Effect of interleukin 2 on Kupffer cell activation. Interleukin 2 primes and activates Kupffer cells to suppress hepatocyte protein synthesis in vitro

Interleukin 2 (IL-2) is an essential mediator of the immune response and has also been shown to be protective in experimental models of sepsis. Macrophages have IL-2 receptors but their function is unknown. We investigated the effect of IL-2 on Kupffer cells, the fixed macrophages of the liver, using an in vitro rat hepatocyte-Kupffer cell coculture system. In this model, endotoxin (lipopolysaccharide) triggers Kupffer cells to induce suppression of hepatocyte protein synthesis. We found that pretreatment with 10 U/mL or more of IL-2 primed Kupffer cells, significantly reducing the concentration of lipopolysaccharide necessary to trigger Kupffer cell-mediated suppression of hepatocyte protein synthesis. Higher concentrations of IL-2 (greater than or equal to 1 x 10(4) U/mL) alone were capable of priming and triggering Kupffer cells to suppress hepatocyte protein synthesis. These data show that IL-2 increases Kupffer cell sensitivity to endotoxin, suggesting that IL-2 may play an important role in regulating macrophage responses to septic stimuli.     

Autoimmune reactions in patients with M-component and peripheral neuropathy.

A study of 17 patients with autoimmune axonal or demyelinating peripheral neuropathy in combination with M-component is described. The M-component was associated with MGUS (monoclonal gammopathy of undetermined significance) in 12 patients, CLL in one patient, WaldenstrÖm's disease in one patient, and myeloma in three patients. Immunohistological examination with direct and indirect fluorescence showed binding of antibodies to nerve structures of the same class and light chain as seen in the M-component. In five cases of IgM M-component, the demyelinating neuropathy was caused by binding of the IgM M-protein and complement C3b to myelin-associated glycoproteins (MAG). In 12 cases with axonal neuropathy, binding of IgG to the connective tissue of the peri- and endoneurium was found in 50% of cases, IgM in five cases, and IgD in one case. None of the patients had central nervous system (CNS) symptoms. The clinical and therapeutic difficulties are discussed; only two patients with an acute course responded to immunosuppression. A marked co-expression of other autoimmune phenomena is interpreted in the light of cross-reactions between the autoantibody and similar tissue autoantigens.     

The development of cellular polarity in transport epithelia.

From the above discussion, it can be seen that the establishment of epithelial polarity plays a critical role in mammalian development. Functional and structural transitions in the vectorial processes of epithelial tissues in the developing embryo accompany critical events during development. Pathophysiologic states may arise due to either genetic or acquired abnormalities of polarity. Immaturity of vectorial transport functions frequently accompany the onset of premature birth and result in abnormal function of transport epithelia. Further definition of the molecular mechanisms that lead to the establishment and maintenance of epithelial polarity, as well as the developmental sequence of vectorial transport functions in developing epithelia, will lead to better understanding and treatment of fundamental disease states in the fetus and newborn.     

Distribution and structure of identified tonic and phasic synapses between L-neurones in the locust ocellar tract.

The ultrastructures and distributions of the discrete anatomical synapses which constitute two distinct types of output connections made by individual ocellar L-neurons, L1-3, are described. Outputs to neurones L4-5 are excitatory and transmit tonically, whereas reciprocal connections among the three L1-3 neurones are inhibitory and incapable of transmission for longer than a few milliseconds. The tonically transmitting synapses are located in the lateral ocellar tract and are made between the axons of L1-3, which do not receive inputs, and short branches of L4-5, which make no outputs. Each excitatory connection is composed of a few hundred discrete anatomical synapses, each characterised by a bar-shaped presynaptic density which is 0.15-1.5 microns in length and associated with a large number of round synaptic vesicles. Two postsynaptic profiles are apposed to each presynaptic density. Associated with tonic synapses are abundant invaginations of the presynaptic membrane. Synapses of the reciprocal, inhibitory, phasic connections occur in the protocerebral arbors of L1-3, among numerous output synapses of these neurones. Each phasic connection is composed of a few tens of discrete anatomical synapses. Each bar-shaped presynaptic density is associated with two postsynaptic profiles, and is 0.1-1.0 microns long. Compared with the tonic, excitatory connection, there are fewer vesicles and fewer invaginations of the presynaptic membrane associated with each synapse.     

Relationship between maternal glycaemia and birth weight in glucose-tolerant women from different ethnic groups in New Zealand.

AIM: The aim of this study was to compare the population attributable fraction(PAF) for a large baby (> or =4 kg) due to glycaemia, weight and smoking in glucose-tolerant women from different ethnic groups. METHODS: A retrospective review of screening for gestational diabetes (GDM)and associated birth weight was undertaken in New Zealand European (n= 529), Maori (n= 540) and Pacific (n= 916) women. The proportion with a large baby was compared by 1-h post 50-g glucose challenge test tertile and maternal weight tertile. RESULTS: Large babies were more common from Pacific and European than Maori women (24.3%, 18.8%, 8.9%, respectively; P<0.001). Birth weight increased significantly with increasing glucose among Pacific women (P<0.001) even after adjusting for maternal weight and other confounders. The risk of having a large baby was 2.56 (1.82-3.60)-fold greater in women in the highest maternal weight tertile (> or =84 kg), with a significantly greater PAF in Pacific women(27.2%, 12.9%, 16.4%, respectively; P<0.001). The odds ratio (OR) of having a large baby increased with even mildly elevated maternal 1-h glucose concentrations [OR for 5.6-6.2 mmol/l: 1.54 (1.11-2.14); for > or =6.3 mmol/l: 2.06 (1.50-2.82)], with no ethnic differences in PAF (11.1-11.8%, 16.7-18.7%, respectively). Smoking and being Maori were associated with smaller babies. CONCLUSIONS: Increased maternal weight and glycaemia are associated with a greater proportion of large babies among glucose-tolerant women. Growth of Pacific babies may be more sensitive to a higher maternal glucose when the mother is obese.