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Biomedical subjects

W Y Hu

Publications and source records attributed to W Y Hu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ethical dilemmas in palliative care: a study in Taiwan.

OBJECTIVES: To investigate the incidence and solution of ethical dilemmas in a palliative care unit. DESIGN: Health care workers recorded daily all dilemmas in caring for each patient. SETTING: Palliative care unit of National Taiwan University Hospital in Taiwan. PATIENTS: Two hundred and forty-six consecutive patients with terminal cancer during 1997-8. MAIN MEASUREMENT: Ethical dilemmas in the questionnaire were categorised as follows: telling the truth; place of care; therapeutic strategy; hydration and nutrition; blood transfusion; alternative treatment; terminal sedation; use of medication, and others. RESULTS: The type and frequency of ethical dilemmas encountered were: place of care (33.3%); truth-telling (32.1%); hydration and nutrition (25.2%); therapeutic strategy (24.8%), and use of medication (19.1%). Ethical problems relating to the place of care and to therapeutic strategy were unlikely to be solved with increased hospital stay and some ethical dilemmas remained unsolved even in the final week in hospital, including place of care (23.2%), truth-telling (17.1%) and therapeutic strategy (11.4%). Problems of truth-telling occurred in nearly half (42.6%) of patients over sixty-five-years-old. Conflicts about blood transfusion were experienced in all patients below 18-years-old, and the dilemmas concerning the place of care occurred most frequently with head and neck cancer patients (43.8%). CONCLUSIONS: The solution of ethical dilemmas required refocusing by medical professionals on the importance of continuing communication. Improved ethical training for professionals would contribute to solving the moral dilemmas of palliative care.

Aged↗
PubMed2000

Phenotypic modulation by fibronectin enhances the angiotensin II-generating system in cultured vascular smooth muscle cells.

We previously demonstrated that homogeneous cultures of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats produce angiotensin II (Ang II) in response to increases in the levels of angiotensinogen, cathepsin D, and angiotensin-converting enzyme (ACE). The change of VSMCs from the contractile to the synthetic phenotype increased the amount of synthetic organelles, resulting in the production of proteases and growth factors. To evaluate the contribution of the synthetic phenotype to the generation of Ang II, we examined the effect of fibronectin (FN), which reportedly induces the synthetic phenotype, on the Ang II-generating system in VSMCs. Cultured VSMCs from Wistar-Kyoto rats were incubated with an active fragment of FN, Arg-Gly-Asp-Ser, for 24, 48, or 72 hours after synchronization of the cell cycle with 0. 2% calf serum for 48 hours. Immunofluorescence and protein levels of alpha-smooth muscle (SM) actin and expression of SM22alpha mRNA, apparent in the contractile phenotype, were suppressed by FN, whereas expression of matrix Gla mRNA and osteopontin mRNA and protein, apparent in the synthetic phenotype, was increased. FN (1 to 1000 microg/mL) dose-dependently increased DNA synthesis in the VSMCs, which was inhibited by the Ang II type 1 receptor antagonist CV-11974. Ang II-like immunoreactivity as determined by radioimmunoassay was significantly increased in conditioned medium from the VSMCs. In addition, mRNA for the Ang II-generating proteases cathepsin D and ACE was increased by FN. Expression of transforming growth factor-beta1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNAs was also increased by FN. These results indicate that the changes accompanying the alteration to the synthetic phenotype in homogeneous cultures of VSMCs increase expression of proteases such as cathepsin D and ACE, which then produce Ang II, and that these changes increase expression of growth factors that then induce growth of VSMCs.

Angiotensin II↗
PubMed2000

Retirement planning and long-term risk.

Many defined contribution plan participants have available to them various measures of short-term risk. However, some of these participants don't understand that reducing short-term risk comes at the cost of increasing the risk of not reaching their retirement income goal. This article looks at the relationship between short- and long-term risk and their impact on retirement savings.

Humans↗
PubMed1999

Metabolism of methyl tert-butyl ether and other gasoline ethers by human liver microsomes and heterologously expressed human cytochromes P450: identification of CYP2A6 as a major catalyst.

To reduce the production of carbon monoxide and other pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Previously, we demonstrated that human liver is active in metabolizing MTBE to tert-butyl alcohol (TBA) and that cytochrome P450 (CYP) enzymes play a critical role in the metabolism of MTBE. The present study demonstrates that human liver is also active in the oxidative metabolism of ETBE and TAME. A large interindividual variation in metabolizing these gasoline ethers was observed in 15 human liver microsomal samples. The microsomal activities in metabolizing MTBE, ETBE, and TAME were highly correlated among each other (r, 0.91-0. 96), suggesting that these ethers are metabolized by the same enzyme(s). Correlation analysis of the ether-metabolizing activities with individual CYP enzyme activities in the liver microsomes showed that the highest degree of correlation was with human CYP2A6 (r, 0. 90-0.95), which is constitutively expressed in human livers and known to be polymorphic. CYP2A6 displayed the highest turnover number in metabolizing gasoline ethers among a battery of human CYP enzymes expressed in human B-lymphoblastoid cells. Kinetic studies on MTBE metabolism with three human liver microsomes exhibited apparent Km values that ranged from 28 to 89 microM and the V(max) values from 215 to 783 pmol/min/mg, with similar catalytic efficiency values (7.7 to 8.8 microl/min/mg protein). Metabolism of MTBE, ETBE, and TAME by human liver microsomes was inhibited by coumarin, a known substrate of human CYP2A6, in a concentration-dependent manner. Monoclonal antibody against human CYP2A6 caused a significant inhibition (75% to 95%) of the metabolism of MTBE, ETBE, and TAME in human liver microsomes. Taken together, these results clearly indicate that in human liver, CYP2A6 is the major enzyme responsible for the metabolism of MTBE, ETBE, and TAME.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice.

Previous experiments in vitro have suggested that cytochrome P450 2E1 (CYP2E1) is involved in acetone catabolism by converting acetone to acetol and then to methylglyoxal, both intermediates in the gluconeogenic pathway. In the present study, CYP2E1-null mice were used to demonstrate the role of CYP2E1 in acetone catabolism in vivo. The blood acetone level in male CYP2E1-null mice was 3.3 +/- 0.9 microg/mL, which was similar to levels of their sex- and age-matched parental lineage strains C57BL/6N (2.3 +/- 0.2 microg/mL) and 129/Sv (3.5 +/- 0.3 microg/mL) mice (both are CYP2E1 wild-type). After fasting for 48 hr, the blood acetone levels in the CYP2E1 wild-type mice were increased by 2.5- to 4.4-fold, but that in the CYP2E1-null mice increased 28-fold. These results clearly demonstrate that CYP2E1 plays a vital role in the catabolism of acetone under fasting conditions.

Acetone↗
PubMed1999

Metabolism of methyl tert-butyl ether and other gasoline ethers in mouse liver microsomes lacking cytochrome P450 2E1.

To reduce the production of pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE) and other ethers such as ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Metabolism of these gasoline ethers is catalyzed by cytochrome P450 (P450) enzymes. P450 2E1, which metabolizes diethyl ether, was suggested to be an enzyme involved. The present study used 2E1 knock-out mice (2E1-/-) to assess the contribution of 2E1 to the metabolism of MTBE, ETBE and TAME. Liver microsomes prepared from the 2E1 knock-out mice lacked 2E1 activity (assayed as N-nitrosodimethylamine demethylation), but were still active in metabolizing all three gasoline ethers. The levels of ether-metabolizing activity (nmol/min per mg) in the liver microsomes from 7 week old female 2E1 knock-out mice were 0.54+/-0.17 for MTBE, 0.51+/-0.24 for ETBE and 1.14+/-0.25 for TAME at a 1 mM substrate concentration. These activity levels were not significantly different from those of the sex- and age-matched C57BL/6N and 129/Sv mice, which are the parental lineage strains of the 2E1 knock-out mice and are both 2E1+/+. Our results clearly demonstrate that 2E1 plays a negligible role in the metabolism of MTBE, ETBE and TAME in mouse livers.

Aging↗
PubMed1999

Contribution of synthetic phenotype on the enhanced angiotensin II-generating system in vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVE: We have demonstrated that cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR), but not from normotensive Wistar-Kyoto (WKY) rats, produce angiotensin II (Ang II) in a homogeneous culture with increased levels of angiotensinogen, cathepsin D and angiotensin converting enzyme (ACE) at early passages. In the current study, we investigated how changes in the cell phenotype affect the Ang II-generating system and the growth of VSMC from SHR. DESIGN AND METHODS: We evaluated basal DNA synthesis by [3H]thymidine incorporation, immunofluorescence of alpha-smooth muscle (SM) actin, mRNA expression of phenotype markers such as SM22alpha appeared by contractile phenotype, Ang II-generating system components and growth factors by reverse transcription and polymerase chain reaction analysis, and Ang II levels by radioimmunoassay in quiescent VSMC from WKY/Izumo rats and SHR/Izumo at passages 4, 8 and 12. RESULTS: Basal DNA synthesis in VSMC from WKY rats increased with increasing passage number, whereas in cells from SHR it was markedly higher at early passages and was not affected by the passages. At early passage numbers, immunofluorescence of alpha-SM actin was stronger in VSMC from WKY rats than in cells from SHR, but decreased after several passages. Expression of SM22alpha mRNA was higher in VSMC from WKY rats than in cells from SHR at early passages, and decreased after several passages in cells from both rat strains. Expression of matrix Gla mRNA was higher in VSMC from SHR than in cells from WKY rats at early passage, and increased after several passages in cells from both rat strains. Ang II was not detected at early passages but increased in VSMC from WKY rats with increasing passage, whereas it was detected in VSMC from SHR at early passages and did not change with the passages. Expression of angiotensinogen mRNA was higher in VSMC from SHR than in cells from WKY rats, and was not affected by the passages. Expressions of cathepsin D and ACE mRNA were higher in VSMC from SHR than in cells from WKY rats at early passage, and were increased by the passages in VSMC from WKY rats. Expressions of transforming growth factor-beta1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNA were significantly higher in VSMC from SHR than in cells from WKY rats, and were increased by the passages. CONCLUSION: These data indicate that early in culture VSMC from SHR have the synthetic phenotype, whereas VSMC from WKY rats have the contractile phenotype which then changes to the synthetic phenotype after increased passage numbers, with increased expression of cathepsin D and ACE, which produce Ang II, and increased expression of Ang II-related growth factors, which induce the exaggerated growth observed in VSMC from SHR.

Angiotensin II↗
PubMed1999

Low dose of eicosapentaenoic acid inhibits the exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats through suppression of transforming growth factor-beta.

OBJECTIVE: To evaluate effects of eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, on the exaggerated growth of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). DESIGN: Cultured VSMC were prepared by an explant method from thoracic aortas in 8-week-old male Wistar-Kyoto (WKY)/Izumo rats and SHR/Izumo. Effects of EPA on basal DNA synthesis, expression of growth factors and cyclin-dependent kinase 2 (cdk2) activity were examined in VSMC from WKY rats and SHR. METHODS: The cell cycles were synchronized with serum deprivation, then DNA synthesis in VSMC was measured by [3H]-thymidine incorporation. Fatty acid composition of the phospholipid fraction in VSMC was measured by gas chromatography. Expression of platelet-derived growth factor (PDGF) A-chain, transforming growth factor (TGF)-beta1 and basic fibroblast growth factor (bFGF) mRNAs was evaluated by reverse-transcription and polymerase chain reaction analysis. Cdk2 activity was determined by autoradiography after polyacrylamide gel electrophoresis of VSMC extracts that had been immunoprecipitated with anti-cdk2 antibody and protein A sepharose, and then incubated with 32P-ATP and histone H1. RESULTS: High concentrations (40 and 80 micromol/I) of EPA significantly inhibited basal DNA synthesis in VSMC from both rat strains. Low dose (20 micromol/l) of EPA significantly inhibited basal DNA synthesis in VSMC from SHR, whereas the same dose of EPA stimulated DNA synthesis in VSMC from WKY rats. In analysis of fatty acid composition, low dose of EPA was considerably incorporated in VSMC. Low dose of EPA significantly inhibited angiotensin II- and phorbol ester milisterol-stimulated DNA synthesis in VSMC from both rat strains, whereas EPA did not affect PDGF-AA-stimulated DNA synthesis in VSMC from either rat strain. Low dose of other polyunsaturated fatty acids such as docosahexaenoic acid, arachidonic acid and linoleic acid did not significantly affect basal DNA synthesis in VSMC from either strain. Low dose of EPA significantly inhibited expression of TGF-beta1 mRNA in VSMC from SHR, whereas EPA did not affect expression of PDGF A-chain and bFGF mRNAs in VSMC from SHR. Cdk2 activity in VSMC from SHR was higher than that from WKY rats. Low dose of EPA inhibited cdk2 activity in VSMC from SHR, whereas it stimulated the activity in VSMC from WKY rats. CONCLUSION: Low dose of EPA exerted specific inhibition of the exaggerated growth of VSMC from SHR through the suppression of TGF-beta.

Animals↗
PubMed1999

Production of angiotensin II by homogeneous cultures of vascular smooth muscle cells from spontaneously hypertensive rats.

Production of angiotensin II (Ang II) in spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMC) has now been investigated. A nonpeptide antagonist (CV-11974) of Ang II type 1 receptors inhibited basal DNA synthesis in VSMC from SHR, but it had no effect on cells from Wistar-Kyoto (WKY) rats. Ang II-like immunoreactivity, determined by radioimmunoassay after HPLC, was readily detected in conditioned medium and extracts of SHR-derived VSMC, whereas it was virtually undetectable in VSMC from WKY rats. Isoproterenol increased the amount of Ang II-like immunoreactivity in conditioned medium and extracts of SHR-derived VSMC, whereas the angiotensin-converting enzyme inhibitor delapril significantly reduced the amount of Ang II-like immunoreactivity in conditioned medium and extracts of these cells. Reverse transcription-polymerase chain reaction analysis revealed that the abundance of mRNAs encoding angiotensinogen, cathepsin D, and angiotensin-converting enzyme was greater in VSMC from SHR than in cells from WKY rats. The abundance of cathepsin D protein by Western blotting was greater in VSMC from SHR than in cells from WKY rats. Ang I-generating and acid protease activities were detected in VSMC from SHR, but not in cells from WKY rats. These results suggest that SHR-derived VSMC generate Ang II with increases in angiotensinogen, cathepsin D, and angiotensin-converting enzyme, which contribute to the basal growth. Production of Ang II by homogeneous cultures of VSMC is considered as a new mechanism of hypertensive vascular disease.

Angiotensin II↗
PubMed1999

The induction of liver microsomal cytochrome P450 by Glycyrrhiza uralensis and glycyrrhetinic acid in mice.

The effect of Glycyrrhiza uralensis Fisch (GRZ) aqueous extract and one of its active principles Glycyrrhetinic acid (GRT) on hepatic cytochrome P450 in mice were investigated. Oral administration of GRZ at 10 g/kg/d or GRT at 50 mg/kg/d for 7 days was found to increase the P450 contents up to 4.6 fold compared with the controls. The activities of aryl hydrocarbon hydroxylase (AHH, 3.1 and 3.3 fold), aminopyrine N-demethylase (ADM, 4.2 and 3.2 folds), and 7-ethoxycumarin O-deethylase (ECOD, 2.8 and 2.5 fold) were also shown to be increased. Western blot analysis showed that the subtypes of P450 isoforms induced selectively by GRZ and GRT included CYP1A1 (1.8 and 1.5 fold over that of the control, respectively), CYP2B1 (both 1.3 fold), and CYP2C11 (3.2 and 3.0 fold). Moreover, significant positive correlation between the P450 content or the isoforms and the corresponding enzyme activities mentioned above was observed.

Animals↗
PubMed1998

Bunazosin hydrochloride inhibits exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats by suppressing the response to growth factors.

Selective alpha1-adrenoreceptor blockers were recently reported to have an in vivo antiproliferative effect on hypertensive cardiovascular organs. Cultured vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) show exaggerated growth compared with cells from Wistar-Kyoto (WKY) rats. We investigated the effects of an alpha1-adrenoreceptor blocker, bunazosin hydrochloride (HCl), on the growth of VSMCs from SHRs. In the absence of serum, bunazosin HCl significantly inhibited basal DNA synthesis by VSMCs from SHRs, but not by cells from WKY rats. In the presence of serum, bunazosin HCl significantly inhibited DNA synthesis by VSMCs from both rat strains. Angiotensin (Ang) II, platelet-derived growth factor (PDGF)-AA, and epidermal growth factor (EGF) dose-dependently increased DNA synthesis by VSMCs from SHRs, but not by VSMCs from WKY rats. Bunazosin HCl significantly suppressed the response of DNA synthesis to PDGF-AA and EGF, but not to Ang II, in VSMCs from SHRs. Expression of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGFbeta1), and PDGF messenger RNA (mRNA) was markedly greater in VSMCs from SHRs than in cells from WKY rats. Bunazosin HCl significantly inhibited the expression of bFGF and TGFbeta1 mRNA in VSMCs from SHRs, but not in cells from WKY rats. These findings suggest that the inhibition of growth factor hyperresponsiveness and inhibition of the expression of growth factors in VSMCs from SHRs are associated with the antiproliferative effect of bunazosin.

Adrenergic alpha-Antagonists↗
PubMed1998

Target choice and orientation preference of the insertion sequence IS903.

We have examined the targeting preference of the bacterial insertion element IS903 by determining the sites of insertion of a large number of transposition events into the 55-kb conjugative plasmid pOX38. Despite the large target size, all the insertions were clustered in four small distinct regions associated with conjugal DNA transfer. Within these regions, many different sites were used for insertion; however, there were a few sites that IS903 inserted into more than once. Alignment of the insertion sites showed that there was no consensus sequence within the 9-bp target duplication but that there were preferred sequences located symmetrically on either side of the target. This is consistent with target recognition by a dimer or multimer of transposase, with either sequence-specific or structure-specific interactions on both sides of the target. We show further that when one of these preferred regions was cloned into a second conjugative plasmid, pUB307, it was still a preferred target, implying that all the sequences necessary for target selection are contained within this DNA segment. Also, we observed a very strong preference for insertion in a single orientation in pUB307. We examined the possibility that either DNA replication from the origin of vegetative replication, oriV, or the origin of transfer, oriT, might determine this orientation effect. We find that reversing the direction of vegetative replication had no effect on the orientation of transposon insertions; however, reversing the direction of DNA transfer abolished the orientation effect. This supports the idea that conjugal DNA transfer imparts a polarity on the target that is sensed by the transposon.

Base Sequence↗
PubMed1998

Abnormal regulation of transforming growth factor-beta receptors on vascular smooth muscle cells from spontaneously hypertensive rats by angiotensin II.

The effects of angiotensin II (Ang II) on the expression and characteristics of transforming growth factor-beta (TGF-beta) receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were investigated. TGF-beta-induced stimulation of DNA synthesis by VSMC from WKY rats was abolished with Ang II, whereas basal and TGF-beta-stimulated DNA synthesis by VSMC from SHR was increased with Ang II. Ang II stimulated DNA synthesis by VSMC from WKY rats in the presence but not in the absence of neutralizing antibody to TGF-beta1. Antibody to TGF-beta1 enhanced the stimulatory effect of Ang II on DNA synthesis by VSMC from SHR. Ang II increased the specific binding of TGF-beta to VSMC from WKY rats by increasing both the expression of the lower-affinity of TGF-beta receptors as well as the total number of TGF-beta binding sites. In contrast, VSMC from SHR showed a higher affinity and number of TGF-beta receptors in the absence of Ang II than did cells from WKY rats, and these parameters were not affected by Ang II. Ang II increased the expression of TGF-beta type I receptor mRNA in VSMC from WKY rats but had no effect of TGF-beta receptor type I or II mRNA in VSMC from SHR, which predominantly express the type II receptor. These results indicate that an increase in the expression of the TGF-beta type I receptor by Ang II may facilitate the ability of endogenous TGF-beta to counteract the stimulatory effect of Ang II on growth in VSMC from WKY rats, whereas endogenous TGF-beta induced by Ang II cannot counteract the growth-promoting action of Ang II in VSMC from SHR. The abnormal regulation of TGF-beta receptors by Ang II may be associated with the exaggerated growth of VSMC from SHR.

Angiotensin II↗
PubMed1998

Inhibitory effects of captopril on c-myc expression during left ventricular hypertrophy.

AIM: To study the molecular mechanism of captopril (Cap) on the inhibition of left ventricular hypertrophy (LVH), disclose the expression and distribution of c-myc in different cell types in left ventricle (LV) in spontaneously hypertensive rats (SHR). METHODS: Cap 100 mg.kg-1.d-1 was given p.o. to SHR. Systolic blood pressure (SBP), left ventricular weight (LVW), and body weight (BW) were measured at 16-wk old. The level of angiotensin II (Ang II), c-myc mRNA, and oncoprotein were determined by immunohistochemical method, Northern blot, and Western blot, respectively. RESULTS: Cap reduced SBP, LVW/BW in SHR, with a decrease of Ang II and c-myc expression in LV. Local cardial Ang II mainly distributed in cardiomyocytes. Cap inhibited cardial Ang II production and c-myc expression (histochemical staining intensity index, 0.49 +/- 0.04 vs 0.83 +/- 0.24, P < 0.01). The c-myc oncoprotein was prevailingly located in cardiac fibroblasts. The c-myc oncoprotein in Cap treated SHR was lower than that of WKY. CONCLUSION: High expression of c-myc in fibroblasts played an important role in the development of LVH in SHR. Inhibitory effects of Cap on LVH was associated with a decreased myocardial Ang II and interstitial fibroblasts c-myc expression. The c-myc oncoprotein post-transcriptional translation was also interrupted by Cap.

Angiotensin II↗
PubMed1997

Sequences of exon 6 and the adjacent intron boundaries of the rat platelet-derived growth factor A-chain gene: implications for alternative splicing.

Platelet-derived growth factor (PDGF) is a potent stimulator of vascular smooth muscle cell growth. Two isoforms of PDGF A-chain mRNA that either include (long form) or exclude (short form) exon 6 are produced as a result of alternative splicing in mouse, rabbit, and human. The short form of PDGF A-chain is expressed in both resting and activated cells, while the long form is present predominantly in activated cells. Reverse transcription-polymerase chain reaction analysis with primers encompassing exon 6 revealed the presence of both long- and short-form PDGF A-chain transcripts in rat vascular smooth muscle cells. The nucleotide sequences of exon 6 and its intron boundaries were determined from rat vascular smooth muscle cell cDNA and rat leukocyte genomic DNA. Translation of the long form of PDGF A-chain mRNA was shown to terminate in the 70-base pair exon 6. Conserved sequences that may contribute to the regulation of alternative RNA splicing were identified in intron 5.

Alternative Splicing↗
PubMed1996

Aortic arch interruption associated with ruptured cerebral aneurysm.

The authors present a case of aortic arch interruption in an adult, an anomaly that was discovered coincidentally during angiography for ruptured cerebral aneurysm. The presentation in adulthood with rupture of the aneurysm and the successful surgical treatment of both abnormalities are unusual.

Adult↗