Insulin-dependent diabetes, an autoimmune disease

In type I (insulin-dependent) diabetes evidence for an autoimmune process is now fully established. This is also true for a similar disease observed in the NOD mouse and the BB rat. In addition to circulating antipancreatic antibodies, we demonstrated T-lymphocyte mediated cellular immunity in both these diabetic animals and in the human. Immunological abnormalities precede the development of diabetes and may be responsible for beta cell alteration. Evidence for this interpretation appears stronger for cell-mediated than for humoral immunity. However, full demonstration and understanding of the relationship between anti-beta cell immunity and beta cell alteration still raise many unresolved problems.     

Glycopeptides in soluble egg antigen of Schistosoma mansoni: isolation, characterization, and elucidation of their immunochemical and immunopathological relation to the major egg glycoprotein (MEG)

The major egg glycoprotein (MEG) of Schistosoma mansoni was purified by ion-exchange chromatography of glycoprotein fraction obtained from soluble egg antigen (SEA) by lectin affinity chromatography. Small carbohydrate-rich fragments (CRF) contained in the glycoprotein fraction of SEA were isolated by ultrafiltration followed by dialysis (10 to 13 kd). Comparison of MEG and CRF yielded the following results: purified MEG (70 kd) contains about 77% carbohydrate, and CRF contains 92.5% carbohydrate. When radioiodinated and run by SDS-PAGE, each yielded a single band with respective Rf values of around 0.33 and 1.0 CRF is capable of inhibiting, in a Farr-type RIA, the binding of 125I-MEG to serum from chronically infected mice. Furthermore, CRF and MEG exhibit a single and continuous line of radioimmunodiffusion. CRF, unlike SEA, SEA glycoproteins, or purified MEG, is incapable of eliciting delayed footpad swelling in egg-sensitized mice or of inducing granulomatous hypersensitivity, when given at amounts equivalent to or higher than MEG by protein or carbohydrate content. Thus, whereas SEA, SEA glycoproteins, or MEG elicited in a representative test net swelling of 0.28 mm, 0.34 mm, and 0.29 mm, respectively, CRF gave net swellings of 0.06 mm, similar to the control value (0.07 mm) in unsensitized mice. Also, mice sensitized to viable eggs, SEA, or purified MEG exhibited, after i.v. challenge with viable eggs, a mean area of granulomas in the lungs of 12,389 micron2, 16,412 micron2, and 12,354 micron2, respectively, as compared with 7940 micron2 in CRF-sensitized mice and 8428 micron2 in unsensitized control mice. Thus, CRF appears to contain fragments of MEG that are serologically active but immunopathologically inactive at the concentrations used.     

Schistosoma mansoni: radiometric assay of lectin binding specificities of the major egg glycoprotein and its carbohydrate-rich fragment

The binding by lectins of the Schistosoma mansoni major egg glycoprotein and of a carbohydrate-rich fragment which is serologically cross-reactive with it was studied. The major egg glycoprotein was purified from a crude soluble egg antigen by a succession of affinity chromatography procedures on concanavalin A-sepharose and by ion-exchange chromatography. The carbohydrate-rich fragment was isolated by ultrafiltration of the crude glycoprotein fraction initially obtained from the crude soluble egg antigens. The major egg glycoprotein and the carbohydrate-rich fragment contain 77 and 92.5% carbohydrate, respectively. When radioiodinated and run on SDS-polyacrylamide gel electrophoresis, each of them exhibited a single peak with respective Rf values of 0.33 and 1.0, and their respective molecular weights were 70K and 10-13K. The binding of the radioiodinated major egg glycoprotein and the carbohydrate-rich fragment by peanut agglutinin, Ricinus communis agglutinin-60, wheat germ agglutinin, and lotus agglutinin was studied by double diffusion in agar, and by a radiometric solid-phase assay in which the lectins were used to coat microtiter plates. The latter assay was employed to determine the specificity of the binding by inhibition with the specific sugars. Both the major egg glycoprotein and the carbohydrate-rich fragment bound specifically to concanavalin A columns as indicated by their isolation procedure. They also bound specifically to peanut agglutinin, R. communis agglutinin 60, and lotus agglutinin, while binding by wheat germ agglutinin appeared not to be specific.(ABSTRACT TRUNCATED AT 250 WORDS)     

Energy metabolism of Chironomus anthracinus (Diptera: Chironomidae) from the profundal zone of Lake Esrom,Denmark, as a function of body size,temperature and oxygen concentration

The profundal zone of Lake Esrom, Denmark has a dense population of Chironomus anthracinus, which survives 2–4 months of oxygen depletion each summer during stratification. The metabolism of 3rd and 4th instar larvae was examined in regard to variation in biomass and temperature. Respiration at air saturation was described by a curvilinear multiple regression relating oxygen consumption to individual AFDW and temperature. At 10 °C and varying oxygen regimes the O₂ consumption and CO₂ production of 4th instar larvae were almost unaltered from saturation to about 3 mg O₂ l^–1, but decreased steeply below this level. The respiratory quotient increased from 0.82 at saturation to about 3.4 at oxygen concentrations near 0.5 mg O₂ l^–1. This implied a shift from aerobic to partially anaerobic metabolism. At 0.5 mg O₂ l^–1 the total energy production equalled 20% of the rate at saturation of which more than one third was accounted for by anaerobic degradation of glycogen. This corresponded to a daily loss of 12 µg mg AFDW^–1 or approximately 5% of the body reserves. At unchanged metabolic rate the glycogen store would last three weeks, but long term oxygen deficiency causes a further suppression of the energy metabolism in C. anthracinus.     

The nature of cells generating human myeloma colonies in vitro.

Freshly explanted human myeloma cells formed colonies of monoclonal plasma cells in soft agar in the presence of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. The medium showed peak activity at a dilution of 1:4. 2-mercaptoethanol or monothioglycerol was necessary for colony formation. Other thiols tested were ineffective in promoting colony growth. Colony-forming cells adhered to nylon wool, but not glass beads or plastic dishes. The presence of E-rosetting cells was not required for myeloma colony formation. Antibody prepared against a human myeloma cell line, RPMI 8226, reduced colony formation. These studies demonstrate the usefulness of this bioassay for determining functional properties of the myeloma colony-forming cell.