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Biomedical subjects

C Wang

Publications and source records attributed to C Wang.

At least 127 records · Page 7Linked to original sources
PubMed2001

Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation.

In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and the rate of ectopic discharges of injured sensory neurons were significantly reduced by systemic injection of phentolamine. A pharmacological study indicated that this adrenergic dependency was mediated by alpha(1)-adrenoceptors (alpha(1)-AR). The development of adrenergic sensitivity in injured sensory neurons might have resulted from changes in adrenoceptor expression as a consequence of changed expression of adrenoceptor genes. This possibility was examined by determining the changes in the mRNA expression of 3 subtypes of alpha(1)-ARs, alpha(1a)-, alpha(1b)-, and alpha(1d)-ARs, in the dorsal root ganglia (DRG) after spinal nerve ligation. The L4 and L5 spinal nerves were tightly ligated in Lewis rats. One week later, the L4 and L5 DRG were collected and RNase protection assay (RPA) and in situ hybridization were performed. In the DRG of unoperated rats, a moderate amount of alpha(1a)-AR mRNA was present while the amount of either alpha(1b)-AR or alpha(1d)-AR mRNA was small. After spinal nerve ligation, there was a significant increase in the amount of alpha(1b)-AR mRNA in the nerve ligated DRG as measured by RPA. The amount of alpha(1a)-AR mRNA was decreased to 20% of the normal level while that of alpha(1d)-AR mRNA did not change. The in situ hybridization study showed that the number of alpha(1b)-AR mRNA positive neurons increased in spinal nerve ligated DRG, confirming the results of RPA study. These data suggest that the up-regulated expression of alpha(1b)-AR mRNA in axotomized DRG neurons may play an important role in the development of adrenergic sensitivity in injured sensory neurons and thus contribute to the sympathetically maintained pain in spinal nerve ligated neuropathic Lewis rats.

Animals↗
PubMed2001

The synthesis of nanocrystalline anatase and rutile titania in mixed organic media.

The synthesis of anatase and rutile titania could be achieved in mixed organic media with the variation of alcohols in the media under mild conditions. Although a nonhydrolytic process cannot be excluded, it is suggested that the formation of titania in these systems is based mainly on the hydrolytic process initiated by the water generated as a result of an esterification reaction between the alcohols and acetic acid. It has been found that the phase of the TiO2 produced depends on the choice of alcohols and temperature. Partial morphology and size are also affected by these factors. It is proposed that the viscosity and pressure of the reaction media influence the particle size. X-ray diffraction, transmission electron microscopy, Raman spectroscopy, and UV-visible adsorption spectroscopy were employed to characterize the final products.

Journal Article↗
PubMed2001

Convergence of Y and non-Y channels onto single neurons in the superior colliculi of the cat.

Receptive field properties of single neurons in the cat superior colliculus were examined following selective conduction-block of Y-type fibers in contralateral optic nerve. Although the responses evoked by photic stimuli presented via the Y-blocked eye were significantly weaker than those evoked by stimuli presented via the normal eye, > 85% of collicular cells were binocular. Furthermore, when binocular cells were stimulated via the Y-blocked eye their median upper cut-off velocity (100 degrees /s) was significantly lower than that (400 degrees /s) for stimuli presented via the normal eye. Thus, there is a substantial degree of excitatory convergence of Y- and non-Y- information channels on single collicular neurons and the responses to high velocity of motion appear to depend on the integrity of Y-type input.

Action Potentials↗
PubMed2001

[Percutaneous radiofrequency ablation treatment of hepatocellular cancer].

OBJECTIVE: To evaluate the safety, efficacy and complication of radiofrequency ablation (RFA) in treatment of hepatocellular cancer (HCC). METHODS: 78 HCC patients (58 of Child class A, 14 of Child class B, 6 Child class C) with 110 tumors (with the median diameter of 6.1 cm +/- 2.9 cm and the range of 1.9 to 13.7 cm) were treated by electrodes inserted to the foci percutaneously under ultrasound guidance using RF 2000 generator for 105 times in total (on average for 1.3 times and with 6.3 ablated sessions per patient). After the treatment the patients were followed up for 9.2 months on average (1-16 months). RESULTS: The serum ALT and TBIL were transiently elevated one day after RFA in all patients, and returned to baseline values in 2 weeks. The common response after RFA was mild fever. 6 patients (7.7%) had complications; however, no treatment-related death took place. 43 patients (55.1%) had tumor recurrence 6.1 months after RFA on average. Multivariate analysis demonstrated that the tumor diameter were related significantly to local recurrence (P = 0.0001). There was a significant linear correlation between the number of overlapping ablation sessions and tumor diameter (r = 0.772 16, P = 0.0001) among patients without local recurrence. From further liner regression analysis, a mathematical model: y = -1.794 + 1.733x (P = 0.0001, R-square = 0.5303, y: ablation sessions, x: tumor diameter) was got. CONCLUSION: RFA is a safe and effective nonoperative treatment for HCC.

Adult↗
PubMed2001

CRYP-2/cPTPRO is a neurite inhibitory repulsive guidance cue for retinal neurons in vitro.

Receptor protein tyrosine phosphatases (RPTPs) are implicated as regulators of axon growth and guidance. Genetic deletions in the fly have shown that type III RPTPs are important in axon pathfinding, but nothing is known about their function on a cellular level. Previous experiments in our lab have identified a type III RPTP, CRYP-2/cPTPRO, specifically expressed during the period of axon outgrowth in the chick brain; cPTPRO is expressed in the axons and growth cones of retinal and tectal projection neurons. We constructed a fusion protein containing the extracellular domain of cPTPRO fused to the Fc portion of mouse immunoglobulin G-1, and used it to perform in vitro functional assays. We found that the extracellular domain of cPTPRO is an antiadhesive, neurite inhibitory molecule for retinal neurons. In addition, cPTPRO had potent growth cone collapsing activity in vitro, and locally applied gradients of cPTPRO repelled growing retinal axons. This chemorepulsive effect could be regulated by the level of cGMP in the growth cone. Immunohistochemical examination of the retina indicated that cPTPRO has at least one heterophilic binding partner in the retina. Taken together, our results indicate that cPTPRO may act as a guidance cue for retinal ganglion cells during vertebrate development.

Animals↗
PubMed2001

TAK1 is a ubiquitin-dependent kinase of MKK and IKK.

TRAF6 is a signal transducer that activates IkappaB kinase (IKK) and Jun amino-terminal kinase (JNK) in response to pro-inflammatory mediators such as interleukin-1 (IL-1) and lipopolysaccharides (LPS). IKK activation by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) and TRIKA2 (ref. 5). TRIKA1 is a dimeric ubiquitin-conjugating enzyme complex composed of Ubc13 and Uev1A (or the functionally equivalent Mms2). This Ubc complex, together with TRAF6, catalyses the formation of a Lys 63 (K63)-linked polyubiquitin chain that mediates IKK activation through a unique proteasome-independent mechanism. Here we report the purification and identification of TRIKA2, which is composed of TAK1, TAB1 and TAB2, a protein kinase complex previously implicated in IKK activation through an unknown mechanism. We find that the TAK1 kinase complex phosphorylates and activates IKK in a manner that depends on TRAF6 and Ubc13-Uev1A. Moreover, the activity of TAK1 to phosphorylate MKK6, which activates the JNK-p38 kinase pathway, is directly regulated by K63-linked polyubiquitination. We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A short course of methylprednisolone immunosuppression inhibits both rejection and spontaneous acceptance of rat liver allografts.

BACKGROUND: The effects of immunosuppressive drugs on transplant tolerance have not been extensively studied, although their effect on rejection is well established. METHODS: We examined the effects of a short course of treatment with the immunosuppressive drug methylprednisolone (MP) on the survival of PVG liver allografts in Dark Agouti (DA) recipients that accepted the livers and in Lewis recipients that rejected the livers. Infiltration of liver allografts was examined by immunohistochemical staining of liver sections, and apoptosis was measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling. RESULTS: A 5-day course of MP (days 0 to 4) led to rejection of four of six livers (mean survival time [MST] 99 days) in DA recipients compared with long-term survival (MST >100 days) in untreated animals. Delayed administration of MP (days 3 to 7) exacerbated rejection in DA recipients, and all eight animals rejected the graft (MST 68.5 days). Treatment of Lewis recipients with MP did not significantly prolong survival when administered from days 0 to 4 (MST 13 days), although delay of administration improved the outcome. Treatment from days 3 to 7 resulted in an MST of 21 days, whereas treatment from days 7 to 11 resulted in an MST of 41.5 days. MP treatment from day 3 to day 7 reduced T cells and interleukin 2 receptor-expressing cells but increased the numbers of apoptotic cells infiltrating both DA and Lewis strain allografts. CONCLUSIONS: These results show that immunosuppression with MP inhibits both spontaneous tolerance and rejection of liver allografts in a rat model and question the efficacy of administering MP to all liver allograft recipients from the time of transplantation.

Animals↗
PubMed2001

Effects of macromolecular crowding on the refolding of glucose- 6-phosphate dehydrogenase and protein disulfide isomerase.

The effects of polysaccharide, polyethylene glycol, and protein-crowding agents on the refolding of glucose-6-phosphate dehydrogenase (G6PDH) and protein disulfide isomerase have been examined. By increasing concentration during refolding, the reactivation yields of the two proteins decrease with the formation of soluble aggregates. In the presence of high concentrations of crowding agents the reactivation yields remain constant but with decreased refolding rates. The refolding of G6PDH changes from monophasic to biphasic first-order reactions in the presence of crowding agents, and the amplitude of the new slow phase increases with increasing concentrations of crowding agents. The molecular chaperone GroEL reverses the refolding kinetics of G6PDH from biphase back to monophase and accelerates the refolding process. Our results display the complexity and diversity of the effects of macromolecular crowding on both the thermodynamics and kinetics of protein folding.

Chaperonin 60↗
PubMed2001

[Analysis of P interval dispersion and its correlative factors among Chinese].

OBJECTIVE: To establish mean value of P interval dispersion of 12-lead simultaneous body surface electrocardiogram in healthy Chinese and to analyse its correlative factors. METHODS: 12-lead simultaneous body surface electrocardiogram data were taken from 2078 healthy Chinese aged from 1 to 87 [mean (39.4 +/- 17.3)] years with SR-1000A automated electrocardiography made by Zhongshan, Guangdong province. These data were stored in the floppy disk. RESULTS: Mean value of Pmax, Pmin, Pd and Pcd seemed to be prolonged, and Pcmax, Pcmin to be shortened with increasing of age, but there was no significant difference between age and sex. Mean value of Pmax of the all subjects (1-87 years) was (109.85 +/- 7.88) ms, Pmin (80.97 +/- 11.42) ms, Pcmax (123.13 +/- 12.00) ms, Pcmin (90.85 +/- 14.40) ms, Pd (28.89 +/- 10.74) ms, Pcd (32.39 +/- 12.10) ms; mean values of Pmax, Pmin, Pd and Pcd among the children of 1-14 years were (101.54 +/- 9.49) ms, (76.85 +/- 10.19) ms, (24.82 +/- 7.51) ms and (31.10 +/- 9.89) ms, respectively; 77.04% of Pmax was in II lead and 14.39% in V5 lead, 74.69% of Pmin was in V1 lead and 7.84% in V2 lead. CONCLUSION: The mean value of Pmax is 96-120 ms, Pd 8-50 ms and Pcd 10-56 ms among healthy Chinese. Pd is not significantly related with heart rate, age and sex.

Adolescent↗
PubMed2001

The coiled coils in the design of protein-based constructs: hybrid hydrogels and epitope displays.

Recombinant DNA technology provides a powerful tool for producing protein-based biomaterials. Genetically engineered coiled coils have been used as a structural module for the construction of a variety of bio-based systems useful in drug delivery studies. Two of such approaches developed in the authors' laboratory were described here. One approach was to assemble hybrid hydrogels from coiled coil protein domains and synthetic polymers. Preliminary results showed that temperature-sensitive volume transition of the hybrid hydrogels could be triggered by the thermal unfolding of the engineered coiled coil protein domains. The other approach, discussed in detail, was to construct an epitope display model system based on a coiled coil stem loop peptide self-assembled on a solid substrate. This model construct displayed a constrained nonapeptide sequence, which was found to mediate specific binding with immunocompetent cells bearing complementary surface receptors. These novel approaches will likely find important applications in the rational design of more effective drug delivery systems.

Amino Acid Sequence↗
PubMed2001

Differential effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on in vitro rat t lymphocyte and macrophage functions.

Opioid receptors have been reported on immune cells of several species and shown to subserve effector functions of these cell types. Mu-selective opioid agonists such as morphine are immunosuppressive, whereas certain delta-opioid receptor-selective agonists have been associated with immunopotentiation. We have previously shown that intracerebroventricular administration of the non-peptidic delta-opioid receptor agonists did not alter certain parameters of immunocompetence. In this study, we evaluated the in vitro effects of the novel non-peptidic opioid 4-tyrosylamido-6-benzyl-1,2,3,4 tetrahydroquinoline (CGPM-9) on lymphocyte and macrophage functions. We demonstrated that CGPM-9 enhanced rat thymic lymphocyte proliferative response to concanavalin A (2.85- to 5.5-fold increases), and suppressed LPS-induced nitric oxide (67 to 72 percent reduction) and TNF-alpha production (46 percent reduction) by peritoneal macrophages, compared with untreated control. The mu-opioid receptor selective antagonist CTOP used at equimolar doses, significantly suppressed the effect of CGPM-9 on lymphocyte and macrophage functions (CTOP alone did not show any effect on lymphocyte or macrophage functions). In summary, CGPM-9 activated thymic lymphocyte proliferation and suppressed macrophage functions by acting at mu-opioid receptors. This suggests that opioid receptors on immunocytes may be coupled to different signaling pathways depending on the cell type and effector function being analyzed. The mechanism (s) associated with the differential effect of CGPM-9 on these immune cells remains to be elucidated. The pharmacotherapeutic potential for compounds such as CGPM-9 which potentiate T lymphocyte proliferation and suppress production of macrophage-derived inflammatory cytokines is substantial in research and clinical medicine.

Animals↗
PubMed2001

Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes.

There is strong evidence from epidemiologic studies of an association between chronic exposure to inorganic arsenic (iAs) and hyperpigmentation, hyperkeratosis, and neoplasia in the skin. Although it is generally accepted that methylation is a mechanism of arsenic detoxification, recent studies have suggested that methylated arsenicals also have deleterious biological effects. In these studies we compare the effects of inorganic arsenicals (arsenite (iAs(III)) and arsenate (iAs(V))) and trivalent and pentavalent methylated arsenicals (methylarsine oxide (MAs(III)O), complex of dimethylarsinous acid with glutathione (DMAs(III)GS), methylarsonic acid (MAs(V)), and dimethylarsinic acid (DMAs(V))) in human keratinocyte cultures. Viability testing showed that the relative toxicities of the arsenicals were as follows: iAs(III) > MAs(III)O > DMAs(III)GS > DMAs(V) > MAs(V) > iAs(V). Trivalent arsenicals induced an increase in cell proliferation at concentrations in the 0.001 to 0.01 microM range, while at high concentrations (>0.5 microM) cell proliferation was inhibited. Pentavalent arsenicals did not stimulate cell proliferation. As seen in the viability studies, the methylated forms of As(V) were more cytotoxic than iAs(V). Exposure to low doses of trivalent arsenicals stimulated secretion of the growth-promoting cytokines, granulocyte macrophage colony stimulating factor and tumor necrosis factor-alpha. DMAs(V) reduced cytokine secretion at concentrations at which proliferation and viability were not affected. These data suggest that methylated arsenicals, products of the metabolic conversion of inorganic arsenic, can significantly affect viability and proliferation of human keratinocytes and modify their secretion of inflammatory and growth-promoting cytokines.

Adult↗
PubMed2001

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.

The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.

Amino Acid Sequence↗
PubMed2001

Posttransplant administration of donor leukocytes induces long-term acceptance of kidney or liver transplants by an activation-associated immune mechanism.

Donor leukocytes play a dual role in rejection and acceptance of transplanted organs. They provide the major stimulus for rejection, and their removal from the transplanted organ prolongs its survival. Paradoxically, administration of donor leukocytes also prolongs allograft survival provided that they are administered 1 wk or more before transplantation. Here we show that administration of donor leukocytes immediately after transplantation induced long-term acceptance of completely MHC-mismatched rat kidney or liver transplants. The majority of long-term recipients of kidney transplants were tolerant of donor-strain skin grafts. Acceptance was associated with early activation of recipient T cells in the spleen, demonstrated by a rapid increase in IL-2 and IFN-gamma at that site followed by an early diffuse infiltrate of activated T cells and apoptosis within the tolerant grafts. In contrast, IL-2 and IFN-gamma mRNA were not increased in the spleens of rejecting animals, and the diffuse infiltrate of activated T cells appeared later but resulted in rapid graft destruction. These results define a mechanism of allograft acceptance induced by donor leukocytes that is associated with activation-induced cell death of recipient T cells. They demonstrate for the first time that posttransplant administration of donor leukocytes leads to organ allograft tolerance across a complete MHC class I plus class II barrier, a finding with direct clinical application.

Animals↗
PubMed2001

Histone acetylation and the cell-cycle in cancer.

A number of distinct surveillance systems are found in mammalian cells that have the capacity to interrupt normal cell-cycle progression. These are referred to as cell cycle check points. Surveillance systems activated by DNA damage act at three stages, one at the G1/S phase boundary, one that monitors progression through S phase and one at the G2/M boundary. The initiation of DNA synthesis and irrevocable progression through G1 phase represents an additional checkpoint when the cell commits to DNA synthesis. Transition through the cell cycle is regulated by a family of protein kinase holoenzymes, the cyclin-dependent kinases (Cdks), and their heterodimeric cyclin partner. Orderly progression through the cell-cycle checkpoints involves coordinated activation of the Cdks that, in the presence of an associated Cdk-activating kinase (CAK), phosphorylate target substrates including members of the "pocket protein" family. One of these, the product of the retinoblastoma susceptibility gene (the pRB protein), is phosphorylated sequentially by both cyclin D/Cdk4 complexes and cyclin E/Cdk2 kinases. Recent studies have identified important cross talk between the cell-cycle regulatory apparatus and proteins regulating histone acetylation. pRB binds both E2F proteins and histone deacetylase (HDAC) complexes. HDAC plays an important role in pRB tumor suppression function and transcriptional repression. Histones are required for accurate assembly of chromatin and the induction of histone gene expression is tightly coordinated. Recent studies have identified an important alternate substrate of cyclin E/Cdk2, NPAT (nuclear protein mapped to the ATM locus) which plays a critical role in promoting cell-cycle progression in the absence of pRB, and contributes to cell-cycle regulated histone gene expression. The acetylation of histones by a number of histone acetyl transferases (HATs) also plays an important role in coordinating gene expression and cell-cycle progression. Components of the cell-cycle regulatory apparatus are both regulated by HATs and bind directly to HATs. Finally transcription factors have been identified as substrate for HATs. Mutations of these transcription factors at their sites of acetylation has been associated with constitutive activity and enhanced cellular proliferation, suggesting an important role for acetylation in transcriptional repression as well as activation. Together these studies provide a working model in which the cell-cycle regulatory kinases phosphorylate and inactivate HDACs, coordinate histone gene expression and bind to histone acetylases themselves. The recent evidence for cross-talk between the cyclin-dependent kinases and histone gene expression on the one hand and cyclin-dependent regulation of histone acetylases on the other, suggests chemotherapeutics targeting histone acetylation may have complex and possibly complementary effects with agents targeting Cdks.

Acetylation↗
PubMed2001

Electrochromic nanocrystal quantum dots.

Incorporating nanocrystals into future electronic or optoelectronic devices will require a means of controlling charge-injection processes and an understanding of how the injected charges affect the properties of nanocrystals. We show that the optical properties of colloidal semiconductor nanocrystal quantum dots can be tuned by an electrochemical potential. The injection of electrons into the quantum-confined states of the nanocrystal leads to an electrochromic response, including a strong, size-tunable, midinfrared absorption corresponding to an intraband transition, a bleach of the visible interband exciton transitions, and a quench of the narrow band-edge photoluminescence.

Journal Article↗
PubMed2001

Prolongation of allograft survival with viral IL-10 transfection in a highly histoincompatible model of rat heart allograft rejection.

BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce the immunogenicity of allografts and result in long-term graft survival. In this study, we examine the feasibility of transferring viral interleukin-10 (vIL-10) gene into rat hearts using adenovirus by intracoronary administration. The subsequent effects of delivered vIL-10 alone or with subtherapeutic doses of cyclosporine A (CsA) on parameters of allograft rejection (AR) were also examined. METHODS: Recombinant adenovirus vectors containing vIL-10 (Ad-vIL-10) or beta-galactosidase (Ad-beta-gal) were derived from adenovirus type 5. vIL-10 expression in supernatants of transfected COS7 cell cultures and in transfected heart allografts were examined by enzyme immunoassay (EIA) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat heart transplants (LEWS->ACI) were performed in five groups [group 1: no treatment, group 2: Ad-beta-gal, group 3: AdvIL-10, group 4: CsA (10 mg/kg), and group 5: Ad-vIL10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats. Allograft tissues were also submitted for histological study. RESULTS: vIL-10 expression was shown in both transfected COS7 cells and heart isografts. Animals transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days, P<0.001) when compared to beta-gal transfected controls. Animals treated with a single low dose injection of CsA showed no significant prolongation of graft survival compared to controls (11.7 vs. 10.5 days). Animals treated with both vIL-10 and CsA demonstrated a synergistic prolongation of allograft survival compared with controls and with animals treated with CsA or vIL-10 treatment alone (36.7 days vs. 11.7, P<0.001 or 36.7 vs.19.6, P<0.001, respectively). Histological study showed that allografts from untreated controls exhibited extensive AR with loss of graft architecture by day 7 posttransplant while those from the vIL-10 group showed less AR. The best pathological scores were seen in vIL-10 + CsA-treated animals. CONCLUSIONS: 1) Delivering Ad-vIL-10 into donor hearts by intracoronary perfusion results in overexpression of vIL-10 and significantly prolongs cardiac allograft survival in a highly histoincompatible rat model. 2) Subtherapeutic doses of CsA do not prolong allograft survival, but act synergistically with vIL-10 to significantly prolong graft survival beyond that achieved with either agent alone.

Adenoviridae↗