bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Folic Acid on Pharmacokinetics of Pyrimethamine in Rats
Authors: TSUNEMATSU Kunitoshi , SHIMODA Minora , HAYAMA Toyoaki 
Published: May 2008

AbstractThe effect on pyrimethamine (PYR) pharmacokinetics of folic acid (FA) which potentiated the PYR teratogenesis was studied in rats. Gavage administration of PYR 1.6 mg/kgBW/day from day 11 to day 15 of gestation did not cause any malformation, but with concomitant dosing of FA 50 mg/kg/day in feed caused malformations in 75% of fetuses. Neither the plasma concentration‐time profile nor the plasma protein binding of the gavaged PYR was affected by the concomitant dosing of FA in the non‐pregnant rats. The pregnant rats which received the gavaged PYR with or without FA in feed for 5 days (from day 11 to day 15 of gestation) were killed at 4 or 12 hrs after the last dosing of PYR, and their plasma and fetuses were subjected to determination of PYR. The PYR concentration in the maternal plasma was comparable in both groups. The PYR concentration in fetuses of the PYR alone group was significantly higher than that of the PYR with FA group 4 hr after but not 12 hr after the last dosing. These results indicated that the pharmacokinetics of PYR was not affected by the concomitant dosing of FA, suggesting that FA potentiated the PYR teratogenesis by other mechanisms than pharmacokinetic modifications.
Effects of the Ay Gene on the Sensitive Periods of Hydrocortisone‐Induced Cleft Palate and Palatal Slit in Mice
Authors: HATAKENAKA Noriyuki , TERAMOTO Shoji 
Published: May 2008

AbstractThe effects of the Ay gene on the sensitive periods of hydrocortisone‐induced cleft palate and palatal slit were investigated in C57BL/6 (a/a) and its congenic strain of C57BL/6‐Ay (Ay/a) mice by using the single‐dose administration method. Matings were conducted as follows (femalex male): Group I, a/a × a/a; Group n, a/a ×Ay/a; and Group III, Ay/a × a/a. Pregnant females were subcutaneously given a single dose of 200 or 400 mg/kg of hydrocortisone on day 11, 12, 13 or 14 of pregnancy and killed on day 18 for examination of palatal defects of live fetuses. Cleft palate was produced in all groups by treatment on days 11–13 of pregnancy at a dose of 200 mg/kg without any increase in fetal mortality. In Group I, the maximum incidence was observed on day 11 and followed by a rapid decrease thereafter. In Group U, in which half of the fetuses were expected to carry the Ay gene, the incidence still remained high on day 12, although it was decreased to the level of Group I by day 13. In Group HI, in which maternal mice as well as half of their fetuses carried the Ay gene, significantly higher incidences were observed on days 12 and 13 with the maximum value on day 12 when compared with those in Groups I and/or II. Palatal slit was also induced in all groups on each of treatment days at a dose of 200 mg/kg. Although the incidences in both Groups I and II were high on days 11 and 12 and gradually decreased thereafter, the value on day 13 was significantly higher in Group II than in Group I. In Group IE, the maximum incidence was found on day 12 and the values on days 13 and 14 were still significantly higher than those in Groups I and/or II. These results indicate that the sensitive periods of hydrocortisone‐induced cleft palate and palatal slit are prolonged into the later stage of embryonic development as a result of the Ay‐gene effects.
Campomelic Syndrome Associated with Potter's Syndrome and Car diosplenic Syndrome
Authors: Myong Na Hye , Chi Je G. 
Published: May 2008

ABSTRACT Campomelic syndrome is a heterogeneous group of disorders characterized by short‐limbed dwarfism with congenital bowing or bending of the long bones particularly in the lower limbs and is frequently associated with a variety of non‐skeletal manifestations. Two distinct types are (1) long‐limbed campomelic dysplasia with bent bones of normal length and width: (2) short‐limbed campomelic dysplasia in which the bent bones are short and wide. We reported an autopsy case of this syndrome.This male baby with gestational age of 32 weeks was born to a mother with placenta previa, showing abdominal distention and short‐limbed appearance. Postmortem examination revealed bilaterally enlarged Potter type 1 polycystic kidneys, a pancreatic cyst, and two spleens in the abdominal cavity. Both lungs were hypoplastic and the heart exhibited multiple congenital anomalies such as double outlet right ventricle, pulmonary artery hy‐poplasia, mitral atresia, absence of ductus arteriosus, and inferior vena cava draining into the left atrium. Characteristically both femur bones were curved at proximal two‐thirds with slightly shortened lengths. Both humeri also showed bending of distal one‐third. Other chondro‐osseous abnormalities such as small epiglottis, narrow thorax, dolichoce‐phaly, and bilateral equinovarus deformity were noted. These findings were compatible with campomelic dysplasia of long‐limbed type accompanying unusual sets of non‐skeletal manifestations of Potter's syndrome and cardiosplenic syndrome. Key words: campomelic syndrome, Potter's syndrome, cardiosplenic syndrome
Rib Defects and Pattern Formation of the Thoracic Wall Muscles
Authors: KINOSHITA Yuko , MURAKAMI Gen , KATAMACHI Ikuo , HOSHI Hajime 
Published: May 2008

ABSTRACTA fragment of quail notochord (20 somite stage) was implanted into a host chick embryo (25–30 somite stage) just lateral to the thoracic somites or into the intersomitic space. Around the implanted notochord, aggregates of rib‐forming sclerotomal cells formed a large irregular mass of cartilage, resulting in segmental rib defects without any adverse effect on body wall muscle formation. This contrasted sharply with previous experimental studies in which abnormalities of other somite derivatives, in particular body wall muscles, were always associated with rib defects created by teratogenic agents, surgidal treatment or by genetic means.These results suggest that migration of myogenic cells into the thoracic wall does not require the guidance of rib‐forming sclerotomal cells or their products. Moreover, those myogenic cells can develop into three layers of thoracic wall muscles, independent of skeletal pattern formation.
A Case Report of Lethal Multiple Pterygium Syndrome
Authors: SHIMADA Masami , TAUCHI Moriyuki , SAWADA Kouji , MINATO Michiyoshi , TAKADA Masaaki , TAKAHASHI Shigeru , OKUNI Masahiko , SHEIKH Aleemuzzaman , YAMADA Tsutomu 
Published: May 2008

ABSTRACTWe report a patient with a lethal multiple pterygium syndrome. The patient was the first child born to a 28‐year old mother. The family history was unremarkable; no consanguinity was reported. The patient was the product of a 37‐week gestation by cesarian section, and admitted to our intensive care unit after resuscitation. He weighed 2,158 g, and measured 33cm (CHL). The patient had hydrops, cystic hygroma on the back of the neck, hypertelorism, a flat upturned nose, a highly arched cleft palate, micrognathia, low set ears and multiple pterygia. In addition, the finger showed slender and hypoplastic ridges and creases. The feet showed rocker‐bottom deformities. Furthermore, the genitalia was normally formed male with bilateral cryptorchism. The spine showed scoliosis and lordosis with vertebral bony fusions, separations and reduced intervertebral spaces. The ribs were 11 pairs and gracile. The lung was hypoplastic, and the heart was small but normal in structure. Chromosomal examination revealed a normal male karyotype (46, XY). The infant died within two hours after birth.Gillin and Pryse‐Davis (1976) described three female siblings with this early lethal disorder. This disorder was separated from other conditions associated with pterygia by Hall et al. (1982). At least 30 cases have been reported. However, this type of case seems to have not been reported in Japan. This disorder is considered autosomal‐recessive, but in other report, X‐linked recessive inheritance is proposed. Therefore, further studies are necessary in order to make a more precise etiology of this disorder.
Lack of Constrictive Effects of Cocaine on the Fetal Ductus Arteriosus in the Rat
Authors: UKITA Katsuo , AREHIMA Kazuyoshi , TAKIZAWA Tatsuya , SHIRAI Mitsuyuki , YAMAMOTO Masako , FUKUI Yuko , SHIOTA Kohei 
Published: May 2008

ABSTRACTCocaine (12.5 or 25 mg/kg) was administered intraperitoneally to pregnant rats 15 min to 12 hr prior to Caesarean section on day 20 of gestation. The fetuses were immediately frozen and serially sectioned, and the diameter of their ductus arteriosus (DA) was calibrated. The DA was patent in all the fetuses examined and the DA caliber was not significantly different between the control and the cocaine‐treated groups at any time interval after the cocaine dosing. It was concluded that cocaine has no constrictive effects on the fetal DA in the rat.
Clinical Aspects of Cleft Lip and Cleft Palate Patients Treated at Kanazawa Medical University Hospital from 1974 to 1993*
Authors: TSUKADA Sadao , TANIGUCHI Wakae 
Published: May 2008

ABSTRACT Currently, clefts of the lip, alveolus, and palate are thought to be the most common congenital malformations. In this study, we examined 1,565 cases of clefts we treated over the last 18 years, in order to summarize the clinical features and to evaluate the treatment outcomes.This study involved 589 cleft lip (CL) cases, 576 cleft lip and palate (CLP) cases, 286 cases of cleft palate (CP), 81 cases of submucous CP and 33 cases of CL and submucous CP. The familial incidence was 11.1% (174 cases). Overall, the average incidence of associated congenital abnormalities was 27.9%. Approximately half of the patients with CP alone or with submucous CP were found to have additional congenital malformations. Standeard surgical techniques for unilateral and bilateral CL cases were the Skoog's and Millard's methods, respecively, which resulted in satisfactory outcomes. As a primary operation for CP, pushback procedure was performed using a partial mucosal flap from the palate. Using this procedure 96.5% of 455 cases achieved satisfactory nasopharyngeal closure. The main objective in the treatment of CL patients is not only the repair of growing tissues but also appropriate morphological, functional and psychological reconstruction for the purpose of correcting growth inhibitory problems caused by anatomical malposition.Surgical procedures for CP patients are designed to meet several needs: correction of anatomical abnormalities of the palate and pharynx, achievement of proper nasopharyngeal closure necessary for normal phonation, prevention of growth disturbances of the maxilla, improvements in hearing and auditory tube function, and normalization of occlusion.
Chromosomally Abnormal Gametes as a Cause of Developmental and Congenital Anomalies in Humans*
Authors: KAMIGUCHI Yujiroh , TATENO Hiroyuki , MIKAMO Kazuya 
Published: May 2008

ABSTRACT Human gamete chromosome studies using 702 oocytes and 15,864 spermatozoa were reviewed. These studies were chosen because they were carried out with our improved chromosomal technique, the gradual fixation‐air drying method, which has been proven to be very reliable.The incidence of aneuploidy was about eight times as high in the oocytes (11.0%) as in the spermatozoa (1.4%), whereas that of structural chromosome aberrations was three times as high in the spermatozoa (14.1%) as in the oocytes (4.7%). In the spermatozoa, segregation errors leading to aneuploidy were found randomly among eight chromosome groups (A‐G and sex chromosome). In contrast, they did not occur randomly in the oocytes. The observed frequency was significantly higher in group G and significantly lower in group A, as compared with the theoretical frequencies which were calculated according to the assumption that the segregation errors had taken place with an equal chance in each of 23 chromosomes. About 60% of the segregation errors were found to be due to so‐called nondisjunction (loss or gain of dyads) and about 40% were due to so‐called predivision (loss or gain of monads). The incidence of aneuploid oocytes increased slightly with the increase of donor age, although showing no statistical significance. The incidence of spermatozoa with structural chromosome aberrations vaned considerably from donor to donor (3.6–24.8%). However, there was no positive correlation between the occurrence of these spermatozoa and the age of donors or the habit of smoking.Incidences of chromosome aberrations in the human gametes (22.8% in oocytes and 15.5% in spermatozoa) were far higher than those in experimental animals. These seem to be associated closely with the characteristics of human reproduction and are responsible for a great part of human embryonic loss and developmental anomalies.
Congenital Humero‐radio‐ulnar Synostosis with Constriction Ring and Flexion Contracture of the Fingers: A Case Report
Authors: KURIMOTO Sarina , KOJIMA Tadao , HIRAKAWA Masahiko , KONNO Midori 
Published: May 2008

ABSTRACTCongenital humero‐radio‐ulnar synostosis (HRUS) is a rare malformation. Some cases are hereditary in origin and some are sporadic. We report on a sporadic case of HRUS.A patient with HRUS is described who had constriction ring on the left upper limb and flexion contracture of the wrist joint and fingers. There was no range of motion nor crease at the elbow joint. Hypoesthesia was noted at the distal part of the ring of the upperarm as she did not respond to pin‐prick. But circulatory failure like cyanosis or congestion was not seen on the extremity. No operation was performed to release the constrictive ring because it was not so deep. Only splint was applied to correct flexion contracture of the thumb, middle finger and ring finger. Three months later, examination of the thumb and fingers showed full extention. The sense to pain by pin‐prick has been improved as the ring on the upperarm shallowed. A minor ischemic change may have been caused by the ring and followed by the contracture and the sensory disturbance. Synostosis also may have been related with the ring.
Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*
Authors: INOUYE Minoru 
Published: May 2008

AbstractThe developing mammalian brain is highly susceptible to ionizing radiation. A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8–15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum, on the other hand, the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormality, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15–25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation.Radiation‐induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation, bringing with it the risk of producing malformations and tumors. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair which is rarely complete. In fact they show very slow repair of cellular damage. Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism.
A Case of Multiple Pterygium Syndrome Associated with Chronic Idiopathic Intestinal Pseudo‐Obstruction Syndrome
Authors: IITANI Hidemi , KUSUDA Satoshi 
Published: May 2008

AbstractMultiple pterygium syndrome (MPS) is a rare condition characterized by pterygia of the neck, finger, antecubital, popliteal, and intercrural areas. The present case study describes a male patient afflicted with this condition. This case has two unique features 1) the patient exhibited both mental and physical retardation at 2 years of age, a rare symptom of this disorder, and 2) the patient also had chronic idiopathic intestinal pseudo‐obstruction syndrome (CIIPS). Although the pathogenesis of both MPS and CIIPS is unclear, some features of the present case suggest a possible pathogenic mechanism.
In Vitro Developmental Toxicity of Aspirin and Its Major Metabolites on Cultured Fetal Mouse Palates
Authors: KOSAZUMA Tsuneo , CHOU Ming‐Jen , KAWAUCHI Saju , SHIOTA Kohei 
Published: May 2008

AbstractPalatal primordia of day‐12.5 ICR mouse fetuses were cultured in a chemically‐defined serumless medium by a suspension culture technique, and the developmental toxicity of aspirin and its metabolites on in vitro palatogenesis was studied. Explanted fetal palates were exposed in vitro for 72 hr to 0.5‐2 mM aspirin (ASP), 0.25‐2 mM salicylic acid (SA), 0.5‐2 mM salicyluric acid (SUA), 1–2 mM 2,3‐dihydroxybenzoic acid (3DHB), or 1–2 mM 2,5‐dihydroxybenzoic acid (5DHB). After 72 hr culture, ASP at 2 mM and SA at 0.25 mM inhibited the growth and fusion of palatal shelves, and SUA at 1 mM prevented palatal fusion. On the other hand, 3DHB and 5DHB did not exert any significant toxic effects on cultured palates at concentrations up to 2 mM. Judging from the 50% inhibitory concentration (IC50), SA (IC50= 0.9 mM) was the most toxic of the 5 compounds tested, with a decreasing order of ASP (IC50= 1.5 mM), SUA (IC50= 1.6 mM), and DHBs (IC50= over 2 mM for both 3DHB and 5DHB). With respect to developmental toxicity, cultured fetal mouse palates showed the susceptibility to aspirin and its metabolites which is intermediate between the susceptibility of rat embryos in vivo and that of postimplantation rat embryos cultured in vitro. The significance of fetal organ culture for evaluating developmental toxicity of chemicals is also discussed.
Effects of Acetazolamide on the Development of Mouse Limb Buds In Vitro
Authors: WATANABE Toshiaki 
Published: May 2008

AbstractForelimb buds of mouse embryos were cultured in a serum‐free BGJb medium by a roller system. At the beginning of culture, acetazolamide was added to the final concentration of 10−5 M or 10−4 M. After 6 days of culture, no morphological abnormalities of the developing forelimb buds could be detected. In morphometrical analyses, the morphological scores of antebrachium and hand in the right forelimb of female embryos were 1.8 and 2.2 in the 10−5 M and 10−4 M acetazolamide‐treated groups, respectively, and 1.6 in controls. There was no difference in the size of the forelimb among these groups. Concerning cartilage skeleton, the incidence of bending of the ulnoradius was increased to 64–90% in 10−4 M acetazolamide‐treated group, which was different from the control (0.22%). In addition, there was a significant difference in the protein and DNA contents in only right forelimb buds between the acetazolamide‐treated and control groups. However, there were no differences in sex or laterality in the development of forelimbs and cartilage skeleton. No pathological changes in the cartilage skeleton and mesenchyme were observed in the acetazolamide‐treated forelimbs. From these findings, there is the possibility that acetazolamide per se may primarily interfere with the development of the forelimb in mouse embryos at the molecular level in vitro.
Palatal Slit and Cleft Palate in Rats Treated with Glucocorticoids II. Comparative Teratogenicity of Prednisolone, Triamcinolone Acetonide and Hydrocortisone
Authors: WATANABE Chiaki , ISHIZUKA Yasuo , NAGAO Tetsuji 
Published: May 2008

AbstractThe induction of abnormal palatal development by three glucocorticoids; prednisolone, triamcinolone acetonide and hydrocortisone was evaluated in rat fetuses. Pregnant rats were injected subcutaneously with either prednisolone (12.5‐100 mg/kg/day), triamcinolone acetonide (0.25‐2 mg/kg/day) or hydrocortisone (100 mg/kg/day) on days 14 and 15 of gestation. These females were humanely killed on day 20 of gestation and viable fetuses were inspected for their palatal abnormalities. The frequencies of cleft palate were significantly higher in the group treated with 100 mg/kg/day prednisolone (10.6%), and in the groups treated with 0.5, 1 and 2 mg/kg/day triamcinolone acetonide (8.6%, 26.1% and 58.3%, respectively) than the control frequency of 0%. Triamcinolone acetonide was 70 times as potent as prednisolone in inducing palatal slit, with ED50 value of 1.0 mg/kg/day and 70 mg/kg/day, respectively. Hydrocortisone showed no potentiality for the induction of cleft palate and palatal slit. Other developmental abnormalities including omphalocele and general edema, late resorption, and growth retardation were induced by triamcinolone acetonide and prednisolone. These findings indicate that triamcinolone acetonide has a significantly higher potentiality for the induction of palatal slit in rats, as well as in mice, compared to prednisolone and hydrocortisone.
Congenital Malformations and Deformations in Provincial Hospitals in Indonesia
Authors: KADRI Nartono , ISMAEL Sofyan , RAID Noersida , SURJONO Achmad , HARIANTO Agus , MUSTADJAB Immanual 
Published: May 2008

AbstractA study of congenital malformations and deformations in the neonatal period in 14 hospitals consist of 13 provincial government hospitals as teaching hospitals and one private children and maternity hospital is presented. The incidence of anomalies in the range of 6–15 per thousand of total births. The incidence in boys was higher than girls. Based on the ICD‐10, among the 2,621 anomalies, the most frequent of malformations and deformations were those of the musculoskeletal system (19.6%), followed by the nervous system (18.8%), the digestive system (18.7%), the circulatory system (12.9%), and the cleft lip and cleft palate (8.2%). Corrective and reconstructive surgery were performed by the Subspecialistic Division of the Surgical Department.