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Biomedical subjects

M J Yu

Publications and source records attributed to M J Yu.

15 recordsLinked to original sources
PubMed1998

Influence of destruction of retina-RPE complex on the proliferation of scleral chondrocytes in chicks.

We studied the role of the retina-retinal pigment epithelium (RPE) complex in the proliferation of scleral chondrocytes in chicks. Seventy-two chicks were allocated to one of four groups: intravitreal gentamicin (400 microg) injection (destruction of retina-RPE complex); intravitreal gentamicin injection with goggling; goggling only (form-deprivation myopia); and intravitreal saline injection (control). The chicks were killed and retina-RPE complexes were harvested under a microscope. Retina-RPE complexes were then co-cultured with primary culture of first day scleral chondrocytes in Transwell-COL co-culture systems (Costar), with two different pore sizes (0.4 and 3.0 microm) and serum-deprivation medium. An MTT assay was performed at A550 after 4 days. In the 0.4 microm pore size system, the absorbency at A550 showed no differences between groups. However, in the 3.0 microm pore size system, the absorbency at A550s in the intravitreal gentamicin groups was significantly lower than in the control and the goggle groups (p<0.05), indicating that destruction of the retina-RPE complex inhibited chondrocyte proliferation. The absorbency in the goggle group was higher than in the control group (p<0.05). These results indicate that the retina-RPE complex exerts a positive effect on the proliferation of scleral chondrocytes via a molecule sized between 0.4.and 3.0 microm in diameter.

Animals↗
PubMed1998

Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat.

AIMS: To investigate the longevity and reproducibility of choroidal neovascularisation (CNV) induced by krypton laser photocoagulation in the rat. The presence of cell adhesion molecules (CAMs) and vascular endothelial growth factor (VEGF) during the development of CNV was also studied. METHODS: 67 pigmented rats underwent retinal photocoagulation by krypton laser. The eyes were examined by either single or serial fluorescein angiography at 3 days, 1, 2-3, 4-5, 7-8, and 12 weeks post photocoagulation. The expression of CAMs (ICAM-1, E-selectin, and CD44) and VEGF post photocoagulation was studied by immunohistochemistry. RESULTS: CNV related fluorescein leakage appeared in 46.4% of 766 laser spots delivered to the 58 eyes that were tested at 2-3 weeks post treatment. The ratio of hyperfluorescent laser sites did not change significantly at 8 weeks post laser. The number of leaky spots was independent of the total number of lesions delivered to each eye (at 2-3 weeks post laser 10-15 spots/eye: 44% and 25-30 spots/eye: 49%; t = 0.7673; p = 0.3903). Nine eyes were followed by serial angiography between 2 and 12 weeks. The laser spots with fluorescein leakage at 2 weeks (51.5%) remained leaky at 12 weeks (51.5%). Histopathologically, macrophage accumulation peaked at 5 days and CNV was firstly observed at 1 week post photocoagulation. ICAM-1, E-selectin, CD44, and VEGF were maximally induced at 3-5 days post laser photocoagulation, and were localised to RPE, choroidal vascular endothelial, and inflammatory cells. VEGF was also detected in intravascular leucocytes at the sites of laser lesions. CONCLUSIONS: These studies demonstrated that krypton laser photocoagulation can be successfully used to produce lesions similar to those of human CNV. The response induced remained present for an extended period of time (12 weeks), thus offering a potential model to screen candidate CNV inhibitory agents. In addition, it is proposed that the expression of ICAM-1, E-selectin, CD44, and VEGF before new vessel formation might be linked to the initiation of CNV.

Animals↗
PubMed1998

Isoform expression of Na+-K+-ATPase alpha-subunit in gills of the teleost Oreochromis mossambicus.

Three isoform-specific antibodies, 6F against the alpha1-isoform of the avian sodium pump, HERED against the rat alpha2-isoform, and Ax2 against the rat alpha3-isoform, were used to detect the expression of Na+-K+-ATPase alpha-subunits in gills of a teleost, the tilapia (Oreochromis mossambicus). Tilapia gill tissue showed positive reactions to antibodies specific for alpha1- and alpha3-isoforms. The results of immunoblots were converted to numerical values (relative intensities) by image analysis for comparisons. Relative amounts of alpha1-like isoform alone and consequently the ratio of alpha1-like to alpha3-like isoforms were higher in gills of seawater-adapted tilapia than in those of freshwater-adapted ones, indicating that the two isoforms respond differently to environmental salinities. In the subsequent immunocytochemical experiments, gill mitochondria-rich cells were demonstrated to immunoreact with antibodies specific for alpha1- and alpha3-isoforms. alpha1-like and alpha3-like isoforms of gill Na+-K+-ATPase are suggested to be involved in the ion- and osmoregulation mechanisms in tilapia. Moreover, differential expressions of two isoforms may be associated with different functions, secretion and uptake of ions and acid-base regulation, in gills of seawater- and freshwater-adapted tilapia.

Animals↗
PubMed1993

Benzylamine antioxidants: relationship between structure, peroxyl radical scavenging, lipid peroxidation inhibition, and cytoprotection.

Three homologous series of 3,5-dialkoxy-4-hydroxybenzylamines were prepared and tested (1) as peroxyl radical scavengers in homogeneous aqueous solution, (2) as inhibitors of iron-dependent peroxidation of rabbit brain vesicular membrane lipids, and (3) as cytoprotective agents using primary cultures of rat hippocampal neurons exposed to hydrogen peroxide. The structural requirements for efficient radical trapping in homogeneous solution differed from those for effective lipid peroxidation inhibition: In homogeneous solution a kinetic preference existed for smaller, less sterically encumbered substituents flanking the reactive phenolic hydroxyl group. Lipid peroxidation inhibition, on the other hand, required longer more lipophilic substituents. Consequently, a lipophilic alkoxyl substituent at C3 and a small substituent at C5 appeared optimal for efficient radical scavenging activity in both lipid and homogeneous solution. Maximal cytoprotection of rat hippocampal neurons exposed to hydrogen peroxide was also associated with more lipophilic derivatives although substituent length and substituent bulk may represent independent parameters for relating structure and efficacy in this system.

Animals↗
PubMed1993

[Antiviral activity of mangiferin against herpes simplex virus type 2 in vitro].

The effect of mangiferin, a tetrahydroxy pyrrolidone saponin extracted from the leaves of mango (Mangifera indica), against herpes simplex virus type 2 (HSV-2) in vitro was studied. The 50% effective concentration (EC50) of it against HSV-2 plaque formation in HeLa cells was 111.7 micrograms.ml-1, and the concentrations of 33 and 80 micrograms.ml-1 reduced the virus replicative yields by 90% (EC90) and 99% (EC99), respectively. The therapeutic index (IC50/EC50) was 8.1. Mangiferin did not directly inactivate HSV-2. The results of the drug addition and removal tests suggest that mangiferin inhibits the late event in HSV-2 replication.

Antiviral Agents↗
PubMed1992

Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands.

Compounds exemplified by 2-[2-(5-bromo-1H-indol-3-yl)ethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H)-quinazolinone (3, IC50 = 0.0093 microM using mouse brain membranes) represent a structurally novel series of non-peptide cholecystokinin B receptor ligands. Since asperlicin, a selective CCK-A receptor antagonist, may be regarded as a conformationally constrained 2-substituted-3-phenyl-4(3H)-quinazolinone, the progenitor of compound 3 (compound 2, 2-[2-(1H-indol-3-yl)ethyl]-3-phenyl-4(3H)- quinazolinone) might therefore represent a conformationally flexible pharmacophore of the natural product. To probe possible conformational preferences for this class of receptor ligands, in particular the spatial relationship between the indole and quinazolinone rings, we prepared a series of analogues with methyl substituents on the ethylene bridge as well as congeners with different linkers. The X-ray crystal structure conformation for compound 22 (2-[2-(1H-indol-3-yl)ethyl]-3-]-3-(1-methylethoxy) phenyl]-4(3H)-quinazolinone, IC50 = 0.026 microM) is extended with the two heteroaromatic rings adopting an antiperiplanar arrangement around the central sigma bond of the ethane linker, whereas the solid-state conformation for a less active analogue 19 (2-[2-(1H-indol-3-yl)-1-methylethyl]-3-[3-(1- methylethoxy)phenyl]-4(3H)-quinazolinone, IC50 = 9.1 microM) is folded with the two heteroaromatic systems adopting a synclinal orientation. However, MM2 force field calculations (MacroModel, v 3.0) suggest that the energy difference between the folded and extended conformation is small. Thus, other factors such as unfavorable steric interactions may account for the difference in receptor affinity. For derivatives with one to three methylene units separating the indole and quinazolinone rings, maximal receptor binding activity was found when the distance separating the two heteroaromatic systems is defined by an ethyl group. Introducing unsaturation into the ethylene bridge of compound 3 limited the conformational flexibility of the molecule and decreased its receptor affinity greater than 2 orders of magnitude.

Animals↗
PubMed1992

Phenothiazines as lipid peroxidation inhibitors and cytoprotective agents.

A series of phenothiazines was synthesized and evaluated as in vitro inhibitors of iron-dependent lipid peroxidation. The MIC (minimum tested concentration that gave greater than or equal to 50% inhibition) for 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanolamine methanesulfonate (6) was 0.26 microM. Whereas methyl substitution at N-10 diminished activity nearly 100-fold, other structural modifications such as varying the amine group, the distance separating the amine substituent from the phenothiazine nucleus, and the linking group had little effect. Compound 6 was more effective than probucol, a known antioxidant, in blocking Cu2+ catalyzed oxidation of low-density lipoprotein (LDL) as measured by competitive scavenger receptor mediated degradation of 125I-labeled acetyl-LDL by mouse peritoneal macrophage cells in vitro. At a concentration of 5 microM, compound 6 also protected primary cultures of rat hippocampal neurons exposed to hydrogen peroxide (50 microM) when assessed 18 h later by fluorescein diacetate and propidium iodide uptake.

Animals↗
PubMed1992

A phenothiazine derivative reduces rat brain damage after global or focal ischemia.

BACKGROUND AND PURPOSE: We previously reported that 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanamine hydrochloride is a potent inhibitor of iron-dependent lipid peroxidation in vitro and can protect primary cultures of rat hippocampal neurons from hydrogen peroxide-induced toxicity. Because oxidants may play an important role in mediating postischemic tissue injury, we evaluated this agent in two rat models of transient cerebral ischemia. METHODS: In a model of global forebrain ischemia, 23 male Wistar rats were subjected to 10 minutes of four-vessel occlusion followed by 72 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). In a model of focal stroke, 19 spontaneously hypertensive rats were subjected to 2 hours of tandem middle cerebral and ipsilateral common carotid artery occlusion followed by 24 hours of reperfusion. The rats received three intraperitoneal injections of either vehicle (2% aqueous acacia) or test agent (40 mg/kg). RESULTS: In the global model, the phenothiazine significantly protected the CA1 layer of the hippocampus, with a reduction in mean damage score from 2.1 +/- 0.3 for control rats to 1.0 +/- 0.4 for treated rats (p less than 0.05). In the transient focal stroke model, the compound reduced cortical infarct volume from 130.1 +/- 10.3 mm3 for control rats to 95.2 +/- 24.5 mm3 for treated rats (p less than 0.02). CONCLUSIONS: Although the primary mechanism responsible for the protective effect is unclear at the present time, our study is consistent with the hypothesis that oxidant-mediated lipid peroxidation may be involved in the pathophysiology of postischemic brain injury.

Animals↗
PubMed1990

Atrial natriuretic peptide receptor modulators: effects of disubstituted quinazolines on receptor binding and in vitro biological activity.

Prazosin (25 microM) was found to increase 125I-labeled rat atrial natriuretic peptide ([125I]rANP) receptor binding by 50% (SC50) in bovine adrenal zona glomerulosa membranes. A series of 2,4-disubstituted quinazolines was prepared in order to identify more potent analogues for additional in vitro testing. Compound 7 (N-[3-[[2-(diethyl-amino)-4-quinazolinyl]amino]propyl] guanidine dinitrate) from this series (3 microM) significantly decreased the EC50 for rANP-mediated inhibition of ACTH-stimulated aldosterone synthesis in rat adrenal glomerulosa cells. At a higher concentration (20 microM), compound 7 had no effect on particulate guanylate cyclase from rabbit glomeruli in either the presence or absence of rANP.

Adrenocorticotropic Hormone↗
PubMed1981

Transported enzymes in sciatic nerve and sensory ganglia of rats exposed to maternal antibodies against nerve growth factor.

The accumulations by axoplasmic transport of selected enzyme activities proximal and distal to a ligature placed on the sciatic nerve were monitored in rats exposed in utero to maternal antibodies to nerve growth factor (NGF) and in control rats. Littermates of the animals exposed to anti-NGF were shown elsewhere to have had a 70% reduction in the number of sensory neurons in dorsal root ganglia and a 90% reduction in number of neurons in superior cervical (sympathetic) ganglion. The accumulation of F(-)-sensitive acid phosphatase activity was depressed 75% both proximal and distal to the tie. Accumulation of F(-)-resistant acid phosphatase activity was depressed nearly 50% proximal to the tie. Distal accumulation of this activity did not occur in either group of rats. Accumulation of acetylcholinesterase activity was depressed 30%. Distal accumulation of the activities of beta-glucuronidase and hexokinase was depressed 50%. In the lumbar dorsal root ganglia, dry weight was reduced 40%, and the activities of peroxide-sensitive, F(-)-resistant acid phosphatase and of the mitochondrial enzymes hexokinase, glutamic dehydrogenase, glutamic-oxalacetic transaminase, and NAD-dependent isocitric dehydrogenase were all reduced a little more, 45--50% per ganglion. However, the activities of the lysosomal enzymes, F(-)-sensitive acid phosphatase and beta-glucuronidase, of the peroxide-resistant, F(-)-resistant acid phosphatase, and of the mitochondrial enzyme glutaminase were all reduced about 60% per ganglion. The results of these measurements were interpreted to suggest that much, and perhaps all, of the F(-)-sensitive acid phosphatase activity in motion in peripheral nerve in rat is confined to sensory axons.

Acid Phosphatase↗
PubMed1980

Turnaround of axoplasmic transport of selected particle-specific enzymes at an injury in control and diisopropylphosphorofluoridate-treated rats.

Reversal of direction (turnaround) of axonal transport of particle-specific enzyme activities was studied at a ligature placed on rat sciatic nerve. In the principal experiment, the ligature remained on the nerve in vivo several hours, allowing enzyme activities (acetylcholinesterase, acid phosphatase, and monoamine oxidase) to accumulate immediately proximal to the tie. The nerve was then tied a second time, proximal to the first tie, and incubated in vitro for several more hours. Accumulation of enzyme activities just distal to the second tie was measured. This second accumulation, of activities traveling in the retrograde direction, was shown to be the result of turnaround in several ways. (1) The increase in activity distal to the second tie was equal to the decrease in activity proximal to the first. (2) The increase in enzyme activities distal to the second tie was greatly reduced when the accumulation proximal to the first tie was trapped by placing a third tie between the first and second ties. (3) It was shown that the activity that accumulated distal to the second tie could not have been in retrograde motion at the time of the first tie. (4) Accumulation distal to the second tie was not a function of the length of nerve segment included between the two ties. In contrast to the consistent occurrence of turnaround of orthograde flow, turnaround of retrograde flow could not be demonstrated. Turnaround transport was blocked by incubation in the cold and in the presence of NaCN or vinblastine. The turnaround process operated on all three enzymes studied, suggesting that it operates on lysosomes and mitochondria, as well as on the endoplasmic reticulum-like material bearing acetylcholinesterase. Evidence for the participation of the transport process in the renewal of AChE in the distal portions of the axon was obtained in experiments using diisopropylphosphorofluoridate and cycloheximide.

Acetylcholinesterase↗