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Biomedical subjects

P Chen

Publications and source records attributed to P Chen.

At least 181 records · Page 10Linked to original sources

Effective repeat administration with adenovirus vectors to the muscle.

Effective repeat administration of adenovirus vectors following intranasal or intravenous delivery is hindered by a strong neutralizing antibody response to the vector. Intramuscular administration of adenovirus vectors elicited a neutralizing antibody response that peaked between 14 and 21 days after infection. However, effective repeat intramuscular administration of adenovirus vectors was not hindered by the presence of neutralizing antibodies in the serum. Surprisingly, beta-galactosidase expression in the skeletal muscle of immunized mice was equivalent to that observed in control mice. As expected, these serum neutralizing antibodies effectively blocked repeat administration of adenovirus vectors when delivered via the intravenous route. These results were observed in both C57BL/6 and Balb/c mice and thus do not appear to be strain specific. Successful repeat administration of adenovirus vectors to skeletal muscle has significant implications for the use of adenovirus vectors clinically and for increasing the safety and efficacy of adenovirus vector gene delivery.

Adenoviridae↗

An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy.

Orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) infection was limited until recently by poor graft and patient outcomes caused by recurrent HBV. Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) dramatically improved post-OLT survival, but recurrent HBV still occurred in up to 36% of the recipients. More recently, combination HBIG and lamivudine has been shown to effectively prevent HBV recurrence in patients post-OLT. The aim of the current study is to determine long-term outcome and cost-effectiveness of using combination HBIG and lamivudine compared with HBIG monotherapy in patients who undergo OLT for HBV. A retrospective chart review identified 59 patients administered combination HBIG and lamivudine and 12 patients administered HBIG monotherapy as primary prophylaxis against recurrent HBV. Lamivudine, 150 mg/d, was administered orally indefinitely. HBIG was administered under a standard protocol (10,000 IU intravenously during the anhepatic phase, then 10,000 IU/d intravenously for 7 days, then 10,000 IU intravenously monthly) indefinitely. A decision-analysis model was developed to evaluate the potential economic impact of prophylaxis against HBV with combination therapy compared with monotherapy. Recurrent HBV was defined as the reappearance of hepatitis B surface antigen (HBsAg) after its initial disappearance post-OLT. In the combination-therapy group, no patient redeveloped serum HBsAg or HBV DNA during mean follow-ups of 459 and 416 days, respectively. In the monotherapy group, 3 patients (25%) had reappearance of HBsAg in serum during a mean follow-up of 663 days. Combination therapy resulted in a dominant, cost-effective strategy with an average cost-effectiveness ratio of $252,111/recurrence prevented compared with $362,570/recurrence prevented in the monotherapy strategy. Combination prophylaxis with HBIG and lamivudine is highly effective in preventing recurrent HBV, may protect against the emergence of resistant mutants, and is significantly more cost-effective than HBIG monotherapy with its associated rate of recurrent HBV.

Adolescent↗

Carbon nanotubes: a future material of life.

The synthesis and applications of carbon nanotubes, a new form of crystalline carbon, are reviewed. In particular, the results obtained in the authors' laboratory are summarized, including the preparation of highly crystalline multi-walled carbon nanotubes; also discussed are the valence band and core level structures, the nonlinear optical limiting behavior, the band gap measurement, and the hydrogen uptake by carbon nanotubes, which has been greatly enhanced by alkali-doping.

Carbon↗

Correlations of partial and extensive methylation at the p14(ARF) locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors.

p14(ARF) is a putative tumor suppressor gene thought to modify the levels of p53. CpG sites within the 5'-flanking region and exon 1beta of p14(ARF) are targets of aberrant methylation and transcriptional silencing in human colorectal cancer (CRC). Here we have developed methylation-specific polymerase chain reaction (MSPCR) methods to detect methylation of CpG sites in p14(ARF) in CRC cell lines and primary CRC tumors, and correlated p14(ARF) mRNA expression with methylation in CRC cell lines using competitive quantitative reverse transcription-polymerase chain reaction methods. Ten CRC cell lines were studied; three (DLD-1, HCT15 and SW48) showed extensive methylation and six (Colo320, SW480, HT29, Caco2, SW837 and WiDr) were unmethylated; the other cell line, LoVo, showed partial methylation that affected exon 1beta but not the immediate upstream CpG sites. p14(ARF) mRNA was expressed at extremely low levels in fully methylated cell lines and at 10(4)- to 10(5)-fold higher levels in unmethylated cell lines. p14(ARF) expression in the partially methylated LoVo cell line was intermediate. Treatment of LoVo cells with 2 microM 5-aza-2'-deoxycytidine for 72 h was associated with marked (100-fold) induction of mRNA levels. Of 119 primary CRCs, 18% contained p14(ARF) methylation, although partial methylation was the most common pattern observed (in 67% of methylated tumors). Methylation of p14(ARF) was often accompanied by p16(INK4a) methylation; however, 50% of p14(ARF) methylated tumors contained unmethylated p16(INK4a). Methylation at p14(ARF) was associated with female gender, greater age, proximal anatomic location and poor differentiation, but not stage at diagnosis. A two-step MSPCR method for assaying p14(ARF) methylation in human tumors is described.

Adult↗

Lack of association of rare alleles in the HRAS variable number of tandem repeats (VNTR) region with adult glioma.

HRAS rare alleles have been associated with the increased susceptibility to a variety of cancers. In the present study we examined the hypothesis that HRAS rare alleles are a risk factor for adult glioma in a population-based case-control study of adult glioma in six San Francisco Bay Area counties. We compared the prevalence of rare alleles in the variable number of tandem repeats region of HRAS in the germline DNA from 73 white adults who had gliomas with that of 65 controls. Overall, the prevalence of rare alleles in cases was not different from the prevalence of those in controls according to two definitions of rare alleles. We found that 25 of 73 (34%) of cases versus 25 of 65 (38%) of controls had at least one allele that was not 30, 46, 69, or 87 repeats; 4 of 73 (5%) of cases versus 6 of 65 (9%) of controls carried one or more alleles with 33, 39, 42, 53, 59, 63, 68, 105, or 114 repeats. The proportion of rare alleles was somewhat higher among subjects with anaplastic astrocytoma. Among women, cases were less likely than controls to have HRAS rare alleles, whereas among men, cases were slightly more likely to have HRAS rare alleles, but none of these results approach statistical significance. Our data do not suggest an excess of HRAS rare alleles among adult glioma cases.

Adult↗

Predictors of survival after In vivo split liver transplantation: analysis of 110 consecutive patients.

OBJECTIVE: To determine the factors that influence patient survival after in vivo split liver transplantation (SLT). SUMMARY BACKGROUND DATA: Split liver transplantation is effective in expanding the donor pool, and its use reduces the number of deaths in patients awaiting orthotopic liver transplantation. Early SLTs were associated with poor outcomes, and acceptance of the technique has been slow. A better understanding of the factors that influence patient and graft survival would be useful in widening the application of SLT. METHODS: During a 3.5-year period, 55 right and 55 left lateral in vivo split grafts were transplanted in 102 pediatric and adult recipients. The authors' in vivo split technique has been previously described. Median follow-up was 14.5 months. Recipient, donor, and surgical variables were analyzed for their effect on patient survival after SLT. RESULTS: Overall survival rates of patients who received an SLT were not significantly different from those of patients who received whole organ transplants. Survival of left lateral segment recipients, at median follow-up time, was 76% versus 80% in patients receiving a trisegment. Fifty of 102 patients (49%) were high-risk urgent recipients (United Network for Organ Sharing [UNOS] status 1 and 2A) and 52 (51%) were nonurgent recipients (UNOS status 2B, 3). High-risk recipients had a survival rate significantly lower than that of nonurgent recipients. By univariate comparison, two variables-UNOS status and number of transplants per patient-were significantly associated with an increased risk of death. Preoperative recipient mechanical ventilation, preoperative prothrombin time, donor sodium level, donor length of hospital stay, and warm ischemia time approached significance. The type of graft (right vs. left) did not reduce the survival rate after transplantation. Multivariate logistic regression analysis identified UNOS status and length of donor hospital stay as independent predictors of survival. CONCLUSIONS: Patient survival of in vivo SLT is not significantly different from that of whole-organ orthotopic liver transplantation. The variables affecting outcome of in vivo SLT are similar to those in whole-organ transplantation. in vivo SLT should be widely applied to expand a severely depleted donor pool.

Adolescent↗

Force between charged particles with ion condensation

We have numerically calculated the interaction forces between two highly charged spherical particles embedded in a cloud of small ions with or without charge redistribution on the particle surfaces. Ion condensation near the charged particles leads to reduced electrostatic interaction between the particles, and we find that the effective two-particle interaction is significantly smaller than the values expected from considering only effective single-particle potentials.

Journal Article↗

Radiative corrections in symmetrized classical electrodynamics

The physics of radiation reaction for a point charge is discussed within the context of classical electrodynamics. The fundamental equations of classical electrodynamics are first symmetrized to include magnetic charges: a double four-potential formalism is introduced, in terms of which the field tensor and its dual are employed to symmetrize Maxwell's equations and the Lorentz force equation in covariant form. Within this framework, the symmetrized Dirac-Lorentz equation is derived, including radiation reaction (self-force) for a particle possessing both electric and magnetic charge. The connection with electromagnetic duality is outlined, and an in-depth discussion of nonlocal four-momentum conservation for the wave-particle system is given.

Journal Article↗

Purification and biochemical characterization of mutacin I from the group I strain of Streptococcus mutans, CH43, and genetic analysis of mutacin I biosynthesis genes.

Previously, we reported isolation and characterization of mutacin III and genetic analysis of mutacin III biosynthesis genes from the group III strain of Streptococcus mutans, UA787 (F. Qi, P. Chen, and P. W. Caufield, Appl. Environ. Microbiol. 65:3880-3887, 1999). During the same process of isolating the mutacin III structural gene, we also cloned the structural gene for mutacin I. In this report, we present purification and biochemical characterization of mutacin I from the group I strain CH43 and compare mutacin I and mutacin III biosynthesis genes. The mutacin I biosynthesis gene locus consists of 14 genes in the order mutR, -A, -A', -B, -C, -D, -P, -T, -F, -E, -G, orfX, orfY, orfZ. mutA is the structural gene for mutacin I, while mutA' is not required for mutacin I activity. DNA and protein sequence analysis revealed that mutacins I and III are homologous to each other, possibly arising from a common ancestor. The mature mutacin I is 24 amino acids in size and has a molecular mass of 2, 364 Da. Ethanethiol modification and peptide sequencing of mutacin I revealed that it contains six dehydrated serines, four of which are probably involved with thioether bridge formation. Comparison of the primary sequence of mutacin I with that of mutacin III and epidermin suggests that mutacin I likely has the same bridging pattern as epidermin.

Amino Acid Sequence↗

Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF.

The alternate RNA polymerase sigma factor gene, sigF, which is expressed in stationary phase and under stress conditions in vitro, has been deleted in the virulent CDC1551 strain of Mycobacterium tuberculosis. The growth rate of the DeltasigF mutant was identical to that of the isogenic wild-type strain in exponential phase, although in stationary phase the mutant achieved a higher density than the wild type. The mutant showed increased susceptibility to rifampin and rifapentine. Additionally, the DeltasigF mutant displayed diminished uptake of chenodeoxycholate, and this effect was reversed by complementation with a wild-type sigF gene. No differences in short-term intracellular growth between mutant and wild-type organisms within human monocytes were observed. Similarly, the organisms did not differ in their susceptibilities to lymphocyte-mediated inhibition of intracellular growth. However, mice infected with the DeltasigF mutant showed a median time to death of 246 days compared with 161 days for wild-type strain-infected animals (P < 0.001). These data indicate that M. tuberculosis sigF is a nonessential alternate sigma factor both in axenic culture and for survival in macrophages in vitro. While the DeltasigF mutant produces a lethal infection of mice, it is less virulent than its wild-type counterpart by time-to-death analysis.

Animals↗

TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans.

In C. elegans, the zinc-finger protein TRA-1A is thought to be the final arbiter of somatic sexual identity. We show that fog-3, which is required for germ cells to become sperm rather than oocytes, is a target of TRA-1A. First, northern analyses and RT-PCR experiments indicate that expression of fog-3 is controlled by tra-1. Second, studies of double mutants show that this control could be direct. Third, the fog-3 promoter contains multiple sites that bind TRA-1A in gel shift assays, and mutations in these sites alter activity of fog-3 in vivo. These results establish fog-3 as one of the first known targets of transcriptional regulation by TRA-1A. Furthermore, they show that tra-1 controls a terminal regulator of sexual fate in germ cells, just as it is thought to do in the soma.

Animals↗

Appropriateness of prostate-specific antigen testing.

We established criteria for appropriate use of the prostate-specific antigen (PSA) assay and used them to evaluate PSA test utilization at 1 tertiary care institution. During a 6-month period, 2,330 PSA results were reported for outpatients and 95 for inpatients. We reviewed medical records for a random sample of 338 outpatient results (14.51%) and all 95 inpatient results, of which 21% (71/338) of outpatient and 17% (16/95) of inpatient results were inappropriate according to our test utilization criteria. Among outpatients, 52% of tests were done for screening and 19% for monitoring for cancer recurrence. For inpatients, workup for cancer (53/95 [56%]) was the most frequent indication for testing and screening the second (24/95 [25%]). Of tests failing the criteria, 66 (76%) of 87 resulted from excessively frequent and age-inappropriate screening. We assessed the potential effect on clinical outcome if these tests were not performed. Of the 87 tests considered inappropriate, only 1 test result influenced clinical management for patients younger than 75 years. By instituting simple limits on age and frequency, we estimate that 74% (64/87) of the inappropriate tests could have been eliminated.

Adult↗

Association of an ERCC1 polymorphism with adult-onset glioma.

Gliomas include several histologically distinct types of tumors whose molecular profiles suggest different etiologies. Because the ERCC1 protein is essential for nucleotide excision repair and influences genomic instability, polymorphisms in ERCC1 may play a role in human tumors. We determined the presence of the A versus C polymorphism at nucleotide 8092 of ERCC1 using a single-strand conformational polymorphism assay and DNA sequencing in adults with glioma and controls from a population-based study. Among 318 alleles from 159 controls, 27% (86) were A and 73% were C. Prevalences of the CC genotype were 51% (81 of 159), 48% (30 of 62), 63% (20 of 32), and 82% (23 of 28) for controls and subjects with glioblastoma multiforme, astrocytoma, and oligoastrocytoma, respectively (Fisher's exact P = 0.009). The age-adjusted odds ratio for genotype CC in all cases versus controls was 1.4 (95% confidence interval, 0.9-2.3), whereas that for subjects with oligoastrocytoma versus controls was 4.6 (95% confidence interval, 1.6-13.2). The median age at diagnosis was 46 years for glioma patients with the CC genotype compared with 54 years for patients with the AA or AC genotype (P = 0.04). This is the first study to report a significant association of a polymorphism in ERCC1 with the risk of brain tumors. This A/C polymorphism, which may affect mRNA stability for ERCC1, also results in an amino acid substitution of lysine to glutamine in a recently described nucleolar protein (ASE-1) and T-cell receptor complex subunit CD3epsilon-associated signal transducer (CAST). This finding, if confirmed in other series, may provide a foundation on which to study novel mechanisms of carcinogenesis in subsets of glioma.

Adult↗

Relative bioavailability of salmon calcitonin given intramuscularly.

BACKGROUND: Salmon calcitonin, a polypeptide hormone, is used in the treatment of osteoporosis, hypercalcemia and Paget's disease. The purpose of this study was to evaluate the pharmacokinetics and relative bioavailability of two salmon calcitonin products, Miacalcic (Novartis Pharmaceuticals, Basle, Switzerland) and Calcinin (Purzer Pharmaceuticals, Taipei, Taiwan). METHODS: This was a randomized, single-dose, crossover study conducted under fasting conditions with a washout period of 1 week between doses. Ten healthy male subjects were enrolled in this study. Each subject received a 100 IU dose (20 micrograms; 50 IU/ampule x 2) of salmon calcitonin intramuscularly (i.m.) followed by collection of blood samples at specified time intervals. Serum salmon calcitonin concentrations were measured using a validated radioimmunoassay method with a detection limit of 15.0 pg/ml. Values for the area under the serum concentration from time zero to last time and infinity curve (AUC0-t and AUC0-infinity), peak concentration (Cmax), time to peak concentration, terminal first order rate constant, terminal half-life, mean residence time, total clearance divided by absolute bioavailability, onset time, maximal effect and duration were compared for each product. RESULTS: The 90% confidence intervals for AUC0-t, AUC0-infinity and Cmax after logarithmic transformation were 93.2% to 113.1%, 97.2% to 114.9% and 84.9% to 108.0%, respectively. CONCLUSIONS: Based on the two one-sided tests procedure, we conclude that Miacalcic and Calcinin are bioequivalent.

Adult↗

[Study on hepatitis C virus infection of peripheral blood mononuclear cells in chronic hepatitis C patients].

OBJECTIVE: To demonstrate HCV infection and replication in the peripheral blood mononuclear cells (PBMCs) of hepatitis patients by the methods of molecular biology, immunology and electron microscopy. METHODS: HCV RNA and antigens were detected in the PBMCs of 28 patients with chronic hepatitis C by RT-PCR, Immunohistochemistry and electron microscopy, respectively. RESULTS: The positive rate of HCV RNA and HCV antigens were 77.27% (17/22) and 75.00% (21/28), respectively. Two types of spherical HCV-like particles with diameter of approximately 65 nm and 110 nm were observed in cytoplasmic vesicles by electron microscopy in the PBMCs with high titer of HCV RNA and antigens in 10 patients. The budding and shedding of these particles could also be found in the cytoplasmic vesicles. Immunoelectron microscopy using antibodies against HCV core and NS(3) demonstrated that the particles contained HCV antigens. CONCLUSION: HCV can infect and replicate in the PBMCs of patients with chronic hepatitis C.

Hepacivirus↗

[Effects of hypoxia on expression and activity of matrix metalloproteinase-2 in hepatic stellate cell].

OBJECTIVE: To study the effect of hypoxia on the expression and activity of matrix metalloproteinase-2 (MMP-2) in the hepatic stellate cell (HSC). METHODS: The expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in cultured rat HSC was detected by immunocytochemistry (ICC). The relative amount of MMP-2 and TIMP-2 in the culture supernatant was assayed by ELISA and the activity of MMP-2 in supernatant was examined by zymography. RESULTS: The expression of MMP-2 was enhanced in hypoxia group as compared with that in control one (t' 3.4685, P<0.05 ), while the expression of TIMP-2 was decreased (t'=2.5673, P<0.05). The activity of MMP-2 was lower in hypoxia group than in control one (t'=4.270, P<0.01). Comparing the varied duration of hypoxia, the relative amount of MMP-2 protein was the highest in 6 h group (6h vs 12h, t=4. 0945, P<0.001; 6h vs 24h, t=2.4652, P<0.025), with a contrary curve in TIMP-2. CONCLUSION: Hypoxia promotes the expression of MMP-2 and inhibits the expression of TIMP-2 in HSC. It is more notable at early stage of hypoxia.

Animals↗

A clinical investigation on garlicin injectio for treatment of unstable angina pectoris and its actions on plasma endothelin and blood sugar levels.

To investigate the therapeutic effects and mechanisms of garlicin for treatment of unstable angina pectoris (UAP), garlicin injectio was intravenously dripped 60 mg/day in 34 cases for 10 days. Nitroglycerine was used in 21 cases of the control group. The results showed that the total effective rates in improving symptoms and electrocardiogram after garlicin treatment were respectively 82% and 62%, and that the plasma endothelin and blood sugar levels were markedly lowered in cases with hyperglycemia.

Aged↗

Oxidative stress before and after operation in patients with chronic cholecystitis containing gallstone.

To study the relationship of oxidative, antioxidative constituents and antioxidases in blood with chronic cholecystitis containing gallstone, levels of lipoperoxides (LPO), nitric oxide (NO), vitamin C(VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as well as level of LPO, activities of superoxide dismulase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in erythrocytes were investigated by spectrophotometric assay in 107 patients with this condition (PCg) and 100 healthy volunteers (HVs). Compared with HVs group, the average value of LPO and NO in plasma and that of LPO in erythrocytes of PCg group were significantly increased (P < 0.0001), while that of VC, VE and beta-CAR in plasma and the average activities of SOD, CAT and GSH-Px in erythrocytes were significantly decreased (P < 0.0001). Linear regression and correlation analysis for 107 preoperative PCg showed that the value of LPO and NO in plasma and that of LPO in erythrocytes of PCg gradually increased (P < 0.0001), representing a significant linear positive correlation. The value of VC, VE and beta-CAR in plasma and that of SOD, CAT and GSH-Px in erythrocytes of PCg gradually decreased (P < 0.0001), representing a significant linear negative correlation. Stepwise regression and correlation analysis for 107 preoperative PCg suggested that the closest correlation was observed between the course of disease and the value of NO and VC in plasma and that of SOD, GSH-Px and LPO in erythrocytes, r = 0.7306, F = 32.1408, P < 0.0001. Compared with the preoperative PCg group, the average value of LPO and NO in plasma and that of LPO in erythrocytes of the postoperative PCg group were significantly decreased (P < 0.0001). Furthermore, the average value of VC in plasma and that of SOD, CAT and GSH-Px in erythrocytes of the postoperative PCg group were significantly increased (P < 0.0001), whereas no significant difference was found between their average value of VE and beta-CAR in plasma. These findings suggested that oxidative stress was an aggravating pathological condition in PCg group. Therefore, we recommend that in treating PCg, antioxidants such as VC, VE, beta-CAR should be given in order to alleviate their potential oxidative damages.

Adult↗