PubMed Health⌕ Search

Biomedical subjects

S Donohue

Publications and source records attributed to S Donohue.

10 recordsLinked to original sources
PubMed2002

Antibodies to high-density lipoprotein and beta2-glycoprotein I are inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome.

OBJECTIVE: To determine the prevalence of anti-high-density lipoprotein (anti-HDL) antibodies and to establish a possible relationship between anti-HDL, anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI), and paraoxonase (PON) activity in patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: Thirty-two patients with SLE and 36 with primary APS were enrolled in a cross-sectional study. Twenty age- and sex-matched healthy subjects were used as controls. Serum levels of IgG and IgM aCL, anti-beta(2)GPI, and antiprothrombin antibodies and IgG anti-HDL were measured by enzyme-linked immunosorbent assay. Total cholesterol, HDL cholesterol, HDL(2), and HDL(3) were determined by standard enzymatic techniques. PON activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (TAC) by chemiluminescence. RESULTS: Levels of total HDL, HDL(2), and HDL(3) were reduced in patients with SLE compared with controls (mean +/- SD 0.51 +/- 0.3, 0.37 +/- 0.3, and 0.14 +/- 0.1 mmoles/liter, respectively, versus 1.42 +/- 0.9, 1.01 +/- 0.7, and 0.40 +/- 0.2). Patients with SLE and primary APS had higher titers of anti-HDL antibodies and lower PON activity than controls. In the SLE population, PON activity was inversely correlated with IgG anti-HDL titers (r = -0.48, P = 0.005) whereas in the primary APS population, IgG anti-beta(2)GPI was the only independent predictor of PON activity (r = -0.483, P = 0.003). In the SLE group, anti-HDL was inversely correlated with TAC (r = -0.40, P < 0.02), and PON activity was positively correlated with TAC (r = 0.43, P < 0.02). CONCLUSION: IgG anti-HDL and IgG anti-beta(2)GPI antibodies are associated with reduced PON activity in patients with SLE and primary APS. Since the physiologic role of PON is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in SLE and primary APS.

Adult↗
PubMed2002

The playing habits and other commitments of elite junior Australian football players.

The Victorian Football League Under 18 (VFL U18) competition provides a pathway to the elite senior level of Australian football. Players involved in the VFL U18 competition also play football in other contexts, including for school and local clubs, and can have considerable additional work and educational demands. A total of 103 elite junior Australian football players from six VFL U18 clubs participated in a survey that asked about their football playing habits and other commitments. The median age of players when they first joined their VFL U18 squad was 16.3 years. The players participated in a median of five weekly training sessions during the last two weeks of the 1999 preseason and played a median of five preseason games. Fifty percent of the players expected to participate in 3-4 training sessions per week and 25% expected to play more than two games per week during the 1999 season. Half of the players reported ambitions to play Australian Football League (AFL) football. Further research is needed to determine whether or not high participation levels have negative impacts on performance and injury risk in these players.

Adolescent↗
PubMed2002

Safety attitudes and beliefs of junior Australian football players.

OBJECTIVES: To describe the safety attitudes and beliefs of junior (aged 16-18 years) Australian football players. SETTING: Six Victorian Football League Under 18 (VFL U18) clubs in Victoria, Australia. METHODS: Cross sectional survey. Altogether 103 players completed a self report questionnaire about their safety beliefs and perceptions of support when injured, across three contexts in which they played: VFL U18 club, local club, and school. RESULTS: Although only 6% believed it was safe to play with injuries, 58% were willing to risk doing so. This increased to almost 80% when players perceived that their chances of being selected to play for a senior elite team would be adversely affected if they did not play. There were significant differences in the perceived level of support for injured players and in the ranking of safety as a high priority across the three settings. In general, the VFL U18 clubs were perceived as providing good support for injured players and giving a high priority to safety issues, but local clubs and particularly schools were perceived to address these issues less well. CONCLUSIONS: Junior Australian football players have certain beliefs and perceptions in relation to injury risk that have the potential to increase injuries. These negative beliefs need to be addressed in any comprehensive injury prevention strategy aimed at these players.

Adolescent↗
PubMed2001

4-hydroxy-2-nonylquinoline: a novel iron chelator isolated from a bacterial cell membrane.

The membrane associated iron chelator of Pseudomonas aeruginosa has been extracted from membranes of iron-rich cells with ethanol and purified by reverse phase HPLC. Using 13C NMR and FAB mass spectroscopy, the structure of the chelator has been determined to be 4-hydroxy-2-nonylquinoline. This compound has been previously isolated and named pseudan IX, a name which we use here. We synthesized pseudan IX and show that the spectral properties of the synthesized compound and the purified compound are nearly identical. Also purified from the ethanol extract of membranes is 4-hydroxy-2-heptylquinoline, i.e., pseudan VII. Bacterially purified pseudan IX binds iron as indicated by the incorporation of radiolabeled iron into the chelator and by the formation of pink micelles in a concentrated ethanol extract. The formation of pink micelles upon addition of iron to the synthesized compound indicates that it binds iron.

Chromatography, High Pressure Liquid↗
PubMed2000

Zebrafish dracula encodes ferrochelatase and its mutation provides a model for erythropoietic protoporphyria.

Exposure to light precipitates the symptoms of several genetic disorders that affect both skin and internal organs. It is presumed that damage to non-cutaneous organs is initiated indirectly by light, but this is difficult to study in mammals. Zebrafish have an essentially transparent periderm for the first days of development. In a previous large-scale genetic screen we isolated a mutation, dracula (drc), which manifested as a light-dependent lysis of red blood cells [1]. We report here that protoporphyrin IX accumulates in the mutant embryos, suggesting a deficiency in the activity of ferrochelatase, the terminal enzyme in the pathway for heme biosynthesis. We find that homozygous drc(m248) mutant embryos have a G-->T transversion at a splice donor site in the ferrochelatase gene, creating a premature stop codon. The mutant phenotype, which shows light-dependent hemolysis and liver disease, is similar to that seen in humans with erythropoietic protoporphyria, a disorder of ferrochelatase.

Animals↗
PubMed1997

Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells: potential implications for patients with acute porphyria.

Some patients with acute hereditary porphyrias have seizures and require anticonvulsant therapy, but many anticonvulsants induce exacerbations of the hepatic porphyrias. Recently, several new anticonvulsants have become available. Among these are gabapentin, vigabatrin, felbamate, lamotrigine, and tiagabine. Little is known about their potential for induction of porphyric attacks. We used a cell culture model of primary chicken embryo liver cells, which maintain intact heme synthesis and regulation, to study the effects of these new anticonvulsants on porphyrin accumulation. Treatment of the cells with deferoxamine (250 microM) led to a partial block in heme synthesis, simulating the conditions encountered in human beings with porphyria. Concomitant exposure of these cells to phenobarbital (2 mM) strongly induced accumulation of porphyrins, serving as a positive control in this model. Cells were treated for 20 hours with increasing doses (3.2 to 1,000 microM) of the newer anticonvulsants, with or without deferoxamine. For most of these anticonvulsants 5 to 100 microM is representative of the concentrations achieved in humans with therapeutic doses. Porphyrins were measured spectrofluorometrically as uro-, copro-, and protoporphyrins. Results were confirmed by high-pressure liquid chromatography. Neither vigabatrin nor gabapentin treatment, with or without deferoxamine, led to any increase in porphyrin accumulation. Similar doses of felbamate (with deferoxamine) led to a marked increase in (mainly proto-) porphyrin levels, qualitatively and quantitatively almost identical to the accumulation produced by phenobarbital. Lamotrigine or tiagabine (with deferoxamine) caused similar porphyrin accumulation. Tiagabine treatment up to 100 microM (with deferoxamine) also resulted in very high levels of predominantly proto-porphyrin. In contrast to the other anticonvulsants tested, tiagabine without deferoxamine led to mild porphyrin accumulation. In the presence of deferoxamine, phenobarbital, felbamate, lamotrigine, or tiagabine, but not gabapentin or vigabatrin, increased levels of the mRNA of ALA synthase, the first and rate-controlling enzyme of porphyrin synthesis. Such enzyme induction is a sine qua non for acute porphyric attacks. We conclude that neither vigabatrin nor gabapentin is porphyrogenic, whereas felbamate, lamotrigine, and, especially, tiagabine lead to much accumulation of porphyrins. The latter three anticonvulsants, therefore, may precipitate or exacerbate acute porphyric attacks in humans. We recommend use of vigabatrin or gabapentin, but not felbamate, lamotrigine, or tiagabine, in patients with acute porphyria and seizures.

Animals↗
PubMed1995

Tissue distribution of zinc-mesoporphyrin in rats: relationship to inhibition of heme oxygenase.

Metalloporphyrins, including heme and others that inhibit heme oxygenase, are agents with expanding therapeutic potential. Recent results from our laboratory showed that a combination of heme and zinc-mesoporphyrin was remarkably effective in ameliorating biochemical features of acute porphyria. The aim of this study was to assess plasma clearance, tissue distribution and persistence, stability, toxicology and metabolic effects of zinc-mesoporphyrin, after its i.v. administration to rats. After administration of 15 mumol/kg b.wt. of zinc-mesoporphyrin (bound to serum albumin in a 1:1 molar ratio) the metalloporphyrin was rapidly cleared from plasma (half-life 3.6 h) with uptake primarily into liver and spleen, considerably less into the kidney and none detectable into the heart or brain. Hepatic heme oxygenase activity was undetectable for 4 days and less than 50% of control 1 week later. Inhibition of splenic heme oxygenase activity was also substantial but less marked than in the liver. No mortality was observed in any of the treated animals, and there was no detectable effect on gross or microscopic appearance of the liver, spleen, kidneys, heart, lungs or brain. Blood counts and chemistries remained within normal limits. We conclude that single doses of ZnMP-serum albumin are nontoxic, rapidly cleared from the plasma and persist primarily in the liver and spleen where heme oxygenase is inhibited for prolonged periods.

Animals↗
PubMed1985

The relationship between adolescent life stress events and delinquent conduct including conduct indicating a need for supervision.

Yeaworth, York, Hussey, Ingle, and Goodwin's (1980) Adolescent Life Change Event Scale was administered to 55 adolescents who were on probation or being held in detention for offenses ranging from a felony to conduct indicating a need for supervision (Texas Juvenile Probation Commission, 1983). The offenses committed during the previous 12 months were given weights, and weights obtained by Yeaworth (1980) were used for stress events experienced in the last 12 months. Pearson product moment correlation was computed to obtain a relationship between stress events and offenses. The results suggest that these adolescents are more stressed than nondelinquent adolescents when compared to the Yeaworth (1980) study. Nearly 82 percent of subjects in the present study had experienced the event of "failing one or more subjects in school." The correlation coefficient obtained relating stress events to offenses was -0.01727. The results were interpreted to mean that there is no relationship between total amount of stress experienced and total offenses committed. However, some patterns were found in runaway behavior and truancy that were related to several of the stress events; 87.5 percent of runaway subjects had experienced "hassling with parents," and 43.8 percent had experienced a "family member other than yourself having trouble with alcohol"; 94.1 percent of truancy subjects had experienced "failing one or more subjects in school," and 64.7 percent had experienced "getting into drugs or alcohol."

Acting Out↗