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Biomedical subjects

L J Chen

Publications and source records attributed to L J Chen.

At least 37 records · Page 2Linked to original sources

Leaf-specific upregulation of chloroplast translocon genes by a CCT motif-containing protein, CIA 2.

Chloroplasts are a major destination of protein traffic within leaf cells. Protein import into chloroplasts is mediated by a set of translocon complexes at the chloroplast envelope. Current data indicate that the expression of translocon genes is regulated in a tissue-specific manner, possibly to accommodate the higher import demand of chloroplasts in leaves and the lower demand of plastids in other tissues. We have designed a transgene-based positive screen to isolate mutants disrupted in protein import into plastids. The first locus we isolated, CIA2, encodes a protein containing a motif conserved within the CCT family of transcription factors. Biochemical analysis indicates that CIA2 is responsible for specific upregulation of the translocon genes atToc33 and atToc75 in leaves. Identification of CIA2 provides new insights into the tissue-specific regulation of translocon gene expression.

Amino Acid Motifs↗

Metabolism of (R)-(+)-pulegone in F344 rats.

(R)-(+)-Pulegone, a monoterpene ketone, is a major component of pennyroyal oil. Ingestion of high doses of pennyroyal oil has caused severe toxicity and occasionally death. Studies have shown that metabolites of pulegone were responsible for the toxicity. Previous metabolism studies have used high, near lethal doses and isolation and analysis techniques that may cause degradation of some metabolites. To clarify these issues and further explore the metabolic pathways, a study of (14)C-labeled pulegone in F344 rats at doses from 0.8 to 80 mg/kg has been conducted. High-pressure liquid chromatography (HPLC) analysis of the collected urine showed the metabolism of pulegone to be extensive and complex. Fourteen metabolites were isolated by HPLC and characterized by NMR, UV, and mass spectroscopy. The results demonstrated that pulegone was metabolized by three major pathways: 1) hydroxylation to give monohydroxylated pulegones, followed by glucuronidation or further metabolism; 2) reduction of the carbon-carbon double bond to give diastereomeric menthone/isomenthone, followed by hydroxylation and glucuronidation; and 3) Michael addition of glutathione to pulegone, followed by further metabolism to give diastereomeric 8-(N-acetylcystein-S-yl)menthone/isomenthone. This 1,4-addition not only took place in vivo but also in vitro under catalysis of glutathione S-transferase or mild base. Several hydroxylated products of the two mercapturic acids were also observed. Contrary to the previous study, all but one of the major metabolites characterized in the present study are phase II metabolites, and most of the metabolites in free forms are structurally different from those previously identified phase I metabolites.

Animals↗

[Changes of segmental motion after spinal manipulation in patients with lumbar intervertebral disc protrusion].

OBJECTIVE: To explore the effect of manipulation on segmental motion of lumbar vertebra and the clinical significance before and after treatment, and evaluation with charge couple device (CCD) measurement system. METHODS: CCD and dynamic radiography were conducted in 30 patients before and after treated by manipulation or other conservative therapy, analysis and comparisons in segmental motion ranges of flexion-extension and lateral bending, correlation between data of CCD system and radiography as well as characteristics of lumbar vertebral function recovery after manipulation were performed. RESULTS: Certain correlation between data of CCD and radiography was shown by linear correlation test (r = 0.42-0.72, P < 0.05-0.01). Paired t test showed that the lower lumbar segmental flexion-extension function was significantly recovered (t = 2.26-2.61, P < 0.05-0.01) after manipulation, but the recovery on other segments was insignificant. CONCLUSION: The special designed CCD system is of important clinical significance in assessing segmental lumbar vertebral function. Lower lumbar vertebral flexion-extention functional state is a crucial criterium for evaluation of manipulative therapy in lumbar intervertebral disc protrusion.

Adult↗

[Relationship between heat stress suppression of neuroapoptosis and activation of nuclear kappa B in primary cultured rat cerebellar granule cells].

It has been well demonstrated that heat stress response (HSR) plays a crucial role in protecting cells from injury induced by various pathological stimuli. However, the protective mechanism of HSR is only poorly understood. The object of this article was to further investigate the relationship between the protective role of heat stress response and activation of NF-kappa B in primary cultured rat cerebellar granule cells. Heat stress was induced by hyperthermia (43+/-0.5 degrees centigrade), and DNA binding activity of NF-kappa B was determined with electrophoretic mobility shift assay (EMSA). Neuroapoptosis was measured by Hoechst 33258, agarose gel electrophoresis and flow cytometry (FCM) analysis. The results showed that the neurons treated with low potassium for l6 h could induce neuroapoptosis and promote the activity of nuclear kappa B. Heat stress treatment for 30, 60 and 90 min could suppress neuroapoptosis and the activity of nuclear kappa B induced by low potassium in a time-dependent manner. Activation of NF-kappa B using 100 nmol/L phorbol 12-myristate l3-acetate (PMA) could promote antiapoptotic action of heat stress response. In contrast, when NF-kappa B activation was inhibited by 10 micromol/L pyrrolidine dithiocarbamate derivatives (PDTC), heat stress did not provide protection against cell apoptosis induced by low potassium. The results suggest that the neuroprotection of heat stress has no relation to the suppression of NF-kappa B activity, and activation of NF-kappa B may promote antiapoptotic action of heat stress.

Animals↗

Correlation of coronary angiography with "tombstoning" electrocardiographic pattern in patients after acute myocardial infarction.

BACKGROUND: It has been suggested that a specific pattern of electrocardiographic (ECG) changes following acute myocardial infarction (AMI), the so-called "tombstoning," predicts a poorer outcome, although the cause and associations of such changes are not known. To address the possible cause and implications, we correlated angiographic findings with tombstoning in patients following AMI. METHODS: The study investigated 124 patients with AMI, whose ECGs were taken within 24 h of onset of symptoms and who subsequently underwent angiography. In this population, 24 (19%) patients had a definite tombstoning pattern on their admission ECG. RESULTS: Compared with non-tombstoning ECGs, the significant differences in the tombstoning group are as follows: (1) All patients, including those with inferior infarction, had either total or partial occlusion of the left anterior descending (LAD) artery (100 vs. 44%, p < 0.0001); (2) LAD occlusions were significantly more severe and mostly proximal (100% occlusion: 50 vs. 20.5%, p = 0.02; <50% occlusion: 0 vs. 15.9% p = 0.039; proximal occlusion: 92 vs. 65%, p = 0.017); (3) patients with tombstoning ECGs had a significantly greater incidence of occlusion of all three coronary arteries (54.1 vs. 22%, p = 0.001); (4) tombstoning ECGs were more strongly associated with anterior than with inferior infarction (83.3 vs. 33%, p < 0.0001). CONCLUSIONS: The patients with a tombstoning pattern on the admission ECG, who underwent angiography, were associated with occlusion of a high-grade stenosis of the proximal LAD artery (usually with involvement of more than one artery) and were predominantly seen in association with anterior infarction.

Adult↗

Metabolism and disposition of luminol in the rat.

1. The metabolism and disposition of Luminol (LMN, 3-aminophthalhydrazide), a widely used forensic and laboratory reagent that chemiluminesses upon oxidation, was determined as part of its overall toxicological characterization. 2. Radiolabelled LMN was well absorbed, metabolized and excreted following p.o. administration of a range of doses. About 90% of the total dose was recovered within 24 h of administration in urine in the form of two metabolites identified as LMN N8-glucuronide and LMN N8-sulphamic acid. 3-Aminophthalic acid, the oxidative product of LMN in the light-emitting reaction, was apparently not formed in vivo. 3. Metabolism and disposition of an i.v. administered dose was similar to that following gavage. Little or no LMN-derived radioactivity was present in tissue within 12 h post-dosing. Excretion of radioactivity in bile following i.v. injection was minimal (approximately 8% of the total dose in 6 h) and consisted of the same urinary-excreted glucuronide and sulphate conjugates. 4. LMN was not absorbed dermally in rat, potentially a major route of exposure to human. If the fate of LMN is similar between species, this compound should have little potential for either dermal absorption, bioaccumulation in tissues following other routes of exposure or chronic toxicity in humans.

Administration, Oral↗

Tetrahydroprotoberberines inhibit lipid peroxidation and scavenge hydroxyl free radicals.

AIM: To study the effects of tetrahydroprotoberberines (THPB) on rat liver and brain lipid peroxidation (LPO) and oxygen free radicals generation. METHODS: The malondialdehyde (MDA) levels in rat brain and liver homogenates, induction of MDA by Fe(2+)-Vit C in mitochondria, OH. generation by Fenton reaction, and O2.- generation by pyrogallol oxidation were observed in vitro. RESULTS: (1) THPB lowered the MDA contents in the liver homogenate and mitochondria, and the IC50 values of l-THPB-18 and l-stepholidine (SPD) in the liver mitochondria were 3.1 and 12.7 mumol.L-1 respectively. SPD decreased the MDA contents in the brain homogenate and mitochondria with IC50 values of 102 and 35.0 mumol.L-1 respectively. (2) THPB scavenged OH., and the IC50 values of l-THPB-18 and SPD were 0.21 and 3.8 mumol.L-1 respectively, but no effect on O2.- was observed. CONCLUSION: THPB could reduce the MDA contents and scavenge OH. and THPB-18 was the most potent amongst them.

Animals↗

Behavioral characteristics of olanzapine: an atypical neuroleptic.

AIM: To assess the atypical neuroleptic properties of a novel antipsychotic agent, olanzapine (Ola). METHODS: The action of Ola on apomorpine (Apo)-induced climbing behavior, 5-hydroxy-dl-tryptophan (5-HTP)-induced head twitch response, oxotremorine-induced tremor, and the conditioned avoidance behavior in mice were observed. The catalepsy of mice induced by Ola was also investigated. The single unit extracellular recording technique was used to compare the spontaneous firing rate changes of dopamine (DA) cells in the ventral tegmental area (VTA, A10) and the substantia nigra pars compact (SNC, A9) in rats after i.v. Ola. RESULTS: Ola antagonized the climbing behavior (ED50 1.8 mg.kg-1, p.o.), head twitch behavior (ED50 0.3 mg.kg-1, p.o.), and tremor (ED50 5.2 mg.kg-1, p.o.) in mice. In a conditioned avoidance paradigm in mice, Ola inhibited the avoidance response with an ED50 of 2.72 mg.kg-1 (p.o.). However, the catalepsy was not induced by Ola in mice even under a very high dose of 100 mg.kg-1 (p.o.). Ola selectively increased the firing rate of DA cells in the VTA, but failed to affect that of SNC DA cells. CONCLUSION: Ola distinguished itself from the typical neuroleptic (e.g. haloperidol, Hal) and took resemblance of the atypical neuroleptic (e.g. clozapine, Clo) in 3 aspects: 1) the multiple receptor pharmacodynamics involving D1/D2, 5-HT2 and M-ACh receptors; 2) dose-response separation between the block of conditioned avoidance response and catalepsy induction; and 3) the specificity of action sites of firing rates upon acute drug challenge.

Animals↗

[Neuroprotective effect of alpha-dihydroergocryptine depends on activation of nuclear factor kappa B].

AIM: To investigate the relationship between the neuroprotective effect of alpha-dihydroergocryptine (alpha-DHEC) and the activation of nuclear factor Kappa B (NF-Kappa B). METHODS: Adult male rats were subjected to cerebral ischemia induced by middle cerebral artery occlusion (MCAO). DNA binding activity of NF-Kappa B was determined with electrophoretic mobility shift assay (EMSA) in animals subjected to varying durations of cerebral ischemia. Neuroapoptosis induced by ischemic damage was measured by deoxynucleotidy transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry (FCM) analysis. RESULTS: No change was observed in nuclear NF-Kappa B DNA binding in normal animal. A low level of constitutive NF-Kappa B DNA binding was detected in animals subjected to cerebral ischemia of 1 h, and significant increase in the amount of active NF-Kappa B in nuclear extracts was observed after cerebral ischemia of 3 h, 6 h, and 12 h. Peak of NF-Kappa B DNA binding was observed at the time point of 3 h. Animals subjected to cerebral ischemia of 3 h potentially initiates neuroapoptosis and activates NF-Kappa B in nuclear extract. Alpha-DHEC (100 micrograms.kg-1 and 150 micrograms.kg-1) showed significant protective effect on neuroapoptosis-induced by cerebral ischemia of 3 h, and inhibiting NF-Kappa B activation using 100 mg.kg-1 pyrrolidinedithiocarbamate (PDTC) in the continuous presence of alpha-DHEC, the neuroprotective effect of alpha-DHEC was blocked. CONCLUSION: The findings suggest that the neuroprotetive effect of alpha-DHEC may depend on the activation of NF-Kappa B.

Animals↗

Synthesis and antitumour activity of novel diterpenequinone salvicine and the analogs.

A novel diterpenequinone named salvicine (4), structurally modified derivative of a natural product, and a series of the novel analogs have been prepared. Most of the analogs were found to be potently active against tumor cell lines in vitro. Further study on 4 in vivo demonstrated that it possessed a significant antineoplastic activity against murine S-180 Sarcoma and Lewis lung cancer, and human lung adenocarcinoma xenografts A-549 and LAX-83. The preclinical studies of 4 are now under way.

Animals↗

Distribution and metabolism of (5-hydroxymethyl)furfural in male F344 rats and B6C3F1 mice after oral administration.

(5-Hydroxymethyl)furfural (HMF), a heat-induced decomposition product of hexoses, is present in food and drink. Recent reports have shown HMF to be an in vitro mutagen after sulfate conjugation and to be a promoter as well as a weak initiator of colonic aberrant foci in rats. In order to investigate the metabolic activation further and to provide information for HMF toxicology studies, the disposition of [14C]-HMF has been investigated in male F344 rats and B6C3F1 mice following po administration of either 5, 10, 100, or 500 mg/kg. Tissue distribution results indicated that absorption of HMF was rapid in male rats and mice and that tissue concentrations in male mice at the earliest time point are not linearly proportional to dose. Excretion was primarily via the urine in both, with 60-80% of the administered dose excreted by this route in 48 h. Tissue/blood ratios of HMF-derived radioactivity were greater than 1 for liver and kidney. Three metabolites were identified and quantitated in urine. Formation of one of the metabolites, N-(5-hydroxymethyl-2-furoyl)glycine, was inversely proportional to dose in rats but not mice. None of the metabolites were sulfate conjugates nor likely to be formed from sulfate conjugates. There were relatively low levels of nonextractable radioactivity in liver, kidney, and intestines, indicating that some reactive intermediate(s) may be formed.

Animals↗

Clinical significance of postlaser indocyanine green angiographic hot spots in age-related macular degeneration.

OBJECTIVE: To report the natural history and clinical significance of indocyanine green (ICG) angiographic hot spots in age-related macular degeneration (ARMD) after laser photocoagulation. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Two hundred thirty consecutive patients with exudative ARMD who underwent krypton laser treatment between March 1993 and December 1996. INTERVENTION: Krypton laser photocoagulation was performed on all patients. Digital videoangiograms, including both fluorescein angiography and ICG angiography, were obtained at 2 weeks, 4 weeks, 6 weeks, and 3 months postlaser treatment on each patient and repeated if clinical changes were noted. MAIN OUTCOME MEASURES: Detection by ICG of hyperfluorescent spots (hot spots) within the hypofluorescent laser-treated area. RESULTS: Forty patients (18%) developed ICG hot spots 2 weeks after laser treatment. The hot spots disappeared spontaneously without recurrent choroidal neovascular (CNV) membrane in 31 patients (78%). Recurrent CNV was discovered at the hot spot in four patients and away from the hot spot in five patients. CONCLUSION: The postlaser ICG angiographic hot spot is not rare. These spots tend to disappear spontaneously and do not necessarily represent a recurrent CNV. The presence of a hot spot on ICG angiography is not an indication for immediate laser retreatment.

Aged↗

Subtypes of central nicotinic receptors involved in learning and memory.

AIM: To observe the effects of different subtypes of central nicotinic receptor on learning and memory. METHODS: Passive avoidance response, including step-down avoidance and step-through avoidance in mice and long-term potentiation (LTP) in rat hippocampal slices. RESULTS: Hexamethonium (C6) 7 micrograms/mouse and kappa-bungarotoxin (kappa-BTX) 0.6 microgram/mouse inhibited the acquisition of avoidance conditioning in mice, and kappa-BTX yielded this effect with a dose-response relationship. kappa-BTX 1 mumol.L-1 suppressed the induction of LTP (P < 0.05), but not normal synaptic transmission and maintenance of LTP in rat hippocampal slices. CONCLUSION: The subtypes of central nicotinic receptor sensitive to kappa-BTX play an important role in learning and memory.

Animals↗

Comparison of 12-chloroscoulerine enantiomers on animal behavior to dopamine receptors.

AIM: To compare the pharmacological characteristics of 12-chloroscoulerine (CSL) enantiomers to dopamine (DA) receptors. METHODS: Radioligand receptor binding assay with calf striatum and behavioral tests of mice or rats were used. RESULTS: In the competitive binding assay, the affinities (Ki) of l-CSL to D1 and D2 receptors were 5.7 nmol.L-1, while those of d-CSL for D1 and D2 receptors were 135 and 9150 nmol.L-1, respectively. The Ki of dl-CSL to D1 and D2 receptors were 8.9 and 9.6 nmol.L-1, respectively, which were slightly weaker than that of l-CSL. In the behavioral experiments, CSL enantiomers 5-60 mg.kg-1 antagonized the stereotypy induced by apomorphine in rats, and 5-150 mg.kg-1 produced catalepsy. The enantiomers 10-60 mg.kg-1 reduced the mice jumping behavior induced by amphetamine + levodopa. l-CSL 10-80 mg.kg-1 antagonized the spontaneous locomotor activity of normal or amphetamine-treated mice. CONCLUSION: CSL enantiomers are antagonists to DA receptors: l-CSL > dl-CSL >> d-CSL.

Animals↗

An Arabidopsis mutant defective in the plastid general protein import apparatus.

Elaborate mechanisms have evolved for the translocation of nucleus-encoded proteins across the plastid envelope membrane. Although putative components of the import apparatus have been identified biochemically, their role in import remains to be proven in vivo. An Arabidopsis mutant lacking a new component of the import machinery [translocon at the outer envelope membrane of chloroplasts (Toc33), a 33-kilodalton protein] has been isolated. The functional similarity of Toc33 to another translocon component (Toc34) implies that multiple different translocon complexes are present in plastids. Processes that are mediated by Toc33 operate during the early stages of plastid and leaf development. The data demonstrate the in vivo role of a translocon component in plastid protein import.

Amino Acid Sequence↗

High resolution electron microscopy of amorphous interlayers between metal thin films and silicon.

High-resolution electron microscopy of amorphous interlayers (a-interlayer) formed by solid-state diffusion between metal thin films and silicon is reviewed. In this paper, an overview of the development is presented. Pertinent data obtained on the growth kinetics and structure of a-interlayers in polycrystalline metal thin films on single-crystal silicon are reported. For the Ti/Si, Zr/Si, Hf/Si, V/Si, Nb/Si and Ta/Si systems, the growth of a-interlayer was found to follow a linear law in the initial stage. Si atoms were found to be the dominant diffusing species in the solid phase amorphization in the Ti/Si, Zr/Si, and Hf/Si systems. For the Y/Si system, the stability of amorphous interlayer depends critically on the composition of the amorphous films. Auto-correlation function analysis was utilized to determine the structure of the amorphous interlayers. HRTEM in conjunction with the fast Fourier transform were applied to determine the first nucleated crystalline phase. Simultaneous presence of multiphases was observed to occur in a number of refractory metal/Si systems.

Metals↗