Developmental expression of proenkephalin mRNA in rat striatum and in striatal cultures.

Proenkephalin mRNA shows a biphasic developmental profile in rat striatum, with an initial peak at postnatal day 2, a decline to embryonic levels by day 7, and a second increase to adult levels over the course of the second to 4th week after birth. The same 4-fold increase is seen in cultured striatal neurons, over the same time course but without a biphasic response. Cultured fetal glia also contain proenkephalin mRNA.

Insertion of ganglioside GM1 into rat glioma C6 cells renders them susceptible to growth inhibition by the B subunit of cholera toxin.

The B subunit of cholera toxin does not affect the growth of rat glioma C6 cells which are deficient of its receptor, ganglioside GM1. Insertion of ganglioside GM1 into the plasma membrane of C6 cells renders them susceptible to inhibition of DNA synthesis by the B subunit. Exposure of C6 cells to butyrate induces an elevation of ganglioside GM1 as measured by an increase in binding of iodinated cholera toxin and also results in an inhibition of DNA synthesis by the B subunit.

Supersensitivity to a D-1 dopamine receptor agonist and subsensitivity to a D-2 receptor agonist following chronic D-1 receptor blockade.

The effect of chronic D-1 dopamine (DA) receptor blockade on D-1 DA receptors and DA-mediated behaviors was studied in rats with unilateral, quinolinic acid-induced striatal lesions. Administration of the selective D-1 antagonist SCH 23390 for 15 days increased D-1 receptor numbers in the unlesioned striatum as indicated by [125I]SCH 23982 binding; ipsilateral turning initiated by the D-2 receptor agonist LY 171555 decreased, while grooming produced by the D-1 receptor agonist SKF 38393 intensified. There was, however, no change in the ability of the D-1 agonist to potentiate D-2 agonist-mediated rotation.

The mechanism of cytoplasmic streaming in characean algal cells: sliding of endoplasmic reticulum along actin filaments.

Electron microscopy of directly frozen giant cells of characean algae shows a continuous, tridimensional network of anastomosing tubes and cisternae of rough endoplasmic reticulum which pervade the streaming region of their cytoplasm. Portions of this endoplasmic reticulum contact the parallel bundles of actin filaments at the interface with the stationary cortical cytoplasm. Mitochondria, glycosomes, and other small cytoplasmic organelles enmeshed in the endoplasmic reticulum network display Brownian motion while streaming.

The Stroke Data Bank: design, methods, and baseline characteristics.

The National Institute of Neurological and Communicative Disorders and Stroke initiated the Stroke Data Bank, which is a multicenter project to prospectively collect data on the clinical course and sequelae of stroke. Additional objectives were to provide information that would enable a standard diagnostic clinical evaluation, to identify prognostic factors, and to provide planning data for future studies. A brief description of the structure and methods precede the baseline characterization of 1,805 patients enrolled in the Stroke Data Bank between July 1983 and June 1986.

Assessment of brain dopamine metabolism from plasma HVA and MHPG during debrisoquin treatment: validation in monkeys treated with MPTP.

Homovanillic acid (HVA) is formed from dopamine that escapes conversion to norepinephrine in noradrenergic neurons throughout the body as well as from dopamine synthesized in dopaminergic neurons that are mainly in brain. Debrisoquin has been used to diminish peripheral formation of dopamine to enhance the value of plasma HVA as an index of brain dopaminergic activity. This enhancement may be improved if the residual HVA formed in noradrenergic neurons could be estimated.

Coccus-shaped Bacillus subtilis cells are inhibited at stage 0 of sporulation.

RodA and rodB mutations cause rod-shaped Bacillus subtilis cells to become coccus-shaped when the growth temperature is increased from 30 to 45 degrees C. At 30 degrees C four rod strains sporulated as well as the genetically closely related rod+ strains. In contrast, at 45 degrees C the sporulation frequencies of rod strains decreased approximately 10(2)- to 10(4)-fold, while those of rod+ strains remained either unchanged or decreased only slightly.

Serum antibodies to gangliosides in Guillain-Barré syndrome.

To determine whether antibodies to acidic glycolipids of nervous tissue are present in patients with Guillain-Barré syndrome (GBS), sera from patients with GBS and appropriate control subjects were tested by a thin-layer chromatogram overlay technique. Chromatograms on which the whole ganglioside fractions from peripheral nerve and brain had been separated were overlaid with appropriate dilutions of the patients' sera (1:100 or greater), and antibody binding was revealed with a radiolabeled or peroxidase-labeled second antibody. Antibodies to ganglioside antigens were detected in 5 of 26 patients with GBS.

Evidence that DNA is present in abnormal tubulofilamentous structures found in scrapie.

Abnormal tubulofilamentous structures have been identified in electron micrographs of thin sections and negatively stained impression grids prepared from brains of animals with scrapie and other spongiform encephalopathies, and we showed that such tubules contain a core of filamentous structures resembling scrapie-associated fibrils (SAF). We treated impression grids from brains of scrapie-infected hamsters with several substances that bind to or cleave proteins and nucleic acids to see if they had any effect on the abnormal tubulofilamentous structures. Treatment with three proteolytic enzymes reduced the caliber of the tubules from about 50 nm to 30 nm; subsequent treatment of the 30-nm tubules with DNase I left many typical SAF as well as transitional forms in which twisted SAF emerged from tubules.

Effects of the external ions and metabolic poisoning on the constriction of the squid giant axon after axotomy.

After transecting the squid giant axon in the presence of an artificial external medium, which was composed of the ions normally present in squid blood, the cut ends of the axon constrict. This constriction could be completely blocked by cutting the axon in the presence of an artificial internal medium composed of the ions normally present inside the axon. By interchanging the ions in the internal medium with those in the external medium, it was determined that constriction was stimulated by the high concentrations of calcium, chloride, and magnesium ions present in the external medium and inhibited by the high concentrations of potassium ion in the internal medium.

Dystonia with marked diurnal variation associated with biopterin deficiency.

Two pairs of siblings with severe dystonia with marked diurnal fluctuation had both reduced CSF concentration of biopterin and marked symptomatic improvement of the dystonia in response to levodopa. Whether the reduced concentration of biopterin reflects focal abiotrophy of biopterin-containing neurons or deficiency of biopterin synthesis is uncertain. A fifth individual, who had a systemic deficiency of biopterin synthesis, shared the features of reduced biopterin in CSF, marked diurnal variation in the degree of dystonia, and clinical improvement in response to levodopa.

Methodology for non-invasive mapping of human motor cortex with electrical stimulation.

Different techniques for mapping motor evoked potentials recorded from hand, upper arm, leg and mouth were analyzed. The best results were obtained when: (1) delivering constant voltage stimuli through a bipolar surface stimulator, (2) positioning the anode over the desired scalp location and the cathode 2.5 cm anterior to the anode, (3) maintaining low impedances, and (4) increasing the stimulus intensity over the theoretical motor representation area until a 500-1000 microV muscle response is achieved and then delivering the same stimulus over different scalp locations.

Morphology of interleukin-2-stimulated human peripheral blood mononuclear effector cells killing glioma-derived tumor cells in vitro.

This is the first morphological study of interleukin-2-stimulated human peripheral blood mononuclear (PBM) cells resulting in lymphokine-activated killer (LAK) cell activity against human glioma-derived tumor cells in vitro, in which high-resolution differential interference video light microscopy, scanning electron microscopy, and transmission electron microscopy were used. A subset of cells within the LAK cell population are the effector cells and have an asymmetric cellular architecture characteristic of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Upon binding to target cells, the LAK effector cell nucleus is positioned away from the target cell, whereas the granules, Golgi apparatus, and microtubules orient toward the target cell.

Human gamma enolase: isolation of a cDNA clone and expression in normal and tumor tissues of human origin.

We have isolated and sequenced a cDNA clone encoding the human gamma enolase. Comparison of our cDNA sequence and the rat gamma enolase sequence revealed 97% homology at the level of amino acid sequence. The two coding regions were 91% homologous on the nucleotide level, whereas the 3' noncoding regions were much less homologous (32%).

Release, metabolism and intraneuronal disposition of exogenous, endogenous and newly synthesized norepinephrine in the rat vas deferens.

In the isolated rat vas deferens the release and intraneuronal disposition of endogenous norepinephrine (NE) were compared with those of newly synthesized or exogenous radioactive NE by preloading tissues with trace amounts of tritiated dopamine ([3H]DA) or tritiated NE ([3H]NE) and measuring release of radioactive and endogenous NE and dihydroxyphenylglycol (DHPG). Tissues were examined before and during electrical simulation, exposure to tyramine or exposure to depolarizing concentrations of K+. In [3H]DA-preloaded tissues the [3H]DA was converted readily to [3H]NE.

Comparison of the prevalence of Parkinson's disease in black populations in the rural United States and in rural Nigeria: door-to-door community studies.

A door-to-door survey of Parkinson's disease (PD) in Copiah County, Mississippi, using a pretested screening procedure (with a high sensitivity for detecting PD), followed by examination of all positives by a senior neurologist, revealed similar prevalence ratios for blacks and whites. The same procedure was applied in the community of Igbo-Ora, Nigeria, a black population of West Africa. To assure uniformity in the procedures and application of the diagnostic criteria, a neurologist from each survey site visited the other site.

No response to high-dose muscarinic agonist therapy in Alzheimer's disease.

Cholinergic deficiency is the most consistent transmitter system abnormality in Alzheimer's disease. To test the acute therapeutic efficacy of cholinergic replacement, seven patients with presenile onset of Alzheimer's type dementia received maximum tolerated doses (10 mg/d) of the selective muscarinic agonist, RS-86, in combination with a peripherally active anticholinergic glycopyrrolate (6 mg/d), in a double-blind placebo-controlled design. No consistent, clinically significant cognitive improvement could be discerned in these mild to moderately demented patients, despite attainment of central RS-86 levels approximating those that affect behavior in the experimental animal.

Dynorphin A inhibits and naloxone increases the electrically stimulated release of oxytocin but not vasopressin from the terminals of the neural lobe.

Oxytocin release from the rat neurohypophysis is under endogenous opioid inhibition. It has recently been established that dynorphin precursor-derived peptides are colocalized with vasopressin (VP) in the secretory granules in nerve terminals of the neural lobe, and that the opiate receptors in the neural lobe are restricted to the kappa-subtype. Therefore, we hypothesized that dynorphin, which is copackaged and thus coreleased with VP, is the endogenous opioid that inhibits release from neighboring oxytocin (OT) terminals.

Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation.

Using a new expression vector that allows stable and steroid inducible expression of the human beta 2-adrenergic receptor in mouse L cells, we have examined the functional significance of the highly conserved aspartate residue in the putative second transmembrane region of the receptor. Substitution of aspartate 79 with asparagine produced a mutant receptor that displays the expected affinity and stereoselectivity for antagonists but a 40-, 140-, and 240-fold reduction in its affinity for isoproterenol, epinephrine, and norepinephrine, respectively. This receptor mutant does not display guanine nucleotide-sensitive high affinity binding of agonists.

Gangliosides GM2, IV4GalNAcGM1b, and IV4GalNAcGC1a as antigens for monoclonal immunoglobulin M in neuropathy associated with gammopathy.

It was previously reported that monoclonal IgM from two patients with gammopathy and neuropathy showed similar specificity by reacting with the same group of unidentified minor components in the ganglioside fractions of human nervous tissues (Ilyas, A. A., Quarles, R.

Behavioral effects of chronic exposure to selective D-1 and D-2 dopamine receptor agonists.

Chronic treatment with the selective D-1 agonist SKF 38393 induced behavioral supersensitivity (increased stereotypy and decreased locomotor activity) in response to apomorphine, In contrast, chronic treatment with the selective D-2 agonist LY 171555 resulted in a subsensitive behavioral response to apomorphine challenge. Chronic treatment with the combination of these drugs augmented apomorphine-induced stereotypic behaviors, but these were different in nature from those observed in animals treated with SKF 38393 alone. Chronic SKF 38393 treatment resulted in an enhanced behavioral response to SKF 38393 itself.

Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol.

The intracellular accumulation of unesterified cholesterol was examined during 24 h of low density lipoprotein (LDL) uptake in normal and Niemann-Pick C fibroblasts by fluorescence microscopy with filipin staining and immunocytochemistry. Perinuclear fluorescence derived from filipin-sterol complexes was observed in both normal and mutant cells by 2 h. This perinuclear cholesterol staining reached its peak in normal cells at 6 h.