Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 37 records · Page 2Linked to original sources

PubMed2001

Periodontal health of London women during early pregnancy.

OBJECTIVES: A descriptive cross-sectional study to determine the severity of periodontal disease in early pregnancy and its relation to demographic variables in a South East London population. METHODS: 2,027 pregnant women attending Guy's Hospital for an ultrasound scan at 10 to 14 weeks gestation were assessed. Data were collected via questionnaire and periodontal examination, including plaque and bleeding scores, pocket probing depth and loss of attachment. RESULTS: Mean age was 29.8 years (sd 5.5). Of these, 61.8% were white, 28.5% black, and 9.7% of other ethnic group. A total of 15% reported smoking during pregnancy. The mean number of teeth present was 28 (sd 2) per subject, mean percentage of sites with plaque present was 60.5% (sd 22.6), mean pocket depth was 2.0 mm (sd 0.4), mean loss of attachment was 0.4 mm (sd 0.3), and the mean percentage of sites bleeding on probing was 20.2% (sd 16.3). Linear regression demonstrated that probing depth was related to age, ethnicity, socioeconomic status and plaque score but not to smoking whereas loss of attachment demonstrated relationships with age, smoking status and plaque score but not ethnicity or socioeconomic status. CONCLUSION: There was a relatively high proportion of subjects with deep periodontal pockets in this pregnant population compared to the Adult Dental Health Survey 1998 but with similar levels of loss of attachment and percentage of sites with plaque present. Several demographic factors were associated with the level of periodontal disease in this population.

Adult↗

PubMed2001

Fusion of the NUP98 gene with the LEDGF/p52 gene defines a recurrent acute myeloid leukemia translocation.

BACKGROUND: The NUP98 gene is involved in multiple rearrangements in haematological malignancy. The leukemic cells in an acute myeloid leukemia (AML) patient with a t(9;11)(p22;p15) were recently shown to have a fusion between the NUP98 gene and the LEDGF gene but it was not demonstrated that this fusion was recurrent in other leukaemia patients with the same translocation. RESULTS: We used RT-PCR to analyse the leukemic cells from an AML patient who presented with a cytogenetically identical translocation as the sole chromosomal abnormality. A NUP98-LEDGF fusion transcript was observed and confirmed by sequencing. The reciprocal transcript was also observed. The fusion transcript was not detectable during remission and recurred at relapse. The breakpoints in the NUP98 and LEDGF genes were different to those previously reported. The NUP98 breakpoint occurs in the intron between exons 8 and 9. It is the most 5' breakpoint reported in a translocation involving the NUP98 gene. All of the LEDGF gene is included in the fusion except for exon 1 which codes for the first 24 amino terminal amino acids. CONCLUSIONS: Our results show that fusion of the NUP98 and LEDGF genes is a new recurrent translocation in AML.

Acute Disease↗

PubMed2001

Is there synchronicity in nitrogen input and output fluxes at the Noland Divide Watershed, a small N-saturated forested catchment in the Great Smoky Mountains National Park?

High-elevation red spruce [Picea rubens Sarg.]-Fraser fir [Abies fraseri (Pursh.) Poir] forests in the Southern Appalachians currently receive large nitrogen (N) inputs via atmospheric deposition (30 kg N ha(-1) year(-1)) but have limited N retention capacity due to a combination of stand age, heavy fir mortality caused by exotic insect infestations, and numerous gaps caused by windfalls and ice storms. This study examined the magnitude and timing of the N fluxes into, through, and out of a small, first-order catchment in the Great Smoky Mountains National Park. It also examined the role of climatic conditions in causing interannual variations in the N output signal. About half of the atmospheric N input was exported annually in the streamwater, primarily as nitrate (NO3-N). While most incoming ammonium (NH4-N) was retained in the canopy and the forest floor, the NO3-N fluxes were very dynamic in space as well as in time. There was a clear decoupling between NO3-N input and output fluxes. Atmospheric N input was greatest in the growing season while largest NO3-N losses typically occurred in the dormant season. Also, as water passed through the various catchment compartments, the NO3-N flux declined below the canopy, increased in the upper soil due to internal N mineralization and nitrification, and declined again deeper in the mineral soil due to plant uptake and microbial processing. Temperature control on N production and hydrologic control on NO3-N leaching during the growing season likely caused the observed inter-annual variation in fall peak NO3-N concentrations and N discharge rates in the stream.

Altitude↗

PubMed2001

Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA.

OBJECTIVE: To assess the antiviral efficacy, safety and adherence in patients switched to an abacavir-containing nucleoside reverse transcriptase inhibitor (NRTI) regimen after long-term HIV-1 RNA suppression with a dual NRTI/protease inhibitor (PI) combination. METHODS: In an open-label, multicentre study, patients receiving 2NRTI plus PI for at least 6 months, with a history of undetectable plasma HIV-1 RNA since the initiation of therapy and plasma HIV-1 RNA < 50 copies/ml at screening, were randomly assigned to replace the PI with abacavir (n = 105) or continue the same treatment (n = 106). Clinical assessments included plasma HIV-1 RNA, chemistry, haematology, lymphocyte counts, and adverse event reports. Adherence to treatment was assessed by patient self-report. RESULTS: A significantly longer time to treatment failure was demonstrated in the abacavir arm compared with the PI arm (P = 0.03) while treatment failure was experienced by significantly more patients in the PI arm: 24 (23%) versus 12 (12%) (P = 0.03). Therapy-limiting toxicity led to treatment failure in eight versus 14 cases in the abacavir and PI arms, respectively, whereas virological rebound was the cause in four versus two cases. Significant reductions in cholesterol and non-fasting triglyceride plasma levels at 48 weeks were observed in the abacavir arm (P < 0.001 andP = 0.035, respectively). The number of patients reporting no difficulty in taking their therapy showed a marked increase from baseline in the abacavir arm. CONCLUSION: The replacement of PI by abacavir in a triple combination regimen following prolonged suppression of plasma HIV-1 RNA provides continued virological suppression, significant improvements in lipid abnormalities and enhanced ease of dosing.

Adult↗

PubMed2001

Fluorescence anisotropy: a method for early detection of Alzheimer beta-peptide (Abeta) aggregation.

Time-resolved anisotropy measurements (TRAMS) have been used to study the aggregation of the beta-amyloid (Abeta) peptide which is suspected of playing a central role in the pathogenesis of Alzheimer's Disease (AD). The experiments, which employ small quantities of fluorescently-labelled Abeta, in addition to the untagged peptide, have shown that the sensitive TRAMS technique detects the presence of preformed "seed" particles in freshly prepared solutions of Abeta. More importantly, as 100 microM solutions of Abeta containing tagged Abeta at a concentration level of either 0.5 or 1 microM are incubated, the TRAMS prove capable of detection of the peptide aggregation process through the appearance of a continuously increasing "residual anisotropy" within the time-resolved fluorescence data. The method detects Abeta aggregation in its earliest stages, well before complexation becomes apparent in more conventional methods such as the thioflavin T fluorescence assay. The TRAMS approach promises to provide a most attractive route for establishment of a high-throughput procedure for the early detection of the presence of amyloid aggregates in the screening of biological samples.

Alzheimer Disease↗

PubMed2001

alpha-Synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro.

Some rare inherited forms of Parkinson's disease (PD) are due to mutations in the gene encoding a 140-amino acid presynaptic protein called alpha-synuclein. In PD, and some other related disorders such as dementia with Lewy bodies, alpha-synuclein accumulates in the brain in the form of fibrillar aggregates, which are found inside the neuronal cytoplasmic inclusions known as Lewy bodies. By means of an electron spin resonance (ESR) spin trapping method, we show here that solutions of full-length alpha-synuclein, and a synthetic peptide fragment of alpha-synuclein corresponding to residues 61-95 (the so-called non-Abeta component or NAC), both liberate hydroxyl radicals upon incubation in vitro followed by the addition of Fe(II). We did not observe this property for the related beta- and gamma-synucleins, which are not found in Lewy bodies, and are not linked genetically to any neurodegenerative disorder. There is abundant evidence for the involvement of free radicals and oxidative stress in the pathogenesis of nigral damage in PD. Our new data suggest that the fundamental molecular mechanism underlying this pathological process could be the production of hydrogen peroxide by alpha-synuclein.

Cell Death↗

PubMed2001

Prodomain processing of Asp1 (BACE2) is autocatalytic.

Generation of the amyloid peptide through proteolytic processing of the amyloid precursor protein by beta- and gamma-secretases is central to the etiology of Alzheimer's disease. The highly elusive beta-secretase was recently identified as a transmembrane aspartic proteinase, Asp2 (BACE). The Asp2 homolog Asp1 (BACE2/DRAP) has also been reported to exhibit beta-secretase cleavage of amyloid precursor protein. Most aspartic proteinases are generated as inactive proenzymes, requiring removal of the prodomain to generate active proteinase. Here we show that prodomain processing of Asp1 occurs between Leu(62) and Ala(63) and is autocatalytic. Asp1 cleaved a maltose-binding protein-Asp1 prodomain fusion protein and a synthetic peptide at this site. Mutation of one of the conserved catalytic aspartic acid residues in the active site of Asp1 to asparagine (D110N) abolished this cleavage. Mutation of P(1)' and P(2)' residues in the substrate to phenylalanine reduced cleavage at this site. Asp1 expressed in cells was the mature form, and prodomain processing occurred intramolecularly within the endoplasmic reticulum/early Golgi. Interestingly, a proportion of mature Asp1 was expressed on the cell surface. When full-length Asp1(D110N) was expressed in COS-7 cells, it was not processed, suggesting that no other proteinase can activate Asp1 in these cells.

Amino Acid Sequence↗

PubMed2001

Characterization of the glycosylation profiles of Alzheimer's beta -secretase protein Asp-2 expressed in a variety of cell lines.

Amyloid 39-42 beta -peptides are the main components of amyloid plaques found in the brain of Alzheimer's disease patients. Amyloid 39-42 beta-peptide is formed from amyloid precursor protein by the sequential action of beta- and gamma-secretases. Asp-2 is a transmembrane aspartic protease expressed in the brain, shown to have beta-secretase activity. Mature Asp-2 has four N-glycosylation sites. In this report we have characterized the carbohydrate structures in this glycoprotein expressed in three different cell lines, namely Chinese hamster ovary, CV-1 origin of SV40, and baculovirus-infected SF9 cells. Biantennary and triantennary oligosaccharides of the "complex" type were released from glycoprotein expressed in the mammalian cells, whereas mannose-rich glycans were identified from glycoprotein synthesized in the baculovirus-infected cells. Site-directed mutagenesis of the asparagine residues at amino acid positions 153, 172, 223, and 354 demonstrate that the protease activity of Asp-2 is dependent on its glycosylation.

Alzheimer Disease↗

PubMed2001

3-p-Toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran and 2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran do not act as surfactants or micelles when inhibiting the aggregation of beta-amyloid peptide.

The cmc and IC50 values of the beta-amyloid (Abeta) aggregation inhibitors, 3-p-toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 1, and 2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 2 have been determined. After comparison of the cmc data and biological data (IC50 values), we conclude that these active benzofurans do not act as surfactants or micelles at the concentration required to inhibit beta-amyloid-peptide aggregation.

Amyloid beta-Peptides↗

PubMed2001

The channel-forming protein proaerolysin remains a dimer at low concentrations in solution.

Proaerolysin, the proform of the channel-forming protein aerolysin, is secreted as a dimer by Aeromonas sp. The protein also exists as a dimer in the crystal, as well as in solution, at least at concentrations in the region of 500 microg/ml. Recently it has been argued that proaerolysin becomes monomeric at concentrations below 100 microg/ml and that only the monomeric form of the protoxin can bind to cell surface receptors (Fivaz, M., Velluz, M.-C., and van der Goot, F. G. (1999) J. Biol. Chem. 274, 37705-37708). Here we show, using non-denaturing polyacrylamide electrophoresis, chemical cross-linking, and analytical ultracentrifugation, that proaerolysin remains dimeric at the lowest concentrations of the protein that we measured (less than 5 microg/ml) and that the dimeric protoxin is quite capable of receptor binding.

Aeromonas↗

PubMed2001

Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism.

Most blood plasma proteins are glycosylated. These glycoproteins typically carry sialic acid-bearing sugar chains, which can modify the observed molecular weights and isoelectric points of those proteins during electrophoretic analyses. To explore changes in protein expression and glycosylation that occurred during great ape and human evolution, we subjected multiple blood plasma samples from all these species to high-resolution proteomic analysis. We found very few species-specific differences, indicating a remarkable degree of conservation of plasma protein expression and glycosylation during approximately 12 million years of evolution. A few lineage-specific differences in protein migration were noted among the great apes. The only obvious differences between humans and all great apes were an apparent decrease in transthyretin (prealbumin) and a change in haptoglobin isoforms (the latter was predictable from prior genetic studies). Quantitative studies of transthyretin in samples of blood plasma (synthesized primarily by the liver) and of cerebrospinal fluid (synthesized locally by the choroid plexus of the brain) confirmed approximately 2-fold higher levels in chimpanzees compared to humans. Since transthyretin binds thyroid hormones, we next compared plasma thyroid hormone parameters between humans and chimpanzees. The results indicate significant differences in the status of thyroid hormone metabolism, which represent the first known endocrine difference between these species. Notably, thyroid hormones are known to play major roles in the development, differentiation, and metabolism of many organs and tissues, including the brain and the cranium. Also, transthyretin is known to be the major carrier of thyroid hormone in the cerebrospinal fluid, likely regulating delivery of this hormone to the brain. A potential secondary difference in retinoid (vitamin A) metabolism is also noted. The implications of these findings for explaining unique features of human evolution are discussed.

Animals↗

PubMed2001

Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors.

The trp (transient receptor potential) gene encodes a Ca2+ channel responsible for the major component of the phospholipase C (PLC) mediated light response in Drosophila. In trp mutants, maintained light leads to response decay and temporary total loss of sensitivity (inactivation). Using genetically targeted PIP2-sensitive inward rectifier channels (Kir2.1) as biosensors, we provide evidence that trp decay reflects depletion of PIP2. Two independent mutations in the PIP2 recycling pathway (rdgB and cds) prevented recovery from inactivation. Abolishing Ca2+ influx in wild-type photoreceptors mimicked inactivation, while raising Ca2+ by blocking Na+/Ca2+ exchange prevented inactivation in trp. The results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC activity and facilitating PIP2 recycling. Without this feedback one photon appears sufficient to deplete the phosphoinositide pool of approximately 4 microvilli.

Animals↗

PubMed2001

Determination of the onset of crystallization of N1-2-(thiazolyl)sulfanilamide (sulfathiazole) by UV-Vis and calorimetry using an automated reaction platform; subsequent characterization of polymorphic forms using dispersive Raman spectroscopy.

This work describes the use of UV/visible spectroscopy and calorimetry to follow the onset of crystallization of a commercially available compound, N(1)-2-(thiazolyl)sulfanilamide (sulfathiazole), during crystallization reactions performed using an automated reaction platform. Sulfathiazole has been the subject of numerous publications through which considerable confusion about the morphic form is apparent. This work does not attempt to investigate exhaustively the polymorph issue, but rather to exploit the use of the HEL auto-MATE for monitoring the onset of crystal formation. Real-time calorimetry and UV-Vis spectroscopy are compared as tools for determining the onset of crystallization. Subsequently, differential scanning calorimetry, dispersive Raman, and infrared spectroscopy analysis serve to identify the crystal forms generated by the HEL auto-MATE. A solvent-anti-solvent matrix and several bench-top crystallization experiments were performed to supplement the investigation in terms of generating the desired polymorphs.

Ammonia↗

PubMed2001

Modulation of beta-amyloid production and fibrillization.

Alzheimer's disease (AD) is the most common cause of dementia in old age and presently affects an estimated 4 million people in the U.S.A. and 0.75 million people in the U.K. It is a relentless, degenerative brain disease, characterized by progressive cognitive impairment. In the final stages of the disease, patients are often bedridden, doubly incontinent and unable to speak or to recognize close relatives. Pathological changes of Alzheimer's disease include extensive neuronal loss and the presence of numerous neurofibrillary tangles and senile plaques in the brain. The senile plaques contain amyloid fibrils derived from a 39-43-amino-acid peptide referred to as beta-amyloid or A beta. The basic theory of the so-called 'amyloid hypothesis' is that the deposition of aggregated forms of A beta in the brain parenchyma triggers a pathological cascade of events that leads to neurofibrillary tangle formation, neuronal loss and the associated dementia [1]. Here we discuss progress towards the identification of inhibitors of A beta production and fibrillization.

Alzheimer Disease↗

PubMed2001

A need to try everything: patient participation in phase I trials.

RATIONALE: The area of phase I trials is fraught with ethical dilemmas and controversy. Most existing research focuses on issues of human rights and the informed consent procedure. Little attention has been given to patients' perceptions of participating in such trials. DESIGN: This paper describes a study using qualitative interviews and open-stem questionnaires to begin to explore patients' own perceptions of any benefits from participating in phase I trials. RESULTS: Findings suggest that for some patients, phase I trials fulfil a need to try everything in their fight against cancer. The study also suggests that being on treatment allows some patients to construct their lives meaningfully by providing a supportive structure and enabling hope. Implications for nursing practice and further research are discussed.

Adaptation, Psychological↗

PubMed2001

Drug-induced congestive heart failure in breast cancer survivors.

Breast cancer is the most common cancer among women in the United States. The administration of certain types of chemotherapy may put breast cancer survivors at risk for late effect drug-induced congestive heart failure (CHF). This case study discusses the diagnosis, management, and follow-up of drug-induced CHF in a woman with breast cancer. Discussions of risk factors and secondary and tertiary prevention of CHF caused by anthracycline chemotherapy agents are also included. Recognition of risk factors and symptoms of CHF is essential to minimize the morbidity and mortality that accompanies cardiac failure and is an important part of the comprehensive care of breast cancer patients. Because drug-induced CHF can occur years after the administration of the offending drug, primary care providers need to be aware of the risk of this disorder among breast cancer survivors under their care.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Out-of-hospital defibrillation with automated external defibrillators: postshock analysis should be delayed.

STUDY OBJECTIVE: The American Heart Association protocols for use of automated external defibrillators (AEDs) recommend that a rhythm analysis be done immediately after each defibrillation attempt. However, shock is often followed by electrical silence or marginally organized electrical activity before ventricular fibrillation (VF) or ventricular tachycardia (VT) recurs. The optimal timing of postshock analysis for identification of recurrent VF/VT is unknown. This study examines the time to recurrence of VF/VT after a defibrillation attempt with AED. METHODS: Over an 18-month period, all tapes from patients with out-of-hospital cardiac arrest who received shocks at least once with an AED were screened for recurrent VF/VT. All cases come from a single emergency medical services system providing basic life support, defibrillation with AED, and intubation with an esophageal-tracheal twin-lumen airway device (Combitube) for a population of 633,511 individuals. Pediatric and traumatic cases were excluded. When VF/VT recurred within 3 minutes of the defibrillation attempt, rhythm strips were printed and included in the study. Two cardiology fellows, blinded to the study objectives, measured the time from defibrillation to recurrent VF/VT for each strip. RESULTS: Over the study period, 222 tapes from 96 patients met the inclusion criteria. Only 44 (20%) occurrences of VF/VT had recurred within 6 seconds of defibrillation, 162 (73%) at 60 seconds, and 200 (90%) at 90 seconds. CONCLUSION: Eighty percent of VF/VT recurred more than 6 seconds after defibrillation and were missed when using current American Heart Association AED protocols. Subsequent analysis should be postponed until at least 30 seconds after defibrillation. Performing 30 seconds of chest compressions after defibrillation before subsequent AED rhythm analysis would increase AED identification of VF/VT to 52%.

Adult↗

PubMed2001

Ameloblastoma with mucous cell differentiation.

The finding of pale or clear cells in ameloblastomas is an exceptionally rare--but not unreported--phenomenon. The diagnostic implications of the presence of such cells in ameloblastomas are several and relate mainly to the question of histopathologic differential diagnosis. Although mucous cells in ameloblastomas are an accepted phenomenon, their occurrence has been reported only infrequently. This report describes a case of ameloblastoma exhibiting histopathologic evidence of focal mucous cell differentiation. Issues relating to the differential diagnosis of this lesion are discussed.

Adult↗