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Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 253 records · Page 14Linked to original sources
PubMed1999

Rates of growth and loss of bone mineral in the spine and femoral neck in white females.

This study characterizes the rates of growth and loss of bone mass as a function of age in white females. It combines longitudinal data from several studies of bone mass on healthy white female subjects ranging from age 6 to 90 years. Rates of change in bone area, bone mineral content (BMC) and bone mineral density (BMD) are estimated separately for the spine and the femoral neck of each individual using linear regression. The individual rates of change are then fitted as a nonparametric function of age using weighted moving averages, resulting in a curve of age-specific mean change as a function of age. When the curves of BMD were compared between the hip and the femoral neck, the cessation of bone growth and the onset of bone loss were found to occur at an earlier age at the hip than at the spine. No significant differences in the ages of maximum rates of growth or maximum loss were found between the two skeletal sites. This information will be useful for designing interventions to promote bone growth or retard bone loss.

Adolescent↗
PubMed1999

Alteration of cytoskeletal structure, integrin distribution, and migratory activity by phagocytic challenge in cells from an ocular tissue--the trabecular meshwork.

The trabecular meshwork is a specialized tissue in the anterior chamber of the eye that regulates the aqueous humor outflow and controls the intraocular pressure. Cells in the trabecular meshwork are believed to be essential for maintenance of the outflow system, and their malfunctioning may lead to elevation of intraocular pressure and development of glaucoma. These cells are avid phagocytes. Using an in vitro tissue culture system, we have previously shown that bovine trabecular meshwork cells exhibited a short-term loss of cell-matrix adhesiveness after exposure to latex microspheres. The current study showed that 4 h after phagocytosis, the cytoskeletal structure in trabecular meshwork cells was disrupted, the formation of focal contact formation was limited, and the cellular migratory activity was increased. These in vitro responses paralleled those that occur in vivo. By 24 h, all the changes demonstrated returned to normal. Our data suggest that the short-term loss in cell-matrix cohesiveness observed after phagocytic challenge may be related to the reorganization of cytoskeletal structures and the decline of focal contact formation. The altered cell migration may also be interlinked.

Animals↗
PubMed1999

Feasibility studies of simultaneous multianalyte amperometric immunoassay based on spatial resolution.

A multianalyte immunoassay concept based on the geometric separation of different analyte-specific antibodies has been demonstrated. The assay and amperometric detection are done in a cell with two working electrodes controlled at the same potential, and the amperometric signal at each electrode is monitored. The distance between any two adjacent electrodes in this prototype is 2.5 mm, and during the course of amperometric measurement, the product formed at one electrode does not reach the other working electrode within 20 min after the addition of enzyme substrate. Thus, the method relies on the spatial resolution between the different antibodies being such that measurements are taken before cross-interference due to diffusion can occur. Identical enzyme labels (alkaline phosphatase, ALP) and substrates (p-aminophenyl phosphate, PAPP) are used for all analytes. Alkaline phosphatase-conjugated rat anti-mouse IgG was immobilized by passive adsorption. Our studies showed that this concept is feasible and can be applied to the simultaneous measurement of multiple analytes.

Algorithms↗
PubMed1999

Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex.

Formation of the normal mammalian cerebral cortex requires the migration of GABAergic inhibitory interneurons from an extracortical origin, the lateral ganglionic eminence (LGE). Mechanisms guiding the migratory direction of these neurons, or other neurons in the neocortex, are not well understood. We have used an explant assay to study GABAergic neuronal migration and found that the ventricular zone (VZ) of the LGE is repulsive to GABAergic neurons. Furthermore, the secreted protein Slit is a chemorepellent guiding the migratory direction of GABAergic neurons, and blockade of endogenous Slit signaling inhibits the repulsive activity in the VZ. These results have revealed a cellular source of guidance for GABAergic neurons, demonstrated a molecular cue important for cortical development, and suggested a guidance mechanism for the migration of extracortical neurons into the neocortex.

Animals↗
PubMed1999

Evidences for adduct formation between intracellular non-protein thiols and nitroazoles possessing an alpha,beta-unsaturated carbonyl side chain and the effects on radiosensitization of hypoxic cells.

Reactivity of a number of nitroazole derivatives bearing an alpha,beta-unsaturated carbonyl group on the side chain toward non-protein thiols (NPSH) was examined both in the phosphate buffer solution and in the biological system. These alpha,beta-unsaturated compounds reacted with NPSH, such as glutathione (GSH) and L-cysteine (Cys), in the buffer solution to afford the 1,4-addition products. The reaction gave a second-order rate constant. The adducts of methyl 4-(2'-nitroimidazol-1'-yl)crotonate (1) with GSH and Cys were isolated and characterized as two diastereomers (7a,b and 8a,b) in ca. 1:1 ratio, respectively. Similarly, exposure of EMT6/KU cells to 1 at 1.0 mM for 1 h resulted in depletion of the intracellular NPSH by more than 80%. Over 50% of the depleted NPSH was attributed to the formation of the conjugated diastereomeric adducts. On the other hand, incubation of EMT6/KU cells with 1 at 1.0 mM under hypoxic conditions before X-ray irradiation caused concurrently a sharp reduction of the shoulder of the dose-survival curves (reduced the extrapolation number (n) from 8.0 to ca. 1.0) and an increase in the slope (decreased the mean lethal dose (Do) to ca. 50% of the control level). The observed effects of 1 on the dose-survival curves were due to the NPSH depletion through the Michael addition occurred in the cellular system. A fairly linear relationship was obtained between the n value and the reduced intracellular NPSH level. It indicated that the shoulder effect of the dose-survival curves of hypoxic cells should be the result of the NPSH depletion by the alpha,beta-unsaturated carbonyl group attached to the nitroazoles.

Azoles↗
PubMed1999

HAC-1, a Drosophila homolog of APAF-1 and CED-4 functions in developmental and radiation-induced apoptosis.

We have identified a Drosophila homolog of Apaf-1 and ced-4, termed hac-1. Like mammalian APAF-1, HAC-1 can activate caspases in a dATP-dependent manner in vitro. During embryonic development, hac-1 is prominently expressed in regions where cells undergo natural death. Significantly, hac-1 transcription is also rapidly induced upon ionizing irradiation, similar to the proapoptotic gene reaper. Loss of hac-1 function causes reduced cell death, and reducing the dosage of hac-1 suppresses ectopic cell killing upon expression of the dcp-1 procaspase in the retina but has little effect on reaper, hid, and grim-mediated killing. Our data indicate that caspase activation and apoptosis in Drosophila are independently controlled by at least two distinct regulatory pathways that converge at the level of caspase activation.

Amino Acid Sequence↗
PubMed1999

Sugars as signaling molecules.

Recent studies indicate that, in a manner similar to classical plant hormones, sugars can act as signaling molecules that control gene expression and developmental processes in plants. Crucial evidence includes uncoupling glucose signaling from its metabolism, identification of glucose sensors, and isolation and characterization of mutants and other regulatory components in plant sugar signal transduction pathways. The emerging scenario points to the existence of a complex signaling network that interconnects transduction pathways from sugars and other hormone and nutrient signals.

Carbohydrates↗
PubMed1999

Rapid detection by reverse hybridization of mutations in the UL97 gene of human cytomegalovirus conferring resistance to ganciclovir.

UNLABELLED: BACKGROUND OF STUDY: Diseases due to human cytomegalovirus (HCMV) infection constitute a major threat in marrow and solid organ transplant recipients. Ganciclovir (GCV) is widely used in prophylaxis and pre-emptive therapy of active HCMV infection. Resistance to ganciclovir (GCV) may arise at variable frequency under GCV therapy and is conferred by mutations (i) in the UL97 gene (codons 460, 520, and 591-607) encoding a phosphotransferase which is essential for monophosphorylation of GCV and, to a lesser extent, (ii) in the UL54 gene coding for the DNA polymerase of HCMV. OBJECTIVE: The purpose was to develop a rapid assay to screen for emerging GCV resistance mutations in the UL97 gene of HCMV whereby avoiding virus isolation and nucleotide sequencing procedures. STUDY DESIGN: A nested PCR (nPCR) amplifying UL97 codons 450-672 was developed. Nested amplicons were subsequently sequenced directly. Oligonucleotides for use in a reverse hybridization assay were designed to detect relevant non-synonymous mutations at codons UL97 460, 520, 603 and 607. Strain AD169 served as a wild-type control. RESULTS: UL97-specific nPCR amplicons were obtained from 18 EDTA blood samples of ten transplant recipients receiving GCV for more than 30 days. In three consecutive samples from a single patient a GCV resistance mutation at codon 603 (C-->W) was detected. In addition, two out of four cell culture-adapted HCMV isolates known to exhibit GCV resistance in vitro revealed mutations at codons 460 (M-->V) and 607 (C-->Y), respectively. By reverse hybridization a discrimination of single nucleotide changes at codons 460, 520, 603 and 607 was possible whereby matching exactly the results of the nucleotide sequence analysis for all 23 amplicons examined. CONCLUSIONS: Reverse hybridization appeared to be a rapid and convenient alternative to nucleotide sequencing when screening the UL97 gene of HCMV for selected markers of GCV resistance.

Antiviral Agents↗
PubMed1999

Evaluation of the AmpliSensor PCR and the SHARP signal detection system for the early prediction of symptomatic CMV infection in solid transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is associated with high morbidity and mortality in transplant patients. Specific antiviral treatment at an early stage of CMV infection may effectively ameliorate, but not eliminate CMV disease in these patients. Presently, the pp65 antigenemia test on peripheral leukocytes is the method most widely used for predicting and monitoring transplant patients for active CMV infection. Nucleic acid amplification methods are less well defined since they lack standardisation. OBJECTIVE: A seminested fluorometric PCR assay (AmpliSensor-CMV, BAG, Germany) and a one-step PCR with a signal-amplification step (SHARP, Abbott, Germany) specific for the fragments of the CMV UL 122 and UL 123 genes, respectively, were evaluated for the early diagnosis of CMV infection. DESIGN: A total of 26 recipients of heterogeneous solid organs were monitored prospectively for a median of 99 days after transplantation. By testing 371 clinical samples parallel with the pp65-antigen assay and IgM and IgG EIA assays the sensitivity, specificity, correlation and quantitation potential of both PCRs was evaluated. RESULTS: Eight out of 26 patients developed active CMV infection. A total of 48 samples of these patients exceeded a CMV-DNA load threshold of 15 genome equivalents/10(5) leukocytes (AmpliSensor-CMV) and 41 samples exceeded the critical cut-off for the SHARP system. The AmpliSensor PCR exceeded its threshold consistently before the clinical onset of CMV disease (median 8 days). There was very good agreement between symptomatic CMV infection in patients and AmpliSensor-PCR, SHARP PCR, and pp65-antigen results (kappa-coefficient > 0.900). IgM and IgG EIA showed moderate agreement (kappa-coefficient = 0.591 and 0.552, respectively). CONCLUSION: Both PCRs and pp65 antigen assay correlated significantly better with CMV disease than serodiagnosis. The AmpliSensor PCR allowed more precisely than the SHARP system a quantitative determination of viral load and an early and reliable prediction of active CMV infection. The use of AmpliSensor PCR may improve the diagnosis and management of active CMV infection in organ transplant recipients.

Adult↗
PubMed1999

Predictive chemotherapy of advanced breast cancer directed by MTT assay in vitro.

In order to investigate the predictive value of in vitro MTT assay for directing chemotherapy of breast cancer patients, from 1992 to 1995, 156 advanced breast cancer patients who had evaluable lesions were recruited for a prospective study. Of them 83 had MTT assay before chemotherapy; the 73 patients in the MTT sensitive group received chemotherapy according to the result of the MTT assay. The other 10 patients in the MTT resistant group and 73 patients in the control group were given chemotherapy according to clinicians' discretion. The response rate in the MTT sensitive group was 76.7% (56/73). There was statistically significant difference as compared with 0 (0/10) in the MTT resistant group and 43.8% (32/73) in the control group. Between in vitro and in vivo, the overall coincident rate was 79.5% [(56 + 10)/83]. In the MTT sensitive group, the response rate of the subgroups of lesions and the chemotherapy regiments tended to be higher than that in the control group. Patients in the MTT sensitive group had longer response and survival than those in the control group. However, there was no statistical difference in the median response duration and the median survival between the two groups. Further exploration of in vitro chemosensitivity testing by MTT assay for patients with advanced breast cancer is warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans.

The human cullin protein CUL-2 functions in a ubiquitin-ligase complex with the von Hippel-Lindau (VHL) tumour suppressor protein. Here we show that, in Caenorhabditis elegans, cul-2 is expressed in proliferating cells and is required at two distinct points in the cell cycle, the G1-to-S-phase transition and mitosis. cul-2 mutant germ cells undergo a G1-phase arrest that correlates with accumulation of CKI-1, a member of the CIP/KIP family of cyclin-dependent-kinase inhibitors. In cul-2 mutant embryos, mitotic chromosomes are unable to condense, leading to unequal DNA segregation, chromosome bridging and the formation of multiple nuclei.

Amino Acid Sequence↗
PubMed1999

Expression of integrin receptors in the human trabecular meshwork.

PURPOSE: To examine the expression of integrin receptors in the human trabecular meshwork. METHODS: The expression of integrins in human tissues was visualized by immunohistochemical staining using integrin-specific antibodies. Immunoprecipitation was performed after biotin labeling of cell surface proteins. Reverse transcriptase-polymerase chain reaction was used to detect the presence of mRNA species for integrin subunits. RESULTS: Human trabecular meshwork tissues obtained from donors 2 to 65 years old stained positively for integrins alpha1, alpha3, alpha4, alpha5, alpha6, alphav, beta1, beta3, beta4 and beta5. The staining was observed mostly around the edges of trabecular beams in association with trabecular meshwork cells. The staining intensity did not appear to vary with donor age. In addition, immunoprecipitation of tissue extracts revealed the presence of integrin alpha2 and confirmed the absence of beta2. Results from polymerase chain reactions were consistent with these findings. CONCLUSIONS: A spectrum of integrin receptors that may have important roles in the cell-matrix interactions are demonstrated in the human trabecular meshwork. The repertoire identified in tissues is similar to that found in cultured cells except that the beta4 expression in tissues is lost in cultures.

Adult↗
PubMed1999

The identification of dipalmityl zeaxanthin as the major carotenoid in Gou Qi Zi by high pressure liquid chromatography and mass spectrometry.

The carotenoid in Gou Qi Zi was extracted by hexane, followed by repeated chromatography on a silica column. The major carotenoid recovered from the chromatographic step was subjected to hydrolysis in potassium hydroxide (KOH). The hydrolytic products were separated on a silica column followed by analysis for their molecular sizes by a Micromass Platform LCZ. The retention time of the carotenoid in Gou Qi Zi is 2.3 min. Upon hydrolysis, new carotenoid peaks appeared. The molecular ions detected by APCI- of the carotenoid at 2.3, 6.8 and 28 min are 1044, 806 and 568, respectively. The molecular sizes matched to that of dipalmityl zeaxanthin, monopalmityl zeaxanthin and zeaxanthin, respectively. The monopalmityl zeaxanthin peak appeared first and faded away as the free zeaxanthin peak reached the maximal size.

Carotenoids↗
PubMed1999

CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor CBFA1. To correlate CBFA1 mutations in different functional domains with the CCD clinical spectrum, we studied 26 independent cases of CCD and a total of 16 new mutations were identified in 17 families. The majority of mutations were de novo missense mutations that affected conserved residues in the runt domain and completely abolished both DNA binding and transactivation of a reporter gene. These, and mutations which result in premature termination in the runt domain, produced a classic CCD phenotype by abolishing transactivation of the mutant protein with consequent haploinsufficiency. We further identified three putative hypomorphic mutations (R391X, T200A and 90insC) which result in a clinical spectrum including classic and mild CCD, as well as an isolated dental phenotype characterized by delayed eruption of permanent teeth. Functional studies show that two of the three mutations were hypomorphic in nature and two were associated with significant intrafamilial variable expressivity, including isolated dental anomalies without the skeletal features of CCD. Together these data show that variable loss of function due to alterations in the runt and PST domains of CBFA1 may give rise to clinical variability, including classic CCD, mild CCD and isolated primary dental anomalies.

Animals↗
PubMed1999

Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in the tear film of patients with keratoconus.

PURPOSE: Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in the tear film of patients with keratoconus were measured to elucidate their possible roles in the pathogenesis of keratoconus. METHODS: Tear samples were collected from 15 keratoconus patients and 14 age-similar human control subjects. Levels of alpha1-proteinase inhibitor and alpha2-macroglobulin in each tear sample were quantified and compared between the two groups. RESULTS: Mean values for alpha1-proteinase inhibitor were 101.0+/-35.5 and 106.1+/-41.7 ng/microg protein for the keratoconus and control groups, respectively. The corresponding mean values for alpha2-macroglobulin were 13.5+/-6.8 and 14.8+/-7.5 ng/microg protein. Neither inhibitor showed a statistically significant difference between the keratoconus and control specimens. Subset analysis to evaluate the effects of contact lens wear and the presence of a graft in the fellow eye did not reveal a statistically significant difference. CONCLUSION: The tear film of patients with keratoconus contains normal levels of protease inhibitors. Therefore, the tear film may not be a source of the reduced inhibitor levels shown in the corneas of patients with keratoconus.

Adolescent↗
PubMed1999

A comparison of the antifibrillatory effects of desethylamiodarone to amiodarone in a swine model.

We evaluated the effect of two different doses of desethylamiodarone (DEA) and amiodarone on the ventricular fibrillation threshold (VFT). We ascertained the VFT in 24 pigs randomized to intravenous DEA, amiodarone, or vehicle. Ventricular fibrillation was induced by pacing the right ventricle by using a primary drive train at a cycle length of 270 ms for eight beats of 2-ms duration each. A secondary train of 20 pulses of 4-ms duration (100 Hz) immediately followed this over a total duration of 200 ms synchronized to the primary drive train. The intensity of the secondary train stimuli current was initially 2 mA and was increased by 2-mA increments until sustained VF with hemodynamic collapse was induced. The minimal current strength needed to induce sustained VF was defined as the VFT measured in mA. DEA (10 mg/kg) increased the VFT significantly over baseline from 13.5+/-4.9 to 23.2+/-8.8 mA (p = 0.0076). Amiodarone, 10 mg/kg, increased the VFT significantly over baseline (mean +/- SD) from 14.4+/-3.6 to 23.8+/-6.1 mA (p = 0.0016). An additional dose of amiodarone (15 mg/kg) increased the VFT to 38.5+/-15.9 mA, which is significantly greater than the VFT derived from lower-dose amiodarone (p = 0.046). We showed that DEA (10 mg/kg) has a similar antifibrillatory effect as 10 mg/kg of amiodarone. We also demonstrated a dose-dependent effect on VFT for amiodarone.

Amiodarone↗
PubMed1999

Thromboembolic complications of cardiac radiofrequency catheter ablation: a review of the reported incidence, pathogenesis and current research directions.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) has become established as an effective therapy for the treatment of many cardiac tachyarrhythmias. The principle limitation of conventional RFCA continues to be the risk of thromboembolism. This risk is of particular concern for the ongoing development of the catheter maze procedure for the treatment of atrial fibrillation, which currently involves the creation of extensive linear lesions in the left atrium. METHODS AND RESULTS: A Medline search of the literature over the last ten years was performed. Focused review of the reported thromboembolic complications of RFCA indicates an overall incidence of 0.6%. However, the risk is increased when ablation is performed in the left heart (1.8% to 2%) and for ventricular tachycardia (2.8%). It is of concern that intravenous heparin and the use of temperature feedback to control radiofrequency current do not eliminate the risk of thromboembolic events. CONCLUSION: The thromboembolic complications of RFCA are not eliminated by the treatment of intravenous herapin and mode of temperature control during ablation. Potential approaches to further reduce the risk of thromboembolism include the adjunctive administration of specific inhibitors of platelet activation and aggregation, intraprocedural intracardiac echocardiography, irrigated radiofrequency ablation, and cryoablation catheter systems.

Anticoagulants↗