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Biomedical subjects

S N Wang

Publications and source records attributed to S N Wang.

At least 19 recordsLinked to original sources
PubMed2001

Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells.

AIM: To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC) cells. METHODS: The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG(2) and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX-2) and Bcl-2 were detected by Western dot blotting. RESULTS: Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG(2) and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG(2) cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24 hours incubation with sulindac at 2mmol x L(-1) and 4mmol x L(-1), the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells but not in MKN28 cells. CONCLUSION: Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2 and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater than that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Role of glomerular ultrafiltration of growth factors in progressive interstitial fibrosis in diabetic nephropathy.

BACKGROUND: The present in vivo and in vivo experiments were performed to test the hypothesis that in rats with glomerular proteinuria, the bioactive growth factors transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) are ultrafiltered into tubular fluid, can interact with respective receptors in apical tubular cell membranes, increase the expression and basolateral secretion of C-C-chemokines, which interact with cells in the renal interstitium and indirectly cause myofibroblasts to increase the expression of extracellular matrix proteins. METHODS: HGF and TGF-beta were measured by Western blot and bioassay in glomerular ultrafiltrate that was collected by nephron micropuncture from rats with diabetic nephropathy and control rats. Proximal tubular and collecting duct cells were incubated with diluted proximal tubular fluid or recombinant human HGF (rhHGF) or rhTGF-beta and expression of C-C-chemokines was measured by RT-PCR and ELISA. Interactions of tubular cell chemokines with macrophages and indirectly with myofibroblasts were also examined using cell culture models. RESULTS: In rats with glomerular proteinuria due to diabetic nephropathy mature, bioactive HGF as well as active and latent TGF-beta were detected in early proximal tubular fluid. Specific HGF- and TGF-beta type II receptors were expressed in apical tubular membranes more in diabetic compared to control rats. Incubation of cultured mouse proximal tubular cells (mPTC) or medullary collecting duct cells (mIMCD-3) with diabetic rat proximal tubular fluid increased MCP-1 and RANTES mRNA levels as well as secreted peptide up to threefold. In contrast, high glucose (450 mg/dL), bovine serum albumin (BSA) or rat albumin (each at 100 micrograms/mL) or 10 nmol/L insulin-like growth factor-I (IGF-I; which was also present in glomerular ultrafiltrate in rats with diabetic nephropathy) did not affect expression of these chemokines. Recombinant human TGF-beta as well as rhHGF each increased MCP-1 and RANTES mRNA as well as peptide levels several-fold. In cultured macrophages MCP-1 raised the secretion of TGF-beta, which in turn increased the expression of collagen type I and III as well as fibronectin in renal interstitial myofibroblasts about 2.5 to 4-fold. CONCLUSIONS: Proteinuria-induced progressive renal interstitial fibrosis may be caused by glomerular ultrafiltration of high molecular weight bioactive growth factors, HGF and TGF-beta, which "activate" tubular cells through apical membranes. These apical signals are translated into basolateral events that are recognized by cells in the interstitium, such as the basolateral secretion of the C-C-chemokines MCP-1 and RANTES, which may (via macrophages) stimulate interstitial myofibroblasts, and thus lead to accumulation of extracellular matrix proteins and progressive interstitial fibrosis.

Animals↗
PubMed2000

Growth factor ultrafiltration in experimental diabetic nephropathy contributes to interstitial fibrosis.

Glomerular proteinuria is a risk factor for progression of chronic renal failure and contributes to renal interstitial fibrosis. In experimental diabetic glomerular sclerosis, there is translocation of high-molecular-weight growth factors, namely, hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta, from plasma into tubular fluid, both of which act on tubular cells through apical membrane receptors. In the present studies, the hypothesis is examined that ultrafiltered HGF and TGF-beta induce increased expression of extracellular matrix (ECM) proteins directly in tubular cells, or induce increased expression of cytokines that may act on interstitial myofibroblasts. Incubation of cultured tubular cells with recombinant human (rh) TGF-beta modestly raises expression of collagen type III, but rhHGF dose dependently blocks expression of this ECM protein. Both growth factors raise fibronectin expression up to fourfold and increase expression of platelet-derived growth factor (PDGF)-BB up to sixfold, but not of fibroblast growth factor-2. Pooled, diluted glomerular ultrafiltrate that had been collected by nephron micropuncture from rats with diabetic nephropathy (24-30 wk) also raises expression of fibronectin as well as PDGF-BB in proximal tubular cells. In the presence of neutralizing antibodies that block actions of HGF and TGF-beta, diabetic rat glomerular ultrafiltrate fails to increase tubular cell PDGF-BB expression. In NRK-49F renal interstitial myofibroblasts, rhPDGF-BB, in turn, raises the expression of collagen type III but not type I or fibronectin. The findings provide evidence for ultrafiltered HGF and TGF-beta to contribute to interstitial accumulation of ECM proteins by direct effects on tubular cells as well as indirect mechanisms, via PDGF-BB and its action on myofibroblasts. These events may be important mechanisms of proteinuria-induced renal interstitial fibrosis and accelerated progression of chronic renal failure in diabetic nephropathy and perhaps other proteinuric glomerular diseases.

Animals↗
PubMed1999

Glomerular ultrafiltration of IGF-I may contribute to increased renal sodium retention in diabetic nephropathy.

Insulin-like growth factor-I (IGF-I) is found in plasma at relatively high levels (approximately 40 nmol/L) but <1% is present in the free form and >99% is bound to specific binding proteins to form high-molecular-weight complexes of approximately 50 and approximately 150 kd. We hypothesized that in rats with diabetic nephropathy but not in normal animals, IGF-I-containing binding protein complexes undergo glomerular ultrafiltration, allowing the peptide to interact with IGF-I receptors in apical tubular membranes. By this route, ultrafiltered IGF-I may increase tubular epithelial cell sodium absorption in overt diabetic nephropathy. In serum samples from diabetic rats, IGF-I levels (227 +/- 34 ng/mL) were reduced as compared with control levels (319 +/- 33 ng/mL, P = .05), and IGF-binding protein-2 (IGFBP-2) is increased about 2-fold. In diabetic rats, IGF-I undergoes glomerular ultrafiltration and is present in proximal tubular fluid that was collected by nephron micropuncture at 2.54 +/- 0.54 nmol/L but is below the detection limit in tubular fluid from normal rats. IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 are all present in diabetic rat glomerular ultrafiltrate, but IGFBP-2 levels are greater than those of each of the other three IGFBPs. Neither recombinant human IGF-I (1 nmol/L) nor diabetic rat glomerular ultrafiltrate affect sodium transport in cultured mouse proximal tubular cells. In contrast, rhIGF-I and diabetic rat glomerular ultrafiltrate increase the apical-to-basolateral transport of 22Na+ in distal tubule-like A6 cells through mechanisms involving apical IGF-I receptors. In normal rats, luminal infusion with rhIGF-I or with diabetic rat glomerular ultrafiltrate into late proximal tubules increases distal tubular Na+ absorption. These findings indicate that diabetic glomerular sclerosis causes glomerular ultrafiltration of IGF-I, and they suggest that tubular fluid IGF-I may contribute to sodium (and fluid) retention that is commonly observed in patients with severe diabetic nephropathy.

Animals↗
PubMed1999

Effect of early application of biphasic positive airway pressure on the outcome of extubation in ventilator weaning.

Extubation failure is significantly associated with increased morbidity and mortality in mechanically ventilated patients. In respiratory distress after extubation, non-invasive positive pressure ventilation (NIPPV) has been suggested to avoid the complications of invasive mechanical ventilation. The purpose of this study was to evaluate the effect of early application of NIPPV on extubation outcome. We conducted a prospective study in 93 extubated patients with a mean age of 72.7 +/- 14.7 years (range, 24-93). Elective extubation was performed in 56 patients and unplanned extubation occurred in 37 patients. After extubation, patients randomly received either biphasic positive airway pressure (BIPAP) therapy (n = 47) or unassisted oxygen therapy (n = 46). Non-invasive positive pressure ventilation was delivered via face mask in BIPAP group. Of the 93 extubated patients, 73 (78.5%) were successfully extubated, and 20 (21.5%) had to be re-intubated. There were no significant differences in age, sex, pre-extubation blood gas data between re-intubated patients and those who were not re-intubated. While seven of the 46 patients in the unassisted oxygen therapy group required re-intubation, 13 of the 47 BIPAP-treated patients also required re-intubation. This difference was not statistically significant. The postextubation respiratory management, BIPAP or unassisted oxygen therapy, did not correlate with the extubation outcome, but the elective extubation had significantly better outcome than unplanned extubation. Patients with excessive bronchial secretions and intolerance to the equipment are poor candidates for NIPPV. We conclude that early application of BIPAP support did not predict a favourable extubation outcome. Our experience did not support the indiscriminate use of NIPPV to facilitate ventilator weaning.

Acute Disease↗
PubMed1999

Glomerular ultrafiltration and apical tubular action of IGF-I, TGF-beta, and HGF in nephrotic syndrome.

In nephrotic glomerulopathies, there is ultrafiltration of high molecular weight forms of insulin-like growth factor-I (IGF-I), hepatocyte growth factor (HGF), and transforming growth factor-beta (TGF-beta), which are bioactive in tubular fluid and act through apical tubular receptors. Experimental evidence indicates that ultrafiltered IGF-I, HGF, and TGF-beta may contribute to increased tubular phosphate and sodium absorption, synthesis of extracellular matrix proteins, and secretion of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Through these mechanisms, glomerular proteinuria may contribute to tubulointerstitial pathobiology in nephrotic syndrome.

Animals↗
PubMed1999

Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness.

UNLABELLED: Propofol (iv) depresses cardiovascular function in both humans and animals. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that this effect of propofol results in part from an antagonism of adrenergic control of the heart. Experiments examined effects of propofol on: 1) [3H]CGP12177 (a beta-adrenoceptor antagonist) binding in rat myocardial membranes; and 2) the inotropic and chronotropic actions of isoproterenol in rat left atrial muscle and right atria, respectively. Propofol (25-200 microM) increased the apparent dissociation constant for [3H]CGP12177 without affecting binding site density. Similarly, 200 microM propofol increased the 50% effective concentration values for the dose-dependent positive chronotropic and inotropic actions of isoproterenol in right and left atria, and depressed the maximum increase in spontaneous rate elicited by this beta-adrenoceptor agonist. Other experiments demonstrated that propofol does not alter muscarinic receptor binding as monitored using [3H]quinuclidi-nylbenzilate. In conclusion, these results indicate that propofol can decrease cardiac beta-adrenoceptor responsiveness; however, the concentrations of propofol required suggest that this action contributes to the cardiovascular depression produced by this anesthetic only during large-dose bolus injection. IMPLICATIONS: Experiments in membranes and cardiac preparations isolated from rat heart demonstrate that relatively high concentrations of propofol (25-200 microM) are required to antagonize beta-adrenoceptor binding and tissue responsiveness.

Adrenergic beta-Agonists↗
PubMed1998

Effects of gender on the sensitivity of rat cardiac muscle to extracellular Ca2+.

Experiments were designed to determine if the inotropic response to increasing buffer calcium concentration differs in male and female cardiac muscle. Left atrial and papillary muscles were isolated from hearts of 3-4-month old male and female rats, bathed in Krebs-Henseleit solution (30 degrees C), and stimulated at 1.5 Hz. Isometric developed tension was monitored continuously as extracellular Ca2+ was increased in a cumulative fashion. When compared to male atrial muscle, female atrial preparations were more sensitive to the resulting positive inotropic action; EC50 values were 2.89 +/- 0.22 and 1.86 +/- 0.21 mM in male and female atria, respectively. Two-way analysis of variance (ANOVA) also indicated that there was a significant gender-associated difference in the Ca2+ dose-response curves in atrial muscle. In contrast, papillary muscle did not show a significant gender-related difference in EC50 values (0.88 +/- 0.07 and 0.74 +/- 0.06 mM in males and females); however, the Ca2+ dose-response curves obtained from male and female preparations were found to be significantly different when compared by ANOVA.

Analysis of Variance↗
PubMed1997

Alpha 1D-adrenoceptors play little role in the positive inotropic action of phenylephrine.

This study was designed to determine if the positive inotropic action of alpha 1-adrenergic stimulation in rat heart is mediated via alpha 1D-adrenoceptors. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 1 microM nadolol and paced at 3.0 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine were obtained in the presence and absence of BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4.5] decane-7,9-dione), a selective competitive alpha 1D-adrenoceptor antagonist. BMY 7378 at concentrations up to 30 nM did not significantly affect the positive inotropic response to phenylephrine. In contrast, as reported by other investigators, alpha 1D-adrenoceptor-selective concentrations of this antagonist (3 and 10 nM) did elicit a concentration-dependent right-ward shift in the vasoconstrictor response to phenylephrine in rat abdominal aorta. These data suggest that alpha 1D-adrenoceptors do not play a major role in the positive inotropic action of alpha-adrenoceptor stimulation in rat cardiac muscle.

Adrenergic alpha-Agonists↗
PubMed1997

Traumatic brain injury does not alter cerebral artery contractility.

Previous studies have shown that traumatic brain injury (TBI) significantly reduces cerebral blood flow determined in vivo and reduces vascular reactivity in the pial circulation measured with cranial window preparations. We have now tested the hypothesis that TBI induces these changes by impairing intrinsic contractile activity of cerebral arteries. Anesthetized rats underwent moderate (2.2 atm) and severe (3.0 atm) midline fluid percussion TBI or sham injury following which posterior cerebral or middle cerebral arteries were isolated and isometric force generation was measured. Moderate (n = 5) and severe (n = 3) trauma had no effect on the magnitude of serotonin- or K+-induced force generation or sensitivity to serotonin in arteries isolated within 10 min of TBI. Functional disruption of the endothelium of posterior cerebral arteries isolated 10 min after moderate trauma or sham injury caused a reduction in the active tension response to serotonin that was similar in both groups. Blockade of cyclooxygenase with 5 microM indomethacin had no effect on serotonin-induced force generated by vessels with moderate trauma or in sham-treated rats. Acetylcholine induced an endothelium-dependent relaxation of posterior and middle cerebral arteries; the magnitude of the response was unaffected by moderate TBI. To determine whether prolonged in situ exposure of vessels to the traumatized cerebral milieu could reveal an alteration in intrinsic contractility, posterior cerebral arteries were isolated 30 min after TBI; again, no differences in the tension or relaxation responses were observed. It is concluded that midline fluid percussion TBI did not affect contraction or relaxation of proximal middle or posterior cerebral arteries in rats.

Acetylcholine↗
PubMed1996

Effects of aging on Na(+)-pump current in rat ventricular myocytes.

This study was designed to determine if aging affects ouabain-sensitive Na(+)-pump current (Ip), an electrophysiological measure of Na,K-ATPase activity, in rat heart. Ventricular myocytes were enzymatically isolated from hearts of young adult (4-6 months of age) and aged (28-36 months of age) male Long-Evans rats. Ip was monitored using conventional whole-cell patch-clamp techniques under both maximally stimulating (85 mM intracellular Na+ with 10.8 mM extracellular K+) and 'physiological' (10 mM intracellular Na+ with 5.4 mM extracellular K+) conditions. Values were expressed relative to membrane capacitance to account for the larger cell size of the aged myocytes. Results indicated that maximal Ip is smaller (e.g. approximately 23% at the holding potential of -40 mV) in myocytes isolated from aged as compared to young adult rats. However, neither the voltage-dependence of maximal Ip nor the pump current monitored under 'physiological' conditions were affected by age in general, these data support results of previous biochemical and ion flux studies which demonstrated that aging is associated with a decline in the Na(+)-pump capacity of the myocardium.

Aging↗
PubMed1995

[Study on hsp 70 gene level in cultured smooth muscle cells and aorta from SHR and WKY rats].

Using nucleic hybridization, we investigated hsp 70 gene level on: 1. aorta on spontaneous hypertension rats (SHR); 2. cultured SHR and WKY smooth muscle cells (SMCs) induced by heat shock; 3. cultured SHR and WKY SMCs in 6 weeks and 3 months. The results indicated that hsp 70 mRNA increased in aorta of SHR (6 weeks), in cultured SHR SMCs as compared with WKY SMCs induced by heat shock (42 degrees C, 15 minutes), and in cultured SHR SMCs (6 weeks) as compared with WKY SMCs (6 weeks). Meanwhile, hsp 70 mRNA of cultured SHR SMCs in 6 weeks was higher than that in 3 months. We postulated that overexpression of hsp 70 of cultured SMCs and aorta of SHR in 6 weeks might be related with cellular proliferation during the development of hypertension and that the cultured SHR SMCs might be sensitive to heat shock.

Animals↗
PubMed1994

Antigen expression associated with lymph node metastasis in gastric adenocarcinomas.

A total of 100 gastric adenocarcinomas, comprising 50 cases with lymph node metastasis and 50 cases without lymph node metastasis, were examined for immunohistochemical reactivity with the monoclonal antibody to urokinase-type plasminogen activator (u-PA), Lex related 4C9 antigen, Jun, or to nucleobindin (Nuc). In tumors with lymph node metastasis, 41 (82%) were positive for u-PA and 28 (56%) were positive for Nuc. In tumors without lymph node metastasis, 26 (52%) were positive for u-PA and five (10%) were positive for Nuc. The percentage of cases positive for u-PA or Nuc was significantly higher in tumors with lymph node metastasis than that in tumors without lymph node metastasis (P < 0.01). The expression of u-PA was found to be significantly correlated with that of Nuc (P < 0.001), mode of infiltrative growth (P < 0.05), depth of invasion (P < 0.01), and grade of lymphatic invasion (P < 0.01). However, the expression of Nuc was found to be significantly correlated with the expression of Jun (P < 0.05), depth of invasion (P < 0.01), and grade of lymphatic invasion (P < 0.001). These results suggest that immunohistochemical examination for the expression of u-PA and Nuc in tumor cells may help evaluate the potential of adenocarcinomas of the stomach for lymph node metastasis.

Adenocarcinoma↗
PubMed1994

Postnatal maturation of the response of the canine sinus node to critically timed, brief vagal stimulation.

We have previously demonstrated that vagal phase-response curves (PRC), which characterize the effects of critically timed, brief vagal stimuli on sinus node automaticity, exhibit a fundamentally different shape in the canine newborn than in the adult. In this study we analyzed the changes in sinus cycle length in response to critically timed, brief vagal stimuli, delivered to the decentralized cervical right and left vagosympathetic trunks, in two older age groups: 14 1-mo-old puppies (ages 21-36 d), and eight 2-mo-old puppies (ages 56-62 d). Vagal PRC were constructed by plotting the magnitude (percent change) of the vagal chronotropic response as a function of the phase of the cardiac cycle at which the vagus nerve was stimulated. At 1 mo of age adult-type PRC were observed, but in only six of the puppies (43%) and only in response to right vagal stimulation. By 2 mo of age adult-type PRC were observed in seven of eight puppies (88%) in response to right vagal stimulation and in three of eight (38%) in response to left vagal stimulation. Thus, clear developmental changes in the phase dependence of the vagal chronotropic response can be tracked over the first 2 mo of life in the dog.

Animals↗
PubMed1994

Vasoactive intestinal peptide: electrophysiologic activity in the newborn heart.

We performed intracardiac electrophysiologic studies of the effects of vasoactive intestinal peptide (VIP, 0.125 micrograms/kg/min) on sinus and atrioventricular (AV) nodal function, intracardiac conduction, and myocardial refractoriness in two groups of neonatal dogs (aged 6-16 d). Group I consisted of eight neonates in whom VIP was administered after bilateral vagotomy and beta-blockade with propranolol. Group II consisted of five neonates studied after vagotomy and propranolol, plus total chemical sympathectomy (6-hydroxydopamine). In both groups, VIP resulted in a significant shortening of sinus cycle length. AV nodal conduction time, measured as the AH interval (the time from the onset of the atrial electrogram to the onset of the His bundle electrogram in the His electrode catheter) during atrial pacing, also shortened after VIP. His-Purkinje conduction time and atrial effective refractory periods were unchanged by VIP. In other experiments, the direct chronotropic effect of VIP was evaluated in five isolated neonatal canine hearts using a modified Langendorff technique. In these hearts, the spontaneous cycle length decreased from 403 +/- 88 to 293 +/- 69 ms, or -28 +/- 4% (mean +/- SD), after exposure to 0.1-0.5 nmol of VIP (p < 0.001). In nine other newborns (aged 4-16 days), the effect of selective alpha 1- and alpha 2-adrenergic receptor blockade on the positive chronotropic effect of VIP was evaluated. The effect of VIP on sinus cycle length was not altered by the alpha 1-adrenergic receptor blocker prazosin or by the alpha 2-adrenergic receptor blocker yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Comparison on the kidney nourishing and yang strengthening functions of three different species of herba Cistanches].

Oral administration of water extraction of three kinds of herba cistanches can increase the weight of young mice, prolong the duration of swimming and promote anoxia tolerance in mice. These water decoctions can also increase the body weight, the activities of SOD in serum and the lifespan of "Yang insufficient" model mice induced by administration of hydrocortisone acetate.

Animals↗
PubMed1990

A role for the metal binding domain in determining the DNA sequence selectivity of Fe-bleomycin.

Previous studies of Fe-bleomycin-mediated DNA cleavage have established that the bithiazole moiety + C-terminal substituent of bleomycin are required for DNA binding, while the metal binding domain is responsible for O2 activation. Although recent studies have indicated that the metal binding domain also participates in DNA unwinding, and in determining the sequence and strand selectivity of DNA cleavage, no study has defined the structural domain that bears primary responsibility for the observed pattern of bleomycin-mediated DNA degradation. Presently, by the use of four synthetic analogs of bleomycin demethyl A2 having the functional domains connected by rigid spacers of varying lengths, the source of DNA cleavage specificity has been determined. When the four analogs cleaved 242- and 127-base pair 5'-32P-end-labeled DNA restriction fragments containing isolated Fe-bleomycin cleavage sites, all four produced cleavage at the same preferred sites. Because the (oligo)glycine spacers altered the distance between the domains by as much as 14 A, the identical cleavage patterns argue that the primary determinant of sequence specificity for these analogs is the metal binding domain.

Base Sequence↗