Sterling K. Ainsworth

Autoantibodies in healthy subjects of different age groups

Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.

Autosomal Dominant Polycystic Kidney Disease With Liver and Pancreatic Involvement in Early Childhood

In a patient with autosomal dominant polycystic kidney disease, liver and kidney cysts were found by biopsy at the age of 8 months. Computed tomography at the age of 16 years confirmed the presence of liver and kidney cysts and also revealed pancreatic cysts. Such early onset of liver cysts in a patient with autosomal dominant polycystic kidney disease has not been reported previously.

Gm allotypes in Blacks with systemic lupus erythematosus

Serum samples were collected from 328 healthy American Blacks and from 61 American Blacks with systemic lupus erythematosus (SLE). Sera were typed for the Gm1,2,3,5,6,13,17, and 21 allotypes as well as for the Km(1) allotype. The frequency of Gm phenotype 1,17;5,6,13 was significantly increased in the SLE patients (p = 0.0001, RR = 3.19, EF = 0.29). Our data suggest the existence of at least two immunoglobulin allotype associated genes that somehow interact to increase susceptibility to SLE in Blacks. To our knowledge, this is the first report of an association of Gm and SLE in Blacks.

Direct and indirect immunofluorescent findings in dermatomyositis

Three skin biopsies (proximal nailfold, extensor forearm and buttock) and serum samples were studied by direct and indirect immunofluorescence, immunodiffusion and radioimmunoassay techniques in 6 patients with dermatomyositis. A variety of seroligic and immunopathologic abnormalities was observed in the patients. Three of ft patients had antinuclear antibodies (ANA) of a speckled pattern mixed with a peculiar dot pattern. Epidermal intercellular deposits of immunoglobulins were seen in the nailfold biopsies of 2 patients; one of them also had IgG deposits in the cytoplasm of epidermal cells. Forearm and buttock biopsies were negative.

Toxicity following protein a treatment of metastatic breast adenocarcinoma

The toxic effects of protein A (Prosorba, IMRE Corporation, Seattle, WA) treatments given as part of an on‐line plasmapheresis or off‐line procedure were determined in a Phase I Study. Patients were randomized and treated 12 times either once per week or three times per week with a Prosorba column containing 50 or 200 mg protein A. Treated plasma volumes varied from 150 ml off‐line to 2000 ml on‐line. Seven patients having advanced metastatic breast adenocarcinoma patients were evaluated. All had advanced progressive disease that was resistant to chemotherapy and/or radiation therapy. Greater than 50% regression of measurable tumor volume occurred in four of seven patients; an additional patient responded with 33.5% regression. Two patients with only bony metastases demonstrated stable disease for a 60‐day period. Side effects resulting from protein A treatments included transient fever, chills, rigors, and infrequently nausea, vomiting, diarrhea, episodic hyper and/or hypotension, broncho‐spasm, venospasm, headache, joint and tumor pain. Mild to moderate reactions were seen in all patients regardless of clinical response, but abated spontaneously or were controlled with pretreatment and/or post treatment with antipyretics and/or antihistaminics. The side effects decreased notably during the course of the week with the more intense reaction occurring during the first treatment of the week. Side effects occurred regardless of column size or volume of plasma treated. In the course of 12 treatments, anemia requiring transfusion developed in two of seven patients. Significant tumor regression was obtained in this group of patients with advanced disease. In light of the mild to moderate side effects and tumor regression in five of seven of the patients treated, protein A treatment merits further evaluation to determine the effectiveness of this treatment in breast adenocarcinoma.

In vitro alternative and classical activation of complement by extracts of cotton mill dust: a possible mechanism in the pathogenesis of byssinosis.

Extracts of cotton mill dust (CDE) were shown to activate complement by the classical and alternative pathways. Activation of the classical pathway, presented in this study for the first time, was verified by C1 consumption, C2 destruction, and C4 conversion tests. The component of cotton dust that causes complement activation precipitated in the presence of 20% saturated ammonium sulfate. The data presented suggest that endotoxin is not the principal complement-activating component, as complement activation could not be correlated to endotoxin concentrations of extracts of various parts of the cotton plant. Proteolytic enzymes were also eliminated as possible causative agents of complement cleavage since CDE did not cleave purified C3 in the absence of other complement components. Polyvinylpolypyrrolidone failed to remove the complement-activating component in CDE demonstrating that polyphenolic tannins are not the causative agents. Involvement of complement activation in the pathogenesis of byssinosis could explain in part the mechanism and symptoms of the acute byssinotic reaction.

Immune complexes and antinuclear, antinucleolar, and anticentromere antibodies in scleroderma.

Forty-one patients with various forms of systemic sclerosis (scleroderma) and positive antinuclear antibodies of nucleolar (ten patients), speckled (eleven patients), or centromere pattern (twenty patients) were selected for study of immune complexes by the radioisotope labeled Clq binding and the radioisotope labeled protein A binding methods. The presence of immune complexes was found by the Clq binding assay in sixteen patients (39%) and by a protein A binding assay in eight patients (20%). Overall, 46% of patients (19/41) had immune complexes. A lower incidence of organ involvement and fewer positive results in the screening of serum immune complexes were observed in patients with centromere antibody (35%) than in patients with nucleolar (60%) or speckled pattern (55%). Patients with immune complexes had higher frequencies of kidney, heart, and muscle involvement and digital ulceration than did patients with no detectable immune complexes, but the differences were not statistically significant. Diffuse skin involvement was not related to the presence of immune complexes.

Bioasssays of smooth muscle contracting agents in cotton mill dust and bract extracts: Arachidonic acid metabolites as possible mediators of the acute byssinotic reaction

Byssinosis is an occupational respiratory disease contracted by cotton mill workers who inhale cotton mill dust. The acute byssinotic reaction is characterized by a drop in the 1-sec forced expiratory volume (FEV1.0) on Monday following a weekends absence from work. This physiological reaction is the result of the contraction of bronchial smooth muscle, which causes narrowing of small airways. An isolated tissue bath technique was used to assay smooth muscle contractions induced by cotton dust extract (CDE) and cotton bract extract (CBE). CBE-induced contractions of rat stomach smooth muscle were blocked (82%) by 100 ng/ml methysergide (blocks 5-hydroxytryptamine (5HT) 100%); CDE was not significantly blocked by methysergide (13%). CDE-induced contractions were blocked (100%) by 25 micrograms/ml indomethacin and 100 micrograms/ml salicylic acid (blocks prostaglandin F2 alpha (PGF2 alpha) 100%). The portion of CBE contracting ability not blocked by methysergide was blocked totally by indomethacin. Blocking agents ineffective against CDE or CBE include atropine (acetylcholine blocker), pyrilamine maleate and diphenhydramine (histamine blockers), imidazole and 7-(1-imidazolyl)heptanoic acid (7IHA) (thromboxane blockers), and carboxypeptidase B2 (kinin blocker). The data suggest that cotton bract contains 5HT, which is responsible for a majority of the CBE-induced contraction and a minority of the CDE-induced contraction. The data also suggest that cotton dust and bract contain a substance which causes the release of PGF2 alpha which in turn causes the contraction of smooth muscle. This substance is responsible for a majority of the CDE-induced and a minority of the CBE-induced contractions. Radioimmunoassay (RIA) confirmed PGF2 alpha release from rat fundal smooth muscle when exposed to CDE and CBE. Increased synthesis and release of arachidonic acid metabolites might be a major mechanism in the bronchoconstriction observed in the acute byssinotic reaction.

Byssinosis: Serum Immunoglobulin and Complement Concentrations in Cotton Mill Workers

In two separate studies (labeled A and B), concentrations of IgC, IgM, IgA, C3, and C4 were determined in the sera of byssinotic and non-byssinotic cotton mill workers. In study A, sera were collected on Monday morning and Monday afternoon and Friday afternoon in order to ascertain if the waning byssinotic response from Monday to Friday correlates with changes in serum immunoglobulin and complement concentrations. In study B, sera was collected on Monday morning and afternoon and was performed primarily to evaluate history of atopy and smoking as complicating factors in byssinosis. In study A, the concentrations of all immunoproteins were found to decrease from Monday morning to to Friday afternoon in all textile workers, and in study B only C3 concentration decreased morning to afternoon. There was, however, no difference between the immunoprotein changes for byssinotic workers when compared to non-byssinotic workers in either study. Due to the fact that hypersensitivity pneumonitis causes a decrease in immunoprotein concentrations in affected workers while no decreases are noticed in normal workers, our data do not support an immune complex etiology for byssinosis. In addition, decreased serum C3 concentrations observed in this study could be caused by complement activation; however, there was no difference in complement levels between byssinotic and non-byssinotic textile workers. Therefore, these data neither support nor eliminate the involvement of antibody-independent complement activation in the pathogenesis of byssinosis.

Serum histamine levels following adminstration of ultrastructural tracers in three strains of rats

Intravenous administration of the electron-opaque tracer ferritin resulted in substattial elevation of serum histamine levels in both the Munich-Wistar and Wistar-Furth strains of albino rats. Lewis rats were unaffected. Similarly, infusion of the non-protein tracer dextran was followed by greatly elevated serum histamine concentrations in Munich-Wistar and Lewis, but not in Wistar-Furth, rats. In sharp contrast with these results were those obtained using the tracer polyvinylpyrrolidone (PVP). PVP infusion caused no elevation of serum histamine levels in any of the rat strains studied. Caution in the use of such tracers is thus advised, since serum histamine concentration affects vascular permeability. Careful matching of ultrastructural tracer and strain of experimental amimal is prerequisite in permeability studies.