bluuebunny/crossref_metadata_2025 huggingface dataset:
Teratogenic effects of maternal biotin deficiency on mouse embryos examined at midgestation
Authors: Watanabe Toshiaki , Endo Akira
Published: June 2005

Pregnant mice were fed a basal diet that not only did not contain biotin, but also contained the spray‐dried egg white including avidin that caused the biotin deficiency. The effects of maternal biotin deficiency on craniofacial and limb development in embryos were examined at two stages of midgestation. On day 12.6 of gestation, male and female embryos weighed less and digit development was retarded in the biotin‐deficient group. On day 15.6 of gestation (dg), the embryos also weighed less and external malformations, such as micrognathia (94.8%), micromelia (41.4%), and exencephaly (11.4%), were observed. The inhibition of palatal and digit formation by biotin deficiency at midgestation is responsible for later formation of cleft palate and micromelia. On dg 12.6 the liver biotin level of biotin‐deficient dams was reduced to 20% of control values. Interestingly, the biotin content of the whole embryonic body was about ninefold greater than liver biotin levels in their dams.
An anatomic comparison of cebocephaly and ethmocephaly
Authors: Souza James P. , Siebert Joseph R. , Beckwith J. Bruce
Published: June 2005

Cebocephaly (hypotelorism, single‐nostril nose) and ethmocephaly (hypotelorism, interorbital proboscis) lie in the middle of the spectrum of craniofacial changes associated with holoprosencephaly. Because these defects and thorogh anatomic studies of them are rare, knowledge concerning morphologic as well as pathogenetic relationships is lacking. We report the autopsy findings and anatomic features of the dried skull of a 31 week fetus with cebocephaly and the craniofacial dissection of a 36 week fetus with ethmocephaly. Both manifested dysplastic changes of the ethmoid bone and anterior portion of the sphenoid bone, with concomitant hypotelorism and defects of the medial orbital walls. Through these latter defects, the eyes were joined in the ethmocephalic fetus (synophthalmia). Other changes of bone (single optic foramen, approximated maxillae, choanal atresia, thickened palate) and soft tissue (eccentric or fused extraocular muscles, single optic nerve) in both fetuses resembled those reported in other cases of cebocephaly and ethmocephaly, as well as cyclopia. In the 19th century, both cebocephaly and ethamocephaly were classified as two‐orbit variants of cyclopia, a view supported by the present study.
Route‐dependent pharmacokinetics, distribution, and placental permeability of organic and inorganic selenium in hamsters
Authors: Willhite Calvin C. , Ferm Vergil H. , Zeise Lauren
Published: June 2005

Inorganic selenium (Se) salts (selenite and selenate oxyanions) and the organic selenoamino acids (selenomethionine and seleniferous grains) are teratogenic and embryolethal in domestic and wild birds. Selenium bioaccumulation has been held responsible for reproductive failure among waterfowl at the Kesterson Reservoir (California), the Ouray and Stewart Lake Wildlife Refuges (Utah), and the Carson Sink (Nevada). Anecdotal field and controlled laboratory reports have implicated Se exposure in mammalian embryotoxicity (including human), but developmental toxicity studies in hamsters failed to demonstrate an adverse response, except at maternally toxic doses (Ferm et al., Reprod. Toxicol., in press). Uptake, distribution, and elimination of Se after a single bolus equimolar dose (60 μmol/kg) of selenate or selenomethionine by oral or intravenous administration were compared using day 8 pregnant hamsters. Intravenous selenate was eliminated ten times more rapidly from maternal plasma than oral selenate, but concentrated in liver, kidney, and placenta to the same degree. Intravenous (iv) L‐selenomethionine achieved lower maximum circulating total [Se], but it was eliminated more slowly than iv selenate. Larger areas under the plasma and peripheral tissue [Se]:time curve (AUC) after oral or parenteral selenomethionine than after equimolar selenate were consistent with previous studies in rodents and in humans. Embryonic [Se] plateaued at 3 nmol/g after selenate, but embryonic [Se] after selenomethionine continued to accumulate (80 nmol/g) as gestation progressed. The lack of a teratogenic response in hamsters at doses of either selenate or selenomethionine less than those associated with maternal intoxication cannot be attributed to lack of Se accumulation in early embryonic and placental tissue.
Renal agenesis and dysgenesis: Are they increasing?
Authors: Stroup Nancy E. , Edmonds Larry , O'Brien Thomas R.
Published: June 2005

Data from the Birth Defects Monitoring Program (BDMP) of the Centers for Disease Control (CDC) suggest that the birth prevalence of renal agenesis and dysgenesis combined is increasing. Medical records were reviewed for 1,404 of 1,669 (84%) infants in the BDMP with renal agenesis or dysgenesis noted on the newborn discharge summary to assess whether the observed trend reflects a true increase in one or both conditions or if it reflects changes in diagnostic, coding, or surveillance practices over time. For 1970–1982, the average rate per 100,000 live births and stillbirths was 3.5 for autopsy‐confirmed bilateral renal agenesis and 1.7 for autopsy‐confirmed bilateral renal dysgenesis. The birth prevalence of autopsy‐confirmed bilateral renal agenesis fluctuated within this time period, peaking in 1975, while the rate of autopsy‐confirmed bilateral renal dysgenesis increased steadily by 0.2 cases/100,000 births per year (P<0.001) with small peaks in 1976 and 1979. Unilateral renal agenesis or dysgenesis accounted for 17% of the confirmed cases, but most were detected by autopsy among infants who died shortly after birth rather than by diagnostic procedures such as ultrasound. Diagnostic information in the medical record suggested that the increase in the birth prevalence of renal agenesis and dysgenesis combined in the BDMF is due primary to the increasing prevalence of renal dysgenesis. Since medical records did not include sufficient information on risk factors, detailed analytic studies are needed to identify maternal risk factors that might account for the apparent increase in renal dysgenesis over time.
Exposure of the pregnant rat to warfarin and vitamin K1: An animal model of intraventricular hemorrhage in the fetus
Authors: Howe Andrew M. , Webster Williams S.
Published: June 2005

Pregnant Sprague‐Dawley rats were given daily oral doses of sodium warfarin (100 mg/kg) and concurrant intramuscular injections of vitamin K1 (10 mg/kg). This dosing regimen did not have any apparent deleterious effect on the dams and did not affect the fetuses when administered from day 1 to day 12 of pregnancy. However, similar treatment from day 9 to day 20 caused hemorrhage in the fetuses examined on day 21 of gestation. There were no hemorrhages in the control fetuses from dams receiving vitamin K1 only. The lowest effective dose of warfarin, in conjunction with daily doses of vitamin K1, was 3 mg/kg. This dose caused hemorrhage in 28% of fetuses; the incidence of affected fetuses was not further increased by doses of warfarin up to 100 mg/kg. Hemorrhages affected the fetal brain, face, eyes, and ear and occasionally the limbs. Brain hemorrhages were frequently intraventricular and caused various degrees of hydrocephaly. Bony defects were not a feature of prenatal exposure to warfarin.

These results show that prenatal exposure of the rat to warfarin and vitamin K duplicates the hemorrhagic abnormalities and pathology associated with prenatal exposure to warfarin in the human. It did not induce bony or facial defects probably because the vitamin K‐dependent components of bone development occur postnatally in the rat. This model should allow detailed determination of the role of vitamin K‐dependent proteins in development.
Immunological factors responsible for pathogenetic cell degeneration in pregnancy
Authors: van der Zee D. C. , de Heer E. , Mentink M. M. T. , Vermeij‐Keers C.
Published: June 2005

The placenta has an important role as an immunological barrier during pregnancy. When the placental barrier is disrupted, maternoembryonic transfusion takes place. Several clinical reports relate congenital malformations or abortion to intrauterine bleeding or transplacental transfusion. In an earlier experiment, pathogenetic cell degeneration was induced using an in vitro whole rat embryo culture. Transplacental transfusion was simulated by intracardiac injection of an allogeneic rat‐antirat serum directed against the blood group antigens. The present study examines the morphological and immunological effects on the development of rat embryos 9 to 10 days old (stages 8–10 somites) of the separate administration of primary allogeneic antisera, obtained 10–17 days after immunization, and secondary allogeneic antisera, obtained after booster immunization on day 45–52. Rat‐antirat alloantibodies were directed against the blood group antigens. Transplacental transfusion was simulated by the embryonic intracardiac microinjection of approximately 0.5 μl serum enriched with either primary or secondary obtained allogeneic antibodies. After 48 hours' incubation, the embryos were examined microscopically, and it appeared that the secondary antisera, which had hemolytic activity, was more potent (P<0.005) in the induction of pathogenetic cell degeneration. It is well known that IgG antibodies display hemolytic activity. This finding was confirmed by direct immunofluorescence performed on rat embryos 2, 4, and 6 hours after injection, where incubation with rabbit‐antirat anti‐IgG antibodies gave a strong reaction. The hypothesis discussed is whether or not pathogenetic cell degeneration subsequent to transplacental transfusion of maternal antibodies can be initiated by similar immunological events.
Maternal vitamin A supplementation in relation to selected birth defects
Authors: Werler Martha M. , Lammer Edward J. , Rosenberg Lynn , Mitchell Allen A.
Published: June 2005

High doses of vitamin A cause birth defects in animals. Concern over vitamin A teratogenicity in humans has been prompted by reports of teratogenic effects of the vitamin A analogue, isotretinoin. The pattern of defects observed among isotretinoin‐ and vitamin A‐exposed infants and animals suggests a possible mechanism involving cranial neural crest cell activity. Data from a case‐control study were used to assess maternal use of vitamin A supplements alone and vitamin A‐containing multivitamin supplements in relation to the occurrence of certain birth defects involving structures derived, at least in part, from cranial neural crest cells. Cases were 2,658 infants with such defects (primarily craniofacial and cardiac malformations). Controls were 2,609 infants with other malformations. Vitamin A supplementation was defined as daily use for at least 7 days of retinol alone or with vitamin D, or of fish oils. Information on vitamin A dose and nutrition was not available. The mothers of six controls used vitamin A supplements in each of the first three lunar months of pregnancy in comparison to the mothers of 15, 14, and 10 cases in lunar months 1, 2, and 3, respectively. Relative risk estimates and 95% confidence intervals were 2.5(1.0–6.2) for lunar month 1, 2.3(0.9–5.8) for lunar month 2, and 1.6(0.6–4.5) for lunar month 3. These findings should be considered tentative because no dose information was available, small numbers of cases and controls were exposed to vitamin A supplements, and relative risk estimates were not statistically significant. Separate analyses of the more common intake of multivitamins which contain vitamin A, including “prenatal” vitamins, found relative risks of these defects for daily use approximated unity and 95% confidence intervals excluded even small increases in risk.
Eliciting principles of hazard identification from experts
Authors: Jelovsek Frederick R. , Mattison Donald R. , Young John F.
Published: June 2005

National experts in the field of developmental toxicology were interviewed in order to elicit the principles, or rules‐of‐thumb, they use in determining if a compound or agent is likely to be a developmental hazard during pregnancy. Several levels of individual and cumulative consensus activity were carried out that resulted in consensus in 71 rules and partial consensus in an additional 24 rules of 145 rules initially elicited. Rules could be divided generically into those affecting the expert's confidence in a piece of scientific evidence and those determining the weight of importance of that evidence in deciding about hazard identification. Topically, the rules also divided into those about the general nature or characteristics of a compound, animal studies testing for an effect of the compound, and human reports about the presence or absence of developmental effects associated with the compound. Several conclusions about the methodology include the following: (1) expert systems must be based on the knowledge of more than one expert; (2) considerable human effort is expended in evaluating the certainty of scientific evidence before combining the evidence for problem solving; (3) how experts use evidence of different degrees of uncertainty in their decisions is a major area that is yet to be determined and that may greatly affect subsequent efforts in artificial intelligence; and (4) knowledge elicitation by interview has limitations but is a workable methodology for medical decision making.
Biochemical basis for D,L,‐beta‐hydroxybutyrate‐induced teratogenesis
Authors: Shum L. , Sadler T. W.
Published: June 2005

Previous investigations have demonstrated that a potential mechanism for D,L,‐beta‐hydroxybutyrate (BOHB)‐induced teratogenesis in neurulating mouse embryos (5–6 somite stage) after 24 hours of exposure in vitro is mediated by an inhibition of the pentose phosphate pathway (PPP) (Hunter, et al. '87). Employing conceptuses of an earlier stage (2–3 somite stage), the biochemistry of BOHB‐induced abnormalities was examined further by exposing embryos to 32 mM BOHB for 24 hour and comparing results with controls with respect to the rate of metabolism via the PPP, de novo pyrimidine biosynthesis (PB), and BOHB utilization. Moreover, the capability of these BOHB‐exposed embryos to recover from such an insult was also assessed by transferring them to fresh control medium and allowing them to grow for an additional 36 hours. Both controls and BOHB‐exposed embryos showed a progressive increase in rate of BOHB utilization between days 9 and 11.5 of gestation in vitro. Exposure to the ketone body produced a 100% rate of neural tube defects and a 25.2% decrease in total embryonic protein content. In contrast to results obtained at the 5–6 somite stage, no inhibition of the PPP in whole conceptuses, embryos, or visceral yolk sacs was observed in the group exposed to BOHB at the 2–3 somite stage. Furthermore, a 7.5 mM D‐ribose supplement, an intermediate in the PPP, was unable to rescue the younger embryos from BOHB‐induced abnormalities and growth retardation. On the other hand, BOHB produced a 34.3% decrease in pyrimidine biosynthesis in the 2–3 somite embryos, but not in the visceral yolk sac. In addition, embryos recovered biochemically after being transferred to control medium, demonstrating a 25.5% overshoot in pyrimidine biosynthesis. Therefore, the mechanism of BOHB‐induced teratogenesis appears to differ depending on the stage of embryonic development at the time of initial exposure.
Phenylalanine and its metabolites induce embryopathies in mouse embryos in culture
Authors: Denno Kelly M. , Sadler T. W.
Published: June 2005

The aim of this study was to determine the teratogenicity of phenylalanine (Phe) and Phe metabolites in neurulating mouse embryos. Therefore, the system of whole embryo culture was employed and D9 (neurulating) mouse embryos were exposed to Phe, phenylethylamine (PEA), phe‐nylpyruvic acid (PPA), phenylacetic acid (PAA), 2‐OH phenylacetic acid (2‐OH PAA), and phenyllactic acid (PLA) at concentrations ranging from 0.01 mM to 10 mM for 24 hours. After 24 hours, embryos were examined for morphological abnormalities and protein content by the Lowry method. Phe at 1 and 6 mM concentrations was not teratogenic; however, 10 mM inhibited cranial neural tube closure in 82% of the embryos. PEA was the most toxic factor and concentrations of 1 and 10 mM were embryo‐lethal, whereas neural tube closure defects (NTDs) were observed in 67% of the embryos at 0.1 mM. 2‐OH PAA was the second most toxic metabolite with concentrations of 1 and 10 mM producing NTDs in 10 and 100% of the embryos, respectively. PLA and PAA produced no NTDs at concentrations of 1 mM, 60% at 5 mM, and 100% at 10 mM. Finally, PPA produced approximately 50% NTDs at both 1 mM and 10 mM concentrations. PLA, PAA, 2‐OH PAA, and PPA produced a significant reduction in embryonic protein, and PEA and 2‐OH PAA reduced yolk sac protein values. PEA, 2‐OH PAA, PPA, PAA, and PLA also produced craniofacial abnormalities, i.e., incomplete expansion of the forebrain, collapse of the optic vesicle, and hypoplasia of the mandible and/or the maxilla. In summary, the results showed that the relative teratogenicity of Phe and its metabolites differs and suggested that a metabolite of Phe and/or a combination of Phe and one or more of its metabolites play a role in the phenylketonuric embryopathy.
Genetic control of the survival of murine trisomy 16 fetuses
Authors: Epstein Douglas J. , Vekemans Michel
Published: June 2005

A mouse model that allows for the experimental induction of an aneuploid state has been employed to investigate the factors that factors that control the survival of trisomy 16 fetuses. The prevalence of trisomy 16 fetuses on day 15 of gestation was shown to vary significantly with the genetic background of the female parent. The ability to spontaneously abort a trisomy 16 conceptus was shown to be higher in the mouse strain with a low prevalence of trisomy 16, compared to those mouse strains with a high prevalence of trisomy 16. Furthermore, the maternal ability that selects against, or promotes the survival of a trisomic conceptus was shown to be specific for the trisomy in question.
Ultrastructure of murine trisomy 1 optic cup
Authors: Smith Barbara S. , Walker Nola J.
Published: June 2005

The optic cups of two gestational day 11 trisomy (ts) 1 mouse embryos and a normal littermate control were examined using transmission electron microscopy (TEM). One trisomic embryo had a small lens with a lens stalk; the other was aphakic. The resolution available with TEM allowed detailed evaluation of cell organelles, spatial relationships, and the intra‐ and extracellular structural environment of the optic cup in normal and abnormal mouse embryos. Differences between the normal littermate and the trisomic optic cups, as well as between the two ts 1 structures, included the following: (1) melanin granules in the retinal layer and intraretinal space as well as in the pigment layer, (2) neither pseudostratified nor cuboidal neuroepithelium in trisomic optic cups, (3) increasing cell lysis with severity of eye defect, (4) fusion between retinal and pigment layer cells and cells from the pigment layer and head mesoderm. This investigation not only confirmed some of the abnormal morphology found in light microscopic studies of ts 1 at this gestational age but also identified other anomalies in the ts 1 eye that may play a part in the dysgenesis of this organ. The roles of larger than normal intercellular lacunae, disorganized microtubules, and the connections between different cell types in the ts 1 optic cup require further investigation.
A critical review of the developmental toxicity and teratogenicity of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin: Recent advances toward understanding the mechanism
Authors: Couture Laurie A. , Abbott Barbara D. , Birnbaum Linda S.
Published: June 2005

A specific teratogenic response is elicited in the mouse as a result of exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD; dioxin). The characteristic spectrum of structural malformations induced in mice following exposure to TCDD and structurally related congeners is highly reproducible and includes both hydronephrosis and cleft palate. In addition, prenatal exposure to TCDD has been shown to induce thymic hypoplasia. These three abnormalities occur at doses well below those producing maternal or embryo/fetal toxicity and are thus among the most sensitive indicators of dioxin toxicity. In all other laboratory species tested, TCDD causes maternal and embryo/fetal toxicity but does not induce a significant increase in the incidence of structural abnormalities even at toxic dose levels. Developmental toxicity occurs in a similar dose range across species; however, mice are particularly susceptible to development of TCDD‐induced terata. Recent experiments using an organ culture were an attempt to address the issue of species and organ differences in sensitivity to TCDD. Human palatal shelves examined in this in vitro system were found to approximate the rat in terms of sensitivity for induction of cleft palate. Investigators have suggested that altered regulation of growth factors and their receptors may involve inappropriate proliferation and differentiation of target cells, ultimately producing TCDD‐induced terata. Why the teratogenic effects of TCDD are so highly species and tissue specific, and which animal species most accurately predicts the response of the human embryo/fetus, at the levels of exposure experienced by humans, still remains to be clarified.
Whole embryo culture, teratogenesis, and the estimation of teratologic risk
Authors: New D. A. T.
Published: June 2005

Mammalian whole‐embryo culture systems are now widely used and have proved useful in many studies of normal and abnormal development. The main advantages of these systems are that they allow precise control of experimental conditions and can often provide information unobtainable from in vivo studies; the main disadvantages are the rather short period of embryonic development that can be supported in culture and the present restriction of the techniques to very few species. The possibility of using whole‐embryo culture systems for screening for new teratogenic agents remains controversial, but there are indications that the systems may have more potential in this area than has sometimes been supposed.
Brain hemorrhages in cocaine‐exposed human fetuses
Authors: Kapur Raj P. , Shaw Cheng M. , Shepard Thomas H.
Published: June 2005

Autopsies of 4 fetuses exposed to maternal cocaine are reported. Brain examination revealed hemorrhages in 3 of the fetuses involving the germinal matrix. The hemorrhages resembled subependymal germinal matrix hemorrhages seen as postnatal complications in premature infants with idiopathic respiratory distress syndrome. One of the placentas had sonographic evidence of abruption which could not be confirmed pathologically. The findings are discussed in light of reports of neurobehavioral deficits and other congenital anomalies in children and animals exposed to cocaine in utero. Speculations about the pathophysiologic events leading to these findings are made.
Ameltolide. II: Placental transfer of radiocarbon following the oral administration of a novel anticonvulsant in rats
Authors: Pohland Raymond C. , Vavrek M. Thaddeus
Published: June 2005

The placental transfer of orally administered ameltolide was evaluated to confirm embryonic exposure in the rat developmental toxicity study (Higdon et al., '91). Dissection techniques were used to determine the amount of total radiocarbon that traversed the placenta and distributed within the embryo in pregnant CD rats 0.75, 2, 5, 12, and 24 h after a single oral gavage dose of 50 mg/kg [14C]ameltolide on gestation day 12. Quantification of radiocarbon within placental and embryonic tissues and amniotic fluid was determined and compared with maternal plasma, liver, kidney, uterus, and ovary. Highest concentrations of radiocarbon occurred at 5 h postdose in all tissues sampled (maternal and embryonic) and then declined steadily over the 24‐h time course of the study. Maternal liver contained the highest concentrations of radiocarbon at all time points and peaked at 5.86% of dose at 5 h. Embryonic tissues accounted for less than 0.2% of the administered dose at all time points. Tissue‐to‐maternal plasma ratios indicated that maternal liver and kidney concentrations were higher than maternal plasma concentrations at all time points. Uterine and ovarian concentrations were approximately equal to maternal plasma concentrations at 5, 12, and 24 h postdose. Although placental, embryonic, and amniotic fluid tissue‐to‐maternal plasma ratios were ⩽ 1.0, ratios increased slightly throughout the time course of this study. Results from this study confirm embryonic exposure to radiocarbon associated with [14C]ameltolide and/or its metabolites in the rat developmental toxicity study, which has demonstrated the lack of observable teratogenic effects.
Patterns and trends of multiple congenital anomalies in birth defects surveillance systems
Authors: Khoury Muin J. , Waters Grady D. , Erickson J. David
Published: June 2005

Infants with multiple congenital anomalies (MCA) can provide important clues in the detection of teratogenic agents. Definition, classification, and ascertainment of MCA vary, however. We present comparative epidemiologic data on MCA from two U.S. surveillance systems: the Metropolitan Atlanta Congenital Defects Program, which ascertains major birth defects during the first year of life, and the Birth Defects Monitoring Program, a nationwide system that relies on newborn hospital‐discharge diagnoses. This system has two components: the Commission on Public Hospitals Activities (CPHA) and the McDonnell Douglas Health Information System (MDHIS). Our analyses were based on over 600,000 births occurring in Atlanta, and over 5 million births occurring nationwide. Infants were classified as having MCA if they had two or more major defects from different categories (central nervous system, eye, orofacial, gastrointestinal, cardiovascular, genitourinary, and musculoskeletal). Additional analyses were also done on infants with three or more defects. Compared with the nationwide system, Atlanta showed 1) a much higher rate of MCA (16.2 per 10,000 births vs. 4.9 and 3.8 per 10,000 births in CPHA and MDHIS, respectively) and 2) a higher rate of MCA with chromosomal syndromes (2.0 per 10,000 births vs. 0.6 and 0.3 per 10,000 births in CPHA and MDHIS, respectively). Moreover, in Atlanta, the proportion of MCA with recorded chromosomal syndromes increased substantially during 20 years. These data point to differences in the ascertainment of MCAs in birth defects surveillance systems. More effort is needed to improve the ascertainment and comparability of MCA in surveillance systems, an important step toward better detection of human teratogens.
In vitro effects of glucose and growth factors on limb bud and mandibular arch chondrocytes maintained at various serum concentrations
Authors: Styrud Johan , Eriksson Ulf J.
Published: June 2005

In human and experimental diabetic pregnancy there is an increased risk of congenital malformation in the offspring. Some malformations involve growth retardation and altered chondrocyte differentiation, suggesting that a diabetic milieu may modify embryonic cell replication and the development of (pre)chondrocytes. The aim of the present work was to study the effects of a diabetes‐like environment in vitro on the growth and differentiation of rat chondrocytes in the presence of specific growth factors and different concentrations of serum. This was performed with a modified micromass culture system of embryonic (pre)chondrocytes from the limb bud and mandibular arch areas using medium supplemented with different glucose concentrations and with serum from diabetic rats. An elevated ambient glucose concentration inhibited the growth of mature chondrocytes in vitro, and this effect was diminished in a serum‐rich culture milieu. The (pre)chondrocytes exhibited a marked dependence on the serum level in the culture medium for optimal in vitro development. Diabetic rat serum had the lowest stimulatory capacity of the three different types tested (at similar glucose concentrations), suggesting a deficiency of growth‐stimulating factor(s) rather than the presence of inhibiting factor(s) in this type of serum. One of the deficient factor(s) in diabetic rat serum may be similar to IGF‐II, but a combined deficiency of several growth‐stimulating agents is likely to be present. Chondrocytes originating from the mandibular arch in general appeared more sensitive to MSA and IGF‐II than those from the limb buds. The present observations support the notion that while diabetes‐induced hyperglycemia in the conceptus contributes to severe growth retardation of the mandibular arch, additional factors also play a role.
Induction of tissue transglutaminase and apoptosis by retinoic acid in the limb bud
Authors: Jiang Heng , Kochhar D. M.
Published: June 2005

Mesenchymal cells in the limb buds of midgestation mouse embryos suffer prominent cell death upon exposure to retinoic acid (RA), an event likely associated with the micromelic and phocomelic anomalies of the resultant fetuses. It has been suggested, but not yet shown, that cells die by an active process termed apoptosis rather than by necrotic cytolysis. In certain cell types, investigators have previously observed a specific and early effect of RA on transcriptional activation of the gene for tissue transglutaminase (tTG), an enzyme suspected to play a role in apoptosis. We report here a distinct but transient increase in tTG activity which accompanied the initiation of cell death in the mesenchymal cells located in the central core of RA‐treated limb buds. We also ascertained microscopically that the cytological appearance of the affected cells was consistent with a characterization of the process of cell death as apoptosis. © 1992 Wiley‐Liss, Inc.
Exencephaly and hydrocephaly in mice with targeted modification of the Apolipoprotein B (Apob) gene
Authors: Homanics G. E. , Maeda N. , Traber M. G. , Kayden H. J. , Dehart D. B. , Sulik K. K.
Published: June 2005

Apolipoprotein B (apoB) is a key structural component of several lipoproteins. These lipoproteins transport cholesterol, lipids, and vitamin E in the circulation. Humans that produce truncated forms of apoB have low plasma concentrations of apoB, β‐lipoproteins, cholesterol, and often vitamin E. This condition has been modeled in mice by targeted modification of theapoBgene. Homozygous transgenic mice display all of the hallmarks of the human disorder. Unexpectedly, approximately 30% of the perinatal homozygotes are exencephalic and of those that have closed neural tubes, approximately 30% are hydrocephalic. The latter condition has also been noted in a relatively small proportion of the heterozygous mice. Vital staining of gestational day 9 (GD9) homozygous offspring has illustrated a striking pattern of excessive cell death involving the alar plate of the hindbrain. Histological and scanning electron microscopic analyses have confirmed this finding. We speculate that varying degrees of affect, as noted among GD 9 and 10 embryos, lead to the spectrum of malformations, including hydrocephaly, present in term fetuses. Analysis of vitamin E deficiency as a possible causative factor has illustrated that homozygous fetuses, indeed, show this deficiency. Amelioration of the defects through α‐tocopherol supplementation of the maternal diet has been explored. Further analyses of this transgenic mutant promise to provide significant information relative to the role of deficiency of vitamin E and other apoB dependent compounds in dysmorphogenesis. © 1995 Wiley‐Liss, Inc.
Removal, early hand rearing, and successful reintroduction of an orangutan (Pongo pygmaeus pygmaeus/x abelii) to her mother
Authors: Keiter Mary D. , Reichard Timothy , Simmons Jack
Published: June 2005

A newborn orangutan was removed from her mother 55 h after birth because no nursing had been observed. She was hand reared in a nursery for 3 d and then successfully reintroduced to her mother. Several factors that may have contributed to the successful reintroduction are discussed.
Local adaptation, coadaptation, and population boundaries
Authors: Templeton Allan R. , Hemmer Helmut , Mace Georgina , Seal Ulysses S. , Shields William M. , Woodruff David S.
Published: June 2005

Coadaptation can occur either because of local adaptation in a geographically widespread population and/or because of intrinsic adaptation to the state of other genes or chomosomes. In either event, hybridization between animals with differently coadapted gene or chromosomal complexes can result in a decrease in fertility, viability, etc. in the initial hybrids and especially in later generations. This is known as an outbreeding depression. Moreover, releasing animals not adapted to the local environment can seriously hamper the effectiveness of a reintroduction program, and hybridization can also destroy the local adaptation. Coadapted gene complexes are best detected through studies on natural populations because the adaptive nature of the complex is often only apparent in the natural environment. In the absence of information on natural populations (but ideally as a supplement), the presence of coadapted gene complexes and population boundaries can be detected through mating behavior, a pedigree analysis that can detect outbreeding depressions and distinguish them from inbreeding depressions, or genetic and karyotypic surveys. Once an outbreeding depression has been detected, it can be used to redefine the boundaries of the populations to be managed. Basically, the outbreeding depression is avoided by preventing hybridization between animals with the different coadapted complexes. In some cases, formal subspecific designations have been used to define the population boundaries. Unfortunately, many subspecific designations were made before population‐thinking influenced taxonomy. It is important to emphasize the need to undertake modern biological studies and to collect additional information useful for systematics. If modern biological studies indicate that the subspecies have little or no biological significance, it is best to treat the animals as a single population and disregard the subspecific designations.
Biology, husbandry, and veterinary care of captive Chinese pangolins (Manis pentadactyla)
Authors: Heath Martha E. , Vanderlip Sharon L.
Published: June 2005

We report observations on the biology, diet, husbandry, and veterinary care of four adult Chinese pangolins (Manis pentadactyla) maintained at the University of California, San Diego, for 1.5 years; and the births of two baby pangolins. Experience indicates that the minimum requirements for Chinese pangolins is an enclosure 10–12 m2, 26°C ambient temperature, a nest box with sand floor, and litter boxes placed in one or two corners of the enclosure for defecation and urination. A diet of two cans of cat food (Science Diet or ZuPreem), 6 tablespoons Esbilac, 2 tablespoons psyllium seed powder, and two raw egg yolks provide adequate nutrition for four pangolins for 1–2 days. Veterinary care should include a complete physical examination of integument and organ systems, determination of blood values, fecal analysis, and treatment with the anthelmintic thiabendazole for elimination of internal parasites. Parasites observed in the four pangolins included Strongyloides, hookworms, filarial nematodes (species unidentified), and nematodes of the genus Cylicospirura. The baby pangolins were born in November (male) and February (female), weighed 93 g and 92 g at birth, and lived 1 and 5 days, respectively. All adult pangolins observed strictly nocturnal behavior patterns.
Reproductive and hormonal changes during the estrous cycle and pregnancy in Asian elephants (Elephas maximus)
Authors: Mainka S. A. , Lothrop C. D.
Published: June 2005

Serum progesterone and urinary total estrogen concentrations were determined weekly to bi‐weekly in 2 female Asian elephants for 96 weeks. The mean estrous interval was approximately 16 weeks in the nonpregnant animal. A total of 5 cycles were observed in the 96 week study period. The serum progesterone concentration ranged from 150 pg/ml to greater than 350 pg/ml during the luteal phase of the estrous cycle. The serum progesterone was elevated for 8–12 week weeks of the 16 week estrous cycle. The urinary total estrogen concentration ranged from less than 10 to greater than 300 pg/μg creatinine. The second animal was pregnant at the beginning of the study period. The serum progesterone concentration was elevated (> 100 pg/ml) in the pregnant animal until parturition. The urinary total estrogens increased from approximately 50 pg/μg creatinine to greater than 400 pg/μg creatinine during the first year of pregnancy and remained elevated until parturition. Estrous cycling had not resumed by 3 months post partum.
EFFECT OF TREATMENT OF STARCHY WATER ON QUALITY OF PASTA DURING CONTINUOUS COOKING
Authors: KORZENIOWSKA JOLANTA , KORZENIOWSKI DARIUSZ , DEFRANCISCI LEONARD , HOSKINS DONALD F.
Published: June 2005

Industrial continuous pasta cookers are filled with thousands of liters of cooking water. During the cooking process, the starch leaches from the cooked pasta. As the starch concentration increases, the cooked pasta becomes less firm and stickier. Starchy water must be constantly released to reduce the starch concentration. This requires addition of fresh makeup water and energy used to reheat it. The effects of presteaming freshly extruded pasta and posttreatment at high temperature and pressure of the starchy cooking water on the pasta cooking quality was tested. The posttreatment consisted of elevating the water temperature to 120C and the pressure to 1.0297 × 10

5
 Pa. The viscosity of cooking water decreased from 1.039 × 10−5 m2/s to 7.280 × 10−6 m2/s as a result of the temperature degradation of amylose. Applying high pressure/temperature treatment to the cooking water, as well as straining it through a tight mesh screen, makes it possible to use the same cooking water for a longer period of time. This, in turn, reduces the wastewater produced in continuous cookers, without decreasing the quality of cooked pasta. This results in the conservation of the water and energy.
UPTAKE OF SUCROSE SOLUTION BY EXTRUDED CORN BALLS AND EFFECT ON THE TEXTURAL CHARACTERISTICS
Authors: AGARWAL KALPESH , BHATTACHARYA SUVENDU
Published: June 2005

Extruded corn balls were subjected to dip coating with sucrose solutions (0–70%) at different temperatures (20–50C) to determine several coating characteristics such as total uptake, uptake of solid and dimensionless uptake (sucrose solution uptake/water uptake). Textures of the wet sample, as well as the dried sample, were determined under compressive loading, to obtain the maximum force offered and the deformability modulus. A progressive increase in solid uptake occurs with an increase in concentration and/or temperature while the effect of the latter is low. The deformability modulus of the samples drastically increases because of the absorption of sucrose and because of drying. The desirable high dimensionless uptake can be obtained with a high concentration of sucrose at a low temperature. The uptake of solid generally shows a significant relationship (P ≤ 0.05) with other coating and textural parameters for the wet sample, but not with the dry product.
Human T‐lymphotropic virus type I: A retrovirus causing chronic myeloneuropathies in tropical and temperate climates
Authors: Rodgers‐Johnson P. E. B. , Garruto R. M. , Yanagihara R. , Gajdusek D. C.
Published: June 2005

Human T‐cell lymphotropic virus type I (HTLV‐I), the first human retrovirus to be isolated, is the cause of endemic tropical spastic paraparesis (TSP). Originally, this chronic neurological disorder was described as a disease seen among blacks of low socioeconomic status living in tropical countries, and thus for many decades TSP remained a little known curiosity outside the endemic regions. The link between HTLV‐I infection and TSP was made fortuitously, when antibodies to HTLV‐I were found in serum and cerebrospinal fluid of TSP patients in Jamaica, Colombia, and Martinique. Soon thereafter a similar disorder, designated HTLV‐I associated myelopathy (HAM), was reported from southern Japan. This broadened the geographic and ethnic boundaries of this chronic myelopathy and the disease has now been reported in multiple ethnic groups from more than 40 countries, in both tropical and temperate regions. The name TSP/HAM is now used to include all patients (regardless of race or country of origin) who have HTLV‐I‐positive endemic TSP or HAM.
Estimation of body fat from skinfold thicknesses in middle‐aged and older men and women: A multiple component approach
Authors: Williams Daniel P. , Going Scott B. , Lohman Timothy G. , Hewitt Michael J. , Haber Ann E.
Published: June 2005

The relationship of skinfold thicknesses and body density to body fatness was assessed, and skinfold prediction equations were developed for the estimation of body fatness determined from measures of body density, total body water, and bone mineral in a sample of 91 males and 116 females aged 34–84 years. For a given skinfold thickness, adjustment for individual deviations in the water and bone mineral fractions of the fat‐free body assumed constant by traditional body composition models resulted in absolute reductions in overstimates of body fatness from 4.5 to 1.9% in females and from 2.8 to 1.7% in males for every 15 year increase in age. Percentage fat from density, water, and bone was estimated from skinfold thicknesses with SEEs of 2.9% in males and 3.8% in females. When compared to percentage fat from our multicomponent‐derived criterion, percentage fat from body density and a two‐component model resulted in individual errors ranging from underestimates of 5.6% fat to overestimates of 14.0% fat. The multicomponent prediction equations presented herein should produce more valid estimates of body composition in middle‐aged and older men and women than equations based on two‐component models. © 1992 Wiley‐Liss, Inc.
An inverse relationship between the cost of static posture and the cost of cycling?
Authors: Murray Martyn G. , Narasimh́a Maithreyi , Murgatroyd P. R. , Prentice A. M.
Published: June 2005

To test the hypothesis that both species and individuals with low metabolic costs in locomotion have high energetic costs in maintaining static posture (and vice versa), energy expenditure was measured in men engaged in different activities. Subjects were asked to exercise on a cycle ergometer at different speeds at constant work rates and to maintain a set isometric tension when sitting using different angles of the knee. Individuals with a low energy cost of sitting (minus BMR) had a high energy cost of cycling at 50 rev/min at an external work rate of 25 W (minus energy cost in a sitting position on the cycle). However, there was no significant correlation between the energy cost during a dynamic cycling task and the energy cost during maintenance of a standardized static posture. These findings suggest that mechanisms involved in the conservation of energy expended during cycling may be different from those involved during maintenance of standardized static postures. Curves relating energy expenditure to speed (for a constant work rate) were remarkably flat in the range 20–70 rev/min, indicating a difference in the way energy is conserved in cycling and within gaits. © 1992 Wiley‐Liss, Inc.
Maximal oxygen consumption of Colombian women of differing socioeconomic status
Authors: Spurr G. B. , Reina J. C. , Narvaez J. V. , Dufour D. L.
Published: June 2005

Maximal oxygen consumption (\documentclass{article}\pagestyle{empty}\begin{document}$ {\rm \dot V}_{{\rm O}_2 } $\end{document} max) was measured directly by a treadmill protocol in 23 upper (UEC) and 23 lower (LEC) socioeconomic women, 19–37 years of age, living in Cali, Colombia. There were no statistically significant differences between the two groups in \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm \dot V}_{{\rm O}_2 } $\end{document} max (liters/min). LEC women were shorter and weighed less than UEC subjects, although there was no evidence of undernutrition in the former at the time of testing. The aerobic power of the LEC group was 33.7 ± 4.1 ml/kg · min (mean ± SD) compared to 32.0 ± 2.8 ml/kg · min in UEC women (P = 0.09). From data on 36 of the women, a multiple stepwise regression was used to derive an empirical equation for estimating \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm \dot V}_{{\rm O}_2 } $\end{document} max from submaximal \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm \dot V}_{{\rm O}_2 } $\end{document} and heart rate plus anthropometric variables. The derived equation was verified by application to an independent group of 10 subjects. © 1992 Wiley‐Liss, Inc.
Self‐assessment and physician assessment of sexual maturation in Brazilian boys and girls: Concordance and reproducibility
Authors: Matsudo Sandra Marcela Maheca , Matsudo Victor Keihan Rodrigues
Published: June 2005

This study considered the concordance of self‐assessment and physician assessment of sexual maturity status; breasts, and pubic hair in girls, and genitals and pubic hair in boys. The subjects were Brazilian children, youth and young adults, 174 females and 178 males, 6–26 years of age. Each subject evaluated his/her level of sexual maturation and then was examined by a physician. The sexual maturity ratings of the subjects and physicians were compared. Overall, the results showed moderate to high concordance (60.9–71.3%) for both assessments of secondary sex characteristics; better concordance was found for pubic hair (69.7–71.3%) than for the breasts or genitals (60%). Age did not appear to influence the accuracy of self‐evaluation; rather, accuracy was more dependent on stage of maturation of the subject. Correlations between self‐ and physician assessments, and replicate self‐ and physician assessments were relatively high. © 1994 Wiley‐Liss, Inc.
Relationship between subcutaneous fat distribution and serum lipids and blood pressures in italian men
Authors: Folin Marcella , Contiero Eva
Published: June 2005

The associations of an index of centripetal adipose tissue distribution, based on skinfold thicknesses, with levels of triglycerides, total cholesterol, HDL‐cholesterol, LDL‐cholesterol, blood pressures, and the body mass index (BMI) were analyzed in 197 male blood donors, 20–59 years of age, who were asymptomatic of diabetes and cardiovascular disease. Serum lipid variables were correlated with the BMI independently of the index of centripetal adipose tissue distribution. After adjustment for age, only triglyceride levels were positively correlated with the index of centripetal subcutaneous fat distribution irrespective of the BMI. Thus in the population studied, subcutaneous fat distribution appears to be a weak correlate of cardiovascular disease risk factors, except for triglycerides. © 1994 Wiley‐Liss, Inc.