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J Hanley

Publications and source records attributed to J Hanley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Carotenoid oxidation in photosystem II.

The oxidation of carotenoid upon illumination at low temperature has been studied in Mn-depleted photosystem II (PSII) using EPR and electronic absorption spectroscopy. Illumination of PSII at 20 K results in carotenoid cation radical (Car+*) formation in essentially all of the centers. When a sample which was preilluminated at 20 K was warmed in darkness to 120 K, Car+* was replaced by a chlorophyll cation radical. This suggests that carotenoid functions as an electron carrier between P680, the photooxidizable chlorophyll in PSII, and ChlZ, the monomeric chlorophyll which acts as a secondary electron donor under some conditions. By correlating with the absorption spectra at different temperatures, specific EPR signals from Car+* and ChlZ+* are distinguished in terms of their g-values and widths. When cytochrome b559 (Cyt b559) is prereduced, illumination at 20 K results in the oxidation of Cyt b559 without the prior formation of a stable Car+*. Although these results can be reconciled with a linear pathway, they are more straightforwardly explained in terms of a branched electron-transfer pathway, where Car is a direct electron donor to P680(+), while Cyt b559 and ChlZ are both capable of donating electrons to Car+*, and where the ChlZ donates electrons when Cyt b559 is oxidized prior to illumination. These results have significant repercussions on the current thinking concerning the protective role of the Cyt b559/ChlZ electron-transfer pathways and on structural models of PSII.

Carotenoids↗
PubMed1999

Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing.

Epidemiological studies show that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal cancer incidence. We measured the rate ratio for colorectal adenocarcinoma according to dosage and the timing of exposure by means of a case-control study, nested in a non-concurrent cohort linkage study, using the population of beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 as the source population. Four controls per case, matched on age and gender and alive when the case was diagnosed, were randomly selected. Dispensing rates, calculated over successive time periods, characterized NSAID exposure. We accrued 3844 cases of colon cancer and 1971 cases of rectal cancer. For colon cancer a significant trend towards a decreasing rate ratio was associated with increasing exposure during the 6 months preceding diagnosis (P-trend = 0.002). For both cancers, significant trends were associated with exposure 11-15 years before diagnosis (colon: P-trend = 0.01; rectum: P-trend = 0.0001). At the highest exposure levels the rate ratio for colon cancer was 0.57 (95% confidence interval (CI) 0.36-0.89); for rectal cancer it was 0.26 (95% CI 0.11-0.61). No protection was associated with exposure during other periods. The timing of NSAID use must be considered in planning intervention trials to prevent colorectal cancer. There may be a 10-year delay before any preventive effect will appear.

Aged↗
PubMed1999

The characteristics of false negative cervical smears--implications for the UK cervical cancer screening programme.

OBJECTIVE: To accurately determine whether there are any features of an abnormal cervical smear that predispose to the production of a false negative report, in order to gain insight into why false negative reports are issued, and to establish whether there are steps that can be taken to reduce them. DESIGN: A quantitative retrospective analysis using the AxioHOME microscope of the number, size, and spatial distribution of abnormal cells in a set of 50 slides comprising a mixture of false negative and true positive cervical smears. SETTING: Five different cytology laboratories in the United Kingdom. RESULTS: False negative smears were found to be quantitatively different from true positive smears. They contained significantly fewer abnormal cells (median number of abnormal cells for false negatives = 173, median number of abnormal cells for true positives = 1712; p < 0.004), and these were more likely to be unevenly distributed on the slide. It was possible to predict with a high degree of accuracy whether a smear was a false negative by analysing number and distribution alone (kappa = 0.57). CONCLUSIONS: False negatives are quantitatively different from true positive cervical smears. This has important implications for quality assurance in the UK cervical screening programme. More consideration needs to be given to the effectiveness of existing quality assurance measures, which need to be tailored to the preferential detection of this type of abnormal cervical smear.

Cell Count↗
PubMed1998

Spin-lattice relaxation of the phyllosemiquinone radical of photosystem I.

The spin-lattice relaxation time (T1) of the phyllosemiquinone anion radical, A1-, of the photosystem I (PSI) reaction center, were measured between 4.5 and 85 K by electron spin-echo spectroscopy. The selective removal of the iron-sulfur centers, FA, FB, and FX, from PSI allowed the measurement of the intrinsic T1 of the A1- radical. The temperature dependence of the intrinsic (T1)-1 for A1- was found to be approximately T1.3 +/- 0.1. The spin-lattice relaxation of the reduced form of iron-sulfur center FX was also measured at low temperatures, in FA/FB-depleted PSI membranes. It was found that the fast-relaxing FX center enhances the spin-lattice relaxation of the phyllosemiquinone due to dipolar coupling. The effect of the reduced forms of FA/FB on the T1 of the phyllosemiquinone was minor compared to the effect of FX. By analyzing the data with a dipolar model in the light of limitations imposed by other information present in the literature, the distance between the phyllosemiquinone and FX in PSI is estimated to be 14.8 +/- 4 A.

Benzoquinones↗
PubMed1998

A systematic survey of conserved histidines in the core subunits of Photosystem I by site-directed mutagenesis reveals the likely axial ligands of P700.

The Photosystem I complex catalyses the transfer of an electron from lumenal plastocyanin to stromal ferredoxin, using the energy of an absorbed photon. The initial photochemical event is the transfer of an electron from the excited state of P700, a pair of chlorophylls, to a monomer chlorophyll serving as the primary electron acceptor. We have performed a systematic survey of conserved histidines in the last six transmembrane segments of the related polytopic membrane proteins PsaA and PsaB in the green alga Chlamydomonas reinhardtii. These histidines, which are present in analogous positions in both proteins, were changed to glutamine or leucine by site-directed mutagenesis. Double mutants in which both histidines had been changed to glutamine were screened for changes in the characteristics of P700 using electron paramagnetic resonance, Fourier transform infrared and visible spectroscopy. Only mutations in the histidines of helix 10 (PsaA-His676 and PsaB-His656) resulted in changes in spectroscopic properties of P700, leading us to conclude that these histidines are most likely the axial ligands to the P700 chlorophylls.

Animals↗
PubMed1998

Proxy use of the Canadian SF-36 in rating health status of the disabled elderly.

Professionals have often depended on proxies to assess health status of elderly individuals unable to provide this information. This study set out to estimate agreement between elderly subjects and their proxies on perceptions of health status, when patients were inpatients in a rehabilitation setting or outpatients in a day hospital, and to determine if there were overestimations or underestimations by proxies. Eighty-three consenting elderly patients living in Montreal, Canada, completed a generic health-status questionnaire, the SF-36, and named a significant other and a health care provider who knew them well. These individuals completed the same questionnaire on behalf of the patients. Agreement between patient and proxy was assessed pairwise (patient/health professional and patient/significant other) using intraclass correlation coefficients. The possibility of a biased rating by type of proxy was determined via paired t-tests. When concordance within respondent pairs was examined, results indicated only poor to moderate agreement regardless of setting and type of proxy for all scales. A trend toward underestimating by proxies was found. Proxy completion of health status questionnaires did not provide similar information, but these preliminary findings need replication.

Aged↗
PubMed1998

Prediction of cirrhosis in patients with chronic hepatitis C infection by artificial neural network analysis of virus and clinical factors.

The diagnosis of cirrhosis in patients with hepatitis C virus (HCV) infection is currently made using a liver biopsy. In this study we have trained and validated artificial neural networks (ANN) with routine clinical host and viral parameters to predict the presence or absence of cirrhosis in patients with chronic HCV infection and assessed and interpreted the role of the different inputs on the ANN classification. Fifteen routine clinical and virological factors were collated from 112 patients who were HCV RNA positive by reverse transcriptase-polymerase chain reaction (RT-PCR). Standard and Ward-type feed-forward fully-connected ANN analyses were carried out both by training the networks with data from 82 patients and subsequently testing with data from 30 patients plus performing leave-one-out tests for the whole patient data set. The ANN results were also compared with those from multiple logistic regression. The performance of both ANN methods was superior compared with the logistic regression. The best performance was obtained with the Ward-type ANNs resulting in a sensitivity of 92% and a specificity of 98.9% together with a predictive value of a positive test of 95% and a predictive value of a negative test of 97% in the leave-one-out test. Hence, further validation of the ANN analysis is likely to provide a non-invasive test for diagnosing cirrhosis in HCV-infected patients.

Adult↗
PubMed1998

Controlling confounding when studying large pharmacoepidemiologic databases: a case study of the two-stage sampling design.

Large drug databases have been the source of interesting developments for pharmacoepidemiologic research, because they provide relatively accurate drug exposure histories. An important limitation of these databases is the lack of information on potential confounders. One solution, developed more than a decade ago but not widely used, is "two-stage sampling," in which stage 1 is the collection of information on drug exposure and outcomes, and stage 2 is the collection of confounder data on a subset of the stage 1 sample. The balanced design, wherein an equal number of individuals is selected from each drug exposure/disease category, is usually the most efficient strategy by which to select the stage 2 sample. We illustrate the efficiency of the balanced design in two-stage sampling using data from a provincial health organization and a simulation. We also evaluate the relative importance of factors affecting the precision of the effect estimate of the exposure of interest.

Case-Control Studies↗
PubMed1997

ESEEM study of the phyllosemiquinone radical A1.- in 14N- and 15N-labeled photosystem I.

The phyllosemiquinone radical of the photosystem I reaction center has been studied by electron spin echo envelope modulation (ESEEM) spectroscopy. A comparative analysis of ESEEM data of the semiquinone in 14N- and 15N-labeled PSI and numerical simulations demonstrate the existence of two protein nitrogen nuclei coupled to the semiquinone. One of the 14N couplings is characterized by a quadrupolar coupling constant e2qQ/4h of 0.77 MHz, an asymmetry parameter eta of 0.18, and a hyperfine coupling tensor with an almost pure isotropic hyperfine coupling, i.e. (Axx, Ayy, Azz) = (1.3, 1.3, 1.5 MHz). The second nitrogen coupling is characterized by a quadrupolar coupling constant e2qQ/4h of 0.45 MHz, an asymmetry parameter eta of 0.85, and a weak hyperfine coupling tensor with a dominant anisotropic part, i.e. (Axx, Ayy, Azz) = (-0.2, -0.2, 1.5 MHz). On the basis of a comparison of the 14N-ESEEM data with 14N-NQR and 14N-ESEEM data from the literature, the first coupled nitrogen is assigned to the indole nitrogen of a tryptophan residue. The coupling of the second nitrogen is much weaker and therefore more difficult to assign. However, the simulated spectrum best describes an amino nitrogen of a histidine, although the amide group of an asparagine or glutamine cannot be ruled out. The possible origins of teh nitrogen hyperfine coupling are discussed in terms of the amino acid residues thought to be close to the semiquinone in PSI.

Benzoquinones↗
PubMed1997

Two-stage sampling for etiologic studies. Sample size and power.

Preexisting computerized databases are potentially valuable sources of epidemiologic data. Since such databases are infrequently created specifically for etiologic research, data may be available for the exposure of interest and, through record linkage, for the endpoint of interest, but lacking for potential confounders. Because of the size of these databases, two-stage sampling is an efficient alternative to surveying the entire study population for confounder data. At stage 1, information on exposure and disease status is obtained for the entire study population. Confounder data are collected for probability-selected subsamples at stage 2. Logistic regression is performed on the stage 2 samples, with the parameter estimates and variances appropriately corrected to account for the stage 1 data. In this paper, the authors present methods for determining the required stage 2 sample size in the case of categorical exposure and confounding variables. Sample size tables, power curves, and a computer program have been produced to accommodate a binary exposure and a single binary confounder. With the increasing availability of preexisting yet incomplete databases, the potential for use of two-stage sampling will greatly increase in the future. This investigation provides a basis for estimating the number of participants to sample for the collection of confounder data at the second stage.

Case-Control Studies↗
PubMed1997

Orientation of the phylloquinone electron acceptor anion radical in photosystem I.

The photosynthetic reaction center of photosystem I (PS I) contains a phylloquinone molecule (A1) which acts as a transient electron acceptor. In PS I form the cyanobacterium Synechocystis PCC 6803 under reducing conditions, we have photoaccumulated an EPR signal assigned to the phylloquinone radical anion. The phylloquinone EPR spectrum has been studied in oriented multilayers of PS I using EPR at 9 GHz. In addition, the phyllosemiquinone spectrum has been obtained at 283 GHz using high-field, high-frequency EPR spectroscopy. From the orientation dependence of the spectrum at 9 GHz and the resolved g values obtained at 283 GHz, the phyllosemiquinone ring plane was determined to be almost perpendicular to the membrane (76 degrees) while the oxygen-oxygen (O-O) axis of the quinone was found to make an approximate 63 degrees angle to the membrane plane. The orientation of the ring plane is similar to that determined for the quinone electron acceptor (QA) in the purple bacterial reaction center, while the orientation of the O-O axis is significantly different. The new orientation information, when taken with data in the literature, allows the position of the phylloquinone in the reaction center to be better defined.

Anions↗
PubMed1997

Measurement of patient positioning errors in three-dimensional conformal radiotherapy of the prostate.

PURPOSE/OBJECTIVE: To determine the spatial distribution of setup errors for patients treated with six-field, three-dimensional (3D) conformal radiation therapy for prostate cancer. METHODS AND MATERIALS: Port films for 50 patients were analyzed retrospectively. The port films were digitized and compared, using image registration software, to simulator films (representing the ideal treatment position). Patient positioning uncertainty for a given setup was determined using port films from three projections, two obliques, and one lateral. A total of 1239 port films and 300 simulator films were analyzed for the study. Patient position was analyzed for out-of-plane rotations and time trends over the course of treatment. RESULTS: The distribution of systematic setup errors for the 50 patients, defined as the mean patient displacement for the treatment course, had a mean and standard deviation (SD) of (-0.1 +/- 1.9) mm, (0.4 +/- 1.4) mm, and (-0.3 +/- 1.3) mm in the mediolateral (ML), superior-inferior (SI) and anterior-posterior (AP) directions, and (-0.1 +/- 0.2) for rotational errors. The distribution of random setup errors about the mean approximated a normal distribution and the standard deviations for the population of patients in the ML, SI, and AP directions, were 2.0 mm, 1.7 mm, and 1.9 mm, respectively. The distribution of out-of-plane rotations had 1 SD of 0.9 degrees and 0.6 degrees about the SI and AP axes. Ten of the 50 patients demonstrated a statistically significant time trend in their setup position resulting in shifts ranging from 2 to 7 mm. CONCLUSIONS: The setup verification protocol appears to minimize systematic setup errors to a level that approaches the sensitivity of the image registration technique. The random day to day fluctuations, represented by the average values of the standard deviations, are minor in comparison to the currently used margins, which further emphasizes the effectiveness of this protocol in conjunction with the use of the immobilization device.

Analysis of Variance↗
PubMed1996

Mutagenesis of photosystem I in the region of the ferredoxin cross-linking site: modifications of positively charged amino acids.

The psaD gene isolated from the cyanobacterium Synechocystis sp. PCC 6803 has been mutated in the region encoding a cross-linking site for ferredoxin. A glucose tolerant strain of Synechocystis 6803 was first deleted for psaD, and the resulting PS-I was characterised by EPR and flash absorption spectroscopy. The major modification related to the absence of the PsaD subunit is the disappearance of the first order reduction of ferredoxin which is replaced by a second order reaction. Reconstitution of the deleted PS-I with the purified PsaD polypeptide restored 80% of the fast photoreduction of ferredoxin. The deletion of PsaD has no apparent effect on the main biochemical features of the resulting depleted PS-I complex, with the exception of minor modifications to the FA/FB centers. The deleted strain was transformed by a series of psaD genes mutated at three conserved residues, all located close to the ferredoxin cross-linking site. The resulting photosystem I complexes were extensively studied by flash absorption spectroscopy. Unexpectedly, the change of Lys 106 involved in the cross-linking of ferredoxin for an uncharged amino acid has almost no effect (mutation K106A). However, the functional consequences of more drastic substitutions of either Lys 106 or Arg 111 indicate a role for these two basic amino acids in the binding and submicrosecond reduction of ferredoxin. Various mutations of the unique His at position 97 show that this amino acid is involved in the increased affinity of PS-I for ferredoxin when the pH is lowered. This histidine could be central in regulating in vivo the rate of ferredoxin reduction as a precise sensor of the local proton concentration.

Amino Acids↗
PubMed1996

Investigation of a phase-only correlation technique for anatomical alignment of portal images in radiation therapy.

A new image registration algorithm based on phase-only correlation is applied to portal images in radiation therapy to detect translational shift. The phase-only correlation shows a sharp peak in the correlation distribution as compared to the broad peak computed from conventional correlation using fast Fourier transform. In this paper, the algorithm of phase-only correlation is described and its applicability and robustness are tested when applied to portal images used in clinical radiation oncology. The results achieved give evidence that the phase-only correlation will deliver an alternative approach for image registration and image comparison, that may be applicable in routine clinical practice.

Algorithms↗
PubMed1996

Exposure to varying levels of contaminants and symptoms among workers in two office buildings.

OBJECTIVES: We hypothesized that exposure to contaminants would be associated with symptoms reported by office workers. METHODS: In two mechanically ventilated office buildings in. Montreal, the outdoor air supply was manipulated for 6 weeks, while symptoms were reported and environmental parameters were measured at multiple sites. RESULTS: Contaminant concentrations varied considerably, in part related to experimental changes in outdoor air supply. Eye symptoms were reported with higher dust and with higher concentrations of nitrogen dioxide. Mucosal symptoms were increased with higher TVOCs, higher nitrogen dioxide, and higher total contaminant load. Systemic symptoms were associated with higher dust levels. CONCLUSIONS: Symptoms reported by the workers were associated with increased concentrations of several contaminants and a summary measure of all contaminants.

Air Pollution↗
PubMed1995

The effects of out-of-plane rotations on two dimensional portal image registration in conformal radiotherapy of the prostate.

PURPOSE: Rotations of the patient out of the image plane can significantly degrade the accuracy of two-dimensional (2D) image registration. This study determines the magnitude of the geometric errors introduced by 2D image registration as a result of out-of-plane rotations, and analyzes the dosimetric effects of these errors. METHODS AND MATERIALS: The magnitude of the errors introduced by 2D registration were determined by comparing orthogonal view portal images of a rotated phantom to simulator reference images of the same phantom without rotation. Dosimetric effects were calculated for three-dimensional (3D) conformal prostate treatments by applying the registration errors to patient treatment plans. The calculations were performed using a modified version of the dose calculation software used in our Cancer Center for 3D treatment planning based on computed tomography (CT). A method to detect out-of-plane rotations, specific to pelvic treatments, is introduced that uses the relative displacement of the centers of gravity of the acetabula in lateral images. RESULTS: The inherent uncertainty in the registration algorithm was 0.6 +/- 0.5 mm in translation and 0.7 +/- 0.8 degree in rotation within the image plane. For a 2 degrees out-of-plane rotation, the errors increase to 2.3 +/- 1.0 mm and 1.2 +/- 1.1 degrees. In some clinically realizable treatment scenarios it was observed that the errors introduced by the registration procedure could result in an overdosing of the rectal wall. The method to detect out-of-plane rotations was found to have an accuracy of better than 1 degree for rotations of less than 10 degrees. CONCLUSIONS: The errors introduced to the patient position by 2D image registration have dosimetrically significant consequences for out-of-plane rotations of 2 degrees or more. However, when used in conjunction with the method to detect out-of-plane rotations, 2D registration software was found to cause insignificant dose errors and, thus, become a more reliable and accurate clinical tool.

Humans↗
PubMed1994

The Ste-Justine Adolescent Idiopathic Scoliosis Cohort Study. Part I: Description of the study.

OBJECTIVES: This study determined the impact of adolescent idiopathic scoliosis (AIS) on health and well being in adulthood by comparing AIS subjects, more than 10 years after referral, to non-AIS subjects according to perceived health status, physical activity, fitness, reproductive health, respiratory condition, and back and neck pain. This paper describes the cohort, the design of the study, and response rates. STUDY DESIGN: The study was designed as a comparative retrospective cohort study. A total of 2,092 patients referred for AIS to Ste-Justine Hospital, Montreal, Quebec, between 1960 and 1979 were identified. A population-based control group was selected in 1989-90 by randomly telephoning persons in Quebec. The control group was approximately frequency-matched to the AIS cohort according to age group and broad geographic region of current residence. METHODS: Patients with adolescent idiopathic scoliosis were traced, and a self-administered questionnaire was sent by post in 1989 to subjects whose addresses were found. Identical questionnaires were sent to subjects in the control group. RESULTS: Seventy-one percent of the cohort (1,476 subjects) returned questionnaires in 1989. Subjects who did not respond to the questionnaires were similar to those who did complete the questionnaires on a number of key factors, except that lower response rates were observed for subjects with scoliotic curves under 20 degrees. The control group consisted of 1,755 subjects (55% response rate). It was similar to the general Quebec population and to the AIS cohort on a number of important sociodemographic factors. CONCLUSION: Comparisons on health outcomes between the two study groups should not be affected by differential patterns of selection or response.

Adolescent↗