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Biomedical subjects

C Patterson

Publications and source records attributed to C Patterson.

At least 19 recordsLinked to original sources
PubMed2005

Application of laser spectroscopy for measurement of exhaled ethane in patients with lung cancer.

There is increasing interest in ethane (C(2)H(6)) in exhaled breath as a non-invasive marker of oxidative stress (OS) and thereby a potential indicator of disease. However, the lack of real-time measurement techniques has limited progress in the field. Here we report on a novel Tunable Diode Laser Spectrometer (TDLS) applied to the analysis of exhaled ethane in patients with lung cancer. The patient group (n=52) comprised randomly selected patients presenting at a respiratory clinic. Of these, a sub-group (n=12) was subsequently diagnosed with lung cancer. An age-matched group (n=12) corresponding to the lung cancer group was taken from a larger control group of healthy adults (n=58). The concentration of ethane in a single exhaled breath sample collected from all subjects was later measured using the TDLS. This technique is capable of real-time analysis of samples with accuracy 0.1 parts per billion (ppb), over 10 times less than typical ambient levels in the northern hemisphere. After correcting for ambient background, ethane in the control group (26% smokers) ranged from 0 to 10.54 ppb (median of 1.9 ppb) while ethane in the lung cancer patients (42% smokers) ranged from 0 to 7.6 ppb (median of 0.7 ppb). Ethane among the non-lung cancer patients presenting for investigation of respiratory disease ranged from 0 to 25 ppb (median 1.45 ppb). We conclude that, while the TDLS proved effective for accurate and rapid sample analysis, there was no significant difference in exhaled ethane among any of the subject groups. Comments are made on the suitability of the technique for monitoring applications.

Aged↗
PubMed2005

Association study of detoxification genes in age related macular degeneration.

BACKGROUND/AIMS: Age related macular degeneration (AMD) is a complex disorder leading to loss of central vision, and identification of risk factors associated with susceptibility to AMD has been a key objective for ophthalmic genetics research for almost a decade. This association study has examined genetic polymorphisms in 12 candidate genes as possible risk factors for predisposition to the development of the exudative variant of AMD in a Northern Irish population. The choice of genes was based on their function in the breakdown of industrial pollutants, cigarette smoke, defence against oxidative stress, or involvement in the general ageing process. METHODS: Up to five single nucleotide polymorphisms (SNPs) were typed for CYP1A1, CYP1A2, CYP2E1, CYP2D6, EPHX1, MnSOD, AhR, NAT2, CAT, GPX1, PON1, and ADPRT1 by multiplex snapshot single base primer extension method. Genes showing high linkage disequilibrium (LD) between SNPs were analysed by haplotype analysis. Genes showing low LD were assessed using individual SNPs based on genotypes. RESULTS: After correction for number of genes/SNPs tested, no significant association with AMD was found although several genes merit further investigation. This study suggests that a coding SNP in EPHX1 (Y113H) may be important in AMD and supports a previous observation of an association with exudative AMD. In addition, haplotype analysis highlighted ADPRT1, CYP2D6, and AhR as worthy of further study. CONCLUSION: This study has identified a number of genes requiring further investigation including EPHX1, ADPRT1, CYP2D6, and AhR.

Aged↗
PubMed2004

Keratoconus: an analysis of corneal asymmetry.

BACKGROUND: Keratoconus, a non-inflammatory corneal ectasia, is reported to have bilateral involvement in over 90% of patients. The purpose of this study was to quantify the extent of asymmetry of disease at presentation to a regional corneal clinic. METHODS: Eighty three patients diagnosed at presentation, using a combination of videokeratography, slit lamp examination, and refractive findings were retrospectively selected. On this basis, 73 patients were designated as having evidence of keratoconus in both eyes. In order to quantify the degree of asymmetry between fellow eyes in these bilateral patients, intraclass correlation was calculated for best spectacle corrected visual acuity (BSCVA) and for 13 different topographical indices generated using videokeratography. In order to examine the link between each index and visual function, the intrapatient differences in each index were compared to the intrapatient differences in BSCVA using Pearson's correlation. RESULTS: BSCVA showed a high degree of asymmetry between fellow eyes with a correlation coefficient of r = 0.006. With the exception of area analysed, all of the topographical indices also showed disparity between paired eyes (r = 0.01 to r = 0.25). Pearson's analysis found that the intrapatient differences in the standard deviation of the power (SDP), average corneal power (ACP), central corneal power (K), as well as the composite keratoconus prediction index (KPI) inversely correlated with the intrapatient differences in best spectacle corrected acuity (r = -0.76,-0.75,-0.69, and -0.73 respectively). CONCLUSIONS: This study demonstrates, quantitatively, the asymmetry of disease found in patients at the point of initial diagnosis of keratoconus. It also suggests that increases in indices which reflect various aspects of corneal power as well as the composite index KPI correlate with a decrease in BSCVA.

Adolescent↗
PubMed2004

A multilevel analysis of socioeconomic (small area) differences in household food purchasing behaviour.

STUDY OBJECTIVE: To examine the association between area and individual level socioeconomic status (SES) and food purchasing behaviour. DESIGN: The sample comprised 1000 households and 50 small areas. Data were collected by face to face interview (66.4% response rate). SES was measured using a composite area index of disadvantage (mean 1026.8, SD = 95.2) and household income. Purchasing behaviour was scored as continuous indices ranging from 0 to 100 for three food types: fruits (mean 50.5, SD = 17.8), vegetables (61.8, 15.2), and grocery items (51.4, 17.6), with higher scores indicating purchasing patterns more consistent with dietary guideline recommendations. SETTING: Brisbane, Australia, 2000. PARTICIPANTS: Persons responsible for their household's food purchasing. MAIN RESULTS: Controlling for age, gender, and household income, a two standard deviation increase on the area SES measure was associated with a 2.01 unit increase on the fruit purchasing index (95% CI -0.49 to 4.50). The corresponding associations for vegetables and grocery foods were 0.60 (-1.36 to 2.56) and 0.94 (-1.35 to 3.23). Before controlling for household income, significant area level differences were found for each food, suggesting that clustering of household income within areas (a composition effect) accounted for the purchasing variability between them. CONCLUSIONS: Living in a socioeconomically advantaged area was associated with a tendency to purchase healthier food, however, the association was small in magnitude and the 95% CI for area SES included the null. Although urban areas in Brisbane are differentiated on the basis of their socioeconomic characteristics, it seems unlikely that where you live shapes your procurement of food over and above your personal characteristics.

Adult↗
PubMed2003

Clinical experience of galantamine in dementia: a series of case reports.

OBJECTIVE: To use case studies to add the benefit of personal experience with galantamine to published literature and to demonstrate the type of patients that may benefit from this treatment. METHODS: We describe eleven patients, aged 57-90 years, fulfilling the consensus diagnostic criteria for probable Alzheimer's disease, mixed dementia, vascular dementia, Lewy body dementia or Parkinson's dementia. All patients were treated with galantamine that may enhance cholinergic function in the brain by inhibiting acetylcholinesterase and potentiating the effects of acetylcholine at nicotinic acetylcholine receptors. Clinical features were rated according to eight assessment scales in old age psychiatry and additional information was obtained from family and other carers. In some cases caregiver distress was measured. RESULTS: All patients described showed a general improvement in cognition and neuropsychiatric symptoms, although observed improvements and effects were not always reflected by the results of formal assessments. Several patients became more independent, particularly in their activities of daily living, and treatment was felt to have helped maintain independence in their home environment, either alone or with their family or carers. One man continued in employment. Adverse events included nausea and vomiting. CONCLUSIONS: Outcomes in this case series indicate that galantamine is well tolerated and highlight aspects of the different side-effect profiles of the anticholinesterase inhibitors. Subjective benefits were not always apparent from objective measures. These case studies demonstrate the type of patients that may benefit from galantamine.

Aged↗
PubMed2002

Complementary therapy involvement of physicians: implications for practice and learning.

OBJECTIVE: We studied physicians' current and desired clinical role functions within the complementary health paradigm and their perceptions of the necessary educational programs to support them. DESIGN AND SETTING: A questionnaire to determine clinical activities within different complementary therapies was developed and mailed-out to 837 eligible physicians in Hamilton, Ontario, Canada, using a modified Dillman approach. RESULTS: The overall response rate to the mailed survey was 49.8% (417/837), with response rates of 50.2% (115/229) for family physicians and 49.7% (302/608) for specialists. The amount of interactions around complementary therapies between physicians, their patients and complementary therapists appears to be low. At the same time, there is a growing interest among physicians about complementary therapies, particularly with respect to developing their knowledge about efficacy and enhancing their skills in assessment and counselling. CONCLUSIONS: The differential levels of acceptance of different therapies by physicians will influence integration of complementary therapies in mainstream medicine.

Chi-Square Distribution↗
PubMed2002

Variability of Nt-proANP and C-ANP.

BACKGROUND: Natriuretic peptides are frequently measured in patients with chronic cardiac failure (CCF). We set out to compare the variability of atrial natriuretic peptide (C-ANP) and its precursor N-terminal pro-ANP (Nt-proANP) to decide which would be more suitable for routine use. METHODS: Ten males with compensated CCF (age range 62-76 years) were studied, with matched controls. Blood was withdrawn every 2 min for 90 min from a forearm vein, and plasma C-ANP and Nt-proANP were measured by radioimmunoassay. RESULTS: Levels were elevated in the patient group [C-ANP: median 268 (range 171-423) vs. 40 (28-56) ng L-1, P < 0.0002 Mann-Whitney U-test; Nt-proANP: 1955 (562-4451) vs. 621 (409-961) pmol L-1, P < 0.003]. A similar number of 'peaks' was observed in both groups with both peptides, about one every 10 min, and their relative height was similar in both groups. Variability was greater for C-ANP than for Nt-proANP in both patients [coefficient of variation of means 51 (range 36-70) vs. 3.6 (2.1-6.2)%, P < 0.01; sign test] and controls [65 (49-83) vs. 8.9 (4.7-13.5)%, P < 0.01]. CONCLUSION: Nt-proANP is less variable than C-ANP and hence more suited for diagnostic or prognostic use.

Aged↗
PubMed2002

Socioeconomic differences in food purchasing behaviour and suggested implications for diet-related health promotion.

BACKGROUND: The relationship between socioeconomic position (SEP) and diet has been examined mainly on the basis of food and nutrient intake. As a complement to this work, we focused on the socioeconomic patterning of food purchasing, as many educational dietary messages emphasize behaviours such as food choice when shopping. Also, the type of food people buy influences the quality of their nutrient intake. METHODS: A probability sample of households in Brisbane City, Australia (n = 1003, 66.4% response rate). Data were collected using face-to-face interviews. SEP was measured using education, occupation and household income. Food purchasing was examined on the basis of grocery items (including meat and chicken) and fruit and vegetables. RESULTS: Significant associations were found between each socioeconomic indicator and food purchasing. Persons from socioeconomically disadvantaged backgrounds were less likely to purchase grocery foods that were comparatively high in fibre and low in fat, salt and sugar. The least educated, those employed in blue-collar (manual) occupations and residents of low income households purchased fewer types of fruit and vegetables, and less regularly, than their higher status counterparts. CONCLUSIONS: Health promotion efforts aimed at narrowing socioeconomic differences in food purchasing need to be designed and implemented with an understanding of, and a sensitivity to, the barriers to nutritional improvement that difficult life circumstances can impose.

Australia↗
PubMed2002

Socioeconomic differences among Australian adults in consumption of fruit and vegetables and intakes of vitamins A, C and folate.

OBJECTIVE: To determine whether socioeconomic groups differ in their food intakes for fruit and vegetables, their consumption of fruit and vegetables dense in vitamin A, folate and vitamin C, and their nutrient intakes of vitamin C, folate and vitamin A. METHODS: The 1995 Australian National Nutrition Survey collected food intake data from 8883 adults aged 18-64 years using a 24-h dietary recall. Fruit and vegetables were measured as amount (g) consumed. Intakes of nutrients were estimated from the 24-h dietary recall data. Participants were categorized by whether or not they consumed fruit or vegetables high in vitamin A, folate and vitamin C. Gross annual household income was used to measure socioeconomic position. RESULTS: Participants from low-income households consumed a smaller quantity of fruit and vegetables. They were also less likely to consume fruit and vegetables high in vitamin C, folate and vitamin A. Consistent with these findings, men and women from disadvantaged socioeconomic groups had lower intakes of vitamin C and folate compared with their more affluent counterparts. These differences were small to moderate in magnitude. Vitamin A intakes were not significantly related to income. CONCLUSION: As well as promoting healthy dietary practices, nutrition-promotion strategies should target the nutrient intakes of lower socioeconomic groups. These programmes should focus on improving the quantity and choice of fruit and vegetables consumed by people from low-income households.

Adolescent↗
PubMed2001

Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling.

BACKGROUND: Molecular chaperones recognize nonnative proteins and orchestrate cellular folding processes in conjunction with regulatory cofactors. However, not every attempt to fold a protein is successful, and misfolded proteins can be directed to the cellular degradation machinery for destruction. Molecular mechanisms underlying the cooperation of molecular chaperones with the degradation machinery remain largely enigmatic so far. RESULTS: By characterizing the chaperone cofactors BAG-1 and CHIP, we gained insight into the cooperation of the molecular chaperones Hsc70 and Hsp70 with the ubiquitin/proteasome system, a major system for protein degradation in eukaryotic cells. The cofactor CHIP acts as a ubiquitin ligase in the ubiquitination of chaperone substrates such as the raf-1 protein kinase and the glucocorticoid hormone receptor. During targeting of signaling molecules to the proteasome, CHIP may cooperate with BAG-1, a ubiquitin domain protein previously shown to act as a coupling factor between Hsc/Hsp70 and the proteasome. BAG-1 directly interacts with CHIP; it accepts substrates from Hsc/Hsp70 and presents associated proteins to the CHIP ubiquitin conjugation machinery. Consequently, BAG-1 promotes CHIP-induced degradation of the glucocorticoid hormone receptor in vivo. CONCLUSIONS: The ubiquitin domain protein BAG-1 and the CHIP ubiquitin ligase can cooperate to shift the activity of the Hsc/Hsp70 chaperone system from protein folding to degradation. The chaperone cofactors thus act as key regulators to influence protein quality control.

Carrier Proteins↗
PubMed2001

CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation.

Proper folding of proteins (either newly synthesized or damaged in response to a stressful event) occurs in a highly regulated fashion. Cytosolic chaperones such as Hsc/Hsp70 are assisted by cofactors that modulate the folding machinery in a positive or negative manner. CHIP (carboxyl terminus of Hsc70-interacting protein) is such a cofactor that interacts with Hsc70 and, in general, attenuates its most well characterized functions. In addition, CHIP accelerates ubiquitin-dependent degradation of chaperone substrates. Using an in vitro ubiquitylation assay with recombinant proteins, we demonstrate that CHIP possesses intrinsic E3 ubiquitin ligase activity and promotes ubiquitylation. This activity is dependent on the carboxyl-terminal U-box. CHIP interacts functionally and physically with the stress-responsive ubiquitin-conjugating enzyme family UBCH5. Surprisingly, a major target of the ubiquitin ligase activity of CHIP is Hsc70 itself. CHIP ubiquitylates Hsc70, primarily with short, noncanonical multiubiquitin chains but has no appreciable effect on steady-state levels or half-life of this protein. This effect may have heretofore unanticipated consequences with regard to the chaperoning activities of Hsc70 or its ability to deliver substrates to the proteasome. These studies demonstrate that CHIP is a bona fide ubiquitin ligase and indicate that U-box-containing proteins may comprise a new family of E3s.

Animals↗
PubMed2001

Vezf1/DB1 is an endothelial cell-specific transcription factor that regulates expression of the endothelin-1 promoter.

Coordinated gene regulation within the vascular endothelium is required for normal cardiovascular patterning during development and for vascular homeostasis during adulthood, yet little is known about the mechanisms that regulate endothelial transcriptional events. Vascular endothelial zinc finger 1 (Vezf1)/DB1 is a recently identified zinc finger-containing protein that is expressed specifically within endothelial cells during development. In this report, we demonstrate that Vezf1/DB1 is a nuclear localizing protein that potently and specifically activates transcription mediated by the human endothelin-1 promoter, in a Tax-independent manner, in transient transfection assays. Using a combination of deletion mutagenesis and electrophoretic mobility shift assays, a novel Vezf1/DB1-responsive element was localized to a 6-base pair (bp) motif, ACCCCC, located 47 bp upstream of the endothelin-1 transcription start site. Recombinant Vezf1/DB1 also bound to this sequence, and a 2-bp mutation in this element abolished Vezf1/DB1 responsiveness by the endothelin-1 promoter. Vezf1/DB1 could be identified with a specific antibody in nuclear complexes from endothelial cells that bound to this element. Regulation of endothelin-1 promoter activity by Vezf1/DB1 provides a mechanism for endothelin-1 expression in the vascular endothelium during development and to maintain vascular tone; Vezf1/DB1 itself is a candidate transcription factor for modifying endothelial cell phenotypes in order to appropriately assemble and maintain the cardiovascular system.

3T3 Cells↗
PubMed2001

New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology.

Thrombin is a serine protease that potently activates platelets and catalyzes the conversion of fibrinogen to fibrin. Thrombin also exerts direct effects on vascular cells, such as smooth muscle cells, via interactions with members of the protease-activated receptor family. Evidence in several animal models implicates thrombin-mediated signaling events in the response to injury that typifies vascular lesion formation in atherosclerosis and restenosis. In this review, we examine the activation of protease-activated receptors by thrombin, the downstream signaling events mediated by these receptors, and the physiological role of thrombin in vascular cells and vascular disease.

Animals↗
PubMed2001

Cell cycle in vasculoproliferative diseases: potential interventions and routes of delivery.

Atherosclerosis and restenosis of epicardial vessels are among the greatest challenges facing the clinical cardiologist, and phenotypic modulation and proliferation of smooth muscle cells are major components of the vasculoproliferative response. Proliferation is regulated by the interplay of regulatory proteins at checkpoints in the cell cycle that alter cellular growth. Activation of the cell cycle and the genetic control of its progression are final common pathways in this process. Investigators have postulated that cell-cycle inhibition using drugs and genetic or physical methods has the potential to reverse or prevent the vasculoproliferative process. The current challenge is to translate in vitro data demonstrating the efficacy of cell-cycle inhibition to clinical trials. At present, the steps that must be taken to meet this goal are (1) to design methods of delivery of these agents to specific sites, (2) to identify appropriate cellular targets to elicit cell-cycle arrest, and (3) to improve the therapeutic ratio by minimizing potential side effects. This review discusses current concepts of the cell cycle, target-regulating mechanisms, and possible interventions in vasculoproliferative diseases. We also discuss ongoing clinical trials that use antiproliferative agents in the hope of limiting the course of these diseases, as well as the promise that antiproliferative therapy holds in the coming decade.

Animals↗
PubMed2001

Fourth ventricular injection of CART peptide inhibits short-term sucrose intake in rats.

Expression of CART (cocaine-amphetamine-regulated transcript) in the rat hypothalamus is modulated by nutritional status, and injection of synthetic CART peptide into the forebrain ventricular system suppresses food intake, indicating a possible role in hypothalamic control of energy homeostasis. Its recent identification in cell bodies and central terminals of vagal afferent neurons additionally suggests a role in brainstem mechanisms of meal termination and satiety. We demonstrate here that CART[55-102] (0.2 nmol) suppresses short-term sucrose intake and overnight chow intake in non-food-deprived rats even more when delivered into the fourth ventricle as compared to the lateral ventricle. At the threshold dose (0.02-0.08 nmol) no readily noticeable motor impairments were observed. The results are consistent, but do not prove a site of action within the brainstem, possibly in mediating vagal satiety signals at the level of the NTS.

Afferent Pathways↗