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Biomedical subjects

T Su

Publications and source records attributed to T Su.

71 records · Page 4Linked to original sources

Establishment of National Quality Control Reference Panels and Requirements for Hepatitis B diagnosis reagents in China.

A National Quality Control Reference Panel for Hepatitis B Diagnostic Kits has been established. Markers for these standards which were prepared include National Standards for HBsAg and anti-HBs calibrated against WHO International Standards. In addition, Reference Panels for HBeAg, anti-HBe, anti-HBc, anti-HBc IgM and HBV were established and National Requirements set. These panels have been used for the nationwide evaluation of HB kits and for licensing purposes.

China↗

Interferon-alpha 2b inhibits proliferation of human Tenon's capsule fibroblasts.

To evaluate the potential of interferon-alpha 2b (IFN-alpha) as an antifibrotic treatment after glaucoma filtering surgery, we studied its ability to inhibit mitogen-induced proliferation of human Tenon's capsule fibroblasts in vitro, as shown by [3H]-thymidine incorporation. IFN-alpha inhibited fetal calf serum-induced proliferation in a dose-dependent manner in concentrations ranging from 10 to 10,000 IU/ml (P < 0.001). Inhibition was also found when IFN-alpha was added prior to the mitogen (P = 0.001); this inhibitory effect lasted at least 3 days. We suggest that IFN-alpha deserves further evaluation as a possible agent for the control of ocular fibrosis.

Cell Division↗

High glucose inhibits retinal capillary pericyte contractility in vitro.

PURPOSE: To study the effect of high glucose concentrations on pericyte contractility. METHODS: Bovine retinal capillary pericytes were cultured on silicone rubber sheets, which could be seen to wrinkle when a cell contracted. Cells were grown in glucose, or mannitol, in concentrations ranging from 5 to 40 mMol. Pericyte contractility was expressed as the percentage of cells wrinkling the silicone substratum. Observations were made fortnightly for 8 weeks. RESULTS: Cells grown in glucose exhibited a dose-dependent inhibition of contractility that was significantly greater than that seen with cells grown in mannitol, which were affected to a lesser extent. After returning to normoglycemic conditions for a further 4 weeks, the contractility of cells grown in lower glucose concentrations recovered partially, but cells grown in 40 mMol glucose did not recover at all. Pericyte proliferation was also impaired by the high-glucose growth medium. CONCLUSIONS: Pericyte contractility is inhibited by high glucose concentrations. This is consistent with the hypothesis that increased retinal blood flow may be a factor in the early pathogenesis of diabetic retinopathy.

Animals↗

Inactivation of gamma-aminobutyric acid aminotransferase by various amine buffers.

It is hypothesized that buffers capable of forming a Schiff base with the PLP of gamma-aminobutyric acid aminotransferase (GABA-AT) may lead to denaturation and inactivation of the enzyme. On the basis of this hypothesis three new methods for the selective destruction of GABA-AT in GABAse (a commercial bacterial source of a mixture of GABA-AT and succinic semialdehyde dehydrogenase [SSDH]) and from pig brain are described: (1) dialysis against a primary or secondary amine buffer; (2) gel filtration with a primary or secondary amine buffer as eluent; (3) inactivation with gabaculine followed by dialysis or gel filtration with pyrophosphate buffer. The SSDH activity in GABAse, which remains unchanged by all of these methods, may then be used in a coupled assay to measure the activity of GABA-AT from different sources. These results also suggest that the use of primary and secondary amine buffers should be avoided when inhibitors are being tested with GABA-AT.

4-Aminobutyrate Transaminase↗

A simple method for the in vitro culture of human retinal capillary endothelial cells.

A simple method for the culture of human retinal capillary endothelial cells in vitro is described in this report. Through a process of gentle mechanical disruption and sieving, a sufficient yield of retinal microvessels was obtained from one or two human eyes to allow the culture of endothelial cells in abundance. The cells were factor VIII-positive and demonstrated typical vascular endothelial morphology. Pericyte contamination was prevented by using human platelet-poor serum in primary culture and passaging cells with a low concentration of trypsin. Proliferation assays revealed that the cells grew best in Iscove's modified Dulbecco's modified Eagle's medium with 15% fetal calf serum (FCS). There was no difference in induced proliferation when FCS was compared to human platelet-poor serum. The method seemed to be as good as and much simpler than other recently described techniques. The study of human retinal capillary endothelial cells cultured in this way may shed light on the earliest stages of diabetic retinopathy and other diseases of the retinal microvasculature, particularly AIDS-related retinopathy and radiation retinopathy.

Capillaries↗

Design and synthesis of nonpeptide mimetics of jaspamide.

Jaspamide is a novel metabolite of mixed peptide/polyketide biosynthesis that was isolated from sponges of the genus Jaspis, and that has been reported to exhibit both insecticidal and antifungal activity. We have evaluated three nonpeptide mimetic designs, and have synthesized a nonpeptide mimic of the proposed bioactive region to investigate the structure activity relationship. Structural investigations of potential mimetics, utilizing molecular modeling in conjunction with spectroscopic and crystallographic data, indicate that positioning of the critical functional groups in two mimetics corresponds closely to that observed in jaspamide, and that the flexibility of mimetic 4 approximates that of jaspamide. Initial biological evaluation suggests that lactam mimetic 4 exhibits a biological profile similar to jaspamide.

Antifungal Agents↗

Cytokines, fibrosis and the failure of glaucoma filtration surgery.

Current therapies for the prevention of fibrosis after glaucoma filtering surgery can be effective but often produce unwanted side effects. An understanding of the cellular basis of the fibrotic reaction may lead to better treatments. Wound repair revolves around angiogenesis and the activation of fibroblasts by cytokines. These peptides, a number of which have been described, act together in intricately complicated networks to encourage fibroblast chemotaxis, proliferation and contractility, as well as to stimulate the production of glycosaminoglycans and collagen. Since interferons seem to inhibit many of these responses, they deserve further evaluation in the treatment of ocular fibrosis.

Cytokines↗

Mutagenicity of Alternaria alternata and Penicillium cyclopium isolated from grains in an area of high incidence of oesophageal cancer--Linxian, China.

In order to study the relationship between daily consumption of mouldy food and the incidence of oesophageal cancer, we examined the mutagenicity of Alternaria alternata and Penicillium cyclopium, which seriously contaminate grain in Linxian county, China. We first examined extracts of cultured strains of A. alternata. In the reverse mutation test, positive results were obtained in 85% of strains; positive results were seen in 84% of 19/20 strains in the rec assay. Eight of ten strains induced sister chromatid exchange, and two of eight strains induced chromatid breaks. Six of seven strains induced unscheduled DNA synthesis and DNA synthesis inhibition. One extract induced a higher frequency of sister chromatid exchange in lymphocytes from normal persons than in those from patients with oesophageal cancer, and the spontaneous break-points in patients were related to fragile sites and neoplasia-associated break-points. The toxins alternariol and its monomethyl ether, produced by A. alternata, were examined in the reverse mutation assay and for unscheduled DNA synthesis. The results were similar to those obtained with extracts of the different strains. Alternariol had a four to eight times greater effect than its monomethyl ether. Of 24 strains of P. cyclopium isolated from cereals in Linxian, four were cultured with rice and 19 in Raulin-Thom medium. Cultures in Raulin-Thorn medium, solution and hyphae were then extracted. The strains cultured with rice induced sister chromatid exchange, unscheduled DNA synthesis and DNA synthesis inhibition. The solution extracts of 14 strains were positive in the rec assay, and five strains were positive in the reverse mutation test.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternaria↗

Brain microdialysis and PK/PD correlation of pregabalin in rats.

Pregabalin [PGB, (S)-3-isobutyl GABA, CI-1008] is a derivative of the inhibitory neurotransmitter g-aminobutyric acid (GABA). It has shown anticonvulsant, analgesia and anxiety activity in animal models. In this report, blood-brain barrier (BBB) influx and efflux of PGB were investigated with microdialysis at efficacious doses in rats. BBB influx (CLin) and efflux (CLout) permeability for pregabalin were 4.8 and 37.2 microL/min/g brain, respectively, following an intravenous infusion to rats. The results indicate that PGB is brain penetrable, supporting its anti-epilepsy and other CNS pharmacology. Significant anticonvulsant action of PGB was detected between 2 and 8 hr post oral dose, which is lag behind ECF drug concentrations lees. A PK/PD link model was used to describe the counter-clockwise hysteresis relationship between pregabalin brain ECF concentration and the anticonvulsant effect in rats. The resulting Ce (concentration in effect compartment) versus effect profile exhibits a sigmoidal curve and the calculated ECe50 and Keo values were 95.3 ng/mL and 0.0092 min-1, respectively. The small Keo value suggests that the effect is not directly proportional to the amount of pregabalin in the ECF compartment possibly due to inherent delay.

Acetates↗

Particle-mediated intravascular delivery of oligonucleotides to tumors: associated biology and lessons from genotherapy.

For a solid tumor to become life-threatening, an adequate blood supply has to be established. Although neovascularization has dire consequences for the host, it furnishes a common route through which tumors may be accessed and eradicated by drugs. The fact that a tumor's vasculature is relatively more permeable than that of healthy host tissue means selective delivery of drugs may be achieved. The role played by the cells making up the tumor vascular bed, vascular endothelial cells (VECs), has to be evaluated closely in attempts to design ways for enhancing drug delivery to solid tumors via the vasculature. The two major roles of VECs in the body, as barrier and as transport, are both highly pertinent to drug delivery. Our review examines how VECs may be manipulated in vivo to improve the selective delivery of carriers for oligonucleotide constructs to solid tumors. It also discusses how oligonucleotide drugs may be targeted against tumor VECs on the premise that by killing these cells, the tumor itself will perish. Cationic liposomes and microspheres are the major delivery vehicles discussed, with added analyses of such other nucleic acid carriers as nanospheres, dendrimers, and polyethyleneimine.

Animals↗

Purification of transthyretin by high performance affinity chromatography from human plasma.

The partial purification of human transthyretin (TTR) by high performance affinity chromatography with the help of other separation techniques is described in the present paper. A new affinity medium was prepared with a monosized (ca. 10 microns particle size) macroporous resin as the support and thyroxine (T4) as the ligand. The purification of TTR was carried out in a few simple steps involving serum precipitation, anion exchange, Thyroxine affinity chromatography and gel filtration. The overall yield was 29% and the refined TTR contained less than 2% impurities as analyzed by RP-HPLC. When TTR was administrated to the culture medium DMEM of liver tumor strain SMMC-7721, a true inhibition of cell growth (ca. 50%) was observed as an actual decrease in cell number over time.

Chromatography, Affinity↗