Search PubMed⌕ Search

Biomedical subjects

K Xu

Publications and source records attributed to K Xu.

At least 181 records · Page 10Linked to original sources
PubMed1996

Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35.

Leukotriene C4 (LTC4) synthase catalyzes the conjugation of LTA4 with reduced GSH to form LTC4, the parent of the receptor active cysteinyl leukotrienes implicated in the pathobiology of bronchial asthma. Previous cloning of the cDNA for human LTC4 synthase demonstrated significant homology of its amino acid sequence to that of 5-lipoxygenase activating protein (FLAP) but none to that of the GSH S-transferase super-family. Genomic cloning from a P1 library now reveals that the gene for LTC4 synthase contains five exons (ranging from 71 to 257 nucleotides in length) and four introns, which in total span 2.52 kilobase pairs in length. The intron/exon junctions of LTC4 synthase align identically with those of FLAP; however, the small size of the LTC4 synthase gene contrasts with the > 31-kilobase pair size reported for FLAP. Confirmation of the LTC4 synthase gene size to ensure that no deletions had occurred during the cloning was obtained by two overlapping polymerase chain reactions from genomic DNA, which provided products of the predicted sizes. Primer extension analysis with poly(A)+ RNA from culture-derived human eosinophilic granulocytes or the KG-1 myelogenous cell line revealed multiple transcriptional start sites with prominent signals at 66, 69, and 96 base pairs 5' of the ATG translation start site. The 5'-flanking region revealed a GC-rich promoter sequence consistent with an SP-1 site and consensus sequences for AP-1 and AP-2 enhancer elements, 24, 807, and 877 bp, respectively, 5' from the first transcription initiation site. Southern blot analysis of a genomic DNA (with full-length cDNA as well as 5' and 3' oligonucleotide probes) confirmed the size of the gene and indicated a single copy gene in normal human genomic DNA. Fluorescent in situ hybridization mapped LTC4 synthase to chromosomal location 5q35, which is in close proximity to the cluster of genes for cytokines and receptors involved in the regulation of cells central to allergic inflammation and implicated in bronchial asthma.

5-Lipoxygenase-Activating Proteins↗
PubMed1996

Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide.

The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run-on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.

Animals↗
PubMed1996

Analysis of abrB mutations, mutant proteins, and why abrB does not utilize a perfect consensus in the -35 region of its sigma A promoter.

The Bacillus subtilis global regulator AbrB is a DNA-binding protein composed of six identical monomers of 96 amino acids that shows specificity to the promoter regions of its target genes including its own. We have sequenced thirteen previously uncharacterized abrB mutations. Four mutant AbrB proteins were purified, and their DNA-binding properties and multimeric structures were examined. AbrB23 (R25S) had no appreciable DNA binding activity but retained a hexameric structure, indicating that Arg25 is important in DNA interactions. Three other mutant proteins, AbrB1 (C56Y), AbrB19 (Gln83-->termination codon), and AbrB100 (L69P), showed decreased DNA binding and altered multimeric interactions. Analysis of the expression and AbrB binding affinities of mutant abrB promoters demonstrated that a consensus -35 region is incompatible with proper autoregulation of the abrB gene.

Amino Acid Sequence↗
PubMed1996

L-DOPA modulation of corpus striatal dopamine and dihydroxyphenylacetic acid output from intact and 6-OHDA lesioned rats.

In the present report we examined the differences in in vitro dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) efflux from the corpus striatum (CS) of intact versus 6-hydroxydopamine (6-OHDA) lesioned (in substantia nigra) male rats in response to different doses of two pulse infusions of L-dihydroxyphenylalanine (L-DOPA). In the first experiment, we tested the effects of two 20-min infusions of 5 uM L-DOPA. In the second experiment we repeated this protocol using 50 uM L-DOPA. There was an overall significantly greater output of DA for intact versus 6-OHDA lesioned rats for both doses. Moreover, in Experiment 1, the 5 uM L-DOPA produced a peak DA response to the second infusion which was significantly higher than that of the first infusion in the intact, but not lesioned rats. In Experiment 2, the 50 uM L-DOPA group showed no significant differences in DA output between the two infusions for both intact and lesioned rats. In contrast to DA responses, there were no overall significant differences in DOPAC output between intact and 6-OHDA lesioned rats for both doses. However, for both doses tested, the peak DOPAC output from the second infusion was significantly increased in lesioned, but not intact rats. These data demonstrate that L-DOPA evoked DA and DOPAC output are differentially modulated in intact and 6-OHDA lesioned striatum. The lesions of the striatal dopaminergic system may alter these responses through changes in intraneuronal storage and metabolism of DA following L-DOPA infusion.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

The importance of cytoplasm in early embryonic development.

PURPOSE: A mouse model was used to evaluate the consequences of partial cytoplasm removal, which mimics the consequence of human early embryo fragmentation, at the one-cell stage on embryonic development to the morula and blastocyst stages. RESULTS: Opening the zona pellucida at the zygote stage has no detrimental effect on the number of differentiated or total cells at morula/blastocyst stage. However, reduced cytoplasm significantly affects the number of inner cell mass cells, 21.7 (10% cytoplasm removed) vs 27.6 (control) and 15.1 (20% cytoplasm removed) vs 24.7 (control). CONCLUSIONS: The contribution of cytoplasm of maternal origin is critical to early embryonic development.

Animals↗
PubMed1996

Quantification of mRNAs for three alpha 1-adrenoceptor subtypes in rat aorta by solution hybridization.

We used solution hybridization to quantify mRNAs for alpha 1A-, alpha 1B-and alpha 1D-adrenoceptor(AR) in rat aortae. The results showed that the mRNA for alpha 1A-, alpha 1B- and alpha 1D-AR was 0.28 +/- 0.03 fmol, 0.35 +/- 0.03 fmol and 0.82 +/- 0.09 fmol, respectively, in 40 micrograms total RNA extracted from rat aorta. The dominant expression of alpha 1D-AR further support the recent findings that alpha 1D-AR is a major functional receptor subtype of AR in rat aorta.

Animals↗
PubMed1996

Ascaris, people and pigs in a rural community of Jiangxi Province, China.

A longitudinal investigation on natural populations of Ascaris in humans and pigs and an investigation of soil contamination with Ascaris eggs were carried out from June 1993 to June 1994 in 2 villages, Manhu area, Xinjian County, Jiangxi Province, China. Results from these studies indicate that although human ascariasis is endemic there is significant fluctuation in both prevalence and the mean number of eggs/g faeces (epg) of the communities. Fluctuation of age-stratified prevalence and mean epg was detected in children but not in most adult groups. Most cases of human ascariasis were judged to involve low intensities of infection and a typical overdispersion distribution pattern was observed through the year. It was estimated that during the year, nearly half of the eggs discharged in the environment came from infections in children aged between 2 and 15 years which accounted for about 30% of the total population. Soil in and around houses and in vegetable gardens was found to be contaminated by Ascaris eggs and this situation remained relatively stable throughout the year. Monthly developmental rate of Ascaris eggs in soil was detected and the results suggest that the fluctuation in prevalence observed during the year should be directly attributed to the effect of seasonality of egg development. Features of Ascaris infection in pigs were found to be similar to those in humans except for a lower mean intensity of infection. The possibility of cross-infection of Ascaris between human and pig hosts is discussed.

Adolescent↗
PubMed1996

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer.

A retroviral vector containing the wild-type p53 gene under control of a beta-actin promoter was produced to mediate transfer of wild-type p53 into human non-small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector-related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector-p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Aged↗
PubMed1996

In vitro selection of optimal AbrB-binding sites: comparison to known in vivo sites indicates flexibility in AbrB binding and recognition of three-dimensional DNA structures.

The AbrB protein of Bacillus subtilis regulates expression of numerous genes, primarily through specific binding interactions to DNA regions containing transcriptional promoters. Although over 15 target regions for AbrB binding to chromosomally located sequences have been analysed by DNase I footprinting, no obvious consensus sequence or motif has yet emerged from their examination. Using in vitro selection techniques, we have isolated optimal AbrB-binding sites from oligonucleotides containing 22 or 44 random base pairs. The best of these sites have an apparent in vitro Kd which is fivefold lower than a similar-sized DNA fragment containing the sequence corresponding to the AbrB-binding site on the spo0E gene. We tested one of the sites in vivo and found that it confers AbrB-mediated control upon a promoter not normally regulated by AbrB. In each of four separate trials, the selected sites possess motifs that converge to a simple consensus. It is argued that the nature and spacing of these motifs produce a type of three-dimensional DNA structure recognizable by AbrB, and that known in vivo sites, which lack these motifs, possess an approximation of the optimal structural determinant.

Amino Acid Sequence↗
PubMed1996

Artificial neural network to assist psychiatric diagnosis.

BACKGROUND: Artificial Neural Network (ANN), as a potential powerful classifier, was explored to assist psychiatric diagnosis of the Composite International Diagnostic Interview (CIDI). METHOD: Both Back-Propagation (BP) and Kohonen networks were developed to fit psychiatric diagnosis and programmed (using 60 cases) to classify neurosis, schizophrenia and normal people. The programmed networks were cross-tested using another 222 cases. All subjects were randomly selected from two mental hospitals in Beijing. RESULTS: Compared to ICD-10 diagnosis by psychiatrists, the overall kappa of BP network was 0.94 and that of Kohonen was 0.88 (both P < 0.01). In classifying patients who were difficult to diagnose, the kappa of BP was 0.69 (P < 0.01). ANN-assisted CIDI was compared with expert system assisted CIDI (kappa = 0.72-0.76); ANN was more powerful than a traditional expert system. CONCLUSION: ANN might be used to improve psychiatric diagnosis.

Adult↗
PubMed1996

[Clinical study of scopolamine detoxification for the treatment of heroin addicts].

OBJECTIVE: To evaluate the efficacy of treatment of heroin addicts (n = 100) by scopolamine detoxification (10 days program). METHODS: Methadone detoxification (10 days program) group (n = 50) and clonidine treated group (n = 50) served as controls. RESULTS: The scores of abstinence syndrome in scopolamine detoxification group were lower that those in clonidine treated group in the first three days of protocol, but this difference disappeared in the late stage of treatment. While scopolamine detoxification was effective as methadone detoxification in the control of abstinence syndrome during the first five days of treatment but the difference in the scores of abstinence syndrome between scopolamine and methadone group was observed during the late five days of protocol. The side-effects produced by scopolamine in general were dry mouth, somnolence, tachycardia, blurred vision and so on, which relieved gradually or disappeared with decreasing of its doses. CONCLUSION: Scopolamine does not result in potential dependence and has definite curative effect in the treatment of heroin addiction.

Adult↗
PubMed1996

[Solubilization of beta-bungarotoxin-binding protein from rat diaphragm and inhibition of its binding by some other presynaptic neurotoxins].

The mechanism of the transmitter release-blocking action of beta-bungarotoxin at neuromuscular junctions is probably related to the binding of the toxin to a presynaptic voltage-dependent K+ channel. In this paper we report the solubilization of beta-bungarotoxin-binding protein from rat diaphragm membrane preparations with Triton X-100. The specific binding activities of the detergent extracts are 200-400 fmol/mg of protein, and the yields are about 50%-70%. The binding of 125I-beta-bungarotoxin to the extracts could be completely inhibited by dendrotoxin, with an IC50 of about 8 x 10(-8) mol.L. Another beta-neurotoxin, beta-agkistrodotoxin, however, could not inhibit the 125I-beta-bungarotoxin binding at all. This indicates that the acting sites of beta-agkistrodotoxin on the presynaptic membranes are different from those of beta-bungarotoxin.

Animals↗
PubMed1996

[A measurement of cytoplasmic estradiol and progesterone receptors in endometrium of patients with habitual abortion].

Estradiol and progesterone receptors in the endometrium of eight patients with habitual abortion in proliferative and secretory phases were measured by DCC. The serum estradiol (E2) and progesterone (P) were detected by radioimmunoassay, and the endometrium was histologically studied. The results showed that the level of serum E2 was normal in the proliferative and secretory phases. In 5/8 patients, the serum P level was below 11 ng/ml. The estradiol receptor of patients was not different from that of normal women in the proliferative and secretory phases, but the progesterone receptor was significantly lower than that of normal women in the proliferative and secretory phases. These suggest that the lower level of progesterone and progesterone receptor in the endometrium may be one of the causes of habitual abortion.

Abortion, Habitual↗