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Biomedical subjects

Bing Chen

Publications and source records attributed to Bing Chen.

86 records · Page 5Linked to original sources

Antihyperalgesia effect of BmK AS, a scorpion toxin, in rat by intraplantar injection.

The antihyperalgesia effect of BmK AS, a novel sodium channel-specific polypeptide modulator from Chinese scorpion venom in rats was investigated in this study. PWLs (paw withdrawal latency) were increased to 150+/-28, 203+/-34 and 250+/-17% of the control by administration of BmK AS (10 microl) at the concentration of 0.001, 0.01 and 0.1 mg/ml in carrageenan-induced inflamed rats, respectively. Meanwhile, PWLs were enhanced to about 126+/-4, 132+/-4 and 140+/-6% of the control at the same applied concentration of BmK AS in normal rats. The results suggest that BmK AS can induce peripheral antihyperalgesia and antinociception, which probably by modulating the sodium channel on nociceptive afferent pathway.

Analgesics↗

A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis.

With the advent of HIV and the widespread emergence of drug-resistant strains of Mycobacterium tuberculosis, newer control strategies in the form of a better vaccine could decrease the global incidence of tuberculosis. A desirable trait in an effective live attenuated vaccine strain is an ability to persist within the host in a limited fashion in order to produce important protective antigens in vivo. Attenuated M. tuberculosis vaccine candidates have been constructed by deleting genes required for growth in mice. These candidate vaccines did not elicit adequate protective immunity in animal models, due to their inability to persist sufficiently long within the host tissues. Here we report that an auxotrophic mutant of M. tuberculosis defective in the de novo biosynthesis of pantothenic acid (vitamin B5) is highly attenuated in immunocompromised SCID mice and in immunocompetent BALB/c mice. SCID mice infected with the pantothenate auxotroph survived significantly longer (250 days) than mice infected with either bacille Calmette-Guerin (BCG) vaccine or virulent M. tuberculosis (77 and 35 days, respectively). Subcutaneous immunization with this auxotroph conferred protection in C57BL/6J mice against an aerosol challenge with virulent M. tuberculosis, which was comparable with that afforded by BCG vaccination. Our findings highlight the importance of de novo pantothenate biosynthesis in limiting the intracellular survival and pathogenesis of M. tuberculosis without reducing its immunogenicity in vaccinated mice.

Animals↗

[Tissue engineered tendon with skin fibroblasts as seed cells, a preliminary study].

OBJECTIVE: To investigate the effect of tissue engineered tendon using autologous dermal fibroblasts in repairing tendon damage. METHODS: Skin tissues were resected from abdomen of 5 pigs. Fibroblasts were isolated from the skin pieces and cultured in vitro. Bundles of polyglycolic acid (PGA) were arranged in parallel and mixed with the suspension of fibroblasts to form a cell-scaffolded construct, which was further cultured in vitro for 1 week. The tendon of musculus flexor digitorum superficialis of pig's right leg was cut with a defect 3 cm long and then bridged with the cultured construct. Six weeks later, specimens of the regenerated tendon of right musculus flexor digitorum superficialis and specimens of corresponding left leg were taken for gross examination, microscopy and biomechanical analysis. RESULTS: After implantation of the fibroblast-biomaterial complex the wounds healed up and the pigs moved well. The histology of the implanted tendon was similar to that of natural tendon. The breaking strength and maximum tensile force were 173.0 +/- 18.2 N and 18.9 +/- 1.9 MPa, reaching 57.4% and 51.9% of those of normal tendon respectively. CONCLUSION: Skin fibroblasts can be used as seed cells to regenerate tendon with normal structure and function.

Animals↗

Variant-type PML-RAR(alpha) fusion transcript in acute promyelocytic leukemia: use of a cryptic coding sequence from intron 2 of the RAR(alpha) gene and identification of a new clinical subtype resistant to retinoic acid therapy.

The physiologic actions of retinoic acids (RAs) are mediated through RA receptors (RARs) and retinoid X receptors (RXRs). The RAR(alpha) gene has drawn particular attention because it is the common target in all chromosomal translocations in acute promyelocytic leukemia (APL), a unique model in cancer research that responds to the effect of RA. In the great majority of patients with APL, RAR(alpha) is fused to the PML gene as a result of the t(15;17) translocation. Three distinct types of PML-RAR(alpha) transcripts, long (L), short (S), and variant (V), were identified. The V-type is characterized by truncation of exon 6 of PML and in some cases by the insertion of a variable "spacer" sequence between the truncated PML and RAR(alpha) mRNA fusion partners, although the precise mechanisms underlying formation of the V-type transcript remain unclear. To get further insights into the molecular basis of the t(15;17), we sequenced the entire genomic DNA region of RAR(alpha). Of note, all previously reported "spacer" sequences in V-type transcripts were found in intron 2 of the RAR(alpha) gene and most of these sequences were flanked by gt splice donor sites. In most cases, these "cryptic" coding sequences maintained the ORF of the chimeric transcript. Interestingly, two cases with a relatively long spacer sequence showed APL cellular and clinical resistance to RA treatment. In these cases, the aberrant V-type PML-RAR(alpha) protein displayed increased affinity to the nuclear corepressor protein SMRT, providing further evidence that RA exerts the therapeutic effect on APL through modulation of the RAR-corepressor interaction. Finally, among patients with the L- or S-type PML-RAR(alpha) fusion transcript, some consensus motifs were identified at the hotspots of the chromosome 17q breakpoints within intron 2 of RAR(alpha), strengthening the importance of this intron in the molecular pathogenesis of APL.

Antineoplastic Agents↗

[Randomized double-blind clinical trial of moderate dosage naloxone in acute moderate and severe traumatic brain injury].

OBJECTIVE: To evaluate the efficacy and safety of moderate dosage naloxone in acute moderate and severe traumatic brain injury. METHODS: A randomized double-blind prospective clinical trial was done to compare the differences of naloxone and saline in acute moderate and severe traumatic brain injury. Naloxone or saline placebo was intravenously given for 10 days. We followed up for at least 1 month. The indexes of assessment of prognosis were Glasgow outcome scale, verbal function and motor function. RESULTS: Forty cases were enrolled in the clinical trial, evenly divided into the naloxone group, and the saline group. On the 10th day after the treatment, Glasgow coma scale, improvement of abnormity of blood pressure, rhythm of the heart and breath in the naloxone group were significantly higher than those in the saline group. The mortalities of the naloxone group and the saline group were 0 and 5% respectively. After the one-month follow-up, Glasgow outcome scale and verbal function in the naloxone group were significantly higher than those in the saline group. In addition, a patient was found with mania possibly caused by naloxone. CONCLUSION: Early application of moderate dosage naloxone in acute traumatic brain injury may significantly reduce the mortality rate and improve the recovery of nerve function.

Adolescent↗

Asian scorpion BmK venom induces plasma extravasation and thermal hyperalgesia in the rat.

In the present study, the effects of scorpion Buthus martensi Karsch (BmK) venom on plasma extravasation and paw withdrawal latency (PWL) to radiant heat have been investigated in rats. BmK venom (20-200 microg/kg) by subcutaneous injection under the surface of the rat hindpaw causes dose-dependant increased plasma extravasation that could be partially inhibited by intraperitoneal (i.p.) injected morphine (6 mg/kg). Peak plasma extravasation was reached at 10 min and persisted for 60 min at a dose of 200 microg/kg. BmK venom induced cutaneous hyperalgesia as indicated by decreased PWL to radiant heat in the ipsilateral paw following subcutaneous injection of 20 microg/kg BmK venom without effect on PWL of the contralateral hindpaw. Meanwhile, it was found that i.p. morphine injection could inhibit this decreased ipsilateral PWL. The results thus suggest that BmK venom could induce peripheral inflammation in rat by subcutaneous injection, and may prove a valuable animal model for investigating the pathophysiology of a number of inflammatory diseases and identifying potential anti-inflammatory and analgesic drugs.

Animals↗

c-Fos expression in rat spinal cord induced by scorpion BmK venom via plantar subcutaneous injection.

The aim of this study was to assess the cell-type and distribution of highly activated neurons in rat spinal cord underlying nociceptive responses induced by scorpion BmK venom using Fos immunohistochemistry. BmK venom was intraplantarly injected into one hind paw of a conscious rat. Fos-like immunoreactive neurons were found to predominantly distribute at L4-5 segments in the rat spinal cord after BmK venom application. c-Fos labeling was most dense in the medial half portion of laminae I-II, moderately dense in laminae V-VI and less dense in laminae III-IV, VII-X. c-Fos labeling could be detected at 0.5 h, reached the peak at 2 h, decreased steeply from 4 h and then almost disappeared at 24 h. Ten to fifty micrograms of BmK venom was deemed to be a sufficient dosage to evoke c-Fos expression. On the other hand, c-Fos expression induced by BmK venom could be suppressed partially by systemic morphine in a dose-dependent manner. The results suggest that the different extent of activities of neuronal subpopulation in the spinal cord involved in nociceptive transmission manifesting as c-Fos expression, were mainly correlated with mechanisms underlying the generation, maintenance and/or modulation of spontaneous pain and hyperalgesia evoked by BmK venom.

Afferent Pathways↗

Dynamic determination and possible mechanism of amino acid transmitter release from rat spinal dorsal horn induced by the venom and a neurotoxin (BmK I) of scorpion Buthus martensi Karsch.

In the present communication, we determined the dynamic release of amino acid transmitters from spinal dorsal horn induced by scorpion Buthus martensi Karsch (BmK) venom and a neurotoxin (BmK I). The results found that glutamate and aspartate release could be evoked significantly within the initial 30 min with the applied doses of either 0.05 and 0.01 mg BmK venom or 0.01 and 0.002 mg BmK I. However, gamma-aminobutyric acid (GABA) release could be largely evoked during the second 30 min by the venom, but not by BmK I. The result suggested that nociceptive afferent fibers could be activated to induce excitatory amino acid release from spinal dorsal horn by nociceptive factors such as BmK I, but the delayed release of GABA might be attributed to the modulating role of some antinociceptive components in the venom.

Animals↗

Infection of mice with aerosolized Mycobacterium tuberculosis: use of a nose-only apparatus for delivery of low doses of inocula and design of an ultrasafe facility.

Aerosolized delivery of virulent or hypervirulent Mycobacterium tuberculosis requires careful consideration of methodology and safety. To maximize safety, we installed a nose-only aerosol apparatus that can reproducibly deliver a low dose (<100 CFU per mouse) of M. tuberculosis in a carefully designed biohazard facility.

Aerosols↗

[Establishment and application of multiplex FISH in detection of the complex chromosome abnormalities in leukemia].

OBJECTIVE: To set up the technical system of multiplex fluorescence in situ hybridization M-FISH and to explore its application in detection of the complex chromosome abnormalities in leukemia. METHODS: The complex chromosome abnormalities of two leukemia patients were analyzed by the combination use of classical cytogenetics, chromosome painting (CP), FISH and M-FISH. RESULTS: In a case of acute lymphoblastic leukemia-L2, the complex karyotype: 46,XY,der(2)t(2;9),der(9)t(9;12;22) was identified by M-FISH, which was detected as 46,XY,der(9)t(9;12) by classical cytogenetics; In a case of acute monocytic leukemia-M5, the complex chromosome abnormalities: 46,XY,der(2)t(2;17), der(10)t(10;11;17), der(11)t(11;?) was revealed by M-FISH, which was confirmed by CP and FISH, and mixed lineage leukemia (MLL) gene was also found involved in this complex chromosome translocation. CONCLUSION: M-FISH was proved to be a powerful tool to examine the complicated karyotypes and hopefully to elucidate nearly all chromosomal aberrations in leukemia and other cancers.

Chromosome Aberrations↗

Effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia.

AIM: To determine the effect of CYP2D6*10 genotype on propafenone pharmacodynamics in Chinese patients with ventricular arrhythmia. METHODS: Seventeen Chinese patients with ventricular premature contractions (VPC> or =1000/d) were recruited. They were normal in routine laboratory testing and administered propafenone hydrochloride 450-600 mg per day in three divided doses. Twelve lead cardiogram and 24 h Holter monitoring were performed before and after 7 d treatment of propafenone. Steady-state peak and trough concentrations of propafenone were measured by HPLC method. CYP2D6*10 genotypes of patients were assayed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Total inhibitory rate of VPC was 79.9 % in 17 patients with ventricular arrhythmia after propafenone treatment. PR interval prolongation was increased from 0.146 s+/-0.018 s to 0.161 s+/-0.022 s (P<0.05). CYP2D6 genotypes played an important role in plasma levels and effects of propafenone. In 450 mg/d group, patients with homozygous mutant of CYP2D6*10 not only had a Cmax of propafenone two times as high as those of wild-type genotype, but also showed a two fold higher inhibitory rate of VPC compared with those with homozygous CYP2D6*1 (P<0.05). CONCLUSION: CYP2D6*10 genotype is relevant to decreased activity of CYP2D6 enzyme in Chinese patients. Elevated plasma concentration is consistent with better efficacy of propafenone in patients with ventricular arrhythmia.

Adult↗

Antisense to cyclin D1 reverses the transformed phenotype of human gastric cancer cells.

AIM:To further investigate the effect of cyclin D1 on the biologic behavior of cancer cells and its potential role in gene therapy of tumor.METHODS:A cyclin D1 subcloning plasmid termed BKSD1 was constructed by subcloning the human cyclin D1 cDNA into Bluescript-KS, a plasmid vector with a pair of T7 and T3 promoters, with recombinant DNA technology of molecular biology. So,it is easy to generate digoxigenin (DIG)-labeled RNA probes of antisense and sense to cyclin D1 using RKSD1 as a template vector. PDORD1AS, an eukaryotic expression vector containing the full-length human cyclin D1 cDNA in its antisense orientation cloned into the retroviral vector pDOR-neo, was successfully constructed with BKSD1 to change restriction sites. A gastric cancer cell line, SGC7901/VCR, was transfected with pDORD1AS by Lipofect Amine-mediated introduction and a subline termed SGC7901/VCRD1AS, which had stable overexpression of antisense RNA to cyclin D1, was obtained by selection in G418. The subline, control subline transfected pDOR-neo and SGC7901/VCR were evaluated by methods of immunohistochemistry, flow cytometry, molecular hybridization, morphology and cell biology.RESULTS:Compared with control cell lines, SGC7901/VCRD1AS had a reduced expression of cyclin D1 (inhibition rate was about 36%), increased cell size and cytoplasm to nucleus ratio, increased doubling time (42.2h to 26.8h and 26.4h), decreased saturation density (18.9X10(4) to 4.8X10(5) and 4.8X10(5)), increased percentage of cells in the G(1)/G(0) phase (80.9%-64.6% and 63.8%), reacquired serum dependence, and a loss of tumorigenicity in nude mice (0/4 to 4/4 and 4/4).CONCLUSION: Stable overexpression of antisense RNA to cyclin D1 can reverse the transformed phenotype of human gastric cancer cells and may provide an approach of gene therapy for gastric cancer.

Journal Article↗

Autologous hematopoietic stem cell transplantation for progressive multiple sclerosis: report of efficacy and safety at three yr of follow up in 21 patients.

OBJECTIVE: To observe the efficacy and toxicity of autologous hematopoietic stem cell transplantation (HSCT) in progressive multiple sclerosis (PMS). METHODOLOGY: Twenty-one patients with PMS were treated with autologous HSCT. Stem cells were mobilized with cyclophosphamide (CY) and granulocyte colony-stimulating factor. After conditioning regimen of CY and total body irradiation or BEAM, stem cells were reinfused. CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion. The probabilities of confirmed progression-free survival and disease activity-free survival were used to assess the efficacy and the adverse experiences were recorded to detect the toxicities. RESULTS: The median follow-up time was 42 (6-65) months. The probabilities of confirmed progression-free survival and the disease activity-free survival were 75% and 33.3%, respectively. The principal adverse events included allergy, infection, elevation of liver enzymes, transient neurologic deterioration and depression. Two patients died of severe pneumonia and varicella-zoster virus hepatitis, at 4.5 and 15 months post-transplant, respectively. CONCLUSIONS: Autologous HSCT seems beneficial to PMS. However, more patients and longer follow up would be required to assess the risk/benefit ratio.

Disease Progression↗

Cold hardiness and supercooling capacity in the pea leafminer Liriomyza huidobrensis.

Pupal SCP (supercooling point) of Liriomyza huidobrensis showed no variation with age, with an average of -20.9 degree C. Low temperature survival of different ages of pupae showed no correlation with their SCP. Nonlinear regression analysis found that the response of L. huidobrensis pupae to exposure time under different low temperature regimes above -5 degree C was best fitted by a logistic equation. Both low temperature and exposure time had significant effects on pupal mortality. Temperatures above 5 degree C do not prevent pupae from emergence. L. huidobrensis was shown to be a freeze susceptible, and at the same time, a chill tolerant insect. It can tolerate subzero temperatures by supercooling. Compared with L. sativae, another dominant leafminer in China, L. huidobrensis is more cold tolerant. Our results explain differences between the species in geographic distribution and phenology.

Animals↗