Role of adrenergic structures in regulating the release by the intestines of hemocoagulating compounds into the blood stream

Experiments on cats were made to study the capability of adrenaline, tropaphen and propranolol of influencing the intensity of the release of hemocoagulating compounds and anticoagulants from the intestinal vessels and tissues to the bloodstream (perfusate). Adrenaline was found to increase the coagulative activity of the perfusate, provoking an enhanced release into it of thromboplastin, an analogue of plasma factor V and antiheparin compounds and suppressing the release of antithromboplastins. The blockade of the alpha-adrenoreceptors was accompanied by a dramatic increase of antithromboplastins to the intestinal perfusate, whereas the depression of the activity of beta-adrenergic structures by reduction of the release of tissue thromboplastin inhibitors. It is concluded that regulation of the release of antithromboplastins in the intestine is mediated by the structures similar in their characteristics to alpha- and beta-adrenoreceptors.     

Analogs of oxytocin containing a modified peptide bond

Analogs of deamino-oxytocin and deamino-oxypressin containing a CH2-NH group instead of an amide bond between positions 8 and 9 were synthesized. All tested compounds exhibit significantly lowered biological activities.     

Post-translational heterogeneity of the human vitamin D-binding protein (group-specific component)

The vitamin D-binding protein in human serum (the group-specific component) is an alpha 2-globulin which is genetically polymorphic in all populations studied. Previous work (J. Svasti and B. H. Bowman (1978) J. Biol. Chem. 253, 5188-5194, and J. Svasti, A. Kurosky, A. Bennett, and B. H. Bowman (1979) Biochemistry 18, 1611-1617) has shown that the electrophoretic variations of the proteins controlled by two allelic genes, Gc1 and Gc2, are due to at least three amino acid substitutions between Gc1 and Gc2 (Svasti et al. (1979] and to heterogeneity in the Gc1 phenotype arising from carbohydrate dissimilarities. Gc1 migrates electrophoretically as two protein bands, while Gc2 migrates cathodally as a single band. This study demonstrates a post-translational glycosylation difference occurring in a single area of the Gc1 sequence which accounts for the heterogeneity observed previously. The glycosylation site, a threonine residue, appears to be in a sequence which differs between Gc1 and Gc2. The O-glycosidic bond, which is typical of mucins, is rare in plasma proteins. The cyanogen bromide fragment containing the galactosamine-containing carbohydrate in Gc1 was partially sequenced through 20 residues from the amino terminus. No detectable galactosamine could be found in the homologous cyanogen bromide fragment in Gc2. A new purification procedure for the vitamin D-binding protein in human plasma has been developed. Three chromatographic steps provide purified protein.     

Rare syndromes. The Kaufman-McKusick syndrome. A review of the 44 cases reported in the literature

The Kaufman-McKusick syndrome (MK 23670) is a rare autosomal recessive disorder characterized by the triad of hydrometrocolpos, postaxial polydactyly, and congenital heart disease. Multiple other anomalies have been ascribed to this syndrome. Hydrometrocolpos, especially if unrecognized, may be a serious, life-threatening condition in the newborn girl. Forty-four cases have been so far reported in the literature. A great phenotypic variability occurs in this syndrome, therefore making it very difficult to identify the disorder at its presentation and classify it correctly. We shall hereafter review current data regarding the prominent clinical features, the diagnosis and treatment of this syndrome. Problems in genetic counseling will be discussed.     

Tolerance induction by the peroral administration of protein antigens

The possibility of inducing systemic tolerance in animals by feeding them with ovalbumin and human serum was studied on mice, rats and rabbits. Antibodies to ovalbumin, human serum albumin and immunoglobulins (IgG, IgA, IgM) were determined by the passive hemagglutination test in the sera of the test and control animals after the second immunization made through a parenteral route. Tolerance to all the antigens under study was obtained in mice and rats, while in rabbits such feeding was found to produce the priming effect. The degree of tolerance was the greater, the more was the dose of the antigen and the longer was the period of feeding. Different proteins showed varying tolerogenic activity; the same degree of tolerance in mice was obtained by feeding them with IgG in a dose of 0.3-0.5 mg and with ovalbumin or human serum albumin in a dose of 6-12 mg (per gram of body weight). Tolerance was determined on day 3 after the course of feeding was over; in 3 weeks tolerance essentially decreased, and in 1.5-2 months it was replaced by normal reactiveness. Tolerance induced by the oral administration of antigens proved to be immunologically specific.     

Physiological assay of liposome-mediated transport of a drug across Xenopus intestine: cell-liposome interaction

(1) The antagonistic effect of atropine methyl bromide entrapped in liposomes on contraction of Xenopus intestine in vitro induced by acetylcholine was studied. The results provided some insight into cell-liposome interaction. (2) Acetylcholine (0.1 mM) was added to the medium in the bath (serosal solution), while liposomes containing atropine methyl bromide in their internal and external phases were added on the mucosal side of the intestine. Large multilamellar liposomes were prepared from egg lecithin (phosphatidylcholine, PC) and cholesterol in various molar ratios. Atropine methyl bromide had most effect in liposomes composed of PC and cholesterol in a ratio of 7:3, less in those with a ratio of 4:5, and none in those with a ratio of 9:1. These effects were parallel with the sizes of these liposomes, determined by quasi-elastic light-scattering; that is, the larger the liposomes, the greater was their effect. Addition (to the liposomes) of phosphatidic acid, the negative charge of which increases the distance between the lamellar layers, increased the effect, indicating that atropine methyl bromide in the space between lamellar layers was effective. Another type of liposomes in which atropine methyl bromide was present only in the external phase of liposomes was as effective as liposomes in which atropine methyl bromide was present in both the internal and external phases. (3) From these results the following new model for liposome-mediated stimulation of transport of atropine methyl bromide is proposed. Large multilamellar liposomes have structural defects in their external lamellae through which atropine methyl bromide in the mucosal solution can penetrate into the space between the external lamellar layers and move into intestinal cells through regions of fusion between the outermost layers of the liposomes and the cell membrane.     

Mutual recognition between polymerized liposomes. IV. Polysaccharide-lectin system.

As a model of cell-cell recognition processes, the association processes of a polysaccharide (mannan)-carrying liposome with a lectin (Concanavalin A, Con A)-carrying polymerized liposome were followed by turbidimetry. The association process was strongly inhibited by the addition of a low molecular weight sugar, methyl-alpha-D-mannopyranoside, which shows that the association between the liposomes is due to the specific interaction between Con A and mannan. The association rate constant obtained was much smaller than the theoretical value for a diffusion-controlled binary association process. This implies that the association rate of liposomes is limited by the recognition between complementary ligands bound on the liposome surfaces. Another reason for the smaller association rate constant in the liposome-liposome system is the repulsive hydration effect. The effect of the surface density of the lectin immobilized on the liposome on the recognition was also examined.