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Biomedical subjects

J E Edwards

Publications and source records attributed to J E Edwards.

At least 55 records · Page 3Linked to original sources
PubMed2000

Candida albicans RIM101 pH response pathway is required for host-pathogen interactions.

The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. The RIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that the RIM101 pathway is necessary in vivo for pathogenesis. First, we show that rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, the rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8(-) mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8(-)/rim8(-) mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.

Animals↗
PubMed2000

Reduced virulence of HWP1-deficient mutants of Candida albicans and their interactions with host cells.

The Candida albicans gene HWP1 encodes a surface protein that is required for normal hyphal development in vitro. We used mutants lacking one or both alleles of HWP1 to investigate the role of this gene in virulence. Mice infected intravenously with the homozygous hwp1 null mutant, CAL3, survived a median of >14 days, whereas mice infected with a control strain containing two functional alleles of HWP1 survived only 3.5 days. After 1 day of infection, all strains produced similar levels of infection in the kidneys, spleen, and blood. However, after 2 and 3 days, there was a significant decrease in the number of organisms in the kidneys of the mice infected with CAL3. This finding suggests that the hwp1 homozygous null mutant is normal in its ability to initiate infection but deficient in its capacity to maintain infection. CAL3 also germinated minimally in the kidneys. The ability of the heterozygous null mutant to germinate and cause mortality in mice was intermediate to CAL3, suggesting a gene dosage effect. To investigate potential mechanisms for the diminished virulence of CAL3, we examined its interactions with endothelial cells and neutrophils in vitro. CAL3 caused less endothelial cell injury than the heterozygous hwp1 mutant. We conclude that the HWP1 gene product is important for both in vivo hyphal development and pathogenicity of C. albicans. Also, the ability to form filaments may be critical for candidal virulence by enabling the fungus to induce cellular injury and maintain a deep-seated infection.

Agar↗
PubMed2000

Women's knowledge of, and attitudes to, contraceptive effectiveness and adverse health effects.

Our objectives were to determine women's knowledge of the effectiveness of different contraceptive methods and the risks of thrombosis with use of hormonal contraceptives, and their attitudes regarding the acceptability of bleeding irregularities and weight change. An additional aim was to determine what information women want to be given about contraceptives. In order to satisfy the study objectives, a series of semi-structured focus groups was conducted with women of differing life-stage and background from Oxford. Quantitative data were collected using a structured questionnaire. Qualitative data were collected through discussion with group members. Forty-five women attended four focus groups. Women were segregated into the following groups: professional working mothers; non-professional mothers; young, unmarried professional women; and undergraduate students. Women tended to overestimate the risks and underestimate the effectiveness of hormonal contraceptives. They were resistant to interference with their bleeding patterns and weight.

Adolescent↗
PubMed2000

Intrasession and intersession reliability of the soleus H-reflex in supine and standing positions.

The Hoffmann reflex (H-reflex) is a measure of motoneuron pool excitability, which is valuable in determining muscle inhibition caused by joint damage (arthrogenic muscle inhibition). In order to detect changes in H-reflex due to injury, the reliability of such a measurement must be established. The purpose of this study was to establish the intrasession and intersession reliability of soleus H-reflex in a supine and standing position. Thirteen healthy volunteers (age 10 +/- 2.63 yr, height 171.35 +/- 10.19 cm, mass 69.62 +/- 13.03 Kg) with no lower extremity orthopedic or neurological disorders within the past year participated in this study. To determine the intrasession and intersession reliability of this measure in a supine resting position and a one-leg standing position, EMG data were collected from the soleus while the tibial nerve was stimulated in the popliteal space. A high voltage (120-200 V), short duration (1.0 msec) stimulus was automatically triggered, eliciting a reflex twitch detected by surface EMG. Several of these measurements were performed with 20 second rest intervals to find the maximum H-reflex. The maximum H-reflex was located by adjusting the intensity of the stimulus. Once a maximum H-reflex was found, 12 measurements were taken in that position with 20 second rest intervals. These steps were repeated for each position (supine and standing) at the same time for 5 consecutive days. Intrasession reliability was computed using 12 measurement trials (12), 12 measurement trials dropping the high and low score (12x), the first 7 measurement trials dropping the high and low score (7x), and the first 5 measurement trials (5). Intrasession and intersession reliability over five consecutive days was estimated using intraclass correlation coefficients (ICC (3, 1)). The supine intrasession reliability measurements were as follows: 0.932 (12), 0.932 (12x), 0.935 (7x), and 0.932 (5). The standing intrasession reliability was 0.853 (12), 0.852 (12x), 0.865 (7x), and 0.862 (5). The intersession reliability was 0.938 in the supine position and 0.803 in the standing position. These results indicate that the H-reflex measured using our protocol in a supine and standing position is a reliable assessment within sessions and between sessions. Five measurements are sufficient to observe reliable measurements within a single session. Most importantly, this data shows that the H-reflex is a reliable assessment that may be used to measure small changes in motoneuron pool excitability over time.

Adult↗
PubMed2000

Pathogenesis I: interactions of host cells and fungi.

The interactions of host cells and fungi during infection represent a complex interplay. Although T helper 1 (Th1)-mediated immunity is primarily responsible for acquired resistance to Paracoccidioides brasiliensis, studies have demonstrated that polymorphonuclear neutrophils play a critical role in providing an early resistance to this organism. One study has shown that the invasiveness of Candida albicans requires adherence, particularly to endothelial cells, which in turn are stimulated to express various cell-markers and pro-inflammatory cytokines as part of a proactive resistance to invasion. Somewhat in contrast to infection with C. albicans, it has been shown that the capsular glucuronoxylomannan of Cryptococcus neoformans causes the shedding of host-cell adherence molecules (L-selectins) needed for the migration of host-inflammatory cells to sites of infection and likely explains, in part, the reduced host inflammatory response to this organism. Resistance to aspergillosis is often associated with the immune status of the host. In one set of studies, it has been demonstrated that lymphocytes have little direct effect on the organism, but that antigen-presenting dendritic cells stimulate the production of Th1 cytokines, suggesting a positive role for the dendritic cell in host-response. Similarly, another study has shown that among the regulatory cytokine networks that Th2-associated cytokines (e.g., interleukin-10) likely play a detrimental role in the resistance of the host to Aspergillus fumigatus.

Animals↗
PubMed1999

Relationship between food deprivation before transport and aggression in pigs held in lairage before slaughter.

Pigs from three farms were deprived of food for up to one hour, 12 hours or 18 hours before being sent for slaughter. In lairage, the animals' behaviour was monitored, and at slaughter a blood sample was collected and analysed for cortisol, lactate and creatine phosphokinase, potential indicators of stress and physical activity. The carcases were assessed for skin damage as an index of fighting, and rigor in the hind leg as an indicator of stress and/or fatigue. Measurements were also made of cold carcase weight, backfat thickness and liver glycogen concentration. General activity was very high on entry to the lairage pen. Drinking and mounting occurred almost immediately. Fighting developed after an exploratory period, and could last up to 60 minutes. There were large differences in the behaviour of pigs from the three farms. Pigs from farm A fought frequently but showed little mounting activity, whereas pigs from farm C were involved in mounting but little fighting. The period of food deprivation had no effect on average skin damage or rigor score, but the frequency of carcases with the highest scores was different The pigs deprived of food for up to an hour had the lowest incidence of severe skin damage and high rigor scores. Boars had a higher incidence of severe skin damage but a lower incidence of carcases with a high rigor score than gilts. Liver glycogen was almost completely depleted in the pigs deprived of food for 12 and 18 hours and was lower in the pigs deprived for up to an hour than in animals fed immediately before slaughter. The period of food deprivation had no effect on the levels of cortisol, creatine phosphokinase or lactate in the blood.

Abattoirs↗
PubMed1999

Effects on cattle of transportation by road for up to 31 hours.

The physiological and behavioural effects on cattle of transporting them for periods of 14, 21, 26 and 31 hours, including a stop for a rest and drink on the lorry after 14 hours, were studied in 120 transported animals and 48 control animals. The physiological measurements indicated that a journey lasting 31 hours was not excessively physically demanding, but many of the animals chose to lie down after approximately 24 hours. The animals that lay down had higher plasma cortisol levels than those that remained standing. Many animals chose not to drink during the rest stop. Physiological measurements made after the journeys indicated that 24 hours in lairage, with hay and water freely available, allowed the animals to recover substantially, although not completely, irrespective of the journey time.

3-Hydroxybutyric Acid↗
PubMed1999

Behavioural and physiological responses of pigs to being transported for up to 24 hours followed by six hours recovery in lairage.

Ninety-six pure-bred Large White pigs weighing 80 to 100 kg were either not transported or transported for eight, 16 or 24 hours, and then either slaughtered immediately on arrival at the abattoir or kept in lairage for six hours before being slaughtered. The pigs travelling for eight, 16 or 24 hours lost 2.2, 2.0 and 4.3 per cent of liveweight, respectively, and the pigs travelling for 24 hours lost 2.6 per cent of hot carcase weight Both liveweight and hot carcase weight recovered during the lairage period although there was a net liveweight loss in comparison with the control animals. Only transport for 24 hours led to losses in carcase weight The concentration of non-esterified fatty acids increased with the time spent travelling. The concentrations of cortisol, creatine phosphokinase and lactate were all low in comparison with the levels found in commercially slaughtered animals. Plasma albumin and protein concentrations indicated that the animals were becoming dehydrated during the longer journeys. The animals lay down for most of the journey and appeared to be asleep. During the period in lairage, the animals transported for eight hours had two distinct periods of feeding and drinking but spent most of the time lying down, but those transported for 16 and 24 hours showed far more eating and drinking activity. All the groups appeared tired, but the urge to eat of the groups transported for 16 hours, and especially 24 hours appeared to be more important. There were behavioural and the physiological differences between the transported groups and the controls. Six hours in lairage with access to food and water allowed most of the physiological parameters to return to pretransport levels.

Animals↗
PubMed1999

Effects of lairage time on body temperature and glycogen reserves of broiler chickens held in transport modules.

Commercial broiler chickens killed in two processing plants, one in the south of England, the other in Scotland, in two seasons (winter and summer) and on two occasions in each season, were used to investigate the effects of killing the birds immediately on arrival or holding them in lairage for one, two, three or four hours. The two most important consequences of holding the birds in lairage were that their body temperature increased and their liver glycogen was depleted. The body temperature increased with the time they were held in lairage, although most of the increase occurred in the first hour and the increase was greater in summer when ambient temperatures were higher. Liver glycogen depletion became apparent after about one to two hours in lairage. No evidence was obtained that the birds were significantly dehydrated or physically stressed by being kept longer in lairage.

Animal Welfare↗
PubMed1999

Effect on young calves of a one-hour feeding stop during a 19-hour road journey.

This study examined the effects of transporting calves less than four weeks of age on a journey at the limit of the maximum time laid down by recent EU legislation. In both summer and winter, 45 calves were transported by road for 19 hours. The journey included a one-hour break on the lorry in which the calves were given either a glucose/electrolyte solution, water, or nothing at all. Control groups of 15 calves remained on farm and were fed normally. The effects of the journey were greater during winter when liveweight loss was greater and more prolonged, and the calves suffered a depression in body temperature. Mid-journey feeding was of minimal benefit. Feeding electrolytes reduced the extent of dehydration as measured by changes in plasma total protein and albumin concentrations, but there was some indication that giving water alone was detrimental. Most of the variables which changed during the journey had recovered in line with the values in the control animals within 24 hours of the end of the journey, but the calves' liveweight and plasma creatine kinase activity took up to seven days to stabilise. The study highlighted the problem that young calves have in maintaining body temperature during transport, especially during colder weather.

Animal Feed↗
PubMed1999

Reporting of adverse effects in clinical trials should be improved: lessons from acute postoperative pain.

We assessed the quality of assessment and reporting of adverse effects in randomized, double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain. Reports were identified by systematic searching of a number of bibliographic databases (e.g., MEDLINE). Information on adverse effect assessment, severity and reporting, patient withdrawals, and anesthetic used was extracted. Compliance with former guidelines for adverse effect reporting was noted. Fifty-two studies were included; two made no mention of adverse effects. No method of assessment was given in 19 studies. Twenty trials failed to report the type of anesthetic used, eight made no mention of patient withdrawals, and nine did not state the severity of reported adverse effects. Only two studies described the method of assessment of adverse effect severity. When all adverse effect data were pooled, significantly more adverse effects were reported with active treatment than with placebo. For individual adverse effects, there was no difference between active (acetaminophen 1000 mg or ibuprofen 400 mg) and placebo; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg. Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain. All studies published after 1994 complied with former guidelines for adverse effect reporting. Different methods of assessing adverse effects produce different reported incidence: patient diaries yielded significantly more adverse effects than other forms of assessment. We recommend guidelines for reporting adverse effect information in clinical trials.

Acetaminophen↗
PubMed1999

National epidemiology of mycoses survey (NEMIS): variations in rates of bloodstream infections due to Candida species in seven surgical intensive care units and six neonatal intensive care units.

Candida species are the fourth most frequent cause of nosocomial bloodstream infections, and 25%-50% occur in critical care units. During an 18-month prospective study period, all patients admitted for > or = 72 hours to the surgical (SICUs) or neonatal intensive care units (NICUs) at each of the participant institutions were followed daily. Among 4,276 patients admitted to the seven SICUs in six centers, there were 42 nosocomial bloodstream infections due to Candida species (9.8/1,000 admissions; 0.99/1,000 patient-days). Of 2,847 babies admitted to the six NICUs, 35 acquired a nosocomial bloodstream infection due to Candida species (12.3/1,000 admissions; 0.64/1,000 patient-days). The following were the most commonly isolated Candida species causing bloodstream infections in the SICU: Candida albicans, 48%; Candida glabrata, 24%; Candida tropicalis, 19%; Candida parapsilosis, 7%; Candida species not otherwise specified, 2%. In the NICU the distribution was as follows: C. albicans, 63%; C. glabrata, 6%; C. parapsilosis, 29%; other, 3%. Of the patients, 30%-50% developed incidental stool colonization, 23% of SICU patients developed incidental urine colonization, and one-third of SICU health care workers' hands were positive for Candida species.

Candidiasis↗
PubMed1999

Secretion of pancreatic digestive enzymes induced in rats by first-time oral exposure to kidney bean E2L2 lectin is mediated only in part by cholecystokinin (CCK).

The acute effects of kidney bean (Phaseolus vulgaris) E2L2 lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and alpha-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (< or = 90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats with L-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.

Animals↗
PubMed1999

Unanticipated heterogeneity in growth rate and virulence among Candida albicans AAF1 null mutants.

The disruption of a specific gene in Candida albicans is commonly used to determine the function of the gene product. We disrupted AAF1, a gene of C. albicans that causes Saccharomyces cerevisiae to flocculate and adhere to endothelial cells. We then characterized multiple heterozygous and homozygous mutants. These null mutants adhered to endothelial cells to the same extent as did the parent organism. However, mutants with presumably the same genotype revealed significant heterogeneity in their growth rates in vitro. This heterogeneity was not the result of the transformation procedure per se, nor was it caused by differences in the expression or function of URA3, a marker used in the process of gene disruption. The growth rate among the different heterozygous and homozygous null mutants was positively correlated with in vivo virulence in mice. It is possible that the variable phenotypes of C. albicans were due to mutations outside of the AAF1 coding region that were introduced during the gene disruption process. These results indicate that careful phenotypic characterization of mutants of C. albicans generated through targeted gene disruption should be performed to exclude the introduction of unexpected mutations that may influence pathogenicity in mice.

Alleles↗
PubMed1999

Elucidating the origins of nosocomial infections with Candida albicans by DNA fingerprinting with the complex probe Ca3.

Computer-assisted DNA fingerprinting with the complex probe Ca3 has been used to analyze the relatedness of isolates collected from individuals with nosocomial bloodstream infections (BSIs) and hospital care workers (HCWs) in the surgical and neonatal intensive care units (ICUs) of four hospitals. The results demonstrate that for the majority of patients (90%), isolates collected from commensal sites before and after collection of a BSI isolate were highly similar or identical to the BSI isolate. In addition, the average similarity coefficient for BSI isolates was similar to that for unrelated control isolates. However, the cluster characteristics of BSI isolates in dendrograms generated for each hospital compared to those of unrelated control isolates in a dendrogram demonstrated a higher degree of clustering of the former. In addition, a higher degree of clustering was observed in mixed dendrograms for HCV isolates and BSI isolates for each of the four test hospitals. In most cases, HCW isolates from an ICU were collected after the related BSI isolate, but in a few cases, the reverse was true. Although the results demonstrate that single, dominant endemic strains are not responsible for nosocomial BSIs in neonatal ICUs and surgical ICUs, they suggest that multiple endemic strains may be responsible for a significant number of cases. The results also suggest that cross-contamination occurs between patients and HCWs and between HCWs in the same ICU and in different ICUs. The temporal sequence of isolation also suggests that in the majority of cases HCWs are contaminated by isolates from colonized patients, but in a significant minority, the reverse is true. The results of this study provide the framework for a strategy for more definitive testing of the origins of Candida albicans strains responsible for nosocomial infections.

Candida albicans↗