantages of the applications of laser equipment for fetal surgery are discussed.It has long been known that arhinencephaly is often associated with agenesis of the corpus callosum. The relationship between agenesis of the olfactory bulb and that of the corpus callosum is not fully understood. In this review, an example of fetal laser surgery exo utero was introduced, in which fissuration of the corpus callosum was induced after the destruction of the anlage of the olfactory bulbs in the mouse embryo. It was thus elucidated that agenesis of the olfactory bulbs induced the agenesis of the corpus callosum.
Heat Shock Proteins in Normal and Stressed Mammalian Embryonic Development
Authors: WALSH David , ZHU Xiao‐Ou , GRANTHAM Jane , TAYLOR Rosanne , INOUYE Minoru , EDWARDS Marshall J. 
Published: May 2008

AbstractThe heat shock response is associated with a characteristic inhibition of normal transcription and translation with enhanced synthesis of a multigene family of Heat Shock Proteins (HSP), a common cellular mechanism to all living organisms including the most primitive species. Elevated body temperature or hyperthermia can result from many agents including fever, hot weather and heavy exercise. In more modern surroundings induced hyperthermia can be achieved by hot baths, saunas, specific drugs, electromagnetic radiation and ultrasound. Hyperthermia during pregnancy has been shown to cause a wide spectrum of effects in all species studied, including humans. The outcome depends on the duration and severity of the heat shock experienced by both the mother and the embryo and the stage of embryonic or fetal development. In severe exposures in utero embryonic death and resorption or abortion are probably the most common outcomes. In less severe exposures major or minor developmental defects can result, with the CNS a major target for its effects. Heat shock can interrupt cell differentiation at critical stages of organogenesis which may lead to apoptosis. All living organisms appear to have developed protective mechanisms collectively known as the heat shock response. Heat shock triggers the abrupt suspension in the normal protein synthesis and the concurrent induction of heat shock genes (hsp) and the synthesis of a set of multi‐gene protein families known as the heat shock proteins (HSP). Each hsp has at least two copies, one which appears to function in normal embryonic development (cognate) and another that is stress‐induced (inducible) and can result in acquired thermotolerance, offering some protection against further damage. The inducible HSP are usually activated at critical inductive stages of organ development, suggesting they play a major role in cell differentiation. The HSPs appear to protect cells through their chaperone functions by binding to adhesive sites on newly synthesised or heat damaged and partially unfolded structural and functional proteins. This prevents the formation of functionless aggregates. Heat shock transcription factors (HSF) bind to a heat shock element (HSE) and initiate hsp activation. Although this research has defined some pathways indicating how and why heat can cause some defects, a means of preventing them has not yet emerged.
Midkine, A New Heparin‐Binding Growth/Differentiation Factor: Expression and Distribution during Embryogenesis and Pathological Status
Authors: SUN Xue‐Zhi , FUKUI Yoshihiro 
Published: May 2008

AbstractMidkine (MK) is a 13 kDa heparin‐binding growth factor found as a product of a retinoic acid‐responsive gene. MK is rich in basic amino acids and cysteine and its sequence is not homologous with any other proteins so far reported, so it is a new family of heparin‐binding growth factor. It has been found that MK exerts variety of biological activities such as neurite‐promoting, neuronal cell survival and differentiation‐inducing activities. MK is strictly expressed during the mouse embryogenesis; among the adult organs, it is detected only in the kidney. MK is also strongly expressed in a number of human carcinomas and specifically localized in senile plaques in the brain of patients with Arzheimer disease. More recently, it has been reported that MK is an important molecule regulating inflammation response and tissue repair. These results demonstrated that the relevance of MK not only in normal development, but also in processes leading to tissue repair or diseases. Increased MK gene expression is a common phenomenon observed in many human carcinomas, therefore MK is of significant interest in cancer biology. As a new growth/differentiation factor, many issues including the detailed sites and the precise time of MK expression, the exact cellular source which synthesizes and secretes MK, the signal transducing receptors for MK, the mechanisms underlying those developmentally regulated expression and its potential clinical significance still remain unknown. To elucidate the molecular mechanisms of MK action will lead not only to a deeper understanding of developmental processes, but also to the ultimate obtaining a key to diagnose and treat human carcinomas.
The Distribution of Tenascin in Rat Embryos with Normal Heart and Cardiovascular Anomalies Induced by Bis‐Diamine
Authors: IWASAKI Keisuke , IKEDA Takayoshi , OHTANI Hiroshi , MATSUO Takeshi , HIGAMI Yoshikazu , SHIMOKAWA Isao 
Published: May 2008

AbstractThe mesenchyme in the truncal ridge and aortico‐pulmonary (A‐P) septum in the developing heart expresses tenascin (TN), a component of extracellular matrices. We observed immunohistochemically the localization of TN with reference to fibronectin (FN) distribution in rat embryonic hearts at gestation days 12. 13 and 14 and compared the results with those in bis‐diamine‐induced cardiovascular anomalies. In control rat embryonic hearts, TN was distributed in the dorsal mesocardium and the distal part of the truncal ridge at gestation day 12, and in part of the conal and truncal ridges, A‐P septum and proximal wall of aortic arch arteries at gestation days 13 and 14. The conotruncal regions with TN expression may correspond to the areas where cardiac neural crest cells migrate in the heart. In bis‐diamine‐treated rat hearts showing conotruncal anomalies, TN was localized in incompletely fused and hypoplastic conotruncal ridges, but the intensity and area of staining were decreased suggesting a decreased neural crest cell migration. FN was diffusely distributed in both the normal and anomalous embryonic hearts, including atrioventricular cushion tissue in addition to the region expressing TN. TN was densely distributed in the fusing area of the conal and truncal ridges in comparison to FN, suggesting that TN may be mainly expressed during the time of fusion of conal and truncal ridges to form the A‐P septum in the embryonic heart. In conclusion, bis‐diamine may cause the poor development of neural crest derived tissue, subsequently bringing about hypoplasia of the A‐P septum and truncal and conal ridges.
Teratology and the Web: Homepage of the Journal ‘Congenital Anomalies’
Authors: MATSUI Kohji A. , YASUDA Mineo 
Published: May 2008

Abstract:This note presents current state and background of the homepage of Congenital Anomalies, the online version of the official Journal of the Japanese Teratology Society, and also introduce some of the teratology‐related web sites, in the hope that the usage of these and the other Internet tools will contribute greatly toward the advancement of teratology studies. Due to the cross‐disciplinary concepts and principles in the field of teratology, no single web site can provide exhaustive coverage of teratology. Nevertheless, there is indeed a great deal of useful information for a teratologist available on the Web. Proper usage of the Internet by exchanging and sharing valuable information can yield the mutual understanding and better collaboration, which in turn is indispensable for the overall measures of congenital anomalies.
A Comparison of Infants Affected with Congenital Abnormalities Born in the Inpatient Clinic or Treated in the Outpatient Clinic of the Same Hospital in the United Arab Emirates
Authors: HOSANI H. AL , SAADE D. , ZAKARIA M. , EDWARDS M.A. , CZEIZEL A.E. 
Published: May 2008

ABSTRACTCases with congenital abnormalities were evaluated in the inpatient and outpatient materials of AI Mafraq Hospital in the United Arab Emirates between 1992 and 1994. The quality of data and diagnostic skill were appropriate. The baseline birth prevalence of total congenital abnormalities was 38.9 per 1000 which corresponded to the international figures based on nearly complete ascertainment. The cases of inpatient clinic may represent the general features of congenital abnormalities in the United Arab Emirates and particular clusters of different congenital abnormalities were not found.
Lack of Teratogenicity of 3‐Chloro‐4‐(Dichloromethyl)‐5‐Hydroxy‐2 (5H)‐Furanone (MX) in Embryonic Mouse Palate Culture in vitro
Authors: TERAMOTO Shoji , SHIMIZU Naoko , HOJO Hitoshi , KOBAYASHI Hiroko 
Published: May 2008

ABSTRACT3‐Chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) is known as a by‐product of wood pulp manufacture and a contaminant of chlorinated drinking water. Since our previous studies (Teramoto et al., 1998, 1999) demonstrated in a micromass in vitro test a strong inhibitory effect of MX on rat embryo cell differentiation, the potential teratogenicity was investigated in this study by using a suspension organ culture system. Twelve‐day mouse embryo palatal explants were cultivated for 72 hr in the MX‐containing medium at a concentration of 0, 1, 10, 100 or 300 μg/ml and examined for closure of the palatal shelves. All control explants showed almost complete closure of the palatal shelves. Similar results were also obtained in the MX‐treated explants at concentrations up to and including 100 μg/ml. Immunohistochemistry revealed no difference between the control and MX‐treated explants in distribution of PCNA‐and TUNEL‐positive cells in the palatal mesenchyme and medial edge epithelium, respectively. When the MX concentration was raised to 300 μg/ml, palatal shelves remained wide open. However, histopathology revealed extensive pyknosis of the mesenchymal cells and loss of the epithelium. These results may indicate that MX is cytotoxic against the mouse palate at a high concentration, and that it has no cleft‐palate inducing effects in mice.
The Safety of Penicillin V: Oral Penamecillin Use During Pregnancy The Importance and Limitation of Recall Bias
Authors: CZEIZEL A.E. , ROCKENBAUER M. , SøRENSEN H.T. , OLSEN J. 
Published: May 2008

ABSTRACTThe purpose of the study was to check the human teratogenic potential of penicillin V: oral penamecillin treatment during pregnancy in the population‐based dataset of the Hungarian Case‐Control Surveillance of Congenital Abnormalities between 1980 and 1996. The pairs of cases with congenital abnormalities and their matched population controls without congenital abnormalities were evaluated, in addition the data of total population and of patient control groups as referents were compared with the data of congenital abnormality groups. In the three study groups there were 38,151 pregnant women who had newborn infants without any defects (population control group), 22,865 pregnant women who had newborns or fetuses with congenital abnormalities, and 812 mothers of informative offspring with Down syndrome (patient controls). In the population control group 2,246 (5.9%) pregnant mothers were treated with penamecillin, in the case group 1,597 (7.0%) pregnant women had penamecillin treatment while in the patient control group 63 (7.9%) mothers used penamecillin during pregnancy. The use of penamecillin treatments during pregnancy was higher in the total case (i.e., congenital abnormality) group, than in the total population control group. However, the highest use of oral penamecillin was found in the patient control group. The case‐matched population control pair analysis did not show a higher use of medically documented penamecillin during the second‐third months of pregnancy, i.e., in the critical period for most major congenital abnormalities. In addition, an association between medically documented penamecillin use during the second and third months of gestation and different congenital abnormality groups was not found when total population control group or patient control groups were used as referent. Thus, the reported higher use of penamecillin among the mothers of cases and patient controls can be explained mainly by recall bias. Thus, treatment with oral penamecillin during pregnancy did not indicate detectable teratogenic risk to the fetus.
Immunohistochemical Distribution of HNK‐1 and N‐CAM in Rat Embryos Treated with Bis‐Diamine
Authors: FUJINO Hidetoshi , NAKAGAWA Masao , SHIMADA Morimi 
Published: May 2008

ABSTRACTBis‐diamine is known to induce congenital anomalies including cardiac defects, thymic hypoplasia and snout defects in rat embryos. Cardiovascular lesions consist of persistent truncus arteriosus, tetralogy of Fallot and aortic arch anomalies, which are often found in DiGeorge syndrome. In the the present study, we investigated effects of bisdiamine on cardiac neural crest cells, which may be important to the teratogenecity. A single dose of 200 mg bis‐diamine was administered to pregnant rats at 10.5 embryonic day (ED). Immunohistochemical studies were performed on embryos at 11.5, 12.5 and 13.5 ED using anti‐HNK‐1 and anti‐N‐CAM antibodies. The embryos at 11.5 and 12.5 ED showed the similar distributional patterns of either HNK‐1 or N‐CAM positive cells in control and bis‐diamine treated embryos. N‐CAM immunoreactivities in the splanchnic mesoderm were quite weakly detectable in the bis‐diamine treated embryos at 12.5 ED. Closure of the neural tube was delayed in the treated embryos at this period. Immunohistochemistry of the control embryos at 13.5 ED demonstrated a continuous chain of N‐CAM expression between the neural plexus near the foregut and the fourth aortic arch, while no apparent continuity of N‐CAM positive tissue was observed in the bis‐diamine treated embryos. These findings suggested that bis‐diamine reduced the amount of neural crest cells which appeared to participate in the aortic arch formation or conotruncal septation. The primary effect of bis‐diamine in the induction of various congenital anomalies including cardiovascular malformations may be an inhibition of the normal development of the neural tube and neural crest.
Hydrocephalus manifestation in the genetic polydactyly/arhinencephaly mouse (Pdn/Pdn)
Authors: Naruse Ichiro , Ueta Etsuko 
Published: May 2008

ABSTRACT  The genetic polydactyly/ariiinencephaly mouse, Pdn/Pdn, exhibits severe polydactyly both in the fore‐and hindlimbs, hydrocephalus, and agenesis of the olfactory bulbs, corpus callosum, and anterior commissure. The mechanism of hydrocephalus manifestation in Pdn/Pdn was investigated in the present study. Ink was injected into the left lateral ventricle in the Pdn/Pdn and +/+ newborn mice. After incubation at 32°C for different time intervals, the heads were fixed in Bouin's solution and were subsequently decalcified in 0.5 mol/L of EDTA solution, paraffin sectioned, and stained with hematoxylin and eosin.Ink spread into the 3rd and right lateral ventricles and flowed to the 4th ventricle and Magendie's foramen rapidly in Pdn/Pdn mice. This rapid spread was due to the dilatation of the interventricular foramen and that the lateral ventricle was directly connected with enlarged 3rd ventricle in Pdn/Pdn. In spite of the rapid spread of ink in the cerebrospinal fluid pathway, ink was not observed in the subarachnoid space around the superior sagittal sinus at 3.5 or 10 hours in Pdn/Pdn mice.The superior sagittal sinus was narrower in Pdn/Pdn than in +/+, and the arachnoid villi were not observed in Pdn/Pdn. From these observations, we suggested that absorption of cerebrospinal fluid from the arachnoid villi in the superior sagittal sinus stagnated and that stagnation of the fluid in the ventricles was the cause of hydrocephalus in Pdn/Pdn mice.
Permeameter Data Verify New Turbulence Process for MODFLOW
Authors: Kuniansky Eve L. , Halford Keith J. , Shoemaker W. Barclay 
Published: May 2008

AbstractA sample of Key Largo Limestone from southern Florida exhibited turbulent flow behavior along three orthogonal axes as reported in recently published permeameter experiments. The limestone sample was a cube measuring 0.2 m on edge. The published nonlinear relation between hydraulic gradient and discharge was simulated using the turbulent flow approximation applied in the Conduit Flow Process (CFP) for MODFLOW‐2005 mode 2, CFPM2. The good agreement between the experimental data and the simulated results verifies the utility of the approach used to simulate the effects of turbulent flow on head distributions and flux in the CFPM2 module of MODFLOW‐2005.