Structural aspects of recognition motifs contributing to autoimmune responses.

Sequence analysis of autoimmune-associated antibodies has suggested a structural relatedness between genes used to encode autoantibodies and those encoding unrelated antibodies without autoreactive specificities. Subsequently, the basis for cross-reactive idiotypes across germ-line lineages, as well as conserved interspecies cross-reactivities of autoantigens among serologically similar antibodies, may result from evolutionary duplication of particular types of recognition motifs. As a first step toward elucidating structural recognition principles underlying possible cross-reactive epitopes involved in autoimmune pathologies, structural features of selected motifs associated with native ligand binding are examined for their inherent occurrence in antibody and T-cell receptor repertoires. This analysis considers the putative recognition features representative of common motif subsets shared with loop structures in CDR2 and FR3 regions of antibodies such as charge-2x-charge-x-charge or hydrogen bond donor (acceptor)-2x-charge-x-hydrogen bond donor (acceptor) type motifs, where x is any residue that can participate in maintaining a loop conformation. Such tracts encoded in the CRD2 and FR3 regions of heavy chains of antibodies and T-cell receptors (TCRs) associated with autoimmune dysfunction, with non-autoreactive antibodies, and with native host proteins. Such evolutionarily conserved motifs may be targets for complementary interactions involving autoantibodies and receptors.     

Kinetics of phenylalanine absorption by the rat intestine in vivo after distal resection

The kinetics of L-phenylalanine absorption across rat small intestine in sham and 50% distal resected animals, in vivo, have been studied by perfusing jejunal loops and monitoring the disappearance of the substrate from the perfusate. After 5 months postresection the total phenylalanine absorption was increased. The relationship between total absorption of substrate and its concentration in the bulk phase shows a non-saturable component and a saturable one that can be inhibited by methionine, both in control and remnant jejunum. The slope of the line that represents the non-saturable component is greater in remnant jejunum, indicating that the apparent mass-transfer coefficient, K'D, was increased by distal resection. The kinetic analysis of the saturable component shows that Jmax was unaltered and the apparent semisaturation constant, K'M, was slightly decreased by distal small intestine resection. Correction of the kinetic constant for the unstirred water layer effects shows that the differences between 'real' KD values of the two experimental groups increase whereas 'real' KM values do not change significantly. This indicates that the observed increase in total intestinal absorption in resected animals appears to result from an increase in the intestinal passive permeability.     

Factors governing the production of juvenile Atlantic salmon in Scottish streams

Data are presented to show how the number and growth of juvenile salmon in streams in the Scottish Highlands are influenced by various physical (temperature, water chemistry, depth and velocity, type of substratum) and biotic (food resources, competition, recruitment) factors.     

Cultured astrocytes from a syncytium after maturation

The formation of functional gap junctions between astrocytes was investigated during differentiation of these cells in culture. Precursor cells of GFA (glial fibrillary acidic) protein-positive astrocytes were cultured in a chemically defined medium as a homogeneous population. These cells were rarely coupled to one neighbour, as revealed by electrical and dye coupling and never formed a large syncytium, as investigated by injection and spread of Lucifer Yellow. Differentiation with respect to GFA protein accumulation can be induced in these cells by culturing in horse serum-containing medium. The formation of functional junctions developed within 2 weeks in about 20% of the cells. Coupled cells formed a large syncytium. When the astrocytes were co-cultured with primary cerebellar cells (consisting predominantly of small neurons) after the switch to serum-containing medium the percentage of coupled astrocytes increased to about 65%. Again the coupled cells formed a large syncytium. Since no physical contact was possible between the astrocyte cultures and the primary cerebellar cells the stimulation of coupling had to be signalized by soluble factor(s).     

Effects of cytochalasin B on Na+ content and cell volume of Entamoeba histolytica

Cells of Entamoeba histolytica accumulated K+ and extruded Na+ compared to the concentrations of those ions present in the growth medium. Pinocytic activity, measured by the uptake of horseradish peroxidase of 125I-polyvinylpyrrolidone, was high (up to 0.3 ml/ml cells per h). Upon addition of cytochalasin B, at a concentration (20 microM) that completely blocked pinocytosis, cells lost up to 40% of their Na+ content within 90 min; K+ content was not affected or increased slightly compared to control cells without the inhibitor. Cation loss was associated with cell shrinkage. The dose-response curves for the effects of cytochalasin B on pinocytosis and Na+ content were identical. These data provide direct evidence that pinocytosis is an important component of the homeostatic system for Na+.     

B cells in patients with X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) has been described as a disorder in which pre-B cells fail to differentiate into B cells. However, a small number of B cells have been seen occasionally in patients with this disorder. Because the phenotype of these cells might be helpful in defining the site of the defect in XLA, immunofluorescent staining techniques were used to characterize the B cells that can be found in patients with XLA. Surface IgM-positive B cells could be detected in the peripheral circulation of all seven patients studied. These B cells constituted a very small percentage of the total lymphocytes (0.01 to 0.3% compared with 3.2 to 13.7% in controls) and differed in phenotype from control B cells. They were much more brightly stained for surface IgM (p less than 0.001) and less brightly stained for Ia (p less than 0.01). This phenotype is similar to that described for immature B cells in the mouse. Over 80% of the patients' B cells expressed surface IgD, and all expressed the B cell marker B1, but only 35% expressed the B cell marker B2. This B cell marker, which is the C3d receptor and the Epstein-Barr virus receptor, is expressed later in ontogeny than B1 and can be detected on over 80% of control B cells. All B cells expressed either kappa or lambda light chain. These findings indicate that the defect in differentiation of pre-B cells into B cells is not absolute in patients with XLA. The immature phenotype of the B cells additionally suggests that there may be a block in the maturation of B cells at more than one stage of differentiation in this disorder.     

Antibiotic sensitivity of the erythromycin-resistant strain E of Rickettsia prowazekii cultured in the vector's body

Experiments on the laboratory cultures of lice infected by Weigl's method revealed that the spontaneous, erythromycin-resistant mutant of R. prowazekii strain E, adapted to the vector's organism, retained its resistance to erythromycin during 50 successive passages without the maintenance concentrations of this antibiotic. The above strain remained sensitive to tetracycline and levomycetin. Its level of sensitivity to the latter antibiotics was similar to that of R. prowazekii strains cultivated in the vector's organism for a long time.     

Oxidised glutathione reductase activity in mouse epidermis: TPA induced change and its modulation by vitamin A

Single cutaneous application of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) increased epidermal oxidised glutathione reductase activity in adult mouse by almost 100%. Pretreatment of animals with vitamin A for a week resulted in 75% inhibition of TPA induced change in the enzyme activity which remained unaffected in skin treated with vitamin A alone. This biochemical change in skin induced by TPA and modulated by vitamin A has been discussed in relation to epidermal hyperplasia.