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At least 1,099 records · Page 61Linked to original sources
PubMed2005

Aplasia cutis congenita of the scalp: how much therapy is necessary in large defects?

AIM: To show that local antibiotic management and a regular inspection of aplasia cutis congenita of the skull can give an excellent result. METHOD: This case reports a girl born with aplasia cutis congenita of the skull presenting with a large aplasia of the epidermis, dermis, subcutaneous tissue and galea, including a bone defect without any additional risk factor, e.g. early eschar formation, cerebrospinal fluid leakage or uncommon dural blood vessels. RESULTS: A primarily conservative treatment with local wet and antibiotic dressings together with a systemic antibiotic treatment for the first 2 wk led to an excellent result and thus prevented untimely operative and peri-operative procedures. CONCLUSIONS: Here we have shown that conservative treatment might be an option, even if the wound diameter is greater than 1 cm(2), to prevent infants from any untimely operative procedure with an elevated operative risk if any additional risk factors are excluded.

Anti-Bacterial Agents↗
PubMed2006

A comprehensive study of the spatial and temporal expression of the col5a1 gene in mouse embryos: a clue for understanding collagen V function in developing connective tissues.

Collagen V is a quantitatively minor component of collagen I fibrils and the defective product of classic Ehlers-Danlos syndrome (EDS). To provide new insights into its embryonic function, a continuous evaluation of the expression pattern of proalpha1(V), a chain common to all collagen V molecular forms, was performed by in situ hybridization of developing mouse from 7.5 days after conception (dpc) to birth. Proalpha1(V) transcripts were first detected at 8.5 dpc, signals being considerably augmented at 16.5 dpc and declining at birth. Hybridization signals were, at first, exclusively detected in the dorsal aorta wall, heart, and adnexa. At 10.5 dpc, col5a1 expression was found in the heart, dorsal aorta wall, branchial arches, mesonephrotic tubules, and intestinal mesenchyme and coincided with proalpha1(I) developmental expression. Later stages exhibited an intense signal in more restricted regions, notably the skin, the bones and vertebral column, the cornea, the tendons and ligaments, the peritoneal membranes, the umbilical cord, and the salivary gland. The data revealed the important contribution of collagen V to the development of functional connective tissues. Proalpha1(V) signals were exclusively detected in the flattened cells of the surface ectoderm at 10.5 dpc. By 12.5 dpc, when cells had become cuboidal, the signal switched to the dermal fibroblasts. Thus, type V collagen appears to contribute to epidermis differentiation. Our data also suggest that collagen V participates in bone formation and/or mineralization and in the renewal of stromal cells in the cornea. The results underscore the role of collagen V in developing embryos and provide important clues for analyzing the phenotype of mouse models for EDS.

Animals↗
PubMed2005

Gene therapy for autosomal dominant disorders of keratin.

Dominant mutations that interfere with the assembly of keratin filaments cause painful and disfiguring epidermal diseases like pachyonychia congenita and epidermolysis bullosa simplex. Genetic therapies for such diseases must either suppress the production of the toxic proteins or correct the genetic defect in the chromosome. Because epidermal skin cells may be genetically modified in tissue culture or in situ, gene correction is a legitimate goal for keratin diseases. In addition, recent innovations, such as RNA interference in animals, make an RNA knockdown approach plausible in the near future. Although agents of RNA reduction (small interfering RNA, ribozymes, triplex oligonucleotides, or antisense DNA) can be delivered as nucleotides, the impermeability of the skin to large charged molecules presents a serious impediment. Using viral vectors to deliver genes for selective inhibitors of gene expression presents an attractive alternative for long-term treatment of genetic disease in the skin.

Animals↗
PubMed1995

Fusion from myoblasts to myotubes is dependent on the rolling stone gene (rost) of Drosophila.

The development and differentiation of the body wall musculature in Drosophila are accompanied by changes in gene expression and cellular architecture. We isolated a Drosophila gene, termed rolling stone (rost), which, when mutated, specifically blocks the fusion of mononucleated cells to myotubes in the body wall musculature. beta 3 tubulin, which is an early marker for the onset of mesoderm differentiation, is still expressed in these cells. Gastrulation and mesoderm formation, as well as the development of the epidermis and of the central and peripheral nervous systems, appear quite normal in homozygous rolling stone embryos. Embryonic development stops shortly before hatching in a P-element-induced mutant, as well as in 16 EMS-induced alleles. In mutant embryos, other mesodermal derivatives such as the visceral mesoderm and the dorsal vessel, develop fairly normally and defects are restricted to the body wall musculature. Myoblasts remain as single mononucleated cells, which express muscle myosin, showing that the developmental program of gene expression proceeds. These myoblasts occur at positions corresponding to the locations of dorsal, ventral and pleural muscles, showing that the gene rolling stone is involved in cell fusion, a process that is independent of cell migration in these mutants. This genetic analysis has set the stage for a molecular analysis to clarify where the rolling stone action is manifested in the fusion process and thus gives insight into the complex regulating network controlling the differentiation of the body wall musculature.

Animals↗
PubMed2000

Costello syndrome: report of six patients including one with an embryonal rhabdomyosarcoma.

UNLABELLED: Costello syndrome was first described in 1971. Besides papillomata, which were part of the initial description, patients tends to develop benign tumours of ectodermal origin. Aetiology is yet unknown but it is supposed to be the result of a sporadic dominant mutation. We report six patients with typical clinical findings and emphasise the importance of cardiac manifestations and the tendency to develop tumours. One patient developed an embryonal rhabdomyosarcoma, the occurrence of which has been reported twice before in patients with Costello syndrome. CONCLUSION: There might be a causal link between the development of rare tumours and this genetic disorder which may provide a new clue concerning the identification of the gene involved in Costello syndrome.

Cardiomyopathy, Hypertrophic↗
PubMed1996

[The Adams-Oliver syndrome in Spain: the epidemiological aspects].

Adams and Oliver (1945) described a family with several affected individuals with terminal transverse limb reduction defects and aplasia cutis congenita of the scalp. The clinical expression was highly variable and the pattern showed a family transmission compatible with an autosomal dominant condition. Since the first description, many cases have been published with this pattern of anomalies being known as Adams-Oliver syndrome. Here we present five affected patients ascertained among the 21,835 malformed infants registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC). Epidemiological aspects and clinical features of the patients are presented and compared with data from the literature.

Abnormalities, Multiple↗
PubMed2003

Clinical and molecular analysis of nine families with Adams-Oliver syndrome.

Adams-Oliver syndrome (AOS) is defined by the combination of limb abnormalities and scalp defects, often accompanied by skull ossification defects. We studied nine families affected with AOS, eight of which have not been clinically described before. In our patients, scalp abnormalities were most often found, followed by limb and skull defects. The most common limb abnormalities appeared to be brachydactyly, syndactyly of toes 2 and 3 and hypoplastic toenails. Additional features observed were cutis marmorata telangiectatica congenita, cryptorchidism and cardiac abnormalities. In an attempt to identify the disease-causing mutations in our families, we selected two genes, ALX4 and MSX2, which were considered serious candidates based on their known function in skull and limb development. Mutation analysis of both genes, performed by direct sequencing, identified several polymorphisms, but no disease-causing mutations. Therefore, we can conclude that the AOS in our set of patients is not caused by mutations in ALX4 or MSX2.

DNA Mutational Analysis↗
PubMed1978

[Study of the formation and the normal and pathological evolution of the eye neural primordium (author's transl)].

The analysis of duplicate embryos, cyclops and colobomic fissure defects show that: 1. - optic vesicle and colobomic fissure are inducted by the prechordal plate. The combined inductive influence of prechordal plate and notochord carry eye absence out; 2. - initial failure of the colobomic fissure is always associated with retina folds and produce lens, vitreous and optic nerve anomalies; 3. - colobomic fissure is one indispensable anatomic structure to the optic fiber migration from the retina to the optic pedicle. Retina cutting in 4 days old chick embryos determine the disappearing of the pedicle cells. Contact between the optic fiber and the pedicle cells determine the glial cells differentiation. The colobomic fissure is a very important period of the eye evolution and the eye organisation.

Animals↗
PubMed2025

Novel compound heterozygous DOCK6 variants expand the mutational spectrum in prenatal diagnosis of Adams-Oliver syndrome 2.

BACKGROUND: Adams-Oliver syndrome (AOS) is a rare developmental disorder, and the DOCK6 gene is an identified AOS gene. This report highlights the prenatal diagnosis of AOS-2 by ultrasonography and genetic testing. METHODS: A growth-restricted fetus with bilateral ventriculomegaly, paraventricular calcifications, and ventricular septal defect underwent trio-whole-exome sequencing (trio-WES). Functional validation of the splice-altering variant was performed via minigene assays and protein structural modeling. RESULTS: Trio-WES revealed compound heterozygous DOCK6 variants: a paternal frameshift (c.3190_3191del; p. Leu1064Valfs60) and a maternal splice-site variant (c.3241-1G > T). Minigene assays demonstrated that c.3241-1G > T caused intron 26 retention (486 bp), introducing a premature termination codon (p. Val1081Glufs37). Structural modeling confirmed the loss of critical DHR2 domains in both truncated proteins. CONCLUSIONS: This study expands the mutational spectrum of DOCK6 and underscores the importance of combining prenatal imaging with functional genomics for early diagnosis of AOS2.

Adult↗
PubMed2003

Caspase-3 mediates retinoid-induced apoptosis in the organogenesis-stage mouse limb.

BACKGROUND: Caspases are key mediators in the regulation and execution of apoptosis, a crucial part of the morphogenetic process during limb development. Caspase-8 and -9 are upstream caspases. Caspase-8 mediates the extrinsic pathway of apoptosis triggered by signaling through TNF-R1 family receptors. Caspase-9 is activated during the intrinsic pathway downstream of mitochondria. Caspase-3 is an effector caspase that initiates degradation of the cell in the final stages of apoptosis. Vitamin A is a potent teratogen that causes limb reduction defects in embryos exposed during organogenesis. Previous in vitro studies have shown that exposure of the organogenesis-stage murine limb to vitamin A results in excessive levels of apoptosis. The goal of this work was to characterize the involvement of caspase-3, -8, and -9, as well as cytochrome-c release from the mitochondria, in the apoptotic cascade induced by vitamin A. METHODS: Limb buds from gestational day 12 CD-1 mice were cultured in a chemically defined medium in the absence or presence of vitamin A. Cultures were terminated after 6 days to examine the effect of the drug on gross morphology. Apoptosis was detected by TUNEL staining after culture for 24 hr. Caspase activation was determined by Western blotting and localized by immunohistochemistry of control and treated limbs. The release of cytochrome-c into the cytoplasm was assessed by Western blotting after cell-fractionation. RESULTS: Limbs cultured in the presence of vitamin A showed a dose-dependent growth reduction and dysmorphogenesis of the cartilaginous anlagen. Apoptosis was increased in the interdigital, anterior, and posterior marginal zones and in the apical ectodermal ridge. Western-blotting confirmed the presence of activated caspase-3 that increased with time in culture and vitamin A concentration. Cleaved caspase-3 immunoreactivity colocalized with TUNEL stained limb regions and increased dramatically with increasing drug concentrations. In contrast, procaspase-8 and -9 were not activated. Exposure to high concentrations of vitamin A did, however, increase cytoplasmic cytochrome-c, suggesting mitochondrial involvement. CONCLUSIONS: Caspase-3 is a key effector caspase in the apoptotic pathway induced by Vitamin A. While caspases-8 and -9 are not responsible for the activation of caspase-3 in response to the drug, cytochrome-c release from mitochondria may play an upstream role.

Animals↗
PubMedDate not supplied

Modified overdentures for the management of oligodontia and developmental defects.

A technique for the construction of complete dentures over unaltered natural teeth has been described and illustrated for three different situations. The procedure is straightforward and simple and varies only slightly from conventional overdenture construction. The technique offers several advantages for a patient who wishes to keep the remaining natural teeth unaltered but who requires significant functional or esthetic improvement. Since the teeth are unaltered, any type of future treatment may be considered at any time without being compromised. This is an important factor to consider for the young patient. The cost, when compared to the fabrication of a fixed or cast removable prosthesis, is significantly less, while still providing acceptable esthetics and function. The versatility of this procedure allows its use in a number of situations which are not amenable to more complicated treatment methods.

Adolescent↗
PubMed1993

Control of imaginal cell development by the escargot gene of Drosophila.

Mutations in the escargot (esg) locus, which codes for a zinc-finger-containing protein with similarity to the product of the snail gene, cause a variety of defects in adult structures such as loss of abdominal cuticle and malformation of the wings and legs. esg RNA is expressed in wing, haltere, leg and genital imaginal discs and in abdominal histoblast nests in the embryo. Expression in imaginal tissues is also found in third instar larvae. In esg mutant larvae, normally diploid abdominal histoblasts replicate their DNA without cell division and become similar in appearance to the polytene larval epidermal cells. A similar phenotype was also found in imaginal discs of larvae mutant for both esg and the Drosophila raf gene. These results suggest that one of the normal functions of esg may be the maintenance of diploidy in imaginal cells.

Abdomen↗
PubMed1994

Mutations in some Polycomb group genes of Drosophila interfere with regulation of segmentation genes.

Mutations in several Polycomb (Pc) group genes cause maternal-effect or zygotic segmentation defects, suggesting that Pc group genes may regulate the segmentation genes of Drosophila. We show that individuals doubly heterozygous for mutations in polyhomeotic and six other Pc group genes show gap, pair rule, and segment polarity segmentation defects. We examined double heterozygous combinations of Pc group and segmentation mutations for enhancement of adult and embryonic segmentation defects. Posterior sex combs and polyhomeotic interact with Krüppel and enhance embryonic phenotypes of hunchback and knirps, and polyhomeotic enhances even-skipped. Surprisingly, flies carrying duplications of extra sex combs (esc), that were heterozygous for mutations of even-skipped (eve), were extremely subvital. Embryos and surviving adults of this genotype showed strong segmentation defects in even-numbered segments. Antibody studies confirm that expression of eve is suppressed by duplications of esc. However, esc duplications have no effect on other gap or pair rule genes tested. To our knowledge, this is only the second triplo-abnormal phenotype associated with Pc group genes. Duplications of nine other Pc group genes have no detectable effect on eve. Expression of engrailed (en) was abnormal in the central nervous systems of most Pc group mutants. These results support a role for Pc genes in regulation of some segmentation genes, and suggest that esc may act differently from other Pc group genes.

Abdomen↗
PubMed2005

Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull.

Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.

Animals↗
PubMed1999

Drosophila center divider gene is expressed in CNS midline cells and encodes a developmentally regulated protein kinase orthologous to human TESK1.

The Drosophila center divider gene (cdi) was isolated in an enhancer trap screen undertaken to identify genes involved in embryonic central nervous system (CNS) midline cell development. Three independent lines with P-element insertions at 91F were analyzed that all showed prominent beta-galactosidase expression in the CNS midline precursor cells and other cell types. Null mutations were created by imprecise P-element excision and shown to be larval lethal, although no severe CNS defects were observed in mutant embryos. The DNA surrounding the sites of insertion was cloned and found to contain a transcription unit that was dynamically expressed in a pattern corresponding to the enhancer trap line beta-galactosidase expression. Sequencing of cDNA clones revealed that the cdi gene encodes a 1140-amino acid protein that is an ortholog of the mammalian testis-specific TESK1 protein kinase. This serine/threonine kinase is distinct from other protein kinases because of sequence differences in the residues conferring substrate specificity. The unique sequence is conserved in Cdi, suggesting that Cdi/TESK1 represents a novel class of signaling proteins.

Amino Acid Sequence↗
PubMed1998

The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2.

We report the embryonic phenotype of muscleblind (mbl), a recently described Drosophila gene involved in terminal differentiation of adult ommatidia. mbl is a nuclear protein expressed late in the embryo in pharyngeal, visceral, and somatic muscles, the ventral nerve cord, and the larval photoreceptor system. All three mbl alleles studied exhibit a lethal phenotype and die as stage 17 embryos or first instar larvae. These larvae are partially paralyzed, show a characteristically contracted abdomen, and lack striation of muscles. Our analysis of the somatic musculature shows that the pattern of muscles is established correctly, and they form morphologically normal synapses. Ultrastructural analysis, however, reveals two defects in the terminal differentiation of the muscles: inability to differentiate Z-bands in the sarcomeric apparatus and reduction of extracellular tendon matrix at attachment sites to the epidermis. Failure to differentiate both structures could explain the partial paralysis and contracted abdomen phenotype. Analysis of mbl expression in embryos that are either mutant for Dmef2 or ectopically express Dmef2 places mbl downstream of Dmef2 function in the myogenic differentiation program. mbl, therefore, may act as a critical element in the execution of two Dmef2-dependent processes in the terminal differentiation of muscles.

Animals↗
PubMed1995

Suppressor of Hairless is required for signal reception during lateral inhibition in the Drosophila pupal notum.

Suppressor of Hairless (Su(H)) activity is zygotically required in larval imaginal discs for the singling out of adult sense organ precursor (SOP) cells: loss of Su(H) function results in too many proneural cluster cells adopting the SOP fate, while overexpression of the Su(H) protein prevents SOP specification. Su(H) null mutant alleles are recessive lethal at the late larval and early pupal stages. The development of Su(H) mutant cells in pupae was therefore studied in somatic clones. Clonal analysis first showed that Su(H) is required for the regular spacing of microchaete precursor cells, as clusters of mutant SOPs were detected at positions where singled out sense organ cells are normally found. Second, Su(H) mutant SOPs produced neuron-like cells, consistent with a late defect in Notch (N) signalling. Third, a careful cell-by-cell analysis of clone borders showed that Su(H) mutant cells may adopt the SOP fate even when directly adjacent to wild-type cells. Finally, quantitative clone border analysis indicates that the relative level of Su(H) gene dosage appears to bias the selection of the future SOP: cells with a higher level of Su(H) activity are more likely to adopt the epidermal fate. These results show that notum cells strictly require Su(H) activity for receiving the lateral inhibitory signal. Thus, the DNA-binding protein encoded by the Su(H) gene may act downstream of the N receptor to implement the epidermal, non-SOP fate.

Animals↗
PubMed2003

Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm.

FGF4, a member of the fibroblast growth factor (FGF) family, is absolutely required for periimplantation mouse development, although its precise role at this stage remains unknown. The nature of the defect leading to postimplantation lethality of embryos lacking zygotic FGF4 is unclear and little is known about downstream targets of FGF4-initiated signaling within the various cellular compartments of the blastocyst. Here we report that postimplantation lethality of Fgf4(-/-) embryos is unlikely to reflect strictly mitogenic requirements for FGF4. Rather, our results suggest that FGF4 is required to maintain trophectoderm and primitive endoderm identity at embryonic day 4.5. This result is consistent with the reported in vitro activity of FGF4 in maintaining trophoblast stem cells and with the requirement for receptor tyrosine kinase signaling in primitive endoderm formation. Thus, postimplantation lethality of Fgf4(-/-) embryos likely results from the failure of proper differentiation and function of extraembryonic cell types.

Animals↗