bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Molecular Genetics of Inherited Hydrocephalus*
Authors: SAKURAGAWA Norio , YOKOYAMA Yasunobu
Published: May 2008

ABSTRACTCongenital hydrocephalus has a broad spectrum of etiology and has not been elucidated in terms of pathogenesis or mechanism of hydrocephalus. Recent advance of molecular genetics disclosed the genetic defects of X‐linked hydrocephalus (HSAS), MASA syndrome and X‐linked spastic paraplegia (SPGI), characterized by mutations in LICAM, a gene coding for a neural cell adhension molecule. Meanwhile, genetic heterogeneity in X‐linked hydrocephalus has been pointed out; linkage to markers within Xq27.3. We reviewed inherited hydrocephalus and chromosomal aberrations with hydrocephalus because fibroblasts from patients with these disorders may be useful for a molecular genetic approach to inherited hydrocephalus. Animal models of congenital hydrocephalus are also very important for a comparative mapping analysis between mice and human. We have tried to clone a candidate gene of hydrocephalus using fibroblasts which show a de nove chromosomal aberration [t(4;16)(q35;q22.1)], because the synteny conservation locus for mouse hydrocephalus‐3 (hy‐3) gene is suggested to be located in the long arm of human chromosome 16. A rearranged band of 1.2 Mb was detected by Pulse‐Field Gel Electrophoresis (PFGE) with Not I digestion using the calretinin probe. It may exist within 1.2 Mb distal apart from calretinin gene. Further analysis is carried out in order to clone this candidate gene of congenital hydrocephalus.
Behavioral Characteristics of the Mentally Retarded with Arithmetic Tasks: From a Special Educational Point of View*
Authors: SUZUMURA Kinya
Published: May 2008

ABSTRACTVarious types of errors are shown in a mentally retarded boy (CA 12:10, Tanaka‐Binet IQ 45–50) engaging in a standardized arithmetic achievement test for first‐grade pupils. The following issues on behavioral characteristics of the mentally retarded with arithmetic tasks are discussed from a special educational point of view.

1. Production of correct solutions depends heavily on self‐regulation, motivation and metacognition levels of the retarded with arithmetic tasks. Therefore, maintaing appropriate levels of these processes is a fundamental principle in encouraging the mentally retarded to do their best.

2. How the retarded deal with a task on figures depends on how the figures appear to them. It is a perceptual problem rather than an arithmetic one.

3. While the retarded can do well on a task by manipulating the objects in question in his daily life, they cannot solve the same task in an achievement test situation. They attempt to solve a task using a familiar strategy and are difficult to change the one used. They adopt a known strategy with a clue of particular word, phrase or part of story to deal with the tasks.

4. Realization of how to use the counting principles develops step by step, but understanding process of every principle on cardinal progression is one thing and that on multiple progression is another.
The Role of Apoptosis in the Manifestation of Polydactyly and Arhinencephaly in Genetic Mutant Mouse Pdn/Pdn*
Authors: NARUSE Ichiro , KEINO Hiromi , TANIGUCHI Masahiko , MASAKI Shigeo
Published: May 2008

Abstract Pdn/Pdn mouse exhibits preaxial polydactyly and arhinencephaly, including various brain abnormalities such as the absence of corpus callosum and hydrocephaly. We have investigated the mechanism of the manifestation of polydactyly. The abolishment of the deep preaxial mesodermal programmed cell death, foyer primaire préxial (fpp), has been considered to be the starting point of the manifestation of preaxial polydactyly. With this hypothesis, we electrocauterized the fpp region of Pdn/Pdn embryos, because Pdn/Pdn lacks fpp. After surgery, Pdn/Pdn embryos were developed using whole embryo culture system or exo utero method. They exhibited 5 digits in their limbs which received surgery in fpp region.

Meanwhile, much more apoptotic degenerations were observed in the brains of Pdn/Pdn newborns and embryos than normals. Anti‐single‐stranded DNA antibody was used to detect the localization of apoptotic cell death in the brains of Pdn/Pdn mice. TRPM‐2 gene has been considered to be an indicator of apoptosis. The brains of Pdn/Pdn newborns and embryos showed higher TRPM‐2 gene expression in Northern blot analysis. From these results, we speculated that abnormal apoptosis in the periventricular zone induced the expansion of the ventricle followed by hydrocephaly.
Species Difference in Developmental Toxicity of an N‐Phenylimide Herbicide between Rats and Rabbits and Sensitive Period of the Toxicity to Rat Embryos
Authors: KAWAMURA Satoshi , KATO Terushige , MATSUO Masatoshi , SASAKI Madoka , KATSUDA Yoko , HOBERMAN Alan M. , YASUDA Mineo
Published: May 2008

An N‐phenylimide herbicide, S‐53482, exhibited developmental toxicity in rats in the absence of maternal toxicity at a dose of 30 mg/kg. The developmental toxicities noted were embryolethality, teratogenicity (mainly ventricular septal defect [VSD] and wavy ribs) and growth retardation. In contrast to rats, the herbicide showed no developmental toxicity in rabbits even at a maternal toxic dose of 3,000 mg/kg. There was a remarkable species difference between rats and rabbits. A single dose of S‐53482 was administered to pregnant rats on one of gestation days 11 through 15 (detection of plug = day 0). Day 12 of gestation was the most sensitive day for embryonic death, VSD, and decreased fetal body weight. It is likely that there is a common mechanism for the three types of developmental toxicity and that S‐53482 does not produce VSD by its direct damage to embryonic heart tissue.
Flow Cytometric Analysis for the Evaluation of the Rat Sperm Viability and Number in the Male Reproductive Toxicity Studies
Authors: TAKIZAWA Setsuko , KATOH Chiaki , FUKATSU Nobuko , HORII Ikuo
Published: May 2008

Abstract We investigated the application of flow cytometric analysis to evaluate the rat sperm viability and number in the male reproductive toxicity studies. Flow cytometric procedure has been developed to evaluate sperm number and viability that uses fluorescent dye (propidium iodide, PI) to distinguish between viable (negative staining) and dead (positive staining) sperm. Sperm samples were collected from the caudal epididymides of SD rats (13–21 weeks old). PI staining patterns/viabilities were compared among several ranges of sperm concentrations, and several kinds of sperm viability. Viabilities determined by flow cytometry (FC) were also compared with motility by direct microscopical observation in several kinds of sperm viability. No notable changes in the PI staining patterns/viabilities were observed in the range from 1 × 105 to 6 × 106 sperm/ml. Essentially similar results were obtained from both FC and microscopical analyses for three degrees of viability sperm: live sperm (general preparation as a control), weakly viable sperm (mixed by vortex mixer for 30 seconds), and dead sperm (treated with 90°C or Triton X‐100).

Viabilities of normal rat samples were 95.0 ± 4.0% in FC and 93.7 ± 4.6% in microscopical observation, indicating good correlation in both analyses. Sperm numbers with FC analysis were approximately 0.8 × 106 to 1.8 × 106 sperm per mg indicating good correlation with those by microscopy.

It was concluded that the present flow cytometric procedure was objective, rapid and reliable, and that it was one of the useful methods for measuring the number and evaluating the viability of sperm collected from the caudal epididymides of rats in the male reproductive toxicity studies.
Eyelid and Pinnal Development after Maternal Treatment with Cortisone Acetate in NC‐eob Mouse Fetuses with a Genetically Determined Open‐Eyelid Malformation
Authors: FUJII Sakiko , KANEDA Masahiro , TERAMOTO Shoji
Published: May 2008

ABSTRACT NC‐eob mice are mutants having open eyelids at birth with complete penetrance. The present study was aimed at investigating the possible effects of cortisone acetate (CA) on the eyelid closure of NC‐eob mice. For comparison, fusion of pinnae to the scalp was also investigated. NC strain mice were used as a control. Females were given daily subcutaneous doses of 0, 20, 40 or 80 mg/kg of CA on days 13 to 15 of gestation. Live fetuses were removed from the uteri on day 16 or 18 of gestation. Day‐18 fetuses were weighed along with the placenta and examined for external abnormalities. Day‐16 fetuses were fixed in Bouin's fluid and examined for the developmental stages of eyelid closure and pinnal fusion. In day‐18 NC and NC‐eob fetuses, decreases in body weight and placental weight and an increase in the incidence of cleft palate were observed in a dose‐related manner. However, no eyelid closure occurred in any NC‐eob fetuses. In day‐16 NC‐eob fetuses, although slight enhancement of the eyelid growth and epidermal differentiation was seen, eyelid openings remained wide. Clear accelerating effects of CA treatment were noted for the pinnal fusion. In CA treated NC fetuses, both eyelid closure and pinnal fusion were clearly accelerated. These results indicate that the effects of CA on the eyelid development in NC‐eob fetuses are insufficient for closing eyelids.
Maternal Hyperthermia and the Formation of Cataracts in the Lens of the Embryonic and Fetal Guinea Pig.
Authors: SMITH Murray , EDWARDS Marshall , WAUGH Patrick
Published: May 2008

The effects of maternal hyperthermia on the prenatal development of the guinea pig lens is described with particular reference to cataract formation. Cataracts were observed at birth most commonly following maternal hyperthermia in early pregnancy (E11‐25) but also at mid‐pregnancy (E39‐46) and in late pregnancy (E56‐60). Cell death was observed in the lens and neural retina up to 8 hours following heating at E21 and vacuoles were frequently found in the lens fibres immediately beneath the anterior lens epithelium. After heating at E18 and observation at E26 the vesicles in the anterior part of the lens fibres were of varying sizes with the smaller appearing to coalesce into larger vesicles. These vacuoles may be an example of compromised lens fibres whose cellular changes may remain latent and form cataracts in later life following any event which alters fluid balance of the lens.
Delay in the Development of the Secondary Palate in Ay/a Mouse Embryos
Authors: HATAKENAKA Noriyuki , AOYAMA Hiroaki , KANEDA Masahiro , TERAMOTO Shoji
Published: May 2008

The effects of the Ay gene on the normal development were investigated by using a inbred strain of C57BL/6 (a/a) and its congenic strain of C57BL/6‐Ay (Ay/a) mice. Three mating groups (female× male), i. e., group I, a/a × a/a; group II, a/a × Ay/a; and group III, Ay/a × a/a, were set, and the rating of normal development was compared among the groups on gestation days 13, 14, 15 or 16 with special attention to the secondary palate. On day 13, the palates were wide‐open and the palatal shelves were vertical in all embryos in all groups. In group I, both shelves became horizontal in 63.3% of the embryos on day 14. The incidences of embryos having completely closed palates were 95.8% and 100% on days 15 and 16, respectively. In group II, in which half of the embryos were expected to carry the Ay gene, the frequencies of shelf horizontalization on day 14 (31.1%) and of the complete closure on day 15 (74.3%) were significantly lowered as compared with those in group I, although the external morphological rating was comparable. On day 16, however, the palatal closure was completed in almost all embryos. In group III, in which maternal mice as well as half of their embryos carried the Ay gene, the external morphological rating was delayed as compared with that in either group I or II, and the frequencies of shelf horizontalization on day 14 and of the complete closure on day 15 were as low as 10.9% and 39.6%, respectively. The palatal closure was not yet completed in 15.3% of the embryos on day 16. These results indicate that the Ay gene causes a delay in shelf horizontalization and closure of the secondary palate of mouse embryos as compared with the a gene.
Exposure to Ethylnitrosourea Before Implantation Induces Congenital Malformations in Mouse Fetuses
Authors: NAGAO Tetsuji
Published: May 2008

Abstract The effects of ethylnitrosourea (ENU) on the development of preimplantation mouse embryos were investigated. ICR mice were treated intraperitoneally with single doses of 25, 50 or 100 mg ENU/kg body weight on day 0, 1, 2 or 3 of gestation, or with single doses of 25, 50 or 75 mg ENU/kg on day 8 of gestation. The uterine contents were examined on day 18 of gestation, and viable fetuses were inspected for external and skeletal malformations. No significant differences were observed in the number of implants between the ENU‐treated groups on day 1, 2 or 3 of gestation and controls, while the number of implants in all of the groups treated with ENU on day 0 of gestation was significantly decreased compared to that in the control group. The frequencies of early postimplantation deaths were significantly increased in all of the groups treated with ENU on each gestational day before implantation, compared to the control frequencies. ENU treatment before implantation caused dose‐dependent increases in the incidence of externally or skeletally malformed fetuses. Cleft palate, exencephaly and umbilical hernia were the most common types of external malformations in the groups treated with ENU before implantation and in the control group. The skeletal malformations seen in the ENU‐treated groups were malformed vertebrae, malformed ribs, and bending of appendicular skeleton. Fused ribs was the most common skeletal malformation seen in the control fetuses. The type distributions of external and skeletal malformations induced by the treatment with ENU before implantation is quite different from those of fetal malformations induced by the treatment with ENU at the organogenesis stage. The results in the present study demonstrate that embryos before implantation in the uterus are susceptible with regard to the induction of congenital malformations by chemicals, and I propose that a large portion of the external malformations in fetuses treated at the preimplantation stages is the result of increased yields of spontaneously‐occurring malformations.
Prenatal Tobacco and Maldevelopment of the Brain*
Authors: TANAKA Harumi
Published: May 2008

ABSTRACT Maldevelopment of the brain in offspring whose mothers smoked during pregnancy is being evaluated and reviewed using our Japanese data. In addition to the criteria for the fetal tobacco syndrome (FTS), I proposed the term, “fetal tobacco effects (FTE)”, when the gestational age is <37 weeks. Maternal factors during pregnancy including coffee drinking or polydrug use, and malconditions, such as premature rupturing of the membranes or placental abnormalities, were present at higher frequencies in FTE than FTS, although the factors of smoking and light drinking during pregnancy did not differ between them. As an indicator of maldevelopment of the brain, CNS involvement was more frequent and severer in FTE than in FTS. These findings suggest that factors in addition to smoking causing reduction in the gestation period may contribute to CNS involvement. As to the concomitant effects of ethanol and tobacco on maldevelopment of the brain, CNS involvement was highest in the offspring of women who both smoked and drank heavily. In conclusion, based on the concept of FTE in addition to FTS, a causal relationship between prenatal smoking and maldevelopment of the brains of offspring has to be investigated, especially as to factors modifying the effects of tobacco during pregnancy.
Collaborative Behavioral Teratology Study of Phenytoin: A Test Battery for Neurobehavioral Developmental Toxicity in Rats.
Authors: FUKUNISHI Katsuhiro , TERADA Yoshiki , TACHIBANA Toshiaki , TANIMURA Takashi
Published: May 2008

Abstract: At the Behavioral Teratology Meeting (BTM) of the Japanese Teratology Society in 1992, a core test battery was proposed from a practical and simple point of view as an estimation of developmental neurobehavioral toxicity for use in pharmaceutical drug screening. The validity of the core test battery is being examined in a new series of collaborative studies. The present study is the first such study; phenytoin, a well‐known behavioral teratogen, was selected as the test compound, and 32 laboratories took part in a behavioral teratology study of phenytoin using the new test battery.

Sprague‐Dawley strain rats from four breeds were used. Phenytoin (200 mg/kg) was administered orally to pregnant rats from days 10 to 14 of gestation (sperm detection = day 0), and in the male offspring, the survival rate, development of physical landmarks, functional developments, open field test scores, and Biel water maze test results were assessed and the brain weights were measured. The shuttle box conditioned avoidance test was also performed in some laboratories.

In the present collaborative study, by taking an aggregate of the relative values converted from the measured values of each breed (providing a much larger sample size than that recommended by reproduction toxicity study guidelines), a high detectability level for phenytoin's effects was established.

Under these conditions, the effects of phenytoin on eye opening, incisor eruption, the surface righting reflex, the negative geotaxis reflex, and performance of the open field test, Biel water maze test and shuttle box conditioned avoidance test were observed. It was found that present collaborative study made it possible to evaluate the detectable capacity of each of these test battery items. In addition, the critical period of abnormalities demonstrated in many test items was identified, and the results of several previous reports were confirmed. Furthermore, a breed difference in the effect of phenytoin for several test items was found.

The present results established that the core test battery accurately detected the effects of phenytoin.
Pathogenesis of Congenital Diaphragmatic Hernia Induced by Transplacental Infusion of Bisdiamine into Rats
Authors: HASHIMOTO Ryozo , INOUYE Minoru , MURATA Yoshiharu
Published: May 2008

Abstract: We studied the pathogenesis of congenital posterolateral diaphragmatic hernia induced by bisdiamine in rats. The frequency of live fetuses with left congenital diaphragmatic hemia (which resembles a hernia through the foramen of Bochdalek in man) was high (78.4%) when pregnant rats were administered bisdiamine by gavage once at a dose of 400 mg/kg on day 9 of pregnancy. Then the bisdiamine‐treated rat fetuses were examined at successive developmental stages. Histopathological observation revealed that l) in the control fetus on day 14 of pregnancy, the mesothelial cells lining the pleural aspect of the pleuroperitoneal fold were eventually clustered close to the pleuroperitoneal opening, giving the appearance of a high wave lapping the shore; 2) in the affected fetus on day 14 of pregnancy, the mesothelial cells of the pleural aspect of the fold were scarce; 3) in the affected fetuses during days 14–16 of pregnancy, primary lung hypoplasia was seen. On day 19 of pregnancy, no remarkable differences in the gross appearance of the right lung were found between the affected and control fetuses. Each lung (right and left) of the affected embryos may be considered to have the potential for further growth and development. The development of the mesothelium of the pleura may be greatly influenced by the growth and enlargement of the thorax (mainly the lung), and a retardation of lung growth near the time of pleuroperitoneal canal closure may induce the hernia in diaphragm.
Teratogenic effect of bis‐diamine on embryonic rat heart
Authors: Nakagawa Masao , Nishijima Setsuko , Fujino Hidetoshi , Hanato Takashi , Okamoto Nobuhiko
Published: May 2008

ABSTRACT  Bis‐diamine induces conotruncal anomalies including persistent truncus arteriosus, tetralogy of Fallot, interruption of the aortic arch, and ventricular septal defect in rat embryos when administered to the mother. Bis‐diamine also induces extracardiac malformations including thymic hypoplasia, facial dysmorphism, forelimb anomalies and diaphragmatic hernia. However, the teratogenic mechanisms of this chemical in early developing rat hearts have not been fully established. Chimeric studies in chick and quail embryos demonstrated that the cranial neural crest cells reached the cardiac outflow tract, contributing to aorticopulmonary and truncal septation. Since an ablation of the cranial neural crest also produced the conotruncal anomalies, bis‐diamine is proposed to disturb the normal migration of cardiac neural crest cells to the heart. Based on our data concerning cardiac anomalies induced by bis‐diamine, we reviewed how the cardiac malformations were morphologically established in early developing rat hearts. Our data showed that 1) cardiovascular anomalies induced by bis‐diamine are time‐ and species or strain‐ dependent. 2) bis‐diamine reduces the number of neural crest cells migrating to participate in the conotruncal septation, 3) bis‐diamine induces anomalous coronary arteries, thin ventricular walls and epicardial defects, and 4) some embryos cultured in the medium containing bis‐diamine had extra‐cardiac abnormalities including abnormal location of the otic placodes and delay in mid brain closure. Conclusively, bis‐diamine does not appear to merely affect the cardiac development, but rather disturbs normal development of all the organs contributed to by neural crest cells.
Antisense attenuation of nestin accumulation causes neural tube deformation in rat embryo cultures
Authors: Matsuda Motoko
Published: May 2008

ABSTRACT The roles of nestin in neural tube development were studied using immunostaining and antisense experiments in rat embryos. Nestin was detected in the neural tube of embryos of day 10.5 of gestation (E10.5), while no nestin staining was observed in E9.5 embryos in which the neural plate comprised 3 to 4 layers of neuroepithelial cells. As embryos developed, the neural tube became comprised of multiple cell layers and staining was observed in filamentous structures spanning from the ventricular surface to the pial surface of the neural tube. Nestin accumulation was suppressed in the neural tube of embryos treated with nestin antisense oligodeoxynucleotide (ODN). The treated embryos showed two types of neural tube deformation. One type was a thin neural tube which had 3 to 4 layers of neuroepithelial cells and the other was a local distribution of neuroepithelial cells near the basement membrane. While neuroepithelial cells in the neural tube were fewer in embryos treated with nestin antisense ODN than in controls, the percentage of Islet‐1‐positive neurons relative to the neuroepithelial cells was not different between the treated and control embryos. These results suggested that nestin plays roles in the proliferation of neural tube cells and in the formation and the maintenance of multiple cell layers in the neural tube but not in suppression of development of Islet‐1‐positive neurons.
Phenotypic differences in the brains and limbs of mutant mice caused by differences of Gli3 gene expression levels
Authors: Naruse Ichiro , Keino Hiromi , Yamada Yasukazu , Masaki Shigeo , Hui Chi‐chung
Published: May 2008

ABSTRACT  The genetic polydactyly/arhinencephaly mouse, Pdn/Pdn, exhibits severe polydactyly both in the fore‐and hindlimbs, agenesis of the olfactory bulbs, corpus callosum, anterior commissure, and hydrocephalus. A candidate gene for the Pdn mouse has been speculated to be Gli3, because Pdn has been considered to be an allele of Xt whose responsible gene has been clarified to be Gli3. Recently, it has been cleared that retro‐transposons are inserted into nitron 3, upstream of zinc finger domain, of the Gli3 gene in the Pdn mouse, resulting to the severe suppression of Gli3 gene expression in Pdn/Pdn embryos. Meanwhile, XtJ/XtJ mice exhibit more severe polydactyly than that of Pdn/Pdn. Arhinencephaly and microholoprosencephaly including agenesis of the olfactory bulbs, corpus callosum, anterior commissure, hippocampal commissure, habenular commissure, and posterior commissure, and moreover, the cerebral cortical plates and hippocampus are not formed in the XtJ/XtJ mice. The XtJ/XtJ mouse has a large deletion in Gli3 structural gene and shows null expression. From these corroborations, we speculated that the differences in the Gli3 gene expression levels resulted in the phenotypic differences between the Pdn/Pdn and XtJ/XtJ mice.
Comparative study of mouse trisomy 16 and bis‐diamine treated fetuses: Discrimination of possible contribution of neural crest cells to malformations
Authors: Aso Sunao , Miyabara Shinichi , Sugihara Hajime , Winking Heinz
Published: May 2008

ABSTRACT  In order to directly compare the malformation complex induced by genetic and environmental factors, mouse trisomy 16 (Ts 16) fetuses and bis‐diamine treated (BDT) mouse fetuses in which pregnant females were orally dosed with 3.0 mg and 1.0 mg/B.W. (g) bisdiamine eight hours apart on 9 days of pregnancy, were examined. Cystic hygroma with generalized edema appeared in most Ts 16 and in less than 50% of BDT fetuses. Blunt snout or facial cleft with aplasia or hypoplasia of the olfactory bulb was observed in BDT fetuses. The thymus was markedly to moderately hypoplastic in Ts 16, and absent or markedly hypoplastic in BDT fetuses. Parathyroid glands were inclined to be unsettled in relative location to the thyroid in Ts 16 and absent in BDT fetuses. Aortic arch abnormalities were present in approximately half of the cases of Ts 16 and in the majority of cases of BDT fetuses. In the conotruncal region, double outlet right ventricle and persistent truncus arteriosus were dominantly observed in Ts 16 and BDT fetuses, respectively. Atrioventricular septal defect was observed in every Ts 16 and in about 30% of BDT fetuses. These results indicate that not only environmental factors but also genetic factors can experimentally induce DiGeorge‐Iike anomaly in mice. Abnormal development relevant to neural crest cells seems to occur typically in BDT fetuses, and incompletely in Ts 16 fetuses.
Diagnostic perspective of fetal alcohol and tobacco syndromes
Authors: Tanaka Harumi
Published: May 2008

ABSTRACT  Maldevelopment of the brain in offspring whose mothers drank and/or smoked during pregnancy was evaluated using Japanese data. The diagnostic criteria for fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE) revealed that FAS infants exhibited a severer degree of CNS involvement than FAE infants. In addition to the criteria for fetal tobacco syndrome (FTS), we proposed the term “fetal tobacco effects (FTE)” for when the gestational age is less than 37 weeks. Maldevelopment of the brain was not severer in FTS than FTE, to which factors other than smoking causing a reduction in the gestational period, and ones during pregnancy and delivery may contribute. The effects on the CNS of alcohol were more frequent and severer than those of tobacco. CNS involvement was shown to increase with increasing consumption of alcohol or tobacco.
Timing of implantation in New Zealand White rabbits
Authors: Nishimura Michiyo
Published: May 2008

ABSTRACT  The timing of implantation was investigated in Kbl:NZW rabbits to assess the appropriate period of administration of test compounds recommended in the ICH Guideline for reproductive and developmental toxicity studies. After copulating in the morning (day 0 of gestation), pregnant rabbits were euthanized in the morning daily on days 6–9 of gestation. Their uteri were morphologically examined and the process of implantation was investigated. On day 6 of gestation, blastocysts had fixed their position in the uterine lumen for implantation, but they had not yet attached to the uterine mucosa. On day 7 of gestation, implantation sites were macroscopically recognized as protrusions of the uterine wall. Histological examination revealed that ob‐placental implantation occurs in the antimesometrial region on days 7 and 8, while placental implantation occurs in the mesometrial region on days 8 and 9 of gestation. It was also found that organogenesis progresses in parallel with implantation.
Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐methoxyphenyl)ethane (methoxychlor) in rats and rabbits
Authors: Shimizu Naoko , Aoyama Hiroaki , Hojo Hitoshi , Takahashi Ken L. , Kikuta Masayuki , Kushida Hiromi , Kawakatsu Hisao , Teramoto Shoji
Published: May 2008

ABSTRACT  The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of methoxychlor in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147, 2–1–18, 2000). Methoxychlor dissolved in corn oil was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,1,50, or 150 mg/kg/day and to pregnant Kbl:JW rabbits on GD 6–27 at a dose of 0,1, 15, or 45 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.

Adverse effects on maternal animals were found at 2 higher doses in both species; i.e. vaginal red discharge (rat only), abortion or premature delivery (rabbit only), and significantly decreased body weight gains and food consumption. While the numbers of corpora lutea and implants were comparable between the control and treated groups in both species, slight increase in the percent resorptions and fetal deaths in rats and a reduction of fetal weights in both species were observed at the highest dose. Anogenital distance and testicular histology were not affected in rats. Although fetal examination revealed significant increase in the incidences of 27 presacral vertebrae at 2 higher doses in rabbits, there was no treatment‐related increase in the incidence of malformations in rats and rabbits.

Based on these results, it is concluded that methoxychlor causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in decreased fetal weights and an increased incidence of fetal resorptions or skeletal variations at maternally toxic doses.
Postnatal survival of rat offspring prenatally exposed to pure 2,4‐Dichlorophenoxyacetic acid (2,4‐D)
Authors: Fofana Djibril , Kobae Hidehiko , Sameshima Kiyoko , Miyata Koicbiro
Published: May 2008

ABSTRACT  In previous report on prenatal developmental effects of pure 2,4‐dichlorophenoxyacetic acid (2,4‐D) in rat, we found that this chemical was maternally toxic, embryolethal, and that it induced urogenital malformations in the fetuses. In the present report, we investigated the postnatal survival of the offspring prenatally exposed to 2,4‐D during organogenesis, to determine the participation of urogenital malformations on postnatal survival. We used doses of 70 mg, 110 mg and 150 mg, which were each found to induce significant urogenital malformations, when administered in different periods of organogenesis: GD 6 to 15, GD 6 to 10, and GD 11 to 15. We found that 2,4‐D has a significant influence on progeny viability by increasing the postnatal death. The kidney and urinary tract malformations induced in the fetuses might be the cause of the increased rate of postnatal death. 2,4‐D did not impair the postnatal growth of the unaffected offspring.
Necessity to establish new risk assessment and risk communication for human fetal exposure to multiple endocrine disruptors in Japan
Authors: Todaka Emiko , Mori Chisato
Published: May 2008

ABSTRACT  Our recent study clearly shows that fetuses are exposed to multiple chemicals including endocrine disruptors in Japan. Although the embryo and fetus stages are the most sensitive period to chemicals in humans' life cycle, the health effects of the chemicals such as endocrine disruptors to them are largely unknown. The conventional risk assessment method cannot assess the risk to fetuses precisely. Now we need a new risk assessment, in which the target is fetuses and not the adults, in addition to the conventional risk assessment At the same time, we also need a new strategy to practically eliminate the risk for the future generations. To make the strategy effective, we suggest a new approach to reduce the risk and avoid the possible adverse health effects, using primary, secondary and tertiary preventions as they are used in public health. We also suggest a new concept of “pre‐primary prevention” to reduce the risk for fetuses. Furthermore, to make this method even more practical, we suggest a new risk communication method. In this paper, we present a framework of risk avoidance of multiple chemical exposure to fetuses.
Enrichment of fetal cells from maternal blood by magnetic activated cell sorting (MACS) with fetal cell specific antibodies: One‐step versus two‐step MACS
Authors: Zhao Xaio Xi , Ozaki Yasuhiko , Suzumori Nobuhiro , Sato Tsuyoshi , Suzumori Kaoru
Published: May 2008

ABSTRACT  We report here the results of fetal cell enrichment from maternal blood in 58 pregnant women by the use of magnetic activated cell sorting (MACS) with erythroblast‐specific and/or maternal cell specific antibodies. Two approaches were compared; one‐step MACS to enrich CD71+ (a membrane‐bound marker) or GPA+ (another marker, glycophorin A) fetal cells versus two‐step MACS to deplete CD14+ maternal cells and subsequently to enrich fetal (CD71+ or GPA+) cells. The existence of fetal cells was ensured by both FISH with Y‐specific probes and karyotyping of respective anuniotic and/or chorionic vullus cells, the results being applied for comparison of detection rate for XY fetuses between the two MACS procedures.

In 24 (38.8%) of the 58 blood samples examined, Y‐positive cells were observed by FISH, whereas there were 38 true XY fetuses later confirmed by karyotyping, including two cases of 47, XY,+21. On the other hand, in Y‐negative cells by FISH, there were two cases of 47, XX,+18. The average number of cells sorted did not differ among one‐step MACS procedures with anti‐CD14, anti‐CD71 and anti‐GPA antibodies. With the latter, 12 (75%) of 16 Y‐positive fetuses were detected, while only one (20%) of 5 Y‐positive fetuses was detected by two‐step MACS with anti‐CD14/anti‐GPA antibodies. The detection rate significantly varied (p = 0.0024) between the two procedures, although the numbers of cases examined were small. There was no statistical difference (p > 0.05) between one‐step and two‐step MACS with other combinations of antibodies. These findings indicate that one‐step MACS using the anti‐GPA antibody is more effective than two step MACS for enrichment of fetal cells from maternal blood.
Perinatal development of the rat hip joint with restrained fetal movement
Authors: Hashimoto Ryuju , Kihara Isao , Otani Hiroki
Published: May 2008

ABSTRACT  We compared the structures of the femoral head (FH) of neonates between normal and operated legs with restrained fetal movement using an exo utero technique. At embryonic day (E) 16.5, one hind limb was sutured onto the embryonic membrane and the fetuses were allowed to develop exo utero until the term (E22.5). There was no significant difference in the largest diameter of the FH between the non‐operated and operated side FH in the operated neonates and the FH of the non‐operated neonates. By scanning electron microscopy, roughness and collagen fiber bundles, which were detected on the surface of the operated side FH at E18.5, disappeared at E22.5. However, the operated side FH was deformed and the surface cell arrangement was more irregular than that of the controls at E22.5 by light microscopy. These results suggest that the abnormality of cell arrangement caused by the restraint of fetal movement may induce the deformity and irregularity of the FH surface, although this operation may not disturb the basic cellular activities such as cell proliferation as well as the secretion of cartilage matrix and collagen fibers. To further investigate the recovery process in the operated newborns after releasing the restraint, we bred them artificially for a considerable period after birth. The operated side FH surface of the neonate bred for 45 hours was smoother than that at E22.5 and similar to that of the non‐operated side FH. This result suggests that the proper movement of the extremities after birth may recover the deformity caused by restrained fetal joint movement
An examination of different fetal specific antibodies and magnetic activated cell sorting for the enrichment of fetal erythroblasts from maternal blood
Authors: Zhao Xiao Xi , Ozaki Yasuhiko , Suzumori Nobuhiro , Sato Takeshi , Suzumori Kaoru
Published: May 2008

ABSTRACT  The aim of the present study was to compare the rates of fetal cells obtained after separation from maternal blood by magnetic activated cell sorting (MACS) using different fetal specific antibodies, and to evaluate the potential role of this method in the prenatal diagnosis of fetal trisomies. Peripheral blood samples were obtained from 42 women carrying chromosomally normal fetuses and from 4 women with aneuploid fetuses (2 cases of 47,XX,+18 and 2 of 47,XY,+21) at 9–20 weeks of gestation. After fetal cells were enriched by MACS with three different monoclonal antibodies (GPA, CD71, CD14), fluorescence in situ hybridization (FISH) with chromosome X, and Y‐specific probes was performed to detect the rates of fetal cells in the samples sorted. FISH with chromosome 13‐, 18‐, and 21‐specific probes was carried out to compare proportions of cells with three‐signal nuclei in chromosomally normal and abnormal groups. In male infants, X‐and Y‐positive cells were detected in 80%, 73.3%, and 66.6% of samples after the separation by antibodies CD14, GPA, and CD71, respectively. The percentage of nuclei with three signals was increased in pregnancies with trisomy, ranging between 2% and 5.18%. Pregnancies with normal fetuses showed 0 to 3.7% of nuclei with three signals. The data demonstrate that fetal cell detection varies depending on the antibodies used for cell sorting. This study provides further evidence on the feasibility of screening for fetal chromosomal abnormalities by enriching maternal blood for fetal cells and using FISH.
FROM BOYER'S SCHOLARSHIP OF TEACHING TO THE AACSB'S INSTRUCTIONAL DEVELOPMENT: IMPLICATIONS FOR FACULTY REWARD SYSTEMS
Authors: Staff Marcia J.
Published: May 2008

Finally, the scholarship of teaching, in which research is conducted on effective and appropriate teaching methods, must be emphasized for all scholars. Teaching that is not grounded in the most recent research is not appropriate for a college or university setting.
Water Content and Water Evolution from Reaction‐Bonded Aluminum Oxide (RBAO) Powder Precursors
Authors: Temuujin Jadambaa , Coronel Jose , Minjigmaa Amgalan , MacKenzie Kenneth
Published: May 2008

Water evolution behavior from reaction‐bonded aluminum oxide (RBAO) powder precursor was studied by the Carl‐Fischer titration method. RBAO mixtures were milled for 4 and 8 h in absolute ethanol and water–ethanol mixtures containing 5 and 10 vol% water. The water content was then determined under dynamic heating conditions from 20°C to 250°C and static heating at 250°C. When the aluminum content is increased from 30 to 60 vol%, the water content of the milled powder precursor mixtures also increased. The higher water contents observed in powders milled in absolute ethanol are discussed in terms of the possible interaction of the ethanol with the surface of the aluminum particles.
Preparation of Nano Carbonate‐Substituted Hydroxyapatite from an Amorphous Precursor
Authors: Li Yanbao , Li Dongxu , Weng Wenjian
Published: May 2008

Carbonated amorphous calcium phosphate (CACP) precursors were precipitated by the wet chemical method at 5°C in the presence of poly(ethylene glycol) and carbonates. The nano carbonate‐substituted hydroxyapatite (HAp) was obtained after heat treat CACP precursors at a low temperature (800°C) for 3 h. The calcium phosphates were investigated by X‐ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma, thermal gravimetric and differential thermal analysis, transmission electron microscopy, and scanning electron microscopy. The results show that calcium phosphate particles with a Ca/P molar ratio of 1.73 are AB‐type carbonate‐substituted HAp with about 50 nm in diameter.
Synthesis and Characterization of Hydroxyapatite–Wollastonite Composite Powders by Sol–Gel Processing
Authors: Encinas‐Romero Martín A. , Aguayo‐Salinas Salvador , Castillo Santos J. , Castillón‐Barraza Felipe F. , Castaño Víctor M.
Published: May 2008

Composites of hydroxyapatite–wollastonite were synthesized by a sol–gel route using calcium acetate and triethyl phosphate as precursors of hydroxyapatite and high‐purity natural wollastonite added in ratios of 20, 50, and 80 wt%. These composites were characterized by thermal analysis, X‐ray diffraction, FT‐IR and Raman spectroscopy, and scanning and transmission electron microscopic techniques. Formation of hydroxyapatite occurs at a relatively low temperature, about 420°C, accompanied by calcium carbonate; wollastonite remains unreacted. The composites were purified by heat treatment to a higher temperature and washed with hydrochloric acid and distilled water, to produce B‐type carbonated hydroxyapatite–wollastonite composites as final products.
Development and Application of Refractory Materials for Molten Aluminum Applications
Authors: Hemrick James G. , Headrick William L. , Peters Klaus‐Markus
Published: May 2008

Two new refractory materials have been developed for use in molten aluminum contact applications that exhibit improved corrosion and wear resistance leading to improved thermal management through reduced heat losses caused by refractory thinning and wastage. The development of these materials was based on an understanding of the corrosion and wear mechanisms associated with currently used aluminum contact refractories through physical, chemical, and mechanical characterization and analysis performed by Oak Ridge National Laboratory (ORNL) and the University of Missouri, Rolla Rolla (UMR), along with their industrial partners, under the ITP Materials project “Multifunctional Metallic and Refractory Materials for Energy Efficient Handling of Molten Metals.” Spent castable refractories obtained from a natural gas‐fired reverberatory aluminum alloy melting furnace were analyzed, leading to identification of several refractory degradation mechanisms and strategies to produce improved materials. The newly developed materials have been validated through an R&D industrial trial.
Distribution of cells containing FMRFamide‐related molecules in the embryonic development of Ophryotrocha labronica (Polychaeta: Dorvilleidae)
Authors: Franchini Antonella
Published: May 2008

Abstract. The timing and spatial distribution of cells containing FMRFamide‐related molecules in the embryogenesis of the polychaete Ophryotrocha labronica were studied immunocytochemically. FMRFamide‐like molecules emerge early during embryonic development. They are found at the one‐cell stage, are asymmetrically distributed in the first phases of cleavage, associated with gastrular movements, and label the central nervous system morphogenesis. Moreover, during embryogenesis, the pattern of gut cells with the FMRFamide‐like phenotype that is present in adults is already established. The early occurrence of FMRFamide‐like molecules in O. labronica suggests that these molecules are involved as pre‐nervous growth signals in the regulation of basic neuronal cell behaviors.
Flowering Patterns in a Seasonal Tropical Lowland Forest in Western Amazonia
Authors: Stevenson Pablo R. , Castellanos Maria Clara , Cortés Ana Isabel , Link Andrés
Published: May 2008

The phenological behavior of many tropical plant species is highly dependent on rainfall, but these plants may also respond to changes in photoperiod. Without a better knowledge of the proportion of species responding to different factors, it is difficult to predict how global climate change may affect natural ecosystem processes. The aim of this study was to describe flowering patterns for more than 100 species in Tinigua Park, Colombia, and to propose which factors may trigger flower production (e.g., rainfall, temperature, cloud cover, and photoperiod). Data gathered in 5.6 km of phenological transects during 4 yr and complementary information indicated that the vast majority of species showed intraspecific synchronization, and annual production was the most common pattern, followed by episodic frequency. The annual patterns were common in tree species, while episodic patterns were common in lianas. Simple and multiple regression analyses suggested several aspects of photoperiod as the most likely triggers for flowering in most species. However, the fact that many of these species produce flowers in different periods each year, suggests that the proportion of species responding to photoperiodic cues is less that 23 percent in this community. The flowering times of taxonomically related species seldom showed significantly staggered distributions; however they do not necessarily occur at the same time, suggesting that flowering patterns are not strongly constrained by phylogeny.
Estimating Fine Root Turnover in Tropical Forests along an Elevational Transect using Minirhizotrons
Authors: Graefe Sophie , Hertel Dietrich , Leuschner Christoph
Published: May 2008

Growth and death of fine roots represent an important carbon sink in forests. Our understanding of the patterns of fine root turnover is limited, in particular in tropical forests, despite its acknowledged importance in the global carbon cycle. We used the minirhizotron technique for studying the changes in fine root longevity and turnover along a 2000‐m‐elevational transect in the tropical mountain forests of South Ecuador. Fine root growth and loss rates were monitored during a 5‐mo period at intervals of four weeks with each 10 minirhizotron tubes in three stands at 1050, 1890, and 3060 m asl. Average root loss rate decreased from 1.07 to 0.72 g/g/yr from 1050 to 1890 m, indicating an increase in mean root longevity with increasing elevation. However average root loss rate increased again toward the uppermost stand at 3060 m (1.30 g/g/yr). Thus, root longevity increased from lower montane to mid‐montane elevation as would be expected from an effect of low temperature on root turnover, but it decreased further upslope despite colder temperatures. We suggest that adverse soil conditions may reduce root longevity at high elevations in South Ecuador, and are thus additional factors besides temperature that control root dynamics in tropical mountain forests.
The energy cascade from warm dark matter decays
Authors: Valdés M. , Ferrara A.
Published: May 2008

We use a set of Monte Carlo simulations to follow the cascade produced by a primary electron of energy Ein in the intergalactic medium. We choose Ein= 3–10 keV as expected from the decay of one of the most popular warm dark matter (WDM) candidates, sterile neutrinos. Our simulation takes into account processes previously neglected such as free—free interactions with ions and recombinations, and uses the best available cross-sections for collisional ionizations and excitations with H and He and for electron—electron collisions. We precisely derive the fraction of the primary electron energy that heats the gas, ionizes atoms and produces line and continuum photons as a function of the ionization fraction. Handy fitting formulae for all the above energy depositions are provided. By keeping track of the individual photons, we can distinguish between photons in the Lyα resonance and those with energy E < 10.2 eV that do not interact further with gas. This separation is important because a Lyα background can heat or cool the gas depending on the nature of the photons, and can have effects on the 21-cm radiation emitted by neutral H, which will probably become detectable at z > 6 in the near future by the next generation radio interferometers.