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PubMed1990

Histochemical studies on hyaluronic acid in the developing human retina.

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and the Streptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks' gestation to the neonatal stage.

Aged↗
PubMed1991

Histochemical organization and cellular composition of ductal buds in developing human breast: evidence of cytochemical intermediates between epithelial and myoepithelial cells.

In developing human breast, terminal end buds (TEBs), lateral buds (LBs), and lobules of three to five alveolar buds (ABs) predominate in prepubertal females, whereas lobules of ABs and lobules of up to 60 ductules predominate in pubertal females. The appearance of clefts in TEBs and LBs suggests that they are precursors of ABs. In histological sections the ductal buds are composed of a heterogeneous collection of cells that include cortical and peripheral cells. The cortical cells can line small lumina in TEBs/LBs, whereas the peripheral cells which cap their distal tips are more irregular and loosely packed. Monoclonal antibodies (MAb) to epithelial milk-fat globule membranes and antiserum to epithelial membrane antigen immunocytochemically stain the cortical cells, particularly where such cells line lumina, and weakly stain the peripheral cap cells. Similar histochemical staining patterns are observed in desialylated sections with peanut lectin. Antiserum and MAb to smooth muscle actin moderately stain the peripheral cap cells, and this staining increases the closer the peripheral cells become to the myoepithelial cells of the subtending duct. Similar but weaker staining patterns are observed with antibodies to vimentin. Keratin MAb PKK2 and LP34, which stain myoepithelial cells in preference to epithelial cells in main ducts, as well as MAb to epithelium-specific keratin 18, all stain many of the cortical/luminal cells in buds and lobules of developing breast; the peripheral cap cells are relatively unstained. It is suggested that the undifferentiated peripheral cap cells show transitional forms both to the cortical epithelial cells that eventually line the lumina and to the myoepithelial cells of the subtending duct.

Actins↗
PubMed1991

Expression of bone sialoprotein (BSP) in developing human tissues.

Bone sialoprotein (BSP) and its messenger RNA were localized in developing human skeletal and nonskeletal tissues by means of immunohistochemistry and in situ hybridization. Both protein and mRNA were found in mature, bone-forming cells but not in their immature precursors. In addition, osteoclasts displayed positive immunostaining and high densities of autoradiographic grains by in situ hybridization experiments. BSP was expressed in fetal epiphyseal cartilage cells, particularly in hypertrophic chondrocytes of growth plates. Though neither the protein nor the mRNA were identified in a variety of other connective and nonconnective tissues, an unexpected finding was the expression of BSP in the trophoblast cells of placenta. These findings show that BSP is primarily an osteoblast-derived component of the bone matrix expressed at late stages of differentiation. We have also found that osteoclasts produce BSP, possibly as a mediator of cell attachment to bone.

Animals↗
PubMed1988

A human development intervention in the Philippines: effect on child morbidity.

The pilot phase of a human development intervention in the Philippines focused on improving child health. Selected household practices which influence health were targeted for modification to reduce the incidence of child morbidity. Completion rates of 69.5% of recommended activities led to a decrease of 70.0% of reported diarrhea and fever. Local health leaders and promoters were involved in providing administration and instruction, which served to increase local problem-solving skills and self-reliance. Essential components of an effective intervention are identified.

Child, Preschool↗
PubMed1986

Characterization of microsomal ATPases from developing human placenta.

Activities and some properties of microsomal ATPases have been studied in developing human placenta. The enzyme activities (Na+ + K+ + Mg2+, Mg2+, and Ca2+ dependent) in the placenta increase steadily with gestational age until the 18th to 21st week, and decrease in the second half of pregnancy. Mg2+-dependent and Na+ + K+ + Mg2+-dependent ATPases possess nearly the same Km (apparent) for ATP, while the Ca2+-dependent enzyme shows a different one. Mg2+-dependent ATPase shows higher substrate affinity than Ca2+-dependent ATPase, although the Vmax of the Mg2+-dependent enzyme is lower than that of the latter. However, for each enzyme, the Km remains almost constant and Vmax varies during ontogenic development. Vmax of the enzymes decline at term. The enzymes are heat-labile, unaffected by amino acids, namely, L-phenylalanine, L-leucine, and L-tryptophan, and deoxycholate inhibits the enzyme activities by about 50%.

Adenosine Triphosphatases↗
PubMed1990

Pulmonary elastic fibers in normal human development and in pathological conditions.

Normal human pulmonary elastic fiber development and development in some pathological conditions were examined using elastic stains by light microscopy, electron microscopy, and immunohistochemistry. In normal development elastic fibers, composed mainly of microfibrils, first appeared around primitive bronchioles at 10 weeks of gestation. As they matured, their appearance became more amorphous, and they extended into the peripheral alveolar walls. Development of elastic fibers was retarded in the hypoplastic lungs of the oligohydramnios syndrome, diaphragmatic hernia, and hydrops fetalis. Elastic development was also retarded in congenital pulmonary lymphangiectasia and in focal areas of lungs with pulmonary dysplasia. Distribution of well-developed elastic fibers was found around the dilated bronchioles and alveoli in cases of congenital cystic adenomatoid malformation and extralobar pulmonary sequestration. Elastic fibers were distributed irregularly and unevenly in the lungs of bronchopulmonary dysplasia and ventilated cases of Wilson Mikity syndrome. In addition, four very immature infants who had progressively deteriorating respiratory function showed an almost total lack of elastic fibers in their alveolar walls.

Chronic Disease↗
PubMed1992

Localisation of endothelin like immunoreactivity in adult and developing human gut.

The distribution of immunoreactivity for the potent vasoconstrictor endothelin-1 was studied in adult and developing human gut using antisera to endothelin-1 (1-21) and the C terminus of big endothelin-1. The coexistence of these peptides with other neuropeptides was investigated using comparative immunocytochemistry. Endothelin-1 like immunoreactivity was detected in extracts of adult (range 20-60 fmol/g wet weight) and fetal (33 fmol/g) gastrointestinal tract and was shown by chromatography to be the predominant isoform of endothelin present in both. It was localised by immunocytochemistry to ganglion cells in the submucous and myenteric plexuses and to scattered nerves, whereas big endothelin-1 like immunoreactivity was found in the submucous plexus only. Colocalisation studies showed immunoreactivity for both endothelin-1 and vasoactive intestinal peptide in the same ganglion cells of the submucous plexus. Although endothelin-1 immunoreactivity was not detected by immunocytochemistry in the fetal human gut until the 32nd week of gestation, big endothelin-1 was found as early as 11 weeks in the developing neural structures and epithelial cells. The latter were shown to be endocrine cells by their immunoreactivity for chromogranin. Our results indicate that endothelin is a neuropeptide found in adult human gut which shows transient expression in endocrine cells during development.

Adult↗
PubMed1987

S-100 protein in Schwann cells of the developing human peripheral nerve. An immunohistochemical study.

From approximately 7 weeks gestational age in developing human peripheral nerve, as in adult nerve, S-100 protein was found to be expressed solely and uniformly by Schwann cells associated with axons. In embryos younger than 7 weeks S-100 was much less constant and many cells did not show clear staining. The trigger for the initial appearance of the protein at around this age remains unclear although a relationship of S-100 expression in Schwann cells to close axonal contact is suggested. The value of S-100 protein in distinguishing Schwann cells from perineurial cells in normal nerves and nerve sheath tumours remains unclear.

Embryo, Mammalian↗
PubMed1990

Analysis of major histocompatibility complex gene products in tissues isolated from the developing human nervous system.

We have examined the expression of the major histocompatibility complex (MHC) class I and II gene products in the developing human fetal peripheral nervous system. As determined by RNA blot hybridization analysis, MHC class I RNA was readily detectable in extracts prepared from dorsal root ganglia (DRG) obtained from aborted human fetal material. However, utilizing similar methodology, it was not possible to detect MHC class II RNA. In conjunction with these studies, expression of MHC class I and II proteins in primary human fetal DRG tissue was examined by fluorescence-activated flow cytometry and protein immunoblotting. Consistent with the detection of MHC-specific RNA, the accumulation of MHC class I-specific protein was readily detectable in human fetal DRG neural cell populations with little, if any, accumulation of MHC class II-specific protein evident. These studies suggest that MHC gene products may be expressed early in the development of the human nervous system resulting in the generation of specific immunocompetent neural cell populations.

Flow Cytometry↗
PubMed1989

Histochemical study of the differentiation of microglial cells in the developing human cerebral hemispheres.

Applying nucleoside diphosphatase (NDPase) histochemistry, the appearance and differentiation of microglial cells in the developing human cerebral hemispheres were investigated by light and electron microscopy. In the pallium of the 38 days old human embryo, a few round NDPase-positive cells (round cells) were observed in the expanding zone. Although distinct blood vessels had not yet formed within the wall of the pallium, some cellular elements resembling haemopoietic cells were noticed in the expanding zone. In the 51 days old fetus, blood vessels displaying NDPase activity were seen in the mantle and marginal layers, and some invaded the matrix. Several round NDPase-positive cells were distributed, mainly around the vascular sprouts (primitive blood vessels) in the matrix. In the marginal layer, NDPase-positive cells exhibiting short cytoplasmic processes were encountered (poorly ramifying cells). In the 58, 66 and 82 days old fetuses, the round NDPase-positive cells were seen mainly in the matrix or subcortical layer where vascular sprouts were conspicuous and the poorly ramifying cells were in the subcortical and marginal layers. In the two latter fetuses, NDPase-positive cells showing long highly ramifying cytoplasmic processes (highly ramifying cells) were noted mainly in the marginal layer and sometimes in the subcortical layer. In the 5 months old fetuses, numerous NDPase-positive cells were distributed in the mantle, subcortical and marginal layers, and most of them appeared to belong to the populations of the poorly or highly ramifying cells. On the basis of the ultrastructural features, the round cells and highly ramifying cells were regarded as amoeboid cells and microglial cells, respectively. These findings suggest that at least some amoeboid cells are transformed into microglial cells via the stages of poorly ramifying microglial cells, and also that, in the human cerebral hemispheres, appearance of the microglial elements is closely related with vascularisation, especially in the early developmental stages.

Brain↗
PubMed1989

Studies on copper-zinc superoxide dismutase expression in developing human liver and kidney.

CuZn superoxide dismutase levels were found to be high in developing human kidney and liver compared to some other tissues including lung. In kidney, the enzyme was expressed in proximal and distal tubules, loop of Henle and collecting tubules and after 35 weeks of gestation it appeared to be distributed basally in proximal cells and luminally in distal cells. Glomerular structures were generally negative. CuZn superoxide dismutase was widely expressed in developing liver, with hepatocytes and bile duct epithelium demonstrating positivity. The low level of expression of CuZn superoxide dismutase in the glomerulus compared with the tubules was not expected since intrinsic glomerular cells demonstrate greater production of reactive oxygen species in response to some stimuli than do tubular cells. Expression of this enzyme may be determined by the need to generate hydrogen peroxide.

Cytosol↗
PubMed1988

Behavioral research toward prevention of childhood injury. Report of a workshop sponsored by The National Institute of Child Health and Human Development, Sept 3-5, 1986.

At a recent workshop sponsored by the National Institute of Child Health and Human Development, Bethesda, Md, injury and child behavior researchers recommended continued expansion of both directed research on control of specific injuries and basic research on mechanisms that underlie many or all injuries. Prevention of injuries that are not amenable to environmental control will require change in human behavior. Important research questions to address this goal include the following: How do identified risk factors influence the occurrence of injuries? How do children learn behaviors that alter the rate of injury? How do child developmental factors contribute to safety and injury? Innovative methods are needed, such as measure of environmental hazards, exposure to risk, and precursors of serious injuries. These approaches expanded by a broadened base of investigators should help reduce childhood mortality and morbidity due to injuries.

Adolescent↗
PubMed1991

Intelligence at six years in relation to neonatal bilirubin levels: follow-up of the National Institute of Child Health and Human Development Clinical Trial of Phototherapy.

Results of the National Institute of Child Health and Human Development Randomized Controlled Trial of Phototherapy were examined for the relationship of neonatal bilirubin level to neurological and developmental outcome at 6-year follow-up. This analysis focused on 224 control children with birth weight of less than 2000 g. Bilirubin levels were maintained below previously specified levels by the use of exchange transfusion only (24%). Rates of cerebral palsy were not significantly higher for children with elevated maximum bilirubin level than for those whose level remained low. No association was evident between maximum bilirubin level and IQ (Full Scale, Verbal, or Performance) by simple correlation analysis (r = -.087, P = .2 for Full Scale) or by multiple linear regression adjusting for factors that covary with IQ (beta = -.15, P = .58). IQ was not associated with mean bilirubin level, time and duration of exposure to bilirubin, or measures of bilirubin-albumin binding. Thus, over the range of bilirubin levels permitted in this clinical trial, there was no evidence of bilirubin toxicity to the central nervous system. Measures used to control the level of bilirubin in low birth weight neonates appear to prevent effectively the risk of bilirubin-induced neurotoxicity.

Bilirubin↗
PubMed1979

Effects of the vestibular system on human development, part 2: Effects of vestibular stimulation on mentally retarded, emotionally disturbed, and learning-disabled individuals.

In Part 1 of this two-part series, studies concerned with the effects of vestibular stimulation on human development and function were reviewed and some implications for therapy were suggested. In Part 2, three categories of dysfunction with possible links to the vestibular system are discussed. Studies in the category of mental retardation evaluate motor development and sensory preference. Possible vestibular associations with emotional disturbance are examined by review of studies concerned with etiology, motor activity, speech, and clinical observations. A brief review of studies concerned with early identification and speech and language factors of learning-disabled children constitutes the third category. Interpretations are drawn and some implications for therapy are made.

Affective Symptoms↗
PubMed1990

Scientist-administrators at the National Institute of Child Health and Human Development as contributors to the scientific enterprise.

At the National Institute of Child Health and Human Development (NICHD), as in other government research supporting agencies, scientist-administrators who are "program staff" work to accomplish their organization's set of research priorities using established mechanisms for supporting research. At the same time, the definition of their work is given to their interpretation, which, in turn, is guided by their understanding of their scientific discipline and their commitment to it. The tension that may arise between the organization-guided role and the science-guided role is more apparent than real because the major responsibility of "program staff" within the Institute is to cultivate a grant portfolio addressing scientific issues relevant to the mission of the Institute and exemplifying the most advanced research concepts and methodologies. When the overlap between the mission of the Institute and the direction of science is small, the push to increase it leads to new and imaginative solutions that benefit both the Institute and the science.

Administrative Personnel↗
PubMed1991

An immunohistochemical study of bronchial cells producing surfactant protein A in the developing human fetal lung.

A study on immunohistochemical localization of pulmonary surfactant protein A (SP-A) in the developing human fetal lung was performed using a monoclonal antibody, PE10, against human SP-A. At 21 weeks of gestation, a few bronchial cells positive to PE10 were observed to be scattered in the main and segmental bronchi. The number of these cells appears to increase until the 32nd week of gestation, and then decrease thereafter, almost disappearing by 39 weeks. On the other hand, alveolar type II cells and Clara cells positive to PE10 began to appear at 29 weeks, increase in number until around 39 weeks, and remain constant throughout adulthood. A few bronchial glandular cells positive to PE10 were still noticed in the fetal lung. This is the first report of the presence of SP-A-containing cells in the fetal lung. This is the first report of the presence of SP-A-containing cells in the human fetal bronchial epithelium (not Clara cells in the terminal bronchiolus), proving the regularity of the sequential distribution of SP-A-containing cells in the bronchoalveolar system during pulmonary development.

Aged↗