Inhibitory interactions in neuronal networks including cells of the auditory cortex and the medial geniculate body

The use of the method of cross-correlation analysis has made it possible to identify some specific features of inhibition in neuronal networks including cells from various loci of the auditory cortex (AC) and the medial geniculate body (MGB). It was demonstrated that inhibitory MGB (AC) neurons possess “convergent” properties which are manifested in the fact that one neuron simultaneously excites cells located in various loci of the AC and MGB, and “divergent” properties which are manifested in the fact that one and the same neuron may simultaneously inhibit neighboring cells and neurons from one or several AC (MGB) loci. There are short-axon inhibitory neurons in the AC which selectively act on the activity of one neighboring cell. An inhibitory AC neuron may be simultaneously included in the circuit of afferent and backward inhibition. Reciprocal connections between inhibitory MGB neurons were found. Simultaneous afferent inhibition of remote AC cells may lead to synchronization of their activity. The results make it possible to explain deviations from the principle of tonotopic organization in the AC and MGB. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 6, pp. 1046–1058, November–December, 1994.     

The Involvement of Dopamine in Strengthening Cortical Signals Activating NMDA Receptors in the Striatum (a hypothetical mechanism)

A possible mechanism is proposed for the enhancement/weakening of those cortical signals in the cortex-basal ganglia-thalamus-cortex neural network which induce/do not induce opening of NMDA channels in the spiny neurons of the striatum and which can be regarded as strong/weak in terms of this measure. The mechanism is based on the modulatory influences of dopamine on changes in the efficiency of corticostriatal inputs. In the absence of dopamine, relative increases in the intensity of strong (weak) cortical signals can lead to the induction of long-term potentiation (depression) of corticostriatal synapses. In this case, because of the differently directed influences on thalamic cells of signals passing via strionigral and striopallidal cells, strong signals at the output of the thalamus are weakened, while weak signals are strengthened. Activation of dopamine D₁ (D₂) receptors on strionigral (striopallidal) neurons may facilitate increases in the extent of long-term potentiation/depression (decreases in the extent of long-term potentiation/depression or induction of long-term potentiation/depression). The consequence of this is that strong signals at the output of the thalamus can be strengthened synergistically, while weak signals cab be weakened synergistically. Background cortical signals evoking tonic release of dopamine in the striatum can decrease strengthening because of weakening of the modulatory influence of dopamine on the modification of corticostriatal synapses.     

Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells

Cytokine-induced killer (CIK) cells are non-major histocompatibility complex-restricted cytotoxic cells generated by incubation of peripheral blood lymphocytes with anti-CD3 monoclonal antibody (MoAb), interleukin-2 (IL-2), IL-1, and interferon-gamma. Cells with the greatest effector function in CIK cultures coexpress CD3 and CD56 surface molecules. CIK cell cytotoxicity can be blocked by MoAbs directed against the cell surface protein leukocyte function associated antigen-1 but not by anti-CD3 MoAbs. CIK cells undergo release of cytoplasmic cytotoxic granule contents to the extracellular space upon stimulation with anti-CD3 MoAbs or susceptible target cells. Maximal granule release was observed from the CD3+ CD56+ subset of effector cells. The cytoplasmic granule contents are lytic to target cells. Treatment of the effector cells with a cell-permeable analog of cyclic adenosine monophosphate (cAMP) inhibited anti-CD3 MoAb and target cell- induced degranulation and cytotoxicity of CIK cells. The immunosuppressive drugs cyclosporin (CsA) and FK506 inhibited anti-CD3- mediated degranulation, but did not affect cytotoxicity of CIK cells against tumor target cells. In addition, degranulation induced by target cells was unaffected by CsA and FK506. Our results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP- sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be- identified target cell surface molecules.     

Interval between insulin injection and breakfast in diabetes

The relationship between the insulin-breakfast interval, postprandial increase in blood glucose, and glycaemic control was studied in 58 children with diabetes. Patients recorded insulin-breakfast intervals in a home diary over a seven day period, and during a 24 hour period at the weekend provided eight serial capillary dried blood spots for glucose analysis. The highest mean blood glucose value occurred two hours after breakfast and showed a significant correlation with fructosamine concentrations. Weekend insulin-breakfast intervals ranged from 2-30 minutes, with 70% reporting intervals of less than 15 minutes. There was a significant correlation between the weekend insulin-breakfast interval and the after breakfast increase in blood glucose with a mean increment of 0.4 mmol/l in the 30 minute group and 7.2 mmol/l in the 2 minute group. Over the whole study period, children with mean insulin-breakfast intervals of two to 12 minutes had a mean fructosamine concentration of 376 mumol/l compared with 341 mumol/l in those with intervals of 15-35 minutes. This study has shown that the interval between insulin injection and breakfast significantly influences the morning postprandial rise in blood glucose and consequently short term glycaemic control. It is therefore important that patients are encouraged to leave an interval of about 30 minutes between insulin injection and breakfast.     

Socio-demographic factors and self-reported funtional status: the significance of social support

Background  

The aim of the present work was to investigate the relative importance of socio-demographic and physical health status factors for subjective functioning, as well as to examine the role of social support.     

In vitro and in vivo activity of murine lymphokine-activated killer cells after cryopreservation

The in vitro and in vivo effects of cryopreservation on the cytotoxic activity of murine lymphokine-activated killer (LAK) cells were studied. LAK cells were generated by incubation of spleen lymphocytes of BALB/c mice for 3 days with recombinant interleukin-2 (rIL-2) and subsequent cryopreservation. Cytotoxicity was determined in a 51Cr release assay. After thawing, cytotoxic activity was reduced (40.4% 51Cr release at an effector:target cell ratio of 40:1 as compared to 68.5% 51Cr release before freezing) and could be restored to precryopreserved levels by reincubation with rIL-2 for 2 days after thawing (78.8% 51Cr release). These cells were then tested in BALB/c mice injected with RAW 112 cells, a pre-B-cell lymphoma line. The results demonstrate that the survival rate of mice injected with cryopreserved and restimulated LAK cells (50% survival greater than 180 days after injection) did not differ significantly from that of mice injected with fresh unfrozen LAK cells (60% survival greater than 120 days, 50% survival greater than 180 days). Cryopreserved LAK cells have potential use in adoptive immunotherapy.