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)

The effect of short-term (mean 2.4 months), low-dose (5 mg/kg) cyclosporin A (CyA) on renal function and blood pressure was studied in eight patients with psoriasis. Studies were undertaken before, during and after treatment. Glomerular filtration rate (GFR) post-treatment was significantly higher than pretreatment or during treatment (pre, 119 +/- 7; during, 113 +/- 9; post, 133 +/- 11 ml/min per 1.73 m2; pre vs. during, NS; during vs. post, P < 0.01; pre vs. post, P < 0.05); effective renal plasma flow (ERPF) was unchanged (pre, 515 +/- 38; during, 485 +/- 49; post, 560 +/- 45 ml/min per 1.73 m2). There was no change in the urinary excretion of either albumin or the enzymes N-acetyl-glucosaminidase, lactate dehydrogenase, alanine aminopeptidase and alkaline phosphatase. There was a decrease in exchangeable sodium which persisted post-treatment (pre, 56 +/- 3; during, 49 +/- 3; post, 49 +/- 3 mmol/kg LBM; pre vs. during, P = 0.07; during vs. post, NS; pre vs. post, P = 0.06). Blood pressure assessed as either a single reading, or the mean of a 24 h ambulatory recording, increased during treatment (single reading: pre, 113/73; during, 126/83; post, 114/70 mmHg; mean 24 h: pre, 114/71; during, 123/76; post, 120/72 mmHg). Thus, short-term use of CyA at a dose of 5 mg/kg for the treatment of psoriasis is associated with a significant increase in blood pressure, but only a transient mild reduction in GFR, which did not reach significance.
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PMID:The effect of short-term low-dose cyclosporin on renal function and blood pressure in patients with psoriasis. 850 48

Human monocyte/macrophage lineages have unique phagocytic and immune-regulatory functions. We established a promonocytic cell line from the peripheral blood of a patient with psoriasis vulgaris. The newly established cells, termed YAP cells, grew in a suspension culture. In Wright-Giemsa-stained preparations, YAP cells were round or polygonal in shape. Transmission electron microscopy showed that the cells had clear nuclei with well-defined nucleoli. There were frequent mitochondria, a relatively abundant endoplasmic reticulum profile, free ribosomes and an occasional Golgi apparatus. Cytochemical studies showed a positive reaction for alpha-naphthyl butyrate esterase, which was completely inhibited by sodium fluoride, a diffuse positive reaction for periodic acid-Schiff, and a negative result for alkaline phosphatase and peroxidase. A large population of YAP cells reacted with the CD4, CD11b, CD25 and CD33 surface markers, but not with CD2, CD3, CD8 or CD19. We also found that YAP cells produced considerable amounts of TNF alpha, which was detected in the culture supernatant when the cells were treated with 1 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA). Chromosome analyses showed that YAP cells contained a variety of marker chromosomes. It should be stressed that YAP cells were derived from a patient with a non-neoplastic disorder, whereas most monocytic cell lines previously reported are of malignant origin. This newly established cell line might be valuable for studying the pathogenesis of psoriasis, especially the role of monocytes/macrophages in the aetiology of the disease.
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PMID:Establishment and characterization of a novel human promonocytic cell line from peripheral blood of a patient with psoriasis. 873 64

The activity of gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDG), N-acetyl-beta-D-glucosaminidase (NAG) was assessed in 53 patients with psoriasis (PS), 24 PS patients with affected kidneys, 50 patients with type 1 diabetes mellitus(DM). Enhanced activity of the enzymes occurred not only in nephropathy patients but also in those without proteinuria. AP and NAG were more active in PS, while LDG and NAG in DM. Both in PS and DM, NAG activity rose 3-4-fold compared to control. A direct correlation was found between enzymuria and uremia, glycemia (in hyperglycemia only) and cholesterolemia. An inverse relationship existed between enzymuria and uricosuria. The above changes in enzymic activity are attributed to impairment of tubules of the kidney induced by PS and DM. Diagnostic significance of enzymuria as a marker of early tubular involvement is confirmed by investigations of renal biopsies.
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PMID:[Urinary enzymes in the assessment of the early stage of kidney involvement in psoriasis and diabetes mellitus]. 877 18

Numerous investigations have been carried out to describe the cellular biological changes in lesional and symptomless psoriatic skin. Although these studies have increased our knowledge of the pathogenesis of psoriasis, our insight into the relevance of the individual changes in the whole pathogenic process is still limited. Studies on the transition between symptomless and lesional skin are of importance in assessing the pathogenic relevance of the individual aspects. In this paper, the literature is reviewed with respect to the transitional changes; in particular, studies on changes at the margin of the psoriatic lesion and the response of the symptomless skin to standardized injury are reviewed. From the available studies it may be concluded that changes in the stroma (i.e. increased expression of tenascin and increased endothelial alkaline phosphatase activity) are early pathogenic features. The appearance of a predominantly lymphocytic infiltrate, in particular the extravasation of CD4+ T lymphocytes, and the suprabasal expression of keratin 16 are intermediary stages. Relatively late in the pathogenesis are increased recruitment of cycling epidermal nuclei, parakeratosis, decreased expression of filaggrin and premature expression of involucrin. In order to discover the pathogenic relevance of molecules which might have an impact on the development of psoriasis, sequential studies during transition from symptomless to lesional skin are worthwhile.
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PMID:Transition from symptomless to lesional psoriatic skin. 913 48

We studied phenotypic variations of apolipoprotein E (apoE) and the corresponding allele frequencies in 100 Japanese patients with psoriasis vulgaris (PV). The phenotypes of apoE were examined using analytical isoelectric focusing followed by immunoblotting with goat anti-apoE antibody and alkaline phosphatase-conjugated rabbit antigoat IgG. The phenotypic frequency of apoE3/2 in PV was significantly higher than in healthy controls, and this elevation was associated with an increased frequency of the epsilon 2 allele. Therefore, it is suggested that the apoE molecule plays an important role in the development of PV.
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PMID:Association of apolipoprotein allele epsilon 2 with psoriasis vulgaris in Japanese population. 934 68

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.
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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

The aim of the study was to investigate the rate of bone formation in patients with psoriatic arthritis (PsA) compared to controls and patients with psoriasis vulgaris without PsA (PS). Osteocalcin (OC) and other parameters of bone turnover were measured in 32 patients with PsA and 17 patients with PS and compared to controls (n = 50). Patients with PsA do not generally present with different OC levels (3.0 +/- 1.6 ng/ml), than controls (3.6 +/- 1.17 ng/ml), if disease activity or sex are not considered. Women with PsA had significantly lower OC levels (2.28 +/- 0.44 ng/ml) than female controls (4.11 +/- 1.7 ng/ml) or women with PS (3.0 +/- 0.89 ng/ml). However, mean disease activity (2.27 +/- 1.0 vs 2.95 +/- 0.92) was also significantly lower in women than men. Furthermore, we found a significant correlation between alkaline phosphatase (AP) and OC in all patients with PsA (r = 0.49, P < 0.05). Disease activity of PsA had an influence on OC levels. Patients with no disease activity had lower OC levels (2.2 +/- 0.7 ng/ml) than patients with a high activity (OC 3.92 +/- 1.25, P < 0.05). Similar results were obtained with alkaline phosphatase. In addition, we found a significant correlation between clinical activity and OC (r = 0.38, P < 0.02) and alkaline phosphatase (r = 0.49, P < 0.01). Patients with PsA show a corresponding increase in OC levels. if disease activity is high. The proliferative changes in active PsA may be related to inflammatory mechanisms coupled with bone formation.
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PMID:Serum osteocalcin levels in patients with psoriatic arthritis: an extended report. 1098 32

Psoriatic plaque contains an increased number of mast cells that are thought to play an important role in the initiation and maintenance of the disease through the release of mediators such as histamine, proteoglycans, proteinases and cytokines. To verify the possible participation of these cells in the chronic inflammatory cutaneous response in psoriasis, we performed a double-blind controlled study to investigate the presence and activation of tryptase-positive mast cells in the lesional skin of 19 patients affected by active psoriasis vulgaris minima compared with five healthy, age-matched subjects. Psoriatic patients were randomized into two groups (A and B). The first group was treated with cetirizine (10 mg/three times a day for 15 days) and the second one was treated with placebo. Both groups underwent clinical staging [psoriasis area and severity index (PASI) score] and immunohistochemical evaluation [alkaline phosphatase antialkaline phosphatase (APAAP) procedure] before and after treatment. In group A, the PASI score ranged from 3.8 (SE +/- 1.00) to 1.8 (SE +/- 0.68) and in group B, from 5.0 (SE +/- 0.98) to 3.4 (SE +/- 0.47). The mean number of tryptase-positive mast cells for field, mainly distributed in the perivascular and periadnexal sites, ranged from 40.8 (SE +/- 7.15) to 21.6 (SE +/- 3.04) in group A and from 25.1 (SE +/- 3.78) to 26.3 (SE +/- 3.59) in group B (ANOVA test f = 6.95; gl = 1.16; p = 0.02). In our psoriatic patients, cetirizine significantly reduced the expression of tryptase-positive mast cells and produced a clinical improvement in erythema, suggesting a multilevel immunopharmacologic modulation of this antihistamine in psoriasis.
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PMID:Cetirizine reduces the number of tryptase-positive mast cells in psoriatic patients: a double-blind controlled study. 1151 56

Nutritional rickets has occasionally been described in children with lamellar ichthyosis, but their vitamin D endocrine status has not been described. We report 3 cases of vitamin D-deficiency rickets associated with ichthyosis in African children. A 13-month-old Nigerian boy with lamellar ichthyosis had rib beading, elevated alkaline phosphatase, and rachitic changes on radiographs. His rickets did not resolve with calcium therapy, and his 25-hydroxyvitamin D level was low. His rickets resolved with parenteral vitamin D treatment, but his skin did not improve. Topical 0.005% calcipotriene (an analog of 1,25-dihydroxyvitamin D that has been useful in treating adults with psoriasis) was similarly ineffective in improving the child's skin condition. An 8-year-old Nigerian boy with life-long skin findings consistent with lamellar ichthyosis had windswept deformity of the legs with rib beading and enlargement of the wrists and ankles. Radiographs showed active rickets, and the boy had an elevated alkaline phosphatase level and a decreased calcium level. Before knowing that his 25-hydroxyvitamin D level was low, he was treated with calcium and showed radiologic improvement. The skin did not improve with resolution of the rickets but did improve with unilateral topical application of 0.005% calcipotriene. A 7-year-old South African girl presented with progressive windswept deformities of the legs and a 4-year history of skin disease (and a skin biopsy consistent with X-linked ichthyosis). Radiographs and biochemical data confirmed active rickets. Her rickets improved dramatically with vitamin D treatment. Thus, 3 African children with ichthyosis developed vitamin D-deficiency rickets, probably because of a combination of impaired skin production and sunlight avoidance. This is consistent with previous findings of hypovitaminosis D in adults with ichthyosis and other disorders of keratinization. Measurement of 25-hydroxyvitamin D may be indicated in children with ichthyosis to identify those at risk for vitamin D-deficiency rickets, because it is possible that the cutaneous synthesis of vitamin D in such children is impaired. Although the ichthyosis did not improve with resolution of vitamin D deficiency and rickets, 1 of 2 children treated with topical calcipotriene showed improvement in the treated areas of skin. Calcipotriene does not seem to be effective in reversing systemic vitamin D deficiency but can be effective in improving the severity of skin disease in children with ichthyosis.
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PMID:Nutritional rickets in ichthyosis and response to calcipotriene. 1523 83

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.
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PMID:High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract. 1536 50


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