Search tips
Search criteria

Results 1-24 (24)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
Document Types
1.  Assessing patterns of hybridization between North Atlantic eels using diagnostic single-nucleotide polymorphisms 
Heredity  2014;112(6):627-637.
The two North Atlantic eel species, the European eel (Anguilla anguilla) and the American eel (Anguilla rostrata), spawn in partial sympatry in the Sargasso Sea, providing ample opportunity to interbreed. In this study, we used a RAD (Restriction site Associated DNA) sequencing approach to identify species-specific diagnostic single-nucleotide polymorphisms (SNPs) and design a low-density array that combined with screening of a diagnostic mitochondrial DNA marker. Eels from Iceland (N=159) and from the neighboring Faroe Islands (N=29) were genotyped, along with 94 larvae (49 European and 45 American eel) collected in the Sargasso Sea. Our SNP survey showed that the majority of Icelandic eels are pure European eels but there is also an important contribution of individuals of admixed ancestry (10.7%). Although most of the hybrids were identified as F1 hybrids from European eel female × American eel male crosses, backcrosses were also detected, including a first-generation backcross (F1 hybrid × pure European eel) and three individuals identified as second-generation backcrosses originating from American eel × F1 hybrid backcrosses interbreeding with pure European eels. In comparison, no hybrids were observed in the Faroe Islands, the closest bodies of land to Iceland. It is possible that hybrids show an intermediate migratory behaviour between the two parental species that ultimately brings hybrid larvae to the shores of Iceland, situated roughly halfway between the Sargasso Sea and Europe. Only two hybrids were observed among Sargasso Sea larvae, both backcrosses, but no F1 hybrids, that points to temporal variation in the occurrence of hybridization.
PMCID: PMC4023445  PMID: 24424165
admixture analysis; anguilla; hybridization; RAD sequencing; SNPs
2.  Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors 
British Journal of Pharmacology  2012;167(1):164-182.
Positive allosteric modulation of α4β2 nicotinic acetylcholine (nACh) receptors could add a new dimension to the pharmacology and therapeutic approach to these receptors. The novel modulator NS9283 was therefore tested extensively.
Effects of NS9283 were evaluated in vitro using fluorescence-based Ca2+ imaging and electrophysiological voltage clamp experiments in Xenopus oocytes, mammalian cells and thalamocortical neurons. In vivo the compound was tested in models covering a range of cognitive domains in mice and rats.
NS9283 was shown to increase agonist-evoked response amplitude of (α4)3(β2)2 nACh receptors in electrophysiology paradigms. (α2)3(β2)2, (α2)3(β4)2 and (α4)3(β4)2 were modulated to comparable extents, but no effects were detected at α3-containing or any 2α : 3β stoichiometry nACh receptors. Native nACh receptors in thalamocortical neurons similarly displayed DHβE-sensitive currents that were receptive to modulation. NS9283 had favourable effects on sensory information processing, as shown by reversal of PCP-disrupted pre-pulse inhibition. NS9283 further improved performance in a rat model of episodic memory (social recognition), a rat model of sustained attention (five-choice serial reaction time task) and a rat model of reference memory (Morris water maze). Importantly, the effects in the Morris water maze could be fully reversed with mecamylamine, a blocker of nACh receptors.
These results provide compelling evidence that positive allosteric modulators acting at the (α4)3(β2)2 nACh receptors can augment activity across a broad range of cognitive domains, and that α4β2 nACh receptor allosteric modulation therefore constitutes a promising therapeutic approach to symptomatic treatment of cognitive impairment.
PMCID: PMC3448921  PMID: 22506660
Nicotinic acetylcholine receptors; α4 nACh receptors; β2 nACh receptors; allosteric modulation; cognitive dysfunction; therapeutics
3.  The high-affinity phosphate transporter Pst in Proteus mirabilis HI4320 and its importance in biofilm formation 
Microbiology  2009;155(Pt 5):1523-1535.
Proteus mirabilis causes urinary tract infections (UTIs) in individuals requiring long-term indwelling catheterization. The pathogenesis of this uropathogen is mediated by a number of virulence factors and the formation of crystalline biofilms. In addition, micro-organisms have evolved complex systems for the acquisition of nutrients, including the phosphate-specific transport system, which has been shown to be important in biofilm formation and pathogenesis. A functional Pst system is important during UTIs caused by P. mirabilis HI4320, since transposon mutants in the PstS periplasmic binding protein and the PstA permease protein were attenuated in the CBA mouse model of UTI. These mutants displayed a defect in biofilm formation when grown in human urine. This study focuses on a comparison of the proteomes during biofilm and planktonic growth in phosphate-rich medium and human urine, and microscopic investigations of biofilms formed by the pst mutants. Our data suggest that (i) the Δpst mutants, and particularly the ΔpstS mutant, are defective in biofilm formation, and (ii) the proteomes of these mutants differ significantly from that of the wild-type. Therefore, since the Pst system of P. mirabilis HI4320 negatively regulates biofilm formation, this system is important for the pathogenesis of these organisms during complicated UTIs.
PMCID: PMC2889415  PMID: 19372157
4.  Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis 
Clinical Microbiology Reviews  2008;21(1):26-59.
Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.
PMCID: PMC2223845  PMID: 18202436
5.  Multilocus Sequence Typing of the Pathogenic Fungus Aspergillus fumigatus▿  
Journal of Clinical Microbiology  2007;45(5):1469-1477.
A multilocus sequence typing (MLST) scheme was devised for Aspergillus fumigatus. The system involved sequencing seven gene fragments and was applied to a panel of 100 isolates of A. fumigatus from diverse sources. Thirty different sequence types were found among the 100 isolates, and 93% of the isolates differed from the other isolates by only one allele sequence, forming a single clonal cluster as indicated by the eBURST algorithm. The discriminatory power of the MLST method was only 0.93. These results strongly indicate that A. fumigatus is a species of a relatively recent origin, with low levels of sequence dissimilarity. Typing methods based on variable numbers of tandem repeats offer higher levels of strain discrimination. Mating type data for the 100 isolates showed that 71 isolates were type MAT1-2 and 29 isolates were MAT1-1.
PMCID: PMC1865896  PMID: 17376886
6.  Candida albicans Strain Maintenance, Replacement, and Microvariation Demonstrated by Multilocus Sequence Typing 
Journal of Clinical Microbiology  2006;44(10):3647-3658.
We typed 165 Candida albicans isolates from 44 different sources by multilocus sequence typing (MLST) and ABC typing of rRNA genes and determined their homozygosity or heterozygosity at the mating-type-like locus (MTL). The isolates represented pairs or larger sets from individual sources, which allowed the determination of strain diversity within patients. A comparison of replicate sequence data determined a reproducibility threshold for regarding isolates as MLST indistinguishable. For 36 isolate sets, MLST and ABC typing showed indistinguishable or highly related strain types among isolates from different sites or from the same site at different times from each patient. This observation included 11 sets with at least one isolate from a blood culture and a nonsterile site from the same patient. For one patient, strain replacement was evidenced in the form of two sets of isolates from different hospital admissions where the strain types within each set were nearly identical but where the two sets differed both by MLST and ABC typing. MLST therefore confirms the existing view of C. albicans strain carriage. Microvariation, evidenced as small differences between MLST types, resulted in most instances from a loss of heterozygosity at one or more of the sequenced loci. Among isolate sets that showed major strain type differences, some isolates could be excluded as likely examples of handling errors during storage. However, for a minority of isolates, intermittent differences in ABC type for tightly clustered MLST types and intermittent appearances of MTL homozygosity lead us to propose that some C. albicans isolates, or all isolates under yet-to-be-determined conditions, maintain a high level of genetic diversity by mechanisms such as recombination, gene conversion, or chromosomal ploidy change.
PMCID: PMC1594753  PMID: 17021093
8.  Temporal epileptic seizures and occupational exposure to solvents. 
Long term exposure to organic solvents is usually not considered as a possible cause of chronic epileptic seizures. A case that shows a remarkable coincidence between exposure to organic solvents and occurrence of epileptic seizures is reported. The man was a 58 year old sign writer with lifelong exposure to a mixture of organic solvents (mainly cyclohexanone, white spirit, and isopropanol). Epileptic seizures of temporal type were occurring in relation to solvent exposure. The seizures disappeared shortly after stopping exposure but returned just after a short term re-exposure to cyclohexanone. The case history suggests that exposure to organic solvents may elicit or maintain epileptic seizures despite medical treatment.
PMCID: PMC1128001  PMID: 8044237
9.  Irregularly shaped small shadows on chest radiographs, dust exposure, and lung function in coalworkers' pneumoconiosis. 
The predominant shapes of small opacities on the chest radiographs of 895 British coalminers have been studied. The aims were to determine whether irregular (as distinct from rounded) small opacities can be identified reproducibly, whether their occurrence is related to dust exposure, and whether they are associated with excess prevalence of respiratory symptoms or impairments of lung function. Six of the doctors responsible for regular radiological surveys of all British coalminers each classified all 895 radiographs twice and independently, using the International Labour Organisation's 1980 classification system. The majority view was that 39 films showed predominantly irregular small opacities, 131 showed predominantly small rounded opacities, and 587 showed no small opacities. Readers' opinions varied about the presence and shapes of shadows on the other 138 films. In general, consistency between readers (and within readers on repeated viewings) was satisfactory. The occurrence and profusion of irregular shadows were related significantly both to the men's ages and additionally to their cumulative exposure to respirable coalmine dust as determined from 15 years' dust monitoring close to where the miners had worked. For any given level of exposure, the average level of profusion of the small irregular opacities was less than the corresponding profusion of small rounded opacities. The prevalence rates of chronic cough and phlegm, and of breathlessness, were higher in those with small irregular opacities than in those with no small opacities (category 0/0), but the differences were not statistically significant after adjustment for other factors including smoking habits. The presence of irregular (but not rounded) small shadows was associated with an impairment in respiratory function averaging about 190 ml deficits in both FEV1 and FVC. These deficits were not explicable in terms of the men's ages, body sizes, and smoking habits and they were in addition to the lung function losses attributable to the miners' dust exposure as such. It is concluded that the presence and profusion of small irregular opacities should be taken into consideration when assessing the severity of coalworkers' simple pneumoconiosis.
PMCID: PMC1007944  PMID: 3342187
10.  Exposure to respirable coalmine dust and incidence of progressive massive fibrosis. 
Data gathered since 1953 concerning more than 30,000 coalminers while employed at 24 collieries in England, Scotland, and Wales have been used to study the incidence of progressive massive fibrosis (PMF) in working coalminers. Results refer to 52,264 approximately five year intervals when the miners were at risk of an attack of PMF. One objective of the present study was to describe how the five year attack rate of PMF was related to miners' age, colliery, and simple pneumoconiosis category at the start of the periods at risk. The main objective was to estimate the relation between exposure to dust and incidence of PMF and to examine how this relation changes in the presence of coalworkers' simple pneumoconiosis (CWSP). Film readings, in some cases based on clinical assessments only, showed 462 attacks of PMF over the five year risk periods. The men concerned had experienced higher cumulative exposures to dust than their colleagues of similar age at the same collieries, a result found at 65 of the 68 age colliery groups where an attack had occurred. The association was highly significant statistically. Simple pneumoconiosis clearly predisposed to PMF, with five year attack rates of 13.9%, 12.5%, 4.4%, and 0.2% among men with categories 3, 2, 1, and 0 respectively at the start of the risk periods. Once simple pneumoconiosis category 1 or more had been attained, those with higher cumulative exposure to dust were not at greater risk of an attack of PMF than other men with the same CWSP category. Among most miners, those with category 0, however, the risks of an attack of PMF increased clearly with exposure. Risks of an attack were higher among older men irrespective of CWSP category. In addition, there were large colliery specific variations in incidence related to variations in the carbon content of the coal though not fully explained by them. It is concluded that cumulative exposure to respirable dust is the decisive central factor in the development of PMF. Its effect is primarily in causing simple pneumoconiosis category 1 or higher which predisposes to PMF, though the dust related incidence among men with category 0 is not negligible in view of the large numbers at risk. Continuation of the policy to minimise dust concentrations underground therefore seems the only secure strategy to limit, and eventually eliminate, PMF.
PMCID: PMC1007898  PMID: 3676119
11.  Dust exposure, pneumoconiosis, and mortality of coalminers. 
General mortality in approximately 25 000 British coalminers over 22 year periods ending in 1980 was 13% lower on average than in English and Welsh men in the same regions of Britain. There were significant within region variations between collieries, and standardised mortality ratios increased during the later years of the follow up, approaching or slightly exceeding 100 in most of the 20 coalmines studied. Age specific comparisons of 22 year survival rates were made in subgroups. Relative risks of death from all non-violent causes for men with the earliest stage of progressive massive fibrosis (PMF category A), compared with risks in miners with no pneumoconiosis (category O), ranged from 1.2 in those aged 55-64 initially to 3.5 for those aged 25-34. Mortality in miners with higher categories of PMF (B or C) was even more severe. Survival rates in men with category 1 simple pneumoconiosis were about 2% to 3% lower than in miners with radiographs classified as category O, but there was no consistent evidence of an increase in mortality with increasing category of simple pneumoconiosis. Mortality from all non-violent causes increased systematically with increases in estimates of exposure to dust before the start of the follow up. That gradient was attributable primarily to deaths certified as due to pneumoconiosis and those recorded as due to bronchitis and emphysema (p less than 0.001). There was some evidence of a dust related increase in deaths from cancers of the digestive system (p approximately equal to 0.05), but none of an association between exposure to coalmine dust and lung cancer. Lung cancer mortality, assessed over 17 year periods, was about 5.5 times higher in smokers than in life long non-smokers. Smokers with no pneumoconiosis had slightly higher lung cancer death rates than smokers with pneumoconiosis. We conclude that miners exposed to excessive amounts of respirable coalmine dust are at increased risk of premature death, either from progressive massive fibrosis or from chronic bronchitis or emphysema.
PMCID: PMC1007567  PMID: 4063215
12.  Severe acquired immunodeficiency in European homosexual men. 
Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.
PMCID: PMC1499130  PMID: 6805793
13.  Coalworkers' simple pneumoconiosis and exposure to dust at 10 British coalmines. 
Five physicians' radiological assessments of coalworkers' simple pneumoconiosis (CWP) in 2600 coalminers at 10 British collieries have been studied in relation to the individuals' estimated lifetime (mean 33 years) exposure to respirable coalmine dust. Estimates of exposure were based on 20 years of observations at each colliery. Radiographic classifications were clearly associated with the measures of dust exposure. Important unexplained differences between some of the collieries were disclosed. Among men with similar cumulative dust exposures those with longer exposure time had higher prevalence of CWP. In general there was no evidence that the quartz concentrations experienced (average 5% of mixed dust) affected the probability of developing coalworkers' simple pneumoconiosis. Some men reacted unfavourably (two or more steps of change on the 12-point radiological scale) over a 10-year period to coalmine dust with a relatively high quartz content.
PMCID: PMC1008956  PMID: 7066228
14.  Classification of chest radiographs for epidemiological purposes by people not experienced in the radiology of pneumoconiosis. 
Under controlled conditions 16 people (eight non-medical) inexperienced in the radiology of occupational lung diseases repeatedly classified 300 selected chest radiographs using the 1971 ILO U/C International Classification of Radiographs of Pneumoconioses. Eight experienced medical readers had previously classified 220 of the selected radiographs for profusion of small rounded opacities. Variability among readers was greater in experimental panels than among the experienced readers. But the average consistency between pairs of novice readers in their use of the 12 categories of profusion for the same radiographs was similar (about 29%) to the average consistency among the experienced readers. Subsequent work with nine of the participants showed that eight of them were able to produce classifications of coal miners' chest radiographs that correlated well with estimates the miners' exposures to respirable coal mine dust. It is concluded that the ILO classification scheme provides a sound descriptive system for recording the appearances of chest radiographs. Under controlled conditions the scheme may be used for epidemiological studies by those with no specialist knowledge or clinical experience. This presupposes that the radiographs concerned will have been examined previously for diagnostic purposes by a suitable qualified physician.
PMCID: PMC1008883  PMID: 7272238
15.  Probable malignant transformation of a pulmonary hamartoma. 
Thorax  1979;34(4):557-558.
PMCID: PMC471118  PMID: 505356
16.  Lung cancer and coal workers' pneumoconiosis. 
British Medical Journal  1979;2(6183):208.
PMCID: PMC1595839  PMID: 466357
17.  Pneumoconiosis and chronic bronchitis. 
British Medical Journal  1977;2(6100):1478.
PMCID: PMC1632617  PMID: 589282
18.  Pneumoconiosis and chronic bronchitis. 
British Medical Journal  1977;2(6084):424-427.
Data from a major long-term epidemiological survey in the British coalmining industry were examined to determine whether bronchitis offered any protective action against the development of pneumoconiosis. No evidence of such an effect was found.
PMCID: PMC1631190  PMID: 890324
20.  A comparison of conventional and grid techniques for chest radiography in field surveys 
Washington, J. S., Dick, J. A., Jacobsen, M., and Prentice, W. M. (1973).British Journal of Industrial Medicine,30, 365-374. A comparison of conventional and grid techniques for chest radiography in field surveys. The effect on the quality of chest radiographs using a reciprocating grid with a moderately high kilovoltage (96 to 105 kV) has been studied. A total of 1 710 mineworkers had two postero-anterior chest radiographs taken at the same visit to a linked pair of mobile ϰ-ray units. One film was taken with conventional exposure factors and the other with moderately high kilovoltage and a reciprocating grid. The grid was exchanged between the two units according to a randomized plan so that the first radiograph was not always taken with the same technique.
The 3 420 films so produced were subsequently assessed for quality by five doctors experienced in reading chest films. The films were examined singly in random order and the reader did not know which technique had been used for a given film.
Four of the readers recorded improved quality using the grid technique for films from men whose antero-posterior chest measurements exceeded 254 mm (10 in), but they preferred the conventional exposure technique for films from men whose chest measurements were less than 254 mm. Results from all film pairs where a difference in quality was recorded showed no overall advantage for either technique.
PMCID: PMC1069477  PMID: 4753720
21.  Role of dust in the working environment in development of chronic bronchitis in British coal miners 
Rogan, J. M., Attfield, M. D., Jacobsen, M., Rae, S., Walker, D. D., and Walton, W. H. (1973).British Journal of Industrial Medicine, 30, 217-226. Role of dust in the working environment in development of chronic bronchitis in British coal miners. In the course of a long-term prospective study of chronic respiratory disease in British coal miners the effects on pulmonary ventilatory function of exposure to airborne dust, of simple pneumoconiosis, and of chronic bronchitis have been examined in a group of 3581 coalface workers.
The men were employed in 20 collieries throughout the British coalfields. Their cumulative exposures to coal mine dust in the respirable range (1-5 μm) were calculated from detailed dust sampling results at their work places during a 10-year period and from estimates of earlier exposures based on records of their industrial histories.
A progressive reduction in FEV1·0 with increasing cumulative exposure to airborne dust has been demonstrated. This effect was evident also in a subgroup of the men studied who reported no signs of mild bronchitic symptoms (cough and phlegm for at least three months in a year).
Among men with pneumoconiosis there was no evidence of a reduction of FEV1·0 in excess of that attributable to their dust exposures, smoking habits, age, and physique.
Increasing severity of bronchitic symptoms was associated with a loss in FEV1·0 greater than that expected from the effects of dust exposure as measured, smoking, age, and physique. Possible explanations for this phenomenon are discussed. It is suggested that the results may indicate that once early bronchitic symptoms are present the disease may progress and ventilatory capacity may deteriorate independently of factors initiating the disease process.
PMCID: PMC1009515  PMID: 4723786
22.  Postnatal growth and function of the pre-acinar airways 
Thorax  1972;27(3):265-274.
The postnatal growth of the pre-acinar or conducting airways of the lung was examined by measuring the dimensions of selected axial pathways in lungs at different stages of development. The material included both formalin-fixed specimens and bronchograms. A method of comparing the relative sizes of each part of the pathways was developed which allowed for differences between the number of branches or generations measured in each specimen. The results indicate that the pre-acinar airways of the infant may be regarded as a miniature version of those in the adult and that this relationship persists during postnatal growth. Each individual branch grows in a symmetrical fashion both in length and in diameter and bears a constant relation to the whole. The physiological function of the conducting airways during growth was investigated using published data on the breathing pattern of infants. Particular attention was given to the conditions of airflow, to the warming and humidification of inhaled air, and to the filtration of airborne dust.
PMCID: PMC472584  PMID: 5039441
24.  Is the operative delivery rate in low-risk women dependent on the level of birth care? A randomised controlled trial 
Bjog  2011;118(11):1357-1364.
To investigate possible differences in operative delivery rate among low-risk women, randomised to an alongside midwifery-led unit or to standard obstetric units within the same hospital.
Randomised controlled trial.
Department of Obstetrics and Gynaecology, Østfold Hospital Trust, Tromsø, Norway.
A total of 1111 women assessed to be at low risk at onset of spontaneous labour.
Randomisation into one of three birth units: the special unit; the normal unit; or the midwife-led unit.
Main outcome measures
Total operative delivery rate, augmentation, pain relief, postpartum haemorrhage, sphincter injuries and intrapartum transfer, Apgar score <7 at 5 minutes, metabolic acidosis and transfer to neonatal intensive care unit.
There were no significant differences in total operative deliveries between the three units: 16.3% in the midwife-led unit; 18.0% in the normal unit; and 18.8% in the special unit. There were no significant differences in postpartum haemorrhage, sphincter injuries or in neonatal outcomes. There were statistically significant differences in augmentation (midwife-led unit versus normal unit RR 0.73, 95% CI 0.59–0.89; midwife-led unit versus special unit RR 0.69, 95% CI 0.56–0.86), in epidural analgesia (midwife-led unit versus normal unit RR 0.68, 95% CI 0.52–0.90; midwife-led unit versus special unit RR 0.64, 95% CI 0.47–0.86) and in acupuncture (midwife-led unit versus normal unit RR 1.45, 95% CI 1.25–1.69; midwife-led unit versus special unit RR 1.45, 95% CI 1.22–1.73).
The level of birth care does not significantly affect the rate of operative deliveries in low-risk women without any expressed preference for level of birth care.
PMCID: PMC3187863  PMID: 21749629
Birth outcome; birth unit; low-risk birth; midwife-led unit

Results 1-24 (24)