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M Walker

Publications and source records attributed to M Walker.

At least 109 records · Page 6Linked to original sources
PubMed2001

Simocyclinones: diversity of metabolites is dependent on fermentation conditions.

Simocyclinones, a novel group of angucyclinone antibiotics, are produced by Streptomyces antibioticus Tü 6040. The compounds show antibacterial and antitumor properties. In submerged cultivation, the production of simocyclinones is strongly dependent on the carbon and nitrogen sources used in a chemically defined medium. Productivity of distinct components and diversity of simocyclinone compounds are influenced by the medium composition. Four series of simocyclinone compounds were detected by high-performance liquid chromatography (HPLC) diode array detector (DAD) and HPLC electrospray ionization (ESI) mass spectrometry (MS) analysis, isolated and the structures determined by nuclear magnetic resonance (NMR) techniques. Under optimized conditions, simocyclinone D8 was produced in an amount of 300 mg l(-1) and simocyclinone C4 in a concentration up to 50 mg l(-1).

Chromatography, High Pressure Liquid↗
PubMed2001

The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems.

Cell death in gliomas may occur either by apoptosis, or, in the case of high grade tumours, by necrosis, but questions remain as to the pathogenesis and relationship between these processes. The development of cell death was investigated in multicellular glioma spheroid cultures. Spheroids model the development of cell death due to diffusion gradients in a three-dimensional system without confounding influences of immune response, pressure gradients, etc. Spheroid cultures were established from four malignant glioma cell lines: U87, U373, MOG-G-CCM and A172; harvested from culture at weekly intervals and stained with Haematoxylin and Eosin (H&E), TdT-mediated dUTP-X nick end labelling (TUNEL) and by immunohistochemistry for vimentin, Glial Fibrillary Acidic Protein (GFAP) and Ki67. Annexin V flow cytometry and counts of apoptotic cells on H & E stained sections were performed to assess levels of apoptosis. Modes of cell death were also characterized by electron microscopy. Spatially separate zones of proliferation, differentiation and central cell death developed with increasing spheroid diameter. Central cell death developed at a predictable radius (300-400 microm) for each cell line. Ultrastructural examination showed this to be necrotic in type. Apoptosis was most reliably assayed by morphological counts using H & E. Basal levels of apoptosis were low (< 0.5%), but increased with increasing spheroid diameter (> 2% in U87). In particular, levels of apoptosis rose following development of central necrosis and apoptoses were most abundant in the peri-necrotic zone. There were quantitative differences in the levels of apoptosis and necrosis between glioma cell lines. The predictable onset of necrosis in the spheroids will allow us to investigate the pathogenesis of necrosis and events in prenecrotic cells. There is a relationship between the development of necrosis and apoptosis in this model and these processes can be separately assayed. Further in vitro and genetic studies will enable us to study these events and interactions in greater detail than is possible using other cell culture and in vivo systems.

Annexin A5↗
PubMed2001

Lichen myxoedematosus with associated cardiac abnormalities.

We describe a 42-year-old woman who developed lichen myxoedematosus. Twenty years after the onset of the disease she became breathless and hypertensive, and an echocardiogram showed a mass on the mitral valve, which was thought to be a mucin deposit. Her hypertension was resistant to treatment with combination antihypertensives. To our knowledge, this is the first report to link lichen myxoedematosus with a valvular mucinous mass. This case also demonstrates the slow clinical progression of the disease over 20 years.

Adult↗
PubMed2001

Elevated plasma non-esterified fatty acid levels and insulin secretion in non-diabetic relatives of type 2 diabetic patients.

OBJECTIVE: High non-esterified fatty acid (NEFA) levels impair glucose-stimulated insulin secretion from islets derived from non-diabetic Zucker rats that are genetically predisposed to diabetes. We therefore examined the effect of elevated plasma NEFA levels on insulin secretion in non-diabetic first-degree relatives of type 2 diabetic patients who are at increased risk of developing diabetes. SUBJECTS AND STUDY DESIGN: Normal glucose tolerant relatives (n = 9) and control subjects with no family history of diabetes were pair-matched for age, sex, body mass index (BMI), insulin sensitivity and early insulin response during an oral glucose tolerance test (OGTT). Plasma NEFA levels were raised from 0 to 340 minutes by the infusion of 20% Intralipid and heparin. From 180 minutes, insulin secretion rates (IRSs) were assessed by stepped low-dose glucose infusion. RESULTS: The mean (geometric mean +/- 95% CI) NEFA levels were comparable between relatives and control subjects (2.7 [2.1-3.6] and 2.1 [1.7-2.7] mmol/l, paired analysis, NS). Similarly, plasma glucose levels achieved at each glucose infusion step were comparable between the groups. However, there were no significant differences between the groups for ISR throughout the study. CONCLUSIONS: Sustained elevation of plasma non-esterified fatty acid levels does not decrease insulin secretion in non-diabetic relatives of type 2 diabetic patients, and is therefore unlikely to be important in the development of the impaired pancreatic beta-cell function in type 2 diabetes mellitus.

Adult↗
PubMed2001

Manipulating the in vivo mRNA expression profile of FSH beta to resemble that of LH beta does not promote a concomitant increase in intracellular storage of follicle-stimulating hormone.

The beta-subunits of luteinizing hormone (LH beta) and follicle-stimulating hormone (FSH beta) are differentially expressed, and this may contribute to the unique expression and storage patterns of LH and FSH. Therefore, to determine if the in vivo expression profile of FSH beta could be altered to that of LH beta, a truncated ovine FSH beta (oFSH beta) gene, which would encode a mRNA lacking the putative destabilizing 3' untranslated region, was fused downstream of the ovine LH beta (oLH beta) promoter and expressed in transgenic mice. In two independent lines, line 16 and 17, we measured oFSH beta, mouse LH beta (mLHbeta) and mouse FSH beta (mFSH beta) mRNA levels: (i) after castration in males; (ii) after administering inhibin to ovariectomized mice; and (iii) during the oestrous cycle. In each experiment, the expression profile of oFSH beta mRNA mimicked mLH beta and not mFSH beta mRNA. In addition, after actinomycin D treatment of pituitary cultures, while mFSH beta mRNA did decay, there was no measurable decay of the oFSH beta mRNA transcript. These differences increased total FSH beta steady-state mRNA expression levels in male transgenics. However, there was no detectable increase in pituitary FSH by either radioimmunoassay or western blotting analysis of pituitary extracts. Subsequent analysis revealed that pituitary FSH beta in line 16 was heavily glycosylated; in contrast, pituitary FSH beta in line 17 was largely unmodified. These differences in post-translational modification of the beta-subunit, and the lack of intracellular storage, contributed to increased plasma FSH levels and ovulation rate in line 16, but not line 17. In conclusion, the expression profile of oFSH beta mRNA was manipulated to mimic mLH beta mRNA and this increased FSH beta mRNA expression levels, but did not increase storage of FSH. This suggests that, regardless of the levels of synthesis, post-translational sorting preferentially promotes FSH secretion from the pituitary.

Animals↗
PubMed2001

Non-diabetic relatives of Type 2 diabetic families: dietary intake contributes to the increased risk of diabetes.

AIMS: Non-diabetic first degree relatives of Type 2 diabetic patients are at increased risk of developing diabetes and cardiovascular disease. This is assumed to reflect a shared genetic predisposition. The aim of this study was to test the hypothesis that lifestyle factors, specifically dietary factors, are also important to the increased risk in non-diabetic relatives. METHODS: Dietary intake was assessed using a validated food frequency questionnaire in 149 non-diabetic first degree relatives (age 20-65 years) from families of North European extraction with two or more living Type 2 diabetic family members, and 143 age- and sex-matched control subjects from the background population with no family history of diabetes. RESULTS: Relatives reported higher absolute intakes of total fat (mean (95% confidence intervals) 83 (76-91) vs. 71 (66-76) g/day, P = 0.01), saturated fat (SFA; 39 (36-43) vs. 33 (30-36) g/day, P < 0.01) and cholesterol (391 (354-427) vs. 318 (287-349) mg/day, P < 0.01), and a lower intake of non-starch polysaccharide (P < 0.05). Considered as percentage of total daily energy intake, relatives had higher intakes of total fat (P < 0.01) and SFA (P < 0.02), and a lower intake of carbohydrate (P < 0.02). These differences remained after exclusion of suspected under- and over-reporters of dietary intake. CONCLUSIONS: Non-diabetic relatives of Type 2 diabetic patients were found to consume diets that will promote rather than prevent the development of diabetes and cardiovascular disease. This suggests that the increased risk to non-diabetic relatives is therefore not entirely genetic, and there is scope for decreasing the risk through lifestyle modification.

Adult↗
PubMed2001

Ameloblastoma with mucous cell differentiation.

The finding of pale or clear cells in ameloblastomas is an exceptionally rare--but not unreported--phenomenon. The diagnostic implications of the presence of such cells in ameloblastomas are several and relate mainly to the question of histopathologic differential diagnosis. Although mucous cells in ameloblastomas are an accepted phenomenon, their occurrence has been reported only infrequently. This report describes a case of ameloblastoma exhibiting histopathologic evidence of focal mucous cell differentiation. Issues relating to the differential diagnosis of this lesion are discussed.

Adult↗
PubMed2001

The effect of variable heart rate decelerations on intraventricular hemorrhage and other perinatal outcomes in preterm infants.

OBJECTIVE: We investigated the hypothesis that repetitive variable heart rate decelerations in labor are associated with an increased incidence of neonatal complications in premature infants. METHODS: This was a retrospective case-control study. Singleton fetuses weighing between 750 and 2500 g at 25-35 weeks' gestation were considered for the study. Fetuses delivered by Cesarean section prior to labor were excluded. Heart rate traces were retrieved from an electronic archive and were assessed for the presence of variable decelerations. Cases had at least three variable decelerations in the hour prior to delivery and were matched 1:1 with controls for gestation, sex and birth weight. RESULTS: A review of 6500 deliveries yielded 41 matched pairs. The groups were compared for the following outcomes. Measures of acute morbidity were cord pH at delivery, 5-min Apgar score and resuscitation; measures of chronic morbidity were intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis and death. There was no difference in measures of acute morbidity between the groups. The incidence of chronic morbid outcome measures in the cases was six (15%) vs. one (2.5%) in controls (p = 0.01). CONCLUSIONS: This study suggests that variable decelerations in preterm infants are associated with chronic morbidity, particularly intraventricular hemorrhage through a mechanism independent of fetal acidemia. Further study is required to determine whether these infants would benefit from early Cesarean section.

Acute Disease↗
PubMed2001

Weight change, body weight and mortality: the impact of smoking and ill health.

OBJECTIVES: This paper examines the influence of cigarette smoking and ill health on the relationship between weight change, body weight and subsequent mortality to determine whether weight loss and leanness in middle to older age is deleterious to health. METHODS: Men aged 40-59 years at screening drawn from one general practice in each of 24 British towns, who completed a questionnaire 5 years after screening (Q5) and provided full information on changes in weight and smoking status (n = 7065) were then followed up for an average of 13.8 years. RESULTS: In all men a shallow U-shaped relationship was seen between body mass index (BMI) at Q5 and all-cause mortality rates. Weight loss and substantial weight gain (> or =10%) were associated with increased mortality rates compared to the stable weight group. The increased risk associated with weight loss was seen in long- term non-smokers (n = 4101) and recent ex-smokers (n = 722) but not in current smokers (n = 2242) after adjustment for a wide range of potential confounders. However, the increased risk was markedly attenuated after exclusion of those with ill health (relative risk [RR] = 1.16, 95% CI : 0.84-1.59 and RR = 0.79, 95% CI : 0.29-2.20 for long-term non-smokers and recent ex-smokers, respectively). Moderate weight gain (4-10%) was associated with lower risk of mortality than observed in those with stable weight but only in recent ex-smokers and in current smokers, not in long-term non-smokers. A positive association was seen between BMI at Q5 and all-cause mortality in non-smokers and this was strengthened by exclusion of men with weight loss. CONCLUSION: The increased risk of mortality associated with weight loss or low body weight in middle-aged and older men appears to be a direct consequence of ill health leading to weight loss and leanness. In healthy non-smoking men weight loss and leanness are not associated with increased mortality and moderate weight gain (4-10%) was neither deleterious nor beneficial.

Adult↗
PubMed2001

Percutaneous, intramuscular neuromuscular electrical stimulation for the treatment of shoulder subluxation and pain in chronic hemiplegia: a case report.

This case report describes the first survivor with chronic stroke who was treated with percutaneous, intramuscular neuromuscular electrical stimulation (NMES) for shoulder subluxation and pain. The patient developed shoulder subluxation and pain within 2 mo of his stroke. After discharge from acute inpatient rehabilitation, he developed shoulder and hand pain, which was treated with subacromial bursa steroid injection and ibuprofen with eventual resolution. The patient remained clinically stable until approximately 15 mo after his stroke-when he developed severe shoulder pain associated with shoulder abduction, external rotation, and downward traction. The patient could not tolerate transcutaneous NMES because of the pain of stimulation. At approximately 17 mo post-stroke, the patient's posterior deltoid, middle deltoid, and supraspinatus muscles were percutaneously implanted with intramuscular electrodes. After 6 wk of percutaneous, intramuscular NMES treatment, marked improvements in shoulder subluxation and pain, and modest improvements in activities of daily living and motor function were noted. One year after the onset of treatment, the patient remained pain free, but subluxation had recurred. However, the patient was able to volitionally reduce the subluxation by abducting his shoulder. The patient remained pain free for up to 40 mo after the initiation of percutaneous, intramuscular NMES treatment. This case report demonstrates the feasibility of using percutaneous, intramuscular NMES for treating shoulder subluxation and pain in hemiplegia.

Electric Stimulation Therapy↗
PubMed2001

Intramuscular electromyographically controlled neuromuscular electrical stimulation for ankle dorsiflexion recovery in chronic hemiplegia.

We report three cases of survivors of chronic stroke treated with active repetitive movement training of the paretic ankle dorsiflexors mediated by intramuscular electromyographically controlled neuromuscular electrical stimulation (NMES). These case reports demonstrate the feasibility of using intramuscular electromyographically controlled NMES for facilitating ankle dorsiflexion recovery among survivors chronic stroke with moderate hemiplegia. Relevant issues for clinical implementation and future investigations are reviewed.

Ankle↗
PubMed2001

Intramuscular electromyographically controlled neuromuscular electrical stimulation for upper limb recovery in chronic hemiplegia.

We report three cases of survivors of chronic stroke who were treated with active repetitive movement training of the paretic finger extensors mediated by intramuscular electromyographically controlled neuromuscular electrical stimulation for the purpose of motor relearning. These case reports demonstrate the feasibility of using intramuscular electromyographically controlled neuromuscular electrical stimulation for facilitating the upper limb motor recovery of chronic stroke survivors with mild to moderate hemiplegia.

Adult↗
PubMed2001

No nameless faces.

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Attitude of Health Personnel↗
PubMed2001

Effects of combined water potential and temperature stresses on Cryptosporidium parvum oocysts.

Hosts infected with the parasite Cryptosporidium parvum may excrete oocysts on soils in watersheds that supply public drinking water. Environmental stresses decrease the numbers of oocysts after deposition on soils. However, the rates and effects of combined stresses have not been well characterized, especially for the purposes of estimating decrease in numbers. We subjected oocysts to combined stresses of water potential (-4, -12, and -33 bars), above-freezing temperatures (4 and 30 degrees C), and a subfreezing temperature (-14 degrees C) for 1, 14, and 29 days and one to six freeze-thaw cycles (-14 to 10 degrees C) to estimate coefficients to characterize population degradation using multiplicative error and exponential decay models. The experiments were carried out in NaCl solutions with water potentials of -4, -12, and -33 bars, in combination with temperature stresses at levels that could be expected in natural soils. Increased water potential increased the rate of population degradation for all temperature conditions investigated. Enhanced degradation leads to estimated rates of population degradation that are greater than those that have been reported and used in previous studies conducted to assess risk of water supply contamination from sources of C. parvum.

Animals↗
PubMed2001

Post-immunisation gastritis and Helicobacter infection in the mouse: a long term study.

BACKGROUND AND AIMS: Helicobacter pylori is a major cause of peptic ulcers and gastric cancer. Vaccine development is progressing but there is concern that immunisation may exacerbate Helicobacter induced gastritis: prophylactic immunisation followed by challenge with H felis or H pylori can induce a more severe gastritis in mice than seen with infection alone. The aim of this study was to investigate the relationship between immunity to Helicobacter infection and post-immunisation gastritis. METHODS: (1) C57BL/6 mice were prophylactically immunised before challenge with either H felis or H pylori. Histopathology and colonisation were assessed one month post-challenge. (2) C57BL/6 mice were prophylactically immunised against H felis infection and gastritis assessed up to 18 months post-challenge. RESULTS: Prophylactic immunisation induced a reduction in bacterial colonisation following H felis challenge which was associated with increased severity of active gastritis with neutrophil infiltration and atrophy. However, immunised mice challenged with H pylori SS1 had little evidence of pathology. Long term follow up showed that post-immunisation gastritis was evident at three months. However, from six months onwards, although immunised/challenged mice still developed gastritis, there was no significant difference between inflammation in these mice and infected controls. Post-immunisation gastritis was not associated with the serum antibody response. Immunisation prevented the formation of secondary lymphoid aggregates in the gastric tissue. CONCLUSION: The H felis mouse model of post-immunisation gastritis is the most extreme example of this type of pathology. We have shown in this model that post-immunisation gastritis is a transient event which does not produce long term exacerbation of pathology.

Analysis of Variance↗
PubMed2001

Geographic variation in incidence of coronary heart disease in Britain: the contribution of established risk factors.

OBJECTIVE: To determine the extent to which geographic variation in the incidence of major coronary heart disease (CHD) in Great Britain may be explained by established risk factors. DESIGN: Prospective study. SETTING: 24 British towns with widely differing CHD mortality. SUBJECTS: 7735 men followed up from screening in 1978-80 for 15 years. MAIN OUTCOME MEASURES: Percentage of variance between the towns in major CHD incidence that can be explained by individual characteristics of men in the towns. RESULTS: Age standardised incidence rates over a 15 year period varied from 0.52% per annum in Maidstone to 1.07% per annum in Dewsbury and tended to follow the known pattern of higher rates in Scottish and northern English towns and lower rates in southern English towns ("north-south gradient"). Higher town incidence rates were related to prevalence of current cigarette smoking, low physical activity, and low alcohol consumption, and to mean body mass index, mean systolic blood pressure, low mean height, and prevalence of manual social class, but not to mean serum total cholesterol. The 95% range for true age adjusted CHD incidence (over 15 years) was estimated as 0.58-1.03% per annum among British towns. After adjustment for baseline smoking status, physical activity, body mass index, alcohol consumption, systolic blood pressure, serum total cholesterol, occupational social class, and height, this variation was reduced by 50%. A model based on these eight variables accounted for the major part of the north-south gradient. CONCLUSIONS: Much of the variation in CHD incidence among British towns was accounted for by established risk variables. The remaining unexplained variation may be related to measurement error in the established risk variables, to environmental factors such as climate, or to the combined effect of a wide range of minor risk factors.

Adult↗