Relative orientation of quadrupole tensors from two-dimensional multiple-quantum MAS NMR.
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Biomedical subjects
Publications and source records attributed to J McManus.
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The question of whether or not higher-order (five-, seven- and nine-quantum) multiple-quantum magic angle spinning (MQMAS) experiments yield isotropic NMR spectra of half-integer quadrupolar nuclei with higher resolution than the basic three-quantum MAS experiment is examined. The frequency dispersion is shown theoretically to be greatly increased in higher-order MQMAS spectra, but it is argued that whether or not this translates into an increase in resolution depends upon the ratio of the homogeneous to inhomogeneous contributions to the isotropic linewidth. Experimentally, it is demonstrated using three-, five- and seven-quantum 45Sc MAS NMR and three- and five-quantum 27Al MAS NMR of crystalline samples that higher-order MQMAS experiments can yield a real and useful increase in resolution but that, owing to the presence of inhomogeneous broadening in the isotropic spectra, this increase is less than the theoretically predicted value. A number of practical issues relating to resolution in MQMAS NMR are also pointed out.
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism, and has been hypothesized to exert either pro- or anti-atherogenic effects, depending on its localization. Decreased plasma LPL activity is associated with the high triglyceride (TG);-low HDL phenotype that is often observed in patients with premature vascular disease. In contrast, in the vessel wall, decreased LPL may be associated with less lipoprotein retention due to many potential mechanisms and, therefore, decreased foam cell formation. To directly assess this hypothesis, we have distinguished between the effects of variations in plasma and/or vessel wall LPL on atherosclerosis susceptibility in apoE-deficient mice. Reduced LPL in both plasma and vessel wall (LPL(+/-)E(-/-)) was associated with increased TG and increased total cholesterol (TC) compared with LPL(+/+)E(-/-) sibs. However despite their dyslipidemia, LPL(+/-)E(-/-) mice had significantly reduced lesion areas compared to the LPL(+/+)E(-/-) mice. Thus, decreased vessel wall LPL was associated with decreased lesion formation even in the presence of reduced plasma LPL activity. In contrast, transgenic mice with increased plasma LPL but with no increase in LPL expression in macrophages, and thus the vessel wall, had decreased TG and TC and significantly decreased lesion areas compared with LPL(+/+)E(-/-) mice. This demonstrates that increased plasma LPL activity alone, in the absence of an increase in vessel wall LPL, is associated with reduced susceptibility to atherosclerosis. Taken together, these results provide in vivo evidence that the contribution of LPL to atherogenesis is significantly influenced by the balance between vessel wall protein (pro-atherogenic) and plasma activity (anti-atherogenic).
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OBJECTIVE: To document the influence of hospital prescribers on prescribing in general practice. DESIGN AND PARTICIPANTS: Five percent of members of the Irish College of General Practitioners (n = 92) prospectively recorded 40 consecutive prescriptions. INTERVENTIONS: The name, dose and amount of medicine prescribed as well as the indication for therapy, details of their practice, distribution of private/GMS patients, and the number of years since qualification were recorded. The cost of individual prescriptions was calculated based on the ingredient cost and the number of days of treatment. This was subsequently correlated with the origin of the prescription. Each prescription was classified as either new or repeat. MAIN OUTCOME MEASURES AND RESULTS: Of 3286 prescriptions, 69% were for the state-supported General Medical Services (GMS) patients and 31% for private patients. Repeat prescriptions constituted 51%; 49% were new prescriptions. While hospital doctors initiated only 8% of private prescriptions, they initiated 38% of GMS prescriptions, particularly repeat prescriptions and those for cardiovascular, hormonal and centrally-acting agents. Prescriptions for anti-infectives, oral contraceptives, dermatological preparations and musculoskeletal drugs were mostly initiated in general practice. The median cost for hospital-initiated GMS prescriptions (5.93 Pounds) was greater than the cost of general practitioner (GP)-initiated prescriptions (3.49 Pounds; p < 0.01). Prescriptions from GPs who were qualified for less than 10 years and those with a mixed urban and rural practice were less costly (p < 0.05) than those issued by doctors qualified for over 10 years or working predominantly in an urban or rural area. These findings may also reflect differences in patient population, morbidity and demography. CONCLUSIONS: Our study indicates that hospital-initiated prescriptions are responsible for a significant proportion, both in volume and cost of GP prescribing.
The development of a school-based comprehensive and cost-efficient oral health care program requires careful planning centered on the needs expressed by the community. Gaining the support and the cooperation of school officials and parents creates an environment that has a significantly greater opportunity for success. Location, appropriate design of the facility and support from a local charitable organization further insure excellent access and expeditious care.
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Three studies examined the hypothesis that a child's prosocial self-schema predicts prosocial behavior. In Study 1, only self-aware boys showed a self-schema-behavior relation. Study 2 altered both salience of donating opportunity and relationship of recipient to donor. The hypothesized Self-Awareness x Self-Schema interaction was significant, and there were no gender differences. Study 3 systematically manipulated the salience of the donating opportunity. All participants were self-aware. For boys in high and low salience conditions, prosocial self-schema predicted donating behavior. For girls, prosocial self-schema predicted behavior only in the high salience condition. The findings demonstrate that self-schemas can regulate behavior when participants are self-aware. Girls, however, may require higher salience of the donating opportunity for the self-schema to affect their behavior.
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There is still disagreement concerning the optimal procedure for the diagnosis of milder degrees of hyperglycaemia in pregnancy. We have compared the results of a 75 g oral glucose tolerance test (OGTT) and a standardised breakfast test performed one week apart in 102 non-diabetic women with a singleton pregnancy. There was poor correlation between the two tests (r = 0.15) at two hours, and neither test was predictive of adverse maternal or fetal outcome. One hundred and four patients with impaired glucose tolerance, diagnosed at 30 weeks' gestation by 75 g OGTT, subsequently had a breakfast and lunch meal profile. There was no significant correlation between the two-hour OGTT value and either the two hour post-breakfast value (r = 0.35) or the maximum profile value (r = 0.33). Using the WHO diagnostic criterion of > 8 mmol/l for the OGTT and a maximum glucose concentration > 6.8 mmol/l for the meal profile, there was no relationship between an abnormal result in either test and pregnancy outcome. In our obstetric environment, the 75 g OGTT, a standardised breakfast test, and a structured meal profile, all failed to provide a useful indication of pregnancy outcome in mothers not already known to have diabetes.
Current models for RNA synthesis involve an RNA polymerase that tracks along a static template. However, research on chromatin loops suggests that the template slides past a polymerase immobilized in a large transcription factory. The evidence for immobilized polymerases is reviewed, and a model for transcription by such fixed enzymes is presented. According to the model, gene activation would involve reducing gene-factory distance and increasing the affinity of a promoter for a factory. Locus controlling regions and enhancers would attach to a factory and increase the chances that a promoter could bind to a polymerase; after transcriptional termination, the gene would detach from the factory. As some RNA processing occurs cotranscriptionally, processing sites are also likely to be associated with the factory.
OBJECTIVE: To investigate the effect of different oestrogens and progestogens, at various concentrations, on the oxidation of low density lipoproteins (LDL) in vitro. METHODS: Oestradiol, oestrone, oestriol and equilin, as well as medroxyprogesterone acetate, norgestrel and norethisterone, were added to isolated male LDL, before it was oxidised in the presence of copper ions at 37 degrees C. The oxidation process was monitored spectrophotometrically by the production of conjugated dienes. The lag time to oxidation and the maximum rate of propagation of the reaction were used as measures of the resistance and susceptibility of the LDL to oxidation respectively. RESULTS: The lag time was increased from 43.7 +/- 1.5 min (mean +/- SEM) for LDL without any added hormone, to 81.2 +/- 1.0 min by 1 microM oestradiol (P < 0.01), 77.9 +/- 4.6 min by 1 microM oestrone (P < 0.01), 67.6 +/- 6.2 min by 1 microM equilin (P < 0.01), and 51.8 +/- 2.8 min by 1 microM oestriol (P < 0.05). The maximum rate of propagation of the reaction was decreased from 0.23 +/- 0.01 nmol conjugated dienes/mg LDL-protein/min (mean +/- SEM) (control LDL) to 0.14 +/- 0.006 nmol/mg/min by oestradiol (P < 0.01), 0.15 +/- 0.009nmol/mg/min by oestrone (P < 0.01), 0.17 +/- 0.012 nmol/mg/min by equilin (P < 0.01) and 0.19 +/- 0.014 nmol/mg/min (P < 0.05) by oestriol. The progestogens alone had no antioxidant effect, nor did their addition to the oestrogens influence their antioxidant activity. CONCLUSIONS: These results demonstrate that all oestrogens investigated have an inhibitory effect on LDL oxidation in vitro. The magnitude of this effect varied, being of the order oestradiol > oestrone > equilin > oestriol.
Recent experiments suggest that active polymerases are concentrated in large structures, 'factories', within eukaryotic nuclei. Data concerning the structure of these factories is reviewed.
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Chromosomes from the fission yeast Schizosaccharomyces pombe have been introduced into mouse cells by protoplast fusion. In most cell lines the yeast DNA integrates into a single site within a mouse chromosome and results in striking chromosome morphology at metaphase. Both light and electron microscopy show that the yeast chromosome region is narrower than the flanking mouse DNA. Regions of the yeast insert stain less intensely with propidium iodide than surrounding DNA and bear a morphological resemblance to fragile sites. We investigate the composition of the yeast transgenomes and the modification and chromatin structure of this yeast DNA in mouse cells. We suggest that the underlying basis for the structure we see lies above the level of DNA modification and nucleosome assembly, and may reflect the attachment of the yeast DNA to the rodent cell nucleoskeleton. The yeast integrant replicates late in S phase at a time when G bands of the mouse chromosomes are being replicated, and participates in sister chromatid exchanges at a high frequency. We discuss the implications of these studies to the understanding of how chromatin folding relates to metaphase chromosome morphology and how large stretches of foreign DNA behave when introduced into mammalian cells.
Total knee arthroplasty (TKA) without resurfacing of the patella by a single surgeon was reviewed retrospectively in 125 patients: 66 patients (79 knees) were included in the final study group, 32 patients were deceased, 13 were without current address and not able to be contacted, and 14 patients were unable to complete a questionnaire because of severe illness or language barrier. All patients had a diagnosis of osteoarthrosis. The decision to leave the patella unresurfaced was based on the presence of satisfactory patellar articular cartilage, absence of eburnated bone, congruent patellofemoral tracking, normal anatomic patellar shape, and no evidence of crystalline disease or an inflammatory synovitis. A lateral retinacular release was performed in 13 knees (16.5%) to facilitate congruent patellar tracking. The follow-up period averaged 7.5 years (range, 2.4-15.5 years). There were no component revisions and no reoperations. The mean Knee Society score improved from 23.2 to 89.9 postoperatively and the function score improved from 58.4 to 92.0 postoperatively. Mild anterior knee pain was reported in 19%. Satisfaction with the surgical result was expressed in 89.5% of patients; 4% were somewhat satisfied; 2.6% were somewhat dissatisfied; and 4% were neutral. Of the patients who had mixed bilateral TKA (one TKA with unresurfaced patella, the other resurfaced), 46% rated both as equal; 46% preferred the TKA with the resurfaced patella; and 7.7% preferred the unresurfaced patella. In patients meeting the selection criteria outlined above, TKA without resurfacing of the patella provided satisfactory long-term results and a high degree of patient satisfaction with an absence of mechanical complications and no reoperations at the average 7.5-year follow-up evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)