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Biomedical subjects

P Chen

Publications and source records attributed to P Chen.

At least 73 records · Page 4Linked to original sources

The decline of training in open biliary surgery: effect on the residents' attitude toward bile duct surgery.

BACKGROUND: After more than a decade of growth for laparoscopic cholecystectomy and decline in open cholecystectomy, the impact on the training of resident's in other open biliary operations can be analyzed quantitatively. METHODS: The national operative statistics for residents' operations from 1988 to 2001 (data in the public domain) were analyzed by regression analysis to establish trends and to calculate the rate of change. For laparoscopic biliary operations, the changes in laparoscopic and open operations over time and the number of operations per trainee each year were used to measure the growth of a laparoscopic operation and to predict future trends. A survey of attitude, management algorithm, and self-confidence for coping with unexpected events in laparoscopic cholecystectomy also was conducted for senior residents and recent graduates. RESULTS: In 2001, open cholecystectomy decreased to 28%, open common duct exploration to 27%, sphincteroplasty to 20%, of 1988 (baseline year) levels. Cholecystostomy and choledochoenteric bypass decreased to 70% and 75%, respectively. The decline began before the era of laparoscopic cholecystectomy, but accelerated after its introduction. Many of the recent graduates surveyed in one program indicated a preference for a nonsurgical, mainly endoscopic, approach for all bile duct conditions, but also for the assistance of senior surgeons in the operative management of unexpected events. CONCLUSION: The popularity of noninvasive therapy in biliary surgery significantly reduced the resident's exposure to open biliary surgery, adversely affecting their confidence in the management of unexpected events encountered during laparoscopic operations. Supplemental and remedial education measures must be instituted in training programs.

Attitude of Health Personnel↗

Immunohistochemical identification of components of the chemoattractant signal transduction pathway in vomeronasal bipolar neurons of garter snakes.

The chemosignal transduction pathway in the vomeronasal sensory epithelium of garter snakes involves activation of G-protein-coupled receptors and subsequent generation of second messengers leading to production of an electrical signal. Calcium imaging experiments demonstrate that ligand binding to the receptor leads to an increase in intracellular calcium and that the phosphatidylinositol-turnover pathway plays a major role in this Ca(2+) increase. Here, we demonstrate, using immunohistochemistry, that IP(3) receptors are largely distributed in dendritic regions of the epithelium, ryanodine receptors are confined to the somata region, and Na(+)/Ca(2+) exchanger protein is expressed throughout the vomeronasal (VN) sensory epithelium.

Animals↗

A phase I study of 99mTc-hR3 (DiaCIM), a humanized immunoconjugate directed towards the epidermal growth factor receptor.

A phase I trial was conducted to evaluate the safety, tumour and normal tissue localization, pharmacokinetics and radiation dosimetry of Tc-hR3, a humanized monoclonal antibody directed towards the epidermal growth factor receptor, in 12 patients with recurrent or metastatic epithelial malignancies. Patients were injected intravenously with 3.0 mg or 6.0 mg (1010 MBq) of Tc-hR3. Blood and plasma concentrations of radioactivity were measured and a complete 24 h urine collection was obtained. Whole-body images were acquired up to 24 h post-injection and normal organ uptake quantified. Radiation dosimetry was estimated using MIRDose. Safety was evaluated by clinical observation, biochemical/haematological testing and by measuring immune response to Tc-hR3. There were no adverse effects, no changes in biochemical/haematological indices and no immune response to Tc-hR3. Tc-hR3 was rapidly cleared from the blood with a distribution half-life of 10.8+/-3.8 min. The volume of distribution, and clearance, were 180+/-37 ml.kg and 14+/-3 ml.kg.min, respectively. The elimination phase could not be discerned due to increasing blood radioactivity at later times. About 19-24% was excreted in the urine. Normal tissue uptake was mainly in the liver (44-50%), spleen (3-4%) and kidneys (3%). Imaging was positive in one patient with squamous cell carcinoma of the mouth and an involved cervical lymph node. The whole-body radiation dose from Tc-hR3 was 1.34+/-0.02x10 mSv.Bq. We conclude that Tc-hR3 exhibited an excellent safety profile. Future studies to determine the sensitivity and specificity of imaging with Tc-hR3 in a larger group of patients with pre-selection for epidermal growth factor receptor positivity are planned.

Adolescent↗

Genetic parameters and trends for lean growth rate and its comvonents in U.S. Yorkshire, Duroc, Hampshire, and Landrace pigs.

Records on 361,300 Yorkshire, 154,833 Duroc, 99,311 Hampshire, and 71,097 Landrace pigs collected between 1985 and April of 2000 in herds on the National Swine Registry Swine Testing and Genetic Evaluation System were analyzed. Animal model and REML procedures were used to estimate random effects of animal genetic, common litter, maternal genetic, and the covariances between animal and maternal for lean growth rate (LGR), days to 113.5 kg (DAYS), backfat adjusted to 113.5 kg (BF), and loin eye area adjusted to 113.5 kg (LEA). Fixed effects of contemporary group and sex were also in the statistical model. Based on the single-trait model, estimates of heritabilities were 0.44, 0.44, 0.46, and 0.39 for LGR; 0.35, 0.40, 0.44, and 0.40 for DAYS; 0.48, 0.48, 0.49, and 0.48 for BF; and 0.33, 0.32, 0.35, and 0.31 for LEA in the Yorkshire, Duroc, Hampshire, and Landrace breeds, respectively. Estimates of maternal genetic effects were low and ranged from 0.01 to 0.05 for all traits across breeds. Estimates of common litter effects ranged from 0.07 to 0.16. A bivariate analysis was used to estimate the genetic correlations between lean growth traits. Average genetic correlations over four breeds were -0.83, -0.37, 0.44, -0.07, 0.08, and -0.37 for LGR with DAYS, BF, and LEA, DAYS with BF and LEA, and BF with LEA, respectively. Average genetic trends were 2.35 g/yr, -0.40 d/yr, -0.39 mm/yr, and 0.37 cm2/yr for LGR, DAYS, BF, and LEA, respectively. Results indicate that selection based on LGR can improve leanness and growth rate simultaneously and can be a useful biological selection criterion.

Adipose Tissue↗

Early graft function after pediatric liver transplantation: comparison between in situ split liver grafts and living-related liver grafts.

BACKGROUND: The systematic application of living-related and cadaveric, in situ split-liver transplantation has helped to alleviate the critical shortage of suitable-sized, pediatric donors. Undoubtedly, both techniques are beneficial and advantageous; however, the superiority of either graft source has not been demonstrated directly. Because of the potential living-donor risks, we reserve the living donor as the last graft option for pediatric recipients awaiting liver transplantation. Inasmuch as no direct comparison between these two graft types has been performed, we sought to perform a comparative analysis of the functional outcomes of left lateral segmental grafts procured from these donor sources to determine whether differences do exist. METHODS: A retrospective analysis of all liver transplants performed at a single institution between February 1984 and January 1999 was undertaken. Only pediatric (<18 years) recipients of left lateral segmental grafts procured from either living-related (LRD) or cadaveric, in situ split-liver (SLD) donors were included. A detailed analysis of preoperative, intraoperative, and postoperative variables was undertaken. Survival was estimated using the Kaplan-Meier method, and comparison of variables between groups was undertaken using the t test of Wilcoxon rank sum test. RESULTS: There were no significant differences in the preoperative variables between the 39 recipients of SLD grafts and 34 recipients of LRD grafts. The donors did differ significantly in mean age, ABO blood group matching, and preoperative liver function testing. Postoperative liver function testing revealed significant early differences in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, prothrombin time, and alkaline phosphatase, with grafts from LRD performing better than those from SLD. SLD grafts also had significantly longer ischemia times and a higher incidence of graft loss owing to primary nonfunction and technical complications (9 vs. 2, P<0.05). However, six of these graft losses in the SLD group were because of technical or immunologic causes, which, theoretically, should not differ between the two groups. Furthermore, these graft losses did not negatively impact early patient survival as most patients were successfully rescued with retransplantation (30-day actuarial survival, 97.1% SLD vs. 94.1% LRD, P=0.745). In the surviving grafts, the early differences in liver function variables normalized. CONCLUSIONS: Inherent differences in both donor sources exist and account for differences seen in preoperative and intraoperative variables. Segmental grafts from LRD clearly performed better in the first week after transplantation as demonstrated by lower liver function variables and less graft loss to primary nonfunction. However, the intermediate function (7-30 days) of both grafts did not differ, and the early graft losses did not translate into patient death. Although minimal living-donor morbidity was seen in this series, the use of this donor type still carries a finite risk. We therefore will continue to use SLD as the primary graft source for pediatric patients awaiting liver transplantation.

Adult↗

Immunocytochemical localization of GABA(B) receptors in mesencephalic trigeminal nucleus neurons in the rat.

We examined immunoreactivities for gamma-aminobutyric acidB-receptor (GABA(B)R) subtypes, GABA(B)R1 and GABA(B)R2, in the mesencephalic trigeminal nucleus neurons (MTN neurons) of the rat. Immunoreactivity for GABA(B)R1 was prominent in cell bodies of MTN, whereas that for GABA(B)R2 was very weak, if existed. For electron microscopy, the immunogold-silver method for GABA(B)R1 was combined with the immunoperoxidase method for glutamic acid decarboxylase (GAD: the synthetic enzyme of GABA). Immunogold-silver particles indicating GABA(B)R1 immunoreactivity were distributed widely in the cytoplasm of the cell bodies postsynaptic to GAD-immunoreactive axon terminals, but were rarely associated with synaptic membrane specialization or extrasynaptic sites of plasma membrane. It has been indicated that GABA(B)R1 may not be transported to plasma membrane when no GABA(B)R2 exists. Thus, it was presumed that GABA(B)R1 in the cell body of the rat MTN neurons might not be involved in the synaptic transmission.

Animals↗

Observation of plasma focusing of a 28.5 GeV positron beam.

The observation of plasma focusing of a 28.5 GeV positron beam is reported. The plasma was formed by ionizing a nitrogen jet only 3 mm thick. Simultaneous focusing in both transverse dimensions was observed with effective focusing strengths of order tesla per micron. The minimum area of the beam spot was reduced by a factor of 2.0+/-0.3 by the plasma. The longitudinal beam envelope was measured and compared with numerical calculations.

Journal Article↗

Catalyst screening by electrospray ionization tandem mass spectrometry: Hofmann carbenes for olefin metathesis.

A new screening methodology, which combines in situ synthesis of complexes with an assay by electrospray ionization tandem mass spectrometry (ESI-MS), is introduced in order to investigate highly active, cationic ruthenium-carbene catalysts in ring-opening metathesis polymerization (ROMP). The parameter space, whic is defined by systematic variation of four structural features of the catalyst [[R2P(CH2),PR2-kappa2-P]XRu=CHR']+ (the halogen ligand, the diphosphane bite-angle, the steric bulk of the phosphane, and the carbene ligand) and the variation of the metathesis substrate, is mapped out. Chloride as the anionic ligand X, a small chelating angle (n = 1), and reduced steric demand of the substituents R (Cy versus tBu) lead to the most reactive complex in acyclic olefin metathesis, whereas variation of the carbene moiety CHR' has only a modest influence. The overall rate in the gas phase depends on the pi-complex preequilibrium and metallacyclobutane formation, which was found to be the rate-determining step. In ROMP reactions backbiting has a profound influence on the overall rate. Moreover, we were able to establish that the reactivity trends determined in the gas phase parallel solution-phase reactivity. The overall rate in solution is also determined by a favorable dimer/ monomer preequilibrium providing the active catalyst by facile dissociation of dicationic, dinuclear catalyst precursors.

Journal Article↗

[Diagnostic value of transbronchial lung biopsy via fiberbronchoscope of peripheral or diffuse pulmonary disease].

OBJECTIVE: To understand the diagnostic value of peripheral and diffuse pulmonary disease examined with Transbronchial lung biopsy (TBLB) via fiberoptic bronchoscope. METHODS: Four hundred and sixty patients of peripheral and diffuse pulmonary disease were diagnosed with TBLB via fiberoptic bronchoscope without fluoroscopic guidance. The result of clinical data and pathologic diagnosis were underwent retrospectively analyses. RESULTS: Confirmed diagnosis was obtained in 351 patients; the total positive diagnostic rate was 76.3%. Diseases were included lung cancer, pulmonary tuberculosis, diffuse interstitial pulmonary fibrosis, pulmonary sarcoidosis etc. The positive diagnostic rate of TBLB on pleural pulmonary disorders was the lowest. There were no any other serious complications except bleeding, blood sputum, fever and pneumothorax occasionally. CONCLUSIONS: TBLB in diagnoses of peripheral and diffuse pulmonary disease is a reliable, safe, handy cheap, may repeatable operational method.

Adolescent↗

Quantum effects in high-gain free-electron lasers.

A many-particle fully quantized theory for a free-electron laser which is valid in the high-gain regime is presented. We examine quantum corrections for the high-gain single-pass free-electron laser. It is shown that quantum effects become significant when the photon energy becomes comparable to the gain bandwidth. The initiation of the free-electron laser process from quantum fluctuations in the position and momentum of the electrons is considered, and the parameter regime for enhanced start-up is identified. Photon statistics of the free-electron laser radiation are discussed, and the photon number statistics for the self-amplified spontaneous emission are calculated.

Journal Article↗

Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1 alpha in activated T lymphocytes.

Cell adaptation to hypoxia is partially accomplished by hypoxia-inducible transcription factor-1 (HIF-1). Here we report the hypoxia-independent up-regulation of HIF-1 alpha subunit in antigen receptor-activated T cells. This is explained by a selective up-regulation of alternatively spliced mRNA isoform I.1 that encodes the HIF-1 alpha protein without the first 12 N-terminal amino acids. We show that both short (I.1) and long (I.2) HIF-1 alpha isoforms display similar DNA binding and transcriptional activities. Major differences were observed between these two HIF-1 alpha isoforms in their expression patterns with respect to the resting and activated T lymphocytes in hypoxic and normoxic conditions. The T cell antigen receptor (TCR)-triggered activation of normal ex vivo T cells and differentiated T cells results in up-regulation of expression of I.1 isoform of HIF-1 alpha mRNA without an effect on constitutive I.2 HIF-1 alpha mRNA expression. The accumulation of I.1 HIF-1 alpha mRNA isoform in T lymphocytes is also demonstrated during cytokine-mediated inflammation in vivo, suggesting a physiological role of short HIF-1 alpha isoform in activated lymphocytes. The TCR-triggered, protein kinase C and Ca(2+)/calcineurin-mediated HIF-1 alpha I.1 mRNA induction is protein synthesis-independent, suggesting that the HIF-1 alpha I.1 gene is expressed as an immediate early response gene. Therefore, these data predict a different physiological role of short and long isoforms of HIF-1 alpha in resting and activated cells.

Alternative Splicing↗

EGFR overexpression and radiation response in glioblastoma multiforme.

PURPOSE: Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment. METHODS AND MATERIALS: Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5-8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis. RESULTS: Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age. CONCLUSION: The observed relative radioresistance of some GMs is associated with overexpression of EGFR.

Adolescent↗

[Diagnostic and therapeutic value of fiberbronchoscope for the adult in the children with respiratory diseases].

OBJECTIVE: To understand the diagnostic and therapeutic value of fiberbronchoscope for the adult in the children with respiratory diseases. METHODS: The results of diagnostic and therapeutic use in 107 child cases using fiberbronchoscope for adult were analysed. RESULTS: Pathogenic diagnosis was acquired in 107 cases; 17(17/21) cases of bronchial foreign bodies were extracted; 22 cases underwent bronchoalveolar lavage locally. CONCLUSION: Various type of BF of fiberbronchoscope for adult can be used in children at various ages, and to diagnose the child's diseases. Fiberbronchoscope for adult is safe and effective in the removing of foreign body and reliable in the treatment of atelectasis caused by inflammation, post-operation, and aspiration of foreign bodies. Fiberbronchoscope for adult can replace fiberbronchoscope for child unless the latter is used generally.

Adolescent↗

Giant room-temperature magnetoresistance in polycrystalline Zn(0.41)Fe(2.59)O4 with alpha-Fe2O3 grain boundaries.

A tunneling-type magnetoresistance (MR) as large as 158% is observed at T = 300 K in a polycrystalline Zn0.41Fe2.59O4 sample, in which the Zn0.41Fe2.59O4 grains are separated by insulating alpha-Fe2O3 boundaries. The huge room-temperature MR is attributed to the high spin polarization of Zn(0.41)Fe(2.59)O4 grains and antiferromagnetic correlations between magnetic domains on both sides of the insulating alpha-Fe2O3 boundary. The MR exhibits strong temperature dependence below 100 K and its magnitude is enhanced to reach 1280% at 4.2 K, which may arise from the Coulomb blockade effect.

Journal Article↗

Probing conformational changes in the I-like domain and the cysteine-rich repeat of human beta 3 integrins following disulfide bond disruption by cysteine mutations: identification of cysteine 598 involved in alphaIIbbeta3 activation.

We have investigated receptor function and epitope expression of recombinant alpha(IIb)beta(3) mutated at Cys(177) or Cys(273) in the I-like domain as well as Cys(598), located in the fourth repeat of the membrane-proximal cysteine-rich region and mutated in a Glanzmann's thrombasthenia type II patient. The beta(3) mutants beta(3)C177A, beta(3)C273A, and beta(3)C598Y exhibited a decreased electrophoretic mobility in SDS-polyacrylamide gel electrophoresis under nonreducing conditions, confirming the disruption of the respective disulfide loops. Despite reduced surface expression, the alpha(IIb)beta(3)C177A, alpha(IIb)beta(3)C273A, and alpha(IIb)beta(3)C598Y receptors mediated cell adhesion to immobilized fibrinogen and translocated into focal adhesion plaques. The beta(3)C598Y mutation, but not the beta(3)C177A or beta(3)C273A mutations, induced spontaneous binding of the ligand mimetic monoclonal antibody PAC-1, while the beta(3)C177A and beta(3)C273A mutants exhibited reduced complex stability in the absence of Ca(2+). Epitope mapping of function-blocking monoclonal antibodies (mAbs) allowed the identification of two distinct subgroups; mAbs A2A9, pl2-46, 10E5, and P256 did not interact with alpha(IIb)beta(3)C273A and bound only weakly to alpha(IIb)beta(3)C177A, while mAbs AP2, LM609 and 7E3 bound normally to mutant alpha(IIb)beta(3)C273A, but interacted only weakly with mutant alpha(IIb)beta(3)C177A. Furthermore, a cryptic epitope recognized by mAb 4D10G3 and not exposed on wild type alpha(IIb)beta(3) became accessible only on mutant alpha(IIb)beta(3)C177A and was mapped to the 60-kDa chymotrypsin fragment of beta(3). Finally, the ligand-induced binding site (LIBS) epitopes AP5, D3, LIBS1, and LIBS2 were spontaneously expressed on all three mutants independent of RGDS or dithiothreitol treatment. Our results provide evidence that disruption of a single cysteine disulfide bond in the cysteine-rich repeat domain, but not in the I-like domain, activates integrin alpha(IIb)beta(3). In contrast, disruption of each of the disulfide bonds in the two long insertions of the I-like domain predicted to be in close contact with the alpha subunit beta-propeller domain affect the stability of the alpha(IIb)beta(3) heterodimer and inhibit complex-specific mAb binding without affecting the RGD binding capacity of the metal ion-dependent adhesion site-like domain.

Animals↗