In the present study, we demonstrate that a substituted soluble dextran derivative bearing 73% carboxylic groups and 15% benzylamide sulfonate groups, termed CMDBS25, inhibits complement activation and complement-mediated damage in an in vitro model of xenogeneic rejection. Incubation of porcine aortic endothelial cells with normal human serum resulted in time-dependent complement consumption as assessed by C3a generation in the fluid phase and deposition of activated complement fragments C3, C5 and of C5b-9 on target cells. The presence of C5b-9 membrane attack complex was associated with 51Cr release from prelabelled endothelial cells. The addition of 5-25 mg of CMDBS25/ml under the experimental conditions used, inhibited complement activation and C3a generation in a dose-dependent fashion. CMDBS25 (25 mg/ml) totally suppressed iC3b, C5 and C5b-9 cytolytic complex deposition on cells and inhibits by 42% lysis of target endothelial cells. Native dextran had no effect. Our observations document the anti-complementary properties of sulfonated dextran derivatives and their potential as therapeutic agents for the prevention of complement-dependent hyperacute xenograft rejection.

Animals↗

PubMedDate not supplied

Improved serologic detection of hepatitis C virus with a paramagnetic microparticle assay using multiple antigenic sequences.

A paramagnetic microparticle (MP) assay for antibody to hepatitis C virus (anti-HCV) was developed, in which the probe for antibody consisted of synthetic peptides corresponding to HCV capsid and nonstructural c-100 regions, as well as a recombinant protein corresponding to the nonstructural c33c region. Assay performance was evaluated by testing serum from 108 geographically diverse patients with non-A, non-B hepatitis (NANBH). The frequency of anti-HCV reactivity detected with the MP assay and with an enzyme-linked immunosorbent assay (ELISA) for c-100 was 91 and 70 percent, respectively. All c-100 HCV ELISA-reactive specimens also reacted on the MP assay. In addition, anti-HCV seroconversion in three plasma donors was detected one to two blood collection dates earlier by the MP assay than by the c-100 HCV ELISA and at similar blood collection dates by the MP assay and a second-generation anti-HCV ELISA. Serologic responses to the three distinct antigenic regions of HCV in NANBH patients varied: reactivity to all three antigens was most common (49%), reactivity to both capsid and c33c (40%) was next most common, and single-antigen reactivity was rare (4%). MP assay reactivity of 825 volunteer donors was 0.1 percent. These results demonstrate both the utility of additional HCV antigens for an effective anti-HCV screening assay and the application of paramagnetic MP technology to serologic testing for HCV infection.

Antibody Specificity↗

PubMedDate not supplied

Teaching procedural skills: beyond "see one-do one".

Explore the source record for details and available documents.

Clinical Competence↗

PubMedDate not supplied

Biological approaches to cancer therapy.

Advances in the biological approach to cancer therapy are reviewed. The mechanisms of actions, clinical effects and uses of interferons, the first biological modifiers to be used, are reviewed first. The interleukins and monoclonal antibodies are also mentioned in detail. This review also covers the clinical use and production of lymphokine activated killer cells, which are used in conjunction with interleukin-2. A brief review of tumour infiltrating lymphocytes, which comprise a subset of lymphocytes found within solid tumours is given. In mice, tumour infiltrating lymphocytes have been shown to be more therapeutic than lymphokine activated killer cells. Tumour necrosis factor, a protein released by activated macrophages in response to stimulation by endotoxin, is also briefly mentioned although clinical data are disappointing. Finally, the role which oncogenes may play in cancer therapy and understanding is discussed.

Antibodies, Monoclonal↗

PubMedDate not supplied

Purification and properties of a catechol methyltransferase of the yeast Candida tropicalis.

In an effort to investigate catechol methyltransferase activity in sources other than mammalian tissues and cells, a high level of enzyme activity was found in the yeast fungus Candida tropicalis CBS 94. Partial purification of the enzyme (approx. 550 fold with a recovery of 7%) could be achieved by using ion-exchange and gel filtration techniques. The molecular weight was estimated at 32,000 +/- 2,000 by gel filtration on Sephadex G-100. In isoelectric focusing experiments on Sephadex G-75 the enzyme exhibited a pI-value of 5.0 +/- 0.1. In contrast to catechol methyltransferase from various mammalian tissues the enzyme activity was prepared from the pH 5-sediment. The substrate specifity is comparable to other catechol methyltransferases.

Candida↗

PubMedDate not supplied

Immunological studies of catechol methyltransferase from the yeast Candida tropicalis.

Immunization of rabbits with purified catechol methyltransferase from Candida tropicalis yielded a potent antiserum. Ouchterlony double diffusion analysis showed a single precipitin line. There was no cross reactivity with the catechol methyltransferase from rat and bovine liver. Specific antigen-antibody interaction was demonstrated by a potent inhibitory effect of the antibody on the yeast enzyme. Immunological titration and quantitative precipitin reaction of the enzyme showed that the maximum amount of precipitable complex occurred at the equivalence point where enzyme activity was completely inhibited.

Animals↗