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Biomedical subjects

R M Barr

Publications and source records attributed to R M Barr.

At least 37 records · Page 2Linked to original sources
PubMed1994

Platelet activating factor (PAF) and lyso-PAF in psoriasis.

Previous studies have shown that scale from lesional psoriatic skin contains substantial amounts of platelet activating factor (PAF). In this study, PAF and its immediate precursor, lyso-PAF, were measured in exudates from abrasions on lesional and uninvolved psoriatic skin, and from skin of healthy subjects. The mean amounts of PAF recovered from lesional and uninvolved psoriatic skin (n = 13) and from healthy skin (n = 14) were not significantly different (range 0.05-2.14 pmol/sample). Mean recoveries of lyso-PAF from lesional psoriatic skin (n = 9) and skin of healthy subjects (n = 13) were also similar (9.5 +/- 1.9 and 11.0 +/- 1.9 pmol/sample, respectively), but significantly less lyso-PAF was found in exudates from the uninvolved psoriatic skin (n = 9; 3.1 +/- 0.4 pmol/sample; P < 0.01 relative to both lesional psoriasis and healthy skin). The finding of reduced lyso-PAF in uninvolved psoriatic skin was unexpected because increased phospholipase-A2 activity is associated with psoriasis. These results do not support the hypothesis that extracellular PAF contributes significantly to the inflammation associated with psoriasis.

Adolescent↗
PubMed1993

Factors associated with the psychological well-being of adults with acute leukemia in remission.

The relationships among coping responses, social support, personality factors, and psychological well-being in adults with acute leukemia in remission were studied. The psychological well-being measure was related to quality of life. Forty persons (21 male, 19 female), average age 47 years and average time since diagnosis of 24 months, completed demographic questions, the PRF-E, the Symptom Distress Scale, a Coping Responses inventory, the modified Social Support Questionnaire, and the General Behavior Inventory. An R of .80 was obtained between psychological well-being and Endurance, Affiliation, Cognitive Structure, Autonomy, and Nurturance. Findings were related to fighting spirit and confronting coping style, concepts associated with psychological well-being and longevity in cancer patients.

Adaptation, Psychological↗
PubMed1993

Platelet activating factor, lyso-platelet activating factor and arachidonic acid release in normal human skin and the influence of topical steroid treatment.

1. Previous, in vitro, studies have established the synthesis of platelet activating factor (PAF) by the 're-modelling' pathways in which the activation of a phospholipase A2 (PLA2) enzyme catalyses the hydrolysis of an ether-acyl-phosphocholine to give concomitant release of lyso-PAF, the immediate precursor of PAF, and arachidonic acid, the precursor of the icosanoids. The aim of this study was to investigate the relationship between PAF and eicosanoid release in human skin, and to study the effect of treatment of skin with a topical steroid, on the release of PAF, lyso-PAF and arachidonic acid. 2. A novel assay procedure was developed for the simultaneous assay of PAF and lyso-PAF in skin exudates from abrasions and suction blisters in normal human skin. In addition we assayed arachidonic acid and prostaglandin E2 (PGE2), a representative eicosanoid. 3. The mean amounts of mediator recovered in the first 30 min period following abrasion were PAF 0.43, lyso-PAF 11.9, PGE2 25.7 and arachidonic acid 760 pmol/sample. The molar ratio of PAF:lyso-PAF:arachidonic acid in skin exudates from abrasions was 1:30:1800 and in suction blister exudates was 1:90:3660. 4. Time course studies showed a decline in the recoveries of arachidonic acid and lyso-PAF, of about 50% in 2 h. In contrast, PAF was recovered in exudates at a constant rate over 2 h but PGE2 release decreased by more than 90% after the initial 30 min period. 5. Topical application under occlusion, of 0.05% clobetasol propionate, a potent corticosteroid, significantly reduced lyso-PAF by 30% in suction blister exudates but did not significantly alter the concentrations of PAF or arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1993

Increased interleukin 6, but reduced interleukin 1, in delayed pressure urticaria.

Interleukin 1 (IL-1) and interleukin 6 (IL-6) were measured by bioassays in suction-blister exudates from lesional skin, from skin immediately following a pressure challenge, and from control skin (not subjected to pressure) of patients with delayed pressure urticaria. IL-6 activity in lesional exudates was significantly higher than in exudates from the other two sites. IL-1 activity in lesional exudates was not significantly higher than in the control exudates, but significantly less IL-1 activity was found immediately after pressure challenge than from the control site.

Adult↗
PubMed1992

Culture of human dermal fibroblasts in collagen gels: modulation of interleukin 1-induced prostaglandin E2 synthesis by an extracellular matrix.

Human dermal fibroblasts, cultured as suspensions in collagen gels and as monolayers, were stimulated with recombinant human interleukin-1 beta (rIL 1 beta) at 72 h, and prostaglandin E2 (PGE2) was assayed 24 h later. Fibroblasts in gels were less responsive to rIL 1 beta than monolayers, PGE2 synthesis increasing from less than 1 ng/microgram DNA without rIL 1 beta to maxima of 11.3 and 32.9 ng/micrograms DNA, with half maximal release occurring at 7.47 and 0.75 pM rIL 1 beta for the gel and monolayer cultures, respectively. Increased PGE2 was first detected 4 h after addition of rIL 1 beta to gels and was inhibited by 10(-5) M indomethacin. The amount of PGE2 synthesized per fibroblast increased with the time the gels had been in culture when stimulated with rIL 1 beta and was proportional to the number of fibroblasts in the gels, but inversely related to the collagen concentration. A common feature of these experiments was significantly greater induction of PGE2 synthesis at higher cell densities in collagen gels. Exogenous 10(-4) M arachidonic acid further increased PGE2 synthesis by rIL 1 beta-stimulated fibroblasts, but the differential in the amount of PGE2 released from fibroblasts at high and low population densities in the gels was maintained. These results are consistent with interleukin 1 (IL 1) stimulating PGE2 synthesis in dermal fibroblasts by increasing cyclooxygenase activity. Furthermore, the results show that dermal fibroblasts have an additional regulatory mechanism, related to the cell population densities or their interactions with an extracellular matrix, to finely modulate the amount of PGE2 synthesized in response to IL 1.

Arachidonic Acid↗
PubMed1992

Transfusion management of patients with IgA deficiency and anti-IgA during liver transplantation.

Severe anaphylactic or allergic reactions may occur during blood transfusion to patients who are IgA-deficient and have anti-IgA in their blood, particularly those with class-specific antibodies. These patients are a particular challenge to the hospital transfusion service when large volumes of blood components are required for transfusion support, as in liver transplantation. We have successfully provided blood components for 3 such patients undergoing liver transplantation. Red cells were washed manually or by automated technique. Platelets were washed manually. All plasma was from IgA-deficient donors. One patient's entire plasma requirements were supplied by autologous plasmapheresis. Serial determinations of IgA levels and anti-IgA titers in 1 patient demonstrated an abrupt fall in anti-IgA with the appearance of barely detectable amounts of IgA during the surgery. IgA-containing plasma cells were demonstrated in the biopsies of liver homografts of 2 patients following transplantation. IgA deficiency with anti-IgA can be successfully managed during liver transplantation with advance planning.

Adolescent↗
PubMed1991

Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance.

Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis.

Antibodies, Anti-Idiotypic↗
PubMed1990

Adhesive interaction of erythrocytes in vitro in multiple myeloma.

The early stage of rouleaux formation, which can be observed on a microscope slide, was assessed quantitatively for pairs of cells forming adhering doublets. Previous work on normal cells in normal plasma has been extended to blood samples from patients with multiple myeloma, a blood disorder with a large component of high molecular weight immune plasma protein. Cine film records were obtained for each of 19 pairs of cells which made adhesive contact in a cell suspension diluted by myeloma blood plasma. Analysis, restricted to the events of sliding contact between cells, revealed an approximate doubling of peak sliding velocity, a marked reduction in time to half complete sliding interaction (13 compared to 56 sec for normal cells), and a high variance when comparing sliding velocity as a function of position of overlap. We invite consideration that circumstances of low or zero fluid shear rate that can occur in the venous side of the circulation might have a transient but profound affect on local blood viscosity.

Blood Flow Velocity↗
PubMed1989

Effect of dithranol treatment on arachidonic acid and its lipoxygenase products in psoriasis.

The concentrations of arachidonic acid and its lipoxygenase metabolites were measured in exudates from lesional psoriatic skin during treatment with 0.25% dithranol (anthralin) applied topically for 10 days. Dithranol caused a reduction in the concentration of arachidonic acid at 10 days (167 +/- 42 and 358 +/- 55 ng ml-1 treated and control sites respectively, p less than 0.05) concurrent with clinical improvement of the lesions. Neither 12-hydroxyeicosatetraenoic acid nor leukotriene B4 concentrations were significantly affected. These results do not support the view that lipoxygenase products are of major importance in the pathogenesis of psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) does not stimulate proliferation of human neonatal keratinocytes.

We have developed an assay to study the effect of drugs on the proliferation of neonatal human skin-derived keratinocytes in vitro. Expanding populations of neonatal keratinocytes were cultured in low concentrations (0.5%) of fetal calf serum for up to 12 d. Growth of the cultures was determined by measurement of DNA using a sensitive fluorimetric assay. Addition of 10(-9)-10(-6) M 12(RS)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(RS)-HETE) neither stimulated keratinocyte proliferation nor enhanced the incorporation of [3H]thymidine. The ability of neonatal keratinocytes in low serum medium to respond to exogenous factors was demonstrated by increased growth in response to a mixture of cholera toxin, hydrocortisone, and epidermal growth factor. Confluent keratinocyte cultures in 10% human AB serum exposed to 12(S)-HETE for 72 h also showed no changes in DNA, [3H]thymidine incorporation, or labeling index. Metabolism of 12(S)-[3H]HETE was greater in cultures containing low concentrations of serum but there was no evidence for the formation of 12,20-dihydroxyeicosatetraenoic acid.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Prostaglandin D2 and histamine release in cold urticaria unaccompanied by evidence of platelet activation.

Six patients with acquired primary cold urticaria and six normal control subjects were challenged with a 5-minute immersion of an arm in cold water, at 10 degrees C, to induce cold urticaria. Venous blood draining the arm was sampled before and at 5 and 20 minutes after challenge. Prostaglandin D2 levels in the serum increased significantly after cold challenge but did not correlate with the severity of the urticaria. Significant elevations in histamine after cold challenge tended to be higher in the patients with a low threshold to cold reaction. Two markers of platelet activation, platelet factor 4 and beta-thromboglobulin, remained at basal levels 5 minutes and 20 minutes after challenge.

Adult↗
PubMed1988

The in vitro 5-lipoxygenase and cyclo-oxygenase inhibitor L-652,343 does not inhibit 5-lipoxygenase in vivo in human skin.

1 3-hydroxy-5-trifluoromethyl-N-[2-(2-thienyl)-2-phenyl-ethenyl]-benzo(B) thiophene-2-carboxamide (L-652,343) is a 5-lipoxygenase and cyclo-oxygenase inhibitor in vitro. 2 In psoriasis increased concentrations of arachidonic acid transformation products are found in the lesional skin which may be important in the pathogenesis of the disease. We have measured the effect of orally administered L-652,343 on the concentration of LTB4 and prostaglandins in the lesional skin. 3 Eight patients with stable chronic plaque psoriasis received 500 and 250 mg of L-652,343, 12 h apart. A chamber technique was used to collect skin exudate samples from abraded plaques before and at 4, 24 and 48 h after the first dose. Exudates were analysed for LTB4 by a neutrophil chemokinesis assay and for PGE2 and PGD2 by RIA. 4 PGE2 and PGD2 levels were significantly reduced at 4 and 24 h after the first dose of L-652,343 but LTB4 levels were not affected indicating inhibition of the cyclo-oxygenase pathway but not of the 5-lipoxygenase pathway. This shows the importance of confirming that the action of 5-lipoxygenase inhibiting drugs in vitro occurs in vivo.

Adult↗
PubMed1988

The release of prostaglandin D2 from human skin in vivo and in vitro during immediate allergic reactions.

1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused the release of PGD2 and histamine, but not PGE2, from the skin of the atopic subjects. The molar ratio of histamine to PGD2 was about 140:1. Control subjects were unresponsive. 3. PGD2 was released from passively sensitized human skin challenged with antigen in vitro. The time course was similar in vitro and in vivo. The ratio of histamine to PGD2 in vitro was 78:1. 4. The identities of the prostaglandins were confirmed by high performance liquid chromatography and radioimmunoassay to PGD2 and PGE2. 5. PGD2 is the major arachidonic acid cyclo-oxygenase product synthesized by human mast cells. It is pro-inflammatory in human skin but its functions as a mediator in immediate hypersensitivity reactions in human skin are not clear. The results of this study suggest that, relative to histamine, PGD2 contributes little to the oedema and erythema of immediate reactions in human skin.

Adult↗
PubMed1988

Pure red cell aplasia in rheumatoid arthritis.

We report a patient with longstanding rheumatoid arthritis (RA) who developed pure red cell aplasia. This condition is a rare complication of RA. Our patient recovered, apparently in response to treatment with corticosteroids and cyclophosphamide followed by azathioprine.

Adrenal Cortex Hormones↗
PubMed1987

Usefulness of erythrocyte ferritin analysis in hereditary hemochromatosis.

A study was carried out to determine the usefulness of erythrocyte ferritin analysis in identifying homozygotes and heterozygotes in families affected with hereditary hemochromatosis, an autosomal recessive disorder. To select the subjects the genotypes of 60 people from 26 affected families were determined by HLA-A and HLA-B haplotyping. In addition, data for 12 homozygotes for whom erythrocyte ferritin values were available from the literature were included. Likelihood analysis was used to evaluate the diagnostic value of erythrocyte ferritin analysis alone and in combination with serum ferritin testing. An erythrocyte ferritin value of 150 ag/cell or higher combined with a serum ferritin level above the 90th percentile indicated homozygosity, whereas a value of less than 150 ag/cell and a serum ferritin level at or below the 90th percentile indicated that homozygosity could be ruled out with a high degree of confidence. The probability of heterozygosity rose to 92% when the erythrocyte ferritin value was between 29 and 149 ag/cell and to 98% when this result was combined with a serum ferritin level at or below the 90th percentile. Erythrocyte ferritin analysis in combination with serum ferritin testing is useful for identifying homozygotes and a proportion of heterozygotes in families affected with hemochromatosis.

Adult↗
PubMed1987

[New pharmacologic developments in physical urticaria--therapeutic consequences].

Recent evidence suggests that mast cell derived mediators other than histamine are likely to be involved in the pathogenesis of physical urticarias. Much of the work has been performed in idiopathic cold contact urticaria where the presence of neutrophil and eosinophil chemotactic factors, and platelet activating factor-like lipid substances have been previously demonstrated. Now, an increase in prostaglandin D2 measured by GC-MS has been demonstrated in venous blood draining the cold challenged area. This appeared a few minutes later than histamine, but then both substances paralleled the onset, development and subsidence of the urticarial reaction. There appeared to be no quantitative relationship between histamine and PGD2 release. A similar rise in histamine and PGD2 occurred on heat challenge of a subject with the rare localized form of heat urticaria. This rise of both substances was considerably reduced after combined treatment with induction of tolerance and oral indomethacin. The concentrations of PGD2 measured suggested that it plays an indirect role.

Cold Temperature↗
PubMed1987

The effect of prostaglandin D2 on the response of human skin to histamine.

The interaction of prostaglandin D2 (PGD2) and histamine in human skin was studied by intradermal injection of the compounds alone or in combination in healthy volunteers. Responses were recorded by measurement of areas of wheal and erythema, and changes in cutaneous blood flow quantified using a laser Doppler flow meter. The effect of a near-threshold dose of PGD2 on histamine dose-response relationships and on the response to a single low dose of histamine were examined. Histamine caused dose-related increases in blood flow and in areas of wheal and erythema in human skin. Prostaglandin D2 caused dose-related increases in blood flow and erythema area, but not wheal area, in the dose range used. When the compounds were injected together, PGD2 did not potentiate the increase in blood flow and areas of wheal and erythema due to histamine. The modest augmentation of histamine response in the presence of PGD2 could be attributed to summation alone. The role of PGD2 in cutaneous disorders such as the physical urticarias, in which its release has been demonstrated, is therefore uncertain. In the amounts measured in the urticarias, it is unlikely alone to cause a significant cutaneous response; nor does it appear to act by potentiation of the response to histamine.

Adult↗