The Impact of Lipoprotein-Associated Oxidative Stress on Cell-Specific Microvesicle Release in Patients with Familial Hypercholesterolemia.

Objective. Microvesicles (MVs) are small cell-derived particles shed upon activation. Familial hypercholesterolemia (FH) particularly when associated with Achilles tendon xanthomas (ATX) predisposes to atherosclerosis, possibly through oxLDL-C interaction with the CD36 receptor. To investigate the hypothesis that MVs derived from cells involved in atherosclerosis are increased in FH and that CD36 expressing MVs (CD36+ MVs) may be markers of oxLDL-C-induced cell activation, cell-specific MVs were measured in FH patients with and without ATX and their association with atherogenic lipid profile was studied. Approach and Results. Thirty FH patients with and without ATX and twenty-three controls were included. Plasma concentrations of MVs and CD36+ MVs derived from platelets (PMVs), erythrocytes (ErytMVs), monocytes (MMVs), and endothelial cells (EMVs), as well as tissue factor-positive cells (TF+ MVs), were measured by flow cytometry. Total MVs, MMVs, EMVs, ErytMVs, and TF+ MVs were significantly increased in FH patients, compared to controls. CD36+ MVs derived from endothelial cells and monocytes were significantly higher in FH patients and oxLDL-C predicted all the investigated cell-specific CD36+ MVs in FH patients with ATX. Conclusions. MVs derived from cells involved in atherosclerosis were increased in FH and may contribute to elevated atherothrombosis risk. The increased cell-specific CD36+ MVs observed in FH may represent markers of oxLDL-C-induced cell activation.

Psychosocial adjustment to multiple sclerosis: exploration of identity redefinition.

PURPOSE: As multiple sclerosis (MS) often occurs in the prime of life and is unpredictable in nature, there is likely to be a strong psychological effect, with changes in values and beliefs and how the individual sees him or her self. This article presents the findings of a focus group study which aimed to explore the subjective experiences of living with, and adjusting to, MS. METHOD: Seven individuals who had been diagnosed with MS for at least 5 years reflected on their reactions to being diagnosed, how they cope with the day to day challenges of the disease, and the changes that they have experienced. Data were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS: Diagnosis was met with negative reactions: denial, concealment and diminished confidence. However, the majority reported that, over time, there were positive changes in terms of their values and outlook. It would appear that the functional difficulties and psychological challenges, such as uncertainty and depression, are ameliorated to some extent by an increased appreciation for life and spirituality. CONCLUSIONS: The findings provide insight into the psychological process of identity redefinition associated with adjusting to MS. Given this, interventions should target role/identity re-examination to assist individuals with MS in better managing the disease and enjoying life.

Cryptosporidium in farmed animals: the detection of a novel isolate in sheep.

We describe the discovery of polymorphisms in the Cryptosporidium oocyst wall protein (COWP) gene conferring a novel restriction fragment length polymorphism (RFLP) pattern in 26/60 (43%) isolates from a flock of sheep sampled following a waterborne outbreak of human cryptosporidiosis. The sheep isolates showed identical PCR-RFLP patterns to each other by COWP genotyping but different from those of most currently recognised genotypes, including the major Cryptosporidium parvum genotypes 1 and 2. Sequence analysis of the 550bp amplicon from the COWP gene was compared with a DNA coding region employed in previous studies and showed the novel isolate to differ from other Cryptosporidium species and C. parvum isolates by 7-21%. The sheep-derived isolates were compared at this and further three Cryptosporidium gene loci with isolates from other farmed animals. The loci employed were one in the thrombospondin related adhesive protein (TRAP-C2) gene and two in the 70kDa heat shock protein (HSP70) gene (CPHSP1 and 2). Other animal samples tested in our laboratory were from clinically ill animals and all contained C. parvum genotype 2. The sheep in which the novel isolate was identified were healthy and showed no symptoms of cryptosporidiosis, and the novel sheep isolate could represent a non-pathogenic strain. Our studies suggest that a previously undetected Cryptosporidium sub-type may exist in sheep populations, reflecting the increasingly recognised diversity within the parasite genus.

A survey of ethnic foods for microbial quality and aflatoxin content.

A range of ethnic foods was examined for their microbiological content in relation to total viable counts (TVC) of aerobic bacteria, counts of presumptive coliforms, yeast and mould counts; presence of Salmonella spp., Listeria monocytogenes, Escherichia coli O157:H7 and Campylobacter spp.; total enumeration of Clostridium perfringens, Staphylococcus aureus and Bacillus spp.; identification of moulds and the presence of total aflatoxins. Samples, which included cereals, nuts, dried fruits, herbs and spices, were obtained from local retail outlets and distributors. It was established that three samples of pistachio nuts contained significant levels of aflatoxins. The concentration of total aflatoxins in these three nut samples ranged from 15 to 259 microg/kg of sample. Only two other samples contained trace amounts of aflatoxins, all other samples analysed were found to be free of any detectable level of aflatoxins. TVCs, coliform counts and yeast and mould counts varied widely depending on the matrix tested. Generally, rice, wheat and peanuts produced low counts whereas other nuts, gram flour and spices produced much higher counts. Cl. perfringens, Staph. aureus, and Bacillus spp. were common in spices, nuts and gram flour, however, Listeria monocytogenes was only detected in four samples and in no sample could Salmonella spp, E. coli O157:H7 or Campylobacter spp. be detected.

Motherhood in the teens and twenties: some surprises.

We report a study of the association of health and social support variables with motherhood in teenagers and older mothers. Both teenage and older mothers reported poorer physical and mental health and fewer and less frequent social contacts than their nulliparous peers. Contrary to expectation, however, older mothers reported less extensive and less adequate social support networks than did teenagers.

Teenage mothers and their peers: a research challenge.

Recent reports have highlighted the adverse health experience of teenage mothers. The question of how these mothers' perceptions of their own health status and social networks differ from those of their nulliparous peers is explored in this pilot study, which highlights some practical problems associated with research in this important field.

PIP: This pilot study was undertaken to identify practical problems in studying the effects of teenage motherhood, and compare the assessments of perceived health status and social networks of teenage mothers with those of their nulliparous peers. A total of 55 teenage mothers with one child were matched with the control group of nulliparous teenagers with no history of pregnancy concerning the date of birth, type of house, and postcode. Different results between the groups were manifested despite the comparable characteristics. Upon initial analysis, Vitality and Mental Health sub-scales of the short form 36 mean scores on mothers were significantly lower than the control. Mean scores on the B subscales were significantly higher in the General Health Questionnaire, showing high levels of insomnia/anxiety. With regard to self-assessed health status, the number of people providing support or the degree of satisfaction felt with the support in both groups did not have any significant differences. Although findings in this study highlights some practical problems related to teenage motherhood, detailed screening interviews of a large number of respondents is required to obtain a closely match in the control group.

A reciprocal allosteric mechanism for efficient transfer of labile intermediates between active sites in CAD, the mammalian pyrimidine-biosynthetic multienzyme polypeptide.

Carbamoyl phosphate is the product of carbamoyl phosphate synthetase (CPS II) activity and the substrate of the aspartate transcarbamoylase (ATCase) activity, each of which is found in CAD, a large 240-kDa multienzyme polypeptide in mammals that catalyses the first three steps in pyrimidine biosynthesis. In our study of the transfer of the labile intermediate between the two active sites, we have used assays that differentiate the synthesis of carbamoyl phosphate from the overall reaction of CPS II and ATCase that produces carbamoyl aspartate. We provided excess exogenous carbamoyl phosphate and monitored its access to the respective active sites through the production of carbamoyl phosphate and carbamoyl aspartate from radiolabelled bicarbonate. Three features indicate interactions between the folded CPS II and ATCase domains causing reciprocal conformational changes. First, even in the presence of approximately 1 mM unlabelled carbamoyl phosphate, when the aspartate concentration is high ATCase uses endogenous carbamoyl phosphate for the synthesis of radiolabelled carbamoyl aspartate. In contrast, the isolated CPS II forward reaction is inhibited by excess unlabelled carbamoyl phosphate. Secondly, the affinity of the ATCase for carbamoyl phosphate and aspartate is modulated when substrates bind to CPS II. Thirdly, the transition-state analogue phosphonacetyl-L-aspartate is a less efficient inhibitor of the ATCase when the substrates for CPS II are present. All these effects operate when CPS II is in the more active P state, which is induced by high concentrations of ATP and magnesium ions and when 5'-phosphoribosyl diphosphate (the allosteric activator) is present with low concentrations of ATP; these are conditions that would be met during active biosynthesis in the cell. We propose a phenomenon of reciprocal allostery that encourages the efficient transfer of the labile intermediate within the multienzyme polypeptide CAD. In this model, binding of aspartate to the active site of ATCase causes a conformational change at the active site of the liganded form of CPS II, which protects it from inhibition by its product, carbamoyl phosphate; reciprocally, the substrates for CPS II affect the active site of ATCase by increasing the affinity for its substrates, endogenous carbamoyl phosphate and aspartate, and thus impede access of exogenous carbamoyl phosphate or the transition-state analogue. Reciprocal allostery justifies the close association of the enzyme activities within the polypeptide and ensures that carbamoyl phosphate is efficiently synthesised and is dedicated to the second step of pyrimidine biosynthesis. These conditions fulfill those required for metabolic channeling in the cell.

The implications of teenage pregnancy and motherhood for primary health care: unresolved issues.

Teenage pregnancy and motherhood have implications for several different aspects of primary health care. First, the provision of health education and contraceptive services is obviously relevant to the prevention of unplanned teenage pregnancy. Secondly, appropriate obstetric care should be provided for teenagers, who are at high risk of developing complications in pregnancy and childbirth. Thirdly, and perhaps even more significantly, there is the implication of care required to deal with longer-term adverse health consequences associated with teenage pregnancy. In each of these areas, certain issues remain unresolved. This paper identifies key questions that remain unanswered, including the possibility of long-term adverse physical and psychological health consequences for teenage mothers and their children. The conclusion is that further research addressing these unresolved issues is necessary in order to inform health professionals and allow the implications for primary care to be assessed.

PIP: The issues of teenage pregnancy and motherhood impact upon several different aspects of primary health care. The provision of health education and contraceptive services is relevant to the prevention of unplanned teenage pregnancy. For teenagers who do become pregnant, appropriate obstetric care must be provided. Teenagers are at high risk of developing complications during pregnant and childbirth. Finally, care must also be delivered to manage the longer-term adverse health consequences associated with teenage pregnancy. Issues remain unresolved in each of these areas of health care delivery. The authors identify the questions which remain unanswered, including the possibility of long-term adverse physical and psychological health consequences for teen mothers and their children. Further research addressing the unresolved issues is needed to inform health professionals and allow the implications for primary care to be assessed.

Asbestos and lung cancer in Glasgow and the west of Scotland.

OBJECTIVE: To quantify the relation between lung cancer and exposure to asbestos in men in west Scotland and to estimate the proportion of lung cancer which may be attributed to exposure to asbestos. DESIGN: An ecological correlation study of the incidence of lung cancer in men and past asbestos exposure. The unit of analysis was the postcode sector. Correction was made for past cigarette smoking, air pollution, and deprivation. SETTING: The region covered by the west of Scotland cancer registry, containing 2.72 million people and including Glasgow and the lower reaches of the River Clyde, where shipbuilding was once a major industry. SUBJECTS: All men diagnosed with lung cancer between 1975 and 1984 whose residence at the time of registration was within the west of Scotland. MAIN OUTCOME MEASURE: The population attributable risk for asbestos related lung cancer. RESULTS: An estimated 5.7% (95% confidence interval 2.3 to 9.1%) of all lung cancers in men registered in the west of Scotland during the period 1975-84 were asbestos related, amounting to 1081 cases. CONCLUSIONS: A considerable proportion of cases of lung cancer in men in Glasgow and the west of Scotland from 1975 to 1984 were asbestos related. Most of these may not have been considered for compensation by the Department of Social Security. Given the very small annual number of recorded cases of asbestosis this condition is probably not a prerequisite for the development of asbestos related lung cancer. A heightened awareness of the increasing incidence of asbestos related neoplasms and their more thorough investigation are recommended.