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Biomedical subjects

J Zhang

Publications and source records attributed to J Zhang.

At least 325 records · Page 18Linked to original sources

Kinetics and morphologies of viscoelastic phase separation.

In this paper, the effects of relaxational bulk modulus and the average composition of polymers on the viscoelastic phase separation are investigated in detail. It is found that there are two typical morphologies, i.e., moving droplet phase and phase inversion, and the relaxation of the dynamical asymmetry and the amplification of the concentration fluctuation are responsible for the appearance and evolution of different morphologies of viscoelastic phase separation. It is found that, for the viscoelastic phase separation, the scattering function has two peaks. The growth exponents of the main and the secondary peaks in the late stage are almost the same and approximately 0.6, which also agrees with the experimental observations. On the other hand, the growth exponent of the secondary peak increased from approximately 0.42 to approximately 0.66 with increase of straight phi(0) from 0.275 to 0.4, in the intermediate stage.

Journal Article↗

A novel mechanism of dopamine neurotoxicity involving the peripheral extracellular and the plasma membrane dopamine transporter.

Chinese hamster ovary cells stably expressing a rat dopamine transporter (designated D8 cells) and neuroblastoma SK-N-SH cells were used as two model systems to study dopamine neurotoxicity. Within 24 h, 1-10 mM dopamine induced D8 cells into apoptosis while 20-200 microM dopamine induced SK-N-SH cells into cell death. The viability of both cell types decreased in a dose-dependent manner. However, the dopamine uptake activity of D8 cells at 10 mM was not significantly higher than the uptake at 100 microM, suggesting that it was not the high concentration of intracellular dopamine that induced D8 cells into apoptosis, but rather dopamine found in the extracellular space. Furthermore, cocaine, an inhibitor of dopamine uptake, could not block cell death induced by dopamine. Forskolin, an agonist of protein kinase A (PKA), stimulated dopamine uptake in D8 cells and blocked apoptosis induced by the drug. These results suggest that the dopamine transporter mediates a dopamine-dependant apoptotic signal transduction pathway that is independent of dopamine uptake into the cell.

Animals↗

Light and electron microscopic observations of a direct projection from mesencephalic trigeminal nucleus neurons to hypoglossal motoneurons in the rat.

A direct projection from rat mesencephalic trigeminal nucleus (Vme) neurons to the hypoglossal nucleus (XII) motoneurons was studied using a double labeling method of anterogradely biotinylated dextran amine (BDA) tracing combined with retrogradely horseradish peroxidase (HRP) transport at both light and electron microscopic levels. BDA was iontophoresed unilaterally into the caudal Vme, and 7 days later HRP was injected into the ipsilateral tongue to label hypoglossal motoneurons. The BDA-labeled fibers were seen descended along Probst' tract and were traced to the caudal medulla. In this course, the fibers gave off axon collaterals bearing varicosities in the trigeminal motor nucleus (Vmo), the parvicellular reticular formation (PCRt), the dorsomedial portions of the subnuclei of oralis (Vodm) and interpolaris (Vidm) and in the XII ipsilaterally. The labeling of terminals was most dense in the PCRt at the levels of caudal pons and rostral medulla, which displayed a "dumbbell-shaped" form in the transverse planes. In the XII, labeled terminals were distributed mainly in the dorsal compartment of the nucleus. One hundred sixty-eight appositions made by BDA-labeled terminals on HRP-labeled motoneurons were seen in the dorsal compartment (71%) and in the lateral subcompartment (24%) of the ventral XII. Under electron microscopy BDA-labeled boutons containing clear, spherical synaptic vesicles were found to form synaptic contacts with the somata and dendrites of hypoglossal motoneurons with asymmetric specializations. The present study provides new evidence that the trigeminal proprioceptive afferent neurons terminate in the XII and make synaptic contacts with their motoneurons.

Animals↗

[A further study on potential of microsatellite analysis of urine in diagnosis of bladder cancer].

OBJECTIVES: To investigate the application value of microsatellite analysis of voided urine in diagnosis of bladder cancer and compare the advantages and disadvantages of this method and urine cytology. METHODS: Thirteen microsatellite markers, including the nine markers used in the authors' previous study and another four new markers, were tested on urine DNA from 143 individuals with or without bladder lesions in a blinded fashion. Urine cytology was applied at the same time. RESULTS: The urine DNA from 89% (97/109) of the patients with bladder cancer, 86% (6/7) of the patients with inverted papilloma of the bladder, 3 out of 7 patients with cystitis and one patient with hematuria of unknown cause showed alterations, at least, in one of the 13 microsatellite markers, while the 19 individuals without bladder lesion had no change at any of these loci. Nucleic atypia or suspicious cancer cells were detected by routine cytology in the urine of the 3 patients with cystitis and one patient with hematuria of unknown cause who showed alterations of microsatellite in their urine sediments. Among the 81 cases of bladder cancer whose urine was examined by both microsatellite analysis and routine cytology, 73 cases (90%), of various stage or grade, were identified by microsatellite analysis, while only 41 cases (51%), mainly at advanced stage, were detected by cytology. Cancer cells were detected in the urine sediments of 4 of the 12 cases that were not identified by microsatellite analysis. CONCLUSION: Microsatellite analysis of urine is useful for detection of bladder cancer. Microsatellite analysis and urine cytology could be complementary to each other.

Female↗

[Diagnosis and treatment of hypoglossal neurinoma].

OBJECTIVE: To investigate the symptoms, diagnosis, operative approaches and prognosis of hypoglossal neurinoma. METHODS: The clinical symptoms, radiological features, prevalence, operative approaches and prognosis of 9 cases of hypoglossal neurinoma were analyzed. RESULTS: Cases of neurinoma of the hypoglossal nerve accounted for 1.9% of the cases of skull base neoplasm in the same period. Most of the tumor was in the shape of dumbbell, involving both intracranial and extracranial segments of the nerve. In a few cases, the tumor mainly involved the intracranial segment of hypoglossal nerve. All the cases were operated on, of which 7 through extreme-far-lateral approach, 1 through extreme-far-lateral approach combined with cervical approach, and one through the midline approach. Total resection was achieved in all cases. Follow up was performed in 7 cases, among which 5 cases returned to their work, 1 resumed the ability of self-care, and one still required care of others. CONCLUSION: As the hypoglossal canal is next to the jugular foramen and foramen magnum, preoperative diagnosis of the hypoglossal neurinoma is difficult. The most common initial symptom is atrophy of tongue muscle. Radical resection is the best choice of treatment. The extrem-far-lateral approach is the best approach for operation. The prognosis is inspiring after operation.

Adult↗

A comparison between microsatellite analysis and cytology of urine for the detection of bladder cancer.

We have studied, in a blinded fashion, cytology and microsatellite analysis on urine sediments of 143 Chinese with or without bladder lesions. Microsatellite analysis succeeded in all 143 individuals, while cytology could not be performed on 42 subjects due to insufficient urine samples. Both microsatellite analysis and routine urine cytology succeeded in 81 bladder cancer patients. Seventy-three patients (90%) were identified by microsatellite analysis, while only 41 patients (51%) were identified by cytology. However, four patients were identified by routine cytology but not by microsatellite analysis. Our results proved that microsatellite analysis is more sensitive than routine cytology but the two methods are complementary to each other.

Adult↗

Determination of L-cysteine in amino acid mixture and human urine by flow-injection analysis with a biamperometric detector.

Based on the electrocatalytic oxidation of cysteine at pretreated platinum electrode and the flow-injection biamperometry for irreversible couple, a novel electrochemical detector is proposed for the selective determination of cysteine in amino acid mixtures and human urine samples. A thin-layer flow through cell was used to achieve large electrode surface area to volume ratio. Two identical pretreated platinum electrodes were mounted in the cell with an applied potential difference of 10 mV. By coupling two independent and irreversible electrode processes, namely, the oxidation of cysteine and the reduction of platinum oxide, the biamperometric detection scheme has been established. The resulting current is linear to cysteine over the range 4 x 10(-7)-4 x 10(-5) M with the detection limit 1 x 10(-7) M (15 pmol). The selectivity of the detector is tested by 55 foreign species including 26 ions, 11 amino acids, 6 vitamins, and 12 other compounds possibly found in urine. The detector performs well as a routine assay, showing high efficiency (180 samples/h) and good reproductivity shown by a RSD of 0.6% for eight repeated determinations of 2 x 10(-6) M cysteine. The urine samples are detected directly without the need of pretreatment or adding other reagents.

Amino Acids↗

Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene.

We have identified two elastin gene (ELN) mutations located in cis in two related families with supravalvular aortic stenosis (SVAS). These mutations included an in-frame duplication in exon 18 (1034-1057dup) and a single base substitution in exon 26 (1829G-->A) predicted to result in the amino acid substitution R610Q. Haplotype analysis in one of the families identified an individual with a recombination between exon 18 and 26 of the elastin gene. This individual was unaffected and carried the exon 18 insertion mutation but not 1829G-->A. Skin fibroblasts were established from this recombinant normal individual and from an affected individual carrying both of the mutations. Reverse transcription/polymerase chain reaction (RT-PCR) analysis indicated that the expression of the mutant allele was reduced to 12%-27% of the normal allele in the affected but not in the unaffected individual. RNA-blot hybridization and immunoprecipitation experiments revealed reduced steady-state elastin mRNA levels and tropoelastin synthesis in the affected individual. RT-PCR analysis of the mRNA rescued by cycloheximide treatment indicated that mutation 1829G-->A created a cryptic donor splice site within exon 26, resulting in the deletion of four nucleotides at the 3'-end of exon 26 and a frameshift in the mRNA. This frameshift mutation generated a premature termination codon in the domain encoded by exon 28, clearly resulting in nonsense-mediated decay (NMD) of this frameshift RNA product. Despite considerable variability in the molecular nature of mutations responsible for SVAS, the unifying mechanism appears to be the generation of null alleles by NMD leading to elastin haploinsufficiency.

Alleles↗

Neuroblastoma tumor cell-binding peptides identified through random peptide phage display.

Random peptide phage display libraries have been employed widely to identify protein-protein interactions, using as targets either purified proteins, intact cells, or organs. To isolate peptides that bind to human neuroblastoma cells, we have used a phage display approach with the neuroblastoma cell line WAC 2 as the target. In particular, two bacteriophages, t147 and t160, displaying peptides p147 and p160, respectively, were isolated by repeated display cycles. Binding of t147 and t160 to WAC 2 cells was abrogated by pretreatment with the peptides p147 and p160, respectively, which strongly support that cellular binding of both phages is dictated by their displayed peptides. Immunofluorescence analysis by confocal light microscopy revealed that the major proportion of t147 remains on the surface of WAC 2 cells and that only a fraction is taken up into the cells. In contrast, the vast majority of t160 is internalized. K(+) depletion reduced the number of the phages internalized by the cells to approximately 20% for t160 and to 10% for t147, indicating that the phage internalization was through receptor-mediated endocytosis. Phage t147 appears to bind to a range of tumor cell lines, including neuroblastoma, breast cancer, glioblastoma and C-cell carcinoma, but less so to non-tumor lines, such as erythrocytes, lymphocytes, monocytes and epithelial cells. Phage t160 bound to a range of neuroblastoma cell lines and a breast cancer cell line, but not to other tested cell lines. While neither of the displayed peptides conferred a narrow tissue specific binding ability, they do provide a basis for targeted drug delivery in selected experimental or natural tumor systems.

Amino Acid Sequence↗

Differential osteopontin expression in lung cancer.

Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.

Adenocarcinoma↗

Peroxisome proliferator-activated receptor gamma inhibits transforming growth factor beta-induced connective tissue growth factor expression in human aortic smooth muscle cells by interfering with Smad3.

Activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) after balloon injury significantly inhibits VSMC proliferation and neointima formation. However, the precise mechanisms of this inhibition have not been determined. We hypothesized that activation of PPAR gamma in vascular injury could attenuate VSMC growth and matrix production during vascular lesion formation. Since connective tissue growth factor (CTGF) is a key factor regulating extracellular matrix production, abrogation of transforming growth factor beta (TGF-beta)-induced CTGF production by PPAR gamma activation may be one of the mechanisms through which PPAR gamma agonists inhibit neointima formation after vascular injury. In this study, we demonstrate that the PPAR gamma natural ligand (15-deoxyprostaglandin J(2)) and a synthetic ligand (GW7845) significantly inhibit TGF-beta-induced CTGF production in a dose-dependent manner in HASMCs. In addition, suppression of CTGF mRNA expression is relieved by pretreatment with an antagonist of PPAR gamma (GW9662), suggesting that the inhibition of CTGF expression is mediated by PPAR gamma. To elucidate further the molecular mechanism by which PPAR gamma inhibits CTGF expression, an approximately 2-kilobase pair CTGF promoter was cloned. We found that PPAR gamma activation inhibits TGF-beta-induced CTGF promoter activity in a dose-dependent manner, and suppression of CTGF promoter activity by PPAR gamma activation is completely rescued by overexpression of Smad3, but not by Smad4. Furthermore, PPAR gamma physically interacts with Smad3 but not Smad4 in vitro in glutathione S-transferase pull-down experiments. Taken together, the data suggest that PPAR gamma inhibits TGF-beta-induced CTGF expression in HASMCs by directly interfering with the Smad3 signaling pathway.

Aorta↗

A simple enantioselective synthesis of serratenediol.

[reaction: see text] A short synthesis of serratenediol is described, which involves a number of powerful key steps including (1) catalytic enantioselective syntheses of the phenyl sulfone and acylsilane shown above, (2) their coupling, and (3) further stereoselective cationic cyclizations.

Stereoisomerism↗

Highly effective transition structure designed catalyst for the enantio- and position-selective dihydroxylation of polyisoprenoids.

[structure: see text] The chiral monocinchona derivative shown, synthesized in one step from two efficiently prepared chiral building blocks, was designed under mechanistic guidance as a catalyst for the enantio- and position-selective dihydroxylation of the terminal isopropylidene group of polyisoprenoids. Its efficacy as a synthetic reagent for this purpose was demonstrated for several different substrates.

Alkenes↗

Human immunodeficiency virus type 1 RNA in peripheral blood mononuclear cells of patients receiving prolonged highly active antiretroviral therapy.

The levels of early spliced mRNA and genomic RNA of human immunodeficiency virus (HIV) type 1 in peripheral blood mononuclear cells (PBMC) of 14 patients who were receiving highly active combination antiretroviral therapy for > or =116 weeks were determined. The level of viral genomic RNA was below the level of detection in the plasma of these patients (<50 copies/mL), but cell-associated viral tat, rev, and nef mRNA were detected in 86% (12 of 14) of the patients. Cell-associated viral genomic RNA was detected in 57% (8 of 14) of the patients. Early viral spliced mRNA was detected in the PBMC of all patients who had positive results of testing for HIV-1 genomic RNA, and the level of viral genomic RNA in these patients was 34-2214 copies per 10(6) cells.

Anti-HIV Agents↗

Direct measurements of the enthalpy of solution of solid solute in supercritical fluids: study on the CO2-naphthalene system.

A setup for a calorimeter for simultaneously measuring the solubility and the solution enthalpy of solid solutes in supercritical fluids (SCFs) has been established. The enthalpy of solution of naphthalene in supercritical CO2 was measured at 308.15 K in the pressure range from 8.0-11.0 MPa. It was found that the enthalpy of solution (deltaH) was negative in the pressure range from 8.0 to 9.5 MPa, and the absolute value decreased with increasing pressure. In this pressure range, the dissolution of the solute was enthalpy driven. However, the deltaH became positive at pressures higher than 9.5 MPa, and the dissolution was entropy driven. Monte Carlo simulation was performed to analyze the local structural environment of the solvated naphthalene molecules in supercritical CO2 under the experimental conditions for the calorimetric measurements. By combining the enthalpy data and the simulation results, it can be deduced that the energy level of CO2 in the high compressible region is higher than that at higher pressures, which results in the large negative enthalpy of solution and the larger degree of solvent-solute clustering in the high compressible region.

Journal Article↗

Involvement of nitric oxide released from microglia-macrophages in pathological changes of cathepsin D-deficient mice.

Cathepsin D (CD) deficiency has been shown to induce ceroid-lipofuscin storage in lysosomes of mouse CNS neuron (Koike et al., 2000). To understand the behavior of microglial cells corresponding to these neuronal changes, CD-deficient (CD-/-) mice, which die at approximately postnatal day (P) 25 by intestinal necrosis, were examined using morphological as well as biochemical approaches. Light and electron microscopic observations revealed that microglia showing large round cell bodies with few processes appeared in the cerebral cortex and thalamus after P16. At P24, microglia often encircled neurons that were occupied with autolysosomes, indicating increased phagocytic activity. These morphologically transformed microglia markedly expressed inducible nitric oxide synthase (iNOS), which was also detected in the intestine of the mice. To assess the role of microglial nitric oxide (NO) in neuropathological changes in CD-/- mice, l-N(G)-nitro-arginine methylester (l-NAME), a competitive NOS inhibitor, or S-methylisothiourea hemisulfate (SMT), an iNOS inhibitor, was administered intraperitoneally for 13 consecutive days. The total number of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells counted in the thalamus was found to be significantly decreased by chronic treatment of l-NAME or SMT, whereas neither the neuronal accumulation of ceroid-lipofuscin nor the microglial phagocytic activity was affected by these treatments. Moreover, the chronic treatment of l-NAME or SMT completely suppressed hemorrhage-necrotic changes in the small intestine of CD-/- mice, resulting in normal growth of the body weight of the mice. These results suggest that NO production via iNOS activity in microglia and peripheral macrophages contributes to secondary tissue damages such as neuronal apoptosis and intestinal necrosis, respectively.

Animals↗

Hot electrons in the interaction of femtosecond laser pulses with foil targets at a moderate laser intensity.

Characteristics of hot electrons produced in the interaction of femtosecond laser pulses with foil targets were investigated at a moderate laser intensity. Both outgoing and ingoing hot electrons from the femtosecond laser plasma were studied. A collimated jet of outgoing hot electrons was observed in the target normal direction. An ingoing energetic hot-electron beam was found in the laser propagation direction, while the low-energy ingoing electrons spread into wider cone angle due to the collisional effects in the plasma and target material. These observations were supported by three-dimensional Monte Carlo simulations. The hot-electron temperature obtained from electron spectra and absorption experiments implies that resonance absorption is partially responsible for the generation of hot electrons.

Journal Article↗