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Biomedical subjects

G V Johnson

Publications and source records attributed to G V Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1988

Dose- and time-dependent hippocampal cholinergic lesions induced by ethylcholine mustard aziridinium ion: effects of nerve growth factor, GM1 ganglioside, and vitamin E.

Ethylcholine mustard aziridinium ion (ECMA) was infused intracerebroventricularly (icv) to rats followed by measurement of two markers of presynaptic cholinergic neurons, choline acetyltransferase (ChAT) activity and high affinity choline transport (HAChT), in the hippocampus and cortex. Bilateral icv administration of 1, 2, or 3 nmol of ECMA per side produced dose-dependent reductions in each marker in the hippocampus, but not in the cortex, one week after treatment. Reductions of 52% and 46% for ChAT activity and HAChT, respectively, were produced in the hippocampus by 3 nmol ECMA. Measurement of these two markers at different times after icv infusion of 2 nmol ECMA/ventricle revealed that the activity of ChAT was reduced to a greater extent than was HAChT in the hippocampus 1 day and 1, 2, 4, and 6 weeks after treatment. The maximal reductions of ChAT activity and HAChT (61% and 53%, respectively) were reached between 1 and 2 weeks after ECMA administration. There was no evidence of regeneration of either marker at 4 or 6 weeks posttreatment. HAChT and ChAT activity in the cortex were not altered at any of the posttreatment times examined. ECMA-induced deficits in hippocampal ChAT activity and HAChT were not counteracted by the following treatments: (i) daily administration of GM1 ganglioside (10 mg/kg, intraperitoneally (ip)) from the day prior to infusion of ECMA until 2 weeks later; (ii) daily administration of GM1 ganglioside between 2 and 6 weeks after infusion of ECMA; and (iii) icv administration of nerve growth factor (NGF) twice per week for 2 weeks after ECMA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effects of aluminum on agonist-induced alterations in cyclic AMP and cyclic GMP concentrations in rat brain regions in vivo.

Aluminum administered intracerebroventricularly (icv) (1 mumol) caused a significant decrease in cyclic GMP in the cortex after 3 days and a significant increase in cyclic AMP in the cortex after 14 days. Pilocarpine administration to untreated rats elevated cyclic AMP and cyclic GMP levels in specific brain regions. These pilocarpine-induced increases in the cyclic nucleotide concentrations were significantly attenuated in rats that had been treated with aluminum 14 days previously. Isoproterenol administration to control rats did not alter cyclic AMP concentrations; however, cyclic AMP concentrations were significantly reduced in the cortex of aluminum-treated animals after isoproterenol administration. Apomorphine elevated cyclic GMP concentrations in the cerebellum, hippocampus, and striatum of naive rats. This apomorphine-induced elevation in cyclic GMP concentrations was significantly potentiated in aluminum-treated rats. These results indicate that: (1) cyclic AMP synthesis in the cortex is most sensitive to aluminum; (2) agonist-stimulated changes in cyclic nucleotide concentrations can be altered by pretreatment with aluminum; (3) effects of aluminum persist for at least 2 weeks after central administration; and (4) modulation of the metabolism of cyclic nucleotides may play a role in the neurotoxic effects of aluminum.

Aluminum↗
PubMed1987

Aluminum alters cyclic AMP and cyclic GMP levels but not presynaptic cholinergic markers in rat brain in vivo.

Oral administration of 0.3% aluminum (citrate or sulfate salt) for 4 weeks significantly elevated adenosine 3',5'-monophosphate (cyclic AMP) levels in rat cortex, hippocampus, striatum and cerebellum. The largest effect observed was a 60% increase in cortical cyclic AMP levels in rats administered aluminum sulfate. The effects of orally administered aluminum on guanosine 3',5'-monophosphate (cyclic GMP) levels were less widespread. Dietary aluminum citrate only elevated cyclic GMP levels in the hippocampus, while aluminum sulfate caused significant increases in the cerebellum, hippocampus and striatum. Aluminum citrate administered i.c.v. (1 mumol, 2 weeks postadministration) elevated cyclic AMP levels in the cortex, but had no effect on cyclic GMP levels. Aluminum administered either orally or i.c.v. had no effect on in vivo acetylcholine levels. However, dietary aluminum citrate significantly reduced choline levels in the cortex, hippocampus and striatum. Aluminum administered i.c.v. had no effect on choline acetyltransferase activity or on high-affinity choline transport. These results indicate that: the metabolism of cyclic AMP and of cyclic GMP are more sensitive to aluminum than are presynaptic cholinergic processes; the metabolism of cyclic AMP is more sensitive to the effects of aluminum than is the metabolism of cyclic GMP; and cortical cAMP metabolism is the most sensitive to the presence of aluminum. Possible consequences of elevated levels of cyclic nucleotides induced by aluminum in the brain are proposed.

Administration, Oral↗
PubMed1987

Modulation of carbachol-stimulated inositol phospholipid hydrolysis in rat cerebral cortex.

Cortical slices from rat brain were used to study carbachol-stimulated inositol phospholipid hydrolysis. Omission of calcium during incubation of slices with [3H]inositol increased its incorporation into receptor-coupled phospholipids. Carbachol-stimulated hydrolysis of [3H]inositol phospholipids in slices was dose-dependent, was affected by the concentrations of calcium and lithium present and resulted in the accumulation of mostly [3H]inositol-1-phosphate. Incubation of slices with N-ethylmaleimide or a phorbol ester reduced the response to carbachol. Membranes prepared from cortical slices labeled with [3H]inositol retained the receptor-stimulated inositol phospholipid hydrolysis reaction. The basal rate of inositol phospholipid hydrolysis was higher than in slices and addition of carbachol further stimulated the process. Addition of GTP stimulated inositol phospholipid hydrolysis, suggesting the presence of a guanine nucleotide-binding protein coupled to phospholipase C. Carbachol and GTP-stimulated inositol phospholipid hydrolysis in membranes was detectable following a 3 min assay period. In contrast to slices, increased levels of inositol bisphosphate and inositol trisphosphate were detected following incubation of membranes with carbachol. These results demonstrate that agonist-responsive receptors are present in cortical membranes, that the receptors may be coupled to phosphatidylinositol 4, 5-bisphosphate, rather than phosphatidylinositol, hydrolysis and that a guanine nucleotide-binding protein may mediate the coupling of receptor activation to inositol phospholipid hydrolysis in brain.

Animals↗
PubMed1987

In vitro measurements of cholinergic activity in brain regions of hibernating ground squirrels.

High affinity choline uptake (HACU) and choline acetyltransferase (ChAT) activity were measured in synaptosomal P2 fractions from four brain regions in a mammalian hibernator, the golden-mantled ground squirrel. The 14CO2 evolution from [6-14C]glucose was also measured. Comparisons were made across the euthermic (not hibernating) and hibernation state in synaptosomes from cortex (CTX), preoptic area and hypothalamus (POA/HYP), olfactory apparatus (OA), and hippocampus (HPC). HACU was significantly increased in the CTX, from hibernating ground squirrels compared to euthermic animals. ChAT activity was significantly increased in the CTX and OA from hibernating animals. No change in either cholinergic marker was evident for the POA/HYP and HPC. The evolution of 14CO2 from [6-14C]glucose was generally, though not significantly, higher for synaptosomes from euthermic animals compared to hibernating animals. The results are discussed with reference to the involvement of cholinergic mechanisms in the control of hibernation.

Animals↗
PubMed1987

Management of severely displaced medial epicondyle fractures.

The role of surgical fixation of the displaced medial epicondyle fracture remains controversial. We reviewed 20 patients with displaced (mean 10 mm) fractures, all associated with elbow dislocation. All elbows were therefore unstable, and all were managed nonoperatively. Although all fractures healed by fibrous union, the functional results were good. Clinical and radiological tests were used to assess the static stability of the ulnar collateral ligament. All patients had demonstrable ulnar collateral ligament laxity, but only one patient had slight impairment of elbow function. None had late-onset ulnar neuritis. We have shown that even the severe forms of this injury can be managed without internal fixation.

Adolescent↗
PubMed1986

Aluminum increases cyclic AMP in rat cerebral cortex in vivo.

In vivo concentrations of cyclic AMP were elevated in the cerebral cortex of rats that were administered aluminum citrate by either of two routes; in the diet for one month or via a single intracerebroventricular injection two weeks prior to the experiment. These treatments did not alter the in vivo concentrations of cyclic GMP or acetylcholine. Aluminum treatment also altered the response of cortical cyclic AMP to the administration of pilocarpine and of apomorphine. It is proposed that the neurotoxicity of aluminum is not due to effects on acetylcholine but may be due to altered protein phosphorylation as a consequence of the chronic elevation of cyclic AMP.

Administration, Oral↗
PubMed1986

Aluminum impairs glucose utilization and cholinergic activity in rat brain in vitro.

The effects of AlCl3 on the production of 14CO2 from [U-14C]glucose and high affinity choline transport in rat brain synaptosomes, and on carbachol-stimulated hydrolysis of phosphoinositides in cortical slices were studied. In buffer containing either high K+ (50 mM) or low K+ (4.9 mM), 1 mM AlCl3 significantly depressed the synaptosomal production of 14CO2 from [U-14C]glucose to 54% and 44% of control rates, respectively. At a concentration of 0.1 mM, AlCl3 depressed the evolution of 14CO2 from [U-14C]glucose from synaptosomes incubated in the high K+ buffer, but did not significantly change 14CO2 production from synaptosomes in the low K+ buffer. Aluminum chloride also inhibited high affinity choline transport in synaptosomes prepared from rat cortex and from hippocampus with an IC50 of approximately 0.5 mM. In brain slices the carbachol-stimulated hydrolysis of phosphoinositides was inhibited by AlCl3 in a dose-dependent manner. One millimolar, 0.5 mM and 0.1 mM AlCl3 inhibited the carbachol-stimulated release of inositol phosphates by 75%, 44% and 33%, respectively. These same concentrations of AlCl3 inhibited the incorporation of [3H]inositol into phospholipids. This inhibitory effect was not dose-dependent as all 3 concentrations of AlCl3 inhibited phospholipid labelling to the same extent (27-37%). These results are discussed in relation to the in vivo neurotoxicity of aluminum.

Aluminum↗
PubMed1986

Increased aerobic glucose oxidation by cAMP in cultured regenerated skeletal myotubes.

Previous studies of embryonic rat skeletal muscle cultures suggested that there was a correlation between intracellular adenosine 3',5'-cyclic monophosphate (cAMP) concentration and activities of enzymes of oxidative energy metabolism. We investigated the ability of agents that elevate intracellular cAMP by three different mechanisms (activation of adenylate cyclase, inhibition of phosphodiesterase, and analogues) to alter not only the activities of 11 glycolytic and mitochondrial enzymes but also the rate of flux through aerobic glucose oxidation in intact myotubes derived from regenerating rat muscle satellite cells. The enzyme activities were not consistently altered when cAMP was elevated, with the exception of the electron transport enzyme, NADH cytochrome c reductase, whose activity was elevated by exposure of the myotubes to cholera toxin (110% of control), 3-isobutyl-1-methylxanthine (112%), caffeine (119%), and 8-bromoadenosine 3',5'-cyclic monophosphate (120%). The rate of flux of aerobic glucose oxidation was elevated by all agents (116-157% of control) except cholera toxin. This study allowed us to compare the metabolic characteristics of myotube cultures derived from satellite cells with those from embryonic muscle, from a previous study. Despite differences between these two models, together, the data present strong evidence that an increase in intracellular cAMP can cause an increase in oxidative capacity.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Quinacrine and 2-(4-phenylpiperidino)cyclohexanol (AH5183) inhibit acetylcholine release and synthesis in rat brain slices.

The effects of 2-(4-phenylpiperidino)cyclohexanol (AH5183) and quinacrine, two potent inhibitors of acetylcholine transport into vesicles isolated from Torpedo electric organ, were examined on acetylcholine metabolism in rat cortical slices. K+-stimulated acetylcholine release was reduced in a concentration-dependent manner by AH5183 and quinacrine, with IC50 values of 1 microM and 50 microM, respectively. Both drugs also reduced the synthesis of acetylcholine in slices and inhibited synaptosomal high affinity choline transport. The inhibitory effect of AH5183 appears to be directed primarily on the release of acetylcholine while the major effect of quinacrine is on the synthesis of acetylcholine. Examination of the subcellular distribution of acetylcholine in brain slices incubated in high K+ showed that AH5183 increased S3 (cytoplasmic) acetylcholine levels but did not alter P3 (vesicular) acetylcholine levels. P3 acetylcholine levels were reduced by AH5183 in a low K+ media while the S3 acetylcholine levels were the same as controls. These results are consistent with the concept that there is a small, active, highly labile fraction of vesicles that are the source of the released acetylcholine and that the loading of these vesicles is blocked by AH5183.

Acetylcholine↗
PubMed1985

Halothane-induced alterations of glucose and pyruvate metabolism in rat cerebra synaptosomes.

Synaptosomes isolated from rat cerebra were used to study the effects of the inhalational anesthetic, halothane, on cholinergic processes. To identify possible mechanisms responsible for the depression of acetylcholine synthesis, we examined the effects of halothane on precursor metabolite metabolism involved with supplying the cytosol with acetyl-CoA for acetylcholine synthesis. Three percent halothane/air (vol/vol) depressed 14CO2 evolution from labeled pyruvate and glucose. Steady-state 14CO2 evolution from [1-14C]glucose was depressed 84% by halothane, while 14CO2 evolution from [6-14C]glucose and [3,4-14C]glucose was decreased 67 and 52%, respectively, when compared with control conditions. Halothane inhibited the activities of both pyruvate dehydrogenase (14% depression) and ATP-citrate lyase (32% depression). Total synaptosomal acetyl-CoA concentrations were unaffected by halothane. Three percent halothane/air (vol/vol) caused a 77% increase in medium glucose depletion rate from 1.38 nmol (mg protein)-1 min-1 to 2.44 nmol (mg protein)-1 min-1. Production of lactate by the synaptosomes in the presence of halothane increased by 231% from a control rate of 1.44 nmol (mg protein)-1 min-1 to 4.77 nmol (mg protein)-1 min-1. Lactate production rate from pyruvate was also enhanced by 56% in the presence of halothane. These data lend support to the concept that the NAD+/NADH potential may be involved in the halothane-induced depression of acetylcholine synthesis.

ATP Citrate (pro-S)-Lyase↗
PubMed1985

Choline uptake, acetylcholine synthesis and release, and halothane effects in synaptosomes.

Synaptosomes isolated from rat cerebra were used as a model to study the effects of halothane on choline uptake and acetylcholine synthesis and release processes. Synaptosomes are membrane-bound particles that are formed by gentle disruption of brain tissue. These particles include the presynapse, cleft, portions of postsynaptic membrane, and all other components contained in brain nerve terminals necessary for neurotransmitter synthesis, storage, and release. Halothane (3% in air, vol/vol) caused a "competitive-like" inhibition of choline uptake in synaptosomes but had no effect on the enzymatic activity of choline acetyl-transferase (ChAT). Three percent halothane depressed synaptosomal acetylcholine (ACh) synthesis by 86% while ACh release from synaptosomes was inhibited 50%. It is suggested that halothane inhibits ACh synthesis by directly interfering with the carrier-mediated transport system of choline. Since halothane also inhibits ACh release, as well as choline uptake, it is probable that the anesthetic is acting upon more than one site in these cholinergic nerve terminals. These data require an interpretive evaluation that cannot fit the "unitary" hypothesis as the mechanism of action of general anesthetics.

Acetylcholine↗
PubMed1966

A Cobalt Requirement for Symbiotic Growth of Azolla filiculoides in the Absence of Combined Nitrogen.

Cobalt was shown to be essential for the symbiotic growth of Azolla filiculoides and Anabacna azollac in the absence of fixed nitrogen. Addition of 0.01 mug/liter cobalt resulted in large increases in yield, chlorophyll content and nitrogen fixation as compared to control cultures without cobalt. Cobalt was not required for the growth of Azolla when nitrate nitrogen was supplied. The number of Anabaena azollae cells in the fronds of Azolla appeared to be decreased by ommission of cobalt from the culture medium containing nitrate nitrogen. It is concluded that cobalt is essential for the symbiotic growth of Azolla in the absence of combined nitrogen and it is suggested that the cobalt requirement is associated with the growth of Anabaena azollae.

Journal Article↗
PubMed1966

Enzymes of the glyoxylate cycle in rhizobia and nodules of legumes.

The relatively high level of fatty acids in soybean nodules and rhizobia from soybean nodules suggested that the glyoxylate cycle might have a role in nodule metabolism. Several species of rhizobia in pure culture were found to have malate synthetase activity when grown on a number of different carbon sources. Significant isocitrate lyase activity was induced when oleate, which presumably may act as an acetyl CoA precursor, was utilized as the principle carbon source. Malate synthetase was active in extracts of rhizobia from nodules of bush bean (Phaseolus vulgaris L.), cowpea (Vigna sinensis L.), lupine (Lupinus angustifolius L.) and soybean (Glycine max L. Merr.). Activity of malate synthetase was, however, barely detectable in rhizobia from alfalfa (Medicago sativa L.), red clover (Trifolium pratense L.) and pea (Pisum sativum L.) nodules. Appreciable isocitrate lyase activity was not detected in rhizobia from nodules nor was it induced by depletion of endogenous substrates by incubation of excised bush bean nodules. Although rhizobia has the potential for the formation of the key enzymes of the glyoxylate cycle, the absence of isocitrate lyase activity in bacteria isolated from nodules indicated that the glyoxylate cycle does not operate in the symbiotic growth of rhizobia and that the observed high content of fatty acids in nodules and nodule bacteria probably is related to a structural role.

Journal Article↗