bluuebunny/crossref_metadata_2025 huggingface dataset:
Methylphenidate analogs with behavioral differences interact differently with arginine residues on the dopamine transporter in rat striatum
Authors: Volz Trent J. , Bjorklund Nicole L. , Schenk James O.
Published: June 2005

The methylphenidate analogs N‐methyl‐4‐methyl‐methylphenidate and N‐benzylmethylphenidate are believed to interact differently with the dopamine transporter (DAT) in vitro and in vivo. Herein, we report that methylphenidate and N‐methyl‐4‐methyl‐methylphenidate, but not N‐benzylmethylphenidate, protect the rat striatal DAT from the arginine‐selective chemical modifying agent, phenylglyoxal. This suggests that methylphenidate and N‐methyl‐4‐methyl‐methylphenidate, but not N‐benzylmethylphenidate, interact with the guanidine groups of arginine residues in the DAT of rat striatum. This differential interaction may, at least in part, explain the in vitro and in vivo differences between N‐methyl‐4‐methyl‐methylphenidate and N‐benzylmethylphenidate. Synapse 57:175–178, 2005. © 2005 Wiley‐Liss, Inc.
Metabotropic glutamate receptor protein expression in the prefrontal cortex and striatum in schizophrenia
Authors: Gupta Daya S. , McCullumsmith Robert E. , Beneyto Monica , Haroutunian Vahram , Davis Kenneth L. , Meador‐Woodruff James H.
Published: June 2005

We investigated the expression of metabotropic glutamate receptors (mGluR) in the prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the release and reuptake of synaptic glutamate and mediate some molecular correlates of neuroplasticity, including long‐term potentiation. The mGluRs are expressed widely in the PFC and striatum, regions often implicated in the pathophysiology of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might contribute to glutamatergic dysfunction observed in the PFC and striatum in schizophrenia. Accordingly, we measured the expression of metabotropic glutamate receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases, 9 controls) by Western blot analysis. We found an increase in the expression of mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no changes in the expression of mGluR4a or mGluR5 were detected in this region. In the striatum we found no changes in the expression of any of the mGluRs studied. These results suggest that alterations of mGluR1a and mGluR2/3 expression in the PFC may contribute to the pathophysiology of schizophrenia, and support targeting these receptors for the generation of novel treatment modalities for this disabling illness. Synapse 57:123–131, 2005. © 2005 Wiley‐Liss, Inc.
Developmental consequences of neuromuscular junctions with reduced presynaptic calcium channel function
Authors: Xing Bin , Long A. Ashleigh , Harrison Douglas A. , Cooper Robin L.
Published: June 2005

Evoked neurotransmitter release at the Drosophila neuromuscular junction (NMJ) is regulated by the amount of calcium influx at the presynaptic nerve terminal, as for most chemical synapses. Calcium entry occurs via voltage‐gated calcium channels. The temperature‐sensitive Drosophila mutant, cacTS2, has a reduced amount of calcium entry during evoked stimulation. We have used this mutation to examine homeostatic regulatory mechanisms during development of the NMJ on muscle 6 within the developing larva. The amplitude of the excitatory postsynaptic potentials are reduced for both the Ib and Is motor neurons in 3rd instar larvae which have been raised at 33°C from the 1st instar stage. Larvae raised at 25°C and larvae pulsed at 33°C from the late 2nd instar for various lengths of time show a reduced synaptic efficacy as a 3rd instar. The results indicate that the nerve terminal cannot fully compensate physiologically in the regulation of synaptic transmission during larval life for a reduced amount of evoked calcium entry. Morphological comparisons of Ib and Is terminals in relation to length and numbers of varicosities are significantly reduced in cacTS2, which also suggests a lack in homeostatic ability. These findings are relevant since many deficits in synaptic transmission in various systems are compensated for either physiologically or structural over development, but not in this case for reduced calcium entry during evoked transmission. Synapse 57:132–147, 2005. © 2005 Wiley‐Liss, Inc.
Picomolar concentrations of hibernation induction delta opioid peptide [D‐Ala2,D‐Leu5]enkephalin increase the nerve growth factor in NG‐108 cells
Authors: Tsai Shang‐Yi , Hayashi Teruo , Su Tsung‐Ping
Published: June 2005

The delta opioid peptide [D‐Ala2,D‐Leu5]enkephalin (DADLE) has been shown to be a neuroprotective agent via mechanisms that are not totally understood. We previously demonstrated that the i.p. injection of DADLE in mice causes an increase of nerve growth factor (NGF) in the brain. To further clarify the NGF‐increasing action of DADLE, we examined here the NGF‐increasing effect of DADLE in vitro, using cultured NG‐108 cells. DADLE dose‐dependently increases the immunoreactive level of NGF in NG‐108 cells in a bell‐shape manner, with the effective DADLE concentrations in the picomolar range (0.01–100 pM). Also, DADLE at 1 pM selectively increases c‐Jun and c‐Fos, but not c‐Rel. These results indicate that DADLE is one of the most potent agents in increasing the NGF in the biological system and that this action of DADLE involves selective increases of c‐Jun and c‐Fos, transcription factors that promote the NGF expression. Synapse 57:179–181, 2005. Published 2005 Wiley‐Liss, Inc.
Trypan blue in the rat embryo
Authors: Davis Howard W. , Gunberg David L.
Published: June 2005

Seventy‐five embryos were obtained from rats 48, 72, or 96 hours after injection of the maternal animal with the teratogenic dye trypan blue on day 9 of gestation. Low‐magnification examinations of these fixed and cleared embryos revealed distinct deposits of trypan blue in the caudal segments of the gut. Light‐microscope examinations revealed dye deposits in the gut endoderm and cells of the adjacent mesenchyme. The implications of these observations are discussed.
Two familial translocations involving the 6–12 group. With meiotic studies in one
Authors: McDermott A. , Insley J. , Rushton D. I. , Edwards J. H.
Published: June 2005

Two infants are reported with congenital malformtions. In each case, the infant had a karyotype containing an abnormal chromosome and one parent was a balanced structural heterozygote.

Data on the phenotypes of the propositi are presented with familial studies on blood group markers and chromosome analysis, including paternal meiosis in the case in which the father carried the balanced translocation.

In the first case, the infant had a duplication of part of the long arms of one of the 6‐X‐12 group, probably number 11; the mother had a balanced interchange probably between chromosome 11 and 12. In the second, the infant had a duplication of part of the long arms of another chromosome in the 6‐X‐12 group, probably number 8, while the father had a balanced interchange between this chromosome and number 18. Meiotic studies indicated that the interchange chromosomes usually formed a quadrivalent during the first meiotic division; when univalents formed, the cells tend to degenerate.
Teratology in the Macaca mulatta
Authors: Courtney K. D. , Valerio D. A.
Published: June 2005

The effects of acetylsalicylic acid, meclizine hydrochloride, methamphetamine hydrochloride, clomiphene citrate, vincristine sulfate, and 6‐aminonicotinamide on fetal development of the Macaca mulatta were studied.

Two monkeys administered acetylsalicylic acid 40 mg/kg/day from the 25th day of gestation to term produced normal young. Seven pregnant monkeys given meclizine hydrochloride 10 mg/kg/day during various five‐day intervals had normal progeny. Five monkeys given methamphetamine hydrochloride 0.5 mg/kg/day from implantation to term had four normal young and one abortion. Clomiphene citrate administered to 18 pregnant monkeys during various stages of organogenesis resulted in 16 normal offspring and two stillbirths.

Two of the five monkeys that received vincristine sulfate produced offspring with congenital malformations. One, given a single injection of 0.175 mg/kg on the twenty‐ninth day of gestation, had an offspring with encephalocele. One administration of 0.15 mg/kg on the twenty‐seventh day of gestation produced syndactyly in the offspring of another. The other monkeys, which received 0.15 or 0.20 mg/kg on the twenty‐eighth, thirty‐third, or thirty‐fourth day of gestation, produced normal offspring.

Seven monkeys were treated with 6‐aminonicotinamide at different stages of gestation. Four, treated from the twenty‐sixth to twenty‐ninth days, aborted, the other three had normal young.

Retrospective studies of therapeutic agents used at various times during pregnancy in monkeys in the colony have shown that hydroxyprogesterone caproate (Delalutin), chloramphenicol succinate (Chloromycetin), lincomycin hydrochloride (Lincocin), and benzathine penicillin G and procaine penicillin G (Longicil) have no apparent effect on the developing monkey fetus.
Congenital malformations in the rat following induced hyperthermia during gestation
Authors: Edwards M. J.
Published: June 2005

Hyperthermia induced in pregnant rats by exposures for 40 to 60 minutes in an incubator that raised deep body temperatures from 38.1 ± 0.51 to 42.7 ± 0.62°C produced increased fetal resorptions, retardation of growth, and a number of development defects. Grossly apparent fetal malformations included microphthalmia following hyperthermia on day 9 of pregnancy, anencephaly on day 10, and defects of tails, limbs, toes, palate, and body on days 12 to 14.
Effects of N‐nitroso‐N‐methylurea on enzymatic ontogeny associated with teratogenesis
Authors: Johnson E. Marshall , Lambert Carol
Published: June 2005

The teratogenic effects of N‐nitroso‐N‐methylurea on the rat embryo were investigated. Skeletal malformations were produced in rat embryos by a dose of 20 mg/kg of maternal body weight on day 13 of pregnancy. The structurally malformed fetuses had multiple malformations including: clubfeet, syndactyly, cleft palate, micrognathia, crooked tail, and hydrocephalus. Drug administered on day 8 or 10 at dosages of 5–20 mg/kg gave no malformations at term but tended to increase fetal mortality. A dose of 20 mg/kg on day 13, however, resulted in a high incidence of congenital malformations but did not increase the resorption rate. To correlate the structural malformations with biochemical changes, zone electrophoretic separation of several enzyme systems was carried out in starch and polyacrylamide gels. Variations from the normal isozyme patterns of lactate dehydrogenase, glucose‐6‐phosphate dehydrogenase, and nonspecific esterases were found in abnormally developing embryos and organs.
Sporadic congenital malformations of newborn inbred mice
Authors: Kalter Harold
Published: June 2005

A retrospective study was made of sporadic congenital malformations in newborn mice of nine inbred strains maintained in this laboratory. Young of seven of the strains had externally observable anomalies. In four the frequency was 0.1–0.5% and the defects formed no obvious pattern. In another it was about 4% and consisted mostly of preaxial polydactyly of the forefoot.

In the remaining two the frequency was greater and some of the malformations appeared to constitute particular syndromes. In the C57BL/6JKt strain the overall frequency of malformed offspring was 10.1% and the abnormalities included eye defects, polydactyly, and otocephaly. Those of the eye (microphthalmia and anophthalmia) were commonest and affected females and right eyes much more often than males and left ones. In the A/JKt strain the total frequency of malformed offspring was 10.4% and the abnormalities included cleft lip with or without cleft palate, open eyelid, and polydactyly. Cleft lip was commonest and did not show a sex or side preference.

The use of inbred strains to investigate the etiology of sporadic congenital malformations of probable multifactorial origin is to be encouraged.
Oxygen consumption in normal and trypan blue‐treated chick embryos
Authors: Kaplan Stanley , Johnson E. Marshall
Published: June 2005

A teratogenic dose of trypan blue (1% dissolved in saline) was injected into the yolk sac of 48‐hour chick embryos. Twelve hours later the embryo preparations (embryo plus area opaca) were isolated and placed in Warburg vessels in a protein‐free culture medium containing glucose and a buffered saline. Oxygen consumption was measured in these dye‐treated preparations and in two classes of controls, unopened and saline‐injected.

Qo2 (μl O2 consumed/mg dry wt/hr) in trypan blue‐treated preparations was significantly higher than in either class of controls. This is apparently a result of two combined effects of the dye on the tissues studied: (1) a true increase in oxygen consumption; and (2) a decrease in dry weight.

These results show that the teratogenic effects of trypan blue can be detected at the biochemical level within 12 hours of treatment. It is suggested that trypan blue acts as an uncoupling agent on the tissues of the early chick embryo.
Respiratory changes observed in abnormally developing rat embryos
Authors: Netzloff M. L. , Johnson E. M. , Kaplan S.
Published: June 2005

Abnormally developing embryos from maternal rats treated with the teratogenic folic acid antagonist 9‐methyl pteroylglutamic acid were evaluated for their capacity to consume oxygen in a Warburg constant volume respirometer. Experimental and control embryonic preparations, with extraembryonic membranes intact, were maintained individually in culture media during the full time course of a manometric determination.

During the period of the vitamin deficiency the experimental embryonic preparations were found to consume oxygen at a significantly greater rate than did control embryos of the same age. The Qo2 for the abnormally developing embryos returned to the control value 24 hours after maternal treatment was terminated. During the period of vitamin deficiency the dry and wet weights of the experimental embryos were less than those of the controls. Subsequent to the deficiency period these attributes gradually returned to control levels.

Changes in the oxygen consumption of experimental embryonic preparations were related to the embryo itself and not to the surrounding extraembryonic membranes.
Effect of phenobarbital and SKF 525‐A on the teratogenicity of cyclophosphamide in mice
Authors: Gibson James E. , Becker Bernard A.
Published: June 2005

Maternal nontoxic dosages of cyclophosphamide are teratogenic in Swiss‐Webster mice. Phenobarbital induces and SKF 525‐A inhibits liver drug‐metabolizing enzymes in mice. The purpose of this study was to evaluate the effect of SKF 525‐A and phenobarbital on the teratogenicity and development of alkylating activity after cyclophosphamide. Mice were pretreated intraperitoneally with SKF 525‐A (32 mg/kg) or phenobarbital (50 or 100 mg/kg) on days 8, 9, and 10 of gestation. Cyclophosphamide (20 mg/kg, ip) was administered to all groups on day 10. Phenobarbital and SKF 525‐A were not teratogenic. Cyclophosphamide significantly (P < 0.05) reduced the weight of fetuses examined on day 18 of gestation (control, 1.52 vs 0.89 g). SKF 525‐A pretreatment on days 8, 9, and 10 significantly reduced fetal weight from cyclophosphamide (0.79 vs 0.89 g). Phenobarbital pretreatment significantly reversed cyclophosphamide weight effect (1.23 vs. 0.89 g). SKF 525‐A significantly increased the incidence of resorptions, open eyes, polydactyly, aphakia, hydronephrosis, absence or nonossification of ribs, bone fusion. and bone curvature. Phenobarbital abolished cyclophosphamide‐induced limb defects, hydrocephalus, exencephaly, cleft palate, aphakia, and hydronephrosis. Phenobarbital did not affect cyclophosphamide‐induced polydactyly or open eyes. Phenobarbital pretreatment increased and SKF 525‐A pretreatment decreased the concentration of nitrobenzyl pyridine alkylating product of cyclophosphamide (100 mg/kg) in plasma. The teratogenicity of cyclophosphamide may be separate from its alkylating activity.
Microscopic studies of achondroplastic rabbit cartilage
Authors: Shepard Thomas H. , Fry Louis R. , Moffett Benjamin C.
Published: June 2005

The cartilage of long bones in newborn achondroplastic (ac/ac) dwarf rabbits was compared with that of phenotypically normal littermates using histologic, histochemical, and electron‐microscopic procedures. The dwarf cartilages contained (1) dead chondrocytes (nuclear pyknosis and absence of surrounding moat) distributed with increasing frequency from the periphery to the center of the resting cartilage (littermate controls showed far fewer and a random distribution of dead chondrocytes); (2) fewer chondrocytes in the isogenous groups or capsules of central portion of the metaphyseal growth plate compared to controls; and (3) less cartilage matrix. Based on these observations it is suggested that a metabolic defect may become expressed specifically in achondroplastic cartilage cells when they are isolated from their vascular supply.
The effects of teratogenic doses of hypoxia on the blood pressure of chick embryos
Authors: Grabowski Casimer T. , Tsai Enoch N. C. , Toben Howard R.
Published: June 2005

Exposure of chick embryos to moderate hypoxia (6–10% O2 for 4–6 hours) induces a marked blood‐volume increase. This treatment also precipitates hemorrhage that can cause death or malformation or both when localized near rapidly developing structures. To determine whether the hypoxia‐induced hypervolemia can raise embryonic blood pressure to a hemorrhage level, the mean ventricular blood pressure (MVBP) of 587 embryos was measured before, during, and after treatment. The mean MVBP of 3‐day embryos rose from 11.1 mm water to 14.7 mm during the first two hours of hypoxia, dropped slowly during the rest of treatment, then increased again after exposure to air. The highest mean values (16.4 mm) were obtained two hours after treatment, coinciding with the time of maximum hemorrhage. The range of MVBP at that time was wide (6.0–27.0 mm) and in many embryos was twice as high as normal. The MVBP gradually returned to normal 2–13 hours after treatment. Maximum increases in the MVBP of 4 to 5‐day embryos also occurred during the second hour after treatment, but recovery after that was faster than at three days.

In a parallel experiment hypervolemia was induced by sequential injection of saline into the ventricles of 3‐day embryos, in between pressure measurements. The MVBP rose slowly up to 30 mm water. Bleeding usually began at pressures of 18 mm. Hypervolemia induced by hypoxia appears to be responsible for the blood‐pressure increases and the development of teratogenically important hemorrhage.
Serum proteins and disazo dye teratogenesis
Authors: Beaudoin Allan R.
Published: June 2005

Serum proteins of pregnant rats were analyzed by paper electrophoresis following administration of the teratogenic disazo dyes trypan blue, Evans blue, Niagara blue 4B, Niagara sky blue 6B, Congo red, and Niagara blue 2B. Sera were obtained from blood taken by cardiac puncture just before dye injection, 48 hours after dye injection; and again at autopsy. All of the dyes tested caused a reduction in serum albumin and total protein concentration and an elevation in the concentration of beta or alpha‐2 globulins at some time during pregnancy. The remaining serum fractions reacted variably to the dye treatment. In spite of the rather consistent results presented in this paper, and similar findings reported for other teratogens, there is no direct proof that altered serum proteins, per se, are causally related to the production of malformations.
Response of the lateral motor column to multiple forelimbs in Rana pipiens
Authors: Pollack Emanuel D.
Published: June 2005

The lateral motor columns of a recently metamorphosed frog (Rana pipiens) that had three functional forelimbs on the left side were analyzed for differences on the two sides of the spinal cord. It was found that there was no gross hyperplasia on the left side, nor were there significant differences between the mean nuclear areas of the cells of the two sides. Significant differences did occur, however, in the distribution of nuclear sizes of the two sides. A greater proportion of the cells of the left side had large nuclear areas than did those of the right side. This points to a response of the lateral motor column to an increased periphery by increasing sizes of certain cells rather than by increasing cell numbers.
Fetal weight and intrauterine position in rats
Authors: Barr Mason , Jensh Ronald P. , Brent Robert L.
Published: June 2005

Fetal weight data from 28 litters of Wistar rats were analyzed for the effect of position in the uterine horn on fetal weight. The deviation of each fetus from the mean weight of all fetuses in a uterine horn was divided by the standard deviation of the mean. The standard scores thus obtained were studied for position effect. A pattern of fetal weights was found in which the heaviest fetus occupied the middle position with a progressive decrease in weights toward the ovarian and cervical ends of the horn. The lightest fetus in each horn was most likely to be found occupying either one of these extreme positions. These results are discussed with respect to a hemodynamic theory of fetal growth control that has been postulated for the guinea pig and mouse, and it is concluded that this theory is not applicable to the normal rat pregnancy.
Effects of ovariectomy and hypervitaminosis A on lysosomes of the rat conceptus
Authors: Schultz Richard L.
Published: June 2005

This report is concerned with some biochemical effects of ovariectomy and hypervitaminosis A on cell organelles, with particular emphasis on the lysosomes, of embryos, yolk sacs, and placental labyrinths of 13‐day pregnant rats. The two parameters considered were lysosomal stability and the distribution of enzymes in fractions obtained by differential centrifugation. Lysosomal stability was determined by measuring (1) the amount of “free” enzyme activity, i.e., the amount of enzyme in the cytoplasmic extracts of the three tissues measured in the presence of isotonic sucrose and (2) the amount of “nonsedimentable” enzyme. Excess vitamin A produced no change in the latency of acid phosphatase or β‐glucuronidase in any of the tissues when compared with controls. Following ovariectomy there was marked labilization of both enzymes in embryos, increased labilization of β‐glucuronidase in placentas, and little change in yolk sacs.

The distributions of the lysosomal enzymes in control fractions were not the same in the three tissues, indicating differences in size, shape, and/or density of the lysosomes. There was no change in the distribution of reference enzymes after hypervitaminosis A. Ovariectomy produced increased solubilization of β‐glucuronidase in the three tissues and a lesser increase in soluble acid phosphatase in embryos, indicating lack of uniformity in the lysosomes.
The relation of sex‐associated facial profile reversal and stages of human palatal closure
Authors: Burdi Alphonse R. , Silvey Ralph G.
Published: June 2005

This report is concerned primarily with the chronological relations among stages of palatal closure, changes in facial profile, and the sex of a select group of human embryos representing the critical period of palate development. Histological serial sections of 40 human embryos ranging in age from 6 to 9 weeks and free from gross defects were studied using light microscopy and graphic reconstructions. Maxillary prognathism usually occurred concomitantly with vertically oriented palatal shelves. As the shelves progressively assumed a horizontal position prior to palatal closure, a profile reversal occurred, i.e., the lower jaw became prognathic. Both profile reversal and reorientation of the palatal shelves occurred earlier in males (seventh week) than females (eighth week). These patterns suggest a sexual dimorphism in which the palatal shelves in females are apart and vertical for a relatively longer time than in males. Also, the concordance between palatal‐shelf elevation and mandibular prognathism suggests that the forward repositioning of the lower jaw may contribute to the removal of the tongue from between the palatal shelves.
Relation of dosage and time of administration of diphenylhydantoin to its teratogenic effect in mice
Authors: Harbison Raymond D. , Becker Bernard A.
Published: June 2005

Diphenylhydantoin was teratogenic and caused prenatal death in Swiss‐Webster mice. Most deaths resulted after single treatment on days 10, 11, 12, 14, and 15. Fetal body weight was significantly reduced in a dose‐related manner after single treatment on days 9 to 15. Single injections of diphenylhydantoin produced open eye, ectrodactyly, cleft lip, cleft palate, hydronephrosis, and internal hydrocephalus. Skeletal defects noted were incomplete ossification of sternebrae or cervical centra, unfused sternebrae, and fused vertebrae. Long bones were shortened in a day‐ and dosage‐dependent fashion. Mortality, teratogenesis, and effect on fetal growth were day‐ and dosage‐dependent as was the spectrum of anomalies produced.
Congenital defects in guinea pigs: Fetal resorptions, abortions, and malformations following induced hyperthermia during early gestation
Authors: Edwards M. J.
Published: June 2005

Hyperthermia was induced in guinea pigs for 1 hour daily on eight, four, or two occasions on days 4–32 of gestation. Maternal core temperature was elevated for about 90 minutes during and after each exposure and the mean maximum elevation was approximately 3.6°C above normal. There was little effect on gestation or fetal development of treatment during days 4–11 of pregnancy. Fetal resorption occurred following exposure on days 11–15 and abortion was common following exposure on days 15–18. Developmental abnormalities were noted in newborn offspring following heat treatment during days 11–32 and were most common after exposure on days 18–25. Microphthalmia and coloboma followed exposure during the earlier part of this period and micrencephaly during days 15–27. Cataract, exomphalos, talipes, abnormalities of bone development, incisor teeth, and digits of the forelimbs, and renal agenesis occurred in various frequencies particularly following exposure on days 18–25. Amyoplasia affecting muscles of the neck, forelimbs, thorax, and abdomen, which was associated with reduced size of the cervical and thoracic spinal cord, followed exposure on days 26–31. The techniques used to induce hyperthermia are described and possible adverse effects of hyperthermia on fetal development are discussed.
Evaluation of the prenatal effects of massive doses of insulin in rats
Authors: Ream John R. , Weingarten Peter L. , Pappas Arthur M.
Published: June 2005

Pregnant rats were injected intraperitoneally with large doses of insulin. Controls were given intraperitoneal saline. Rats allowed food ad libitum maintained lowered blood‐sugar levels and did not go into hypoglycemic shock; fasted rats died. Fifty‐four rats produced 532 fetuses, gross and microscopic examination of which revealed no skeletal or other abnormalities. Some implications are discussed.
The effect of trypan blue on expressivity of the brachyury gene, “T,” in mice
Authors: Hamburgh Dr. Max , Herz Ronald , Landa George
Published: June 2005

Male mice heterozygous for the brachy gene (T/+) were mated to Swiss albino females. On day 8 of pregnancy the females were injected with 0.2 ml of 1% trypan blue solution. A control group consisted of Swiss albino females mated to +/+ males and injected with trypan blue on day 8 of gestation. Trypan blue produced taillessness in all heterozygous (T/+) offspring, while +/+ offspring had no major tail abnormalities.
Organ culture of limb buds from riboflavindeficient and normal rat embryos in normal and riboflavindeficient media
Authors: Shepard Thomas H. , Bass Glenda L.
Published: June 2005

Embryonic limb cultures from control and riboflavin‐deficient galactoflavin‐treated rats were explanted on gestation day 12.5 and grown in vitro for seven days. The riboflavin‐deficient limb buds failed to grow in riboflavin‐deficient medium but exhibited near‐normal protein synthesis and increase in size in medium supplemented with riboflavin. The growth of control limb buds was not impaired by exposure to deficient medium. The conclusion is that the major mechanism for production of limb defects functions at a local cell level rather than these resulting from physiologic impairment of the embryo.
Teratogenic compounds in Veratrum californicum (Durand). IX. Structure‐activity relation
Authors: Keeler Richard F.
Published: June 2005

The structures and configurations of three naturally occurring steroidal alkaloid teratogens from Veratrum californicum that induce cyclopia in sheep have been elucidated. The probable teratogenic structural requirements were examined in light of known structural and configurational information on active and nonactive compounds. Methods are proposed that will enable elucidation of the precise structural requirements for this teratogenic effect.
Epidemiological Observations on bovine viral diarrhea‐mucosal disease virus‐induced congenital cerebellar hypoplasia and ocular defects in calves
Authors: Kahrs Robert F. , Scott Fredric W. , de Lahunta Alexander
Published: June 2005

Congenital cerebellar hypoplasia occurred in five calves in two New York State dairy herds in which bovine viral diarrhea‐mucosal disease occurred while the dams were pregnant. Clinical and serological evidence linked the virus infection with the anomalies. The dams of the calves were estimated to have been infected between days 102 and 183 of pregnancy.
Teratogenic effects of direct injection of aqueous and protein‐bound trypan blue into the bloodstream of 3‐day chick embryos
Authors: Kaplan Stanley , Johnson E. Marshall
Published: June 2005

To test the direct teratogenic effects of trypan blue in chick embryos 1 μl of 0.1% dye (dissolved in isotonic saline or 9‐day chick embryonic serum) was injected into the vitelline veins at 72 hours of incubation. It was carried from the injection site into the embryonic circulation within seconds after injection. The types and sites of abnormalities produced were noted 1 day later. Of the various types of controls, 65% were normal, 18% died within 1 day of treatment, and 17% had abnormalities. None among the experimental specimens was normal, 62% died within 1 day of treatment, and 38% had abnormalities. In all groups the malformations consisted of hematomas of the head, caudal region or both. Trypan blue caused more deaths when administered in serum than in saline.
Attempts to isolate H‐1 virus from spontaneous human abortions: A negative report
Authors: Newman Stephen J. , McCallin Paul F. , Sever John L.
Published: June 2005

In previous studies the H‐1 virus was reported to have been isolated from up to 20% of human tumors, placentas, and embryos. In the present investigation no H‐1 virus could be recovered from 50 spontaneous human abortions. None of the sera that were available from the gravid women had detectable hemagglutination‐inhibiting antibody to H‐1 or RV virus. The relation of H‐1 virus to human abortions and other human disease remains in question.
Postnatal effects on some behavioral and neural parameters in mice treated with β‐2‐thienylalanine in utero
Authors: Capobianco John O. , Beck Sidney L.
Published: June 2005

A genetically heterogeneous group of pregnant mice from a fourway outcross of C3H/HeH, CBA/Gr, A/Gr, and C57BL/Gr strains was treated by ip injections of 40, 60, or 70 mg of β‐2‐thienylalanine on each of days 10, 11, and 12 of gestation. Significant differences in brain and body weights were observed in their progeny at 23 days postnatal when compared with solvent‐treated controls. Brain weight of experimental animals was significantly decreased, whereas body weight was significantly increased. Experimental animals had a significantly higher frequency of sound‐induced seizures at 23 days than did untreated controls but not significantly higher than solvent‐treated controls.
Chromosomal breakage and teratogenesis
Authors: Roux C. , Emerit I. , Taillemite J. L.
Published: June 2005

The teratogenic and cytogenetic effects of three substances — thalidomide, rubidomycin, and trypan blue — were studied. For teratogenic studies fetuses were examined at the end of pregnancy. For cytogenetic studies chromosome‐breaking properties of the substances were first tested in vitro, on human blood cultures. Next, in vivo studies were performed (1) on the blood (rats) or bone marrow (rabbits) of treated pregnant females and (2) in embryos examined 2 hours after the last application of the substance tested. A significant increase of chromosomal anomalies was found in the embryos in the three experiments. The possible causal relation between the teratogenic and cytogenetic effects is discussed.
Spontaneous congenital limb malformations in nonhuman primates: A review of the literature
Authors: Morris Laura Newell
Published: June 2005

Occurrence of split hand and foot anomaly in two male Macacamulatta at the Regional Primate Research Center, University of Washington, prompted a survey of the literature pertinent to limb abnormalities among nonhuman primates. In some primate populations the incidence of limb abnormalities is significantly higher than in human populations. The etiology of the abnormalities is uncertain and genetic and nongenetic factors may be responsible. Differential mortality and fertility rates are inconclusive; population and pedigreestudies are needed to determine their etiology and possible significance for understanding primate evolution.
Effects of 5 days of hypoxia on the blood of chick embryos
Authors: Ackerman Neil R. , Ramm Gordon M.
Published: June 2005

Chick embryos of 2–14 days of age were incubated in 13% oxygen for 5 days. Experimental embryos demonstrated lowered red blood cell levels, enhanced mean erythrocyte volumes, greater percentages of immature red blood cell stages, and depressed embryonic weights and stages when compared with their controls. Generally, embryos older than 13 days at the termination of the hypoxic incubation were less affected by the low oxygen treatment than younger ones.
Umbilical vein entering the right atrium: Comments on a previously reported human case
Authors: Monie I. W.
Published: June 2005

An abnormal umbilical vein that terminated in the right atrium, which was described by Mende in 1826, is considered to be an example of persistence of the right umbilical vein in man. A similar abnormality has been found in rat fetuses following the administration of certain teratogens to females during pregnancy.
Urogenital abnormalities produced in rat fetuses with chlorcyclizine
Authors: Auerbach Carol , Barrow Mark V.
Published: June 2005

Chlorcyclizine was given to pregnant rats in daily doses of 60 or 80 mg/kg on days 12‐16 of gestation. The lower dose induced hydronephrosis and hydroureter in 37% of fetuses and undescended testes in 55% of the males whereas at the higher dose only 4% were hydronephrotic although 100% of the males were cryptorchid. Histological examination revealed the hydronephrosis and hydroureter to be secondary to either ureteral aplasia or persistence of the ureteropelvic membrane. The same membrane was observed in fetuses exposed to the higher dose although hydronephrosis was infrequent in these animals. Sections revealed dysplasia, tubular disorganization, and increased connective tissue in most kidneys from fetuses treated with the higher dose. A hypothesis to explain these findings is that the ureteropelvic membrane or atresia is present at both doses but urine production is reduced at the higher dose and thus no hydronephrosis results.
Distribution and metabolism of triamcinolone acetonide in mice sensitive to its teratogenic effects
Authors: Zimmerman Ernest F. , Bowen Donna
Published: June 2005

Since glucocorticoids cause a high frequency of cleft palate in the A/J mouse strain the distribution of labeled triamcinolone acetonide and the presence of its metabolites in embryos and pregnant females were investigated. 3H‐Triamcmolone acetonide (5 mg/kg) was primarily excreted by the females through the enterohepatic circulation. Organic‐solvent extraction and subsequent thin‐layer chromatography revealed at least six metabolites, plus 38‐50% of unmetabolized drug, in maternal liver; however, only about 9% of unmetabolized steroid was present in bile. After 0.5 hr of administration of a dose of labeled triamcinolone acetonide causing 100% cleft palate practically all the radioactivity in embryos and placentas was unmetabolized drug, embryo concentration being 1 × 10−6 M. Thereafter, the concentration of drug in embryos and placentas fell markedly. It is concluded that triamcinolone acetonide and not its metabolites is the teratogenic agent.
Skeletal defects in embryonic chicks induced by administration of beta‐aminopropionitrile
Authors: Hall B. K.
Published: June 2005

Teratogenic skeletal defects were produced when beta‐amino‐propionitrile (BAPN) was injected onto the chorioallantoic membrane of 7‐day chick embryos at doses between 0.156 and 1.25 mg BAPN/embryo. The mandible became bent and buckled, the upper jaw shortened, and the tibia and fibula bent into an S‐shaped configuration. Apparently the weakened bone was unable to withstand normal growth pressures. Massive osteogenesis was initiated on the concave surface of the bent tibia forming an exostosis. The histology and histochemistry of these bones were described.
Isolated cleft palate in mice after transportation during gestation
Authors: Brown K. S. , Johnston M. C. , Niswander J. D.
Published: June 2005

Subjecting pregnant mice to a 48‐hour transportation process during the 5 days of gestation prior to embryonic palate closure increased the frequency of isolated cleft palate (CP) in the fetuses examined just before delivery. The increase in CP rate was dependent on the mouse strain and the time of gestation during which transportation was carried out. Fourteen litters of A/J mice shipped on day 13 had 27% CP and 15% when shipment was made as early as day 10. In 14 litters of DBA/2J shipped day 13 there was 3% CP whereas ten litters of C57BL/6J and five litters of CBA/J shipped on day 13 had no CP. In ten litters of C3H/J shipped on day 12 there was one CP and none in ten litters shipped on days 13 or 14. The rank of relative CP susceptibility in the strains was the same as that produced by cortisone injection. This relation is interpreted in terms of interaction between variable maternal blood corticosterone levels in response to “stress” and variable fetal teratologic responsiveness.
Is insulin a teratogen?
Authors: Landauer Walter
Published: June 2005

A review is given of the literature on the supposed causative relation between hypoglycemia and teratogenicity in the origin of malformations due to treatment with insulin and certain sulfonamides. An appendix reports antiteragenic effects of insulin in combination with 3‐acetylpyridine.
Syndactyly in a rhesus monkey: A case report
Authors: Primack A. , Young D. , Homan E.
Published: June 2005

Congenital anomalies of the hands and feet of rhesus monkeys (Macaca mulatta) are rare. A case of such anomalies, with x‐rays of the bony deformities, is reported.
The effects of various levels of dietary protein on retinoic acid‐induced teratogenicity in rats
Authors: Nolen Granville A.
Published: June 2005

The teratogenic effects of single oral doses of 10 mg/kg retinoic acid given on day 9 of pregnancy was compared in rats fed 2.5, 5, 10, 20, or 30% dietary protein. Low levels of dietary protein alone did not affect reproduction and were not frankly teratogenic, but did retard skeletal ossification in fetuses of females fed 2.5% protein. Fetal growth was depressed in the groups fed 2.5, 5, or 10% protein. In rats treated with retinoic acid the resorption rate and the incidence of defective fetuses was increased by protein deficiencies. Serum analyses on gestation days 3, 9, and 21 revealed significantly lower BUN levels on days 9 and 21 in females fed 2.5 or 5% protein compared to those fed 20 or 30% protein, but the total proteins and albumin were not lower in these two groups until day 21. The administration of retinoic acid increased the level of protein in sera and livers and decreased the level of liver lipids in rats fed the lower levels of dietary protein, indicating that the retinoic acid increased protein synthesis.
The incidence of congenital malformations in a Chinese population: The Taipei collaborative study
Authors: Emanuel Irvin , Huang Shih‐Wen , Gutman Laura T. , Yu Fu‐Chi , Lin Chia‐Chin
Published: June 2005

Data are presented from an epidemiological survey of congenital malformations in 25,814 consecutive single and multiple births occurring in six hospitals in Taipei, Taiwan. All malformed babies were examined by at least one of four study physicians. The malformation rate was 13.23/1000 total single births, and ranged from 8.66 to 20.27/1000 births in the six hospitals. There also was significant interhospital variation in fetal death rate early neonatal death rate, and rate of multiple births. No significantly greater incidence of malformations in twins than nontwins was noted. Compared to other populations there were intermediate rates of anencephaly (1.17/1000 births), low rates of spina bifida (0.16/1000) and hydrocephalus (0.35/1000), and high rates of cleft lip with or without cleft palate (1.92/1000), radial polydactyly (1.02/1000), osteogenesis imperfecta (0.16/1000), and conjoined twins (1 in 6454 births). Methodological problems of incidence studies of congenital malformations are discussed.
Effects of methylmercury on prenatal development in mice
Authors: Spyker Joan M. , Smithberg Morris
Published: June 2005

Single doses (2, 4, or 8 mg/kg) of methylmercury dicyandiamide (MMD) were given ip to 129/SvS1 and A/J pregnant mice on days 6‐13 of gestation and fetuses were examined on day 15 or 18. Results indicated that MMD (1) retarded growth in both strains; (2) retarded stage of development in 129s; (3) was embryolethal and teratogenic (brain, palate, or facial defects) in 129s when administered on days 9‐13 but not on days 6‐8; (4) was not embryolethal in As; and (5) was teratogenic (palate and jaw defects) in As when injected on days 9‐13. All of the quantities measured were found to vary with day of treatment, dose, and strain.
The distribution of hydrocortisone‐14C, corticosterone‐14C, and deoxycorticosterone‐14C in pregnant mice
Authors: Waddell William J.
Published: June 2005

The distributions of the glucocorticoid hydrocortisone‐14C and the mineralocorticoid deoxycorticosterone‐14C were compared with that of the natural murine hormone corticosterone‐14C by whole‐body autoradiography in pregnant A/J mice at 12.5 days of gestation. The patterns of distribution were similar for the three compounds. At 3 h after injection the highest concentrations of radioactivity were in maternal liver, bile, intestinal contents, kidney, and urine and uterine luminal fluid. Radioactivity in embryos was less than that in most maternal tissues. Embryonic brain had a slightly higher content and the embryonic palatal buds no higher amount of radioactivity than other embryonic tissues. The intense accumulation in the uterine lumen after all of the compounds suggests a secretory mechanism by the yolk sac that is not specific for a particular steroid.
The teratogenic activity of α thalidomide analogue, EM12, in rabbits, rats, and monkeys
Authors: Schumacher Herbert J. , Terapane John , Jordan Robert L. , Wilson James G.
Published: June 2005

ABSTRACT The teratogenic activity of a stable analogue of thalidomide, 2(2,6‐dioxopiperiden‐2‐yl)‐phthalimidine (EM12), has been compared in monkeys, rabbits, and rats. After oral administration of 25‐250 mg/kg, EM12 was teratogenic in monkeys and rabbits but only slightly so in rats. After iv injection of the compound dissolved in dimethyl sulfoxide and water, teratogenic effects were observed both in offspring of rabbits and rats receiving doses of 10 mg/kg. The malformations observed in monkeys and rabbits were identical with those observed after thalidomide treatment, but those in rats were not the typical thalidomide‐type deformities.
Teratogenic drug screening. Present procedures and requirements
Authors: Tuchmann‐Duplessis H.
Published: June 2005

The basic principles of teratogenic drug testing are similar to those underlying the detection of toxic actions in adults. The greatest drawback in predicting from experimental data the effects of drugs on man lies in the different reactions among species. Consequently the selection of animal species for teratogenic drug testing is extensively discussed. Rodents should not be abandoned for drug testing as long it is not established that embryos of other animal species react more like human embryos. Drug testing also reveals that a large variety of mechanisms can be implicated in the production of developmental defects.
Correlation of chick embryo teratogenicity with the nicotinic activity of a series of tetrahydropyrimidines
Authors: Upshall D. G.
Published: June 2005

Nicotine, anabasine, nornicotine, β‐nicotyrine, and 34 substituted 1,4,5,6‐tetrahydropyrimidines, 2‐imidazolines, and 4,5,6,7‐tetrahydro‐1, H‐l, 3‐diazepines were injected into the yolk sac of chick eggs on day 4 of incubation at a dose of 1 or 2.5 mg/egg. The embryopathic results were compared with toxicological and pharmacological data and chemical structure. Abnormalities were similar to those induced by nicotine and anabasine but only compounds with nicotinic activity, as measured on the chick spinalis muscle, were teratogenic. All but one of the teratogenic compounds were 2‐pyridylsubstituted, and in this series teratogenic and nicotinic potency decreased in the order 3′‐>4′‐>2′‐pyridyl. There was a highly significant negative correlation between spine length and nicotinic potency of the compounds.
Effects of hyperoxia on chick embryos injected with trypan blue
Authors: Hoffman David J. , Ramm Gordon M.
Published: June 2005

Ten‐day chick embryos (1) received yolk‐sac injections of 0.1 ml of 1.5% trypan blue in sterile saline, (2) were placed into a hyperoxic environ‐ment of 45% oxygen, or (3) were exposed to trypan blue plus hyperoxia, and examined 5 h later. Hyperoxia virtually eliminated trypan blue‐induced mortality and caused considerable reduction in the appearance of hemorrhages. Blood pH and plasma glucose and potassium concentrations remained relatively stable, compared to embryos not subjected to hyperoxia. Embryonic wet weight, how‐ever, increased. It is suggested that hyperoxia functioned protectively by either (1) acting against electron transport inhibition or (2) permitting the normal passage of oxygen to lysosomes.
Congenital malformations of the central nervous system in rats produced by maternal zinc deficiency
Authors: Warkany Josef , Petering Harold G.
Published: June 2005

Teratogenic effects of maternal zinc deficiency in rats have been observed, confirming previous reports. The deficient diet differed in several re‐spects from that used by Hurley and coworkers but the results were essentially the same. Special attention was given to malformations of the central nervous system and to tissue anomalies not recognizable by gross inspection of the fetuses.
The effects on mouse development of interactions of 5‐fluorouracil with Strong's luxoid gene and its plus and minus modifiers
Authors: Forsthoefel Paulinus F.
Published: June 2005

Pregnant females of five lines of mice selected for plus‐ and minus‐modifying genes of the limb‐skeleton effects of Strong's luxoid gene (lst) were each injected ip on days 8–11 of gestation with a single dose of 0.25, 0.50, or 0.75 mg of 5‐fluorouracil (5‐FU). The incidence and degree of expression of effects (cleft palate, neural hernia, eye defects, radial and tibial hemimelia, polydactyly, ectrodactyly, tail kinks, etc) varied according to the day of injection, dose of 5‐FU, genotype of the embryo ( + / +, + lst, lst/lst), and residual genotype (plus‐ or minus‐modifying genes of lst). 5‐FU increased the expression of the effects of lst on the skeleton. This action of 5‐FU was inhibited by minus and promoted by plus‐modifying genes of lst. Thus, 5‐FU and 1st may affect skeleton development in similar ways.