Sphere-forming abilities in culture condition are considered a hallmark of cancer stem-like cells, which represents tumor cell invasiveness and stem-like characteristics. We aimed to show that the sphere-forming subpopulation of human malignant melanoma cell line WM-266-4 acts differently to zebrafish embryo extracts compared with their bulk counterpart. Spheres were maintained in neural stem cell culture conditions. The embryos of zebrafish at specific developmental stages were collected and the extracts were purified under 100 kDa. Spheres were treated with embyo extracts and proliferation assay and immunocytochemistry were conducted. Spheroid cells expressed nestin and epidermal growth factor receptor (EGFR) but not melanoma antigen recognized by T-cells (MART)1, indicating their stem-l...
Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivo analysis of glycinergic synaptic transmission has been pursued in zebrafish using...Full Text Available
Over the last decade, the use of the zebrafish as a genetic model has moved beyond the proof-of-concept for the analysis of vertebrate embryonic development to demonstrated utility as a mainstream...Full Text Available
Low membrane permeability is one of the major obstacles to the successful cryopreservation of zebrafish embryos. The aim of the present study was to explore if this could be overcome by yolk...Full Text Available
BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available
BackgroundGene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish...Full Text Available
The zebrafish is emerging as a prominent model system for studying the genetics of human development and disease. Genetic alterations that underlie each mutant model can exist in the form of...Full Text Available
During formation of the optic projection in astray/robo2 mutant zebrafish, optic axons exhibit rostro-caudal pathfinding errors, ectopic midline crossing and...Full Text Available
Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
Binding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand-activated EGFR is also rapidly internalized...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
The primary aim of this study was to develop a model system that uses epidermal cells (keratinocytes and accessory pigmented cells) cultured on a reconstituted basement membrane biomatrix for use in...Full Text Available
The immunogenicity of allogeneic cultured human epidermal keratinocytes (cHEKs) has been studied in several models with contradictory results. We studied human T-cell activation in an in vitro...Full Text Available
We review visually guided behaviors in larval zebrafish and summarise what is known about the neural processing that results in these behaviors, paying particular attention to the progress made in the last 2 years. Using the examples of the optokinetic reflex, the optomotor response, prey tracking and the visual startle response, we illustrate how the larval zebrafish presents us with a very promising model vertebrate system that allows neurocientists to integrate functional and behavioral studies and from which we can expect illuminating insights in the near future.
... electrocutaneous stimuli, and the nerve fibres innervating ... layer or at the epidermal-dermal interface. ... 2) Vestibular prosthesis and for limb prosthesis ...
BackgroundVisual acuity, the ability of the visual system to distinguish two separate objects at a given angular distance, is influenced by the optical and neuronal properties of...Full Text Available
Recently, we cloned purpurin cDNA as an upregulated gene in the axotomized fish retina. The retina-specific protein was secreted from photoreceptors to ganglion cell layer during an early stage of optic nerve regeneration in zebrafish retina. The purpurin worked as a trigger molecule for axonal regrowth in adult injured fish retina. During zebrafish development, purpurin mRNA first appeared in ventral retina at 2 days post-fertilization (dpf) and spread out to the outer nuclear layer at 3 dpf. Here, we investigated the role of purpurin for zebrafish retinal development using morpholino gene knockdown technique. Injection of purpurin morpholino into the 1-2 cell stage of embryos significantly inhibited the transcriptional and translational expression of purpurin at 3 dpf. In the purpurin mo...
BackgroundMutations that disrupt the conversion of prelamin A to mature lamin A cause the rare genetic disorder Hutchinson-Gilford progeria syndrome and a group of laminopathies....Full Text Available
The lipid composition of skin is important to a variety of functions served by this organ. Therefore, skin expresses multiple enzymes that synthesize and metabolize lipids. An important class of lipid...Full Text Available
During development, multipotent neural precursors give rise to oligodendrocyte progenitor cells (OPCs), which migrate and divide to produce additional OPCs. Near the end of embryogenesis and...Full Text Available
Somite boundary formation is crucial for segmentation of vertebrate somites and vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2 transposon-mediated...Full Text Available
Transient receptor potential (TRP) ion channels have been implicated in detecting chemical, thermal and mechanical stimuli in organisms ranging from mammals to Caenorhabditis elegans....Full Text Available
The recent introduction of several transposable elements in zebrafish opens new frontiers for genetic manipulation in this important vertebrate model. This review discusses transposable elements as...Full Text Available
BackgroundIn humans, myocardial infarction is characterized by irreversible loss of heart tissue, which becomes replaced with a fibrous scar. By contrast, teleost fish and urodele...Full Text Available
BackgroundVariation of gene number among species indicates that there is a general process of new gene origination. One of the major mechanism providing raw materials for the origin...Full Text Available
The neuronal networks in spinal cord can produce a diverse array of motor behaviors. In aquatic vertebrates such as fishes and tadpoles, these include escape behaviors, swimming across a range...Full Text Available
alpha-actinins are actin microfilament crosslinking proteins. Vertebrate actinins fall into two classes: the broadly-expressed actinins 1 and 4 (actn1 and actn4)...Full Text Available
Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited...Full Text Available
Various hypotheses have been proposed to explain the molecule processes of sarcomere assembly, partially due to the lack of systematic genetic studies of sarcomeric genes in an in vivo...Full Text Available
Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development....Full Text Available
Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous...Full Text Available
Zebrafish transgenesis is a powerful and increasingly common strategy to assay vertebrate transcriptional regulatory control. Several challenges remain, however, to the broader application of...Full Text Available
BackgroundGATA-2 is a transcription factor required for hematopoietic stem cell survival as well as for neuronal development in vertebrates. It has been shown that specific expression...Full Text Available
BackgroundThe genomic organisation of the Major Histocompatibility Complex (MHC) varies greatly between different vertebrates. In mammals, the classical MHC consists of a large number...Full Text Available
Vascular endothelial growth factor (VEGF) is a mitogen that is critically involved in vasculogenesis, angiogenesis, and hematopoiesis. However, what and how transcription factors participate in the regulation of vegf gene expression are not fully understood. Here we report the cloning and sequencing of the zebrafish vegf promoter which revealed that the promoter contains a number of bone morphogenetic protein (BMP)-activated Smad binding elements (SBE), implicating Smad1 and Smad5 in the regulation of BMP-induced expression of vegf. Electrophoretic mobility shift assays of adding recombinant Smad proteins to the SBE-containing DNA oligonucleotides that represent portions of zebrafish vegf promoter resulted in mobility shift of the oligonucleotides. These changes demonstrate potential interactions between Smad1/5 and the vegf promoter. Reporter activity assays using the wild-type or SBE-deleted vegf promoters to drive the luciferase reporter ...
Epidermal gamma delta T cells (γδ T) and Langerhans cells (LC) are immune cells altered by exposure to ultraviolet radiation (UVB), a powerful stressor resulting in immune suppression....Full Text Available
Epidermal growth factor (EGF) stimulates adenylyl cyclase in the heart via activation of the stimulatory GTP-binding protein Gs. Therefore, employing peptides corresponding to regions in the cytosolic...Full Text Available
Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to "2"3"9PuO_2- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)
Strategies to combine aspirated marrow cells with scaffolds to treat connective tissue defects are gaining increasing clinical attention and use. In situations such as large defects where initial...Full Text Available
Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available
Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2...Full Text Available
It is generally accepted that hypoxia and recovery from oxygen deprivation contribute to the breakdown and ulceration of human skin. The effects of these stresses on proliferation, differentiation...Full Text Available
Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions....Full Text Available
Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction...Full Text Available
A 72-year-old male presented with a large ulceroproliferative lesion over left gluteal region. After histopathological confirmation of squamous cell carcinoma, the lesion was excised with wide margins....Full Text Available
BackgroundThe epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand...Full Text Available
Objective: The aim of this study was to characterize using flow cytometry cultured human primary keratinocytes isolated from the epidermis and hair follicles by different methods. Methods:...Full Text Available
Glioblastoma, the most common malignant brain tumor, is among the most lethal and difficult cancers to treat. Although epidermal growth factor receptor (EGFR) mutations are frequent in glioblastoma,...Full Text Available
Normal mouse epidermis constitutively expresses prostaglandin-H synthase 1 (PGHS-1) but no PGHS-2. Acute inflammation and epidermal hyperplasia, (hyperplastic transformation), as evoked in adult mouse...Full Text Available
Activation of beta-adrenergic or muscarinic acetylcholine receptors expressed in transfected cells or epidermal growth factor receptors in human keratinocytes produces 15% to 200% changes in cellular...Full Text Available
Action potentials from the brain control the activity of spinal neural networks to produce, by as yet unknown mechanisms, a variety of motor behaviors. Particularly lacking are details on how identified descending neurons integrate diverse sensory inputs to generate specific locomotor patterns. We have examined the operations of the principal neurons in an intriguing midbrain nucleus, the nucleus of the medial longitudinal fasciculus (nMLF), in the larval zebrafish. The nMLF is the most rostral grouping of neurons that projects from the brain well into the spinal cord of teleost fishes, yet there is little direct physiological data available regarding its function. We report here that a distinct set of large, individually-identifiable neurons in nMLF (the MeL and MeM neurons) are activated...
The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and cornified layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, differentiation, and cell death. To determine genes responsible for initiating and maintaining a cornified epidermis, organotypic cultures comprised entirely of stratified KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array profile of submerged cultures containing KCs predominantly in a proliferative (relatively undifferentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct profile of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, differentiation, and cell death. ...
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...
Fish retinal ganglion cells (RGCs) can survive and regrow their axons after optic nerve injury. Injured RGCs express anti-apoptotic proteins, such as Bcl-2, after nerve injury; however, upstream effectors of this anti-apoptotic protein are not yet fully understood. Heat shock proteins (HSPs) play a crucial role in cell survival against various stress conditions. In this study, we focused on HSP70 expression in the zebrafish retina after optic nerve injury. HSP70 mRNA and protein levels increased rapidly 2.3-fold in RGCs by 1-6 h after injury and returned to control levels by 1-3 days. HSP70 transcription is regulated by heat shock factor 1 (HSF1). HSF1 mRNA and phosphorylated-HSF1 protein rapidly increased by 2.2-fold in RGCs 0.5-6 h after injury. Intraocular injection of HSP inhibitor I s...
Hyperosmotic stress is known to significantly enhance net uptake of inorganic ions into plant cells. Direct evidence for cell turgor recovery via such a mechanism, however, is still lacking. In the...Full Text Available
It was shown that the incorporation of "1"4C-linoleic acid in cerebrosides of normal and psoriatic human skin is different. In psoriatic epidermis and corium the turnover of this fatty acid is significantly elevated. It is suggested that in psoriasis the epidermal cell is not able to build up a regular carbohydrate sequences of lipids because the false carbohydrate chain activates the degradation of glycolipids and in compensating for the increased degradation raises the synthesis rate of glycolipids. (orig./MG).
BackgroundThe Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis....Full Text Available
The expression status of the estrogen receptor alpha (ERα) and that of the epidermal growth factor receptor Her-2/neu frequently correlate inversely in breast cancers. While ERα-dependent...Full Text Available
To elucidate the mechanism of sunlight-induced skin damage, guinea pigs exposed to UV light (280-320 nm, UV B, 4J/cm"2) and a homogenate of the epidermis was examined by means of the thiobarbituric acid (TBA) test. Three hours after the exposure, TBA-malondialdehyde adducts had increased while glutathione reductase activity had decreased, indicating lipid peroxidation. To detect the initial species, spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was applied to a suspension of illuminated epidermal cells (0.5 J/cm"2). An ESR signal obtained only with irradiation comprised a 1 : 2 : 2 : 1 quartet [a (N) =a (#beta#H) =1.49 mT] attributable to a spin adduct of hydroxyl radicals. These results suggest that sunlight exposure of skin may lead to hydroxyl radical generation and simultaneous lipid peroxidation. (author).
The purpose of this study was to prepare recombinant human epidermal growth factor (rhEGF) collagen sponges for topical applications and investigate the effects of different types of crosslinked collagen sponges as platforms for the controlled release of rhEGF. The microstructure and the drug release rates of collagen sponges were modified through treatment with different types (glutaraldehyde (GTA), genipin and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)), different concentrations of crosslinking agents and various preparation conditions. A controlled release profile was observed for the crosslinked collagen sponges as compared to the non-crosslinked ones. The results indicated that the GTA crosslinked sponges have the most potent controlling effect. As the amount of GTA increased, a greater rigidity of the collagen sponge structure combined with a lower hydrophilicity was observed, leading to a decreased drug release rate and an increased water uptake. ...
The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at ...
Transforming growth factor beta (TGF-@b) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-@b and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-@b and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role i...
Abstract in english Odontopus brevirostris (Hustache, 1936) feeding on Annona squamosa L., A. cherimola Mill., A. glabra L., and A. muricata L. was observed. The last three host plants are recorded for the first time. The endophitic oviposition occurs in the veins of the ventral surface of the young leaves. The larvae, leaf miners, eat the parenchyma and the adults make small holes in the leaves. The pupation occurs in spherical cocoons protected by a sort of nest (pupation chamber) between the two epidermal layers.
Two patients are described in whom sunburn and electron beam radiodermatitis, respectively, were critical determinants in localizing the initial presentation of drug eruptions. In the first instance, a severe sunburn of the back and thighs was followed 7 months later by the appearance of a toxic epidermal necrolysis drug reaction to trimethoprim-sulfamethoxazole in the exact sites of the previous bullous sunburn reaction. In the second patient, a radiodermatitis of the left upper arm due to electron beam therapy for metastatic breast cancer was followed 7 weeks later by a codeine drug reaction confined to the area of the radiodermatitis. In both instances, oral rechallenge with the offending drug reproduced the eruption.
Trastuzumab increases survival amongst women with human epidermal growth factor receptor (HER)-2 receptor positive metastatic breast cancer, but maternal and fetal risks are associated with advanced disease and its treatment in pregnancy. We present a case of a primigravid with HER-2 positive metastatic breast cancer who received trastuzumab throughout pregnancy. She presented with cerebral metastases, requiring surgical decompression and resection. Reversible oligohydramnios developed during pregnancy. Fetal safety data on trastuzumab in pregnancy is limited, but case reports suggest a recurring pattern of (mostly reversible) oligohydramnios.
Evolutionary conservation of DNA sequences provides a tool for the identification of functional elements in genomes. We have created a database of evolutionary conserved regions (ECRs) in vertebrate genomes entitled ECRbase that is constructed from a collection of pairwise vertebrate genome alignments produced by the ECR Browser database. ECRbase features a database of syntenic blocks that recapitulate the evolution of rearrangements in vertebrates and a collection of promoters in all vertebrate genomes presented in the database. The database also contains a collection of annotated transcription factor binding sites (TFBS) in all ECRs and promoter elements. ECRbase currently includes human, rhesus macaque, dog, opossum, rat, mouse, chicken, frog, zebrafish, and two pufferfish genomes. It is freely accessible at http://ECRbase.dcode.org.
Scrotal skin of black Long-Evans rats and human thigh skin were maintained in vitro as organ cultures for as long as 14 days, and examined histologically using the combined skin splitting and Dopa techniques. Selected rat skin cultures received testosterone in the culture medium and/or were irradiated with ultraviolet light (290 to 320 nm uvl). With increased time in culture, scrotal melanocytes round up and there is an increase in epidermal pigmentation. Human skin behaves similarly; after eight days in vitro human melanocytes also become rounded, but remain strongly Dopa-positive. Addition of exogenous testosterone to cultured rat skin maintains dendritic morphology of melanocytes, but cell body size is still reduced. uvl irradiation stimulates melanocytes in rat skin cultures, maintaining their dendritic morphology and increasing epidermal and dermal pigmentation. Cultured skin receiving both uvl and testosterone illustrates a synergistic ...
Cadmium is a non-essential heavy metal found abundantly in the environment. Children of women exposed to cadmium during pregnancy display lower motor and perceptual abilities. High cadmium body burden in children is also related to impaired intelligence and lowered school achievement. However, little is known about the molecular and cellular basis of developmental neurotoxicity in the sensitive early life stages of animals. In this study, we explore neurological deficits caused by cadmium during early embryonic stages in zebrafish by examining regionalization of the neural tube, pattern formation and cell fate determination, commitment of proneural genes and induction of neurogenesis. We show that cadmium-treated embryos developed a smaller head with unclear boundaries between the brain subdivisions, particularly in the mid-hindbrain region. Embryos display normal anterior to posterior regionalization; however, the commitment of neural progenitor cells was affected ...
Summary Background Pemphigus vulgaris and pemphigus foliaceus are rare, potentially life-threatening, autoimmune disorders characterized by antibodies to epidermal adhesion molecules. Clinical characteristics are painful chronic erosions of mucous membranes and of the skin. There are only few published studies on the impact of the disease on the health status (HS) of patients with these conditions. Objectives To assess the impact of disease on the HS of patients with pemphigus. Methods Fifty-eight patients enrolled at the Bullous Skin Diseases Unit of IDI-IRCCS in the period January-June 2006 were assessed for their HS using the Medical Outcomes Study 36-item short form health survey (SF-36) questionnaire and for anxiety and depression using the Institute for Personality and Ability Testin...
AbstractBackground In recent years nano-metaloxides which easily penetrate into the cells with special interest due to their higher chemical reactivity as compared to that of similar materials in the bulk form. Of particular interest are nano-TiO2 and ZnO, which have been widely used for their bactericidal and anticancerous properties. Purpose The aim of the present study was to examine the bactericidal properties of nano-TiO2 and ZnO combined with visible light on S. aureus and S. epidermitis, known for their high prevalence in infected wounds. Study Using the technique of electron-spin resonance (ESR) coupled with spin trapping, we examined the ability of TiO2 and ZnO nanoparticle suspensions in water to produce reactive oxygen species (ROS) with and without visible light irradiation. Th...
Abstract This study aimed at developing a suitable cryopreservation protocol for embryonic stem (ES)-like cells of a tiny freshwater fish Leopard danio (Brachydanio frankei). Embryonic stem (ES)-like cells derived from blastomeres of the early blastulae stage of the developing embryo were cultured in vitro in a medium containing Leibowitz-15 supplemented with 10% foetal bovine serum, leopard danio embryo extract, sodium bicarbonate, sodium selenite, basic fibroblast growth factor, epidermal growth factor and leukaemia inhibitory factor. The ES-like cells showed properties similar to ES cells in other species. They were morphologically small, round to polygonal and present in patches and extensively expressed alkaline phosphatase and stage-specific embryonic antigen. The toxicity and chilli...
The presence of endothelin (ET)-like immunoreactivity and the cardiovascular effects of mammalian ET-1 in fish have been reported. To identify ET-related peptides in fish, we screened the cDNA library of the salmon (Oncorhynchus keta) stomach by means of rapid amplification of cDNA ends, and we cloned cDNAs encoding an ET-related peptide. The salmon ET-related sequence of 21 amino acids is identical to the trout ET-1 peptide recently purified from kidney specimens of Oncorhynchus mykiss. The deduced amino acid sequence of salmon pre-proET-1 (PPET-1) comprises 244 amino acids, including a putative signal sequence and mature ET-1, as well as big ET-1 and ET-1-like sequences. This precursor, the first reported PPET-1 sequence for Salmoniformes, Teleostei, has low homology with the sequences of human, mouse, frog (Xenopus laevis), and zebrafish (Danio rerio) PPET-1 (26%, 29%, 24%, and 39%, respectively). PMID:16740985
Goosecoid is a homeobox gene first isolated from a Xenopus dorsal lip cDNA library. Homologous genes have been isolated from mouse, zebrafish, and chick. In all species examined, the gene is expressed and plays an important role during the process of gastrulation in early embryonic development. The authors report here the cloning of the human goosecoid (GSC) from a genomic library and the sequence of its encoded protein. The genomic organization and protein sequence of the human gene are highly conserved with respect to those of its Xenopus and mouse counterparts: all three genes consist of three exons, with conserved exon-intron boundaries. The sequence of the homeo-domain is 100% conserved in most vertebrates. Using somatic cell hybrid and chromosomal in situ hybridization, the gene was mapped to chromosome 14q32.1. 30 refs., 3 figs., 2 tabs.
Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid substitution were observed in ...
Iron overload has been described in patients undergoing chronic hemodialysis. The present study was undertaken to evaluate a rapid, noninvasive method for determination of skin iron by the technique of diagnostic x-ray spectrometry (DXS). Thirty-five patients receiving chronic hemodialysis treatment entered the study and were compared with 25 normal controls. Since pathological skin iron deposition occurs mainly at the dermal-epidermal junction in the basal cells of the epidermis, measurements were made in the thenar eminence representing mainly epidermal tissue (FeE), and in the forearm representative mainly of dermis (FeD). The mean +/- SD FeE iron concentrations were equivalent to 14.5 +/- 8.8 and 18.2 +/- 10.2 parts per million wet weight tissue (ppm) and both were significantly higher than in normal controls in which they averaged 9.2 +/- 2.5 ppm (P less than 0.005) and 10.2 +/- 3.2 ppm (P less than 0.001), respectively. There was ...
We have compared the kinetics for repair of UV-induced cyclobutane pyrimidine dimers in the DNA of keratinocytes in human skin and in cell culture. A small area of the buttocks of volunteers was exposed to UVB-irradiation and biopsies were taken at various time intervals. Epidermal keratinocytes in culture from the same subjects were exposed to UVC with doses chosen to elicit comparable yields of dimers in cellular DNA. The initial density of pyrimidine dimers and the kinetics of their removal were assessed utilizing the dimer-specific T4 endonuclease V and sedimentation of the unlabeled DNA through alkaline sucrose gradients. The position of DNA in the gradients was determined using a monoclonal antibody against random sequences of single-stranded DNA in a sensitive immunoassay. The initial dimer frequency was 3.9-6.7 per 10(8) daltons DNA. About 40% of the dimers were removed within 1 h, 70% in 6 h, and 90% in 24 h for both in vivo and in vitro samples. The early ...
We have compared the kinetics for repair of UV-induced cyclobutane pyrimidine dimers in the DNA of keratinocytes in human skin and in cell culture. A small area of the buttocks of volunteers was exposed to UVB-irradiation and biopsies were taken at various time intervals. Epidermal keratinocytes in culture from the same subjects were exposed to UVC with doses chosen to elicit comparable yields of dimers in cellular DNA. The initial density of pyrimidine dimers and the kinetics of their removal were assessed utilizing the dimer-specific T4 endonuclease V and sedimentation of the unlabeled DNA through alkaline sucrose gradients. The position of DNA in the gradients was determined using a monoclonal antibody against random sequences of single-stranded DNA in a sensitive immunoassay. The initial dimer frequency was 3.9-6.7 per 10(8) daltons DNA. About 40% of the dimers were removed within 1 h, 70% in 6 h, and 90% in 24 h for both in vivo and in vitro samples. The early ...
Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of ["1"2"5I]EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM ["1"2"5I]EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium azide inhibited internalization of label, whereas a ...
Although the intracellular ultrastructural processing of epidermal growth factor (EGF) and its receptor have been described in cell culture systems, very few studies have examined this phenomenon in intact tissues. We have examined the ultrastructural and biochemical handling of (/sup 125/I)EGF in the epidermis and hair follicle bulb of intact, viable, 3- to 5-day-old rat skin the EGF receptor distribution of which has already been documented and in which EGF has been shown to be biologically active. After incubation of explants with 10 nM (/sup 125/I)EGF for 2.5 h at 25 degrees or 37 degrees C, radiolabel was detected over the basal cells of the epidermis and hair follicle outer root sheath, confirming previous light microscope observations. More specifically, silver grains were observed near coated and uncoated plasma membrane and coated membrane invaginations, Golgi apparatus, lysosomal structures, and nuclei. Sodium azide inhibited internalization of label, ...
It is now known that various growth factors may also act in the central nervous system. Among them, it has recently been shown that epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) may possess trophic effects in the mammalian brain. We report here on the respective autoradiographic distribution of ["1"2"5I]EGF and ["1"2"5I]IGF-I receptor binding sites in the rat brain, both during ontogeny and in adulthood. It appears that ["1"2"5I]EGF sites are mostly found in the rat forebrain during brain development. On the other hand, ["1"2"5I]IGF-I sites are more widely distributed both during ontogeny and in adulthood. These results reveal the plasticity of the expression of EGF and IGF-I receptor sites in the mammalian brain. This could be relevant for the respective role of these two growth factors in the development and maintenance of neuronal function.
Recently, various types of allogeneic skin substitutes including cultured epidermal substitute (CES), cultured dermal substitute (CDS), and cultured skin substitute (CSS), which are composed of keratinocytes and/or fibroblasts as the cellular component(s), have been used as biological wound dressings. In our study, the allogeneic CDS was prepared by plating fibroblasts on a spongy collagen. The clinical evaluation was conducted using fresh or cryopreserved allogeneic CDS. In 145 of our clinical cases, 95% (138/145) of various wounds were evaluated as achieving good or excellent results, including 96% (22/23) of deep dermal burns (DDB) and dermal burns (DB), 100% (53/53) of partial-thickness donor wounds, 91% (21/23) of traumatic skin defects, 100% (5/5) of pressure ulcers, 82% (9/11) of chronic skin ulcers, 100% (6/6) of coverage for debrided DB, and 92% (22/24) of coverage for autologous meshed graft. The results obtained in our study suggest that the allogeneic ...
Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for noninvasive determination of iron and zinc in two distinct skin areas, representing predominantly dermal and epidermal tissues, in 56 patients with beta-thalassemia major and intermedia. The mean iron levels in the skin of patients with beta-thalassemia major and intermedia were elevated by greater than 200% and greater than 50%, respectively, compared with control values. The zinc levels of both skin areas examined were within the normal range. The data indicate that the rate and number of blood transfusions, which correlated well with serum ferritin levels (r . 0.8), are not the only factors that determine the amount of iron deposition in the skin (r less than 0.6). Other sources of iron intake contribute to the total iron load in the tissues, particularly in patients who are not given multiple transfusions. The noninvasive quantitation of skin levels may reflect the extent ...
The endothelin-B (ETB) receptor is a G-protein-coupled receptor that binds endothelin ligands and is essential for the development of epidermal melanocytes and enteric neurons. Recent reports indicate that ETB is localized to nuclei in cardiac ventricular myocytes, although it has been thought that ETB is localized mainly on the plasma membrane. It remains unknown, however, whether this unique distribution of ETB occurs in other tissues. To elucidate the subcellular distribution of ETB in the intestine, we performed immunofluorescence of ETB in mouse intestine using a specific antibody. ETB-like immunoreactivity was detected in both the mucosal and muscle layers. In the mucosal layer, villous epithelial cells, stromal cells of the lamina propria, and cryptic cells were immunostained. Subcellularly, ETB is localized mainly to the nuclei of villous epithelial cells. In the muscle layer, immunoreactivity of ETB was localized to the myenteric plexus. These findings ...
Statements about the dynamic processes of uptake, transport, and deposition of Ca and Mg in norway spruce and Scots pine are made in this paper. Concerning the storage of these elements it is shown that there are great differences in their functional importance in cell metabolism. There is evidence that the role of Mg in enzyme and protein metabolism is of far greater significance for the understanding of Mg-deficiency symptoms than its function as the central atom of the chlorophyll complexes. In regard to the transport and especially to the incorporation of Ca into the needles differences between species were evident, expressing the special status of pine among the gymnosperms. With increasing needle age an accumulation of Ca-oxalate crystals, which are physiologically inert, could be proved for the studied conifers. This was interpreted as a 'detoxication' from surplus Ca to hold constant the level of the physiologically active fraction. Accordingly, the low Ca-contents of yellowed ...
The cause of the Gulf War Syndrome may be related to soldiers being exposed to insecticides (e.g., permethrin (P)), insect repellents (e.g., N,N-diethyl-m-toluamide (DEET)), an organophosphate nerve agent simulant (e.g., diisopropyl fluorpohosphate (DFP)), and/or prophylactic treatment (e.g., pyridostigmine bromide (PB)) against potential nerve gas attacks. The purpose of this study was to assess the dermal disposition of [14C]permethrin in ethanol or ethanol:water (3:2) in the isolated perfused porcine skin flap (IPPSF) model with simultaneous dermal exposure to DEET or DFP. These IPPSFs were also simultaneously perfused arterially with or without PB, DFP, or DFP + PB. The results indicated that DFP + PB significantly increased [14C]permethrin absorption compared to controls (1.06% dose vs 0.14% dose). PB significantly increased [14C]permethrin disposition in the stratum corneum (SC) in aqueous mixtures only (9.40 vs 3.35% dose), while topical DEET or topical DFP reduced ...
Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated form of the human ...
Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic ...
Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as ...
Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly ...
Recent advances in cell culture technology permit the generation of large stratified epithelial sheets appropriate for wound coverage. Autografts (sheets prepared from the patient's own skin) have proven life-saving in the treatment of large third-degree burns and have been successfully employed in the management of chronic ulcers. Allografts (sheets prepared from the skin of an unrelated donor) have also been used. In our experience, cultured allografts derived from neonatal foreskin provide a potent stimulus to healing in a variety of partial thickness wounds. Their application is a simple outpatient procedure which involves no discomfort for the patient. In contrast to autografting, no biopsy is necessary and use of cultured allogenic cells permits immediate grafts availability and possibility of stockpiling and preserving grafts for future use. Preparation of epithelial sheets suitable for grafting is also faster and easier with newborn than with adult donor cells. Newborn ...
Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec later but ATP or BK did not desensitized to PDGF. Homologous desensitization was seen with all agonists. Heterologous ...
The disruption of primary innate immune function of the epidermal layer of the skin accounts for the susceptibility of individuals using bleaching agents to localized or systemic infections. This subverted innate immunity in these people may lead to other pathological conditions. The resultant effects of skin bleaching and phagocytes activation in response to infections have not been studied in Nigerians using bleaching agents. The present study therefore assessed the levels of C-reactive protein (CRP), albumin, total antioxidant potential (TAP), total plasma peroxides (TPP), oxidative stress index (OSI) and malonaldehyde (MDA) in the users bleaching agents. Thirty (30) people who had used bleaching agents for average of 4.9 + 1.2 years participated in this study. They were recruited from various schools and markets within the city of Ibadan, Oyo State, Nigeria. Thirty apparently healthy staffs of University College Hospital Ibadan, Ibaadan, Nigeria, who had never ...
Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the nucl2048 These connections are made via membrane-bound receptors and transmitted to the nucleus, where ...