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Biomedical subjects

Hui Li

Publications and source records attributed to Hui Li.

At least 307 records · Page 17Linked to original sources

Alpha-2 adrenoceptor mediating the facilitatory effect of norepinephrine on the glycine response in the spinal dorsal horn neuron of the rat.

Effects of norepinephrine (NE) on the glycine-mediated inhibitory response were investigated in neurons acutely dissociated from the rat spinal dorsal horn, using nystatin perforated patch recording mode under voltage-clamp conditions. NE reversibly and concentration dependently facilitated Cl(-) current induced by 3 x 10(-5) M glycine. NE neither changed the reversal potential of the glycine response nor affected the affinity of glycine to its receptor. This effect could be mimicked by clonidine (10(-7) M) and blocked by yohimbine (10(-6) M), respectively. N-[2(methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-89), an inhibitor of protein kinase A, effectively mimicked the effect of NE on glycine response, whereas chelerythrine (an inhibitor of protein kinase C) failed. NE further enhanced glycine response even in the presence of chelerythrine or stearoylcarnitine chloride (another inhibitor of protein kinase C) or chelerythrine together with stearoylcarnitine chloride. The present results suggest that alpha2-adrenoceptor is involved in the potentiation of NE on glycine response in freshly isolated spinal dorsal horn neurons. Activation of alpha2-adrenoceptor down-regulates the activity of protein kinase A that results in the potentiation of the glycinergic inhibitory effects within the spinal dorsal horn.

Alkaloids↗

SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers.

We identify a gene, SLC5A8, and show it is a candidate tumor suppressor gene whose silencing by aberrant methylation is a common and early event in human colon neoplasia. Aberrant DNA methylation has been implicated as a component of an epigenetic mechanism that silences genes in human cancers. Using restriction landmark genome scanning, we performed a global search to identify genes that would be aberrantly methylated at high frequency in human colon cancer. From among 1,231 genomic NotI sites assayed, site 3D41 was identified as methylated in 11 of 12 colon cancers profiled. Site 3D41 mapped to exon 1 of SLC5A8, a transcript that we assembled. In normal colon mucosa we found that SLC5A8 exon 1 is unmethylated and SLC5A8 transcript is expressed. In contrast, SLC5A8 exon 1 proved to be aberrantly methylated in 59% of primary colon cancers and 52% of colon cancer cell lines. SLC5A8 exon 1 methylated cells were uniformly silenced for SLC5A8 expression, but reactivated expression on treatment with a demethylating drug, 5-azacytidine. Transfection of SLC5A8 suppressed colony growth in each of three SLC5A8-deficient cell lines, but showed no suppressive effect in any of three SLC5A8-proficient cell lines. SLC5A8 exon 1 methylation is an early event, detectable in colon adenomas, and in even earlier microscopic colonic aberrant crypt foci. Structural homology and functional testing demonstrated that SLC5A8 is a member of the family of sodium solute symporters, which are now added as a class of candidate colon cancer suppressor genes.

Adenocarcinoma↗

Role of soil manganese in the oxidation of aromatic amines.

Soil-induced oxidation and subsequent polymerization of aromatic amines is an important pathway for reducing the mobility of amines in soils and their hazard potential in the environment. This study assesses the hypothesis that manganese(III/IV) oxides/hydroxides play a significant role in the oxidation of aromatic amines in whole soils. Aromatic amines including alpha-naphthylamine, p-methoxyaniline, and aniline were allowed to react in aqueous whole soil suspensions for 5 d. Irreversible binding and/or transformation of amines were estimated using a rigorous extraction method and extractable transformation products were analyzed by matrix-assisted laser desorption/ ionization mass spectrometry. The Mn speciation shifts in the soil residue after amine-soil reactions were measured using a successive fractionation method and in-situ using X-ray absorption near-edge structure spectroscopy. A fraction of each of the three amines became irreversibly sorbed, and a large polymer formation was observed for alpha-naphthylamine and p-methoxyaniline. The increase in the irreversibly sorbed/transformed amine fraction over time was concomitant with the reduction of Mn(III/IV) to Mn(II), although oxidation by Mn(III/IV) was not sufficient to account for all amine irreversibly lost. Oxidation by soil Mn did contribute to immobilizing amines within organic matter and to the formation of large aromatic amine polymers, which serves to reduce mobility and bioavailability of aromatic amines in the natural environment.

Adsorption↗

[Transcranial Doppler monitoring of cerebral blood flow velocity during extracorporeal membrane oxygenation in sheep].

OBJECTIVE: To investigate the hemodynamics during extracorporeal membrane oxygenation (ECMO) and the value of transcranial Doppler (TCD) monitoring. METHODS: ECMO was conducted on 14 sheep. TCD monitoring was conducted at different time-points to examine the bilateral cerebral blood flow velocity (CBFV), including systolic peak flow velocity (Vs), end-diastolic flow velocity (Vd), mean flow velocity (Vm), and pulse index (PI, Vs-Vd/Vm). The general condition, blood pressure, heart rate, and temperature were observed. Two weeks after, the surviving 9 sheep were killed, their brains were taken out and morphological and pathological examinations were done. RESULTS: Anesthesia showed little effect on CBFV. After the ligation of carotid artery and vein, the CBFV pattern only changed slightly, Vs and PI decreased, and Vm and Vd remained almost unchanged. During ECMO with either greater or smaller volume, especially the former, the CBFV pattern showed a non-pulse waves, Vs markedly decreased with a value hardly different from that of Vd, Vs, Vd, and Vm were 62%, 75%, and 69% of the values in normal condition. The pre-ECMO CBFV was not significantly different from those examined any day after ECMO. The differences of pH and PO(2) in femoral artery during different stages were insignificant. PaCO(2) during ECMO with great flow volume and during mechanical ventilation after ECMO was significantly lower than that before ECMO (P < 0.05). The MABP of femoral artery during ECMO with small flow volume was significantly lower than that before ECMO (P < 0.05). Vm was positively correlated with MABP and not correlated with heart rate and temperature. The gross observation of the sheep's brain was normal. Small foci of malacia were seen in the brains of 4 sheep. CONCLUSION: Hemodynamics changes remarkably during ECMO. TCD monitors the CBFV continuously during ECMO, thus helping maintaining the stability of CBFV and protect the brain.

Animals↗

IL-10 synergistically enhances GM-CSF-induced CCR1 expression in myelomonocytic cells.

CC chemokine receptor 1 (CCR1) has been implicated in inflammation. The present study examined the signaling mechanisms that mediate GM-CSF/IL-10-induced synergistic CCR1 protein expression in monocytic U937 cells. GM-CSF alone markedly increased both the mRNA and protein expression of CCR1. IL-10 augmented GM-CSF-induced CCR1 protein expression with no effect on mRNA expression. PD098059 and U0126 (two MEK inhibitors), and LY294002 (a PI3K inhibitor) inhibited GM-CSF/IL-10-induced CCR1 gene and protein expression. PD098059, U0126, and LY294002 also attenuated chemotaxis of GM-CSF/IL-10-primed U937 cells in response to MIP-1alpha. Immunoblotting studies show that GM-CSF alone induced ERK2 phosphorylation; whereas, IL-10 alone induced p70(S6k) phosphorylation in U937 cells. Neither cytokine when used alone induced PKB/Akt phosphorylation. Combined GM-CSF/IL-10 treatment of U937 cells induced phosphorylation of ERK2, p70(S6k), and PKB/Akt. PD098059 and U0126 completely abrogated ERK2 phosphorylation; whereas, LY294002 completely blocked PKB/Akt and p70(S6k) phosphorylation. Our findings indicate that IL-10 may potentiate GM-CSF-induced CCR1 protein expression in U937 cells via activation of PKB/Akt and p70(S6k).

Chemokine CCL3↗

Photochemistry of dianthrylsilanes: a study of sigma,pi-interaction.

In this article, we demonstrated by the application of time-resolved spectroscopy, X-ray structural analysis and other spectroscopic techniques that 9-Anthrylsilanes exhibits sigma,pi-interaction between 9-anthryl group and the Si-Si linkage in anthryl-disilanes, ASi(2), ASi(2)A, and ASi(3)A which does not occur in the analogous alkyl derivatives as well as the pyrenylsilane derivatives, in spite of the fact that the 0,0-band of PSi(2) is about 12.8 KJ more energetic than that of ASi(2) (Figure 1). More interestingly, the X-ray structural studies reveal that ASi(3)A exists in a butterfly-like structure in agreement with other spectroscopic analyses that the two anthryl groups do not interact in their excited states, while those in ASi(2)A do. This is in contrast to the analogous pyrenylsilanes; the trisilanes exhibits a stronger excimer interaction than that of disilane.(10b) Our results show that the sigma,pi-interactions in ASi(3)A has imparted rigidity to the tri-silyl linkage. Potential applications of anthrylsilanes in material sciences will be explored.(5) This work provides evidence that sigma,pi-interaction between the 9-anthryl group and disilyl linkage does play an important role in the properties of disilanes. We attribute this enhanced sigma,pi-interaction to the nature of the lowest excited state (S(1) state) of anthracenes, the L(a) transition, which has a much higher oscillator strength than the S(1)L(b)-transition of pyrenes (Figure 1). We define the interaction in anthracene as a sigma,pi(S(1,)L(a)) interaction. This interaction lends a substantial barrier to the Si-Si bond with the excited anthryl nucleus in anthrylsilanes. The scope and potential applications of this phenomenon are discussed.

Journal Article↗

Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury.

The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. In the present study, we show that the cellular constituents of small vessels, endothelial cells (EC) and pericytes express novel splice variants of RAGE mRNA coding for the isoforms that lack the N-terminal V-type immunoglobulin-like domain (N-truncated) or the C-terminal transmembrane domain (C-truncated), as well as the known full-length mRNA. The ratio of the expression of the three variants was different between EC and pericytes; the content of the C-truncated form was highest in EC, whereas the full-length form was the most abundant in pericytes. Transfection experiments with COS-7 cells demonstrated that those variant mRNAs were translated into proteins as deduced; C-truncated RAGE was efficiently secreted into the culture media, and N-truncated RAGE was located mainly on the plasma membrane. The three isoforms were also detected in primary cultured human EC and pericytes. Further, full-length and C-truncated forms of RAGE bound to an AGE-conjugated column, whereas N-truncated RAGE did not. The AGE induction of extracellular-signal-related kinase phosphorylation and vascular endothelial growth factor in EC and of the growth and cord-like structure formation of EC was abolished completely by C-truncated RAGE, indicating that this endogenous secretory receptor (endogenous secretory RAGE) is cytoprotective against AGE. The results may contribute to our understanding of the molecular basis for the diversity of cellular responses to AGE and for individual variations in the susceptibility to diabetic vascular complications.

Alternative Splicing↗

Substitution of the adenovirus serotype 5 knob with a serotype 3 knob enhances multiple steps in virus replication.

Adenovirus (Ad) serotype 5 (Ad5) continues to be the predominant vector used for cancer gene therapy. However, many tumor types are reported to be relatively refractory to Ad5 infection because of low surface expression of the native Ad5 receptor, CAR. The observation that many tumor cells are CAR deficient has necessitated the development of CAR-independent infection strategies, including the introduction of heterologous ligand sequences into the virus fiber gene and immunological or chemical modifications of the capsid proteins. Alternatively, native Ad5 tropism can be modified by substituting the knob region from other Ad serotypes such as Ad type 3 (Ad3) into the Ad5 knob region. To date, the effect(s) of tropism modification on the replication and oncolytic capacity of these chimeric Ad vectors has not been fully evaluated. To address this issue, Ad5 vectors and isogenically matched chimeric vectors with Ad3 tropism (Ad5/3) were compared in this study. Various parameters of virus infection were compared, including binding, nuclear translocation, E1A transcription, transgene expression, de novo virus production, and oncolysis. Overall, the chimeric Ad5/3 virus was progressively more efficient at each step of the replication cycle compared with its Ad5 counterpart. The higher replication efficiency of the chimeric Ad5/3 vector translated into improved therapeutic efficacy in a murine in vivo tumor rejection model. These findings suggest that in addition to the initial target cell interaction, multiple mechanisms contribute to the enhanced replication of the chimeric Ad5/3 vector. Furthermore, the data demonstrate that alternative Ad serotype receptors can be used to improve infection and subsequent oncolytic replication, which is particularly relevant in gene therapy applications for tumors that are inefficiently infected with Ad5.

Adenovirus E1A Proteins↗

Particle energization in an expanding magnetized relativistic plasma.

Using a 21 / 2-dimensional particle-in-cell (PIC) code to simulate the relativistic expansion of a magnetized collisionless plasma into a vacuum, we report a new mechanism in which the magnetic energy is efficiently converted into the directed kinetic energy of a small fraction of surface particles. We study this mechanism for both electron-positron and electron-ion (m(i)/m(e)=100, m(e) is the electron rest mass) plasmas. For the electron-positron case, the pairs can be accelerated to ultrarelativistic energies. For electron-ion plasmas, most of the energy gain goes to the ions.

Journal Article↗

Synthesis and potential antimetastatic activity of monovalent and divalent beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D-glucopyranosides.

Anomers of monovalent and divalent beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy-D-gluco-pyranosides were synthesized under different glycosylation conditions, and evaluated for in vitro antimetastatic activity. Three compounds showed promising inhibitory effects on cancer cell attachment, spreading, migration, and invasion.

Amino Sugars↗

Determination of hydrochlorothiazide and rutin in Chinese herb medicines and human urine by capillary zone electrophoresis with amperometric detection.

In this paper, capillary zone electrophoresis with amperometric detection (CZE-AD) was firstly applied to the simultaneous determination of rutin (RT) and hydrochlorothiazide (HCT) in compound Chinese herb medicines and human urine samples. The two analytes could be perfectly analyzed within 12 min and showed significant current responses at carbon electrode under the optimum conditions. It was found that the linear range of HCT was from 2.0 x 10(-6) to 1.0 x 10(-4) mol l(-1) and that of RT was from 1.0 x 10(-6) to 1.0 x 10(-4) mol l(-1). Their sensitivity was determined by linear regression and calculated as 7.02 x 10(4) and 2.17 x 10(5) nA l mol(-1), respectively, and their detection limits were 5.0 x 10(-7) and 2.0 x 10(-7) mol l(-1), respectively (S/N=3). Above results demonstrated that this method was of high sensitivity, good repeatability, high selectivity and could be used in metabolic kinetics studies of medicines. Satisfactory results were obtained when this method was used to simultaneously analyze the amounts of RT and HCT in one general compound Chinese herb medicine-Zhen Ju jiang Ya Pian and human urine samples.

Drugs, Chinese Herbal↗

Effect of diluting agent on sensitivity in capillary electrophoresis with amperometric detection.

Besides the running buffer, pH of buffer, separation voltage and sampling time, the diluting agent was studied in this paper as one of the important factors influencing the sensitivity in capillary electrophoresis (CE) with amperometric detection (AD) when electrokinectic sampling was used. Clonidine hydrochloride, hydrochlorothiazide and rutin, which are positively charged, neutral and negatively charged, respectively, in aqueous solutions, could be perfectly separated by CE with 25 mmol x L(-1) Na(2)B(4)O(7) - 50 mmol x L(-1) NaH(2)PO(4) as running buffer and detected by measuring their current responses with AD. Before CE running, some kinds of diluents including water, methanol, formamide, running buffer, hydrochloric acid and sodium hydroxide were, respectively, applied to dilute the stock solutions of above three analytes and their effects on the sensitivity of CE-AD were investigated. The results showed that for electrokinetic injection, the current responses of these three analytes were greatly affected in different ways when different diluting agents were used. This method was applied to simultaneously determine the active ingredients in one Chinese compound hypotensor named Zhen Ju Jiang Ya Pian, in which the contents of clonidine hydrochloride, hydrochlorothiazide and rutin is very different as 0.03 mg : 5 mg : 20 mg per tablet, and satisfactory results were obtained by adjusting their sensitivity by selecting the suitable diluting agent.

Buffers↗

Intraprotein electrostatics derived from first principles: divide-and-conquer approaches for QM/MM calculations.

Two divide-and-conquer (DAQ) approaches for building multipole-based molecular electrostatic potentials of proteins are presented and evaluated for use in QM/MM calculations. One approach is a further development of the neutralization method of Bellido and Rullmann (J Comput Chem 1989, 10, 479-487) while the other is based on removing part of the electron density before performing the multipole expansion. Both methods create systems with integer charges without using charge renormalization. To determine their performance in terms of location of cuts and distance to QM region, the new DAQ approaches are tested in calculations of the proton affinity of N(zeta) of Lys55 in the inhibitor turkey ovomucoid third domain. Finally, the two methods are used to build a variety of MM regions, applied to calculations of the pK(a) of Lys55, and compared to other computational methodologies in which force field charges are employed.

Journal Article↗

Prevalence of Parkinson's disease and related disorders in the elderly population of greater Beijing, China.

A lower prevalence of Parkinson's disease (PD) has been reported for Chinese populations, but it is unclear whether this observation reflects a lower disease risk or is an artifact of case finding. We ascertained the prevalence of PD in elderly residents of an area that was a composite of 27 urban and rural communities of Greater Beijing, China. A team of university neurologists went door-to-door throughout the study area, examining 5,743 residents (at age 55 years or older) and made preliminary determinations of which residents had PD or other types of parkinsonism. Final determinations were made after follow-up and reevaluation of those persons who were either deemed to have parkinsonism or were suspected of having the condition (n = 144; median follow-up = 40 months). Based on stringent diagnostic criteria, 110 persons were identified to have parkinsonism, of whom 64 (58%) had PD. The prevalence of PD increased with advancing age and was about 1% overall and for each gender. In rural communities, 22 persons had PD, but 20 persons (91%) were first diagnosed for this condition by the study neurologists. The prevalence figures obtained in this study are similar to some of the highest prevalence figures reported in the West.

Aged↗

Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines.

A series of 6-aralkyl substituted 2,4-diaminothieno[2,3-d]pyrimidines in which the 6-aryl group is separated from the thieno[2,3-d]pyrimidine ring by two to five methylene groups were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds in which the thieno[2,3-d]pyrimidine ring is separated from the 6-aryl substituent by three methylene groups were the most potent inhibitors of the series (with IC(50) values ranging from 0.24 and 11.0 microM) but those with two methylene groups between the aromatic rings were the most selective agents.

Animals↗

Acute increase of umbilical artery vascular flow resistance in compromised fetuses provoked by uterine contractions.

BACKGROUND: An impaired placental circulation is involved in the mechanism of late fetal heart rate (FHR) decelerations. OBJECTIVES: To explore umbilical artery (UA) Doppler velocimetry changes in response to uterine contractions during the oxytocin challenge test (OCT) and assess the potentially clinical value of 'OCT Doppler velocimetry'. METHODS: 111 women with pregnancy complications were subjected to an OCT with simultaneous recordings of FHR and UA pulsatility index (PI). Positive OCT cases (late FHR decelerations) were compared with negative OCT cases (normal FHR patterns). Only negative OCT cases were allowed a trial of vaginal delivery. RESULTS: The UA PI was higher in OCT positive (N=21) than in negative cases (N=90) during uterine contractions and relaxations (P<0.05), but not during basal measurements. A positive OCT, but not negative, was associated with an increase of PI during contractions and relaxations compared with basal measurements (P<0.05). Fetal growth restriction (N=58), operative delivery for fetal distress (ODFD) in labor (N=10), and birth asphyxia (N=8) were not associated with PI changes significantly different from cases without these complications. CONCLUSIONS: During uterine contractions and relaxations, but not during basal measurements, a significantly higher UA PI evolved in OCT positive cases compared with OCT negative cases. This indicates a pathophysiological mechanism disclosed only during uterine activity. Although these changes would not have been revealed by traditional Doppler velocimetry, the data suggest a limited predictive value of 'OCT Doppler velocimetry' on the short-term neonatal outcome.

Adult↗

Development of the peritoneal lymphatic stomata and lymphatic vessels of the diaphragm in mice.

The generation and development of the peritoneal lymphatic stomata (PLS) and lymphatic vessels of the diaphragm were studied in mice at gestational ages from the embryonic to the postnatal period with TEM, SEM and enzyme histochemistry and the PLS data were quantitatively analyzed with computer-assisted image processing technology (Elescope image analysis software). The results showed that the diaphragmatic mesothelium was covered only by flattened mesothelial cells (FMC) at the 13th embryonic day (ED 13). At ED 15, some cuboidal mesothelial cells (CMC) and immature lymphatic stomata (NLS) were found scattered on the diaphragmatic mesothelium. The sub-peritoneal lymphatic capillaries did not appear until ED 18. However, no absorptive function was observed in NLS when trypan blue granules were injected into the peritoneal cavity. At postnatal day 1 (PND 1), the endothelial cytoplasm processes of the diaphragm lymphatic capillaries span the connective tissue fibers and the basal membrane of CMC to form the subperitoneal channels. These channels were connected with NLS and serve as the absorptive route between the peritoneal cavity and the sub-peritoneal lymphatic vessels. The trypan blue absorption test demonstrated that postnatal PLS possessed an absorptive function and had transformed to mature lymphatic stomata (MLS) by PND 1. Thus, NLS were renamed of MLS. At PND 5, the cuboidal mesothelial cell ridge (CMCR) appeared with increased CMC areas. At PND 10, CMCR were fused to form the band-like CMC area with much more MLS distributed in the muscular portion of the diaphragm. With distribution area and density of PLS increasing and growth of lymphatic vessels, an increased absorptive function from the peritoneal cavity was observed in the experiment.

Animals↗

Regulation of anti-phosphatidylserine antibodies.

The degree of heavy chain (H) editing, the types of Vkappa editors, and the pattern of Jkappa usage are correlated with a range of the affinity of anti-DNA. This range was determined by the number and location of arginine (R) residues in the VH. We, here, changed a key arginine residue in the VH of anti-DNA transgene to glycine, which sharply reduces the affinity for dsDNA. However, complete reversion of this anti-DNA to germline enhances the affinity for phosphatidylserine (PS). The B cells of this low-affinity anti-DNA and anti-PS transgenic mouse are tightly regulated by receptor editing. Thus, anti-PS B cells are another example of a constitutive self-antigen regulated in the bone marrow.

Animals↗