Biomedical subjects
Publications and source records attributed to J Petersen.
We describe a patient with chyluria due to abdominal Bancroftian filariasis. The patient showed two unusual complications, an immune complex glomerulonephritis and a chronic urinary infection. We also discuss the use of the CT whole body scanner in the diagnosis and delineation of the extent of the disease.
In rheumatoid arthritis both lymphocyte-mediated and antibody-mediated immune reactions are important for the inflammatory lesions. In vivo activated B lymphocytes/plasma cells, T lymphocytes and monocytes/macrophages (Mo) are intimately involved in the disease process. Several clinical observations suggest an immunosuppressive action of gold salts. In humans, gold salts interfere with a number of Mo functions in vitro, including cellular interactions between Mo and T lymphocytes. Some workers have shown that the activation of human T lymphocytes is inhibited by gold salts, most probably secondary to an inhibition of Mo-T cell cooperation. Recent experiments indicate that gold salts also affect the in vitro differentiation of human B lymphocytes in response to polyclonal activators. Both the gold atom and the SH group seem to be important for the immunosuppressive actions of gold salts.
Explore the source record for details and available documents.
The vitamin B12 (cobalamin) binding proteins, transcobalamin and haptocorrin, were measured in serum and synovial fluid of 12 patients with rheumatoid arthritis (RA) and 11 patients with traumatic synovitis (TS). Levels of both the cobalamin-binding proteins of synovial fluid were markedly elevated in RA compared with TS. In serum, the haptocorrin concentrations were significantly increased in RA vis-à-vis TS. In synovial fluid of RA patients, the transcobalamin and haptocorrin concentrations were positively correlated to the concentrations of macrophages and polymorphonuclear granulocytes, respectively. The demonstration of increased synovial fluid transcobalamin/total protein and haptocorrin/total protein ratios in RA vis-à-vis TS provides further evidence of a local production or liberation of the cobalamin-binding proteins in synovial fluid of patients with RA.
The influence of synovial fluid and blood monocytes on autologous lymphocyte proliferation in vitro was investigated in patients with rheumatoid arthritis (RA) and traumatic synovitis (TS). In cultures stimulated with PHA, PWM and ConA, thymidine incorporation by RA blood mononuclear cells (BMC) increased considerably in most cases after addition of 10% or 30% synovial fluid monocytes and a similar effect was seen after stimulation with Candida extract or PPD. A comparable helper activity was observed after addition of synovial fluid monocytes to monocyte-depleted blood cells in RA. The augmenting effect of synovial fluid monocytes was likewise demonstrated in TS patients. Synovial fluid mononuclear cells (SMC) from RA and TS patients displayed low proliferative responses to PHA and ConA in comparison with BMC, while the responses to microbial antigens were similar or greater. The proliferative activity of SMC or of monocyte-depleted synovial fluid cells after polyclonal and antigenic stimulation was not affected by addition of blood monocytes. This was observed in both RA and TS patients. It is concluded that the regulatory properties of synovial fluid monocytes in RA and TS do not explain the low proliferative responses of SMC to polyclonal activators.
The immunosuppressive drugs cyclosporin A (CyA) and methylprednisolone (MP) abolished the elaboration of the lymphokine leukocyte migration inhibitory factor (LIF) by mononuclear cells challenged by recall antigen. Suppression in both cases was reversible upon removal of the drugs, and participation of T suppressor cells of their mediators could not be demonstrated. The CyA-induced effect was exerted in the early stage of lymphocyte activation (less than 60 min), whereas MP still inhibited LIF release when added 60 min after the antigen. In contrast to earlier findings that the drugs failed to affect the release of T cell-activating factor (TAF) and lymphocyte-activating factor (LAF) from macrophages (M-phi's) stimulated by phorbol myristate acetate. MP (but not CyA) markedly reduced TAF production by M-phi's incubated with tuberculin. M-phireover, partially purified TAF and LAF both restored LIF production in the presence of CyA (but not MP), an effect not mimicked by the T cell product T cell growth factor. However, suppression by both drugs was abrogated by exogenous cGMP. Hence, CyA seems to obstruct the interaction between TAF/LAF and the immune T cell, whereas MP affects antigen-induced T cell activation at the Mo level as well as the level of lymphokine production and/or release. The effects of both drugs seem related to intracellular events involving cGMP.
With the purpose of detecting granulocyte-specific membrane-directed autoantibodies, IgG was isolated from 14 patients with Felty's syndrome, from 5 patients with rheumatoid arthritis associated with neutropenia, and from 3 rheumatoid factor positive patients with autoimmune neutropenia. By means of indirect immunofluorescence suspensions of leukocytes from healthy controls were tested for their ability to bind whole IgG fractions or F(ab')2 fragments of IgG isolated from the neutropenic patients. By this method, whole IgG preparations from neutropenic patients and normal controls were invariably found to bind to the surface of granulocytes and a minor proportion of lymphocytes. In contrast. F(ab')2 fragments of IgG from the neutropenic patients failed to bind to the surface of granulocytes. Both whole IgG fractions and F(ab')2 fragments displayed displayed antinuclear antibody activity ruling out the possibility of loss of antibody reactivity during the preparation of F(ab')2 fragments. The neutropenia seen in rheumatoid arthritis with or without splenomegaly thus does not seem to be induced by granulocyte-specific membrane-directed IgG autoantibodies, but rather by a non-specific attachment of IgG most probably in immune complex bound form to Fc gamma receptors on neutrophils which thereby acquire surface properties facilitating removal from the circulating blood cell pool.
A direct plaque forming cell (PFC) assay for the detection of complement fixing IgM-rheumatoid factor (RF) secreting lymphocytes was evaluated. The specificity of the RF-PFC assay was demonstrated by the inhibitory action of exogenous human IgG. The sensitivity of the RF-PFC assay was similar to that of a reverse PFC assay detecting all cells secreting IgM (IgM-PFC). In blood from 75% of seropositive patients with rheumatoid arthritis (RA) RF-PFC were demonstrated, median value 6.8 (range: 0.4-1477) RF-PFC/10(6) mononuclear cells. Practically no RF-PFC were detected in seronegative RA patients and controls. Despite the fact that most IgM-RF undoubtedly is produced outside the blood, a positive correlation was found between the number of RF-PFC and the Waaler-Rose titer in serum. The number of circulating IgM secreting cells did not differ significantly between seropositive RA patients, seronegative RA patients and controls. Comparison of RF-PFC and IgM-PFC in seropositive patients revealed that in mean 7% of IgM-secreting cells in blood secrete IgM-RF.
In order to determine the borderlines of the benign partial epilepsy of children with centrotemporal spike foci ('Rolandic epilepsy') 43 patients with epilepsy and spike foci in the centrotemporal region or elsewhere drawn from the EEG files were re-evaluated as adults. The prognosis was equally good whether the spike focus was in the centrotemporal region or elsewhere, and synchronous paroxystic activity did not make the prognosis worse, but focal temporal low frequency activity did. It is suggested that borderline cases exist between 'Rolandic epilepsy' and other age dependent epilepsies.
In 25 patients with cerebral arteriovenous malformation (AVM) computer tomography (CT) was compared with dynamic and static intravenous radionuclide angioscintigraphy (99mTc-labelled red blood cells). The diagnosis was verified by arteriography performed 2-20 years prior to this study. Scintigrams and CT-scans were evaluated 'blindly' by independent observers after pooling of the patient studies with 20 and 20 control studies, respectively. Only images strictly characteristic of AVM were classified as positive. The nosographic sensitivity of both methods was about 70%, in a few patients they were supplementary. Neither CT nor scintigraphy were able to detect lesions of less than 2 cm diameter. The methods seem to be of equal and rather high specificity, and are both well suited as screening procedures. CT provides additional information as to other intracranial abnormalities. The screening method of first choice when AVM is suspected may be CT or angioscintigraphy, depending on availability of equipment and expertise.
Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E-rosettes, have no surface-membrane-bound Ig, but Fc-receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4- and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato-splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.
By means of recently developed immunochemical assays increased levels of the complement C3c and C3d split products were found in synovial fluids of patients with rheumatoid arthritis (RA) as compared with synovial fluids of patients with traumatic synovitis (TS). In plasma, only the C3d levels were significantly increased compared with plasma levels of patients with TS. Both split products were higher in RA synovial fluids (SF) than in RA plasma. A positive correlation between the C3d concentrations in plasma and the presence of IC in serum was found, and between the C3c levels and the concentration of polymorphonuclear cells in SF of RA patients. Due to differences in turn-over of C3c and C3d determination of plasma C3d levels may be a useful parameter for the evaluation of immunological activity in RA, while measurement of C3c in the synovial fluid may elucidate the actual inflammatory activity in the synovial membranes.
Explore the source record for details and available documents.
High-affinity 86Rb-binding has been related to tryptic cleavage and fluorescence from intrinsic and extrinsic probes in order to examine the relationship of cation binding to structural transitions in the alpha-subunit of pure membrane-bound Na+,K+-ATPase from the outer renal medulla. Native Na+,K+-Atpase binds two Rb+ ions per alpha-subunit (12.3 nmol/mg protein) with high affinity (Kd = 7.5 microM) in 25 mM Tris-HCl, pH 7.5. Enzyme with one molecule of covalently attached fluorescein per alpha-subunit has the same capacity (12.8 nmol/mg protein) but a much lower affinity for Rb+ (Kd = 29.2 microM). The changes in conformational state of the protein are correlated with occupancy of the high-affinity sites for Rb+, also at concentrations of Rb+ below the Kd. Titration at varying ionic strength suggests that the E2-form is the relaxed or native conformation of the alpha-subunit. Changes in tryptic digestion pattern and in fluorescence are parallel events both in the conditions of the binding assay and at physiological ionic strength. Reversible blocking of sulfhydryl groups with Thimerosal (ethylmercurythiosalicylate) abolishes the fluorescence responses to K+ or Rb+ without affecting the capacity or the affinity for binding of 86Rb. The demonstration of high-affinity binding of Rb+ without coupling to a conformational change suggests that the E1-form of the protein exposes sites for tight binding of K+ or Rb+ at the cytoplasmic membrane surface.
Explore the source record for details and available documents.
Glomerular filtration rate (GFR; 51Cr-EDTA clearance), serum creatinine concentration and urinary excretion of prostaglandins were measured in 8 patients with systemic lupus erythematosus (SLE) before and after 2 weeks of treatment with acetylsalicylic acid (ASA). ASA 65 mg/kg or up to 4 g/daily was given as a sustained release preparation. The serum salicylate concentration ranged from 0.3 to 1.6 mmol/l. Serum creatinine after 1 and 2 weeks and GFR after 2 weeks of ASA treatment showed no significant changes. There was a clearcut decrease in urinary excretion of prostaglandins PGE2 and PGF2 alpha, by 44% and 50%, respectively. It is concluded that therapeutic doses of ASA do not cause deterioration of GFR in patients with SLE and normal or moderately reduced renal function.
The influence of cyclosporin A (CyA) and methylprednisolone (MP) on the elaboration of the human lymphokine, leukocyte migration inhibitory factor (LIF) was investigated. Both CyA and MP at pharmacological concentrations inhibited the release of LIF from immune lymphocytes challenged by recall antigen. By contrast, the release of LIF in response to polyclonal activation by phytohaemagglutinin A was not affected by CyA or by MP. CyA and MP had no effect on the production of the monokine, T-lymphocyte-activating factor (TAF) by stimulated blood monocytes. However, addition of partially purified TAF to antigen-stimulated lymphocytes completely abrogated the inhibitory effect of CyA, but not that of MP. Thus, CyA and MP affect antigen-induced production of LIF by immune lymphocytes by different mechanisms.
The mechanism of action of the immunosuppressive drug, cyclosporin A (CyA), was analyzed with respect to antigen-induced production of the human lymphokine, leukocyte migration inhibitory factor (LIF). Mononuclear cells as well as purified T-cells did not elaborate LIF in the presence of pharmacological concentrations of CyA. CyA-induced immunosuppression was competitively reversed by addition of the partially purified monokines, T-cell-activating factor (TAF) and lymphocyte-activating factor (LAF). CyA did not affect T-cell priming with antigens. The drug failed to abolish LIF production if added 60 min after challenge of T-cells with recall antigen in the presence of TAF. Furthermore, addition of TAF within 15 min to CyA-treated T-cells resulted in unaltered LIF production. These results suggest that CyA suppresses the early stage of the immune response by competing with the function of TAF/LAF on the immune T-cell.