Biomedical subjects
Publications and source records attributed to H Su.
In this paper, the enhancement effect of lead was studied in air-acetylene flame. It was found that microemulsion could produce remarkable sensibilization effect. The method has been applied to the determination of lead in copper and waste water.
Glycosaminoglycans (GAGs) are a family of acidic heteropolysaccharides, including such molecules as chondroitin sulfate, dermatan sulfate, heparin and keratan sulfate. Cleavage of the O-glycosidic bond within GAGs can be accomplished by hydrolases as well as lyases, yielding disaccharide and oligosaccharide products. We have determined the crystal structure of chondroitinase B, a glycosaminoglycan lyase from Flavobacterium heparinum, as well as its complex with a dermatan sulfate disaccharide product, both at 1.7 A resolution. Chondroitinase B adopts the right-handed parallel beta-helix fold, found originally in pectate lyase and subsequently in several polysaccharide lyases and hydrolases. Sequence homology between chondroitinase B and a mannuronate lyase from Pseudomonas sp. suggests this protein also adopts the beta-helix fold. Binding of the disaccharide product occurs within a positively charged cleft formed by loops extending from the surface of the beta-helix. Amino acid residues responsible for recognition of the disaccharide, as well as potential catalytic residues, have been identified. Two arginine residues, Arg318 and Arg364, are found to interact with the sulfate group attached to O-4 of N-acetylgalactosamine. Cleavage of dermatan sulfate likely occurs at the reducing end of the disaccharide, with Glu333 possibly acting as the general base.
1. Acetylcholine released from basal forebrain cholinergic fibres suppresses intrinsic bursting in cortical pyramidal cells through activation of muscarinic receptors. The signal transduction pathway mediating this action is not known. We used intracellular recordings from CA1 pyramidal cells in hippocampal slices to investigate the involvement of protein kinase C (PKC) in this cholinergic function. 2. Bath-applied carbachol (CCh; 5 microM) consistently suppressed intrinsic bursting in an atropine-sensitive (1 microM) manner. 3. Intrinsic bursting was suppressed by 4beta-phorbol 12,13-dibutyrate (PDBu; 5-10 microM), a potent PKC activator, but not by the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (PDC; 50 microM). Prior application of the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7; 10 microM) extracellularly or intracellularly prevented the PDBu effect. 4. Pretreatment with H7, but not with the broad-spectrum kinase inhibitor N-(2-guanidino-ethyl)-5-isoquinoline-sulfonyl hydrochloride (HA1004; 10 microM), prevented the CCh-induced suppression of bursting. 5. The active component of the spike after-depolarization (ADP) was reduced by CCh in an atropine-sensitive manner. This effect was mimicked by PDBu, but not by PDC. It was prevented by pretreatment with H7, but not with HA1004. 6. Blocking most K+ currents with Ca2+-free, TEA-containing saline induced large TTX-sensitive plateau potentials lasting > 150 ms, driven by a persistent Na+ current. These potentials were suppressed by PDBu, but not by PDC. Pretreatment with H7 prevented the PDBu-induced suppression of the plateau potentials. 7. We conclude that cholinergic suppression of intrinsic bursting in hippocampal CA1 pyramidal cells is mediated by muscarinic activation of PKC, which down-regulates the persistent Na+ current underlying slow depolarizing potentials in these neurons.
The human immunodeficiency virus type I is strongly regulated at the transcriptional level through the interaction of an 86-amino acid protein (Tat) with a viral messenger RNA transcript. Accordingly, the binding of this protein and other cellular factors to the RNA has constituted a significant target for the development of anti-HIV drugs. In the present work, we describe the detection of the binding of two Tat-derived peptides, of 12 and 40 amino acids in length, with chemically synthesized RNA by an acoustic wave sensor. Immobilization of the nucleic acid to the sensor surface, which was incorporated in an on-line system, was effected using the biotin-neutravidin interaction. As expected, the changes in series resonance frequency and motional resistance for the two peptides indicate reversible interactions in both cases that can be further characterized by the calculation of kinetic off-rates. Of particular interest is the nature of the two frequency-based signals, which are in opposite directions for the two peptides. These results together with those obtained for the surface interactions of neutravidin and biotinylated RNA confirm that the thickness shear mode sensor, mass-response model involving the well-known Sauerbrey expression is invalid when applied to operation in liquids.
Resistance to the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis has been mapped to MHC class II-restricted, IL-12-dependent CD4+ T cells that secrete a type 1 profile of proinflammatory cytokines, which includes IFN-gamma and TNF-alpha. The relative contribution of IFN-gamma is controversial, however, due to variation in results presented by different laboratories. To determine whether C. trachomatis strain differences contributed to this apparent conflict, the relative resistance of IFN-gamma-deficient mice to murine and human strains of C. trachomatis was compared. All human serovars were much more sensitive to the direct inhibitory actions of IFN-gamma than the MoPn strain. Furthermore, genital clearance of human serovar D in the C57BL/6 mouse was mediated by class II-independent mechanisms that probably involved local production of IFN-gamma by cells of the innate immune system. TNF-alpha also contributed indirectly to host resistance against all strains tested. The differential susceptibility of distinct C. trachomatis strains to effector cytokines such as IFN-gamma could not have been predicted by interstrain biologic variation or by the profile of cytokines stimulated during infection. These findings indicate that strain variation should be considered in situations where related isolates of a given parasite produce conflicting data in models of infection and immunity. They also suggest that stimulation of mucosal IFN-gamma activity is a relevant goal for a human chlamydial vaccine.
Phenylketonuria (PKU), with its associated hyperphenylalaninemia (HPA) and mental retardation, is a classic genetic disease and the first to have an identified chemical cause of impaired cognitive development. Treatment from birth with a low phenylalanine diet largely prevents the deviant cognitive phenotype by ameliorating HPA and is recognized as one of the first effective treatments of a genetic disease. However, compliance with dietary treatment is difficult and when it is for life, as now recommended by an internationally used set of guidelines, is probably unrealistic. Herein we describe experiments on a mouse model using another modality for treatment of PKU compatible with better compliance using ancillary phenylalanine ammonia lyase (PAL, EC 4.3.1.5) to degrade phenylalanine, the harmful nutrient in PKU; in this treatment, PAL acts as a substitute for the enzyme phenylalanine monooxygenase (EC 1.14.16.1), which is deficient in PKU. PAL, a robust enzyme without need for a cofactor, converts phenylalanine to trans-cinnamic acid, a harmless metabolite. We describe (i) an efficient recombinant approach to produce PAL enzyme, (ii) testing of PAL in orthologous N-ethyl-N'-nitrosourea (ENU) mutant mouse strains with HPA, and (iii) proofs of principle (PAL reduces HPA)-both pharmacologic (with a clear dose-response effect vs. HPA after PAL injection) and physiologic (protected enteral PAL is significantly effective vs. HPA). These findings open another way to facilitate treatment of this classic genetic disease.
The effects of the SAS gene on follicular growth were studied by feeding Sudan IV and Sudan Black B, on follicular maturity by measuring P4 and E2 output of the 5 largest follicles (F1 to F5) in vitro, and on ovarian response (plasma progesterone, P4, and oestradiol, E2) to administration of porcine follicle-stimulating hormone (pFSH) and porcine luteinising hormone (pLH) in old laying hens. Albino hens had fewer dye rings in the yolks of their eggs than non-albinos (8.32 compared to 8.59) and the yolks from albinos weighed less. The numbers of normal and atretic follicles larger than 3 mm in diameter did not differ between the two genotypes. The P4 outputs from the F1 and F2 follicles were significantly greater for albino hens, but P4 production of other follicles was not different for the two genotypes. The P4 output of the F1 follicle in response to pLH was dose-dependent and greater for albino hens than for non-albinos. Porcine LH did not increase the follicular E2 output in either genotype. Administration of pLH, but not pFSH, increased plasma P4 and E2 concentrations, with no difference between genotypes. These data suggest that the F1 follicles for albino hens are precocious, resulting in a reduced growth period and a smaller weight at ovulation.
Chlamydia trachomatis is a major cause of sexually transmitted disease (STD) worldwide. Antibiotics are effective in treating infection; however, reinfection is common. This observation has led to the conclusion that infection fails to elicit a protective antichlamydial immune response. It was postulated that high reinfection rates might be due to early eradication of organisms from genital tissue after antibiotic intervention, which could negatively influence the development of naturally acquired protective immunity. This hypothesis was tested by use of a murine model of female genital infection. The findings show that doxycycline intervention of infection, although very effective in eradicating chlamydiae from genital tissue and preventing upper genital tract disease, significantly inhibits the development of protective immunity. If antibiotic intervention of human chlamydial genital infection has a similar effect on protective immunity, it could have important implications in the understanding of immunity to infection and future public health efforts to control chlamydial STD.
OBJECTIVE: Neonatal rat astrocytes transplanted into host brains migrate in specific patterns, which are determined by the developmental stage of the host brain and the region of implantation. We hypothesized that the differentiation state of the implanted astrocytes could also affect astrocyte migration. METHODS: Astrocytes derived from neonatal rats (1-4 d) were placed in culture and exposed to growth- or differentiation-promoting agents (e.g., epidermal growth factor or dibutyryl cyclic adenosine monophosphate). Treated cells were then injected into different regions of the adult rat brain. At 3, 6, and 9 days after implantation, the extent and pattern of astrocyte migration after injection into the cortex, hippocampus, and corpus callosum were assessed. RESULTS: Astrocytes pretreated with either factor did not migrate during the first 3 days after implantation into the host cortex and hippocampus, whereas untreated cells migrated extensively by Day 3. After 9 days, implanted cells that had been pretreated with dibutyryl cyclic adenosine monophosphate began to demonstrate migratory activity, whereas those exposed to epidermal growth factor remained at the site of implantation. These findings corresponded to the effects of these agents in culture. On the other hand, cells implanted into the corpus callosum migrated in spite of pretreatment. CONCLUSION: Epidermal growth factor and dibutyryl cyclic adenosine monophosphate each altered the cells in culture such that they were inhibited from migrating after transplantation into the host cortex and hippocampus. This finding suggests that the activation of either growth or differentiation cascades partially inhibits the migratory ability in these cells either through effects on their internal migratory potentials or their responsiveness to external migratory signals. In contrast, cells implanted into the corpus callosum migrated in spite of pretreatment, suggesting that this structure may present migratory cues sufficient to override the effects of treatment.
Chondroitinase B, a glycosaminoglycan lyase from Flavobacterium heparinum, has been crystallized by hanging-drop vapor diffusion in space group P21 with unit-cell parameters a = 50.6, b = 74.5, c = 58. 7 A, beta = 92.9 degrees and one molecule in the asymmetric unit. This enzyme degrades dermatan sulfate, a glycosaminoglycan primarily made up of a disaccharide repeating unit of iduronic acid and N-acetylgalactosamine. A complete native data set has been collected from a single crystal to 2.2 A resolution using a rotating-anode source.
OBJECTIVE: To explore the mechanisms of As2O3 inducing apoptosis and growth inhibition in K562 cells and provide theoretical basis for clinical application. METHODS: The effects of As2O3 on BCR/ABL protein tyrosine phosphorylation(PTP) and its signal transduction as well as the expression of apoptosis-related genes were studied by means of immunoprecipitation, Western blot, biochemical method and immunofluorescence. RESULTS: Tyrosine phosphorylation of several cellular proteins especially BCR/ABL protein was decreased by 1 mumol/L As2O3, but not by 0.1 mumol/L As2O3. As2O3 had no effect on PTP activity, downregulated the expression of JAK2 protein, but did not affect the expressions of STAT1 and STAT2 proteins and the STAT1 protein tyrosine phosphorylation. As2O3 had no effect on the expression of the apoptosis-related genes like Bcl-2, Bcl-xL/S, Bax, ICH-1L, p53, PARP, either, but downregulated PML protein expression in K562 cells. CONCLUSION: As2O3 might induce K562 cell apoptosis and inhibit its growth by reducing tyrosine phosphorylation of cellular proteins especially BCR/ABL protein and/or by downregulating JAK2 protein expression to interfere with the BCR/ABL protein signal transduction.
OBJECTIVE: To determine the characteristic predictors of acute respiratory distress syndrome (ARDS) in the high altitude area of China. METHODS: According to the diagnostic criteria of ARDS, 2 325 cases were screened in the recent 10 years. Except malignant tumors, cardio-cerebrovascular diseases, chronic obstructive pulmonary disease, and chronic multiple organ failure, the causes of death were analysed retrospectively. RESULTS: 94 cases (4.04%) were diagnosed as ARDS, but in the primary case record, only 27 cases (1.16%) had been diagnosed as ARDS/MOF. Of the 94 ARDS patients, 79 complicated by extrapulmonary organ damage involving the kidney, heart, liver, gastro-intestinal tract, and brain. A total of 305 organs were involved (average 3.24 organs each case). Lung failure only accounted for 15 cases. CONCLUSIONS: The combination of the diagnostic criteria of ARDS for high altitude area and flate area, injury severity scale, blood gas monitoring, and integrated traditional Chinese medicine and western medicine may improve the prognosis of ARDS.
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One hundred and one cases of carotid atherosclerosis(CAS) were diagnosed by ultrasonography. The intermediate(IMT) of common carotid endomembrane in CAS group was much thicker than that in the healthy group(P < 0.01). There was no significant difference between the two groups in the peak velocity in systolic stage(MAX), the velocity in diastolic stage(MIN), resistance index(RI) and vessel size. The atheromatous plagues were usually flat plaques, seen at the bifurcation of common carotid artery. They belong to early pathological changes. It seems that the plaques don't affect MAX, MIN and RI of the common carotid artery.
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The aim of this study was to evaluate the biocompatibility of Chinese nitinol alloy intravascular stent. Sixteen Chinese nitinol alloy intravascular stents with 4 mm ID were implanted in the left and right iliac arteries of 8 normal dogs and were observed for one to six months. The results showed that the stents implanted were completely covered by a thin layer of the neointima after one month and the surface of neointima was covered by a monolayer of endothelium-like cells. These suggest that the Chinese nitinol alloy has very good biocompatibility.
A software package and its design idealogy for the self-constructed CCD-ICP-OES are described. The MS Windows 95TR was used as the operating platform. The Software package written in MS Visual C + + TR V 4.2 included the control of grating and CCD, the dynamic monitoring, the treatment of spectral signal, the fixing of wavelength position, the automatic fixing of spectral line, the quantitative analysis, the stripping method, the Kalman filter and the artificial neural network.
The algorithm bases for the Savitzy and Golay smoothing, spectrum stripping, Kalman filtering and the artificial neural network programs used in the self-constructed CCD-ICP-OES are described.