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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 1,207 records · Page 67Linked to original sources

Characterization of long-term potentiation of C-fiber-evoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 receptors.

Impulses in afferent C fibers, e.g., during peripheral trauma, may induce plastic changes in the spinal dorsal horn that are believed to contribute to some forms of hyperalgesia. The nature of lasting changes in spinal nociception are still not well understood. Here we characterized the long-term potentiation (LTP) of spinal field potentials with a negative focus in superficial spinal dorsal horn evoked by supramaximal electrical stimulation of the sciatic nerve in urethan-anesthetized adult rats. The field potentials studied in this work had high thresholds (>/=7 V, 0.5 ms), long latencies (90-130 ms), and long chronaxy (1.1 ms) and were not abolished by muscle relaxation and spinalization. Thus they were evoked by afferent C fibers. In response to 1-Hz stimulation of afferent C fibers, amplitudes of C-fiber-evoked field potentials remained constant, whereas number of action potentials of some dorsal horn neurons increased progressively (wind-up). In all 25 rats tested, high-frequency, high-intensity stimulation (100 Hz, 30-40 V, 0.5 ms, 400 pulses given in 4 trains of 1-s duration at 10-s intervals) always induced LTP (to approximately 200% of control), which consistently lasted until the end of recording periods (4-9 h). This tetanic stimulation also significantly decreased mean threshold of C-fiber-evoked field potentials. The C-fiber volley, which was recorded simultaneously in sural nerve, was, however, not affected by the same tetanic stimulation. High-frequency, low-intensity stimulation (100 Hz, 3 V, 0.5 ms) never induced LTP in six rats tested. At an intermediate frequency, high-intensity stimulation (20 Hz, 40 V, 0.5 ms, 400 pulses given in 4 trains of 5 s at 10-s intervals) induced LTP in four out of six rats, which lasted until end of recording periods (3-6 h). In the remaining two rats, no LTP was induced. Low-frequency, high-intensity stimulation (2 Hz, 30-40 V, 0.5 ms, 400 pulses) induced LTP that lasted for 2-8 h in four out of five rats. Intravenous application of neurokinin 1 (NK1) or neurokinin 2 (NK2) receptor antagonist RP 67580 (2 mg/kg, n = 5) or SR 48968 (0.3 mg/kg, n = 5) 30 min before high-frequency, high-intensity stimulation blocked the induction of LTP in all rats tested. In contrast, the same dose of their inactive enantiomers RP 68651 (n = 5) or SR 48965 (n = 5) did not affect the induction of LTP. Spinal superfusion with RP 67580 (1 microM) from 30 min before to 30 min after high-frequency, high-intensity stimulation blocked induction of LTP in all five rats tested. Spinal application of SR 48968 (10 nM) prevented LTP in five out of seven rats. However, when spinal superfusions with RP 67580 (1 microM, n = 3) or SR 48968 (10 nM, n = 3) were started 1 h after high-frequency, high-intensity stimulation, established LTP was not affected. Thus the activation of neurokinin receptors is necessary for the induction but not for the maintenance of LTP of C-fiber-evoked field potentials in spinal dorsal horn. This model may be useful to study plastic changes in spinal cord induced by peripheral C-fiber stimulation. The LTP of C-fiber-evoked field potentials may be a mechanism underlying some forms of hyperalgesia.

Animals↗

Severe myopia as a risk factor for progressive visual field loss in primary open-angle glaucoma.

The optic nerve head in severely myopic eyes may be particularly vulnerable to glaucomatous damage. To study this hypothesis, we examined 122 primary open-angle glaucoma eyes with fair to good control of the intraocular pressure and a sign of baseline optic nerve damage. Then, parameters for the progression of the visual field defects were evaluated by multivariate analysis. A high mean intraocular pressure (p = 0.007) and a large refractive error (p = 0.023) were significant risk factors for subsequent visual field loss. A high baseline cup-to-disk ratio (p = 0.100) was a marginal risk factor. Nonsignificant parameters included patient age (p = 0.692), the use of beta-adrenergic antagonists (p = 0.384), gender (p = 0.831) and left versus right side (p = 0.977). When the refractive error was used to subclassify patients into severely myopic (< or = -4 dpt), mildly myopic (-0.25 to -4 dpt), or emmetropic and hyperopic (> or = 0 dpt), only severe myopia was a significant risk factor for progressive visual field loss. Severe myopia, but not mild myopia, is a significant risk factor for subsequent visual field loss in patients with primary open-angle glaucoma.

Adolescent↗

Students' stress in China, Japan and Korea: a transcultural study.

In this transcultural comparison of stress among Chinese, Japanese and Korean students, the authors examined stressors with the Stress Questionnaire Form for College Students, strategies for coping with Ways of Coping-Revised, and physical reactions to the stressors with the Physical Symptom Scale of Stress. Compared to the Japanese and Korean students, Chinese students had a multitude of stressors and experienced the highest level of stress. In coping with stressful events, Koreans were the most active, Chinese the least active and Japanese were intermediately active. Physical symptoms were found to be most serious in Koreans and less serious in Chinese and Japanese. Coping techniques seemed unrelated to alleviating physical symptoms in Koreans but mildly related in Chinese and Japanese.

Adaptation, Psychological↗

Paradoxical action of activin A on folliculogenesis in immature and adult mice.

Activin A is a gonadal protein originally isolated from follicular fluid and is recognized as a local regulator of granulosa cell differentiation. Whether activin A promotes folliculogenesis, however, still remains unclarified. The present study was designed to elucidate the effect of activin A on follicular growth in in vitro follicle culture systems. Preantral follicles, 100-120 microm in diameter, were mechanically isolated from BDF1 hybrid immature mice (11 days old) and adult mice (8 weeks old), then cultured for 4 days in a serum-free medium supplemented with activin A (100 ng/ml), FSH (100 mIU/ml), and a combination of both. Follicular diameter was measured daily, and the amount of estradiol and inhibin released at day 4 was determined by RIA. Preantral follicles collected from immature mice showed a significant increase in diameter when cultured with activin A or both activin A and FSH. FSH alone showed no significant effect on the diameter of follicles from immature mice. In contrast, the diameter of preantral follicles from adult mice significantly increased in response to FSH. Activin A did not stimulate growth of follicles from adult mice, and more interestingly, blocked the effect of FSH. The inhibitory action of activin A was in part restored by co-culture with follistatin (100 ng/ml). These results indicate that activin A is folliculogenetic in the prepubertal mouse, but not in adults.

Activins↗

Phosphorylation of the lutropin/choriogonadotropin receptor facilitates uncoupling of the receptor from adenylyl cyclase and endocytosis of the bound hormone.

Stably transfected cell lines expressing the wild-type rat LH/CG receptor (rLHR) or a full-length rLHR in which S635, T638, S639, S649 and S653 were simultaneously mutated to alanine residues (designated rLHR-5S/T-->A) were used to probe the importance of receptor phosphorylation on the regulation of receptor functions. The mutant receptor binds hCG with high affinity and transduces the hormonal signal into increases in cAMP and inositol phosphate accumulation comparable in magnitude to those elicited by the wild-type receptor. In contrast to cells expressing rLHR-wt, which respond to hCG or phorbol 12-myristate 13-acetate stimulation with an increase in rLHR phosphorylation, the phosphorylation of rLHR in cells expressing rLHR-5S/T-->A is severely blunted. Likewise, the phorbol 12-myristate 13-acetate-induced desensitization of hCG-induced cAMP accumulation is drastically reduced in cells expressing rLHR-5S/T-->A. In contrast, the hCG-induced desensitization of hCG-induced cAMP accumulation is delayed, but not abolished, in cells expressing rLHR-5S/T-->A. Lastly, the rate of internalization of the receptor-bound hCG is slower in cells expressing rLHR-5S/T-->A than in cells expressing rLHR-wt. These results show that phosphorylation of rLHR is necessary, but not sufficient, for uncoupling of the receptor from adenylyl cyclase and for endocytosis of the receptor-bound hormone.

Adenylyl Cyclases↗

Estrogen-related receptor alpha 1 functionally binds as a monomer to extended half-site sequences including ones contained within estrogen-response elements.

The human estrogen-related receptor alpha 1 (hERR alpha 1) is an orphan member of the steroid/thyroid hormone receptor superfamily. A cDNA encoding this protein was originally isolated on the basis of sequence similarity in its DNA-binding domain with estrogen receptor alpha (ER alpha). Previously, we reported the purification of hERR alpha 1 from HeLa cell nuclear extracts on the basis of its ability to bind two sites in the late promoter of simian virus 40 (SV40). We have now determined the primary structure and the DNA and protein binding specificities of hERR alpha 1 and developed in vivo and in vitro assays for its functional activities. hERR alpha 1 was found to bind as a monomer, with a high-affinity binding site containing the extended half-site sequence 5'-TCAAG-GTCA-3'. Binding sites for hERR alpha 1 were identified in many cellular promoters, including some that were previously shown to function as estrogen-response elements (EREs). hERR alpha 1 was shown to function as a sequence-specific repressor of the SV40 late promoter in both cell culture and cell-free transcription systems. It was also shown to interact with both ER alpha and the transcription factor TFIIB by direct protein-protein contacts. Thus, hERR alpha 1 may play a role in the response of some genes to estrogen via heterodimerization with ERs or competition with ERs for binding to EREs.

Base Sequence↗

The six N-linked carbohydrates of the lutropin/choriogonadotropin receptor are not absolutely required for correct folding, cell surface expression, hormone binding, or signal transduction.

Using two separate methods, we have determined that all six potential sites for N-linked glycosylation on the rat lutropin/choriogonadotropin receptor (rLHR) contain carbohydrates. The functional roles of the carbohydrates were analyzed initially through the use of two nonglycosylated receptor mutants rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A). Although Western blot analyses demonstrated both mutant receptors to be stably expressed, little or no hCG binding activity could be detected in detergent solubilized extracts of 293 cells expressing either nonglycosylated LHR mutant. Although this loss of hCG binding was concluded to be due to misfolding, it was unknown whether this misfolding was due to the absence of carbohydrates or to the multiple amino acid substitutions that had been introduced into the polypeptide. To differentiate between these possibilities, hCG binding assays were performed with nonglycosylated receptors obtained after tunicamycin treatment of cells expressing the wild-type rLHR. Even though these wild-type receptors were confirmed to be devoid of all N-linked carbohydrates by Western blots, they were found to bind hCG with a normal high affinity. In addition, tunicamycin-derived, nonglycosylated LHRs were present at the cell surface and exhibited a phenotype consistent with mature receptors due to their capability to mediate hCG-stimulated cAMP production as well as bind oLH with high affinity. These results indicate that the loss of high affinity hormone binding by rLHR(N(77,152,173,269,277,291)Q) and rLHR(N(77,152,269,277,291)Q;T(175)A) is simply due to the collective amino acid substitutions rather than to the absence of carbohydrates. Therefore, N-linked carbohydrates are not absolutely required for the proper folding of the rLHR into a mature receptor capable of binding hormone and signaling. These results are in marked contrast to the follitropin receptor (FSHR), a very similar receptor which has been shown to strictly require N-linked carbohydrates for folding of the nascent protein.

Animals↗

Defective phototransductive disk membrane morphogenesis in transgenic mice expressing opsin with a mutated N-terminal domain.

Retinitis pigmentosa is a heterogeneous group of inherited retinal disorders in which the photoreceptor cells degenerate. A line of transgenic mice expresses a mutant opsin gene that encodes three missense mutations near the amino terminus, including P23H, which is the basis for a common form of dominant retinitis pigmentosa. By studying the photoreceptor cells of these mice and their normal littermates, we found that: (1) opsin was routed correctly, (2) the concentration of opsin in the disk membranes appeared normal by freeze fracture analysis, (3) the amount of disk membrane shedding was normal, but (4) the basal disks of the outer segments were disorganized, indicating defective disk membrane morphogenesis. Defective disk membrane morphogenesis appears to result in the formation of fewer mature disks, thus accounting for observed gradual shortening of the photoreceptor outer segments with age. We suggest that abnormal disk membrane morphogenesis is the primary cellular defect that leads to blindness, and that it arises from the inability of nascent disk membranes, containing normal and mutant opsin, to interact normally with each other.

Animals↗

Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study.

For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.

Child↗

Evaluation of evaporative heat transfer characteristics of helmets.

The prime purpose of a safety helmet is to protect against occupational hazards. However, thermal comfort is one important ergonomics requirement for a helmet to be accepted by its wearer. To design and manufacture a thermally comfortable helmet, a method for testing and evaluating the thermal properties is essential. Research has long focused on the evaluation of dry heat transfer (conduction, convection and radiation). Evaporative heat transfer was not much addressed. In order to analyze the wet heat transfer (evaporation) component, a sweating thermal head manikin has been used. In this study the method has been further improved by constructing a new sweating head manikin. The surface of the head manikin is divided into five zones which can provide more detailed information about the environmental effects on the heat transfer from the head when a helmet is worn. Water supply (simulated sweating) is also improved by use of an electronic pumping system which provides a steady and adjustable flow rate of water to the head manikin. Experiments were conducted within a climatic chamber with this improved method under different test conditions: the ambient temperature and the head manikin surface temperature are set at the same level: 34 +/- 0.5 degrees C; two levels of head surface wettedness: 0.44 and 1.0; two levels of ambient humidity: 30% and 60%; and two levels of wind speed: 0.4 m/s and 1.0 m/s. Seven different helmets were used in the experiments. The results showed that the improved method revealed more detailed information about the evaporative heat transfer; it is easier to use and control; less error is involved with the measurement.

Ergonomics↗

Drug policy in China. Transformations, current status and future prospects.

The pharmaceutical sector in China developed rapidly with the implementation of the market-oriented economic reforms, which began at the end of the 1970s. From 1980 to 1988 the production of drugs quadrupled, subsequently increasing at an annual rate of 20%, and consumption of drugs correspondingly increased. The increase in drug production was largely a result of the increase in the number of pharmaceutical companies, particularly the number of private joint ventures, of which there were none in 1980 and 1900 in 1994, accounting for 37% of the total number of pharmaceutical companies. With the transformation of the Chinese pharmaceutical market, some new problems have appeared. The low efficiency of pharmaceutical companies, poor-quality drugs, unfair competition and misuse of drugs have been of great concern to the Chinese government. Some countermeasures have been taken, but the problems remain. Increases in the age of the Chinese population, increases in income and changes in disease patterns, together with membership of the World Trade Organization will promote the development of the pharmaceutical market. However, health-insurance reform, an essential drug list, the separation of drugs from services, and controls on the increases in hospital revenue will reduce the demand for drugs. Pharmaceutical companies in China face both opportunities and challenges. The trend in development of the pharmaceutical market depends on the outcome of the interaction between the factors that increase, and those that decrease, the demand for drugs. While the general trend is towards an increase in the demand for drugs and the expansion of the pharmaceutical market, downward fluctuation is inevitable if effective health reforms of cost control are introduced nationwide.

China↗

Acute study on the neuronal excitability of the cochlear nuclei of the guinea pig following electrical stimulation.

To help deaf patients who cannot benefit from the cochlear implant due to interruption of the auditory nerve, a central auditory prosthesis has been developed to directly stimulate the cochlear nucleus in the brainstem. The electrode array lies on the surface of the cochlear nucleus and is designed to stimulate at 250 pulses/sec. To examine the safety of this prosthesis, guinea pig cochlear nuclei were stimulated acutely with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250, 500 or 1,000 pulses/s and charge intensities of 1.8, 2.8, 3.5 or 7.1 microC/phase cm(-2). The electrically evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following this acute electrical stimulation. Respiration rate and body temperature were also monitored during the experiment. The amplitudes and latencies of the EABR waves were measured and compared among the before, during and after stimulation periods. The results showed that respiration rate and body temperature remained within normal limits for the duration of the acute stimulation. During and after electrical stimulation, no change was found in the EABR waveform, dynamic ranges and threshold with up to 6 h direct continuous stimulation of the cochlear nucleus. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. However, a slight temporary reduction in the amplitude of the EABR waves was observed at 30-60 min during the course of acute stimulation using the highest charge density (7.1 microC/phase cm(-2)). This reduction showed a stronger correlation with the stimulus current, charge/phase and charge density than threshold. The present findings suggest that acute bipolar electrical stimulation with surface electrodes at rates up to 1,000 pulses/s and charge density up to 7.1 microC/phase cm(-2) is safe for neuronal excitability of the cochlear nucleus in guinea pig.

Animals↗

A 120 kilobase resolution contig map of the rice genome.

92% of the rice genome (4.3 x 10(8) bp, 2n = 24) was covered by 631 contigs of various length, which were generated by fingerprinting from a representative and genetically stable bacterial artificial chromosome (BAC) library of the Guang Lu Ai 4 (a O. Sativa variety) genome with the average insert of 120 kb in length. To form the contig map, 565 molecular markers of RFLP, STS, cDNA and anchor set derived from two O. Sativa varieties were by colony hybridization mapped to the contigs, which were then assigned to and ordered along the particular chromosomes according to the marker colinearity. Being highly conserved DNA sequences shared among the genomes of rice, barley, wheat, oat, maize, sorghum and sugar cane, 89 anchor markers mapped help to identify the rice genes through the information provided by the maps of relative genomes, and vice versa. Numerous repeated DNA sequences of various length were identified and mapped to the chromosomes. Physical distances have been determined for hundreds pairs of adjacent markers, which would facilitate the identification by map-based cloning the rice genes of interest. The accuracy of clone overlaps in contigs was further confirmed by the existence in contigs of well fit stacks of marker-lodged clones independently identified by hybridization. Large scale DNA sequencing of individual chromosomes could now be initiated simply by selecting and sequencing the minimally overlapped BAC clones of the contigs.

Alkyl and Aryl Transferases↗

[Protein kinase C involved in the protecttve effect of anoxic preconditioning on vascular smooth muscle cells].

It has been known that anoxic preconditioning (APC) has protective effects not only on cardiomyocyte, but also on vasculature. However, the effects of APC on vascular smooth muscle cells (VSMC) is unknown. On the model of anoxia/reoxygenation (A/R) injury of rabbit VSMC, the effect of APC was observed. It was found that APC could increase the survival rate of VSMC after A/R injury, lower the leakage of lactate dehydrogenase (LDH) and protein from cells, and attenuate peroxidation injury and calcium overload of VSMC. The results also showed that PMA, an activator of protein kinase C (PKC), could mimic, but H7 or polymyxin B (inhibitors of PKC) could abolish the above protective effect of APC. It is suggested that the protective effect of APC on VSMC during A/R injury might be due to the activation of PKC.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

[The protective effect of SOD on injury of bone marrow hematopoietic progenitor cells of mice under 4 degrees C storage].

The protective effect of Cu, Zn, SOD on bone marrow hematopoietic progenitor cells of mice, under 4 degrees C storage was studied. The results showed, if 1.65 U or 0.165 U/ml SOD was added to the cell suspension for 3 days at 4 degrees C, the production rate of CFU-GM, CFU-E, BFU-E, CFU-Meg and CFU-Mix were 6.2, 2.6, 2.9, 4.0 and 5.1 times that of control group (without SOD) respectively. The survival rate of hematopoietic progenitor cells increased obviously. The mechanism of SOD effect is supposed to prevent hematopoietic progenitor cells from death, instead of the regulating proliferation. It may be closely related to the antioxidation of SOD which scavenges the superoxide free radicals.

Animals↗

[Drug resistance mechanism of doxorubicin-resistant human gastric cancer cells BGC-823/DOX].

To further investigate drug resistance mechanism of BGC-823/DOX, we analysed the amplication, transcription and overexpression of genes associated with drug resistance by Southern blot, RT-PCR, immunohisto clogical assay and the concentration of Doxorubicin in the cells by flow cytometry. The results showed that parent cells of BGC-823 were cell line with intrinsic drug resistance similar to the gastrointestinal tumors. Multidrug resistance was the main mechanism of drug resistance in BGC-823/DOX. There was a significant difference between the doxorubicin-resistant cells line from parent cells with intrinsic drug resistance and from parent cells without intrinsic drug resistance in drug resistance.

ATP-Binding Cassette Transporters↗

[Establishment and characterization of doxorubicin-resistant BGC-823/DOX of human gastric cancer cell line].

To study drug resistance mechanism of gastrointestinal tumor, doxorubicin resistant cell line of human gastric cancer, we developed BGC-823/DOX, by increasing doses of doxorubicin. We completed chromosomal analysis, double time of cell grow, cell cycle distributions, drug resistance and cross-resistance, and studied reversing drug resistance. The results showed that chromosome of BGC-823/DOX was subtriploid karyotype. Cell morphology, double time, cell cycle distributions were different from its parent cells and 6.35 times more resistant to cytotoxic action of doxorubicin, cross-resistant to VP-16. Verapamil showed modified effect on doxorubicin resistance. BGC-823/DOX with doxorubicin resistance has many characteristics of gastrointestinal tumors.

Adenocarcinoma↗