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Biomedical subjects

A Whelan

Publications and source records attributed to A Whelan.

At least 73 records · Page 4Linked to original sources
PubMed1989

Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rheumatoid arthritis.

Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.

Antibodies, Monoclonal↗
PubMed1989

Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads.

Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

Arthritis, Rheumatoid↗
PubMed1989

Expression and regulation of the HLA-DR antigen on circulating monocytes isolated from patients with rheumatoid arthritis.

Using a modified radioimmunoassay, surface labeling of HLA-DR antigens on monocytes revealed reduced densities in patients with active rheumatoid arthritis (RA) (P less than 0.001) and in gold-treated patients (P less than 0.01) versus normal controls. Significant enhancement of DR antigen expression (P = 0.01), with values similar to those of normal monocytes, occurred in patient monocytes preincubated at 37 degrees C overnight, but not in monocytes preincubated at 4 degrees C. This suggested that a temperature-dependent metabolic process is required to enhance antigen expression. The addition of cycloheximide totally inhibited the enhancement of DR antigen density. Incubation of monocytes with exogenous prostaglandin E2 (10(-5)M final concentration) caused a reduction of DR densities on control and on RA monocytes, although this decrease was more marked in the controls. Addition of indomethacin did not affect DR antigen levels on control monocytes, but greatly enhanced the expression of DR antigens on RA monocytes. When HLA-DR antigen levels were estimated in detergent-solubilized membrane preparations, monocytes from patients with active RA demonstrated normal-to-increased densities compared with control monocytes. Thus, although RA monocytes possess a normal ability to synthesize DR molecules, surface expression of these molecules is inhibited; this inhibition may be mediated by prostaglandin E2 acting as a negative suppressive signal.

Arthritis, Rheumatoid↗
PubMed1989

Immunohistological features in the synovium obtained from clinically uninvolved knee joints of patients with rheumatoid arthritis.

The spectrum of immunohistological change in the affected joints of patients with rheumatoid arthritis has been well described. In this study, the immunohistological features in synovial membrane obtained from apparently uninvolved knee joints of 16 patients with active untreated rheumatoid arthritis were examined and compared to tissue from control subjects. Synovial tissue was obtained by needle biopsy. Hyperplasia of the synovial lining layer, present in 69%, was the most frequently observed abnormality in synovium obtained from uninvolved joints. Perivascular mononuclear cell infiltration was present in 31% and consisted predominantly of helper T-cells. Increased vascularity and fibrin deposition were not notable features. Clinically overt synovitis emerged in only two patients during a follow-up period of up to 36 months. In conclusion, a considerable degree of histological change was observed in the apparently uninvolved knee joints of patients with active rheumatoid arthritis. The presence of subclinical synovitis challenges current concepts of disease activity and clinical remission. Further study is required to determine whether the features described may be associated with progressive joint erosion.

Arthritis, Rheumatoid↗
PubMed1989

The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis.

The immunohistologic characteristics of synovial membrane obtained from patients with active rheumatoid arthritis (RA) were correlated with disease activity and spontaneous in vitro synthesis of IgM rheumatoid factor (RF) by peripheral blood mononuclear cells (MNC). Positive correlations were found between the intensity of inflammatory cell infiltration and both disease activity (p = 0.0007) and RF synthesis (p = 0.028). Moreover, the intensity of both T cell and B cell infiltration correlated significantly with disease activity. Within the group studied 3 previously described immunohistologic categories were identified. These categories could not be distinguished by clinical measurements, but did differ with respect to their capacity for spontaneous in vitro IgM RF synthesis by blood MNC. Our study provides evidence that a relationship does exist between the immunohistologic characteristics and disease severity in RA. Furthermore, the concept of distinct histologic categories of RA representing different immunopathogenic mechanisms is supported.

Adult↗
PubMed1988

Analysis of the histologic variation of synovitis in rheumatoid arthritis.

One hundred forty-five synovial biopsy specimens were obtained from 30 procedures performed on the knee joints of 29 patients with rheumatoid arthritis. All patients had clinically active rheumatoid arthritis and none had received slow-acting disease-modifying drugs or intraarticular corticosteroids. Scores were assigned to each biopsy specimen for each of 6 histologic features to quantify variation within each joint. In the majority of knee joint biopsies, there was considerable clustering of scores for all histologic features. Thus, on a scale of 0-10, 82% of the scores for synoviocyte hyperplasia were within 1 point of the median score for a given joint. Similarly, between 69% and 85% of the scores for the remaining features (fibrosis, vessel proliferation, perivascular infiltrates, focal aggregates, and diffuse infiltrates of lymphocytes) were within 1 point of the median values. Multiple biopsies were obtained at arthroscopy in 8 patients. Tissue was selected from areas of apparent maximal and minimal involvement, to enhance the likelihood of regional histologic variation. Of the scores for synoviocyte hyperplasia, 91% were within 1 point of the median values for a given joint, and of the scores for the remaining 5 features, 72-94% fell within 1 point of the median values. In addition, highly significant statistical correlations of the intensity of synovial lining layer hyperplasia, vessel proliferation, mononuclear cell infiltration, fibrosis, and clinical measurements of synovitis were observed.

Arthritis, Rheumatoid↗
PubMed1988

Myeloid antigen expression on common acute lymphatic leukaemia blasts after culture.

Blast cells from seven out of ten patients with common acute lymphoblastic leukaemia (cALL) developed the myeloid antigen MY7 (CD13) after culture, and one of these coexpressed the myeloid antigen MY9 (CD33). CD13 expression appeared to be independent of maturation since it could be induced more readily in cultures which did not contain the differentiation promoter 12-O-tetradecanoyl-phorbol 13 acetate (TPA). CD13 expression in culture was not seen on one null ALL, or 6 B-CLL investigated or on normal tonsillar B cells or PBMC under similar conditions. CD13 expression on cALL blasts probably represents evidence of abnormal gene expression in the leukaemic cells. However the absence of CD13 expression on the earlier B null ALL or the later B-CLL suggests we cannot exclude the possibility that CD13 expression is a feature of normal precursor B cells.

Adult↗
PubMed1988

Antibodies to Proteus in rheumatoid arthritis.

Increased levels of Proteus antibodies were found in patients with rheumatoid arthritis and coeliac disease, when compared to normal controls or patients with SLE and sarcoidosis.

Antibodies, Bacterial↗
PubMed1987

Characterization and quantification of solubilised HLA-DR antigens from circulating human monocytes using an immunoblotting procedure.

An immunoblotting technique was modified to detect and biochemically characterize HLA-DR antigens expressed on circulating human monocytes. Membrane proteins of peripheral blood monocytes were solubilised using the mildly anionic detergent, sodium deoxycholate. These solubilised proteins were resolved by SDS-PAGE and transferred electrophoretically to nitrocellulose. The HLA-DR antigen was detected using a polyclonal antiserum and two monoclonal anti-HLA-DR antibodies. Both immunoperoxidase and 125I autoradiography techniques were used for visualisation of the antigen. The resolution of HLA-DR reactive material was increased when proteins were renatured with 4M urea after blotting. Immunoprobing of a sample of solubilized membrane proteins showed three bands of HLA-DR antigenic reactivity at molecular weights 65kDa, 55kDa and 46kDa. After storage at -70 degrees C for 2 months, only the 46kDa HLA-DR antigen band was detectable. Nonetheless, the 2-chain HLA-DR molecule was found to be an extremely stable complex which could not be dissociated by boiling in sample buffer containing 5% 2-mercaptoethanol and 2% SDS. A stronger reducing agent, 25 mM dithiothreitol, was required to split the HLA-DR molecule into its alpha and beta subunit chains. Finally, in a study of circulating monocytes from normal subjects, the immunoblotting technique was shown to quantitate solubilised HLA-DR antigen in a reproducible manner.

Electrophoresis, Polyacrylamide Gel↗
PubMed1986

Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment.

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.

Adult↗
PubMed1986

Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients.

Eleven patients with active rheumatoid arthritis were monitored prospectively while receiving up to 1 gm of gold sodium thiomalate. There was a significant decrease in serum and synovial fluid IgG, IgA, and IgM rheumatoid factor (RF) levels over the period of study. Comparison of changes in serum RF and total immunoglobulin levels indicated a selective effect on RF production. These observations were supported by changes in the spontaneous in vitro production of IgM-RF and total IgM by peripheral blood mononuclear cells. Studies of synovial membrane synthesis showed a downward trend in immunoglobulin and RF production, but this did not reach statistical significance. A differential effect on the various RF classes was also noted. The most profound effect was on IgM-RF production; whereas, changes in IgG-RF production were least affected. These results suggest a selective and differential effect of gold salts on RF production.

Adult↗
PubMed1986

Studies on the accessory requirement for T lymphocyte activation by concanavalin A.

In this study we have examined the interactions between accessory cells (AC) and T cells in response to Con A. Highly purified peripheral blood T cells and AC exposed to a variety of treatments were used. We found that untreated AC provided optimal help for T cell proliferation and this was not mediated by soluble factors since whole cells could not be replaced with supernatants from activated AC. Furthermore, cycloheximide-treated AC were able to supply the accessory signal although unable to elaborate soluble activation factors. To find out more about the accessory signal, we examined the ability of monocytes mildly fixed with glutaraldehyde to supply help. These cells were completely unable to perform as AC, although they were viable and had unaltered surface antigen expression. They could not secrete activation factors, but this alone could not explain their inability to supply help because this function was not restored with the addition of soluble activation factors. This indicated that AC-T cell contact was of prime importance to accessory function. To investigate the possibility that AC work by cross-linking structures on the lymphocyte surface, we attempted to substitute for the soluble Con A plus AC with Con A bound to the surface of erythrocytes. Comparable stimulation was observed, suggesting that the cross-linking of Con A-bound structures on the lymphocyte surface generates the accessory signal.

Antigen-Presenting Cells↗
PubMed1985

CSF myelin basic protein in multiple sclerosis.

Cerebrospinal fluid (CSF) from 221 patients with multiple sclerosis (MS) and 85 patients with other neurological disorders (OND) was examined using a competitive radioimmunoassay for myelin basic protein (MBP) immunoreactivity. MBP was found in 46 of 55 MS patients (84%) examined within six weeks of relapse but in only 11 of 85 patients (13%) with OND. There was a significant correlation between the concentration of MBP in the CSF and relapse severity in patients seen within four weeks of the onset of symptoms (p less than 0.01). Of 44 patients in remission, MBP was detected in 12, and these patients had a significantly higher tendency to subsequent relapse (p less than 0.05). In 72 patients with progressive disease the presence of MBP in the CSF reflected the confidence of clinical diagnosis. The results of this study suggest that measurement of MBP in the CSF gives an objective method of monitoring disease activity in patient with MS.

Acute Disease↗
PubMed1985

Suspected and clinically definite multiple sclerosis: the relationship between CSF immunoglobulins and clinical course.

CSF immunoglobulins were examined in 103 patients with clinically definite multiple sclerosis, 106 patients with either suspected or progressive possible multiple sclerosis and 72 patients with other neurological diseases. Raised CSF IgG index and oligoclonal banding were found in 71% and 75% of clinically definite multiple sclerosis patients respectively and both tests were abnormal in 11% of patients with other neurological diseases. The CSF IgG index and the presence of oligoclonal IgG did not relate to the severity or duration of established disease in these patients. In patients with suspected and progressive possible multiple sclerosis, both a raised IgG index and the presence of oligoclonal banding were found significantly more frequently than in the OND group. Abnormalities of these parameters were significantly correlated with the presence of an abnormal evoked response in these patients (chi 2 = 10.16 p less than 0.01). When 47 patients with suspected multiple sclerosis were studied prospectively the presence of oligoclonal banding at presentation was associated with development of further disease activity.

Brain Stem↗
PubMed1985

Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors.

Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The invitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation.

Arthritis, Rheumatoid↗
PubMed1980

A randomized, double-blind therapeutic trial of 0.25% desoxymethasone and 0.1% hydrocortisone 17-butyrate in the treatment of varicose eczema.

A double-blind, randomized trial was carried out in 60 patients with varicose (hypostatic) eczema to compare the efficacy and tolerance of treatment with 0.25% desoxymethasone in an oily cream base, the oily cream base alone, and 0.1% hydrocortisone 17-butyrate cream. The creams were applied twice daily and patients' progress followed for up to 38 days. Clinical ratings based on an assessment of individual signs and symptoms, the area of skin involved and the physician's overall impression demonstrated a significant difference from the oily cream base in favour of both active treatments within the first 10 days. No significant difference between the two active treatments was shown. All three treatments were well tolerated by the patients.

Administration, Topical↗