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Biomedical subjects

N Zhang

Publications and source records attributed to N Zhang.

At least 55 records · Page 3Linked to original sources

[Clinicopathologic analysis of ovarian serous and mucinous borderline tumors].

OBJECTIVE: To understand the clinicopathological features of ovarian borderline tumors and evaluate the significance of various histological appearances. METHODS: Forty-five patients with borderline tumors were analyzed retrospectively. The stage distribution was stage I, 34 patients, stage II, 4 patients and stage III, 7 patients. RESULTS: Forty-five cases of borderline tumors accounted for 25.4% of ovarian epithelial malignant tumors. The ratio of serous borderline tumors (SBTs) to mucinous borderline tumors (MBTs) was approximately 1:1.3. Nine of eleven SBTs with exophytic growth presented peritoneal implants, of which two were invasive and seven noninvasive. Two SBTs and 1 MBT recurred after 5, 4, and 1 years respectively. Thirty-three cases were followed from 2 to 9 years. The 5-year survival rate was 100% (Kaplan-Meir method). CONCLUSIONS: The prognosis of the SBTs is favorable. SBTs with exophytic growth are often associated with peritoneum implants.

Adenocarcinoma, Mucinous↗

[The effect of mouthguard on strength of the musculus deltoideus].

OBJECTIVE: To investigate the effect of mouthguard on strength of musculus deltoideus and to observe the possibility of its improving sports ability. METHODS: The custom mouthguards were fabricated respectively for 8 subjects with soft resin by direct method. The activities of the musculus deltoideus and masseter were tested by means of electromyograph (EMG), while the subjects lay, made maximum voluntary biting with mouthguard and pressed 5 kg. The EMG potentials were transferred to a computer. The data were handled and the integral values of EMG were exported. RESULTS: The subjects set a great value on the mouthguard's comfort, retention and protection. The EMG values of the musculus deltoideus and masseter of the subjects biting with mouthguards were 1.1600 v/s and 0.3825 v/s, and the values of those biting without mouthguards were 0.6125 v/s and 0.213 8 v/s, respectively. The muscular strength of the former was significantly improved compared with that of the latter (P < 0.01). CONCLUSIONS: Wearing a mouthguard and maximum voluntary biting can enhance the masseter force and reflectively improve the musculus deltoideus strength.

Electromyography↗

Mechanisms of multiple organ damages in acute necrotizing pancreatitis.

OBJECTIVE: To determine the role of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), and evaluate the progress from SIRS to MODS and the therapeutic strategies for acute necrotizing pancreatitis (ANP). METHODS: Rat ANP models were made by retrograde injection of 3.5% sodium taurocholate 2.5 ml/kg into the pancreatic duct. Serum interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF alpha), amylase, endotoxin, and albumin were examined. The morphology and pathology of the pancreas, liver, lung, kidney and heart after ANP were observed. Finally, TNF alpha mRNA in the liver, lung, kidney and heart after ANP were observed by reverse transcriptase-polymerase chain reactions, and the efficiency of somatostatin and growth hormone were also observed in this experiment. RESULTS: ANP led to remarkable elevation of the inflammatory mediators which were positively correlated with the development of ANP and MODS. Somatostatin and growth hormone inhibited inflammatory mediators and TNF alpha mRNA overexpressions, reduced the risk of MODS, corrected hypoalbuminemia, reversed negative nitrogen balance, and controlled the reduction of cell groups with functions and reasonably intervened SIRS caused by ANP. CONCLUSION: TNF alpha mRNA plays an important role in ANP progression. The amelioration of ANP by combination treatment with somatostatin and growth hormone leads to the reduction of complications and marked increase in survival.

Animals↗

[A study of the correlation between p16 protein expression and DNA quantitative analysis in human gastric carcinoma cells].

OBJECTIVE: To investigate p16 protein expression and its correlation with DNA quantity in gastric carcinoma (GC) cells. METHODS: p16 protein expression was quantitatively determined by flow cytometry (FCM) in 41 cases of GC and 10 cases of normal gastric tissues. DNA quantitative analysis of 41 cases of GC was performed by image cytometry (ICM). RESULTS: p16 protein expression in GC was significantly lower than that in normal gastric tissues (respective FI: 0.81 plus minus 0.09 and 1.00 plus minus 0.11, P < 0.01). The expression of p16 protein did not show correlation with such factors as sex and age in GC, but it was significantly stronger in well differentiated GC than that in poorly differentiated GC (P < 0.05). The mean of DNA relative ploid (U value) in GC was from 1.14 to 2.98. U value becomes higher with the increase in grading (P < 0.01). There was significant negative linear correlation between p16 protein expression and U value in GC (P < 0.01). CONCLUSION: Abnormal expression of p16 protein is closely correlated to the occurrence, development and malignancy degree of GC. The level of p16 protein expression implies important clinical significance for GC treatment and may serve as an indicator to predict the prognosis of patients.

Adenocarcinoma↗

[Inhibition of proliferation and induction of apoptosis by simvastatin in K562 leukemic cell line].

OBJECTIVE: To investigate the anti-apoptotic mechanism and explore approach to inhibiting proliferation and inducing apoptosis of chronic myclogenous leukemia (CML) cells. METHODS: K562 cell line was used to evaluate the effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and the combination of simvastatin with chemotherapeutic agents on the proliferation and apoptosis of CML cells. RESULTS: Simvastatin could significantly inhibit proliferation and induce apoptosis of K562 cells, and could increase the sensitivity of K562 cells to chemotherapeutic agents. Addition of mevalonate, the immediate product of HMG-CoA, could completely reverse this effect. CONCLUSION: Simvastatin inhibited proliferation and induced apoptosis of K562 cells through inhibiting the metabolic pathway of mevalonate. It is promising that HMG-CoA reductase inhibitors may be an effective chemotherapeutic approach to the treatment of CML.

Antineoplastic Agents↗

Mutagenesis of N-terminal Amino Acid Residues in beta-subunit of Glutaryl-7-amino-cephalosporanic Acid Acylase C130.

In many GL-7ACA acylases, the first Ser residue at the N-terminal of beta-subunit is the catalytic center. In order to investigate relationship between the N-terminal structure and catalytic activities, peptide replacement and site-directed mutagenesis were performed at the N-terminal of beta-subunit of GL-7ACA acylase C130. When the N-terminal 8 amino acid residues of C130 were replaced by the corresponding sequence of penicillin acylases PAC and PGA, respectively, the first mutant B8PAC lost the activity of the acylase, and the second mutant B8PGA had lower activity with the K(m) value increasing from 0.44x10(-3)mol.L(-1) to 0.55x10(-3) mol.L(-1), and the k(cat) decreasing from 4.92 s(-1) to 1.64 s(-1). Although the substitution of Trp (beta4) by Tyr did not change the K(m) value, the k (cat) decreased to 2.29 s(-1). When the Trp was substitued by Leu, both the K ( m ) and k ( cat ) values decreased. Compared with the wild type, mutations of Ser (beta3) to Met, Ala and Cys caused decrease of K(m) values by 52.27%, 43.18% and 38.64%, respectively. Mutation of Asn (beta2) to Gln caused the K ( m ) value being increased by 5-fold, and k ( cat ) decreased by 10-fold. These results suggested that the N-terminal amino acid residues of beta-subunit in GL-7ACA acylase C130 are important for enzyme function.

Journal Article↗

[Mitochondrial DNA mutations in matrilineal nonsyndromic deafness pedigrees of southwest China].

OBJECTIVE: To identify the incidence of the 1555A-->G mutation and explore the audiological features of pedigrees with matrilineal non-syndromic deafness in Southwest of China so as to provide the theoretical evidence for establishing the method of gene diagnosis. METHODS: Six pedigrees with 102 members were evaluated audiologically and clinically. DNA was extracted from their blood samples. All subjects were screened for mitochondrial DNA 1555A-->G mutation by Alw 26I restriction endonuclease digestion. RESULTS: Seventeen maternal relatives of aminoglycoside antibiotic induced deafness (AAID) pedigree 1 and pedigree 2, carried 1555A-->G mutation. 10 maternal relatives of Non-AAID pedigree 6 also carried 1555A-->G mutation. No mutation was found among paternal relatives and pedigrees 3, 4 and 5. CONCLUSION: The same audiological features of these pedigrees are: bilateral and symmetrical progressive sensorineural hearing loss with variable age of onset. The 1555A-->G mitochondrial mutation is one of the hereditary factors for this disorder. 4 Aminoglycoside antibiotic plays an important role in developing deafness. The incidence of the 1555A-->G mutation in AAID and matrilineal non-syndromic deafness pedigrees is fairly high. Screening for mitochondrial 1555A-->G mutation may be of great clinical use fullness.

Aminoglycosides↗

[The diagnosis and treatment of isolated sphenoid sinus disease].

OBJECTIVE: To detail the underlying symptoms and signs of patients with isolated sphenoid sinus inflammatory disease and enhance the initial diagnostic accuracy. METHOD: 49 patients with isolated sphenoid sinus inflammatory disease were reviewed, and the outcomes of the endoscopic surgery were compared with the non-endoscopic surgery. RESULT: In patients who underwent endoscopic sphenoidotomy, 31 were virtually free from symptoms and 5 still experienced mild headache and hyposmia but their radiographic finding had become normalized. None of them need re-operation within 6-48 months follow-up. However, in patients with non-endoscopic sinus irrigation, only one was free from the symptoms and 5 patients underwent re-operation because of recurrence. CONCLUSION: Nasal endoscopy and CT/MRI scan could provide a precise diagnosis for isolated sphenoid sinus disease and endoscopic surgery is valuable in its treatment.

Adolescent↗

[Determination of trace cadmium in human hair, fingernail and toenail for ten years by flame atomic absorption spectrometry].

The human hair, fingernail and toenail were collected from one person quarterly for about ten years, respectively thirty-three, forty-one and thirty-nine shares. The contents of traces cadmium in hair, fingernail and toenail have been determined by flame atomic absorption spectrometry, and the results were satisfactory. From a changing curve in human hair, fingernail and toenail cadmium by age, we found that the range of cadmium contents in hair was 0.0100-0.4100 microgram.g-1, in fingernail 0.0295-0.5314 microgram.g-1, in tene-nail 0.0899-1.274 micrograms.g-1, respectively. In the changing curve there is a nonlinear characteristic.

Cadmium↗

Differential processing of UV mimetic and interstrand crosslink damage by XPF cell extracts.

We have recently developed a mammalian cell free assay in which interstrand crosslinks induce DNA synthesis in both damaged and undamaged plasmids co-incubated in the same extract. We have also shown using hamster mutants that both ERCC1 and XPF are required for the observed incorporation. Here, we show that extracts from an XPF patient cell line differentially process UV mimetic damage and interstrand crosslinks in vitro. XPF extracts are highly defective in the stimulation of repair synthesis by N:-acetoxy-N:- acetylaminofluorene, but are proficient in the stimulation of DNA synthesis by psoralen interstrand crosslinks. In addition, we show that extracts from the hamster UV140 mutant, which has high UV sensitivity, but moderate mitomycin C sensitivity, are similar in both assays to XPF cell extracts. These findings support the hypothesis that the activities of XPF in nucleotide excision repair (NER) and crosslink repair are separable, and that mutations in XPF patients result in the abolition of NER, but not recombinational repair pathways, which are likely to be essential as has been observed in ERCC1 homozygous -/- mice.

Animals↗

Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta.

Microglia are the major target of HIV-1 infection in the brain. Microglial infection is CD4-dependent, but the role of chemokine receptors CCR5 and CCR3 and their natural ligands in modulating HIV-1 infection in microglia has been questioned. In primary human fetal microglial cultures, we demonstrate that HIV-1 infection of these cells is dependent on CCR5, since an antibody to CCR5 completely blocked productive infection. Anti-CCR3, in contrast, had a smaller inhibitory effect which was not statistically significant. The chemokine ligands for CCR5, RANTES and MIP-1beta, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1alpha failed to show inhibition. Interestingly, when microglial cultures were treated with antibodies specific to each of these chemokines, HIV-1 infection was enhanced by anti-RANTES and anti-MIP-1beta, but not by anti-MIP-1alpha. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNbeta, a known anti-viral cytokine, also provided potent inhibition of viral infection as well as induction of all three chemokines in microglia. These results suggest the possibility that type I interferon can down-modulate microglial HIV-1 infection in vivo by multiple mechanisms.

AIDS Dementia Complex↗

4-Anilino-6,7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor kinase and their bioisosteric relationship to the 4-anilino-6,7-dialkoxyquinazoline inhibitors.

The synthesis and SAR of a series of 4-anilino-6, 7-dialkoxyquinoline-3-carbonitrile inhibitors of epidermal growth factor receptor (EGF-R) kinase are described. Condensation of 3, 4-dialkoxyanilines with ethyl (ethoxymethylene)cyanoacetate followed by thermal cyclization gave, regiospecifically, 6,7-dialkoxy-4-oxo-1, 4-dihydroquinoline-3-carbonitriles. Chlorination (POCl(3)) followed by the reaction with substituted anilines furnished the 4-anilino-6, 7-dialkoxyquinoline-3-carbonitrile inhibitors of EGF-R kinase. An alternate synthesis of these compounds starts with a methyl 3, 4-dialkoxybenzoate. Nitration followed by reduction (Fe, NH(4)Cl, MeOH-H(2)O) gave a methyl 2-amino-4,5-dialkoxybenzoate. Amidine formation using DMF-acetal followed by cyclization using LiCH(2)CN furnished a 6,7-dialkoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile, which was transformed as before. Compounds containing acid, ester, amide, carbinol, and aldehyde groups at the 3-position of the quinoline ring were also prepared for comparison, as were several 1-anilino-6,7-dimethoxyisoquinoline-4-carbonitriles. The compounds were evaluated for their ability to inhibit the autophosphorylation of the catalytic domain of EGF-R. The SAR of these inhibitors with respect to the nature of the 6,7-alkoxy groups, the aniline substituents, and the substituent at the 3-position was studied. The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF-R or HER-2. It was found that 4-anilinoquinoline-3-carbonitriles are effective inhibitors of EGF-R kinase with activity comparable to the 4-anilinoquinazoline-based inhibitors. A new homology model of EGF-R kinase was constructed based on the X-ray structures of Hck and FGF receptor-1 kinase. The model suggests that with the quinazoline-based inhibitors, the N3 atom is hydrogen-bonded to a water molecule which, in turn, interacts with Thr 830. It is proposed that the quinoline-3-carbonitriles bind in a similar manner where the water molecule is displaced by the cyano group which interacts with the same Thr residue.

Aniline Compounds↗

Integrated sample collection and handling for drug discovery bioanalysis.

An integrated sample handling process for drug discovery bioanalysis is described. The streamlining of study design, sample collection and automatic bioanalytical sample processing is demonstrated. Specific details for the entire procedure regarding the time saved, ease of automation and integration are defined. Details of sample handling involved a sample collection map, sample collection formatting and volume, dilution schemes for high concentration samples, choice of biological fluid and evaluating the capabilities of two liquid-handling workstations. Numerous comparisons were conducted between the new approaches and the conventional sample handling approaches. The precision and accuracy obtained from the new integrated sample handling process were comparable to those obtained from a conventional approach, as were pharmacokinetic profiles and parameters. This new sampling process greatly improved the efficiency of drug discovery bioanalysis. The integration of pre-clinical protocol design, sample collection and bioanalysis processes was also achieved.

Animals↗

Automating solid-phase extraction: current aspects and future prospects.

This paper reviews current trends and techniques in automated solid-phase extraction. The area has shown a dramatic growth the number of manuscripts published over the last 10 years, including applications in environmental science, food science, clinical chemistry, pharmaceutical bioanalysis, forensics, analytical biochemistry and organic synthesis. This dramatic increase of more that 100% per year can be attributed to the commercial availability of higher throughput 96-well workstations and extraction plates that allow numerous samples to be processed simultaneously. These so-called parallel-processing workstations represent the highest throughput systems currently available. The advantages and limitations of other types of systems, including discrete column systems and on-line solid-phase extraction are also discussed. Discussions of how automated solid-phase extractions can be developed, generic approaches to automated solid-phase extraction, and three noteworthy examples of automated extractions are given. The last part of the review suggests possible near- and long-term directions of automated solid-phase extraction.

Automation↗

A mutation in the Lunatic fringe gene suppresses the effects of a Jagged2 mutation on inner hair cell development in the cochlea.

Recent studies have demonstrated that the Notch signaling pathway regulates the differentiation of sensory hair cells in the vertebrate inner ear [1] [2] [3] [4] [5] [6] [7] [8] [9]. We have shown previously that in mice homozygous for a targeted null mutation of the Jagged2 (Jag2) gene, which encodes a Notch ligand, supernumerary hair cells differentiate in the cochlea of the inner ear [7]. Other components of the Notch pathway, including the Lunatic fringe (Lfng) gene, are also expressed during differentiation of the inner ear in mice [6] [7] [8] [9] [10]. In contrast to the Jag2 gene, which is expressed in hair cells, the Lfng gene is expressed in non-sensory supporting cells in the mouse cochlea [10]. Here we demonstrate that a mutation in the Lfng gene partially suppresses the effects of the Jag2 mutation on hair cell development. In mice homozygous for targeted mutations of both Jag2 and Lfng, the generation of supernumerary hair cells in the inner hair cell row is suppressed, while supernumerary hair cells in the outer hair cell rows are unaffected. We also demonstrate that supernumerary hair cells are generated in mice heterozygous for a Notch1 mutation. We suggest a model for the action of the Notch signaling pathway in regulating hair cell differentiation in the cochlear sensory epithelium.

Animals↗