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Biomedical subjects

S Tong

Publications and source records attributed to S Tong.

At least 145 records · Page 8Linked to original sources

Trousseau's syndrome. Devastating coagulopathy in the absence of heparin.

Two patients with Trousseau's syndrome experienced frequently recurring concomitant arterial and venous thrombotic events that resulted in sequential amputation and loss of the lower extremities. Serial examination of the blood in the patients demonstrated that these devastating thrombotic events were preceded by severe disseminated intravascular coagulopathy that occurred within an interval of a few hours. Warfarin therapy was without effect in preventing the occurrence of these events. Both patients demonstrated the absolute need for intravenous heparin, which effectively prevented the thrombotic events; when it was discontinued, the immediate consequences were disastrous and resulted in death. Techniques for long-term outpatient heparin therapy are discussed.

Blood Coagulation Tests↗

Interaction of the oncolytic drug, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea with the mixed-function oxidase system in rats.

Effects of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) on the hepatic mixed-function oxidase system in male rats were studied both in vivo and in vitro. A single dose of CCNU (40 mg/kg) caused a significant reduction in hepatic mixed-function oxidase activities within 3 days after administration. The depression was prolonged for cytochrome P-450, total haem and the metabolism of several type I substrates lasting up to 10 weeks after a single dose. By contrast, aniline hydroxylase, cytochrome b5 and NADPH-cytochrome c reductase activities returned to near control levels after week two. Microsomal enzymes in the kidneys of treated animals however, were unaltered. Serum glutamic pyruvic and glutamic oxaloacetic transaminase and bilirubin levels, indicators of hepatotoxicity, were greatly elevated 3 days after CCNU treatment. These parameters fell rapidly but were still above control levels to the end of the 10-week study. When added in vitro, CCNU reduced apparent cytochrome P-450 content and the metabolism of type I substrates in microsomes from untreated, phenobarbital (PB) and 3-methylcholanthrene (3-MC)-pretreated rats. Total haem and NADPH-cytochrome c reductase were not affected whereas aniline hydroxylase activity was activated. CCNU interacted with hepatic microsomes to produce a type I difference spectrum.

Aniline Hydroxylase↗

Cell lines from xeroderma pigmentosum complementation group A lack a single-stranded-DNA-binding activity.

Human fibroblasts and HeLa cells contain two major DNA-binding activities for superhelical DNA, which can be separated by phosphocellulose chromatography. The DNA-binding activity which elutes first from the column coelutes with and is probably identical to a single-stranded-DNA-binding activity. The second activity has been characterized previously. It binds preferentially to super-helical DNA containing DNA damage, but does not bind to single-stranded DNA. Five cell lines derived from patients with the repair-deficiency syndrome xeroderma pigmentosum (XP) were analyzed for the presence of these binding activities. Four of the cell lines were from the A-complementation group and one was from the D-complementation group of XP. The binding activity with preference for damaged DNA was present in all cell lines. The single-stranded-DNA-binding activity was present in the XP-D cell line but was absent or reduced in all of the four XP-A cell lines tested.

Adult↗

Metabolism of 6-nitrobenzo[a]pyrene by hamster embryonic fibroblasts and its interaction with nuclear macromolecules.

Incubation of 6-nitrobenzo[a]pyrene (6-nitroBaP) with hamster embryonic fibroblasts led to formation of both organic solvent-soluble and water-soluble products. High-pressure liquid chromatographic analysis of organic solvent-soluble extracellular metabolites showed the predominant presence of dihydrodoils, with only small amounts of phenolic products. This differed from microsomal metabolism, using hepatic preparations from 3-methylcholanthrene-pretreated rats, where a major phenolic peak was obtained. Subsequent treatment of aqueous layer with beta-glucuronidase, however, revealed that most of the phenols were associated with glucuronic acid to form water soluble products. Interaction of 6-nitroBaP with nuclear macromolecules from HEF was also studied. The chemical interacted with both DNA and RNA, but the specific activity was highest with nuclear proteins. This binding profile was found to be similar to that when benzo[a]pyrene was used, although the affinity toward protein binding was slightly higher for 6-nitroBaP.

Animals↗

Stimulation of microsomal drug oxidation in liver and kidney of rats treated with the oncolytic agent cis-dichlorodiammineplatinum-II.

In vitro drug metabolism from liver and kidney of rats was studied for up to 12 days following a single intraperitoneal injection of the antineoplastic drug cisplatinum. At 3,5, and 8 days posttreatment, hepatic cytochrome P-450 dependent enzyme activity was increased 20-45%, but levels of cytochromes P-450 and b5 were unaltered. Hepatic in vitro stimulated thiobarbituric acid reactive (TBAR) substances were increased at all times, with a maximum of 20 times normal on day 5. Renal aniline hydroxylase activity was elevated 25-95% throughout the first 8 days. Renal in vitro stimulated TBAR substances were not significantly altered. In vitro addition of cisPt to control microsomes resulted in no consistent, dose-related changes in substrate metabolism.

Animals↗

Sex-dependent differences in the effects of portacaval anastomosis on hepatic monooxygenases in rats.

Previous work revealed that portacaval anastomosis (PCA) in rats results in hepatic atrophy and marked decreases in components of the microsomal monooxygenase system such as cytochrome P-450. In the present study, the effects of PCA on hepatic monooxygenase activity were studied in more detail. We report that PCA, in general, produces effects resembling those of castration. Thus, in male rats, PCA depressed the activity of highly sex-dependent enzymes such as ethylmorphine and aminopyrine demethylases. Similar effects were produced by castration, and the combination of PCA and castration produced the same effect as either treatment alone. In male rats, non-sex-dependent enzymes such as aniline hydroxylase and NADPH-cytochrome c reductase were unaffected by either PCA or castration. By contrast, in female rats, neither PCA nor castration significantly affected microsomal monooxygenase activities. In male rats, PCA was accompanied by a 75% reduction in serum testosterone levels and a 6-fold increase in total estrogen levels. We conclude that these effects of PCA in male rats were due, in large measure, to a demasculinizing effect.

Animals↗

Alterations in hepatic and renal levels of glutathione and activities of glutathione S-transferase from rats treated with cis-dichlorodiammineplatinum-II.

Adult female rats were treated intraperitoneally with 8 mg/kg of cis-dichlorodiammineplatinum(II). At various times after treatment 1, 3, 5, 8, 12 days replicate animals were killed and liver and kidney cytosols examined for activity of glutathione-dependent transferase activities and levels of glutathione. Hepatic levels of glutathione were depressed by 13-28% at 1, 3, 5 days after dosing. Renal levels of glutathione were increased by 3-5 fold at 8 and 12 days after drug administration. Renal levels of glutathione were decreased at nearly all times studied with a nadir at 5 days. Activity of glutathione s-acryl transferase was increased and S-epoxidetransferase was decreased at 5, 8, 12 days after dosing. When cisplatinum was added to incubation mixtures in vitro, no changes in enzyme activities were observed. When cisplatin and reduced glutathione were determined chromatographically in tissue cytosols from treated rats, 30% of the recovered platinum was associated with glutathione. In tissue cytosols, greater than 95% of the total platinum content was retained in the supernatant when protein was precipitated with trichloroacetic acid, while only 3-5% of the protein was retained.

Animals↗

Nonelectrolyte diffusion across lipid bilayer systems.

The permeability coefficients of a homologous series of amides from formamide through valeramide have been measured in spherical bilayers prepared by the method described by Jung. They do not depend directly on the water:ether partition coefficient which increases regularly with chain length. Instead there is a minimum at acetamide. This has been ascribed to the effect of steric hindrance on diffusion within the bilayer which increases with solute molar volume. This factor is of the same magnitude, though opposite in sign to the effect of lipid solubility, thus accounting for the minimum. The resistance to passage across the interface has been compared to the resistance to diffusion within the membrane. As the solute chain length increases the interface becomes more important, until for valeramide it comprises about 90% of the total resistance. Interface resistance is also important in urea permeation, causing urea to permeate much more slowly than an amide of comparable size, after allowance is made for the difference in the water:ether partition coefficient. Amide permeation coefficients have been compared with relative liposome permeation data measured by the rate of liposome swelling. The ratios of the two measures of permeation vary between 3 and 16 for the homologous amides. The apparent enthalpy of liposome permeation has been measured and found to be in the neighborhood of 12 kcal mol-1 essentially independent of chain length. Comparison of the bilayer permeability coefficients with those of red cells shows that red cell permeation by the lipophilic solutes resembles that of the bilayers, whereas permeation by the hydrophilic solutes differs significantly.

Amides↗

Pre-core mutation associated with lack of hepatitis B e antigenaemia in Moroccan asymptomatic carriers of the virus.

Recently, ongoing chronic liver disease with persistent viraemia has been described in hepatitis B virus (HBV) carriers despite the presence of anti-HBe. This has been attributed to infection with pre-C-region-mutated HBV variants. To investigate the possible existence and the prevalence of HBV variants in Morocco and the correlation between HBV DNA detection by polymerase chain reaction and pre-S1 antigenaemia, we tested twenty blood donors, HBsAg chronic carriers for more than one year. The diagnosis of such HBeAg-negative HBV variants was determined by a previously described rapid detection method using selective oligonucleotide hybridization. Probes M0, M1 and M2 correspond, respectively, to a non-mutated distal pre-C sequence, a one-point-mutated sequence with a TAG stop codon at pre-C codon 28 and a two-point-mutated sequence with codon 28 TAG and codon 29 GAC. All the 5 HBeAg-positive samples hybridized with the M0 wild-type probe only. Among the anti-HBe-positive samples, one hybridized with the M0 probe only, whereas another hybridized with none of the oligoprobes. The 13 remaining HBeAg-negative cases hybridized with the M1, M2 or combined M0, M1 and M2 probes. Seven of the 13 HBeAg-negative samples hybridized with more than one probe. DNA sequencing confirmed mixed distal pre-C sequence changes in samples hybridizing with more than one probe. These data demonstrate the existence, in patients, of HBV variants containing an inactive pre-C region and hence the incapacity to synthesize pre-C-region-derived HBeAg.

Base Sequence↗

Maternal and foetal activin A levels: associations with normal and abnormal labour.

In pregnancy the feto-placental unit is the major source of activin A. However, the role(s) of activin A in late pregnancy remain uncertain and controversial. In particular, whether activin A levels alter in association with labour is unclear. In a cross-sectional cohort study, maternal serum samples were collected from women at term prior to elective Caesarean section (n=11), during labour prior to a spontaneous vaginal delivery (n=31), an instrumental vaginal delivery (n=16) or an emergent Caesarean section (n=7). Umbilical artery blood samples were collected from 75 pregnancies, after an elective Caesarean section (n=9), a normal vaginal delivery (n=37), an instrumental vaginal delivery (n=15) or an emergent Caesarean section (n=14). Levels of activin A were measured and compared according to modes of delivery.Maternal, but not foetal, serum activin A was increased significantly in women who were delivered by an intrapartum Caesarean section compared to other modes of delivery. Foetal, but not maternal, serum activin A was significantly correlated with umbilical artery pH. Maternal serum activin A is increased in women undergoing an intrapartum Caesarean section compared to either a vaginal delivery or an elective Caesarean section. The mechanism(s) underlying this observation are not clear.

Activins↗

Interactions between environmental lead exposure and sociodemographic factors on cognitive development.

A total of 375 children who lived in Port Pirie, South Australia, and surrounding towns were followed from birth to ages 11-13 y. Possible interactions between lifetime average blood lead concentration and sociodemographic factors (including gender, parents' occupational prestige [as a surrogate of socioeconomic status], quality of home environment, and maternal intelligence quotient) on children's intelligence quotients were examined. Although no statistically significant interaction between blood lead concentration and any of these covariates was found, the results suggested that-after adjustment for a wide range of covariates--children from socially disadvantaged backgrounds (adjusted regression coefficient = -9.6 intelligence quotient points per log unit of blood lead concentration; 95% confidence interval = -2.5, -17.7) were more sensitive to the effects of lead than those of a higher socioeconomic status (adjusted regression coefficient = -2.9; 95% confidence interval = 3.8, -9.6). In addition, girls (adjusted regression coefficient = -7.4; 95% confidence interval = -1.7, -13.1) were more sensitive to the effects of lead than boys (adjusted regression coefficient = -2.6; 95% confidence interval = 2.9, -8.0). These results were basically consistent with our findings observed at ages 2 y, 4 y, and 7 y.

Adolescent↗

Ross River virus disease in Australia: epidemiology, socioecology and public health response.

Societal and ecosystem change have a potentially profound impact of on human health and well-being. Alteration in the pattern of infectious diseases could be one of the most significant results of this process. Arboviral infections are a global public health issue with significant morbidity and mortality burden in the human population. Ross River virus (RRV) infection is the most common arboviral disease in Australia and some Pacific island nations. The present paper aims to illustrate the epidemiological and socioecological implications of RRV infection in Australia and to make recommendations for public health response to this disease.

Alphavirus Infections↗

Would general practitioners support a population-based colorectal cancer screening programme of faecal-occult blood testing?

BACKGROUND: The success of a population-based screening for colorectal cancer (CRC) is determined to a large extent by general practitioner (GP) attitudes, beliefs and support. The extent to which GPs support population-based CRC screening remains unclear. AIMS: To assess the knowledge, attitudes and practices of GPs in relation to CRC screening, and to identify the determinants of GP support for population-based faecal-occult blood testing (FOBT). METHODS: A cross-sectional postal survey was conducted with a random sample of 692 GPs in Queensland, -Australia. We assessed GP knowledge, attitudes and practices concerning CRC screening in relation to their stance on population-based FOBT screening. RESULTS: Although the response rate was low (41%), participants were representative of Queensland GPs in general. Of 284 participating GPs, 143 (50.5%) indicated that they would support a population-based FOBT screening programme, 42 (14.8%) would not and 98 (34.6%) were unsure. Belief in FOBT test efficacy (P <0.001), possession of CRC guidelines (P <0.05) and belief in earlier stage detection (P <0.05) were major determinants of support for population-based FOBT screening. No significant association was observed for doctor's sex, location of practice, age, year completed medical training, membership of a Division of General Practice, number of weekly consultations, number of patients investigated for CRC per month, size of practice, own family history of CRC, interest in further information on CRC screening or treatment, and current use of FOBT with asymptomatic patients aged > or =40 years. CONCLUSIONS: GP support for FOBT population-based screening appears to have increased over recent years. The knowledge and attitudes/beliefs of GPs are key determinants of their support.

Adult↗