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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 865 records · Page 48Linked to original sources

Comparison of acid anhydrides with carboxylic acids in enantioselective enzymatic esterification of racemic menthol.

Optical resolution of racemic menthol has been efficiently achieved by lipase-catalyzed enantioselective esterification in an organic solvent. The performance of the reaction using an acid anhydride as an acyl donor was compared with that using its corresponding free acid. The reactivities of acid anhydrides were found to be higher than their corresponding free acids, but acid anhydrides were also found to be easily hydrolyzed into free acids under the catalysis of the same enzyme. The existence of a too-high concentration of an acid anhydride in a micro-aqueous reaction system will cause dehydration and thus deactivation of the enzyme, and will enhance non-selective esterification of a chiral alcohol, which will reduce the optical purity of the product. All these drawbacks, however, could be effectively overcome in a semi-batch reaction system into which propionic anhydride was continuously fed. This system showed some advantages over a batch reaction system using free propionic acid: the reaction time of dl-menthol was shortened by half, the stability of the enzyme was much enhanced, and the optical purity of the product (l-menthyl ester) was kept at a similarly high level (> 98% ee).

Acids↗

[The relationship between in vitro chemosensitivity of human breast cancer to MDR related drugs and expression of mdr-1 gene].

OBJECTIVE: To study the relationship between in vitro chemosensitivity of human breast cancer to MDR related drugs and expression of mdr-1 gene. METHODS: We measured the chemosensitivity of 56 human breast cancers to MDR related drugs by MTT assay in vitro and level of mdr-1 mRNA in these samples by RT-PCR technique. RESULTS: The expression of mdr-1 gene in the breast cancer resistant to drugs in vitro was increased significantly. The level of mdr-1 mRNA was not correlated with Imax%, but correlated with IC50 statistically. CONCLUSION: These results support that the increased expression of mdr-1 gene is a major cause of resistance to MDR related drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[A four-box multi-function testing system of pharmacology reaction].

The organism position matrix method, a new method of testing pharmacology reaction is proposed. On the basis of the method, we have developed a four-box multi-function testing system which can test the spontaneous activity, analgesic effect, and learning and memory ability of 1 to 4 mice in three dimensions respectively. Four quantitative parameters, the total distance, the movement intensity, the vertical number and the jumping number are put forward to describe the spontaneous activity. The starting time of continuous jumping and the jumping number are used to describe the analgesic effect. The time from the electrical shock to escape onto a safety platform and the number of the electrical shock are used to describe the learning and memory ability. The system has the characteristics of good repeatability, high efficiency, quantitative and automatic control.

Animals↗

[Intraoperative extra strong electrical stimulation in the treatment of peripheral nerve injury].

In order to enhance the therapeutic effectiveness of peripheral nerve injury, intraoperative extrastrong electrical stimulation was used in peripheral nerve surgery. In 16 cases of incomplete peripheral rnerve injuries or poorly regeneratedn erves, continuous intraoperative electrophysiological monitoring was used for guidance of neurolysis. Meanwhile, extrastong electrical stimulation was applied. The latency and amplitude before and after electrical stimulation were recorded and the extent of improrement was compared. In all cases, the latency and amplitude were improved after neurolysis and electrical stimulation. Clinical follow-up also showed that the function of corresponding innorvated muscle was improved. Continuous intraoperative extrastrong electrical stimulation could be used as an practical measure to increase the effectiveness of peripheral nerve treatment.

Adolescent↗

[Experimental study of the mechanism on blood supply to delayed separated skin flap by ultrasonic Doppler].

In order to investigate the mechanism of blood supply to the delayed separated skin flap and the time and criteria for its transfer, 5 small-sized Banna pigs were selected to produce 14 skin flaps. In the experimental group the skin flap on one side was made from the middle of the back having an extra-thin steel sheet intervened between the flap and the soft tissue of the back whereas the flap on the opposite side without a steel sheet intervened was served as the self-control. The skin flaps were examined 3,7,10 and 20 days after the operation and 3,7 and 10 days after transfer, respectively, by (1) gross observation; (2) ultrasonic Doppler; (3) superficial skin temperature measurement and; (4) histomorphological examination. In the experimental group the survival rate of the flap was 100 percent whereas in the control group all of the flaps had necrosis from 30 to 50 percent after the flap being transfered. In the experimental group, the echo sound from the arterial blood flow from ultrasonic Doppler was heard at the pedicle 7 days after the operation, and as time elapsed, the echo sound spread distally, whereas in the controls no echo sound could be heard over the skin flap. There was significant difference statistically between the experimental and control groups in the temperature of the flaps while the flaps were being transferred (P < 0.01). The external diameters of the blood vessels in the central area of the skin flap were larger in the experimental group, 0.8 to 1.2 mm in comparison to 0.4 mm.

Animals↗

[Effects of sevoflurane on contractility of isolated thoracic aorta rings in rabbits].

The objective of this paper was to observe the effects of sevoflurane on isolated rabbit aortic rings and the mechanisms of the effects. Twenty-four vascular rings collected from different New Zealand rabbits were randomly divided into 4 groups: Group 1 endothelium-inact rings; Group 2 endothelium-denuded rings; Group 3 endothelium-intact rings plus indomethacin; Group 4 endothelium-denuded rings plus indomethacin. When stable active tension produced by phenylephrine (1 x 10(-6) mol.L-1) was obtained, sevoflurane was added into the tissue bath. The anesthetic gas was increased in 0.5% increments every 10 min until the 4% of sevflurane after which 5% was administered. In rings of Group 3 and Group 4, indomethacin (2.8 x 10(-5) mol.L-1) was added to the bath 10 min before the addition of sevoflurane. The results showed that sevoflurane relaxed all groups of rings dose-dependently and this action was non-endothelium dependent and indomethacin had no effect on it. It suggests that sevoflurane relaxes peripheral vessels perhaps by affecting vascular muscle directly.

Anesthetics, Inhalation↗

Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search.

Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families with markers in this region resulted in significant evidence of linkage in the combined set of 91 families. The data provide strong evidence of a major prostate cancer susceptibility locus on chromosome 1.

Adult↗

The extreme C terminus of progesterone receptor contains a transcriptional repressor domain that functions through a putative corepressor.

Binding of a hormone agonist to a steroid receptor leads to the dissociation of heat shock proteins, dimerization, specific DNA binding, and target gene activation. Although the progesterone antagonist RU486 can induce most of these events, it fails to activate human progesterone receptor (hPR)-dependent transcription. We have previously demonstrated that a conformational change is a key event leading to receptor activation. The major conformational distinction between hormone- and antihormone-bound receptors occurs within the C-terminal portion of the molecule. Furthermore, hPR mutants lacking the C terminus become transcriptionally active in the presence of RU486. These results suggest that the C terminus contains a repressor domain that inhibits the transcriptional activity of the RU486-bound hPR. In this study, we have defined a 12 amino acid (12AA) region in the C terminus of hPR that is necessary and sufficient for the repressor function when fused to the C-terminal truncated hPR or to the GAL4 DNA-binding domain. Mutations in the 12AA domain (aa 917-928) generate an hPR that is active in the presence of RU486. Furthermore, overexpression of the 12AA peptide activates the RU486-bound wild-type hPR without affecting progesterone-dependent activation. These results suggest that association of the 12AA repressor region with a corepressor might inactivate hPR activity when it is bound to RU486. We propose that binding of a hormone agonist to the receptor changes its conformation in the ligand-binding domain so that association with coactivator is promoted and activation of target gene occurs.

HeLa Cells↗

Cloning and sequencing of the gene for an enhancing factor from Pseudaletia separata entomopoxvirus.

An enhancing factor (EF) has been shown to increase the susceptibility of the armyworm, Pseudaletia separata, to this nuclear polyhedrosis virus. Using amino acid microsequencing data obtained from the purified EF protein, we cloned and sequenced the gene for EF. The deduced amino acid sequence exhibited a significant similarity to major spindle proteins, fusolins, whose function is unknown, from Heliothis armigera, Choristoneura biennis and Melolontha melolontha entomopoxviruses.

Amino Acid Sequence↗

Dissociation of affinity and efficacy in KOR-3 chimeras.

KOR-3 chimeras were constructed in which the first coding exon of KOR-3 was exchanged for the corresponding first coding exon of either MOR-1 (MOR-1/KOR-3) or DOR-1 (DOR-1/KOR-3). All three clones were expressed in CHO cells and characterized with regards to their binding profiles for orphanin FQ/nociceptin (OFQ/N) and a variety of opioids as well as their functional activities in cyclase studies. 125I[Tyr14]OFQ/N labels both KOR-3 (KD 37 pM) and the MOR-1/KOR-3 chimera (KD 39 pM) equally well. Although its affinity for the DOR-1/KOR-3 chimera is quite good (KD 135 pM), it is slightly lower than the other two. Competition studies confirm the high affinity of OFQ/N for all three clones. However, several competitors clearly distinguish the chimeras from KOR-3. OFQ/N(1-11) competes KOR-3 (Ki 55 nM) over 6-fold more potently than either of the chimeras. (Ki values > 350 nM). Conversely, the modest affinity of naloxone benzoylhydrazone for KOR-3 (310 nM) is greatly increased in both the MOR-1/KOR-3 (Ki 69 nM) and DOR-1/KOR-3 (Ki 74 nM) chimeras. The remainder of the opioids tested have no appreciable affinity against any of the clones. Functionally, OFQ/N inhibits forskolin-stimulated cAMP accumulation in both the KOR-3 and the MOR-1/KOR-3 chimera by almost 40%, with IC50 values in the low nanomolar range. Little activity is seen against the DOR-1/KOR-3 chimera. Naloxone benzoylhydrazone inhibits cAMP accumulation in the KOR-3 and the DOR-1/KOR-3 chimera. Although naloxone benzoylhydrazone has higher affinity for the MOR-1/KOR-3 chimera in binding studies than KOR-3 itself, it is inactive in cyclase studies using the MOR-1/KOR-3 chimera, implying that the replacement of the first coding exon increases affinity while decreasing intrinsic activity.

Animals↗

More sensitive way to determine iron using an iron(II)-1,10-phenanthroline complex and capillary electrophoresis.

Iron is one of the major metal species of concern in many samples, such as in serum, foods, drinking waters, etc. In this paper, we present a more sensitive way to determine the iron concentration in water solutions by using an iron(II)-1,10-phenanthroline complexing system with high-performance capillary electrophoresis, and have applied this method to the determination of the levels of iron in serum samples. The technique uses ammonium acetate-acetic acid (50 mM NH4Ac-HAc, pH 5.0) as a running buffer, and the detection wavelength is set at 270 nm instead of 508 nm. This new approach enhances the molar absorbance of the Fe(II)-1,10-phenanthroline complex by about eight-fold compared with that obtained at 508 nm. By combining the larger light output of the deuterium (D2) lamp and the lower noise level at 270 nm, the sensitivity was improved at least twenty-fold compared to that at 508 nm. The detection limit for iron(II) is lower than 5 x 10(-9) M, which has never been reached by reported spectrophotometric methods or with the recently published HPCE method. The effects of pH, buffer concentration and operation voltages on the sensitivity and resolution are also discussed. The signal response is linear over two orders of magnitude (r2 = 0.995) and the iron recovery for samples reached 99-101%. The technique described here is much more sensitive, fast and simple and is suitable for determining trace amounts of iron in biological, food, water and other samples.

Buffers↗

Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals.

Following infection with cytomegalovirus, human granulocyte-macrophage progenitors carry the viral genome but fail to support productive replication. Viral transcripts arise from a region encompassing the major regulatory gene locus; however, their structure differs significantly from productive phase transcripts. One class, sense transcripts, is encoded in the same direction as productive phase transcripts but uses two novel start sites in the ie1/ie2 promoter/enhancer region. These transcripts have the potential to encode a novel 94 aa protein. The other class, antisense transcript, is unspliced and complimentary to ie1 exons 2-4, and has the potential to encode novel 154 and 152 aa proteins. Consistent with a role in latency, these transcripts are present in bone marrow aspirates from naturally infected, healthy seropositive donors but are not present in seronegative controls. Sense latent transcripts are present in a majority of seropositive individuals. Consistent with the expression of latent transcripts, antibody to the 94 aa and 152 aa proteins is detectable in the serum of seropositive individuals. Thus, latent infection by cytomegalovirus is accompanied by the presence of latency-associated transcripts and expression of immunogenic proteins. Overall, these results suggest that bone marrow-derived myeloid progenitors are an important natural site of viral latency.

Adult↗

CD40L is important for induction of, but not response to, costimulatory activity. ICAM-1 as the second costimulatory molecule rapidly up-regulated by CD40L.

The CD40 ligand (CD40L):CD40 interaction plays an important role in the activation of both T and B cells. However, the mechanisms by which this interaction is involved in activation of T cells is still unclear. Here we show that CD40L is not essential for T cell response to TCR engagement if the APC have costimulatory activity, although it is essential for T cell-mediated induction of such costimulatory activity. To determine the molecular basis of this activity, we have produced three mAbs that appear to recognize the costimulatory molecules rapidly induced by CD40L. Two of them recognize CD44H, which we showed to have CD28-independent costimulatory activity for T cells. The molecule recognized by the remaining mAb is hereby identified as ICAM-1. Furthermore, ICAM-1-mediated costimulation is likely to serve for a function similar to that mediated by the B7:CD28 interaction, as targeted mutation of CD28 renders T cell responses to Con A more dependent on ICAM-1.

Animals↗

Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis.

The mechanism of CD40 ligand (CD40L)-mediated in vivo activation of CD4(+) T cells was examined by investigation of the development of experimental allergic encephalomyelitis (EAE) in CD40L-deficient mice that carried a transgenic T cell receptor specific for myelin basic protein. These mice failed to develop EAE after priming with antigen, and CD4(+) T cells remained quiescent and produced no interferon-gamma (IFN-gamma). T cells were primed to make IFN-gamma and induce EAE by providing these mice with B7.1(+) antigen-presenting cells (APCs). Thus, CD40L is required to induce costimulatory activity on APCs for in vivo activation of CD4(+) T cells to produce IFN-gamma and to evoke autoimmunity.

Animals↗

Linkage disequilibrium analysis of G-olf alpha (GNAL) in bipolar affective disorder.

This study examines G-olf alpha as a possible candidate gene for susceptibility to bipolar affective disorder (BPAD) using the Transmission Disequilibrium Test (TDT). G-olf alpha, which encodes a subunit of a G-protein involved in intracellular signaling, maps within a region of chromosome 18 that has been implicated by two different linkage studies as a potential site of BPAD susceptibility loci. The expression pattern of G-olf alpha in the brain, its coupling to dopamine receptors, and the effects of lithium salts on G-proteins all support G-olf alpha as a candidate gene for BPAD. Our study population consisted of 106 probands and sibs with bipolar I disorder, with a median age-at-onset of 21.5 years ascertained from the United States. There was no evidence of linkage disequilibrium between BPAD and any of the observed G-olf alpha alleles in our sample. Division of families based on sex of the transmitting parent did not significantly change the results. This sample had good power (78%) to detect linkage disequilibrium with alleles conferring a relative risk equal to that estimated for the putative 18p locus (2.58). Our results do not support a major role for G-olf alpha as a susceptibility locus for BPAD in a substantial portion of our sample. Other genes lying near G-olf alpha within the linked region on chromosome 18 cannot be excluded by our data. This study illustrates the use of the TDT in evaluating candidate genes within linked chromosome regions.

Alleles↗