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Biomedical subjects

W Tang

Publications and source records attributed to W Tang.

At least 91 records · Page 5Linked to original sources
PubMed2000

Estimation of human exposure to styrene and ethylbenzene.

In the present studies, human exposure to styrene and to ethylbenzene (EB) is assessed on the basis of literature data. Total styrene and total EB exposure result from inhalation and from food intake. Styrene and EB inhaled represent the greatest proportion of the total intake. Styrene and EB content in food is mainly caused by migration from polymer packaging material. The daily styrene exposure is estimated to range from 18.2 to 55.2 microg/person, corresponding to an annual exposure of 6.7 to 20.2 mg/person. The daily EB exposure is estimated to be about 130 microg/person, corresponding to an annual exposure of 46 mg/person. Cigarette smoking is another important factor for styrene and EB intake by smokers.

Benzene Derivatives↗
PubMed2000

Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control.

The tumor suppressor p53 is considered as the guardian of the genome which is activated following genotoxic stress. In many cell types, p53 mediates G1 cell cycle arrest as the predominant cellular response. Inactivation of wild-type p53 leads to loss of G1/S checkpoint control and to genomic instability, including increased spontaneous homologous recombination (HR). To determine whether regulation of the G1/S checkpoint is required for suppression of HR, we assessed recombination events using a plasmid substrate that stably integrated into the genome of p53-null mouse fibroblasts. Exogenous expression of a temperature-sensitive p53 protein (Ala135 to Val), which had lost trans-activation function and could not regulate G1/S transition when in mutant conformation, reduced HR rates to the same extent as wild-type p53. Furthermore, a p53 construct with an alternatively-spliced carboxy terminus also retained this ability in the absence of both activities, G1/S control and non-sequence specific DNA binding as mediated by the carboxy terminus. Our data dissociate regulation of HR by p53 from its role as a cell cycle checkpoint protein. The results support a model which extends p53's role as a guardian of the genome to include transactivation-independent regulatory functions in DNA repair, replication and recombination.

3T3 Cells↗
PubMed2000

Thymidine phosphorylase expression in tumor stroma of uterine cervical carcinomas: histological features and microvessel density.

Immunohistochemical staining was performed on 91 cases of uterine neoplasm in order to determine if expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (TP) correlates with tumor microvessel density (MVD) and histological parameters of uterine carcinomas in tumor cells and in tumor stroma. The sample group consisted of 72 primary invasive squamous cell carcinomas of the cervix (ISC) and 19 cervical intraepithelial neoplasms (CIN) of the uterus. In ISC of the cervix, TP expression in tumor stroma showed a significant correlation with a non-keratinizing histological subtype (P < 0.001) and with an infiltrating invasive pattern (P < 0.001). However, in tumor cells the TP expression showed a higher correlation with a keratinizing histological subtypes (P = 0.009). MVD was significantly higher (P = 0.002) in tumors showing high TP expression in stroma than in tumors with low expression. These findings suggest that the TP expression in stromal cells, rather than in tumor cells, may play a role in promoting microvessel growth in cervical squamous cell carcinoma, and angiogenesis may also have an association with tumor cell invasion.

Carcinoma, Squamous Cell↗
PubMed2000

Endotoxin downregulates hepatic expression of P-glycoprotein and MRP2 in 2-acetylaminofluorene-treated rats.

In liver, the ATP-dependent transporters P-glycoprotein (PGP) and multidrug resistance protein-2 (MRP2) are involved in the secretion of numerous drugs and toxins in bile. Although constitutive levels of PGP and MRP-2 are decreased in rat liver after exposure to endotoxin, it is possible that induced forms of these transporters may be alternately affected. In vitro, the hepatocarcinogen, 2-acetylaminofluorene (AAF) induces expression of PGP and MRP2. Thus, we examined the influence of endotoxin on the expression of PGP and MRP2 in AAF-treated rats. Expression of PGP and MRP2 was analyzed on Westerns and by RT-PCR in livers obtained from endotoxin and control groups. In vivo, AAF treatment significantly induced PGP/mdr1 expression and imposed a significant reduction in the expression of spgp. MRP2 protein and mRNA levels were not altered by AAF administration. Endotoxin administration to both AAF-treated and non-AAF-treated rats elicited significant reductions in the protein and mRNA expression of MRP2 and PGP (P < 0.05). Our data indicate that endotoxin suppresses the overexpression of PGP and constitutive expression of MRP2 in AAF-treated rats. Furthermore, in vivo administration of AAF, which maximally induces PGP does not induce MRP2.

2-Acetylaminofluorene↗
PubMed2000

Attractin: a cub-family protease involved in T cell-monocyte/macrophage interactions.

Attractin is a rapidly upregulated membrane-associated molecule on activated T cells. It is a member of the CUB family of extracellular guidance and development proteins, sharing with them a protease activity similar to that of Dipeptidyl peptidase IV (DPPIV/CD26). Most remarkably, and in sharp contrast to CD26, it is released from the T cell and is presumed to be a major source of a soluble serum-circulating attractin. Genomic sequencing reveals that the soluble form is not a proteolytic product of the membrane form, but is in fact the result of alternative splicing. Recent results prove that the loss of murine membrane attractin results in the mahogany mutation with severe repercussions upon skin pigmentation and control of energy metabolism. In each of these latter instances, there is a strong likelihood that attractin is moderating the interaction of cytokines with their respective receptors. We propose that attractin is performing a similar function in the immune system through capture and proteolytic modification of the N-terminals of several cytokines and chemokines. This regulatory activity allows cells to interact and form immunoregulatory clusters and subsequently aids in downregulating chemokine/cytokine activity once a response has been initiated. These two properties are likely to be affected by the balance of membrane-expressed to soluble attractin.

Alternative Splicing↗
PubMed2000

Effects of pHGF on renal cellular DNA synthesis after partial hepatectomy in rats.

The effects of pro-hepatocyte growth factor (pHGF) on the changes of renal cellular proliferative cycle of partial hepatectomized rats were observed by flow cytometry (FCM). S phase fraction (SPF) of control rats (group A) accounted for 7.58% and increased gradually within 6 h, following a peak at 12th or 36th h after operation, but in pHGF-treated rats (group B) the peak appeared at 24th h after operation. Proliferation index (PI) of group A was 13.2% before partial hepatectomy, increased within 6 h and reached a peak at 12th or 36th h after operation, and in group B the peak appeared at 48th h after operation. There were significant differences in SPF and PI between two groups (P < 0.01). These findings suggest that pHGF may nonspecifically promote the DNA synthesis of renal cells.

Animals↗
PubMed2000

Comparison of the accumulation and efflux kinetics of technetium-99m sestamibi and technetium-99m tetrofosmin in an MRP-expressing tumour cell line.

The potential clinical use of technetium-99m labeled sestamibi (Tc-MIBI) and tetrofosmin (Tc-Tfos) to image tumours is currently being evaluated. In this study. the accumulation and efflux of Tc-MIBI and Tc-Tfos in the nasopharyngeal carcinoma cell line CNE-1 were examined in the presence or absence of various inhibitors of P-glycoprotein (PGP) and/or multidrug resistance associated protein (MRP) activity [GG918, PSC833, verapamil (Vrp), cyclosporin A (CsA) and buthionine sulfoximine (BSO)]. Reverse-transcriptase polymerase chain reaction analysis and immunodetection of the CNE-1 cells detected expression of MRP, MRPI and MRP2 but not PGP. Tc-MIBI and Tc-Tfos accumulation was increased (P < 0.0001) and efflux decreased (P < 0.05) in the presence of BSO, CsA, Vrp and PSC833 but not GG918, which is a specific inhibitor of PGP. The absolute accumulation of Tc-MIBI was approximately twofold higher than that seen with Tc-Tfos, whereas the addition of inhibitors caused a much greater suppression of Tc-Tfos transport (>2 times greater than for Tc-MIBI). However, no qualitative differences in inhibitors were seen between Tc-MIBI and Tc-Tfos. These results suggest that both Tc-MIBI and Tc-Tfos are substrates for the MRP transporter and that PSC833, Vrp, CsA and BSO but not GG918 can inhibit MRP activity. These results indicate that Tc-MIBI and Tc-Tfos may be suitable imaging agents for detecting MRP-mediated drug resistance in human cancers.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Expression of Bcl-2 but not Bax or p53 correlates with in vitro resistance to a series of anticancer drugs in breast carcinoma.

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2, bax and p53. The in vitro chemosensitivity of the 177 breast carcinomas was assessed by the histoculture drug response assay (HDRA) using mitomycin C (MMC), 5-fluorouracil (5-Fu), adriamycin (ADM), cisplatin (CDDP), and cyclophosphamide (CPA). The susceptibility of Bcl-2-negative tumors to all the drugs killing was significantly higher than that of Bcl-2-positive tumors. No relationship between Bax or p53 immunoreactivity and sensitivity for any of anticancer drugs studied was demonstrated. Immunohistochemical results regarding Bcl-2 are promising in the evaluation of the sensitivity of cancer cells to a series of anticancer drugs and might be therapeutically useful as an indicator of response to adjuvant chemotherapy for breast cancer.

Antineoplastic Agents↗
PubMed2000

Kinetic studies of the reactions of some metal reconstituted metallothioneins with the electrophilic disulfide 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB).

Rabbit liver Pt7MT, Zn7MT, Bi7MT were reconstituted and the kinetic studies of the reactions with electrophilic disulphide 5, 5'-dithiobis-(2-nitrobenzoic acid) (DTNB) were investigated to explore the possible mechanism of metals release from metallothioneins. It is revealed that the Pt7MT, Zn7MT react with DTNB biphasically, yielding a four-term rate law: Rate = k1f [MT] + k2f [DTNB][MT] + k1s [MT] + k2s [DTNB][MT]. Zn7MT reacts with disulphide DTNB more rapidly and has significantly greater observed rate constants ks, kf than Pt7MT. The kinetic data for Bi7MT indicate that the reaction is monophasic and the rate law is proved to be: Rate = k1 [MT] + k2 [DTNB][MT]. The observed pseudo-first order rate constants for above MTs are insensitive to pH value. Based on the available experimental data, the different kinetic behaviors of MTs reactions with electrophilic disulphide DTNB and a possible mechanism to release the coordinated metal ions are discussed.

Animals↗
PubMed2000

Binding properties of an orally active platinum anti-tumor drug JM216 with metallothionein in vivo.

The abilities of the orally active platinum anti-tumor drug JM216 [trans-bis-acetato-cis-dichloroammine (cyclohexylamine) platinum (IV)] to induce the biosynthesis of metallothionein (MT) were investigated in rabbits given oral administrations or injections s.c. It is revealed that oral administration of JM216 can induce the MT synthesis in the liver but not in the kidney. The hepatic MT contained 7.11 +/- 0.11 Zn and only little Pt or Cu. Injections of JM216 to rabbits can greatly elevate the MT levels in the liver, but increase the renal MT levels only slightly. The MT content as well as Pt concentration in the liver was much higher than that in the kidney. The metal stoichiometry in the purified renal MT was determined to be 4.41 +/- 0.04 Zn, 0.36 +/- 0.11 Pt and 2.50 +/- 0.18 Cu per mole protein. The hepatic MT was still characterized as Zn7MT. Both the treatment with oral administration and injections s.c. cannot lead to the increase of Pt content in the kidney. The oxidation state of platinum in the MT from the kidney was determined to be +2 by X-ray photoelectron spectroscopy. As compared with zinc compounds, JM216 was a very poor stimulator for MT biosynthesis in vivo. Pre-injections with Zn(NO3)2 significantly enhanced the MT levels as well as the Pt concentration compared with that resulting from injections with JM216 alone. Based on the experimental data, the role of MT in relation to its involvement in the metabolism and the mechanism of detoxification of Pt(IV) complexes are discussed.

Animals↗
PubMed2000

Kinetic studies of imidazole and its methyl derivative binding to metmyoglobin: effects of substitute methyl on the binding affinity.

The binding of imidazole and imidazole derivatives (4- and 2-MeIm) to the metMb was studied by 1H NMR spectroscopy to elucidate the effects of different methyl substitution positions on the affinity and kinetics of binding to metMb. These exogenous ligands can form stable complexes with metMb except 2-MeIm. Kinetics and equilibrium data for the binding of imidazole and 4-MeIm to metMb have been obtained by 2D EXSY, and the reasons for the different affinity are also discussed.

Animals↗
PubMed2000

Somatodendritic localization of Translin, a component of the Translin/Trax RNA binding complex.

Recent studies implicating dendritic protein synthesis in synaptic plasticity have focused attention on identifying components of the molecular machinery involved in processing dendritic RNA. Although Translin was originally identified as a protein capable of binding single-stranded DNA, subsequent studies have demonstrated that it also binds RNA in vitro. Because previous studies indicated that Translin-containing RNA/single-stranded DNA binding complexes are highly enriched in brain, we and others have proposed that it may be involved in dendritic RNA processing. To assess this possibility, we have conducted studies aimed at defining the localization of Translin and its partner protein, Trax, in brain. In situ hybridization studies demonstrated that both Translin and Trax are expressed in neurons with prominent staining apparent in cerebellar Purkinje cells and neuronal layers of the hippocampus. Subcellular fractionation studies demonstrated that both Translin and Trax are highly enriched in the cytoplasmic fraction compared with nuclear extracts. Furthermore, immunohistochemical studies with Translin antibodies revealed prominent staining in Purkinje neuron cell bodies that extends into proximal and distal dendrites. A similar pattern of somatodendritic localization was observed in hippocampal and neocortical pyramidal neurons. These findings demonstrate that Translin is expressed in neuronal dendrites and therefore support the hypothesis that the Translin/Trax complex may be involved in dendritic RNA processing.

Animals↗
PubMed2000

End-tidal carbon dioxide as a noninvasive indicator of cardiac index during circulatory shock.

OBJECTIVE: To document the relationships between cardiac index and end-tidal carbon dioxide tension (PetCO2 during diverse low-flow states of circulatory shock. DESIGN: Randomized, prospective, controlled studies on animal models of hemorrhagic, septic, and cardiogenic shock. SETTING: University-affiliated research laboratory. SUBJECTS: Sixteen anesthetized domestic pigs weighing 35-45 kg. INTERVENTIONS: Hemorrhagic shock was induced in five pigs by bleeding followed by reinfusion of shed blood. Septic shock was induced in five pigs by infusion of live Escherichia coli. Cardiogenic shock followed an interval of global myocardial ischemia after inducing and reversing ventricular fibrillation in six pigs. MEASUREMENTS AND MAIN RESULTS: PetCO2 was continuously measured. Cardiac index was measured intermittently by using conventional thermodilution techniques. Cardiac index was correlated with PetCO2 by polynomial regression and Bland-Altman analyses. PetCO2 was highly correlated with cardiac index during hemorrhagic shock (r2 = .69, p < .01), septic shock (r2 = .65, p < .01), and cardiogenic shock (r2 = .81, p < .01). PetCO2 predicted thermodilution cardiac index with bias of -11+/-27 (+/-2 SD) mL/min/kg during hemorrhagic shock, 1.3+/-20.4 (+/- 2 SD) mL/min/kg during septic shock, and -1+/-12 (+/-2 SD) mL/min/kg during cardiogenic shock. CONCLUSIONS: Cardiac output and PetCO2 were highly related in diverse experimental models of circulatory shock in which cardiac output was reduced by >40% of baseline values. Therefore, measurement of PetCO2 is a noninvasive alternative for continuous assessment of cardiac output during low-flow circulatory shock states of diverse causes.

Animals↗
PubMed2000

Echo-Doppler observations during cardiac arrest and cardiopulmonary resuscitation.

We describe a series of investigations that used transesophageal echo-Doppler observations during cardiac arrest and cardiopulmonary resuscitation. Regular contractions of the left atrium persisted during the initial 7 mins of untreated ventricular fibrillation. Ventricular chamber deformation and mitral valve closing and opening followed precordial compression and relaxation. Stroke volumes computed from differences between diastolic and systolic areas of the left ventricle were predictive of the success of the resuscitation. Progressive decreases in left ventricular compliance were associated with decreases in left ventricular diastolic and stroke volumes and progressed to a stone heart.

Animals↗
PubMed2000

Low-energy biphasic waveform defibrillation reduces the severity of postresuscitation myocardial dysfunction.

Both clinical and experimental studies have demonstrated substantial impairment of ventricular function after resuscitation from cardiac arrest. Indeed, postresuscitation myocardial dysfunction has been implicated as a potentially important mechanism, accounting for fatal outcomes after successful resuscitation in 70% of victims within the first 72 hrs. Recent experimental studies implicated the total electrical energy delivered during defibrillation as an important correlate with the severity of postresuscitation myocardial dysfunction and postresuscitation survival. This prompted us to investigate the option of using lower electrical energy biphasic waveform defibrillation. We compared the effects of low-energy biphasic waveform defibrillation with conventional monophasic waveform defibrillation after a short (4 mins), intermediate (7 mins), or prolonged (10 mins) interval of untreated ventricular fibrillation. Biphasic waveform defibrillation with a fixed energy of 150 joules proved to be as effective as conventional monophasic damped sine waveform defibrillation for restoration of spontaneous circulation, with significantly lower delivered energy. This was associated with significantly less severity of postresuscitation myocardial dysfunction. The low-energy biphasic waveform defibrillation is, therefore, likely to be the future direction of transthoracic defibrillation in settings of cardiopulmonary resuscitation.

Animals↗