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PubMed1999

Isolated deficient alpha6beta4 integrin expression in the gut associated with intractable diarrhea.

BACKGROUND: An infant born with pyloric atresia had development of intractable diarrhea and was found to have total epithelial detachment of gastric and small and large bowel mucosa. She had no skin abnormalities. Parental consanguinity and pyloric atresia in a sibling who died without autopsy suggest an inherited origin for this disorder. The purpose of this study was to examine defects in intestinal and skin cell adhesion. METHODS: Histologic, immunohistochemical, and ultrastructural characteristics of the skin and gut of the patient were compared with that of normal control subjects. Distribution of adhesion molecules was determined. RESULTS: Immunofluorescent analysis of the digestive mucosa showed alpha6beta4 integrin expression deficiency at the epithelial cell-lamina propria junction. Ultrastructural examination of the digestive mucosa revealed a complete epithelial detachment with a cleavage plane lying between the lamina densa and the basal pole of the enterocytes. Consistent with the absence of skin blistering, integrin alpha6beta4 was expressed at the dermal-epidermal junction. Electron micrographs of skin biopsy specimens showed the presence of normal hemidesmosomes and the absence of dermal-epidermal dysadhesion. CONCLUSION: It was postulated that this patient had protracted diarrhea related to epithelial detachment of the digestive mucosa as a consequence of a deficiency of an integrin alpha6beta4 isoform specific to the gut.

Antigens, Surface↗
PubMed2004

Hyperkeratosis in cystathionine beta synthase-deficient mice: an animal model of hyperhomocysteinemia.

Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations. Patients with severe hyperhomocysteinemia have fine hair and thin skin, but it is unclear whether these changes are related to CBS deficiency or are coincidental. To investigate these aspects of hyperhomocysteinemia, we characterized skin abnormalities of CBS-deficient mice, a murine model of severe hyperhomocysteinemia. Histological and histomorphometric analyses revealed that CBS-deficient mice have wrinkled skin with hyperkeratinosis of the epidermis and thinning of the dermis.

Animals↗
PubMed1982

Reflex heating of the skin and telethermography.

Thermography is a very instructive method of showing the interaction between direct changes in heat radiation of the surface of the skin and its relation to reflex processes. Short reflex arcs, such as the axon reflex, and long reflex arcs, such as the flush phenomenon provoked by visceral cutaneous reflexes, can be illustrated by thermography. Reflex changes in skin temperature by cooling the skin of patients with cold contact urticaria with the short-term development of large areas of warmed skin and also reflex changes in cholinergic urticaria after prior heating of such skin areas where the urticarial eruption follows are reflected in the picture of telethermography. Reflex arcs between extremities affect the arterial blood flow and show individual variation, as in the case of the cessation of permanent local vasoconstriction by indirect cooling. The thermographic illustration of convective heat transport to the skin surface can be obstructed by the cooling effect of sweat secretion, e.g., water vapor exudation and by changes in conductive heat transport in abnormal skin.

Adult↗
PubMed2001

Elderly and sun-affected skin. Distinguishing between changes caused by aging and changes caused by habitual exposure to sun.

OBJECTIVE: To review and distinguish between skin changes produced by aging and changes produced by habitual exposure to sun. QUALITY OF EVIDENCE: The literature was searched from 1969 to 1999 for articles on dermatoheliosis and sun-damaged skin. Surprisingly few were found comparing the difference between elderly skin and sun-damaged skin. A few articles focused on certain small aspects of sun-damaged skin. Many excellent articles described particular changes (e.g., actinic keratosis), but few covered all the changes due to aging and to sun. MAIN MESSAGE: Skin changes due to aging can be distinguished from those due to sun damage. All changes due to sun exposure can be grouped under the term dermatoheliosis; five parts of the skin are involved: epidermis (actinic keratosis), dermis (solar elastosis), blood vessels (telangiectasia), sebaceous glands (solar comedones), and melanocytes (diffuse or mottled brown patches). Habitual exposure to sun and a white skin are prerequisites for developing these changes. Knowing the difference between changes caused by sun and by aging can help physicians predict which patients are most likely to get skin cancers. CONCLUSION: Knowledge of these common skin changes will help physicians diagnose and manage the skin abnormalities of elderly people and of people with dermatoheliosis.

Aged↗
PubMed1990

Severe hypersensitivity to mosquito bites associated with natural killer cell lymphocytosis.

A 2-year-old girl showed exaggerated skin reactions to mosquito bites and associated general symptoms, including a high temperature, lymphadenopathy, and hepatosplenomegaly. Peripheral blood lymphocytes contained a high percentage of CD2+, CD3-, CD4-, CD8-, CD11b+, CD16+, CD38+, CD56+, CD57-, and HLA-DR+ large granular lymphocytes that exhibited a marked natural killer cell activity. Immunohistochemically, biopsy specimens taken from the lesional skin demonstrated an infiltrate of the cells bearing the natural killer cell phenotype, indicating a role of these cells in the development of the abnormal skin reactions to mosquito bites and other systemic manifestations. Our case suggests that natural killer cell lymphocytosis may show severe hypersensitivity to mosquito bites as the most outstanding manifestation.

Animals↗
PubMed2000

Immunohistochemical localization of transforming growth factor-alpha and epithelial growth factor receptor in human fetal developing skin, psoriasis and restrictive dermopathy.

Keratinocytes release a number of cytokines interacting with other intra- and subepidermal cells during the initiation and the perpetuation of skin inflammatory reactions. Cultured human keratinocytes overexpressing the transforming growth factor alpha (TGF-alpha) assumed a spindled morphology and displayed increased locomotion. Moreover, the receptor for TGF-alpha, the epithelial growth factor receptor (EGFR), is important for autocrine growth, promotion of cell survival, and regulation of cell migration. The expression of TGF-alpha and EGFR has not been widely studied in human developing skin and their roles in geno-dermatosis are not known. In this study, we investigated the expression of TGF-alpha and EGFR by immunohistochemistry in human developing skin at different gestational ages (14 th week, 20 th week, and 34 th week), in six patients with psoriasis, and, for the first time, in an infant affected with restrictive dermopathy, a very rare lethal genodermatosis, characterized by abnormal skin growth and differentiation with thin, tightly adherent skin. TGF-alpha and EGFR were expressed in the basal layer at the 14 th week and in all epidermal layers at the 20 th and 34 th week of gestation. In psoriasis, TGF-alpha was overexpressed in all layers of epidermis, while EGFR was expressed in the basal and first suprabasal layers. In restrictive dermopathy, we observed no expression of both TGF-alpha and EGFR at the level of the skin. The other organs showed comparable patterns to those of an age-matched infant. In conclusion, TGF-alpha and EGFR interact strictly to promote skin development during the intrauterine life. An interactive autocrine growth cycle between TGF-alpha and EGFR is present in psoriasis. A skin-localized alteration of the expression of TGF-alpha and EGFR may be at the basis of restrictive dermopathy. The delay of growth and differentiation of the skin in restrictive dermopathy may be related to the absent expression of TGF-alpha, which is probably due to a down regulation of EGFR by an abnormal autocrine mechanism.

Aged↗
PubMed1984

Cutaneous vasculitis and immune complexes in severe bronchiectasis.

Four patients with severe bronchiectasis (chronic bronchial suppuration) are described who developed cutaneous lesions associated with exacerbations of their respiratory disease. The skin abnormalities consisted of purpuric lesions in three patients and an erythematous vasculitis in one. Circulating immune complexes were present in all patients and in three skin biopsy specimens showed deposition of C3, IgG, and IgA in dermal blood vessels. Haemophilus influenzae had been isolated from the sputum of all four patients and in two patients was present at the time the cutaneous lesions appeared. It is suggested that local immune complex deposition was responsible for the skin lesions which occurred during acute exacerbations of bronchiectasis.

Aged↗
PubMedDate not supplied

Pseudo oculomotor palsy as the presenting sign of linear scleroderma.

A case of linear scleroderma presenting as a pseudo oculomotor palsy is reviewed. The patient's facial skin abnormalities suggested the underlying etiology. This case illustrates a previously unreported finding in linear scleroderma, mydriasis without atrophy, reminding the clinician to look at the skin in patients with unexplained unilateral pupillary disturbances.

Biopsy↗
PubMed1998

Health status assessment of drug addicts in Alexandria.

The case-control study was conducted among addicts in Alexandria to determine the different health problems among them, as well as to study the correlation between addiction and these problems. One hundred drug addicts and eighty apparently healthy controls were included in this study. The whole sample was subjected to the following: filling a predesigned questionnaire sheet, clinical and electrocardiogram (ECG) examination, measurements of Body Mass Index (BMI), complete blood picture and antistreptolysin O titre (ASO), testing for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti HBc), skin scrapings from superficial fungal lesions in addition to complete urine and stool examination. The results revealed that chest rhonchi, hepatomegaly, central nervous system (CNS) abnormalities, skin lesions lymphadenopathy, underweight and anaemia were significantly higher among addicts than the controls. Hepatitis B virus (HBV) exposure and HBsAg seropositivity were found 48.0% and 21.0%, respectively among addicts compared to 26.3% and 5.0%, respectively among the controls. The intravenous injections and tattooing were the most risky routes for HBV infection among addicts. A positive correlation was revealed between HBV exposure and both the duration and the number of daily injections. Chest X-ray suggestive of pulmonary tuberculosis were found in 7.0% of the addicts. Addiction potentiated the risk of fungal infection among low social class, but it had no effect on the relationship between anaemia and social class nor on that between loss of appetite and underweight.

Adolescent↗
PubMed2005

A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice.

Psoriasis is a common, persistent skin disorder characterized by recurrent erythematous lesions thought to arise as a result of inflammatory cell infiltration and activation of keratinocyte proliferation. Unscheduled angiogenic growth has also been proposed to mediate the pathogenesis of psoriasis although the cellular and molecular basis for this response remains unclear. Recently, a role for the angiopoietin signaling system in psoriasis has been suggested by studies that demonstrate an up-regulation of the tyrosine kinase receptor Tie2 (also known as Tek) as well as angiopoietin-1 and angiopoietin-2 in human psoriatic lesions. To examine temporal expression of Tie2, we have developed a binary transgenic approach whereby expression of Tie2 can be conditionally regulated by the presence of tetracycline analogs in double-transgenic mice. A psoriasis-like phenotype developed in double-transgenic animals within 5 days of birth and persisted throughout adulthood. The skin of affected mice exhibited many cardinal features of human psoriasis including epidermal hyperplasia, inflammatory cell accumulation, and altered dermal angiogenesis. These skin abnormalities resolved completely with tetracycline-mediated suppression of transgene expression, thereby illustrating a complete dependence on Tie2 signaling for disease maintenance and progression. Furthermore, the skin lesions in double-transgenic mice markedly improved after administration of the immunosuppressive anti-psoriatic agent cyclosporine, thus demonstrating the clinical significance of this new model.

Angiopoietins↗
PubMed1975

Acute, generalized panniculitis with amylase and lipase in skin.

A patient had an unusual acute, generalized panniculitis. The patient had a five-fold elevation of urinary amylase level and a slightly elevated serum lipase leval without any signs or symptoms of pancreatic disease. A secretin test caused an eightfold elevation in urinary amylase level and some elevation of serum lipase and amylase levels, whereas study of duodenal drainage revealed no abnormalities. Skin specimens from the lesions showed considerable amylase and lipase activity, whereas specimens from controls and from subsequent patients with panniculitis showed no such abnormalities. Autopsy showed a normal pancreas, both grossly and microscopically.

Abscess↗
PubMed1983

Cell-free synthesis and transport of precursors of mutant ornithine carbamoyltransferases into mitochondria.

Synthesis, mitochondrial transport and processing of ornithine carbamoyltransferase (EC 2.1.3.3) were studied in mutant mice strains (sparse-fur, spf, and sparse-fur with abnormal skin and hair, spf-ash) which exhibit a deficiency in this enzyme. Spf mice have an increased amount (about 150% of control) of the enzyme with abnormal kinetic properties, whereas spf-ash mice have a decreased amount (about 10% of control) of the enzyme with apparently normal kinetic properties. Precursors of the mutant enzymes were synthesized in a reticulocyte lysate cell-free system. The hepatic level of translatable mRNA coding for the enzyme and the rate of the enzyme synthesis in liver slices of spf mice were 58 and 60% of the controls, respectively. In the case of spf-ash mice the activity of translatable mRNA for the enzyme was 10% of the controls. These results indicate that the decreased amount of ornithine carbamoyltransferase protein in spf-ash mice is due mainly to a decreased level of translatable mRNA for the enzyme, whereas the increase in the enzyme amount in spf mice is presumably the result of a decreased rate of enzyme degradation. The subunit molecular weight of the spf enzyme precursor was practically the same as that of the normal enzyme precursor (Mr 40 000). Both precursors synthesized in vitro could be taken up and processed similarly to an apparently mature form (Mr 37 000). In the case of spf-ash enzyme, two discrete in vitro products were observed on sodium dodecyl sulfate polyacrylamide gel; one comigrated with the normal enzyme precursor and the other moved slightly slower. Both products appeared to be taken up and processed to the mature form of the enzyme.

Animals↗
PubMed1978

Linoleic acid effects on epidermal DNA synthesis and cutaneous prostaglandin levels in essential fatty acid deficiency.

An essential fatty acid (EFA) deficient state has been induced in hairless mice. The epidermal changes included hyperkeratosis, hypergranulosis and acanthosis. Epidermal DNA synthesis was increased 3-fold compared with normal diet mice. Prostaglandin E (PGE) and prostaglandin F (PGF) levels, measured by radioimmunoassay, were much reduced in the EFA deficient mice skin. 10% Linoleic acid applied topically for 2 weeks corrected the gross and histological skin abnormalities and reduced epidermal DNA synthesis to normal values. The levels of PGE and PGF were only partially corrected. Linoleic acid applied to normal diet mice increased skin levels of PGE and PGF compared with the control vehicle treated normal diet mice. These results provide further evidence for the importance of essential fatty acids in the control of epidermal proliferation and differentiation. The importance of PGE and PGF in controlling epidermal DNA synthesis in EFA deficiency is less clear.

Animals↗
PubMed2005

Expression of nerve growth factor in itchy skins of atopic NC/NgaTnd mice.

Although the possible involvement of neurotrophic factors in itchy skins of atopic dermatitis has been predicted, the exact mechanism by which itch is induced remains unclear. Since nerve growth factor (NGF) has crucial effects on development and functions of sensory nerves, we determined production of NGF and extension of nerve fibers in skins of NC/NgaTnd mice with or without atopic dermatitis. NC/NgaTnd mice spontaneously develop atopic dermatitis-like skin lesions when they are raised in air-unregulated conventional circumstances. We quantified scratching behavior of NC/NgaTnd mice during the development of dermatitis using a novel analytical system and compared to clinical skin severity scores. A significant correlation between the severity of dermatitis and the increase in the number of scratches was identified, indicating that scratching behavior may associate with clinical skin conditions. NGF contents in the skin lesions of conventional NC/NgaTnd mice were significantly higher than those in SPF mice. Positive reactions for NGF were observed in keratinocytes and fibroblasts in affected skins of conventional NC/NgaTnd mice. Immunohistochemical analysis showed the extension of protein gene product 9.5-positive nerve fibers from the dermis toward the epidermis at the skin lesions. These results suggest that sensory nerves induced by NGF may contribute to development of itch, and that NGF produced at the affected site may provide abnormal skin sensitivity in atopic dermatitis.

Animals↗
PubMed1999

Laser resurfacing: a safe and predictable method of skin resurfacing.

Skin resurfacing with lasers for skin restoration has been the most exciting advance in cosmetic surgery in the past 2 years. This method has effectively replaced chemical peel and dermabrasion as modes for skin rejuvenation, yet surprisingly, very little has been published on its effectiveness. Our aim is to delineate clear indications, methods and results of laser skin resurfacing. Laser resurfacing has evolved over the past 13 years and our current method has emerged from this experience. This method has been employed on 258 consecutive patients treated over the past 2 years. A total of 201 patients were treated for photodamaged skin, 53 for facial acne scarring and four for post-surgical scars. Each of these conditions has in common the pathological finding of contour irregularity of the involved abnormal skin. The CO2 Ultrapulse laser's advantage is the predictable ability to vaporize the upper layer of elevated skin, tighten collagen bundles and induce a local inflammatory reaction with epithelial proliferation. This paper presents a clear, concise, and conservatively oriented technique, including pre- and post-operative care of laser skin resurfacing. The technique presented is conceived to correct precisely the underlying pathological condition and can be used in conjunction with other cosmetic procedures. A total of 200 patients underwent full face resurfacing, 41 periorbital, 13 perioral and four for facial scars. Of the patients, 78% were female and 22% were male. The results of each patient were judged by an independent observer. Some 92% were found to have either an excellent or very good result; 2% were judged to be satisfactory; and 6% were from outside the region or were lost to follow-up. Minor complications included 12% transient post-inflammatory hyperpigmentation, 3% acute acne and 1% herpes type 1. There were no major complications, including hypertrophic scarring. A total of 15% required some type of secondary touch-up resurfacing. Our method of laser skin resurfacing offers a consistent method for dramatic improvement of facial skin quality for those patients with photodamage and acne scarring, while minimizing risk.

Acne Vulgaris↗
PubMed1998

Effect of targeted mutation in collagen V alpha 2 gene on development of cutaneous hyperplasia in tight skin mice.

Collagen V plays a major regulatory role in the formation of heterotypic fibers of the dermis and cartilaginous tissues as well as in the assembly of extracellular matrix. The pN/pN mouse, which is defective in collagen V alpha 2 gene, exhibits skeletal abnormalities, skin fragility, and alterations in the collagen fiber organization, whereas the TSK/+ mouse, which is defective in fibrillin-1, the major component of microfibrils present in the extracellular matrix, develops cutaneous hyperplasia and autoimmunity. We have studied the role of collagen V in the formation of heterotypic collagen fibers in F1 mice, which are obtained by breeding pN/pN with TSK/+ mice. Our results show that F1 progeny neither develop cutaneous hyperplasia nor produce anti-topoisomerase I autoantibodies, unlike TSK/+ mice. The diameter of the collagen fibrils in the skin is also comparable to that found in control mice. Thus, the phenotypic changes observed in the TSK mouse could be reversed by genetic complementation with a collagen V-defective mouse.

Alleles↗
PubMed1982

Patterns of breast skin thickness In normal mammograms.

Measurement of the mammographic skin thickness over different parts of the breast was performed in 150 normal patients. The patients were divided into three groups based on breast size and the skin thickness in these three groups compared. The results showed that skin thickness decreased with increasing breast size and that the upper limit of normal was greater than the previously quoted normal range at 3.0 mm. Measurement over different parts of the breast showed that medial exceeded lateral skin thickness by up to 100%, and similarly for the inferior and superior measurements. These findings in the normal breast are of importance in deciding on the presence or absence of abnormal skin thickening as an indicator of underlying breast disease.

Adult↗
PubMed2000

Magnetic resonance imaging detection of occult skin and subcutaneous abnormalities in juvenile dermatomyositis. Implications for diagnosis and therapy.

OBJECTIVE: To assess the utility of magnetic resonance imaging (MRI) of skin, subcutaneous tissue, and fascia in evaluating disease activity in juvenile dermatomyositis (DM). METHODS: Short tau inversion recovery (STIR) MRI of the proximal thighs and buttocks, cutaneous assessment, and other measures of disease activity were prospectively obtained in 26 children meeting criteria for probable or definite juvenile DM. Also undergoing STIR MRI assessment were 8 subjects who were being evaluated for muscle disorders and who were not diagnosed as having juvenile DM. RESULTS: Skin, subcutaneous, or fascial edema of the thighs and buttocks were seen on STIR MRI in up to 85% of juvenile DM patients at baseline evaluation compared with no more than 38% of the comparison group without juvenile DM. In juvenile DM, STIR MRI skin and subcutaneous edema scores correlated (r(s) = 0.51, P = 0.008), as did fascial and muscle edema scores (r(s) = 0.58, P = 0.002). Skin global disease activity scores correlated with MRI skin edema scores (r(s) = 0.41, P = 0.04), and serum aldolase levels correlated with both MRI skin and subcutaneous edema scores (r = 0.44 and 0.40, P = 0.03 and 0.05 respectively). The extent and severity of STIR MRI changes in the skin, subcutaneous tissue, and fascia were not predicted by most other measures of juvenile DM disease activity. Five juvenile DM patients with thigh MRI subcutaneous edema developed clinically apparent calcinosis at the same location within 9 months. CONCLUSION: Edema or inflammation in the skin, subcutaneous tissue, and fascia, found on STIR MRI, is common in juvenile DM patients and is often undetected by standard assessments. These MRI changes can precede the development of calcinosis. STIR MRI may be a useful adjunct for assessing disease activity and guiding the treatment of juvenile DM.

Adolescent↗