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Biomedical subjects

P Wen

Publications and source records attributed to P Wen.

At least 19 recordsLinked to original sources
PubMed2003

Realistic human head model for EEG from both the geometry and conductivity aspects.

This paper describes modelling and simulation of a had model which incorporates both the geometries and conductivities of the human head. It focuses on the inclusion of tissue conductivity inhomogeneity in a realistically-shaped head model, and investigates the impact of this inclusion on the potential distribution within the model. The result show that the impact, which has been neglected in realistic head models so far, is significant.

Brain↗
PubMed2001

Transplant coronary artery disease: a novel model independent of cellular alloimmune response.

BACKGROUND: Allograft coronary atherosclerosis (TxCAD) is the leading cause of death after the first year after transplantation. TxCAD is believed to be a form of chronic rejection of the cardiac allografts. This study was undertaken to determine whether TxCAD could develop in the absence of a cellular alloimmune response. METHODS AND RESULTS: Inbred lean Zucker rats (>26 generations) served as donors and recipients of the cardiac grafts. Donor hearts were explanted at 60 or 90 days. Explanted hearts were processed for coronary artery histological analysis. Cytokine expression was determined by reverse transcription-polymerase chain reaction, and the presence of T cells within the explanted hearts was evaluated by immunohistochemistry. Forty-six transplantations were made, and TxCAD developed in all but one of the transplanted hearts. Overall, one third of the vessels examined were affected by TxCAD, and in roughly half of these vessels, the disease was severe. Native hearts were free of atherosclerosis. Interleukin-2 was absent from the transplanted hearts, and T cells were present in minimal amounts (<1 per low-power field). CONCLUSIONS: TxCAD developed in the absence of a cellular alloimmune response in these genetically similar donors and recipients. The observed TxCAD was significant and comparable to what is found in rat allografting models.

Animals↗
PubMed2001

Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex.

Here we show that presenilin-1 (PS1), a protein involved in Alzheimer's disease, binds directly to epithelial cadherin (E-cadherin). This binding is mediated by the large cytoplasmic loop of PS1 and requires the membrane-proximal cytoplasmic sequence 604-615 of mature E-cadherin. This sequence is also required for E-cadherin binding of protein p120, a known regulator of cadherin-mediated cell adhesion. Using wild-type and PS1 knockout cells, we found that increasing PS1 levels suppresses p120/E-cadherin binding, and increasing p120 levels suppresses PS1/E-cadherin binding. Thus PS1 and p120 bind to and mutually compete for cellular E-cadherin. Furthermore, PS1 stimulates E-cadherin binding to beta- and gamma-catenin, promotes cytoskeletal association of the cadherin/catenin complexes, and increases Ca(2+)-dependent cell-cell aggregation. Remarkably, PS1 familial Alzheimer disease mutant DeltaE9 increased neither the levels of cadherin/catenin complexes nor cell aggregation, suggesting that this familial Alzheimer disease mutation interferes with cadherin-based cell-cell adhesion. These data identify PS1 as an E-cadherin-binding protein and a regulator of E-cadherin function in vivo.

Animals↗
PubMed2001

Comparison study of different head model structures with homogeneous/inhomogeneous conductivity.

Most of the human head models used in dipole localisation research, which have been reported in the literature to date, assume a simplified cranial structure wherein the head is modelled as a set of distinct homogenous tissue compartments. The inherent inhomogeneity of the tissues has so far been ignored in these models due to the difficulties involved in obtaining the conductivity characteristics with sufficiently high enough spatial resolution throughout the head. A technique for developing an inhomogeneous head model based on the generation of pseudo-conductivity values from the existing but sparse conductivity values is proposed in this paper. Comparative studies are conducted on different model structures and different mechanisms for generating the pseudo conductivities. An evaluation of the results of these studies as reported in this paper, shows that contrary to current simplifying assumptions, tissue inhomogeneity has a major influence on the computation of electrical potential distributions in the head.

Brain↗
PubMed2001

Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats.

BACKGROUND: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. OBJECTIVE: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. MATERIALS AND METHODS: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. RESULTS: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). CONCLUSION: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease.

Animals↗
PubMed2001

[Fluorescence spectra of the rare earth complex-PAA-g-PE films].

The acrylic acid (AA) was grafted onto the PE film surface through UV photograft polymerization. With certain pH value, the grafted films were made to react with the alcohol-water solution of Eu3+ and alpha-thenoyltrifluoroacetone (TTA) or with the chloroform-water solution of Tb3+ and acetyl actone (AcAc), thus causing the preparation of the red or green fluorescent films. As compared with the corresponding Eu(TTA)3.(H2O)2 or Tb(AcAc)3.(H2O)2 solid complexes, both the excitation and emission spectra of the fluorescent films changed remarkably. It's predictable that chemical bond combination has occurred between the rare earth complexes and the macromolecular material. In addition, the IR spectra of the fluorescent films were also observed.

Acrylates↗
PubMed2000

Distant enhancers stimulate the albumin promoter through complex proximal binding sites.

The albumin-alpha-fetoprotein locus epitomizes the main features of transcriptional regulation of fetal and adult hepatocyte-specific genes: developmentally regulated promoters and strong distant enhancers. Full enhancer activity required only a proximal albumin-promoter region containing the TATA box, hepatic nuclear factor 1 (HNF1), and nuclear factor Y (NF-Y) sites. Deletion of the HNF1 site abrogated enhancer and promoter activity, whereas methylation of the site reduced all activity by about 3-fold. Deletion of the NF-Y site attenuated activity by about half, but much of the activity could be replaced by juxtaposition of an upstream region (designated distal element IV). Gel shift and competition analysis demonstrated that binding of architectural factors overlapped NF-Y binding. Moreover, a mutation that eliminated NF-Y binding but only minimally perturbed the surrounding region did not affect enhancer function. In plasmids with a second promoter, the enhancers simultaneously stimulated both albumin and alpha-fetoprotein promoters with minimal competition, but surprisingly some mutations in the albumin promoter attenuated expression from both promoters, whereas another uncoupled their expression. With single promoters, the function of the proximal promoter region was controlled by three parameters in the following hierarchy: HNF1 binding > local architecture > NF-Y binding, but integrated two-promoter function had a much greater dependence on NF-Y.

Albumins↗
PubMed1999

The inhomogeneous conductivity property of cranial tissues and its representation in numerical head models.

The inhomogeneous conductivity of cranial tissues is discussed in this paper. A novel approach for including detailed tissue inhomogeneity is proposed and developed using pseudo-conductivity values which are derived from the limited data available from physiological experiments. Simulation studies of the effects caused by the inclusion of inhomogeneity in the EEG forward problem are also presented in this paper. The results suggest that the accurate representation of the tissue inhomogeneity improves the quality of the computed EEG forward solution. Conclusions about the effects of inhomogeneity on the potential distribution are given.

Brain↗
PubMed1999

[Influence of icariin on cell membrane of highly metastatic human lung tumor cell line].

In this study, flow cytometry (FCM) and fluorescent probe technique were used to explore the influence of icariin (ICA) on cell membrane of PG. The data suggested that ICA could inhance membrane fluidity of PG and increase the expression of membrane HLA-ABC antigen. This could be one of the anticancer mechanisms of ICA.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Dehydroepiandrosterone reduces proliferation and differentiation of 3T3-L1 preadipocytes.

The purpose of these studies was to determine whether the antiobesity actions of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) observed in vivo are due to an influence on proliferation and/or differentiation in monolayer cultures of 3T3-L1 preadipocytes. For the proliferation study (Exp. 1), cells were grown in plating medium containing DHEA at 0, 5, 25, 50, or 100 microM for 1-4 d. DHEAS was added at the 100 microM level only. For the differentiation study (Exp. 2), cultures were grown in plating medium containing DHEA at 0, 5, 30, 60, 120, or 240 microM for 2-6 d. DHEAS was added at the 240 microM level only. In Exp. 3, the effect of DHEA on mature adipocytes was determined by exposing adipocytes grown in plating medium to DHEA at 0, 75, 125, and 250 microM for 1-4 d. In Exp. 1, preadipocyte proliferation decreased as the level of DHEA increased in cultures of 3T3-L1 cells. DHEAS had no effect on preadipocyte proliferation. The antiproliferative effect of DHEA was partially reversed by the addition of 1 microM mevalonic acid to proliferating cultures containing 25 microM DHEA. In Exp. 2, preadipocyte differentiation decreased as the level of DHEA in the cultures increased. In contrast, neither DHEAS nor mevalonic acid treatment influenced preadipocyte differentiation decreased as the level and duration of DHEA treatment increased in cultures of mature adipocytes. These data support the hypothesis that DHEA, but not DHEAS, is the active form of the steroid that attenuates obesity via altering preadipocyte proliferation and differentiation. The addition of 1 microM mevalonic acid to cultures of 3T3-L1 preadipocytes partially reversed DHEA's antiproliferative effects.

3T3 Cells↗
PubMed1998

A novel nk-2-related transcription factor associated with human fetal liver and hepatocellular carcinoma.

A novel cDNA was partially isolated from a HepG2 cell expression library by screening with the promoter-linked coupling element (PCE), a site from the alpha-fetoprotein (AFP) gene promoter. The remainder of the cDNA was cloned from fetal liver RNA using random amplification of cDNA ends. The cDNA encodes a 239-amino acid peptide with domains closely related to the Drosophila factor nk-2. The new factor is the eighth vertebrate factor related to nk-2, hence nkx-2.8. Northern blot and reverse transcriptase polymerase chain reaction analysis demonstrated mRNA in HepG2, two other AFP-expressing human cell lines, and human fetal liver. Transcripts were not detected in adult liver. Cell-free translation produced DNA binding activity that gel shifted a PCE oligonucleotide. Cotransfection of nkx-2.8 expression and PCE reporter plasmids into HeLa cells demonstrated transcriptional activation; NH2-terminal deletion eliminated this activity. Cotransfection into AFP-producing hepatocytic cells repressed AFP reporter expression, suggesting that endogenous activity was already present in these cells. In contrast, cotransfection into an AFP-negative hepatocytic line produced moderate activation of the AFP gene. The cardiac developmental factor nkx-2.5 could substitute for nkx-2.8 in all transfection assays, whereas another related factor, thyroid transcription factor 1, showed a more limited range of substitution. Although the studies have yet to establish definitively that nkx-2.8 is the AFP gene regulator PCF, the two factors share a common DNA binding site, gel shift behavior, migration on SDS-acrylamide gels, and cellular distribution. Moreover, the nk-2-related genes are developmental regulators, and nkx-2.8 is the first such factor associated with liver development.

Amino Acid Sequence↗
PubMed1998

Results of linear accelerator-based radiosurgery for intracranial meningiomas.

OBJECTIVE: We report the outcomes of patients treated with linear accelerator-based radiosurgery for intracranial meningiomas at our institution. METHODS: We reviewed 127 patients with 155 meningiomas treated with stereotactic radiosurgery (SRS) at the study institutions between October 1988 and December 1995. RESULTS: There were 86 female and 41 male patients (median age, 61.5 yr; range, 19.9-87.9 yr). The median follow-up period was 31 months (range, 1.2-79.8 mo). The median tumor volume was 4.1 cc (range, 0.16-51.2 cc), and the median marginal dose was 15 Gy (range, 9-20 Gy). The tumor locations were as follows: convexity, 31 tumors; parasagittal/falcine, 39 tumors; cranial base, 82 tumors; and ventricular/pineal, 3 tumors. There were 106 benign, 26 atypical, and 18 malignant meningiomas and 5 cases of meningiomatosis. SRS was performed on 48 lesions as the initial treatment and on 107 lesions as adjunct therapy. Freedom from progression was observed in 107 patients (84.3%) at a median time of 22.9 months (range, 1.2-79.8 mo). Twenty patients (15.7%) had disease progression (16 marginal [12.6%] and 4 local [3.1%]) at a median time of 19.6 months (range, 4.1-69.3 mo); the median time for freedom from progression for the benign, atypical, and malignant meningiomas was 20.9, 24.4, and 13.9 months, respectively. Actuarial tumor control for the patients with benign meningiomas was 100, 92.9, 89.3, 89.3, and 89.3% at 1, 2, 3, 4, and 5 years, respectively. Six patients (4.7%) had permanent complications attributable to SRS (median time, 10.3 mo; range, 4.3-18.0 mo); 13 patients died as a result of causes related to the meningiomas (median, 17.5 mo; range, 4.3-37.3 mo). The 1-, 2-, 3-, 4-, and 5-year survival probability for the entire group of patients was 90.3, 82.6, 73.6, 70.5, and 68.2%, respectively; for patients with benign meningiomas, excluding death resulting from intercurrent disease, the survival probability was 97.6, 94.8, 91.0, 91.0, and 91.0%, respectively. The 1-, 2-, 3-, and 4-year survival probability for the patients with atypical and malignant meningiomas was 91.7, 83.3, 83.3, and 83.3% and 92.3, 64.6, 43.1, and 21.5%, respectively. CONCLUSION: Even though complications from SRS are expected more frequently with large tumors near critical structures, SRS is a safe and effective means of treating selected meningiomas.

Adult↗
PubMed1997

Pulmonary intralobar sequestration in a patient with cystic fibrosis.

We report a case in which pulmonary Intralobar Sequestration (ILS) was an incidental finding at autopsy in an adult with Cystic Fibrosis. Two aberrant arteries from the descending thoracic aorta supplied a bronchial cystic lesion in the right lower lobe. Termination of the segmental bronchus and scar formation proximal to the cyst suggested prior bronchial obliteration. The elastic configuration of the aberrant aortic-derived vessels of the sequestration contrasted sharply with massively hypertrophied, muscular, bronchial arteries which supplied the bronchiectatic upper lobe. Sections of inferior pulmonary ligament were studied in five additional patients with CF but without ILS. Small muscular arteries were consistently noted within the inferior pulmonary ligament. These histologic findings support the concept that the vascular portion of ILS is congenital, whereas the bronchocystic component, in some cases, may be acquired.

Adult↗
PubMed1997

Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth.

Chronic systemic delivery of therapeutic proteins, such as inhibitors of angiogenesis, present a number of difficult pharmacological challenges. To overcome these problems for one such protein, we constructed retroviral and adenoviral vectors that express a novel, secretable form of the antiangiogenic protein, platelet factor 4 (sPF4). Vector-mediated sPF4 transduction selectively inhibits endothelial cell proliferation in vitro, and results in hypovascular tumors that grow slowly in vivo. Additionally, tumor-associated angiogenesis is inhibited and animal survival is prolonged, following transduction of established intracerebral gliomas by an sPF4-expressing adenoviral vector. These data support the concept that targeted antiangiogenesis, using virally mediated gene transfer, represents a promising strategy for delivering antiangiogenic therapy.

Adenoviridae↗
PubMed1997

Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector.

Recent data suggest that many tumors, such as malignant gliomas, have disrupted pRB function, either because of RB-1 gene mutations or as a result of mutations affecting upstream regulators of pRB such as cyclin D1 or p16/INK4a/MTS1 (ref. 1-5). Tumor suppression by pRB has been linked to its ability to repress E2F-responsive promoters such as the E2F-1 promoter. Thus, a prediction, which has not yet been demonstrated experimentally in vivo, is that E2F-responsive promoters should be more active in tumor cells relative to normal cells because of an excess of "free" E2F and loss of pRB/E2F repressor complexes. We demonstrate that adenoviral vectors that contain transgenes driven by the E2F-1 promoter can mediate tumor-selective gene expression in vivo, allowing for eradication of established gliomas with significantly less normal tissue toxicity than seen with standard adenoviral vectors. Our data indicate that de-repression of the E2F-1 promoter occurs in cancer cells in vivo, a finding that can be exploited to design viral vectors that mediate tumor-selective gene expression.

Adenoviruses, Human↗
PubMed1997

Dehydroepiandrosterone-sulfate (DHEAS) reduces adipocyte hyperplasia associated with feeding rats a high-fat diet.

OBJECTIVE: To determine if chronic administration of a low level of dehydroepiandrosterone-sulfate (DHEAS) (10 micrograms/ml drinking water) attenuates adiposity in male Osborne-Mendel rats fed low-fat (11% of kcals) vs high fat (46% of kcals) diets. DESIGN: Rats were randomly assigned to one of four treatment groups for 6 wk in this 2 x 2 factorial study. The main effects tested were diet (low vs high fat) and DHEAS (- or +). SUBJECTS: Male Osborne-Mendel rats (initial body wt approximately 265 g). MEASUREMENTS: Adipocyte mass, size and number from two major fat depots (retroperitoneal, epididymal); mass of one subcutaneous adipose depot (inguinal); serum levels of triglycerides, insulin, glucose and DHEAS; brown adipose tissue (BAT) mass; body weight gain, food and water consumption, and residual carcass composition. RESULTS: DHEAS treatment had no effect on weight gain, food consumption or water intake. DHEAS-treated rats fed the high-fat diet had smaller fat pads containing fewer adipocytes and less carcass lipid than the non DHEAS-treated rats fed the high-fat diet. In contrast, DHEAS-treated rats fed the low-fat diet had similar levels of adipose tissue mass and cellularity compared to control animals fed the low-fat diet. CONCLUSION: Administration of a low dose of DHEAS (10 micrograms/ml or 0.8 mg/kg body wt/d) in the drinking water of young male Osborne-Mendel rats fed a high-fat diet for 6 wk reduced carcass lipid, fat depot mass and retroperitoneal and epididymal adipocyte number compared to their high-fat-fed cohorts. In this study, the antiobesity effects of DHEAS were specific to the level of dietary fat used.

Adipocytes↗
PubMed1997

Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin.

PURPOSE: Immunotoxins could improve outcome in small-cell lung cancer (SCLC) by targeting tumor cells that are resistant to chemotherapy and radiation. N901 is a murine monoclonal antibody that binds to the CD56 (neural cell adhesion molecule [NCAM]) antigen found on cells of neuroendocrine origin, including SCLC. N901-bR is an immunoconjugate of N901 antibody with blocked ricin (bR) as the cytotoxic effector moiety. N901-bR has more than 700-fold greater selectivity in vitro for killing the CD56+ SCLC cell line SW-2 than for an antigen-negative lymphoma cell line. Preclinical studies suggested the potential for clinically significant cardiac and neurologic toxicity. We present a phase I study of N901-bR in relapsed SCLC. PATIENTS AND METHODS: Twenty-one patients (18 relapsed, three primary refractory) with SCLC were entered onto this study. Successive cohorts of at least three patients were treated at doses from 5 to 40 microg/kg/d for 7 days. The initial three cohorts received the first day's dose (one seventh of planned dose) as a bolus infusion before they began the continuous infusion on the second day to observe acute toxicity and determine bolus pharmacokinetics. Toxicity assessment included nerve-conduction studies (NCS) and radionuclide assessment of left ventricular ejection fraction (LVEF) before and after N901-bR administration to fully assess potential neurologic and cardiac toxicity. RESULTS: The dose-limiting toxicity (DLT) of N901-bR given by 7-day continuous infusion is capillary leak syndrome, which occurred in two of three patients at the dose of 40 microg/kg (lean body weight [LBW])/d. Detectable serum drug levels equivalent to effective in vitro drug levels were achieved at the 20-, 30-, and 40-microg/kg(LBW)/d dose levels. Specific binding of the immunotoxin to tumor cells in bone marrow, liver, and lung was observed. Cardiac function remained normal in 15 of 16 patients. No patient developed clinically significant neuropathy. However, a trend was noted for amplitude decline in serial NCS of both sensory and motor neurons. One patient with refractory SCLC achieved a partial response. CONCLUSION: N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 microg/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study.

Adult↗