bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital Hydrocephalus: Role of Transplacental Myxovirus Infection
Authors: TAKANO Tomoyuki , UNO Masaaki , YAMANO Tsunekazu , SHIMADA Morimi 
Published: May 2008

AbstractThe definite etiology in most cases of congenital hydrocephalus still remains unknown. Many studies have been reported on the experimental hydrocephalus induced by viral infection other than TORCH (Toxoplasma, Other agents, Rubella virus, Cytomegalovirus and Herpes simplex type 1 and 2 viruses). Above all mumps virus induces a high frequency of hydrocephalus. Several pediatric cases of hydrocephalus after mumps virus infection have been reported. These cases are thought to be caused by ependymitis due to mumps virus infection. Clinical cases of congenital hydrocephalus possibly caused by intrauterine mumps or influenza virus infection are also accumulating. The definitive evidence of a teratogenic potential for mumps and influenza virus, however, has been obscure yet. Our experimental studies demonstrated that mumps and parainfluenza virus type 3 could induce hydrocephalus by destructive ependymal infection in suckling hamsters. However, the transplacental infection of these viruses was rare. These results show that myxoviruses such as mumps and parainfluenza virus have a strong affinity to ependymal cells, and then they cause resultant ependymal destruction. We suggest that when the placenta is impaired so severely that these viruses are able to pass through the placental barrier, maternal infection would cause the hydrocephalus to the infant.
Inborn Errors of Peroxisome Biogenesis and Brain Malformation: Clinical and Biochemical Studies*
Authors: SUZUKI Yasuyuki , SHIMOZAWA Nobuyuki , ORII Tadao 
Published: May 2008

AbstractZellweger's cerebro‐hepato‐renal syndrome is characterized by the absence of peroxisomes, severe neurologic manifestations, and neuropathological findings such as polymicrogyria and neuronal heterotopia which are based on disturbances of neuronal migration. We investigated the pathogenesis of peroxisome‐deficient disorders in attempts to clarify the molecular basis of these brain dysgenesis. Complementation analysis revealed that at least 9 genes contribute to the formation of peroxisomes. One of these gene products, peroxisome assembly factor‐1 (PAF‐1), was isolated, using a functional cloning method and a mutant Chinese hamster ovary cell line with defective peroxisomes. PAF‐1 restored the peroxisomes and biochemical abnormalities in fibroblasts from patients with Zellweger syndrome and who belonged to complementation group F. Defects in PAF‐1 would result in dysfunction of peroxisomal membrane or in the transport machinery of peroxisomal proteins, and metabolic disturbances such as accumulation of very long chain fatty acids and defects in plasmalogen may occur.
Retinoids and Retinoid Receptors in Teratogenesis*
Authors: KOCHHAR Devendra M. 
Published: May 2008

AbstractThere is overwhelming evidence that vitamin A (retinol), presumably through its metabolite retinoic acid, participates in organogenesis at several stages and sites during normal development. Besides the important role of retinol and retinoic acid (RA) as micronutrients in growth and development, these retinoids and their synthetic analogs are now viewed as drugs for treatment of oncologic and dermatologic diseases. An excess of vitamin A, RA, or several other synthetic analogs are teratogenic. Mechanisms involved in teratogenesis remain unsolved but are under active investigation in many laboratories. The attention has recently focused on a series of endogenous proteins which serve as nuclear receptors for natural retinoids as means to discover how retinoids intervene in diverse cellular functions and which of their cellular and molecular targets are crucial to the developing embryo. There are two classes of receptors, termed retinoic acid receptors (RARs) and retinoid X receptors (RXRs). This brief review summarizes the results of our recent studies which suggest that: 1) the teratologic effects of retinoids are mediated by the nuclear receptors; 2) the heterodimer RXR/RAR pathway is the major mechanism for the induction of teratogenesis; 3) RXR‐selective synthetic retinoids have diminished teratogenicity; and 4) an overexpression of specific RARs in response to RA disrupt skeletal morphogenesis resulting in limb reduction defects.
Teratogenic Characteristics by Single Dosing of Antineoplastic Platinum Complexes in Rats
Authors: MURANAKA Ri‐ichi , FUKIISHI Yonetaka , TSUIKI Hisashi , HASEGAWA Yasuhiko 
Published: May 2008

AbstractWe investigated the embryolethality and teratogenicity of a new platinum complex, 254‐S, and cisplatin (CDDP) by single dosing to dams on one day during the period of organogenesis. The results are summarized as follows: (1) Embryolethality was maximal after 254‐S treatment on day 7 of gestation (Day 7) and after CDDP treatment on Days 6 to 9. It decreased with advancing gestational age. (2) Both 254‐S and CDDP were teratogenic. The critical period for induction of malformation appeared twice for 254‐S, at Days 6 to 9 and at Days 14 to 15, and once for CDDP, at Days 5 to 8. (3) The types of malformations induced by 254‐S or CDDP were different, indicating different mode of teratogenesis. 254‐S caused malformations mainly in the craniofacial or limb bud areas in the biphasic manner, whereas CDDP caused malformations mainly of the limb buds in the monophasic manner. (4) Malformations of the limb/digit and tail that are known to have critical periods during the late stage of organogenesis were induced by treatment with 254‐S on Day 7 and with CDDP on Day 5 or 6.
Vasoactive Intestinal Polypeptide‐containing Neurons and Processes in the Developing Hippocampus of Rats Prenatally Exposed to Methylazoxymethanol Acetate
Authors: FUNAHASHI Atsushi 
Published: May 2008

AbstractDevelopmental alteration of the dendritic arborization and axonal boutons of vasoactive intestinal polypeptide (VIP) neurons in the CA1 hippocampus was immunohistochemically examined in both control and microcephalic rats at postnatal days 15 and 60. Microcephaly was induced by prenatal exposure to methylazoxymethanol acetate (MAM; 20 mg/kg) on day 15 of gestation (MAM rats). In the control at postnatal day 15, VIP‐immunoreactive axonal boutons were densely aggregated specifically in the stratum pyramidale. At postnatal day 60, these axonal boutons in the stratum pyramidale of the controls were somewhat less dense. Another aggregation of axonal boutons was also observed along the upper part of the stratum oriens near the alveus border (area A). In the MAM rats at postnatal day 15, on the other hand, VIP‐immunoreactive neurons in the CA1 hippocampus were decreased in number and the dendritic arborization of these neurons was very poor compared with the controls. The density of VIP‐immunoreactive axonal boutons was remarkably lower than the controls. In the MAM‐rats at postnatal day 60, density of the axonal boutons was almost similar with that of MAM‐rats at postnatal day 15 in the stratum pyramidale, whereas a drastic increase was observed in area A, which made the bouton aggregation more dense than in the controls at postnatal day 60. These observations suggest that there is an area‐dependent difference in the development of VIP neurons in the CA1 hippocampus which may be related to the area‐dependent heterogeneous vulnerability of VIP neurons to MAM exposure.
Incidence and Familial Occurrence of the Congenital Anomalies of the Face, Hand and Foot
Authors: OKA Ichiro , NATSUI Makoto , GOTO Takahiro , KAMIYA Noriaki , YAMADA Atsushi , FUJITA Shinya 
Published: May 2008

AbstractWe made an epidemiological study of congenital anomalies of the face, hand and foot in newborns from 1973 to 1992 in Miyagi Prefecture which has a population of about two million. In these twenty years 579,766 babies were born in Miyagi Prefecture. Out of these newborns 3,416 babies with 3,759 congenital anomalies of the face, hand and foot were registered. Of all registered congenital anomalies, face anomalies were most commonly encountered, followed by hand and foot anomalies. Among face anomalies, in order of frequency, accessory ear was the most common, next cleft lip with or without cleft palate, cleft palate alone, cryptotia and microtia. The occurrence ratio per 10,000 live births was 9.6 in accessory ear, 6.7 in cleft lip, 6.1 in cleft lip with cleft palate, 4.2 in cleft palate alone, 2.9 in cryptotia, and 1.8 in microtia. In hand and foot anomalies, polydactyly was the most common and syndactyly the next. Incidence ratio of polydactyly was 5.8 in the hand and 6.4 in the foot. Polydactyly was the most frequent in the preaxial ray in the hand and in the postaxial ray in the foot. About half of cases of postaxial polydactyly the foot was associated with syndactyly between the fourth and fifth toe. In addition, we reported on variation of the incidence ratio and familial occurrence of congenital anomalies of the face, hand and foot.
Functional Damage in the Developing Brain Induced by Maternal Environmental Agents: Ethanol, Tobacco and Low‐Copper Level
Authors: TANAKA Harumi 
Published: May 2008

AbstractTo evaluate tests for behavioral teratology in animals, brain dysfunction caused by maternal environmental agents is compared both epidemiologically and experimentally. Ethanol: The features of CNS involvement in human FAS (fetal alcohol syndrome) and FAE (fetal alcohol effects) are developmental delay and intellectual impairment. One of the most vulnerable structures in the rat fetus exposed to ethanol in utero is the synaptic formation in the hippocampus. What test for brain dysfunctions, such as deficits in learning, inhibition and attention, is there? Tobacco: Thirty‐three percent of human FTS (fetal tobacco syndrome) cases have CNS involvement, which is characterized by developmental delay, and behavioral problems such as a short attention span and hyperactivity. As to the concomitant effects of ethanol and tobacco on human offspring, CNS involvement appeared to be most specific for alcohol exposure, but was also observed slightly with smoking without drinking. How can the effects of concomitant substances be discriminated in an animal test? Low‐copper level in brain: Related to the development of their offspring, abnormal movements in brindled mutant mouse heterozygotes are observed. These findings may be influenced by both copper and oxygen radical metabolism. The teratogenic effects of triethylene tetramine dihydrochloride, a chelating drug for copper on the fetal mouse brain are noted both grossly and microscopically. How can the abnormal CNS development in relation to a certain biochemical mechanism be detected by means of an animal test? In conclusion, to examine behavioral teratology in animals, specificity and accuracy should be considered in comparison with in humans.
Effects of Bis‐diamine to Cardiac Mesenchymal Cell Migration of the Chick Embryo
Authors: SUMIDA Hiroshi , NAKAMURA Harukazu , MATSUO Tatsuhiro , YASUDA Mineo 
Published: May 2008

Summary Bis‐diamine is a teratogen which induces conotruncal anomalies in rats and chicks. Bis‐diamine induces endocardial cushion defects in rats but it does not induce in chicks. In the present study, we examined effects of bis‐diamine to chick embryonic cardiac mesenchymal cells. Chick embryos of 3 days incubation (E3, H. H. stage 17–28) were treated with 100 μg of bis‐diamine dissolved in 50 μl dimethylsulfoxide. The conotruncal and atrioventricular cushions of the E6 embryos treated with bis‐diamine were cultured with chicken serum. After 48 h of incubation, the culture was fixed with 4% formaldehyde. The area of grown out mesenchymal cells from the transplanted tissue was measured, and then the migration distance of mesenchymal cells was computed from the area.In the group treated with bis‐diamine, the migration distance of conotruncal cushion mesenchymal cells was significantly shorter than that of controls. However, the migration distance of atrioventricular cushion mesenchymal cells was not diminished. By scanning electron microscopy, the superior endocardial cushion of E4.5 or E5 embryos treated with bis‐diamine was slightly hypoplastic compared with the inferior endocardial cushion. In spite of hypoplasia of the superior and inferior endocardial cushions, these cushions fused in E6 embryos treated with bis‐diamine.These results have shown that bis‐diamine affects migration activity of conotruncal cushion mesenchymal cells but it does not severely affect that of the atrioventricular cushion in chicks. This portionally different effect of bis‐diamine can explain that bis‐diamine does not frequently induce endocardial cushion defects in chicks.
Sex Differences in the Rat Brain: A Procedure for Estimating Developmental Toxicity
Authors: Sumida Hiroyuki , Moriya Tokuharu , Handa Jun , Yamashita Takumi , Nakamori Kouta , Nishizuka Masako , Arai Yasumasa 
Published: May 2008

AbstractThe sexually dimorphic nucleus of the preoptic area (SDN‐POA) and the anteroventral periventricular nucleus of the preoptic area (AVPvN‐POA) are sexually dimorphic regions in the rat brain. These regions are sensitive to reproductive function‐related drugs, and thus applied for aromatase inhibitor evaluation in the present study. Effects of NKS01 (an aromatase inhibitor) and tamoxifen on the SDN‐POA and AVPvN‐POA were examined. Five mg of NKS01 or its vehicle was injected to SD male and female rats from days 1 to 14 (the day of birth = day 0). Other 10 males and 10 females received a single injection of 100 μg tamoxifen on day 1. Rats in each group were sacrificed at day 30 or 60. The SDN‐POA was examined at days 30 and 60, and the AVPvN‐POA at day 60. When NKS01 was given to male rats for the first 14 days of life, a significant reduction of SDN‐POA size was observed on day 60. When tamoxifen was given, SDN‐POA reduction in size was also observed at days 30 and 60 in male rats. As for the AVPvN‐POA, tamoxifen markedly reduced volume in female rats, resulting in polycystic ovaries at day 60. This may be due to an estrogenic property of tamoxifen. On the other hand, NKS01 was not significantly effective in the AVPvN‐POA, although the volume of the nucleus in NKS01 males was inclined to increase. From these results, as well as the SDN‐POA, the AVPvN‐POA may be useful to evaluate the side effect of reproductive function‐related drug.
Visualization of Intracranial Structures in Early Human Embryos using 3‐D Computer Graphics Technique
Authors: SOARES Sergio BRANCO , OHATA Kenji , HAKUBA Akira , NAKATSU Tomoko , UWABE Chigako , SHIOTA Kohei 
Published: May 2008

AbstractIn classic human embryology, one of the most important techniques to observe embryonic structures three‐dimensionally (3‐D) was to reconstruct embryos or their parts using wax plate models from serial histological sections. However, wax plate reconstruction does not allow observation of internal structures and lumens unless the models are cut after reconstruction. The development of computer graphics has enabled us to reconstruct various biologic structures on the viewing screen and to manipulate the computer images as freely as we desire. Nevertheless, until now computer reconstruction has not been used frequently to study human organogenesis. We reviewed and photographed serial histological sections of early human embryos, projected these photographed slides onto a screen and traced the outlines of specific structures under study on a digitizing pad that was interfaced with a 16 bit computer. The digitized images were combined using a software for 3‐D reconstruction. With this technique, we were able to visualize the anatomical localization and interrelation of various structures inside the human head during the embryonic period. The 3‐D reconstruction technique should be of potential use for the study of normal and abnormal morphogenesis.
Congenital Anomalies in Singapore
Authors: TAN K. L. , CHIA H. P. 
Published: May 2008

Abstract A 3‐year study (Jan. 1986‐Dec. 1988) in the Kandang Kerbau Hospital revealed 678 infants with birth defects in 44,842 livebirths, (15.13 per 1,000 live births, 95% confidence intervals, CI 14.0–16.2). There were 161 cases with musculoskeletal abnormalities (3.5 per 1,000, 95% CI 3.06‐4.19), 111 gastrointestinal system malformations (2.47 per 1,000, 95% CI 2.04‐2.58), 88 chromosomal abnormalities (1.96 per 1,000, 95% CI 1.57‐2.42), 78 cardiovascular system abnormalities (1.74 per 1,000, 95% CI 1.38‐2.17), 73 urogenital system defects (1.63 per 1,000, 95% CI 1.28‐2.05), and 52 central nervous system defects (1.16 per 1,000, 95% CI 0.87‐1.52). The prevalence of cleft lip, cleft palate, and cleft lip/palate was 1.72 per 1,000, and Down's Syndrome 1 in 700. At review, six weeks later, the false positive rate was 4% in the infants with defects, and in the group of 709 normal controls (matched by race, maternal age, ward class and time/date of birth), the false negative rate was 0.84%.The strongest risk factors were a family history of birth defects (odds ratio, OR 3.3, 95% CI 1.8‐6.4), and previous abnormal sibling(s) (OR 2.4, 95% CI 1.1–5.3). Other risk factors included drug intake during pregnancy (OR 1.2, 95% CI 0.8‐2.0), becoming significant with ingestion during the first trimester (OR 1.4, 95% CI 1.1‐1.8). Traditional medicine (mainly Chinese herbs during pregnancy) had a slightly higher risk (OR 1.4, 95% CI 1.0–2.0).The National University Hospital keeps a register of birth defects; trained nurses interview all mothers using a set questionnaire. Evaluation of 11,460 livebirths over a 3‐year period (1991–1993) revealed 472 cases (41.19 per 1,000 livebirths, 95% CI 37.48‐44.90) with 171 musculoskeletal defects (14.92 per 1,000 livebirths, 95% CI 12.69‐17.16), 105 cardiovascular defects (9.16 per 1,000, 95% CI 7.41‐10.91), 64 urogenital defects (5.58 per 1,000, 95% CI 4.22‐6.95), 30 gastrointestinal defects (2.62 per 1000, 95% CI 1.68‐3.55), 35 mixed system defects (3.06 per 1,000, 95% CI 2.04‐4.07), and 18 chromosomal abnormalities (1.57 per 1,000, 95% CI 0.85‐2.30). The prevalence of cleft lip/cleft lip and palate was 1.48 per 1,000. This higher prevalence could be due to the present practice of routine screening of every infant on the first day of life, together with a careful assessment for musculoskeletal defects, especially congenital dislocation of the hips.
Anomalies of Cartilaginous and Ossified Axial Skeleton in Rat Fetuses Treated with Cyclophosphamide: Type, Frequency, and Stage Specificity
Authors: IGARASHI Eiki 
Published: May 2008

AbstractThe purpose of the present study was to assess the type, frequency and stage specificity of axial skeletal anomalies induced by cyclophosphamide (CP). Female Crj: Wistar rats were mated with male rats (vaginal sperm = gestation day 0, GDO). They were then injected intravenously with 5 mg/kg of CP in a saline solution on GD7, 8, 9, 10, 11, 12, 13, or 14, or with saline on GD8 for controls. Dams were sacrificed on GD20. Fetuses were stained with alcian blue and alizarin red S. Eighteen types of axial skeletal anomaly were detected, e. g., shifted ventral lamina, cervical rib, cleft arch of the atlas, axis fused to atlas, sternebral misalignment, bipartite sternum, fused ribs, change in pre‐sacral vertebral number, supernumerary rib, misdirected transverse process, anteriorly‐shifted spinous process, short spinous process, fused vertebral bodies, cartilaginous short rib at Th.7, short or absent rib at Th.12 or 13, dumbbell‐shaped vertebral body, wavy rib, and rib cartilage not attached to the sternal cartilage. The present experimental study indicates that: 1) observations of cartilaginous skeletons can provide more information than observations of ossified skeletons; 2) the pattern of CP‐induced anomalies along the anterior–posterior axis may depend on the sequence of development progression among structures, spinous process, vertebral arch, vertebral body, rib/transverse process; and 3) in more cranial vertebrae, anteriorly‐shifted anomalies, such as anteriorly‐shifted ventral lamina and anteriorly‐shifted spinous processes, rather than posteriorly‐shifted anomalies, may be the primary indicators for detecting developmental toxicity, since CP injection increased the frequencies of these anomalies.
Variant Patterns of Palatal Rugae Induced by Chemicals in Mouse Fetuses
Authors: YASUDA Mineo , HORIE Shigeaki , MATSUI Kohji A. , TAKAGI Toshio N. , YAMASHITA Keisuke 
Published: May 2008

AbstractThe oral surface of the mouse palate has eight or nine pairs of transverse ridges, or rugae. We have reported that various teratogens induce abnormal patterns of palatal rugae in mice. In the present note, we show examples of palatal ruga anomalies induced by several teratogens in mouse fetuses near term. Defined variant patterns are supernumerary, division, lateral or medial bifurcation, short, maldirection, cross, modified cross, lateral or medial fusion, lateral or medial bifurcation, median fusion, median division, and numerical reduction. In some cases naming of observed variants may be difficult, but differential diagnosis between variations in the “normal” range and “anomalous” variants seems rather easy.
Effects of Restrained Fetal Movement on the Development of the Rat Hip Joint
Authors: KIHARA Isao , HASHIMOTO Ryuju , OTANI Hiroki 
Published: May 2008

ABSTRACTThe effect of fetal movement on the development of the hip joint was examined by restraining the leg movement using exo utero operation in rat fetuses. At embryonic day (E) 16.5, when the hip joint cavity starts to form, one side of the hind limb was sutured onto the embryonic membrane. After exo utero development to E18.5, the hip joint of the operated side was compared morphologically with those of the unoperated side, sham‐operated and unoperated in utero controls. The largest diameter of the femoral head (FH) and the gross morphology of the joint cavity of the operated side was not different from those of controls. By light microscopy (LM), the surface of the control E18.5 FH and acetabulum was smooth and covered by thin scale‐shaped cells which were partially pyknotic, and oval‐shaped cells underneath were rather regularly arranged in a thickness of a few cells. By transmission electron microscopy (TEM), scale‐shaped cells covered the FH surface incompletely, and the spaces in‐between were filled with the intercellular matrix. Oval‐shaped cells underneath had well developed rough endoplasmic reticulums. By scanning electron microscopy (SEM), mounds and grooves on the FH surface were evident at E17.0 but became unclear at E18.5. Subsurface collagen fibers formed a coarse meshwork at E17.0 but formed bundles at E18.5. On the operated side, by LM, the surface of the FH and acetabulum was irregular and lined by spindle‐shaped cells, whereas the underlying mesenchymal cells also showed an irregular cell shape and arrangement. By TEM, collagen fibrils in intercellular spaces were dense but did not generally form bundles. By SEM, the FH surface was rugged with banks and subsurface collagen fibers did not form bundles but remained as a dense meshwork. These results suggest that the fetal hind limb movement influences development of the surface structure of the FH and acetabulum and that this system may be useful to study prenatal etiology of the congenital dislocation of the hip.