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PubMed2006

Loss of Alx4, a stromally-restricted homeodomain protein, impairs mammary epithelial morphogenesis.

Postnatal development of the mammary gland is determined by reciprocal interactions between the ductal epithelia and adjacent stroma. Alx4 is a mesenchymally restricted homeodomain transcription factor expressed in a number of developing tissues, including skin appendages such as hair follicles, whiskers and teeth. We show here that Alx4 is expressed in a subset of ERalpha-expressing mammary stromal cells adjacent to terminal end buds and alveoli during puberty and pregnancy, respectively. Alx4 expression is induced in mammary stromal cells at the onset of puberty and can be induced in prepubescent mice by administration of 17beta-estradiol. In order to determine the role of Alx4 during mammary gland development, we characterized mammary gland development of mice homozygous for the null allele of Alx4, lst(D). Mammary glands from animals lacking Alx4 activity exhibit profound alterations in ductal morphogenesis. Overall development is delayed, ducts being grossly distorted in size and structure. Terminal end buds are also disoriented, displaying aberrant architecture during bifurcation. Despite the developmental delay, the ductal network typically reaches the limits of the fat pad. However, during puberty and in the adult virgin mice, the frequency and density of branch points is significantly reduced. We show further that the defective ductal morphogenesis is due to defects in stromal cells. Specifically, when injected into the cleared fat pad of wild-type recipients, mixed populations of wild-type epithelial cells and Alx4-deficient stromal cells give rise to retarded ductal morphogenesis. Wild-type stromal cells mixed with Alx4-deficient epithelial cells result in normal progression of ductal development. Defective branching morphogenesis in Alx4-deficient females is not due to a loss in expression of HGF, since the level of HGF message in mammary stromal cells is similar in mutant and wild-type littermates. MMP3 is similarly expressed while a 40% increase in MMP2 and a 50% decrease in MMP9 message levels in Alx4-deficient mice relative to their wild-type littermates is observed. Thus, the activity of the stromally restricted homeodomain factor, Alx4, is required for normal branching morphogenesis of the ductal epithelia during pubescent mammary gland development.

Animals↗
PubMed1994

Maternal estimates of developmental age in preschool children.

OBJECTIVE: To investigate the accuracy of maternal estimates of developmental age in preschool children with suspected developmental delay. METHODS: In a sample of 139 preschool children, aged 5 to 60 months, mothers were asked before evaluation to estimate the developmental age of their child. Maternal estimates were converted to a developmental quotient (DQ) and compared with results from standardized tests of cognitive functioning, adaptive abilities, expressive and receptive language, and visual-motor skills. RESULTS: A high correlation was found (r = 0.82; p < 0.0001) between maternal-estimate DQ and actual DQ (mean of test scores). Most mothers estimated within 15% of their child's actual functioning, and 84% of mothers estimated within +/- 5 months of actual functioning. Multiple regression found no factors that would identify mothers who were more or less accurate in estimating developmental age. Maternal-estimate DQ was sensitive (83%) and specific (83%) for mental retardation. CONCLUSION: Maternal estimates provide an accurate measure of developmental functioning and could be successfully incorporated into routine developmental surveillance of preschool children.

Child Development↗
PubMed2004

Developmental and behavioral status of infants and young children awaiting heart or heart-lung transplantation.

OBJECTIVE: Research into cognitive development and behavior in children undergoing heart or heart-lung transplantation has focused mainly on older children, with investigation of children undergoing transplantation as infants or toddlers being largely retrospective. This study was conducted, therefore, to obtain pretransplant baseline measures of development and behavior for preschool-aged children. METHODS: Children <3.5 years old were assessed before transplantation (n = 35) and compared with a group of children awaiting conventional cardiac surgery, a group undergoing bone marrow transplantation, and a group of healthy children. Development was measured by using the Ruth Griffiths Mental Development Scales, and behavior was measured with the Achenbach Child Behavior Checklist. RESULTS: Within the transplant group, 17 had congenital heart disease (CHD), and 18 had cardiomyopathy (CM). Although the overall mean developmental scores were within the normal range for the transplant, conventional cardiac surgery, and bone marrow transplantation groups, scores were significantly lower than those of the healthy group. Within the transplant group, those with CHD had a significantly lower mean developmental quotient than those with CM. Furthermore, the CHD patients obtained significantly lower scores than those with CM on areas of development covering locomotor abilities, speech and hearing, eye-hand coordination, and performance. CONCLUSIONS: In common with other groups of ill children, patients awaiting heart or heart-lung transplantation are at risk for developmental delay. Diagnosis is a salient factor in determining outcome in most areas of development. Psychosocial interventions need to be targeted to maximize developmental potential before transplantation.

Child Behavior↗
PubMed1998

Correlations between intestinal parasitosis, physical growth, and psychomotor development among infants and children from rural Nicaragua.

The correlations between malnutrition, parasitosis (especially helminth infections), and child development are complex, and studies of these interrelationships will allow health agencies to maximize screening and intervention strategies for developing countries. We examined these correlations in a cross-sectional program in Carazo State, Nicaragua. Nine hundred sixty-one children in two age strata (ages 0-24 months and ages 2-10 years) from one urban and three rural communities were screened for intestinal parasites (direct smear and ZnSO4 flotation), malnutrition, and developmental delays. Nutritional status was determined as weight-for-age (WFA), weight-for-height (WFH), and height-for-age (HFA). Developmental status (normal, suspect) was determined for the four subtests of the Denver II Screening Test. The prevalence of malnutrition was 14.6% (WFA), 8.4% (WFH), and 36.3% (HFA). Parasitosis was more prevalent in children less than 24 months of age with low HFA, whereas in older children low WFA was more closely associated with parasitic infections. Ascaris and Trichuris were more prevalent in malnourished children. On the Denver II, suspect test results in all four categories (language, social, gross motor, and fine motor) were associated with low WFA, and suspect language tests were associated with both intestinal parasites (P = 0.0003) and Ascaris infection in particular (P = 0.044). Developmental disabilities are a significant and frequently undetected health problem in developing countries, and malnutrition associated with intestinal helminth infections may be an important contributory factor for these disabilities.

Body Height↗
PubMedDate not supplied

Self-injurious behavior as a challenge for the dental practice: a case report.

Patients who present self-injurious behavior (SIB) can be considered a treatment challenge in the dental office or hospital setting. Oral structures can play various roles in the process of self injury. In this paper, the authors report a case of SIB in the form of cheek-biting on an adolescent with a history of hydrocephalus and developmental delay, which was successfully treated with a modified standard maxillary orthodontic retainer. Early detection and intervention in SIB cases in patients with developmental disabilities influence the successful outcome of the therapeutic interventions, enhancing the patient's quality of life.

Adolescent↗
PubMed2003

The pineapple eye gene is required for survival of Drosophila imaginal disc cells.

Each ommatidium of the Drosophila eye is constructed by precisely 19 specified precursor cells, generated in part during a second mitotic wave of cell divisions that overlaps early stages of ommatidial cell specification. Homozygotes for the pineapple eye mutation lack sufficient precursor cells due to apoptosis during the period of fate specification. In addition development is delayed by apoptosis during earlier imaginal disc growth. Null alleles are recessive lethal and allelic to l(2)31Ek; heteroallelic combinations can show developmental delay, abnormal eye development, and reduced fertility. Mosaic clones autonomously show extensive cell death. The pineapple eye gene was identified and predicted to encode a novel 582-amino-acid protein. The protein contains a novel, cysteine-rich domain of 270 amino acids also found in predicted proteins of unknown function from other animals.

Amino Acid Sequence↗
PubMed1982

Children of methadone-maintained mothers: follow-up to 18 months of age.

Limited information is available on the long-term effects of in utero methadone exposure. This report describes the somatic and neurobehavioral findings of children in the first 18 months of life born to methadone-maintained mothers and to a matched drug-free comparison group of mothers. Findings during the neonatal period were (1) a 75% incidence of moderate-to-severe narcotic abstinence syndrome, (2) a significant incidence of head circumferences below the third percentile, and (3) elevated systolic blood pressure. In follow-up, the methadone children had (1) a significantly higher incidence of otitis media; (2) a significant incidence of head circumferences below the third percentile; (3) neurologic findings of tone discrepancies, developmental delays, and poor fine motor coordination; (4) a high incidence of abnormal eye findings; and (5) significantly lower scores on the Bayley mental and motor developmental indices. These neurobehavioral findings in children of methadone-treated mothers at 18 months of age may be predictors of later learning and behavioral problems.

Abnormalities, Drug-Induced↗
PubMed2000

Midgestation lethality in mice deficient for the RecA-related gene, Rad51d/Rad51l3.

Homologous recombination (HR) occurs in all organisms, and is important for repair of DNA damage, chromosome segregation during meiosis, and genetic diversification. Genes critical for recombinational DNA repair and meiotic recombination include members of the RecA/RAD51 family, of which seven have been identified in mammals. Here, we describe the disruption of Rad51d (recently designated Rad51l3) in mice and its phenotypic consequences. Rad51d-deficient mice die between 8.5 and 11.5 dpc. The affected embryos are smaller than littermates, posteriorly truncated, and developmentally delayed. Embryonic fibroblasts from mutant embryos could not be propagated more than one generation in culture. Rad51d-deficient blastocysts were not sensitive to gamma radiation or methylmethanesulfonate (MMS) in blastocyst outgrowth experiments. The variable and generalized developmental progression defects in Rad51d-deficient embryos suggests that mutant cells may undergo delayed or suboptimal repair of DNA damage, resulting in accumulated degrees of mutation and/or cell cycle perturbation that are incompatible with normal embryonic development. genesis 26:167-173, 2000.

Animals↗
PubMed1999

Multimodality evoked potential findings in infants with congenital heart defects.

Evoked potentials are sensitive prognostic tools in young infants at risk for developmental disability. The objective of this prospective study was to determine whether infants with congenital heart defects demonstrate evoked potential abnormalities prior to or following open heart surgery, and to examine the association between these abnormalities and developmental status 1 year following surgery. A consecutive series of newborns (less than 1 month old) and infants (1 month to 2 years old) were recruited. Somatosensory and brain stem auditory evoked potentials were carried out before or after cardiac surgery, or both. One year later, neurologic examination and standardized measures of motor performance and functional independence were carried out. Twenty-seven newborns and 31 infants underwent perioperative somatosensory evoked potential recordings. Results indicate that perioperative somatosensory evoked potential abnormalities were common in newborns (41%) but not in infants (13%) with congenital heart defects. Brainstem conduction times were within normal limits in all subjects; however, 32% presented with mild elevations in hearing thresholds. All newborns with abnormal somatosensory evoked potentials had abnormal neurologic examinations both perioperatively and again 1 year after open heart surgery. Moreover, standardized developmental assessments 1 year following surgery indicate that all newborns with somatosensory evoked potential abnormalities had developmental deficits in one or more domains. Somatosensory evoked potential abnormalities in the perioperative period are common in newborns with congenital heart defects, and are strongly predictive of persistent developmental delay later.

Brain↗
PubMed1991

Early diagnosis and referral of children with developmental disabilities.

Recent legislation has created a national program for providing early intervention, including identification, remediation and counseling, for children with developmental disabilities. Providing such services requires interaction between early childhood intervention professionals and primary care physicians in an unprecedented manner. Family physicians and other primary care professionals can identify at-risk children at an early stage. The physician's knowledge of the family can be crucial in the successful delivery of high-quality medical care to this population. This article describes a practical, four-stage approach to primary care participation in the identification, referral and follow-up of developmentally delayed and handicapped children.

Child↗
PubMed2004

Glucose homeostasis in the newborn.

Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.

Fasting↗
PubMed1989

Functional development of the visual system in normal and protein-deprived rats. VII. Lamination of oxidative enzyme activity in the visual cortex during post-natal development.

Lamination of activity of two mitochondrial enzymes-succinate dehydrogenase (SDH) and menadione-dependent alpha-glycerophosphate dehydrogenase (M-GPDH) - was examined in the visual cortex of control (C) and protein-deprived (PD) rats from 10 days old to adult. In C rats, lamination of enzyme activity was evident from 10 days by a band of higher activity in lamina IV. A band of higher SDH activity was seen in superficial lamina VI from 15 days. Lamination of M-GPDH activity became less pronounced with increasing age, whereas distinct bands of high SDH activity in lamina IV and VI remained also in adult rats. PD rats showed a developmental delay of approximately 5 days with regard to the general increase in neuropile activity. A band of higher enzyme activity in lamina IV was present from 10 days, but it was markedly less distinct in the PD rats compared to the C rats between 15 and 25 days. A band of higher SDH activity in superficial lamina VI was not seen until 25 days in PD rats. No apparent differences were seen between adult C and PD rats. The observed developmental alterations are discussed in relation to other delays, distortions and deficits found in the visual system of PD rats.

Animals↗
PubMed2000

The Myxococcus xanthus wbgB gene encodes a glycosyltransferase homologue required for lipopolysaccharide O-antigen biosynthesis.

Myxococcus xanthus is a gram-negative soil bacterium that initiates a complex developmental program in response to starvation. A transposon insertion (Tn5-lac omega109) mutant with developmental deficiencies was isolated and characterized in this study. A strain containing this insertion mutation in an otherwise wild-type background showed delayed developmental aggregation for about 12 h and sporulated at 1-2% of the wild-type level. Tn5-lac omega109 was found to have disrupted the M. xanthus wbgB gene, which is located 2.1 kb downstream of the M. xanthus lipopolysacharide (LPS) O-antigen biosynthesis genes wzm wzt wbgA. The deduced polypeptide sequence of WbgB shares significant similarity with bacterial glycosyltransferases including M. xanthus WbgA. The wbgB::Tn5-lac omega109 mutant was found to be defective in LPS O-antigen synthesis by immunochemical analysis. Further mutational analysis indicated that the defects of the wbgB::Tn5-lac omega109 mutant were not the result of polar effects on downstream genes. Various motility assays demonstrated that the Tn5-lac omega109 mutation affected both social (S) and adventurous (A) gliding motility of M. xanthus cells. The pleiotrophic effects of wbgB mutations indicate the importance of LPS O-antigen biosynthesis for various cellular functions in M. xanthus.

Amino Acid Sequence↗
PubMed1989

Marital transitions. A child's perspective.

Despite a recent leveling off of the divorce rate, almost half of the children born in the last decade will experience the divorce of their parents, and most of these children will also experience the remarriage of their parents. Most children initially experience their parents' marital rearrangements as stressful; however, children's responses to their parents marital transitions are diverse. Whereas some exhibit remarkable resiliency and in the long term may actually be enhanced by coping with these transitions, others suffer sustained developmental delays or disruptions. Others appear to adapt well in the early stages of family reorganizations but show delayed effects that emerge at a later time, especially in adolescence. The long-term effects are related more to the child's developmental status, sex, and temperament; the qualities of the home and parenting environments; and to the resources and support systems available to the parents and child than they are to divorce or remarriage per se. In recent years, researchers have begun to move away from the view that single-parent and remarried families are atypical or pathogenic families and are focusing on the diversity of children's responses and to the factors that facilitate or disrupt the development and adjustment of children experiencing their parents' marital transitions.

Adaptation, Psychological↗
PubMed1997

Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.

Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The viral envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10(-8) M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor. gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV-positive mothers. Vasoactive intestinal peptide and related factors may provide a therapeutic strategy in preventing developmental deficits.

Animals↗
PubMed2004

[Psychological condition of children from pregnancies after assisted reproduction in the third year of life].

OBJECTIVE: To analyse psychological development of children born after assisted reproductive technology. DESIGN: Psychological analysis of the child's development related to the technology of assisted reproduction, length of pregnancy and multiple birth was performed and compared with the control group. SETTING: Institute for the Care of Mother and Child, Prague. METHODS: Out of the total number of 123 children born after assisted reproductive technology during the 1st half of the year 1998 in the Center ISCARE IVF, psychological development was evaluated in 109 children (88.6%). Ninety four children from this sample were assessed using mental, motor and behavior scales of the Bayley Scales of Infant Development II. RESULTS: Mental and motor development of infants born after intracytoplasmatic injection (ICSI) and after in-vitro-fertilisation (IVF) was not significantly different. Fullterm singletons born after assisted reproductive technology did not differ from control fullterm children. There was a developmental delay in both fullterm and preterm children from multiple pregnancies in comparison to control children. No child had serious impairment of psychic functions (developmental index <50). There were no significant differences in behavior records between children born after assisted reproductive technology and control children, but some parents had problems in educational care of their children born after assisted reproductive technology. CONCLUSION: From children born after assisted reproductive technology, those from multiple pregnancies may be at risk for later psychological development. The occurrence of educational problems in assisted reproductive families indicates a need of accessible professional care in this field.

Adult↗
PubMed1994

Assessing child development.

The family practitioner has an important role in the detection of infants and young children with developmental delays. The physician may be the first or only professional in regular contact with infants and young children. Interpretation of a child's developmental status is best done with a clear understanding of the child's family and social environment, and the family practitioner is in a unique position to possess this knowledge by virtue of his or her established relationship with the family.

Child↗
PubMed1992

Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy.

Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC following exposure during early pregnancy, the current experiments were designed to evaluate the effect of exposure to MBC during early pregnancy on developmental parameters of offspring. Rats were administered MBC at 0, 100, 200, 400, or 600 mg/kg/day during Days 1-8 of pregnancy and killed on Day 11 or Day 20 of gestation. On Day 11, embryos were assessed for survival rate, growth parameters, and anomalies. On Day 20, standard developmental toxicity evaluations were performed. Doses of 200 to 600 mg/kg/day MBC reduced embryonic survival by Day 11; exposure to MBC at 100 to 600 mg/kg/day reduced the number of fetuses surviving on Day 20. Evidence of developmental delay was apparent on Day 11 at all doses, and fetal weight was reduced by Day 20. MBC produced a dose-dependent increase in developmental defects seen on Day 11 and in several malformations observed on Day 20. MBC exposure during the first week of pregnancy was shown to be embryotoxic, resulting in embryonic death, growth retardation, and developmental abnormalities when evaluated on Days 11 or 20 of gestation.

Abnormalities, Drug-Induced↗