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Biomedical subjects

Z Lu

Publications and source records attributed to Z Lu.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Clinical evaluation of frameless stereotaxy in minimally invasive neurosurgery].

OBJECTIVE: To evaluate the utility of frameless stereotaxy in minimally invasive neurosurgery. METHODS: A retrospective review of 200 cases of craniotomy and laminotomy procedures using frameless stereotaxy systems performed from December 1999 to June 2001 was made, including 43 cases of AVM, 39 cases of aneurysm, 30 of meningioma, 27 of cavenous malformation, 19 of glioma, 8 of neuronoma, 5 of pituitary tumor, 4 of angioreticuloma, 3 of metastatic tumor, 14 cases of craniotomy with other causes, and 8 spinal tumors. Data of MRI or CT, conducted one day before the operation, were entered into the neuronavigation systems and analyzed. A 3-D simulation of model of cranium or spinal cord was reestablished and operative approach was designed. During the operation, the lesion can be located accurately. RESULTS: The lesions and important anatomical structures were accurately located and the location errors of lesions were within the limit of 2 mm. Postoperative neurological complications occurred only in 10 cases (5.0%). No operative death occurred. CONCLUSION: The frameless stereotaxy is very helpful for brain and spinal surgery, especially for the cases with lesions located deep in the brain. Its accuracy of location is very important in protecting normal brain tissues. The neuronavigation systems are changing the pattern of traditional neurosurgical procedures and serve as the guarantee of minimally invasive neurosurgery.

Humans↗
PubMed2001

Density and kinetics of I(Kr) and I(Ks) in guinea pig and rabbit ventricular myocytes explain different efficacy of I(Ks) blockade at high heart rate in guinea pig and rabbit: implications for arrhythmogenesis in humans.

BACKGROUND: Class III antiarrhythmic agents commonly exhibit reverse frequency-dependent prolongation of the action potential duration (APD). This is undesirable because of the danger of bradycardia-related arrhythmias and the limited protection against ventricular tachyarrhythmias. The effects of blockade of separate components of delayed rectifier K(+) current (I(K)) may help to develop agents effective at high heart rate. METHODS AND RESULTS: We assessed the density and kinetics of the 2 components of the delayed rectifier K(+) current, I(Kr) and I(Ks), in rabbit and guinea pig ventricular myocytes. The effects of their specific blockers (chromanol 293B for I(Ks) and E-4031 for I(Kr)) on the action potential was studied at different heart rates by use of whole-cell patch-clamp techniques. In guinea pig ventricular myocytes only, blockade of I(Ks) causes APD prolongation in a frequency-independent manner, whereas blockade of I(Ks) in rabbit ventricular myocytes shows reverse frequency dependence, as does blockade of I(Kr) in both species. This result can be explained primarily by the higher density of I(Ks) in guinea pig ventricle and by its slow deactivation kinetics, which allows I(Ks) to accumulate at high heart rate because little time is available for complete deactivation of it during diastole. CONCLUSIONS: Density and kinetics of components of I(K) explain why blockade of I(Ks) is more effective at high heart rate in the guinea pig ventricle than in the rabbit ventricle, without adverse effects at low heart rate.

Action Potentials↗
PubMed2001

Improved synthesis and evaluation of 17-substituted aminoalkylgeldanamycin derivatives applicable to drug delivery systems.

The 17-methoxy group of geldanamycin was substituted with 1,3-diaminopropane and 1,3-diamino-2-hydroxypropane to introduce a primary amino group useful for conjugation with targeting moieties and drug carriers. We have developed a procedure that has provided improved yield and reproducibility of the syntheses. Both geldanamycin derivatives demonstrated antiproliferative activity towards the human ovarian carcinoma cell line, A2780.

Antibiotics, Antineoplastic↗
PubMed2001

The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis.

We have shown elsewhere that equine-2 influenza virus (EIV; subtype H3N8) induced pronounced cell death in infected cells through apoptosis as demonstrated by DNA fragmentation assay and a combined TUNEL and immunostaining scheme. In this study, we investigated the mechanism of EIV-mediated cytotoxicity on a permissive mammalian epithelial cell line, Madin-Darby canine kidney (MDCK) cells. EIV infection increased the cellular levels of oxidative stress and c-Jun/AP-1 protein (which is known to be affected by oxidative stress), as well as its DNA binding activity. Increased production of TGF-beta1, an inducer of c-Jun N-terminal kinase or stress-activated protein kinase (JNK/SAPK) activation, was also detected in EIV-infected MDCK cells. It has been reported that TGF-beta may initiate a signaling cascade leading to JNK/SAPK activation. Addition of c-Jun antisense oligodeoxynucleotide, antioxidant N-acetyl-cysteine (NAC), JNK/SAPK inhibitor carvedilol, or TGF-beta-neutralizing antibody effectively blocked c-Jun/AP-1 upregulation and TGF-beta1 production mediated by EIV infection. These treatments also attenuated EIV-induced cytopathogenic effects (CPE) and apoptosis. Our results suggest that a stress-activated pathway is involved in apoptosis mediated by EIV infection. It is likely that EIV infection turns on the JNK/SAPK cascade, which modulates the activity of apoptosis-promoting regulatory factor c-Jun/AP-1 and epithelial growth inhibitory cytokine TGF-beta.

Animals↗
PubMed2001

Dependence of reversed-phase retention of ionizable analytes on pH, concentration of organic solvent and silanol activity.

In reversed-phase chromatography, the retention of ionizable analytes is influenced by the ionic properties of the packing caused by surface silanol groups. We have measured the ion-exchange properties of both reversed-phase bonded phases and their underlying base materials. The probe used in this part of the study was bretylium tosylate. The acquired knowledge is then used for a complete and quantitative understanding of the retention behavior of ionizable compounds as a function of the pH of the mobile phase and the solvent composition. We have studied the retention pattern of a broad range of acids, bases, and polyfunctional analytes over the pH range from 2 to 11 and from water to 80% acetonitrile. A few application examples demonstrate the relevant findings.

Hydrogen-Ion Concentration↗
PubMed2001

Transcriptional regulation of the lung fatty acid synthase gene by glucocorticoid, thyroid hormone and transforming growth factor-beta 1.

Fatty acid synthase (FAS) is a key enzyme in the biosynthesis of lung surfactant. FAS expression in fetal lungs is increased by glucocorticoids and this effect is largely due to increased transcription. The stimulatory effect of glucocorticoid on FAS expression is antagonized by thyroid hormone and transforming growth factor-beta 1 (TGF-beta 1). To determine the glucocorticoid responsive regions of the FAS gene we employed deletion analysis and reporter gene assays. A549 cells were transfected with various FAS gene constructs ligated to the firefly luciferase gene and cultured with dexamethasone (Dex) for 24 h after which luciferase activity was measured. Dex increased luciferase expression in response to a fragment in the promoter and 5'-flanking region of the FAS gene, from -1592 to +65 bp. This increase was antagonized by triiodothyronine (T(3)) and TGF-beta 1. Serial deletions showed that the full response to Dex and T(3) were retained in the 89 bp -33/+56 bp fragment whereas the response to TGF was mediated by the immediately upstream -104/-34 bp sequence. The Dex responsive region of the FAS gene could not be separated from the minimal promoter showing that they are intimately associated. The extents of Dex stimulation and antagonism by T(3) and TGF in A549 cells were similar to those noted on parameters of FAS expression in fetal lung explants. These data show that the effects of Dex, T(3) and TGF on FAS expression are mediated by DNA sequences in the promoter region of the gene.

Cell Line↗
PubMed2001

Effects of phosphocreatine on apoptosis in a cell-free system.

The characteristic morphological and biochemical changes during caspase-mediated apoptosis can be reproduced to a large extent in a Xenopus laevis egg extract cell-free system by addition of mouse liver nuclei and exogenous cytochrome c. We show that in this system phosphocreatine accelerated the apoptotic morphological changes of the nuclei, but selectively inhibited DNA fragmentation. Western blot showed that the degradation of lamins A and C is accelerated, which is possibly responsible for the nuclear changes during cell apoptosis. However, the degradation of ICAD/DFF45-like protein in the egg extracts is inhibited in a time-dependent manner. Exogenous creatine, ATP, and several organic acids have no effect on DNA fragmentation, excluding the possibility that creatine, ATP, or acidic conditions resulting from phosphocreatine are responsible for inhibiting DNA fragmentation. Lithium chloride, a kinase inhibitor, can overcome the phosphocreatine effects and can restore DNA fragmentation. Our results indicate that phosphocreatine protects ICAD/DFF45-like protein from proteolysis, probably through kinase actions, resulting in its resistance to caspase cleavage and leading to an inhibition of DNA fragmentation.

Adenosine Triphosphate↗
PubMed2001

Three loci modify growth of a transgene-induced mammary tumor: suppression of proliferation associated with decreased microvessel density.

In earlier studies it was observed that the genetic background significantly affected the phenotype of a transgene-induced mammary tumor. Tumors arising in an (I/LnJ x PyMT) F1 hybrid background appeared earlier than in the FVB/N-TgN(MMTV-PyVT)(634Mul) parent, but accumulated less tumor mass, indicating a net decrease in tumor growth. Quantitative genetic mapping in a backcross identified three loci that were associated with the decreased proliferative capacity of the I/LnJ F1 tumors. Molecular analysis of the tumors suggests that these loci may act by restricting the tumor's ability to recruit microvessels. The three loci, designated Mmtg1-3, are unlinked to the angiogenic genes Fgf2, Flt1, Flk4, Flk1, Vegf, and Vegfc, as well as the precursors of the endogenous antiangiogenic molecules angiostatin and endostatin. The Mmtg loci may therefore provide novel targets for antiangiogenic therapeutic strategies.

Animals↗
PubMed2001

CXCR-4 desensitization is associated with tissue localization of hemopoietic progenitor cells.

The chemokine stroma-derived factor (SDF)-1, and its receptor, CXCR-4, have been shown to be essential for the translocation of hemopoietic stem cells from the fetal liver to the bone marrow (BM). We hypothesized that if CXCR-4 plays a crucial role in the localization of human hemopoiesis, stem cells from distinct tissue sources should demonstrate distinct CXCR-4 expression or signaling profiles. CD34(+) cells from BM were compared with blood: either mobilized peripheral blood or umbilical cord blood. Unexpectedly, significantly higher levels of CXCR-4 surface expression on CD34(+) cells from blood sources, mobilized peripheral blood, or cord blood were observed compared with BM (p = 0.0005 and p = 0.002, respectively). However, despite lower levels of CXCR-4, responsiveness of the cells to SDF-1 as measured by either calcium flux or transmigration was proportionally greatest in cells derived from BM. Further, internalization of CXCR-4 in response to ligand, associated with receptor desensitization, was significantly lower on BM-derived cells. Therefore, preserved chemokine receptor signaling was highly associated with marrow rather than blood localization. To test the functional effects of perturbing CXCR-4 signaling, adult mice were exposed to the methionine-SDF-1beta analog that induces prolonged down-regulation/desensitization of CXCR-4 and observed mobilization of Lin(-), Sca-1(+), Thy-1(low), and c-kit(+) hemopoietic progenitor cells to the peripheral blood with a >30-fold increase compared with PBS control (p = 0.0007 day 1 and p = 0.004 day 2). These data demonstrate that CXCR-4 expression and function can be dissociated in progenitor cells and that desensitization of CXCR-4 induces stem cell entry into the circulation.

Adult↗
PubMed2001

Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular protons.

Tertiapin-Q (TPN(Q)), a honey bee toxin derivative, inhibits inward-rectifier K(+) channels by binding to their external vestibule. In the present study we found that TPN(Q) inhibition of the channels is profoundly affected by extracellular pH. This pH dependence mainly reflects titration of histidine residue 12 in TPN(Q) by extracellular protons, since it largely vanishes when the histidine residue is replaced with alanine. Not surprisingly, this alanine derivative of TPN(Q) binds to the channel with much lower affinity. Quantitative thermodynamic cycle analysis shows that deprotonation of the histidine residue reduces the TPN(Q)-ROMK1 binding energy by 1.6 kcal/mol. To eliminate pH sensitivity but retain high affinity, we derivatized TPN(Q) by replacing histidine 12 with lysine. This derivative-denoted tertiapin-KQ (TPN(KQ))-not only is practically insensitive to extracellular pH but also binds to the channel with even higher affinity than TPN(Q) at extracellular pH 7.6.

Alanine↗
PubMed2001

A model of interfacial inactivation for papain in aqueous organic biphasic systems.

A model was proposed to describe the effects of the main factors in aqueous-organic two-liquid-phase media on the stability of papain. The relationships between the half-life of papain activity and these factors including interfacial tension, stirring rate, phase volume ratio and temperature were investigated. The results showed that these factors had notable effects on papain stability except temperature. The correlation coefficient between the model and the experimental data were 0.829, which indicated the model is practicable.

Journal Article↗
PubMed2001

Ultrafast liquid chromatography/ultraviolet and liquid chromatography/tandem mass spectrometric analysis.

Optimal liquid chromatography/mass spectrometric [LC/MS(/MS)] analysis depends on both the LC selectivity and the electrospray efficiency. Here, we outline a simple and comprehensive LC/MS/MS strategy for the rapid analysis of a wide range of pharmaceutical compounds. To achieve ultrafast LC separation with little sacrifice in peak capacity, one needs to start with a column that provides a good peak capacity at short gradient run times; secondly, it is important to use high flow rates to achieve a good gradient peak capacity. Following this strategy, it was possible to baseline-resolve a mixture (containing acidic, neutral, and basic pharmaceutical analytes) in seconds. By coupling the selectivity provided by fast LC separation with the specificity of MS/MS detection, it is possible to separate and identify a wide range of analytes in 1-min gradient analyses. Also, the impact of mobile phase pH on both the chromatographic selectivity and the MS/MS sensitivity is demonstrated.

Chromatography, Liquid↗
PubMed2001

A new method for protein coexpression in Escherichia coli using two incompatible plasmids.

It is commonly believed that incompatible plasmids carrying the same replicon cannot coexist stably in one Escherichia coli cell. However, we found that two incompatible plasmids carrying different antibiotic resistance genes, if under the selection pressure of the two antibiotics, can coexist in E. coli for at least 14 h, which is adequate for routine culture and protein expression. Based on this discovery, we developed a new method to coexpress foreign proteins in E. coli using two incompatible plasmids. The coding regions of the two subunits (DFF45 and DFF40) of the human DNA fragmentation factor (DFF) were cloned into two incompatible bacterial expression vectors-pET-21a with ampicillin resistance and pET-28a with kanamycin resistance, respectively. The two resulting plasmids were used to cotransform E. coli BL21(DE3) cells. After selection by ampicillin and kanamycin simultaneously, cotransformants that contain both recombinant plasmids were obtained. Induced by isopropyl beta-d-thiogalactoside, DFF45, and DFF40 were coexpressed efficiently in the presence of the two antibiotics. The coexpression product contained adequate soluble portions for both DFF45 and DFF40, while all DFF40 was insoluble if expressed alone. The coexpression product also exhibited the same caspase-activated DNase activity as its natural counterparts, which cannot be obtained if its two subunits are expressed separately.

Apoptosis Regulatory Proteins↗
PubMed2001

The mechanical study of vascular endothelial growth factor on the prevention of restenosis after angioplasty.

The mechanism of vascular endothelial growth factor (VEGF) on the prevention of restenosis after angioplasty was investigated. The cultured vascular endothelial cells (VEC) were incubated with the conditioned medium (CM) from vascular smooth muscle cells (VSMC) infected with recombinant adenoviruses containing the hVEGF165 gene. To observe the effects of VEGF on proliferation and NO, ET, 6-keto-PGF1 alpha secretion of VEC, WST-1 method, Griess method and radioimmunoassay were used respectively. The PDGF-B mRNA transcription in VECs was detected by RT-PCR. It was showed that NO, 6-keto-PGF1 alpha and OD value were markedly increased in a dose-dependent manner in the VEGF-treated groups as compared with those in the control group, while ET and PDGF-B mRNA were significantly decreased in the VEGF-treated groups (P < 0.05 or P < 0.01). Adenovirus vector mediated hVEGF165 gene could promote the proliferation of VECs and improve NO, PGI2 secretion, inhibit ET secretion and PDGF-B mRNA transcription in the VECs. The above results offered further theoretical evidence for VEGF on the prevention of restenosis after angioplasty.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Proliferative capacity of single isolated CD34+ hematopoietic stem/progenitor cells in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) results from somatic mutations of the X-linked PIG-A (phosphatidylinositol glycan-class A) gene, which occurs on a hematopoietic stem cell level, leading to a proportion of blood cells being deficient in all glycosylphosphatidylinositol (GPI)-anchored surface proteins. Although these GPI-deficient cells can explain many of the clinical symptoms of PNH, the pathogenesis of PNH is still somewhat obscure and many questions remain. To assess the hematopoietic defect involved in PNH, CD34+ CD59+ (normal phenotype hematopoietic stem/progenitor) and CD34+ CD59- (PNH phenotype) cells from PNH patients (n = 16) and CD34+ CD59+ cells from healthy volunteers (n = 10) were sorted as single cells into 96-well flat-bottom culture plates containing culture medium supplemented with stem cell factor, interleukin (IL)-3, erythropoietin, granulocyte-macrophage-colony-stimulating factor (GM-CSF), G-CSF, IL-6, thrombopoietin, and Flt-3 ligand. We found that the single PNH CD34+ CD59- cells had a growth advantage over the single CD34+ CD59+ cells to some extent, but they both had impaired growth abilities compared with CD34+ cells from healthy volunteers.

Adolescent↗
PubMed2001

Heterologous expression of the single-mutation glucose isomerase (GIG138P) gene in Streptomyces lividans and its genetic instability.

A 1.3-kb PstI-BamHI fragment containing the single-mutation glucose isomerase (GIG138P, GI1) gene and its natural promoter was inserted into PstI-BglII linearized Streptomyces vector pIJ702. The ligation mixture was then introduced into Streptomyces lividans TK54 protoplasts; transformants were identified based on their thiostrepton resistance (ThR) and insertional inactivation of the melanin phenotype; and three white colonies, XY-2, 6, and 9, harboring recombinant expression plasmid pYH703, were obtained. Enzyme assay and SDS-PAGE analysis indicated that the GI1 gene was expressed, the intracellular GI1 specific activity was 6 U/mg, and GI1 accounted for 20% of the soluble proteins in S. lividans. Restriction analysis and Southern blot of pYH703 showed the existence of plasmid deletion, presumably owing to the interaction between the mel and GI1 sequences. Continuous liquid cultures of the recombinant strain demonstrated that the GI1 specific activity and GI1 expression in S. lividans decreased, and more obviously under non-selective conditions.

Aldose-Ketose Isomerases↗