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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 199 records · Page 11Linked to original sources
PubMed1999

Variable selection and multivariate methods for the identification of microorganisms by flow cytometry.

BACKGROUND: When exploited fully, flow cytometry can be used to provide multiparametric data for each cell in the sample of interest. While this makes flow cytometry a powerful technique for discriminating between different cell types, the data can be difficult to interpret. Traditionally, dual-parameter plots are used to visualize flow cytometric data, and for a data set consisting of seven parameters, one should examine 21 of these plots. A more efficient method is to reduce the dimensionality of the data (e.g., using unsupervised methods such as principal components analysis) so that fewer graphs need to be examined, or to use supervised multivariate data analysis methods to give a prediction of the identity of the analyzed particles. MATERIALS AND METHODS: We collected multiparametric data sets for microbiological samples stained with six cocktails of fluorescent stains. Multivariate data analysis methods were explored as a means of microbial detection and identification. RESULTS: We show that while all cocktails and all methods gave good accuracy of predictions (>94%), careful selection of both the stains and the analysis method could improve this figure (to > 99% accuracy), even in a data set that was not used in the formation of the supervised multivariate calibration model. CONCLUSIONS: Flow cytometry provides a rapid method of obtaining multiparametric data for distinguishing between microorganisms. Multivariate data analysis methods have an important role to play in extracting the information from the data obtained. Artificial neural networks proved to be the most suitable method of data analysis.

Bacillus subtilis↗
PubMed1999

IFN-gamma down-regulates MHC expression and antigen processing in a human B cell line.

IFN-gamma is a crucial mediator in the induction of cell-mediated Th1-type responses but is predominantly a negative regulator of B cell differentiation and proliferation. This cytokine is therefore a key factor in determining Th1 vs Th2 differentiation. This study investigates the action of IFN-gamma in modulation of HLA-DR expression and Ag presentation by EBV-transformed human B cell lines. In contrast to its action on the monocyte/macrophage, IFN-gamma down-regulates surface MHC expression on these B cells, and this regulation is posttranscriptional. In parallel with MHC down-regulation, there is a reduced capability to process and present exogenous protein and peptide Ag to T cell hybridomas. IFN-gamma does not change the rates of fluid phase endocytosis or exocytosis in this model system but correlates with an up-regulation of the lysosomal enzymes cathepsins B and D.

Animals↗
PubMed1999

HPLC/tandem electrospray mass spectrometry for the determination of Sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish.

Ciguatera is a significant food-borne disease caused by potent polyether toxins (ciguatoxins) which accumulate in the flesh of ciguateric reef fish at risk levels > 0.1 ppb for Pacific ciguatoxins. Research on ciguatera has been severely hindered by the lack of analytical methods that detect and characterize low levels of ciguatoxin in crude extracts of fish. Here we report a new procedure for ciguatoxin analysis based on gradient reversed-phase HPLC/tandem mass spectrometry (HPLC/MS/MS). The method gave a linear response to pure Pacific and Caribbean ciguatoxins (P-CTX-1 and C-CTX-1) and the structurally related brevetoxin (PbTx-2) spiked into crude extracts of fish. Levels equivalent to 40 ppt P-CTX-1, 100 ppt C-CTX-1, and 200 ppt PbTx-2 in fish flesh could be detected by HPLC/MS/MS. Using P-CTX-1 as an internal standard, the analysis of extracts of 30 ciguateric fish from the Caribbean Sea (8 toxic, 12 borderline, and 10 nontoxic by mouse bioassay) confirmed the reliability of the method and allowed an estimated risk level of > 0.25 ppb C-CTX-1 to be established. HPLC/MS/MS provides a sensitive analytical approach, not previously available, for the determination of Pacific and Caribbean ciguatoxins at sub-ppb levels in fish flesh.

Animals↗
PubMed1999

Induction of labor and the relationship to cesarean delivery: A review of 7001 consecutive inductions.

OBJECTIVE: The goal of this project was to study the increasing risk of induction of labor in a community hospital and to determine whether it had an adverse effect on the rate of cesarean delivery. STUDY DESIGN: From January 1, 1990, through July 31, 1997, 18,055 consecutive singleton pregnancies in women who were candidates for labor were reviewed via a comprehensive perinatal database. The risk of and indication for induction were reviewed. Cesarean delivery rates were calculated for nulliparous and multiparous patients by indication for induction and were compared with rates for patients who had spontaneous labor. Overall trends in cesarean delivery were reviewed for the duration of the study period. RESULTS: The annual induction rate significantly rose from 32% to 43% at the conclusion of the study period. Labor was induced in nearly 40% of nulliparous patients. Postdate pregnancy was the most common indication for induction, although few patients were at or beyond 42 weeks' gestation. The cesarean delivery rate remained at or below 20% for the years of the study. No increase was noted in spite of the increasing risk of induction. However, for nulliparous patients who had elective induction of labor, the risk of cesarean delivery was twice that of nulliparous patients who had spontaneous labor. CONCLUSION: The use of induction methods has significantly increased in this community hospital. More than 40% of patients are now candidates for induction. The cesarean delivery rate remains low in this facility in spite of a marked increase in risk of operative delivery for nulliparous patients who undergo induction.

Causality↗
PubMed1999

Cost-sharing and pharmaceutical utilisation and expenditure in Russia.

This paper presents estimates of the impact of exemption status, and other socio-economic variables, on pharmaceutical use in Russia. Estimates are derived from a newly collected household survey covering around four thousand households. Separate results for a zero-inflated negbin model of utilisation of prescriptions and for a two-part model of the overall level of household expenditure on pharmaceuticals are presented. Full exemption from prescription charges is shown to increase the utilisation of prescription items and reduce the probability of the households incurring drug expenditure.

Cost Sharing↗
PubMed1999

Evidence of in situ stability of the type IV collagen triple helix in human inflammatory bowel disease using a denaturation specific epitope antibody.

A peptide specific antibody (AH1OW1) was raised against an epitope, AH10 (aa 449-463), of the alpha1(IV) chain adjacent to a cleavage site for matrix metalloproteinases (MMP)-2 and -9 within the triple helix of type IV collagen. The antibody only reacted with denatured and reduced preparations of type IV collagen, or with pepsin isolated type IV collagen digested with MMP-2 and MMP-9. The specificity of this antibody for the denatured triple helix was demonstrated by the lack of staining with pre-immune antibody and by pre-incubation of AH1OW1 antibody with excess AH10 peptide epitope. The AH1OWI antibody was used to detect whether proteolysis of type IV collagen occurs in ulcerative colitis, an inflammatory bowel condition often characterised by a large influx of granulocytes and macrophages and an associated tissue destruction. However, no evidence of in situ proteolysis of the basement membrane type IV collagen was observed. Only in the most actively inflamed mucosa was staining with AH1OW1 antibody observed in the mucosal connective tissue. Digestion of frozen sections of bowel with MMP-1, MMP-2, MMP-3 and MMP-9 did not result in the exposure of the AH10 epitope. These data demonstrate the stability of intact type IV collagen and indicate that susceptibility of alpha1(IV) chain to digestion with MMP-2 and MMP-9 may require other proteolytic/denaturing events in the molecule.

Adult↗
PubMed1999

Determination of metaldehyde in suspected cases of animal poisoning using gas chromatography-ion trap mass spectrometry.

A method was developed to detect the molluscicide metaldehyde in samples of stomach contents for forensic toxicology investigations. Gas chromatography-ion trap mass spectrometry in full-scan mode was used to identify and quantify metaldehyde. The limit of detection based on mass chromatograms for the m/z 89 ion was 3 microg/g. Mean recoveries from six different spiked samples were 74% at 25 microg/g and 94% at 500 microg/g. The relative standard deviation of six replicate determinations of a sample containing 632 microg/g metaldehyde was 7.3%.

Acetaldehyde↗
PubMed1999

Observations on the phylogeny of the cestode order Pseudophyllidea Carus, 1863.

A preliminary phylogenetic analysis of the Pseudophyllidea, based on the 16 type-genera of putative families, indicates that a division into two suborders is reasonable. The subordinal grouping are, on the whole, congruent with those suggested by earlier workers, but the positions of three genera, Hexagonoporus, Cephalochlamys and Parabothriocephalus, are somewhat anomalous with respect to earlier work.

Animals↗
PubMed1999

Phylogenetic analysis among the families of the Cyclophyllidea (Eucestoda) based on comparative morphology, with new hypotheses for co-evolution in vertebrates.

Phylogenetic analysis of the families of the Cyclophyllidea based on comparative morphology revealed support for monophyly of the order. Four equal length trees (CI = 0.71) resulted from analysis of 42 binary and multistate characters. Major conclusions are the following: (1) a basal position for the arostellate groups, with Mesocestoididae + Nematotaeniidae representing the basal subclade; (2) polyphyly for the Anoplocephalidae with sister-group associations postulated respectively for Anoplocephalinae + Thysanosomatinae and Linstowiinae + Inermicapsiferinae; (3) recognition within the rostellate cyclophyllideans of taeniid, dilepidid and davaineid subclades and the Dipylidiidae: (4) designation of Metadilepididae + Paruterinidae as sister taxa; (5) monophyly for the Davaineidae with all inclusive subfamilies; and (6) a close relationship for the Hymenolepididae and acoleate cyclophyllideans. Monophyly for such classically defined groups as the Mesocestoididae, Taeniidae and Davaineidae is corroborated. Polyphyly of the Dilepididae sensu lato, with independence of the Dipylidiidae, Dilepididae sensu Bona (1994), the Metadilepididae + Paruterinidae, and the Gryporhynchidae is confirmed. As presented these constitute testable hypotheses for monophyly and relationships among the families of the Cyclophyllidea. Initial diversification of the cyclophyllideans occurred in mammalian hosts and three independent events of colonisation of avian taxa are postulated. Origins of the cyclophyllideans extend into the Mesozoic or earlier, with extant taxa representing lineages that were persistent across the extinction event that defines the Cretaceous-Tertiary boundary.

Anatomy, Comparative↗
PubMed1999

Directed evolution of a fungal peroxidase.

The Coprinus cinereus (CiP) heme peroxidase was subjected to multiple rounds of directed evolution in an effort to produce a mutant suitable for use as a dye-transfer inhibitor in laundry detergent. The wild-type peroxidase is rapidly inactivated under laundry conditions due to the high pH (10.5), high temperature (50 degrees C), and high peroxide concentration (5-10 mM). Peroxidase mutants were initially generated using two parallel approaches: site-directed mutagenesis based on structure-function considerations, and error-prone PCR to create random mutations. Mutants were expressed in Saccharomyces cerevisiae and screened for improved stability by measuring residual activity after incubation under conditions mimicking those in a washing machine. Manually combining mutations from the site-directed and random approaches led to a mutant with 110 times the thermal stability and 2.8 times the oxidative stability of wild-type CiP. In the final two rounds, mutants were randomly recombined by using the efficient yeast homologous recombination system to shuffle point mutations among a large number of parents. This in vivo shuffling led to the most dramatic improvements in oxidative stability, yielding a mutant with 174 times the thermal stability and 100 times the oxidative stability of wild-type CiP.

Coprinus↗
PubMed1999

The distribution of individual inbreeding coefficients and pairwise relatedness in a population of mimulus guttatus

In order to infer population structure at the individual level, we estimated individual inbreeding coefficients and examined the relationship between geographical distance and genetic relatedness from polymorphic microsatellite data for a population of Mimulus guttatus that has an intermediate selfing rate. Expected heterozygosities for five microsatellites ranged from 0.79 to 0.93. The population inbreeding coefficient was calculated to be 0.19 (SE=0.023). A method-of-moments estimator developed by Ritland (1996b) was used to estimate the distribution of inbreeding among and relatedness between individuals of a natural population. The mean individual inbreeding coefficient (F=0.16) did not differ significantly from the population-level estimate. Most of the individuals appeared to be outbred, and there were very few plants that had estimated inbreeding coefficients greater than one-half. Individuals sampled from one transect showed significantly more inbreeding than individuals sampled along the other (P=0.005). There was no apparent relationship between interplant distance (range: 0-14 m) and mean genetic relatedness between individuals. These results represent the first application of polymorphic microsatellites to estimate fine-scale genetic population structure.

Journal Article↗
PubMed1999

Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1.

Hoyeraal-Hreidarsson (HH) syndrome is a multisystem disorder affecting boys characterized by aplastic anaemia (AA), immunodeficiency, microcephaly, cerebellar-hypoplasia and growth retardation. Its pathogenesis is unknown. X-linked dyskeratosis congenita (DC) is an inherited bone-marrow-failure syndrome characterized by skin pigmentation, nail dystrophy and leucoplakia which usually develop towards the end of the first decade of life. AA occurs in >90% of cases of DC. We speculated that mutations in the gene responsible for X-linked DC (DKC1) may account for the HH syndrome, due to the phenotypic similarities between the disease in respect of AA and gender bias. We therefore analysed the DKC1 gene in two HH families. In one family a nucleotide change at position 361(A --> G) in exon 5 was found in both affected brothers; in the other family a nucleotide change at position 146(C --> T) in exon 3 was found in the affected boys. The finding of these two novel missense DKC1 mutations demonstrates that HH is a severe variant of DC. They also show that mutations in DKC1 can give rise to a very wide clinical spectrum of manifestations. Boys with unexplained AA or immunodeficiency should be tested for mutations in DKC1 even though they may lack diagnostic features of DC.

Amino Acid Substitution↗
PubMed1999

'Listen, listen trust your own strange voice' (psychoanalytically informed conversations with a woman suffering serious illness).

This paper argues that the authentic voice of suffering can be denied to people with serious illness. Anguish and expressions of grief are sometimes replaced by joviality. Amid suffering, voices of anguish become strange inner voices that challenge defences of cheeriness and so are avoided, go unheard or are ignored. Bolstered by the everydayness of ward events and hospital life, suppression, repression and denial mean that people with serious illness can suffer without a voice. Listening to others requires the ability to listen to one's own inner voices and recognize how they might guide exchanges. By avoiding conducting conversations in ways dictated by our own fears, worries and fantasies we can listen, and in doing so allow shifts in awareness. Silent suffering can change to expressive suffering allowing a person to reach an autonomous self and so an authentic voice. The seriousness of a situation can be grasped and so life appreciated for what it is. Decisions can be made, business finished and relationships esteemed or otherwise. Through the format of brief therapeutic conversations, listening has a role to play in helping people with serious illness discover their autonomous and authentic voice. The discussion concludes with the suggestion that the need for throughput and roles and tasks demanded on nurses in general settings limits time and resources, and so liaison mental health nursing has a role to play. A specialist practitioner might offer conversational therapies, support nursing and medical staff and teach psychological concepts, thus contributing to an environment in which uncertainty is tolerated.

Defense Mechanisms↗
PubMed1999

'A heavy and blessed experience': a psychoanalytic study of community Macmillan nurses and their roles in serious illness and palliative care.

This paper explores the psychoanalytic ideas of containment as described by Wilfred Bion and applies them to the work of community Macmillan nurses and to the ways in which they might understand and structure therapeutic conversations with people that are seriously ill. Case vignettes show the application of psychoanalytic thinking in context. The discussion offers the idea that the impact of physical illness is such that the emotional issues of patients, their families and fellow palliative care workers can saturate nurses. To protect themselves, nurses and other health workers might assimilate the emotional traumas of others into physical symptoms, and so they are ignored or overlooked in favour of drug therapies, pre-occupations with breaking through silences and other concrete or demonstrable methods of treatment. An environment is needed in which a person with serious illness and his or her family member is helped to make sense of their experiences and so integrate them into a meaningful life continuum. Similar provisions are needed for nurses. Appropriate methods of clinical supervision might help these important provisions.

Adaptation, Psychological↗