Search PubMed⌕ Search

Biomedical subjects

J Ashworth

Publications and source records attributed to J Ashworth.

53 records · Page 3Linked to original sources
PubMed1988

Amyloid P component binds to keratin bodies in human skin and to isolated keratin filament aggregates in vitro.

Dermal keratin bodies, consisting mainly of keratin intermediate filament aggregates (KIFA) coated with IgM anti-KIF autoantibodies, are present in normal human skin and occur in increased quantities in certain skin diseases. Keratin bodies are normally rapidly removed, but in primary localized cutaneous amyloidosis (PLCA) they are converted by an unknown mechanism to amyloid. Amyloid P component (AP), a glycoprotein identical to, and derived from, the normal plasma protein serum amyloid P component (SAP), is present in all forms of amyloid including PLCA. We investigated the interaction between SAP, keratin bodies, and KIFA. Immunofluorescence staining of normal skin using fluoresceinated anti-SAP and rhodamine-conjugated anti-IgM, or AE-1/AE-3 anti-keratin antibodies followed by Texas Red-conjugated anti-mouse immunoglobulin, showed that 52% +/- 4 (mean +/- sem, n = 6) of keratin bodies bound anti-SAP. Similar findings were present in a biopsy from a patient with lichen planus. Isolated KIFA, prepared by 8M urea extraction of normal human epidermis or cultured keratinocytes, were preincubated with normal human serum as a source of SAP and then stained with fluoresceinated anti-SAP. Bright fluorescence seen when the incubation medium contained Ca++ was absent in the presence of ethylenediamine tetraacetic acid. Specific Ca++-dependent binding of SAP to KIFA was confirmed using immunoblotting. Binding of SAP to KIFA did not prevent their degradation following exposure to trypsin or alpha-chymotrypsin. Similarly, partial enzymatic digestion of KIFA did not abrogate their ability to bind SAP. Our findings, that SAP is associated with keratin bodies in skin and exhibits Ca++-dependent binding to KIFA in vitro, identify keratin filaments as a newly recognized ligand for SAP.

Benzothiazoles↗
PubMed1988

Effects of topical corticosteroid therapy on Langerhans cell antigen presenting function in human skin.

We have investigated the mechanisms by which topical corticosteroids modulate cutaneous immune reactions in man. Volunteers applied clobetasone butyrate 0.05% (Eumovate; EV), betamethasone valerate 0.1% (Betnovate; BV), clobetasol propionate 0.05% (Dermovate; DV), and control vehicles twice daily to forearm skin for 7 days. Steroid therapy significantly decreased the number of HLA-DR/T6 (CD1a) positive Langerhans cells (LCs) per mm2 in suction blister-derived epidermal sheets, expressed as a mean percentage of controls, as follows: EV 69.2%; BV 67.3%; DV 37.8%. LC antigen presenting capacity was determined in the allogeneic and autologous epidermal cell-lymphocyte reactions. The LC-dependent allostimulatory capacity of epidermal cells, expressed as a mean percentage of controls, was also significantly reduced by steroid therapy: EV 45.1%; BV 41.9%; DV 23.4%. Following therapy with clobetasol propionate 0.05%, the capacity of epidermal cells to present tetanus toxoid to, and to augment concanavalin A mediated lymphocyte stimulation of, autologous lymphocytes was reduced to 33.6% and 19.7% respectively of controls. Depression of epidermal cell allostimulatory capacity was not the result of a steroid-induced decrease in the production of epidermal cell-derived thymocyte activating factor (ETAF)/interleukin 1 by keratinocytes, since it could not be reversed by addition of exogenous interleukin 1. Indomethacin, added to block any potential prostaglandin synthesis during the culture period, did not restore the allostimulatory capacity of epidermal cells from steroid-treated sites. Addition of epidermal cells from DV-treated sites depressed the capacity of control epidermal cells to stimulate lymphocytes in the allogeneic epidermal-lymphocyte reaction. Our results demonstrate that the anti-inflammatory action of topical corticosteroids in man is associated not only with a reduction in the number of HLA-DR/T6 positive LCs, but also with a marked decrease in Langerhans cell-dependent T lymphocyte activation. The effects of the different steroids on both of these parameters correlated with their potency as determined in the standard occlusive vasoconstrictor assay. Topical corticosteroids are widely used for the treatment of inflammatory skin disorders, and inhibit not only the elicitation phase, but also the induction phase, of allergic contact dermatitis reactions.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigen-Presenting Cells↗
PubMed1988

The lateral spread of clobetasol 17-propionate in the stratum corneum in vivo.

Radiolabelled clobetasol 17-propionate in two different bases, propylene glycol (PG) and di-n-butyl adipate (BA), was applied to the backs of 10 normal male volunteers, and the application sites protected. After 8 h samples of stratum corneum (SC) were taken from the application site and an adjacent site, and the level of steroid measured. At the application site there were higher concentrations of the PG formulation at the deeper levels of the SC. At the adjacent sites there were higher concentrations of the BA formulation at the superficial levels. The mean radioactivity at the adjacent sites expressed as a percentage of that at the corresponding application sites (+/- SEM) was 7.8 +/- 5.3% for the BA formulation and 3.0 +/- 2.9% for the PG, (P = 0.0002). Total percentage of the applied dose in the skin adjacent to the application site was 11.7 +/- 6.3% for the BA formulation and 5.3 +/- 5.7% for the PG (P less than 0.0002). Clobetasol 17-propionate, therefore, moves laterally to a greater extent in BA than in PG.

Adipates↗
PubMed1988

Carney's triad.

A 26 year old female presented with partial expression of Carney's triad. This is the first Australian report of the condition. The role of surgery and the need for vigilance to detect the occurrence of the complete triad are stressed.

Adult↗
PubMed1987

Lymphomatoid papulosis/pityriasis lichenoides in two children.

Two children developed lymphomatoid papulosis/pityriasis lichenoides at ages 3 and 6 years. Follow-up continued for 13 years in the former patient and for 6 years in the latter. Both children now have continuing low-grade disease activity requiring in the one case topical corticosteroid therapy and in the other low-dose systemic steroid therapy. These children are reported to emphasize to pediatricians, pediatric pathologists, and hematologists that pseudolymphomatous conditions can exist in young children and do not require potent cytotoxic therapy. In both of our patients, the initial diagnosis was thought to be an aggressive lymphoma.

Child↗
PubMed1987

A comparison of the dermal lymphoid infiltrates in discoid lupus erythematosus and Jessner's lymphocytic infiltrate of the skin using the monoclonal antibody Leu 8.

Jessners lymphocytic infiltration of the skin (14 cases) and discoid lupus erythematosus (13 cases) were studied and the lymphoid infiltrates in the dermis were compared in the two conditions, using a standard immunoperoxidase technique. Mouse monoclonal antibodies were used to identify T helper lymphocytes, T suppressor lymphocytes and, using the antibody Leu 8, "immunoregulatory lymphocytes". It was shown that the proportions of Leu 8 positive cells was significantly different in the two conditions. The average percentage of Leu 8 positive lymphocytes in the dermal infiltrate found in the cases of Jessner's was 65% (range 40-80%) whereas the average percentage in the cases of discoid LE was 15% (range 2-30%). This observation is further evidence that Jessner's lymphocytic infiltration and chronic discoid lupus erythematosus should be regarded as separate entities.

Adult↗
PubMed1985

A dermatosis associated with bacterial overgrowth in jejunal diverticula.

A patient is described with an unusual skin eruption associated with bacterial overgrowth in jejunal diverticula and malabsorption. The initial skin changes were frankly vasculitic with "target' lesions, whilst older lesions showed a psoriasiform scale and a tendency to central clearing. The illness was associated with raised levels of IgM and IgG containing circulating immune complexes and deposition of IgM and IgG in the dermis. It was suppressed by oral antibiotic therapy. There are similarities between the findings in this patient and those described in the intestinal bypass syndrome.

Antigen-Antibody Complex↗
PubMedDate not supplied

Six-month prospective cross-over study to determine the effects of 1.1% amino acid dialysate on lipid metabolism in patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the effect of 1.1% amino acid dialysate (AAD) (Nutrineal, Baxter, Castlebar, Ireland) on lipid metabolism in hyperlipidemic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Patients were alternately assigned to receive AAD in the first (group A), or the second (group B), 6 months of a prospective cross-over study. SETTING: University teaching hospital. PATIENTS: Eighteen stable CAPD patients with a serum cholesterol 5.5 mmol/L or greater. INTERVENTIONS: One post prandial exchange of AAD during a 24-hour period for 6 months. MAIN OUTCOME MEASURES: A significant change in serum lipid levels. RESULTS: Patients in group A (n = 10) received a single daily exchange of AAD in place of their post prandial dextrose exchange for the first 6 months, and then crossed over to the dextrose phase. Patients in group B (n = 8) continued their usual dextrose dialysis for the first 6 months and then crossed over to receive AAD in the latter 6 months. Measurements of serum lipids and lipoproteins along with other biochemical parameters were made at regular intervals. Although a downward trend in mean serum total cholesterol was seen on AAD in group A, no significant change in total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol was observed in any group. Mean serum triglycerides fell on AAD in both groups, but were not statistically significant. Serum lipoprotein(a) [Lp(a)] and apolipoprotein B were elevated in both groups but did not change on AAD or with time. No change was observed in serum apoprotein A1 levels. Serum Lp(a) was not correlated to dialysate protein excretion. No change in mean serum albumin was observed, in either group, on AAD. KT/V urea, total weekly creatinine clearance, net ultrafiltration, and dialysate protein excretion remained unchanged on AAD. CONCLUSIONS: The use of AAD, although clinically safe and without side effects, had no effect on the dyslipidemia in our group of CAPD patients.

Adult↗