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Biomedical subjects

X Q Wang

Publications and source records attributed to X Q Wang.

At least 19 recordsLinked to original sources

Effects of the Dzyaloshinskii-Moriya interaction on low-energy magnetic excitations in copper benzoate.

We have investigated the physical effects of the Dzyaloshinskii-Moriya (DM) interaction in copper benzoate. In the low-field limit, the spin gap is found to vary as H(2/3)ln((1/6)(J/mu(B)H(s)) (H(s): an effective staggered field induced by the external field H) in agreement with the prediction of conformal field theory, while the staggered magnetization varies as H(1/3) and the ln((1/3)(J/mu(B)H(s)) correction predicted by conformal field theory is not confirmed. The linear scaling relation between the momentum shift and the magnetization is broken. We have determined the coupling constant of the DM interaction and have given a complete quantitative account for the field dependence of the spin gaps along all three principal axes, without resorting to additional interactions such as interchain coupling. A crossover to strong applied field behavior is predicted for further experimental verification.

Journal Article↗

Effects of aging and AT-1 receptor blockade on NO synthase expression and renal function in SHR.

In an earlier study, we found increased NO production and NO synthase (NOS) expression in renal and vascular tissues of prehypertensive and adult spontaneously hypertensive rats (SHR). This study was designed to determine the effects of aging and AT-1 receptor blockade (losartan 30 mg/kg/day beginning at 8 weeks of age) on NO system in this model. Compared to the Wistar Kyoto (WKY) control rats, untreated SHR showed severe hypertension, elevated urinary NO metabolite (NO(chi)) excretion, marked upregulations of renal and vascular eNOS and iNOS proteins, normal renal function and heart weight at 9 weeks of age. Hypertension control with either AT-1 receptor or calcium channel blockade (felodipine 5 mg/kg/day) mitigated upregulation of NOS isoforms in the young SHR. With advanced age (63 weeks), the untreated SHR showed increased proteinuria, renal insufficiency, cardiomegaly, reduced urinary NO(chi) excretion and depressed renal and vascular NOS protein expressions as compared to the corresponding WKY group. AT-1 receptor blockade prevented proteinuria, renal insufficiency, cardiomegaly, and renal and vascular NOS deficiency. Thus, in young SHR, hypertension results in compensatory upregulation of renal and vascular NOS, which can be attenuated by vigorous antihypertensive therapy. With advanced age, untreated SHR exhibit cardiomegaly, renal dysfunction and marked reductions of eNOS and iNOS compared with the aged WKY rats. Hypertension control with AT-1 receptor blockade initiated early in the course of the disease prevents target organ damage and preserves renal and vascular NOS.

Aging↗

Developmental exposure to polychlorinated biphenyls affects sexual behavior of rats.

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that have the potential to disrupt reproduction through a variety of different pathways. In the present study, we investigated the effects of fetal and lactational PCB exposure on reproductive behavior in male and female laboratory rats. These pregnant rats were injected daily with either 2,4,2',4'-tetrachlorobiphenyl (PCB 47) at the dosage of 1 or 20 mg/kg body weight or 3,4,3',4'-tetrachlorobiphenyl (PCB 77) at the dosage of 0.25 or 1 mg/kg body weight or sesame oil (control group) from gestational days 7 to 18. Offspring were then tested for sexual behavior as adults. Exposure to both PCB 77 and PCB 47 reduced the level of sexual receptivity in the female offspring, but had no detectable effects on the sexual behavior of the male offspring. In addition to changes in adult sexual behavior in the females, both PCBs produced a significant increase in the females' anogenital distance, suggesting a modification of androgen responsiveness in females resulting from PCB exposure during development. Similar effects were not seen with the males.

Analysis of Variance↗

A colorimetric bead-binding assay for detection of intermolecular interactions.

We have developed a new technique that rapidly and reproducibly allows direct visualization of molecular interactions, including receptor-ligand binding. The technique can be easily applied to examine binding between proteins and glycoproteins, or proteins and glycolipids, including gangliosides. In this novel bead-binding assay, the suspected 'ligand' molecule is bound to 0.2- or 1.0- micro m colored FluoSphere beads. These coated beads are then mixed directly with 150- micro m Sepharose or 50- to 75- micro m agarose beads coated with the second 'target' molecule. Binding between molecules is easily detected by immunofluoresence microscopy as colored rosettes or aggregations formed by clustering of the smaller fluorescent beads around the larger non-fluorescent bead. The validity of this technique for glycolipid binding to protein was verified through demonstration of the known interaction between the beta subunit of cholera toxin with ganglioside GM1. The bead-binding technique facilitated the novel observations of interaction between ganglioside GT1b with the alpha5 subunit of alpha5beta1 integrin and the interaction of GM3 with the epidermal growth factor receptor. A modification of this technique, in which the coated beads are bound to protein fixed on plates, allows a quantifiable colorimetric assay of interaction. This versatile and rapid technique will have widespread applications for in vitro systems and may also be useful for in vivo analysis of binding to cell surface receptor molecules.

Animals↗

HLA matching for simultaneous pancreas-kidney transplantation in the United States: a multivariable analysis of the UNOS data.

BACKGROUND: As the incidence of diabetic nephropathy increases, especially in minority populations, more simultaneous pancreas-kidney (SPK) transplants are being performed both in the United States and worldwide. The role of matching on SPK outcomes and organ allocation remains controversial. The purpose of this analysis was to determine the influence of HLA matching using currently employed criteria on 5-year SPK graft survival. METHODS: We performed an analysis of all 3,316 SPK transplants performed in the United States reported to the United Network for Organ Sharing (UNOS) between December 31, 1988 and December 31, 1994. Kaplan-Meier unadjusted 1- and 5-year graft survival with log rank comparisons and Cox multivariable regression models that adjusted for 12 confounding variables were used to analyze the influence of HLA matching on outcomes. RESULTS: Despite low-grade HLA or DR matching or high levels of common reactive groups (CREG) mismatching, 1- and 5-year allograft survival rates were 90% and 78% for kidney, and 85% and 75% for pancreas transplantation. CONCLUSIONS: SPK transplantation is associated with excellent outcomes independent of the level of HLA matching. These data support the hypothesis that SPK transplants need not be allocated based on matching criteria, thus minimizing organ ischemia time and promoting a more racially equitable allocation for SPKs in the US today.

Adult↗

Overexpression, purification, crystallization and preliminary crystallographic studies on a thermostable beta-glycosidase from Thermus nonproteolyticus HG102.

A thermostable beta-glycosidase (Tn-gly) from Thermus nonproteolyticus HG102 has been cloned and overexpressed in Escherichia coli. The recombinant enzyme, with a molecular mass of 48.9 kDa, was purified to homogeneity. It can hydrolyze a wide range of oligosaccharides and perform transglycosylation. Crystals of the recombinant enzyme were grown by the hanging-drop vapour-diffusion technique with MPD and NaCl as precipitants. They belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 66.7, b = 94.6, c = 176.5 A.

Crystallization↗

Inhibition of integrin-linked kinase/protein kinase B/Akt signaling: mechanism for ganglioside-induced apoptosis.

Ganglioside GT1b inhibits keratinocyte attachment to and migration on a fibronectin matrix by binding to alpha(5)beta(1) and preventing alpha(5)beta(1) interaction with fibronectin. The role of gangliosides in triggering keratinocyte apoptosis, however, is unknown. Addition of GT1b to keratinocyte-derived SCC12 cells, grown in serum-free medium but exposed to fibronectin, suppressed Bad phosphorylation, activated caspase-9, and inhibited cyclin D and E expression, resulting in cell cycle arrest at G(1) phase and initiation of apoptosis. The mechanism of GT1b activation of caspase-9 involved inhibition of beta(1) integrin serine/threonine phosphorylation and decreased phosphorylation of both integrin-linked kinase and protein kinase B/Akt at its Ser-473 site, leading to cytochrome c release from mitochondria. Consistently, blockade of GT1b function with anti-GT1b antibody specifically activated the Ser-473 site of Akt, markedly suppressing apoptosis. The ganglioside-induced inhibition of Akt phosphorylation was GT1b-specific and was not observed when cells were treated with other keratinocyte gangliosides, including GD3. These studies suggest that the modulation of keratinocyte cell cycle and survival by GT1b is mediated by its direct interaction with alpha(5)beta(1) and resultant inhibition of the integrin/integrin-linked kinase/protein kinase B/Akt signaling pathway.

Apoptosis↗

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity.

Zinc is coreleased with glutamate from excitatory nerve terminals throughout the central nervous system and acutely inhibits N-methyl-d-aspartate (NMDA) receptor activation. Here we report that cultured murine cortical neurons briefly exposed to sublethal concentrations of zinc developed increased intracellular free Na(+), phosphorylation of Src kinase at tyrosine 220, and tyrosine phosphorylation of NMDA receptor 2A/2B subunits, in a fashion sensitive to the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, PP2. Functionally, this zinc exposure produced a delayed increase in NMDA receptor current in perforated patch but not conventional whole-cell recordings, as well as an increase in NMDA receptor-mediated cell death. These observations suggest that the effect of synaptically released zinc on neuronal NMDA receptors may be biphasic: acute block, followed by Src family kinase-mediated up-regulation of NMDA receptor activity and cytotoxicity.

Animals↗

[Changes in plasma concentration of interleukin-6 in elderly patients with coronary artery disease complicated with heart failure].

OBJECTIVE: The aim of this study was to observe the concentrations of plasma interleukin-6(IL-6) in elderly patients with coronary artery disease(CAD). METHODS: Forty-eight CAD patients with heart failure, 15 CAD patients without heart failure, and 30 normal subjects were studied. The plasma concentration of interleukin-6(IL-6) was measured by enzyme-linked immunosorbent assay. RESULTS: The plasma concentration of IL-6 in CAD patients with heart failure was significantly higher than that without heart failure and normal subjects, respectively (P < 0.05). There was no significant difference between CAD patients without heart failure and normal subjects in the plasma levels of IL-6. There was a negative correlation between the concentration of IL-6 and left ventricular ejection fraction(LVEF) (r = -0.60, P < 0.01). The plasma concentration of IL-6 of the group with re-hospitalization because of severe heart failure was significantly higher than that of the group without hospital readmission (P < 0.01). CONCLUSION: The plasma concentration of IL-6 in CAD patients with heart failure may provide the important information for the severity of the disease and for the prognostic prediction in the disease.

Aged↗

G protein regulation of ion channels and abscisic acid signaling in Arabidopsis guard cells.

The phytohormone abscisic acid (ABA) promotes plant water conservation by decreasing the apertures of stomatal pores in the epidermis through which water loss occurs. We found that Arabidopsis thaliana plants harboring transferred DNA insertional mutations in the sole prototypical heterotrimeric GTP-binding (G) protein alpha subunit gene, GPA1, lack both ABA inhibition of guard cell inward K(+) channels and pH-independent ABA activation of anion channels. Stomatal opening in gpa1 plants is insensitive to inhibition by ABA, and the rate of water loss from gpa1 mutants is greater than that from wild-type plants. Manipulation of G protein status in guard cells may provide a mechanism for controlling plant water balance.

Abscisic Acid↗

Structure of C-phycocyanin from Spirulina platensis at 2.2 A resolution: a novel monoclinic crystal form for phycobiliproteins in phycobilisomes.

The crystal structure of C-phycocyanin from the cyanobacterium S. platensis has been determined at 2.2 A resolution. The crystals belong to the monoclinic crystal form, which has not been previously reported for phycobiliprotein structures. The structure was solved using the molecular-replacement method with a final R value of 18.9% (R(free) = 23.7%) after model building and refinement. In the crystals used for the study, the C-phycocyanin hexamers formed by face-to-face association of two trimers are arranged in layers rather than in columns. Three different kinds of packing between adjacent hexamers in the layer were compared. The tight packing of two adjacent hexamers formed by four trimers in the asymmetric unit brings beta155 PCB chromophores close together, so it is possible that lateral energy transfer takes place through the beta155-beta155 route.

Amino Acid Sequence↗

A possible role of p73 on the modulation of p53 level through MDM2.

MDM2, one of the transcriptional targets of p53, can target p53 for degradation in a negative feedback loop. The p53-related protein p73, however, can bind to MDM2 but is not consequently down-regulated. Here we demonstrate that p73 could transactivate the MDM2 promoter in p53-null cell lines. In p53-null cell lines, the level of MDM2 was increased by p73 due to increases in transcription and protein stability of MDM2. In transient transfection assays, inhibition of the transcriptional activity of p73 required a higher amount of MDM2 than that of p53. This is probably due to the fact that MDM2 can target p53, but not p73, for degradation. We demonstrated further that the level of p53 could be altered by a cooperation between MDM2 and p73, but not by transcriptional inactive mutants of p73. Expression of p73 resulted in a reduction of the ectopically expressed p53 in transient transfections or of the endogenous p53 induced by Adriamycin- or UV-mediated damage. These reductions of p53 were likely to be due to an increase in MDM2-mediated proteolysis. These results suggest the possibility that different levels of p73 in the cell may act as a mechanism to modulate p53 responses after DNA damage and other stresses and that an increase rather than a decrease in p73 may play a role in tumorigenesis.

DNA Damage↗

Comparison of photovoltaic behaviors for horseradish peroxidase and its mimicry by surface photovoltage spectroscopy.

Surface photovoltage spectroscopy (SPS) was chosen to study the photovoltaic behavior of horseradish peroxidase (HRP), hemin and immobilized hemin (poly(NIPAAm/MBA/hemin)). Different photovoltaic behaviors were observed in these three systems. In air, similar SPS curves were found for HRP and poly(NIPAAm/MBA/hemin) with different response intensities. However, poly(NIPAAm/MBA/hemin) showed a wider changing range upon increasing the positive and negative bias to 1.0 V. The SPS of hemin showed a total different behavior when an external positive potential was applied. In vacuum, clearly different photovoltaic behaviors were found. Moreover, the response value decreased when HRP was exposed to O2, the SPS intensity was different from that in air, and could be altered by changing the external biases. On the other hand, the SPS could not be changed before and after poly(NIPAAm/MBA/hemin) was exposed to O2. These differences may result from different chemical microenvironments for hemin in HRP versus that in poly(NIPAAm/MBA/hemin). It could be concluded that H2O and O2 were important factors affecting the photovoltage response in HRP, but only H2O played this important role in poly(NIPAAm/MBA/hemin).

Horseradish Peroxidase↗

Post-transcriptional regulation of the gli1 oncogene by the expression of alternative 5' untranslated regions.

The oncogene GLI1 is involved in the formation of basal cell carcinoma and other tumor types as a result of the aberrant signaling of the Sonic hedgehog-Patched pathway. In this study, we have identified alternative GLI1 transcripts that differ in their 5' untranslated regions (UTRs) and are generated by exon skipping. These are denoted alpha-UTR, beta-UTR, and gamma-UTR according to the number of noncoding exons possessed (three, two, and one, respectively). The alpha- and beta-UTR forms represent the major Gli1 transcripts expressed in mouse tissues, whereas the gamma-UTR is present at relatively low levels but is markedly induced in mouse skin treated with 12-O-tetradecanoylphorbol 13-acetate. Transcripts corresponding to the murine beta and gamma forms were identified in human tissues, but significantly, only the gamma-UTR form was present in basal cell carcinomas and in proliferating cultures of a keratinocyte cell line. Flow cytometry analysis determined that the gamma-UTR variant expresses a heterologous reporter gene 14-23-fold higher than the alpha-UTR and 5-13-fold higher than the beta-UTR in a variety of cell types. Because expression of the gamma-UTR variant correlates with proliferation, consistent with a role for GLI1 in growth promotion, up-regulation of GLI1 expression through skipping of 5' noncoding exons may be an important tumorigenic mechanism.

5' Untranslated Regions↗

Role of K(+) efflux in apoptosis induced by AMPA and kainate in mouse cortical neurons.

Activation of ionotropic glutamate receptors can induce neuronal apoptosis in vitro and in vivo. We showed previously that activation of the N-methyl-D-aspartic acid (NMDA) subtype of glutamate receptors in a low Ca(2+) and low Na(+) condition induced apoptotic neuronal death, and that the K(+) efflux via NMDA receptor channels was likely a key event in NMDA-induced apoptosis. Since non-NMDA receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and kainate receptors, are also permeable to K(+), we tested the hypothesis that stimulating K(+) efflux via non-NMDA receptor channels could induce apoptosis in cultured cortical neurons. Using a Ca(2+)-free and Na(+)-free external solution, application of kainate revealed outward membrane currents carried by K(+) efflux. In a low Ca(2+)/low Na(+) medium, a 5-h exposure to 50-500 microM AMPA in the presence of the NMDA receptor antagonist MK801 induced dose-dependent neuronal death 24 h after the onset of the insult, accompanied by intracellular K(+) reduction and caspase-3 activation. The AMPA-induced cell death was attenuated by the caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) and by the protein synthesis inhibitor cycloheximide. Reducing K(+) efflux by raising extracellular K(+) concentration from 5 to 25 mM attenuated AMPA-triggered cell death, the Ca(2+) channel antagonist nifedipine showed no effect on the AMPA toxicity. Kainate induced similar neuronal death sensitive to attenuation by Z-VAD-FMK or elevated extracellular K(+).We suggest that the non-NMDA receptor-mediated K(+) efflux may participate in apoptotic process and that blocking excessive K(+) efflux mediated by NMDA and non-NMDA receptors may selectively prevent neuronal apoptosis under certain pathological conditions.

Animals↗

From milliseconds to millions of years: guard cells and environmental responses.

During the past year, significant advances have been made in our understanding of stomatal development and its response to climate change, and in our knowledge of how guard cell Ca(2+) oscillations encode environmental signals. Recent studies on (de)phosphorylation mechanisms have provided new information on how guard cells respond to abscisic acid and blue light.

Abscisic Acid↗