Properties of antibodies cytophilic for macrophages.

Cytophilic activity for macrophages was shown to be a property possessed by most, if not all, of the complement binding 7S gamma(2)-population of guinea pig antibodies. Cytophilic antibodies were also demonstrated in rabbit and mouse antisera to sheep red cells. While each species antibody best sensitized homologous macrophages, cross species sensitization was also observed. The binding site for macrophages resides on the Fc fragment, therefore, on the H chains, and is destroyed by pepsin hydrolysis or reduction and alkylation. The binding reaction is reversible with a high rate of dissociation at 37 degrees C. Cytophilic activity is not complement dependent, and was shown to be that property of opsonizing antibody which provides the receptors that permit the binding of the antibody to the macrophage cell membrane in preparation for phagocytosis.

ROPs in the spotlight of plant signal transduction.

Small guanine nucleotide binding proteins of the Rho family called ROP play a crucial role as regulators of signal transduction in plants. They participate in pathways that influence growth and development, and the adaptation of plants to various environmental situations. As members of the Ras superfamily, ROPs function as molecular switches cycling between a GDP-bound 'off' and a GTP-bound 'on' state in a strictly regulated manner. Latest research provided fascinating new insights into ROP regulation by novel guanine nucleotide exchange factors, unconventional GTPase activating proteins, and guanine nucleotide dissociation inhibitors, which apparently organize localized ROP activation. Important progress has also been made concerning signaling components upstream and downstream of the ROP cycle involving receptor-like serine/threonine kinases and effectors that can manipulate cytoskeletal dynamics, intracellular calcium levels, H2O2 production and further cellular targets. This review outlines the fast developing knowledge on ROP GTPases highlighting their specific features, regulation and roles in a cellular signaling context.

Case for adoptive immunotherapy in cancer.

Patients with normal immune systems may be unable to mount effective defences against solid tumours because of (1) the generation of suppressor T cells in the low zone tolerance response elicited by the low concentrations of antigen furnished by slow growing solid tumours; (2) the ineffectiveness of the cytolytic T-cell response when the tumour cell membrane lacks the major histocompatibility gene products required for linkage to tumour antigens; and (3) the hindrance of antibody-dependent cellular cytotoxicity by antitumour antibodies when the precise requirements for the reaction cannot be fulfilled in the sites occupied by solid tumours. Recent immunological advances suggest that it should be possible to isolate antigens from cancer cells, produce antibodies against these antigens, bind the antibodies to the patient's macrophages and K lymphocytes, and reinject the bound cells into the patients to stimulate lymphokine synthesis and antibody-dependent cellular cytoxicity.

High-frequency low-dose multiple-drug chemotherapy in advanced metastatic breast cancer.

A small group of patients (22) with metastatic breast cancer, most of whom had advanced visceral disease, have been treated since 1973 with low-dose, multiple-drug chemotherapy: vinblastine, 0.05 mg/kg, I.V.; cyclophosphamide, 6 mg/kg P.O.; 5-fluorouracil, 500 mg. P.O., and methotrexate, 0.3 mg/kg P.O. The schedule includes the use of one drug on each of four days every week. The drugs were taken in the sequence listed on alternate days, except that dosages of methotrexate and vinblastine were consecutive. The remission rate was 68% (15/22). The median duration of remission was 30 months. The median survival time of responding patients exceeds 40 months. Of the 15 responding patients, six (40%) remain alive with a mean survival time of more than 46 months. The regimen causes minimal toxicity and has been willingly accepted by patients for as long a period as 54 months. A therapeutic advantage appears to have been achieved by this high-frequency, low-dose schedule.

Molecular and catalytic properties of Arabidopsis thaliana adenylyl sulfate (APS)-kinase.

A cDNA clone (Atakn1) from Arabidopsis thaliana encoding APS-kinase (EC 2.7.1.25) was investigated for structural and catalytic properties of the gene product. Recombinant his10-AtAkn1 formed PAPS at a Vmax of 7.35 U x mg(-1). The Km for APS was 0.14 microM and for ATP 147 microM. APS caused a severe substrate inhibition (K(i) 4.5 microM). The type of inhibition is uncompetitive with respect to MgATP. High ionic strength and reducing thiols stabilized the enzyme activity. Plant APS-kinase is regulated in vitro by the redox charge with thioredoxin as essential activator. Mutagenesis of a serine in S182C and S182F presumed to be involved in the transfer of the phosphoryl group had no effect upon catalytic activity. Using a yeast two-hybrid system with AtAkn1 as bait, an interacting clone was detected from a cDNA library of A. thaliana cv. Columbia that codes for an APS-kinase iso-form (Atakn2). Complementation of APS-kinase-deficient Saccharomyces cerevisiae met14 showed that AtAkn2 is functionally active as APS-kinase. It was immunologically related to AtAkn1 and presumably represents a plastidal iso-form of the plant APS-kinase gene family.