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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2001

Identification of extensive genomic loss and gain by comparative genomic hybridisation in malignant astrocytoma in children and young adults.

Although astrocytomas are the most common central nervous system tumours in all age groups, there is substantial evidence that tumours arising in young patients (< 25 years of age) do not have the same genetic abnormalities that are characteristic of tumours in older patients. Furthermore, novel, consistent changes have not been identified in astrocytomas in children and young adults. We analysed 13 malignant astrocytomas from young patients using comparative genomic hybridisation. Regions of genomic imbalance were identified in 10 cases. The most common recurrent copy number aberrations were loss of 16p (54% of cases), 17p (38%), 19p (38%), and 22 (38%) and gain on 2q (38%), 12q (38%), 13 (38%), 4q (31%), 5q (31%), and 8q (31%). Seven regions of high copy number amplification were observed at 8q21-22 (three cases), 7q22-23 (two cases), and 1p21-22, 2q22, 12q13-pter, 12q15-21, and 13q11-14 (one case each). This study provides evidence of new characteristic chromosomal imbalances from which potential candidate genes involved in the development of malignant astrocytoma in children and young adults may be identified.

Adolescent↗
PubMed2001

Synergism between base excision repair, mediated by the DNA glycosylases Ntg1 and Ntg2, and nucleotide excision repair in the removal of oxidatively damaged DNA bases in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, inactivation of the two DNA N-glycosylases Ntg1p and Ntg2p does not result in a spontaneous mutator phenotype, whereas simultaneous inactivation of Ntglp, Ntg2p and Radlp or Rad14p, both of which are involved in nucleotide excision repair (NER), does. The triple mutants rad1 ntg1 ntg2 and rad14 ntg1 ntg2 show 15- and 22-fold increases, respectively, in spontaneous forward mutation to canavanine resistance (CanR) relative to the wild-type strain (WT). In contrast, neither of these triple mutants shows an increase in the incidence of Lys+ revertants of the lys1-1 ochre allele. Furthermore, the rad1 ntg1 ntg2 mutant is hypersensitive to the lethal effect of H2O2 relative to WT, rad1 and ntg1 ntg2 mutant strains. Moreover, the rad1 ntg1 ntg2 strain is hypermutable (CanR and Lys+) upon exposure to H2O2, relative to WT, rad1 and ntg1 ntg2 strains. Mutagen sensitivity and enhanced mutagenesis in the rad1 ntg1 ntg2 triple mutant, relative to the other strains tested, were also observed upon exposure to oxidizing agents such as tertbutylhydroperoxide and menadione. In contrast, the sensitivity of the rad1 ntg1 ntg2 triple mutant to gamma-irradiation does not differ from that of the WT. However, the triple mutant shows an increase in the frequency of Lys+ revertants recovered after gamma-irradiation. The results reported in this study demonstrate that base excision repair (BER) mediated by Ntglp and Ntg2p acts synergistically with NER to repair endogenous or induced lethal and mutagenic oxidative DNA damage in yeast. The substrate specificity of Ntg1 p and Ntg2p, and the spectrum of lesions induced by the DNA-damaging agents used, strongly suggest that oxidized DNA bases, presumably oxidized pyrimidines, represent the major targets of this repair pathway.

Alleles↗
PubMed2001

Role of frequency doubling perimetry in detecting neuro-ophthalmic visual field defects.

PURPOSE: To report the ability of frequency doubling perimetry to detect "neuro-ophthalmic" field defects, characterize them as hemianopic or quadrantanopic, and differentiate glaucomatous from "other" neuro-ophthalmic field defects. METHODS: Sixty eyes of 30 normal subjects, 50 eyes of 29 patients with glaucomatous defects, and 138 eyes of 103 patients with "typical" neuro-ophthalmic field defects underwent automated perimetry using the Swedish Interactive Threshold Algorithm and frequency doubling perimetry. The sensitivity and specificity for identification of a field defect (frequency doubling perimetry 20-5 and 20-1 screening tests), or to characterize hemianopia/quadrantanopia (full threshold test) were determined. Ability to discriminate glaucomatous defects was determined by comparing frequency doubling perimetry full threshold test in glaucoma to pooled results of normal and neuro-ophthalmic groups. RESULTS: On frequency doubling perimetry, a single point depressed to less than 1% probability had a sensitivity of 97.1% (20-5 test) and 95.7% (20-1 test) for detecting a neuro-ophthalmic visual field defect. The corresponding specificities were 95% using pooled results in normal subjects and patients with glaucoma and "other" neuro-ophthalmic field defects. In 20-5 screening a single abnormal point depressed to less than 2% probability level had a sensitivity of 98.6% (specificity 85%). Two abnormal points in the 20-1 screening depressed to less than 1% probability level had a specificity of 100% (sensitivity 84.8%). In frequency doubling perimetry full threshold, sensitivity and specificity for detection of hemianopia were 86.8% and 83.2%; for quadrantanopia they were 79.2% and 38.6%. The sensitivity and specificity for categorizing a defect as glaucomatous were 86% and 74.7%. CONCLUSIONS: Frequency doubling perimetry is a sensitive and specific test for detecting "neuro-ophthalmic" field defects. The presence of two abnormal points (20-1 screening program) "rules in" the presence of a field defect. A normal 20-5 program (absence of a single abnormal point) almost "rules out" a defect. Frequency doubling perimetry could not accurately categorize hemianopic, quadrantanopic, or glaucomatous defects.

Child↗
PubMed2001

Changes in the performances of filter media during clogging and cleaning cycles.

The performance of two filter media used in industrial air cleaning were studied both in the initial state (new filter) and after a number of collection and pulse pressure cleaning cycles. The main difference between them is that one has anti-clogging properties and the other does not. The test aerosol is composed of alumina particles with a median volumetric diameter of 2.6 microm (MMAD=4.8 microm) generated at a concentration of 700 mg x m(-3). Filtration took place at a velocity of 2 cm x s(-1). Two parameters, namely pressure drop and efficiency, were monitored according to the collection and cleaning cycles. The comparison of the filtration efficiency of the two media and that of the corresponding industrial dust separator at the end of the cycles showed a close agreement. The separation efficiency calculated with a new medium (corresponding to initial switch-on of the installation) was low and increased very quickly during the cycles. Finally, a phenomenological model was developed to represent the increase in pressure drop of a filter medium after cleaning and was found to be in close agreement with the experimental values.

Equipment Failure Analysis↗
PubMed2001

An evaluation of physiological demands and comfort between the use of conventional and lightweight self-contained breathing apparatus.

The additional physiological strain associated with the use of self-contained breathing apparatus (SCBA) is mostly linked to the additional weight. Lightweight and conventional SCBA were assessed in a submaximal step test performed in full firekit (total weights 15 and 27 kg, respectively). Factors assessed were: comparative energy expenditure of the two sets, relationship between comparative energy expenditure and aerobic fitness and subjective discomfort. Measured variables were: oxygen consumption, heart rate, estimated VO2max and subjective discomfort (body part discomfort scale). The lightweight SCBA displayed a significant oxygen consumption benefit, which was independent of dynamic workrate and valued at 0.2561 min(-1). Mean heart rate responses were significantly lower with the light set. No relationship was found between comparative energy expenditure and aerobic fitness. The light set was rated as significantly more comfortable than the heavy. Further research is required to assess the extent of the energy consumption benefit in realistic fire suppression protocols and the contribution of ergonomic factors to the energy and comfort benefits.

Adult↗
PubMed2001

SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety.

SB-243213 (5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline hydrochloride) is a new, selective 5-hydroxytryptamine (5-HT)2C receptor inverse agonist. SB-243213 has high affinity for the human 5-HT2C receptor (pK(i) 9.37) and greater than a 100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and ion channels. In in vitro functional studies, SB-243213 acted as an inverse agonist at the human 5-HT2C receptor with a pK(b) of 9.8. In in vivo studies, SB-243213 was a potent inhibitor of central 5-HT2C receptor-mediated function in rats, blocking meta-chlorophenylpiperazine-induced hypolocomotion with an ID50 of 1.1 mg/kg p.o. and a long duration of action (>8 h). In rats, SB-243213 exhibited anxiolytic-like activity in both the social interaction and Geller-Seifter conflict tests. Importantly, unlike diazepam, chronic administration of SB-243213 did not result in the development of either tolerance to the anxiolytic-like effects or withdrawal anxiogenesis. Furthermore, in rodents, SB-243213 did not affect seizure threshold, did not increase body weight or induce catalepsy, but attenuated the haloperidol-induced catalepsy. SB-243213 did not affect amphetamine-, MK-801- or phencyclidine-induced hyperactivity. In conclusion, SB-243213 may possess an improved anxiolytic profile compared to benzodiazepines. SB-243213 also modulates dopaminergic transmission, lacks pro-psychotic properties and may have utility in the treatment of schizophrenia and motor disorders.

Animals↗
PubMed2001

[Spread of Enterobacteriaceae producing broad-spectrum beta-lactamase and the development of their incidence over a 16-month period in a university hospital center].

Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLE) constitute with methicillin-resistant Staphylococcus aureus the main multiresistant bacteria recovered in French hospitals. Our objectives were to evaluate these ESBLE diffusion in our teaching hospital and to follow their incidence during a 16-month period, whereas a control programme (barrier precautions) had been implemented in the beginning of 1999. This study was conducted in a teaching hospital containing 1800 beds, from February 1999 to May 2000. All ESBLE isolated in clinical or screening samples were included. Duplicates (same bacteria in the same patient) were excluded. The detection of the ESBL was performed with the double-disk diffusion test. Incidence densities were determined with their 95% confidence interval (CI95%). Their evolution by four-month period was evaluated with the chi-square test for trend. During the 16-month period, 229 ESBLE were isolated. The incidence was 0.35 per 1000 patient-days (PD) (CI95% = [0.30-0.40]) for the whole hospital. It was 0.47/1000 PD (CI95% = [0.38-0.56]) in medical wards, 0.29/1000 PD (CI95% = [0.20-0.38]) in surgical wards and 1.32/1000 PD (CI95% = [0.90-1.74]) in intensive care units. Enterobacter aerogenes strains represented more than 75% of all ESBLE, whereas Klebsiella pneumoniae stains represented only 8.6%. During the study, the incidence of ESBLE and the proportion of strains acquired in our hospital decreased significantly (p < 0.0001 and p < 0.001 respectively). Indeed, between the first eight-month period and the last one, the incidence of ESBLE acquired in our hospital decreased by 55%, whereas the incidence of imported strains increased slightly. This study shows that the diffusion of ESBLE concerns the entire hospital. The implementation of a control programme of the spread of multiresistant bacteria allowed us to reduce significantly the incidence of ESBLE. This incidence seemed to be stable for several months. The implementation of a policy which restricts antimicrobial use would allow us to complete the the efficacy of barrier precautions.

Academic Medical Centers↗
PubMed2001

Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2.

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis during development, but little is known about the factors that control its expression. We provide the first example of tissue specific loss of VEGF expression as a result of targeting a single gene, Cbfa1/Runx2. During endochondral bone formation, invasion of blood vessels into cartilage is associated with upregulation of VEGF in hypertrophic chondrocytes and increased expression of VEGF receptors in the perichondrium. This upregulation is lacking in Cbfa1 deficient mice, and cartilage angiogenesis does not occur. Finally, over-expression of Cbfa1 in fibroblasts induces an increase in their VEGF mRNA level and protein production by stimulating VEGF transcription. The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation.

3T3 Cells↗
PubMed2001

[Tension force in dynamic splints made of neoprene].

Dynamic splints are the most difficult ortheses to make. Unrestricted finger joint mobility is usually prevented by the size of their components. Ortheses made out of neoprene material have the advantage of being pliable and at the same time can be constructed as dynamic splints. Neoprene material elasticity allows conforming it into a tube that can be fitted over a finger, spreading uniform pressure. A traction slip can be cemented to the neoprene finger tube. With neoprene splints, lever arms are more efficient. Their tubular design applies and spreads traction and countertraction forces in all directions. Neoprene material's elasticity contributes in reducing edema formation as well as distributes forces applied to the finger over a large area. The risk of excessive pressure is the only drawback of an elastic tubular design, it may cause pain and tissue ischemia. A meticulous tailoring prevents this potential risk.

Biomechanical Phenomena↗
PubMed2001

A relationship between RP4 plasmid acquisition and phenotypic changes in Pseudomonas fluorescens R2fN.

The physiological behaviour of Pseudomonas fluorescens strain R2fN was compared to that of transconjugants [R2fN(RP4)], and two aggregation phenotypes were identified (Agr- and Agr+). Agr+ phenotype is characterized by the appearance of macroscopic aggregates when cells are growing in liquid media. Transconjugants exhibited Agr+ phenotype whereas wild type strain represented Agr-. Evidence is presented to support correlation between Agr+ phenotype acquisition and the presence of the broad-host range plasmid RP4 in strain R2fN. In addition, according to bacterial adherence to hydrocarbon test the transconjugant cells appeared to be very hydrophilic whereas wild type R2fN cells were hydrophobic.

Bacterial Adhesion↗
PubMed2001

A sequence and structural study of transmembrane helices.

A comparison is made between the distribution of residue preferences, three dimensional nearest neighbour contacts, preferred rotamers, helix-helix crossover angles and peptide bond angles in three sets of proteins: a non-redundant set of accurately determined globular protein structures, a set of four-helix bundle structures and a set of membrane protein structures. Residue preferences for the latter two sets may reflect overall helix stabilising propensities but may also highlight differences arising out of the contrasting nature of the solvent environments in these two cases. The results bear out the expectation that there may be differences between residue type preferences in membrane proteins and in water soluble globular proteins. For example, the beta-branched residue types valine and isoleucine are considerably more frequently encountered in membrane helices. Likewise, glycine and proline. residue types normally associated with 'helix-breaking' propensity are found to be relatively more common in membrane helices. Three dimensional nearest neighbour contacts along the helix, preferred rotamers, and peptide bond angles are very similar in the three sets of proteins as far as can be ascertained within the limits of the relatively low resolution of the membrane proteins dataset. Crossing angles for helices in the membrane protein set resemble the four helix bundle set more than the general non-redundant set, but in contrast to both sets they have smaller crossing angles consistent with the dual requirements for the helices to form a compact structure while having to span the membrane. In addition to the pairwise packing of helices we investigate their global packing and consider the question of helix supercoiling in helix bundle proteins.

Amino Acid Sequence↗
PubMed2001

Qualitative methodologies and community participation in examining reproductive experiences: the Harlem Birth Right Project.

OBJECTIVES: Racial disparities in health present a challenge to public health because of the complexity of interacting social forces. The Harlem Birth Right Project sought to improve understanding of these forces by using qualitative and community participatory methods. In this paper we 1) describe the process of qualitative inquiry and community involvement, 2) evaluate the impact of community participation, and 3) present a brief summary of the findings on social context as it relates to pregnancy outcomes of women in Harlem. METHODS: We operationalized the qualitative method by combining participant observation, longitudinal case studies, and focus groups. An ethnographic survey was used to verify and triangulate findings across methods of data collection. We involved the community in the design, implementation, and analysis by collaborating with community-based organizations, setting up a community advisory board, and the use of dialogue groups and community meetings. RESULTS: The use of qualitative methods and community partnership uncovered important aspects of the social context of women's lives that may not have emerged through traditional epidemiologic research. We found that pregnancy may serve as a catalyst to increase perception of the magnitude of preexisting social stressors. Several stressors and chronic strains associated with structural forces were identified. For example, the high percentage of households headed by women is seen as one consequence of larger structural forces. While social support networks serve as an important coping mechanism to buffer against the stress caused by these structural forces, the types of support women seek differs by social strata, and some strategies were identified as being substantially more effective than others. CONCLUSIONS: Qualitative and community participatory research can be successfully conducted to support public health goals and can derive important new information on the social context of women's lives.

Community Participation↗
PubMed2001

Resolution of cis-trans ambiguities between HLA-DRB1 alleles using single-strand conformation polymorphisms and sequencing.

DNA-based typing of HLA alleles occasionally results in the inability to assign a specific allele because of ambiguity in associating two or more polymorphisms to the same or to alternate homologs (cis/trans ambiguity). Since most individuals are heterozygous at a given HLA locus, the highest level of confidence in definition is obtained when the alleles are tested in isolation. By using single-strand conformation polymorphisms (SSCP) to separate heterozygous HLA-DRB1 alleles, followed by sequencing of separated conformers, we have achieved resolution of previously ambiguous assignments without the need for additional probes or primers.

Alleles↗
PubMed2001

Evaluation of amylase and lipase in the diagnosis of acute pancreatitis.

BACKGROUND: The diagnosis of acute pancreatitis relies heavily on a raised amylase. METHODS: In the present study patients were prospectively categorized, without knowledge of pancreatic enzyme levels, into acute pancreatitis (AP; n = 51), disease controls (n = 35), indeterminate as to pancreatitis (n = 189) or exclusions (non-pancreatitis diseases where amylase may be elevated; n = 53). RESULTS: Enzyme levels were analysed by receiver operator characteristics (ROC) curves, with specificity > 80%. Day 1 serum lipase gave the greatest diagnostic accuracy (area under ROC curve = 0.128; P = 0.041 vs serum amylase). At the calculated diagnostic threshold of 208 U/L, lipase gave a sensitivity of 67% and a specificity of 97%. Other diagnostic thresholds (day 1) were: serum total amylase, 176 U/L (ROC 0.104, sensitivity 45%, specificity 97%), urinary total amylase, 550 U/L (ROC 0.108, sensitivity 62%, specificity 97%) and serum pancreatic isoamylase, 41 U/L (ROC 0.107, sensitivity 63%, specificity 85%). At delayed diagnosis (3 days) no enzyme was superior to lipase. The combination of lipase and amylase did not increase diagnostic accuracy. CONCLUSION: Serum lipase is recommended for diagnosis of AP, both early and late in the disease. Although highly specific when elevated, all pancreatic enzymes have low sensitivity for diagnosis.

Acute Disease↗