Firing activity and postsynaptic properties of morphologically identified neurons of ventral oral pontine reticular nucleus

The ventral part of the oral pontine reticular nucleus (vRPO) is an important region for the generation and maintenance of REM sleep. Firing activity and synaptic response properties of morphologically identified vRPO neurons have been investigated in urethane-anaesthetized cats. Extracellular recordings were performed through recording micropipettes and neurons were extracellularly stained with biocytin. Two types of neurons were identified under spontaneous conditions: type I neurons (77%) are characterized by non-rhythmic firing; type II neurons (23%) display single spikes firing rhythmically at between 7 and 22 Hz. Type I neurons displayed ellipsoid somata with thick dendritic trunks and axons that arose from either the soma or the initial dendritic segment; these axons could not be clearly followed. Type II neurons showed polygonal somata with radial dendrites; their axons branched at a small distance from the soma. Electrical stimulation of the contralateral vRPO elicited responses in both neuron types (57% and 31%, respectively); this effect was blocked by the non-NMDA glutamatergic receptor antagonist CNQX. Electrical stimulation of the PpT evoked orthodromic responses in type I neurons (41%) and inhibited the firing rate of all type II neurons for 50-100 ms. Both effects were blocked by the muscarinic receptor antagonist atropine. The cholinergic agonist, carbachol, increased the firing rate in most type I neurons and inhibited most type II neurons in these animals.The results demonstrated that the activity of vRPO neurons is modulated through the postsynaptic activation exerted by extrinsic afferents on cholinergic and glutamatergic receptors.     

DTNBP1 haplotype influences baseline assessment scores of schizophrenic in-patients

Dysbindin gene (DTNBP1) has been associated with schizophrenia, but literature findings are inconsistent, and further analyses are required. This study is aimed to investigate if a set of DTNBP1 variations might influence clinic psychotic phenotype or treatment response in a sample of 240 Korean schizophrenic in-patients. Four variants have been selected (rs3213207; rs1011313; rs16876759; rs2619522) on the basis of previous findings of association with schizophrenia, bipolar disorder and antidepressant response. Single marker analysis gave marginal results. Haplotype analysis identified a significant association between A–A (rs3213207(A/G), rs1011313(A/G)) haplotype and lower PANSS total and positive scores at baseline (p = 0.01; 0.02) and at discharge (p = 0.008; 0.005). Covariate analysis revealed a more stable significant association between A–A haplotype and baseline scores. These results suggest a protective effect of A–A haplotype on psychotic positive symptoms at baseline.     

Role of cellulosic and noncellulosic membranes in hyperhomocysteinemia and oxidative stress

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.     

Cytogenetic analysis of a mesenchymal hamartoma of the liver

Cytogenetic analysis of a mesenchymal hamartoma of the liver in a 3-year-old child revealed a balanced translocation between chromosomes 15 and 19 as the sole chromosome change.     

Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists.

The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.     

Impairments in spatial generalization of visual skills after V4 and TEO lesions in macaques (Macaca mulatta)

The authors tested the spatial generalization of shape and color discriminations in 2 monkeys, in which 3 visual field quadrants were affected, respectively, by lesions in area V4, TEO, or both areas combined. The fourth quadrant served as a normal control. The monkeys were trained to discriminate stimuli presented in a standard location in each quadrant, followed by tests of discrimination performance in new locations in the same quadrant. In the quadrant affected by the V4 + TEO lesion, the authors found temporary but striking deficits in spatial generalization of shape and color discriminations over small distances, suggesting a contribution of areas V4 and TEO to short-range spatial generalization of visual skills.     

Optimization of multiple spin-echo sequences for 3D polymer gel dosimetry

The overall performance of polymer gel dosimeters for three-dimensional radiation dosimetry is determined by the temporal and spatial stability of the gels, dose sensitivity and image quality with respect to both systematic and stochastic deviations. The dose resolution (D(p)delta) is determined by the dose sensitivity and the signal-to-noise ratio (SNR) in the dose images. The dose sensitivity can be altered by changing the chemical composition of the polymer gel. The SNR is determined by the scanner and the imaging sequence. In the dose verification of conformal radiotherapy treatments the chosen number of slices may reach a number of 10-20. For these experiments, to obtain a sufficient SNR within a reasonable measurement time using a certain MR scanner, the imaging sequence should be optimized. A few other studies have emphasized the importance of optimizing the imaging sequence with respect to dose resolution (D(p)delta) or SNR but do not give quantitative values for the optimal sequence parameters for scanning a polymer gel dosimeter in three dimensions. In this paper, it is proved that a multiple spin-echo sequence is preferable to a single spin-echo sequence. It is also shown that when using a multiple spin-echo sequence it is not the inter-echo time that should be optimized but the number of echoes. An algebraical expression is derived for the dose resolution in terms of sequence parameters. A mathematical formalism and look-up tables are provided that can be used to optimize both a single and a slice-selective multiple spin-echo sequence to acquire a set of dose images at various locations. The use of the optimization protocol is illustrated by some examples. The optimization protocol enables the user to derive the optimal sequence parameters to acquire a set of dose maps obtained by quantitative T2 imaging for each polymer gel dosimeter within the shortest time possible.     

Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV.

The clinical and biochemical observations in a patient with a mild form of Ehlers-Danlos syndrome (EDS) type IV are described. The patient's skin fibroblasts produced markedly diminished amounts of type III collagen. SDS-polyacrylamide gel electrophoresis of collagens produced by cells obtained from other, non-cutaneous tissues showed two forms of collagen alpha 1(III) chains, a normal and a slow migrating, mutant form. Further analysis confirmed that the type III collagen molecules containing mutant alpha chains which were overmodified had a lower thermal stability and were poorly secreted into the extracellular medium. The protein defect was mapped by in situ cyanogen bromide digestion and was located in alpha 1(III) CB9, the C-terminal peptide of the collagen triple helix. This study shows that non-cutaneous connective tissues can be a useful source for the study of type III collagen defects in patients with EDS type IV.