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PubMed1996

Synthesis, NMR Characterization, and a Simple Application of Lithium Borotritide.

LiBH(4) is a powerful and selective reagent for regiospecific reduction reactions. A simple synthesis of LiB(3)H(4) at near theoretical specific radioactivity is reported. We have treated Li(3)H synthesized from tritium gas ((3)H(2), approximately 98%) with BBr(3) to produce LiB(3)H(4) (specific activity = 4120 GBq/mmol = 110 Ci/mmol. The maximum theoretical specific activity of LiB(3)H(4) is 4252 GBq/mmol = 115.04 Ci/mmol; 1 matom of (3)H = 1063 GBq = 28.76 Ci.) The tritium labeling performance of the reagent was tested by an exemplary reduction of 2-naphthaldehyde to 2-naphthalenemethanol. LiB(3)H(4) and the reduction products were characterized by a combination of (1)H, (3)H, and (11)B NMR techniques, as appropriate.

Journal Article↗
PubMed1988

Tricyclic antidepressants, mianserin, and ouabain stimulate inositol phosphate formation in vitro in rat cortical slices.

The ability of tricyclic antidepressants, monoamine oxidase inhibitors, mianserin and ouabain to stimulate hydrolysis of inositol phosphates was examined in rat cerebral cortex slices using a direct assay which involves labelling with [3H]inositol and assaying [3H]inositol phosphates in the presence of lithium. Desimipramine, imipramine, chlorimipramine, mianserin, and ouabain stimulated [3H]inositol phosphate accumulation in a concentration-dependent manner. The monoamine oxidase inhibitors, pargyline and nialamide were without effect. The stimulation of [3H]inositol phosphate accumulation caused by the various substances was not blocked by the antagonists prazosin, ketanserin, atropine, or mepyramine. In contrast, the antagonists prazosin, ketanserin, atropine and mepyramine selectively blocked stimulation of [3H]inositol phosphate accumulation caused by noradrenaline, serotonin, carbachol and histamine respectively. When desimipramine was substituted for lithium in the assay procedure, carbachol was ineffectual in stimulating [3H]inositol phosphate accumulation. In these experiments the control (unstimulated) values were much higher than in the normal (when lithium is present) assay procedure. Desimipramine is quite effective in stimulating [3H]inositol phosphate accumulation either in the presence or absence of lithium in the incubation medium. This is not the case for carbachol where it was essential to have lithium in the incubation medium in order to obtain a stimulation of [3H]inositol phosphate accumulation. Furthermore, in the case of carbachol stimulation, most of the radioactivity was associated with a peak corresponding to inositol monophosphate, while for desimipramine stimulation two clear peaks corresponding to inositol monophosphate and inositol bisphosphate were apparent.

Animals↗
PubMed1979

133Xenon washout in the paranasal sinuses--a diagnostic tool for assessing ostial function.

A 133Xenon washout test is presented and interpreted. It was developed on the basis of studies into the accumulation of aerosols of different makes (lithium chloride in the form of ultrasonic, vibratory and pressurized aerosols) in the paranasal sinuses and sequential scintigraphy with radioactively labeled aerosols (99m Technetium colloidal sulfur) and is designed to shed light on the gas exchange in the paranasal sinuses and the patency of their orifices. The test constitutes a valuable addition to the battery of diagnostic tools for assessing paranasal sinus function and, at the same time, documents the true value of aerosol therapy.

Frontal Sinus↗
PubMed1977

Effects of estradiol on in vitro nucleoside incorporation and methylation of rat uterine ribonucleic acid.

The in vitro nucleoside incorporation and methylation of uterine RNA was examined by incubating immature rat uteri with either 3H-uridine, 3H-uridine-3H-cytidine, and/or 14C-methyl-methionine. Radioactivity was determined in extracted RNA which was fractionated by gel electrophoresis or by differential solubility in zine acetate or lithium chloride. Estradiol (E2)-treated uteri respond by showing a maximum in vitro incorporation of nucleosides into total RNA and high M.W. RNA within one hr of in vivo treatment. Nucleoside incorporation into low M.W. RNA increased gradually throughout the first 3 hrs of a 4-hr hormone treatment period. E2 in vivo also caused increased in vitro methylation of total, high, and low M.W. uterine RNA fractions. Methylation of all fractions increased through the first 3 hrs of hormone treatment, but greater methylation of low M.W. RNA was apparent. The data indicate that in vivo E2 treatment stimulates an initial transitory stage of in vitro nucleoside incorporation into uterine RNA followed by a more prolonged interval of RNA methylation.

Animals↗
PubMed1984

Inositol phospholipid hydrolysis in rat cerebral cortical slices: I. Receptor characterisation.

Characterisation of receptor-mediated breakdown of inositol phospholipids in rat cortical slices has been performed using a direct assay which involves prelabelling with [3H]inositol. When slices were preincubated with [3H]inositol, lithium was found to greatly amplify the capacity of receptor agonists such as carbachol, noradrenaline, and 5-hydroxytryptamine to increase the amount of radioactivity appearing in the inositol phosphates. Using a large variety of agonists and antagonists it could be shown that cholinergic muscarinic, alpha 1-adrenoceptor, and histamine H1 receptors appear to be linked to inositol phospholipid breakdown in cortex. The large responses produced by receptor agonists allowed a clear discrimination between full and partial agonists as well as quantitative analysis of competitive antagonists for each receptor. Whereas carbachol and acetylcholine (in the presence of a cholinesterase inhibitor) were full agonists, oxotremorine and arecoline were only partial agonists. Very low concentrations of atropine shifted the carbachol dose-response curve to the right and allowed inhibition constants for the antagonist to be easily calculated. The nicotinic antagonist, mecamylamine, was ineffective. Noradrenaline adrenaline were full agonists at alpha 1-adrenoceptors, but phenylephrine and probably methoxamine were partial agonists. Prazosin, but not yohimbine, potently and competitively antagonised the noradrenaline inositol phospholipid response. Mepyramine but not cimetidine competitively antagonised the histamine response. These data provide strong confirmation for the potentiating effect of lithium on neurotransmitter inositol phospholipid breakdown and emphasise the ease with which functional responses at a number of cortical receptors can be characterised.

Animals↗
PubMed1990

Further evidence against the coupling of dopamine receptors to phosphoinositide hydrolysis in rat striatum.

The effects of D1 and D2 dopamine receptor agonists on phosphoinositide hydrolysis were studied by measuring the accumulation of radioactive inositol phosphates in slices of rat corpus striatum prelabelled with [3H]inositol. All assays were performed in the presence of lithium. Neither the D1 receptor agonist SKF 38393 nor the D2 receptor agonist quinpirole, alone or in combination, had an effect on basal accumulation of inositol phosphates. The muscarinic receptor agonist carbachol produced a robust increase in the accumulation of inositol monophosphate and a smaller increase in the accumulation of inositol bisphosphate. These effects were not altered by the presence of quinpirole. Additionally, quinpirole also had no effect when assays were conducted in the presence of the muscarinic receptor antagonist scopolamine, the glutamic acid receptor antagonist kynurenic acid, and the antioxidant glutathione. These results are discussed in relation to recent contradictory reports and lend support to the position that D2 dopamine receptors are not coupled to phosphoinositide hydrolysis in rat striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Profile of phosphatidylinositol metabolism stimulated by carbachol and glutamate in primary cultures of rat cerebellar neurons.

The formation of inositol phosphates, after stimulation of primary cultures of cerebellar neurons of the neonatal rat, in the presence of lithium chloride, by glutamate, carbachol, norepinephrine, histamine and Mg2+-free conditions, was measured by anion exchange high-pressure liquid chromatography (HPLC) with on-line radioactivity detection. All of the above agents caused a persistent, dose-dependent and calcium-sensitive preferential accumulation of inositol-4-phosphate, while the levels of inositol-1-phosphate were virtually unaffected. Agonist stimulation produced also a transient increase of a second peak which co-eluted with the standard for inositol 1,4-bisphosphate. However, no significant accumulation of inositol-1,4,5-trisphosphate and inositol-1,3,4,5-tetrakisphosphate was detected, possibly due to the fast kinetics of the metabolism of inositol phosphate. The results indicate that receptor-stimulated metabolism of inositol phosphate, in cultures of cerebellar granule cells, is due to a preferential hydrolysis of polyphosphoinositides and leads to the formation of inositol-4-phosphate through several calcium- and lithium-sensitive enzymatic steps.

Animals↗
PubMed1981

Methylation of membrane proteins in human erythrocytes. Identification and characterization of polypeptides methylated in lysed cells.

An in vitro system was developed for studying protein methylation reactions in human red blood cells. Packed erythrocytes were lysed by freeze-thawing in the presence of S-adenosyl[methyl-3H]methionine. Specific incorporation of base-labile methyl groups into the band 3 anion transport protein and the major sialoglycoprotein (glycophorin, periodic acid-Schiff reagent-1) was demonstrated by dodecyl sulfate gel electrophoresis at pH 2.4, selective extractions with Triton X-100 and lithium diiodosalicylate, and protease sensitivity. Two other unidentified intrinsic membrane proteins with Mr = 96,000 and 23,500 were also methylated. Little radioactivity was incorporated into membrane proteins when membranes were incubated with S-adenosyl-L-[methyl-3H]methionine in the absence of cytosol. No evidence was obtained for incorporation of methyl label into extrinsic proteins including bands 1, 2, 2.1, 4, 5, 6, or in zone 4.5. Proteolytic digestion of intact cells and isolated membranes revealed that one site of methylation on the band 3 polypeptide may be at the inner surface of the membrane near the junction of the cytoplasmic domain and the membrane domain. The rates of hydrolysis of the incorporated methyl groups were characterized over a range of pH values. These rates were compared to those of methyl esterified amino acids and peptides, including aspartic acid beta-methyl ester which has been isolated from proteolytic digests of methylated erythrocyte membranes (Janson, C. A., and Clarke, S. (1980) J. Biol. Chem. 225, 11640-11643). We find that the rates of base-catalyzed hydrolysis of beta-methyl esters of aspartic acid and gamma-methyl esters of glutamic acid are highly sensitive to the presence of substituents on the alpha-carboxyl and alpha-amino groups. The rate of hydrolysis of the membrane-incorporated methyl groups are consistent with those of internal aspartic acid and glutamic acid methyl ester residues.

Chymotrypsin↗
PubMed1984

Thyrotropin-releasing hormone-stimulated [3H]inositol metabolism in GH3 pituitary tumor cells. Studies with lithium.

GH3 pituitary tumor cells were labeled to isotopic equilibrium with [3H]inositol. Thyrotropin-releasing hormone (TRH), which has been shown to stimulate inositol phospholipid metabolism in these cells, enhanced the accumulation of [3H]inositol-derived radioactivity in the cell's acid-soluble fraction. Separation of the [3H]inositol metabolites by ion-exchange chromatography revealed that TRH induced a rapid rise in the cellular content of [3H]inositol mono-, bis-, and trisphosphate. The latter two metabolites accumulated in a multiphasic manner with an initial peak 5-10 sec after TRH addition. This was followed by a short-lived decline and a secondary rise which left the metabolite levels elevated for at least 50 min. The GH3 cell [3H]inositol monophosphate and [3H] inositol content also rose in response to TRH, but the latter accumulated with a considerably slower time course than the phosphorylated derivatives. None of these responses could be mimicked by the calcium ionophore A23187. Incubation of GH3 cells with TRH in the presence of lithium led to an enhanced accumulation of [3H]inositol monophosphate and, to a lesser extent, of [3H]inositol bis- and trisphosphate. This accumulation rose in a linear fashion with time for at least 20 min, by which point 50% of the [3H]inositol-containing phospholipids had been depleted. When lithium was added 30 min after TRH, [3H]inositol monophosphate accumulated at the same rate as was found when TRH and lithium were added together, indicating that the TRH-induced phospholipid response in GH3 cells does not desensitize. Under normal conditions, approximately equal amounts of the three [3H]inositol phosphates were formed within 5 sec of TRH addition. However, when TRH was added to cells grown chronically in lithium-containing medium, or to cells incubating at a subphysiological temperature (25 degrees), greater than 90% of the metabolites formed were the bis- or trisphosphates. This indicates that the primary event stimulated by TRH is the breakdown by phospholipase C of phosphatidylinositol 4,5-bisphosphate and, perhaps also, of phosphatidylinositol 4-phosphate.

Animals↗
PubMed1978

Neutrophilic leukocyte membrane proteins. I. Isolation.

Rabbit exudate-derived PMN were homogenized and the cell membranes isolated on a two-phase aqueous system. Glycoproteins were extracted from cell membranes with lithium diiodosalicylate. SDS polyacrylamide gel electrophoretic analysis showed a consistent pattern of three major glycoprotein entities. Cells radioiodinated supravitally showed most of the radioactivity associated with larger glycoprotein entities whereas PMN membranes radiolabeled after isolation yielded a single major peak of radioactivity associated with a much smaller protein entity. Heterologous antisera against rabbit PMN, PMN membranes, and membrane glycoproteins were all cytotoxic for PMN in the presence of complement, and all bound to the PMN surface as demonstrated with immunocolloidal gold on electron microscopy. The data suggest that one or more glycoprotein entities are membrane-associated ectoglycoproteins which can be radiolabeled supravitally.

Animals↗
PubMed2006

Boron containing macromolecules and nanovehicles as delivery agents for neutron capture therapy.

Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when non-radioactive boron-10 is irradiated with low energy thermal neutrons to yield high linear energy transfer (LET) alpha particles ((4)He) and recoiling lithium -7((7)Li) nuclei. For BNCT to be successful, a sufficient number of (10)B atoms ( approximately 10(9) atoms/cell) must be selectively delivered to the tumor and enough thermal neutrons must be absorbed by them to sustain a lethal (10)B(n, alpha) (7)Li capture reaction. BNCT primarily has been used to treat patients with brain tumors, and more recently those with head and neck cancer. Two low molecular weight (LMW) boron delivery agents currently are being used clinically, sodium borocaptate and boronophenylalanine. However, a variety of high molecular weight (HMW) agents consisting of macromolecules and nanovehicles have been developed. This review will focus on the latter which include: monoclonal antibodies, dendrimers, liposomes, dextrans, polylysine, avidin, folic acid, and epidermal and vascular endothelial growth factors (EGF and VEGF). Procedures for introducing boron atoms into these HMW agents and their chemical properties will be discussed. In vivo studies on their biodistribution will be described, and the efficacy of a subset of them, which have been used for BNCT of tumors in experimental animals, will be discussed. Since brain tumors currently are the primary candidates for treatment by BNCT, delivery of these HMW agents across the blood-brain barrier presents a special challenge. Various routes of administration will be discussed including receptor-facilitated transcytosis following intravenous administration, direct intratumoral injection and convection enhanced delivery by which a pump is used to apply a pressure gradient to establish bulk flow of the HMW agent during interstitial infusion. Finally, we will conclude with a discussion relating to issues that must be addressed if these HMW agents are to be used clinically.

Animals↗
PubMedDate not supplied

[Use of metal salts for radioprotection of plants during radioactive pollution of the territory].

The applying salts of some metals to radionuclide contaminated soddy-podzolic soil in the zone of Chernobyl nuclear power station or the spraying of plants by its solutions are showing the radioprotective effect (salts of iron, zinc, cobalt and manganese) and decreasing the uptake of 90Sr and 137Cs through roots (salts of zinc, manganese, boron, lithium, cobalt and copper).

Chlorides↗
PubMed1985

Direct cross-linking of 125I-labeled glucagon to its membrane receptor by UV irradiation.

125I-labeled glucagon was directly crosslinked to its receptor in isolated liver plasma membranes and on the surface of intact hepatocytes, by using a UV irradiation procedure. This investigation resulted in the identification of a glucagon-receptor complex of apparent Mr 62,000. The specificity of labeling was shown by the interference of unlabeled hormone at physiological concentration with incorporation of radioactive glucagon into the 62,000 Mr species. The receptor behaved as a typical integral membrane protein: it was not released by extraction with lithium diiodosalicylate or at basic pH but was solubilized by digitonin treatment. Reduction of the receptor polypeptide with dithiothreitol resulted in a decrease in its electrophoretic mobility, suggesting the presence of intramolecular disulfide bonds. Soluble glucagon-receptor complexes adsorbed to Con A-Sepharose and could be eluted with methyl alpha-D-mannoside, indicating that the receptor molecule is a glycoprotein. Treatment of glucagon-labeled liver plasma membrane with endoglycosidase F resulted in the appearance of four intermediate species, indicating that glucagon receptor contains at least four N-linked oligosaccharide chains.

Animals↗
PubMed1971

X-ray fluorescence: detection of lead in wall paint.

An instrument has been developed for the in situ determination of lead on painted surfaces. It utilizes, as a source of gamma rays, radioactive cadmium-109 and its daughter silver-109 (metastable) to excite the K series x-rays of lead, and a solid-state, lithium-drifted germanium detector. The device, which is capable of detecting 0.26 milligram of lead per square centimeter of paint [approximately 3 percent (by weight) of lead in a single coat] beneath ten layers of lead-free paint, has been tested in a preliminary survey of several tenement apartments in New York City.

Cadmium↗
PubMed1978

Radioactive pollutant determinations using gamma-ray spectroscopy.

Qualitative and quantitative determination of radionuclide contamination in environmental samples is often complicated by the presence of uranium- and thorium-series radioelements as well as 40K. High resolution gamma-ray spectroscopy with lithium-drifted germanium detectors provides a method for the determination of man-made radio-nuclide contaminants in many matrices with a minimum of chemical separation. Methods have been studied for increasing the efficiency of such determinations by using large samples in reentrant beakers ("Merinelli beakers") and small samples inside the well of a recently developed Ge(Li) well detector. Specific examples for the determination of 129I(16 m.y. half-life) in the well detector and recent fall-out in grass samples are presented.

Environmental Exposure↗
PubMed1986

Neuronal efflux of noradrenaline induced by tris or lithium as substitutes for extracellular sodium.

Vasa deferentia of either untreated or reserpine (R) and/or pargyline (P) pretreated rats were incubated with 3H-noradrenaline and then washed with amine- and Ca2+-free solution until (after 100 min) the efflux of radioactivity largely originated from adrenergic nerve endings; COMT was inhibited by U-0521 (U). After 110 min of wash out, the sodium chloride in the wash-out solution was replaced by an equimolar concentration of either Tris-HCl or LiCl. This caused a desipramine-sensitive (i.e., carrier-mediated) efflux of tritiated noradrenaline. The initial increase of the "low Na+"-induced efflux dependent on the experimental conditions: it was most pronounced when the axoplasmic concentration of noradrenaline was high (RPU) and relatively small when MAO and vesicular storage were intact (U). The effects of Li+ and Tris+ differed with regard to the time course of the efflux of tritium: under all three experimental conditions (RPU, PU, U), Tris+ caused the rate of efflux of tritium to increase gradually within the 30 min period of observation, while Li+ either had a "peak-effect" (RPU, PU) or a "plateau-effect" (U). Under "U-conditions" Tris+ caused a slowly increasing, pronounced increase with time of the efflux of both, 3H-noradrenaline and 3H-DOPEG; whereas Li+ caused only a small and sustained increase of the efflux of 3H-noradrenaline and a decrease in the efflux of 3H-DOPEG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inositol metabolism in WRK-1 cells. Relationship of hormone-sensitive to -insensitive pools of phosphoinositides.

Previous studies have indicated the existence of two separate pools of phosphoinositides in WRK-1 cells; one is labile and hormone-sensitive with respect to turnover, while the other is stable. Hormonal stimulation results in a rapid increase in 32Pi incorporation into the sensitive pool, while in the absence of hormone, incorporation of 32Pi into this pool is slow. Results are quite different when [3H]inositol is the precursor utilized. Incorporation of [3H]inositol into hormone-sensitive phosphoinositides is not stimulated in the presence of hormone, suggesting entry of this exogenous precursor into the cycle by a route other than the resynthetic phase of the cycle. Furthermore, failure of hormone to induce loss of [3H]phosphoinositide in pulse-chase experiments in the absence of lithium suggests reutilization of the [3H]inositol moiety generated by phosphodiesteratic cleavage of hormone-sensitive phosphoinositide. Time course studies indicate that the relative rates of incorporation of [3H]inositol into sensitive and insensitive phosphoinositide remain constant from 2 to 24 h. Several factors are capable of increasing [3H]inositol incorporation into hormone-insensitive phosphoinositide including vasopressin, calcium ionophores, and manganese. On the other hand, vasopressin treatment appears to decrease incorporation of [3H]inositol into the hormone-sensitive pool, probably by shifting the equilibrium between phosphoinositides and inositol phosphates, since the decrease in radioactivity observed in the phosphoinositides is equaled by the increase observed in that in the inositol phosphates.

Animals↗