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Biomedical subjects

J Bailey

Publications and source records attributed to J Bailey.

At least 37 records · Page 2Linked to original sources
PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗
PubMed2003

Ethnic variation in type of genital herpes simplex virus infection in a South London genitourinary medicine clinic.

The aims of this study were to investigate the prevalence of herpes simplex virus (HSV) types 1 and 2 in the study population and correlate the results with clinical and demographic details. Consecutive HSV isolates from 334 clinic attendees were typed by immunofluorescence. Patient information was collected from the case notes. Overall, HSV-1 was isolated from 48 and HSV-2 from 287 samples, respectively. There was no significant difference in isolation rates according to gender. However, 33% of white patients' isolates typed as HSV-1, while only 6% of the isolates from the black population were HSV-1 (P < 0.001). Initial infections were seen in 81% of HSV-1 infections and 48% of HSV-2 infections, respectively. A wide discrepancy was observed in the prevalence of HSV-1 and HSV-2 infections between the ethnic groups in this population, which was not explained in terms of gender or age. This may reflect different exposure to HSV-1 in childhood or different sexual practices. The increased prevalence in genital HSV-1 reported in recent studies was not seen in this population. However, the differing proportions of primary and first episode infections may reflect a changing epidemiology.

Antibodies, Viral↗
PubMed2003

Rapid screening of 2-[18F]-fluoro-2-deoxy-D-glucose infusions for volatile organic compound contaminants by solid phase microextraction with gas chromatography-selective ion monitoring mass spectrometry (SPME-GC-SIMMS).

A method compatible with radioactive samples, capable of detecting trace volatile components in a sample volume of ca. 1cm(3) of 2-[18F]-fluoro-2-deoxy-D-glucose solution is described. The approach, based on solid phase micro-extraction gas chromatography-mass spectrometry with a carboxen/polydimethylsiloxane based fibre, was optimised with respect to extraction time (10 min), extraction temperature (60 degrees C) and phase volume ratio (1). The analysis time, including extraction, was less than 20 min with linear responses for acetonitrile and ethanol over the ranges: 0.09-80 microg cm(-3) (22 degrees C, acetonitrile) and 0.78-79 microg cm(-3) (22 degrees C, ethanol). The detection limits were estimated to be ca. 0.78 microg cm(-3) for ethanol and 0.09 microg cm(-3) for acetonitrile. Stability studies indicated analyte losses of up to 75% over 24h and analysis of aged 2-[18F]FDG samples showed that levels of ethanol and acetonitrile were not less than 100 microg cm(-3), indicative of levels substantially greater than this in the original infusions given to human subjects.

Calibration↗
PubMed2001

A photolysis-triggered heme ligand switch in H93G myoglobin.

Resonance Raman spectroscopy and step-scan Fourier transform infrared (FTIR) spectroscopy have been used to identify the ligation state of ferrous heme iron for the H93G proximal cavity mutant of myoglobin in the absence of exogenous ligand on the proximal side. Preparation of the H93G mutant of myoglobin has been previously reported for a variety of axial ligands to the heme iron (e.g., substituted pyridines and imidazoles) [DePillis, G., Decatur, S. M., Barrick, D., and Boxer, S. G. (1994) J. Am. Chem. Soc. 116, 6981-6982]. The present study examines the ligation states of heme in preparations of the H93G myoglobin with no exogenous ligand. In the deoxy form of H93G, resonance Raman spectroscopic evidence shows water to be the axial (fifth) ligand to the deoxy heme iron. Analysis of the infrared C-O and Raman Fe-C stretching frequencies for the CO adduct indicates that it is six-coordinate with a histidine trans ligand. Following photolysis of CO, a time-dependent change in ligation is evident in both step-scan FTIR and saturation resonance Raman spectra, leading to the conclusion that a conformationally driven ligand switch exists in the H93G protein. In the absence of exogenous nitrogenous ligands, the CO trans effect stabilizes endogenous histidine ligation, while conformational strain favors the dissociation of histidine following photolysis of CO. The replacement of histidine by water in the five-coordinate complex is estimated to occur in < 5 micros. The results demonstrate that the H93G myoglobin cavity mutant has potential utility as a model system for studying the conformational energetics of ligand switching in heme proteins such as those observed in nitrite reductase, guanylyl cyclase, and possibly cytochrome c oxidase.

Animals↗
PubMed2001

Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes.

Ineffectual wound healing in hyperglycaemic patients suffering from diabetes mellitus is characterised by a reduction in capillary reformation (angiogenesis). Basic fibroblast growth factor (FGF-2) is secreted by fibroblasts, macrophages and in particular endothelial cells (EC) in response to tissue injury and is important in promotion of neovascularisation. Recently, glycation of FGF-2 has been shown to significantly reduce its activity in vitro. We have examined the kinetics of FGF-2 glycation and compared its ability with that of native FGF-2 to activate mitogenesis, capillary formation and associated signal transduction in bovine aortic EC (BAEC). FGF-2 was exposed to 0.25 M glucose-6-phosphate (G-6-P) for 24-72 h and the degree of glycation determined by matrix assisted laser desorption ionisation mass spectrometry. Native FGF-2 was heterogeneous with Mw in the range 15,153.6-17,903 Da. After 24 h incubation with G-6-P there was evidence of glycation, and the mass increase corresponded to addition of 2.7 mol of G-6-P residues; after 48 h, 4 mol sugar was added and this increased to 8.7 after 72 h. Dimerisation of FGF-2 was observed after 72 h of treatment. Induction of mitogenesis in BAEC was significantly reduced by 25%-40% after treatment for 48-96 h with glycated (24 h) FGF-2 (gFGF-2; 100 pg/ml-5 ng/ml; P < 0.05), whilst capillary tubule formation was significantly reduced by between 60% and 90% (100 pg/ml-1 ng/ml; P < 0.05) after 5 days compared to native FGF-2. Subsequent investigation of the signal transduction molecules associated with mitogenesis showed a reduction in FGF-2 induced tyrosine phosphorylated proteins of approximate Mw 20-150 kDa between 10 min and 24 h, in particular, mitogen activated protein kinase (MAPK)/early response kinase (ERK-1, ERK-2), after glycation. To determine the reason for reduced angiogenic activity of gFGF-2, we compared its binding characteristics to that of native FGF-2. Total binding of gFGF-2 to the cell surface was significantly reduced in BAEC analysed by FACS compared to native FGF-2 (P < 0.05). Further investigation using 125I-labelled differentially washed samples, demonstrated a significant reduction in gFGF-2 binding to the high affinity tyrosine kinase receptor (46%) compared to native FGF-2. In summary, glycation of FGF-2 in vitro occurs rapidly within 24 h in the presence of elevated levels of G-6-P. Glycation caused a significant reduction in the ability of FGF-2 to bind to the tyrosine kinase receptor and activate signal transduction pathways responsible for both mitogenesis and capillary formation in BAEC. These results could help to explain the mechanism behind impaired wound healing in patients with diabetes mellitus.

Animals↗
PubMed2001

Implementation and evaluation of local-level priority setting for stroke.

We aimed to develop and evaluate a prioritisation process to combine the evidence base with stakeholder involvement within a stroke programme for a Health Improvement Programme (HImP). Implementation involved: formation of a district stroke group (DSG); review of the evidence; survey of DSG members; survey of other key professionals; consensus within the DSG; consultation with local users of the service. Evaluation was through semi-structured interviews and documentary analysis. The process was accepted as appropriate and valuable by the majority of participants, and a district HImP implementation group allocated pound sterling 100 000 for stroke development as a result of this process. However, some felt that stroke itself had been an imposed, rather than an agreed, local priority. The priority setting process was not clear to all participants and change of personnel, particularly in the NHS trusts, led to some perceived lack of ownership. Professionals from secondary care participated, but later criticised the process when they felt that the priorities in the HImP could limit their ability to access money for other service developments. The user consultation days occurred too late to influence the 1999/2002 HImP. We have shown that it is possible to develop an approach that is broadly accepted by stakeholders and balance the evidence base with local ownership. The participation of stakeholders, clarity of procedures, local ownership and awareness of local politics are important in effective priority setting. The model developed will be of value in other settings.

Evidence-Based Medicine↗
PubMed2001

Axillary and tympanic membrane temperature recording in the preterm neonate: a comparative study.

STUDY AIMS: The aim of this study is to compare axillary temperature recordings with those of the tympanic membrane, in healthy preterm neonates, to ascertain whether there is any significant difference between the two recordings, in particular in relation to postnatal age, and if so to evaluate the clinical implications. RATIONALE: Immature thermoregulatory mechanisms, and small body size, mean preterm neonates are prone to temperature maintenance problems, and thermal stress is associated with increased morbidity and mortality. In order to ensure minimal handling, the ideal method of temperature recording would be rapid, painless and reproducible, and accurately reflect core temperature, whilst considering safety, comfort, ease of procedure and cost effectiveness. Recording of the tympanic membrane temperature is rapid and noninvasive, however, the accuracy of this method in preterm neonates has not been established. STUDY DESIGN: A comparative descriptive design was used, to describe differences in the recorded temperature in healthy preterm neonates, of gestational age of 27-37 weeks, related to temperature recording. METHOD: A second comparison was undertaken to establish difference in mean temperature recordings dependant on postnatal age of the baby in days. The sample included all babies fitting the selection criteria, admitted to the Neonatal Unit during the study period. Following approval by the local research ethics committee tympanic membrane and axillary temperatures were recorded consecutively for 7 days (n=154), using the Genius Model 3000A tympanic thermometer and a glass and mercury thermometer. RESULTS: A t-test demonstrated a statistically significant difference between the recordings (P < 0.05), tympanic membrane recordings being higher. However, analysis of variance indicated that this difference was not associated with postnatal age, and thus the presence of vernix in the auditory canal (P > 0.05). The findings were not, however, deemed clinically significant in that no change in care or treatment resulted from differences in temperature recordings. CONCLUSIONS: Whilst the findings cannot be applied to sick preterm neonate, it was concluded that tympanic membrane temperature recordings in healthy preterm neonates are safe, accurate, easy, and comfortable for the baby, and appropriate with this client group provided staff are trained in the technique.

Age Factors↗
PubMed2001

Antibody responses of cattle immunized with the Tf190 adhesin of Tritrichomonas foetus.

The antibody response patterns of cattle after subcutaneous and intranasal immunizations with adhesin Tf190 of Tritrichomonas foetus were investigated. Reactions of antibody from cattle parenterally immunized with Tf190 revealed antigen specificity and Tf190 sensitization in the majority of the animals, as determined by Western blotting. The results also demonstrated strong preimmune immunoglobulin G2 (IgG2) binding to T. foetus antigens not seen in IgG1 profiles. Subcutaneous injections of Tf190 resulted in significant (P < 0.05) increases in serum IgG1 and IgG2 titers over time, as determined by parasite specific enzyme-linked immunosorbent assay. Immune sera also significantly inhibited parasite adhesion to mammalian cell lines compared to the level of inhibition obtained with preimmune sera (P < 0.05). Intranasal immunization with Tf190 failed to produce measurable parasite-specific antibody in serum; however, this immunization route did result in significant (P < 0.05) increases in parasite-specific IgA titers in cervical mucus secretions from immunized animals that were more resistant to intravaginal challenge with T. foetus than controls. These results suggest that systemic immunization with Tf190 results in serum antibody production and antiparasitic adhesin antibodies. Additionally, the results of challenge experiments with intranasally immunized animals suggests that Tf190 primes protective immune responses that lead to lower rates of infection among these animals.

Adhesins, Bacterial↗
PubMed2001

US artifacts: effects on out-of-plane us images reconstructed from three-dimensional data sets.

Three-dimensional volumetric data sets of stacked ultrasonographic (US) scans were obtained in vitro and in vivo to investigate the effect of common US artifacts on cross-sectional images reconstructed out-of-plane to the plane of acquisition of these data sets. The appearance of the artifacts on the reconstructed images was different from that on the source images. Such artifacts have the potential to simulate pathologic abnormalities.

Artifacts↗
PubMed2001

Early experience with transmission of data from moving ambulances to improve the care of patients with myocardial infarction.

We conducted a feasibility study of a mobile unit capable of recording a 12-lead electrocardiogram (ECG) and transmitting it to a receiving hospital workstation. Two ambulances were equipped with the mobile unit and the ECGs recorded were compared with standard ECGs recorded on the hospital ward after admission. In six months, 62 patients participated in the study. The ambulance crew transmitted messages to the coronary care unit for 56 patients. Thirty-five patients were directed to the coronary care unit, four were directed to the emergency department as no beds were available and then transferred to the coronary care unit later, and the remaining 23 were directed to the emergency department. Comparative hospital and mobile ECGs were available for 31 patients. Although the mobile unit recorded smaller R- and S-wave deflections than on the standard hospital ECGs, the medical and nursing staff were able to differentiate between normal and abnormal tracings. The mobile unit may be useful to triage patients with chest pain before they reach hospital.

Ambulances↗
PubMed2001

Colonic mucosal prostaglandin E2 and cyclooxygenase expression before and after low aspirin doses in subjects at high risk or at normal risk for colorectal cancer.

UNLABELLED: Development of potential cancer chemopreventive drugs involves the systematic evaluation of these drugs in preliminary Phase I and II studies in human beings to identify the optimal drug dose, drug toxicity, and surrogate end point biomarker modulation. OBJECTIVES: We tested the hypothesis that aspirin, at a single, once-daily 81-mg dose, will reduce colonic mucosal concentration of prostaglandin estradiol (E2) in individuals at high risk for colorectal cancer development similar to our prior observations in a young normal-risk population. METHODS: Aspirin was administered at a dose of 81 mg once daily for 28 days in a cohort of 92 matched high-risk and normal-risk colorectal cancer subjects. Prostaglandin E2 and cyclooxygenase expression were assayed from distal sigmoid biopsies from all of the subjects before and after treatment. RESULTS: The mean prostaglandin E2 for normal-risk subjects before aspirin treatment was 11.3 +/- 1.7 pg/microg (mean +/- SE) tissue protein and after aspirin treatment was 4.9 +/- 0.91 pg/microg tissue protein (P < 0.0001). In high-risk subjects, mean pretreatment prostaglandin E2 was 14.4 +/- 1.7 pg/microg tissue protein and after aspirin treatment was 4.7 +/- 0.70 pg/microg tissue protein (P < 0.0001). Aspirin treatment did not alter cyclooxygenase-1 protein expression. CONCLUSIONS: Aspirin treatment at a dose of 81 mg reduces colorectal mucosal prostaglandin E2 concentration after 28 daily doses. Risk for colorectal carcinoma did not modify colorectal mucosal baseline or post-aspirin prostaglandin E2, or cyclooxygenase expression. Colorectal mucosal prostaglandin concentration may be used as a "drug-effect surrogate biomarker," that is, a surrogate to assess sufficient delivery and tissue effect of a chemopreventive agent.

Adult↗
PubMed2001

An outbreak of viral gastro-enteritis at a charity function.

One hundred and thirty-eight people of 431 who attended a charity function fell ill with gastro-enteritis mainly between 12 and 72 hours later. Three people were ill at the event, and a further three became ill within two hours of the event. A cohort study undertaken using a postal questionnaire showed that illness was statistically associated with having eaten cream, mints, or profiteroles. The duration of illness ranged from two to 120 hours, with a median of 48 hours. Twenty-three of the cases sent a stool sample to the laboratory. Six of these were taken to the laboratory within three days of the onset of illness and examined for bacteria before being sent for virological examination by electron microscopy (EM) and polymerase chain reaction (PCR). All six were positive for small round structured virus (SRSV) on PCR, and negative on EM. The illness was likely to have been transmitted both by foodborne transmission and person to person spread at the event.

Cohort Studies↗
PubMed2000

Temporal changes in collagen composition and metabolism during rodent palatogenesis.

Cleft lip and palate is a common craniofacial malformation in man. The aetiology is multifactorial and not known. Since collagen is a major structural component of the developing palate, we studied its composition and metabolism during palate shelf formation and elevation in the rat. Palatal shelves were harvested at embryonic days (E) 15, 16 and 17 as well as post-partum. Palatal collagen increased threefold from E15 to E17 and tenfold from E17 to 5-day-old pups. Palatal calcification was seen in the main, post-partum. Collagen cross-linking, which may be important in shelf elevation and union, varied. The concentration of hydroxylysyl-pyridinolone cross-links was greatest prior to shelf elevation, declining thereafter. Similarly, the highest concentration of dihydroxylysinononorleucine was seen at E16 and this supports the concept of a compliant mesenchymal shelf responding to an intrinsic elevating force. We then determined if enzymes responsible for matrix degradation, matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMPs) altered over the same time periods. MMP-2, and TIMP-1 and TIMP-2 were identified by gelatin zymography and reverse zymography, respectively. MMP-3 activity was determined with a fluorogenic substrate assay. TIMP-1, TIMP-2 and MMP-3 levels remained constant from E15 to E17. The MMP-2 levels showed a significant elevation from E15 to E16 and E16 to E17. This suggests the regulation of extracellular matrix is likely to be of importance in palate morphogenesis.

Animals↗
PubMed2000

Direct reversal of DNA damage by mutant methyltransferase protein protects mice against dose-intensified chemotherapy and leads to in vivo selection of hematopoietic stem cells.

Direct reversal of O6 adducts caused by chemotherapy agents is accomplished in mammalian cells by the protein O6-methylguanine DNA methyltransferase (MGMT). Some tumors overexpress MGMT and are resistant to alkylator therapy. One future approach to treatment of these tumors may rely on concurrent pharmacological depletion of tumor MGMT with O6-benzylguanine (6-BG) and protection of sensitive tissues, such as hematopoietic stem and progenitor cells, using genetic modification with 6-BG-resistant MGMT mutants. We have used retroviral-mediated gene transfer to transduce murine hematopoietic bone marrow cells with MGMT point mutants showing resistance to 6-BG depletion in vitro. These mutants include proline to alanine and proline to lysine substitutions at the 140 position (P140A and P140K, respectively), which show 40- and 1000-fold resistance to 6-BG compared with wild-type (WT) MGMT. Lethally irradiated mice were reconstituted with murine stem cells transduced with murine stem cell virus retrovirus expressing each mutant, WT MGMT, or mock-infected cells and then treated with a combination of 30 mg/kg 6-BG and 10 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or with 40 mg/kg BCNU alone. Compared with mice treated with BCNU alone, significant myeloid toxicity and death occurred in mice reconstituted with mock-infected or WT MGMT (<0.1 probability of survival) or the P140A mutant (0.13 probability of survival) MGMT cDNAs. In contrast, after an initial period of mild cytopenia, mice reconstituted with the P140K mutant (0.83 probability of survival) recovered nearly normal blood counts, even during continued treatment. Comparison of peripheral blood neutrophils after completion of 5 weekly treatments in these animals showed a direct correlation between the treatment and in vivo selection for progeny of transduced cells (pretreatment, approximately 8-12% transduced cells; no treatment, approximately 6% transduced cells; BCNU only, 51% transduced cells; 6-BG/BCNU, 93% transduced cells). To determine whether this selection occurred at the stem cell level, bone marrow from each treatment group was infused into secondary recipients. Whereas animals that received bone marrow from untreated animals reconstituted with 2% transduced cells, animals receiving marrow from 6-BG/BCNU-treated animals reconstituted with 94% transduced cells, demonstrating nearly complete selection for stem cells in the primary animals. Mice reconstituted with marrow from animals treated with BCNU only demonstrated 23% transduced cells, consistent with partial selection of stem cells in the primary mice. The levels of transduced cells also correlated with survival during a second round of intensive combination chemotherapy (probability of survival: 6-BG/BCNU, 1.0; BCNU alone, >0.70; no treatment, <0.1). These data demonstrate that mutant MGMT expressed in the bone marrow can protect mice from time- and dose-intensive chemotherapy and that the combination of 6-BG and BCNU leads to uniform selection of transduced stem cells in vivo in mice.

3T3 Cells↗
PubMed2000

Acquisition of hearing aids and assistive listening devices among the pediatric hearing-impaired population.

Sufficient access to health care is of concern to the indigent population in the US and to their health care providers. This study was undertaken to elucidate the rate of the follow-up among lower socioeconomic hearing-impaired pediatric patients who had received a recommendation for hearing aids and/or assistive listening devices. Our question was, would the families' financial situation have a negative effect on the acquisition of hearing aids and assistive listening devices? Fifty patients, age 0-18 years, who had been seen in our clinic over 2 years were evaluated via a telephone survey. The survey consisted of seven questions, including whether or not the devices or aids were obtained, what type was purchased, where the device was being used, and the child's apparent performance with the device. Eighty-two percent of our patients were on TennCare, a state mandated Medicaid HMO system. Two-thirds of these TennCare patients are at or below the poverty level and the remaining one-third is either disabled or uninsurable according to the Aid for Dependent Children (AFDC) with indeterminate income. In addition the TennCare organization did not cover hearing amplification equipment for these children. The study showed that the majority of the patients did follow-up as recommended. Furthermore, this equipment is easily obtainable for the pediatric indigent population due to financial resources available in the community outside the mandated Medicaid system.

Adolescent↗