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Biomedical subjects

Ping Chen

Publications and source records attributed to Ping Chen.

At least 109 records · Page 6Linked to original sources

[Relationship between secretory otitis media and language disorder in children: analysis of 1108 cases].

OBJECTIVE: To discuss the relationship between secretory otitis media (SOM) and language disorder in children. METHOD: In 1108 language disorder cases, auditory brainstem responses (ABR) and acoustic immittance were measured respectively. According to the ABR threshold, all the children were divided into four groups: the normal group, the mild hearing loss group, the middle hearing loss group and the severe hearing loss group. RESULT: Of all the ears examined, 59.5% had hearing loss, while 12.64% had SOM. In the children of language disorder, the distribute of the "B" type tympanograph from much to little was:the mild hearing loss group, the middle hearing loss group, the severe hearing loss group and the normal group ( P < 0.01). The average hearing threshold of a part children with SOM decreased after therapy ( P < 0.01). The children with the severe hearing loss had no evident changes after therapy. CONCLUSION: Hearing disorder is the main cause of language disorder in children. While SOM recovers in children with mild or middle hearing loss, the language in part of them could be improved. However, the language in those who with severe hearing loss probably remains the primary level.

Adolescent↗

[Construction of reversed caspase-3 and it's effect on apoptosis induction in human lung adenocarcinoma cell line A549].

OBJECTIVE: To investigate the effect of reversed caspase-3 expression vector on apoptosis of human lung adenocarcinoma cell line A549. METHODS: Reversed pcDNA 3.1-rev-caspase-3 plasmid and wild type pcDNA3.1-caspase-3 plasmid were constructed by genetic recombination. Three experiments (groups) with A549 cells were carried out: a group of transfection with pcDNA 3.1-rev-caspase plasmid, a group of transfection with pcDNA 3.1-caspase plasmid, and a control group of transfection with pcDNA 3.1 plasmid. Intervention with DEVD-fmk, an inhibitor of caspase-3, was carried out in the first two groups. The activity of caspase-3, the apoptosis and the growth of A549 cells were measured. RESULTS: (1) The activity of caspase-3 in the pcDNA 3.1-rev-caspase-3 plasmid group and pcDNA 3.1-caspase-3 plasmid group was (11.87 +/- 0.92)% and (5.34 +/- 0.38)%, respectively, significantly higher in the former group (t = 16.02, P < 0.01). After intervention with DEVD-fmk, the activity of caspase-3 in pcDNA 3.1-rev-caspase-3 plasmid group and in pcDNA 3.1-caspase-3 plasmid group was (7.04 +/- 0.48)% and (4.51 +/- 0.20)%, respectively, also significantly higher in the former group (t = 11.86, P < 0.01). (2) Flow cytometry showed that the apoptosis rate of A549 cells in pcDNA 3.1-rev-caspase-3 plasmid group, pcDNA 3.1-caspase-3 plasmid group and pcDNA 3.1 plasmid group was (20.1 +/- 3.5)%, (7.8 +/- 2.8)% and (1.4 +/- 0.3)%, respectively. The difference of the apoptosis rate was significant (F = 44.01, P < 0.01). (3) The survival rates of A549 cells in the pcDNA 3.1-rev-caspase-3 plasmid group, pcDNA 3.1-caspase-3 plasmid group and pcDNA 3.1 plasmid group were (35.7 +/- 1.1)%, (72.8 +/- 2.9)% and (85.4 +/- 4.8)%, respectively. The survival rate of A549 cells in pcDNA 3.1-rev-caspase-3 plasmid group was lower than those in the other two groups (F = 375.07, P < 0.01). CONCLUSIONS: pcDNA 3.1-rev-caspase-3 in A549 cells has a strong activity and can resist caspase-3 inhibitor in A549 cells. It can also induce A549 cell apoptosis and inhibit the growth of A549 cells.

Adenocarcinoma↗

[Characteristics of hearing loss in 299 high-risk neonates].

OBJECTIVE: To compare the occurrence of hearing loss in neonates with hyperbilirubinemia, hypoxic-ischemic encephalopathy (HIE) and very low-birth weight infant (VLBW) body mass, and to provide evidence for early intervention. METHODS: Totally 299 high-risk neonates (598 ears) were divided into six groups: pure hyperbilirubinemia group, pure HIE group, hyperbilirubinemia with HIE group, hyperbilirubinemia with VLBW group, HIE with LBWI group, hyperbilirubinemia with VLBW and HIE mass group. Auditory brainstem response (ABR) was detected in all groups. RESULTS: The hearing threshold of ABR and the abnormal rate of hyperbilirubinemia with LBWI and HIE were much higher than that of pure hyperbilirubinemia and pure HIE neonates. CONCLUSIONS: Of the three high-risk factors, hearing loss occurs more often and more serious in neonates with hyperbilirubinemia and with VLBW while as HIE body mass. So the babies should receive hearing screening with ABR and be treated in time or following up as early as possible.

Evoked Potentials, Auditory, Brain Stem↗

[Preliminary study on the effects of an artificial liver support system in the treatment of medicamentous liver insufficiency].

OBJECTIVES: To study the effectiveness of an artificial liver support system. METHODS: Thirty-two patients with medicamentous liver insufficiency were treated with an artificial liver support system in addition to the routine medicinal therapy. Thirty patients treated with routine medicinal therapy only served as controls. RESULTS: The clinical symptoms (e.g. hepatic encephalopathy) and the laboratory indices (serum total bilirubin and prothrombin time) of the treatment group patients were obviously improved compared with those of the control group patients (P < 0.05). The cure rate and hospitalization days were 90.6% (26/32) and 47 days respectively in the treatment group, and 43.3% (13/30) and 72 days in the control group (P < 0.05). CONCLUSION: Using an artificial liver support system combined with routine medicinal therapy is more effective than using medication alone.

Adult↗

[Absorption line intensities of phosphine in the regions 1 950-2 480 cm(-1) and 3 280-3 580 cm(-1) studied by Fourier-transform spectroscopy].

The data of line intensities of the fundamental and low overtone absorption bands of phosphine are the basic reference data for the applications in quantative analysis and astronomy. The method of high-resolution Fourier-transform spectroscopy study on the absorption line intensities is discussed. With a series of measurement and fitting the line profiles, altogether 1760 absorption lines intensities of phosphine were obtained, corresponding to five bands in the 1950-2480 cm(-1) region and four bands in the 3 280-3 580 cm(-1) region. The accuracy of the line intensities was estimated to be +/-6%.

Absorption↗

Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.

A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent antiproliferative activity against hematological and solid tumor cell lines. Compound 13 was orally active in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels. On the basis of its robust in vivo activity and favorable pharmacokinetic profile, 13 was selected for additional characterization for oncology indications.

Adenosine Triphosphate↗

Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice.

Ion channels in the degenerin-epithelial sodium channel (DEG-ENaC) family perform diverse functions, including mechanosensation. Here we explored the role of the vertebrate DEG-ENaC protein, acid-sensing ion channel 2 (ASIC2), in auditory transduction. Contributions of ASIC2 to hearing were examined by comparing hearing threshold and noise sensitivity of wild-type and ASIC2 null mice. ASIC2 null mice showed no significant hearing loss, indicating that the ASIC2 was not directly involved in the mechanotransduction of the mammalian cochlea. However, we found that (1) ASIC2 was present in the spiral ganglion (SG) neurons in the adult cochlea and that externally applied protons induced amiloride-sensitive sodium currents and action potentials in SG neurons in vitro, (2) proton-induced responses were greatly reduced in SG neurons obtained from ASIC2 null mice, indicating that activations of ASIC2 contributed a major portion of the proton-induced excitatory response in SG neurons, and (3) ASIC2 null mice were considerably more resistant to noise-induced temporary, but not permanent, threshold shifts. Together, these data suggest that ASIC2 contributes to suprathreshold functions of the cochlea. The presence of ASIC2 in SG neurons could provide sensors to directly convert local acidosis to excitatory responses, therefore offering a cellular mechanism linking hearing losses caused by many enigmatic causes (e.g., ischemia or inflammation of the inner ear) to excitotoxicity.

Acid Sensing Ion Channels↗

Characteristics of structure, composition, mass spectra, and iron release from the ferritin of shark liver (Sphyrna zygaena).

The ferritin consists of a protein shell constructed of 24 subunits and an iron core. The liver ferritin of Sphyrna zygaena (SZLF) purified by column chromatography is a protein composed of eight ferritins containing varying iron numbers ranging from 400+/-20 Fe3+/SZLF to 1890+/-20 Fe3+/SZLF within the protein shell. Nature SZLF (SZLFN) consisting of holoSZLF and SZLF with unsaturated iron (SZLFUI) to have been purified with polyacrylamide gel electrophoresis (PAGE) exhibited five ferritin bands with different pI values ranging from 4.0 to 7.0 in the gel slab of isoelectric focusing (IEF). HoloSZLF purified by PAGE (SZLFE) not only had 1890+/-20 Fe3+/SZLFE but also showed an identical size of iron core observed by transmission electron microscopy (TEM). Molecular weight of approximately 21 kDa for SZLFE subunit was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Four peaks of molecular ions at mass/charge (m/z) ratios of 10611.07, 21066.52, 41993.16, and 63555.64 that come from the SZLFE were determined by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF MS), which were identified as molecular ions of the ferritin subunit (M+) and its polymers, namely, [M]2+, [M]+, [2M]+, and [3M]+, respectively. Both SZLFE and a crude extract from shark liver of S. zygaena showed similar kinetic characteristics of complete iron release with biphasic behavior. In addition, a combined technique of visible spectrometry and column chromatography was used for studying ratio of phosphate to Fe3+ within the SZLFE core. Interestingly, this ratio maintained invariable even after the iron release, which differed from that of other mammal ferritins.

Animals↗

Suppression of malignant growth of human breast cancer cells by ectopic expression of integrin-linked kinase.

Allelic loss at the short arm of chromosome 11 is one of the most common and potent events in the progression and metastasis of breast cancer. Here, we present evidence that the Integrin-Linked Kinase (ILK) gene maps to the commonly deleted chromosome 11p15.5 and suppresses malignant growth of human breast cancer cells both in vitro and in vivo. ILK is expressed in normal breast tissue but is downregulated in metastatic breast cancer cell lines and in advanced breast cancers. Transfection of wild-type ILK into the MDA-MB-435 mammary carcinoma cells potently suppressed their growth and invasiveness in vitro and reduced the cells' ability to induce tumors and metastasize in athymic nude mice. Conversely, expression of the ankyrin repeat or catalytic domain mutants of ILK failed to suppress the growth of these cells. Growth suppression by ILK is not due to apoptosis but is mediated by its ability to block cell-cycle progression in the G1 phase and by modulating the levels of integrins. These findings directly demonstrate that ILK deficiency facilitates neoplastic growth and invasion and suggest a novel role for the ILK gene in the suppression of tumor metastasis.

Animals↗

Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear.

Several basic helix-loop-helix (bHLH) genes have been shown to be essential for the generation of the auditory sensory hair cells or the spiral ganglion (SG) neurons that innervate the hair cells in the cochlea, as well as a variety of cell types in the other nervous systems. However, it remains elusive what cellular context-dependent mechanisms confer the inner ear-specific neuronal or sensory competency/identities. We explored the possibility that one of the mechanisms responsible for generating cellular diversity in the nervous system through cooperative action of bHLH and LIM-homeodomain (LIM-HD) transcriptional factors might also contribute to the inner ear-specific sensory and/or neuronal competency. Here, we show that Islet1 (Isl1), a LIM-HD protein, is expressed early in the otocyst in the region that gives rise to both the auditory sensory organ, the organ of Corti, and SG neurons. Subsequently, the expression of Isl1 is maintained in SG neurons but is transitory in the sensory lineage. At embryonic day 12 (E12) in mice, the expression of Isl1 marks distinctively the ventral portion of the nascent cochlear epithelium encompassing the primordial organ of Corti. At E13, Isl1 is maintained at relatively high levels in the sensory primordium while down-regulated in the other regions of the cochlear duct. As the sensory epithelium starts to differentiate, it is down-regulated in the entire cochlear epithelium. The expression of Isl1 in the developing inner ear reveals an early and likely a common step in the development of both sensory and neuronal lineages of the inner ear, and suggests its potential role in the inner ear-specific sensory and neuronal cell development.

Animals↗

Imidazoquinoxaline Src-family kinase p56Lck inhibitors: SAR, QSAR, and the discovery of (S)-N-(2-chloro-6-methylphenyl)-2-(3-methyl-1-piperazinyl)imidazo- [1,5-a]pyrido[3,2-e]pyrazin-6-amine (BMS-279700) as a potent and orally active inhibitor with excellent in vivo antiinflammatory activity.

A series of novel anilino 5-azaimidazoquinoxaline analogues possessing potent in vitro activity against p56Lck and T cell proliferation have been discovered. Subsequent SAR studies led to the identification of compound 4 (BMS-279700) as an orally active lead candidate that blocks the production of proinflammatory cytokines (IL-2 and TNFalpha) in vivo. In addition, an expanded set of imidazoquinoxalines provided several descriptive QSAR models highlighting the influence of significant steric and electronic features. The H-bonding (Met319) contribution to observed binding affinities within a tightly congeneric series was found to be significant.

Animals↗

Overriding imatinib resistance with a novel ABL kinase inhibitor.

Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL kinase domain point mutations that interfere with drug binding. Crystallographic studies predict that most imatinib-resistant mutants should remain sensitive to inhibitors that bind ABL with less stringent conformational requirements. BMS-354825 is an orally bioavailable ABL kinase inhibitor with two-log increased potency relative to imatinib that retains activity against 14 of 15 imatinib-resistant BCR-ABL mutants. BMS-354825 prolongs survival of mice with BCR-ABL-driven disease and inhibits proliferation of BCR-ABL-positive bone marrow progenitor cells from patients with imatinib-sensitive and imatinib-resistant CML. These data illustrate how molecular insight into kinase inhibitor resistance can guide the design of second-generation targeted therapies.

Amino Acid Substitution↗

Preparative separation of flavonoid glycosides in leaves extract of Ampelopsis grossedentata using high-speed counter-current chromatography.

Preparative separation of flavonoid glycosides in leaves extract of Ampelopsis grossedentata was conducted using high-speed counter-current chromatograph (HSCCC) with a solvent system composed of n-hexane-ethyl acetate-methanol-water (1:6:1.5:7.5, v/v). In a single operation, 28 mg of 5,7-dihydroxy-3',4'-trihydroxyflavone-3-O-6''-rhamnose and 18 mg of 5,7-dihydroxy-3',4'-dihydroxyflavone-3-O-6''-rhamnose was obtained from 150 mg of the extract. The chemical structure of the two compounds was elucidated by electrospray ionization (EIS) MS and NMR.

Ampelopsis↗

Novel oligosaccharide side chains of the collagen-like region of BclA, the major glycoprotein of the Bacillus anthracis exosporium.

Spores of Bacillus anthracis, the causative agent of anthrax, are enclosed by a prominent loose fitting layer called the exosporium. The exosporium consists of a basal layer and an external hairlike nap. The filaments of the nap are composed of a highly immunogenic glycoprotein called BclA, which has a long, central collagen-like region with multiple XXG repeats. Most of the triplet repeats are PTG, and nearly all of the triplet repeats contain a threonine residue, providing multiple potential sites for O-glycosylation. In this study, we demonstrated that two O-linked oligosaccharides, a 715-Da tetrasaccharide and a 324-Da disaccharide, are released from spore- and exosporium-associated BclA by hydrazinolysis. Each oligosaccharide is probably attached to BclA through a GalNAc linker, which was lost during oligosaccharide release. We found that multiple copies of the tetrasaccharide are linked to the collagen-like region of BclA, whereas the disaccharide may be attached outside of this region. Using NMR, mass spectrometry, and other analytical techniques, we determined that the structure of the tetrasaccharide is 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-beta-d-glucopyranosyl-(1-->3)-alpha-l-rhamnopyranosyl-(1-->3)-alpha-l-rhamnopyranosyl-(1-->2)-l-rhamnopyranose. The previously undescribed nonreducing terminal sugar (i.e. 2-O-methyl-4-(3-hydroxy-3-methylbutamido)-4,6-dideoxy-d-glucose) was given the trivial name anthrose. Anthrose was not found in spores of either Bacillus cereus or Bacillus thuringiensis, two species that are the most phylogenetically similar to B. anthracis. Thus, anthrose may be useful for species-specific detection of B. anthracis spores or as a new target for therapeutic intervention.

Bacillus anthracis↗