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Biomedical subjects

P Lu

Publications and source records attributed to P Lu.

At least 73 records · Page 4Linked to original sources

[Epidemiological aspects of the genotype of hepatitis C virus].

OBJECTIVE: To research the epidemiological characteristics of genotype of hepatitis C virus. METHODS: 107 HCV isolates from 7 cities in southern, northern and northeast of China were analyzed using PCR and second generation line probe assay (INNO-LiPA). RESULTS: The analysis of HCV genotypes showed that: 1. HCV l b was the common genotype (83 17%), however the frequency of genotype l b in northeast (72.22%) was lower than northern (87.65%, P <0.01), and the frequency of the genotype 2 was in low level (6.86%). The rate of coinfection with l b and other genotype was 10.29%. 2. The rate of infection with genotype l b in female patients was higher (93.61%) than that in male (75.0%) showing statistical significance (P <0.01). 3. In three age groups (< 30, 30 - 49 and > 50 years old) the rates of infection with genotype l b were 77.77%, 83.92% and 90.90%, respectively. 4. The detection rates of genotype l b in patients with infection period > 10 years and <10 years were 100% and 80.43% respectively (P <0.01). CONCLUSIONS: There are some relationship between HCV genotype and HCV geographic distribution, sex, age and infection period of patients.

Adolescent↗

[Study on human leucocyte antigen-DQ region gene polymorphism in cases of habitual abortion with anticardiolipin antibody].

OBJECTIVE: To investigate the relationship between human leucocyte antigen(HLA)-DQ region gene polymorphism and habitual abortion with anticardiolipin antibody(ACL). METHODS: Polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) was used to type HLA-DQA1 and HLA-DQB1 alleles in 30 cases of habitual abortion with anticardiolipin antibody and 90 women with normal pregnancy history. RESULTS: The frequency of DQB1 * 0303 was found to be significantly higher in ACL(+) habitual abortion group (33.3%) than those in normal control group (P < 0.05). Whereas, there was no significant difference found not only in frequency of other DQB1 alleles, but also in frequency of DQA1 alleles and DQA1-DQB1 haplotypes between two groups. CONCLUSION: The results show an association between ACL(+) habitual abortion and HLA-DQB1 * 0303, which suggest DQB1 * 0303 may be susceptible gene to ACL(+) habitual abortion.

Abortion, Habitual↗

[The research of a multimedia consultative system for prosthodontics].

OBJECTIVE: To study how to develop the consultative multimedia system for prosthodontics facilitating the communication between the dentists and patients, using multimedia techniques. METHODS: The Founder Author Tools V2.1 was used to develop the consultative system in the Pwin95/98 environment. Many forms (such as the articles, pictures, sound and video) of the prosthodontic knowledge were edited in this system. RESULTS: The consultative multimedia system for prosthodontics was developed, and there were three main parts of the system: (1) the background of medical departments, (2) introductions of the medical specialists (including their photos and working time), (3) introducing the common acknowledge of prosthodontics. CONCLUSION: The visualization of the prosthodontic problems consulted by patients frequently can facilitate the communication between the dentists and patients and spare visit time. This system are welcome by the patients.

Communication↗

Validation of a new technique to detect malingering of cognitive symptoms: the b Test.

We administered the b Test, a new measure to identify malingering requiring recognition of overlearned information, to 34 suspected malingerers and to 161 subjects in various clinical groups (moderate to severe head injury, elderly depressed, learning disability, schizophrenia, right and left CVA, and elderly normals). Comparisons of groups revealed more commission and omission errors in the suspected malingerers relative to all groups except the right stroke patients. In addition, suspected malingerers took longer to complete the task than all groups except right and left stroke patients and normal elderly. A cutoff of >2 commission errors produced a sensitivity of 76.5% and specificity for all comparison groups combined of 82.6%. Lower sensitivity rates were documented for omissions (58.8 using cutoff of >40) and time (57.6% using cutoff of >12 minutes), but specificity remained high at 85.1% and 83.9%, respectively. Thus, the b Test shows considerable potential as a malingering detection tool.

Journal Article↗

Insights into the structure and substrate interactions of the P-glycoprotein multidrug transporter from spectroscopic studies.

The P-glycoprotein multidrug transporter is a 170-kDa efflux pump which exports a diverse group of natural products, chemotherapeutic drugs, and hydrophobic peptides across the plasma membrane, driven by ATP hydrolysis. The transporter has been proposed to interact with its drug substrates within the membrane environment; however, much remains to be learned about the nature and number of the drug binding site(s). The two nucleotide binding domains are responsible for ATP binding and hydrolysis, which is coupled to drug movement across the membrane. In recent years, P-glycoprotein has been purified and functionally reconstituted in amounts large enough to allow biophysical studies. The use of spectroscopic techniques has led to insights into both its secondary and tertiary structure, and its interaction with nucleotides and drugs. In this review, we will summarise what has been learned by application to purified P-glycoprotein of fluorescence spectroscopy, circular dichroism spectroscopy and infra-red spectroscopy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Reversed-phase high-performance liquid chromatographic investigation of urinary normal and modified nucleosides of cancer patients.

Post-transcriptional modifications in RNA give rise to free modified ribonucleosides circulating in the blood stream and excreted in urine. Due to their abnormal levels in conjunction with several tumor diseases, they have been suggested as possible tumor markers. The developed RP-HPLC method has been applied to analyze the urinary nucleosides in 34 urinary samples from 15 kinds of cancer patients. The statistical analyses showed the urinary nucleoside excretion, especially modified nucleoside levels, in cancer patients were significantly higher than those in normal healthy volunteers. Factor analysis was used to classify the patients with cancer and normal healthy humans. It was found that using 15 urinary nucleoside levels or only five modified nucleoside levels as data vectors the factor analysis plot displayed two almost separate clusters representing each group.

Chromatography, High Pressure Liquid↗

Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells.

P-glycoprotein-mediated multidrug resistance can be reversed by the action of a group of compounds known as chemosensitizers. The interactions with P-glycoprotein of two novel hydrophobic peptide chemosensitizers (reversins 121 and 205) have been studied in model systems in vitro, and in a variety of MDR1-expressing intact tumor cells. The reversins bound to purified P-glycoprotein with high affinity (77-154 nM), as assessed by a quenching assay using fluorescently labeled purified protein. The peptides modulated P-glycoprotein ATPase activity in Sf9 insect cell membranes expressing human MDR1, plasma membrane vesicles from multidrug-resistant cells, and reconstituted proteoliposomes. Both peptides induced a large stimulation of ATPase activity; however, higher concentrations, especially of reversin 205, led to inhibition. This pattern was different from that of simple linear peptides, and resembled that of chemosensitizers such as verapamil. In both membrane vesicles and reconstituted proteoliposomes, 1-2 microM reversins were more effective than cyclosporin A at blocking colchicine transport. Reversin 121 and reversin 205 restored the uptake of [3H]daunorubicin and rhodamine 123 in MDR1-expressing cells to the level observed in the drug-sensitive parent cell lines, and also effectively inhibited the extrusion of calcein acetoxymethyl ester from intact cells. In cytotoxicity assays, reversin 121 and reversin 205 eliminated the resistance of MDR1-expressing tumor cells against MDR1-substrate anticancer drugs, and they had no toxic effects in MDR1-negative control cells. We suggest that peptides of the reversin type interact with the MDR1 protein with high affinity and specificity, and thus they may be good candidates for the development of MDR1-modulating agents to sensitize drug resistance in cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular evaluation of biopsy and autopsy specimens from patients receiving in vivo retroviral gene therapy.

We used the polymerase chain reaction (PCR) to assay for the presence of retroviral vector and replication-competent retrovirus (RCR) in autopsy and biopsy specimens from patients who received inoculations of retroviral vector producer cells (VPCs) into brain tumors or apparently normal tissues surrounding resected tumors. The PCR assays were capable of detecting 1 or more proviral copies of vector or RCR in 500,000 cells. Of 113 patients treated in clinical trials between 1994 and 1997, autopsy specimens were available from 32 patients. Brain tumor biopsies were also available from 24 patients. A total of 346 specimens was analyzed. Vector DNA was detected in 55% of tumor samples and 22% of brain samples obtained from resection margins. In contrast, most of the nonbrain tissues were negative for vector DNA; only low levels (<0.03%) of vector sequence were detected in 6 of 240 (2.5%) nonbrain tissues. Vector DNA was not detected in gonadal tissues from 12 men and 10 women. More importantly, RCR was not detected in any of the 134 biopsy and autopsy tissues tested, including all brain tumor, brain, and gonadal specimens. These results comprise the largest data set on molecular analysis of autopsy specimens from patients receiving retroviral gene therapy and indicate that distribution of retroviral vectors following injection of high doses of VPCs is limited to the site of inoculation.

Autopsy↗

Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1.

We followed 145 men with chronic hepatitis B virus (HBV) hepatitis for 10 years to determine whether exposure to aflatoxin, or concomitant exposure to hepatitis C virus (HCV), or family history of hepatocellular carcinoma (HCC) increased the risk of developing HCC. We collected 8 monthly urine samples before beginning follow-up and pooled them to detect aflatoxin metabolite M1 (AFM1). AFM1 was detected in 78 (54%) of the subjects. The risk of HCC was increased 3.3-fold (with a 95% confidence interval of 1.2-8.7) in those with detectable AFM1 (above 3.6 ng/L). This relative risk was adjusted for age and for HCV status. The attributable risk from exposure to detectable AFM1 was 0.553 (0.087, 0.94). The relative risk of fatal cirrhosis for those with elevated AFM1 was 2.8 (0.6, 14.3), and the odds of having a persistently elevated alanine transaminase (ALT) were 2.5-fold greater in those with detectable AFM1 (P =.007). Concomitant infection with HCV increased the risk of HCC 5.8-fold (2. 0-17), adjusted for age and AFM1 status. A family history of HCC increased the risk of HCC 5.6-fold, adjusted for age and AFM1. Four men with detectable AFM1 and HCC all had missense mutation in codon 249 of the p53 gene in cancer tissues. This study shows that exposure to AFM1 can account for a substantial part of the risk of HCC in men with chronic HBV hepatitis and adds importantly to the evidence that HCV and family history of HCC increase the risk of HCC in men with chronic HBV hepatitis.

Adolescent↗

Distribution of retroviral vectors and vector producer cells using two routes of administration in rats.

The clinical use of retroviral vector producer cells (VPCs) to deliver retroviral vectors efficiently to target cells has been investigated as a method to increase efficiency of gene delivery, presumably as a result of continued vector production in vivo. Studies were conducted in rats to evaluate the distribution of vector to distal organs and tissues as measured by transduction. Rats were treated with two doses of VPCs using two routes of administration: (1) subcutaneous injection, chosen to maximize both the dose and exposure of animals, thereby enabling identification of potential target organs under worst-case conditions; and (2) direct injection into brain parenchyma, chosen to mimic the intended clinical route of administration and provide an estimate of risk to patients receiving this therapy. Twelve organs or tissues were collected 7 days after administration of VPCs and analyzed by PCR for the presence of vector and vector producer cell sequences. Vector was detected most frequently at the site of injection by either route of administration. Less frequently, vector was detected in draining lymph nodes at the higher dose only using either route of injection. Single specimens of lung and contralateral skin were positive for vector following subcutaneous administration only. Vector was detected in gonadal tissue from a single low-dose male following subcutaneous administration, but this finding was not reproduced in any high-dose male or any males injected intracerebrally. In contrast, VPCs were detected only at the site of administration. The frequency of detection of VPCs 7 days after administration was higher when rats were injected by the intracerebral route. Based on these studies, gene transfer to distal organs or gonadal tissue following intracerebral administration of VPCs is not considered to be a risk to patients undergoing retroviral vector gene therapy for the treatment of brain cancer (glioblastoma multiforme; GBM).

Animals↗

Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations.

AIMS: To determine the effects of mibefradil on the nletabolism in human liver microsomal preparations of the HMG-CoA reductase inhibitors simvastatin, lovastatin, atorvastatin, cerivastatin and fluvastatin. METHODS: Metabolism of the above five statins (0.5, 5 or 10 microM), as well as of specific CYP3A4/5 and CYP2C8/9 marker substrates, was examined in human liver microsomal preparations in the presence and absence of mibefradil (0.1-50 microM). RESULTS: Mibefradil inhibited, in a concentration-dependent fashion, the metabolism of the four statins (simvastatin, lovastatin, atorvastatin and cerivastatin) known to be substrates for CYP3A. The potency of inhibition was such that the IC50 values (<1 microM) for inhibition of all of the CYP3A substrates fell within the therapeutic plasma concentrations of mibefradil, and was comparable with that of ketoconazole. However, the inhibition by mibefradil, unlike that of ketoconazole, was at least in part mechanism-based. Based on the kinetics of its inhibition of hepatic testosterone 6beta-hydroxylase activity, mibefradil was judged to be a powerful mechanism-based inhibitor of CYP3A4/5, with values for Kinactivation, Ki and partition ratio (moles of mibefradil metabolized per moles of enzyme inactivated) of 0.4 min(-1), 2.3 microM and 1.7, respectively. In contrast to the results with substrates of CYP3A, metabolism of fluvastatin, a substrate of CYP2C8/9, and the hydroxylation of tolbutamide, a functional probe for CYP2C8/9, were not inhibited by mibefradil. CONCLUSION: Mibefradil, at therapeutically relevant concentrations, strongly suppressed the metabolism in human liver microsomes of simvastatin, lovastatin, atorvastatin and cerivastatin through its inhibitory effects on CYP3A4/5, while the effects of mibefradil on fluvastatin, a substrate for CYP2C8/9, were minimal in this system. Since mibefradil is a potent mechanism-based inhibitor of CYP3A4/5, it is anticipated that clinically significant drug-drug interactions will likely ensue when mibefradil is coadministered with agents which are cleared primarily by CYP3A-mediated pathways.

Aryl Hydrocarbon Hydroxylases↗

Dynamic redistribution of calmodulin in HeLa cells during cell division as revealed by a GFP-calmodulin fusion protein technique.

It has been suggested by many studies that Ca2+ signaling plays an important role in regulating key steps in cell division. In order to study the down stream components of calcium signaling, we have fused the gene of calmodulin (CaM) with that of green fluorescent protein (GFP) and expressed it in HeLa cells. The GFP-CaM protein was found to have similar biochemical properties as the wild-type CaM, and its distribution was also similar to that of the endogenous CaM. Using this GFP-tagged CaM as a probe, we have conducted a detailed examination of the spatial- and temporal-dependent redistribution of calmodulin in living mammalian cells during cell division. Our major findings are: (1) high density of CaM was found to distribute in two sub-cellular locations during mitosis; one fraction was concentrated in the spindle poles, while the other was concentrated in the sub-membrane region around the cell. (2) The sub-membrane fraction of CaM became aggregated at the equatorial region where the cleavage furrow was about to form. The timing of this localized aggregation of CaM was closely associated with the onset of cytokinesis. (3) Using a TA-CaM probe, we found that the sub-membrane fraction of CaM near the cleavage furrow was selectively activated during cell division. (4) When we injected a CaM-specific inhibitory peptide into early anaphase cells, cytokinesis was either blocked or severely delayed. These findings suggest that, in addition to Ca2+ ion, CaM may represent a second signal that can also play an active role in determining the positioning and timing of the cleavage furrow formation.

Calmodulin↗

Modern woman medical education in China after the introduction of western medicine.

In 1879, Nanhua (Southern China) Medical School, the earliest school for western medical professionals in China, first admitted women to study medicine in separate class. In 1885, Yamei King became the first woman conferred a medical doctor degree from the US. The first woman medical school, the Canton Woman Medical School, began to enroll students. In 1933, of the 3655 students in the 28 medical schools, 619 were female, representing 16.94% of the total. Among these schools, 2 were exclusively for females, 3 for males, the remaining 23 for both sexes. In 1934, special committee for nurse and midwife were set up in the medical education committee in Ministry of Education. Up to this year, there were 2 state - run, 10 province - run and 206 private - nurse's schools, and 21 schools for midwife training.

China↗

[Apoptosis of human gastric cancer cells induced by bcl-2 antisense oligodeoxynucleotides].

OBJECTIVE: To study the regulation of bcl-2 gene expression and induction of apoptosis by bcl-2 antisense oligodeoxynucleotides (AS-ODN) on human gastric cancer cell line BGC-823 in vitro. METHODS: Two bcl-2 AS-ODNs were synthesized, one covering the initiation sequence of translation of bcl-2 mRNA (AS-ODN1) and the other covering the protein coding region (AS-ODN2). BGC-823 cells in logarithmic phase of growth were cultured in the presence of free or liposome (DOTAP)-encapsulated AS-ODN. Cell growth was assessed by MTT method. The expression of bcl-2 at mRNA and protein levels was examined by RT-PCR and flow cytometry, respectively. Electron microscopy and flow cytometry were used to demonstrate apoptotic changes in AS-ODN-treated cells. RESULTS: Both AS-ODNs inhibited proliferation of BGC-823 cells. The inhibitory activity of AS-ODN2 was stronger than that of AS-ODN1. AS-ODNs encapsulated in liposome led to more marked inhibition of cell growth than free AS-ODNs. Both AS-ODNs reduced bcl-2 expression of BGC-823 cells at mRNA and protein levels. Apoptosis of BGC-823 cells were demonstrated by the appearance of apoptotic bodies, chromatin condensation and pre-G1 peak on flow cytometric analysis. CONCLUSION: Antisense oligodeoxynucleotide of bcl-2 decreases bcl-2 gene expression and induces apoptosis of human gastric cancer cells in vitro.

Apoptosis↗

[A study of dental cast by using 3D laser non-contact measurement and analysis].

OBJECTIVE: To research and develop a new scanning 3-D digitization system for noncontact measuring of dental cast. METHODS: By using two pulsate motor to make the synthetic movement of the dental cast, a special semiconductor laser and two special line-array CCD, the 3D coordinate could be gotten from the surface of the dental cast in any where. The program which is developed by Visual C++ language and run under the Windows surroundings can control the scanner, rebuild the 3D graphics and measure the coordinate of the dental cast. RESULTS: The system offers 70 mm x 70 mm x 70 mm measurement scope, 0.01 mm resoling power < 0.1 mm mean deviation, 25 mins for single cast scanning. CONCLUSION: This system provides many advantages such as in precision, simplicity, high efficiency, and wide range of measurement contents with complete direct view. It also supplied us some new functions which can not be done with traditional way of measurement.

Dental Casting Technique↗

[Operative results of tethered cord syndrome].

OBJECTIVE: To evaluate the treatment results of 22 cases of spinal tethered cord syndrome (TCS) using microneurosurgical technique. METHODS: Form 1994 to 1997, 22 cases of TCS verified by MRI were treated. All patients'tips of conus were below L(2) vertebra shown by MRI. In this group, 4 cases had lipid disease in the sacral canal, 5 piloidal sinus, and 13 thick filum. The patients were operated on using linear incision. The incision included the terminal conus and the whole filum. Under the microscope, the adhesions of the caudal equine were separated and the filum was found out. The caudal equine was well combed. Lipoma and piloidal sinus were removed totally or partially. Loosening the spinal conus and repairing the dural matter prevented re-adhesion and re-tether. RESULTS: Follow-up (0.5 - 3 years) showed that all of the patients were recovered in different levels. CONCLUSIONS: TCS should be found as early as possible and treated under the microsurgical technique.

Adolescent↗

[Selectivity tuning in multi-binary eluents for reversed-phase liquid chromatography (RPLC)].

In this article, the retention equation and the relationship between retention parameters and the parameters of molecular structure deduced from statistical thermodynamics in RPLC have been used to explain the difference of selectivity towards a particular species of compounds polycyclic aromatic hydrocarbons (PAHs). Methanol/water, acetonitrile/water and isopropanol/acetonitrile have been provided in advance, then the retention behaviors of sixteen PAHs under three binary solvent systems have been investigated. It is found that each pair of binary solvents of methanol/water, acetonitrile/water and isopropanol/acetonitrile has its own unique selectivity. The best selectivity obtained for acenaphthene and fluorene is methanol/water system for fluoranthene and pyrene is acetonitrile/water, and for benzo[g,h,i]perylene and dibenzo[a,h]anthracene is isopropanol/acetonitrile. So a three-stepwise gradient elution of multi-binary mobile phase can be chosen for separation of 16 PAHs.

Acenaphthenes↗