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Biomedical subjects

J Curd

Publications and source records attributed to J Curd.

9 recordsLinked to original sources

Complement levels in patients with hepatic dysfunction.

Total hemolytic complement activity and serum complement protein concentrations were compared in 17 hospitalized patients with normal hepatic function and 16 patients with liver disease due to alcohol (15 patients) or acetaminophen toxicity (one patient). In contrast to the control patients, individuals with hepatic dysfunction had decreased total CH50 levels and low concentrations of total C3, C4, C5, factor B, and the regulatory proteins factor I and beta-1H. These patients also had increased C4d/C4 ratios, indicating classical pathway activation. The level of complement deficiency appears to correlate with either prolongation of the prothrombin time or depression of serum albumin concentration. These results indicate that patients with hepatic disease have severe complement depletion that is probably multifactorial in origin. This impairment in complement function will contribute to the impaired antibacterial host defense of the patient with chronic hepatic disease.

Complement System Proteins

A novel bioassay to predict the clinical response to cryofiltration treatment. A preliminary report.

Phagocytosis by normal human mononuclear monocytes grown in vitro was examined after incubation with known concentrations of aggregated human gamma-globulin (AHG) and in plasma obtained from patients suffering from immunologic diseases. When the phagocytes were pretreated with AHG, an inverse relationship between amounts of AHG and phagocytosis of radiolabeled Candida albicans was found. Inhibition of phagocytosis by patient plasma was independent of other laboratory determinations including antinuclear antibody, C3, C4, CH50, DNA-binding and circulating immune complexes. Plasma from 5 patients subjected to cryofiltration treatment (CFT) demonstrated less inhibition after than before CFT. This lessened inhibition of phagocytosis in vitro correlated with the clinical response due to CFT. The response to CFT could not be predicted by the conventional laboratory parameters investigated. Improvement between pre- and post-CFT plasma estimated by using the present bioassay may provide a quantitative description of which patient may benefit from plasmapheresis treatment procedures.

Biological Assay

Detection of in vitro and in vivo cleavage of high molecular weight kininogen in human plasma by immunoblotting with monoclonal antibodies.

Purified human high-mol-wt kininogen (HMWK), the cofactor of the contact phase of blood coagulation, migrated as a single band (approximately 110,000 mol wt) in a continuous buffer sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), but appeared as two separated bands (approximately 120,000 and 105,000 mol wt) when analyzed in a discontinuous buffer SDS-PAGE system. After elution from SDS polyacrylamide gels, each of the two bands showed coagulant activity. Six murine monoclonal antibodies (Mabs) against HMWK were produced and purified. In immunoblotting studies, three Mabs bound to the isolated alkylated heavy chain and one to the alkylated light chain of HMWK, whereas the remaining two bound only to the single-chain or unreduced two-chain molecule. None of the Mabs inhibited the clotting activity of HMWK or its binding to kaolin. Two of the Mabs, one directed against the light chain and one against the heavy chain, were used as specific probes to study HMWK in plasma samples using an immunoblotting technique. The anti-light chain Mab identified two distinct bands (approximately 120,000 and approximately 105,000 mol wt) in normal human plasma, but not in plasma from patients with hereditary HMWK deficiency. The anti-heavy chain Mab detected two additional bands (approximately 60,000 and approximately 54,000 mol wt) corresponding to low-mol-wt kininogen (LMWK) in normal plasma. A sensitive and specific quantitative immunoblotting assay of HMWK antigen in plasma was developed. Moreover, the immunoblotting technique with the anti-light chain Mab was used to detect the cleavage of HMWK in plasma samples after in vitro or in vivo activation of the contact system. The anti-light chain Mab demonstrated in vivo activation and cleavage of HMWK during an angioedema attack in a patient with hereditary angioedema and C1-inhibitor deficiency.

Antibodies, Monoclonal

Immunologic dynamics in cryapheresis for rheumatoid arthritis.

Five patients with erosive rheumatoid arthritis (RA) who had previously experienced a favorable response to lymphoplasmapheresis were treated with cryapheresis. Cryapheresis was performed 9 times in 3 weeks using a membrane filtration device that selectively removes plasma proteins with molecular weights greater than 100,000 daltons. Four of the 5 patients so treated improved clinically. The membranes selectively removed more immunoglobulins and complement components that were part of circulating immune complexes than those that were not. Plasma or albumin replacement was not necessary in these patients. Cryapheresis might be a safe and effective technology in treating patients with refractory RA.

Adult

Cold dependent activation of complement in systemic lupus erythematosus. A unique cause for a discrepancy between clinical and laboratory parameters.

A 31-year-old woman with systemic lupus erythematosus (SLE) was studied because she developed markedly reduced total hemolytic complement activity at a time when her disease was clinically inactive. Functional assays demonstrated reduced activities of C1, C4, and C2, but normal concentrations of C3 and the terminal (C5-9) components were present. Antigenic concentrations of C1, C4, and C2 were normal. Plasma or serum obtained from blood allowed to clot at 37 degrees C had normal complement activity. Complement activity was depleted when the patient's serum was incubated in the cold. At reduced temperatures, the patient's serum (or purified IgG) depleted complement activity of normal human sera. A second patient with SLE was also demonstrated to have this same phenomenon. Cryoglobulins were not detectable in these patients. These data indicate that in vivo the patients' complement was normal and that the observed in vitro reduction was caused by cold dependent activation of the classical pathway.

Adolescent

Calcaneal abnormalities in articular disorders. Rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and Reiter syndrome.

The calcaneus of normal control patients, and those with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and Reiter syndrome was studied. Pathological abnormalities of the plantar aponeurosis, Achilles tendon, and retrocalcaneal bursa account for the radiographic alterations. In normal individuals, lateral radiographs show the thickness of the Achilles tendon to be not greater than 8 mm; the retrocalcaneal bursa creates a radiolucency which extends at least 2 mm below the superior surface of the calcaneus. In patients with any of these 4 articular disorders, Achilles tendinitis produces thickening of the tendon, and retrocalcaneal bursitis obliterates the normal radiolucency.

Adult

The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin.

Specific antibodies to digoxin were isolated from antisera of sheep immunized with a digoxin-human serum albumin conjugate. The antibody was purified by adsorption to an immunoadsorbent, synthesized by coupling a ouabain-ribonuclease conjugate to bromoacetyl-cellulose, followed by elution with 25 mM ouabain. Ouabain was dissociated from antibody by denaturation in 6 M guanidine. The renatured antibody bound 1.6 mol of digoxin per mol and had an association constant of 1.6 x 10(8) M(-1). At near-stoichiometric concentrations, either purified antibody to digoxin, or its papain-digested product (Fab-Fc), reversed digoxin-induced: (a) inhibition of (86)Rb transport in human erythrocytes, (b) increase in developed tension in isolated guinea-pig atrial strips, and (c) ventricular tachycardia in intact dogs, and also corrected digoxin-induced automaticity in isolated guineapig atrial strips.

Adsorption

Radiographic abnormalities of rheumatoid arthritis in patients with diffuse idiopathic skeletal hyperostosis.

Radiographic abnormalities of rheumatoid arthritis (RA) in 8 patients with diffuse idiopathic skeletal hyperostosis (DISH) included atypical features: lack of osteoporosis, bone sclerosis and proliferation about erosions, osteophytosis, and bony ankylosis. Atypical clinical features included a high incidence of flexion contractures of elbows, wrists, ankles, or knees. It is not surprising that bone production occurs about involved articulations in patients with RA-DISH, as the latter disorder is characterized by bony proliferation at sites of ligament and tendon attachment to bone in the axial and extraaxial skeleton, perhaps related to stress.

Aged