Neutron spectroscopic studies of the crystal field in HoBa2Cu3Ox (6 <= x <= 7).
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Biomedical subjects
Publications and source records attributed to A Taylor.
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Bovine photoreceptor (rod outer segment) proteins were selectively degraded by an ATP- and ubiquitin-dependent mechanism in rabbit reticulocyte lysate and human retinal pigment epithelial cell supernatant. Proteolysis of 37, 40, 58, 68 and approximately 100 kDa proteins was accompanied by the formation of high mass (> 150 kDa) species (putative ubiquitin-protein conjugates. To identity degraded substrates, the photoreceptor GTP-binding protein, transducin (Gt alpha beta gamma), was purified by GTP elution. Degradation of transducin (> or = 50% loss of each subunit) by retinal pigment epithelial cell supernatant was ubiquitin-dependent (EC50 = 1.2 microM). Formation of high mass transducin species was coincident with degradation. These data identify a selective proteolytic mechanism that may regulate the photoreceptor GTP-binding protein.
Vein graft atherosclerosis is a common and serious complication of coronary artery bypass grafting (CABG). There is mounting evidence that lipoprotein abnormalities play an equally important role in the development of lesions in saphenous vein grafts after CABG as in native coronary vessel disease. The potential benefit of low-dose lipid lowering combination therapy in these patients has not been investigated. In a randomized, double-blind, placebo-controlled study, we compared the efficacy and safety of a low-dose combination of colestipol 10 g and simvastatin 10 mg/day (CS) to colestipol 10 mg and bezafibrate 400 mg/day (CB) for 2 months in 33 patients with serum total cholesterol > 6.5 mmol/l and triglyceride < 4.5 mmol/l who had undergone CABG for severe coronary artery disease. In the CS group, total cholesterol decreased by 29% and low-density lipoprotein (LDL) cholesterol by 42%; similarly, CB reduced total cholesterol by 17%, LDL cholesterol by 23%, triglyceride by 19%, and increased high-density lipoprotein (HDL) cholesterol by 14%. Lipoprotein (a) and hemostatic factors were unaffected by either therapy in this study. Both combination therapies were well tolerated with no significant clinical or biochemical side effects. We conclude that low-dose combinations of colestipol and simvastatin or colestipol and bezafibrate are effective and well tolerated in the management of moderate hyperlipidemia in patients who had undergone CABG.
The metabolism of S12813, (3-(2-[4-phenyl piperazin-1-yl] ethyl)-2-oxo-2,3-dihydro oxazolo [4,5-b] pyridine chlorohydrate), in rat liver slice incubates was examined by high performance liquid chromatography combined with mass spectrometry. Electrospray ionization was used together with tandem mass spectrometric techniques of analysis (MS/MS). Polar phase I and phase II metabolites were identified as C-oxidation products, which were then conjugated to form either sulphate or glucuronide metabolites. On the basis of the identifications made, a metabolic pathway of S12813 in rat liver slices has been proposed.
This report describes the effects of succinylcholine (SCh) on the secondary endings of cat soleus muscle spindles and attempts to explain them in terms of the action of the drug on intrafusal fibres. All but 2 of 41 secondary endings studied in detail showed a significant response to a single intravenous injection of 200 micrograms kg-1 SCh. This consisted of a rise in the resting rate or development of a resting discharge if the spindle had previously been silent and an increase in the response to stretch. The increases in the responses to stretch were weaker than those observed for primary endings of spindles, but were much larger than those of tendon organs, which showed very little effect with this concentration of drug. The response to SCh showed two features consistent with its action being mediated via an intrafusal muscle fibre contraction rather than a direct depolarising action on the afferent nerve ending. In the presence of SCh, secondary endings were able to maintain a discharge during muscle shortening at rates, on average, more than 5 times greater than under control conditions. Secondly, the increase in spindle discharge produced by SCh showed a length dependence similar to that for fusimotor stimulation. Further support for the action of SCh being principally via an intrafusal fibre contraction was provided by the observation that its effects were abolished by the neuromuscular blocker gallamine triethiodide.(ABSTRACT TRUNCATED AT 250 WORDS)
Nine hundred and nineteen injecting drug users (IDUs) were interviewed in Glasgow, Scotland during 1990 and 1991, as part of a wider study of HIV risk behaviour, about their injecting and sexual behaviour outside the city in the previous two years. Forty-five percent of respondents injected outside Glasgow, 6% shared needles and syringes (n/s) and 20% had sexual intercourse. Much activity occurred outside Scotland but mainly within the UK, particularly London. Predictors of n/s sharing outside Glasgow during the previous two years included current injecting with and passing on of used n/s and sexual intercourse with casual partners. Predictors of sexual behaviour outside Glasgow included passing on used n/s, having sexual intercourse with casual partners and, for females, engaging in prostitution. Glasgow IDUs are a highly mobile group and although HIV prevalence remains low within this population, considerable potential for importation/exportation of HIV and other bloodborne and sexually transmitted infections exists. Further work is required to establish why IDUs travel to, and engage in high-risk activities in locations outside their home environment, and detailed data about activities such as frequency of condom usage and n/s cleaning practices need to obtained. While there is a widespread network of services for IDUs in the UK, information provided usually relates to local services and may not fully address the needs of this mobile population. Therefore, we recommend that IDUs be provided with details of facilities such as n/s exchange schemes and drug-treatment establishments in centres to where they most commonly travel.
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Serum cortisol levels were measured in 163 women on the third day after childbirth. Significantly elevated levels of cortisol were found to be associated with the "blues," and significantly lower levels characterized women who exhibited mild hypomania (the "highs"). Low levels of cortisol were independently associated with epidural anesthesia, while elevated levels were related to assisted delivery. There was no significant association with breast or bottle feeding. Changes in serum cortisol were thus found to parallel the mild bidirectional changes in affect that frequently follow childbirth.
This study investigated the relationship between psychological factors and circulating immune cell populations in postpartum women. The study group was 75 women who had vaginal deliveries and were free of psychotropic medication. Four days postpartum each subject completed three mood questionnaires, and a small blood sample was taken. All questionnaire scores were shown to be highly inter-correlated and principal component factor analysis revealed a single factor which we term dysphoria. This factor was significantly associated with lower total circulating lymphocyte counts. The effect was strongest for T cells (largely attributable to a reduction in CD4+ ve T helper cells) and weaker for NK cell counts. No evidence was found of a mediating role for serum cortisol although serum cortisol levels were weakly related to immune status. This study has thus demonstrated that changes in the distribution of the lymphocyte pool are associated with relatively minor differences in postpartum affect.
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The objective of this study was to examine the clinical predictive value for the achievement of pregnancy in vivo of the assessment of human semen quality by computer-assisted semen analysis using the Hamilton-Thorn Motility Analyser (HTM-S), alongside classic World Health Organization (WHO) techniques. A prospective follow-up study of 303 couples attending a regional infertility clinic providing tertiary level services to the population of a single geographical region was undertaken. Couples attending the infertility clinic, in whom the female partner was normal on conventional investigations (history, examination, evidence of ovulation, laparoscopy), were studied. After initial assessment, couples were followed for a median of 15 months and treatment-independent pregnancies observed and related to the results of semen assessment. During the period of follow-up, the treatment-independent pregnancy rate was 52%. Several measures of semen quality, determined both manually and by the HTM-S, were found to be predictive of the achievement of pregnancy and were related to the time taken to conceive. Couples who conceived had higher sperm concentrations and motilities, determined both manually and by the HTM-S, as well as differences in sperm head morphometry and sperm velocity determined by the HTM-S. Using multiple logistic regression, the prognostic accuracy of the HTM-S alone was similar to manual techniques, although data from the computer assisted sperm analysis system were preferred. Using proportional hazards regression, several variables were related to the achievement of pregnancy, particularly morphometry and motility. It was concluded that a strong case can be made for the introduction of automated assessment of human semen in routine service andrology laboratories.
A comparative assessment of the conventional criteria of semen quality (sperm concentration, motility and morphology) was undertaken by standard laboratory techniques and by means of a computer-assisted image analysis system (the Hamilton-Thorn HTM-S 2030) in an open prospective study, in the context of a service andrology laboratory. A total of 1435 semen samples submitted by couples in the course of routine infertility investigations were examined by both methods, and the results compared. It was observed that the method did not provide comparable data on semen quality, either in respect of sperm concentration or graded motility, while the morphometric data generated by the HTM-S did not appear to be related to conventional morphology assessment. The clinical value of such systems in the assessment of the classical determinants of semen quality requires formal assessment in properly conducted large scale prospective studies.
Tc-99m MAG3 scans were obtained in two neonates in whom previous Tc-99m DTPA scans had been interpreted as showing possible obstruction. In both patients, Tc-99m MAG3 provided superior diagnostic images and allowed obstruction to be excluded. The favorable dosimetry of MAG3, coupled with the fact that its clearance is two to three times higher than that of DTPA, makes MAG3 an excellent radiopharmaceutical for pediatric patients, particularly in those patients with impaired renal function and possible obstruction.
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OBJECTIVE: To determine the effects of nephrectomy on the immune response of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Five patients with RCC were monitored before and over a period of up to 3 months after nephrectomy. The aspects measured were the phenotypic expression of markers on circulating lymphocytes, circulating concentrations of cytokines, markers of inflammatory and immune responses, and natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC). The suppressive activity of patients' plasma on NK activity and ability to generate interleukin-2 (IL-2) induced LAK cells in PBMC of normal volunteers was also investigated. RESULTS: The results indicated that high CD4/8 ratios were present pre-nephrectomy with evidence of inflammatory responses and immune activation in some patients, particularly those with metastatic disease. CONCLUSION: The effect of nephrectomy was to decrease the inflammatory response and increase immune activation. Various defects in NK cell activity and LAK cell generation were demonstrated pre-surgery which slowly improved once the primary tumour had been removed and it is suggested that such defects could have contributed to tumour growth and development due to an ineffective immune response.
This study ascertained the prevalence of diabetes and compared the prevalence of cardiovascular risk factors among people with and without diabetes. Data were collected as part of the South Australian Health Omnibus Survey which involved a representative population sample of 6398 adults in metropolitan and country South Australia who were interviewed in their own homes. The self-reported prevalence of diabetes was found to be 3 per cent overall. This varied from approximately 1 per cent in the 15- to 39-year age group to 10.5 per cent in people aged over 80 years. Those with diabetes had a higher prevalence of cardiovascular risk factors than those without diabetes. There is a need for improved vigilance with people who have diabetes and interventions to modify the risk factors associated with cardiovascular disease.
Comparisons were made between the results of testing muscle spindle primary afferents with low-frequency, large-amplitude sine waves of muscle stretch and with repeating ramp-and-hold stretches. Three different situations were explored, namely, activation with succinylcholine (SCh), generation of various fusimotor outflow patterns by brainstem stimulation and fusimotor activation by stimulation of single ventral root gamma-axons. With ramp-and-hold stretches the effects of bag1 fibre contraction were thought to be generally better represented by increases in the dynamic response to stretch (delta DD) than by increases in dynamic index. The equivalent effect on the sine wave response was an increase in the magnitude of the fitted sine (delta Mag). Static effects were best measured by increases in the initial frequency for ramps (delta IF) and by increases in the fitted centre frequency (delta CF) for sines. There was good agreement between sine and ramp testing in the case of SCh effects, but much less consistency during brainstem stimulation. Sine wave testing can be regarded as less efficient than ramp testing in distinguishing between static and dynamic actions because dynamic fusimotor stimulation causes equal rises in CF and Mag, but fourfold larger rises in DD than in IF. Ramp responses with combined dynamic and static fusimotor stimulation showed increases of both IF and DD as expected, but whilst sine wave responses always showed increase in CF, they often showed no increase in Mag. Comparisons of the effects of SCh, central stimulation and fusimotor stimulation showed that it is important to recognize the different effects of chain and bag2 intrafusal fibre activation as components of static fusimotor excitation. Stimulation of driving static axons (chain activation) raised the IF and CF often with 1:1 or 1:2 driving during the shortened phase of ramps and sines. However, the stretch response in both cases was either unchanged or reduced. Stimulation of a non-driving static fusimotor axon (bag2 activation) caused a marked rise in CF for sine waves and a fall in Mag, but a modest increase in ramp stretch sensitivity (DD) with no increase in dynamic index. A way is described for measuring flattening of sine wave responses as a possible way of detecting chain fibre activation. The consequences of these findings are discussed in relation to previous reports of the use of sine wave testing for assessing fusimotor mechanisms.
Vasopressin stimulates transepithelial water flow in the toad urinary bladder. We report here that N-ethyl maleimide (NEM) (0.1 mM) produces a similar increase in osmotic water flow when applied to the mucosal surface of the tissue. NEM-induced water flow is sensitive to inhibitors of hormone-induced water flow, including serosal acidification, or exposure to quinidine or cytoskeleton-disruptive drugs. NEM-induced water flow is additive with that induced by a submaximal, but not a maximal, dose of vasopressin. The response to mucosal NEM is not reversed on removal of the reagent, but established NEM-induced water flow can be inhibited by serosal acidification or quinidine. Like vasopressin, mucosal NEM induces the appearance of fusion profiles and intramembranous particle aggregates (putative water channels) in the apical plasma membrane of the granular cells, and the incidence of particle aggregates correlates with water flow. NEM does not cause an increase in intracellular cAMP. Our data suggest that NEM stimulates transepithelial water flow by irreversibly activating cellular mechanisms normally triggered by vasopressin, hence causing the insertion of water channels.