Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermatitis herpetiformis (DH) is a chronic subepidermal blistering disease, in which a perivascular cellular infiltrate, composed mainly of CD4+ T lymphocytes together with a varying number of neutrophils and eosinophils, is thought to be important in the pathogenesis of blister formation. The aim of this study was to investigate the potential role of cytokines such as the interleukins IL-4 and IL-5 and to quantify the distribution of T cells as well as their state of activation using alkaline phosphatase-antialkaline phosphatase and reverse transcriptase-polymerase chain reaction (RT-PCR) procedures in seven patients with typical clinical and histological features of DH. A strong extracellular staining with anti-IL-4 monoclonal antibody was detected in the upper dermis with a prevalent perivascular pattern in perilesional areas, whereas in the dermal-epidermal separation sites there was an intense, scattered distribution. IL-5 was intensely expressed, mainly at the intracellular level, by eosinophils and lymphocytes. Concerning RT-PCR, five DH patients showed a strong positive signal for both IL-4 and IL-5 cytokines while two patients showed a faint signal for both IL-4 and IL-5; these last two cases were histologically poor in inflammatory cells. In view of these results, it can be hypothesized that the recruitment of eosinophils and neutrophils in DH may be induced not only by granulocyte macrophage colony-stimulating factor and IL-8 as previously demonstrated, but also by Th2 cytokines as well.
Br J Dermatol 1998 Feb
PMID:Th2-like cytokine activity in dermatitis herpetiformis. 960 68

Mutation of the hairless (hr) gene in mice causes severe abnormalities during the first hair follicle regression (catagen), resulting in complete baldness. Here, we further characterize how hairlessness develops in HRS/J hairless mouse skin (hr) by histology, histochemistry, immunohistology, and in situ hybridization. We show that, in hr skin, only two defined epithelial cell populations in the distal outer root sheath (ORS) retain their integrity, whereas the rest of the ORS disintegrates. The surviving distal ORS forms the characteristic utriculi, whereas the remnants of the bulge get isolated from other epithelial compartments, but retain the capacity to proliferate and to produce either columnar epithelial outgrowths or selected dermal cysts. Normal dermal papilla structures get lost during the development of hairlessness. Based on the patterns of keratin 17 mRNA and neural cell adhesion molecule antigen expression, and on the distribution of alkaline phosphatase activity, we propose that dermal cysts in hr skin arise from (i) the central ORS, (ii) bulge-derived cells, or (iii) the disintegrating proximal ORS under the influence of dermal papilla remnants. The hr mutation seems to disrupt the integrity of key functional tissue units in the hair follicle, possibly due to a dysregulation of normal, catagen-associated apoptosis and/or an impairment of cell adhesion, whereas the distal follicle epithelium (including its stem cell region) seems to be largely protected from this. Thus, hairless mice offer a unique model for dissecting the as yet obscure functional properties of the hr gene product in maintaining follicle integrity during normal catagen.
J Invest Dermatol 1998 Jun
PMID:Towards defining the pathogenesis of the hairless phenotype. 962 Feb 97

The derivatives of fumaric acid show antipsoriatic effects but details of the mechanism of action are largely unknown. The study focused on the effect of fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its derivatives for 48 hrs. The effect of fumarates was investigated semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP-ELISA technique. The semiquantitative evaluation revealed that in the micromolar dose range investigated only dimethyl-fumarate demonstrated substantial growth inhibition and down-regulation of the cell surface markers. In the quantitative evaluation, dimethyl-fumarate significantly (p</=0.05) suppressed the expression of ICAM-1 (84%) and HLA-DR (67%) on HaCaT keratinocytes at a subtoxic concentration of 4.0 microM as compared to untreated controls (100%). In contrast, concentrations of 4.0, 12 and 35 microM dimethyl-fumarate had no influence on the ICAM-1 and HLA-DR expression on IFN-gamma-exposed normal human epidermal keratinocytes in primary cultures. Thus, there is experimental evidence that dimethyl-fumarate may exert its antipsoriatic effect not only as an antiproliferative agent but also by down-regulation of ICAM-1 and HLA-DR molecules on hyperproliferative keratinocytes.
Eur J Dermatol
PMID:The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1 and HLA-DR expression on hyperproliferative keratinocytes. Quantification by a culture plate-directed APAAP-ELISA technique. 964 87

Terbinafine is an allylamine antifungal agent first launched in the USA in May 1996 with an estimated 7.5 million individuals worldwide having used the drug. Given orally it is effective for the treatment of dermatophyte infections and is prescribed predominantly for the superficial mycoses. Adverse effects have been reported in 46.7% of patients receiving the oral drug (compared with 29.2% receiving placebo, the attributable risk to terbinafine being 17.5%). Thus, oral terbinafine is associated with the rare development of symptomatic idiosyncratic hepatobiliary dysfunction (1:45,000-1:54,000) and we now describe three patients who developed this disorder whilst taking the medication. The hepatitis produced has the features of both hepatocellular necrosis (with elevations of hepatic enzyme concentrations) and cholestatic injury (with elevations of alkaline phosphatase and cholesterol levels), the latency period between the start of medication and the development of liver injury being approximately 4-6 weeks. The US terbinafine product monograph recommends that serum hepatic enzymes should be assessed in individuals receiving terbinafine for more than 6 weeks, as a result of which some physicians monitor these values at baseline and at 4-6 weeks.
Clin Exp Dermatol 1998 Mar
PMID:Hepatitis associated with terbinafine therapy: three case reports and a review of the literature. 969 7

Some studies have suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency. We followed 24 sunscreen users and 19 controls over 2 years, including two summers, two winters and a basal period (winter). Vitamin D, parathormone and bone biological markers were evaluated each season. Mean levels of 25-hydroxyvitamin D rose in summer, with the increments being significantly higher for the second year in the control group. Levels decreased in winter in both groups, and were significantly lower in sunscreen users. We did not observe any significant change in parathormone, tartrate resistant phosphatase, total alkaline phosphatase, osteocalcin, urine hydroxyproline or urine calcium. Clinically prescribed sunscreen creams (sun protection factor 15) caused a minor decrease in 25-hydroxyvitamin D levels, which did not induce secondary hyperparathyroidism or an increment in bone biological markers.
Br J Dermatol 1998 Sep
PMID:Clinically prescribed sunscreen (sun protection factor 15) does not decrease serum vitamin D concentration sufficiently either to induce changes in parathyroid function or in metabolic markers. 976 86

A unique hybrid oligonucleotide composed of both RNA and DNA has been shown to correct a point mutation in a site-specific and inheritable manner in extrachromosomal and chromosomal targets. In order to develop new gene therapeutics for skin, we tested two oligonucleotides that were shown to create a point mutation in alkaline phosphatase and beta-globin genes in several epithelial cell types. Highly transformed epithelial cells (HeLa) exhibited a conversion frequency of 5% by both RNA-DNA oligonucleotides. In comparison, other immortalized epithelial cells (HaCaT) or human primary keratinocytes did not show any detectable level of gene conversion by the restriction fragment length polymorphism analysis, indicating less than 1% conversion frequency. The concentration of the oligonucleotide in the nuclei of HeLa cells was similar to that of HaCaT or human primary keratinocytes measured by a radiolabeled or a fluorescein-conjugated oligonucleotide. Moreover, the RNA-DNA oligonucleotide exhibited a prolonged stability in the nucleus. Thus, neither uptake nor nuclear stability of the oligonucleotide appears to be a limiting factor in gene targeting events under our experimental conditions. These results indicate that the frequency of gene targeting varies among different cells, suggesting that cellular recombination and DNA repair activities may be important.
J Invest Dermatol 1998 Dec
PMID:Different frequency of gene targeting events by the RNA-DNA oligonucleotide among epithelial cells. 985 35

We report a case of acute febrile neutrophilic dermatosis, Sweet's syndrome, associated with chronic myelogenous leukemia (CML) in which we found rearrangement of the bcr gene in DNA obtained from a skin lesion as well as in blood DNA by Southern blot analysis. This indicated the presence of CML cells within the skin lesion. To our knowledge, this is the first report in which the presence of CML cells is shown within skin lesions of Sweet's syndrome. In our patient, leukocyte alkaline phosphatase activities returned to normal levels when he was suffering from Sweet's syndrome and decreased again to below normal levels after it subsided. Whether the normalization of leukocyte alkaline phosphatase activity is common among CML patients with Sweet's syndrome remains to be determined.
J Am Acad Dermatol 1999 Feb
PMID:Sweet's syndrome associated with chronic myelogenous leukemia: demonstration of leukemic cells within a skin lesion. 1002 63

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.
Br J Dermatol 1999 Jun
PMID:The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis. 1035 73

Microbiological aspects are considered to be of pathophysiological importance in psoriasis, but there has so far been no information regarding cytomegalovirus (CMV) infection. This is of interest due to the high prevalence of latent infection in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. To detect active infection we analysed CMV antigen expression of peripheral blood mononuclear cells (PBMC) from psoriatic patients (n = 30) in comparison with healthy volunteers (n = 65). Using three monoclonal antibodies and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique), we frequently found CMV antigenaemia in psoriasis (43%) compared with healthy laboratory staff (12%, P < 0. 01) and blood donors (6%, P < 0.001). Clearance of CMV antigenaemia was observed with antipsoriatic treatment. CMV antigenaemia was symptomless, and was associated with seropositivity for anti-CMV IgG but not IgM antibodies, indicating subclinical activation of latent infection. Serological investigations in 85 psoriatic patients gave no evidence for a higher prevalence of latent CMV infection. In psoriatic lesions, CMV DNA was only rarely detected by polymerase chain reaction. As it has been shown that tumour necrosis factor (TNF)-alpha can induce CMV reactivation, we determined TNF-alpha plasma concentrations and mRNA expression in PBMC from psoriatic patients. Elevated TNF-alpha levels were found and correlated with the frequency of CMV antigen-expressing PBMC, suggesting a critical role of TNF-alpha in CMV activation. We speculate that active, subclinical CMV infection may be of pathophysiological importance in psoriasis.
Br J Dermatol 1999 Jul
PMID:A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression. 1041 21

Numerous spontaneous and experimentally induced mouse mutations develop a hair phenotype, which is often associated with more or less discrete abnormalities in hair follicle development. In order to recognize these, it is critically important to be able to determine and to classify accurately the major stages of normal murine hair follicle morphogenesis. As an aid, we propose a pragmatic and comprehensive guide, modified after previous suggestions by Hardy, and provide a list of easily recognizable classification criteria, illustrated by representative micrographs. Basic and more advanced criteria are distinguished, the former being applicable to all mouse strains and requiring only simple histologic stains (hematoxylin and eosin, Giemsa, periodic acid Schiff, alkaline phosphatase activity), the latter serving as auxiliary criteria, which require a pigmented mouse strain (like C57BL/6J) or immunohistochemistry (interleukin-1 receptor type I, transforming growth factor-beta receptor type II). In addition, we present simplified, computer-generated schematic drawings for the standardized recording and reporting of gene and antigen expression patterns during hair follicle development. This classification aid serves as a basic introduction into the field of hair follicle morphogenesis, aims at standardizing the presentation of related hair research data, and should become a useful tool when screening new mouse mutants for discrete abnormalities of hair follicle morphogenesis (compared with the respective wild type) in a highly reproducible, easily applicable, and quantifiable manner.
J Invest Dermatol 1999 Oct
PMID:A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis. 1050 36


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