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Biomedical subjects

R Guo

Publications and source records attributed to R Guo.

161 records · Page 9Linked to original sources

Preliminary studies on antigenic variation of poliovirus using neutralizing monoclonal antibodies.

Cross-neutralization assays were done using 85 strains of poliovirus type 1 with five groups of monoclonal antibodies. These strains were classified into 10 subgroups which had marked differences in antigenicity. Subgroups P1-2 (28%) and P1-5 (43%) were dominant and have been epidemic in China in recent years. These two subgroups were antigenically different from the Sabin-1 strain, but according to their responses to one group of monoclonal antibodies they had antigenic epitopes in common with the Mahoney and Brunhilde strains. Similarly, 91 strains of type 3 poliovirus were classified into six subgroups with another five groups of monoclonal antibodies. The results showed that strain P3/Yunnan/2/84, which was isolated from cases of poliomyelitis in a local epidemic in the Yunnan province of China in 1984, and strain P3/Finland/23127/84, which was isolated in Finland in 1984, were both antigenically different from the Sabin-3 strain and the reference virulent strain.

Animals↗

[Effect and toxicity of entrapped polysiloxane 5-Fu polycondensate].

Entrapped 5-Fu polysiloxane polycondensate (DMS-Fu) and equivalent doses of 5-Fu were tested on S-180 mice. At the dose of 100 mg/kg, the inhibition potency of these two compounds on tumor was similar, but the inhibition on the body weight was more marked in 5-Fu treated mice. At the dose of 250 mg/kg, all mice treated with 5-Fu died of toxicity but the mice treated with DMS-Fu survived and showed no obvious toxic effect. At the dose of 150-200 mg/kg, the peripheral white blood cells and the bone marrow nucleated cells of 5-Fu treated mice were seriously reduced, which lasted for several days before recovery. In the DMS-Fu group, the inhibition was mild.

Animals↗

Peroxylated and hydroxylated uroporphyrins: a study of their production in vitro in enzymic and chemical model systems.

In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.

Chromatography, High Pressure Liquid↗

Porphyrins in urine, plasma, erythrocytes, bile and faeces in a case of congenital erythropoietic porphyria (Gunther's disease) treated with blood transfusion and iron chelation: lack of benefit from oral charcoal.

Congenital erythropoietic porphyria is a rare genetic disorder in which deficiency of uroporphyrinogen III synthase results in excessive production of Type I porphyrins. The main clinical features are severe photodestruction of the skin and haemolytic anaemia. Treatment consists of shielding from light, blood transfusions and splenectomy, but is generally unsatisfactory. Previous studies have suggested that oral charcoal may be of benefit by binding porphyrins in the gut. A trial was therefore undertaken to evaluate this possibility. Porphyrins in urine, plasma and erythrocytes were measured by HPLC in a 23-year-old male patient with congenital erythropoietic porphyria, during an 8 week "run-in" period, and for a further 3 weeks when oral charcoal was given. Total urinary porphyrin excretion was 79-283 mumol/24 h consisting of 75% uroporphyrin I, 15% coproporphyrin I and smaller amounts of hepta-, hexa-, and pentacarboxylic porphyrins. Similar proportions were found in plasma and erythrocytes. During the first 24 h of charcoal administration a minor decrease in plasma and erythrocyte porphyrins was detected but this was not maintained during the remainder of the trial. In bile and faeces coproporphyrin I constituted approximately 95% of the porphyrins, with 2-3% coproporphyrin III and smaller amounts of pentaporphyrins I and III, but only trace amounts of uroporphyrin I. Oral charcoal was of no value in this case. Reasons are discussed in the context of biochemical differences between this patient with classical Gunther's disease and the similar clinical syndrome due to deficiency of uroporphyrinogen decarboxylase.

Adult↗

Acetylator phenotyping via analysis of four caffeine metabolites in human urine by micellar electrokinetic capillary chromatography with multiwavelength detection.

The simultaneous analysis of 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 5-acetylamino-6-amino-3-methyluracil (AAMU), 1-methylxanthine (1X) and 1-methyluric acid (1U), the four urinary metabolites of caffeine employed for acetylator phenotyping in man, by micellar electrokinetic capillary chromatography (MECC) is reported. Using on-column fast scanning multiwavelength detection is shown to permit unambiguous identification of AAMU, AFMU, 1X and 1U in the three-dimensional electropherograms obtained with both direct urine injection or application of extracted urine. The phenotype status of a number of healthy volunteers, some with known acetylator status, were determined using peak height ratios of AFMU/1X, (AFMU + AAMU)/1X and compared to those obtained by high performance liquid chromatography (HPLC) employing the AFMU/1X peak height ratio. Another set of MECC data was obtained after deliberate conversion of AFMU to AAMU, the results being expressed by AAMU/1X,AAMU/(1U + 1X) or AAMU/(AAMU + 1U + 1X) ratios. The data suggest that most reliable data are obtained when phenotyping is conducted under conditions of complete conversion of AFMU to AAMU. Phenotyping employing caffeine and analysis of its urinary metabolites by MECC is shown to be simple and, with automated instruments, potentially suitable for routine use and large-scale population analysis. The agreement of MECC data obtained from three different instruments demonstrates the high level of maturity of this emerging technology.

Acetylation↗

Identification of differentially expressed genes induced by angiotensin II in rat cardiac fibroblasts.

1. Cardiac fibroblasts play an important regulatory role in cardiac remodelling by undergoing proliferation, differentiation and upregulating various gene products, including some cytokines and extracellular matrix (ECM) proteins. A highly potent mediator of cardiac remodelling is angiotensin (Ang) II. 2. In the present study, the suppression subtractive hybridization method was used to identify differentially expressed cDNAs in adult rat cardiac fibroblasts induced by AngII. 3. Following mRNA isolation of non-stimulated and AngII-stimulated cells, cDNAs of both populations were prepared and subtracted by suppression polymerase chain reaction. Sequencing of the partially enriched cDNAs identified 36 genes differentially expressed, including ECM proteins (pro-alpha(1) collagen type III, fibronectin), structural protein (spectrin), enzyme (GTP-specific succinyl-CoA synthetase), transcriptional regulators (glucocorticoid-induced leucine zipper, inhibitor of DNA binding 3) and proteins involved in cell division control (cdc2) or cell signalling (insulin-like growth factor binding protein-3, mutant p53-binding protein, grp75, CGI-121, protein phosphatase type 2A, tspan-2 and Sam68). 4. The diversity of genes identified in the present study further emphasises the central role of AngII in the regulation of cardiac remodelling.

Angiotensin II↗