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Biomedical subjects

Ping Zhao

Publications and source records attributed to Ping Zhao.

At least 55 records · Page 3Linked to original sources

[Responses of canopy stomatal conductance of Acacia mangium forest to environmental driving factors].

Employing Granierś probes, this paper measured the sap flow of 14 sample trees in an Acacia mangium forest on the Heshan hilly lands of Guangdong Province, and recorded the photosynthetic active radiation (PAR), air relative humidity (RH) , and air temperature (T) above the forest canopy. The whole-tree transpiration (E), stand transpiration (Et), and mean canopy stomatal conductance (gc) were calculated, and the relationships between tree morphological characters and whole-tree water use as well as the responses of gc to PAR and vapor pressure deficit (D) were analyzed. The results showed that the whole-tree transpiration had logarithmical positive correlations with tree diameter at breast height (DBH) (P < 0.0001) , sapwood area (P < 0.0001) and canopy size (P = 0.0007), and an exponential positive correlation with tree height (P = 0. 014). The maximum gc (gc max) changed with PAR hyperbolically (P < 0.0001), and with D logarithmically (P < 0.0001). The sap flow measurement system used in this study was reliable and accurate in estimating the transpiration of whole-tree and stand and the canopy stomatal conductance, being an effective tool in studying the relationships between forest water use and environmental factors.

Acacia↗

[Effects of shexiang baoxin pill on carotid atheromatous plaque].

OBJECTIVE: To study the effects of Shexiang Baoxin Pill (SBP) in treating carotid atherosclerosis (CAS). METHODS: Forty-one CAS patients were randomly assigned to 2 groups, the SBP group (31 cases) treated with SBP plus routine treatment and the control group (10 cases) with routine treatment only. Both were treated for 6 months. The changes of carotid atheromatous plaque (CAP), C reactive protein (CRP), fibrinogen (FIB), D-dimer and blood lipids, etc. were observed. RESULTS: After treatment, average number, total scores and area of plaque, as well as levels of CRP, FIB and D-dimer decreased significantly in the SBP group (P < 0.05 or P < 0.01), and were lower than those in the control group after treatment respectively (P < 0.05). No severe adverse reaction occurred in both groups. CONCLUSION: SBP is a safe and effective remedy for treatment of CAS.

Adult↗

[Antigenicity of hepatitis C virus F protein and serum prevalence of anti-F in HCV-infected patients].

OBJECTIVE: To examine the antigenicity of hepatitis C virus (HCV) F protein and investigate serum prevalence of anti-F in HCV-infected patients. METHODS: Eleven pairs of overlapping primers were used to synthesize the full-length HCV f gene, from which the truncated HCV f65 gene fragment was amplified by PCR. HCV f65 gene was then cloned into pET32a(+), and transformed into E. coli strain Plyss (DE3). This recombinant E.coli was induced by IPTG for the production of HCV F65 protein. The expressed HCV F65 protein, purified by Ni-NTA agarose, was further used in ELISA to detect serum anti-F, and to immunize rabbits for making polyclonal anti-F. The rabbit polyclonal anti-F was purified by Staphylococcus aureus protein A agarose. RESULTS: After recombinant pET32a(+)-f65 was constructed successfully, HCV F65 protein was expressed and purified. The purified HCV F65 protein was used as a capture antigen in ELISA to detect serum anti-F in HCV infected patients (n = 30). The result showed that the mean A450 value and the positive rate of serum anti-F were 0.125+/-0.061 and 63.3%, respectively. The rabbit-derived polyclonal anti-F reacted specifically with HCV F65 protein, of which the titer was 1:30,000. CONCLUSION: Our expressed HCV F65 protein is of antigenicity, and can be used to determine serum anti-F. Anti-F IgG does exist in the sera of the HCV-infected patients. Moreover, the rabbit-derived polyclonal anti-F can be used to detect HCV F protein.

Animals↗

Human in vitro glutathionyl and protein adducts of carbamazepine-10,11-epoxide, a stable and pharmacologically active metabolite of carbamazepine.

The clinical use of carbamazepine (CBZ), an anticonvulsant, is associated with a variety of idiosyncratic adverse reactions that are likely related to the formation of chemically reactive metabolites. CBZ-10,11-epoxide (CBZE), a pharmacologically active metabolite of CBZ, is so stable in vitro and in vivo that the potential for the epoxide to covalently interact with macromolecules has not been fully explored. In this study, two glutathione (GSH) adducts were observed when CBZE was incubated with GSH in the absence of biological matrices and cofactors (e.g., liver microsomes and NADPH). The chemical reactivity of CBZE was further confirmed by the in vitro finding that [14C]CBZE formed covalent protein adducts in human plasma as well as in human liver microsomes (HLMs) without NADPH. The two GSH adducts formed in the chemical reaction of CBZE were identical to the two major GSH adducts observed in the HLM incubation of CBZ, indicating that the 10,11-epoxidation represents a bioactivation pathway of CBZ. The two GSH adducts were isolated and identified as two diastereomers of 10-hydroxy-11-glutathionyl-CBZ by NMR. In addition, the covalent binding of [14C]CBZE was significantly increased in the HLM incubation upon addition of NADPH, indicating that CBZE can be further bioactivated by HLMs. To our knowledge, this is the first time the metabolite CBZE has been confirmed for its ability to form covalent protein adducts and the identity of the two CBZE-glutathionyl adducts has been confirmed by NMR. These represent important findings in the bioactivation mechanism of CBZ.

Carbamazepine↗

Nuclear imaging of Met-expressing human and canine cancer xenografts with radiolabeled monoclonal antibodies (MetSeek).

PURPOSE: Met, an oncogene product and receptor tyrosine kinase, is a keystone molecule for malignant progression in solid human tumors. We are developing Met-directed imaging and therapeutic agents, including anti-Met monoclonal antibodies (MetSeek). In this study, we compared two antibodies, Met5 and Met3, for nuclear imaging of human and canine Met-expressing tumor xenografts in nude mice. EXPERIMENTAL DESIGN: Xenografts representing cancers of three different human tissue origins and metastatic canine prostate cancer were raised s.c. in host athymic nude mice. Animals were injected i.v. with I-125-Met5 or I-125-Met3, posterior total body gamma camera images were acquired for several days postinjection, and quantitative region-of-interest activity analysis was done. RESULTS: PC-3, SK-LMS-1/HGF, and CNE-2 xenografts imaged with I-125-Met5 were compared with PC-3, SK-LMS-1/HGF, and DU145 xenografts imaged with I-125-Met3. Nuclear imaging contrast was qualitatively similar for I-125-Met5 and I-125-Met3 in PC-3 and SK-LMS-1/HGF host mice. However, by region-of-interest analysis, the set of human tumors imaged with I-125-Met3 exhibited a pattern of rapid initial tumor uptake followed by a continuous decline in activity, whereas the set of human tumors imaged with I-125-Met5 showed slow initial uptake, peak tumor-associated activity at 1 day postinjection, and persistence of activity in xenografts for at least 5 days. GN4 canine prostate cancer xenografts were readily imaged with I-125-Met5. CONCLUSIONS: We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5.

Animals↗

Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas.

PURPOSE: Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features and the role of HGF in ESCC. EXPERIMENTAL DESIGN: One hundred and forty-nine patients with ESCC were studied. Pretherapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8). The function of HGF was shown by invasion chamber assay. RESULTS: Pretherapy serum HGF was found to be significantly higher in patients with ESCC than in control subjects. The levels of HGF correlated significantly with advanced tumor metastasis stage and survival. Multivariate analyses showed that serum HGF level in cell migration was an independent prognostic factor. Increased HGF serum levels correlated positively with serum levels of VEGF and IL-8. Our results also showed that HGF was overexpressed in ESCC tissues and cell lines. In vitro study showed that HGF could stimulate ESCC cell to express VEGF and IL-8 and markedly enhance invasion and migration of ESCC cells. Furthermore, HGF-induced IL-8 and VEGF expression was dependent on extracellular signal-regulated kinase signaling pathways. The inhibition of extracellular signal-regulated kinase activation reduced HGF-mediated IL-8 and VEGF expression. CONCLUSIONS: Our results suggest that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC. HGF may be involved in the progression of ESCC as an autocrine/paracrine factor via enhancing angiogenesis and tumor cell invasion and migration.

Aged↗

Development of a real-time RT-PCR assay for detection and quantitation of parainfluenza virus 3.

A TaqMan-based real-time RT-PCR assay was developed to detect and quantify human parainfluenza virus 3 (PIV3). Two sets of primer-probe pairs were designed based on the nucleotide (nt) sequence of the nucleocapsid (N) gene. The primer-probe pairs were derived from the 3' end of the N gene (set 1) and the 5' region of the gene (set 2), respectively. Using real-time RT-PCR, the sensitivity of set 1 was determined to be about 9 copies of PIV3 genome, while the sensitivity of set 2 was about 93 copies of PIV3 genome. Set 1 was chosen for subsequent experiments. This primer-probe pair detected PIV3, but not any of several other respiratory viruses, indicating that the assay is PIV3 specific. For clinical evaluation, the assay was employed to test 80 nasopharyngeal aspirates from children with respiratory symptoms. The results confirmed the presence of PIV3 in 12 specimens previously identified as positive by culture confirmation, and showed all of which contained more than 100 copies of PIV3 genome. In addition, the method also detected PIV3 genomes in specimens found negative by culture confirmation, indicating the value of this RT-PCR assay. These data thus demonstrate the application of the real-time RT-PCR assay for the detection and quantification of PIV3 in clinical specimens.

Child↗

A simple sequential incubation method for deconvoluting the complicated sequential metabolism of capravirine in humans.

Capravirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1, undergoes extensive oxygenations to numerous sequential metabolites in humans. Because several possible oxygenation pathways may be involved in the formation and/or sequential metabolism of a single metabolite, it is very difficult or even impossible to determine the definitive pathways and their relative contributions to the overall metabolism of capravirine using conventional approaches. For this reason, a human liver microsome-based "sequential incubation" method has been developed to deconvolute the complicated sequential metabolism of capravirine. In brief, the method includes three fundamental steps: 1) 30-min primary incubation of [(14)C]capravirine, 2) isolation of (14)C metabolites from the primary incubate, and 3) 30-min sequential incubation of each isolated (14)C metabolite supplemented with an ongoing (30 min) microsomal incubation with nonlabeled capravirine. Based on the extent of both the disappearance of the isolated precursor (14)C metabolites and the formation of sequential (14)C metabolites, definitive oxygenation pathways of capravirine were assigned. In addition, the percentage contribution of a precursor metabolite to the formation of each of its sequential metabolites (called sequential contribution) and the percentage contribution of a sequential metabolite formed from each of its precursor metabolites (called precursor contribution) were determined. An advantage of this system is that the sequential metabolism of each isolated (14)C metabolite can be monitored selectively by radioactivity in the presence of all relevant metabolic components (i.e., nonlabeled parent and its other metabolites). This methodology should be applicable to mechanistic studies of other compounds involving complicated sequential metabolic reactions when radiolabeled materials are available.

Biotransformation↗

Prenatal hypoxia-induced adaptation and neuroprotection that is inducible nitric oxide synthase-dependent.

The incidence of perinatal stroke is approximately 0.025%. About two thirds of these patients develop long-lasting neurological deficits. Preconditioning-induced neuroprotection, a phenomenon in which application of a stimulus induces brain ischemic tolerance, is investigated to improve outcome after a perinatal stroke. We applied prenatal hypoxia to fetuses by exposing 22-day pregnant mother rats to 15% oxygen for 30 min and subjected newborns with or without this prenatal hypoxia to brain ischemia 48 h later. Newborns with the prenatal hypoxia had a lower mortality rate, less brain tissue and neuronal loss and fewer active caspase 3 (an indicator for cell apoptosis) positive brain cells than newborns with the brain ischemia only. This neuroprotection was abolished by an inhibitor of inducible nitric oxide synthase (iNOS). The expression of iNOS proteins but not endothelial and neuronal NOS proteins was increased by the prenatal hypoxia. Thus, the prenatal hypoxia-induced neuroprotection may be iNOS-dependent.

Adaptation, Physiological↗

Inhibition of Pkhd1 impairs tubulomorphogenesis of cultured IMCD cells.

Fibrocystin/polyductin (FPC), the gene product of PKHD1, is responsible for autosomal recessive polycystic kidney disease (ARPKD). This disease is characterized by symmetrically large kidneys with ectasia of collecting ducts. In the kidney, FPC predominantly localizes to the apical domain of tubule cells, where it associates with the basal bodies/primary cilia; however, the functional role of this protein is still unknown. In this study, we established stable IMCD (mouse inner medullary collecting duct) cell lines, in which FPC was silenced by short hairpin RNA inhibition (shRNA). We showed that inhibition of FPC disrupted tubulomorphogenesis of IMCD cells grown in three-dimensional cultures. Pkhd1-silenced cells developed abnormalities in cell-cell contact, actin cytoskeleton organization, cell-ECM interactions, cell proliferation, and apoptosis, which may be mediated by dysregulation of extracellular-regulated kinase (ERK) and focal adhesion kinase (FAK) signaling. These alterations in cell function in vitro may explain the characteristics of ARPKD phenotypes in vivo.

Animals↗

Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles.

SARS-CoV is a newly identified coronavirus that causes severe acute respiratory syndrome (SARS). Currently, there is no effective method available for prophylaxis and treatment of SARS-CoV infections. In the present study, the influence of small interfering RNA (siRNA) on SARS-CoV nucleocapsid (N) protein expression was detected in cultured cells and mouse muscles. Four siRNA expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were prepared, and their inhibitory effects on expression of N and enhanced green fluorescence protein (EGFP) fusion protein were observed. A candidate siRNA was proved to down-regulate N and EGFP expression actively in a sequence-specific manner. The expression vector of this siRNA was constructed and confirmed to reduce N and EGFP expression efficiently in both cultured cells and adult mouse muscles. Our findings suggest that the siRNA should provide the basis for prophylaxis and therapy of SARS-CoV infection in human.

Animals↗

Planar waveguide-based silica-polymer hybrid variable optical attenuator and its associated polymers.

We have proposed a silica-polymer hybrid variable optical attenuator that we made by creating two trenches along the core of a straight silica planar waveguide and filling the trenches with a polymer. The polymer, which had a superhigh thermo-optic coefficient, was specially designed and developed in this study to lower the power consumption of the device. We achieved a maximum attenuation of -29 dB for the device by changing the polymer's temperature by only 7 degrees C. The device has a very low power consumption at 2-3 mW/channel, making it a good candidate for integration with arrayed waveguide gratings.

Journal Article↗

Evaluation of time-dependent inactivation of CYP3A in cryopreserved human hepatocytes.

Irreversible CYP3A inhibition by drugs constitutes one of the major causes of inhibition-based drug interactions. We evaluated time-dependent inactivation of CYP3A in cryopreserved human hepatocytes for six structurally diverse compounds known to exhibit this property. Inactivation kinetic parameters were also determined using human liver microsomes. Except for diclofenac, which did not cause CYP3A inactivation either in microsomes or in hepatocytes at concentrations up to 100 microM, time-dependent inactivation was observed in hepatocytes for amprenavir, diltiazem, erythromycin, raloxifene, and troleandomycin. The observed inactivation potency in hepatocytes (observed IC50) was compared with the potency predicted using microsomal parameters (predicted IC50). Despite satisfactory prediction for troleandomycin (1.35 and 2.14 microM for the predicted and observed IC50, respectively), over-prediction of inactivation was observed for raloxifene, amprenavir, and erythromycin (observed IC50 values 6.2-, 55-, and 7.8-fold higher, respectively, than the predicted IC50). By contrast, the observed IC50 for diltiazem in hepatocytes was approximately 4-fold lower than the IC50 predicted from microsomal data (under-prediction). After correcting for factors including nonspecific binding and inactivator consumption, prediction was significantly improved for raloxifene (the observed IC50 then became 2-fold higher than the predicted IC50) and for amprenavir to a lesser extent. A specific P-glycoprotein inhibitor, 4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-[2-(3.4-dimethoxyphenyl)ethyl]-6,7-dimethoxyquinazolin-2-amine (CP-100356), modulated the observed CYP3A inactivation potency by erythromycin and troleandomycin. In summary, these studies reveal three important factors that must be considered when microsomal inactivation parameters are used to predict inhibition-based drug interactions in intact cell systems.

Cryopreservation↗

[Clinico-pathological characteristics of surgical effect on periampullary cancers: report of 631 cases].

OBJECTIVE: To analyze the differences and relationships among periampullary cancers. METHODS: A retrospective study was accomplished on the clinical manifestation, pathological behavior and postoperative survival of 631 patients with periampullary cancer hospitalized from Jan 1980 to Dec 2003. RESULTS: The characteristics of different periampullary cancers, in the order of carcinoma of head of pancreas (n = 352), carcinoma of common bile duct (n = 42), carcinoma of Vater's ampulla (n = 189), and duodenal cancer (n = 48) were as follows: (1) the mean duration of symptoms were 11.9 +/- 1.3, 5.8 +/- 0.9, 6.3 +/- 0.6, and 18.3 +/- 4.0 weeks (F = 6.18, P < 0.01); (2) the serum total bilirubin was 225 +/- 10, 345 +/- 35, 235 +/- 13, and 50 +/- 13 micromol/L(chi(2) = 68.49, P < 0.01); (3) the mean tumor size was 6.0 +/- 2.2, 3.0 +/- 1.3, 3.0 +/- 1.9, and 4.8 +/- 3.9 cm respectively (chi(2) = 255.7, P < 0.01); (4) adenocarcinoma accounted for 88%. Distant metastasis occurred in 98 cases, mostly to liver, abdominal cavity, and omentum. Local invasion mainly occurred in duodenum (chi(2) = 10.76, P < 0.01), common bile duct (chi(2) = 15.16, P < 0.01), and periampullary tissues (chi(2) = 22.49, P < 0.01), and great vessels (chi(2) = 51.25, P < 0.01). (5) the T staging (chi(2) = 11.68, P < 0.01) and lymph node status (chi(2) = 8.33, P < 0.05) of the removed tumor specimens were different among different kinds of carcinomas; (6) local invasion of duodenum (chi(2) = 10.76, P < 0.01), common bile duct (chi(2) = 15.16, P < 0.001), periampullary tissues (chi(2) = 22.49, P < 0.01), and great vessel (chi(2) = 51.25, P < 0.01) occurred in unresectable carcinomas; (7) the resection rates were 13% (n = 46), 50% (n = 21), 74% (n = 139), and 56% (n = 27) respectively (chi(2) = 205.6, P < 0.01); (8) the postoperative median survival periods were 6.0 +/- 0.3, 13.0 +/- 1.2, 22.0 +/- 1.6, and 13.0 +/- 2.5 months respectively (chi(2) = 173.47, P < 0.01). CONCLUSION: Different tumor has its predominant clinical manifestation, pathological character, the probability of resection, and postoperative median survival. The prognosis after surgical treatment may be decided by biological behavior of tumor itself.

Adenocarcinoma↗

Hepatitis G virus genomic RNA is pathogenic to Macaca mulatta.

AIM: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum. METHODS: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological, histological assays. RESULTS: Serum HGV RNA was detectable in all the 3 Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohis-tochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes. RT-PCR and quantitative PCR results showed that HGV could replicate in liver. CONCLUSION: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.

Alanine Transaminase↗

Enhanced growth of human met-expressing xenografts in a new strain of immunocompromised mice transgenic for human hepatocyte growth factor/scatter factor.

Downstream signaling that results from the interaction of hepatocyte growth factor/scatter factor (HGF/SF) with the receptor tyrosine kinase Met plays critical roles in tumor development, progression, and metastasis. This ligand-receptor pair is an attractive target for new diagnostic and therapeutic agents, preclinical development of which requires suitable animal models. The growth of heterotopic and orthotopic Met-expressing human tumor xenografts in conventional strains of immunocompromised mice inadequately replicates the paracrine stimulation by human HGF/SF (hHGF/SF) that occurs in humans with cancer. We have therefore generated a mouse strain transgenic for hHGF/SF (designated hHGF-Tg) on a severe combined immunodeficiency (SCID) background. We report here that the presence of ectopically expressed hHGF/SF ligand significantly enhances growth of heterotopic subcutaneous xenografts derived from human Met-expressing cancer cells, including the lines SK-LMS-1 (human leiomyosarcoma), U118 (human glioblastoma), and DU145 (human prostate carcinoma), but not that of M14-Mel xenografts (human melanoma that expresses insignificant levels of Met). Our results indicate that ectopic hHGF/SF can specifically activate Met in human tumor xenografts. This new hHGF-Tg strain of mice should provide a powerful tool for evaluating drugs and diagnostic agents that target the various pathways influenced by Met activity.

Animals↗