bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral Disorders Complicating Developmental Anomalies of the Brain: Sleep Behavioral Disorders*
Authors: HASHIMOTO Toshiaki 
Published: May 2008

Abstract Polysomnography in 3 1 patients with cerebral malformations was performed. In 9 cases, the hormone secretion rhythms during sleep (GH, PRL, LH, FSH and ACTH and/or cortisol) were examined.EEG showed abnormalities in 27 of the 31 pathologic patients. A defect and poor presentation of the sleep spindle was observed in 20 cases. Patients with cerebral malformations appeared to be poor sleepers. The amount and number of wakefulness increased. A decrease in REM sleep period was observed in 19 of the 36 records. 17 of the 31 pathologic patients showed abnormal proportions of time spent in the different stages of sleep with respect to the total sleeping time. 15 of the 31 pathologic patients showed more than one discrepant cycling of sleep parameters. Abnormal hormone secretion was observed in all 9 patients who were examined.The above results show that patients with cerebral malformations have various abnormalities of sleep behaviors, and that polysomnography is useful for studying sleep behavior in patinets with cerebral malformations.
Biochemical and Morphological Investigation on the Ataxic Mutant Shambling Mouse
Authors: YAMAGUCHI Tomoko , KATAGIRI Noriko , IHNUMA Mono 
Published: May 2008

ABSTRACT Ataxic Shambling mouse was investigated biochemically as well as morphologically to find any specific changes which would be compatible with their ataxic behaviors. Biochemical studies revealed that calcium uptake by the brain synaptosomes of ataxic mouse was decreased to about 30% at 30 mM potassium medium of the control and that the neuron specific enolase activity was lowered a half the value of control synaptosomes, while morphological investigations by Baker's staining for phospholipids disclosed little evidences of phospholipidosis in the nervous tissues and in other organs of the ataxic Shambling mouse. NAD dehydrogenase as well as myosin ATPase staining on the hindlimb muscles of the ataxic Shambling mouse showed a local atrophy and a certain derangement of muscle fibers.These results were discussed in relation to our previous finding of lowered phosphatidylserine synthesis by the brain microsomes which participated at the neuronal transport and transmission in the synaptosomes. Consequently, the ataxic behaviors of Shambling mouse would be ascribed to defective metabolism of phspholipids and decreased brain specific enolase in the synaptosomal fractions which may possibly result in reduced calcium uptake by the synaptosomes regulating neural transmission processes.
Prevention of Genetic Polydactyly in Polydactyly Nagoya (Pdn) Mice in Vitro by Surgical Treatment of Foot Plate during Embryogenesis
Authors: NARUSE Ichiro , KAMEYAMA Yoshiro 
Published: May 2008

Abstract Pdn/Pdn fetuses show preaxial Polydactyly of duplicated or triplicated metacarpal/metatarsal type in the fore‐ and hindlimbs. Pdn/+ fetuses show one extra digit of distal phalangeal type preaxially in the hindlimb and deformity of distal phalanx of the 1st digit in the forelimb. Normal patterns of physiological cell death in the preaxial apical ectodermal ridge (AER) and the deep preaxial mesoderm (fpp) were disrupted in Pdn/Pdn embryos. It was supposed that delayed involution of preaxial AER might have caused the abolishment of fpp, which in turn could have induced polydactyly in Pdn/Pdn.In order to induce cell death in the fpp region artificially, tissue destruction of the fpp region of right fore‐ and hindfoot plates of Pdn/Pdn, Pdn/+ and +/+ embryos was performed by an electric knife on day 11.5 of gestation, and the embryos were cultured in the rotator culture system for 20 hours. The non‐treated left foot plates served as the controls.In Pdn/Pdn embryos, the non‐treated left foot plates showed abnormal protuberance and/or the extra digital rays preaxially. But the treated right foot plates did not exhibit these abnormal characteristics. Instead they revealed 5 digital rays of mesodermal condensation in the histological sections.These results indicated that the restriction of the artificial tissue destruction in the fpp region could prevent the manifestation of preaxial extra digits in Pdn mice.
Monitoring of Birth Defects and Epidemiology*
Authors: ASHIZAWA Masami , KURACHI Keiichi 
Published: May 2008

Abstract A monitoring of birth defects based on systematic collection and accumulation of data in a defined population or selected hospitals using definite diagnostic criteria offers per se indispensable source of information for epidemiological studies such as retrospective case‐control study or prospective cohort study.Each results of statistics or monitorings of birth defects currently conducted in Japan were briefly stated.The on‐going investigation data on congenital malformations about over 1,524,700 births performed since 1972 by Japan Association for Maternal Welfare were reviewed. Osaka and Kanagawa Programs, population‐based, have so far totally over 181,000 and 160,000 births resp.Factors increasing malformations suggested were stillbirth, low birth weight, small for gestational dates, consanguinity and smoking during pregnancy from Kanagawa Program. As an example of on‐going international collaborative study by the members of ICBDMS, data have been collected on limb reduction deformities. However, it might be more standardized in various aspects.Three statistical techniques — Z‐test, cusum test and sequential method were adapted to distinguish a significant increase from a baseline frequency or to identify significant temporal changes. Although abrupt fluctuations were encountered, overall patterns about 17 marker‐defects revealed to be fairly stationary in these years.Collection of sufficient numbers of cases and controls or exposed and unexposed enough to detect significantly so far unknown complicated factors is not always easy. To clarify unknown factors (polygenic, multifactorial, synergism or spontaneous errors of development), co‐work or co‐ordinated study of epidemiology and experimental teratology would be desirable to fill the gap between them.
Preaxial Polydactyly and Hallux Varus: Classification of Hallux Varus and Relationship between Hallux Varus and Preaxial Polydactyly
Authors: MIURA Takayuki , NAKAMURA Ryougo , TORII Syuuhei , HANAKI Kazuharu , YOSHIHASHI Yuuji 
Published: May 2008

Abstract The clinical features of 18 patients diagnosed as having preaxial Polydactyly and hallux varus were studied.There are three types of hallux varus: 1) the medial great toe is pushed out by the lateral overlapping great toe, 2) the great toe is inverted by the deformed first metatarsus, and 3) the great toe is inverted by anchoring substance of the hypoplastic or degenerative medial great toe.The general diagnosis of “hallux varus” may be reasonable based on the common appearance, but the clinical features of these three types differ from each other. The patients with hallux varus caused by anchoring of the hypoplastic or degenerative medial great toe should be strictly differentiated from the patients with hallux varus due to deformity of the metatarsus. Special consideration for treatment is needed for each type.
Ethical Problems in Teratology*
Authors: OKAMOTO Naomasa , BABA Kazuo 
Published: May 2008

Abstract A symposium on the ethical problems in teratology was held to consider the problems that may occur in the research and therapy of the medical sciences. Selected titles of the symposium were as follows: 1. Some cytogenetical aspects of artificial fertilization. 2. Abortion: Ethical issues and Japanese attitudes. 3. Ethical problems of congenital malformations; “fetal therapy in utero” 4. Ethics in autopsy of human fetuses and newborns with congenital anomalies. 5. Genetic counseling. 6. Logic and ethics of learning (Gakumon).These broad problems were discussed in all their aspects.
Structure and Functions of Cell Surface Glycoconjugates in Brain Morphogenesis*
Authors: OOHIRA Atsuhiko , MATSUDA Motoko , MATSUI Fumiko , SHOJI Ryujiro , WATANABE Kimi 
Published: May 2008

Abstract Migration of newly‐generated neuroblasts to their definitive locations to form the laminated architecture of the brain is crucial in brain morphogenesis. In order to understand the molecular mechanism operative in the neuroblast migration, cell surface or pericellular glycoconjugates were isolated from the rat brains at various developmental stages. Hyaluronate (HA), chondroitin sulfate proteoglycans (CS‐PGs), heparan sulfate proteoglycans (HS‐PGs) and polysialosyl glycoproteins (N‐CAMs) have been characterized so far. Our biochemical and immunohistochemical experiments indicate that HA and a CS‐PG participate in construction of the hydrated extracellular milieu for the directional migration of neuroblasts.Dissociated fetal brain cells reaggregated and formed a tissue configuration, in aggregating culture for 48 h, similar to that observed in the original brain primordium. Therefore, one can consider that the in vitro process is regulated at least in part by the mechanism operative in brain morphogenesis in vivo. It was suggested that HS‐PGs and N‐CAMs were involved in the in vitro process of the tissue self‐organization as cell membrane components.From these findings and others, we conclude that some developmental changes in the structure and the contents of these cell surface glycoconjugates of the brain are implicated in neuroblast migration in brain morphogenesis.
Development of the Vertebrate Heart and the Extracellular Matrix*
Authors: HIRAKOW Reiji 
Published: May 2008

Abstract Three major topics in vertebrate cardiogenesis were surveyed with special attention given to the cellular migration and the extracellular matrix (ECM).1. Prior to primitive tubular heart formation, cardiogenic (lateral mesoderm) cells migrate on the endoderm to the definitive position ventral to the foregut. SEM observations of newt embryos revealed a subtle network of fine fibrils on the endodermal cell surface. These ECM fibrils were proved to be composed of fibronectin by immuno‐SEM method using latex beads.2. The epicardium does not differentiate in situ from so‐called “epi‐myocardium”, but is formed in such a way that tips of mesothelial cell clusters extending from the septum transversum region attach to the dorsal side of the cardiac loop and spread gradually over the myocardium, eventually covering the entire heart. Using ruthenium red‐containing fixative, precipitated ECM was found specifically on the myocardium.3. Cells of the cushion mesenchyme are known to be liberated from the endothelial cells and migrate into the cardiac jelly. There is growing evidence that ECM affects the cellular behavior in this process. Furthermore, neural crest cells were shown to contribute to mesenchyme formation in the outflow tract. Disturbed formation of the cushion tissue likely results in various malformations of the heart.
Behavioral Teratology Symposium “Advances in Behavioral Teratology Testings”
Authors: TANIMURA Takashi , KIHARA Takahide 
Published: May 2008

Abstract The Behavioral Teratology Meeting, a satellite meeting to the Annual Meeting of the Japanese Teratology Meeting hold a symposium on behavioral teratology on July 24, 1986 in Tokyo. The invited to this symposium were four American speakers who came to Japan to attend the 4th International Congress of Toxicology.Presentations of these guest speakers appear as review articles in Congenital Anomalies following this communication. In general discussion, many critical and suggestive comments were expressed by the participants on the selected topics of behavioral teratology; 1) species and strains, 2) developmental stage, 3) positive controls, 4) procedures and 5) interpretation, and these were briefly introduced.
Dose‐Response Relationships in Prenatal Toxicity*
Authors: NEUBERT Diether , OCHERT Gerd , PLATZEK Thomas , CHAHOUD Ibrahim , FISCHER Bernd , MEISTER Reinhard 
Published: May 2008

Abstract Data and considerations on the significance of establishing dose‐response relationships in embryotoxicity (and especially teratogenicity) are presented here.The problems discussed include the following topics:‐ analysis and transformation of experimental data;‐ dose‐response curves for various embryotoxic effects;‐ reproducibility of studies on prenatal toxicity;‐ prenatal versus maternal toxicity;‐ quantitative risk assessment;‐ “threshold” for teratogenic effects;‐ analyses of combinations of teratogens;‐ relationship between molecular events and chemical teratogenicity.
Congenital Diaphragmatic Hernia Induced by Nitrofen in Mice and Rats: Characteristics as Animal Model and Pathogenetic Relationship between Diaphragmatic Hernia and Lung Hypoplasia
Authors: NAKAO Yoshitaka , UEKI Reiko 
Published: May 2008

Abstract Congenital diaphragmatic hernia (CDH) and lung hypoplasia were induced in high frequency and dose‐dependently in the offspring from dams, treated orally with 2,4‐dichlorophenyl‐p‐nitrophenyl ether (nitrofen) during pregnancy in CD‐I mice and CD rats. Both in mice and rats, CDH found in the fetal and neonatal periods was a posterolateral type of diaphragmatic hernia (DH) showing a distinct side‐preponderance: the left‐side preponderance in mice and right‐side preponderance in rats. CDH in the offspring, surviving after weaning, was mostly of retrosternal type in mice and of pericardial type in rats. CDH induced experimentally in the present study can be regarded as an excellent animal model for human CDH in terms of both anatomical features and the time of appearance of different types of CDH as well as clinical symptoms.Lung hypoplasia was observed in the offspring with and without CDH; though its severity was greater in those with CDH. The offspring with severe lung hypoplasia died of respiratory insufficiency during the neonatal period, regardless of the presence or absence of CDH. These findings suggest that lung hypoplasia is not a consequence of CDH, but that a common pathogenetic process in the early embryonic stage might involve both lung hypoplasia and CDH.
Biochemical Studies on the Effect of Maternal Hyperphenyl‐alaninemia on Fetal Brain Maturation of Mice
Authors: YAMAWAKI Yasushi , OHYA Noriaki , SHIMADA Morimi 
Published: May 2008

Abstract The effects of maternal hyperphenylalaninemia during pregnancy on the biochemical maturation of neonatal mice brains were examined, thus establishing the critical concentration of phenylalanine in maternal blood and the critical period of maternal hyperphenylalaninemia during pregnancy. Hyperphenylalaninemia was induced by giving chow supplemented with 3%, 4%, 5%, or 6% phenylalanine (Phe.) and 0.12% p‐chlorophenylalanine (PCPA) for at least one month and then throughout pregnancy. Some of the pregnant mice fed the 6% Phe. diet before pregnancy received a normal diet after conception (6%: A).Offspring from each group were decapitated two days after birth. Their brains were removed and then divided into the cerebrum and the brain stem including the cerebellum. Total protein, RNA and DNA were measured biochemically. All kinds of markers of the newborn mice born to the 5% and 6% mothers, the weight and the contents of the protein, RNA and DNA, were reduced significantly in both the cerebrum and brain stem. In the 4% group, however, only the brain stem was affected. The 3% group showed reductions neither in the weight nor the protein and nucleic acids contents in both the cerebrum and brain stem. In the 6%:A group, in which the diet was returned to normal just after conception, total protein, RNA and DNA were reduced in the brain stem, but not in the cerebrum.These results suggest that the critical concentration of maternal blood phenylalanine during pregnancy in the mouse is 11mg/dl, which is that corresponding to the 3% group, and also suggest that it is too late to begin the low phenylalanine diet after conception.
Abnormal Cerebral Vascularity in Mice with Histogenetic Disorders of the Cerebral Cortex and Postnatal Manifestation of Hydrocephalus
Authors: KIMURA Shoko , FUKUI Yoshihiro , KAMEYAMA Yoshiro 
Published: May 2008

Abstract Pregnant mice were exposed to 60Co gamma‐irradiation on day 13 of gestation, and the offspring after birth were examined in histological sections and microvascular specimens with India ink, in order to know the pathological changes leading to postnatal manifestation of hydrocephalus. The cerebrospinal fluid pressure was also measured.The offspring from birth to 12 days of age showed microcephaly or dysgenetic hydrocephaly with severely deranged cerebral cortical architecture. The microvascular specimens of these brains showed a deranged vascular pattern and poor vascular network in the brain mantle. Its severity was in proportion to that of the disorder of the cortical architecture. These brains were involved with blood congestion and perivascular hemorrhage in the periventricular white matter, and consequently with cystic degeneration and pseudoventricle formation, which changes became evident at 7 to 10 days of age. The cerebrospinal fluid pressure was not different from that of non‐treated control mice until 12 days of age. Around 14 days of age, the pressure began to increase concurrently with an external appearance of vaulted skull, indicating a transformation from degenerative ex vacuo type of hydrocephaly to progressive high‐pressure hydrocephalus.These results suggested that histogenetic disorders of the cerebral cortex caused abnormal vascular formation in the brain mantle and that the consequent intracerebral circulatory disturbance played a significant role for degenerative changes of the brain tissue and a failure of the cerebrospinal fluid dynamics at the time of brain growth spurt.
Chondrodysplasia Punctata with Myopathic Involvement
Authors: NOGAMI Hiroshi , OKI Takashi , ISHIDA Yoshihito , MURACHI Shunji , IYODA Kazuhito 
Published: May 2008

Abstract Histopathological examination of the muscle and the iliac crest cartilage were performed in a one year 6‐month‐old girl with chondrodysplasia punctata. The patient's mother was also affected.Light micrographs of the cartilage revealed long, tongue‐like processes extending into the osseous tissue in the osteochondral junction. Electron micrographs of the cartilage showed an increased number of lipid droplets in chondrocytes and more numerous hydroxyapatite clusters and matrix vesicles in the inter‐territorial matrix. Pathological findings of the biopsied muscle included derangement and/or missing cross‐striations, together with many vacuoles in the muscle fibers. These degenerative changes in both the muscle and the cartilage as well as many associated complications may suggest that chondrodysplasia punctata is a generalized metabolic disorder.
Cytochemical Maturation of the Notochord in Dysraphic Mice
Authors: WILSON DORIS B. , WYATT DARLENE P. 
Published: May 2008

AbstractFunctional aspects of notochordal maturation in dysraphic loop‐tail (Lp) mice were analyzed by means of ultrastructural cytochemistry on embryos at 9–12 days of gestation. Notochordal cells in normal (+/+; Lp/+) and dysraphic abnormal (Lp/Lp) embryos showed ultrastructural features consistent with secretory activity, particularly at 10 and 11 days. With specific cytochemical staining, glycogen was observed as thiocarbohydrazide‐silver proteinate particles sparsely scattered throughout notochordal cells of normal and abnormal embryos at 9 and 10 days, with aggregates common at 11 and 12 days. With tannic acid and ruthenium red treatment, the perinotochordal space in abnormals showed differences in the density of stained filaments from that in normal embryos, suggesting a defect in glycosaminoglycan deposition. In abnormal embryos, the notochord became located relatively more distant from the open neural folds than from the closed neural tube in normal littermates, and the arrangement of the adjacent mesenchymal cells was irregular and less dense than that in the normal embryos. Thus, although the ultrastructure of the notochordal cells was relatively normal, the features indicative of aberrant interactions among the notochord, neural folds, and adjacent mesenchymal cells may be of significance in the etiology of dysraphism in this mutant.
Strain Difference in Effects of Ethanol Treatment on Fetal Development in C57BL and DBA Mice
Authors: FUKUI Yoshihiro , NARUSE Ichiro , HOSHINO Kiyoshi , KAMEYAMA Yoshiro , TAKEUCHI Yoshiki 
Published: May 2008

AbstractPregnant C57BL and DBA mice were treated with i. p. injection twice of 25% ethanol (3.97 g/kg × 2), four hours apart, on day 7, 8, 9, 10, 11, 12 or 13 of gestation. They were killed on day 18 of gestation, and the fetuses were examined for external and skeletal malformations. In order to determine the blood ethanol levels, nonpregnant animals were treated with the same dose of ethanol and then killed at 0.5‐16 hours after injection.Fetal mortalities of DBA mice were higher than those of C57BL mice. The body and brain growth retardations were severer and the incidence of malformations was higher in C57BL mice than in DBA mice. The most frequently observed malformations were microphthalmia and digital malformations in C57BL mice, and open eyelids in DBA mice. Blood ethanol reached the maximum level within half an hour after the second injection in both strains, and was significantly higher in DBA mice than in C57BL mice 2–15 hours after the second injection. It is difficult to explain the strain difference of embryotoxicity between C57BL and DBA mice on the basis of only the difference in blood ethanol level in the present study.
Effects of Phenytoin on Morphology of Otolith in the Rat Fetuses
Authors: MURAKAMI Yoshinori , OGASAWARA Hiroyuki , MISAWA Noriko , FURUKAWA Yasuo 
Published: May 2008

AbstractThe effect of phenytoin on morphology of otoliths was investigated in rat fetuses. Pregnant rats were administered with phenytoin (PHT) 50, 100 and 200 mg/kg/day on days 11–14 of pregnancy and the fetuses were removed on day 20 of pregnancy. Methyl salicylate cleared specimens were prepared and the otoliths were scored for morphological completeness.Otolith score decrease was observed only in utricles of the fetuses treated with PHT 200 mg/kg/day with a statistical difference. The most remarkable morphological change in otoliths was that the utricular otolith and the saccular otolith were connected and the otoconial crystals were visible between utricular and saccular otoliths. The frequency of this conjoined utricule and saccule was about 30% of the fetuses treated with PHT 200 mg/kg/day. From these results, the threshold level of PHT for induction of otolith abnormalities was estimated to be between 100 and 200 mg/kg/day.
Contiguous Gene Syndromes as Multiple Anomalies Syndromes: Molecular Basis and Approach to Gene Cloning
Authors: NIIKAWA Norio 
Published: May 2008

AbstractRecent knowledge on molecular basis of several contiguous gene syndromes as multiple anomalies syndromes, such as Prader‐Willi syndrome (PWS), Angelman syndrome (AS), Beckwith‐Wiedemann syndrome (BWS), tricho‐rhino‐phalageal syndrome types I (TRPS I) and II (TRPS II or LGS), and complex glycerol kinase deficiency (CGKD), are reviewed. Based on the results of DNA deletion studies and on the evidence for the genomic imprinting mechanism of both PWS and AS, a model for the occurrence of the two syndromes is proposed. Also, a strategy of the microdissection/microcloning technique as a reverse genetics technique, i. e., direct cloning of chromosomal DNAs from a defined region of human chromosome, particularly for the cloning of the exostosis gene in TRPS, is presented.