Biomedical subjects

M E Kelly

Publications and source records attributed to M E Kelly.

At least 37 records · Page 2Linked to original sources

PubMed1998

Identification of a novel Lymantria dispar nucleopolyhedrovirus mutant that exhibits abnormal polyhedron formation and virion occlusion.

In previous studies on the formation of Lymantria dispar nuclear polyhedrosis virus (LdMNPV) few polyhedra (FP) mutants, several polyhedron formation mutants (PFM) were identified that appeared to be unique. These viral mutants are being characterized to investigate the processes of polyhedron formation and virion occlusion. LdMNPV isolate PFM-1 is one of these mutants, and is described in this report. Genetic techniques were used to determine if isolate PFM-1 contained a mutation in the polyhedrin or 25K FP gene. Wild-type viruses were recovered after coinfection of Ld652Y cells with isolate PFM-1 and a FP mutant, and with isolates PFM-1 and PFM-C (isolate PFM-C contains a mutation in the polyhedrin gene). These viruses were analyzed by genomic restriction endonuclease digestion and found to be chimeras of the original PFMs used in the coinfections. Marker rescue studies mapped the mutation in isolate PFM-1 to a genomic region that does not include the polyhedrin or 25K FP genes. Isolate PFM-1 produced approximately 14-fold fewer polyhedra than LdMNPV isolate A21-MPV, an isolate that produces wild-type levels of polyhedra, and approximately 2-fold more polyhedra compared to the FP isolate 122-2. Polyhedra generated by isolate PFM-1 were normal in size and shape but contained very few viral nucleocapsids. The same amount of budded virus (BV) was released from cells infected with isolates PFM-1 and A21-MPV. In contrast, isolate 122-2 yielded significantly more BV than isolates PFM-1 and A21-MPV.

Animals↗

PubMed1998

Activation of a nonspecific cation current in rat cultured retinal pigment epithelial cells: involvement of a G(alpha i) subunit protein and the mitogen-activated protein kinase signalling pathway.

1. Whole-cell patch-clamp recording techniques were used to investigate the G protein subtype and related signalling molecules involved in activation of a nonspecific cation (NSC) current in rat cultured retinal pigment epithelial (RPE) cells. 2. Under control conditions, in 130 mM NaCl with K+ aspartate in the pipette, cytosolic dialysis with guanosine-5'-O-(3-triphosphate) (GTPgammaS, 0.1 mM) activated a large non-inactivating NSC current in 80% of the cells recorded from. 3. Loading RPE cells with antibodies (10 microg-ml(-1)) against the alpha subunit of all PTX-sensitive G proteins (G(alpha i/o/t/z)) reduced NSC current activation to 11%, while loading RPE cells with antibodies directed specifically against the alpha subunits of the Gi subclass (G(alpha i-3)) completely abolished current activation. In RPE cells loaded with anti-G(alpha s) activation of the NSC current was unaffected. 4. Investigation of the potential downstream mediators in the G(alpha i) NSC channel pathway revealed that activation of the cation conductance was unaffected by treatment of RPE cells with the selective protein kinase C inhibitor GF 109203X (3 microM) or the selective CaM kinase II inhibitor KN-93 (50 microM). However, NSC current activation was delayed and the current amplitude reduced in the presence of the nonselective kinase inhibitor H-7 (100 microM) or the selective inhibitor of MAPKK (MEK) activation, PD 98059 (50 microM). 5. In the absence of GTPgammaS, the NSC current was not activated by superfusion of the cells with the cyclic GMP kinase activator dibutyryl-cyclic GMP or with the adenylate cyclase activator forskolin. 6. These results support the involvement of a G protein of the G(alpha i) subclass in the activation of a NSC current in rat RPE cells, and suggest a potential modulatory role for MAP kinase-dependent phosphorylation in current regulation.

Animals↗

PubMed1998

Actions of substance P on membrane potential and ionic currents in guinea pig stellate ganglion neurons.

Neuropeptides are known to modulate the excitability of mammalian sympathetic neurons by their actions on various types of K+ and Ca2+ channels. We used whole cell patch-clamp recording methods to study the actions of substance P (SP) on dissociated adult guinea pig stellate ganglion (SG) neurons. Under current-clamp conditions, SG neurons exhibited overshooting action potentials followed by afterhyperpolarizations (AHP). The K+ channel blocker tetraethylammonium (1 mM), the Ca2+ channel blocker Cd2+ (0.1-0.2 mM), and SP (500 nM) depolarized SG neurons, decreased the AHP amplitude, and increased the action potential duration. In the presence of Cd2+, the effect of SP on membrane potential and AHP was reduced. Under voltage-clamp conditions, several different K+ currents were observed, including a transient outward K+ conductance and a delayed rectifier outward K+ current (IK) consisting of Ca(2+)-sensitive [IK(Ca)] and Ca(2+)-insensitive components. SP (500 nM) inhibited IK. Pretreatment with Cd2+ (20-200 microM) or the high-voltage-activated Ca2+ channel blocker omega-conotoxin (10 microM) blocked SP's inhibitory effects on IK. This suggests that SP reduces IK primarily through the inhibition of IK(Ca) and that this may occur, in part, via a reduction of Ca2+ influx through voltage-dependent Ca2+ channels. SP's actions on IK were mediated by a pertussis toxin-insensitive G protein(s) coupled to NK1 tachykinin receptors. Furthermore, we have confirmed that 500 nM SP reduced an inward Cd(2+)- and omega-conotoxin-sensitive Ba2+ current in SG neurons. Thus the actions of SP on IK(Ca) may be due in part to a reduction in Ca2+ influx occurring via N-type Ca2+ channels. This study presents the first description of ionic currents in mammalian SG neurons and demonstrates that SP may modulate excitability in SG neurons via inhibitory actions on K+ and Ca2+ currents.

Animals↗

PubMed1998

Acute effects of lead, steel, tungsten-iron, and tungsten-polymer shot administered to game-farm mallards.

Sixteen-bird groups (sexes equal) of adult mallards (Anas platyrhynchos) were orally dosed with eight #4 steel short, eight #4 lead shot, eight BB-size tungsten-iron shot, eight BB-size tungsten-polymer shot, or were sham-dosed and maintained for 30 days (16 January 1996 to 15 February 1996). Half of the lead-dosed ducks (five males, three females) died during the study, whereas no ducks died in the other dosage groups. For lead-dosed ducks, hematocrit and hemoglobin concentration were decreased on day 15 of the trial, but not on day 30. Delta aminolevulinic acid dehydratase activity in lead-dosed ducks was lower when compared to steel-dosed ducks only. Plasma activities of selected enzymes were elevated in lead-dosed ducks when compared to enzyme activities of ducks in the other groups. For lead-dosed ducks, relative heart, liver, and kidney weights increased in comparison to relative weights of those organs of ducks in other groups. Histology of tissues indicated that renal nephrosis accompanied by biliary stasis was present in the eight lead-dosed ducks that died. For the eight lead-dosed ducks that survived, six had mild to severe biliary stasis. Mild biliary stasis was noted in five tungsten-iron dosed ducks and three tungsten-polymer dosed ducks. Amounts of lead in the femur, liver, and kidneys were higher in lead-dosed ducks than in ducks of the other four groups. Small amounts of tungsten were detected in the femur and kidneys of two tungsten-polymer dosed ducks. Higher concentrations of tungsten were detected in the femur, liver, and kidneys of all tungsten-iron dosed ducks. The rate of shot erosion was highest (80%) for the tungsten-polymer shot, followed by tungsten-iron (55%), lead (50%), and steel shot (33%). Results indicated that tungsten-iron or tungsten-polymer shot (8 shot/duck) orally administered to mallards did not adversely affect them during a 30-day trial.

Alanine Transaminase↗

PubMed1997

The effect of several putative cognition enhancers on a water maze acquisition deficit produced by pCPA + scopolamine combination treatment.

A combined treatment of a 3-day regimen of pCPA and low-dose scopolamine produced a significant deficit in the acquisition of a water maze task, which has been suggested as a model for the cognitive deficits of Alzheimer's disease. The putative cognition enhancers oxotremorine, captopril, ondansetron, and tacrine were used in attempts to alleviate the water maze impairment. The effects of oxotremorine were difficult to determine due to nonspecific motor effects causing alterations in swimming speed. No evidence for cognition-enhancing properties of captopril was found. Ondansetron showed a cognition-enhancing effect on one of 4 days, but only at a relatively high dose (1 mg/kg i.p.). Tacrine, however, alleviated the pCPA + scopolamine-induced cognitive deficit. This study may thus provide evidence for the usefulness of tacrine in treating spatial deficits in dementia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Buspirone fails to affect cocaine-induced conditioned place preference in the mouse.

The conditioned place preference (CPP) procedure was employed to examine the effects of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist, buspirone, on cocaine reinforcement. Cocaine (5.0 mg/kg, S.C., 30 min) produced a significant place preference whereas buspirone (0.5-2.0 mg/kg, I.P., 30 min) per se failed to induce a CPP. Buspirone pretreatment (0.5-2.0 mg/kg, I.P.) 30 min prior to cocaine (5.0 mg/kg, S.C., 30 min) conditioning had no effect on the acquisition of cocaine-induced CPP. Pretreatment with buspirone on the postconditioning test day also failed to affect the expression of an already established place preference response to cocaine. These results demonstrate an inability of buspirone to block both the acquisition and the expression of cocaine reward, as modeled in the CPP paradigm.

Animals↗

PubMed1997

Mammalian retinal pigment epithelial cells in vitro respond to the neurokines ciliary neurotrophic factor and leukemia inhibitory factor.

We examined whether primary cultures of rat retinal pigment epithelial (RPE) cells and RPE cells of an immortalized rat cell line, BPEI-1, would be responsive to the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF), which are known to be potent trophic factors for neuronal cells. Primary RPE cell cultures were characterized by indirect immunofluorescence and exhibited positive immunoreactivity for RET-PE2, a monoclonal antibody that recognizes RPE cells, and for the intermediate filaments cytokeratin and vimentin. The survival of cultured RPE cells in serum-free defined medium in the presence of CNTF or LIF was investigated during a 0- to 5-day period. Both CNTF and LIF, at concentrations of 1-50 ng/mL (4-200 pM), markedly enhanced RPE cell survival. Bromodeoxyuridine labelling of RPE cells revealed an increased mitotic activity in cell cultures treated with either CNTF or LIF in comparison to untreated serum-free cultures. Increases in cell survival and proliferation after neurokine treatment were also observed with the BPEI-1 cell line. However, in comparison to the primary RPE cultures, LIF was more effective than CNTF in promoting survival of the cell line over a 5-day treatment period. These studies demonstrate that the neurokines CNTF and LIF are potent trophic factors for mammalian RPE cells in vitro and may serve as candidate therapeutic agents in degenerative conditions that affect the retina and RPE.

Animals↗

PubMed1997

The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents.

The anxiolytic potential of the selective sigma2 ligand 1-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3H),4-piperidine] [corrected] (Lu 28-179) was assessed in various animal models of anxiety in rodents. Lu 28-179 facilitated the exploratory behavior of mice and rats in the black and white two-compartment box over a large dose range. In the rat, the minimal effective dose (MED) was 0.18 nmol/kg (0.1 microg/kg), and in the mouse, the MED was 0.00018 nmol/kg (0.1 ng/kg). The anxiolytic-like effect was maintained after treatment with 1 microg/kg/day for up to 14 days, and no anxiogenic-like effects were seen upon withdrawal from repeated treatment. Lu 28-179 increased the time that pairs of rats spent in active social interaction (unfamiliar high-light conditions), MED = 0.1 ng/kg. Daily treatment with Lu 28-179 (1.8 nmol/kg = 1 microg/kg/day) for up to 4 weeks increased the social interaction time significantly compared with controls, and no anxiogenic-like effects were seen upon withdrawal. Furthermore, Lu 28-179 reversed shock-induced suppression of drinking in the rat (MED = 18,000 nmol/kg = 10 mg/kg). Lu 28-179 did not inhibit footshock-induced ultrasonic vocalization in the rat or isolation-induced aggressive behavior in the mouse. Lu 28-179 was over 100 times more potent than diazepam in the rat and mouse black and white test box and the rat social interaction test, whereas the potency of Lu 28-179 was comparable to that of lorazepam in reversal of shock-induced suppression of drinking. Lu 28-179 neither induced sedation nor impaired motor coordination, even at high doses (70,000 nmol/kg = 40 mg/kg). In conclusion, Lu 28-179 exerts potent and long-lasting anxiolytic-like effects in rodents without inducing sedation and withdrawal anxiogenesis.

Animals↗

PubMed1996

Efferent projections of the anterior perirhinal cortex in the rat.

Because convulsive seizures develop very rapidly from kindling sites in the anterior perirhinal cortex, we studied perirhinal efferents by using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PhAL). PhAL injections into the anterior perirhinal cortex labelled a prominent network of fibers within the frontal cortex that was most dense within layers I and II and layer VI. As individual PhAL injection sites within the perirhinal cortex were restricted to one or two adjacent laminae, we were able to determine that layer V was the main source of the perirhinofrontal projection. This was confirmed by frontal cortex injections of the retrograde tracer Fluorogold (FG). Other cortical areas with densely labelled fibers following perirhinal PhAL injections included the agranular insular, infralimbic, orbital, parietal, and entorhinal cortices. Moderate to mild fiber labelling was also noted in the posterior piriform, temporal and occipital cortices, and the claustrum. Subcortical labelling was seen in the nucleus accumbens; fundus striati; basal and lateral amygdala nuclei; the "acoustic thalamus"; and the central grey. Several of these cortical and subcortical projections were bilateral. The different laminar origin of these perirhinal efferents is discussed. These results confirmed our prediction of extensive direct projections from the anterior perirhinal cortex to the frontal cortex in the rat. The significance of this projection is discussed with special reference to the anatomical basis of convulsive limbic seizures.

Animals↗

PubMed1996

G protein-mediated activation of a nonspecific cation current in cultured rat retinal pigment epithelial cells.

We used whole-cell patch-clamp recording techniques to investigate G protein-activated currents in cultured rat retinal pigment epithelial (RPE) cells. Using 140 mM KCl intracellular and 130 mM NaCl extracellular solutions, rat RPE cells possessed both inward and outward K+ currents. Upon addition of the nonhydrolyzable guanine triphosphate analogue, guanosine-5'-O-(3-thiophosphate) (GTPgammaS, 0.1 mM), to the recording electrode, a nonspecific cation (NSC) current was elicited. The NSC current had a mean reversal potential of +5.7 mV in 130 mm extracellular NaCl with Cs+-aspartate in the pipette, and was not affected by alterations in the extracellular Ca2+ or Cl- concentration. The GTPgammaS-activated current was found to be permeable to several monovalent cations (K+, Na+, choline, TRIS, and NMDG). Addition of fluoroaluminate, an activator of large molecular weight heterotrimeric GTP-binding proteins (G proteins), to the intracellular recording solution activated the NSC current. The G protein involved was pertussis toxin (PTX)-sensitive, since GTPgammaS failed to activate the NSC current in cells pretreated with PTX. Further investigation of second messenger molecules suggested that activation of the NSC current was not affected by alterations in intracellular Ca2+ or ATP. From these results, we conclude that a G protein-regulated NSC current is present in rat RPE cells. Activation of the NSC current may sufficiently depolarize RPE cells to activate outward K+ currents. This would provide a mechanism by which these cells could rid themselves of accumulated K+.

Adenosine Triphosphate↗

PubMed1996

Acute and chronic arecoline: effects on a scopolamine-induced deficit in complex maze learning.

These studies tested the effect of arecoline, a nonselective muscarinic agonist, administered either acutely or by chronic peripheral infusion via osmotic minipumps, on a scopolamine-induced deficit in a Stone (14 unit) T-maze task in rats. Scopolamine alone (0.125-1.0 mg/kg, IP) dose-dependently impaired maze acquisition, increasing maze run-times and to a lesser extent, the number of errors committed. Neither acute administration of arecoline (5.0 and 10.0 mg/kg, IP), when tested against a deficit induced by scopolamine (0.25 mg/kg, IP), nor chronic arecoline administration (30 and 50 mg/kg per 24 h), when tested against a deficit induced by scopolamine (0.5 mg/kg), were able to ameliorate the decrements in maze performance. In fact, the higher dose of arecoline (50 mg/kg per 24 h) infused over 10 days potentiated the scopolamine-induced deficit, with respect to latency. These data indicate that dose selection is of great importance when employing arecoline in tests of learning and memory and that the influence of the method of administration of arecoline on the behavioural outcome warrants further study.

Animals↗

PubMed1996

Selective effects of 8-OH-DPAT on social competition in the rat.

Previous research has demonstrated that dominant-subordinate relationships measured in small groups of rats competing for access to palatable food or fluids can be disrupted by both anxiolytic and anxiogenic drugs, and it has been proposed as a possible animal model of anxiety. The present study investigated the effects of the selective 5-HT1A agonist 8-OH-DPAT on the rank order of triads of rats measured in terms of access to sweetened milk. The effect of 8-OH-DPAT on locomotor activity and intake of sweetened milk was also determined. 8-OH-DPAT (25 and 37.5 micrograms/kg) significantly increased the subordinate animals position in the social hierarchy without effect on the individual intakes of sweetened milk or locomotor activity. The same doses administered to dominant animals had no effect on any of the parameters measured. The 8-OH-DPAT-induced increase in social competition in subordinate rats was dissociable from effects on feeding behavior and locomotor activity. The results from this study provide further evidence that social competition in groups of rats may represent a model that can be used to detect drugs acting via receptor mechanisms believed to be implicated in anxiety.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Combined pCPA and muscarinic antagonist treatment produces a deficit in rat water maze acquisition.

A 3-day treatment with p-chlorophenylalanine (pCPA, 100 mg/kg/day) produced a significant decrease (63-89%) in 5-HT levels in both the hippocampus and the cortex of rats, while noradrenaline, adrenaline, and dopamine levels were unaffected. Treatment with pCPA alone did not affect the acquisition of a spatial learning task in the water maze. Treatment with low doses of either scopolamine (0.25 mg/kg) or atropine (10 mg/kg) was also insufficient to cause a significant impairment of water maze acquisition. However, a combined treatment of a 3-day pCPA regimen with the low dose of atropine or scopolamine produced a significant deficit in the acquisition of a water maze task.

Animals↗

PubMed1996

Seizure-induced differential expression of messenger RNAs for neurotrophins and their receptors in genetically fast and slow kindling rats.

Levels of messenger RNAs for brain-derived neurotrophic factor, nerve growth factor and neurotrophin-3, and their high-affinity receptors, TrkB and TrkC, were analysed in the brains of genetically fast and slow kindling rats using in situ hybridization. Basal expression of neurotrophins and Trk messenger RNAs in the hippocampal formation, amygdala, frontoparietal and piriform cortices did not differ between the two strains. At 2 h after the third generalized grade 5 seizure, induced by kindling stimulations in the amygdala, increased expression of brain-derived neurotrophic factor messenger RNA was detected in the dentate gyrus granule cell layer, amygdala, frontoparietal and piriform cortices of the fast kindlers. Similar seizure-evoked increases of brain-derived neurotrophic factor messenger RNA levels were also observed in the amygdala and piriform cortex of slow kindlers. However, in these animals, brain-derived neurotrophic factor messenger RNA expression was not significantly altered by the seizures in the dentate gyrus granule cell layer and frontoparietal cortex. Furthermore, the seizure-induced increase of nerve growth factor, TrkB and TrkC messenger RNAs and decrease of neurotrophin-3 messenger RNA levels in the dentate gyrus granule cell layer was only observed in fast, but not in slow, kindlers. The neurotrophins are believed to regulate synaptic plasticity and efficacy and to facilitate long-term potentiation and kindling epileptogenesis. The present data suggest that the slow and fast kindling rates in the two strains studied here might partly be due to differences in seizure-evoked neurotrophin and Trk synthesis.

Amygdala↗

PubMed1996

Differential sensitivity of various temporal lobe structures in the rat to kindling and status epilepticus induction.

Using focal brain stimulation (kindling), discrete seizures can be triggered from many neuroanatomic sites with varying degrees of facility. From several of these sites, protracted seizures or status epilepticus (SE) also can be triggered. To date, no comparison has been made between different brain sites in their sensitivity both to kindling and to SE development. In this report, we have compared the kindling profiles of three amygdala nuclei, namely the basal (BL), central (CE), and medial (ME) nuclei, to the adjacent piriform (PIR) and perirhinal (PRH) cortices. In addition, three weeks following kindling, the susceptibility of each kindled site to status epilepticus (SE) was assessed by exposing the site to 60 min of electrical stimulation. We observed that (a) during the course of daily kindling, the afterdischarge threshold dropped progressively and significantly in all structures, (b) the rate of kindling in the PRH and PIR cortices and the CE amygdala was significantly faster than either the BL or ME amygdala, (c) when discrete convulsions were triggered, the latency to forelimb clonus in the PRH cortex and CE amygdala was significantly shorter than the other three structures, and (d) despite being slower to kindle than most other sites, stimulation of the BL nucleus most readily triggered SE. The kindling data suggest that discharges triggered from the PRH and CE more readily access motor systems supporting limbic convulsions than discharges triggered from the BL, ME nuclei or the PIR cortex. On the other hand, the SE data indicate that the mechanisms and circuits associated with the development of discrete kindled seizures are not identical to those associated with the induction of limbic SE.

Amygdala↗

PubMed1996

Perirhinal cortex involvement in limbic kindled seizures.

Investigations into the anatomical substrate of temporal lobe epilepsy have yielded a number of important observations regarding the involvement of the piriform and perirhinal cortical areas in temporal lobe seizure propagation. Although early reports indirectly suggested that the circuits of the piriform cortex might act as a critical conduit for limbic seizure discharges to access motor systems, recent reports more strongly implicate the perirhinal cortex in this process. In the following report, we provide a brief summary of the earlier work involving the piriform cortex and its potential involvement in kindled limbic seizures. This is followed then by the results of several recent in vivo and in vitro electrophysiological studies that ascribe a critical importance for the perirhinal cortex in convulsive limbic seizures. Finally, since our anatomical studies indicated that the perirhinal cortex densely innervates the frontal motor cortex, we examined the involvement of this latter region in amygdala kindled seizures using the reversible functional lesion of cortical spreading depression. Based on these findings we suggest that the circuits of the perirhinal cortex may be important in the amplification and distribution of temporal lobe seizure discharges, providing access to structures that are capable of driving a convulsive response.

Amygdala↗

PubMed1996

Calcium-activated potassium current in cultured rabbit retinal pigment epithelial cells.

Calcium-activated potassium current was studied in cultured rabbit retinal pigment epithelial (RPE) cells using whole-cell and single channel patch-clamp recording techniques. When K+ was the principal cation in the electrode, depolarizing voltage steps from a holding potential of -60 mV activated outwardly rectifying current. Outward K+ current was increased by the Ca2+ ionophore ionomycin and reduced when the extracellular Ca2+ concentration was decreased from 2.5 mM to 100 nM in the presence of ionomycin. Outward K+ current recorded in the presence of ionomycin was blocked by iberiotoxin and by charybdotoxin. Single channel recording from cell-attached and excised membrane patches revealed a large conductance Ca2+-activated K+ (K(Ca)) channel. Identification of K(Ca) channels was based on: 1) the voltage-dependence of channel opening; 2) the large unitary conductance (> 200 pS with symmetrical 130 mM K+); 3) the dependence of the reversal potential on the K+ gradient; and 4) increased channel opening after exposure of the cytosolic surface of excised membrane patches to elevated Ca2+. These results demonstrate that Ca2+-activated K+ channels are present in rabbit RPE cells and may play an essential role in the regulation of membrane potential and ion transport.

Animals↗

PubMed1995

Apolipoprotein E restricts interleukin-dependent T lymphocyte proliferation at the G1A/G1B boundary.

Apolipoprotein E (apoE), a lipid transport protein important in cholesterol homeostasis, inhibits the proliferation of interleukin-dependent lymphocytes. Growth factor-responsive cells are blocked in the G1A phase of the cell cycle. Suppression by apoE is independent of growth factor, as evidenced by the fact that interleukin-2 (IL2)- and IL4-dependent proliferation of HT-2 T lymphocytes is equally inhibited. apoE has no effect on IL2-augmented killing of target cells by cytotoxic T cells, indicating that it has no direct effect on signaling via interleukin receptors. The data are consistent with inhibition by apoE of an event or pathway distal to receptor signaling and required for G1A transition, or G1B entry.

Animals↗