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Effect of a spirocyclic cyclodipeptide derivate of MIF on passive avoidance behavior and amnesia in rats.

Cyclo (1-amino-1-cyclopentane-carbonyl-L-alanyl)-c(Acp-Ala), a derivative of MIF (prolyl-leucyl-glycinamide) affected passive avoidance behavior of rats when administered at different phases of the step-through type of experimental paradigm. c(Acp-Ala) given s.c. or orally in a 1 mg/kg dose increased avoidance latencies not only when administered before, or immediately after the shock trial but also when given before the pretraining trial, i.e. at the first exposure of animals to the experimental situation without shock treatment. The notion is discussed, that it is the influence of c(Acp-Ala) on processing of information received during the pretraining trial that manifests itself in the facilitation of avoidance response. The drug appears to have a long-term action since it was active when given 20 h before the pretraining trial or the shock trial or the test of retention. c(Acp-Ala) when administered immediately after the shock trial, attenuated amnesia in rats induced by electroconvulsive shock (ECS).

Animals↗

Possible role of macrophage glycolipids as receptors for migration inhibitory factor (MIF).

Guinea pig peritoneal exudate cells incubated with water soluble glycolipids obtained from macrophages show an enhanced response to migration inhibitory factor. Incorporation of these glycolipids into liposomes greatly facilitates their interaction with indicator cells. Enhancement of peritoneal exudate cell responsiveness to migration inhibitory factor was specific for glycolipids from guinea pig macrophages. Glycolipids extracted from guinea pig brain and polymorphonuclear leukocytes as well as several bovine and porcine glycolipids had no effect. Specificity of enhancement was not due merely to a preferential association of macrophage glycolipids with indicator cells. The possible role of macrophage glycolipids as receptors for MIF is discussed.

Animals↗

Functional activation of immune lymphocytes by antigenic stimulation in cell-mediated immunity. IV. Role of macrophage and its soluble factor in antigen-induced MIF production of immune T lymphocytes.

Histocompatibility-linked restriction of macrophage-T lymphocyte interaction in antigen-induced MIF production by sensitized lymphocytes was examined, by using combinations of inbred strain 2, strain 13, and JY-1 guinea pigs. The effective interaction of the antigen-bearing macrophages with the immune T lymphocytes was observed when the donor of the antigen-bearing macrophages and that of the immune lymphocytes shared Ia antigens of the major histocompatibility complex. Identities of B antigens and S antigens were not important for this cooperation. It was further demonstrated that the previously reported soluble factor derived from LPS-stimulated peritoneal adherent cells (macrophages) could help antigenic activation of the immune lymphocytes across the strain barrier provided a small number of macrophages (0.01%) from syngeneic strain were present. These results show that the presence of macrophages is absolutely required to present antigen to immune T lymphocytes in a genetically restricted manner and the soluble factor from macrophages appears to give a nonspecific effect on the lymphocyte activation in addition to or in collaboration with antigenic stimulation.

Animals↗

[Infusion therapy with mif (melanocyte inhibiting factor) in Parkinson's disease (author's transl)].

On the basis of reports in the literature and of our own clinical experience it appears that melanocyte inhibiting factor (MIF) is a very promising therapeutic agent in the management of Parkinson's disease. Besides theoretical considerations relating to biochemical and pathophysiological spheres, the question of the current dosage for clinical usage seems to be of the utmost importance. We are of the opinion that the currently-employed dosage of 400 mg daily is still too low. Hence, the present investigation will be continued with a view to establishing the optimum dosage for maximal therapeutic effect.

Aged↗

Partial purification and chemical characterization of macrophage cytotoxicity factor (MCF, MAF) and its separation from migration inhibitory factor (MIF).

Macrophage cytotoxicity factor (MCF) was purified in 3 consecutive steps including adsorption chromatography on Matrex Gel Red A, hydrophobic chromatography on phenylalanine-Sepharose, and isoelectric focusing. MCF was characterized as a protein with a m.w. of approximately 30,000 by gel filtration on Sephadex G-100 with 2 isoelectric points at 7.4 and 8.4 in the presence of urea. The unpurified supernatant was fairly stable provided that manipulations favoring adsorption to membrane materials used for dialysis or ultrafiltration were omitted. The partially purified preparation was highly unstable. Trypsin treatment did not affect MCF activity, whereas chymotrypsin destroyed it. Treatment with glycosidases and neuraminidase or cultivation of cells in the presence of 2-deoxy-D-glucose or tunicamycin did not impair the MCF activity. MCF was separated from migration inhibitory factor (MIF) by 2 methods: first, isoelectric focusing in the presence of urea, and second by gel filtration on Ultrogel. MCF could be separated from interferon by chromatography on poly(I)-Sepharose.

Animals↗

Production of leucocyte inhibitory factor (LIF) and macrophage inhibitory factor (MIF) by PHA-stimulated lymphocytes.

Supernatants from human mononuclear cells cultured with PHA inhibited the migration of both human polymorphonuclear leucocytes and guinea-pig peritoneal exudate cells, but not human mononuclear cells. Using ultrafiltration it was shown that these supernatants contained two inhibiting factors, the one with a molecular weight of 15,000-50,000 inhibited only guinea-pig peritoneal exudate cells (MIF), whereas the fraction containing molecules of a size between 50,000 and 75,000 specifically inhibited the migration of polymorphonuclear leucocytes (LIF). The polymorphonuclear leucocyte inhibiting activity was heat labile. It is suggested that the leucocyte migration inhibition test is dependent upon the production of a lymphokine (LIF) which acts specifically on polymorphonuclear leucocytes causing their inhibition of migration.

Animals↗

Melanization stimulating factor (MSF) and melanization inhibiting factor (MIF) in the integument of fish.

The present studies were directed to demonstrate that adult fish skin contains putative factors that affect chromatophore and/or chromatoblast function. This hypothesis is based upon the possibility that hypo and/or hyperpigmented areas of the skin are so pigmented because of the localized expression of intrinsic factors that are either stimulatory or inhibitory to the differentiation of specific pigment cell types. In all the morphological and biochemical experiments carried out, we used culture media conditioned by dorsal (DCM) or ventral (VCM) skin from different species of fish. Both DCM and VCM were capable of stimulating differentiation of melanophores in neural crest explants. While the stimulation of melanization is an activity present in both dorsal and ventral skin, an inhibitory activity is also present in ventral skin at such a concentration that it overrides the stimulatory activity afforded by DCM. With biochemical assays, we demonstrated that the three important sequential enzymatic steps in melanogenesis are all stimulated by the conditioned media in a dose-dependent manner and this results in an increase in the amount of melanin present in cultured cells. The results of our investigations provide strong evidence that there are intrinsic pigment cell regulatory factors in the integument of fish, the inhibitory activity being stronger in the ventrum, and that those factors strongly influence, perhaps even determine, the pigment patterns of fish.

Animals↗

The macrophage migration inhibition (MIF) assay as a marker of colorectal cancer. Studies in patients with colorectal cancer, noncolonic neoplasms, and conditions predisposing to colorectal cancer.

A specific macrophage migration inhibition assay, using patient lymphocytes incubated with a human colonic cancer extract, was studied in 92 patients with proven colorectal cancer and in 134 other individuals (20 normal controls, 80 patients with various nonmalignant gastrointestinal diseases, and 34 patients with extracolonic malignancies). A positive response was obtained in 78 of 92 colorectal cancer patients, but in none of the 20 normal controls. A positive response occurred in four of 34 patients with extracolonic malignancies and in approximately half of patients with colonic adenomas and in one third of patients with ulcerative colitis. The significance of positive results in these patients (with diseases considered premalignant) is unclear, and is being studied further. In patients with previous resection of colorectal cancers, positive responses were frequent during the first year following resection, and rare thereafter. The results suggest that this method may be useful as a clinical marker for colorectal cancer, and warrants further technical refinement and study of specific patient populations.

Antigens, Neoplasm↗