Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Skin Abnormalities”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources
PubMedDate not supplied

Genetic analysis of skin wound healing and scarring in a porcine model.

Contraction is a normal part of skin wound healing and wound closure; however, excessive contraction and severe scarring concern patients and physicians alike. The present study has investigated the degree and kinetics of wound contraction in a porcine model of wound healing, to elucidate the genetic and molecular basis for abnormal skin wound healing and scarring. Healing of excisional skin wounds in juvenile female Yorkshire pigs closely resembled normal healing in humans. In contrast, identical wounds in female red Duroc pigs contracted significantly more, forming hypercontracted, hyperpigmented scars. Yorkshire x red Duroc F1 animals healed without hyperpigmentation, but with significantly greater wound contraction than observed in either parent breed. To examine the genetic transmission of the hypercontractile phenotype, all F1 animals were bred to a single Yorkshire boar, generating 20 backcross animals. All backcross animals healed with significantly less contraction than the normal Yorkshire animals. These findings suggest that the genetic contribution to scar phenotype in this animal model is complex, with a limited number of major genes controlling wound contraction, and an unknown number of minor genes that appear to modulate the impact of the major genes.

Analysis of Variance↗
PubMed1994

Cutaneous nerve fibre depletion in vibration white finger.

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the 'white attacks'. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1996

An evaluation of clinical indicators for severe paediatric illness.

To help reduce paediatric morbidity and mortality in the developing world, WHO has developed a diagnostic and treatment algorithm that targets the principal causes of death in children, which include acute respiratory infection, malaria, measles, diarrhoeal disease, and malnutrition. With this algorithm, known as the Sick Child Charts, severely ill children are rapidly identified, through the presence of any one of 13 signs indicative of severe illness, and referred for more intensive health care. These signs are the inability to drink, abnormal mental status (abnormally sleepy), convulsions, wasting, oedema, chest wall retraction, stridor, abnormal skin turgor, repeated vomiting, stiff neck, tender swelling behind the ear, pallor of the conjunctiva, and corneal ulceration. The usefulness of these signs, both in current clinical practice and within the optimized context of the Sick Child Chart algorithm in a rural district of western Kenya, was evaluated. We found that 27% of children seen in outpatient clinics had one or more of these signs and that pallor and chest wall retraction were the signs most likely to be associated with hospital admission (odds ratio (OR) = 8.6 and 5.3, respectively). Presentation with any of these signs led to a 3.2 times increased likelihood of admission, although 54% of hospitalized children had no such signs and 21% of children sent home from the outpatient clinic had at least one sign. Among inpatients, 58% of all children and 89% of children who died had been admitted with a sign. Abnormal mental status was the sign most highly associated with death (OR = 59.6), followed by poor skin turgor (OR = 5.6), pallor (OR = 4.3), repeated vomiting (OR = 3.6), chest wall retraction (OR = 2.7), and oedema (OR = 2.4). Overall, the mortality risk associated with having at least one sign was 6.5 times higher than that for children without any sign. While these signs are useful in identifying a subset of children at high risk of death, their validation in other settings is needed. The training and supervision of health workers to identify severely ill children should continue to be given high priority because of the benefits, such as reduction of childhood mortality.

Cause of Death↗
PubMedDate not supplied

Hutchinson-Gilford progeria syndrome: a pathologic study.

Hutchinson-Gilford progeria syndrome is an extremely rare condition with features of premature and accelerated aging. The pattern of inheritance if unclear, although both autosomal recessive and autosomal dominant modes have been proposed. The children usually present in late infancy and early childhood with a characteristic phenotype of alopecia; short stature; abnormal skin, teeth, and nails; beaked nose; loss of subcutaneous fat; and failure to thrive. This condition has been reported on all inhabited continents and has been described in all major races. Laboratory findings note an increased urinary excretion of hyaluronic acid. Death results from cardiovascular abnormalities in the majority of cases and usually occurs in the second decade of life. There is no effective treatment. We report the pathologic changes noted at autopsy on a 20-year-old woman with classic features of Hutchinson-Gilford progeria syndrome.

Adult↗
PubMed1995

Cutaneous eruption in a patient with cardiac myxoma.

Atrial myxoma was diagnosed in a young woman who had cutaneous and constitutional manifestations clinically suggestive of cutaneous vasculitis without cardiac signs or symptoms. Scrupulous physical and laboratory examinations excluded additional medical disorders. The patient was totally cured by surgical removal of the tumor. Various aspects of the association of cardiac myxoma with dermatological findings are discussed, emphasizing the importance of echocardiography in the diagnostic workup of various skin abnormalities, including unexplained vasculitis, even in the absence of cardiac findings.

Adult↗
PubMed1988

Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line.

The sparse fur with abnormal skin and hair (Spf-ash) mouse is a model for the human X-linked hereditary disorder, ornithine transcarbamylase (OTC) deficiency. In Spf-ash mice, both OTC mRNA and enzyme activity are 5% of control values resulting in hyperammonemia, pronounced orotic aciduria and an abnormal phenotype characterized by growth retardation and sparse fur. Using microinjection, we introduced a construction containing rat OTC cDNA linked to the SV40 early promoter into fertilized eggs of Spf-ash mice. The expression of the transgene resulted in the development of a transgenic mouse whose phenotype and orotic acid excretion are fully normalized. Thus, the possibility of correcting hereditary enzymatic defect by gene transfer of heterologous cDNA coding for the normal enzyme has been demonstrated.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

[Prenatal diagnosis of several hereditary skin diseases].

Twenty-two control women and 5 women at risk for delivering a baby with Brocq's ichthyosiform erythroderma or fatal epidermolysis bullosa were investigated in order to make prenatal diagnosis of inherited fetal skin diseases. Fetal skin abnormalities were detected in 3 of the 5 high-risk patients, and their pregnancies were terminated. There was a spontaneous abortion with a normal fetus in 1 case. In one woman, pregnancy progressed to term delivery of a normal girl. Methodologic aspects of obtaining fetal skin samples and the results of their morphologic studies are discussed.

Biopsy↗
PubMed1996

A transgenic mouse model that recapitulates the clinical features of both neonatal and adult forms of the skin disease epidermolytic hyperkeratosis.

Keratins are the major structural proteins of keratinocytes, which are the most abundant cell type in the mammalian epidermis. Mutations in epidermal keratin genes have been shown to cause severe blistering skin abnormalities. One such disease, epidermolytic hyperkeratosis (EHK), also known as bullous congenital ichthyosiform erythroderma, occurs as a result of mutations in highly conserved regions of keratins K1 and K10. Patients with EHK first exhibit erythroderma with severe blistering, which later is replaced by thick patches of scaly skin. To assess the effect of a mutated K1 gene on skin biology and to produce an animal model for EHK, we removed 60 residues from the 2B segment of HK1 and observed the effects of its expression in the epidermis of transgenic mice. Phenotypes of the resultant mice closely resembled those observed in the human disease, first with epidermal blisters, then later with hyperkeratotic lesions. In neonatal mice homozygous for the transgene, the skin was thicker, with an increased labeling index, and the spinous cells showed a collapse of the keratin filament network around the nuclei, suggesting that a critical concentration of the mutant HK1, over the endogenous MK1, was required to disrupt the structural integrity of the spinous cells. Additionally, footpad epithelium, which is devoid of hair follicles, showed blistering in the spinous layer, suggesting that hair follicles can stabilize or protect the epidermis from trauma. Blisters were not evident in adult mice, but instead they showed a thick, scaly hyperkeratotic skin with increased mitosis, resulting in an increased number of corneocytes and granular cells. Irregularly shaped keratohyalin granules were also observed. To date, this is the only transgenic model to show the typical morphology found in the adult form of EHK.

Age Factors↗
PubMed1983

Carcinoembryonic antigen in skin and related tumours as determined by immunohistological techniques.

Common benign skin abnormalities and related tumours were investigated for the presence of carcinoembryonic antigen (CEA) using immunohistological techniques in formalin-fixed tissue. CEA could be detected in all 10 squamous cell carcinomas examined, a finding which contrasted with those in earlier reports. CEA was not seen in normal skin but was present in the skins of 12-18-wk-old fetuses. Hence, CEA can be considered to be a true oncofetal antigen for ectodermal tissue. The antigen was not detected in seborrheic keratoses but was present in all 10 cases of keratoacanthoma. CEA was found in only one out of 10 basal cell carcinomas, the tumour being metatypical (basosquamous) in type. CEA was also observed in the minority of cases of solar keratosis and Bowen's disease. If the presence of CEA in proliferating epidermal tissue is associated with malignant transformation, both solar keratosis and Bowen's disease are indeed premalignant lesions whilst keratoacanthoma is the non-metastasizing variant of squamous cell carcinoma. Finally, the absence of CEA in basal cell carcinoma may help to explain its 'reluctance' to spread by metastasis.

Adult↗
PubMed2006

Delayed wound healing and epidermal hyperproliferation in mice lacking JunB in the skin.

The cutaneous response to injury and stress comprises a temporary change in the balance between epidermal proliferation and differentiation as well as an activation of the immune system. Soluble factors play an important role in the regulation of these complex processes by coordinating the intercellular communication between keratinocytes, fibroblasts, and inflammatory cells. In this study, we demonstrate that JunB, a member of the activator protein-1 transcription factor family, is an important regulator of cytokine expression and thus critically involved in the cutaneous response to injury and stress. Mice lacking JunB in the skin develop normally, indicating that JunB is neither required for cutaneous organogenesis, nor homeostasis. However, upon wounding and treatment with the phorbol ester 12-O-decanoyl-phorbol-13-acetate, JunB-deficiency in the skin likewise resulted in pronounced epidermal hyperproliferation, disturbed differentiation, and prolonged inflammation. Furthermore, delayed tissue remodelling was observed during wound healing. These phenotypic skin abnormalities were associated with JunB-dependent alterations in expression levels and kinetics of important mediators of wound repair, such as granulocyte macrophage colony-stimulating factor, growth-regulated protein-1, macrophage inflammatory protein-2, and lipocalin-2 in both the dermal and epidermal compartment of the skin, and a reduced ability of wound contraction of mutant dermal fibroblasts in vitro.

Animals↗
PubMed2005

Cutaneous lasers.

Over the past few decades, lasers have gained increasing use in medicine. Clinical indications for the use of lasers in plastic surgery include facial rejuvenation, tattoo removal, hair removal, and improvement in various congenital and acquired skin abnormalities. With the advent of new lasers, patients of all ethnic backgrounds can be treated effectively.

Acne Vulgaris↗
PubMed2001

Interleukin 20: discovery, receptor identification, and role in epidermal function.

A structural, profile-based algorithm was used to identify interleukin 20 (IL-20), a novel IL-10 homolog. Chromosomal localization of IL-20 led to the discovery of an IL-10 family cytokine cluster. Overexpression of IL-20 in transgenic (TG) mice causes neonatal lethality with skin abnormalities including aberrant epidermal differentiation. Recombinant IL-20 protein stimulates a signal transduction pathway through STAT3 in a keratinocyte cell line, demonstrating a direct action of this ligand. An IL-20 receptor was identified as a heterodimer of two orphan class II cytokine receptor subunits. Both receptor subunits are expressed in skin and are dramatically upregulated in psoriatic skin. Taken together, these results demonstrate a role in epidermal function and psoriasis for IL-20, a novel cytokine identified solely by bioinformatics analysis.

Animals↗
PubMed1989

Psychophysical observations on patients with neuropathic pain relieved by a sympathetic block.

Patients with sympathetically maintained pain (SMP) were tested with noxious heat pulses, innocuous mechanical stimuli, and transcutaneous electrical nerve stimulation before and during local anesthetic sympathetic blocks that relieved their pain. The perceived intensity of the pain evoked by these stimuli was measured by the patients' responses on a visual analog scale and compared to the responses obtained when the same stimuli were applied to contralateral normal skin. In 5 of 7 patients tested, graded noxious heat stimuli (43-51 degrees C) applied to painful skin resulted in heat-pain intensity ratings that were essentially identical to the responses obtained when the same stimuli were applied to the normal side. Of the remaining two patients, one was clearly hypoalgesic for heat-pain and the other was probably hyperalgesic. The normal and subnormal heat-evoked responses obtained from abnormal skin were unchanged during completely successful sympathetic blocks. Trains of noxious heat pulses (52 degrees C) evoked summation of the second pain sensation in each of the 4 patients tested. This summation effect was normal and unaffected by a sympathetic block. Four of the patients had allodynia evoked by mechanical stimulation. In each of the 3 allodynia cases tested, transcutaneous nerve stimulation at an intensity that was at threshold for detection evoked burning pain and a coexistent sensation of tingle, indicating that both sensations were due to the activation of A beta axons. Patients without touch-evoked pain reported that electrical stimuli at threshold for detection produced only the sensation of tingle. The pains evoked by touch and by threshold-strength nerve stimulation were eliminated during sympathetic block. In patients with allodynia, trains of gentle mechanical stimuli and trains of threshold-strength electrical nerve stimuli produced summation of the intensity of the burning pain sensation when the stimuli were presented at 0.3 Hz. These results add to a growing body of evidence indicating that the touch-evoked pain of some patients is due to abnormal central activity evoked by input from A beta low-threshold mechanoreceptors. The coexistence of A beta-evoked pain with normal heat-evoked pain and normal heat-pain summation suggests that the central abnormality cannot be a simple hypersensitivity of wide-dynamic-range neurons. The effect of sympathetic blockade on A beta-evoked pain and its summation suggests that the crucial sympathetic interaction may take place centrally. The results show that there is considerable heterogeneity of sensory abnormalities among patients with SMP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2001

Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease.

We present three patients with variegated aneuploidy and premature centromere division (PCD), a rare chromosomal abnormality in humans. Comparison of these three and eight other patients with variegated aneuploidy related to PCD demonstrates a phenotype comprising most frequently microcephaly, CNS anomalies (with cerebellar affection and migration defects), mental retardation, pre-and postnatal growth retardation, flat and broad nasal bridge, apparently low-set ears, eye and skin abnormalities, and ambiguous genitalia in male patients. The occurrence of Wilms tumor in three patients, rhabdomyosarcoma in two others and acute leukemia in a fifth characterizes this condition as a chromosome or genome instability disorder with a high risk of malignancy. FISH studies in uncultured blood and buccal smear cells demonstrate that the random aneuploidies are not limited to cultured cells, but also occur in vivo.

Abnormalities, Multiple↗
PubMed2002

Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours.

To examine the consequences of repressing beta-catenin/Lef1 signalling in mouse epidermis, we expressed a DeltaNLef1 transgene, which lacks the beta-catenin binding site, under the control of the keratin 14 promoter. No skin abnormalities were detected before the first postnatal hair cycle. However, from 6 weeks of age, mice underwent progressive hair loss which correlated with the development of dermal cysts. The cysts were derived from the base of the hair follicles and expressed morphological and molecular markers of interfollicular epidermis. Adult mice developed spontaneous skin tumours, most of which exhibited sebaceous differentiation, which could be indicative of an origin in the upper part of the hair follicle. The transgene continued to be expressed in the tumours and beta-catenin signalling was still inhibited, as evidenced by absence of cyclin D1 expression. However, patched mRNA expression was upregulated, suggesting that the sonic hedgehog pathway might play a role in tumour formation. Based on our results and previous data on the consequences of activating beta-catenin/Lef1 signalling in postnatal keratinocytes, we conclude that the level of beta-catenin signalling determines whether keratinocytes differentiate into hair or interfollicular epidermis, and that perturbation of the pathway by overexpression of DeltaNLef1 can lead to skin tumour formation.

Animals↗
PubMed2003

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Animals↗
PubMedDate not supplied

Molecular and cell biology of porcine HSP47 during wound healing: complete cDNA sequence and regulation of gene expression.

Heat shock protein (HSP) 47 is a major stress-inducible protein that is localized to the endoplasmic reticulum of avian and mammalian cells and is thought to act as a molecular chaperone specific for the processing of procollagen. However, limited information is available regarding the regulation of HSP47 during wound healing. Using a polymerase chain reaction strategy, screening of a cDNA library, and RACE-polymerase chain reaction approaches, the sequence of a full-length porcine HSP47 cDNA has been identified. The cDNA contained 2096 bp that encodes for an 18 amino acid signal peptide and a mature protein coding region consisting of 401 amino acid residues. It also included 108 bp of the 5' noncoding region and a 731-bp 3' noncoding region. The deduced amino acid is 83% identical to chicken, 87% identical to mouse, 88% identical to rat, and 91% identical to human HSP47. It also shares between 26% and 30% identity with different members of the serine protease inhibitor superfamily. The protein contains a RDEL endoplasmic reticulum retention signal, and two potential glycosylation sites. All of these features are characteristic of HSP47 in higher vertebrates. Heat shock treatment of porcine fibroblasts led to up-regulation of HSP47 at both the transcriptional and translational levels. HSP47 protein levels were also up-regulated during skin wound healing in a pig model. Moreover, a higher molecular weight complex at approximately 140 Kda containing HSP47 was detected at the stage of healing that was coincident with the maximal transcriptional expression of HSP47 during wound healing in this animal model. Further investigation of how HSP47 is regulated during normal and abnormal skin wound healing may lead to new therapeutic approaches to improve the healing process.

Animals↗
PubMed2002

Tyr-TGFalpha transgenic mice develop ocular melanocytic lesions.

Transforming growth factor-alpha (TGFalpha) has been implicated in melanocyte transformation, as it is expressed in melanocytic lesions and in melanoma cells. We investigated its role in melanoma development using a transgenic mouse model. The mice were generated by microinjection of a transgene with 270 bp of the mouse tyrosinase promoter and the cDNA for human TGFalpha. No significant skin abnormalities were found, but individuals from three transgenic lines developed ocular melanocytoses (seven out of 10 transgenics), usually after a long latency period. In particular, the melanocyte component of the choroid was thicker than in non-transgenic controls, consistent with hyperplasia. The retinal pigment epithelium was unaffected. Melanocytic lesions were also present in the posterior eye, and abnormal distributions of melanocytes were found in neural tissue of the brain, skeletal muscle of the head and the Harderian glands, indicating migration from the choroid. It was concluded that mice engineered to express the normal growth factor TGFalpha from a tyrosinase promoter spontaneously developed melanocytic lesions in the eye but not the skin.

Animals↗