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Biomedical subjects

P D Mier

Publications and source records attributed to P D Mier.

At least 37 records · Page 2Linked to original sources
PubMed1987

Reduction of leukotriene B4-induced intraepidermal accumulation of polymorphonuclear leukocytes by methotrexate in psoriasis.

The leukotriene B4 (LTB4)-induced intraepidermal accumulation of polymorphonuclear leukocytes (PMN) was quantified, using an elastase assay, in psoriatic patients receiving methotrexate and in untreated psoriatic patients. Methotrexate in therapeutic dosages inhibited PMN infiltration in six patients who had improved considerably on treatment with the drug, a gradual increase being seen during the days on which no methotrexate was taken. Two patients were in relapse, despite methotrexate treatment, and both failed to show any change in LTB4-induced accumulation of PMN.

Adult↗
PubMed1986

A new approach to the measurement of phospholipase A2 in tissue homogenates and its application to human skin.

We describe a new approach to the quantification of tissue phospholipase A2 based on the observation that the Vmax is increased by several orders of magnitude in the presence of high concentrations of dimethyl sulphoxide. The enzyme from human skin showed optimal activity at 30% dimethyl sulphoxide and pH 6-7.5, and had an absolute dependence on Ca2+ (apparent Km = 1.4 mmol/l). The relationship between reaction velocity and substrate concentration did not follow Michaelis-Menten kinetics. The enzyme was inhibited by p-bromophenacyl bromide, half-maximal inhibition occurring at 2.4 mumol/l. Surprisingly, assay of specimens of various human tissues indicated that, with the exception of pancreas, skin contained higher levels of phospholipase A2 activity than any other tissue investigated. Equally surprising was that primate skin (in particular human) seems considerably more active than that of other mammals. Speculatively, these findings may be related to the high levels of free fatty acids occurring on the skin surface.

Animals↗
PubMed1986

Elastase, a marker for neutrophils in skin infiltrates.

The enzyme elastase (EC 3.4.21.37) has proved to be a convenient and extremely sensitive marker for the quantification of neutrophils in cutaneous infiltrates. Fluorometric assay using the synthetic substrate MeOSuc-Ala-Ala-Pro-Val-N-methylcoumarin permitted the measurement of this enzyme in as few as five cells and was linear up to about 1000 cells per sample. The mean activity of lysates of human blood-derived neutrophils was 0.57 +/- 0.08 pmol of 7-amino-4-methyl-coumarin released per hour per neutrophil. Extracts of normal human skin contained no measurable elastase activity but resulted in a slight inhibition of the neutrophil enzyme (mean 12%). Application to the in vivo situation has been demonstrated by the use of leukotriene B4 as chemotactic agent. A reproducible neutrophil infiltrate was found at a dose of 2 ng, well below the threshold for the appearance of microabscesses.

Humans↗
PubMed1985

Isolation and preliminary biochemical characterization of the human epidermal Langerhans cell.

A method is described for the isolation of human epidermal Langerhans cells (LC). Following the disaggregation of the epidermis by gentle trypsinization, the cell suspension is incubated with the fluorescein-conjugated monoclonal antibody OKT6. Using a fluorescence-activated cell sorter, a subpopulation is selected on the basis of positive fluorescence and low forward-scatter, the latter parameter reducing contamination by LC-keratinocyte clusters. The LC averaged 1.7% of the original epidermal preparation. The purity averages 83% as judged either by OKT6 binding or by ATPase activity. Biochemical measurements indicated that the activity of lysosomal enzymes was low with the exception of alpha-mannosidase, which was about 12-fold higher than that of the keratinocyte. The activities of 3 enzymes of intermediary metabolism suggest that the utilization of glucose by the LC is considerably greater than that of the keratinocyte.

Acid Phosphatase↗
PubMed1985

Glycoprotein metabolism in skin cancer: synthesis, pool size, and partial characterization of glycoproteins in the rat basosquamous cell carcinoma.

Uptake of fucose, glucosamine, galactose, and mannose and the incorporation of these sugars into glycoconjugates have been quantified in a model epithelial tumor, the basosquamous cell carcinoma of the rat. Following isolation of glycoprotein and papain digestion, the fucosylated glycopeptides were fractionated according to molecular weight (Mr) and by affinity chromatography. Analysis of cellular material revealed a 2- to 3-fold reduction in the proportion of high-Mr fucopeptides synthesized by the tumor compared with normal epidermis, accompanied by a profound block in the incorporation of galactose into glycoconjugates. Parallel investigation of carbohydrate removed from the cell surface with trypsin or spontaneously shed into the medium indicated a striking decrease in the total release of fucopeptides from the tumor; the Mr was (respectively) normal or increased. Thus the fucopeptide abnormality appears to be accounted for almost entirely by a shift toward accumulation of low-Mr material at internal locations within the cell.

Animals↗
PubMed1985

The 'metabolic burst' in polymorphonuclear leukocytes from patients with quiescent psoriasis.

We report an investigation of peripheral blood polymorphonuclear leukocytes (PMN) from untreated patients with mild, quiescent psoriasis. Four aspects of the 'metabolic burst' were measured to illustrate phagocytosis-related events. These were: myeloperoxidase activity, hydrogen peroxide release, superoxide production and luminol-amplified chemiluminescence. Our study does not support the concept of an intrinsic abnormality of the PMN in psoriasis, but provides additional evidence for disease activity-dependent changes in phagocytic behaviour. Possible interactions with certain humoral factors, the so-called opsonins, are discussed.

Adult↗
PubMed1984

Monocyte function is normal in quiescent psoriasis.

We report an investigation of peripheral blood monocytes from untreated patients with mild, quiescent psoriasis. Possible metabolic changes were monitored by the determination of 3 enzymes representing different pathways of glucose metabolism and 2 lysosomal enzymes. Signal processing was evaluated by the measurement of cyclic AMP levels before and after hormonal stimulation. Luminol-amplified chemiluminescence provided an objective approach to assessing phagocytic capacity. Finally, the pattern of maturation of normal and psoriatic monocytes has been compared during culture in vitro. Our results were uniformly and wholly negative; we conclude that the concept of an "intrinsic" abnormality of the psoriatic monocyte may be excluded. Possible reasons for discrepancies in the literature are discussed.

Adult↗
PubMed1984

Metabolic changes in the psoriatic lesion during therapy.

Three marker enzymes were measured during treatment of psoriatic plaques with two different therapies. During treatment with clobetasol propionate the epidermal enzymes (acid phosphatase and glucose-6-phosphate dehydrogenase) returned to normal within 14 days whereas capillary alkaline phosphatase remained at the original level. By contrast, all three marker enzymes reverted to normal at the same tempo during PUVA therapy, reaching the control range after 4-8 weeks.

Acid Phosphatase↗
PubMed1983

Altered intracellular enzyme activity of monocytes and lymphocytes in Hodgkin's disease.

To evaluate metabolic functionality of monocytes and lymphocytes in Hodgkin's disease (HD) we studied 3 enzymes of the intermediary metabolism, G-6-PDH, PHI, ICDH, and the acid hydrolases, NAG and ACP. These enzymes were measured in purified cell fractions of 9 patients with advanced disease and 11 normal controls. The cells were isolated with cell scatter-monitored counterflow centrifugation. Enzymes were measured in the cell lysates by means of fluorimetric microassays. In the monocytes of HD patients a significantly increased G-6-PDH activity was found (P less than 0.01), indicating an enhanced activity of the hexose monophosphate shunt. The other enzymes showed no clear differences compared to normal controls. The lymphocytes of HD patients showed a significantly augmented activity of both G-6-PDH (P less than 0.001) and PHI (P less than 0.01), pointing to an increased HMPS and glycolytic activity. These findings are in support of an enhanced metabolic activity of both monocytes and lymphocytes in HD.

Acetylglucosaminidase↗
PubMed1983

Effects of PUVA on human blood monocytes in vitro.

Adherent monolayer cultures of monocytes at two stages of maturation were exposed to long-wave ultra-violet radiation in the presence and absence of 8-methoxypsoralen. A remarkably predictable, dose-related lethal effect was seen, suggesting that mesenchymal cells in general may be sensitive to photochemotherapy (PUVA). Both monocytes and macrophages were lethally damaged with doses that may reach the dermis in the course of normal clinical therapy.

Dose-Response Relationship, Drug↗
PubMed1983

Metabolic changes at the margin of the spreading psoriatic lesion.

Keratotome slices were cut across the margins of rapidly-spreading psoriatic plaques. Each slice was divided into eight sections and in each section we measured the percentage cells in S phase and the levels of glucose-6-phosphate dehydrogenase (both related to epidermal proliferation), acid phosphatase (associated with keratinization) and alkaline phosphatase (a marker for dermal capillaries). Disturbances in the epidermis extended only 2 to 4 mm into the 'uninvolved' skin, whereas the capillaries were metabolically abnormal for a distance of about 2 cm ahead of the advancing edge of the plaque. This implies that changes in the capillary may precede those in the epidermis during the spread of the psoriatic lesion.

Acid Phosphatase↗