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Developmental effects of pcbs on the hard clam (Mercenaria mercenaria).

Development of hard clam (Mercenaria mercenaria) larvae was examined as a potential biomarker of exposure to polychlorinated biphenyls (PCBs). Clams from clean sites in Massachusetts Bay were thermally induced to spawn in the laboratory using seawater, and the gametes were collected and pooled by sex prior to fertilization. The larvae were cultured in seawater amended with Aroclor 1254, at concentration ranges bracketing environmentally relevant levels. A dose-response relationship was observed for larval development in the presence of Aroclor 1254; at higher doses, fewer larvae developed to the normal straight-hinge, or D-shaped stage, relative to the controls, while the number of abnormally shaped larvae increased.

Animals↗

Environmental and developmental effects on external gill loss in the red-eyed tree frog, Agalychnis callidryas.

I examined the effects of development, hatching, and oxygen availability on external gill loss in red-eyed tree frogs, Agalychnis callidryas. Under natural conditions, the arboreal embryos maintained large external gills until hatching, which occurred from 5-8 d after oviposition. At hatching, when tadpoles entered the water, external gills began to regress. In older hatchlings this process was extremely rapid. Gill circulation was lost on average within 16 min and sometimes within 5 min. Gills often regressed completely in under 2 h. Younger hatchlings reduced gill circulation, shortened and adducted their gills, then resumed normal circulation for some time after hatching; half had completely lost external gills within 24 h. Experimentally increasing the area of egg surface exposed to the air induced loss of external gills in unhatched embryos. Older hatchlings in hypoxic water without access to air maintained their external gills. This suggests that loss of external gills is a response to increased oxygen availability, rather than a response to hatching per se. Extended maintenance of external gills by large, late-hatching embryos may facilitate continued rapid development in closely packed eggs.

Adaptation, Physiological↗

Temperature-sensitive mutations in Drosophila melanogaster. XII. The genetic and developmental effects of dominant lethals on chromosome 3.

Out of 25,000 EMS-treated third chromosomes examined, ten dominant temperature-sensitive (DTS) lethal mutations which are lethal when heterozygous at 29 degrees C but survive at 22 degrees C were recovered. Seven of the eight mutations mapped were tested for complementation; these mutants probably define eight loci. Only DTS-2 survived in homozygous condition at 22 degrees C; homozygous DTS-2 females expressed a maternal effect on embryonic viability. Two of the mutant-bearing chromosomes, DTS-1 and DTS-6, exhibited dominant phenotypes similar to those associated with Minutes. Each of the seven mutants examined exhibited a characteristic phenotype with respect to the time of death at 29 degrees C and the temperature-sensitive period during development. Only DTS-4 exhibited dominant lethality in triploid females.

Alkanesulfonates↗

Issues in risk assessment for developmental effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

Recent risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds have focused on adverse effects observed in rodent offspring exposed while in utero during critical gestational periods as among the most sensitive adverse effects attributable to TCDD exposure. In addition, these risk assessments have converged on the use of body concentration (or "body burden") of TCDD as a dose metric superior to administered dose for cross-species comparisons and risk assessments, due to the interspecies differences in elimination kinetics and substantial persistence of these compounds. The detailed, although incomplete, data that are available on maternal-fetal distribution of TCDD and related compounds illustrate differences in distribution among these compounds that impact assessments on a body-burden basis. These data also demonstrate differences in distribution after subchronic or chronic administration compared to acute administration. Some data are now also available addressing inconsistencies that may arise from the use of TCDD toxic equivalency factors (TEFs), which were derived on an administered-dose basis, in evaluating responses to mixtures of dioxins on a body-burden basis in the context of chronic exposure situations. Finally, the use of body burden as a dose metric does not account for or eliminate the substantial differences in sensitivity to dioxin observed across species or between different strains of the same species and, thus, does not eliminate the need to consider the relative sensitivity of humans compared to laboratory animal models in risk assessments. Additional research areas that may increase the foundation for interspecies extrapolations are discussed.

Animals↗

Developmental Effects of Sandoz 6706 on Activities of Enzymes of Phenolic and General Metabolism in Barley Shoots Grown in the Dark or under Low or High Intensity Light.

The activities of three enzymes of phenolic biosynthesis and six of general metabolism were studied at 24-hour intervals between the 3rd and 8th day after planting in barley shoots treated with the chlorosis-inducing herbicide Sandoz 6706 and grown in the dark or under high or low intensity light. The herbicide had no effect on fresh weight or soluble protein (per shoot) in plants grown in the dark or under low intensity light, but slightly decreased these parameters in plants grown for more than 5 days under high intensity light. In dark-grown seedlings the herbicide had no detectable effects on plastid ultrastructure or on the activity of malate dehydrogenase, cytochrome c oxidase, NADP-cytochrome c reductase, triose phosphate isomerase, peroxidase, catalase, shikimate dehydrogenase, phenylalanine ammonia-lyase, or chalcone-flavanone isomerase. Under low intensity light, Sandoz 6706-treated plants developed plastids with single thylakoids extending across the organelle, and the activity of all enzymes examined was increased to varying degrees. When the herbicide-treated plants were grown under high intensity light, plastid lamellar organization was severely disrupted. Activities of shikimate dehydrogenase and chalcone-flavanone isomerase were markedly enhanced, phenylalanine ammonia-lyase activity slightly promoted, and catalase activity severely inhibited. The other enzymes were not appreciably affected by Sandoz 6706 under high intensity light. It is concluded that the changes in plastid ultrastructure and enzyme activities of the herbicide-treated plants are largely secondary photomorphogenetic or photooxidative responses in the carotenoid-free plants in which chlorophylls accumulate in reduced amounts (low intensity light) or are completely absent (high intensity light).

Journal Article↗

Environmental and developmental effects on the biosynthesis of UV-B screening pigments in Scots pine (Pinus sylvestris L.) needles.

The major UV-B screening pigments of the epidermal layer of Scots pine (Pinus sylvestris) needles are flavonol 3-o-glycosides (F3Gs) esterified with hydroxycinnamic acids at positions 3" and 6". Acylation is the last step in biosynthesis and is catalysed by position-specific hydroxycinnamoyl transferases (3" and 6"HCT). The UV-B dependence of these enzyme activities was studied in primary needles of Scots pine seedlings grown under different UV-B conditions in environmentally controlled sun simulators. 6"HCT activity was induced upon UV-B irradiation while 3"HCT activity was not induced but showed high constitutive values. To investigate the biosynthesis of diacylated F3Gs during needle development under natural conditions, the HCT activities and metabolite contents were analysed in needles of field-grown mature pine trees. Accumulation of diacylated compounds as well as of 6"HCT activity occurred transiently in the first year of needle development only. In contrast, 3"HCT activity exhibited broad maxima in two consecutive years during needle growth. The data suggest that acylated F3Gs are first formed as soluble compounds which are then translocated into the cell wall to be bound by their hydroxycinnamoyl residues.

Acyltransferases↗

Developmental effects of ectopic expression of the glucocorticoid receptor DNA binding domain are alleviated by an amino acid substitution that interferes with homeodomain binding.

Steroid hormone receptors are distinguished from other members of the nuclear hormone receptor family through their association with heat shock proteins and immunophilins in the absence of ligands. Heat shock protein association represses steroid receptor DNA binding and protein-protein interactions with other transcription factors and facilitates hormone binding. In this study, we investigated the hormone-dependent interaction between the DNA binding domain (DBD) of the glucocorticoid receptor (GR) and the POU domains of octamer transcription factors 1 and 2 (Oct-1 and Oct-2, respectively). Our results indicate that the GR DBD binds directly, not only to the homeodomains of Oct-1 and Oct-2 but also to the homeodomains of several other homeodomain proteins. As these results suggest that the determinants for binding to the GR DBD are conserved within the homeodomain, we examined whether the ectopic expression of GR DBD peptides affected early embryonic development. The expression of GR DBD peptides in one-cell-stage zebra fish embryos severely affected their development, beginning with a delay in the epibolic movement during the blastula stage and followed by defects in convergence-extension movements during gastrulation, as revealed by the abnormal patterns of expression of several dorsal gene markers. In contrast, embryos injected with mRNA encoding a GR peptide with a point mutation that disrupted homeodomain binding or with mRNA encoding the DBD of the closely related mineralocorticoid receptor, which does not bind octamer factors, developed normally. Moreover, coinjection of mRNA encoding the homeodomain of Oct-2 completely rescued embryos from the effects of the GR DBD. These results highlight the potential of DNA-independent effects of GR in a whole-animal model and suggest that at least some of these effects may result from direct interactions with homeodomain proteins.

Animals↗

Linguistic and developmental effects on the production and perception of stop consonants.

This study examined production and perception of the contrast between /t/-/d/ by subjects differing in native language and age. Acoustic analysis revealed that native speakers of English realized word-initial /t/ with significantly longer VOT values (approximately 85 ms) than native speakers of Spanish (approximately 19 ms). Native English and Spanish adults realized /t/ with VOT values that were non-significantly longer than those of 9-year-olds of the same native language background. Native English adults prevoiced /d/ more often than English children, but Spanish adults and children realized /d/ with lead VOT values in nearly every instance. In a labelling task, the native English speakers showed steeper identification functions, and category boundaries at significantly longer VOT values, than age-matched native Spanish subjects. The boundaries of both the native English and Spanish adults occurred at significantly longer VOT values than those of children who spoke the same language. Three possible explanations are offered for the effect of age on stop voicing judgments: the auditory processing of acoustic parameters associated with stops changes with age; listeners require an increasingly long VOT interval to perceive /t/ as they get older because they produce /t/ with somewhat longer VOT values; listeners 'attune' their perception to optimally match the stops they hear.

Adult↗

An organizational guide for an effective developmental program in the NICU.

Many newborn intensive care units have put a great deal of energy and resources into their efforts to provide developmentally supportive care. Yet, without consistent leadership and clear accountabilities, developmental care will depend on the individual philosophy, or even the mood, of the health care professional at the bedside. Under these circumstances, infants and families experience an unpredictable and inconsistent quality of care. This article presents a guide to assist nurseries in structuring successful programs of developmentally supportive, family-centered care through well-described accountabilities that translate into consistent, high-quality care for infants and families in the NICU.

Guidelines as Topic↗

Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents.

There are close physiologic similarities between humans and macaques that make them well suited for preclinical testing of biopharmaceutics. These include menstrual cycles of similar length and hormonal control, comparable cellular and endocrine processes of implantation, and similar timetables of prenatal development. Three teratogenic agents have induced abnormal development of the macaque thymus that is a key organ in the development of the fetal immune system. Embryonic exposure to triamcinolone acetonide, a potent corticosteroid, during critical periods of thymus development caused marked hypoplasia, depletion of thymic lymphocytes, and reduction of epithelial elements. Aplasia and hypoplasia of the thymus were a distinct feature of the "retinoid syndrome" in cynomolgus macaques following exposure to 13-cis-retinoic acid (Accutane) in early pregnancy, the time of neural crest migration. Experimentally induced zinc deficiency in rhesus macaques from conception to 1-year of age caused severe alterations in immunocompetence. More recent studies have shown that the levels of IgG and IgA in cervicovaginal lavages of the rhesus macaque exhibit specific temporal patterns during the normal menstrual cycle. Taken together, theses data suggest that several macaque species are appropriate animal models for preclinical safety assessment of immunomodulatory drugs. Current teratology protocols in these models may require slight modifications to adequately assess the safety of these biologics.

Adjuvants, Immunologic↗

Developmental effects of propyphenazone in analgesic and antipyretic combination with caffeine or paracetamol.

The aim of the study was to determine the influence of an over-the-counter (OTC) mixture of propyphenazone with caffeine or paracetamol on prenatal development. Propyphenazone:caffeine and propyphenazone:paracetamol mixtures were prepared with constant 3:1 and 3:5 ratios, respectively. Three dose levels of each of the mixtures were administered separately in Tween-80 water suspension once a day to pregnant Wistar rats on gestation days 8-14. The low dose was similar to the OTC preparations, 2.1 mg/kg of propyphenazone, 0.7 mg/kg of caffeine or 3.5 mg/kg of paracetamol. The middle dose was 21.0, 7.0 or 35.0 mg/kg, and the highest 210.0, 70.0 or 350.0 mg/kg for propyphenazone, caffeine or paracetamol, respectively. On day 21 of gestation the fetuses were delivered by hysterectomy. Dead or live fetuses, resorptions and the number of implantation sites were counted. Live fetuses were examined for external, visceral and skeletal malformation. Postimplantation mortality was calculated. Dose-dependent effects in the middle and high dose groups on fetal body weight/length and placental weight were found. No increase in external or internal congenital anomalies was found in any of the mixture-exposed groups. Prenatal coadministration of propyphenazone with caffeine or paracetamol caused intrauterine growth retardation but did not increase external or internal congenital anomalies. The risk of midline defects (umbilical hernia and gastroschisis) is discussed.

Acetaminophen↗

Developmental effects of hypoxia and indomethacin on distribution of vascular resistances in lamb lungs.

The influence of postnatal age on the distribution of vascular resistances was studied in in situ, isolated, blood perfused lungs of lambs aged 6-12 h, 2-4 d, 2 wk, and 1 mo. The pressure gradients across the upstream, downstream, and compliant middle segments were determined by an inflow-outflow occlusion technique during mild hyperoxia (FIO2 = 0.28) and severe hypoxia (FIO2 = 0.04) under control and indomethacin-treated conditions. The greatest response to hypoxia was seen in the middle segment. A lesser, but significant response was also seen in the upstream segment. Indomethacin accentuated the hypoxic response of the total circuit and the middle segment at all ages, and the upstream segment in the two younger age groups. An age-dependent increase in total hypoxic reactivity was seen in control lungs, but not in indomethacin-treated lungs. When the pressure gradient across the middle segment alone was considered, an age-dependent increase in hypoxic reactivity was seen in controls and a decrease was seen in indomethacin-treated lungs. In contrast there were no age-dependent changes in the hypoxic responses of the upstream or downstream segments. These data suggest that the predominant site of hypoxic pulmonary vasoconstriction and dilator prostaglandin activity lies within the middle gradient in newborn lamb lungs. Furthermore, the age-dependent changes in the hypoxic response of the middle gradient appear to be altered by the modulating influence of dilator prostaglandins.

Aging↗

Developmental effects of intrauterine growth retardation on cerebral amino acid transport.

Early restriction of nutrients during the perinatal period of life can modify the development of the mammalian fetus and have marked repercussions on the ontogeny of the CNS. The brain is vulnerable to undernutrition, with delayed morphologic and biochemical maturation leading to impaired functions. The aim of the present investigation was to assess whether modified brain neurotransmitter and amino acid concentrations found in an animal model of intrauterine growth retardation were related to modified blood-brain amino acid transport properties. Four amino acids were tested: alanine and taurine, plus two neurotransmitter precursors, tryptophan and tyrosine. Intrauterine growth retardation was induced by restriction of maternal-fetal blood flow from the 17th d of gestation. Blood-brain transport of these amino acids was measured by i.v. injection of radiolabeled amino acids in 7-d-old, 21-d-old, and 60-d-old intrauterine growth-retarded or control rats. No major statistical differences were revealed either for brain regional transport or between intrauterine growth-retarded animals and controls at any age studied. Transfer coefficients and influxes remained statistically similar for almost all brain regions in both groups. A significant decrease and different time course for amino acid transport with age related to the blood-brain barrier maturation are confirmed in this model. Our results are related to a major role of the blood-brain barrier as a part of mechanisms leading to "brain growth sparing."

Age Factors↗