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Biomedical subjects

G Maguire

Publications and source records attributed to G Maguire.

29 records · Page 2Linked to original sources

Cholesteryl ester transfer protein and high density lipoprotein responses to cholesterol feeding in men: relationship to apolipoprotein E genotype.

The apolipoprotein (apo) E isoform is an important determinant of the plasma lipoprotein distribution of apoE and of the metabolism of apoE-containing lipoproteins. We have determined the effects of apoE genotype on the plasma lipoprotein response to cholesterol feeding in 30 young normal male subjects (5 E3/2, 11 E3/3, 14 E4/3) under rigorously controlled dietary conditions. Two diets, differing only in cholesterol content (low cholesterol (LC): 80 mg cholesterol/1000 kcal and high cholesterol (HC): 320 mg cholesterol/1000 kcal), were compared using a random crossover design. At the end of the HC as compared to the LC period, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and HDL2-C increased by an average of 15%, 21%, 7%, and 23%, respectively, for the three genotype groups combined (P < 0.001 for each). The LDL-C response to dietary cholesterol did not differ among the apoE genotypes. However, the increase in HDL-C varied significantly according to the apoE genotype (E3/2: 0 change, E3/3: +4%, E4/3: +12%; P < 0.05). The plasma cholesteryl ester transfer protein (CETP) response to cholesterol feeding also differed amongst the three apoE genotype groups (E3/2: +37%, E3/3: +18%, E4/3: +9%) (P < 0.05). ApoE genotype has significant and opposite effects on plasma CETP and HDL-C responses to dietary cholesterol in men.

Adipose Tissue↗

Observations on the synthesis and in vivo photodynamic activity of some benzochlorins.

An improved synthesis of benzochlorins is reported. Demetallation of the meso-hydroxymethylvinyl derivative of octaethylporphyrin, followed by treatment with sulfuric acid results in cyclization to generate the corresponding octaethylbenzochlorin in high yield. Prolonged treatment with acid generates the sulfonated derivative. These sensitizers were shown to be efficient photodynamic agents in vivo. Animals bearing a transplanted N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide induced urothelial tumor were treated with either the benzochlorin or its sulfonated derivative. Irradiation of tumors 24 h later resulted in a significant tumoricidal effect in a short term assay. We conclude that benzochlorins warrant further examination as potential agents for use in photodynamic therapy.

Animals↗

Amacrine cells in the tiger salamander retina: morphology, physiology, and neurotransmitter identification.

Amacrine cells of the vertebrate retina comprise multiple neurochemical types. Yet details of their electrophysiological and morphology properties as they relate to neurotransmitter content are limited. This issue of relating light responsiveness, dendritic projection, and neurotransmitter content has been addressed in the retinal slice preparation of the tiger salamander. Amacrine cells were whole-cell clamped and stained with Lucifer yellow (LY), then processed to determine their immunoreactivity (IR) to GABA, glycine, dopamine or tyrosine hydroxylase (TOH), and glucagon antisera. Widefield, ON-OFF amacrine cells were glycine-IR. The processes of these cells extended laterally in the inner plexiform layer (IPL) from 250-600 microns. They were either multistratified in the IPL or monostratified near the IPL midline. Three multistratified ON-OFF narrowfield glycine-IR cells also were found. Four types of ON amacrine cells were found to be GABA-IR; all types had their processes concentrated in the proximal IPL (sublamina b). Type I cells were narrowfield (approximately 100 microns) with a compact projection. Type II cells were widefield (220-300 microns) with a sparse projection. Type III cells had an asymmetrical projection and varicose processes. Type IV cells were pyriform and monostratified in sublamina b. One narrowfield ON-OFF amacrine cell, with processes broadly distributed in the middle of the IPL, was GABA-IR. This cell appeared similar to an ON-OFF cell that was glycine-IR and may comprise a type in which GABA and glycine colocalize. Another class of amacrine cell, with processes forming a major plexus along the distal border of the IPL and a lesser plexus in the proximal IPL, produced slow responses at light ON and OFF; these cells were dopamine/TOH-IR. A narrowfield class of transient ON-OFF amacrine cell, with processes ramifying throughout both sublaminae a and b of the IPL, were glucagon-IR; these cells appeared to be dye-coupled at the soma. We have shown that, with respect to GABA, glycine, dopamine, and glucagon, salamander amacrine cells fall into rather discrete groups on the basis of ramification patterns in the IPL and responses to photic stimulation. The physiological, structural, and neurochemical diversity of amacrine cells is indicative of multiple and complex roles in retinal processing.

Ambystoma↗

Synaptic and voltage-gated currents in interplexiform cells of the tiger salamander retina.

We have correlated the membrane properties and synaptic inputs of interplexiform cells (IPCs) with their morphology using whole-cell patch-clamp and Lucifer yellow staining in retinal slices. Three morphological types were identified: (a) a bistratified IPC with descending processes ramifying in both sublaminas a and b of the inner plexiform layer (IPL), and an ascending process that branched in the outer plexiform layer (OPL) and originated from the soma, (b) another bistratified IPC with descending processes ramifying in both sublaminas a and b, and an ascending process that branched in the OPL and originated directly from IPC processes in the IPL, and (c) a monostratified IPC with a descending process ramifying over large lateral extents within the most distal stratum of the IPL, and sending an ascending process to the OPL with little branching. Similar voltage-gated currents were measured in all three types including: (a) a transient inward sodium current, (b) an outward potassium current, and (c) an L-type calcium current. All cells generated multiple spikes with frequency increasing monotonically with the magnitude of injected current. The IPCs that send their descending processes into both sublaminas of the IPL (bistratified) receive excitatory synaptic inputs at both light ON and OFF that decay with a time constant of approximately 1.3 s. Slowly decaying excitation at both ON and OFF suggests that bistratified IPCs may spike continuously in the presence of a dynamic visual environment.

Animals↗

Gamma-aminobutyrate type B receptor modulation of L-type calcium channel current at bipolar cell terminals in the retina of the tiger salamander.

Bipolar-cell axon terminals receive direct synaptic input from amacrine-cell processes, suggesting a possible pathway for modulation of transmitter release. In retinal slices, bath-applied baclofen, a gamma-aminobutyrate type B (GABAB) receptor agonist, reduced a patch-clamp-recorded L-type calcium channel current in a population of bipolar cells with axon terminals that ramify along the midline of the inner plexiform layer. Lucifer yellow staining revealed that this current was found only in bipolar cells that retain axon terminals and their associated telodendria, suggesting that the current is generated at the terminal and also possibly modulated there. T-type calcium currents were found in all bipolar cells, including those without axon terminals, but were not modulated by baclofen. The baclofen-induced reduction of calcium current was enhanced by guanosine 5'-[gamma-thio]triphosphate and eliminated by guanosine 5'-[beta-thio]diphosphate added to the cytoplasm by the patch recording electrode, suggesting that the GABAB receptors act through a guanine nucleotide-binding regulatory protein (G protein). Baclofen also reduced an excitatory synaptic input to a population of amacrine cells with processes that ramify along the midline of the inner plexiform layer--cells probably postsynaptic to the bipolar terminals. This suggests that GABAB receptors modulate not only the calcium current but also transmitter release by a pathway involving G proteins and L-type calcium channels.

Animals↗

Amacrine cell interactions underlying the response to change in the tiger salamander retina.

The neural circuitry and pharmacology underlying transient signal formation at the bipolar-amacrine cell interface were studied. Synaptic currents were measured with whole cell patch clamp in retinal slices. Cell types were identified with Lucifer yellow staining. Activity was initiated with puffs of kainate of known time course and spatial spread delivered at bipolar dendrites. OFF bipolar cells responded to kainate with a sustained inward current, but ON bipolar cells were silent. Two types of amacrine cell were found: (1) narrow field cells, with processes that extended laterally less than 200 microns, responding with a sustained inward current, and (2) wide field cells, with processes that extended laterally by up to 1 mm, responding with a brief transient inward current followed by a more sustained outward current. We pharmacologically dissected the synaptic interactions underlying the transient current in the wide field amacrine cell. In the presence of 5-aminovaleric acid (AVA), the time course of this transient current was increased so that it resembled the response of bipolar cells. Because AVA is a GABAB antagonist, it appears to block an opposing signal that truncates the sustained excitatory bipolar input, thereby generating the transient. GABAB specificity is confirmed by (1) block of the transient inward current by baclofen, a GABAB agonist, and (2) block of the baclofen effect by AVA. The site of GABAB action appears to be presynaptic to the amacrine cell membrane because neither baclofen nor AVA, in combination with picrotoxin, had a direct effect at the amacrine cell membrane. GABAB receptors are often found at presynaptic terminals where they modulate calcium or potassium conductances. It has been shown that bipolar cell terminals receive a GABAergic synaptic input (Vaughn et al., 1981; Wu et al., 1981; Tachibana and Kaneko, 1987). The narrow field sustained-responding amacrine cells appear to be GABAergic (Werblin et al., 1988). This suggests that transient activity measured in wide field amacrine cells is formed at a population of bipolar cell terminals by GABAergic feedback from narrow field amacrine cells at GABAB receptors.

Animals↗

Neural interactions mediating the detection of motion in the retina of the tiger salamander.

The neural circuitry underlying movement detection was inferred from studies of amacrine cells under whole-cell patch clamp in retinal slices. Cells were identified by Lucifer yellow staining. Synaptic inputs were driven by "puffing" transmitter substances at the dendrites of presynaptic cells. Spatial sensitivity profiles for amacrine cells were measured by puffing transmitter substances along the lateral spread of their processes. Synaptic pathways were separated and identified with appropriate pre- and postsynaptic pharmacological blocking agents. Two distinct amacrine cell types were found: one with narrow spread of processes that received sustained excitatory synaptic current, the other with very wide spread of processes that received transient excitatory synaptic currents. The transient currents found only in the wide-field amacrine cell were formed presynaptically at GABAB receptors. They could be blocked with baclofen, a GABAB agonist, and their time course was extended by AVA, a GABAB antagonist. Baclofen and AVA had no direct affect upon the wide-field amacrine cell, but picrotoxin blocked a separate, direct GABA input to this cell. The narrow-field amacrine cell was shown to be GABAergic by counterstaining with anti-GABA antiserum after it was filled with Lucifer yellow. Its narrow, spatial profile and sustained synaptic input are properties that closely match those of the GABAergic antagonistic signal that forms transient activity (described above), suggesting that the narrow-field amacrine cell itself is the source of the GABAergic interaction mediating transient activity in the inner plexiform layer (IPL). Other work has shown a GABAB sensitivity at some bipolar terminals, suggesting a population of bipolars as the probable site of interaction mediating transient action. The results suggest that two local populations of amacrine cell types (sustained and transient) interact with the two populations of bipolar cell types (transient forming and nontransient forming). These interactions underlie the formation of the change-detecting subunits. We suggest that local populations of these subunits converge to form the receptive fields of movement-detecting ganglion cells.

Animals↗

On the nature of the active component of haematoporphyrin derivative--Part 2.

It has been suggested recently that neither an ester nor an ether linkage was present in the tumour-localising component of Photofrin II (PFII) (a commercial preparation of DHE). We now report that our chemical and spectroscopic studies, establish the presence of an ester linkage with the possibility that an ether linkage may also be involved.

Chromatography, High Pressure Liquid↗

Expression of CB2 cannabinoid receptor mRNA in adult rat retina.

To date, two cannabinoid receptors, CB1 and CB2, have been cloned. The CB1 receptor has been found in a variety of tissues, particularly in the brain. CB2 receptor mRNA is mainly expressed in the immune system, though one group has found it in mouse cerebellum. Previous immunostaining studies in our lab demonstrated the presence of CB1 receptors in the retina though little evidence exists for the presence of CB2. The putative endogenous ligand for CB2 has been found in retina, however, suggesting that further study of CB2 in retina is warranted. Because glutamate is toxic to retinal ganglion cells in glaucoma and activation of CB2 receptors may be able to protect neurons from glutamate-induced death, we examined the expression of CB2 mRNA in adult rat retina in order to better understand possible neuroprotective mechanisms relevant to glaucoma. Using in situ hybridization, we demonstrated that CB2 cannabinoid receptor messenger RNA was clearly expressed in the adult rat retina, including the somas of retinal ganglion cells. Antisense cRNA probe detected strong signals in the retinal ganglion cell layer, the inner nuclear layer, and the inner segments of photoreceptor cells. Using reverse transcription polymerase chain reaction (RT-PCR) in both rat and mouse tissue, we obtained an RT-PCR product with the same sequence as that reported for CB2 in the GenBank database, thus confirming the presence of CB2 mRNA in retina. The presence of CB2 in retina provides new evidence for the presence of CB2 in the central nervous system (CNS) and an excellent model for its study.

Animals↗

Computerized long-term trending of respiratory parameters.

This paper presents a program that analyzes data recorded from a Puritan-Bennett 7200a mechanical ventilator. The program generates graphs of major ventilatory parameters, as well as the derivatives of the parameters, such as respiratory rate and minute volume with respect to time. The program also creates a series of reports that summarizes setting changes, alarm violations and resets, and lung mechanics maneuvers during the process of respiratory therapy. These graphs and reports provide clinicians with information, which was not captured for review before, in an organized format allowing them to easily identify trends and, in some cases, events that may affect the patient. The results of a clinical study are also presented. The study was designed to determine the effect of routine patient care on the primary and derived respiratory data so that a correct interpretation of the recorded data could be made. The study showed that the data acquisition program was not sensitive to routine bedside activities, and some significant events, such as patient disconnects, are identifiable in a timely manner and with good accuracy.

Adult↗