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Biomedical subjects

C M Hsieh

Publications and source records attributed to C M Hsieh.

At least 55 records · Page 3Linked to original sources
PubMed1995

Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells.

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1 beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1 beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This IL-1 beta-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.

Animals↗
PubMed1995

The ATF site mediates downregulation of the cyclin A gene during contact inhibition in vascular endothelial cells.

Contact inhibition mediates monolayer formation and withdrawal from the cell cycle in vascular endothelial cells. In studying the cyclins--key regulators of the cell cycle--in bovine aortic endothelial cells (BAEC), we found that levels of cyclin A mRNA decreased in confluent BAEC despite the presence of 10% fetal calf serum. We then transfected into BAEC a series of plasmids containing various lengths of the human cyclin A 5' flanking sequence and the luciferase gene. Plasmids containing 3,200, 516, 406, 266, or 133 bp of the human cyclin A promoter directed high luciferase activity in growing but not confluent BAEC. In contrast, a plasmid containing 23 bp of the cyclin A promoter was associated with a 65-fold reduction in activity in growing BAEC, and the promoter activities of this plasmid were identical in both growing and confluent BAEC. Mutation of the activating transcription factor (ATF) consensus sequence at bp -80 to -73 of the cyclin A promoter decreased its activity, indicating the critical role of the ATF site. We identified by gel mobility shift analysis protein complexes that bound to the ATF site in nuclear extracts from growing but not confluent BAEC and identified (with antibodies) ATF-1 as a binding protein in nuclear extracts from growing cells. Also, ATF-1 mRNA levels decreased in confluent BAEC. Taken together, these data suggest that the ATF site and its cognate binding proteins play an important role in the downregulation of cyclin A gene expression during contact inhibition.

Activating Transcription Factor 1↗
PubMed1995

Disappearance of cyclin A correlates with permanent withdrawal of cardiomyocytes from the cell cycle in human and rat hearts.

The regulated expression of cyclins controls the cell cycle. Because cardiomyocytes in adult mammals withdraw permanently from the cell cycle and thus cannot regenerate after injury, we examined cyclin expression during development by comparing cyclin A-E mRNA levels in fetal and adult human hearts. Cyclin B mRNA was detectable in adult hearts, although at a level markedly lower than that in fetal hearts. Levels of cyclin C, D1, D2, D3, and E mRNA were essentially identical in the two groups. In contrast, cyclin A mRNA was undetectable in adult hearts whereas cyclin A mRNA and protein were readily detectable in fetal hearts and cardiomyocytes, respectively. We then measured cyclin A mRNA and protein levels in rat hearts at four stages of development (fetal and 2, 14, and 28 d). Cyclin A mRNA and protein levels decreased quickly after birth (to 37% at day 2) and became undetectable within 14 d, an observation consistent with reports that cardiomyocytes stop replicating in rats by the second to third postnatal week. This disappearance of cyclin A gene expression in human and rat hearts at the time cardiomyocytes become terminally differentiated suggests that cyclin A downregulation is important in the permanent withdrawal of cardiomyocytes from the cell cycle.

Adult↗
PubMed1994

Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis.

Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis.

Animals↗
PubMed1994

Transforming growth factor-beta 1, but not dexamethasone, down-regulates nitric-oxide synthase mRNA after its induction by interleukin-1 beta in rat smooth muscle cells.

Nitric oxide (NO), which accounts for the biologic properties of endothelium-derived relaxing factor, is synthesized from L-arginine by nitric-oxide synthase (NOS). Two classes of NOS have been identified: a constitutive, calcium-dependent isozyme (cNOS) and an inducible, calcium-independent isozyme (iNOS). NO is generated after the induction of iNOS by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha. As a potent vasodilator, NO may have an important role in the severe hypotension of septic shock. We investigated whether dexamethasone and transforming growth factor-beta 1 (TGF-beta 1) suppress iNOS mRNA after its induction by IL-1 beta. We found that IL-1 beta induced iNOS mRNA in rat aortic smooth muscle cells (RASMC) in a dose- and time-dependent fashion. IL-1 beta promoted a dramatic and prolonged induction of RASMC iNOS mRNA that peaked at 48 h. Dexamethasone prevented this induction of iNOS mRNA only when given before the addition of IL-1 beta. In contrast, TGF-beta 1 inhibited the induction of iNOS mRNA and NO production in RASMC both before and after the addition of IL-1 beta. After 24 h of IL-1 beta stimulation, TGF-beta 1 down-regulated the iNOS mRNA that had been induced during this initial time period. In nuclear run-on experiments, we found that the down-regulation of iNOS mRNA by TGF-beta 1 in RASMC occurred at the transcriptional level. Our observation that TGF-beta 1 mediates inhibition of RASMC iNOS mRNA after its induction by cytokines may be an important insight into the treatment of septic shock.

Amino Acid Oxidoreductases↗
PubMed1994

Tissue-specific expression of Ran isoforms in the mouse.

Ran genes encode a family of well-conserve small nuclear GTPases (Ras-related nuclear proteins), whose function is implicated in both normal cell cycle progression and the transport of RNA and proteins between the nucleus and the cytoplasm. Previous studies of Ran proteins have utilized cell-free systems, yeasts, and cultured mammalian cells. We have now characterized patterns of Ran gene expression in the mouse. Serum starvation suppressed Ran gene transcription in mouse 3T3 cells. Ran mRNA reappeared in cells within 3 h after refeeding. A single Ran mRNA species was detected at low levels in most somatic tissues of the adult mouse. In testis, this Ran mRNA was abundant, as were other larger transcripts. Analysis of testis-derived Ran cDNA clones revealed the presence of two transcripts, one specifying an amino acid sequence identical to that of human Ran/TC4 and one specifying an amino acid sequence 94% identical. Northern blotting and reverse transcriptase-PCR assays with oligonucleotide probes and primers specific for each transcript demonstrated that the isoform identical to Ran/TC4 was expressed in both somatic tissues and testis, while the variant form was transcribed only in testis. The existence of tissue-specific Ran isoforms may help to rationalize the diverse roles suggested for Ran by previous biochemical studies.

3T3 Cells↗
PubMed1993

Influence of temperature of flushing solution on lung preservation.

For lung transplantation the technique of flushing the donor pulmonary vascular bed may provide advantages in lung preservation such as rapid cooling and washout of blood. However, rapid cooling of the ischemic lung may also produce adverse effects. The aim of this study was to compare methods of cold flushing and topical cooling, and to evaluate the effect of temperature of the flushing solution on lung preservation. A total of 25 rabbit lungs were studied. Using an ex vivo rabbit lung model, postischemic function was assessed by the ability of the lung to oxygenate perfused blood and by measurement of pulmonary artery and airway pressures. The lungs in group I were preserved with simple immersion at 10 degrees C for 30 hours. The lungs in groups II through V were flushed with solution containing phosphate-buffered dextran (LPD) at different temperatures (groups II and IV, 10 degrees C; groups III and V, 23 degrees C) and stored at 10 degrees C for various ischemic periods (groups II and III, 30 hours; groups IV and V, 36 hours). Pulmonary vascular resistance during flushing at 10 degrees C was significantly higher than that at 23 degrees C (p < 0.001). Flushing resulted in better preservation than topical hypothermia. Flushing at 23 degrees C resulted in superior postischemic function compared with flushing at 10 degrees C. We conclude that in lung preservation, uniform flushing with LPD solution improves the ischemic tolerance as compared with topical hypothermia, and that flushing with solutions at too low temperatures may have adverse effects on lung preservation.

Animals↗
PubMed1992

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Plasma atrial natriuretic factor concentrations in a canine model of right heart pressure overload.

Two studies were carried out in order to evaluate the plasma atrial natriuretic factor (ANF) concentrations, as well as hemodynamic and renal profiles in a chronic canine model of right heart pressure overload induced by pulmonary artery (PA) banding. In study I (n = 6), the animals were submitted to a gradual increase in pressure to clarify whether an increase in pressure or atrial distension was the main stimulus to ANF secretion. In study II (n = 6), right heart pressure overload was produced more rapidly, resulting in fluid retention and weight gain, thereby completing the model of right heart failure, and allowing an evaluation of the mechanisms involved in ANF resistance. In study I there were significant increases in right atrial pressure over baseline at 20 weeks, ANF levels at 24 weeks and right atrial area at 28 weeks following PA banding. In study II right heart pressures and ANF levels were higher than baseline at 12 weeks (p less than 0.0001), and fluid retention developed between 12-24 weeks in all dogs. The results suggest that increased right heart pressure, rather than atrial size, is a primary stimulus to ANF secretion in chronic right heart pressure overload. Despite the increases in right atrial pressure, clinical fluid retention occurred only with elevations of renin and aldosterone.

Aldosterone↗
PubMed1991

A reevaluation of heparin requirements for cardiopulmonary bypass.

We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.

Animals↗
PubMed1990

Cardiopulmonary exercise testing after single and double lung transplantation.

The cardiopulmonary response to exercise was investigated in six single and six double lung transplant recipients using a three-minute incremental work rate protocol on a cycle ergometer. Maximum VO2 averaged 44.2 +/- 9.2 percent and 48.5 +/- 5.0 percent of predicted maximal VO2 in the single and double lung transplant groups, respectively. No evidence of ventilatory limitation to exercise was found in either group. Circulatory factors that may have limited exercise capacity included anemia and submaximal heart rates. There was a strong correlation between VO2/kg at venous blood lactate level of 2.2 mEq/L and vital capacity/body surface area in the single, but not in the double, lung recipients. Maximum VO2 in these lung transplant recipients was comparable to previously published values in heart-lung transplant recipients. The factors that limit maximum exercise capacity after lung transplantation deserve further study.

Adult↗
PubMed1990

[Results of pulmonary angioplastic operations for cases of bronchogenic carcinoma].

Pulmonary artery reconstruction for bronchogenic carcinoma was performed in 36 patients (5.8%) in our department between 1955 and 1988 for the purpose of preservation of pulmonary function. Twenty-six patients had squamous cell carcinoma (72.2%) and 24 had Stage IIIA. The operative procedures were sleeve resection of the main pulmonary artery (P.A.) and end-to-end anastomosis in 20 cases, wedge resection of P.A. and transverse suture in 14 and window type resection of P.A. and patch closure in 2. In 28 patients bronchoplastic procedures were combined. Three patients (8.3%) died within 30 days after operation. Postoperative complications were relatively high in the patients with combined operations. The 5-year survival rates were 45.7%. Postoperative pulmonary functions were evaluated with spirometric examinations and pulmonary scintigrams. There were no differences in postoperative pulmonary functions between pulmonary angioplastic procedures and simple lobectomies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1990

[The comparison of the binding of Ru486 to progesterone receptor of pituitary and endometrium in ovariectomized rat].

Following intramuscular injections of increasing doses of Ru486 (0.1 mg/kg-2 mg/kg), free progesterone binding sites remaining in pituitary and endometrium in estrogen-primed OVX rats decreased. Thirty minutes after administration of Ru486 (2 mg/kg) the binding sites of progesterone receptor in both tissues showed a significant initial decrease, and then gradually reached the lowest level in 2 h. Afterwards the levels of progesterone receptor began to increase. The results suggested that Ru486 could interact with progesterone receptor in both tissues. However, the binding ability of Ru486 for different tissue was not exactly the same, and Ru486 binding to the progesterone receptor in endometrium might be easier.

Animals↗
PubMed1989

Recovery of elevated atrial natriuretic peptide in pressure-overload right heart failure.

Elevation of the plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was observed in canine chronic right heart failure (RHF) secondary to right ventricular (RV) pressure overload. Pressure overload on the right heart was gradually increased using an inflatable cuff. The interval between banding and the onset of RHF was 152 +/- 52 days. Seventeen RHF dogs were produced and divided into Group I (n = 11) and Group II (n = 6). At the onset of RHF, Group I dogs were either sacrificed for study of the heart, or unbanded to allow recovery from RHF. The dogs in Group II were maintained in RHF for 3 additional months before being either sacrificed or unbanded. Following unbanding, the ANP level of Group I recovered from 108 +/- 36 (n = 11) to 20 +/- 6 pg/ml (n = 6) at 1 month and was maintained at 27 +/- 7 pg/ml (baseline, 21 +/- 5 pg/ml, n = 11) at 4 months. ANP levels of Group II declined from 165 +/- 55 (n = 6) to 87 +/- 2 pg/ml (n = 3) at 1 month and further decreased to 42 +/- 14 pg/ml (n = 3) 4 months after unbanding. Thus, compared to Group I, Group II had a high ANP level before unbanding and a delay in recovery of the ANP levels despite normalization of the right atrial pressure (RAP). Four months after release of pressure overload, the right atrial hypertrophy persisted in the unbanded dogs; however, Group I unbanded dogs showed a better reversal of the right atrial hypertrophy than Group II unbanded dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The effect of ischemic time and temperature on lung preservation in a simple ex vivo rabbit model used for functional assessment.

Despite 25 years of research in lung transplantation, little progress has been made in methods for improving lung preservation. To evaluate many factors that may affect lung function after preservation, we have developed a simple, reliable, and inexpensive animal model. This consists of an isolated rabbit lung preparation perfused with blood and ventilated with a closed-circuit system. Heart-lung blocks were harvested and the left lung was assessed after ligation of the right pulmonary artery and right main-stem bronchus. On completion of a storage period, the left lung was ventilated and perfused with fresh rabbit venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of infused and effluent blood, oxygen uptake, mean pulmonary artery perfusion pressure, and mean airway pressure. A control group and six preservation groups were evaluated, each with different storage temperatures (38 degrees C, 34 degrees C, 23 degrees C, 15 degrees C, 10 degrees C, and 4 degrees C). For each temperature, ischemic periods ranging from 1 to 30 hours were studied. In the control group, the lungs were assessed immediately after being harvested. In the preservation groups, the lungs were kept partially inflated, stored at a predetermined temperature by immersion, and later assessed after variable ischemic periods. Our studies demonstrated the following: (1) The degree of impaired lung function produced by ischemia is reflected by a decrease in oxygen uptake and in oxygen tension of the effluent pulmonary venous blood and an increase in pulmonary artery perfusion pressure; (2) hypothermia improves ischemic tolerance; (3) preservation of lung at 10 degrees C is superior to preservation at 15 degrees C and 4 degrees C. This screening model has allowed evaluation of independent multiple factors and methods pertinent to lung preservation and enables one to assess lung function reliably and rapidly.

Animals↗