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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 91 records · Page 5Linked to original sources
PubMed2001

Carbonyl sulfide derived from catalytic oxidation of carbon disulfide over atmospheric particles.

The formation of carbonyl sulfide (COS) by catalytic oxidization of carbon disulfide (CS2) over atmospheric particle catalysts was explored through FT-IR, MS (mass spectrometry), and a fixed-bed stainless steel reactor. Also the crystallizing conditions and specific surfaces (areas) of the catalysts were investigated by means of X-ray diffraction (XRD) and BET. Some oxides such as CaO, Fe2O3, Al2O3, and SiO2 were investigated under the conditions similar to the atmospheric particles as a comparison. The results showed that atmospheric particles and the oxide catalysts exhibited considerable oxidizing activity for CS2 at ambient temperature to form COS. Elemental sulfur as well as COS was one of the main products; even CO2 could be produced by a secondary reaction on some catalysts. Among the catalysts, CaO showed the strongest catalytic activity for oxidizing CS2. The catalytic activities of Fe2O3 and Al2O3 decreased considerably as compared with CaO, and SiO2 had the weakest catalytic activity. Atmospheric particles' catalytic activity is between Fe2O3's and Al2O3's. The atmospheric particles we collected mainly consist of Ca(Al2Si2O8).4H2O, which is also the main component of cement. COS, the main product, is formed by the catalytic oxidizing reaction of CS2 with adsorbed "molecular" oxygen overthe catalysts' surfaces. The concentration of adsorbed oxygen over catalysts' surfaces may be the key factor contributed to the oxidizing activities. This paper first revealed that CS2 could be catalytically oxidized over atmospheric particles to form COS. It induced that this reaction may be another important source of atmospheric COS from CS2.

Air Pollutants↗
PubMed2001

Insights into long-range structural effects on the stereochemistry of aldol condensations: a practical total synthesis of desoxyepothilone F.

A processable total synthesis of a potent antitumor agent, desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), has been accomplished. The route is highly convergent. The new technology has also been applied to a total synthesis of 12,13-desoxyepothilone (dEpoB). The crucial point of departure from previous syntheses of dEpoB and dEpoF involves presentation of the C1-C11 sector for Suzuki coupling with C3 in reduced form. Hitherto, the required S stereochemistry at C3 had been implemented via reduction of a keto function after Suzuki coupling. Whereas that chemistry worked quite well in a synthesis of dEpoB, it was not transferable to a high-yielding synthesis of dEpoF. The reduction of the keto group at C3 via a Noyori protocol after Suzuki coupling had proved to be very difficult. In our current approach, two consecutive aldol reactions are used to fashion the acyl sector. In the first aldol condensation, C6 becomes attached to C7. Following protection at C7, a two-carbon acetate equivalent is used to join C2 and C3 with very high asymmetric induction at C3. Only after this center has been implemented is the Suzuki reaction conducted. This major advance allowed us to synthesize dEpoF in a straightforward fashion. These findings found ready application in the total synthesis of dEpoB. Another part of the study involved analysis of the factors associated with aldol condensations joining C6 to C7. In the work described herein, the consequences of the status of C3 in promoting the C6-C7 aldol coupling are probed in detail. Dramatic stereochemical long-range effects uncovered during the study are described, and a working model to explain these effects has emerged.

Antineoplastic Agents↗
PubMed2001

Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop.

Protein kinase PKR is activated by double-stranded RNA (dsRNA) and phosphorylates translation initiation factor 2alpha to inhibit protein synthesis in virus-infected mammalian cells. PKR contains two dsRNA binding motifs (DRBMs I and II) required for activation by dsRNA. There is strong evidence that PKR activation requires dimerization, but the role of dsRNA in dimer formation is controversial. By making alanine substitutions predicted to remove increasing numbers of side chain contacts between the DRBMs and dsRNA, we found that dimerization of full-length PKR in yeast was impaired by the minimal combinations of mutations required to impair dsRNA binding in vitro. Mutation of Ala-67 to Glu in DRBM-I, reported to abolish dimerization without affecting dsRNA binding, destroyed both activities in our assays. By contrast, deletion of a second dimerization region that overlaps the kinase domain had no effect on PKR dimerization in yeast. Human PKR contains at least 15 autophosphorylation sites, but only Thr-446 and Thr-451 in the activation loop were found here to be critical for kinase activity in yeast. Using an antibody specific for phosphorylated Thr-451, we showed that Thr-451 phosphorylation is stimulated by dsRNA binding. Our results provide strong evidence that dsRNA binding is required for dimerization of full-length PKR molecules in vivo, leading to autophosphorylation in the activation loop and stimulation of the eIF2alpha kinase function of PKR.

Amino Acid Sequence↗
PubMed2001

[Effective suppression of the infection and pathogenesis of simian immunodeficiency virus in transgenic lymphocytes mediated by self-cleavagble ribozyme].

OBJECTIVE: To obtain transgenic lymphocytes that are resistant to the infection and pathogenesis of simian immunodeficincy virus (SIV). METHODS: A self-cleaving ribozyme was formed by introducing a fragment of ribozyme target sequence cleft by hammerhead ribozyme to the ribozyme downstream. Self-cleavable ribozyme gene was synthesized, amplified and cloned at the XhoI SalI site of pBluescript SK. The construct bearing 10 copies of ribozyme was obtained through successively cloning four times. The in vitro activity of self-cleavable ribozyme was tested, and then the self-cleaving ribozyme gene was transferred into mammalian expression vector pCI before transfection. The expression vectors harboring self-cleavable ribozyme gene were transfected into lymphocytes with liposome-mediated transfection method. The transfected cell clones were selected in the culturing medium containing 400 mg/L G418. The resistance of transgenic cell to simian immunodeficency virus infection was evaluated by immunofluorescence assays. RESULTS: more than 85% of decameric ribozyme self-cleaved into monomeric ribozymes after incubation for 15 minutes at 37 degrees C. The number of cleavage products of decameric ribozyme during the first 25 minutes exceeds those of the monomeric ribozyme by 13.31% though the molar mass average of decameric ribozyme is less than 1/10 of that of the monomer ribozyme. The Northern dot blot results demonstrated that the monomer ribozyme gene and the decameric ribozyme gene had been transfected and expressed in the cells. SIV challenge trials showed that after 6 days after inoculation of SIV the cells transfected with the monomer ribozyme gene grew normally, no fused cell was observed; and most of the cells transfected with decameric gene grew well, but a few fused cells were observed; The inhibition rate was 100% for the cells transfected with monomer ribozyme gene to the SIV antigen positive cells, 91.2% for the cells transfected with decameric ribozyme gene, and 48% for the cells transfected with the empty expression vector. CONCLUSION: The lymphocytes transfected with self-cleavable ribozyme gene make a strong resistance to SIV infection and pathogenesis. The cells transfected with monomeric ribozyme gene show a better inhibiting effect on SIV infection and pathogenesis in comparison with the cells transfected with decameric ribozyme gene.

Animals↗
PubMed2001

Chronic nicotine alters NO signaling of Ca(2+) channels in cerebral arterioles.

Smoking is a major health hazard with proven deleterious effects on the cerebral circulation, including a decrease in cerebral blood flow and a high risk for stroke. To elucidate cellular mechanisms for the vasoconstrictive and pathological effects of nicotine, we used a nystatin-perforated patch-clamp technique to study Ca(2+) channels and Ca(2+)-activated K(+) (BK) channels in smooth muscle cells isolated from cerebral lenticulostriate arterioles of rats chronically exposed to nicotine (4.5 mg/kg per day of nicotine free base, 15 to 22 days via osmotic minipump). Two major effects were observed in cells from nicotine-treated animals compared with controls. First, Ca(2+) channels were upregulated (0.48+/-0.03 pS/pF [20 cells] versus 0.35+/-0.01 pS/pF [31 cells], P:<0.005) and BK channels were downregulated (12+/-3 pA/pF [14 cells] versus 34+/-7 pA/pF [14 cells], P:<0.05), mimicking the effect of an apparent decrease in bioavailability of endogenous NO. Second, normal downregulation of Ca(2+) channels by exogenous NO (sodium nitroprusside [SNP], 100 nmol/L) and cGMP (8-bromo-cGMP, 0.1 mmol/L) was absent, whereas normal upregulation of BK channels by these agents was preserved, suggesting block of NO signaling downstream of cGMP-dependent protein kinase. In pial window preparations, chronic nicotine blunted NO-induced vasodilation of pial vessels and the increase in cortical blood flow measured by laser-Doppler flowmetry, demonstrating the importance of Ca(2+) channel downregulation in NO-induced vasorelaxation. These findings elucidate a new pathophysiological mechanism involving altered Ca(2+) homeostasis in cerebral arterioles that may predispose to stroke.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Binding of 13-HODE and 15-HETE to phospholipid bilayers, albumin, and intracellular fatty acid binding proteins. implications for transmembrane and intracellular transport and for protection from lipid peroxidation.

Transport and utilization of fatty acids (FA) in cells is a multistep process that includes adsorption to and movement across the plasma membrane and binding to intracellular fatty acid binding proteins (FABP) in the cytosol. We monitored the transbilayer movement of several polyunsaturated FA and oxidation products (13-hydroxy octadecadienoic acid (HODE) and 15-hydroxytetraenoic acid (HETE)) in unilamellar protein-free phospholipid vesicles containing a fluorescent pH probe. All FA diffused rapidly by the flip-flop mechanism across the model membrane, as revealed by pH changes inside the vesicle. This result suggests that FA oxidation products generated in the cell could cross the plasma or nuclear membrane spontaneously without a membrane transporter. To illuminate features of extra- and intracellular transport, the partitioning of unsaturated FA and oxidized FA between phospholipid vesicles and albumin or FABP was studied by the pyranin assay. These experiments showed that all polyunsaturated FA and oxidized FA (13-HODE and 15-HETE) desorbed rapidly from the phospholipid bilayer to bind to bovine serum albumin, which showed a slight preference for the unsaturated FA over the oxidized FA. FABP rapidly bound FA in the presence of phospholipid bilayers, with a preference of 13-HODE over the unsaturated FA and with a specificity depending on the type of FABP. Liver FABP was significantly more effective than intestinal FABP in binding 13-HODE in the presence of vesicles. The more effective binding of the FA metabolite, 13-HODE, than its precursor 18:2 by FABP may help protect cellular membranes from potential damage by monohydroxy fatty acids and may contribute a pathway for entry of 13-HODE into the nucleus.

Animals↗
PubMed2001

Vascular grafts in the rat model: an anatomic study.

Vascular grafts in animal models have been used extensively in the microsurgical laboratory, and the rat offers an excellent source of graft to meet these needs. In this study, we compiled a list of vessels that were previously identified in experimental literature for use as vascular grafts in the rat model. We then dissected and measured both arterial and venous grafts taken from these sites in 12 adult rats. The surgical procedure for approaching each vascular graft was recorded. The diameter and harvestable length, the start and end points, and the number of branches of the graft were tabulated. We believe that these data will provide valuable insight applicable to the use of the rat vascular graft in microsurgical research and training.

Animals↗
PubMed2001

Expression of C1 esterase inhibitor by the baculovirus expression vector system: preparation, purification, and characterization.

C1 esterase inhibitor (C1INH) is an important regulator of the classical complement pathway. Hereditary deficiency of C1INH causes angioedema of the skin, gut, and respiratory tissues that may be fatal. C1INH replacement therapy may be lifesaving for patients with this disorder. The objective of this study was to evaluate the use of the baculovirus expression vector system for mass producing biologically active human recombinant (rC1INH). A recombinant baculovirus was constructed coding the human native (nC1INH) sequence under control of the polyhedrin promoter. Spodoptera frugiperda Sf-9 insect cells were infected with this recombinant baculovirus in a medium-scale (10-L) bioreactor to produce rC1INH with a specific activity of 45 U/mg. Purification of rC1INH from the culture harvested at 60 h postinfection yielded 5.9 microg rC1INH/mL supernatant of a 75-kDa product with a specific activity of 31,000 U/mg purified rC1INH compared to 71,000 U/mg purified nC1INH from human serum using the same procedure. This rC1INH was about 25 kDa smaller than nC1INH, suggesting that Sf-9 cells express underglycosylated rC1INH. Glycan analysis showed that both N-glycan and O-glycan chains were present in rC1INH. The N-glycan chains, released using PNGaseF and fluorescently labeled, were analyzed using exoglycosidase treatment and capillary electrophoresis. Their high-mannose structure was consistent with the known failure of the insect cell glycosylation pathway to afford the fully elaborated biantennary structures found on human native nC1INH.

Animals↗
PubMed2001

Surface modification of stainless steel by grafting of poly(ethylene glycol) for reduction in protein adsorption.

The surface of stainless steel was first modified by the silane coupling agent (SCA), (3-mercaptopropyl)trimethoxysilane. The silanized stainless-steel surface (SCA-SS surface) was subsequently activated by argon plasma and then subjected to UV-induced graft polymerization of poly(ethylene glycol)methacrylate (PEGMA). The chemical structures and composition of the pristine, silane-treated, plasma-treated and PEGMA graft-polymerized stainless-steel coupon surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The graft polymerization of PEGMA onto the plasma-pretreated SCA-SS surface was studied with different argon plasma pretreatment time, macromonomer concentration, and UV graft polymerization time. In general, a brief plasma pretreatment, high PEGMA concentration, and long UV graft polymerization time readily resulted in a high graft concentration. The PEGMA graft-polymerized stainless-steel coupon (PEGMA-g-SCA-SS) with a high graft concentration, and thus a high PEG content, was found to be very effective in preventing bovine serum albumin and gamma-globulin adsorption.

Adsorption↗
PubMed2001

Neurotransmitter dopamine applied in electrochemical determination of aluminum in drinking waters and biological samples.

It was demonstrated that the decrease of the differential pulse voltammetric (DPV) anodic peak current of dopamine (3,4-dihydroxyphenylethylamine, DA) was linear with the increase of aluminum (Al) concentration. Under optimum experimental conditions (pH 4.6, 1.2 x 10(-3) M DA, and 0.04 M NaAc-HAc buffer solution), the linear range is 4.0 x 10(-7)-8.0 x 10(-5) M, the detection limit is 1.4 x 10(-7) M, and the relative standard deviation for 4 x 10(-5) M Al(III) is 3.5% (n=8). Many foreign species, especially some low-molecule-weight biological molecules, were chosen for interference testing. The proposed method was applied to the determination of Al in biological samples such as synthetic renal dialysate, Ringer's solution, human blood, cerebrospinal fluid of a patient, and urine of a diabetic patient. The corresponding recoveries were generally between 95 and 105%. The basic principle of the method was determined by examining Al complexed with DA. This results in the blockage of the electroactive sites on DA, followed eventually by the reduction of the electrochemical response of DA. This result was verified by examining the behavior of DA, both in the presence and absence of Al, using electrochemical, UV-Vis, Raman, and (13)C NMR spectroscopic methods.

Aluminum↗
PubMed2001

A meta-analysis of the use of typical antipsychotic agents in bipolar disorder.

BACKGROUND: The potential benefits of typical antipsychotic agents in bipolar disorder are offset by serious treatment-associated side effects. Despite these concerns and the availability of mood stabilizing agents, the treatment of bipolar disorder with typical antipsychotic agents appears to be widespread. METHODS: A Medline search identified 16 publications that outlined medication use among 2378 bipolar disorder patients. Meta-analysis was used to estimate a weighted average of the relative proportions of the treatment use, where the weights were the reciprocals of the estimated variances for each study. RESULTS: Overall, 84.7% of bipolar patients received typical antipsychotic agents, with a loading toward a greater in-patient (90.7%) relative to out-patient (65.3%) use. Monotherapy accounted for 53.8% of typical antipsychotic use, and typical antipsychotic/mood stabilizer combination therapy accounted for 47.4%. In four studies where length of treatment data were available, the median of minimum typical antipsychotic use was 2.5 months, with 96.0% of the patients receiving typical antipsychotic agents. LIMITATIONS: The meta-analytic technique employed in this analysis is limited by the possible inclusion of studies with unreliable study designs or biased treatment practices, publication bias in which some studies may not have been reported, and possible lack of identification of all relevant studies. CONCLUSIONS: Typical antipsychotic agents are commonly used in the treatment of bipolar disorder, possibly due to dissatisfaction with mood stabilizer monotherapy especially in psychotic mania, the high prevalence of psychotic symptoms in acute mania, inappropriate continuation of typical antipsychotic agents after initial stabilization, and/or unavailability or unfamiliarity with new treatments. These findings also suggest that typical antipsychotics may have not only antipsychotic effects in mania but perhaps also antimanic properties.

Antimanic Agents↗
PubMed2001

Olanzapine versus haloperidol in schizoaffective disorder, bipolar type.

BACKGROUND: The present analysis was performed on data from a subsample of patients with schizoaffective disorder, bipolar type, who participated in a multicenter, double-blind study comparing olanzapine to haloperidol. METHODS: Patients with schizoaffective disorder bipolar type, characterized as currently manic, mixed, depressed, or euthymic, were assessed weekly for 6 weeks during treatment with either olanzapine or haloperidol. Manic symptoms were measured using the sum of six items of the BPRS, and depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. In addition, cognitive functioning was measured using the sum of seven items from the PANSS. Repeated measures analyses were performed using random coefficients regression of the serial measurement of manic, cognitive, and depressive symptoms. RESULTS: A significant treatment difference was detected overall, indicating that olanzapine was significantly more effective than haloperidol in reducing symptoms of depression and improving patients' cognitive symptoms. The superiority of olanzapine over haloperidol in the reduction of manic symptoms did not reach statistical significance (P=.052). The greatest improvement in both manic and cognitive symptoms was seen in the olanzapine-treated 'currently manic' subgroup, and least improvement in the haloperidol-treated 'euthymic' subgroup. Depressive symptoms were most improved in the olanzapine-treated 'depressed' subgroup, and least improved in the corresponding haloperidol subgroup. CONCLUSIONS: Overall, olanzapine was superior to haloperidol with respect to thymoleptic effects in patients with schizoaffective disorder, bipolar type.

Administration, Oral↗
PubMed2001

Amplification and cloning of the full-length genome of Japanese encephalitis virus by a novel long RT-PCR protocol in a cosmid vector.

A novel and rapid full-length long RT-PCR technique was established to produce genome-length cDNA from Japanese encephalitis virus. In vitro positive strand RNA transcripts from the full-length RT-PCR amplicon including T7 promoter sequences at the 5' end were proved to be infectious upon transfection. The full-length amplicon without the T7 promoter was cloned into a cosmid vector under the SP6 promoter. This stable clone, designated as pJEV-1, was characterised further and used as a genetic resource for generation of infectious RNA transcripts, gene manipulation and expression. The 'run-off' transcript from pJEV-1 with vector sequences at the either end of the insert was not infectious, but transcripts of the full-length PCR amplicon from pJEV-1 produced infectious virus upon transfection. A transcript with an engineered Xho I site from two ligated PCR fragments amplified from pJEV-1 was also infectious. Furthermore, the coding region for premembrane and envelope proteins (preM-E) from pJEV-1 was subcloned and expressed in the Drosophila Expression System. The expressed protein showed correct molecular size and was immunoreactive with a Japanese encephalitis virus E protein-specific antibody. The derivation of genome-size cDNA from Japanese encephalitis virus and the stable clone will facilitate investigation of this virus and elucidation of its pathogenesis at the molecular level.

Animals↗
PubMed2001

Immune related genetic polymorphisms and schizophrenia among the Chinese.

Genetic association studies were conducted among two independent cohorts of Chinese ethnicity. The samples consisted of cases and unrelated controls, ascertained from Guangzhou, China, and Singapore. The studies were prompted by our earlier report of an association between schizophrenia and HLA DQB1 alleles (HLA DQB1*0602 and HLA DQB1*0303) in the Singapore sample. Polymorphisms of HLA DQB1 and flanking markers on chromosome 6p21.3 were investigated in the first part of the study. A significant negative association with HLA DQB1*0402 was detected in the Guangzhou sample (Odds ratio, OR 0.26, 95% confidence intervals, CI 0.1, 0.6; p < 0.02, corrected for multiple comparisons). Additional analysis of the Guangzhou and Singapore samples revealed associations at three other anonymous markers flanking HLA DQB1. In the second part of the study, three polymorphisms at the Interleukin-1 gene cluster (IL-1, chromosome 2q13-q21) were investigated in both cohorts, since associations with schizophrenia have been reported in another sample. Persuasive evidence for an association at IL-1 was not detected in either sample. Our results suggest a susceptibility locus for schizophrenia in the HLA region among the Chinese, but further clarification is necessary.

Adult↗
PubMed2001

Chromatographic separation and spectrometric identification of the oxidation products from a tetrahydro-isoquinoline alkaloid.

The oxidation chemistry of 3',4'-deoxynorlaudanosoline carboxylic acid, a tetrahydroisoquinoline alkaloid, has been studied by electrochemical approaches. Four reaction products were isolated by semi-preparative high performance liquid chromatography and identified structurally by nuclear magnetic resonance, mass spectrometry, ultraviolet-visible spectrophotometry and electrochemistry studies. An oxidation mechanism was proposed.

Alkaloids↗
PubMed2001

Vasoregulatory function of the heme-heme oxygenase-carbon monoxide system.

Arterial vessels express one or more heme oxygenase (HO) isoenzymes that catalyze the metabolism of heme to carbon monoxide (CO) and biliverdin. Carbon monoxide promotes vasorelaxation through mechanisms that, depending on the vessels, involve activation of soluble guanylate cyclase, stimulation of calcium-activated potassium channels, or diminished synthesis of constrictor mediators, such as, endothelin and 20-HETE. Inhibitors of HO elicit vasoconstriction in vivo and in isolated pressurized arterioles. Inhibitors of HO also enhance myogenic vasoconstriction, as well as the constriction induced by phenylephrine in several vessels. The blood pressure of awake rats is increased by acute treatment with HO inhibitors, a response that is accompanied by attenuation of baroreflex activity. All in all, it would appear that a product of HO activity manufactured by arterial vessels, presumably CO, promotes vasodilation and decreases the reactivity of vascular smooth muscle to myogenic stimuli and constrictor agonists. In doing so, CO of vascular origin may contribute to the implementation of antihypertensive mechanisms. Carbon monoxide produced in central nervous system structures, for example, the nucleus tractus solitarii, also appears to support a blood pressure-lowering mechanism linked to inhibitory modulation of baroreceptor reflex activity.

Animals↗
PubMed2001

Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion.

The objective of the present study was to investigate the influence of formulation factors on the physical properties of hot-melt extruded granules and compressed tablets containing wax as a thermal binder/retarding agent, and to compare the properties of granules and tablets with those prepared by a high-shear melt granulation (MG) method. Powder blends containing phenylpropanolamine hydrochloride, Precirol and various excipients were extruded in a single-screw extruder at open-end discharge conditions. The extrudates were then passed through a 14-mesh screen to form granules. The extrusion conditions and the optimum amount of wax to function as the thermal binder were dependent on the properties of the filler excipients. At the same wax level, drug release from tablets decreased in the order of using microcrystalline cellulose (MCC), lactose and Emcompress as the filler excipient. The observed differences in the dissolution properties of the tablets were due to the differences in the solubility, swellability and density of the filler excipients. Replacing Precirol with Sterotex K, a higher melting point wax, resulted in slightly increased dissolution rates, when the extrusion was performed at the same temperature conditions. Hot-melt extruded granules were observed to be less spherical than high-shear melt granules and showed lower values of bulk/tap densities. However, tablets containing MCC or lactose granules prepared by hot-melt extrusion (HME) exhibited higher hardness values. Slower drug release rates were found for tablets containing MCC by HME compared with MG. Analysis of the hot-melt extruded granules showed better drug content uniformity among granules of different size ranges compared with high-shear melt granules, resulting in a more reproducible drug release from the corresponding tablets.

Adrenergic alpha-Agonists↗