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Biomedical subjects

R C Baker

Publications and source records attributed to R C Baker.

122 records · Page 7Linked to original sources
PubMedDate not supplied

Phosphatidylethanol stimulates calcium-dependent cytosolic phospholipase A(2) activity of a macrophage cell line (RAW 264.7).

The synthesis of inflammation mediators produced from arachidonic acid is regulated primarily by the cellular concentration of free arachidonic acid. Since intracellular arachidonic acid is almost totally present as phospholipid esters, the concentration of intracellular arachidonic acid is primarily dependent on the balance between the release of arachidonic acid from membrane phospholipids and the uptake of arachidonic acid into membrane phospholipids. Cytosolic phospholipase A(2) is a calciumdependent enzyme that catalyzes the stimulus-coupled hydrolysis of arachidonic acid from membrane phospholipids. Following exposure of macrophages to various foreign or endogenous stimulants, cytosolic phospholipase A(2) is activated. Treatment with these compounds may also stimulate phospholipase D activity, and, in the presence of ethanol, phospholipase D catalyzes the synthesis of phosphatidylethanol. A cell-free system was used to evaluate the effect of phosphatidylethanol on cytosolic phospholipase A(2) activity. Phosphatidylethanol (0.5 microM) added to 1-stearoyl-2-[(3)H]-arachidonoyl-sn-glycero-3-phosphocholine vesicles stimulated cytosolic phospholipase A(2) activity. However, high concentrations (20-100 microM) of phosphatidylethanol inhibited cytosolic phospholipase A(2) activity. Phosphatidic acid, the normal phospholipase D product, also stimulated cytosolic phospholipase A(2) activity at 0.5 microM, but had an inhibitory effect on cytosolic phospholipase A(2) activity at concentrations of 50 and 100 microM. Ethanol (20-200 mM), the precursor of phosphatidylethanol, added directly to the assay did not alter cytosolic phospholipase A(2) activity. These results suggest that phosphatidylethanol alters the physical properties of the substrate, and at lower concentrations of anionic phospholipids the substrate is more susceptible to hydrolysis. However, at high concentrations, phosphatidylethanol either reverses the alterations in physical properties of the substrate or phosphatidylethanol may be competing as the substrate. Both interactions may result in lower cytosolic phospholipase A(2) activity.

Animals↗
PubMedDate not supplied

Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.

Acetylcholine↗
PubMedDate not supplied

Effects of single or repeated dermal exposure to methyl parathion on behavior and blood cholinesterase activity in rats.

The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD(50)) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1-3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory.

Administration, Cutaneous↗
PubMedDate not supplied

Differential CNS sensitivity to PIA and theophylline in long-sleep and short-sleep mice.

Long sleep (LS) and short sleep (SS) mice have a differential sensitivity to the behavioral actions of an adenosine agonist, R-phenylisopropyl-adenosine (PIA) that parallels their differential sensitivity to the soporific effects of ethanol. In addition to being more sensitive to the sedative effects of PIA, LS mice also show a greater excitatory response to an adenosine antagonist, theophylline (1,3-dimethylxanthine). The brain concentrations of both PIA and theophylline following drug administration do not differ in LS and SS mice, suggesting that the central nervous system of the LS mouse is more sensitive to both adenosine receptor agonists and antagonists. However, LS and SS mice made tolerant to ethanol did not show cross-tolerance to PIA. These results suggest that genetic selection for ethanol sensitivity has resulted in a parallel CNS sensitivity to purinergic drugs, but that acute alterations in sensitivity due to the development of ethanol tolerance do not involve changes in purinergic systems.

Adenosine↗
PubMedDate not supplied

Ceramide composition of whole brain synaptosomal gangliosides from mice genetically bred for divergent ethanol sensitivities.

A comparison of the two major ceramide molecular species (d18:1-C18:0 and d20:1-C18:0) of synaptosomal gangliosides GM1, GD1a+GT1a, GD1b, GT1b, revealed a difference between the ceramide composition of ethanol-sensitive LS and ethanol-insensitive SS whole brain synaptosomal gangliosides. In all comparisons, the ratio of the two major molecular species, (d18:1-C18:0/d20:1-C18:0) was less for LS than for SS mice.

Animals↗
PubMedDate not supplied

Meningitis complicating acute bacteremic facial cellulitis.

Eighty cases of acute bacteremic facial cellulitis, 34 buccal and 46 preseptal, were reviewed from the years 1977 through 1982. The epidemiology, clinical presentation, laboratory parameters and course of cellulitis in these two locations were similar. The white blood cell count was over 15,000 in three-fourths of the patients. Haemophilus influenzae type b was cultured from the blood of 67 patients, Streptococcus pneumoniae from 12 and Streptococcus pyogenes from 1. Seven patients had culture-proved meningitis, six with H. influenzae type b and one with S. pneumoniae. Five of these patients had sparse clinical evidence of meningitis, and three of these had meningitis apparent by culture only. We conclude that meningitis may occur in association with acute bacteremic facial cellulitis and may be inapparent both clinically and by initial laboratory examination. We suggest aggressive initial evaluation and treatment of these infants pending culture results.

Acute Disease↗
PubMedDate not supplied

Initial sensitivity of rat inbred strains to acute alcohol.

The ethanol sensitivity of eight inbred strains and one heterogeneous stock of rats has been determined by the assessment of "sleep time" and blood alcohol levels upon awakening. In addition, levels of liver alcohol and aldehyde dehydrogenases and phenobarbital-inducible aldehyde dehydrogenase were determined. These data are presented as baseline values for correlation and selective breeding studies using the heterogeneous rats.

Alcoholism↗
PubMedDate not supplied

Ethanol tolerance of cerebellar purkinje neurons from selectively outbred mouse lines: in vivo and in vitro electrophysiological investigations.

The electrophysiological activity of cerebellar Purkinje neurons was characterized in long sleep (LS: ethanol sensitive) and short sleep (SS: ethanol insensitive) mice made tolerant to ethanol. After 1 to 4 weeks of feeding on a liquid ethanol diet, mice of both lines were less sensitive to the sedative and ataxic effects of parenteral ethanol than were controls. In addition, cerebellar Purkinje cells in ethanol-fed LS and SS mice were less responsive than the controls to the depressant effects of ethanol applied via bath perfusion in vitro and via local pressure ejection application in vivo. Tolerance to the electrophysiological effects of ethanol were already apparent after 7 to 9 days on the ethanol diet, and the degree of tolerance did not increase significantly in either mouse line fed ethanol for an additional 1-3 weeks. Finally, the differences in ethanol sensitivities of naive mice (LS greater than SS) were maintained following the development of tolerance. We conclude that tolerance to both the cellular and behavioral depressant effects of ethanol can be observed after chronic feeding with ethanol in LS and SS mice, and that there are no significant differences in the degree of tolerance developed by these mice. In addition, our data suggest that the inherited differences in ethanol sensitivity between LS and SS mice, and the changes in ethanol sensitivity which occur in these mice with chronic exposure to this depressant agent, are mediated by different mechanisms.

Action Potentials↗
PubMedDate not supplied

Pathogenesis of Salmonella enteritidis infection in laying chickens. I. Studies on egg transmission, clinical signs, fecal shedding, and serologic responses.

Laying hens were inoculated orally, intracloacally (IC), or intravenously (IV) with Salmonella enteritidis phage type 8 isolates from a human (E700-87) eggs (Y-8P2), or the ovary of a hen (27A). Oral or IV inoculation of 2 x 10(8) to 4 x 10(8) colony-forming units (CFU) of E700-87 caused depression, anorexia, reduced egg production, diarrhea, and some mortality. Lower doses resulted in milder clinical signs. S. enteritidis was cultured from the shells of a few eggs but not from egg contents. Fecal shedding persisted for up to 6 weeks in some birds. Isolate Y-8P2 (10(6) CFU) also caused anorexia, diarrhea, and a drop in egg production. Hens inoculated orally or IC were less severely affected than those inoculated IV. Fecal shedding was intermittent and lasted up to 18 days. Eggshells from the IC-inoculated birds had the highest rate of contamination, and S. enteritidis was isolated from the albumen of 11 and yolk of three of 726 eggs. Oral inoculation of 10(6) CFU of isolate 27A resulted in a bacteremic infection with seeding of the liver, spleen, peritoneum, ovule, and oviduct. However, the birds remained clinically normal with normal egg production. S. enteritidis was cultured from the yolk and albumen of a small number of eggs until 11 days postinfection. Antigen prepared from S. enteritidis detected antibody in more sera than did commercially available S. pullorum antigen in agglutination tests.

Animals↗