bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of the Induction of Chromosomal Errors, Interchromosomal Effects in Chinese Hamsters Heterozygous for Inversions
Authors: NARUKAWA Takashi
Published: May 2008

ABSTRACT Using Chinese hamsters heterozygous for inversions of chromosomes 1 or 4 [INV(1)37Idr and INV(4)Idr], as well as karyotypically normal animals, interchromosomal effects on meiotic disjunctions were investigated by chromosomal analysis of the meiotic cells and one‐cell conceptuses. The mean frequency of nondisjunction at the first meiosis in five normal +/+ males was calculated at 1.28%, by doubling the frequency (0.64%) of hyperhaploid second meiotic (MII) cells, and there was no significant difference in the frequency among individuals. Among males heterozygous for INV(1)37Idr or INV(4)25Idr inversion, the frequencies of hyperhaploid cells with an extra inversion‐unrelated chromosome were 0.52% and 0.43%, respectively, which were not significantly different from the frequency of hyperploid MII cells in +/+ males (0.52%). In one‐cell conceptuses obtained from crosses between karyotypically normal females and males heterozygous for INV(1)37Idr or INV(4)25Idr, 1.18% and 1.22% of conceptuses had an extra inversion‐unrelated chromosome, respectively. The frequency of nondisjunction during meiotic divison in males heterozygous for these inversions was not significantly different from that in controls. The results therefore suggest that the presence of inversions in meiotic cells exerts no influence on disjunctions of normal bivalents and MII chromosomes unrelated to the inversions.
Prevalence and Mortality Rates of Microcephaly in Japan, 1969–1992
Authors: IMAIZUMI Yoko
Published: May 2008

ABSTRACTThe prevalence and death rates for microcephaly were analyzed using Japanese Vital Statistics for the period 1969–1992. The prevalence rate was 0.23 per 10,000 births in 1979 and the overall rate was 0.20 during the period 1979–1982. The prevalence rate slightly increased with paternal age, whereas the rate remained constant with maternal age except the 40 years age group. Overall death rates per 10,000 population under 20 years of age were 0.094 for males and 0.090 for females. In both sexes, the death rate gradually decreased with age. The proportion of deaths with microcephaly under 5 years old was 78% and under 20 years old was 97%. Geographical variations in the death rate of microcephaly were observed with the highest death rate in Tottori Prefecture (0.245), and the lowest in Fukui Prefecture (0.018). The mean age at death in microcephalics increased from about 3 years in 1969–1971 to 13 years in 1990–1992 for both sexes.
Behavior of Human Neonates*
Authors: KAWASAKI Chisato
Published: May 2008

ABSTRACT Clinical methods of neonatal neurobehavioral evaluation are outlined, and the conceptual basis and the procedures of Brazelton's Neonatal Behavioral Assessment Scale (NBAS) which is most widely used is described in detail. The studies which have been conducted to date using the NBAS are reviewed, and future directions in the assessment of neonatal behavior are explored. Infants showed following behavioral characteristics: Healthy Japanese infants show higher habituation and orientation scores with lower motor activity score than American Caucasian counterparts. Japanese infants with intra‐uterine growth retardation (IUGR) show mild deviation of Apgar score, and maternal toxemia has an effect on the neonatal behavior as well as neurological signs. In Japanese infants, the mental‐motor development during infancy is significantly correlated with the neonatal behavior and family environment. Studies of normal and high‐risk infants revealed that both perinatal complications and cultural background affect the neonatal behavior.
Radiation‐induced Anomalies: Report of a Study Conducted in Chernobyl*
Authors: SATOW Yukio , LAZJUK Gennady , TCHAIJUNUSOVA Nailya , ROZENSON Raphail , TAKEICHI Nobuo , KIMURA Akiro , KATOH Osamu , KAWAISHI Kuniko
Published: May 2008

At the 34th Annual Meeting of the Japanese Teratology Society held in July 1994, the first author was asked by President Hiroshi HARA to report on the results of the international joint study on congenital anomalies that we were conducting in the former Soviet Union. It was only a short time ago that the study was begun and long‐term observation needs to be made hereafter, but we made an interim report on the results obtained so far. In this report we describe (1) the results of a joint study made with Director Gennady Lazjuk of the Institute for Hereditary Diseases in Minsk, Republic of Belarus, mainly with regard to congenital anomalies that have increased after the Chernobyl nuclear power plant accident, (2) the results obtained in a study made with Dr. Anatoly Vacilez, Chief, Department of Obstetrics and Gynecology, Gomel District Hospital in Belarus, a heavily contaminated area in Belarus, and (3) the congenital anomalies that can be considered to have occurred as a result of the approximately 570 nuclear tests made over a period of 40 years from 1949 to 1989 in Semipalatinsk, Republic of Kazkh.
Congenital Anomalies of the Elbow Joint: Clinical Features and Classification
Authors: OGINO Toshihiko , ISHII Seiichi , SUGIMOTO Yoshihiro
Published: May 2008

In order to examine the distribution of different types of congenital anomalies of the elbow joint and discuss their classification, a total of 94 patients, 96 congenital anomalies of the elbow joint, were analyzed. They were classified according to the elbow deformity itself as follows; radio‐ulnar synostosis in 59 cases (61%), radial head dislocation in 23 cases (24%), ankylosis of the elbow joint in eight cases (8%), severe flexion contracture of the elbow joint in three cases (3%), and complete or partial aplasia of the elbow joint in three cases (3%). On the other hand, congenital elbow deformities can be classified into three types according to the associated anomalies. In 78 patients, in which congenital elbow deformity appeared as an independent deformity, there were radio‐ulnar synostosis in 56 patients, radial head dislocation in 19 patients, ankylosis of the elbow joint in two patients, and hypoplasia of trocholea in one patient. In the 13 patients, which congenital elbow deformity appeared as a part of congenital upper limb anomalies, the underlying congenital anomalies of the upper limb were ulnar deficiency in eight patients, radial deficiency in two patients, transverse deficiency in two patients, and phocomelia in one patient. In five patients, elbow deformity appeared as a part of congenital syndromes. Classification according to associated anomalies seems to be more suitable in order to examine the real distribution of different types of congenital deformities of the elbow joint as a part of the upper limb.
Congenital Anomalies Induced by Toxoplasma Infection
Authors: YOKOTA Kazuko
Published: May 2008

Abstract A comprehensive review regarding congenital toxoplasmosis, which is caused by transmission of Toxoplasma gondii from an infected mother to her fetus during pregnancy, is presented. In most cases in humans the route of infection is oral and by either of the two forms of Toxoplasma; cysts in the raw flesh of an infected animal and oocysts in the feces of an infected cat. The clinical manifestations in 9 cases of congenital toxoplasmosis encountered by the author are preserted. The findings of computed tomography (CT) and magnetic resonance imaging (MRI) in 3 of these cases are presented. Delayed migration and myelination are suggested to have occurred in 2 cases in which abnormal MRI findings were noted. These MRI findings reflected the clinical manifestations and may also have reflected the pathologic findings.

Experimental studies of transplacental infection following oral inoculation of Toxoplasma oocyst were performed in 3 groups of mice, in which infection of the dams was acute, subchronic, or chronic. The incidence of congenital infection was markedly higher in the acute infection group than in the subchronic or chronic infection groups. The incidence of 19S‐Toxoplasma (T)‐IgM positivity was also higher in the acute infection group than in either of the other two groups. Women should avoid contact with materials that have potentially been contaminated with cat feces, because Toxoplasma in the form of oocyst evacuated in cat feces is very highly infectious.

Congenital toxoplasmosis is often accompanied by severe sequelae involving the central nervous system, but treatment is not effective once the symptoms are manifested. Early diagnosis and early treatment, before symptoms are manifest, are therefore important for the prevention of congenital toxoplasmosis.
A Study on the Growth and Development of the Cranial Base in the Japanese Unilateral Cleft Lip and Palate: Comparison with the Japanese Skeletal Class I Occlusion
Authors: UMEMURA Sachio , YAMAGUCHI Toshio
Published: May 2008

Abstract The purpose of this study is to investigate the growth and the developmental dimension and the feature of cranial base transition in unilateral cleft lip and palate (UCLP). With regared to this proposition, we have already submitted a paper in which we compared our study with skeletal reversed occlusion on a scholary journal. The authors will present this proposition in comparison with skeletal class I. The subject group consisted of 15 males and 12 females with UCLP. The control group consisted of 11 males and 14 females with skeletal class I. Standared lateral cephalometric radiographs taken at first medical examination and three years later were used. The three linear dimensions (S‐N, S‐Ba, N‐Ba) and craniobasal angle (N‐S‐Ba) were measured.

The results were as follows: 1) Females showed no significant difference in S‐N, S‐Ba and N‐Ba but males had smaller S‐Ba and N‐Ba in the UCLP as compared with the control at the first examination and 3 years later. 2) There were no significant difference in the three distance items, S‐N, S‐Ba, N‐Ba, for females but significantly larger changes in N‐Ba appeared in the UCLP as compared with the controls for males. 3) The cranial base angle (N‐S‐Ba) showed no significant difference between the UCLP and controls for both male and female subjects at any observation time.

From the above evidences, it is estimated that the cranial base size and angle in the UCLP as compared with those of controls show no consistent trend owing to possible involvement of differential growth pattern between the anterior cranial base and posterior cranial base. The growth of cranial base itself per se seems to be influenced mutually at minimal level by the maxillofacial growth. This suggests growth patterns of cranial base and maxillofacial region are independent from each other.
Long‐lasting Effect of Maternal Hyperphenylalaninemia during Pregnancy on Postnatal Brain Development of Mice: Biochemical and Morphological Studies
Authors: YAMAWAKI Yasushi , OHYA Noriaki , SHIMADA Morimi
Published: May 2008

Abstract The effect of maternal hyperphenylalaninemia on postnatal brain development was examined. Maternal hyperphenylalaninemia was induced by giving chow supplemented with 6% phenylalanine (Phe.) and 0.12% p‐chlorophenylalanine (PCPA) for at least one month before coupling and then throughout pregnancy. Offspring from hyperphenylalaninemic mothers were given a normal diet from the first day after birth.

Infant mice were killed on the 21st, 28th and 56th day after birth. The protein, RNA and DNA in the brain were measured to determine the biochemical changes. Maturation of the dendrite of pyramidal cells was also examined by the Golgi method. The body weight of the offspring born to mothers, which had been treated with Phe. and PCPA during pregnancy, was significantly less than that of the control. The gain of cerebral weight showed a similar pattern with that to the body weight.

The total protein, RNA and DNA contents in the cerebrum of the treated group were also reduced significantly on 21st, 28th and 56th days after birth. The dendritic arborization of the cortical pyramidal neurons in the layer V showed significant reductions in the offspring born to hyperphenylalaninemic mothers compared with the age‐matched control at 21, 28 and 56 days after birth.

These findings suggest that maternal hyperphenylalaninemia during pregnancy causes an irreversible retardation of the neuronal maturation both biochemically and morphologically, and subsequently gives rise to disorders of the higher cortical functions.
Effects of Serum to Cushion Mesenchymal Cell Migration of the Developing Chick Heart in Vitro
Authors: SUMIDA Hiroshi , NAKAMURA Harukazu , ISHITOU Yukiko , YASUDA Mineo
Published: May 2008

Summary Migration of cardiac mesenchymal cells of chick embryos was examined in vitro. The conotruncal cushion and atrioventricular cushion cells of 6‐day‐old chick embryos were cultured on collagen gel in Dulbecco's modified Eagle's medium with chicken serum of calf serum, or no serum. After 48 hr of incubation, the culture was fixed with 4% formaldehyde, and photographed. The migration area of mesenchymal cells spread from the transplanted tissue was measured by digitizing the photographs. Then, the migration distance of mesenchymal cells was computed from the area with a personal computer.

Mesenchymal cells cultured with chicken serum migrated a significantly longer distance than those with calf serum or no serum. Under the designed conditions, the migration distance of the mesenchymal cells of the conotruncal cushion was longer than that of the atrioventricular cushion.

These results show that certain factor(s) in serum stimulates migration activity of cardiac mesenchymal cells, but the mammalian factor(s) is not cross‐reactive to cardiac mesenchymal cells of birds. Different effects of the serum from different species on the migration activity of chick cardiac mesenchymal cells were shown in the present results. At the same time, it was revealed that migration activity of mesenchymal cells of the conotruncal cushion is different from that of the atrioventricular cushion.
Behavioral Characteristics of Rats Selectively Bred for High and Low Avoidance Shuttlebox Response
Authors: OHTA Ryo , MATSUMOTO Aki , HASHIMOTO Yutaka , NAGAO Tetsuji , MIZUTANI Masahiro
Published: May 2008

Abstract Selective breeding of rat strains showing high and low avoidance behavior in the shuttlebox test has been performed since 1985. To elucidate the postnatal behavior of the high and low avoidance strains, animals from both lines were subjected to an open‐field test, wheel cage activity test and Biel maze test in the 13th, 14th and 16th generations, respectively. No significant differences in any parameter in the open‐field test were observed between high and low avoidance lines. However, animals from the high avoidance line showed higher motor activity in the wheel cage and fewer errors in the Biel maze than the low avoidance line.
Comparative Susceptibility of a Wild‐Derived Strain of Mus musculus molossinus and Laboratory Mice to Teratogenesis by Ethylnitrosourea
Authors: NAGAO Tetsuji , TAKASHIMA Hiromasa , MIYASHITA Nobumoto , FUJIKAWA Kazuo , MORIWAKI Kazuo
Published: May 2008

ABSTRACT A wild‐derived strain of Japanese house mice, Mus musculus molossinus (MSM), was compared with laboratory mice (DBA/2N, C57BL/6, C3H/He, BDF1, and ICR) for the susceptibility to teratogenic effect of ethylnitrosourea (ENU). ENU was applied i.p. to mice in each strain on day 7 of gestation. On day 18 of gestation, uterine contents were examined and viable fetuses were inspected for external and skeletal malformations. The dose (mg/kg) required to induce 25% embryonic lethality (LD25) was 46 in MSM and 28–54 in the laboratory mice. The frequencies of external and of skeletal malformations at LD25 were, respectively, 8 and 47% in MSM, 29–97% and 65–95% in the laboratory mice. Thus, MSM was less susceptible to ENU teratogenesis compared to any of the laboratory mice used and the difference in the susceptibility between MSM and the laboratory mice was more marked for external malformations than for skeletal malformations. These results are compatible with the hypothesis that laboratory mice may have genetic traits that facilitate teratological assays of drugs.
Frequency and Type of Malformations in the Offspring of C57BL/6 Male Mice Treated with Ethylnitrosourea
Authors: NAGAO Tetsuji , FUJIKAWA Kazuo
Published: May 2008

Male mice of inbred strain C57BL/6 were intraperitoneally treated with ethylnitrosourea (ENU). On days 64–80 after the treatment, the males were mated with untreated virgin females of the same strain and allowed to utilize sperm that were spermatogonial stem cells at the time of treatment. On day 18 of gestation, viable fetuses were inspected for external malformations. The frequency of externally malformed fetuses in the ENU‐treated series increased significantly over the control level. Malformations occurred spontaneously in the control series were microphthalmia and micrognathia. In the ENU‐treated series as well, they occurred and no other malformations were encountered. The frequencies among total malformations of microphthalmia were 95% and 92% in the control and the ENU‐treated series, respectively. Based on these results and other data, we propose that the male‐mediated teratogenesis represents spontaneous teratogenesis that is enhanced over the normal level by paternally transmitted germ‐line mutation(s).
Immunohistochemical Evaluation of Glucocorticoid Receptors in Developing Eyelids of NC‐eob Mouse Fetuses with Genetically Determined Open‐Eyelid Malformation
Authors: FUJII Sakiko , HOJO Hitoshi , KANEDA Masahiro , TERAMOTO Shoji
Published: May 2008

NC‐eob mice are mutants having open eyelids at birth. Previous studies have revealed that this defect is related to the absence of epidermal differentiation at the tip of the developing eyelids on gestation day (GD) 16, and that maternal treatment with cortisone acetate (CA), a glucocorticoid compound, which has an ability to accelerate epidermal differentiation, is not effective against the epithelium in NC‐eob fetuses although the eyelid growth is slightly enhanced.

In this study, transverse sections of the eyelids of NC‐eob fetuses on GDs 14 and 15 were evaluated immunohistochemically for glucocorticoid receptors (GRs) by using coisogenic NC fetuses as a control. For comparison, GRs in the palate were also investigated. On GD 14, the GR density in both the epithelium and mesenchyme of the eyelids was comparable between NC‐eob and NC fetuses. On GD 15, on the other hand, the GR density in the mesenchyme was significantly lower in NC‐eob than in NC, while no such change was found in the epithelium. The GR density in the palate of NC‐eob fetuses was comparable to that of NC fetuses in both the epithelium and mesenchyme on any of the gestation days examined.

These results suggest that the low density of GR in the eyelid mesenchyme of NC‐eob fetuses on GD 15 may be one of the reasons for the insufficient development of the eyelids after treatment of their mothers with CA.
Carnitine and Coenzyme A Decrease Valproic Acid‐Induced Neural Tube Defects in Mice
Authors: NAGAO Tetsuji , SHIROTA Mariko , SATO Masako
Published: May 2008

Abstract The effects of the administration of L‐carnitine or coenzyme A (Co A) on valproic acid (VPA)‐induced teratogenesis were examined in mice. VPA (300, 400, 500, 600, and 700 mg/kg, s. c.), L‐carnitine (100, 200, and 400 mg/kg, s. c.), or Co A (10, 100, 200 mg/kg, i. v.) was injected on day 8 of gestation (plug day = day 0). Exencephaly was induced dose‐dependently by single injections of VPA. Administration of L‐carnitine or Co A alone at any of the dose levels tested did not induce embryocidal or teratogenic effects. In combined treatment experiments, L‐carnitine (400 mg/kg) significantly reduced VPA (500 and 600 mg/kg)‐induced exencephaly, while L‐carnitine did not decrease VPA‐induced open eyelids. Co A (200 mg/kg) also significantly reduced VPA‐(600 mg/kg) induced exencephaly. The results demonstrate the attenuation of VPA teratogenicity by L‐carnitine and Co A.
Triphalangeal Thumb in the Typical Cleft Hand
Authors: MIURA Takayuki , HORII Emiko
Published: May 2008

Abstract Ten hands of six patients with only a single digit retained on the radial side of the cleft were observed from a group of 63 patients with typical cleft hand. All patients were bilaterally involved, and five were complicated with cleft foot. There were two types of retained thumb: a triphalangeal thumb with characteristic metacarpal bone(s), six hands of four patients; and a normal diphalangeal thumb, four hands of two patients. The metacarpal and distal phalangeal bone(s) of the triphalangeal thumb in typical cleft hand had signs of digital ray union: double epiphysis, deltametacarpal, bifurcated or perforated distal phalanx.
Determination of the No‐Effect Dose of Bis(tri‐n‐butyltin)oxide (TBTO) for Maternal Toxicity and Teratogenicity in Mice
Authors: FAQI Ali S. , SCHWEINFURTH Hermann , CHAHOUD Ibrahim
Published: May 2008

ABSTRACT Tri‐n‐butyltin oxide (TBTO) is a biocide used in wood preservatives and ship paint system. Available literature data on maternal toxicity and embryotoxicity of TBTO in mice appears to be contradictory. The purpose of the study was to determine a no‐observed‐adverse‐effect‐level (NOAEL) for these parameters and to reevaluate terato‐genic potency of the substance. Pregnant mice were treated orally by gavage daily with 0.5, 1.5, 4.5, 13.5, or 27 mg TBTO/kg body weight (b.w.) on days 6–17 of gestation. The control group received 5 ml/kg b.w. peanut oil daily during the entire treatment period. Evidence of maternal toxicity was only observed at the dose level of 27 mg TBTO/kg. In this group 3 of 40 animals died during the treatment period. The number of implantation sites, number of viable fetuses, fetal sex ratio, number of dead fetuses as well as the number of resorptions showed no dose‐related effects. The fetuses of dams exposed to the highest dose (27 mg TBTO/kg b.w.) revealed a high incidence of cleft palate (11.4%) when compared to the fetuses of the vehicle control group (0.8%). Additionally at this dose level 2 fetuses (1.2%) exhibited a bent radius; 8 fetuses (5%) were observed with a short mandible, and 5 fetuses (3%) showed a fusion of occipital bones with their basal parts. No signs of maternal and prenatal toxicity could be detected in mice under the experimental conditions chosen up to the dose of 13.5 mg TBTO/kg b.w. which represents a no‐observed‐adverse‐effect level (NOAEL).
Modified Susceptibility to Teratogenesis in the Offspring of Male Mice Exposed to Mutagens
Authors: NAGAO Tetsuji , FUJIKAWA Kazuo
Published: May 2008

Preconceptual exposure of male mice to a mutagen can increase the incidence of malformations in the offspring. In mutagenized spermatogonial stem cells, genetic changes responsible for F1 malformations were produced in a manner similar to that involved in the production of specific locus mutations. Irrespective of the kind of mutagens applied, the germ cell stage treated and the strain of mice used, resulting F1 malformations showed type distributions that were indistinguishable from the spectrum of those occurring spontaneously. When a teratogen was applied at the organogenic stage, embryos whose sires were preconceptually exposed to a mutagen showed higher susceptibility to induced malformations than those derived from untreated males. Experimental results pertaining to these contentions are summarized and the possible implications are discussed.
Morphology and Morphometry of the Deformed Cervical Vertebrae in a Mutant Knotty‐Tail (knt/knt) Mouse
Authors: MATSUURA Tetsuro , NARAMA Isao , OZAKI Kiyokazu , NAKAJIMA Hiroo , NISHIMURA Masahiko , IMAGAWA Tomohiro , KITAGAWA Hiroshi , UEHARA Masato
Published: May 2008

Mice with short and knotty tails arose as a spontaneous mutant in an ICR strain, and they have been named knotty‐tail mouse (gene symbol; knt). They also have a minor anomaly of the cervical vertebrae, especially in the axis. In this study, the cervical vertebrae of knotty‐tail (knt/knt) mice were investigated by morphological and morphometric examinations during the prenatal and postnatal period. From the observation of double‐stained preparations of knt/knt mice, morphological changes of cervical vertebrae were confined to the vertebral arch of the axis, which was asymmetrical and hypoplastic. From the morphometric analyses, outside of the axis, minor anomalies (i. e., broadened cervical vertebrae in the transverse direction, shortened and broadened ventral tuberculum of the atlas, thickened ventral lamina of 6th cervical vertebra) were maintained in the cervical vertebrae of knt/knt mice. Morphological deformity, reflecting an adult osseous anomaly, had been already formed in the cartilaginous axis prenatally. In the papain‐digested preparations of knt/knt mice, a bony invagination into the canal was detected in the axis, and the morphometric analyses on axis revealed that the growth of spinous process was apparently disturbed in comparison with that of ICR mice.
Normal Outcome Following Administration of Gonadotropin‐Releasing Hormone (GnRH) Agonist during Early Pregnancy
Authors: UEHARA Shigeki , SAKAHIRA Hiroshi , TAMURA Mitsutoshi , WATANABE Takanori , YAJIMA Akira
Published: May 2008

We observed an unusual case of a woman who had received a gonadotropinreleasing hormone (GnRH) agonist (GnRH‐a), leuprolide acetate, during the first trimester and early in the second trimester of pregnancy. Nevertheless, the pregnancy was uncomplicated and a healthy male infant (2,670 g) was born after spontaneous labor at the 38th week of gestation. The infant suffered no malformations or respiratory complication and he achieved normal growth. Although GnRH‐a is known to induce pregnancy loss, the drug does not appear to be teratogenic. Accordingly, a pregnancy that occurs during GnRH‐a therapy and progresses normally should not be terminated for fear of its teratogenic effects.
Terminology of Developmental Abnormalities in Common Laboratory Mammals (Japanese Version 1)
Authors: HORIMOTO Masao , ARIYUKI Fumio , DAIDOHJI Syunpei , FUJII Toshiyuki , FUKUNISHI Katsuhiro , HANADA Satoshi , IKEGAWA Sunao , ISHII Hiroyuki , INOUE Tatsuo , IWASE Takayuki , MATSUURA Masao , MATSUZAWA Toshiaki , NISHI Naoki , OHKUBO Yasutaka , SANBUISSHO Atsushi , SEKIYA Kiminori , TANI Mizuno , TANIGUCHI Hidemi , YOKOMOTO Yasuki , YOSHIDA Jun‐ichi , TAKAHASHI Michihito , YASUDA Mineo
Published: May 2008

Abstract: This paper is the first version of a Japanese glossary of terms for structural developmental abnormalities in laboratory animals, mainly rats, mice and rabbits. This is a translation of the glossary entitled Terminology of Developmental Abnormalities in Common Laboratory Mammals that was edited by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology (IFTS glossary). The purpose of the present Japanese glossary is to provide a common vocabulary, terms and definitions in the description of abnormalities observed in reproductive and developmental toxicity studies. The glossary contains 868 observations, synonyms, related terms, definitions of the abnormalities and non‐preferred terms for external, visceral and skeletal abnormalities in fetuses or neonates of laboratory animals. Modifying terms used repeatedly in the glossary (e. g., absent, atresia) are listed separately in Appendix A, and syndrome names that are generally known are listed in Appendix B. Translation was made into Japanese based on the following: 1) Observations are translated in order of organ/finding (e. g., thymus/absent, maxilla/fused) with exception of the terms in common use, 2) Words are appended where appropriate, when literal translation does not provide an adequate description, 3) A supplementary explanation is appended as an “annotation”, where appropriate, 4) Among the synonyms or related terms, the terms listed in Appendix A or the same Japanese translations as the observations are not described repeatedly, and 5) Non‐preferred terms are not literally translated, and only those terms which are considered as adequate as Japanese are described. Suggestions, questions, and additions are welcomed on the Japanese terms and translations in the glossary. Revisions of the Japanese glossary are planned based on the comments received.
Application of an Original Computerized Database (UR‐DBMS) for Diagnosis of the Malformation Syndromes
Authors: NARITOMI Kenji
Published: May 2008

ABSTRACT

“University of the Ryukyus‐Database for Malformation Syndromes (UR‐DBMS)” is a computerized database available as a diagnostic aid for malformation syndromes, chromosomal aberrations and other genetic diseases. This UR‐DBMS had been originally programmed by the author since 1989. The first version was established and opened to Japanese dysmorphologists in 1991. The newest version 5, started to be opened since 1998 in the form of a CD‐ROM disk, composed of four major data files and three other supporting files with a total volume about 400 MB. The main UR‐DBMS file includes clinical findings and notes of about 6,300 diseases/genes as well as 1,200 photographic data quoted from two major publishers in USA. Reference file includes almost all titles of the papers concerned. Abstract file has about 30,000 abstracts. Mutation file includes information for about 800 allelic variants identified so far, updated daily through Online MIM. These data were summarized and combined from several leading English textbooks and refined through Online MIM. UR‐DBMS uses an original systematized code to obtain quick and complete results in referring the database.

UR‐DBMS was applied in the diagnosis of 51 newly visited patients with malformations and mental retardation from 1996 to 1997. As a result, clinical diagnoses were obtained or highly suspected in about 75% of the patients. It is confirmed that UR‐DBMS is a useful aid for clinical geneticists to obtain correct or near correct diagnoses, especially when they must check further examinations to rule out and refine the diagnoses.
Inauguration of the Korean Congenital Anomalies Society
Authors: CHO Ja‐Yeon
Published: May 2008

Abstract The First International Congenital Anomalies Symposium was held in Chunchon, Korea, on June 3‐5, 1998. The Korean Congenital Anomalies Society was formally established during the Symposium. The historical background of the Society was briefly reviewed.
Carbamazepine‐Induced Brain Weight Reduction in Chick Embryos
Authors: SONODA Tohru , KONO Keiichiro , ITOKAZU Naoya , SUGIMOTO Tohru
Published: May 2008

Abstract The antiepileptic drug carbamazepine (CBZ) had been considered to be relatively safe for the fetus. We examined the teratogenicity of CBZ using chick embryos, with particular focus on the brain. A single dose of 5 mg was injected into the yolk sac of White Leghorn chick embryos at 24, 72, 120, 168 or 216 hours of incubation. On day 19 of incubation, embryos were removed, and counted and recorded as either live or dead. Each live embryo was inspected for the presence of external abnormalities, and body and brain weight were measured. There was no statistically significant difference between treated groups and control groups at all hours of incubation for mean body weight and incidence of embryo death. Mean brain weight was significantly lighter in treated groups at 120 and 168 hours of incubation. A significant difference in mean brain/body weight ratio was observed only at 120 hours of incubation. External abnormalities in treated embryos were not found with any consistency and these incidences were not significantly higher compared to those in the control groups. This experiment provides evidence regarding the risk of teratogenesis due to CBZ in the brain of chick embryo. The 120 hours of incubation in chick embryos corresponds to the 34‐36th day after conception in humans.
Defective Myosin Genes in Mutant Mice and Human Diseases
Authors: YONEZAWA Satoshi , MASAKI Shigeo , ONO Takao , HANAI Atsuko , KAGEYAMA Takashi , MORIYAMA Akihiko , SONTA Shinichi
Published: May 2008

Myosins are highly divergent actin‐based molecular motors. In five of eight classes expressed in mammals, defects in genes have been identified in mutant mice and/or human diseases. A mutated myosin II‐7 gene is one of the causes of human familial hypertrophic cardiomyopathy (FHC). The defective myosin Va gene is responsible for Griscelli disease, which is characterized by partial albinism and immunodeficiency, while in its mouse homologue coat color dilution is seen with or without neurological defects. There are three classes of myosins, VI, VII and XV, that are essential in the inner ear function. In humans, mutations in the VIIa gene are associated with three deafness‐related diseases, Usher 1B/DFNB2/DFNA11, providing the first example of exhibition of recessive‐ and dominant‐inherited disorders by different mutations in a single myosin gene.

There are variations in phenotype between human diseases and their mouse models, which appear to be explicable on the basis of differences in tissue expression patterns of the given myosin between mouse and man. In FHC and Usher 1BDFNB2DFNA11, a wide spectrum of clinical symptoms are observed. Evidence has accumulated suggesting that the more functionally important the mutation site of the molecule, the more serious and severe the symptoms, although involvement of additional factors such as modifier genes and genetic background can not be ruled out. Molecular genetic analyses of a variety of dilute alleles in mice have greatly facilitated our understanding of genotype‐phenotype correlations, including information about structurally and functionally important domains of the myosin Va protein and cell‐type‐specific functions of different isoforms produced by alternative splicing.
The central nervous system in microcephalic primordial dwarfism: Is there a characteristic developmental brain pathology in Seckel or Seckel‐like syndrome?
Authors: Schmitt Horst P. , Sergi Consolato
Published: May 2008

ABSTRACT In spite of the description of more than 70 cases of Seckel syndrome (SS) or Seckel‐like primordial microcephalic dwarfism, reports about investigations into the central nervous system pathology in SS remaind infrequent Here we comment on the thorough neuropathological examination of the brain in a familial case of Seckel‐like microcephalic dwarfism. The male fetus of a 6 gravida, 3 para was aborted at 19 weeks of gestation after prenatal ultrasound examination with the demonstration of severe microcephaly and retarded intrauterine development The propositus had two healthy sisters. Of two aborted fetuses and one deceased sibling, the deceased had also exhibited a Seckel‐like phenotype as well as, in MRI scans, micrencephaly, callosal agenesis and pachygyria. Neuropathological examination of the brain in the propositus resulted in the demonstration of two main categories of changes: (1) defective telencephalic midline structures (arhinencephaly as well as callosal, septal, fornical, and hippocampal agenesis), and (2) impairment of migration (micrencephaly with lack of cortical neuroblasts in both the telencephalon and the rhombencephalon as well as heterotopias in the former). These findings corresponded with those described in the few neuropathological and neuroradiological literature reports, indicating that there appears to be in SS‐like primordial microcephalic dwarfism and a characteristic, although not specific brain pathology which might be adequately summarized by the designation mediodysgenetic micrencephaly. The genetic background of SS as a basis for the CNS maldevelopment is discussed.
Developmental abnormalities induced by ionizing and nonionizing radiation
Authors: Inouye Minoru , Sun Xue Zhi
Published: May 2008

ABSTRACT Embryos are more susceptible to ionizing radiation than adults. Heterotopic gray matter was found in the brain of victims prenatally exposed to the atomic bomb. We reproduced this malformation in mice. Many cells in the ventricular zone, except for radial glial fibers, were destroyed by radiation. Following the proliferation of surviving cells, postmitotic neurons migrated to the cortical plate. Some neurons in areas missing radial fibers could not migrate and remained as heterotopic gray matter. On the other hand, there is no evidence of human congenital abnormalities caused by nonionizing radiation. Teratogenicity of microwaves in experimental animals is regarded as their thermal effect. However, some studies have reported effects of radio frequency and extremely low‐frequency electromagnetic fields on cell proliferation and differentiation.
Increasing incidence of congenital heart disease in patients with Down syndrome
Authors: Sonoda Tohru , Kouno Keiichiro , Sawada Kazumi , Koizumi Hirohiko , Takagi Junichi , Yamasaki Shunsuke
Published: May 2008

ABSTRACT Our impression that the incidence of congenital heart disease in patients with Down syndrome was increasing in our outpatient clinic was investigated. The change in the incidence of congenital heart disease was investigated during the period from January 1981 to December 1998 in 196 patients with Down syndrome diagnosed by chromosomal analysis. Of the 196 patients, 99 (50.5%) had congenital heart disease. The incidence increased during study period: 35.4% (1981–1983), 44.9% (1984–1986), 46.4% (1987–1989), 69.0% (1990–1992), 53.8% (1993–1995), and 81.3% (1996–1998). The number and the mean age of new outpatients were found to decrease. The incidence of Down syndrome patients whose disease was chromosomally proven by other institutions was increasing. The incidence of congenital heart disease in patients with Down syndrome is currently increasing in our outpatient clinic. However many factors might contribute to this phenomenon.
Incidence and types of congenital cardiovascular malformations in Japanese trisomy 21 fetuses around 20 weeks
Authors: Miyabara Shinichi , Ando Masahiko , Suzumori Kaoru , Nishibatake Makoto , Saito Nakamichi , Sugihara Hajime , Ikenoue Tsuyomu
Published: May 2008

ABSTRACT In order to clarify the incidence and types of cardiovascular malformations in Japanese trisomy 21 fetuses, seventeen cases were investigated at around 20 weeks of pregnancy. Cardiovascular malformations were observed in 8 of 17 cases (47.1%). The incidence of cardiovascular malformations was not greatly different from the estimated incidence (50%) in Japanese children with Down syndrome. The preferential elimination would not exist in trisomy 21 fetuses around 20 weeks relevance to cardiovascular malformations. Atrioventricular (AV) septal defect, tetralogy of Fallot and Ebstein's anomaly were observed in one case each. Bicuspid aortic valve and abnormal branching of the aortic arch were present in three and two cases, respectively. AV septal defect, which is perceived as a specific malformation of trisomy 21, was not recognized in high frequency in the present fetal study. A 13‐week‐old fetus showed multiple malformations; AV septal defect, tetralogy of Fallot and dysplastic bicuspid aortic valve. This case displayed an early morphology of AV septal defect which has rarely been reported in trisomy 21 fetuses. Possible pathogenesis of AV septal defect was discussed in relation to animal models of human trisomy 21. The present study indicated
An autopsy case of cyclopia with 13 trisomy with special reference to histological abnormalities of the eyeball
Authors: Kawasaki Hideya , Baba Satoshi , Kosugi Isao , Tsutsui Yoshihiro , Miura Kutsutoshi , Omori Hajime , Tokunaga Naoki , Kobayashi Takao
Published: May 2008

ABSTRACT We present an autopsy case of cyclopia and alobar holoprosencephaly and Polydactyly with 13 trisomy. A 27 year‐old Japanese female at the 27th gestational week was diagnosed as hydramnios and the fetus showed hydrocephalus and intrauterine growth retardation. The fetus was suspected to be cyclopic and holoproscncephalic by ultrasonograph and MRI images. The mother delivered a stillborn male baby at the 30th week of gestation. At autopsy, the baby showed true cyclopia having one eyeball and two irides in a single ocular opening, and one proboscis. On histological analysis of the eye, there was marked dysplastic hyperplasia of the retina with rosettes, focal degeneration of the retina with calcification, and prominent proliferation of glial cells beneath the hyperplastic retina. Multiple glomerular structures in the cerebral cortex and aplasia of the corticospinal tract were observed. In the spinal cord, a few neurons with pyknosis were observed in the ventral horn. Although no mutation was detected in the Sonic hedgehog in the present case, we reviewed recent studies concerning the molecular mechanisms of cyclopia and holoprosencephaly.
Effects of maternal uninephrectomy on the development of fetal rat kidney with special reference to the proliferative activity and epidermal growth factor (EGF).
Authors: Okada Toshiya , Mitsuoka Koji , Mukamoto Masafumi , Nakamura Jun , Morioka Hiroshi , Morikawa Yoshio
Published: May 2008

ABSTRACT Immunolocalization of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF) and EGF receptor (EGFR) in the kidney of fetal rats from uninephrectomized mothers were examined. As the index of proliferative activity, PCNA positive cell ratios in glomeruli and proximal tubules were determined. In the fetuses from uninephrectomized mothers and sham‐operated mothers, the PCNA positive cells were seen predominantly in the nephrogenic zone of the kidney. On fetal day 22, the PCNA positive cell ratio in the glomerulus of the fetus from uninephrectomized mothers (E fetus) was significantly lower than that in the glomerulus of the fetus from sham‐operated ones (C fetus). The proximal tubular cells showed positive reaction to EGF and EGFR antibodies in both fetuses. On fetal day 22, the reactions of the proximal tubules to EGF and EGFR antibodies were stronger in E fetus than in C fetus.

These results indicate that maternal uninephrectomy causes decreased proliferative activity of the glomerulus and increased reactions of the proximal tubules to EGF and EGFR antibodies in fetal rat kidney, suggesting accelerated development of the kidney.
FGFR2 mutation and genotype‐phenotype analysis in eight Japanese patients associated with Apert syndrome
Authors: Tsukuno Mail , Suzuki Hideaki , Ninomiya Kunitoshi , Eto Yoshikatsu , Kurihara Kunihiro
Published: May 2008

ABSTRACT Apert syndrome, one of craniosynostosis syndromes caused by allelic mutations of fibroblast growth factor receptor 2 (FGFR2), is characterized by symmetrical bony syndactyly of the hands and the feet. With the mutation analysis on FGFR2 gene from eight Japanese patients with Apert syndrome, two common mutations in the seven patients, 3 cases of Ser252Trp and 4 cases of Pro253Arg were detected. In the remaining patient with an atypical phenotype of the syndrome, however, no mutations were found in the regions of the FGFR2 gene responsible for Apert syndrome and other cranio‐synostosis syndromes. In this study, the correspondence with paternal age and genotype‐phenotype correlation was not clarified. Further analysis including mass screening is necessary to discuss those correspondences in the Japanese patients associated with Apert syndrome.
Induction of cleft palate in aniline hydrochloride‐treated rats: Possible effect of maternal methemoglobinemic hypoxia
Authors: Matsumoto Kiyoshi , Seki Nobuyuki , Fukuta Katsuhiro , Ooshima Yojiro
Published: May 2008

ABSTRACT  Aniline hydrochloride (AH), a methemoglobin formation‐stimulating substance, at a dosage level of 520 mg/kg which does not induce apparent fetal death, was injected subcutaneously into pregnant rats once on day 14, 15 or 16 of gestation in order to assess the stage specificity of cleft palate induction. Also, doses of 260, 390, 520 and 650 mg/kg were administered to pregnant rats on day 15 of gestation, and the dose‐response relationships with respect to fetal cleft palate and maternal methemo‐globinemia induction were studied. In the stage‐specificity study, paleness, decreased body weight gain and elevated methemoglobin concentration were noted in the dams treated with AH. Upon fetal examinations, although reduced body weight was noted in all AH‐treated groups, cleft palate was observed only in fetuses from those dams treated on day 15 of gestation. In the dose‐dependency study, AH induced maternal methemoglobinemia, decreased fetal body weight and increased the incidence of cleft palate dose dependently when administered at dosage levels of 260, 390, 520 and 650 mg/kg on day 15 of gestation. Additionally, administration of methylene blue, a methemoglobinemia‐preventing substance, to the AH‐treated dams ameliorated maternal methemoglobinemia and reduced the incidence of fetal cleft palate. In summation, it is considered that AH stage‐specifically induces cleft palate in rats and that cleft palate is caused not by a direct teratogenic effect of AH but by maternal hypoxia due to methemoglobinemia.
Infertility and assisted reproductive technologies: Bright and dark sides
Authors: Suzumori Kaoru
Published: May 2008

ABSTRACT  Infertility is defined as a couples failure to conceive following 2 years of unprotected sexual intercourse, affects 10% of reproductive age couples in Japan. There are 3 main causes: (1) ovarian failure‐anovulation (29%); (2) tubal factor‐anatomic defects of the female genital tract (36%); (3) male factor‐abnormal spermatogenesis (31%). The goal of the infertility evaluation are to determine the probable cause of infertility regarding prognosis and to provide guidance regarding options for treatment In the event an obstruction of the fallopian tubes is discovered or spermatogenesis cannot be improved, assisted reproductive technologies (ART) such as gamete intrafallopian tube transfer (GIFT) and in vitro fertilization with embryo transfer (IVF‐ET) are recommended. Since the successful birth of Louise Brown by this IVF‐ET, an explosion of ART has occurred all over the world in the last decade. In this review we discuss the revolution brought about by ART focusing on results in Japan, and clarify ethical issues that must be resolved.
The morphological development of human basal ganglia
Authors: Nunta‐aree S. , Ohata K. , Soares S. B. , Haque M. , Takami T. , Inoue Y. , Hakuba A. , Hara M.
Published: May 2008

ABSTRACT  Human embryos were studied to clarify controversies surrounding the developmental morphology of the basal ganglia and related structures. Eleven human embryos at Carnegie stages 12 through 21 were examined and reconstructed by the three‐dimensional computer graphics technique. Findings on the neural morphology and telencephalic arteries reveal that (1) all parts of the basal ganglia and the amygdala are telencephalic structures; (2) the medial part of globus pallidus, preoptic area and medial septal nucleus originate from the medial ganglionic eminence; (3) the olfactory bulb, prepiriform area, caudate head, caudate body, caudate tail, nucleus accumben septi, putamen, lateral part of globus pallidus and the amygdala originate from the lateral gangiionic eminence.