Biomedical subjects

D Chen

Publications and source records attributed to D Chen.

At least 505 records · Page 28Linked to original sources

PubMed1997

Time-frequency analysis of the first heart sound. Part 1: Simulation and analysis.

The authors propose a simulated first heart sound (S1) signal that can be used as a reference signal to evaluate the accuracy of time-frequency representation techniques for studying multicomponent signals. The composition of this simulated S1 is based on the hypothesis that an S1 recorded on the thorax over the apical area of the heart is composed of constant frequency vibrations from the mitral valve and a frequency modulated vibration from the myocardium. Essentially, the simulated S1 consists of a valvular component and a myocardial component. The valvular component is modelled as two exponentially decaying sinusoids of 50 Hz and 150 Hz and the myocardial component is modelled by a frequency modulated wave between 20 Hz and 100 Hz. The study shows that the simulated S1 has temporal and spectral characteristics similar to S1 recorded in humans and dogs. It also shows that the spectrogram cannot resolve the three components of the simulated S1. It is concluded that it is necessary to search for a better time-frequency representation technique for studying the time-frequency distribution of multicomponent signals such as the simulated S1.

Animals↗

PubMed1997

Time-frequency analysis of the first heart sound. Part 2: An appropriate time-frequency representation technique.

A simulated first heart sound (S1) signal is used to determine the best technique for analysing physiological S1 from the following five time-frequency representations (TFR): the spectrogram, time-varying autoregressive modelling, binomial reduced interference distribution, Bessel distribution and cone-kernel distribution (CKD). To provide information on the time and frequency resolutions of each TFR technique, the instantaneous frequency and the -3 dB bandwidth as functions of time were computed for each simulated component of the S1. The performance index for selecting the best technique was based on the relative error and the correlation coefficient of the instantaneous frequency function between the theoretical distribution and the computed TFR. This index served to select the best technique. The sensitivity of each technique to noise and to small variations of the signal parameters was also evaluated. The results of the comparative study show that, although important limitations were found for all five TFRs tested, the CKD appears to be the best technique for the time-frequency analysis of multicomponent signals such as the simulated S1.

Heart↗

PubMed1997

Ascaris peritonitis and peritoneal granuloma in China.

This article is a survey of the Chinese literature of perforation of gastrointestinal tract by ascaris. We wish to draw attention to the acute abdominal disease of ascaris infection, and acute ascaris peritonitis as a result of perforation, most cases being found in children. The disease has very high morbidity (24/112; 21.4%) and high mortality (17/112; 15.2%). Early detection and operation are of critical importance. Perforation of gastrointestinal tract by ascaris may develop into peritoneal granuloma, which has a different clinical presentation and outcome.

Adolescent↗

PubMed1997

Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts.

Normal bone formation is a prolonged process that is carefully regulated and involves sequential expression of growth regulatory factors by osteoblasts as they proliferate and ultimately differentiate. Since this orderly sequence of gene expression by osteoblasts suggests a cascade effect, and BMP-2 is capable of initiating and maintaining this effect, we examined the effects of BMP-2 on expression of other BMPs and compared these effects with the expression pattern of bone cell differentiation marker genes in primary cultures of fetal rat calvarial (FRC) osteoblasts. To examine the gene expression profile during bone cell differentiation and bone formation, we also examined the effects of rBMP-2 on bone formation in vivo and in vitro. rBMP-2 stimulated bone formation on the periosteal surface of mice when 500 ng/day rBMP-2 was injected subctaneously. When rBMP-2 was added to primary cultures of FRC osteoblasts, it accelerated mineralized nodule formation in a time and concentration-dependent manner (10-40 ng/ml). rBMP-2 (40 ng/ml) enhanced BMP-3 and -4 mRNA expression during the mineralization phase of primary cultures of FRC osteoblasts. Enhancement of BMP-3 and -4 mRNA expression by rBMP-2 was associated with increased expression of bone cell differentiation marker genes, alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), osteopontin (OP), and bone sialoprotein (BSP). These results suggest that BMP-2 enhances expression of other BMP genes during bone cell differentiation. BMP-2 may act in a paracrine fashion in concert with other BMPs it induces to stimulate bone cell differentiation and bone formation during remodeling.

Amino Acid Sequence↗

PubMed1997

Exocytotic proteins in enterochromaffin-like (ECL) cells of the rat stomach.

Proteins participating in vesicular docking and fusion have been identified in the nervous system. Such proteins appear to be important for the molecular regulation of exocytosis also in non-neuronal cells. The enterochromaffin-like (ECL) cells of the gastric acid-secreting (oxyntic) mucosa secrete histamine and chromogranin A-derived peptides, such as pancreastatin. Using immunohistochemistry, we have examined whether the ECL cells of the rat stomach, identified with antibodies to histidine decarboxylase (HDC, the histamine-forming enzyme), express the same exocytotic proteins as neurons. The ECL cells displayed immunoreactivity for synaptophysin, synaptotagmin III, vesicle-associated membrane protein-2 (VAMP-2), cysteine string protein (CSP), vesicular monoamine transporter-2 (VMAT-2), synaptosomal-associated protein of 25 kDa (SNAP-25), syntaxin, and Munc-18, but not for synaptotagmin I/II and VAMP-1. Synaptophysin and VMAT-2 could be detected not only in the ECL cells, but also in a population of HDC-negative cells. The demonstration of synaptotagmin III in only a limited number of ECL cells suggests the existence of a subpopulation of ECL cells. The results show that several exocytotic proteins, previously identified in neurons, are present in rat stomach ECL cells. Hence, proteins engaged in vesicular docking and in the fusion of granule/vesicle membrane with plasma membrane seem to exist in both neurons and endocrine cells.

Animals↗

PubMed1997

Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group.

PURPOSE: This study assesses the efficacy and safety of fluconazole therapy in patients with acquired immunodeficiency syndrome (AIDS) and mild to moderately severe manifestations of disseminated histoplasmosis. PATIENTS AND METHODS: This was a multicenter, open-label, nonrandomized prospective trial. All patients had AIDS and disseminated histoplasmosis. Patients were treated with 1,200 mg of fluconazole given by mouth once on the first day, then 600 mg once daily for 8 weeks, and those patients who improved clinically were then assigned fluconazole maintenance therapy 200 mg once daily for at least 1 year. Interim analysis revealed a high failure rate (10 of 20, 50%), causing revision of the protocol to increase the fluconazole dose to 1,600 mg given once on the first day, then 800 mg once daily, and the duration to 12 weeks for induction therapy and then 400 mg daily for 1 year for maintenance therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-six of 49 patients (74%; 95% confidence interval [CI]: 59% to 85%) with mild to moderately severe clinical manifestations who entered into the revised study responded to 800 mg of fluconazole daily for 12 weeks as induction therapy. Of the seven patients who failed induction therapy because of progression of histoplasmosis, one died of the infection. Of 36 patients who entered into the maintenance phase of the study receiving 400 mg of fluconazole daily for 1 year, 11 (30.5%) relapsed, including one who died (2.8%). Two of the 49 patients (4.1%) were removed because of grade 4 adverse events, alkaline phosphatase elevation for one and aspartate aminotransferase elevation in the other. The relapse-free rate at 1 year was 53% (95% CI: 32% to 89%), prompting closure of the study. CONCLUSIONS: Fluconazole 800 mg daily is a safe and moderately effective induction therapy for mild or moderately severe disseminated histoplasmosis in patients with AIDS. On the basis of historic comparison, fluconazole 400 mg daily is less effective than itraconazole 200 to 400 mg daily or amphotericin B 50 mg given weekly as maintenance therapy to prevent relapse.

AIDS-Related Opportunistic Infections↗

PubMed1997

Permeation through the calcium release channel of cardiac muscle.

Current voltage (I-V) relations were measured from the calcium release channel (CRC) of the sarcoplasmic reticulum of cardiac muscle in 12 KCl solutions, symmetrical and asymmetrical, from 25 mM to 2 M. I-V curves are nearly linear, in the voltage range +/- 150 mV approximately 12kT/e, even in asymmetrical solutions, e.g., 2 M // 100 mM. It is awkward to describe straight lines as sums of exponentials in a wide range of solutions and potentials, and so traditional barrier models have difficulty fitting this data. Diffusion theories with constant fields predict curvilinear I-V relations, and so they are also unsatisfactory. The Poisson and Nernst-Planck equations (PNP) form a diffusion theory with variable fields. They fit the data by using adjustable parameters for the diffusion constant of each ion and for the effective density of fixed (i.e., permanent) charge P(x) along the channel's "filter" (7-A diameter, 10 A long). If P(x) is described by just one parameter, independent of x (i.e., P(x) = P0 = -4.2 M), the fits are satisfactory (RMS error/RMS current = 6.4/67), and the estimates of diffusion coefficients are reasonable D(K) = 1.3 x 10(-6) cm2/s, D(Cl) = 3.9 x 10(-6) cm2/s. The CRC seems to have a small selectivity filter with a very high density of permanent charge. This may be a design principle of channels specialized for large flux. The Appendix derives barrier models, and their prefactor, from diffusion theories (with variable fields) and argues that barrier models are poor descriptions of CRCs in particular and open channels in general.

Calcium↗

PubMed1997

Permeation through an open channel: Poisson-Nernst-Planck theory of a synthetic ionic channel.

The synthetic channel [acetyl-(LeuSerSerLeuLeuSerLeu)3-CONH2]6 (pore diameter approximately 8 A, length approximately 30 A) is a bundle of six alpha-helices with blocked termini. This simple channel has complex properties, which are difficult to explain, even qualitatively, by traditional theories: its single-channel currents rectify in symmetrical solutions and its selectivity (defined by reversal potential) is a sensitive function of bathing solution. These complex properties can be fit quantitatively if the channel has fixed charge at its ends, forming a kind of macrodipole, bracketing a central charged region, and the shielding of the fixed charges is described by the Poisson-Nernst-Planck (PNP) equations. PNP fits current voltage relations measured in 15 solutions with an r.m.s. error of 3.6% using four adjustable parameters: the diffusion coefficients in the channel's pore DK = 2.1 x 10(-6) and DCl = 2.6 x 10(-7) cm2/s; and the fixed charge at the ends of the channel of +/- 0.12e (with unequal densities 0.71 M = 0.021e/A on the N-side and -1.9 M = -0.058e/A on the C-side). The fixed charge in the central region is 0.31e (with density P2 = 0.47 M = 0.014e/A). In contrast to traditional theories, PNP computes the electric field in the open channel from all of the charges in the system, by a rapid and accurate numerical procedure. In essence, PNP is a theory of the shielding of fixed (i.e., permanent) charge of the channel by mobile charge and by the ionic atmosphere in and near the channel's pore. The theory fits a wide range of data because the ionic contents and potential profile in the channel change significantly with experimental conditions, as they must, if the channel simultaneously satisfies the Poisson and Nernst-Planck equations and boundary conditions. Qualitatively speaking, the theory shows that small changes in the ionic atmosphere of the channel (i.e., shielding) make big changes in the potential profile and even bigger changes in flux, because potential is a sensitive function of charge and shielding, and flux is an exponential function of potential.

Computer Simulation↗

PubMed1997

A pattern classification procedure integrating the multivariate statistical analysis with neural networks.

A new procedure integrating multivariate statistical analysis with artificial neural networks (ANN) for complex pattern classification is proposed. Firstly, a specially designed statistical analysis algorithm called correlative component analysis (CCA) was used to identify the classification characteristics (CC) from original high-dimensional pattern information. These CC were then used as input data to the ANN for pattern classification. The proposed new procedure not only effectively decreased the dimensionality of original patterns, but also took advantage of the self-learning power of the ANN. Further, a typical example of classifying natural spearmint essence was employed to verify the effectiveness of the new pattern classification method. The study showed that this novel integrated procedure provides better results than those obtained using individual methods separately.

Algorithms↗

PubMed1997

Passivation of metallic stents after arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening.

OBJECTIVES: This study sought to test the hypothesis that direct gene transfer of an endothelial cell mitogen could passivate metallic stents by accelerating endothelialization of the prosthesis. BACKGROUND: Thrombosis and restenosis comprise the principal clinical manifestations of compromised biocompatibility of endovascular stents. Previous studies have demonstrated that endothelial recovery at sites of balloon injury is a critical determinant of consequent intimal thickening and mural thrombus. We therefore investigated the potential for an endothelial cell mitogen delivered as plasmid DNA to optimize stent biocompatibility. METHODS: Naked plasmid DNA encoding vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) (phVEGF165) was delivered locally using a hydrogel-coated balloon angioplasty catheter to 16 rabbit iliac arteries in which metallic stents had been placed at the site of balloon injury; the contralateral iliac artery of each rabbit was balloon injured and stented but not transfected. RESULTS: Stent endothelialization was accelerated by phVEGF165 gene transfer (87.38 +/- 5.06% vs. 33.13 +/- 9.73% [mean +/- SEM] of the planimetered stent surface in the treated vs. contralateral limb, p = 0.005). This was associated with a significant reduction in mural thrombus (3.7 +/- 2.4% vs. 32.7 +/- 9.7%, p = 0.01) at day 7 and intimal thickening (maximal intimal area 0.61 +/- 0.09 vs. 1.44 +/- 0.12 mm2, p < 0.0001) at day 28. No benefit was observed from pCMV-luciferase in 14 similarly instrumented control rabbits. CONCLUSIONS: These findings indicate that arterial gene transfer of naked plasmid DNA encoding for an endothelial cell mitogen may successfully passivate endovascular stents by accelerating stent endothelialization, thereby reducing in-stent thrombus and obstruction due to intimal thickening.

Angioplasty, Balloon↗

PubMed1997

Direct effects of triiodothyronine on human internal mammary artery and saphenous veins.

OBJECTIVE: Thyroid hormone (3,5,3'-triiodo-L-thyronine is under investigation as a positive inotrope and vasodilator for patients undergoing cardiac surgery. This study determined the direct effects of triiodothyronine on human blood vessels. DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins were obtained from patients undergoing coronary artery bypass surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue baths containing Krebs-Ringer bicarbonate solution at 37 degrees C. Rings were prestretched in vitro to resting tensions analogous to mean arterial or central venous pressures in vivo and then constricted with potassium or phenylephrine. Rings were exposed to increasing concentrations of triiodothyronine (4 x 10(-12) to 1 x 10(-4) mol/L) to obtain dose-response curves. MEASUREMENTS AND MAIN RESULTS: High concentrations (> or = 3.3 x 10(-5) mol/L) of trilodothyronine produced dose-dependent relaxation of preconstricted rings. The relaxation was not selective for arteries or veins at arterial resting tensions, and with either potassium or phenylephrine as a vasoconstrictor. Propranolol had little effect on subsequent triiodothyronine-induced relaxation of potassium-constricted rings at resting arterial tensions. CONCLUSIONS: Triiodothyronine, in supraphysiological and suprapharmacological concentrations, dilates preconstricted rings of human blood vessels in vitro; however, triiodothyronine had no demonstrable vasomotor effects on human internal mammary artery or saphenous vein in clinically relevant concentrations (10(-9) to 10(-8) mol/L). Triiodothyronine administration in vivo most likely has little direct effect on the tone of human vascular smooth muscle, particularly coronary artery bypass conduits.

Blood Pressure↗

PubMed1997

Induction of cell cycle arrest and B cell terminal differentiation by CDK inhibitor p18(INK4c) and IL-6.

Cell cycle arrest and cell death are tightly coupled to terminal differentiation of B cells to plasma cells in vivo. This process was recapitulated in vitro by stimulation of IgG-bearing human B lymphoblastoid cells with interleukin-6 (IL-6), which led to orderly cell cycle arrest, differentiation, and apoptosis. In terminally differentiated plasmacytoid cells, phosphorylation of pRb was suppressed, correlating with the activation of the D-type cyclin-dependent kinase (CDK) inhibitors p18(INK4c) and p21(WAF1/CIP1). The expression of CDK6, however, remained unchanged. Activation of p18 by IL-6 was rapid, concomitant with marked enhancement of its association with CDK6 and cell cycle arrest. Overexpression of p18 in IgM-bearing lymphoblastoid cells, which differentiated in response to IL-6 but did not exit the cell cycle, reconstituted coupled differentiation and cell cycle arrest. Thus, CDK inhibitors, in particular p18, are likely to play a pivotal role in controlling cell cycle arrest and cell death in terminal differentiation of late-stage B cells to plasma cells via inhibition of pRb phosphorylation by CDK6.

Apoptosis↗

PubMed1997

Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells.

Dendritic cells (DCs) are potent antigen-presenting cells that prime naive cytotoxic T-cells (CTLs). In this study, we have fused DCs with MC38 carcinoma cells. The fusion cells were positive for major histocompatibility (MHC) class I and II, costimulating molecules and intercellular cell adhesion molecule-1 (ICAM-1). The results show that the fusion cells stimulate naive T cells in the primary mixed lymphocyte reaction (MLR) and induce MC38 tumor-specific CTLs in vivo. Antibody-mediated depletion experiments demonstrate that induction of CD4+ and CD8+ CTLs protects against challenge with tumor cells. We also show that immunization with the fusion cells induces rejection of established metastases. These findings represent the first demonstration that fusions of DCs and tumor cells can be used in the treatment of cancer.

Adenocarcinoma↗

PubMed1997

Reciprocal relation between VEGF and NO in the regulation of endothelial integrity.

Balloon angioplasty disrupts the protective endothelial lining of the arterial wall, rendering arteries susceptible to thrombosis and intimal thickening. We show here that vascular endothelial growth factor (VEGF), an endothelial cell mitogen, is upregulated in medial smooth muscle cells of the arterial wall in response to balloon injury. Both protein kinase C (PKC) and tyrosine kinase pp60src mediate augmented VEGF expression. In contrast, nitric oxide (NO) donors inhibit PKC-induced VEGF upregulation by interfering with binding of the transcription factor activator protein-1 (AP-1) to the VEGF promoter. Inhibition of VEGF promoter activation suggests that NO secreted by a restored endothelium functions as the negative feedback mechanism that downregulates VEGF expression to basal levels. Administration of a neutralizing VEGF antibody impaired reendothelialization following balloon injury performed in vivo. These findings establish a reciprocal relation between VEGF and NO in the endogenous regulation of endothelial integrity following arterial injury.

Animals↗

PubMed1997

High efficiency reporter gene transfection of vascular tissue in vitro and in vivo using a cationic lipid-DNA complex.

Efficient transfection conditions for a number of human, rat and rabbit primary cells and established lines of vascular origin have been determined using a complex of a commercially available cationic lipid transfection agent (Tfx-50) and luciferase reporter plasmid constructs. The optimised conditions have also been successfully applied to rabbit carotid arteries in vivo and a series of human arteries in vitro. The most critical factors influencing the efficiency of gene transfection with this protocol are: DNA concentration; ratio of lipid reagent to DNA; transfection time and the presence or absence of serum. Immunohistochemical analysis shows that a high percentage of cells (approximately 30-80% dependent on lineage) were transfected under optimal conditions with minimal toxicity effects. Similar analyses performed on undamaged rabbit carotid vessels transfected in vivo and human arteries transfected in vitro show high-efficiency transfer and strong expression of the luciferase vector as demonstrated by reporter gene expression. The optimisation of gene transfer into vascular cells with this cationic lipid complex will be valuable for molecular studies of genes implicated in cardiovascular diseases and as a possible method of gene delivery with therapeutic intent.

Animals↗

PubMed1997

Improved efficiency of arterial gene transfer by use of poloxamer 407 as a vehicle for adenoviral vectors.

Improvement in the efficiency of adenovirus-mediated arterial gene transfer may augment the utility of cardiovascular gene therapy. In vitro studies suggest that poloxamer 407 enhances transfection efficiency of adenoviral vectors in vascular smooth muscle cells. The aim of the present study was to investigate whether poloxamer 407 facilitates adenovirus-mediated arterial transfection in vivo as well. Gene transfer was performed in balloon-injured rat carotid arteries using E1- adenoviral vectors diluted in either poloxamer 407 or phosphate buffered saline (PBS). Transfection efficiency was significantly higher in rats transfected using a nuclear beta-galactosidase expressing adenovector diluted in poloxamer 407 versus PBS (morphometry, 13.2 +/- 1.3% versus 4.1 +/- 0.4% transfected medial cells, P = 0.0001; chemiluminescence; 1.4 +/- 0.2 versus 0.4 +/- 0.2 mU beta-galactosidase/mg protein, P = 0.004). Moreover, in the presence of poloxamer 407, it was possible to reduce the incubation time of adenoviral vectors from 20 to 10 min without compromising transfection efficiency. Poloxamer 407 did not evoke specific tissue toxicity. Site-specificity of arterial gene transfer, assessed by PCR, was not altered by administration of poloxamer 407. These findings suggest that poloxamer 407 may be useful to improve the efficiency of adenovirus-mediated arterial gene transfer.

Adenoviridae↗

PubMed1997

Induction of antigen-specific antitumor immunity with adenovirus-transduced dendritic cells.

Transduction of dendritic cells (DC) can result in presentation of tumor-associated antigens and induction of immunity against undefined epitopes. The present studies demonstrate adenovirus (Ad)-mediated transduction of the beta-galactosidase gene in mouse DC. Similar transductions have been obtained with the gene encoding the DF3/MUC1 tumor-associated antigen. We show that the Ad-transduced DC are functional in primary allogeneic mixed lymphocyte reactions. Mice immunized with Ad-transduced DC develop cytotoxic T lymphocytes that are specific for the beta-galactosidase or DF3/MUC1 antigens. The results also demonstrate that Ad MUC1-transduced DC induce a specific response which inhibits the growth of DF3/MUC1-positive tumors. These findings support the usefulness of Ad-transduced DC for in vivo immunization against tumor-associated antigens.

Adenoviridae↗

PubMed1997

The natural history of borderline hypertension in a Chinese population.

One hundred and thirty-one borderline hypertensive patients were followed up for 17 years. A cohort of normotensives strictly matched by age, sex, region and occupation served as controls (1:1). It was found that 64.6% of borderline hypertensive patients developed into established hypertensives after 17 years follow-up, 25.5% restored to normotensives and 13.8% remained unchanged. The total mortality rate of borderline hypertensives was higher than that of normotensives (27.9 vs 13.4/1000 person years), and the relative risk of total death in borderline hypertensives was 2.35. The main cause of death was stroke, accounting for 42.5% of the total death rate. The relative risk rates of occurrence and death associated with stroke were 8.3 and 11.6, respectively. It is concluded that the main complication of borderline hypertension was stroke rather than coronary heart disease, which was similar to that of established hypertension in this area. Part of the borderline hypertensives need to be treated to reduce the risk of cardiovascular complications.

Adult↗