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Biomedical subjects

W Tang

Publications and source records attributed to W Tang.

At least 253 records · Page 14Linked to original sources

cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor.

A lambda gt11 cDNA library was constructed from poly-A rich RNA prepared from circulating murine yolk sac derived nucleated erythroblasts, on day 9 of gestation. In addition to the embryonic globin genes, this library was found to contain clones for the hematopoietic specific p45 NF-E2, as well as p18 NF-E2 and p45 NF-E2 related factor 1 (Nrf 1) genes. Using a degenerate oligonucleotide 17mer probe coding for a part of the highly conserved DNA binding domain for p45 NF-E2, we have isolated murine Nrf 2, a second murine homologue related to p45 NF-E2. The murine Nrf 2 gene is expressed not only in erythroid cells, but also in the 3T3 murine fibroblast cell line.

Amino Acid Sequence↗

Hepatocyte growth factor remains as an inactive single chain after partial hepatectomy or unilateral nephrectomy.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and renal tubular epithelial cells. HGF is proteolytically activated in the tissue injured by hepatotoxin or nephrotoxin, suggesting that HGF functions as a crucial growth factor for tissue regeneration following hepatotoxin- or nephrotoxin-induced injury. In this study, we analyzed the molecular form of HGF after partial hepatectomy or after unilateral nephrectomy. The active form of HGF was not detected under our experimental conditions after these operations. Thus, HGF may play little role in liver regeneration after partial hepatectomy and in compensatory renal enlargement after unilateral nephrectomy.

Animals↗

Interaction of cis- and trans-diamminedichloroplatinum with metallothionein in vivo.

The properties of platinum (II) complexes to induce the biosynthesis of metallothionein (MT) were investigated in rabbits following injections of K2PtCl4, cis and trans isomers of DDP (diammine-dichloroplatinum). It was demonstrated that cis-DDP has an ability to induce MT specifically in the liver, whereas trans-DDP appears to be unable to stimulate the biosynthesis of MT in either the liver or the kidneys. In contrast, K2PtCl4 is effective to elevate the MT level in both tissues. However, all of these platinum complexes are rather poor stimulators for MT biosynthesis compared to cadmium and zinc compounds. Preinjection with Zn(NO3)2 significantly enhances the amount of Pt associated with the MT fractions compared to that resulting from injections with either cis- or trans-DDP without Zn(NO3)2 pretreatment. Metallothionein containing Pt was purified and identified from the liver and kidneys of rabbits after preinjections with Zn(NO3)2 followed by repeated injections of cis-DDP and trans-DDP, respectively. It was found for the first time that a relatively higher degree of Pt was associated with MT fractions in the case of trans-DDP treatment than that of cis-DDP injection. On this basis, the role of MT was discussed in relation to its involvement in the metabolism of cis-DDP, and the difference of the antitumor activity and toxicity between cis- and trans-DDP.

Animals↗

Platinum binding to metallothionein. Analysis of circular dichroism spectra of complexes formed between metallothionein and platinum from cis- and trans-diamminedichloroplatinum.

The first observation of the circular dichroism (CD) spectral features of platinum-saturated metallothionein, Pt7MT, is presented. It is characterized by two intensive bands with maxima at 235 nm (-) and 255 nm (+). Properties of the reactions of cis- and trans-diamminedichloroplatinum (DDP) with rabbit liver MT have been studied by monitoring the CD spectral changes. The overall rate of the reaction between trans-DDP and MT is determined to be significantly faster than that for cis-DDP and MT. The stepwise incorporation of Pt into Zn7MT resulted in a nonsystemic changes in the CD spectral envelope. These data argue that Pt(II) replaces Zn(II) in ZnMT in a nonspecific, "distributed" manner across both domains, because the onset of clustering was observed after 5 mol equiv of Pt was bound. A dynamic mechanism has been proposed in which the reaction proceeds via the formation of an intermediate, RS-Pt (NH3)2-SR. As it is converted to the product, the ammine ligands are lost very slowly, especially in the case of cis-DDP, because of the strong requirement of Pt for square planar coordination, which comprises the rate-limiting step.

Animals↗

Functional expression of a vertebrate inwardly rectifying K+ channel in yeast.

We describe the expression of gpIRK1, an inwardly rectifying K+ channel obtained from guinea pig cardiac cDNA. gpIRK1 is a homologue of the mouse IRK1 channel identified in macrophage cells. Expression of gpIRK1 in Xenopus oocytes produces inwardly rectifying K+ current, similar to the cardiac inward rectifier current IK1. This current is blocked by external Ba2+ and Cs+. Plasmids containing the gpIRK1 coding region under the transcriptional control of constitutive (PGK) or inducible (GAL) promoters were constructed for expression in Saccharomyces cerevisiae. Several observations suggest that gpIRK1 forms functional ion channels when expressed in yeast. gpIRK1 complements a trk1 delta trk2 delta strain, which is defective in potassium uptake. Expression of gpIRK1 in this mutant restores growth on low potassium media. Growth dependent on gpIRK1 is inhibited by external Cs+. The strain expressing gpIRK1 provides a versatile genetic system for studying the assembly and composition of inwardly rectifying K+ channels.

Amino Acid Sequence↗

Effect of arrest time on the hemodynamic efficacy of precordial compression.

OBJECTIVES: To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. INTERVENTIONS: Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. CONCLUSIONS: The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.

Animals↗

Angiotensin II increases glucose uptake and glucose transporter-1 mRNA levels in astroglia.

In this study, we have investigated the effects of angiotensin II (ANG II) on glucose uptake into astroglia cultured from adult rat hypothalamus and brain stem. ANG II (30 min to 4 h; 10(-9) to 10(-6) M) stimulated time- and concentration-dependent increases in the uptake of 2-deoxy-D-[3H]glucose into cultured astroglia. This effect of ANG II (10(-7) M) is via AT1 receptors and protein kinase C (PKC), since it was inhibited by losartan (10(-6) M) and staurosporine (10(-6) M), respectively. Furthermore, this ANG II action was inhibited by both cycloheximide (1 microgram/ml) and actinomycin D (10(-6) M), indicating that synthesis of new glucose transporters is involved. This was confirmed by the finding that ANG II (30 min to 4 h; 10(-9) to 10(-5) M) stimulated time- and concentration-dependent increases in the steady-state levels of glucose transporter-1 (GLUT-1) mRNA in these cultures. In addition, the increase in steady-state levels of GLUT-1 mRNA elicited by ANG II was mediated by AT1 receptors and PKC. These data suggest that ANG II stimulates glucose uptake into cultured astroglia via a pathway that involves AT1 receptors, PKC, and increased steady-state levels of GLUT-1 mRNA.

Angiotensin II↗

Mechanisms of myocardial hypercarbic acidosis during cardiac arrest.

During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.

Acidosis↗

Cytokine and hormonal stimulation of human osteosarcoma interleukin-11 production.

Osteoclast-mediated bone resorption plays a crucial role in osseous remodeling. Osteoblasts are important regulators of this activity, in part through their ability to produce osteoclast-regulating soluble factors such as interleukin-6 (IL-6). IL-11 is a newly appreciated pleotropic cytokine whose spectrum of biological activities overlaps with that of IL-6. As a result, we hypothesized that osteoblasts are an important skeletal source of this cytokine. To test this hypothesis, we characterized the IL-11 production of unstimulated and stimulated SaOS-2 human osteosarcoma cells. Unstimulated cells produced modest amounts of IL-11. The osteotropic agents recombinant IL-1 (0.25-5 ng/ml), transforming growth factor-beta 1 (0.1-10 ng/ml), PTH (10(-8)-10(-11) M), and PTH-related peptide ((10(-8)-10-11 M) further increased SaOS-2 cell IL-11 protein production and messenger RNA accumulation. These stimulatory effects were dose and time dependent, and the IL-11 that was produced was bioactive, as demonstrated by its ability to stimulate the proliferation of T10D plasmacytoma cells. The protein kinase-C activator, 12-O-Tetra-decanoylphorbol 13-acetate, and a variety of cAMP agonists [forskolin, prostaglandin E1, prostaglandin E2, and (Bu)2AMP] also stimulated osteoblast IL-11 protein production and messenger RNA accumulation. In contrast, recombinant IL-4, recombinant interferon-gamma, and endotoxin did not stimulate SaOS-2 cells in a similar fashion. Importantly, the ability to produce IL-11 was not a unique property of SaOS-2 cells, because primary human trabecular bone osteoblasts also produced significant amounts of bioactive IL-11 when stimulated with transforming growth factor-beta 1. These studies demonstrate that appropriately stimulated human osteoblasts and osteoblast-like cells are potent producers of IL-11 and suggest that osteoblast-derived IL-11 may be an important component of the cytokine network mediating osteoblast-osteoclast communication in normal and pathological bone remodeling.

Adolescent↗

Mechanical ventilation may not be essential for initial cardiopulmonary resuscitation.

BACKGROUND: In a rodent model of cardiac arrest and resuscitation in which the inspired gas mixture was enriched with oxygen, resuscitability and survival were unaffected by positive pressure ventilation. In the present study, in a larger animal model, tidal volumes generated during precordial compression and with spontaneous gasping were quantitated. METHODS: Domestic pigs with an average weight of 34 kg were anesthetized with pentobarbital. Ventricular fibrillation (VF) was induced electrically. Precordial compression was begun after 4 min of untreated VF. Each of 22 animals received one of two interventions in conjunction with precordial compression: positive pressure ventilation with oxygen or oxygen supplied at the port of a tracheal tube at ambient pressure. After 8 min of precordial compression, defibrillation was attempted. RESULTS: Only very moderate increases in arterial PCO2 were documented during cardiopulmonary resuscitation in the absence of mechanical ventilation but arterial oxygen tension was consistently in excess of 100 mm Hg. Cardiac resuscitability and 48-h survival were approximately the same in animals maintained on inspired oxygen whether or not they were mechanically ventilated (7/11 or 8/11). In the absence of mechanical ventilation, precordial compression and spontaneous gasping yielded minute volumes that exceeded 5 L. CONCLUSION: Positive pressure mechanical ventilation did not improve resuscitability or postresuscitation outcome in this porcine model of cardiac arrest.

Animals↗

Airway protection during experimental CPR.

BACKGROUND: Experimental studies recently demonstrated that positive pressure ventilation may not be essential for initial cardiopulmonary resuscitation. Nevertheless, oxygen enrichment of inspired gas mixtures and spontaneous gasping were associated with increased resuscitability and survival after cardiac arrest. However, as yet unresolved is the benefit of early airway control under conditions simulating "sudden death" due to ventricular fibrillation. METHODS: Twenty adult, male Sprague-Dawley rats were randomly assigned to one of two groups in which the airway was unprotected or protected by an oropharyngeal airway of our design. Cardiac arrest was induced by an alternating current delivered to the right ventricular endocardium. Oxygen was delivered to a hood that was loosely applied over the head of the each animal at a flow rate of 1 L/min. Precordial compression was initiated after 4 min of untreated ventricular fibrillation and defibrillation was attempted 6 min later. After spontaneous circulation had been restored, a tracheostomy was performed and the animals were mechanically ventilated with 100% oxygen for an additional interval of 1 h. Animals were then returned to their cages and observed for an additional 24 h. RESULTS: Spontaneous circulation was restored in each of the animals who had an oropharyngeal airway and nine of ten animals in the absence of an artificial airway. In each group, seven animals survived for more than 24 h. Animals in which the airway had been protected had significantly greater frequency of spontaneous gasping (28 +/- 13/min vs 13 +/- 9/min; p < 0.05) and significantly higher arterial oxygen saturation (77 +/- 19% vs vs 55 +/- 25%; p < 0.05). CONCLUSION: In the setting of experimental cardiac resuscitation, the insertion of an artificial airway increased the frequency of spontaneous gasping and arterial oxygenation. Nevertheless, no significant differences in resuscitability or postresuscitation survival were associated with insertion of the artificial airway.

Airway Obstruction↗

Accurate coronary calcium phosphate mass measurements from electron beam computed tomograms.

Precipitates of calcium phosphate in coronary arteries always indicate the presence of atherosclerosis. The mass of these precipitates is related to the severity of atherosclerosis. To determine the accuracy of electron beam computed tomographic (CT) mass estimates, we imaged 21 human hearts inside an anthropomorphic chest phantom using an Imatron C-100 electron beam CT scanner (Imatron, San Francisco, CA). We then incinerated the 63 imaged coronary arteries and weighed the mineral ash. We calculated the mass estimates from the images using an algorithm derived from a model that assumes simple radiographic properties of the coronary arteries. We also calculated the currently used coronary calcium score for each artery. Although both the mass estimates and the scores correlated with the actual mass of the incinerated specimens (r = .97 and r = .93), the correlation with the mass estimates was better (P = .02; William's test). The regression equation relating the actual mass to the mass estimates was y = 1.37 x + 14, indicating that the CT mass estimates consistently underestimate actual coronary calcium phosphate mass. We conclude that relative mass estimates using electron beam CT scanning are accurate and that both these and the currently employed calcium scores reflect the actual mass of precipitated calcium phosphate in diseased coronary arteries.

Algorithms↗

Validity of newborn oscillometric blood pressure.

The objective of this study was to determine the validity of oscillometric blood pressure in relation to arterial blood pressure. Thirty-one newborns were studied. Clinical characteristics, complications, and treatment interventions were documented. Arterial pressure (every 2 sec) and oscillometric pressure (every 3 min) were concurrently recorded for 1-2 h. Serial observations of oscillometric pressure followed the trend of arterial pressure in the individual newborn. However, the study averaged oscillometric pressures were lower than the arterial pressures: systolic, by 1 mmHg; mean, by 5.3 mmHg (p < 0.0001); and diastolic, by 4.6 mmHg (p < 0.0001). The variance of individual, 15-min averaged, and 1-h averaged observations of oscillometric pressure in relation to arterial pressure was examined. Variance for individual observations may be large. The least variance of oscillometric pressure was in the 1-h averaged mean pressure, in which the difference was +/- 2 mmHg in 77% and +/- 4 mmHg in 95% of observations. Clinical characteristics, with the exception of birth weight and treatment interventions, did not affect the variance of oscillometric pressure. This study implies that the offset in relation to arterial pressure should be established for each oscillometric pressure monitoring system. Hourly averaged mean oscillometric pressure is satisfactory for many newborn assessments and management circumstances. However, arterial pressure may be necessary to accurately document transient hypertension or hypotension or an unstable blood pressure.

Birth Weight↗

[The transphincteric approach excision of rectal villous adenomas].

Twenty-four patients with rectal villous adenomas were operated on which posterior transphincteric approach. They had benign villous adenona in (13 patients), villous adenomas showing atypia (2), and villous adenomas developed malignancy (9). All the patients gained excellent results, except one with wounded infection after operation. No patient died at operation. No patient developed rectal fistula and incontinence of feces. The different methods of operation with excised villous adenoma of the rectum were discussed and compared. We conclude that the posterior transsphincteric approach is better than others.

Adenoma, Villous↗

Hepatic, renal, and cerebral tissue hypercarbia during sepsis and shock in rats.

Earlier observations had indicated profound increases in the carbon dioxide tension of the myocardium, gastric wall, liver parenchyma, and renal cortex in the setting of extreme low-flow states of cardiac arrest and resuscitation, hemorrhagic shock, and anaphylactic shock. In venous blood draining the intestines, kidneys, and pelvic viscera, significant increases in PCO2 have also been observed during septic shock. In the present study, we investigated hepatic, renal, and cerebral cortical tissue carbon dioxide tension during intra-abdominal sepsis and shock in Sprague-Dawley rats. Peritonitis was induced by cecal ligation and fecal spillage. Over an interval of 320 +/- 60 minutes, we measured progressive reduction in mean aortic pressure from 152 +/- 11 mm Hg to 25 +/- 8 mm Hg and a decline in cardiac index from 492 +/- 75 ml/kg/min to 169 +/- 57 ml/kg/min. These hemodynamic deficits were accompanied by increases in liver tissue PCO2, from 58 +/- 4 mm Hg to 110 +/- 27 mm Hg (p = 0.006), in renal tissue PCO2, from 38 +/- 7 mm Hg to 115 +/- 24 mm Hg (p < 0.001), and in cerebral cortical tissue CO2, from 59 +/- 6 mm Hg to 108 +/- 16 mm Hg (p = 0.001). Arterial blood lactate content increased from 0.8 to 5.26 +/- 0.2 mmol/L (p = 0.001). Increases in blood lactate content preceded the changes in tissue PCO2 in each of these organs. These studies demonstrate that tissue hypercarbia is a more general phenomenon of low flow states, including that of circulatory shock associated with septic peritonitis.

Animals↗

Synthesis of novel androgen-linked phosphoramide mustard prodrugs and growth-inhibitory activity in human breast cancer cells.

Two steroid-linked phosphoramide mustard prodrugs, 7a and 7b, synthesized. The androgens testosterone and 19-nortestosterone were linked through the 17beta-position via an acetal bond to aldophosphamide (3). Proton-catalyzed, as well as cytochrome P450-mediated cleavage of the acetal bond resulted in the release of 3 which decays into the ultimate cytotoxic species, phosphoramide mustard. In a competitive cellular binding assay, the new prodrugs displayed approximately 10-12% affinity to androgen binding proteins in breast cancer cells, relative to testosterone (100%). In the sex hormone receptor-negative cell line MDA-MB231, the testosterone conjugate 7a and the 19-nortestosterone conjugate 7b have been found to be as effective as 4-hydroperoxycyclophosphamide (5). Both compounds were more active than 5 in receptor-positive cell lines. No significant differences in response were observed, however, between receptor-negative and receptor-positive cell lines.

Androgen-Binding Protein↗

Offline assessment of atherosclerotic coronary calcium from electron beam tomograms.

Coronary calcium screening using electron beam computed tomography (EBCT) is being applied clinically and for research purposes. We compared the accuracy of a specialized image analysis system with the standard proprietary software in the scanner's host computer. Sixty-seven symptomatic patients underwent coronary angiography and EBCT. Tomograms were analyzed using the proprietary software included in the scanner and with a specialized coronary calcium scoring work station. Sensitivities, specificities, and receiver operating characteristic curve areas were calculated for the proprietary software and the specialized system using the angiographic definition of disease of at least one stenosis causing greater than 50% luminal narrowing. There were no significant differences between the proprietary and the specialized software's accuracy. Receiver operating characteristic curve areas were 0.84 and 0.82 for proprietary software, respectively. During a 50 minute analysis session, the average number of studies analyzed were 12.6 +/- 1.7 using the proprietary software and 23.2 +/- 5.7 using the specialized software (P = .02).Image analysis was thus found to be more rapid using the specialized software. The specialized coronary calcium analysis system is as accurate as the proprietary software for scoring EBCT for coronary calcium. The reduction in analysis time makes the specialized system the preferable method.

Adult↗