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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 451 records · Page 25Linked to original sources

Molecular characterization and expression of the M6 gene of grass carp hemorrhage virus (GCHV), an aquareovirus.

The complete nucleotide sequence of M6 gene of grass carp hemorrhage virus (GCHV) was determined. It is 2039 nucleotides in length and contains a single large open reading frame that could encode a protein of 648 amino acids with predicted molecular mass of 68.7 kDa. Amino acid sequence comparison revealed that the protein encoded by GCHV M6 is closely related to the protein mu1 of mammalian reovirus. The M6 gene, encoding the major outer-capsid protein, was expressed using the pET fusion protein vector in Escherichia coli and detected by Western blotting using chicken anti-GCHV immunoglobulin (IgY). The result indicates that the protein encoded by M6 may share a putative Asn-42-Pro-43 proteolytic cleavage site with mu1.

Amino Acid Sequence↗

Anorectal malformations caused by defects in sonic hedgehog signaling.

Anorectal malformations are a common clinical problem affecting the development of the distal hindgut in infants. The spectrum of anorectal malformations ranges from the mildly stenotic anus to imperforate anus with a fistula between the urinary and intestinal tracts to the most severe form, persistent cloaca. The etiology, embryology, and pathogenesis of anorectal malformations are poorly understood and controversial. Sonic hedgehog (Shh) is an endoderm-derived signaling molecule that induces mesodermal gene expression in the chick hindgut. However, the role of Shh signaling in mammalian hindgut development is unknown. Here, we show that mutant mice with various defects in the Shh signaling pathway exhibit a spectrum of distal hindgut defects mimicking human anorectal malformations. Shh null-mutant mice display persistent cloaca. Mutant mice lacking Gli2 or Gli3, two zinc finger transcription factors involved in Shh signaling, respectively, exhibit imperforate anus with recto-urethral fistula and anal stenosis. Furthermore, persistent cloaca is also observed in Gli2(-/-);Gli3(+/-), Gli2(+/-);Gli3(-/-), and Gli2(-/-);Gli3(-/-) mice demonstrating a gene dose-dependent effect. Therefore, Shh signaling is essential for normal development of the distal hindgut in mice and mutations affecting Shh signaling produce a spectrum of anorectal malformations that may reveal new insights into their human disease equivalents.

Anal Canal↗

Chain length dependence of lipid partitioning between the air/water interface and its subphase: thermodynamic and structural implications.

We have investigated phosphatidylcholines with the same two saturated hydrocarbon chains of 12, 10 and 8 C-atoms. Langmuir trough data could be evaluated towards even small lipid subphase desorption when applying a novel approach that had recently been developed in our laboratory. The C12 lipid turned out to form a nearly insoluble monolayer with slight desorption only beyond 15 mN/m for an area/volume ratio around 1 cm(-1). Above 22 mN/m micellation in the subphase apparently terminates further accumulation in the interface forcing additionally added lipid to enter the bulk volume. A comparatively substantial increase of solubilization was observed for the C10 monolayer. When turning to the C8 lipid partitioning proved to take place in nearly equal parts. In that case, strong multimeric aggregation is indicated to occur in both the interfacial and the bulk volume domains. All the results are quantitatively discussed in the light of basic thermodynamic and structural considerations.

Linear Models↗

A long-lived amphiphilic fluorescent probe studied in POPC air-water monolayer and solution bilayer systems.

A novel amphiphilic fluorescent probe (Fluorazophore-L) with a strongly dipolar, nonionic azoalkane as headgroup and a palmitoyl tail has been synthesized and characterized. Pure Fluorazophore-L was found to be sufficiently amphiphilic to form stable air-water monolayers. An analysis of the surface pressure versus area suggests an area per molecule of about 34+/-2 A(2) at 29 mN m(-1). The partitioning into a lipid membrane model was quantified at the air-water interface by spreading 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) monolayers. Measurements with different molar fractions of Fluorazophore-L revealed a small but significant reduction of the mean area in the mixed monolayer. The excess free energy of mixing (-0.5+/-0.1 kT) indicated a weakly attractive interaction slightly above thermal energy, suggesting a good miscibility of the fluorescent probe within the lipid monolayer without major structural modifications. Spectroscopic measurements confirmed the incorporation of Fluorazophore-L into POPC vesicles. The fluorescence lifetime was very long (125+/-5 ns under air) with monoexponential fluorescence decays.

Fluorescent Dyes↗

Effect of sarsasapogenin and its derivatives on the stimulus coupled responses of human neutrophils.

METHODS: The effects of three sapogenins (sarsasapogenin, tigogenin and hecogenin) on the stimulus-induced superoxide generation and protein tyrosyl phosphorylation in human neutrophils were investigated. RESULTS: When the cells were preincubated with sapogenin, three sapogenins dose-dependently suppressed the superoxide generations induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA), respectively. In both cases, their effects were in the order: sarsasapogenin>tigogenin>hecogenin. While sarsasapogenin suppressed the superoxide generation induced by arachidonic acid (AA) as well, the superoxide generation was scarcely suppressed by tigogenin and significantly enhanced by hecogenin. In parallel to their effects on the superoxide generation, the three sapogenins dose-dependently suppressed the fMLP-induced and PMA-induced tyrosyl phosphorylations of 45 kDa protein in neutrophils, respectively. CONCLUSIONS: Of the sapogenins tested, sarsasapogenin may have the most clinical use as it suppresses superoxide generation.

Arachidonic Acid↗

Imidazoline I(1) receptor-induced activation of phosphatidylcholine-specific phospholipase C elicits mitogen-activated protein kinase phosphorylation in PC12 cells.

In the present study, we tested the hypothesis that the activation of imidazoline I(1)-receptor, which is coupled to phosphatidylcholine-specific phospholipase C, results in downstream activation of mitogen-activated protein kinase (p42(mapk) and p44(mapk) isoforms) in PC12 cells. PC12 cells pretreated with nerve growth factor (50 ng/ml, 48 h) to initiate neuronal differentiation were incubated with [methyl-3H]choline and [3H]myristate. Activation of imidazoline I(1) receptor by rilmenidine (10 microM) caused time-dependent increases in diacylglycerol accumulation and phosphocholine release. The Western blotting analysis showed that rilmenidine (10 microM) produced a time-dependent activation of p42(mapk) and p44(mapk) that reached its maximum at 15 min and returned to control levels after 30 min. This finding was confirmed by immunofluorescence labeling of activated mitogen-activated protein kinase in the same model system. Efaroxan (imidazoline I(1)-receptor antagonist) or tricyclodecan-9-yl-xanthogenate (D609, phosphatidylcholine-specific phospholipase C inhibitor) attenuated the phosphorylation of p42(mapk) and p44(mapk) induced by rilmenidine. Nerve growth factor-induced phosphorylation of both mitogen-activated protein kinase isoforms was not affected by D609. These results support the hypothesis that the activation of the imidazoline I(1) receptor coupled phosphatidylcholine-specific phospholipase C results in the downstream activation of mitogen-activated protein kinase.

Acetylcholine↗

Prediction of adverse outcomes by common definitions of hypertension in pregnancy.

OBJECTIVE: To examine the ability of five common definitions of hypertension in pregnancy to predict adverse maternal and perinatal outcomes. METHODS: We studied 9133 singleton nulliparous pregnancies with early prenatal care from the Collaborative Perinatal Project, a large cohort study conducted between 1959 and 1965. Definitions from five different groups were evaluated. Severe maternal and perinatal morbidity and mortality were used as the outcome measurements. Sensitivity, specificity, and positive predictive value for outcomes were compared across various definitions. RESULTS: Blood pressure alone had very poor discriminatory power to predict adverse outcomes. Positive predictive values of adverse outcomes by the diagnosis of preeclampsia were 18-20% based on antepartum and intrapartum blood pressures and 22-36% based on antepartum blood pressure only. Mild hypertension occurring for the first time in labor and isolated mild systolic hypertension were not associated with adverse outcomes. Similarly, an increase in diastolic blood pressure of 15 mmHg that did not achieve an absolute value of 90 mmHg did not predict adverse outcome. CONCLUSION: Neither blood pressure nor blood pressure and proteinuria are accurate predictors of severe adverse maternal and perinatal outcomes. Mild hypertension occurring for the first time in labor and isolated mild systolic hypertension should not be considered indicators for hypertensive disorders in pregnancy in a research definition.

Adolescent↗

Epidural analgesia and fetal head malposition at vaginal delivery.

OBJECTIVE: To determine if nulliparas who delivered with on-demand epidural analgesia are more likely to have malpositioning of the fetal vertex at delivery than women delivered during a period of restricted epidural use. METHODS: A retrospective cohort of nulliparous women with spontaneous labor delivered during a 12-month period immediately before the availability of on-demand labor epidural analgesia was compared with a similar group of nulliparas delivered after labor epidural analgesia was available on request. The primary outcome variable was a non-occiput anterior position or malpositioned fetal head at vaginal delivery. RESULTS: The frequency of epidural use increased from 0.9% before epidural analgesia became available on demand to 82.9% afterward. Fetal head malpositioning at vaginal delivery occurred in 26 of 434 (6.0%) women delivered in the before period compared with 29 of 511 (5.7%) in the after period (relative risk 0.95, 95% confidence interval 0.6, 1.6). No statistically significant difference in the incidence of fetal head malpositioning was present after patients were stratified by mode of delivery (Mantel-Haenszel weighted relative risk 0.94, 95% confidence interval 0.6, 1.4). The study sample size provided 85% power to detect a two-fold increase in the incidence of fetal malpositioning from a baseline rate of 6% associated with on-demand epidural use. CONCLUSION: Providing on-request labor epidural analgesia to nulliparas in spontaneous labor did not result in a clinically significant increase in the frequency of fetal head malpositioning at vaginal delivery.

Adolescent↗

Labor epidural analgesia and intrapartum maternal hyperthermia.

OBJECTIVE: To determine if women receiving continuous epidural analgesia are more likely to develop intrapartum fever and related neonatal effects. METHODS: We conducted a retrospective cohort analysis of nulliparous women with term gestations in spontaneous labor delivered during a 12-month period immediately before the availability of on-demand labor epidural analgesia (Before group) and a similar group of nulliparas delivered after labor epidural analgesia was available on request (After group). RESULTS: The frequency of epidural increased from 1% before the availability of on-request epidural analgesia to 83% after epidural analgesia was available on request. A maximal temperature of at least 100.4F was detected in three of 498 (0.6%) women in the Before group, and in 63 of 572 women (11.0%) in the After group (relative risk [RR] = 18.3, 95% confidence interval [CI] 5.8, 57.8, P <.01). Logistic regression analysis demonstrated that on-request labor epidural analgesia was associated with an intrapartum temperature of at least 99.5F (RR = 3.0, 95% CI 2.3, 3.6, P <.001) and intrapartum temperature of at least 100.4F (RR = 20.2, 95% CI 7.0, 86.0, P <.001). There were statistically significant increases in the proportion of newborns who had complete blood counts (24% versus 13.5%, RR = 1.5, 95% CI 1.3, 1.8, P <.01) and blood cultures (30.7% versus 8.6%, RR = 1.7, 95% CI 1.2, 2.4, P <.05) in the After period compared with the Before group; however, there was no statistically significant difference in the proportion of infants who received antibiotic therapy for presumed sepsis between the After and Before periods (5.8% versus 4.6%, RR = 1.15, 95% CI 0.8, 1.6, P =.38). No infants in either group had culture-proven sepsis. CONCLUSION: The use of labor epidural analgesia is associated with a clinically significant increase in the incidence of intrapartum fever.

Adult↗

A miniature class V flextensional cymbal transducer with directional beam patterns: the double-driver.

The "double-driver" cymbal, a directional class V flextensional transducer, is described in this paper. Its basic structure is a bilaminar piezoelectric disk with metal caps as mechanical transformers and amplifiers. The directivity was accomplished by exciting the double-driver in a combined flexural and bending mode causing the sound pressure to add in one direction and cancel in the opposite direction. The cardioid beam pattern predicted by finite element modeling agreed well with the experimental measurements. A 3 x 3 double-driver array was constructed to demonstrate that under optimal conditions the array can provide a directional beam pattern with a front-to-back ratio of more than 20 dB.

Ceramics↗

Surgical management of medullary hemangioblastoma. Report of 47 cases.

BACKGROUND: Hemangioblastomas of the medulla are rare and seldom reported. Surgical resection of medullary hemangioblastomas is associated with high morbidity and mortality rates. We present a unique institutional experience over a 12-year period. METHODS: Between 1987 to 1998, 47 hemangioblastomas were surgically resected and analyzed retrospectively. The follow-up ranged from 6 to 136 months with an average of 35 months. RESULTS: Thirty-nine single hemangioblastomas were distributed in 3 anatomical areas: pontomedullary, medullary, and cervico-medullary. They were either focal intramedullary or dorsal exophytic. There were cyst formations in 97.4% of the single hemangioblastomas. The major feeding arteries and the tumor blush could be clearly visualized on angiogram, sometimes even on MRA. All medullary hemangioblastomas were radically removed. Postoperatively, 61.5% patients had clinical improvement, two patients' symptoms remained unchanged and 11 patients deteriorated; of the latter, 8 patients improved later with proper therapy, and 2 patients died. CONCLUSION: Preoperative diagnosis of medullary hemangioblastoma is possible with MRI. With improved microsurgical technique and better understanding of the vascular pattern of the tumor, total surgical resection can be performed with <5% mortality. The surgical strategy is en bloc excision, as piecemeal resection can lead to uncontrollable hemorrhage. Removal of large solid hemangioblastomas may result in severe postoperative edema and/or hemorrhage in the medulla affecting the respiratory and vagal centers. Preoperative embolization through the posterior inferior cerebellar artery (PICA) can be helpful in this situation.

Adolescent↗

Novel monoamine transporter ligands reduce cocaine-induced enhancement of brain stimulation reward.

Six novel monoamine reuptake inhibitors were screened for their intrinsic effects on brain stimulation reward (BSR), as well as for their potential to reduce cocaine-induced reward-enhancement in that paradigm. Two of the compounds, nocaine-3B and 5-ara-74A (disubstituted piperidines) significantly reduced locus of rise (LOR), threshold measure of reward, at some doses. One compound, 1-RV-96A (a hybrid of the GBR and WIN-like agents) significantly reduced reward (increased LOR), but only at the highest dose tested. No effect of dose was found for MC9-20 (a GBR-like acyclic analogue of the N-bisarylmethoxyethyl-N'-phenylpropyl piperazine), nocaine-250B or 4-ara-42C (disubstituted piperidines). When cocaine (10 mg/kg, ip) and selected, hedonically neutral doses of novel compounds were combined, the following findings were obtained: MC9-20 (2.5 mg/kg, ip) showed a significant increase in cocaine-induced reward enhancement (0.2 log units or 53%). In contrast, nocaine-250B and 1-RV-96A (both at 10 mg/kg, ip) demonstrated a significant reduction (0.13 log units or 41%) in cocaine-induced reward enhancement (P<.01 and P<.05, respectively), as measured by changes in LOR. There were no differences in the maximum behavioral output (MAX) at either dose of each of the six drugs, or when selected doses were combined with cocaine. These results indicate that nocaine-250B and 1-RV-96A constitute two potential anticocaine compounds worthy of further behavioral and biochemical evaluation.

Animals↗

Application of double-impedance system and cyclic voltammetry to study the adsorption of fullerols (C60(OH)n) on biological peptide-adsorbed gold electrode.

The adsorption of fullerols (C60(OH)n) on glutathione-adsorbed gold electrode was characterized by using double-impedance system, i.e., electrochemical quartz crystal impedance and electrochemical impedance spectroscopy, and cyclic voltammetry. The time courses of piezoelectric parameters were used to reflect the changes of interfacial physical properties, such as mass, density-viscosity, and dielectric constant, during the adsorptions of peptide and fullerols onto electrode. The electrochemical impedance based on the simple equivalent electric network were also simultaneously measured and provided electrochemical interface information, e.g., double-layer capacitance and charge-transfer resistance. It was found that the double-impedance responses were varied with the forms of glutathione. It was also shown that the frequency curves due to the adsorption of oxidized (GSSG) and reduced (GSH) glutathione could be exhibited as different kinetic equations. The heterogeneous charge-transfer rate constants of ferricyanide/ferrocyanide before and after the peptide and fullerols adsorption were determined by CV and EIS methods. The results showed that the proposed method has potential applications in interfacial studies of biomaterials, since these combined techniques have advantages in real time providing multidimensional piezoelectric and electrochemical impedance information.

Adsorption↗

STAT3 exerts two-way regulation in the biological effects of IL-6 in M1 leukemia cells.

The signal transducer and activator of transcription (STAT) proteins have been implicated in cytokine-regulated proliferation, differentiation and cell survival. Interleukin-6 (IL-6), a pleiotropic cytokine, induces a robust and sustained activation of STAT3 in M1 acute myeloid leukemia cells, which in turn undergo growth arrest, terminal differentiation and apoptosis in response to IL-6. The roles of STAT3 activation in IL-6-mediated responses in M1 cells are not fully understood. We introduced STAT3 antisense cDNA into M1 cells. STAT3 antisense cDNA blocked the expression and IL-6-induced tyrosine phosphorylation and DNA binding of STAT3, and resulted in reduction of both IL-6-induced growth arrest at G(0)/G(1) phase and macrophage differentiation in the M1 transformants. This observation is in accordance with previous reports and confirms that STAT3 plays an essential role in IL-6-induced growth arrest and terminal differentiation in M1 leukemia cells. On the other hand, STAT3 antisense cDNA augmented IL-6-induced apoptosis of M1 cells, which was supported by the cell cycle assay, DNA fragmentation assay and detection of the p17 active fragment of Caspase 3. As proliferation inhibition and differentiation induction stands for a negative signal, while survival maintenance stands for a positive signal, we conclude that STAT3 exerts two-way regulation on the biological effects of IL-6 in M1 leukemia cells.

Animals↗

Pharmacokinetics and tolerability of extended-release clarithromycin.

BACKGROUND: Clarithromycin is a semisynthetic macrolide that exhibits broad-spectrum activity against gram-positive, gram-negative, and atypical respiratory tract and skin/skin structure pathogens, Mycobacterium species, and Helicobacter pylori. It is indicated for the treatment of a wide variety of respiratory and dermatologic infections in children and adults as well as prophylaxis and treatment of Mycobacterium avium complex infection and peptic ulcers due to H. pylori. OBJECTIVE: In this article, we review the results of 3 studies of the steady-state pharmacokinetic profiles of clarithromycin and 14(R)-hydroxy-clarithromycin after multiple oral once-daily doses of 500-mg extended-release (ER) clarithromycin tablets. We also review the drug tolerability in 2 phase III comparative clinical trials of immediate-release (IR) and ER clarithromycin conducted in adults with acute maxillary sinusitis (AMS) and acute exacerbation of chronic bronchitis (AECB). METHODS: In the 3 pharmacokinetic studies, multiple-dose regimens of clarithromycin IR (one 250-mg or 500-mg tablet twice daily) and clarithromycin ER (one or two 500-mg tablets once daily), administered to healthy male and female volunteers, were evaluated. The effect of administration in nonfasting versus fasting conditions was assessed as well. Tolerability information was collected from each adult patient enrolled in phase III efficacy studies conducted to support the application for US Food and Drug Administration approval for the treatment of AMS and AECB. Regimens evaluated were 500 mg IR clarithromycin tablets twice daily or 1000 mg (2 x 500 mg) ER clarithromycin tablets once daily for 7 days (AECB) or 14 days (AMS). RESULTS: Bioavailability of the ER clarithromyin tablet administered with food was equivalent to that of the reference IR tablet, based on area under the plasma concentration-time curve (AUC) for both parent compound and active metabolite. The bioavailability of the ER tablet was 30% lower (based on clarithromycin AUC) when administered under fasting versus nonfasting conditions. Compared with the IR tablet, administration of the ER tablet resulted in significantly lower (P < 0.05) clarithromycin peak plasma concentration (Cmax), delayed time to Cmax, and lower degree of concentration fluctuation, confirming its in vivo extended-release characteristics. The most frequently reported adverse events (AEs) in the phase III clinical trials were diarrhea, abnormal taste, and nausea and were generally mild or moderate. The incidence of AEs was comparable for the 2 formulations. The severity of gastrointestinal AEs was significantly less for the ER formulation than for the IR formulation (P = 0.018), as was the frequency of premature study discontinuation due to gastrointestinal AEs or abnormal taste (P = 0.004). CONCLUSIONS: The results from the 3 pharmacokinetic studies reviewed demonstrate the bioequivalence of the ER and IR formulations and support the use of this clarithromycin ER formulation in a once-daily dosing regimen in phase III clinical trials. The ER tablet should be taken with food to maximize bioavailability. The results of 2 phase III comparative clinical efficacy and safety trials of clarithromycin ER tablets versus IR tablets in AMS and AECB confirm the good tolerability of the ER formulation.

Adolescent↗

The impact of chronic estrogen deprivation on immunologic parameters in the ovariectomized rhesus monkey (Macaca mulatta) model of menopause.

A large clinical literature suggests that estradiol (E(2)) plays a critical role in immune function. To further explore the relationship between E(2) and immune function, we examined a variety of immunological parameters in a rhesus monkey model of menopause and hormone replacement therapy. Rhesus monkeys (Age, 13.7+/-2.6 years) were ovariectomized and received either sham (n=10) or estradiol (n=10) replacement implants. Nine months post-ovariectomy, a variety of immunologic parameters were measured. E(2)-deprivation reduced natural killer cell activity and increased serum soluble gp130 levels. There was a trend for an increased proportion of CD8(+) (P=0.12) and HLA-DR(+)CD3(+) cells (P=0.15) and decreased proportion of eosinophils (P=0.11) in the E(2)-deprived monkeys. There was no difference in leukocyte distribution, CD28, CD56, CD4, CD8/CD45, colony forming units-granulocyte/monocytes formation, peripheral blood mononuclear cell apoptotic rate, or serum TNF, TNF-R1, TNF-R2, IL-6, soluble IL-6R, and IL-1 between the groups. These data demonstrate that E(2)-deprivation affects several aspects of immune function. These findings may have implications for menopause-associated changes of immune function that occur in women.

Animals↗

A novel retroviral vector that allows the magnetic selection of infected cells.

Retroviral vectors are used widely in research and are also being designed for use in gene therapy trials. In practice, these vectors usually contain a marker gene, which is often a drug selection gene. In this report, a novel retroviral vector has been constructed which contains a gene that allows selection for infected cells by a magnet. This gene is a single-chain antibody (sFv) to a specific hapten molecule 4-ethoxymethylene-2-phenyl-2-oxazolin-5-one (phOx). sFv specific for phOx is displayed on the surface of infected cells. This feature allows binding to phOx-BSA coated magnetic beads which are used to isolate the infected cells.

Cell Line↗

Purification and characterization of White Spot syndrome virus (WSSV) produced in an alternate host: crayfish, Cambarus clarkii.

Penaeid shrimp is the natural host of White Spot Syndrome Virus (WSSV) that can cause high mortality in the infected hosts. Attempts to obtain sufficient amounts of purified intact WSSV for characterization have been unsuccessful. Using crayfish, Cambarus clarkii as a proliferation system, a large amount of infectious WSSV was reproduced and intact WSSV viral particles were purified with a new isolation medium by ultra-centrifugation. Purified WSSV particles were very sensitive to organic solvents and the detergent, Triton X-100. The size of the rod-shape, somewhat elliptical, intact WSSV was 110-130x260-350 nm with a long, tail-like envelope extension. The naked viral nucleocapsid was about 80x350 nm, and it possessed 15 spiral and cylindrical helices composed of 14 globular capsomers along its long axis, and a 'ring' structure at one terminus. Distinct WSSV genome DNA patterns were obtained when the purified genomic dsDNA of WSSV was digested with five different restriction enzymes (HindIII, XhoI, BamHI, SalI, and SacI). In addition, at least 13 major and distinct protein bands could be observed when purified intact WSSV viruses were separated by SDS-PAGE followed by Coomassie Brilliant R-250 staining. The estimated molecular weights of these proteins were 190, 84, 75, 69, 68, 58, 52, 44, 28, 27.5, 23, 19, and 16 kD, respectively. Both the 44 and 190 kD proteins were easily removed if the hemolymph from the WSSV infected crayfish was transiently treated with 1% Triton X-100 before it was subjected to gradient centrifugation, indicating that both of them are located on the surface of the viral envelope. These characteristics are consistent with WSSV isolated from the penaeid shrimp.

Animals↗