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Biomedical subjects

D Cheng

Publications and source records attributed to D Cheng.

At least 55 records · Page 3Linked to original sources
PubMed2000

The intrauterine device: still misunderstood after all these years.

The intrauterine device (IUD) is one of the most effective, safe, and economic methods of contraception today. It is used by more women worldwide than any other reversible method of birth control, yet less than 1% of women in the United States use the IUD. Still remembering the tragedy of the notorious Dalkon Shield, American pharmaceutical companies and clinicians have been wary about promoting any IUD, leaving most physicians inadequately trained in the two IUDs available in the United States. Most significantly, misconceptions about the IUD's safety, mechanism of action, complication rates, and liability have severely limited the utilization of the IUD by many practitioners and women in the United States who may greatly benefit from it.

Adolescent↗
PubMed2000

P73 gene expression in ovarian cancer tissues and cell lines.

Thep73 gene, a homology of p53, is a new candidate of imprinting and tumor suppressor gene. To investigate the role of p73 in ovarian cancer, we studied the allelic expression in 56 cases of ovarian cancer using StyI polymorphism analysis. We also examined p73 expression by semi-quantitative reverse transcription-PCR as well as by Western blot analysis and DNA methylation study of the CpG island in exon 1 in ovarian cancer tissues and cell lines. Loss of heterozygosity was found in 8.3% (2 of 24) of the cases. Biallelic expression was demonstrated in 91.7% (22 of 24) of the tumor samples, in 70.8% (17 of 24) of the normal samples, and in 1 ovarian cancer cell line. Imbalanced expression and monoallelic expression were found in three and two pairs of matched samples, respectively. Overexpression of p73 was found in advanced ovarian cancer rather than in early-stage disease or in borderline ovarian tumor. No significant difference was found in the p53 expression. Three cell lines with absent p73 protein expression and one tumor sample with monoallelic expression were methylated in the CpG island. Demethylation in SKOV3 cell line using 5-azacytidine can reactivate the expression of this gene in both the mRNA and the protein level. Our results indicated that p73 was not imprinted in most of the ovarian cancer and normal tissues, but it could be involved in the advanced ovarian cancer through overexpression. DNA methylation may contribute to the lack of p73 expression.

Adenocarcinoma, Clear Cell↗
PubMed2000

[The acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmonary hypertension in rats].

OBJECTIVE: To investigate the effect of tetrandrine (Tet) pulmonary targeting microspheres on hypoxic pulmonary hypertension and its selective role on pulmonary circulation. METHODS: Tet pulmonary targeting microspheres were synthesized by spraying desiccation, the content of tetrandrine in pulmonary targeting microspheres is 32%. Twenty Wistar rats were exposed to hypoxia for three weeks, the rats were given Tet pulmonary targeting microspheres and Tet aqueous solution respectively and another 10 rats were as normal control. The mean pulmonary arterial pressure (mPAP) was measured by a right cardiac catheterization, mean systemic blood pressure (mSBP) was measured by left femoral catheterization. RESULTS: At the end of hypoxic treatment, rats developed pulmonary hypertension. mPAP in the rats receiving Tet pulmonary targeting microspheres decreased more obviously than the rats receiving Tet aqueous solution (P < 0.05), and the effects maintained for 60 min after administration. However, the mSBP remained normal in rats receiving Tet pulmonary targeting microspheres. CONCLUSION: Tet pulmonary targeting microspheres can improve the effect of Tet on the hypoxic pulmonary hypertension and Tet has the selective role on the pulmonary circulation.

Alkaloids↗
PubMed2000

[Changes of type I collagen in the lungs of rats with hypoxic pulmonary hypertension].

The changes of type I collagen in the lung tissues of rats with hypoxic pulmonary hypertension (HPH) and its relationship to the mean pulmonary arterial pressure (mPAP) were investigated. The blood dynamic indexes of pulmonary circulation were measured by using Swan-Ganz. The distribution of type I collagen in pulmonary arteries, bronchi and plumonary interstitial was observed by using streptavidin peroxidase method (SP). The morphologic changes of small pulmonary arteries and the level of type I collagen were determined by image pattern analysis technique and gray scale scanning, respectively. The results showed, compared with the controls, mPAP of the hypoxic rats elevated (from 2.12 +/- 0.25 to 3.95 +/- 0.43 kPa, P < 0.01), their small pulmonary arteries, walls thickened (MT% from 16.35 +/- 2.64 to 35.83 +/- 3.55, MA% from 26.83 +/- 3.40 to 59.68 +/- 4.90, P < 0.01) and lumen narrowed. The distribution of type I collagen was mainly in the external layer of pulmonary arterial walls; the positive degrees of gray scale scanning increased and had a positive linear relationship to the mPAP and MT%. These findings suggest that the increase of type I collagen contents in pulmonary arteries is closely related to the development of HPH.

Animals↗
PubMed2000

[Effects of endothelin receptor antagonist on the hypoxic pulmonary hypertension].

This investigation was made to elucidate the role of endothelin (ET) in hypoxic pulmonary hypertension and the preventing effects of BQ-123, an ETA receptor antagonist. Thirty male Wistar rats were divided into three groups and exposed to air, isobaric hypoxia or isobaric hypoxia plus BQ-123 for 3 weeks. The pulmonary artery pressure was measured by right cardiac catheterization. The plasma level of ET-1 was measured by RIA method. Histologic sections of the lungs were examined by a computerized image analyser. In hypoxic rats, the pulmonary artery pressure and the thickness of wall of arteriole were significantly increased, and right ventricular hypertrophy was developed. The plasma level of VEGF in rats treated with hypoxia (192.3 +/- 43.1 pg/ml) was significantly increased as compared with that of normal rats (128.2 +/- 28.1 pg/ml), P < 0.01. Chronic BQ-123 treatment prevented the developments of pulmonary hypertension, thickening of pulmonary arteriole and right ventricular hypertrophy induced by hypoxia. These result indicate that chronic hypoxia can result in hypoxic pulmonary hypertension and increased plasma level of ET-1, and the ETA receptor antagonist can prevent hypoxic pulmonary hypertension.

Animals↗
PubMed2000

[Effect of raw radish on pharmacological action of ginseng].

Ginseng decoction can increase the memory-improvement, weary-resistance, antihypoxia, sedation in mice, and increase the weight of spleen and accessory sexual gland, but reduce the weight of thymus. Raw radish can decrease these pharmacological effects in varying degrees, except the sedation.

Animals↗
PubMed1999

Interaction in vivo and in vitro between the yeast fimbrin, SAC6P, and a polymerization-defective yeast actin (V266G and L267G).

A mutant yeast actin (GG) has decreased hydrophobicity in a subdomain 3/4 hydrophobic plug believed to be involved in a hydrophobic cross-strand "plug-pocket" interaction necessary for actin filament stability. This actin will not polymerize in vitro but is compatible with cell viability. We have assessed the ability of Sac6p, the yeast homologue of the actin filament stabilizing and bundling protein fimbrin, to restore polymerization in vitro and to facilitate GG-actin function in vivo. Sac6p rescues GG-actin polymerization at 25 degrees C but not at 4 degrees C. The actin polymerizes into bundles at room temperature with a fimbrin:actin molar ratio of 1:4. At this ratio, every actin monomer contacts a Sac6p actin binding domain. Following cold-induced depolymerization, actin/Sac6p mixtures repolymerize beginning at 15 degrees C instead of the 25 degrees C required for de novo assembly, because of the presence of residual actin-Sac6p nuclei. Generation of haploid Deltasac6/GG-actin cells from either diploid or haploid cells was unsuccessful. The facile isolation of cells with either mutation alone indicates a synthetic lethal relationship between this actin allele and the SAC6 gene. Sac6p may allow GG-actin function in vivo by stabilizing the actin in bundles thereby helping maintain sufficient levels of an otherwise destabilized actin monomer within the cell.

Actins↗
PubMed1999

Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains.

Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis and is involved in atherosclerosis. ACAT-1 protein is located mainly in the ER. The hydropathy plot suggests that ACAT-1 protein contains multiple transmembrane segments. We inserted either the hemagglutinin tag or the HisT7 tag at various hydrophilic regions within the human ACAT-1 protein and used immunofluorescence microscopy to determine the topography of the tagged proteins expressed in mutant Chinese hamster ovary cells lacking endogenous ACAT. All of the tagged proteins are located mainly in the ER and retain full or partial enzyme activities. None of the tagged proteins produces detectable intracellular degradation intermediates. Treating cells with digitonin at 5 micrograms/ml permeabilizes the plasma membranes while leaving the ER membranes sealed; in contrast, treating cells with 0.25% Triton X-100 or with cold methanol permeabilizes both the plasma membranes and the ER membranes. After appropriate permeabilization, double immunostaining using antibodies against the N-terminal region and against the inserted tag were used to visualize various regions of the tagged protein. The results show that human ACAT-1 in the ER contains seven transmembrane domains.

Algorithms↗
PubMed1999

Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins.

Site-1 protease (S1P) is a subtilisin-related protease that cleaves sterol regulatory element-binding proteins (SREBPs) in the endoplasmic reticulum lumen, thereby initiating a process by which the transcriptionally active NH(2)-terminal fragments of SREBPs are released from membranes. In the current experiments, we transfected cDNAs encoding epitope-tagged hamster S1P into HEK-293 cells or mutant hamster cells that lack S1P. Protease protection assays showed that the bulk of S1P is in the endoplasmic reticulum lumen, anchored by a COOH-terminal membrane-spanning segment. Cleavage of the NH(2)-terminal signal sequence of S1P generates S1P-A (amino acids 23-1052), which is inactive. The protein is self-activated by an intramolecular cleavage at Site-B, generating S1P-B (amino acids 138-1052) and liberating a 115-amino acid propeptide that is secreted intact into the medium. The sequence at Site-B is RSLK, which differs from the RSVL sequence at the cleavage site in SREBP-2. S1P-B is further cleaved at an internal RRLL sequence to yield S1P-C (amino acids 187-1052). Mutational analysis suggests that S1P-B and S1P-C are both active in cleaving SREBP-2 in a fashion that requires SREBP cleavage-activating protein. The activity of S1P-C may be short-lived because it appears to be transported to the Golgi, a site at which SREBP-2 cleavage may not normally occur. These data provide the initial description of the processing of a subtilisin-related protease that controls the level of cholesterol in blood and cells. In an accompanying paper (Cheng, D., Espenshade, P. J., Slaughter, C. A., Jaen, J. C., Brown, M. S., and Goldstein, J. L. (1999), J. Biol. Chem., 274, 22805-22812), we develop an in vitro assay to characterize the activity of purified recombinant S1P.

Amino Acid Sequence↗
PubMed1999

Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins.

We describe a permanent line of Chinese hamster ovary cells transfected with a cDNA encoding a truncated form of Site-1 protease (S1P) that is secreted into the culture medium in an enzymatically active form. S1P, a subtilisin-like protease, normally cleaves the luminal loop of sterol regulatory element-binding proteins (SREBPs). This cleavage initiates the two-step proteolytic process by which the NH(2)-terminal domains of SREBPs are released from cell membranes for translocation to the nucleus, where they activate transcription of genes involved in the biosynthesis and uptake of cholesterol and fatty acids. Truncated S1P (amino acids 1-983), produced by the transfected Chinese hamster ovary cells, lacks the COOH-terminal membrane anchor. Like native S1P, this truncated protein undergoes normal autocatalytic processing after residue 137 to release an NH(2)-terminal propeptide, thereby generating an active form, designated S1P-B. Prior to secretion, truncated S1P-B, like native S1P-B, is cleaved further after residue 186 to generate S1P-C, which is the only form that appears in the culture medium. The secreted enzyme, designated S1P(983)-C, cleaves a synthetic peptide that terminates in a 7-amino-4-methyl-coumarin fluorochrome. This peptide, RSLK-MCA, corresponds to the internal propeptide cleavage site that generates S1P-B as described in the accompanying paper (Espenshade, P. J., Cheng, D., Goldstein, J. L., and Brown, M. S. (1999), J. Biol. Chem. 274, 22795-22804). The secreted enzyme does not cleave RSVL-MCA, a peptide corresponding to the physiologic cleavage site in SREBP-2. However, S1P(983)-C does cleave after this leucine when the RSVL sequence is contained within a 16-residue peptide corresponding to the central portion of the SREBP-2 luminal loop. The catalytic activity of S1P(983)-C differs from that of furin/prohormone convertases, two related proteases, in its more alkaline pH optimum (pH 7-8), its relative resistance to calcium chelating agents, and its ability to cleave after lysine or leucine rather than arginine. These data provide direct biochemical evidence that S1P is the protease that cleaves SREBPs and thereby functions to control lipid biosynthesis and uptake in animal cells.

Amino Acid Sequence↗
PubMed1999

Large pleural effusions occurring after coronary artery bypass grafting. Cardiovascular Surgery Associates, PC.

BACKGROUND: Large pleural effusions sometimes occur after coronary artery bypass grafting (CABG), but their characteristics and clinical course are largely unknown. OBJECTIVE: To describe the clinical course and pleural fluid findings in patients with large pleural effusions occurring after CABG. DESIGN: Retrospective case series. SETTING: Tertiary care, university-affiliated, nonprofit teaching hospital. PATIENTS: 3707 patients who had CABG between 1 February 1996 and 1 August 1997. MEASUREMENTS: Chest radiographs were reviewed, and information on pleural fluid findings, pleural effusion treatment, and cardiac surgery was obtained from medical records and a cardiac surgery database. RESULTS: Pleural effusions that occupied more than 25% of the hemithorax were found in 29 patients (0.78%). Seven of the effusions were attributed to congestive heart failure, 2 were attributed to pericarditis, and 1 was attributed to pulmonary embolism. The explanation for the remaining 19 effusions was unclear. All but 2 effusions were predominantly left-sided. Of these 19 effusions, 8 were bloody and 11 were nonbloody. Bloody effusions usually occurred earlier, contained higher lactic acid dehydrogenase levels, and were frequently eosinophilic. Nonbloody effusions tended to be more difficult to manage. CONCLUSIONS: Large pleural effusions may develop in a small proportion of patients after CABG. The cause of many of these effusions is unclear. Most bloody effusions can be managed with one to three therapeutic thoracenteses. Resolution of nonbloody effusions may require anti-inflammatory agents, tube thoracostomy, or intrapleural injection of sclerosing agents.

Aged↗
PubMed1999

Etiology of preoperative anemia in patients undergoing scheduled cardiac surgery.

PURPOSE: Ten percent of our cardiac surgical patients have preoperative anemia. Anemia diagnosed before scheduled cardiac surgery is a strong predictor of the need for homologous blood transfusion (RBC) perioperatively but the cause of this preoperative anemia is not known. The purpose of this study was to evaluate the etiology of preoperative anemia. METHODS: Seventy-five consecutive anemic cardiosurgical patients (Hb = < 120 g x L(-1) the day before surgery) were studied prospectively. All had multiple diagnostic blood tests done in the preoperative period to diagnose the cause of the anemia and subsequently underwent non-emergency cardiac surgery. Anesthesia and RBC transfusion were standardized according to the protocol. Data in respect to operation, RBC and other blood product transfusion during operation and hospital stay were recorded. RESULTS: Hospital-acquired anemia was present in 37.3% of anemic patients (hemoglobin decrease during hospitalization before surgery > or =9 g x l(-1)). The second most common diagnosis was iron deficiency anemia (29.3% patients) followed by anemia of chronic renal disease (10.7% patients). When coronary angiography was performed close to operation time, patients had a higher decrease in hemoglobin concentration during hospitalization --suggesting that blood loss during angiography was, in part, responsible for anemia. Seventy-five percent of anemic patients were transfused with RBC perioperatively compared with our overall transfusion rate of 30% of cardiac surgery patients. CONCLUSIONS: In the majority of patients, preoperative anemia is potentially preventable. Investigation and treatment of anemia before cardiac surgery should be a priority in preparing the patient for surgery.

Aged↗
PubMed1999

Activation of acyl-CoA cholesterol acyltransferase: redistribution in microsomal fragments of cholesterol and its facilitated movement by methyl-beta-cyclodextrin.

Acyl-CoA cholesterol acyltransferase (ACAT) (EC 2.3.1.26) in the yolk sac membrane of chicken eggs plays an important role in the transport of lipids, which serve as both structural components and as an energy source during embryogenesis. ACAT from the yolk sac membrane of chicken eggs 16 d after fertilization has higher activity and better stability than its mammalian liver counterpart. During our study of the avian enzyme, ACAT was found to be activated up to twofold during storage at 4 degrees C. The activation was investigated, and data suggest that redistribution of cholesterol within microsomal vesicles leads to the increase. Methyl-beta-cyclodextrin (MbetaCD) increases activation an additional twofold, possibly by facilitating the movement of cholesterol within microsomal fragments and allowing redistribution of cholesterol in lipid bilayers to a greater extent. Treatment of microsomes with MbetaCD removes cholesterol from the membranes. Controlled amounts of cholesterol can be restored to the membranes by mixing them with cholesterol-phosphatidylcholine liposomes in the presence of MbetaCD. Under these conditions, the plot of ACAT vs. cholesterol mole fraction in the liposomes is sigmoidal. The finding that MbetaCD can enhance cholesterol transfer between liposomes and microsomes and reduce the limitation of slow movement of nonpolar molecules in aqueous media should make cyclodextrins more useful in in vitro studies of apolar molecule transport between membrane vesicles.

Animals↗
PubMed1999

Duration of preoperative amiodarone treatment may be associated with postoperative hospital mortality in patients undergoing heart transplantation.

OBJECTIVE: To assess the effect of preoperative amiodarone treatment on patient mortality after heart transplantation. DESIGN: Retrospective study. SETTING: Single-institution university hospital. PARTICIPANTS: One hundred six consecutive patients with heart transplants. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were grouped according to duration of preoperative amiodarone treatment, and posttransplant mortality before hospital discharge was compared with patients not treated with amiodarone. The authors collected cardiovascular data in the preoperative and postoperative periods. There was a significant increase in posttransplant mortality before hospital discharge in patients treated with amiodarone for more than 4 weeks in the preoperative period (p < 0.05). Patients treated with amiodarone had significantly lower (p < 0.05) heart rates (mean heart rate, 103+/-19 beats/min) in the early postoperative period than patients not treated with amiodarone (mean heart rate, 111+/-15 beats/min), but there was no relationship with mortality (p = not significant). Patients who died had a significantly lower (p < 0.05) postoperative cardiac index (2.2+/-0.7 to 2.5+/-0.7) in the first 24 hours after cardiopulmonary bypass compared with patients who survived to hospital discharge (3.0+/-0.7 to 3.1+/-0.9), but there was no relationship to amiodarone treatment (p = not significant). CONCLUSION: Preoperative amiodarone treatment for more than 4 weeks may be associated with a significant increase in postoperative mortality in patients undergoing heart transplantation. Therefore, the indications for amiodarone must be carefully considered and, if needed, the maintenance dose should be kept to a minimum.

Amiodarone↗
PubMed1999

Expression and translocation of Rac2 in eosinophils during superoxide generation.

Eosinophils induce tissue injury by releasing granule-associated cytotoxic proteins, lipid mediators and superoxide anions in response to appropriate stimuli. Superoxide generation associated with respiratory burst is largely dependent on the assembly of the NADPH oxidase complex in the membrane, consisting of membrane-bound cytochrome b558 and translocated p47phox and p67phox. The activation of this complex is critically dependent on the translocation of GTP-bound Rac1, or its homologue Rac2, from the cytosol to the membrane in neutrophils. Rac expression has not yet been fully characterized in eosinophils. We proposed that eosinophils translate and express Rac2 and its GDP-dissociation inhibitor, RhoGDI. Furthermore, we hypothesized that Rac2 translocates along with p47phox and p67phox proteins from the cytosol to the plasma membrane during respiratory burst. By reverse transcription-polymerase chain reaction analysis and sequencing of the amplified product, guinea-pig eosinophils were found to express Rac2 mRNA, exhibiting 93% homology with the human Rac2 sequence. Rac1 mRNA was also detected in eosinophils but not its translated product. In contrast, Rac2 protein expression was detected using a specific antibody. In subcellular fractions, Rac2 was found to translocate, along with p47phox and p67phox, from cytosol to plasma membrane-associated fractions following phorbol myristate acetate stimulation, while RhoGDI remained within cytosolic fractions. These findings suggest that Rac2 is preferentially expressed and activated in eosinophils, and is likely to be a crucial regulator of the release of reactive oxygen species from these cells during inflammatory reactions.

Amino Acid Sequence↗