A novel intermediate filament-associated protein, NAPA-73, that binds to different filament types at different stages of nervous system development.

The antigen recognized by the E/C8-monoclonal antibody is expressed in various avian embryonic cell types known also to express neurofilament (NF) immunoreactivity. To determine whether the E/C8-antigen corresponds to any of the known NF components, we compared their subcellular locations, immunocross-reactivities, and electrophoretic behaviors. We found that the E/C8-antibody binds to NF bundles in electron microscope preparations of neurons, but does not correspond to any of the known NF proteins by immunological or electrophoretic criteria. Immunoadsorption with the monoclonal antibody resulted in co-purification of a 73,000-D protein with one of the known NF proteins in homogenates from 20-d embryonic chick brains, but with vimentin intermediate filament protein in similarly prepared homogenates from 4-d embryonic chicks. We suggest that the E/C8-antigen is an intermediate filament-associated protein that binds to different filament types at different stages of development. We have named it NAPA-73, an acronym for neurofilament-associated protein, avian-specific, 73,000 D, on the basis of its binding specificity in mature neurons.

A subpopulation of cultured avian neural crest cells has transient neurogenic potential.

Neural crest cells of vertebrate embryos produce neurons, glia, pigment cells, and connective tissue in vivo and in vitro. To test the developmental potential of apparently undifferentiated crest cells, we have used the monoclonal antibody A2B5, which recognizes a cell surface glycolipid characteristic of neurons, to identify and immunoablate a subpopulation of cultured avian neural crest cells with a neuronal phenotype. Our results indicate that a limited neurogenic precursor subpopulation is present in cultures of avian neural crest cells and that the fate of this subpopulation can be influenced by environmental conditions arising when dispersal of neural crest cells is delayed.

NUMB localizes in the basal cortex of mitotic avian neuroepithelial cells and modulates neuronal differentiation by binding to NOTCH-1.

The importance of lateral inhibition mediated by NOTCH signaling is well demonstrated to control neurogenesis both in invertebrates and vertebrates. We have identified the chicken homolog of Drosophila numb, which suppresses NOTCH signaling. We show that chicken NUMB (c-NUMB) protein is localized to the basal cortex of mitotic neuroepithelial cells, suggesting that c-NUMB regulates neurogenesis by the modification of NOTCH signaling through asymmetrical cell division. Consistent with this suggestion, we show (1) that c-NUMB interferes with the nuclear translocation of activated c-NOTCH-1 through direct binding to the PEST sequence in the cytoplasmic domain of c-NOTCH-1 and (2) that c-NUMB interferes with c-NOTCH-1-mediated inhibition of neuronal differentiation.

Development of the neural crest.

Mutations that affect the morphogenetic behaviour and differentiation of neural crest-derived cells in mouse embryos have been shown to alter genes that code for growth factors or growth factor receptors. Identification of these and other gene products provide opportunities to understand when and how developmentally distinct embryonic cell populations arise, and how interactions between localized developmental cues and responsive cell subpopulations can be modulated during development.

Mouse mutants provide new insights into the role of extracellular matrix in cell migration and differentiation.

Migratory cell populations in the developing embryo disperse, localize and eventually differentiate in environments rich in extracellular matrix material. The extracellular matrix provides both a substratum for migration and a source of differentiative cues for the developing cells. Mutations in mice and other animals that alter embryonic interstitial environments are now providing information about the role of the extracellular matrix in these early developmental processes.

The respiratory system of the marine bacterium Beneckea natriegens. I. Cytochrome composition.

(1) The cytochrome composition of Beneckea natriegens grown under aerobic conditions has been examined. (2) Cell-free extracts obtained by sonication were separated into particulate and supernatant fractions by centrifugation at 150,000 x g. (3) The particulate fraction contained cytochromes b562, b557, b or c554, c549.5, c547, and low concentrations of cytochromes a1 and a2. (Subscripts refer to the wavelength optima of the b and c type cytochrome alpha-peaks in low temperature (77 degrees K) difference spectra.) Also present was a second cytochrome c549.5 which is capable of binding carbon monoxide (cytochrome c549.5(CO)) and which is also found in the supernatant fraction. (4) Reduced plus CO minus reduced difference spectra had spectral peaks corresponding to cytochrome o and two c type cytochromes, and low concentrations of cytochromes a1 and a2. (5) Action spectra for the relief of CO inhibition showed that cytochrome a2, the CO binding c type cytochrome(s) and possibly cytochrome o, but not cytochrome a1, had oxidase activity in intact cells. In cells grown to the late stationary phase, when cytochrome a2 and particularly cytochrome a1 were induced, the primary functual oxidase was cytochrome a1.

Temperature-sensitive mutations that cause stage-specific defects in Zebrafish fin regeneration.

When amputated, the fins of adult zebrafish rapidly regenerate the missing tissue. Fin regeneration proceeds through several stages, including wound healing, establishment of the wound epithelium, recruitment of the blastema from mesenchymal cells underlying the wound epithelium, and differentiation and outgrowth of the regenerate. We screened for temperature-sensitive mutations that affect the regeneration of the fin. Seven mutations were identified, including five that fail to regenerate their fins, one that causes slow growth during regeneration, and one that causes dysmorphic bumps or tumors to develop in the regenerating fin. reg5 mutants fail to regenerate their caudal fins, whereas reg6 mutants develop dysmorphic bumps in their regenerates at the restrictive temperature. Temperature-shift experiments indicate that reg5 and reg6 affect different stages of regeneration. The critical period for reg5 occurs during the early stages of regeneration before or during establishment of the blastema, resulting in defects in subsequent growth of the blastema and failure to differentiate bone-forming cells. The critical period for reg6 occurs after the onset of bone differentiation and during early stages of regenerative outgrowth. Both reg5 and reg6 also show temperature-sensitive defects in embryonic development or in ontogenetic outgrowth of the juvenile fin.

Foot dermatitis in children.

Redness and scaling of the feet in prepubertal children is likely to represent a skin disease other than tinea pedis. If the dermatitis involves the dorsum of the feet, allergic contact dermatitis is a likely cause. In this study, 8/19 (42%) children with involvement of the dorsum of the feet had clinically relevant positive patch tests related to shoe allergens. All who avoided the allergens remained free of disease on a 2-year follow-up examination. Those children with dermatitis on the weight-bearing surface of the foot (juvenile plantar dermatosis) did not have positive patch tests (P = .15).

Diaper dermatitis: current concepts.

Diaper dermatitis may result from prolonged skin contact with wetness and bacteria. Ammonia plays no apparent role in the generation of diaper dermatitis. Candida albicans frequently contaminates a diaper dermatitis and should be considered present in any diaper dermatitis and should be considered present in any diaper dermatitis known to be present for longer than three days. Topical fluorinated glucocorteroids, boric acid, and mercury-containing preparations should be avoided in the diaper area because of their toxicity.

Prevalence of positive epicutaneous tests among infants, children, and adolescents.

We studied 314 otherwise healthy children younger than 18 years of age with epicutaneous testing, and found that 20% of those tested had at least one positive epicutaneous test result. Neomycin, nickel, and potassium dichromate were the most prevalent allergens detected in our study group. We found that sensitization occurred at less than 5 years of age for all but fragrance allergens. Aluminum chambers and the American Academy of Dermatology Patch Test Kit were found to be safe for use in infants, children, and adolescents.

A legacy of violence in nonorganic failure to thrive.

It is often postulated that a mother's past experiences influence her ability to function as a parent. If those past experiences involve her as a victim of abuse, what lies ahead for her offspring? We studied 59 mothers of children referred for nonorganic failure to thrive (NOFTT) to the University of Colorado Health Sciences Center and compared their abuse history with a group of 131 mothers of children with normal growth. The mothers of NOFTT children were younger but of the same socioeconomic groups as the comparison mothers. Mothers of NOFTT children had a significantly higher history of abuse when compared to the comparison group p < 0.001. A surprising 80% of mothers of NOFTT children reported they were victims of abuse. We alert clinicians to the likelihood that mothers of children with NOFTT may be victims of abuse and that successful treatment of the child depends upon treatment of the mother-child dyad.