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PubMed1996

Developmental effects on the adolescent of a temporary ileostomy.

Adolescence is an exciting time of transition, as the child breaks away from a dependent role and establishes an independent adult identity. Adolescents vacillate between dependence and independence as they meet the daily challenges of growing up. The adolescent with a chronic illness, however, may find dependence thrust upon him or her by physical condition and health care needs. This article describes how a temporary ileostomy can interfere with the adolescent's ability to master developmental tasks. Initial findings from semistructured interviews of four teenage boys provide evidence of the effects of a temporary ileostomy on an adolescent's psychosocial development.

Activities of Daily Living↗
PubMed1992

Developmental effects of basic fibroblast growth factor and platelet-derived growth factor on glial cells in a three-dimensional cell culture system.

In order to study peptide growth factor action in a three-dimensional cellular environment, aggregating cell cultures prepared from 15-day fetal rat telencephalon were grown in a chemically defined medium and treated during an early developmental stage with either bovine fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF homodimers AA and BB). A single dose (5-50 ng/ml) of either growth factor given to the cultures on day 3 greatly enhanced the developmental increase of the two glia-specific enzyme activities, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glutamine synthetase (GS), whereas it had relatively little effect on total protein and DNA content. Distinct patterns of dose-dependency were found for CNP and GS stimulation. At low concentrations of bFGF (0.5-5 ng/ml) and at all PDGF concentrations applied, the oligodendroglial marker enzyme CNP was the most affected. A relatively small but significant mitogenic effect was observed after treatment with PDGF, particularly at higher concentrations or after repetitive stimulation. The two PDGF homodimers AA and BB were similar in their biological effects and potency. The present results show that under histotypic conditions both growth factors, bFGF and PDGF, promote the maturation rather than the proliferation of immature oligodendrocytes and astrocytes.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed2000

Use of aggregating brain cell cultures to study developmental effects of organophosphorus insecticides.

Aggregating brain cell cultures of fetal rat telencephalon can be grown in a chemically defined medium for extended periods of time. After a phase of intense mitotic activity, these three-dimensional cell cultures undergo extensive morphological differentiation, including synaptogenesis and myelination. To study the developmental toxicity of organophosphorus compounds (OP), aggregating brain cell cultures were treated with parathion. Protein content and cell type-specific enzyme activities were not affected up to a concentration of 10(5) M. Gliosis, characterized by an increased staining for glial fibrillary acidic protein (GFAP), was observed in immature and in differentiated cells. In contrast, uridine incorporation and myelin basic protein (MBP) immunoreactivity revealed strong differences in sensitivity between these two developmental stages. These results are in agreement with the view that in vivo the development-dependent toxicity is not only due to changes in hepatic detoxification, but also to age-related modifications in the susceptibility of the different populations of brain cells. Furthermore, they underline the usefulness of histotypic culture systems with a high developmental potential, such as aggregating brain cell cultures, and stress the importance of applying a large range of criteria for testing the developmental toxicity of potential neurotoxicants.

Animals↗
PubMed1997

Tree-structured logistic models for over-dispersed binomial data with application to modeling developmental effects.

This article proposes tree-structured logistic regression modeling for over-dispersed binomial data. Recursive partitioning is performed using a combination of statistical tests and residual analysis. The splitting criterion in cross-validation is based on the deviance function. A nested grid algorithm to estimate the bootstrap parameters is developed. The regression tree procedure provides a new approach for exploring in detail the relationship between the binomial response and explanatory variables. The proposed procedure is used to model the relationship between the incidence of malformation and dose and fetal weight using data from a developmental experiment conducted at the National Center for Toxicological Research. A conditional Gaussian chain model is used to account for the effect of fetal weight by dose.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1994

Developmental effects of fumonisin B1-containing Fusarium moniliforme culture extract in CD1 mice.

Pregnant Charles River CD1 mice were treated with a semipurified extract of Fusarium moniliforme culture containing 0, 12.5, 25, 50 or 100 mg FB1/kg each day orally (diluted in distilled water) between gestational days (GD) 7 and 15 to evaluate the developmental toxicity of FB1. Following sacrifice of dams on GD 18, litters were examined for gross abnormalities and divided equally for skeletal or visceral examination by routine techniques. Significant maternal mortality was observed at doses of 50 and 100 mg FB1/kg. Dose-dependent decreases in maternal body weight gains, number of live offsprings per litter, and mean body weight of the offspring were produced at FB1 doses of 25 mg/kg or higher. The percentage of implants resorbed increased at all doses in a dose-dependant manner. A dose-dependant increase, except at the lowest dose tested, in the incidence of ossification deficits involving digits and sternum, short and wavy ribs, and hydrocephalus of lateral and third ventricles was also evident. Cleft palate was seen only at the highest FB1 dose. Maternal intoxication manifested as a dose-dependant increase in the severity of ascites associated mainly with increased histopathologic scores reflecting hepatocellular damage at day 18. Concommittant increases in serum alanine amino transferase (ALT) on GD 12, reflecting parenchymal liver cell damage, was also observed at all doses above 12.5 mg of FB1/kg. These results suggest that FB1-containing F. moniliforme culture extract is developmentally toxic in mice, and that this toxicity may be mediated by maternal hepatotoxicity.

Abnormalities, Drug-Induced↗
PubMed1996

Comparison of the developmental effects of two mercury compounds on glial cells and neurons in aggregate cultures of rat telencephalon.

A three-dimensional cell culture system was used as a model to study the influence of low levels of mercury in the developing brain. Aggregating cell cultures of fetal rat telencephalon were treated for 10 days either during an early developmental period (i.e., between days 5 and 15 in vitro) or during a phase of advanced maturation (i.e., between days 25 and 35) with mercury. An inorganic (HgCl2) and an organic mercury compound (monomethylmercury chloride, MeHgCl) were examined. By monitoring changes in cell type-specific enzymes activities, the concentration-dependent toxicity of the compounds was determined. In immature cultures, a general cytotoxicity was observed at 10(-6) M for both mercury compounds. In these cultures, HgCl2 appeared somewhat more toxic than MeHgCl. However, no appreciable demethylation of MeHgCl could be detected, indicating similar toxic potencies for both mercury compounds. In highly differentiated cultures, by contrast, MeHgCl exhibited a higher toxic potency than HgCl2. In addition, at 10(-6) M, MeHgCl showed pronounced neuron-specific toxicity. Below the cytotoxic concentrations, distinct glia-specific reactions could be observed with both mercury compounds. An increase in the immunoreactivity for glial fibrillary acidic protein, typical for gliosis, could be observed at concentrations between 10(-9) M and 10(-7) M in immature cultures, and between 10(-8) M and 3 x 10(-5) M in highly differentiated cultures. A conspicuous increase in the number and clustering of GSI-B4 lectin-binding cells, indicating a microglial response, was found at concentrations between 10(-10) M and 10(-7) M. These development-dependent and cell type-specific effects may reflect the pathogenic potential of long-term exposure to subclinical doses of mercury.

Animals↗
PubMedDate not supplied

Developmental effects of a chimeric ultraspiracle gene derived from Drosophila and Chironomus.

The ultraspiracle (usp) gene encodes a nuclear receptor that forms a heterodimer with the ecdysone receptor (EcR) to mediate transcriptional responses to the insect steroid hormone, 20-hydroxyecdysone (20HE). The responses ultimately elicit changes associated with molting and metamorphosis. Although Ultraspiracle (USP) is required at several developmental times, it is unclear whether USP plays stage-specific roles in Drosophila. A chimeric transgene (d/cusp), produced by replacing the ligand-binding domain (LBD) of Drosophila USP with the equivalent domain from another Diptera, Chironomus tentans, was tested for its ability to rescue Drosophila usp mutants from early larval lethality. A single copy of the d/cusp was sufficient to rescue transformants from several lines through larval development but they died suddenly during the late third instar. Additional doses of d/cusp were required to allow survival through the adult stage, but they did not restore a normal prepupal contraction. Thus, the arrest at the onset of metamorphosis apparently is caused by the impaired ability of the chimeric USP to mediate a stage-specific function associated with the LBD.

Amino Acid Sequence↗
PubMed1977

Developmental effects of prolonged pregnancy and the postmaturity syndrome.

The development of 40 postterm, postmature infants was compared to that of 40 normal control infants during the first year of life. The postterm, postmature infants had more prenatal complications and received lower Brazelton interaction and motor scores at birth. At four months they scored lower on the Denver developmental scale and were rated "difficult" babies by their mothers. At eight months their Bayley motor scores were equivalent to those of the control infants, but their mental scores were lower. At this time their mothers reported a higher incidence of illnesses and of feeding and sleep disturbances.

Apgar Score↗
PubMed1982

The agouti suppressor (As) coat color mutation in mice: developmental effects on the expression of agouti locus alleles.

The alleles at the agouti locus in the mouse determine whether eumelanin or pheomelanin is synthesized by the follicular melanocytes. The agouti suppressor (As) mutation, which is closely linked to the agouti locus, reduces the amount of pheomelanin produced by whatever agouti alleles are present in the animal's genome. Previous developmental studies have indicated that the agouti alleles exert their influence on the follicular melanocytes via interactions between the developing dermis and epidermis. Using the techniques of dermal-epidermal recombination of embryonic agouti suppressor (AsAw/AsAw), white-bellied agouti (Aw/Aw), yellow (Ay/a), viable yellow (Avy/Avy), black and tan (at/at), and nonagouti (a/a) mouse skin, the present study demonstrates that 1) the dermis is responsible for the development of regional pigmentation patterns in white-bellied agouti mice, and 2) the agouti suppressor mutation interferes with the expression of the white-bellied agouti allele by acting on the dermis as well as the epidermis. In addition, this study provides further evidence for the role of the epidermis in the expression of the agouti locus alleles.

Alleles↗
PubMed1995

Developmental effects of over-expression of normal and mutated forms of a Xenopus NF-kappa B homologue.

High level over-expression of XrelA1, a homologue of the p65 sub-unit of NF-kappa B and of Drosophila dorsal, arrests Xenopus development at the gastrula stage, producing a reduction in the levels of expression of various genes of developmental interest without general reduction in transcription or cessation of cell division. There is little Goosecoid expression, even though a dorsal lip forms. At lower levels XrelA1 mRNA primarily produces disruption of the mid-dorsal axis. A dominant interference gene product, delta 222, produces mainly posterior, but also anterior abnormalities. On the basis of these results we postulate that the role of XrelA1 in the vertebrate embryo is unlikely to be in dorsoventral development, but more likely in the formation of the termini.

Animals↗
PubMed2001

Metamorphosis of summer flounder, Paralichthys dentatus: cell proliferation and differentiation of the gastric mucosa and developmental effects of altered thyroidal status.

Summer flounder, like most marine fishes studied to date, are stomachless at first feeding, and subsequently acquire gastric function during the process of metamorphosis. Stomach formation is controlled largely by thyroxine (T4). In the present work we sought to understand gastric organogenesis in terms of cell proliferation and its relationship to histological differentiation. The objectives of the study were (1) to obtain a developmental pattern of cell proliferation in the gastric mucosa and to relate that pattern to the progress of gastric differentiation; and (2) to understand the regulatory role of T4 on cell proliferation and histological differentiation by altering the thyroidal status of the developing larvae. We observed that (1) in normally developing larvae, cell proliferation increased by early metamorphic climax (MC), remained high until mid-MC, and decreased to basal levels by late MC; concomitantly, the gastric glands appeared and differentiated in the fundic mucosa, and were complete by late MC; (2) T4 accelerated the differentiation of gastric glands and mucus neck cells, while inhibiting the concomitant increase in cell proliferation observed in controls; and (3) the goitrogen thiourea inhibited both cell proliferation and gastric differentiation compared to controls. These results indicate that T(4) is necessary for the three-fold increase in cell proliferation that occurs in early metamorphic climax, but that high T4 levels promote differentiation at the expense of proliferation. The observed effects would be consistent with the normal, metamorphosis-related increase in whole body T4.

Animals↗
PubMed1984

Developmental effects of a temperature-sensitive RNA polymerase II mutation in Drosophila melanogaster.

Drosophila melanogaster possessing a temperature-sensitive (ts) mutation that maps to an X-linked locus ( RpII215 ) (the locus has also been called l(1)L5 and Ultrabithorax -like or Ubl ) encoding a subunit of RNA polymerase II are fertile at 22 degrees C but become sterile when shifted to 29 degrees C. Homozygous RpII215ts adult females shifted to 29 degrees C lay structurally normal eggs for 24 hr, after which increasing numbers of eggs are abnormal. Eggs left to develop at 29 degrees C die as morphologically normal late embryos or first instar larvae when produced by females maintained at 29 degrees C for less than 6 hr. However, eggs produced by females undergoing oogenesis at 29 degrees C for longer than 6 hr develop abnormally, displaying holes primarily in their ventral cuticle and possessing an abnormal pharyngeal apparatus. As exposure of females to 29 degrees C lengthens there is an increase in the severity of these defects. Some of the eggs can be rescued by either mating RpII215ts females to wild-type males or shifting the eggs to 22 degrees C. The percentage of eggs rescued decreases with increased length of oogenesis at 29 degrees C, up to 20 hr, at which point they are no longer rescuable. The terminal phenotype of eggs that fail to be rescued by the above procedure is less extreme than that of eggs for which no rescue attempt was made. Holes in the ventral cuticle are reduced or absent, but pattern formation is disrupted such that segments are often missing, incorrectly oriented or fused. Because the RpII215 locus encodes a subunit of RNA polymerase II, the developmental defects described above are most likely due to reduced or aberrant transcription during oogenesis and early embryogenesis. This postulated effect on transcription results, in part, from the maternal loading of a gene product(s) that is thermolabile in eggs.

Animals↗
PubMed1998

Developmental effects on odor learning and memory in children.

The child version of the California Odor Learning Test (COLT) was designed to assess cognitive functioning in impaired and healthy children. The COLT's rationale was based on two assumptions. First, measures of cognitive functioning are a good index of severity or extent of brain damage if compared between normal and clinical populations. Second, the cognitive-mediated tasks of verbal odor recall, recognition and identification were suitable to evaluate cognitive functioning. The focus of this study was to determine the COLT's ability to detect developmental differences in odor learning and memory. The participants were 51 healthy children who were twice administered the COLT with a weekly delay between tests. They were ascribed to two age-groups (7-10 and 11-15 years old) according to levels of cognitive development. The COLT employed 22 common odors and included two sessions. In the first session, children learned two sets of six odors. The first set was presented three times, the second one once, during a single learning episode. Following learning, children recalled the odors of the first set by name at free recall and category-cued recall. The second session included the following tasks: long-term free odor recall and category-cued odor recall, odor recognition-memory and verbal odor identification. A series of analyses of variance (ANOVAs, p < 0.05) with age as between-subject variable and repeated measurements on recall revealed significant differences between the two groups on the number of odors correctly recalled by name both at free recall, category-cued recall, recognition and identification. There were differences in false alarms at odor recognition between the two groups. Children from both groups benefited from a learning effect over odor trials. A gender effect was found for odor free recall at retest. These results suggest that the COLT has the potential to serve as a useful tool in the assessment of cognitive functioning in children.

Adolescent↗
PubMed1999

Developmental effects of urban storm water in Medaka (Oryzias latipes) and inland silverside (Menidia beryllina).

Stormwater runoff in a coastal urban area (San Diego County, CA) produced significant toxicity to early life stages of medaka (Oryzias latipes) and Menidia (M. beryllina). Exposure of embryos to lower concentrations (5 to 25%) increased the incidence of abnormal swim bladder inflation and other teratogenic responses, whereas higher concentrations resulted in mortality or failure to hatch. Comparisons of EC50s for mortality and failure to hatch with concentrations of individual chemical pollutants (including Cd, Cr, Cu, Pb, Ni, and Zn) revealed low correlations; however, the correlation with total metals was high (-0.84) and corresponded with sample exceedences of Water Quality Criteria (WQC) for Cd, Cu, Pb, and Zn. This strong association between developmental toxicity and toxic metal content of storm water compared favorably with developmental anomalies reported in other studies. Analytical chemistry data for pesticides that may have been in these samples were limited to selected pesticides found usually below detection limits. Greater toxicity of the watershed effluents sampled was generally associated with more developed land surface and less open space. Both medaka and Menidia were found to be useful for studying effects of stormwater on embryonic and early larval development. http://link.springer-ny. com/link/service/journals/00244/bibs/37n2p227.html

Animals↗
PubMed1986

Developmental effects of chemicals and the heat shock response in Drosophila cells.

Exposure of prokaryotic and eukaryotic cells to heat shock (hyperthermia) or to a number of diverse environmental stresses such as teratogens, anoxia, and inhibitors of oxidative phosphorylation results in the enhanced synthesis of a number of proteins which have been previously referred to as heat shock proteins (hsps). More recently, in view of the diverse types of agents that can induce these proteins, they have also been referred to as stress proteins. This phenomenon is one of the most basic regulatory mechanisms in living organisms. Exposure of Drosophila embryos, larvae, or pupae to these types of stresses also results in a variety of developmental abnormalities in the ensuing adult. Although the function(s) of these heat shock proteins has yet to be determined, they are widely thought to play an important role in cell survival and protection following some types of environmental stress. In our laboratory, we have developed an in vitro assay for detecting agents that act as teratogens, utilizing Drosophila embryonic cultures. Drosophila embryonic cells differentiate in vitro to a number of functional cell types including myotubes and ganglia. A number of drugs that have been shown to act as teratogens in mammals have also been found to inhibit muscle and/or neuron differentiation in Drosophila embryonic cultures. We have examined, by two-dimensional gel electrophoresis, the effects of such teratogens on protein synthesis in Drosophila embryonic cells. Inhibition of muscle and/or neuron differentiation correlates well with the induction of two proteins of about 20 kilodaltons. These are identical to two of the heat shock proteins (hsp 23, 22) as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. Heat shock and other treatments such as exposure to some of the metal ions and ether induces the entire set of seven major heat shock proteins in the Drosophila embryonic cells. Dose-response studies of several teratogens show a correlation between the degree of inhibition of differentiation and the level of induction of hsps. Since heat shock proteins have been suggested as possibly serving a protecting role, our present studies are aimed at identifying the role of hsps in teratogenesis and investigating the differential regulation of heat shock genes in response to different external stimuli.

Animals↗
PubMed1998

Developmental effect of polyamine depletion in Caenorhabditis elegans.

Ornithine decarboxylase (ODC) catalyses the conversion of ornithine to putrescine, an obligate precursor to the polyamines spermidine and spermine. We reported previously that homozygous odc-1 (pc13) worms have no detectable ODC activity. Despite their inability to make polyamines, these mutant worms appear normal, but with a slight reduction in total brood size, when grown in complex medium that presumably contains polyamines. We now show that when ODC-deficient worms are transferred to polyamine-free medium, they show a strong phenotype. odc-1 worms have two different fates, depending upon the developmental stage at which polyamines are removed. If the polyamines are removed at the L1 larval stage, the mutant animals develop into adult hermaphrodites that produce very few or no eggs. In contrast, if mutant larvae at the later L4 stage of development are transferred to polyamine-deficient medium, they develop and lay eggs normally. However, approx. 90% of the eggs yield embryos that, although well differentiated, arrest at early stage 3. Either maternal or zygotic expression of ODC provides partial rescue of embryonic lethality. Supplementing deficient medium with the polyamine spermidine allows ODC-deficient worms to develop as on complex medium. Together, these findings suggest that ODC activity is most critically required during oogenesis and embryogenesis and, furthermore, that exogenous polyamines can override the requirement for ODC activity.

Animals↗
PubMed1994

Housing of pregnant rats in metabolism cages: maternal and developmental effects.

The influence of the caging conditions on maternal and gestational variables was assessed for pregnant rats housed individually in two cage types. Plug-positive Sprague-Dawley females were caged either in Makrolon or in metabolism (Tecniplast) cages, and were not disturbed throughout all the gestational period. Cesarean sections were performed on gestation day 20. All live fetuses were examined for external, internal, and skeletal malformations and variations. Pregnant rats were affected by the housing system, as evidenced by a significant weight loss and reduced food consumption in the animals housed in metabolism cages. A moderate increase in the number of total skeletal defects was also observed in the fetuses of dams housed in metabolism cages. An important implication of these results would be that in maternal and developmental toxicity studies of xenobiotics, pregnant animals should not be housed in metabolism cages.

Animals↗
PubMed1998

Developmental effects on intersexual and intrasexual variation in growth and reproduction in a lizard with temperature-dependent sex determination.

The mechanisms that control growth and reproduction have received considerable attention by molecular and cellular endocrinologists, yet there has been relatively little effort to link these two aspects of physiology. On the other hand, evolutionary biologists have long commented on the relationship between growth and reproduction in many species, yet have generally neglected the mechanisms underlying such complex traits. An approach that integrates the multiple proximate levels promises to provide significant insight into the evolution of neuroendocrine control mechanisms. In this chapter, we take this approach in reviewing environmental influences on growth and reproduction in the leopard gecko, Eublepharis macularius. In this species, incubation temperature during embryonic development not only determines gonadal sex, but also underlies within-sex differences in growth, adult morphology, aggressiveness, reproductive physiology and behaviour, and brain organization. Thus, the leopard gecko is an excellent model to elucidate the developmental interactions among the environment and the endocrine and nervous systems that control growth and reproduction.

Animals↗