Search PubMed⌕ Search

Biomedical subjects

R J Williams

Publications and source records attributed to R J Williams.

At least 73 records · Page 4Linked to original sources

Rapid screening for putative exported proteins from Staphylococcus aureus using alkaline phosphatase as a reporter molecule.

Staphylococcus aureus causes a wide range of infections in humans, ranging from superficial skin infections to the more serious toxin-mediated diseases such as toxic shock syndrome. Owing to the increasing resistance of this bacterium to a wide range of antibiotics, the need to determine the virulence factors involved in infection is becoming more important as these molecules are potential therapeutic targets. In this study, we have screened for putative exported proteins from S. aureus on the basis that these proteins are likely to be the first point of contact between the bacterium and host during infection. We have constructed gene fusions between S. aureus DNA and a truncated version of the Escherichia coli phoA gene, and we report on the characterization of the recombinants exhibiting alkaline phosphatase activity. As well as known S. aureus proteins, we have identified a number of putative open reading frames that encode proteins similar to those from nonstaphylococcal species and also unique proteins that do not have any homologues on the current databases.

Alkaline Phosphatase↗

Drinking restraint versus alcohol expectancies: which is the better indicator of alcohol problems?

OBJECTIVE: The relationship between expectancies and other psychological constructs related to drinking is unclear. The current study assesses the power of drinking restraint, measured by the Temptation and Restraint Inventory (TRI), along with alcohol expectancy and drinking refusal self-efficacy, measured by the Drinking Expectancy Profile (DEP), as indicators of alcohol use and problem drinking. METHOD: Volunteer students (N = 359), consisting of 113 men with a mean (+/-SD) age of 25.31 +/- 10.61 years and 246 women with a mean age of 23.04 +/- 8.90, completed the TRI, DEP and Alcohol Dependence Scale (ADS) as well as frequency and quantity measures of self-reported drinking. RESULTS: Drinking Restraint was a stronger indicator of higher scores on the ADS, accounting for 54% and 45% of the variance for men and women, respectively, with Alcohol Expectancies and Drinking Refusal Self-Efficacy being the better indicator of frequency of alcohol consumption, accounting for 20% of the variance for men and 26% for women. Both measures were represented by similar variances within the quantity of drinking measure. CONCLUSIONS: Drinking restraint and alcohol expectancies were seen to measure kindred but unique cognitive subsets, providing further insight into the progression of alcohol problems. Alcohol expectancies and drinking refusal self-efficacy may be acquired early in the development of drinking behavior, as evidenced by stronger associations with risky drinking; drinking restraint and its associated loss of control factors appear to be more specifically related to problem drinking. Alcohol expectancy and drinking refusal self-efficacy may thus have broader use in the assessment of drinking behavior.

Adolescent↗

What is wrong with aluminium? The J.D. Birchall Memorial Lecture.

Aluminium chemistry has features in common with two other groups of elements: (1) divalent magnesium and calcium, and (2) trivalent chromium and iron. The essential differences between the first group and aluminium are explored and it is shown that the much higher acidity of aluminium makes it such a powerful competitor for oxygen-donor ligands, opposite functions of both magnesium and calcium, in cells that its presence is damaging. By way of contrast aluminium is a weaker acid than ferric ions but it is more available. It was necessary for iron to be utilised in the presence of aluminium so special methods had to be devised to distinguish between them. In essence aluminium has always, throughout evolution, been a threat to the biological chemistry of all these three elements. We shall examine this chemistry and then explore the relationship of calcium and aluminium under acid rain conditions.

Aluminum↗

Ca(2+)-permeable AMPA receptors induce phosphorylation of cAMP response element-binding protein through a phosphatidylinositol 3-kinase-dependent stimulation of the mitogen-activated protein kinase signaling cascade in neurons.

Ca(2+)-permeable AMPA receptors may play a key role during developmental neuroplasticity, learning and memory, and neuronal loss in a number of neuropathologies. However, the intracellular signaling pathways used by AMPA receptors during such processes are not fully understood. The mitogen-activated protein kinase (MAPK) cascade is an attractive target because it has been shown to be involved in gene expression, synaptic plasticity, and neuronal stress. Using primary cultures of mouse striatal neurons and a phosphospecific MAPK antibody we addressed whether AMPA receptors can activate the MAPK cascade. We found that in the presence of cyclothiazide, AMPA caused a robust and direct (no involvement of NMDA receptors or L-type voltage-sensitive Ca(2+) channels) Ca(2+)-dependent activation of MAPK through MAPK kinase (MEK). This activation was blocked by GYKI 53655, a noncompetitive selective antagonist of AMPA receptors. Probing the mechanism of this activation revealed an essential role for phosphatidylinositol 3-kinase (PI 3-kinase) and the involvement of a pertussis toxin (PTX)-sensitive G-protein, a Src family protein tyrosine kinase, and Ca(2+)/calmodulin-dependent kinase II. Similarly, kainate activated MAPK in a PI 3-kinase-dependent manner. AMPA receptor-evoked neuronal death and arachidonic acid mobilization did not appear to involve signaling through the MAPK pathway. However, AMPA receptor stimulation led to a Ca(2+)-dependent phosphorylation of the nuclear transcription factor CREB, which could be prevented by inhibitors of MEK or PI 3-kinase. Our results indicate that Ca(2+)-permeable AMPA receptors transduce signals from the cell surface to the nucleus of neurons through a PI 3-kinase-dependent activation of MAPK. This novel pathway may play a pivotal role in regulating synaptic plasticity in the striatum.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Thermodynamic influences on the fidelity of iron-sulphur cluster formation in proteins.

In an organism, two thermodynamic factors are important in ensuring that homometallic [4Fe-4S] cubane clusters are formed in preference to clusters containing heterometals such as Zn or Cu. These are the electronic resonance stabilisation, which boosts the binding of Fe(II) within an Fe-S cluster relative to its normally low position in the Irving-Williams order, and attenuation of the cytoplasmic concentrations of competing metals such as Zn or Cu by specific ligands.

Ferredoxins↗

Bulimic symptoms in adolescent girls and boys.

OBJECTIVE: The factor structure of the Bulimic Investigatory Test (BITE) was examined in adolescent girls and boys. METHOD: Seven hundred and seventy seven adolescents (427 girls and 350 boys) completed the BITE. RESULTS: Consistent with the original scale, one factor describing overall bulimic symptoms was found for the girls. However, two factors were required to summarize the boys' symptoms: "Emotional and Rigid/Disruptive Eating Style" and "Food Preoccupation and Binging." DISCUSSION: The results are discussed in relation to Fairburn's (Fairburn. (1995). Overcoming Binge Eating. New York: Guilford) distinction which separates problem from nonproblem binge eating. Further studies are now needed to examine the mechanisms underlying the development of bulimic eating in boys and young men.

Adolescent↗

Staphylococcus aureus stimulates inducible nitric oxide synthase in articular cartilage.

OBJECTIVE: To determine if Staphylococcus aureus stimulates the L-arginine-nitric oxide (NO) synthase pathway in articular cartilage. METHODS: A heat-killed and sonicated (denatured) S. aureus preparation was added to cultures of bovine articular cartilage. NO production was measured as accumulated nitrite in the culture medium and by the NO synthase-dependent conversion of 3H-L-arginine to 3H-L-citrulline in cartilage homogenates. Inducible NO synthase (iNOS) messenger RNA (mRNA) expression was analyzed by Northern blot. Proteoglycan synthesis was measured by 35SO4 incorporation into glycosaminoglycan. RESULTS: Nitrite accumulation and 3H-L-citrulline formation in cartilage were elevated by denatured S. aureus (compared with unstimulated control cartilage) and inhibited by the NO synthase inhibitor N(G)-monomethyl-L-arginine. Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S. aureus stimulation. Denatured S. aureus suppressed the accumulation of 35SO4-labeled macromolecules representing newly synthesized proteoglycans in bovine articular cartilage. The suppressed proteoglycan synthesis was due to the presence of NO. CONCLUSION: These findings support the hypothesis that a component of S. aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis.

Animals↗

Gender congruence in confirmatory and compensatory drinking.

The relationship between gender-stereotypical traits and drinking behaviors was examined in 422 university students via both positive and negative measures of masculinity and femininity. Two canonical variates summarized the underlying relationships. The 1st canonical variate indicated that both high negative masculinity and low positive femininity predicted alcohol consumption and alcohol-related problems. This behavior was labeled confirmatory drinking because it depicts a style of drinking that reinforces gender-stereotypical images about alcohol use; masculine characteristics are typically associated with high levels of alcohol consumption. The 2nd canonical variate indicated that both low positive masculinity and low positive femininity predicted problem drinking. This behavior was labeled compensatory drinking because drinkers often use alcohol to express their masculinity and femininity. The distinction between confirmatory and compensatory drinking has important implications for the development of more effective education and preventative strategies.

Adult↗

Ebola (subtype Reston) virus among quarantined nonhuman primates recently imported from the Philippines to the United States.

In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission.

Animals↗

Detection of channel catfish virus DNA in latently infected catfish.

Channel catfish virus (CCV) disease is an acute haemorrhagic disease in juvenile channel catfish (Ictalurus punctatus). While fish that survive primary CCV infection are suspected of being carriers of CCV, little is known concerning CCV latency. In this report, fingerling catfish were infected with CCV by experimental immersion challenge. Infected fish displayed clinical signs of CCV disease, but 22% of infected fish survived the acute disease. At 140 days post-infection, PCR analysis detected CCV DNA in the blood, brain, intestines, kidney, liver and peripheral blood leukocytes of latently infected fish. Further analysis indicated the CCV genome may exist as circular or concatemeric DNA during virus latency. This study, employing an experimental model of CCV disease, confirms that CCV establishes a latent infection of channel catfish.

Animals↗

Gender differences in drinking restraint.

OBJECTIVE: This study examines the factor structure and the predictive power of drinking restraint for men and women as measured by the Temptation and Restraint Inventory (TRI). The TRI assesses two factors: Cognitive-Emotional Preoccupation (CEP) and Cognitive-Behavioral Control (CBC). METHOD: A group of 418 drinkers was drawn from a university sample and divided by gender into two groups. Men (n = 122) were of a mean age (+/-SD) of 23 +/- 7 years; women (n = 296) were of a mean age of 22.5 +/- 8 years. Subjects completed the TRI and the Alcohol Dependence Scale (ADS) and validated quantity and frequency of drinking indices. RESULTS: Drinking restraint for the men was found to better predict alcohol dependence, quantity of drinking and frequency of drinking. Moreover, two factors confirming the TRI's CEP and CBC model were extracted for the men, but only one factor was extracted for the women. CONCLUSIONS: It was proposed that, as men tend to drink greater amounts of alcohol more often, they have learned to distinguish more clearly the conflicts in their personal control over drinking. If the TRI is to be used as a diagnostic and treatment tool, it is recommended that clinicians be cognizant of possible gender differences in restrained drinking behavior.

Adolescent↗

Knowledge of fetal alcohol syndrome (FAS) among natives in Northern Manitoba.

OBJECTIVE: To investigate knowledge about fetal alcohol syndrome (FAS) among Natives in northern Manitoba. A second objective was to determine if there are age or gender differences in level of knowledge. A third objective was to examine the relationship between knowledge about FAS and reported frequency of drug and alcohol use during pregnancy. METHOD: A nonrandom sample of 466 Natives from northern Manitoba was interviewed about drug and alcohol use during pregnancy and knowledge of FAS. The sample was proportionately representative of the 26 northern reserves, with an approximately equal number of male and female subjects ranging in age from 13 to 71 years. RESULTS: Northern Manitoban Natives have lower levels of FAS knowledge than the general public. Of this sample, 80% believed drinking alcohol could adversely affect the unborn baby and 36% had heard of FAS, compared to 90% and 64%, respectively, in the general U.S. population. Natives in their 20s and 30s were more knowledgeable than Natives in their 50s and 60s. Females tended to be more knowledgeable than males. Drug and alcohol use during pregnancy is high (51% of women report drinking during one or more pregnancies) and the relationship between FAS knowledge and drug use during pregnancy appears weak. Young people were the most knowledgeable about FAS but also the most likely to report having used drugs or alcohol during pregnancy. CONCLUSIONS: The low levels of knowledge about FAS among the Native population supports the need for continued education. However, the results also suggest that education by itself may be insufficient to make dramatic changes in behavior.

Adolescent↗

Booking clients for addiction treatment: what works best?

Considerable effort has been devoted to trying to improve the nature and quality of drug abuse treatment over the past 30 years. While there is evidence that certain treatment modalities are more effective than others, there is little evidence that inpatient treatment is more effective than outpatient, that treatment of a long duration is more effective than that of a short duration or that intense treatment is more effective than less intense treatment. Attempts to match drug abusers to an optimal treatment type have largely been unsuccessful.

Adult↗

Quantitative evaluation of stigma polymorphism in a tristylous weed, Lythrum salicaria (Lythraceae).

Tristyly involves three different forms of flowers that differ reciprocally in the heights of stigmas and anthers within flowers. Apart from the style and stamen lengths, heterostylous species also demonstrate pollen and stigma polymorphisms. We quantified stigma polymorphism in tristylous Lythrum salicaria by measuring the stigma diameters, structure of papillae, and density and distribution of papillae on the stigma from flower samples of 201 individuals belonging to three morphs. The diameter of the stigma and the distribution of papillae were quantified using a scanning electron microscope, and the structure of papillae was determined using a light microscope. The stigma diameter in the long morph was significantly greater than in the mid and short morphs. While the density of stigmatic papillae was significantly greater in the mid and short morphs than in the long morph, the total number of papillae per stigma did not differ across morphs. The length and diameter of papillae at the apex, neck, and base were significantly greater in the long morph followed by the mid and short morphs. A discriminant function analysis separated the long morph from the mid and short morphs based on the canonical scores of measurements of papillae structure. The stigma polymorphism coupled with those of pollen may play a functional role in self-incompatibility mechanisms.

Journal Article↗