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M Knight

Publications and source records attributed to M Knight.

At least 19 recordsLinked to original sources
PubMed2005

Deep Impact: observations from a worldwide Earth-based campaign.

On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.

Cosmic Dust↗
PubMed2004

Antiplatelet agents for preventing pre-eclampsia and its complications.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), EMBASE (1994 to 2003) and we handsearched the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi-random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia. Interventions were any comparisons of an antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trials for inclusion in the review and extracted data. We entered data into the Review Manager software and double checked. MAIN RESULTS: Fifty-one trials involving 36,500 women are included in this review. There is a 19% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents ((43 trials, 33,439 women; relative risk (RR) 0.81, 95% confidence interval (CI) 0.75 to 0.88); number needed to treat (NNT) 69 (51, 109)).Twenty-eight trials (31,845 women) reported preterm birth. There is a small (7%) reduction in the risk of delivery before 37 completed weeks ((RR 0.93, 95% CI 0.89 to 0.98); NNT 83 (50, 238)). Fetal or neonatal deaths were reported in 38 trials (34,010 women). Overall there is a 16% reduction in baby deaths in the antiplatelet group (RR 0.84, 95% CI 0.74 to 0.96); NNT 227 (128, 909)). Small-for-gestational age babies were reported in 32 trials (24,310 women), with an 8% reduction in risk (RR 0.92, 95% CI 0.85 to 1.00). There were no significant differences between treatment and control groups in any other measures of outcome. REVIEWER'S CONCLUSIONS: Antiplatelet agents, in this review largely low-dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment is best started, and at what dose.

Female↗
PubMed2001

Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival.

Breakdown or absence of vascular oxygen delivery is a hallmark of many common human diseases, including cancer, myocardial infarction, and stroke. The chief mediator of hypoxic response in mammalian tissues is the transcription factor hypoxia-inducible factor 1 (HIF-1), and its oxygen-sensitive component HIF-1alpha. A key question surrounding HIF-1alpha and the hypoxic response is the role of this transcription factor in cells removed from a functional vascular bed; in this regard there is evidence indicating that it can act as either a survival factor or induce growth arrest and apoptosis. To study more closely how HIF-1alpha functions in hypoxia in vivo, we used tissue-specific targeting to delete HIF-1alpha in an avascular tissue: the cartilaginous growth plate of developing bone. We show here the first evidence that the developmental growth plate in mammals is hypoxic, and that this hypoxia occurs in its interior rather than at its periphery. As a result of this developmental hypoxia, cells that lack HIF-1alpha in the interior of the growth plate die. This is coupled to decreased expression of the CDK inhibitor p57, and increased levels of BrdU incorporation in HIF-1alpha null growth plates, indicating defects in HIF-1alpha-regulated growth arrest occurs in these animals. Furthermore, we find that VEGF expression in the growth plate is regulated through both HIF-1alpha-dependent and -independent mechanisms. In particular, we provide evidence that VEGF expression is up-regulated in a HIF-1alpha-independent manner in chondrocytes surrounding areas of cell death, and this in turn induces ectopic angiogenesis. Altogether, our findings have important implications for the role of hypoxic response and HIF-1alpha in development, and in cell survival in tissues challenged by interruption of vascular flow; they also illustrate the complexities of HIF-1alpha response in vivo, and they provide new insights into mechanisms of growth plate development.

Alleles↗
PubMed2001

Differential gene expression in haemocytes of the snail Biomphalaria glabrata: effects of Schistosoma mansoni infection.

Parasite encapsulation and destruction in Biomphalaria glabrata has been shown to involve the cellular component of the snail's internal defence system, the haemocytes. To identify genes involved in the immunobiology of these cells, we used the method of differential display reverse transcriptase polymerase chain reaction (DDRT-PCR) to investigate differential gene regulation in haemocytes isolated from Schistosoma mansoni exposed and unexposed snails. RNA isolated from circulating haemocytes from resistant snails (BS-90 stock), previously exposed to S. mansoni, was analysed using 12 different arbitrary primers in conjunction with an anchored Oligo d(T(11)CG) primer. Transcription profiles between haemocytes of parasite exposed and unexposed snails were compared and a total of 87 differentially regulated bands were identified and isolated. Of these, 65 bands were cloned and used as probes in Southern blots to show the presence of corresponding sequences in the snail genome. RT-PCR was performed to verify the regulation of these transcripts. DNA sequence analysis showed that the majority of the cloned sequences were novel, although a few showed a high degree of sequence similarity to other sequences in the DNA and protein databases. One of these included a differentially expressed transcript that showed a significant degree of sequence identity to E. coli transposase Tn5, an enzyme whose activity is normally associated with generating mobility and instability in the genome.

Amino Acid Sequence↗
PubMed2001

Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review.

OBJECTIVE: To assess the effectiveness and safety of antiplatelet drugs for prevention of pre-eclampsia and its consequences. DESIGN: Systematic review. DATA SOURCES: Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase. INCLUDED STUDIES: Randomised trials involving women at risk of pre-eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet drug. MAIN OUTCOME MEASURES: Pre-eclampsia, preterm birth, fetal or neonatal death, and small for gestational age baby. Studies were assessed for quality of concealment of allocation and losses to follow up. RESULTS: 39 trials (30 563 women) were included, and 45 trials (>3000 women) excluded. Use of antiplatelet drugs was associated with a 15% reduction in the risk of pre-eclampsia (32 trials, 29 331 women; relative risk 0.85, 95% confidence interval 0.78 to 0.92; number needed to treat 100, 59 to 167). There was also an 8% reduction in the risk of preterm birth (23 trials, 28 268 women; 0.92, 0.88 to 0.97; 72, 44 to 200), and a 14% reduction in the risk of fetal or neonatal death (30 trials, 30 093 women; 0.86, 0.75 to 0.98; 250, 125 to >10 000) for women allocated antiplatelet drugs. Small for gestational age babies were reported in 25 trials (20 349 women), with no overall difference between the groups (relative risk 0.92, 0.84 to 1.01). There were no significant differences in other measures of outcome. CONCLUSIONS: Antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.

Aspirin↗
PubMed2001

The relationship between Schistosoma mansoni and Biomphalaria glabrata: genetic and molecular approaches.

Biomphalaria glabrata is a major intermediate host for the helminth parasite Schistosoma mansoni. Beginning in the mid-20th century, studies were carried out with this snail species to identify the immunological and genetic components that might be involved in controlling schistosome development. A number of genetically well-defined snail stocks were derived as a direct result of these studies and have since played major roles in helping investigators to identify important cellular and humoral components in the snail/schistosome relationship. This review will explore the historical development of these stocks and describe some of the major advances in several areas of medical malacology that hawe been made possible be their use.

Animals↗
PubMed2001

Curing cut or ritual mutilation? Some remarks on the practice of female and male circumcision in Graeco-Roman Egypt.

Ancient texts and archaeological artifacts provide the starting point for a review of the surgical aspects of female genital mutilation (FGM) in ancient Egypt. Analysis of the ancient surgical procedure incorporates modern experience on the subject as well as ancient literary and cultural perspectives. Comparison of FGM with ancient Egyptian male circumcision and consideration of motivations for the practice contribute to our understanding of FGM. In particular, the documented association between male circumcision and generative ability suggests a novel comparison with a natural process in the female--the breaking of the hymen on first intromission--and ultimately a new hypothesis for the origin of ancient FGM.

Circumcision, Female↗
PubMed2001

Estimating health needs: the impact of a checklist of conditions and quality of life measurement on health information derived from community surveys.

BACKGROUND: Prevalence estimates of chronic disease vary according to the technique used. Questionnaire surveys may be susceptible to inaccuracies, which may be overcome by addition of a checklist of conditions. This paper presents SF-36 scores and NHS consultation rates for people reporting individual chronic diseases or disabilities in two questionnaire surveys, one of which employed a checklist and one of which did not. We aimed to document differences in estimates of disease prevalence, and to determine whether or not subjective impact on quality of life is the same in people recruited by a checklist as in those who volunteer that they have a chronic disease or disability without the prompt of a checklist. We use these data to estimate the contribution that different chronic diseases and disabilities make to the burden of disease in the community. METHODS: Data were collected in two postal questionnaire surveys conducted in 1991 and 1997 with response rates of 72 per cent and 64 per cent. Both questionnaires included a question on long-standing illness, disability or infirmity, together with the SF-36 health status measure. Respondents to the 1991 survey were asked to specify their illness in a free text response, whereas the 1997 survey offered a checklist of conditions. Prevalence rates of each condition were calculated, together with an 'escalation factor' representing the increase in reporting of specific diseases between the surveys. SF-36 domain and component summary scores were calculated overall and for the groups reporting individual chronic diseases or disabilities. Disease-specific NHS consultation rates were calculated for both surveys. RESULTS: The overall reported rate of chronic disease and disability increased from 28 per cent in 1991 to 42 per cent in 1997. Reported levels of mental health problems and of conditions with a perceived psychosomatic element increased substantially, whereas rates of well-defined conditions were similar. The pattern of SF-36 scores for those reporting chronic disease or disability was similar in the two surveys in spite of very different prevalence rates, and respondents reporting chronic disease had similar levels of health service use. This suggests that they were reporting conditions with similar levels of impact on quality of life. Heart disease, arthritis and mental health problems had the greatest impact on quality of life, and asthma and hypertension the least. CONCLUSIONS: Evidence from SF-36 scores and NHS consultation rates suggests that addition of a checklist of conditions to this community health survey encouraged reporting of illnesses by the genuinely ill and not merely by those who are less severely affected by their disease. This method appears to give a more accurate reflection of health needs than information derived from routine data sources. The combination of prevalence data combined with subjective assessment of quality of life allows an alternative perspective of health needs. This approach highlights the relative importance of musculo-skeletal problems, particularly back pain, and mental health problems to the burden of disease, and the relative lack of importance of conditions such as asthma. It presents a contrast to studies based on other methods of health needs assessment.

Adult↗
PubMed2001

A novel deletion in the flavin-containing monooxygenase gene (FMO3) in a Greek patient with trimethylaminuria.

Mutations of the flavin-containing monooxygenase type 3 gene (FMO3) that encode the major functional form present in adult human liver, have been shown to cause trimethylaminuria. We now report a novel homozygous deletion of exons 1 and 2 in an Australian of Greek ancestry with TMAuria, the first report of a deletion causative of trimethylaminuria. The deletion occurs 328 bp upstream from exon 1. The 3'-end of the deletion occurs in intron 2, 10013 base pairs downstream from the end of exon 2. The deletion is 12226 bp long. For the proband homozygous for the human FMO3 gene deletion, it is predicted that in addition to loss of monooxygenase function for human FMO3 substrates, such as TMA and other amines, the proband will exhibit decreased tolerance of biogenic amines, both medicinal and those found in foods.

Adolescent↗
PubMed2000

Extractionless determination of 6-methoxy-2-naphthylacetic acid, a major metabolite of nabumetone, in human plasma by high-performance liquid chromatography.

Following oral administration of the prodrug nabumetone, the major metabolite 6-methoxy-2-naphthylacetic acid (6-MNA) was determined in human plasma. Minimal sample preparation was followed by reversed-phase liquid chromatography and UV detection, affording high sample throughput. The lower limit of quantification (LLOQ) was 70 ng/ml, at a signal-to-noise ratio of 8:1. The assay method displayed good correlation (r=0.997), and can be readily employed in pharmacokinetic and bioequivalence studies.

Adult↗
PubMed2000

Molecular studies of Biomphalaria glabrata, an intermediate host of Schistosoma mansoni.

The freshwater gastropod Biomphalaria glabrata is one of the most important invertebrate hosts of the helminth parasite Schistosoma mansoni. Investigators are using different strategies to determine the molecular basis of this snail-parasite relationship. Of particular interest are the identification of parasite resistance genes in the snail, and the application of molecular probes to better understand the epidemiology of schistosomiasis. This review will focus on recent advances that have been made on genome analysis of B. glabrata. Much of this work has centred on the use of random amplification of polymorphic DNA-PCR-based technology, with restriction fragment length polymorphism analysis and the generation of expressed sequence tags from the snail. A brief discussion of how parasite products may complicate this analysis is also given, along with an indication of the scope of the problems that lie ahead.

Amino Acid Sequence↗
PubMed2000

Antiplatelet agents for preventing and treating pre-eclampsia.

BACKGROUND: Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, and low dose aspirin in particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES: To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia, and to those with established pre-eclampsia. SEARCH STRATEGY: This review drew on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The Cochrane Controlled Trials Register was also searched, The Cochrane Library 1999 Issue 1, Embase was searched from 1994-1999 and hand searches were performed of the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia, and those with pre-eclampsia before delivery. Women treated postpartum were excluded. Interventions were any comparisons of an antiplatelet agent (such as low dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Assessment of trials for inclusion in the review and extraction of data was performed independently and unblinded by two reviewers. Data were entered into the Review Manager software and double checked. MAIN RESULTS: Forty two trials involving over 32,000 women were included in this review, with 30,563 women in the prevention trials. There is a 15% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents [32 trials with 29,331 women; relative risk (RR) 0.85, 95% confidence interval (0.78, 0.92); Number needed to treat (NNT) 89, (59, 167)]. This reduction is regardless of risk status at trial entry or whether a placebo was used, and irrespective of the dose of asprin or gestation at randomisation. Twenty three trials (28,268 women) reported preterm delivery. There is a small (8%) reduction in the risk of delivery before 37 completed weeks [RR 0.92, (0.88, 0.97); NNT 72 (44, 200)]. Baby deaths were reported in 30 trials (30,093 women). Overall there is a 14% reduction in baby deaths in the antiplatelet group [RR 0.86, (0. 75, 0.98); NNT 250 (125, >10000)]. Small for gestational age babies were reported in 25 trials (20,349 women), with no overall difference between the groups, RR 0.92, (0.84, 1.01). There were no significant differences between treatment and control groups in any other measures of outcome. Five trials compared antiplatelet agents with placebo or no antiplatelet agent for the treatment of pre-eclampsia. There are insufficient data for any firm conclusions about the possible effects of these agents when used for treatment of pre-eclampsia. REVIEWER'S CONCLUSIONS: Antiplatelet agents, in this review largely low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.

Aspirin↗
PubMed2000

The RPM1 plant disease resistance gene facilitates a rapid and sustained increase in cytosolic calcium that is necessary for the oxidative burst and hypersensitive cell death.

Early events occurring during the hypersensitive resistance response (HR) were examined using the avrRpm1/RPM1 gene-for-gene interaction in Arabidopsis challenged by Pseudomonas syringae pv. tomato. Increases in cytosolic Ca2+ were measured in whole leaves using aequorin-mediated bioluminescence. During the HR a sustained increase in Ca2+ was observed which was dependent on the presence of both a functional RPM1 gene product and delivery of the cognate avirulence gene product AvrRpm1. The sequence-unrelated avirulence gene avrB, which also interacts with RPM1, generated a significantly later but similarly prolonged increase in cytosolic Ca2+. Accumulation of H2O2 at reaction sites, as revealed by electron microscopy, occurred within the same time frame as the changes in cytosolic Ca2+. The NADPH oxidase inhibitor diphenylene iodonium chloride did not affect the calcium signature, but did block H2O2 accumulation and the HR. By contrast, the calcium-channel blocker LaCl3 suppressed the increase in cytosolic Ca2+ as well as H2O2 accumulation and the HR, placing calcium elevation upstream of the oxidative burst.

Aequorin↗
PubMed1999

The identification of markers segregating with resistance to Schistosoma mansoni infection in the snail Biomphalaria glabrata.

Both snail and parasite genes determine the susceptibility of the snail Biomphalaria glabrata to infection with the trematode Schistosoma mansoni. To identify molecular markers associated with resistance to the parasite in the snail host, we performed genetic crosses between parasite-resistant and -susceptible isogenic snails. Because resistance to infection in adult snails is controlled by a single locus, DNA samples from individual F2 and F1 backcross progeny, segregating for either the resistant or susceptible phenotypes, were pooled (bulked segregant). Genotypes for both parents were determined with 205 arbitrary decamer primers by random amplified polymorphic DNA-PCR. Of the 205 primers, 144 were informative, and the relative allele frequencies between the pools for these primers were determined. Two primers, OPM-04 and OPZ-11, produced fragments in the resistant parent of one cross that were inherited in a dominant fashion in the resistant F2 and backcross-bulked segregant progeny. Subsequent typing of DNA samples of individual progeny snails showed that the 1.2-kb marker amplified by primer OPM-04 and the 1.0-kb marker produced by primer OPZ-11 segregated in the same dominant fashion with the resistant phenotype. Sequence analysis of the 1.2-kb marker showed that it corresponds to a repetitive sequence in the snail genome with no homology to existing DNA sequences in the public databases. Analysis of the 1. 0-kb marker showed that it also corresponds to a repetitive sequence in the B. glabrata genome that contains an imperfect ORF, with homology to retrovirus-related group-specific antigens (gag) polyprotein.

Animals↗
PubMed1999

Two novel mutations of the FMO3 gene in a proband with trimethylaminuria.

The mammalian flavin-containing monooxygenases catalyze the NADPH-dependent N-oxygenation of nucleophilic nitrogen-, sulfur-, and phosphorus-containing chemicals, drugs, and xenobiotics, including trimethylamine. The FMO3 gene encodes the dominant catalytically active isoform present in human liver. We have identified two missense mutations in the coding region of the gene in a proband with trimethylaminuria (TMA): M66I and R492W. Whereas two mutations (P153L, E305X) accounted for TMA in our eight unrelated previously documented Australian families of British origin, the present report is the first evidence of compound heterozygosity for two rare mutations in a proband with this disorder. This suggests that other rarer alleles, also causing TMA, will be found in the same populations.

Adult↗
PubMed1999

G130V, a common FRDA point mutation, appears to have arisen from a common founder.

Friedreich ataxia (FRDA) is the most common inherited ataxia. About 98% of mutant alleles have an expansion of a GAA trinucleotide repeat in intron 1 of the affected gene, FRDA. The other 2% are point mutations. Of the 17 point mutations so far described, three appear to be more common. One of these is the G130V mutation in exon 4 of FRDA. G130V, when present with an expanded GAA repeat on the other allele, is associated with an atypical FRDA phenotype. Haplotype analysis was undertaken on the four families who have been described with this mutation. The results suggest a common founder for this mutation. Although marked differences in extragenic marker haplotypes were seen in one family, similar intragenic haplotyping suggests the same mutation founder for this family with the differences explicable by two recombination events.

Adaptor Proteins, Signal Transducing↗