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Biomedical subjects

K L Kelly

Publications and source records attributed to K L Kelly.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lithium in hospitalized children at 4 and 8 weeks: mood, behavior and cognitive effects.

Eleven psychiatrically hospitalized children were treated with lithium carbonate for a minimum of 8 weeks. Based on literature review, their psychopathology, diagnoses and family history suggested they would be positive lithium responders. Weekly ratings in behavioral domains showed children's improvement in areas of self control, aggression and irritability, more obvious at 8 than 4 weeks. However, of seven children studied with double blind crossover, improvement behaviorally and cognitively was maintained on placebo. Only three of 11 children improved enough to be discharged on lithium. Implications of lithium's anti-aggressive and anti-manic effects in children are discussed.

Affect↗
PubMed1989

Cytosolic free calcium in adipocytes. Distinct mechanisms of regulation and effects on insulin action.

It has been proposed that an elevation in cytosolic free Ca2+ may play a role in either mediating or antagonizing the ability of insulin to stimulate glucose uptake in adipocytes. This question has been addressed in the present studies using isolated fura-2-loaded rat adipocytes stimulated with a variety of agonists. The effects of insulin, oxytocin, norepinephrine, ATP, and ionomycin on cytosolic free Ca2+ levels were assessed and compared with their effects on transport-limited glucose oxidation. Oxytocin and ionomycin at concentrations which caused 3-5-fold increases in cytosolic Ca2+, by releasing Ca2+ from internal stores, had no effect on insulin-stimulated glucose oxidation. ATP and norepinephrine which caused more modest increases in Ca2+, by mechanisms at least partially dependent on external stores, inhibited insulin-stimulated glucose oxidation. Insulin had no effect on basal Ca2+ levels nor did it modulate the Ca2+ elevation caused by other agonists. These data suggest that insulin-stimulated glucose transport is not associated with an increase in cytosolic Ca2+. In addition, although there appears to be a correlation between inhibition of insulin-stimulated glucose transport and the effect of certain agonists to promote Ca2+ influx, there is not a general obligatory relationship between an elevation in cytosolic Ca2+ and antagonism of this insulin action.

Adenosine Triphosphate↗
PubMed1989

Attention deficit disorder with hyperactivity and methylphenidate: the effects of dose and mastery level on children's learning performance.

This investigation examined the relationship between methylphenidate (MPH) and the learning and recall of paired associations by children with attention deficit disorder with hyperactivity (ADDH). Forty-five children with ADDH were randomly assigned to one of three groups (novel, partial mastery, and mastery learning) that varied in the amount of previous learning of paired associations and participated in a double-blind, placebo-control, repeated-measures-across-dose (crossover) design. Each child received four doses of MPH (5 mg, 10 mg, 15 mg, and 20 mg) and a placebo in a random, counterbalanced sequence. The results indicated that both the rate of acquisition and accuracy in learning paired associations were significantly, but differentially, affected by MPH dose and the degree of learning mastery. The implications of these results for psychopharmacological research and the monitoring of psychostimulant effects on children's learning performance in academic settings are discussed.

Association Learning↗
PubMed1988

Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine, which was both time- and dose-dependent. The stimulatory effect of isoprenaline was inhibited in a dose-dependent manner by oxytocin or insulin. Oxytocin inhibited the incorporation of [Me-3H]choline into phosphatidylcholine in both the presence and the absence of isoprenaline, whereas in the absence of isoprenaline insulin increased the incorporation of [Me-3H]choline into phosphatidylcholine. The effects of isoprenaline, oxytocin and insulin on the incorporation of [3H]choline into phosphatidylcholine were paralleled by changes in the activity of CTP:phosphocholine cytidylyltransferase.

Adipose Tissue↗
PubMed1988

Regulation and function of an insulin-sensitive glycosyl-phosphatidylinositol during T lymphocyte activation.

A combination of metabolic labeling and chemical or enzymatic modification was employed to isolate and biochemically characterize a set of glycosyl-phosphatidylinositol (gly-PI) molecules synthesized by T lymphocytes. Gly-PI displayed unique patterns of synthesis following mitogen activation relative to the phosphoinositides and major structural lipids. The increase with time in gly-PI was paralleled by the appearance of insulin receptors. Gly-PI molecules were sensitive to hydrolysis by a PI-specific phospholipase C and were rapidly (15 sec) degraded in response to insulin binding. The product of this hydrolysis is believed to be a novel inositol phosphate-glycan (IP-gly) that was shown to inhibit the activity of a cAMP-dependent protein kinase. These results demonstrate that T cells contain a structurally related set of gly-PI molecules, at least one of which is sensitive to insulin and may function as a second messenger of hormone action.

Animals↗
PubMed1988

Exposure of binding sites for vitronectin on platelets following stimulation.

Vitronectin is a glycoprotein that mediates cell adhesion and spreading in a number of cell culture systems. Liposomes containing platelet glycoproteins IIb-IIIa complex have been shown to bind vitronectin-coated surfaces through an Arg-Gly-Asp cell attachment mechanism. We examined the expression of the binding sites for vitronectin on the surface of intact, resting platelets and following stimulation. 125I-Labeled vitronectin bound specifically in a saturable manner to platelets treated with physiological concentrations of thrombin. The binding reached saturation at 100 nM concentration, and, at saturation, approximately 5000 specific binding sites were detected per platelet. The binding was divalent cation-dependent and only partially reversible after complete saturation. A synthetic hexapeptide containing the Arg-Gly-Asp sequence inhibited vitronectin binding to platelets. A monoclonal antibody against platelet glycoprotein IIb-IIIa complex also inhibited the binding of vitronectin to stimulated platelets. These data suggest that platelets possess an inducible divalent cation-dependent receptor for vitronectin and that the glycoprotein IIb-IIIa complex is involved in the expression of the vitronectin receptor.

Antibodies, Monoclonal↗
PubMed1988

Inhibition of cyclic AMP-dependent protein kinase by the polar head group of an insulin-sensitive glycophospholipid.

A glycophospholipid has been purified from rat liver membranes and shown to copurify with an insulin-sensitive glycophospholipid isolated from H35 hepatoma cells. The polar head group of this glycophospholipid is a phospho-oligosaccharide generated by treatment with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. It has been proposed that this phospho-oligosaccharide, which is also generated in response to insulin, may play a role in insulin action. Incubation of the catalytic subunit of cyclic AMP-dependent protein kinase with this phospho-oligosaccharide inhibited the activity of the kinase to phosphorylate histone IIA, a purified preparation of phospholipid methyltransferase and kemptide, a phosphate-accepting peptide. Inhibition of kinase activity was dose-dependent and 50% inhibition of histone phosphorylation was demonstrated with a concentration of phospho-oligosaccharide of around 2 microM. This effect was demonstrated in the presence of ATP at concentrations up to 1 mM, indicating that the phospho-oligosaccharide acts at physiological concentrations of ATP and that it does not compete with this nucleotide for the same binding site in the kinase. Inhibition by the phospho-oligosaccharide of kinase activity could be reversed by dilution or dialysis and was not reproduced by up to 50 microM myo-inositol, glucosamine, galactose, myo-inositol 1-phosphate, glucosamine 1-phosphate, galactose 1-phosphate or phosphorylcholine. The inhibitory activity was resistant to mild acid treatment but was labile to treatment with alkali, exposure to nitrous acid or incubation with sodium periodate. The phospho-oligosaccharide had no effect on the phosphorylation of lysine-rich histone by rat brain protein kinase C and on the binding of cyclic AMP to a cyclic AMP-dependent protein kinase. In conclusion, the data in this study suggested that a phospho-oligosaccharide generated from an insulin-sensitive glycophospholipid may play a role in insulin action by modulating cyclic AMP-dependent protein kinase activity.

Animals↗
PubMed1988

Attention deficit disorder and methylphenidate: a multi-step analysis of dose-response effects on children's cardiovascular functioning.

The present study investigated the effects of methylphenidate (MPH) on the resting heart rate of 47 children with Attention Deficit Disorder/Hyperactivity. Children participated in a double-blind, placebo control, within subject (cross-over) design and received each of 5 doses of MPH in a counterbalanced sequence. A multi-step analysis was used to examine the dose-response relationship, contribution of pre-stimulus levels of HR (i.e. the initial value), and potential interaction between dosage and time on resting HR. Results indicated that higher dosages are linearly related to increasing levels of HR and that these effects are dependent upon both the initial HR value and the time course of the medication.

Attention Deficit Disorder with Hyperactivity↗
PubMed1988

Training and proficiency of physicians' office personnel with a new diagnostic test for theophylline.

A new technology, enzyme immunochromatography, permits the quantitative measurement of therapeutic drug levels without the need for an instrument. The simplicity of this technology enables office personnel with minimal training to perform measurements of therapeutic drug concentrations in samples of whole blood within 20 minutes. A training program for office personnel was developed that could be given entirely by telephone. Records of the trainings were kept and subsequently analyzed. A follow-up study consisting of six proficiency sample mailings was done to determine the ability of the trained personnel to perform the test accurately. Additional data on split-sample analyses performed by physicians' office personnel were collected. The data indicate that the telephone training method was satisfactory for initial training, and that acceptable test performance continued over time by office personnel who had completed the training program.

Allied Health Personnel↗
PubMed1987

A phospho-oligosaccharide mimics the effect of insulin to inhibit isoproterenol-dependent phosphorylation of phospholipid methyltransferase in isolated adipocytes.

Addition of isoproterenol to isolated rat adipocytes prelabeled with [32P]phosphate caused an increase in the phosphorylation and activation of phospholipid methyltransferase. 32P-Labeled phospholipid methyltransferase was recovered by immunoprecipitation and gel electrophoresis. Analysis of 32P-labeled peptides revealed one site of phosphorylation regulated by isoproterenol, and analysis of phosphoamino acids demonstrated that the incorporation of [32P]phosphate was on phosphoserine. Incubation of adipocytes with isoproterenol in the presence of insulin or a phospho-oligosaccharide inhibited the phosphorylation and activation of this enzyme. The inhibitory effect of insulin on the phosphorylation of phospholipid methyltransferase was reversible, and it was mimicked by a phospho-oligosaccharide. The phospho-oligosaccharide was generated by hydrolysis of an isolated glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus. The insulin-like effect of this phospho-oligosaccharide on the phosphorylation of phospholipid methyltransferase was demonstrated in isolated adipocytes, and the effect was abolished by treatment of the phospho-oligosaccharide with 10% NH4OH, nitrous acid, or sodium periodate. These data suggest that in intact adipocytes the effect of insulin to inhibit the phosphorylation/activation of phospholipid methyltransferase is mediated by a phospho-oligosaccharide generated by a phosphatidylinositol-specific phospholipase C.

Adipose Tissue↗
PubMed1987

Partial structure of an insulin-sensitive glycophospholipid.

The structure of a glycophospholipid, which has been involved in insulin action, has been investigated using H35 cells and rat liver membranes. The present evidence indicates that this molecule contains a phosphatidyl-chiro-inositol moiety, glycosidically linked to a non-N-acetylated glucosamine. In addition, the polar head group of the lipid contains galactose, probably four residues, and a total number of three phosphates.

Amino Acid Sequence↗
PubMed1987

Identification of a novel insulin-sensitive glycophospholipid from H35 hepatoma cells.

This study identifies and partially characterizes an insulin-sensitive glycophospholipid in H35 hepatoma cells. The incorporation of [3H]glucosamine into cell lipids was investigated. A major labeled lipid was purified by sequential thin layer chromatography using first an acid followed by a basic solvent system. After hydrochloric acid hydrolysis and sugar analysis by thin layer chromatography, 80% of the radioactivity in the purified lipid was found to comigrate with glucosamine. H35 cells were prelabeled with [3H]glucosamine for either 4 or 24 h and treated with insulin causing a dose-dependent stimulation of turnover of the glycophospholipid which was detected within 1 min. The purified glycolipid was cleaved by nitrous acid deamination indicating that the glucosamine C-1 was linked to the lipid moiety through a glycosidic bond. [14C]Ethanolamine, [3H]inositol, and [3H]sorbitol were not incorporated into the purified glycolipid. The incorporation of various fatty acids into this glycolipid was also studied. [3H]Palmitate was found to be preferentially incorporated while myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid were either not incorporated or incorporated less than 10% of palmitate. The purified glycolipid labeled with [3H]palmitate was cleaved by treatment with phospholipase A2 but was resistant to mild alkali hydrolysis suggesting the presence of a 1-hexadecyl,2-palmitoyl-glyceryl moiety in the purified lipid. Treatment of labeled glycophospholipid with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus generated a compound migrating as 1-alkyl,2-acyl-glycerol and a polar head group with a size in the range from 800 to 3500. These findings coupled with the nitrous acid deamination demonstrate that glucosamine was covalently linked through a phosphodiester bond to the glyceryl moiety of the purified glycolipid. These findings suggest that insulin acts on this glycophospholipid by stimulating an insulin-sensitive phospholipase C. This unique glycophospholipid may play an important role in insulin action by serving as precursor of insulin-generated mediators.

Acetylation↗
PubMed1987

Stimulation of adipocyte phospholipid methyltransferase activity by phorbol 12-myristate 13-acetate. Differential regulation of phospholipid methyltransferase and lipolysis.

The present studies demonstrate that treatment of rat adipocytes with the phorbol ester phorbol 12-myristate 13-acetate (PMA) causes a dose-dependent stimulation of phospholipid methyltransferase (PLMT) activity. The stimulatory effect of PMA was not additive with that of isoprenaline or forskolin. The sensitivity of stimulated PLMT activity to inhibition by insulin, however, was decreased in the presence of PMA. The inhibitory effect of a maximal concentration of insulin on PLMT was unchanged in the presence of PMA. In contrast with the effects on PLMT, the lipolytic response of adipocytes to isoprenaline and the anti-lipolytic response to insulin were unaffected by PMA. These data suggest that PLMT is, whereas hormone-sensitive lipase is not, an intracellular target for the action of PMA. The lack of effect of PMA on lipolysis suggests that PLMT and hormone-sensitive lipase can be regulated by separate mechanisms. Furthermore, phorbol esters do not interfere in the regulatory pathway whereby insulin inhibits PMLT or lipolysis.

Adipose Tissue↗