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Biomedical subjects

K Chen

Publications and source records attributed to K Chen.

At least 397 records · Page 22Linked to original sources

Pharmacokinetics of tablet huperzine A in six volunteers.

AIM: To study pharmacokinetics of tablet huperzine A (Hup-A) in Chinese volunteers to help establishing its drug administration schedule. METHODS: For 6 volunteers after a single oral dose of 0.99 mg, drug concentrations in plasma were assayed by reverse phase high pressure liquid chromatography (HPLC) at 0.5, 0.75, 1.0, 1.25, 1.5, 2, 4, 6, 8, and 10 h. The pharmacokinetic parameters were calculated with a 3P87 program by computer. RESULTS: The time course of plasma concentrations conformed to a one-compartment open model with a first order absorption. The pharmacokinetic parameters were as follows: T 1/2ka = 12.6 min, T 1/2ke = 288.5 min, Tmax = 79.6 min, Cmax = 8.4 micrograms L-1, AUC = 4.1 mg L-1 min. CONCLUSION: Hup-A was absorbed rapidly, distributed widely in the body, and eliminated at a moderate rate.

Adult↗

Epidermal growth factor and lipopolysaccharide activate Stat3 transcription factor in mouse liver.

Previous studies demonstrated that the intraperitoneal injection of epidermal growth factor (EGF) into mice resulted in the appearance, within minutes, of several tyrosine-phosphorylated proteins in liver nuclei. Two of these proteins have been identified as the transcription factors p91/p84 (Stat1 alpha/1 beta) (Ruff-Jamison, S., Chen, K., and Cohen, S. (1993) Science 261, 1733-1736). We have now identified, by Western blotting and immunoprecipitation, an additional EGF-modulated transcription factor, Stat3. We find that Stat3 is tyrosine-phosphorylated and present in mouse liver nuclei following either EGF or lipopolysaccharide administration. Gel shift analyses show that Stat3 is capable of specifically binding the SIE (a DNA sequence present in the c-fos promoter). Three active SIE binding complexes (SIF A, B, and C) exist in the nucleus after the administration of EGF: one complex that contains Stat3, one that contains Stat1, and a third complex that appears to contain both proteins. Only one active SIE binding complex, containing Stat3, was detected after the administration of lipopolysaccharide.

Animals↗

Cholinergic modulation of spontaneous activity in rat dorsal cochlear nucleus.

Extracellular recordings were made from brain stem slices to test the effects of bath application of cholinergic agonists and antagonists on the firing rates of spontaneously active dorsal cochlear nucleus neurons. About 90% of neurons responded to carbachol. A higher proportion responded to muscarine than to nicotine. Muscarine elicited larger responses at lower concentrations than nicotine. Responses to either carbachol or muscarine were always blocked by atropine or scopolamine. The nicotinic antagonists d-tubocurarine, hexamethonium, and mecamylamine blocked the responses to nicotine, but did not decrease the responses to carbachol. Regularly firing neurons showed only increases of firing rate during exposure to cholinergic agonists. About half of responsive bursting neurons showed increased firing; half showed increased followed by decreased firing to 10 microM carbachol or muscarine. All phases of the responses of most bursting neurons were greatly decreased or abolished in low calcium, high magnesium medium, while responses of regular neurons were not detectably affected. Thus, cholinergic agonists appear to act directly on regularly firing neurons, while their actions on bursting neurons may require synaptic activity. The data suggest that cholinergic transmission in the dorsal cochlear nucleus is predominantly muscarinic, and that most regularly firing spontaneously active neurons have muscarinic receptors.

Action Potentials↗

Intravenous NBQX inhibits spontaneously occurring sympathetic nerve activity and reduces blood pressure in cats.

2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) has been demonstrated to be a specific and competitive non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonist. Our previous data obtained with the NMDA receptor antagonist MK-801 indicate that blockade of the NMDA receptor affects blood pressure. The purpose of this study was to determine whether the same is true with blockade of the non-NMDA receptor. For this purpose we administered three doses of NBQX (1, 3 and 10 mg/kg i.v.) to anesthetized, artificially ventilated and paralyzed cats while monitoring spontaneously occurring cardiac sympathetic nerve activity, arterial blood pressure and heart rate. The 1 mg/kg dose of NBQX i.v. reduced both sympathetic nerve activity (-29 +/- 7%, P < 0.05, n = 4) and blood pressure (-27 +/- 5 mmHg, P < 0.05). Injection of 3 mg/kg NBQX produced a greater decrease in sympathetic nerve activity (-78 +/- 11%, P < 0.01, n = 8) and mean arterial pressure (-47 +/- 5 mmHg) and also reduced heart rate (-11 +/- 2 beats/min, P < 0.01). The depressant effects of NBQX on sympathetic nerve activity, blood pressure and heart rate were similar regardless of whether activity was recorded from pre- or postganglionic cardiac nerves, or from animals subjected to baroreceptor denervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Measurement of the intracellular concentration of oxygen in a cell perfusion system.

[O2] was measured in the embedding material (alginate) in a typical apparatus for conducting studies of viable cells with NMR, using low frequency EPR. In suspension cultures respiration was independent of [O2] in the perfusing media down to about 1 microM while in alginate beads, the comparable value was 70 microM, indicating that the alginate was a very substantial barrier to the free diffusion of oxygen. With knowledge of [O2] in the various compartments, [O2] in the perfusing medium can be increased and the full power of NMR can be used to provide information on metabolism under various conditions. These results also provide evidence supporting the feasibility and usefulness of EPR techniques using nitroxides to measure [O2] in macroscopic samples such as NMR perfusion tubes. This technique is rapid, apparently nonperturbing, and enables one to differentiate between the concentrations of oxygen in different compartments.

Alginates↗

Identification of human monoamine oxidase (MAO) A and B gene promoters.

The promoter of human monoamine oxidase (MAO) A and B genes have been identified. The core promoter region of MAO A is comprised of two 90 bp repeats each of which contains two Sp1 elements and lacks a TATA box. The MAO B core promoter region contains two sets of overlapping Sp1 sites which flank a CACCC element all upstream of a TATA box. The different organization of the MAO A and B promoters may underlie their different cell and tissue specific expression.

Base Sequence↗

Changes in active life expectancy in Taiwan: compression or expansion?

The 1986-1989 supplements on Elderly Living Conditions to the Monthly Surveys of Human Resources in the Taiwan area are used to estimate active life expectancy and to examine evidence for a compression of disability. Unlike recent results generated in Western countries in favour of the expansion of morbidity hypothesis, our findings tend to support the hypothesis that declining mortality leads to a compression of disability. In Taiwan fatal diseases (e.g. heart disease, stroke, and cancer) play a more important role in disability than to nonfatal diseases (e.g. arthritis, dementia, sensory impairments, and osteoporosis, etc.). Fatal diseases are still the leading causes of disability; modern technology has not prolonged life significantly to Taiwanese who contract such diseases. Hence the improvement in recent life expectancy is very slow and the duration between age at onset of fatal diseases and death tends to be short. As a result of such short duration, the area between the disability and the mortality curve in the life table narrows.

Adolescent↗

Anti-AIDS agents, 10. Acacetin-7-O-beta-D-galactopyranoside, an anti-HIV principle from Chrysanthemum morifolium and a structure-activity correlation with some related flavonoids.

An active anti-HIV principle, acacetin-7-O-beta-D-galactopyranoside, has been isolated from Chrysanthemum morifolium. Seven additional flavonoids isolated from this plant, 13 known related flavonoids, and 14 synthetic flavonoids were also evaluated as inhibitors of HIV replication in H9 cells. A known flavone, chrysin, was found to be the most promising compound in this series. Flavonoids with hydroxy groups at C-5 and C-7 and with a C-2-C-3 double bond were more potent inhibitors of HIV growth. In general, the presence of substituents (hydroxyl and halogen) in the B-ring increased toxicity and/or decreased activity.

Antiviral Agents↗

Two new macrolide sesquiterpene pyridine alkaloids from Maytenus emarginata: emarginatine G and the cytotoxic emarginatine F.

Two new macrolide sesquiterpene pyridine alkaloids, emarginatine F [1] and emarginatine G [2], were isolated from Maytenus emarginata. The structural determinations of 1 and 2 by 2D nmr techniques and spectral comparison with a related compound, emarginatine A [3], are discussed. Biological evaluation showed that emarginatine F [1] demonstrated strong cytotoxicity against human epidermoid carcinoma of the nasopharynx (KB), ileocecal adenocarcinoma (HCT-8), melanoma (RPMI-7951) and medulloblastoma (TE-671) tumor cells, and against murine leukemia (P-388).

Animals↗

New estimation methods that directly use the time accumulated counts in the input function in quantitative dynamic PET studies.

In cardiac dynamic PET studies, the input function can be obtained directly from the reconstructed images. Therefore, there is a need to convert the time accumulated count to the time-activity curve (TAC). Conventionally, this is done by dividing the total counts in a localized region on the reconstructed image obtained during each scan frame period by its frame duration. This conversion, however, can significantly bias the estimates of rate constants of a compartmental model describing the dynamics of a PET tracer. Three new methods are formulated in this study. These new methods either use the accumulated counts in the input function directly or convert the accumulated counts to the input function more accurately. Computer simulation results show, for C-11 acetate and F-18 fluoro-2-deoxy-D-glucose (FDG), that the three new methods proposed can improve significantly the parameter estimates over the ones obtained by the conventional method.

Acetates↗

Comparison of dietary habits, physical activity and body size among Chinese in North America and China.

BACKGROUND: Chinese in North America have higher rates of many chronic diseases than do Chinese in Asia. However, there is a lack of data among comparisons of the environmental and lifestyle factors for Chinese in China and Chinese residing in North America. METHODS: We examined self-reported dietary nutrient intakes, physical activity patterns and body mass index of 2488 healthy Chinese men and women residing in North America (US and Canada) and in the People's Republic of China. RESULTS: On average, Chinese in China consumed more calories (males 2904 kcal in China, versus 2201 kcal in North America; females 2317 Kcal in China, versus 1795 Kcal in North America and more carbohydrate, but less fat (males 72.2 g in China versus 84.5 g in North America, females 56.6 g in China versus 70.8 g in North America), protein, vitamin A, beta-carotene and vitamin C than did Chinese in North America. Per cent calories from fat was 35% for Chinese in North America and 22% for Chinese in China. In contrast, the per cent of calories from carbohydrates was 62-68% in China and 48% in North America. Chinese in China reported spending more time in vigorous activity, sleeping and walking but less hours in sitting than Chinese in North America. Chinese in China weighted less and were leaner than North American Chinese. CONCLUSIONS: These differences in nutrient intakes, physical activity and body size of Chinese living on two different continents suggest possible explanations for observed differences in chronic disease rates in the two populations.

Asian People↗

Cloning of a novel monoamine oxidase cDNA from trout liver.

A trout liver monoamine oxidase (MAO) cDNA was cloned by screening a cDNA library with a human MAO-A cDNA probe. The trout MAO cDNA encodes 499 amino acids, with a molecular mass of 56.6 kDa. The deduced amino acid sequence of trout MAO shows 70% and 71% identity with those of human MAO-A and MAO-B, respectively. Trout MAO contains the pentapeptide sequence Ser-Gly-Gly-Cys-Tyr, to which the cofactor FAD is covalently bound. Transient expression of the cDNA in COS-7 cells shows that trout MAO oxidizes both serotonin [5-hydroxytryptamine (5-HT)] and beta-phenylethylamine (PEA), unlike human MAO-A and MAO-B, which oxidize only 5-HT and PEA, respectively. The Km for 5-HT is similar for trout MAO (130 +/- 17 mM) and human MAO-A (68 +/- 4 mM). The Km for PEA is similar for trout MAO (12.5 +/- 2.0 mM) and human MAO-B (1.5 +/- 0.2 mM). When 5-HT is used as a substrate, trout MAO is more sensitive to clorgyline (IC50, 2.8 +/- 0.2 x 10(-8) M) than deprenyl (IC50, 1.0 +/- 0.1 x 10(-6) M), a result similar to the inhibition selectivity of human MAO-A. However, trout MAO is less sensitive to clorgyline than is human MAO-A (IC50, 5.8 +/- 0.1 x 10(-10) M). Trout MAO is less sensitive to deprenyl (IC50, 4.6 +/- 0.3 x 10(-7) M) than is human MAO-B (IC50, 1.4 +/- 0.1 x 10(-9) M) when PEA is used as the substrate. These results indicate that trout MAO displays substrate and inhibitor selectivities that are not identical to those of either MAO-A and -B, and it therefore represents a novel type of MAO. The structure of trout MAO will provide insights into the substrate and inhibitor selectivities of the MAOs.

Amino Acid Sequence↗

[Influence of acupuncture at zusanli point on function of 5-HT and M receptor in rat's brain and spleen].

5-HT and muscarine (M) receptors total binding capacities (Rt) in different brain areas and spleen were determined using receptor radioligand binding assay (RLBA) after needling zusanli of rats. And the rats without needling and needling Taichong point were used as control. These results showed that 5-HT and M receptors Rt were decreased obviously than control group in rat's cerebral cortex, hippocampus, striatum, spinal cord and spleen when needling zusanli can produce obvious acupuncture analgesia. 5-HT Rt in brain stem and medulla oblongata was obviously decreased and not changed in thalamus. M receptor Rt value was not changed clearly in brain stem and medulla oblongata as well, but it was obviously decreased in thalamus. These results showed that effects of acupoints on Various meridians are different, thus the results of acupuncture at Zusanli are distinct from taichong.

Acupuncture Points↗

The non-NMDA subtype of excitatory amino acid receptor plays the major role in control of cardiovascular function by the subretrofacial nucleus in cats.

Recent studies have reported that microinjection of kynurenic acid (KYN 12.5 nmol), the nonselective Excitatory Amino acid (EAA) antagonist, into the rostral ventrolateral medulla of the cat decreases arterial blood pressure (BP) and inferior cardiac sympathetic nerve discharge. The purpose of our study was to confirm this finding and determine the subtypes of EAA receptor(s) responsible for mediating this effect. This was done by microinjecting various EAA antagonists bilaterally into the SRFN of chloralose-anesthetized animals while monitoring BP and HR. KYN (12.5 nmol; N = 5) produced a decrease in mean BP (31 +/- 9 mmHg, P < .05) with no significant change in HR. To determine the subtype of EAA receptor responsible for eliciting tonic sympathetic outflow from the SRFN, specific antagonists of N-methyl-D-aspartate (NMDA) and non-NMDA EAA receptors were tested. The NMDA receptor antagonist 3-(RS)-Carboxypiperazin-4-yl)-proyl- 1-phosphonic acid (CPP-2.25 nmol; N = 3) microinjected into the SRFN produced a small but significant decrease in BP (-13 +/- 1 mmHg; P < .05). This effect of CPP was significantly less than that seen with KYN. Two antagonists of the non-NMDA subtype of EAA receptor, 6-cyano-7-nitroquinoxaline-2,3-dione (0.05 nmol; N = 4) and gamma-D-glutamylaminomethyl sulphonic acid (2.5 nmol; N = 4), were microinjected into the SRFN. Both of these drugs produced decreases in BP (-29 +/- 4 and -23 +/- 3 mmHg, respectively; P < 0.05) similar to that observed with KYN. No significant changes in HR were noted with CPP, 6 cyano-7-nitroquinoxaline-2,3-dione or gamma-G-glutamylamino-methylsulfonate. These data indicate that a non-NMDA EAA receptor plays the major role in control of cardiovascular function by the SRFN.

6-Cyano-7-nitroquinoxaline-2,3-dione↗