Modulation of the Mesolimbic Dopamine System by Glutamate

Glutamate has been shown to modulate motor behavior, probably via N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that are involved in the control of the mesolimbic dopamine (DA) system, that is, the ventral tegmental area (VTA)-nucleus accumbens (NAC). In the present study, we investigated the effects of uncompetitive (MK-801) and competitive [DL-2-amino-5-phosphonopentanoic acid (AP-5), CGP 40116] NMDA receptor antagonists and NMDA and AMPA on DA release in the mesolimbic system and on motor behavior. Systemic injection and intrategmental infusion of MK-801 increased DA levels in the VTA, but the systemic administration enhanced DA exclusively in the NAC and increased motor behavior. In contrast, intrategmental infusion of AP-5, but not the systemic administration of its lipophilic analogue CGP 40116, decreased the DA release in the two regions without affecting motor behavior. NMDA and AMPA infusion into the VTA increased DA levels in both areas. This increase was accompanied by a strong motor behavioral stimulation after NMDA but only a moderate increase after AMPA infusion. The present results indicate that mesolimbic DA neurons are controlled by the glutamatergic system and that the effects of uncompetitive and competitive NMDA receptor antagonists on DA release are mediated by an interaction with different brain areas. These findings may account for the different effects of NMDA receptor ligands on motor behavior.     

Ligands of the NMDA receptor-associated glycine recognition site and motor behavior

Summary Motor behavior critically depends on glutamatergic functions in the basal ganglia (BG). The dorsal and ventral striatum — the main input structures of the BG - are involved in modulation of stereotyped sniffing behavior, locomotion, catalepsy and prepulse inhibition. The effects of the NMDA receptor have been well characterized in respect to motor behavior in the past. The function of the allosteric glycine site was however disregarded until now, because brain penetrating ligands were missing. The present study summarized the motor behavioral profile of several glycine site ligands (7chlorokynurenate, ACEA 1021, MRZ-2/576, (+) HA-966, D-cycloserine and felbamate). It is shown that through blockade of the glycine site of the NMDA receptor a distinct behavioral profile can be obtained.     

Extreme decrease of linoleic acid in renal medulla from rats after a diet supplemented with cod liver oil

Spontaneously hypertensive (SHR) and normotensive rats were fed a diet supplemented with linseed oil or cod liver oil for 22 weeks. The most remarkable finding was an extreme fall of linoleic acid in lipids from renal medulla after cod liver oil supplementation. In free fatty acids (FFA) eicosatrienoic acid (C2): 3n-9) appeared increased as a sign of essential fatty acid (EFA) deficiency.     

Immunoenzymatic assessment of interferon-gamma in Hodgkin and Sternberg-Reed cells

The typical histological picture seen in Hodgkin's disease is consistent with the release of cytokines and other active mediators by the malignant cells, i.e., Hodgkin and Sternberg-Reed cells. Since interferon-gamma is regarded as an important regulator of the cytokine cascade, we have undertaken an immunohistological assessment of this mediator in Hodgkin's disease tissue biopsies. In approximately 50% of the cases investigated we found Hodgkin and Sternberg-Reed cells to be positive with antibodies against interferon-gamma. These in situ findings were substantiated by immunostaining of Hodgkin's disease-derived cell lines L428 and L540. L540 was consistently positive, whereas L428 was negative. It is noteworthy that L428 exhibit a B-cell pheno- and genotype, whereas L540 is of T-cell origin. These data are consistent with theories that propose that cytokine production by tumour cells is central to the pathogenesis of Hodgkin's lymphoma.     

The new and reproducible Papanicolaou stain. Morphologic and spectrophotometric observations on the influence of stain composition on staining results

The morphologic and spectroscopic characteristics of a new and reproducible modification of the Papanicolaou stain are briefly described. The main features of this modification are (1) replacement of the natural dye hematoxylin by the synthetic and chemically well defined dye thionin, (2) introduction of an alcoholic counterstain consisting of eosin gamma and fast green FCF only and (3) employment of alcoholic solutions only. The absorption characteristics of hematoxylin and thionin bound to chromatin are influenced by the cytoplasmic counterstaining, especially by the two green dyes, the absorption peaks of which are close to those of the nuclear stains. The implications of these results for visual and automated cytologic diagnosis are briefly discussed.     

Indirect selection of bacterial plasmids lacking identifiable phenotypic properties.

A procedure is described that uses an indicator plasmid (pSC201) to identify cells in a bacterial population that have been co-transformed with a second plasmid lacking detectable phenotypic properties. Under appropriate conditions of indirect selection, between 50 and 85% of transformants carrying the indicator plasmid also contain the nonselected plasmid. A temperature-sensitive mutation in the replication functions of the indicator plasmid enables its elimination from doubly transformed bacteria. Using this procedure, we have isolated bacteria that carry only the small cryptic plasmid. P15A, of the Escherichia coli strain 15. This genetic element, which contains only 2,300 nucleotide pairs, is thus capable of functioning as a replicon independently of the two larger plasmids normally associated with it in E. coli 15 strains (Ikeda, Inuzuka, and Tomizawa, 1970).