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Biomedical subjects

David Phillips

Publications and source records attributed to David Phillips.

30 records · Page 2Linked to original sources
PubMed2003

Development of a broadband picosecond infrared spectrometer and its incorporation into an existing ultrafast time-resolved resonance Raman, UV/visible, and fluorescence spectroscopic apparatus.

We have constructed a broadband ultrafast time-resolved infrared (TRIR) spectrometer and incorporated it into our existing time-resolved spectroscopy apparatus, thus creating a single instrument capable of performing the complementary techniques of femto-/picosecond time-resolved resonance Raman (TR3), fluorescence, and UV/visible/infrared transient absorption spectroscopy. The TRIR spectrometer employs broadband (150 fs, approximately 150 cm(-1) FWHM) mid-infrared probe and reference pulses (generated by difference frequency mixing of near-infrared pulses in type I AgGaS2), which are dispersed over two 64-element linear infrared array detectors (HgCdTe). These are coupled via custom-built data acquisition electronics to a personal computer for data processing. This data acquisition system performs signal handling on a shot-by-shot basis at the 1 kHz repetition rate of the pulsed laser system. The combination of real-time signal processing and the ability to normalize each probe and reference pulse has enabled us to achieve a high sensitivity on the order of deltaOD approximately 10(-4) - 10(-5) with 1 min of acquisition time. We present preliminary picosecond TRIR studies using this spectrometer and also demonstrate how a combination of TRIR and TR3 spectroscopy can provide key information for the full elucidation of a photochemical process.

DNA↗
PubMed2003

Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia.

OBJECTIVE: Activin is a growth and differentiation factor of many cell types, and has recently been implicated in inflammatory processes. Clinical data linking activin and its binding protein, follistatin (FS), are lacking. We measured serum levels of activin and FS in patients diagnosed with septicemia. PATIENTS AND MEASUREMENTS: Eight male and seven female patients of different ages, various forms of septicemia and different clinical outcome were investigated and compared with age- and sex-matched healthy controls. Serum concentrations of FS, activin, C-reactive protein (CRP) and blood leukocyte counts were determined during septicemia. RESULTS: The median of the maximum activin concentrations of septicemic patients was 3.9-fold higher than in age- and sex-matched healthy control subjects (P<0.01); the median of the maximum FS concentrations was 2.6-fold higher (P<0.01). The highest increase of activin in septicemic patients was approximately 15.8-fold, whereas FS increased by up to 13.2-fold above normal. FS, activin and CRP serum levels generally paralleled each other, but were not correlated with leukocyte counts or clinical outcome. CONCLUSIONS: Circulatory concentrations of activin and FS are elevated in patients diagnosed with septicemia, consistent with potential roles in the systemic inflammatory response.

Activins↗
PubMed2002

Peripherally metalated secoporphyrazines: a new generation of photoactive pigments.

Base-catalyzed cross condensation of dipropylmaleonitrile 1 with bis(dimethylamino)maleonitrile 2 in an equimolar ratio afforded the porphyrazines 3a, 4a, 5a, 6a and 7a. Subsequent demetalation of 5a with TFA followed by remetalation with Zn(OAc)(2) gave ligand 5c in good yield. Compound 5c was, in turn, selectively oxidized and further peripherally functionalized using Pt(PhCN)(2)Cl(2) and PdCl(2) to yield the novel seco solitaire porphyrazines 10a and 10b. The photophysical profiles of the seco solitaire porphyrazines 10a and 10b were evaluated by means of absorption, emission, and transient absorption spectroscopy. The new pigments 10a and 10b were found to be photochemically more stable than the solitaire complexes 3d and 3e and mediated the generation of singlet oxygen with quantum yields of 0.59 and 0.45, respectively.

Journal Article↗
PubMed2002

Imaging the environment of green fluorescent protein.

An emerging theme in cell biology is that cell surface receptors need to be considered as part of supramolecular complexes of proteins and lipids facilitating specific receptor conformations and distinct distributions, e.g., at the immunological synapse. Thus, a new goal is to develop bioimaging that not only locates proteins in live cells but can also probe their environment. Such a technique is demonstrated here using fluorescence lifetime imaging of green fluorescent protein (GFP). We first show, by time-correlated single-photon counting, that the fluorescence decay of GFP depends on the local refractive index. This is in agreement with the Strickler Berg formula, relating the Einstein A and B coefficients for absorption and spontaneous emission in molecules. We then quantitatively image, by wide-field time-gated fluorescence lifetime imaging, the refractive index of the environment of GFP. This novel approach paves the way for imaging the biophysical environment of specific GFP-tagged proteins in live cells.

Fluorescence↗
PubMed2002

Polymorphisms in the DNA repair enzyme XPD are associated with increased levels of PAH-DNA adducts in a case-control study of breast cancer.

We present findings on the associations between DNA adduct levels in breast tissue, risk of breast cancer, and polymorphisms in the DNA repair enzyme XPD. Breast cancer cases, benign breast disease (BBD) controls, and healthy controls were enrolled. Polycyclic aromatic hydrocarbons (PAH)-DNA adduct levels were measured by immunohistochemistry in breast tissue samples from cases and BBD controls. XPD polymorphisms at codons 312 and 751 was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis using white blood cell DNA. Neither of the polymorphisms were associated with case-control status, both in comparisons of cases and BBD controls, and cases and healthy controls. XPD polymorphisms at codons 312 and 751 were associated with higher levels of PAH-DNA in tumor tissue from breast cancer cases. Subjects with an Asp/Asn or Asn/Asn polymorphic genotype in codon 312 of XPD had elevated levels of PAH-DNA adducts compared to subjects with the Asp/Asp genotype (0.55 optical density (OD) v.s. 0.33 OD, p < 0.01). PAH-DNA adducts were associated with increasing copy number of the Gln allele for the codon 751 polymorphism (p for trend <0.01). Among subjects with the Asp/Asn or Asn/Asn genotype at codon 312, adduct levels were higher in tumor tissue compared to tissue from BBD controls (0.55 OD v.s. 0.36 OD, p = 0.003). Among subjects with the Gln/Gln genotype at codon 751 adduct levels were higher in tumor tissue compared to tissue from BBD controls (0.68 OD v.s. 0.40 OD, p = 0.01). The trend of increasing PAH-DNA adduct levels with either the Asn/Asn or Gln/Gln genotype was greater in tumor tissue than the trend in BBD control tissue.

Analysis of Variance↗
PubMed2002

The photobleaching of disulfonated aluminium phthalocyanine in microbial systems.

Front-face illumination spectroscopic techniques were used to study photobleaching of disulfonated aluminium phthalocyanine (AlPcS2) in the bacteria and yeast cells Escherichia coil, Porphyromonas gingivalis (Gram-negative bacteria), Streptococcus mutans (a Gram-positive bacterium), and the yeast Candida albicans. The photobleaching of AlPcS2 with the microbes studied is complex, involving reactive species generated by type I and type II processes with the rate dependent on the relative contributions of the different photobleaching mechanisms. The average rate of photobleaching of the AlPcS2 monomer in the presence of both E. coli and C. albicans increases as the fluence of the illumination source decreases. The effects of oxygen and sensitiser concentration on the rate of AlPcS2 photobleaching in these systems are also investigated.

Candida albicans↗
PubMed2002

Fluorescence lifetime measurements of disulfonated aluminium phthalocyanine in the presence of microbial cells.

The fluorescence lifetimes of disulfonated aluminium phthalocyanine (AlPcS2) in the presence of several different microbial cells are measured using the technique of time correlated single photon counting (TCSPC) employing front-face illumination. The microbes studied are: Escherichia coli, Porphyromonas gingivalis (Gram-negative bacteria), Streptococcus mutans (a Gram-positive bacterium), and the yeast Candida albicans. Complex fluorescence decays are observed when AlPcS2 is in the presence of these microbes; the fluorescence decay data can be fitted to a distribution of exponential lifetimes indicating that the AlPcS2 molecules experience a range of micro-environments The average fluorescence lifetimes of AlPcS2 in the presence of the microbes studied range from 4.85 to 5.95 ns, indicating differences in the cellular localisation of AlPcS2 with each of the microbes studied. These novel data are presented alongside a brief summary of existing AlPcS2 fluorescence lifetime data measured both in solution and in model biological systems.

Candida albicans↗
PubMed1998

Women users' views on the role and value of the practice nurse.

Aspects of the views of women aged 16-65 years on practice nurses in the primary health care setting are explored. The extent to which women consult practice nurses and the reasons for consultation are first identified. Women's assessments of practice nurses are then examined. The findings are from a 3-year research project where 1251 women completed a postal questionnaire and 70 women were interviewed in depth about issues concerning women's perceptions and experiences of both general practitioners (GPs) and practice nurses. Two thirds of the sample had consulted the practice nurse; 22% about specific women's health issues (including 13% for cervical screening). For most women's health issues, more women expressed a preference to be seen by a general practitioner (GP) than a practice nurse, except for breast examination among women aged 49 to 65 years where 57% expressed a preference for a practice nurse compared with 43% for a GP. Women gave similarly positive evaluations of the approachability of practice nurses and GPs. Positive views of practice nurses were high among older women, women who saw practice nurses in well-women clinics and women who saw practice nurses in relation to women's health issues. Among women who had not consulted a practice nurse, there was both a lack of awareness of the level and range of expertise of practice nurses, and a perception that in the main they offered only minor routine services. Health promotion, disease prevention and family planning do not appear to feature centrally in women's expectations of services provided by the practice nurse.

Journal Article↗
PubMed1998

Leaving paediatrics: the experience of service transition for young disabled people and their family carers.

In February 1994 the Department of Health commissioned the authors of this article to look into the transition between paediatric services and adult services for young physically disabled people in the Trent Region. In carrying out this study 87 young people or carers were interviewed in three districts, Sheffield, Rotherham and Chesterfield. One of the main findings of the research was that there was a great deal of confusion around the notion of 'transition' from one service to another. For many the experience was summed up by feelings of abandonment; while others felt unsure about the implications of moving between services. This is highlighted in the differing perspectives of carers and young people. In this paper we describe the transition procedure in one of the three districts, Sheffield, and highlight the gaps that allow young people to fall through the service's net.

Journal Article↗