Search PubMed⌕ Search

Biomedical subjects

W Cheng

Publications and source records attributed to W Cheng.

At least 73 records · Page 4Linked to original sources
PubMed1998

Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes.

To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT1 receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT1 receptors, which modulate the time and magnitude of this cellular response.

Angiotensin II↗
PubMed1998

Identification of an allosteric binding site on the transcription factor p53 using a phage-displayed peptide library.

Monoclonal antibody PAb1620 recognizes a conformational epitope on the transcription factor p53 and, upon binding, allosterically inhibits p53 binding to DNA. A highly diverse (1.5 x 10(10) members) phage-displayed library of peptides containing 40 random amino acids was used to identify the PAb1620 binding site on p53. Panning this library against PAb1620 resulted in three unique peptides which have statistically significant sequence identities with p53 sufficient to identify the binding site as being composed of amino acids 106-113 and 146-156. Based on these results, we propose a mechanism by which PAb1620 can allosterically inhibit p53 binding to DNA through an indirect interaction between the antibody binding site and the L1 loop (amino acids 112-124) of p53, which is a component of the DNA binding region.

Allosteric Regulation↗
PubMed1998

Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats.

Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple molecular events implicated in this phenomenon remain to be identified. Several defects involving Ca2+ homeostasis, pH, and the expression of p53 and genes of the Bcl-2 protein family may contribute to the activation of myocyte death. Therefore, changes in intracellular pH, cytosolic Ca2+, DNase I and DNase II were measured in myocytes isolated by enzymatic digestion from rats of different ages. Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined. Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months showed that this parameter did not change with age: 3 months, 7.20+/-0.05; 12 months, 7.21+/-0.07; 24 months, 7.18+/-0.09. In contrast, diastolic Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells.

Aging↗
PubMed1998

Investigating the dielectric effects of channel pore water on the electrostatic barriers of the permeation ion by the finite difference Poisson-Boltzmann method.

In this paper, the finite difference Poisson-Boltzmann (FDPB) method with four dielectric constants is developed to study the effect of dielectric saturation on the electrostatic barriers of the permeation ion. In this method, the inner shape of the channel pore is explicitly represented, and the fact that the dielectric constant inside the channel pore is different from that of bulk water is taken into account. A model channel system which is a righthanded twist bundle with four alpha-helical segments is provided for this study. From the FDPB calculations, it is found that the difference of the ionic electrostatic solvation energy for wider domains depends strongly on the pore radius in the vicinity of the ion when the pore dielectric constant is changed from 78 to 5. However, the electrostatic solvation energy of the permeation ion can not be significantly affected by the dielectric constant in regions with small pore radii. Our results indicate that the local electrostatic interactions inside the ion channel are of major importance for ion electrostatic solvation energies, and the effect of dielectric saturation on the electrostatic barriers is coupled to the interior channel dimensions.

Amino Acid Sequence↗
PubMed1998

Apoptosis and myocardial infarction.

Myocardial infarction was produced in rats and the contribution of apoptotic and necrotic myocyte cell death was measured quantitatively. Myocyte cell death by apoptosis involved 2.8 million cells at 2 hours after coronary artery occlusion and necrosis only 90,000 cells. Myocyte apoptosis continued to represent the major form of cell death, affecting 6.6 million cells at 4.5 hours, whereas myocyte necrosis peaked at 1 day, including 1.1 million cells. Apoptotic myocyte cell death was also present in the surviving portion of the wall adjacent to and remote from the infarcted myocardium where it peaked at 1-2 days. At this interval, 700/10(6) and 110/10(6) myocyte nuclei were undergoing apoptosis in the non-infarcted tissue bordering on and away from the ischemic area, respectively. Myocyte necrosis was absent in the viable myocardium after infarction. Since mechanical forces produced by pathologic loads may activate apoptosis, papillary muscles were exposed to high levels of resting tension in vitro and the magnitude of cell death in these samples was determined. Overstretching resulted in a 21-fold increase in apoptotic myocyte cell death which was coupled with the formation of reactive oxygen species, side-to-side slippage of myocytes, and depressed tension generation of the myocardium. In conclusion, apoptotic myocyte cell death plays a major role in ventricular remodeling after infarction, but whether physical forces, oxidant stress, architectural rearrangement of myocytes, and impaired force development of the myocardium in vivo are causaly related requires further investigation.

Animals↗
PubMed1998

A 20-year experience with the Hancock porcine xenograft in the elderly.

BACKGROUND: The availability of 20 years of follow-up data on the Hancock porcine valve (Medtronic Inc, Irvine, CA) allows determination of long-term actual and actuarial failure rates in the elderly. METHODS: We analyzed outcomes after mitral or aortic valve replacement with the Hancock porcine valve in 491 consecutive patients, comparing actual and actuarial valve failure rates in the elderly (age 65 or older) with those in younger patients. RESULTS: The average age of aortic valve replacement recipients was 68+/-14 years (N = 243) and of mitral valve replacement recipients, 64+/-12 years (N = 248). Average follow-up was 7.0 years (1,673 patient-years) for aortic valve replacement and 7.3 years (1,781 patient years) for mitral valve replacement recipients. The median time to reoperation or structural failure was 15.9 years for aortic valve replacement patients and 14.3 years for mitral valve replacement patients. However, few elderly patients survived to 15 years (22% of the elderly aortic valve replacement and 13% of the older mitral valve replacement patients). The 15-year actual reoperation rate was therefore only 10% in the elderly aortic valve replacement compared to 30% in the younger aortic valve replacement patients. For mitral valve replacement, the 15-year actual reoperation rate was 11% in the elderly and 36% in the younger patients. The lifetime reoperation risk (the maximum potential number of patients who might ever undergo reoperation during their lifetime) is the sum of actual survival and actual reoperation rates. The lifetime reoperation risk was 20% or less for elderly aortic valve replacement patients and 18% or less for elderly mitral valve replacement patients. CONCLUSION: These data suggest that about 1 in 10 elderly patients (65 years or older) receiving a Hancock valve will require reoperation within 15 years and less than one in five will ever require reoperation in their lifetimes.

Actuarial Analysis↗
PubMed1998

Gadolinium-infusion magnetic resonance angiogram: a new, noninvasive, and accurate method of preoperative localization of impalpable undescended testes.

PURPOSE: This study investigates the usefulness of Gadolinium (Gd)-infusion magnetic resonance angiogram (MRA) in the detection of impalpable undescended testes. METHODS: Magnetic resonance (MRI) examination was performed in 14 patients with 17 impalpable undescended testes (unilateral, n = 11; bilateral, n = 3). MRAwasthen performed as follows: Gadolinium-DTPA-BMA (Omniscan) at 0.3 mmol/kg body weight was injected intravenously, and dynamic coronal examination using fast spoiled gradient recalled sequences was obtained with images taken at early arterial and delay venous phases. The testis was located by detection of the enhanced pampiniform venous plexus. RESULTS: Of the 17 undescended testes, 11 canalicular hypoplastic testes and 3 intraabdominal testes were detected in both routine MRI and MRA. Three atrophic testes were found in the scrotum by MRA but not detected by routine MRI. The detection rates of impalpable testes by MRI and MRA were 82.4% and 100%, respectively. All imaging findings were confirmed by surgical exploration. There was no morbidity associated with MRA. CONCLUSION: Gd-infusion MRA is an accurate and sensitive method of preoperative localization of impalpable testes and is superior to conventional MRI in the detection of atrophic testes.

Adolescent↗
PubMed1998

The involvement of two or more systems and the severity of associated anomalies significantly influence mortality in esophageal atresia.

PURPOSE: The aim of this study was to examine the influence of associated anomalies in babies born with esophageal atresia (EA). METHODS: A retrospective review of the records of 41 consecutive cases of esophageal atresia managed over an 11-year period was undertaken. RESULTS: A higher incidence of associated anomalies was seen in those babies with lower birth weights. Although all five (100%) babies with EA who weighed less than 1,800 g had associated anomalies, those who weighed 1,800 to 2,500 g and more than 2,500 g were associated with 67% (10 of 15) and 43% (9 of 21) anomalies, respectively. The most common system in which anomalies occurred was the cardiovascular system (37%) followed by gastrointestinal (24%), musculoskeletal (17%), genitourinary (7%), chromosomal (5%), and others (12%). All 17 (41%) babies with no associated anomalies survived. Four of the 10 babies who had two or more systems involvement died, whereas only one of 31 babies with less than two systems involvement died; the difference between these two groups was highly significant (Fisher's Exact test, P = .009). The overall mortality rate was 12%. Three of the deaths were associated with severe anomalies that were incompatible with life such as bilateral renal agenesis, trisomy 18, and complex cardiac anomalies. CONCLUSION: The association of two or more system anomalies and the severity of associated anomalies influence mortality in esophageal atresia.

Abnormalities, Multiple↗
PubMed1998

Murine duodenum does not go through a "solid core" stage in its embryological development.

Embryological development of duodenum is believed to go through a "solid core" stage which subsequently vacuolizes. Failure of vacuolization is thought to be the cause of duodenal atresia. This study examines the embryological development of rat duodenum. Thirty-six time-mated Sprague-Dawley rats were studied. Six fetal duodenal specimens were obtained for each gestational day from day 9 to day 20. These specimens were fixed with formalin, sectioned, stained with haematoxylin and eosin and examined under microscope. The duodenal diameters and the lumen diameters at each gestational date were measured. The foregut started to form at the gestation stage of day 10. The lumen was narrowest on days 12 and 13, but the duodenum did not become a "solid core". No vacuolization was detected through out the development of the duodenum. Embryological development of rat duodenum did not go through a "solid core" stage.

Animals↗
PubMed1998

[Study on a deletion polymorphism of the angiotensin converting enzyme gene in pregnancy induced hypertension].

OBJECTIVE: To study a polymorphism and allele frequency of the angiotensin converting enzyme (ACE) gene in pregnancy induced hypertension (PIH). METHODS: Polymerase chain reaction (PCR) for detection of ACE gene polymorphism was performed to show the deletion/insertion (D/I) polymorphism in intron 16 of ACE gene. A 490 bp(I) and 190 bp(D) PCR products were identified, corresponding to the PCR amplification of the the allele with or without the insertion. RESULTS: Derived allele frequencies for insertion and deletion were the different between 35 PIH and 25 control subjects. Compared the frequency of D allele gene (0.76) and the percentage of the ACE DD genotype (65.7%) in the PIH patients with the frequency (0.28) and the percentage (8.0%) in the control population, they were significant higher in individuals with PIH (P < 0.001). CONCLUSIONS: There was an excess of DD genotype and the frequency of D allele gene in PIH, confirming the genetic variation in the ACE locus could be involved in the risk of PIH and suggesting the ACE gene may contribute to the pathogenesis of PIH.

Adult↗
PubMed1998

[Clinical study on effect of huancongdan capsule in treating senile vascular dementia].

OBJECTIVE: To observe the effect of Huancongdan (HCD) capsule on senile vascular dementia (SVD). METHODS: Seventy two cases of SVD were divided randomly into two groups. The HCD group (37 cases) were treated with HCD and the control group (35 cases) treated with Hydergine. RESULTS: After 2 months of treatment, the clinical symptoms, hyponeural defect, self-care capability and abnormal ratio of whole blood viscosity to plasma viscosity in HCD group were significantly different as compared with before treatment (P < 0.05). CONCLUSION: The effect of HCD for treatment of SVD was affirmative.

Aged↗
PubMed1998

Determination of intraocular lens tilt and decentration using simple and rapid method.

PURPOSE: To determine the tilt and decentration of implanted intraocular lens (IOL) in vivo one year postoperatively. METHODS: A retrospective study was performed on 67 eyes by the method introduced by Guyton using the third and fourth Purkinje imagesm through undilated pupil. RESULTS: The average decentration of implanted IOL was 0.68 mm, and the average tilt was 6.03 degrees. The result was similar to the histopathological study in postmortem eyes and the measurement in vivo. Linear-regression analysis showed there was no relationship between the tilt and decentration and the residual astigmatism, axial length, IOL power, etc. CONCLUSION: The result is similar to the other methods. The method using the third and fourth Purkinje images is simple and easy to perform. It can be used for determining the IOL position through undilated pupil and does not require special apparatus.

Adult↗
PubMed1997

Cloning and expression of a developmentally regulated transcript MXR7 in hepatocellular carcinoma: biological significance and temporospatial distribution.

Using the differential display method to analyze mRNA expression in hepatocellular carcinoma (HCC) and nontumor livers, we cloned a full-length cDNA of 2263 bp, which was designated GTR2-2 and was identical with MXR7. The MXR7 mRNA was detected in 143 of 191 (74.8%) primary and recurrent HCCs taken from 154 patients but only in 5 (3.2%) nontumor livers. MXR7 mRNA was detected in one of two hepatoblastomas but not in hepatocellular adenoma, cholangiocarcinoma, or metastatic carcinomas to the liver. In human cancer of other anatomical sites, MXR7 mRNA was detected in low levels in one Wilms' tumor and in 4 of 40 gastric adenocarcinomas but not in several other types of cancer and 21 nonhepatocellular human tumor cell lines examined. MXR7 mRNA was expressed in high levels in the placenta, fetal liver, lung, and kidney, but it was undetectable in adult liver and was expressed in very low levels in adult lung and kidney. Our observations suggest that the MXR7 gene is regulated developmentally and expressed preferentially in HCC. To study its potential biological significance, we selected 113 patients who had unicentric primary HCC and had been followed for more than 4 years for further analysis. The MXR7 mRNA expression correlated closely with elevated serum alpha-fetoprotein (AFP) levels (88 versus 55%; P = 0.0001) and with expression of AFP mRNA (87 versus 55%; P = 0.005) and CD24 mRNA in HCC (80 versus 50%; P < 0.04), high tumor grade (76 versus 56%; P = 0.05), and tumor invasion (76 versus 55%; P < 0.05), but not with patient outcome. In HCC < or =3 cm, the frequency (77%) of MXR7 mRNA expression was significantly higher than that of elevated serum AFP (43%; P < 0.007) and AFP mRNA expression in HCC (41%; P < 0.004). Thus, MXR7 may serve as a sensitive early tumor marker for HCC and warrants more study to better understand its biological function.

Adolescent↗
PubMed1997

Insulin-like growth factor-1 receptor and its ligand regulate the reentry of adult ventricular myocytes into the cell cycle.

To determine whether insulin-like growth factor-1 (IGF-1) stimulation in vitro of ventricular myocytes isolated from infarcted hearts is characterized by the reentry of cells into the cell cycle, the expression and kinase activity of cyclins E, A, and B and DNA synthesis were evaluated 5 days after coronary artery occlusion and 24 and 48 h following the addition of IGF-1. Myocytes surviving an acute myocardial infarction were employed because of their increase in surface insulin-like growth factor-1 receptors (IGF-1R). Western blot analysis documented that IGF-1 resulted in an upregulation of cyclins D1, E, A, and B in viable postinfarcted myocytes. Cyclin E- and A-associated histone H1 kinase activity and cyclin D1-associated retinoblastoma protein-associated kinase activity also increased, but cyclin B kinase activity was not enhanced by IGF-1. These changes in cyclins and kinase activities were characterized by a significant increase in the number of cells labeled by bromodeoxyuridine, from approximately 630/10(6) to nearly 9, 000/10(6) myocytes. This latter value was reduced by more than 50% by antisense oligodeoxynucleotide to IGF-1R mRNA. However, IGF-1 stimulation did not induce nuclear mitotic division and cytokinesis. In conclusion, the growth-promoting effect of IGF-1 on adult myocytes is regulated by the density of IGF-1R, which conditions the activation of the replicatory machinery of the cells. The failure of IGF-1 to enhance cyclin B kinase activity may be responsible for a block in the cell cycle and the inability of myocytes to progress through the M phase and subsequently divide.

Animals↗
PubMed1997

p53 Induces myocyte apoptosis via the activation of the renin-angiotensin system.

The mechanism by which p53 activates apoptosis in various cell systems is unknown. In the absence of an external death stimulus, p53 and p53-dependent genes, bcl-2 and bax, cannot trigger apoptosis. However, p53 may enhance not only transcription of bax and repress bcl-2, but also may upregulate the local renin-angiotensin system, inducing the formation and secretion of angiotensin II from the cells. To test this hypothesis, adult rat ventricular myocytes were infected with AdCMV.p53, which resulted in downregulation of Bcl-2, upregulation of Bax, and death of 34% of the cells. Gel retardation assays demonstrated p53 binding in the promoters of angiotensinogen and angiotensin II AT1 receptor subtype. Angiotensinogen and AT1 mRNAs increased in AdCMV.p53 cells and this phenomenon was associated with a 14-fold increase in the secretion of angiotensin II. The AT1 receptor blocker losartan and angiotensin II antibody prevented p53-induced apoptosis. Thus, p53 enhances the myocyte renin-angiotensin-system and decreases the Bcl-2/Bax ratio in the cells, triggering apoptosis. The identification of this new pathway in p53-mediated apoptosis may be critical in the alterations of myocardial function in the pathologic heart.

Adenoviridae↗
PubMed1997

Effect of nuclear protein HMG1 on in vitro slippage synthesis of the tandem repeat dTG x dCA.

Tandem repeats of simple doublet and triplet sequences occur with high frequency in the DNA of eucaryotes. Among the most frequent is the repeat of dTG, which has unusual structural properties. We show here that HMG1 (modeled by the second HMG box motif from HMG1 of the rat, HMGb) binds to complexes formed from annealing unequal lengths of dTG x dCA and inhibits the in vitro elongation of these complexes by the Klenow fragment of DNA polymerase I at 37 degrees C. At 46 degrees C, HMGb enhances the elongation. Polylysine inhibits elongation at both temperatures. These results show that the stability of this repeat in vivo can be influenced by the presence of basic proteins in general, and more selectively by the abundant nuclear protein HMG1.

Animals↗
PubMed1997

Apoptosis in the failing human heart.

BACKGROUND: Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. METHODS: Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. RESULTS: Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonstration of DNA-strand breaks in myocyte nuclei was coupled with the documentation of chromatin condensation and fragmentation by confocal microscopy. All these findings reflect apoptosis of myocytes. The percentage of myocytes labeled with BCL2 (which protects cells against apoptosis) was 1.8 times as high in the hearts of patients with cardiac failure as in the normal hearts, whereas labeling with BAX (which promotes apoptosis) remained constant. The near doubling of the expression of BCL2 in the cardiac tissue of patients with heart failure was confirmed by Western blotting. CONCLUSIONS: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.

Apoptosis↗