Oxidative metabolism of murine macrophages.

This unit describes two simple and straightforward microassays that can be used to measure the levels of NO(2)(-) and O(2)(-), respectively that are generated by a small number of immunologically-stimulated macrophages. Detection of these products may be used to identify cytokine(s), microbe(s), or microbial products(s) that regulate oxidative metabolism and effector activity. Although a number of other reliable and sensitive methods are available for assaying these two oxidative metabolites, the microassays described here require little time, technical expertise, or materials.

Phase 2 study of T138067-sodium in patients with malignant glioma: Trial of the National Cancer Institute of Canada Clinical Trials Group.

We studied the activity of T138067-sodium in patients with malignant gliomas. T138067-sodium is a unique new chemotherapy agent that inhibits microtubule formation by binding irreversibly and specifically to beta(1), beta(2)and beta(4) isotypes of 3-tubulin, causing cell arrest at G(2)/M and inducing apoptosis. Patients with recurrent anaplastic astrocytoma or glioblastoma multiforme were treated intravenously with 330 mg/m(2) of T138067-sodium weekly.

C5b-7 and C5b-8 precursors of the membrane attack complex (C5b-9) are effective killers of E. coli J5 during serum incubation.

The finding that C9-deficient sera (C9D) can kill serum sensitive strains of Gram-negative bacteria by us and other investigators, questions the role of C9 in the membrane attack complex as necessary for cell death. In these studies we have demonstrated that C5b-8 complexes generated on E. coli J5 during incubation in C9-depleted and C9-neutralized sera are effective in killing Gram-negative bacteria.

Interaction of anti-cholesterol antibodies with human lipoproteins.

Inoculation of mice with cholesterol-rich liposomes containing the adjuvant monophosphoryl lipid A results in the production of antiserum containing IgM Ab to cholesterol. The specificity of the Ab was to cholesterol and structurally similar sterols containing a 3 beta-hydroxyl group. Anti-cholesterol binding activity was significantly diminished if the 3 beta-hydroxyl was altered by either epimerization, substitution, oxidation, or esterification.

Role of atheroma liposomes and malondialdehyde-modified low-density lipoproteins in complement activation.

We investigated the ability of atheroma-associated liposomes and malondialdehyde (MDA)-modified low-density lipoproteins (MDA-LDL) to activate complement. Complement activation markers C3a, Bb, C4d and SC5b-9 were measured in both normal and complement-deficient sera. We found that MDA-LDL was able to generate C3a and SC5b-9, predominantly by the alternative pathway.