Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil accumulation is a hallmark of the inflammatory process. The ability of neutrophils to release lipid mediators, toxic oxygen metabolites, proteolytic enzymes and cationic proteins may contribute to the tissue pathology seen in inflammatory diseases such as inflammatory bowel disease and psoriasis. The first step in the process of neutrophil diapedesis in a gradient of chemoattraction is adhesion to the microvascular endothelium, a phenomenon mediated by the stimulated activation of the neutrophil CD11a-c/CD18 cell surface glycoprotein complex. We assessed the ability of a monoclonal antibody (MoAb) (hybridoma: SP2/0-Ag. 14XBALB/c spleen cells; isotype: murine IgG1) to CD18 that recognizes the beta chain of LFA1(CD11a/CD18), MAC-1(CD11b/CD18) and CD11c/CD18 to effect the neutrophils response to the proinflammatory chemotaxins leukotriene B4 (LTB4) and 12(R)-hydroxy-5,8,11,14-eicosatetraenoic acid [12(R)-HETE] in the mouse dermis. LTB4 and 12(R)-HETE induce a time and concentration dependent infiltration of s when applied intradermally. LTB4 (100 ng) and 12(R)-HETE (50 micrograms) were injected intradermally in CD-mice (18 g body weight) and assessed for chemotactic activity four h later by the dermal levels of myeloperoxidase (MPO), a neutrophil marker enzyme. CD18 MoAb(0.02 mg) was given intravenously 10 min ahead of dermal chemotaxin injection. LTB4 increased (p less than .01) dermal levels of MPO at 4 h, a neutrophil accumulation inhibited (p less than .005) by CD18 MoAb pretreatment (Mean MPO +/- SEM: Vehicle, 0.049 +/- 0.006U vs LTB4, 0.309 +/- 0.033U vs MoAb, 0.137 +/- 0.012U) (n = 12/group).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD 18 monoclonal antibody inhibits neutrophil diapedesis in the murine dermis induced by leukotriene B4 and 12(R)-hydroxyeicosatetraenoic acid. 197 85

Determination of the cell types proliferating in the dermis of patients with psoriasis should identify those cells experiencing activation or responding to growth factors in the psoriatic dermal milieu. Toward that end, sections of formalin-fixed biopsies obtained from 3H-deoxyuridine (3H-dU)-injected skin of eight psoriatic patients were immunostained, followed by autoradiography. Proliferating dermal cells exhibit silver grains from tritium emissions. The identity of the proliferating cells could then be determined by simultaneous visualization with antibodies specific for various cell types. UCHL1+ (CD45RO+) T cells (recall antigen-reactive helper T-cell subset) constituted 36.6 +/- 3.1% (mean +/- SEM, n = 6) of the proliferating dermal cells in involved skin, whereas Leu 18+ (CD45RA+) T cells (recall antigen naive T-cell subsets) comprised only 8.7 +/- 1.5% (n = 6). The Factor XIIIa+ dermal perivascular dendritic cell subset (24.9 +/- 1.5% of proliferating dermal cells, n = 6) and Factor VIII+ endothelial cells (23.0 +/- 2.3%, n = 6) represented the two other major proliferating populations in lesional psoriatic dermis. Differentiated tissue macrophages, identified by phase microscopy as melanophages or by immunostaining with antibodies to Leu M1 (CD15) or myeloid histiocyte antigen, comprised less than 5% of the proliferating population in either skin type. In addition to calculating the relative proportions of these cells to each other as percent, we also determined the density of cells, in cells/mm2 of tissue. The density of proliferating cells within these populations was increased in involved versus uninvolved skin: UCHL1+, 9.0 +/- 1.7 cells/mm2 versus 1.8 +/- 0.6 cells/mm2, p less than 0.01; Factor XIIIa+, 6.0 +/- 0.7 cells/mm2 versus 1.5 +/- 0.5 cells/mm2, p less than 0.01; Factor VIII+, 5.5 +/- 1.4 cells/mm2 versus 0.0 cells/mm2, p less than 0.05. The presence of preferential active proliferation of a T-cell subset in lesional dermis suggests that activating signals specific for this subset are contained within the psoriatic dermis in vivo. The activation of recall antigen-reactive T cells may be a driving force behind the dendritic cell and endothelial cell proliferation. Alternatively, the selective proliferation and expansion of these two constitutive cell types (Factor XIIIa+ and Factor VIII+) may result in signals that promote activation of UCHL1+ (CD45RO+) T cells.
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PMID:Proliferating cells in psoriatic dermis are comprised primarily of T cells, endothelial cells, and factor XIIIa+ perivascular dendritic cells. 200 55

Serum was obtained from 21 normal and 22 psoriatic subjects, and the severity of skin disease in the psoriatic patients was recorded using the PASI score. The scores ranged from 1.8 to 51.0. The growth stimulatory effect of the sera on normal dermal fibroblasts in cell culture was assessed by measuring [3H]-thymidine uptake. Each serum was assessed at four concentrations (2,5, 10,20%). The psoriatic sera were more growth stimulatory than normal sera, but this difference was statistically significant (P less than 0.02) only at 20% serum concentration. Eleven of the 22 psoriatic serum samples had a mitogenic effect greater than the mean +/- SEM of all the normal sera; these sera were then from patients with PASI scores of 4.5-51.0. Six of these psoriatic subjects were recalled after 5 months; their PASI scores were reassessed, and the mitogenic effect of new serum samples was compared with that of the initial samples. All of these patients displayed a change in serum mitogenic effect, but this was not consistent with the change in severity of skin disease over the corresponding time period. In one subject, the severity of the psoriasis had increased marginally over the 5 months, while the mitogenic effect of her serum decreased significantly (mean counts of 43808 vs. 32660; P = 0.0029).
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PMID:The mitogenic effects of sera from psoriatic subjects on normal dermal fibroblasts: an absence of correlation with the clinical activity of psoriasis. 200 99

Vitamin D3 metabolites have been found to improve psoriasis but their mechanism of action is not clear. Keratinocyte proliferation and differentiation are known to be dependent on calcium concentrations in vitro. The aim of this study was to examine whether 1 alpha,25(OH)2 vitamin D3 had any direct effect on intracellular free calcium concentrations in cultured keratinocytes. A response to 1 alpha,25(OH)2 vitamin D3 was seen in 88% of monolayers of normal human keratinocytes attached to glass coverslips. An increase in intracellular free calcium was seen in 80% of the reactive cultures, with over half the responses occurring within 30 s of exposure to 1 alpha,25(OH)2 vitamin D3 and the remainder occurring within minutes. Responses could be seen at physiological concentrations of 1 alpha,25(OH)2 vitamin D3 and were not blocked by the protein synthesis inhibitor cycloheximide. The response to 1 alpha,25(OH)2 vitamin D3 took the form of rapid transient increases in intracellular free calcium in 29 out of 59 coverslips. The basal intracellular free calcium was calculated to be 245 +/- 47 nM rising to a maximum of 834 +/- 267 nM (mean +/- SEM; n = 20) following exposure to 1 alpha,25(OH)2 vitamin D3. We conclude that 1 alpha,25(OH)2 vitamin D3 acts directly on keratinocytes to increase intracellular free calcium and that this may be relevant to its mechanism of action in psoriasis.
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PMID:1 alpha,25(OH)2 vitamin D3 increases intracellular calcium in human keratinocytes. 201 29

Protein kinase C (PKC) activity was measured in cultures of fibroblasts from biopsies of the involved and uninvolved skin of seven patients with psoriasis and from the skin biopsies of nine normal controls. PKC activity was significantly increased (P less than 0.005) in the particulate fraction of fibroblasts obtained from the involved areas of skin (450 +/- SEM 89 pmol/mg protein/3 min) and the uninvolved skin (394 +/- 94 pmol/mg protein/3 min) in psoriasis as compared to that of controls (103 +/- 24 pmol/mg protein/3 min). The soluble fraction of PKC activity was comparable in controls and in the fibroblasts obtained from involved areas and not significantly different from the values in fibroblasts from uninvolved skin. PKC activity was also measured in the soluble and particulate fractions of lymphocytes from 13 patients with psoriasis and from 14 normal controls. The PKC activity did not differ in the lymphocytes of patients with psoriasis from the controls in either the cytosolic or the membrane fractions. The increase in PKC activity as expressed at the membrane level of psoriatic fibroblasts may be related to an increase in sensitivity of these cells to hormones or growth factors involved in the regulation of their growth.
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PMID:Protein kinase C activity in normal and psoriatic cells: cultures of fibroblasts and lymphocytes. 206 37

In 34 psoriatic patients with various cutaneous manifestations (psoriasis vulgaris, erythroderma psoriaticum, guttate psoriasis), the ability of the RI regulatory subunit of cAMP-dependent protein kinase (PKA) to bind a cAMP analogue (8-azido [32P] cAMP) in erythrocyte membranes was significantly lower than that in 19 normal subjects (mean [SEM] 565 [35] vs 930 [35] fmol/mg protein). This enzyme defect was not found in patients with other forms of dermatitis that can be confused with psoriasis or with other inflammatory diseases. There was a significant negative correlation between the severity of the disease as expressed by the psoriatic area and severity index score and the binding of the cAMP analogue to PKA. A long-term study showed that oral retinoid treatment of psoriatic patients resulted in a correction of the binding defect. Unaffected members of psoriatic families had significantly lower than normal binding of cAMP to PKA (773 [60] fmol/mg protein). This study shows for the first time that in psoriasis a biochemical defect expressed in erythrocytes correlates with the severity of the disease as well as its clinical evolution. These results will be useful in clinical management of psoriatic disease for the choice and follow-up of retinoid therapy.
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PMID:A cAMP binding abnormality in psoriasis. 256 33

The aim of this study was to determine whether levels of biologically active calmodulin are elevated in both lesional and uninvolved epidermis in psoriasis. Epidermal shave biopsies were obtained from normal controls and from both psoriatic plaques and nonlesional psoriatic skin. Following determination of the protein content, the calmodulin activity of the homogenized samples was then measured using a calmodulin-sensitive phosphodiesterase enzyme bioassay. In normal skin, calmodulin activity was 1.29 +/- 0.35 micrograms calmodulin mg-1 epidermal protein (mean +/- SEM, n = 12 volunteers) compared to 7.88 +/- 1.59 micrograms calmodulin mg-1 epidermal protein for plaque (n = 16 patients) and 10.19 +/- 2.35 micrograms calmodulin mg-1 epidermal protein for the uninvolved skin of 12 of these patients. The levels of biologically active calmodulin were therefore elevated in both plaque and uninvolved epidermis of patients with psoriasis compared to epidermis from normal volunteers. These results suggest that an abnormality in the regulation of calmodulin activity may be involved in the pathogenesis of psoriasis.
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PMID:Biologically active calmodulin levels are elevated in both involved and uninvolved epidermis in psoriasis. 632 4

Local regulation of cutaneous blood flow (CBF), i.e., the venoarteriolar reflex mechanism and the autoregulation response, was studied in 27 patients with psoriasis using atraumatic epicutaneous 133Xe-labeling tracer washout technique. Venous stasis of 40 mm Hg induced a significant reduction in CBF--as in normal subjects (i.e., a vasoconstrictor response)-in both involved psoriatic skin (0.47 +/- SEM 0.04, p less than 0.0001) and uninvolved psoriatic skin (0.38 +/- SEM 0.03, p less than 0.0001). The vasoconstrictor response to neural blockade with lidocaine was investigated in two control experiments in psoriatic skin. It was found to be normal: neural blockade with lidocaine 2 cm outside the measured field did not affect the vasoconstrictor response, whereas local infiltration with lidocaine did block the vasoconstrictor reflex. Limb elevation of 40 cm above heart level induced a 2-fold significant increase in the CBF of involved psoriatic skin in 10 patients. This response is a paradoxical deviation from normal local autoregulation of the CBF (p less than 0.002). Limb elevation had no significant influence on CBF of uninvolved psoriatic skin, indicating a normal autoregulation of the CBF. The paradoxical increase in CBF during limb elevation in involved psoriatic skin was not influenced by local neural blockade with lidocaine, or by local neural and vascular, smooth muscle blockade obtained by injection of lidocaine and papaverine. The results indicate that the reason for this paradoxical phenomenon might be due to the special morphology of the capillaries of involved psoriatic skin.
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PMID:Local regulation of cutaneous blood flow in psoriasis. 638 17

Plasma growth-hormone levels in 12 fasting psoriatics were 4.4 +/- 1.4 mU/l (mean +/- SEM), compared to 2.7 +/- 1.7 in 5 patients with eczema and 1.2 +/- 0.3 in 6 normal subjects. The differences in mean values were not statistically significant and were due to exceptionally high levels of growth hormone in five patients with psoriasis and one patient with eczema. In the psoriatic group the exceptional patients were not distinguished by age or the area of involved skin but they tended to be leaner than those with low plasma-growth hormone levels. We conclude that raised plasma growth hormone cannot be the cause of psoriasis but might be a secondary effect of the skin disease in some patients.
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PMID:Growth hormone levels in psoriasis. 647 87

The disappearance rate of 133Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for 133Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content of water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).
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PMID:Cutaneous blood flow in psoriasis. 664 91


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