Near-concentric Fabry-Pérot cavity for continuous-wave laser control of electron waves.

Manipulating free-space electron wave functions with laser fields can bring about new electron-optical elements for transmission electron microscopy (TEM). In particular, a Zernike phase plate would enable high-contrast TEM imaging of soft matter, leading to new opportunities in structural biology and materials science. A Zernike phase plate can be implemented using a tight, intense continuous laser focus that shifts the phase of the electron wave by the ponderomotive potential. Here, we use a near-concentric cavity to focus 7.5 kW of continuous-wave circulating laser power at 1064 nm into a 7 µm mode waist, achieving a record continuous laser intensity of 40 GW/cm2. Such parameters are sufficient to impart a phase shift of 1 rad to a 10 keV electron beam, or 0.16 rad to a 300 keV beam. Our numerical simulations confirm that the standing-wave phase shift profile imprinted on the electron wave by the intra-cavity field can serve as a nearly ideal Zernike phase plate.

Phospholipid metabolism, calcium flux, and the receptor-mediated induction of chemotaxis in rabbit neutrophils.

Rabbit neutrophils were stimulated with the chemotactic peptide fMet-Leu-Phe in the presence of the methyltransferase inhibitors homocysteine (HCYS) and 3-deazaadenosine (3-DZA). HCYS and 3-DZA inhibited chemotaxis, phospholipid methylation, and protein carboxymethylation in a dose-dependent manner. The chemotactic peptide-stimulated release of [14C]arachidonic acid previously incorporated into phospholipid was also partially blocked by the methyltransferase inhibitors. Stimulation by fMet-Leu-Phe or the calcium ionophore A23187 caused release of arachidonic acid but not of previously incorporated [14C]-labeled linoleic, oleic, or stearic acids. Unlike the arachidonic acid release caused by fMet-Leu-Phe, release stimulated by the ionophore could not be inhibited by HCYS and 3-DZA, suggesting that the release was caused by a different mechanism or by stimulating a step after methylation in the pathway from receptor activation to arachidonic acid release. Extracellular calcium was required for arachidonic acid release, and methyltransferase inhibitors were found to partially inhibit chemotactic peptide-stimulated calcium influx. These results suggest that methylation pathways may be associated with the chemotactic peptide receptor stimulation of calcium influx and activation of a phospholipase A2 specific for cleaving arachidonic acid from phospholipids.

Stress hormones: their interaction and regulation.

Stress stimulates several adaptive hormonal responses. Prominent among these responses are the secretion of catecholamines from the adrenal medulla, corticosteroids from the adrenal cortex, and adrenocorticotropin from the anterior pituitary. A number of complex interactions are involved in the regulation of these hormones. Glucocorticoids regulate catecholamine biosynthesis in the adrenal medulla and catecholamines stimulate adrenocorticotropin release from the anterior pituitary. In addition, other hormones, including corticotropin-releasing factor, vasoactive intestinal peptide, and arginine vasopressin stimulate while the corticosteroids and somatostatin inhibit adrenocorticotropin secretion. Together these agents appear to determine the complex physiologic responses to a variety of stressors.

Phospholipid methylation and biological signal transmission.

Many types of cells methylate phospholipids using two methyltransferase enzymes that are asymmetrically distributed in membranes. As the phospholipids are successively methylated, they are translocated from the inside to the outside of the membrane. When catecholamine neurotransmitters, lectins, immunoglobulins or chemotaxic peptides bind to the cell surface, they stimulate the methyltransferase enzymes and reduce membrane viscosity. The methylation of phospholipids is coupled to Ca2+ influx and the release of arachidonic acid, lysophosphatidylcholine, and prostaglandins. These closely associated biochemical changes facilitate the transmission of many signals through membranes, resulting in the generation of adenosine 3',5'-monophophate in many cell types, release of histamine in mast cells and basophils, mitogenesis in lymphocytes, and chemotaxis in neutrophils.

Catechol estrogens: presence in brain and endocrine tissues.

Catechol estrogens have been identified and measured in rat brain and various endocrine tissues with the use of a sensitive radioenzymatic assay. The specificity of this assay was confirmed by thin-layer chromatography and mass spectral analysis of the reaction products. The concentration of catechol estrogens in the hypothalamus and pituitary are at least ten times higher than reported previously for the parent estrogens. Catechol estrogens have potent endocrine effects and, because of their normal occurrence in the hypothalamic-pituitary axis, they have an important role in neuroendocrine regulation.

Octopamine: normal occurrence in sympathetic nerves of rats.

Octopamine has been identified in several organs of normal rats by means of a sensitive enzymatic assay. It is localized within the sympathetic nerve endings.

Pineal gland: 24-hour rhythm in norepinephrine turnover.

There is a 24-hour rhythm in the turnover of norepinephrine in sympathetic nerves innervating the pineal gland. This rhythm persists in blinded animals but is suppressed in normnal rats by light. The rhythm in norepinephrine turnover generates the rhythums in pineal indoleamines and N-acetyltransferase.

Amphetamine in human plasma: a sensitive and specific enzymatic assay.

A sensitive and specific enzymatic-isotopic method of determining plasma amphetamine concentrations in man is described. The assay is based on the transfer of the tritiated methyl group of S-adenosyl-L-[methyl-(3)H]methionine to amphetamine in the presence of a partially purified N-methyltransferase from rabbit lung. With this assay as little as 10 nanograms of amphetamine per milliliter of plasma can be accurately determined. The concentrations of d- and 1-amphetamine in the plasma after 20 to 30 milligrams of the drug had been ingested by human subjects are reported.

Pineal beta-adrenergic receptor: diurnal variation in sensitivity.

The responsiveness of the pineal beta-adrenergic receptor that regulates serotonin-N-acetyltransferase activity is nearly ten times greater at the end of the light period (0600 to 1800 hours) than at the end of the dark period (1800 to 0600 hours). These changes in sensitivity of the postsynaptic beta-adrenergic receptor are related to diurnal changes in the release of noradrenaline from sympathetic nerves innervating the pineal. Supersensitivity of the receptor appears to result from decreased release of the neurotransmitter during daytime, and subsensitivity from increased release at night.

Psychotomimetic N-methylated tryptamines: formation in brain in vivo and in vitro.

The use of a sensitive enzymatic assay demonstrates that tryptamine occurs normally in rat brain. Intracisternal administration of [(14)C]tryptamine results in the formation of N-methyl-and dimethyltryptamine(a psychotomimetic compound)in the rat brain. An enzyme that converts tryptamine and N-methyl-tryptamine to N-methyl-and dimethyltryptamine was found to be present in rat and human brain. The N-methylation of tryptamine was inhibited by normally occurring compounds present in rat brain.

Serum dopamine- -hydroxylase: decrease after chemical sympathectomy.

Dopamine-beta- hydroxylase is an enzyme that is localized to catecholamine-containing vesicles in sympathetic nerves and the adrenal medulla, and is also found in the serum. Treatment of rats with 6-hydroxydopamine, a drug which destroys sympathetic nerve terminals, leads to a decrease in serum dopamine-beta-hydroxylase activity. The decrease is not due to an effect on the adrenal medulla or to an increase in circulating inhibitor or inhibitors of enzyme. These data represent evidence that at least a portion of the circulating dopamine-beta-hydroxylase activity arises from sympathetic nerve terminals.

Delta-9-tetrahydrocannabinol: localization in body fat.

[(14)C]Delta(9)-Tetrahydrocannabinol (Delta(9)THC) was injected subcutaneously in rats every day for 1 to 26 days. Concentrations of Delta(9)THC and its metabolites, 11-hydroxytetrahydrocannabinol and 8,11-dihydroxytetrahydrocannabinol, were determined in various tissues. After a single injection, the concentration of Delta(9)THC in fat was ten times greater than in any other tissue examined, and persisted in this tissue for 2 weeks. With repeated injection, Delta(9)THC and its metabolites accumulated in fat and brain.

Phospholipid methylation unmasks cryptic beta-adrenergic receptors in rat reticulocytes.

The effect of phospholipid methylation on the number of beta-adrenergic receptor binding sites was examined in rat reticulocyte membranes. Stimulation of phosphatidylcholine synthesis by the introduction of the methyl donor S-adenosyl-L-methionine into reticulocyte ghosts increased the number of beta-adrenergic receptor sites. The appearance of beta-adrenergic binding sites was dependent on the formation of phosphatidylcholine by the enzyme that converts phosphatidyl-N-monomethylethanolamine from phosphatidylethanolamine. Both the synthesis of phosphatidylcholine and the unmasking of cryptic receptors were time and temperature dependent and did not occur in the presence of the methyl transferase inhibitor, S-adenosyl-L-homocysteine.

Enzymatic synthesis of melatonin in avian pineal body: extraretinal response to light.

In the chick pineal body, activity of the melatonin-forming enzyme hydroxyindole-O-methyl transferase is greater in the light than in darkness. Neither bilateral enucleation of the eyes nor sympathetic denervation prevented this light-induced elevation of enzyme activity. This fact indicates that in the bird, in contrast to mammals, neither the retinas nor sympathetic innervation of the pineal body are essential for environmental control of melatonin formation.

Adrenal tyrosine hydroxylase: compensatory increase in activity after chemical sympathectomy.

Destruction of peripheral sympathetic nerve endings with 6-hydroxydopamine causes a disappearance of cardiac tyrosine hydroxylase, accompanied by a twofold increase in adrenal tyrosine hydroxylase and a small increase in phenyl-ethanolanine-N-methyl transferase. No change in adrenal catecholamine content occurs under these conditions.

Reduced catechol-O-methyltransferase activity in red blood cells of women with primary affective disorder.

Red blood cell catechol-O-methyltransferase, histamine-N-methyltransferase, and a methanol-forming enzyme were examined in a number of subjects with mental diseases. Catechol-O-methyltransferase activity was significantly reduced in female subjects with primary affective disorder (depression) as compared to normal women and men, men with primary affective disorder, and schizophrenic men and women. In depressed women, histamine-N-methyltransferase activity was elevated and the methanol-forming enzyme was unchanged.

Adrenaline-forming enzyme in brainstem: elevation in genetic and experimental hypertension.

The adrenaline-forming enzyme (phenylethanolamine N-methyltransferase) was elevated in the A1 and A2 regions of the brainstem of 4-week-old spontaneously (genetic) hypertensive rats and in the A1 region of adult experimentally (deoxycorticosterone acetate and sodium chloride) hypertensive rats. The administration of a phenylethanolamine N-methyltransferase inhibitor to experimentally hypertensive animals caused a reduction of the elevated blood pressure to normal values. These results implicate adrenaline-containing neurons in the brainstem in the development of hypertension.

Visual pathway mediating pineal response to environmental light.

Activity of the melatoninforming enzyme, hydroxyindole-O-methyltransferase, in rat pineal is increased when the animal is exposed to continuous darkness, and it is decreased by exposure to continuous light. Response to environmental light is initiated in the retina and transmitted to the pineal by way of the central nervous system and the cervical sympathetics. The central visual pathway essential for mediation of this response is the inferior accessory optic tract. Visual pathways to thalamus and tectum do not participate in this response.

Light-induced changes in pineal hydroxyindole-O-methyltransferase: abolition by lateral hypothalamic lesions.

The activity of hydroxyindole-O-methyltransferase, the melatoninforming enzyme in the pineal gland, is several times greater in rats kept in continuous darkness than in those kept in continuous light. Lesions transecting the medial forebrain bundle in the lateral hypothalamus suppress these differences in enzyme activity and abolish light-induced changes in pineal weight. These findings indicate that the medial forebrain bundle may participate in the control of this enzymatic response to environmental lighting.

Marihuana: studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man.

Delta(9)-Tetrahydrocannabinol (the major active component of marihuana) administered intravenously to normal human volunteers persists in plasma for more than 3 days (t(1/2) = 56 hours). Its metabolites appear in plasma within 10 minutes after administration and persist along with the precursor compound. Delta(9)-Tetrahydrocannabinol is completely metabolized in man, and the radioactive metabolites are excreted in urine and feces for more than 8 days.