epidermal-growth-factor and Skin-Diseases

Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations.

Topics: Dermatologic Agents; Epidermal Growth Factor; Humans; Patient Safety; Recombinant Proteins; Skin Diseases; Wounds and Injuries

Cancer therapies have led to remarkable results due to improved toxicity profiles and effects on survival. While these medical, surgical, and radiation protocols are chiefly responsible for these noteworthy contributions, an unexpected constellation of toxicities has emerged. Most notably, dermatologic adverse events have gained considerable attention, due to their high frequency, visibility, and impact on physical and psychosocial health, all of which affect dose intensity and possibly clinical outcome. Consequently, increased attention to cutaneous health in oncology has resulted in supportive oncodermatology clinical programs and toxicity-driven investigations, aiming to mitigate these untoward events and permit the continued optimization of cancer treatments.

Topics: Antineoplastic Agents; Epidermal Growth Factor; Humans; Neoplasms; Neoplasms, Radiation-Induced; Postoperative Complications; Radiodermatitis; Radiotherapy; Skin Diseases

Transgenic animals have greatly enhanced our understanding of the contribution of various structural and regulatory components to epidermal biology. The expression of mutant versions of these components in the epidermis of transgenic mice has generated animal models of specific human skin diseases.. The expression of mutant keratin genes has produced animal models of epidermolysis bullosa simplex and epidermolytic hyperkeratosis and, in doing so, has focused attention on the genetics of keratins in these and other skin disorders. Similarly, the generation of mice overexpressing growth factors and/or oncogenes, exclusively in the epidermis, has identified the role of these factors in normal skin and produced models of disease states where the regulation of these factors is perturbed.. These models of keratin disorders and other diseases not only enable the determination of the cause of these disorders, but also allow evaluation of novel therapeutic techniques for the amelioration of these skin diseases.

Topics: Animals; Animals, Newborn; Epidermal Growth Factor; Gene Expression; Genes, Dominant; Genes, fos; Genes, ras; Humans; Keratins; Mice; Mice, Transgenic; Models, Biological; Mutation; Phenotype; Skin; Skin Diseases; Skin Neoplasms; Transforming Growth Factor alpha; Transforming Growth Factor beta

Topics: Animals; Cell Communication; Colony-Stimulating Factors; Epidermal Growth Factor; Fibroblast Growth Factors; Growth Substances; Humans; Interleukins; Platelet-Derived Growth Factor; Receptors, Cell Surface; Regeneration; Skin; Skin Diseases; Skin Physiological Phenomena; Transforming Growth Factors

Topics: Amino Acid Sequence; Epidermal Growth Factor; ErbB Receptors; Humans; Keratinocytes; Molecular Sequence Data; Signal Transduction; Skin Diseases; Transforming Growth Factor alpha; Wound Healing

Topics: Animals; Epidermal Growth Factor; Epidermis; ErbB Receptors; Humans; Protein Kinases; Skin Diseases; Transforming Growth Factors

Senile purpura presents itself as a largely unexplored challenge as it has been long thought of as a benign condition without long-term health sequelae. It is becoming increasingly accepted that skin aging not only results in cosmetic disturbances, but as a functional ones. With modern increases in lifespan, skin atrophy associated with solar damage is presenting as a clinically significant inability to mechanically protect patients. This chronic cutaneous insufficiency/fragility syndrome was recently termed dermatoporosis and senile purpura appears to be a visible marker of early stage dysfunction.. To examine the effects of topically human epidermal growth factor on the clinical presence of senile purpura and its effect on skin thickness as measured via cutaneous ultrasound.. Six subjects applied human epidermal growth factor morning and night for six weeks. Clinical outcomes were evaluated by comparing initial clinical photos to 6-week photos and performing a blinded investigator's global assessment (IGA). Skin thickness was evaluated via cutaneous ultrasound measurement.. Ultrasound measurements indicated a mean skin thickening of 195.2 ± 35.7 um (SEM) over 6 weeks. The average number of purpuric lesions decreased from 15 ± 4.6 (SEM) to 2.3 ± 0.7 (SEM) over that same period.. Senile purpura presents itself as a cosmetic disturbance posing significant psychological distress and serves as a marker of the severity of skin thinning. In this study, we demonstrate that topical h-EGF diminishes the appearance of senile purpura by thickening skin and may help prevent the development of late stage dermatoporosis.

Topics: Administration, Cutaneous; Aged; Epidermal Growth Factor; Female; Humans; Male; Purpura; Skin; Skin Aging; Skin Diseases; Treatment Outcome; Ultrasonography

To analyze compounded recombinant human epidermal growth factor (rhEGF) effectiveness on skin lesions through a case series.. Multicentric series of skin lesions treated with topical rhEGF. Site: Patients from 56 different health professionals, three different countries, and two recruitment years.. Seventy-seven patients with skin lesions, mean age of 63.15 years (min = 18, max = 95); 53.2% of patients were men and 46.8% were women; 47 of the lesions were ulcers (venous, arterial, and diabetic foot), others were surgical and traumatic wounds, burns, and scars. Most common pathologies were type 2 diabetes mellitus and chronic venous insufficiency. Mean previous evolution time before inclusion was 29.59 months.. Cures using compounded topical rhEGF most commonly used rhEGF concentration: 30 μg/g; most used excipient: gel; average time between cures: 36 h (24-48); and mean follow-up: 6.6 weeks (max = 20).. Lesions appearance, margins and bed, lesional size evolution, treatment subjective effectiveness, tolerability and comfort through professional oppinion.. Qualitative assessment: effectiveness 8.65, tolerability 9.53, and comfort 8.86 (max = 10). Perilesional skin showed improvement in 93.5% of the cases, lesions margins and wound bed appearance improved in 92.2% of the cases, respectively. Wound area decreased a mean average of 66.7%. About 43.3% of included venous ulcers had a greater than 40% cure rate in 4 weeks.. Heterogeneity of the included pathologies, limited time follow-up in some cases.. Topical rhEGF in individualized formulation (compounding) seems to exhibit effectiveness, comfort, and tolerability. Further larger-size studies with experimental design will allow to establish more precise concentrations, indications, and clinical guidelines.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Recombinant Proteins; Skin Diseases; Treatment Outcome; Young Adult

Topics: Administration, Topical; Adult; Dermal Fillers; Epidermal Growth Factor; Female; Humans; Necrosis; Skin Diseases; Treatment Outcome

Skin tag (STs) are benign connective tissue tumors of the dermis. Some researchers have argued that there is a relationship between skin tag and colon polyps, although the physiopathological mechanisms underlying this relation were not well elucidated. In this study we aimed to investigate the co-existence of colonic adenomatous polyps and ST, additionally to shed light on the physiopathological mechanisms underlying this coincidence.. A total of 45 patients aged between 18 and 60 diagnosed with adenomatous colonic polyps and 45 sex, age, and socio-demographically matched subjects, had no polyps, were enrolled as the control group. Routine blood analysis of all participants, including serum glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), (high-density lipoprotein cholesterol (HDL-C), triglyceride, insulin, IGF-1, and EGF, were performed. The chi-square and independent sample t or Mann Whitney U test were used to determine differences between groups.. The number of participants with ST was significantly higher in the patient group (OR 7.067, p < 0.01). Serum levels of IGF-1 and EGF were statistically similar between the groups. In the subgroup analyses, no difference was found in serum levels of insulin, IGF-1, or EGF between patients with and without ST. However, higher serum levels of insulin and EGF were found in control subjects with ST (p < 0.01 and p < 0.01, respectively). For the entire study group, 67 participants had ST and 23 patients did not. Serum insulin, and IGF-1 were similar, while serum EGF levels were higher in patients with ST (p < 0.01).. Findings of the present study may show a co-existence of colonic polyps and ST. Although previous studies have indicated that insulin resistance may play a role in the pathogenesis of both lesions in diabetic and obese patients, we found no indication of a relationship in nondiabetic and nonobese patients with increased levels of EGF in patients with ST, suggesting an alternative pathogenesis in this patient group.

Topics: Adenoma; Adult; Colonic Neoplasms; Colonic Polyps; Epidermal Growth Factor; Female; Humans; Insulin; Insulin-Like Growth Factor I; Male; Middle Aged; Odds Ratio; Skin Diseases; Turkey

We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR, EGF, CCND1) or antibody-directed cell cytotoxicity (FCGR2A and FCGR3A) on outcome of colorectal cancer (CRC) patients receiving cetuximab-based therapy.. Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1). The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron 1, -216 G > T, -191C > A, R497K), EGF (A61G), CCND1 (A870G), FCGR2A (R131H), FCGR3A (F158V). Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt vs wt/mut vs mut/mut), with the exception of -191C > A EGFR polymorphism (AA patient merged with CA patients).. Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058). CCND1 A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP) was significantly related to EGFR -191C > A polymorphism with a longer TTP in CC patients as compared to others, and to CCND1 A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained CCND1 polymorphism. Overall survival was significantly related to CCND1 polymorphism with a shorter survival in patients bearing the G allele, and to FCGR3A F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients). FCGR3A F158V and CCND1 A870G polymorphisms were significant independent predictors of overall survival.. Present original data obtained in wt KRas patients corresponding to the current cetuximab-treated population clearly suggest that CCND1 A870G polymorphism may be used as an additional marker for predicting cetuximab efficacy, TTP and overall survival. In addition, FCGR3A F158V polymorphism was a significant independent predictor of overall survival.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Carcinoma; Cetuximab; Colorectal Neoplasms; Cyclin D1; Disease Progression; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Introns; Male; Middle Aged; Polymorphism, Genetic; Receptors, IgG; Skin Diseases; Survival Analysis

Fatty acid transport protein (FATP) 4 is one of a family of six FATPs that facilitate long- and very long-chain fatty acid uptake. Mice lacking FATP4 are born with tight, thick skin and a defective epidermal barrier; they die neonatally due to dehydration and restricted movements. Both the skin phenotype and the lethality are rescued by transgene-driven expression of FATP4 solely in suprabasal keratinocytes. Here we show that Fatp4 mutants exhibit epidermal hyperplasia resulting from an increased number of proliferating suprabasal cells. In addition, barrier formation initiates precociously but never progresses to completion. To investigate possible mechanisms whereby Fatp4 influences skin development, we identified misregulated genes in Fatp4 mutants. Remarkably, three members of the epidermal growth factor (EGF) family (Ereg, Areg, and Epgn) showed increased expression that was associated with elevated epidermal activation of the EGF receptor (EGFR) and STAT3, a downstream effector of EGFR signaling. Both Tyrphostin AG1478, an EGFR tyrosine kinase inhibitor, and curcumin, an inhibitor of both STAT3 and EGFR, attenuated STAT3 activation/nuclear translocation, reduced skin thickening, and partially suppressed the barrier abnormalities. These data identify FATP4 activity as negatively influencing EGFR activation and the resulting STAT3 signaling during normal skin development. These findings have important implications for understanding the pathogenesis of ichthyosis prematurity syndrome, a disease recently shown to be caused by FATP4 mutations.

Topics: Animals; Epidermal Growth Factor; Epidermis; Epiregulin; ErbB Receptors; Fatty Acid Transport Proteins; Keratinocytes; Mice; Mice, Mutant Strains; Mice, Transgenic; Mutation; Phenotype; Quinazolines; Signal Transduction; Skin; Skin Diseases; STAT3 Transcription Factor; Tyrphostins

Retinoids are widely used in the treatment of photoaging to stimulate dermal repair. However, retinoids also induce epidermal hyperplasia, which can lead to excessive scaling. Scaling is the major deterrent to topical retinoid therapy. Keratinocyte growth is strongly stimulated via ligand activation of EGFR. We examined regulation of EGFR ligands by retinoids and the role of EGFR in retinoid-induced hyperplasia in human skin in vivo. Topical treatment of human skin with all-trans retinoic acid (tRA) induces EGFR ligands heparin-binding (HB)-EGF and amphiregulin (AR), and reduces betacellulin mRNA levels. Laser capture microdissection-coupled real-time reverse transcription-PCR reveals that tRA increases HB-EGF mRNA throughout the epidermis, whereas AR induction is limited to basal keratinocytes. Topical tRA activates extracellular signal-regulated kinase 1/2 (Erk1/2) downstream EGFR effectors in human skin in vivo. tRA increases the soluble forms of AR and HB-EGF proteins, and induces epidermal hyperplasia, in human skin organ culture. Neutralization of HB-EGF or AR with specific antibodies strongly reduces tRA-induced epidermal hyperplasia. Finally, inhibition of EGFR activation by genistein reduces epidermal hyperplasia caused by topical retinoid treatment. These data demonstrate the central role of EGFR activation in retinoid-induced epidermal hyperplasia, and suggest that EGFR inhibitors can mitigate retinoid-induced scaling.

Topics: Amphiregulin; Antibodies; Cells, Cultured; EGF Family of Proteins; Epidermal Growth Factor; Epidermis; ErbB Receptors; Glycoproteins; Heparin-binding EGF-like Growth Factor; Humans; Hyperplasia; Intercellular Signaling Peptides and Proteins; Ligands; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Retinoids; RNA, Messenger; Skin Diseases; Tretinoin

Epidermal growth factor (EGF) is a potent stimulant of epithelialisation. However, topical application of EGF to achieve facilitated re-epithelialisation in partial thickness wounds has been controversial. A total of 10 pigs, each with eight 4 x 4 cm partial thickness wounds, were treated twice a day for 10 days to observe the effect of human recombinant EGF in concentrations of 0.1, 1, 5, 10, 25 ug/g, vehicle only and two controls. The control and the vehicle-only wounds each demonstrated 100% healing time (HT100) of 9.31 +/- 1.34 and 8.5 +/- 1.12 while the wounds treated with EGF ointment with concentrations of 0.1 (HT100 = 6.4 +/- 0.71), 1 (HT100 = 5.2 +/- 0.63), 5 (HT100 = 5.8 +/- 0.85), 10 (HT100 = 7.1 +/- 1.45) and 25 ug/g (HT100 = 7.4 + 0.57) demonstrated significant reduction in time to achieve re-epithelialisation. Among the EGF-treated wounds, the wounds treated with EGF concentrations of 1 and 5 ug/g achieved the fastest re-epithelialisation with evidence of substantial increase in basal keratinocyte activity observed through Ki-67 activity. In conclusion, this article demonstrates the efficacy of human recombinant EGF in facilitating re-epithelialisation of partial thickness wounds with the most efficient healing found in EGF concentrations of 1 and 5 ug/g.

Topics: Administration, Topical; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Epidermal Growth Factor; Humans; Recombinant Proteins; Skin; Skin Diseases; Swine; Wound Healing; Wounds and Injuries

Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present.. Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3).. Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

Topics: Adult; Animals; Atrophy; Blotting, Western; Cell Proliferation; Cells, Cultured; Epidermal Growth Factor; ErbB Receptors; Female; Filaggrin Proteins; Humans; Hyaluronan Receptors; Hyaluronic Acid; Immunoprecipitation; Intermediate Filament Proteins; Keratinocytes; Male; Membrane Proteins; Mice; Mice, Knockout; Oligosaccharides; Platelet Endothelial Cell Adhesion Molecule-1; Skin; Skin Diseases; Vimentin

Calcyclin is the product of a gene that is regulated in dependence of the cell cycle in fibroblasts in vitro. It has recently been proven to be a sialic acid-binding protein in vitro and in the case of mammalian tissues to bind specifically to annexin II, annexin VI, annexin XI, and glyceraldehyde-3-phosphate dehydrogenase in a Ca(2+)-dependent manner. Since calcyclin can be labelled without impairment of its binding activity, it can be employed as a histochemical tool to localize its accessible ligands. Concomitantly, immunohistochemical localization of calcyclin with a specific antibody is warranted. By using histochemical and immunohistochemical techniques, the expression of calcyclin and its accessible binding sites are demonstrated in serial sections of normal skin and benign, pre-cancerous and malignant tumors of the skin, namely in verruca vulgaris, papillary hidradenoma, syringoma, keratoacanthoma, Bowen's disease, squamous cell carcinoma, melanocytic naevi, primary and metastatic malignant melanoma and non-Hodgkin lymphoma (NHL) of the skin. Cytoplasmic and nuclear expression of calcyclin and its ligands is unexceptionally found in normal skin, epithelial tumors and benign melanocytic tumors. Presence of calcyclin and calcyclin-binding sites is detected in more than 80% of tumor cells in the epithelial lesions. In the group of melanomas and lymphomas heterogeneity is obvious. The application of annexin-specific antibodies raises evidence that members of this protein family co-localize with calcyclin in situ to some extent. These findings suggest that calcyclin and accessible calcyclin-binding molecules, like certain annexins, may be differentially regulated in melanomas and lymphomas in contrast to epithelial lesions with presently undefined biological implications.

Topics: Annexins; Calcium-Binding Proteins; Cell Cycle Proteins; Epidermal Growth Factor; Humans; Immunohistochemistry; Ligands; Precancerous Conditions; Reference Values; S100 Calcium Binding Protein A6; S100 Proteins; Skin; Skin Diseases; Skin Neoplasms; Tissue Distribution

In most malignant and benign skin diseases, the normal pattern of keratin expression is altered. Among other phenotypic changes, the expression of hyperproliferation- and activation-associated keratins K#16 and K#6 is induced. Because the molecular mechanisms and the nuclear regulators involved in this induction are unknown, we have characterized the transcriptional regulators of expression of the keratin K#16 promoter. Our previous studies have shown that the transcription of K#16 is strongly and specifically induced in epidermal keratinocytes by epidermal growth factor (EGF), through the EGF-responsive element (RE). In the present work, using an electrophoretic mobility-shift assay, we have found several nuclear protein binding sites that have been identified as an Sp1 site, an AP2 site, the EGF-RE, and an enhancer element. The function of each site was assessed in transfection assays using specific deletions. Both the Sp1 and EGF-RE sites are essential for K#16 promoter activity. The site that functions as an independent enhancer, E, was found adjacent to and interacting with a sequence recognized by the AP2 transcription factor. This knowledge of the nuclear regulators of expression of the disease-associated K#16 keratin provides insight into the molecular parameters that might be important in skin diseases.

Topics: Base Sequence; Binding Sites; Cell Line; DNA; DNA-Binding Proteins; Enhancer Elements, Genetic; Epidermal Growth Factor; Gene Expression Regulation; HeLa Cells; Humans; Keratinocytes; Keratins; Molecular Sequence Data; Promoter Regions, Genetic; Sequence Deletion; Skin Diseases; Sp1 Transcription Factor; Transcription Factor AP-2; Transcription Factors

Cytokines have profound effects on various aspects of granulomatous tissue formation. However, there is little information regarding their distribution during tissue development. This study investigated the temporal and spatial distribution of transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1) and IL-1 beta in developing granulomatous tissue.. Murine chronic granulomatous air pouches were induced and full thickness biopsies taken at intervals up to 28 days. Samples were prepared for immunohistochemistry and labeled using antibodies against TGF-beta, bFGF, PDGF, EGF, TNF-alpha, IL-1 alpha and IL-1 beta.. Immunoreactivity to TGF-beta, PDGF, TNF-alpha, IL-1 alpha and IL-1 beta was localized to a proportion of macrophages within the granulomatous tissue. Immunopositive macrophage numbers increased with time, and with the exception of PDGF were associated with areas of fibrogenesis between days 14 to 28. Heterogeneous labeling of capillaries for EGF was observed within the granulomatous tissue juxtaposed to dermal musculature. Diffuse labeling of bFGF, associated with extracellular matrix, was always observed. After day 14, bFGF immunoreactivity was discretely localized to endothelial cells and the basement membrane of vessels within the granulomatous tissue. TGF-beta immunoreactivity was also associated with extracellular matrix components, being most intense in the area of fibrogenesis between 14 and 28 days. Occasional fibroblasts were also labeled with TGF-beta in this region.. The spatial and temporal confinement of the individual cytokines suggests that a sequential coordinated process of repair and fibrosis is occurring. It is hoped that these observations will provide a more effective therapeutic approach for the sequential application of cytokines in abnormalities of wound healing.

Topics: Animals; Croton Oil; Cytokines; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Granuloma; Immunohistochemistry; Inflammation; Interleukin-1; Mice; Mice, Inbred Strains; Platelet-Derived Growth Factor; Skin; Skin Diseases; Time Factors; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Wound Healing

Mice homozygous for a disrupted transforming growth factor alpha (TGF alpha) gene are healthy and fertile, although some older mice show evidence of corneal inflammation. In contrast with TGF alpha +/- and +/+ animals, TGF alpha -/- mice have a pronounced waviness of the coat. Histological examination of the skin from TGF alpha -/- mice reveals a dramatic derangement of hair follicles. Mice with a disrupted TGF alpha gene also have curly whiskers, first evident on the day of birth. The phenotype of TGF alpha -/- mice is remarkably similar to that of the mouse mutant waved-1 (wa-1). Offspring resulting from crosses between TGF alpha -/- and wa-1 mice display the curly whisker-coat phenotype, indicating that the basis of the wa-1 phenotype is a mutation in the TGF alpha gene. These observations suggest that TGF alpha plays a pivotal role in determining skin architecture and in regulating hair development.

Topics: Animals; Base Sequence; Chimera; Epidermal Growth Factor; Epithelial Cells; Eye Abnormalities; Female; Gene Deletion; Hair; Keratitis; Male; Mice; Mice, Mutant Strains; Molecular Sequence Data; Mutagenesis, Insertional; Mutation; Oligodeoxyribonucleotides; Skin; Skin Diseases; Transforming Growth Factor alpha; Vibrissae; Wound Healing

Topics: Body Fluids; Endocrine System Diseases; Epidermal Growth Factor; Female; Humans; Male; Milk, Human; Neoplasms; Radioimmunoassay; Semen; Skin Diseases

DNA from Molluscum contagiosum virus (MCV) isolates was analysed by restriction endonuclease cleavage, revealing two virus subtypes. Physical maps of cleavage sites for BamHI, ClaI and HindIII were constructed, and found to differ extensively between the two subtypes. MCV DNA was similar to Orthopoxvirus DNA with respect to size, terminal cross-linking and the presence of inverted terminal repetitions, but did not hybridize with vaccinia virus DNA. The genomes of the two MCV subtypes cross-hybridized and were colinear except for two small regions. There was sequence homology between DNA from corresponding map regions of the MCV subtypes but, in contrast to Orthopoxvirus DNA, no conservation of restriction sites. A synthetic oligonucleotide probe representing a conserved domain of epidermal growth factor, alpha-transforming growth factor and the vaccinia growth factor identified equivalent regions of both MCV genomes as having the potential to encode this domain. This locus is similar to the position of the vaccinia growth factor gene in vaccinia virus DNA. Thus MCV may induce epidermal cell proliferation and tumourigenesis by expression of an epidermal growth factor-like polypeptide.

Topics: Amino Acid Sequence; Animals; DNA, Viral; Epidermal Growth Factor; Genes; Genes, Viral; Humans; Poxviridae; Poxviridae Infections; Skin Diseases

Human peripheral blood leukocytes can stimulate G1(G0)-arrested mouse skin keratinocytes to enter the cell cycle again and synthesize DNA at the maximum rate 15-20 hr later. This growth-promoting activity is released by the monocyte fraction and is shown to have characteristics that have been reported for interleukin 1 (IL-1). Pure IL-1 is active in stimulating keratinocyte cultures as was shown with recombinant human IL-1. An IL-1-like protein released by monocytes-macrophages could explain the hyperproliferative epidermis found in certain types of inflammatory skin diseases.

Topics: Animals; Cell Division; Cells, Cultured; Concanavalin A; DNA Replication; Epidermal Cells; Epidermal Growth Factor; Fibroblasts; Humans; Inflammation; Interleukin-1; Interphase; Leukocytes; Lymphocytes; Mice; Mice, Inbred C3H; Muscles; Skin; Skin Diseases

Specific binding of 125I-labeled epidermal growth factor (EGF) was measured in 62 skin tumors of different severity. Within a group of 28 benign tumors, 11 of 15 condylomata acuminata were receptor positive, whereas the investigated mesenchymal tumors and normal skin as a control were receptor negative. 6 of 18 basal cell epitheliomas bound EGF specifically. In the group of precancerous and malignant skin tumors, 7 of 8 squamous cell carcinomas had the highest number of EGF binding sites and a high affinity state, whereas 5 malignant melanomas were receptor negative. The clinical relevance of these findings is not yet clear due to the short follow-up of the patients.

Topics: Binding Sites; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Condylomata Acuminata; Epidermal Growth Factor; ErbB Receptors; Humans; Iodine Radioisotopes; Melanoma; Receptors, Cell Surface; Skin; Skin Diseases; Skin Neoplasms

Topics: Animals; Cornea; Epidermal Growth Factor; Humans; Mice; Receptors, Cell Surface; Skin; Skin Diseases

Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +/- 3.0 and 52.0 +/- 3.5 (mean +/- SE) micrograms/total vol, or 29.7 +/- 1.1 and 39.8 +/- 1.7 micrograms/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +/- 2.7 micrograms/g creatinine; P less than 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and beta-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +/- 2.6 micrograms/g creatinine) than normal men, but this was not significant (P greater than 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

Topics: Adult; Aged; Circadian Rhythm; Contraceptives, Oral; Cross Reactions; Eating; Epidermal Growth Factor; Female; Gastrointestinal Diseases; Humans; Immune Sera; Male; Middle Aged; Peptic Ulcer; Radioimmunoassay; Reference Values; Skin Diseases