bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of plasma proteins in the palate of fetal mice
Authors: Gustine David L. , Zimmerman Ernest F.
Published: June 2005

Investigations were undertaken to correlate changes in proteins with development and morphogenetic movement of palate shelves in the fetal mouse. Soluble palate proteins were analyzed by polyacrylamide disc gel electrophoresis. Three major groups of proteins were present: (1) three bands at Mx 0.35–0.48 designated αl–3, (2) five bands at Mx 0.70–0.85 designated β1‐5, and (3) one band at Mx 1.0 designated γ. Changes in the relative concentration of some of these proteins occurred during development: by day 15.5 of gestation α3, β4, and β5 had increased while α1, μL2, β1, β2, and β3 had decreased. Comparison of these palate proteins with other fetal and adult tissue proteins indicated that α and γ were probably present in both fetal and adult tissues, but β was present only in fetal tissues. The results showed that α, β, and γ were present in the palate extracellular matrix but β was not found in isolated palate cells. Furthermore, a different electrophoretic distribution of proteins was found for the cell proteins. Further evidence indicated that α and γ were transferrin and albumin, respectively, and that β was a fetal plasma glycoprotein analogous to calf fetuin. The presence of these plasma proteins in the matrix was thought to be due to their circulation throughout the extracellular space of fetal tissues; and the relative change in the proportion of these electrophoretically separable proteins during development to reflect comparable changes in the fetal plasma.
Action of some cardiovascular and neurohumoral agents on the formation of the chick embryo heart. I. Morphology
Authors: Butros Joseph
Published: June 2005

A study of some cardiovascular drugs was made with early chick blastoderms (stages 5–6) cultured in vitro to determine their action on the initiation of heart primordia. Ouabain (16–22 μ/ml) completely prevented the appearance of heart primordia and caused slight cytolysis of the brain and somites. Quinidine (15 μg/ml) caused swelling of the formed hearts but they were noncontracting. Atropine (100 μg/ml) had a slight cytolytic effect on the heart and more so on the brain. Epinephrine (25 μg/ml) had a strong cytolytic action but no selective action on any system. Acetylcholine (up to 500 μg/ml) had no inhibitory effect on development.
Action of spermine on early chick development. I. Morphogenesis and histogenesis
Authors: Butros Joseph
Published: June 2005

Unincubated eggs were injected with spermine (2.61–10 mg/egg) and incubated for 1–7 days. Morphogenetic and histogenetic study of the recovered embryos indicated a teratogenic action of the agent. Abnormalities consisted of lack of head flexures, asymmetry, and general arrest of development at about stage 17. A few bizarre conditions occurred: some specimens consisted of nothing but blood sacs; in a few the neural tube was thrown into highly convoluted folds. The histological picture also indicated a general arrest of development at about stage 17: cells of the neural tube were disaggregated at abrupt points and moved out of the wall, taking a more rounded, smaller form. The most striking change pertained to the blood cells. Whereas day‐7 control embryos had mature erythrocytes, the spermine‐treated ones showed a proliferation of immature erythrocytes in the vessels, heart, and head, which often completely filled these organs.
A case of thoracopagus: Conjoined twins
Authors: Gilbert Enid F. , Suzuki Hiroshi , Kimmel Donald L. , Klingberg William G. , Lancaster Joseph R.
Published: June 2005

A detailed anatomical description of a thoracopagus is presented. The complex venous anomalies were unique in combining absence of the inferior vena cava of one twin with drainage into an atrium of the other twin of its inferior vena cava with all the hepatic veins from the common liver. The other atrium received the entire venous drainage from the upper extremities of both infants.
BAL alleviation of arsenate‐induced teratogenesis in mice
Authors: Hood Ronald D. , Pike Charles T.
Published: June 2005

Treatment of pregnant mice ip with 40 mg/kg aqueous sodium arsenate on gestation day 9 resulted in a significant increase in fetal mortality and malformation, and in fetal weight reduction. Treatment sc with 50 mg/kg BAL 4 h before, concurrently with, or 4 h after arsenate reduced the frequency or severity of malformation compared with the effects of arsenate alone.
Paternal age and congenital cleft lip and cleft palate
Authors: Perry T. B. , Fraser F. C.
Published: June 2005

In an analysis of 679 families no evidence was found of a diference in paternal or meternal ages between complete and incomplete forms of cleft lip, with or without cleft palate, or between familial and nonfamilial cases, It would appear that parental‐age effects for clefts of the lip or palate either do not exist or are so complex that their biological significance is likely to remain obscure.
Independent effects of maternal age and birth order on the incidence of selected congenital malformations
Authors: Hay Sylvia , Barbano Helen
Published: June 2005

Incidence rates, specific for maternal age and birth order, were calculated for 16 categories of congenital malformations reported on birth certificates from a population of more than 8 million registered white, single livebirths. With maternal age held constant none of the malformations showed increasing incidence as birth order increased. Hypospadias, esophageal defects, omphalocele, and Down syndrome showed evidence of decreasing incidence as birth order increased. Some of the other malformation categories showed an excess of first births in most age groups, while no relation to birth order was observed in the incidence of other malformations. By contrast, most of the malformations analyzed exhibited increasing incidence as maternal age increased. Especially high rates of several malformations were observed among first births to women over 40 years of age.
Distribution and fate of nicotine in the rat fetus
Authors: Mosier H. D. , Jansons R. A.
Published: June 2005

[3H] (−)‐Nicotine was administered iv into pregnant Long‐Evans rats on day 19 of gestation or in three consecutive daily doses given on days 16 through 18 of gestation. The concentration of radioactivity and proportions of labeled compounds were determined at intervals from 5 min to 20 h after injection in maternal plasma and liver, decidua basalis, placenta, amniotic fluid, whole fetus, and fetal plasma, brain, lungs, heart, liver, adrenals, kidneys, gonads, and the stomach‐intestine‐spleen‐pancreas en bloc. Nicotine, cotinine, and other metabolites appeared in the fetus within 5 min of injection. The concentration of radioactivity in the fetal plasma exceeded that of the maternal plasma from 30 min through 20 h. Fetal liver had a greater proportion of radioactivity as nicotine than did maternal liver. Fetal plasma as well as most of the fetal tissues had a greater proportion of nicotine to metabolites than did the maternal plasma throughout the time period that was studied. By 60 min an equilibrium was established between maternal plasma and amniotic fluid with respect to concentration of radioactivity. This equilibrium was maintained through 20 h after single injections and also after the three daily injections. The proportions of nicotine to major metabolites were similar in maternal plasma and amniotic fluid at 4 h. The findings show that fetal rat tissues are exposed to levels of nicotine greater than those found in maternal plasma beginning within 30 min of the time nicotine enters the maternal circulation.
Prenatal growth of Wistar rats: Circadian periodicity of fetal growth late in gestation
Authors: Barr Mason
Published: June 2005

Pregnant CFN Wistar rats demonstrated marked fluctuations of body weight within 24‐h periods during late gestation. Maternal weight loss during the daytime phase of the daily cycle was accompanied by a slowdown in fetal growth. The period of rapid maternal weight gain that occurred during the night was paralleled by a period of rapid fetal growth. The periodicity of fetal growth was due to variation in accumulation of solids and not to diurnal fluctuations in relative water content.
Limb development in mouse embryos. I. Analysis of teratogenic effects of retinoic acid
Authors: Kochhar D. M.
Published: June 2005

Retinoic (vitamin A) acid produced phocomelia and micromelia in DBA/2J fetuses when administered to pregnant mice on the 12th or 13th day of gestation. The incidence of forelimb defects was higher after 12th‐ (in embryos having 33–41 somite pairs) than 13th–day treatment (40–51 somite pairs); the reverse was true for hindlimb defects. Hindlimb digits continued to be highly susceptible on the 14th day. Limb defects were not accompanied by body growth retardation or other skeletal malformations except cleft palate. The type and severity of limb defects depended on the average developmental stage of the limb bud at the time of treatment. From the beginning of the period of limb susceptibility, the 12th day, the ontogenetic sequence in which the long bones were rendered abnormal was: radius–ulna, humerus, fibula, tibia, femur or tibia‐femur. The sequence in which the long bones lost their susceptibility to retinoic acid was: humerus, femur, ulna, radius, tibia‐fibula. The radius appeared to be susceptible in some embryos at a time when the other long bones had escaped injury. An analysis of the shape of the same bone affected at different periods of prenatal development led to the following proposal. At earlier stages retinoic acid disrupts cellular activities that normally lead to the spatial organization of the mesenchymal cell condensations, resulting in a modified shape of the cartilage models; at later stages it prevents the enlargement of the condensations that have already appeared, resulting in smaller than normal models.
Hemorrhages in the limbs of fetal rats after amniocentesis and their role in limb malformations
Authors: Singh Shamer , Singh Gajendra
Published: June 2005

Wistar rats were subjected to amniocentesis on the 15th day of gestation and fetuses collected at various intervals (5 min to 2½ h) after the operation; 0.04 ml amniotic fluid was withdrawn through a thin dental needle (0.45 mm diam.) or no. 19 hypodermic needle (1.06 mm diam.) and in some cases sacs were punctured with a pair of iridectomy scissors (about 3 mm diam.) to determine the effect of rate of evaculation of the amniotic fluid through different‐sized openings. Limbs of the fetuses were examined for evidence of hemorrhages and their incidence and severity correlated with the size of the puncture. Hemorrhages were more frequent and more severe in the lower limbs than in other areas; this is correlated with the higher incidence of lower limb malformations reported after amniocentesis by others. To exclude the influence of uterine muscular contractions, some fetuses (15‐day) were removed along with their placentas and intact amniotic sacs and similarly punctured, outside the uterine horns. None showed hemorrhage in any area. The mechanism of the limb malformation seems to be compression of the fetus by uterine muscular contractions, after evacuation of the amniotic fluid, causing hemorrhages, which in turn lead to necrosis and various degrees of limb degeneration.
Congenital pericardial defects
Authors: Chaurasia B. D.
Published: June 2005

A congenital partial defect of the left pericardium associated with a left diaphragmatic hernia and total myeloschisis in a stillborn dicephalus dibrachius triotus female monster is described. It is pointed out that the generally accepted view, viz., that pericardial defects result from either a failure of closure or incomplete closure of the pleuropericardial foramen, holds good only for the partial forms of the pericardial defects. It is proposed that complete defects of the pericardium are due to imperfect development of the pleuropericardial membrane, resulting in a rent, either medial or lateral to the phrenic nerve, through which the lung bud grows into the pericardial cavity. The hypothesis that imperfect development of the pleuropericardial membrane is due to a primary defect in the septum transversum is discussed. Rotation of the heart is proposed as an additional possible factor responsible for preponderance of left‐sided defects.
Sensitivity of embryos and intraspecies differences in mice in response to prenatal administration of corticoids
Authors: Dostál M. , Jelínek R.
Published: June 2005

The susceptibility of different strains of mice to the teratogenic action of corticoids is determined by the sensitivity of the embryo and by the protective properties of the maternal‐embryonic complex. The sensitivity of embryos can be determined by direct injection of corticoids into the amniotic sac while the degree of protective properties can be determined by comparing the effects of corticoids administered intraamniotically (ia) and intramuscularly (im) to different strains of mice. Exploring these relations, we applied 0.1 mg hydrocortisone on day 13 of pregnancy ia and 5.0 mg corlisone acetate on day 12 im to A/J, C57BL/6, CBA, and C57BL/10 mice, and to some of their F1, F2 and F3 matings. The effect was evaluated on day 16 of pregnancy by recording dead fetuses and fetuses with cleft palate. We found (1) there are differences both in sensitivity of embryos and degree of protective properties of maternal‐embryonic complexes; (2) the main factor determining susceptibility of the maternal‐embryonic complex to the teratogenic action of corticoids is degree of protective properties; (3) the differing sensitivity of embryos can be the cause of interstrain differences in susceptibility to corticoids only if there is no substantial difference in protective properties of the maternal‐embryonic complex; (4) the sensitivity of F1 hybrid embryos is essentially influenced by hybrid vigor.
Mucopolysaccharide synthesis in the developing inner ear of manganese‐deficient and pallid mutant mice
Authors: Shrader Ruth E. , Erway Lawrence C. , Hurley Lucille S.
Published: June 2005

Histological development of otoliths was examined in the ears of fetal Mn‐deficient and pallid mutant mice and controls. As judged by 35S incorporation, sulfomucopolysaccharides of the otolithic membrane were secreted by cells in the macular epithelium of the utriculus and sacculus. Normal development of otoliths occurred between days 15 and 16 of gestation and was indicated by the appearance of fine granules of calcium carbonate associated with a metachromatic, PAS‐positive material which specifically incorporated 35S. Manganese deficiency or the pallid gene caused reduced incorporation of 35S in the macular cells, the formation of a nonmetachromatic, variably PAS‐positive matrix which did not contain 35S, and failure of otolithic calcification. Rate‐limiting effects of manganese deficiency on sulfomucopolysaccharide synthesis by periotic chondrocytes were observed, but 35S metabolism in cartilage was unaffected by the pallid gene. The possible role of manganese production of the otolithic defect is discussed.
Persistent cloaca with no urethral, genital, or anal openings
Authors: Fitch Naomi , Artinian Berdj
Published: June 2005

An infant is described with persistent cloaca, severe renal hypoplasia, no urethral, genital, or anal openings, and abnormal feet. This child is almost identical with one described by Kirshbaum in 1950.
Median facial cleft syndrome in half‐sisters. Dilemmas in genetic counseling
Authors: Warkany Josef , Bofinger Mary K. , Benton Corning
Published: June 2005

Two infant gids with median facial cleft syndrome are described. The patients were the children of the same mother but of different fathers. None of the parents had the same or similar malformations. The occurrence of this rare syndrome in half‐sisters is difficult to explain; it poses questions about etiology, usually not considered if malformation syndromes are seen in sisters who are the offspring of the same mother and father, both unaffected.
Apert syndrome and palatal mucopolysaccharides
Authors: Solomon Lawrence M. , Medenica Maria , Pruzansky Samuel , Kreiborg Sven
Published: June 2005

By means of histochemical techniques, six of seven patients with Apert syndrome were found to have a heavy deposit of acid mucopolysaccharides in the soft tissue of their characteristic palatal deformity, whereas only six of 15 patients with other palatal deformities (unassociated with the Apert syndrome) were found to have some acid mucopolysaccharide deposited in their palatal soft tissue. The mucopolysaccharides found in both groups were predominantly hyaluronic acid and to a lesser degree sulfated mucopolysaccharides. Examination of sections of skin from both groups of patients and the internal organs, postmortem, from one of the Apert patients failed to reveal the presence of mucopolysaccharides in these tissues.
Teratogenic effects of methylmercury in the cat: Note on the use of this species as a model for teratogenicity studies
Authors: Khera K. S.
Published: June 2005

Pregnancy was induced in cats by coordinating gonadotropin‐induced behavioral estrus and ovulation with natural matings. Reproductive indices were comparable with those already known for pregnancies in normally cycling estrous cats. Cats were orally administered 0, 0.03, 0.83, 0.25, or 0.75 mg/kg Hg (as CH3HgCl) from day 10–58 of induced pregnancy and at near term fetuses were delivered by Cesarean section. 0.75 mg/kg caused vomiting, ataxia, and death within 32 days of commencement of treatment. At 0.25 mg/kg there was an increased incidence of abortion and fetal anomalies; in surviving fetuses a reduced neuronal population in the external granular layer of the cerebellum was noticed. Minimal or no embryopathic effects were noted at lower doses. Mercury concentrations were determined and were in the following decreasing order: fetal blood > maternal blood > fetal brain. The blood and the brain of the test dams had similar concentrations. The literature on congenital anomalies in cats is briefly reviewed.
Prevention of anencephaly and spina bifida in man
Authors: Renwick J. H.
Published: June 2005

Anencephaly and spina bifida, for some purposes, can be regarded as a single entity (ASB). The seasonal peak incidence has pointed to an influence of potato quality, that quality being worst in May or June. The ASB incidence is highest among infants conceived in late April, the damage occurring predominantly in May or June. In addition to this seasonal relation, I have found two other relations with potato quality. These are a concordance geographically between potato‐blight severity and ASB incidence; and a year‐to‐year concordance between these two variables. Perhaps some metabolite of the infected potato (say a phytoalexin), or a metabolite of one of its pathogens, accumulates during winter storage and is maximal in May or June at the likely time of teratogenesis. The year‐to‐year correlation has been confirmed in previously published data. The claim of 95% preventability in the British Isles by complete potato avoidance, a claim based on these associations, has not yet been tested. However, recent anecdotal data has confirmed that preventability cannot quite reach 100% by this means alone, even in the British Isles. I believe that women of childbearing age in whom conception is a possibility should avoid imperfect potatoes.
Metabolites accumulating in potato tubers following infection and stress
Authors: Kuć Joseph A.
Published: June 2005

A broad spectrum of secondary plant metabolites are found in healthy, infected, and stressed potato tuber tissue. These include: chlorogenic, caffeic, vanillic, p‐hydroxybenzoic, and salicylic acids, scopolin, scopoletin, α‐solanine, α‐chaconine, solanidine, α‐solarnarine, β‐solamarine, rishitin, rishitinol, phytuberin, and lubimin. Infection and stress qualitatively and quantitatively influence these constituents. Chlorogenic and caffeic acids, scopolin, scopoletin, α‐solanine, α‐chaconine, and solanidine rapidly accumulate in injured tubers at or close to the sites of injury. In the 22 cultivars of potato studied α‐ and β‐solamarine were only found to accumulate in foliage or injured tubers of the cultivar Kennebec. Infection of tubers with Phytophthora infestans, the incitant of late blight, or a number of other fungi and bacteria causes accumulation at the site of infection of chlorogenic and caffeic acids, scopolin and scopoletin, rishitin, rishitinol, phytuberin, and at times lubimin. These compounds accumulate at levels that are fungitoxic and they appear part of the mechanism of disease resistance of the potato tuber. Resistant tubers infected with P. infestans accumulate more than 200 times the rishitin and related terpenoids found in uninfected tubers. Chlorogenic acid and caffeic acid, scopolin, scopoletin, α‐solanine, α‐chaconine, and solanidine are normal constituents of potato peel, and their concentration in the peel can be equal to that in injured peeled tubers. Freshly peeled healthy tubers contain little or none of the compounds. The danger of introducing substances potentially toxic to humans into food crops is suggested by tne occurrence of α‐ and β‐solamarine in aged tuber slices of the cultivar Kennebec. These substances might arise from the use of mutants or crosses with wild inedible species in breeding programs.
Supernumerary distal limb elements induced by 5‐fluoro‐2′‐deoxycytidine in mice
Authors: Kleinebrecht J. , Fränz J. , Degenhardt K.‐H.
Published: June 2005

Polydactyly (including triphalangy) in C57BL/10 mice inducedby various dosages of 5‐fluoro‐2′‐deoxycytidine given at gestation day IX or XI isdescribed. These data are compared with those on aplasias in order to elucidate whether polydactyly is truly supernumerary or is the result of malposition of limb elements.
Teratogenic effects of aldrin, dieldrin, and endrin in hamsters and mice
Authors: Ottolenghi Anna D. , Haseman Joseph K. , Suggs Fred
Published: June 2005

Single oral doses of aldrin, dieldrin, and endrin, 1/2 LD50 incorn oil, administered to pregnant golden hamsters on day 7, 8, or 9 of gestationcaused a high incidence of fetal death, congenital anomalies, and growthretardation. The most frequent defects were cleft palate, open eye, andwebbed foot, often occurring in combination. Pregnant CD1 mice given equivalent oral doses of each pesticide on day 9 of gestation showed similar anomalieswithout concurrent increase in fetal mortality or growth impairment.
Scalp‐hair patterning: Its origin and significance relative to early brain and upper facial development
Authors: Smith David W. , Gong Bradley T.
Published: June 2005

Studies of hair‐follicle development and scalp‐hair patterning innormal fetuses and children and in those with disorders of early brain development were indicative of the following hypothesis: hair directional slope is secondary to the plane of stretch exerted on the skin by the growth of underlying tissues during the period of downgrowth of the hair follicles, around 10–12 gestational weeks. The posterior parietal hair whorl was interpreted as the focalpoint from which the growth stretch is exerted by the domelike outgrowth of thebrain during the time of hair follicle development. Anomalies such as encephalocele and dicephaly, which must have antedated hair follicle development, showed expected aberrations in scalp patterning. Among patients with primarymicrocephaly 85% had altered scalp hair patterning, indicating an early onsetof the problem in brain development. This included 25% with no parietal whorl, a finding previously noted only in nonhuman primates. Aberrant scalp patterning was also found to be a frequent finding in five established syndromes, included Down syndrome, in each case being compatible with a problem in early brain development. Thus, aberrant scalp‐hair patterning may be utilized as an indicator of altered size and/or shape of the brain prior to 12 weeks of gestation.
Nonteratogenicity in rats of blighted potatoes and compounds contained in them
Authors: Ruddick Joseph A. , Harwig J. , Scott P. M.
Published: June 2005

A diet supplemented with freeze‐dried blighted potatoes fed to rats had no teratogenic or embryolethal effects. Separate experiments with α‐solanine, scopoletin, cytochalasin B, indoleacetic acid, and α‐chaconine, intubated orally during organogenesis, gave no evidence of teratogenicity attributable to the test compounds.
Aortic arch anomalies associated with the administration of epinephrine in chick embryos
Authors: Hodach Richard J. , Gilbert Enid F. , Fallon John F.
Published: June 2005

Single doses of epinephrine (5 μg) administered to 83 groups of chick embryos (24–190 h) at 2‐h intervals, produced a spectrum of aortic arch anomalies. The epinephrine was placed on the surface, of the extra embryonic membrane over the developing embryo in ovo, at a time when aortic arch morphogenesis is occurring. The peak incidence of anomalies (94%) occurred after treatment during day 5 of incubation (108–112 h). The anomalies involved the 3rd, 4th, and 6th pairs of aortic arches; those involving the right 4th arch (arcus aortae) were consistently associated with ventricular septal defects.
Whole‐body autoradiography of the distribution of β‐aminopropionitrile in pregnant mice and rat fetuses
Authors: Waddell William J. , Wilk A. L. , Pratt Robert M. , Steffek A. J.
Published: June 2005

The distribution of the lathyrogenic compound β‐aminopropioni‐trile (BAPN) was studied by whole‐body auto radiography in pregnant A/J mice and Sprague‐Dawley rat fetuses at gestation day 12.5 and 15.5, respectively. [14C] BAPN was administered iv or sc to the mice and by gavage to the rats; 20 min to 24 h after treatment whole maternal mice and rat fetuses were rapidly frozen and processed for autoradiography. The highest maternal concentration of radioactivity in the mice was in salivary gland, kidney, liver, eye, intestinal wall, inner ear, hair, aorta, and ligaments of the vertebral column. The radioactivity accumulated rapidly in mouse fetuses, with all tissue showing appreciable amounts of radioactivity, including the palatal buds and paraoral tissue. Radioactivity also rapidly accumulated in the rat fetuses with the highest concentration in brain and cartilaginous areas, and lesser amounts in tongue, visceral organs, and palatal shelves. Chromatography of extracts of the tissues used for autoradiography revealed that 20 min after injection about one‐third of the BAPN had been converted to the principal metabolite, cyanoacetic acid (CAA). At later times larger proportions of the BAPN had been converted to CAA.
Cleft lip and palate in finland: Incidence, secular, seasonal, and geographical variations
Authors: Saxén Irma , Lahti Aito
Published: June 2005

Five hundred ninety‐nine cases of cleft lip and cleft palate were reported to the Finnish Register of Congenital Malformations in 1967–71. The incidence per 1000 for oral clefts was 1.72, for cleft lip with or without cleft palate 0.83, and for cleft palate alone 0.86. The only statistically significant incidence alteration during this time was a doubling in the frequency of cleft lip without cleft palate in 1969. Only cleft palate exhibited significant geographical variation in incidence, being high in the eastern part of the country. Some seasonal variation was noted, with a high frequency of cleftlip with or without cleft palate in the fourth quarter of the year, a season when the frequency of cleft palate alone was lowest.
Aneuploidy in mouse embryos induced by diethylstilbestrol diphosphate
Authors: Chrisman C. Larry
Published: June 2005

Mouse embryos were collected from females derived from fourway crosses between inbred strains; the females were each treated with a single ip injection of 1, 0.1, or 0.01 μg diethylstilbestrol diphosphate 6, 24, or 48 h before being killed at day 8.5 of gestation. Chromosome counts from ten metaphase plates from each of 307 embryos recovered from 45 experimental females were compared with counts from103 embryos from 15 controls, which had received injections of 0.85% saline. Statistical analysis of the data revealed that both increases in dose and time of exposure were instrumental in producing aneuploid cells. Analysis of treatment means showed that as either dose or exposure time was increased, the rate of aneuploidy was significantly increased.
Experimental modification of patterns of cell death and chondrogenesis in insulin‐induced micromelia of the developing chick limb: An autoradiographic analysis of 35SO4 uptake into chondroitin sulfate
Authors: Hinchliffe J. R.
Published: June 2005

The etiology of micromelia of chick limb caused by the effect of insulin on development in vivo was investigated with reference to patterns of cell death and chondrogenesis in the femur/tibia/fibula region. Insulin (3 IU) was injected into the sub‐blastodermic fluid of 3½‐day chick embryos. Acid phosphatase staining indicated that insulin had no effect in extending the naturally occurring area of cell death in the “opaque patch” region during stages 24–5 (4½–5 days). Autoradiographic study of 35SO4 incorporation into chondroitin sulfate was carried out by administration of a 2‐h pulse of 40 μCi of 35S‐labeled sulfate to the chorioallantoic membrane of 7‐day chick embryos. The autoradiographs showed that insulin suppressed chondrogenesis (i) in the centers of the heads of tibia and femur and (ii) in the joint region. Cell death was found at the center of these regions of suppressed chondrogenesis which may overlap. It is suggested that insulin interferes in vivo with the nutrition of the cartilage and joint regions, possibly through hypoglycemia. These results conflict with Zwilling's ('59) interpretation that in vivo insulin causes extension of the area of the “opaque patch” region of degeneration and its persistence for a longer time than normal.
Single umbilical artery with caudal defects in human fetuses
Authors: Chaurasia B. D.
Published: June 2005

Single umbilical artery associated with multiple anomalies is described in three stillborn human fetuses. Detailed study of the abdominopelvic arteries showed replacement of the abdominal aorta below the origin of the superior mesenteric artery by the umbilical artery in all three specimens. This finding greatly helps in solving the age‐old riddle of the cause‐effect relation between the umbilical anomaly and its associated defects. Single umbilical artery can give rise to the developmental anomalies in three ways. First by replacing the greater part of the abdominal aorta and disturbing the blood supply of the caudal half of the body during early embryogenesis it can give rise to the developmental anomalies of the cloaca, the genitourinary, gastrointestinal, and central nervous systems, and of the lower limbs; second by impairing the growth of the umbilical mesoderm it can disturb the formation of the infraumbilical portion of anterior abdominal wall and its correlates; and third by disturbing the hemodynamics of the embryo it can give rise to cardiovascular anomalies and possibly also to defects toward the cephalic half of the body. Although single umbilical artery and the associated developmental defects may both be secondary to another regionally operative teratogenic influence the extreme vascular reduction caudal to the aorticoumbilical junction and the concentration of malformations in the caudal half of the body greatly support the angiogenic theory.
Ultrastructural observations on closure of the soft palate in hamsters
Authors: Shah Ravindra M. , Chaudhry A. P.
Published: June 2005

Subcellular events during soft palate closure in hamsters were studied electron microscopically. In the early stages the surface epithelium of the palatal shelves was 2–3 cell‐layers thick and was separated from the underlying mesenchyme by an intact basal lamina. The epithelial cells contained few cytoplasmic organelles and were attached to each other by desmosomes. During further development tonofilaments and lysosomes appeared in the epithelial cells. Prior to fusion the epithelia of the opposing shelves displayed thickening followed by desquamation of the superficial cells. Fusion occurred by means of newly formed desmosomes between the fresh surfaces of the opposing epithelia of the shelves, thereby forming an epithelial seam bounded on each side by the basal lamina. Subsequent thinning and fragmentation of the seam occurred as a result of autophagy, exfoliation, and extrusion of cells through the intercellular spaces. Macrophages appeared at a later stage of soft palate development and removed the cellular debris. At no time during these stages of palatogenesis was there evidence of penetration of the basal lamina on either side of the epithelial seam by the surrounding mesenchyme.
5‐FU in chick embryos as a source of label for DNA and a depressant of protein synthesis
Authors: Ruddick Joseph A. , Runner Meredith N.
Published: June 2005

Single injections of 100 μg of 5‐fluorouracil (5‐FU) containing 1.25 μc of [2‐14C]5‐FU were made into the yolk sac of 4‐day chick embryos. Greater amounts of label were incorporated into DNA than into RNA extracts. The rate of accumulation of protein per embryo was lowered by 5‐FU to a somewhat greater extent than was either DNA or RNA. Chromatography of TCA‐soluble fraction from 5‐day embryos indicated presence of 5‐FU and two peaks of unidentified heavier molecules derived from 5‐FU. Thus the selective depression of protein accumulation and the progressive labeling of DNA from 5‐FU indicate a wider spectrum of metabolic effects in chick embryos than might be expected from the reports of 5‐FU in the literature. These data suggest that 5‐FU may act as a teratogen by one or more routes other than as an analogue of an RNA precursor.
Morphogenesis of cleft palate induced by exogenous factors VI. The question of delayed palatal‐process horizontalization
Authors: Dostál M. , Jelínek R.
Published: June 2005

The course of secondary‐palate closure was studied in control, cortisone‐, and 6‐azauridine‐treated randombred H‐Velaz mice. The size of the gap between the developing palatal processes and wet fetal weight were used as measures of secondary‐palate development and overall fetal development. It was found that 250 mg of 6‐azauridine injected im on day 14 both retarded the rate of fetal development and delayed initiation of horizontalization of palatal processes with regard to developmental age of fetuses; and that 7.5 mg of cortisone acetate injected im on day 12 affected the progress of horizontalization rather than its initiation. The mean distance between ihe medial edges of the palatine processes was significantly higher in cortisone‐treated fetuses than in controls just before horizontalization. According to this finding the supposed discrepancy between the width of the head and the palatal processes (resulting in absolute or relative narrowness of palatal processes when they beccme horizontal) is present, at least in part, even before horizontalization.
Fetal pathology in rats following uterine‐vessel clamping on day 14 of gestation
Authors: Leist K. H. , Grauwiler J.
Published: June 2005

The main uterine vessels of pregnant rats were clamped on day 14 for 30, 60, or 90 min. The fetal death rate was increased by 60 or 90 min clamping, proportional to duration. Some surviving fetuses showed skeletal retardation, bilateral limb anomalies, and cleft palate when examined on day 21. As early as 3 h after declamping, edema was seen in the mesenchymal tissue of the limbplates, together with a marked dilatation of the fetal vessels. Later this tissue became necrotic. The necrotic changes also involved surrounding mesenchyme including developing bone, which resulted in the observed limb malformations. In addition large blisters and hematomas at the tip of the snout may have caused tongue displacement to such an extent that palate closure was mechanically impaired. The malformations thus apparently resulted secondarily from necrosis of mesenchymal tissues that had been fully differentiated. This pathogenesis may be a common one for various malformations after impairment of fetal nutrition in rats at this particular develop mental stage.
Teratogenic and embryolethal effects in mice of fission‐spectrum neutrons and γ‐rays
Authors: Cairnie A. B. , Grahn D. , Rayburn H. B. , Williamson F. S. , Brown R. J.
Published: June 2005

Fission‐spectrum neutrons from the Janus reactor at Argonne National Laboratory were compared with γ‐rays in terms of their relative biological effectiveness (RBE) for embryolethal and teratogenic effects in mice. No evidence was found of any processes that were abnormally sensitive to neutrons. The RBE for killing embryos and producing abnormal embryos or specific abnormalities was between 2 and 3. This is close to the values found in other systems for processes involving cell killing.
Effect of physical activity before pregnancy on fetuses of mice exercised forcibly during pregnancy
Authors: Terada Mitsuyo
Published: June 2005

Colony‐bred ICR‐JCL female mice were subjected to physical training by imposing a daily routine of running 6 days a week for 4 weeks from the 6th‐9th weeks of age. These and nontrained females were mated and some from both groups were forced to exercise (running for 30 min/day) on the 9th‐16th days of gestation. Pregnant mice were killed on the 19th day of gestation. The fetuses of females exercised during midpregnancy showed increased mortality, slight decrease in body weight, and some delayed ossification, but no malformations. Training before pregnancy was effective in decreasing the fetal mortality in the females exercised during midpregnancy.
Lack of in vivo cytogenetic effects of imipramine in rats
Authors: Bishun N. , Smith N. , Williams D. C.
Published: June 2005

The cytogenetic effects of single and multiple intraperitoneal injections of imiprarnine HCl on bone marrow cells of Sprague‐Dawley rats were investigated. There were no significant differences in the frequencies of chromosomal aberrations between the test and control animals.
Teratogenic action of acetazolamide in mice
Authors: Castro‐Correia J. , Sousa‐Nunes A. , Silva‐Bacelar A.
Published: June 2005

Sodium acetazolamide, 1 g/kg/day, was given sc to CR mice, in 3 divided doses, every 8 h, on 1, 2, or 3 days, on the 8th to 12th day of gestation. The maternal toxicity and embryolethality of the acetazolamide were weak but its teratogenicity was marked. The most frequent deformities consisted of eyelid abnormalities, exencephaly, and macroglossia. Limb defects also occurred, mostly of the forelimb, especially the right forelimb. Postaxial polydactyly was much more frequent than postaxial ectrodactyly. The results permit the conclusion that in mice cephalic development is not disturbed by acetazolamide after the 10th day of gestation, and that its highest sensitivity to the drug seems to be on the 8th day.
Some aspects of corticosteroid‐induced cleft palate: A review
Authors: Greene R. M. , Kochhar D. M.
Published: June 2005

Since the discovery 25 years ago that cortisone can produce cleft palate in mouse embryos investigations into possible mechanisms of this corticosteroid‐induced defect have been many and varied. However, the teratogenic mode of action remains not fully clarified. It is with this thought in mind that we have reflected upon what is known concerning corticosteroids and cleft palate. The major metabolic pathways upon which glucocorticoids act as well as their intracellular mode of action are well known. Differential sensitivity of various mouse strains to cortisone treatment as well as recent results from interstrain blastocyst transfer experiments demonstrate that corticosteroid action is influenced by both the fetal and maternal genomes. Labeling experiments indicate that corticosteroid‐induced cleft palate is the result of direct action of the steroid molecule on the fetus, whose own sensitivity to insult, perhaps owing to differences in binding of corticosteroids to tissue proteins, determines the final effect. Possible mechanisms that have been proposed by which corti coids may produce cleft palate include: disruption of glycosaminoglycan or, collagen synthesis or both, intracellular lysosomal membrane stabilization, myopathy, weakened midline fusion, and loss of amniotic fluid. Also discussed is the role of stress and stress‐induced corticosteroids and their possible role in the production of cleft palate.
Tissue phosphatase changes following triamcinolone associated with cleft palate in rats
Authors: Holst P. A. , Mills B. G.
Published: June 2005

One theory of the development of cleft palate in rats involves the action of lysosomal enzymes secreted by epithelial cells at the time of fusion of the palatal shelves. To test this theory we studied the biochemistry of the palates of fetal rats daily between days 14 and 19 (from 3 days before to 3 days after palate closure). Triamcinolone was administered once im on gestation day 14 to Wistar rats; 0.5 mg/kg body weight produced approximately 50% cleft palates. Pooled control palatal tissue was compared with pooled experimental tissue, that from fetuses with clefts being pooled separately from those not affected. Acid phosphatase and β‐glucuronidase were assayed. Concentration vs. time curves for both enzymes were very similar. Prior to the time of palate closure both enzymes were present in low concentration. Between days 16 and 17, the normal time of closure, there was an abrupt increase in enzyme concentration, with experimental tissue showing a significant elevation over control tissue on days 17 and 18. Alkaline phosphatase was also present in small amounts before closure and significantly higher in control tissue on day 17. Protein was depressed in palates having clefts on day 17; thus the ratio of enzyme activities to protein synthesis was significantly elevated at a critical time. Unaffected experimental palates had a normal ratio. These results suggest imbalanced acid phosphatase, β‐glucuronidase, and alkaline phosphatase activity compared with protein synthesis at the time of palate closure following triamcinolone in rats.
Teratologic evaluation of synthetic Δ9‐tetrahydrocannabinol in rats
Authors: Banerjee B. N. , Galbreath C. , Sofia R. D.
Published: June 2005

Δ9‐Tetrahydrocannabinol (THC) was dissolved in propylene glycol and 25, 50, or 100 mg/kg administered daily sc to pregnant Charles River Sprague‐Dawley rats on days 6–15 of gestation (presence of sperm considered day 1). Maternal weight gain was depressed, but a significant decrease in fetal weight occurred only in the 50 mg/kg group. No malformations were noted, only some abnormalities consisting of several instances of rudimentary 14th rib and soft or spongy spinal cords.
Prenatal effects of the cancer chemotherapeutic drug ICRF 159 in mice, rats, and rabbits
Authors: Duke D. I.
Published: June 2005

The antimitotic, anticancer drug ICRF 159 [(±)‐l,2‐bis(3,5‐dioxopiperazine‐1‐yl)propane] when given to pregnant BALB/c mice, Sprague‐Dawley and Wistar rats, and New Zealand White rabbits had mainly embryolethal effects; the margin between no apparent activity and total embryolethality was narrow. A small percentage of fetuses were malformed and some exhibited retarded development. In all three species the time of maximum sensitivity to the drug was early in gestation, between days 6–10 in mice, 6–8 in rats, and 7–10 in rabbits.
The fetal alcohol syndrome
Authors: Jones Kenneth L. , Smith David W.
Published: June 2005

A specific pattern of malformation involving prenatal‐onset growth deficiency, developmental delay, craniofacial anomalies, and limb defects is now recognized in offspring of chronic alcoholic women, Historical evidence suggests that this is not a new observation. A recent French study of 127 offspring of alcoholic mothers indicates that this specific syndrome has been recognized in other parts of the world. Many of the features of this disorder could be related to the kind of malorientation of brain structure seen at the autopsy of one patient described herein. The frequency (43%) of adverse outcome of pregnancy for chronic alcoholic women suggests that serious consideration be given to early termination of pregnancy in severely chronic alcoholic women.
Retrospective and prospective epidemiological studies of 1500 karyotyped spontaneous human abortions
Authors: Boué Joëlle , Boué André , Lazar Philippe
Published: June 2005

Epidemiologic studies, retrospective and prospective, were done on 1500 abortions collected from 1966‐1972. No secular or seasonal variations were observed. From the analysis of the relative frequencies of the different types of chromosome anomalies it is estimated that 1 out of every 2 conceptions has a chromosome anomaly. Maternal‐age influence was found only for the autosomal trisomy group, mainly D and G trisomies. No effect of oral contraceptives was discovered. An increased frequency of chromosome anomalies occurred after ovulation‐inducing therapy and after occupational exposure of the father to irradiation. No variations in the fertility rate and in the frequency of congenital malformations in births following abortions was noted. The incidence of recurring abortion was mainly influenced by the reproductive history of the couple before the karyotyped abortion.
Genetics of urogenital abnormalities in ACI inbred rats
Authors: Cramer Donald V. , Gill Thomas J.
Published: June 2005

The frequency of urogenital abnormalities in adult ACI rats was 18.8%. These abnormalities consisted of a spectrum of defects ranging from focal aplasia of the ureter to the complete absence of the ureter, kidney, and tubular genital tract on the affected side. When ACI rats with normal urogenital tracts were crossed with F344 rats the frequency of the defects decreased to a constant level in the F1, F2, and F3 generations. There was no clearly significant decrease in the frequency of the defects in the backcross offspring of (ACI × F344)F1 × ACI matings, but there was a significant and dramatic decrease in the backcross to F344 rats. Attempts to select against these defects by brother‐sister matings among normal ACI rats were not successful: 5 generations of inbreeding did not alter the frequency of the urogenital abnormalities. The frequency of the abnormalities was the same in the offspring of affected parents as in the offspring of normal parents, indicating homozygosity of the factors responsible for the defects. The results suggest that the transmission of these defects is polygenic.
Physiological effects of hypoxia and trypan blue in 17‐day chick embryos
Authors: Hoffman David J.
Published: June 2005

Seventeen‐day chick embryos were divided into 5 groups and treated as follows: (1) untreated, (2) yolk‐sac injected with 0.1 ml of saturated trypan blue solution solution in sterile saline, (3) saline, (4) hypoxia, i.e., 10.5% oxygen, and (5) hypoxia plus trypan blue, After 5 h hypoxia‐treated embryos had an increased mortality rate, severe hypoglycemia, reduced blood pH, elevated plasma potassium, and reduced CO2 content. Trypan blue treatment induced few deaths and few physiological imbalances. Hypoxia plus trypan blue was without synergistic effects and had effects that did not differ significantly from hypoxia alone. This lack of response of 17‐day chick embryos to high doses of trypan blue may be related to a marked decline in oxygen consumption by the yolk at this age.