In order to establish which neurotransmitters may influence the activity of zona incerta neurones in the sheep which respond selectively to the sight or ingestion of food, we have measured the release of amino acid and monoamine neurotransmitters from this region using microdialysis sampling. Co-ordinates for the placement of microdialysis probes in regions of the zona incerta where cells respond to the sight or ingestion of food were first established by making single-unit extracellular recordings. When animals were food-deprived results showed that release of gamma-aminobutyric acid (GABA) was increased in response to the sight and ingestion of food but not of aspartate, glutamate, taurine, noradrenaline, dopamine or serotonin. This release of GABA was absent when the animals were shown non-food objects or saw or ingested salt solutions. When the same animals were physiologically sodium-depleted GABA release was evoked by the sight and ingestion of salt solutions and release following the sight and ingestion of food was significantly reduced. These results provide further evidence that GABA is an important neurotransmitter in neural circuits controlling the regulation of food intake.

Transforming growth factor-beta 1 (TGF-beta 1) mediates many immunosuppressive effects on immune cells and can inhibit the production of tumor necrosis factor and interleukin 1 (IL 1). However, TGF-beta 1 can stimulate the production of IL 6 and platelet-derived growth factor, indicating that TGF-beta 1 initiates complex effects on the production of cytokines. In this report we show that treatment of peripheral blood monocytes with TGF-beta 1 leads to the induction of a recently described IL 1 receptor antagonist protein (IRAP). The effect of TGF-beta 1 was both dose and time dependent. TGF-beta 1 induced de novo synthesis of IRAP, as Northern blotting experiments indicated a rapid and transient induction of the mRNA encoding IRAP. The induction of IRAP suggests a potential mechanism by which some of the inhibitory effects of TGF-beta 1 are mediated.

The lipopolysaccharide extract from the cell wall of the reference strain for Serratia marcescens serogroup O18 contained, in addition to a neutral glycan characterised previously, an acidic glycan. Acidity was contributed both by D-glucuronic acid and by 4-O-[(R)-1-carboxyethyl]-D-glucose (4-O-Lac-D-Glc). By using n.m.r. spectroscopy, methylation analysis, and chemical degradations, the repeating unit of the acidic glycan was identified as a branched hexasaccharide having the structure shown; an O-acetyl group also present was not located. The glycan is believed to define the O18 serogroup, but is probably not an integral component of the lipopolysaccharide. [formula: see text].

The effect of monoclonal antibodies (MoAbs) recognizing idiotype, IgM heavy chain, and IgD heavy chain on the in vitro DNA synthesis of five randomly selected leukemic human low-malignancy B-cell lymphomas was investigated. In three lymphomas of different histologic subtype, low concentrations of anti-idiotypic (anti-Id) MoAb completely inhibited spontaneous 3H-thymidine uptake of T-cell-- and monocyte-depleted tumor cells, whereas two other tumors were not affected. Maximal inhibition of DNA synthesis was achieved at MoAb concentrations ranging from 0.5 to 250 micrograms/mL and required crosslinking by bivalent antibody but not Fc-mediated effects. While two anti-IgM MoAbs were similarly efficient as anti-Id MoAb in inhibition of DNA synthesis, two anti-IgD MoAbs had no effect. Thus, surface IgD molecules seemed to be neither able to deliver inhibitory signals themselves nor to antagonize IgM-mediated signals when simultaneously crosslinked by anti-Id MoAb. Leukocyte differentiation antigen expression, IgM density, and IgM/IgD ratio on the surface of lymphoma cells did not distinguish between sensitive and resistant tumors. In vitro tumor cell survival was differently affected by prolonged incubation with anti-Id antibody. In a centrocytic lymphoma and an immunocytoma, but not in a chronic lymphocytic leukemia, suppression of 3H-thymidine uptake persisted after removal of MoAb and tumor cell viability decreased during prolonged incubation with anti-Id MoAb. These results suggest that direct inhibitory signaling via surface IgM may contribute to anti-Id MoAb-mediated tumor regression in certain human B-cell lymphomas.

Lipopolysaccharide was isolated from both phases of an aqueous-phenol extraction of defatted cell walls from the reference strain for Serratia marcescens serogroup 021. The product from the aqueous phase was of the R type, lacking a polymeric side-chain. The polymeric fraction of the lipopolysaccharide from the phenolic phase (the 021 antigen) had a disaccharide repeating-unit with the following structure: ----4)-alpha-D-Glcp-(1----4)-beta-D-ManpNAc-(1----.

A neutral glycan containing L-rhamnose and 2-acetamido-2-deoxy-D-galactose is one of two polymers present in the lipopolysaccharide extract from the reference strain for Serratia marcescens serogroup O23. The glycan, which has the disaccharide repeating-unit shown, shares structural features with polymers from several other O serogroups. ----4)-alpha-L-Rhap-(1----4)-beta-D-GalpNAc-(1----.

Microdialysis sampling was used to measure the release of oxytocin (OXY) and monoamine and amino acid transmitters from the region of the medial preoptic area (MPOA) and the bed nucleus of the stria terminalis (BNST) during parturition and suckling in sheep. Results showed that OXY and gamma-aminobutyric acid release increased in both the MPOA and BNST during parturition and suckling. Noradrenaline (NA) release increased in both structures during parturition but not during suckling. Dopamine (DA) release increased in the MPOA and decreased in the BNST during both parturition and suckling. Aspartate release increased in the MPOA during parturition, and the BNST during suckling, and glutamate release increased in the MPOA and BNST at parturition and only in the BNST during suckling. No changes in the release of serotonin or taurine occurred in these structures during parturition or suckling. In a further experiment on 6 estrogen-primed sheep, OXY (10 micrograms/ml) was infused into the MPOA via bilaterally placed microdialysis probes. This treatment inhibited rejection behavior towards lambs, but did not activate positive maternal responses. These OXY infusions also stimulated release of NA. These results show that complex patterns of neurochemical release occur in two closely related areas of the brain, the BNST and MPOA, during parturition when maternal behavior is stimulated. However, while these patterns of release are similar in the two structures, particularly at birth when maternal behavior is stimulated, they are not identical during labor contractions and suckling. The release of oxytocin within the MPOA during parturition may be important for stimulating a reduction in aggression towards lambs, although this action might be mediated via the effect of OXY on NA release.

In addition to a neutral glycan, lipopolysaccharide extracts from the reference strain for Serratia marcescens serogroup O22 contain an acidic polymer which probably defines the serogroup and is of microcapsular origin. The polymer is doubly branched with a heptasaccharide repeating unit and a galactan backbone. By means of spectroscopic and degradative studies, the structure of the repeating unit was established as that shown. [formula: see text]

Serogroups O2 and O3 of Serratia marcescens are differentiated by acidic glycans present in the aqueous phase when lipopolysaccharides are extracted from the reference strains by the aqueous-phenol method. The phenolic phases of these extracts from both strains also contain lipopolysaccharides, from which the same neutral glycan is released on milk acid hydrolysis. The neutral glycan has the disaccharide repeating-unit shown, and accounts for the cross-reactions between the two serogroups and also with serogroup O21: --> 4)-alpha-D-GlcpNAc-(1-->4)-beta-D-ManpNAc-(1--.