A familial case of pulmonary arterial sequestration

The cases of a mother and infant son are reported, both with a rare type of pulmonary sequestration where the arterial supply to the lung arises from the systemic circulation. This is a familial case of arterial sequestration. In both patients, the lung parenchyma was radiologically normal.     

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

1. 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.
2. PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K_i of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the K_i.
3. Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg⁻¹, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated K_i (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.
4. The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.
5. PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg⁻¹ (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.
6. Results of these studies are consistent with a role for 15-LO in atherogenesis.

     

Exploring the social acceptability of skill-mix in dentistry

AIM: To explore lay views on skill-mix in dentistry and the experiences and social acceptability of care provided by operating dental auxiliaries. DESIGN: Qualitative semistructured interviews and focus groups. SETTINGS: Participants' homes and neutral public venues. PARTICIPANTS: Purposive sample of 27 adults ensuring varieties of age, social and cultural backgrounds. RESULTS: Three main themes emerged from the data. The first two (Perceptions of the Nature of Dental Services and Anxiety about Dental Treatment) influenced views in the third (Support for Skill-mix). Perceptions of the nature of services varied between and within participants and depended on the context in which they were being discussed. Consumerist views and greater dental anxiety tended to be related to lower support for skill-mix. However, the possibility of lower treatment costs was seen as beneficial. Public service views saw increased efficiency and access to services as benefits of skill-mix. Views on auxiliaries treating children varied from overt opposition to reluctant acceptance. The need for careful communication of the rationale for skill-mix was highlighted. CONCLUSION: Views on skill-mix varied. Dental anxiety and perceptions of the nature of dental services appeared to influence support of its use. Careful communication of the rationale and potential benefits of skill-mix is needed.     

The physiological demands of horseback mustering when wearing an equestrian helmet

The hottest months on northern Australian cattle stations are from September to November, and it is during these months that horseback cattle mustering occurs. Stockmen wear clothing that restricts heat loss, and protective helmets have recently been introduced. Anecdotal evidence points to the possibility that helmets may increase the probability of developing heat illness, or reducing workplace performance. In this project, we quantified the working (thermal) environment on such cattle stations, and measured the metabolic demands on, and concurrent physiological strain in stockmen during mustering, whilst wearing an equestrian helmet. During horseback work, the average heart rate was 102.0 beats min(-1) (SD 14.0), with almost 90% of the time (238 min) spent working at intensities <50% of the heart rate reserve. The projected metabolic heat production during mustering ranged between 178 and 333 W (women), and between 212 and 542 W (men). The average core temperature was 37.6 degrees C, while the mean skin temperature averaged 34.1 degrees C. It was concluded that the working environment is, on average, thermally uncompensable during the mustering season. However, horseback mustering per se is a relatively low-intensity activity, interspersed with short periods of high-intensity work. This activity level was reflected within core temperatures, which rarely climbed above values associated with light-moderate exercise. Thus, whilst the climatic state was uncompensable, stockmen used behavioural strategies to minimise the risk of heat illness. Finally, it was observed that the helmet, though unpleasant to wear, did not appear to increase thermal strain in a manner that would disadvantage stockmen.     

DNA Methylation Assay for X-Chromosome Inactivation in Female Human iPS Cells

Remarkable interest in the epigenetic status of human induced pluripotent stem (iPS) cells inspired numerous studies of their X-inactivation patterns. However, both the presence and the absence of X-inactivation have been described to date in undifferentiated iPS cells. The reasons for the discordant results between different studies are unclear, and further X-inactivation testing is warranted for all female human iPS cell lines. Some of the inconsistency in the current data most likely results from the use of different X-inactivation assays by different authors. We provide a detailed protocol for a simple, reliable and affordable X-inactivation assay based on promoter methylation and CAG-repeat polymorphism in the human androgen receptor (AR) gene at Xq11.2. This assay is commonly used in clinical genetic laboratories and we propose that it could be ideal for routine assessment and monitoring of the X-inactivation status in female human iPS cell lines.     

1H MRS identifies specific metabolite profiles associated with MYCN-amplified and non-amplified tumour subtypes of neuroblastoma cell lines

Neuroblastoma is the most common extracranial solid malignancy in children. The disease possesses a broad range of clinical phenotypes with widely varying prognoses. Numerous studies have sought to identify the associated genetic abnormalities in the tumour, resulting in the identification of useful prognostic markers. In particular, the presence of multiple copies of the MYCN oncogene (referred to as MYCN amplification) has been found to confer a poor prognosis. However, the molecular pathways involved are as yet poorly defined. Metabolite profiles generated by in vitro (1)H MRS provide a means of investigating the downstream metabolic consequences of genetic alterations and can identify potential targets for new agents. Thirteen neuroblastoma cell lines possessing multiple genetic alterations were investigated; seven were MYCN amplified and six MYCN non-amplified. In vitro magic angle spinning (1)H MRS was performed on cell suspensions, and the spectra analysed to obtain metabolite concentration ratios relative to total choline (tCho). A principal component analysis using these concentration ratios showed that MYCN-amplified and non-amplified cell lines form separate classes according to their metabolite profiles. Phosphocholine/tCho and taurine/tCho were found to be significantly raised (p < 0.05) and glycerophosphocholine/tCho significantly reduced (p < 0.05) in the MYCN-amplified compared with the MYCN non-amplified cell lines (two-tailed t test). (1)H MRS of the SH-EP1 cell line and an isogenic cell line transfected with the MYCN oncogene also showed that MYCN oncogene over-expression causes alterations in phosphocholine, glycerophosphocholine and taurine concentrations. Molecular pathways of choline and taurine metabolism are potential targets for new agents tailored to MYCN-amplified neuroblastoma. Copyright (c) 2007 John Wiley & Sons, Ltd.     

High prevalence of the CD14-159CC genotype in patients infected with severe acute respiratory syndrome-associated coronavirus

To investigate whether genetic factors of innate immunity might influence susceptibility and/or progression in individuals infected with SARS, we evaluated the CD14 gene polymorphism in 198 Hong Kong blood donors and 152 Hong Kong severe acute respiratory syndrome (SARS) patients who were previously genotyped for FcγRIIA polymorphisms. The prevalence of the CD14-159CC polymorphism was significantly higher in the patients with severe SARS than in the those with mild SARS or controls (31% versus 15% [mild SARS] or 20% [controls]; mild SARS: P = 0.029; odds ratio, 2.74; 95% confidence interval, 1.15 to 6.57; controls, P = 0.04; odds ratio, 2.41; 95% confidence interval, 1.05 to 5.54), and both CD14-159CC and FcγRIIA-RR131 are risk genotypes for severe SARS-CoV infection.