Glutamate agonist activity: implications for antipsychotic drug action and schizophrenia.

Antagonist action at dopamine D2 receptors appears to explain many, but not all of the effects of antipsychotic drugs. Because of the interactions of dopamine with glutamate, and the implication of the latter in the etiology of schizophrenia, possible effects of antipsychotic drugs on glutamate receptors were assessed in the present experiments. These studies showed that, at clinically relevant concentrations, the conventional neuroleptic haloperidol and the atypical antipsychotic clozapine had potent augmenting influences on the NMDA receptor.

Intercellular adhesion molecule-1 (ICAM-1) upregulation in human brain tumors as an expression of increased blood-brain barrier permeability.

The distribution of intercellular adhesion molecule (ICAM-1) binding sites was studied in the microvasculature of several types of human brain tumor biopsies (angioma, glioblastoma multiforme and meningioma). Immunoelectron microscopy was performed with the application of immuno-HRP or -gold probes using a pre-embedding technique. Ultrastructural analysis demonstrated a pronounced ICAM-1 upregulation on the luminal EC and/or perivascular surfaces.

Correlations between clinical and neuropathological diagnosis of cortical anomalies in developmentally disabled children.

The capabilities and limitations of clinical diagnoses, particularly brain imaging of cortical anomalies, in developmentally disabled children are reviewed. Some aspects of diagnostic problems in generalized cortical dysgeneses, like lissencephaly type I and II, subcortical heterotopias, generalized polymicrogyria, or focal cortical anomalies and primary micrencephalies, are discussed.

Differential effects of spermine on phosphatidylinositol 3-kinase and phosphatidylinositol phosphate 5-kinase.

The metabolism of phosphoinositides plays an important role in the signal transduction pathways. We report here that naturally occurring polyamines affect the activities of phosphatidylinositol (PI) 3-kinase and PI 4-phosphate (PIP) 5-kinase differently. While polyamines inhibited the PI 3-kinase activity, they stimulated the activity of PIP 5-kinase in the order of spermine > spermidine > putrescine.

Effects of experience on striatal sensory responses.

It has been well documented that striatal neurons encode and process sensory information. It was the aim of the present experiment to determine the extent to which behavioral experience influenced striatal sensory responses. Single units were recorded in the striatum of awake restrained cats as they were adapted to the recording situation.

Characterization of a strain of cerebral endothelial cells derived from goat brain which retain their differentiated traits after long-term passage.

A strain of cerebral endothelial cells was established from isolated cortical microvessels of caprine brain. These cells, which are referred to as EC1 cells, can be routinely subcultured to 32 passages without the loss of differentiated morphologic and immunologic traits. The ability to routinely subculture EC1 cells is an important asset, given that isolated cerebral endothelial cells in mammals generally lose their differentiated traits after only 2 to 3 passages.

Interaction of protein kinase C and phosphoinositides: regulation by polyamines.

Phosphatidylinositol 4,5-bisphosphate (PIP2) activates protein kinase C (PKC) in the presence of phosphatidylserine and calcium. Recently it has been demonstrated that direct interaction of PKC with PIP2 in the absence of divalent cation inactivates this kinase. In the present study, the interaction of natural aliphatic polyamines with phosphoinositides was investigated for its possible relevance to PKC-mediated protein phosphorylation.

Interaction of scrapie agent and cells of the lymphoreticular system.

The current study focused on the role of lymphoid elements of the lymphoreticular system in scrapie pathogenesis. In the first experiment, adherent and non-adherent splenocytes from mice infected with the 139A scrapie strain were prepared. The level of infectivity on a per cell basis was significantly higher in the adherent cell population.

Concentration and distribution of infectivity and PrPSc following partial denaturation of a mouse-adapted and a hamster-adapted scrapie strain.

PrPSc is a specific protein marker for slow infectious diseases known as the transmissible subacute spongiform encephalopathies. Although PrPSc is closely associated with infectivity, it is not known if it is the infectious agent itself, a component of the agent or merely adventitiously associated with infectivity. In the present study we demonstrate that the resistance of PrPSc to partial denaturation and of infectivity to inactivation differs markedly for two scrapie strains.

Magnesium protects phosphatidylinositol-4,5-bisphosphate-mediated inactivation of casein kinase I in erythrocyte membrane.

Recent reports suggest that membrane-bound casein kinase I (MBCK I) activity in erythrocytes is inactivated by exogenously added phosphatidylinositol 4,5-bisphosphate (PIP2) (Bazenet et al. (1990) J. Biol.

Glucose metabolism in mammalian cells as determined by mass isotopomer analysis.

A method using 13C isotopes and GCMS/SIM was developed and was used to study glucose metabolism in several mammalian cell lines. Using [U-13C6]glucose, the 13C isotopomer distributions in glucose, lactic acid, glutamic acid, aspartic acid, and gamma-aminobutyric acid produced by the cells were determined, and glycolysis, gluconeogenesis, and the flux into the amino acid pools were calculated. A 1:1 mixture of [U-13C6]glucose and [1-13C]glucose was used to examine the loss of 1-13C carbon from [1-13C]glucose via the pentose monophosphate pathway in the cells; this new method measures the production of [3-13C]lactic acid and [U-13C3]lactic acid, and thus avoids most systematic errors that result from the endogenous production of 12C-lactic acid during metabolic conversion; in addition, glycolysis and the recycling of glucose and lactic acid can be examined at the same time.

Characterization of proteoglycans in Alzheimer's disease fibroblasts.

Skin fibroblasts lines established from patients with Alzheimer's disease and old normal individuals were cultured with 35S-sodium sulfate and 3H-glucosamine. Proteoglycans were isolated and characterized. Sulfate incorporation into proteoglycans increased in Alzheimer's disease fibroblasts relative to normal controls.

Clozapine's mechanisms of action: non-dopaminergic activity rather than anatomical selectivity.

The mechanisms of clozapine's unusual actions were investigated in anesthetized rats. Sensory field potentials were recorded in the nucleus accumbens, striatum and somatosensory cortex. Both haloperidol and clozapine suppressed responses in the striatum and accumbens.

Protamine induces autophosphorylation of protein kinase C: stimulation of protein kinase C-mediated protamine phosphorylation by histone.

Protein kinase C (PKC), a protein phosphorylating enzyme, is characterized by its need for an acidic phospholipid and for activators such as Ca2+ and diacylglycerol. The substrate commonly used in experiments with PKC is a basic protein, histone III-S, which needs the activators mentioned. However, protamine, a natural basic substrate for PKC, does not require the presence of cofactor/activator.

Variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep.

Ten mouse-passaged scrapie lines were initiated from five sheep with clinical scrapie. Of the lines, five were initiated and passaged exclusively in mice with the s7s7 genotype and the remaining five lines were initiated in mice with the p7p7 genotype, with two of these lines subsequently being passaged exclusively in p7p7 mice and two being passaged mainly in p7p7 mice. Lines were passaged three or four times and two parameters were compared: incubation period and the induction of a weight increase during the preclinical period.

Cloning the ends of size selected Sfi I fragments.

As an initial step in the physical mapping of the fragile X region a library of Sfi I ends was constructed from the size class of human Sfi I DNA fragments, which includes the fragment with the locus DXS105. Since Sfi I recognizes the sequence GGCCNNNNNGGCC and leaves a 3 base indeterminate "sticky" end, we used a mixture of 64 synthetic deoxynucleotide oligomers to modify these ends for cloning. The oligomers were of the general form AATTNNN.

Expression of human Alzheimer amyloid precursor protein in insect cells.

The amyloid beta-peptide is a major constituent of amyloid deposited in the brains of patients with Alzheimer's disease and is derived from a larger precursor protein/s (APP-695, 751, 770). A human cDNA encoding full-length APP-751 was inserted into the genome of Autographa californica nuclear polyhedrosis virus under transcriptional regulation of the viral polyhedrin gene promoter. The recombinant virus was used to infect insect cells, which resulted in the abundant expression of APP-751.

Reassessment of a new model of complete cerebral ischemia in rats. Method of induction of clinical death, pathophysiology and cerebrovascular pathology.

The present study was undertaken to ascertain the role of the microcirculation in the phenomenon of hypoperfusion following complete cerebral ischemia. The experiments were performed on rats under superficial ether anesthesia. Cerebral ischemia was induced by cardiac arrest for 3.

Specific motor abilities associated with speech fluency in Down's syndrome.

Eight adult male stutterers with Down's syndrome (DS) were compared with a matched group of fluent speakers with DS on verbal and manual motor production tasks at two levels of complexity. The simpler tasks involved diadochokinetic rate (syllable repetition) and finger tapping; the more complex tasks involved the imitation of sentences and placing pegs in the grooved pegboard. On both verbal and manual tasks, stutterers were faster on the simpler but slower on the more complex tasks than were the fluent speakers.

Pathogenesis and pathology of scrapie after stereotactic injection of strain 22L in intact and bisected cerebella.

The mechanisms involved in the spread of scrapie within the brain remain unclear. To examine this issue the 22L scrapie strain was injected in one side of the cerebellum of mice in which the cerebellum had been bisected prior to injection. Another group of animals received the same injection into intact cerebella, i.