Characterization of a new antigen-antibody system (Su) in patients with systemic lupus erythematosus.

A new antigen (Su) from calf thymus nuclear extract that reacts with sera from patients with systemic lupus erythematosus (SLE) is described. Antibodies to Su, demonstrated by immunodiffusion, were most frequently found in patients with a diagnosis of probable or definite SLE. Thirty-seven percent of patients with Su antibodies and a diagnosis of SLE were positive for antinuclear antibodies by indirect immunofluorescence, but lacked specific antibodies previously associated with SLE.

Antibodies to nonhistone nuclear antigens and antilymphocyte antibodies among children and adults with systemic lupus erythematosus and their relatives.

Antibodies to nonhistone nuclear antigens are found with increased frequency in the serum of patients with systemic lupus erythematosus (SLE) and their first degree relatives. We measured the prevalence of ANA and antibodies against DNA, RNP, Sm, SSA, and SSB as well as antilymphocyte antibodies (ALA) in the serum of 24 patients with childhood onset SLE and 94 of their first degree relatives and compared the prevalence of these same antibodies in 8 patients with adult onset SLE and 33 of their first degree relatives. Antibodies against DNA, RNP, and Sm occurred more frequently in the serum of adult onset SLE patients.

Clinical relevance of PM-1 antibody and physiochemical characterization of PM-1 antigen.

Using an improved immunodiffusion test with partially purified antigen, PM-1 antibody was identified in the serum of 18 patients. In 67% this system was associated with a polymyositis-scleroderma overlap, it occurred less frequently in polymyositis, dermatomyositis and scleroderma, and was not detected in other rheumatic diseases. The predominant clinical features of PM-1 positive patients were muscle weakness, sclerodactyly, Raynaud's phenomenon and pulmonary disease; widespread sclerodermatous features with infrequent.

Isolation and partial characterization of the rat liver ligandosome fraction.

The subcellular distribution in rat liver of non-latent and latent NADH pyrophosphatase was determined by analytical sucrose density gradient centrifugation. Non-latent NADH pyrophosphatase activity was distributed similarly to the plasma membrane marker, 5'-nucleotidase. However, latent NADH pyrophosphatase was found at the low density region of the gradient, similar to the distribution of galactosyl transferase, a Golgi marker.

Cyclic nucleotide-dependent enzyme secretion in the rat lacrimal gland.

To characterize the role of cyclic nucleotides in secretion of enzymes by the lacrimal gland, pieces of rat exorbital glands were perfused with (1) 8-bromoadenosine-3',5'-cyclic monophosphate (8 Br cyclic AMP), (2) 8-bromoguanosine-3',5'-cyclic monophosphate (8 Br cyclic GMP), (3) forskolin, a stimulator of adenylate cyclase activity, (4) 3-isobutyl-1-methylxanthine (IBMX), an inhibitor of phosphodiesterase activity, or (5) carbachol, a cholinergic agonist. As a measure of enzyme secretion, timed collections of the perifusate effluent were analysed for peroxidase, an enzyme secreted by the lacrimal gland. Control peroxidase secretion was 0.

Mössbauer spectroscopic studies of human haemosiderin and ferritin.

Ferritin and haemosiderin isolated from iron-overloaded human spleens have been investigated by 57Fe Mössbauer spectroscopy at temperatures between 1.3 and 200 K and also in applied magnetic fields. Virtually identical spectra were obtained from both materials at the high and low-temperature ends of this range, and also at 4.

Healing of cervical epithelium after laser ablation of cervical intraepithelial neoplasia.

Healing of cervical epithelium was studied in 30 patients after destruction of cervical intraepithelial neoplasia using a carbon dioxide laser. Repeated examinations, using photography and colposcopically directed punch biopsies, were made from the eighth to the 32nd day after treatment. The biopsy specimens were submitted to examination by light and transmission electron microscopy.

Ca2+-calmodulin-, cyclic AMP- and cyclic GMP-induced phosphorylation of proteins in purified microvillus membranes of rabbit ileum.

Evidence is available to suggest that Ca2+-calmodulin and cyclic nucleotides are involved in the regulation of ion transport in rabbit ileum. Since both Ca2+-calmodulin and cyclic nucleotides exert many of their effects by phosphorylation, the effects of Ca2+-calmodulin and cyclic nucleotides on phosphorylation of purified microvillus membrane from rabbit ileal mucosa were evaluated. Ca2+-calmodulin increased phosphorylation of five microvillus-membrane peptides, with Mr values of 137000, 77000, 58000, 53000 and 50000.

Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes.

A precipitating antigen-antibody system has been characterized that occurs in patients with polymyositis. At least half of the patients not only have polymyositis but also have scleroderma. The proposed name for this antigen found in calf thymus extract (CTE) is PM-Scl, to indicate the almost universal presence of polymyositis and the frequent occurrence of scleroderma in the patients who make antibodies to this antigen.

Comparison of various preparations of nuclear antigens by hemagglutination inhibition (HAI).

A clinical laboratory carrying out tests for antinuclear antibodies requires an efficient, reliable preparation method to produce a high yield of nuclear antigens at low cost and a very sensitive, specific assay method for antigen activity. Various tissues were employed for preparation of small nuclear ribonucleoprotein (snRNP) and Sm antigens for these purposes. Fresh calf thymus cells and nuclei, commercially available calf and rabbit thymus acetone powders, fresh rat kidney and liver cells were used as sources of antigens prepared similarly by methods published previously.

Characterization of the autoimmune antigenic determinant for ribonucleoprotein (RNP) antibody.

Small nuclear ribonucleoprotein complexes are antigens in various autoimmune diseases. The serological pattern of high titers of circulating antibody to nuclear ribonucleoprotein (RNP) antigen is a diagnostic marker for mixed connective tissue disease (MCTD); whereas antibody to Sm is prevalent in systemic lupus erythematosus (SLE). Both calf thymus and rabbit thymus are commonly used, excellent sources for preparation of the corresponding antigens RNP and Sm in clinical and research laboratories (A.

Unexpected potentiation of insulin release by the calcium store blocker TMB-8.

Insulin release from rat pancreatic islets, stimulated by cAMP, 3-isobutyl-1-methylxanthine, or forskolin, is potentiated by TMB-8 [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate], a drug that blocks the efflux of calcium from intracellular calcium stores without affecting influx. There is a short latent period before the potentiation occurs which can be reduced by preincubation with the drug. TMB-8 alone neither stimulates nor inhibits insulin release.

Dantrolene and basal ileal sodium and chloride transport: involvement of calcium stores.

The effect of dantrolene on active ion transport in rabbit ileum was determined using the Ussing chamber short-circuiting technique. Dantrolene prevents the release of calcium from intracellular stores in skeletal muscle and was used to probe the role of intracellular calcium stores in intestinal ion transport. A saturated solution of dantrolene (approx 25 microM) decreased ileal short-circuit current and potential difference, increased conductance and mucosal-to-serosal and net Na and Cl fluxes, but did not alter serosal-to-mucosal Na and Cl fluxes.

Cardiovascular manifestations of mixed connective tissue disease in adults.

To assess the nature and distribution of cardiovascular abnormalities associated with mixed connective tissue disease, we studied 38 patients with overlapping clinical manifestations of systemic lupus erythematosus, progressive systemic sclerosis and polymyositis, and circulating antibodies to nuclear ribonucleoprotein. The protocol included taking a medical history and a physical echocardiogram, and pulmonary function tests. Cardiac catheterization was performed on 17 patients.

Effects of forskolin on insulin release and cyclic AMP content in rat pancreatic islets.

The effects of forskolin, a diterpene stimulator of adenylate cyclase, on cyclic AMP content and insulin release, have been studied in rat pancreatic islets. In the presence of 2.8 mM glucose, 0.

Involvement of Ca2+ in the impaired glucose-induced insulin release from islets cultured at low glucose.

Islet culture at a low glucose concentration results in a progressive impairment of glucose-induced insulin release. The role of Ca2+ in this defect was studied by comparing rat islets cultured for 6 days either at 8.3 mM (control) or 2.

Cytochemical studies on the localization of alkaline phosphatase and HCO-3-activated adenosine triphosphatase in the brush border membrane of rat duodenal enterocytes.

Cytochemical techniques were used to demonstrate, with appropriate controls, alkaline phosphatase and HCO-3-activated adenosine triphosphatase (ATPase) in rat duodenal brush border microvillus membranes. Intense activity of ecto-alkaline phosphatase activity was demonstrated with 2-glycerophosphate as substrate. Although biochemical assays suggested that L-phenylalanine inhibited both alkaline phosphatase and HCO-3-activated ATPase, cytochemical studies indicated that there was marked inhibition of alkaline phosphatase revealing a specific HCO-3-activated ATPase on the inner aspect of the microvillus membrane.

Adoptive transfer of experimental autoimmune thyroiditis (EAT) in guinea pigs: requirement for Ia-positive antigen-presenting cells for in vitro activation of effector T cells.

Lymph node T cells from guinea pigs sensitized in vivo with guinea pig thyroglobulin (GPTG) could transfer experimental autoimmune thyroiditis (EAT) to normal syngeneic recipients after in vitro culture with GPTG or GPTG-pulsed peritoneal exudate cells (PEC). Although EAT effector T cells have been shown previously to be Ia negative at the time of transfer, the addition of specific anti-Ia serum to the cultures inhibited effector cell activation. The inhibitory effect of anti-Ia on effector-T-cell activation was shown to be due to inhibition of the function of antigen-presenting PEC rather than to an effect on the sensitized T cell.

Liver disease in mixed connective tissue disease.

Previous descriptions of mixed connective tissue disease (MCTD) have not included evidence of hepatic involvement. A patient who had MCTD also had severe chronic active hepatitis. Retrospective review of all of our cases of MCTD confirms that liver disease is an uncommon occurrence in MCTD.

AI/RHEUM. A consultant system for rheumatology.

A knowledge-based computer consultant system in the medical specialty area of rheumatology is described. The system, called AI/RHEUM, uses artificial intelligence techniques to provide nonrheumatologist physicians with diagnostic assistance in this specialty area. AI/RHEUM contains in a structured knowledge base formal criteria for 26 rheumatologic diseases.