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Biomedical subjects

David Roberts

Publications and source records attributed to David Roberts.

At least 19 recordsLinked to original sources
PubMed2006

Identification of SmtB/ArsR cis elements and proteins in archaea using the Prokaryotic InterGenic Exploration Database (PIGED).

Microbial genome sequencing projects have revealed an apparently wide distribution of SmtB/ArsR metal-responsive transcriptional regulators among prokaryotes. Using a position-dependent weight matrix approach, prokaryotic genome sequences were screened for SmtB/ArsR DNA binding sites using data derived from intergenic sequences upstream of orthologous genes encoding these regulators. Sixty SmtB/ArsR operators linked to metal detoxification genes, including nine among various archaeal species, are predicted among 230 annotated and draft prokaryotic genome sequences. Independent multiple sequence alignments of putative operator sites and corresponding winged helix-turn-helix motifs define sequence signatures for the DNA binding activity of this SmtB/ArsR subfamily. Prediction of an archaeal SmtB/ArsR based upon these signature sequences is confirmed using purified Methanosarcina acetivorans C2A protein and electrophoretic mobility shift assays. Tools used in this study have been incorporated into a web application, the Prokaryotic InterGenic Exploration Database (PIGED; http://bioinformatics.uwp.edu/~PIGED/home.htm), facilitating comparable studies. Use of this tool and establishment of orthology based on DNA binding signatures holds promise for deciphering potential cellular roles of various archaeal winged helix-turn-helix transcriptional regulators.

Archaea↗
PubMed2005

Functional plasticity of human respiratory tract dendritic cells: GM-CSF enhances T(H)2 development.

BACKGROUND: Dendritic cells within the human respiratory mucosa (RTDCs) are proposed to initiate immune responses to foreign antigens. Their capacity to polarize T-cell responses, however, has not been investigated. OBJECTIVE: To compare RTDCs with peripheral blood dendritic cells (PBDCs) with regard to phenotype, cytokine production, capacity to polarize T-cell responses, and effects of exposure to the pleiotropic cytokine, GM-CSF. METHODS: CD1a(+) RTDCs and CD1c(+) PBDCs were purified from nasal turbinates of patients with nonatopic rhinitis and peripheral blood of healthy individuals, respectively. In some experiments, matched CD1c(+) RTDCs and PBDCs from patients with rhinitis were compared. The phenotype of DC was examined by flow cytometry and cytokine production by cytometric bead array. DCs were cocultured with allogeneic naive CD4(+) T cells, and cytokine production was determined by immunophenotyping, cytometric bead array, and ELISA. RESULTS: Both RTDCs and PBDCs exhibited an immature phenotype, but RTDCs expressed lower levels of MHC class II antigen. Cross-linking of CD40 on PBDCs, but not RTDCs, induced production of IL-12p70. In mixed lymphocyte cultures, RTDCs induced a T(H)1/T(H)2 profile, whereas PBDCs induced a T(H)1 profile. Exposure of RTDCs to GM-CSF induced a T(H)2 pattern of response in the mixed lymphocyte cultures. In contrast, exposure of PBDCs to GM-CSF promoted a T(H)1 response. CONCLUSION: This report emphasizes the importance of studying tissue-derived primary DCs, demonstrates functional plasticity of RTDCs, and implicates GM-CSF in amplifying the potential of RTDCs to initiate T(H)2 responses in the airways.

Adult↗
PubMed2005

Balance in single-limb stance in patients with anterior cruciate ligament injury: relation to knee laxity, proprioception, muscle strength, and subjective function.

BACKGROUND: It has been shown previously that an anterior cruciate ligament injury may affect postural control, measured by balance in single-limb stance. To our knowledge, no studies have reported the influence of measures of impairment on postural control after such an injury. PURPOSE: To assess the influence of knee laxity, proprioception, and muscle strength on balance in single-limb stance and to study the correlation between balance in single-limb stance and subjective estimation of extremity function. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 36 patients with a unilateral, nonoperated, nonacute anterior cruciate ligament injury were examined with regard to anterior knee laxity, proprioception, muscle strength, and stabilometry (amplitude and average speed of the center of pressure movements). Subjective estimation of extremity function was measured on a visual analog scale. RESULTS: The multiple regression analysis showed that high knee laxity values were associated with high amplitude values and low average speed. Poor proprioception and high muscle strength values were associated with low average speed among the women only. Low amplitude values correlated with better subjective function. CONCLUSION: Anterior knee laxity, proprioception, and muscle strength seem to play a role in maintaining balance in single-limb stance. Patients with low amplitude values in stabilometry were those with better subjective function.

Adolescent↗
PubMed2005

Which general practices have higher list inflation? An exploratory study.

BACKGROUND: There is a 7% discrepancy between English population estimates based on census figures and those based on the registered lists of GPs. GP income under the 2004 new contract will be based on registered patient populations but a national 'de-ghosting' exercise will ensue, aiming to eliminate list inflation. OBJECTIVE: To derive an estimate of the variation in list inflation between individual general practices. METHODS: Letters were sent to all men aged 20-29 years and registered at practices based in three inner city Primary Care Trusts (n = 42 712). Non respondents received one further reminder. Cards were issued to each GP listing non responders. Patients were deducted from the GP list after six months if the GP did not verify the address. RESULTS: 42 712 letters were sent. 33.5% of registered patients were eventually deducted from the GP list (deduction figures only available for 20-24 year old group). Practice level deduction rates ranged from 7-76%. Practices with higher deduction rates achieved lower vaccination rates for 2 year olds (Pearson's r = 20.25; P = 0.005) and cervical smear rates (Pearson's r = 20.18; P = 0.04); they also had cheaper prescribing costs per ASTRO-PU (Pearson's r = 20.20; P = 0.03). CONCLUSIONS: If these findings apply to the whole registered population, the national de-ghosting exercise is likely to result in large changes to the list size of some practices. Without correcting for list inflation, primary care research based on patient list size as the denominator may underestimate various measures of GP activity, particularly in deprived inner city areas. Resource allocation is also likely to be distorted by differences in list inflation.

Adult↗
PubMed2005

Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis.

BACKGROUND: Cysteinyl leukotrienes play a disease-regulating role in rhinosinusitis and asthma, particularly aspirin-sensitive disease. They act through 2 G-protein coupled receptors termed cysteinyl leukotriene type 1 receptor (cysLT 1 ) and cysteinyl leukotriene type 2 receptor (cysLT 2 ). We previously compared expression of cysLT 1 on mucosal leukocytes in patients with aspirin-sensitive and aspirin-tolerant rhinosinusitis. OBJECTIVE: To compare expression of cysLT 1 and cysLT 2 on leukocytes, mucus glands, and epithelium in 32 patients with chronic polypoid rhinosinusitis (21 aspirin-sensitive, 11 aspirin-tolerant) and 9 normal controls. METHODS: Total numbers of CD45 + leukocytes, percentages of these cells expressing cysLT 1 or cysLT 2 , and percentages of the total epithelial and glandular areas expressing cysLT 1 or cysLT 2 were measured in sections of nasal biopsies by using immunohistochemistry and image analysis. RESULTS: The percentages of mucosal CD45 + leukocytes expressing cysLT 1 were significantly ( P < .0001) elevated in the aspirin-sensitive but not the aspirin-tolerant patients compared with the controls. In contrast, the percentages of leukocytes expressing cysLT 2 did not differ significantly in the 3 groups. On epithelial and glandular cells, expression of cysLT 2 significantly exceeded that of cysLT 1 in both the patients with rhinosinusitis and the controls ( P < or = .004), although there was no significant difference in the expression of either receptor in the patients with rhinosinusitis (aspirin-sensitive or aspirin-tolerant) and the controls. CONCLUSION: Although cysLT 1 expression predominates on inflammatory leukocytes in patients with aspirin-sensitive rhinosinusitis, the effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. This has potentially important therapeutic implications.

Adult↗
PubMed2005

Physical disability contributes to caregiver stress in dementia caregivers.

BACKGROUND: Previous findings of studies on the impact of physical illness on caregiver health have been inconsistent. The authors wanted to determine whether physical disability, as determined by the SF-12 survey that provides information on both physical and mental health problems, contributes to caregiver stress. METHODS: The authors interviewed 91 primary caregivers (aged 38-85 years) of persons with dementia who had been referred by their family physicians for the first time for formal support services or memory evaluation. Caregivers completed the SF-12 version of the Medical Outcomes Study Short Form Health Survey that generates Mental Component Summary (MCS) and Physical Component Summary (PCS) scores and reported on caregiver stress and concurrent medical conditions and medications. RESULTS: Most caregivers reported stress (76.9%), having medical conditions (72.4%), or taking medications (67%). The MCS but not the PCS scores were significantly lower than community norms, indicating an excess of disability due to mental health problems. Nevertheless, 40.7% had PCS scores indicating some degree of physical disability. Using multiple logistic regression analysis, PCS scores but not the presence of medical problems were independently associated with caregiver stress. CONCLUSIONS: Chronic disability as assessed by SF-12 PCS scores is independently associated with caregiver stress. These data suggest that caregivers of persons with dementia should be assessed for disabling physical conditions and mental health problems. In addition, reducing the impact of physical disability could ameliorate caregiver stress.

Adult↗
PubMed2005

Facial plastic surgery planning using a 3D surface deformation tool.

The range of facial malformations that plastic surgeons are asked to alter is wide. Even a subtle deformity may strongly affect both the way a person perceives herself as well as her quality of life. Moreover, the changes achieved during craniofacial surgery often result in dramatic differences on the face of the patient. Consequently, both surgeons and patients would benefit from the visual approximation of the outcome of the operation provided by adequate three dimensional planning tools. In this paper we propose a three-dimensional texture-mapped surface deformation tool as part of a planning system for rhinoplasty.

Elasticity↗
PubMed2004

The effect of short-duration sub-maximal cycling on balance in single-limb stance in patients with anterior cruciate ligament injury: a cross-sectional study.

BACKGROUND: It has previously been shown that an anterior cruciate ligament (ACL) injury may lead to impaired postural control, and that the ability to maintain postural control is decreased by fatigue in healthy subjects. To our knowledge, no studies have reported the effect of fatigue on postural control in subjects with ACL injury. This study was aimed at examining the effect of fatigue on balance in single-limb stance in subjects with ACL injury, and to compare the effects, and the ability to maintain balance, with that of a control group of uninjured subjects. METHODS: Thirty-six patients with unilateral, non-operated, non-acute ACL injury, and 24 uninjured subjects were examined with stabilometry before (pre-exercise) and immediately after (post-exercise) short-duration, sub-maximal cycling. In addition, the post-exercise measurements were compared, to evaluate the instantaneous ability to maintain balance and any possible recovery. The amplitude and average speed of center of pressure movements were registered in the frontal and sagittal planes. The paired t-test was used for the intra-group comparisons, and the independent t-test for the inter-group comparisons, with Bonferroni correction for multiple comparisons. RESULTS: No differences were found in the effects of exercise between the patients and the controls. Analysis of the post-exercise measurements revealed greater effects or a tendency towards greater effects on the injured leg than in the control group. The average speed was lower among the patients than in the control group. CONCLUSIONS: The results of the present study showed no differences in the effects of exercise between the patients and the controls. However, the patients seemed to react differently regarding ability to maintain balance in single-limb stance directly after exercise than the control group. The lower average speed among the patients may be an expression of different neuromuscular adaptive strategies than in uninjured subjects.

Adolescent↗
PubMed2004

Effects of short-term cycling on knee joint proprioception in ACL-deficient patients.

It has previously been shown that knee injuries with ACL ruptures may lead to decreased proprioception and that exercise in a normal population, uninjured individuals, may reduce the proprioceptive ability. How proprioception is affected by exercise in patients with ACL deficiency has, to our knowledge, not been studied before. Knee joint proprioception was estimated in 36 patients, 18 males and 18 females, with ACL deficiency by measuring thresholds for detection of slow passive motion before and after a short period of exercise on an ergometer bicycle. In addition, the results were compared with a control group of 24 individuals of the same age. We found trends of enhanced proprioception towards extension in the patient group after cycling, but not in the control group. Towards flexion, both groups showed poorer proprioception after cycling. When difference scores of proprioceptive change in each group were compared, a trend towards different reaction upon cycling between the groups was seen in measurement towards extension from 20 degrees where the patients seemed to improve proprioception, which the controls did not. The results are not conclusive in this pilot study, but the possibility that ACL-deficient patients and controls may not react likewise to cycling, as regards their proprioceptive ability, is discussed.

Adolescent↗
PubMed2004

Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions.

Experimenta naturae, like the glucose-6-phosphate dehydrogenase deficiency, indicate that malaria parasites are highly susceptible to alterations in the redox equilibrium. This offers a great potential for the development of urgently required novel chemotherapeutic strategies. However, the relationship between the redox status of malarial parasites and that of their host is complex. In this review article we summarise the presently available knowledge on sources and detoxification pathways of reactive oxygen species in malaria parasite-infected red cells, on clinical aspects of redox metabolism and redox-related mechanisms of drug action as well as future prospects for drug development. As delineated below, alterations in redox status contribute to disease manifestation including sequestration, cerebral pathology, anaemia, respiratory distress, and placental malaria. Studying haemoglobinopathies, like thalassemias and sickle cell disease, and other red cell defects that provide protection against malaria allows insights into this fine balance of redox interactions. The host immune response to malaria involves phagocytosis as well as the production of nitric oxide and oxygen radicals that form part of the host defence system and also contribute to the pathology of the disease. Haemoglobin degradation by the malarial parasite produces the redox active by-products, free haem and H(2)O(2), conferring oxidative insult on the host cell. However, the parasite also supplies antioxidant moieties to the host and possesses an efficient enzymatic antioxidant defence system including glutathione- and thioredoxin-dependent proteins. Mechanistic and structural work on these enzymes might provide a basis for targeting the parasite. Indeed, a number of currently used drugs, especially the endoperoxide antimalarials, appear to act by increasing oxidant stress, and novel drugs such as peroxidic compounds and anthroquinones are being developed.

Animals↗
PubMed2004

Knee joint proprioception in ACL-deficient knees is related to cartilage injury, laxity and age: a retrospective study of 54 patients.

BACKGROUND: ACL-deficient patients have been found to have proprioceptive defects, but the cause of these defects has not been identified nor has the relationship between proprioception and subjective function, laxity, activity level and age been adequately studied. PATIENTS AND METHODS: Therefore, we analyzed proprioception, defined as the threshold to detect a slow passive motion (TTDPM), in relation to activity level, laxity, meniscal injuries, collateral ligament injuries, cartilage injuries, age and subjective function in 54 patients with a previous ACL rupture. We used multiple pair-wise correlation analyses, followed by a stepwise linear regression model. RESULTS: We found that poorer proprioception was related to lateral cartilage lesions, increased laxity and older age while a high activity level before injury was related with better proprioception after injury. The results also suggest a relation between proprioception and subjective knee function. INTERPRETATION: Anatomical injuy classification may need to be considered when discussing proprioceptive ability in patients with an ACL injury, laxity is related to proprioception and proprioception may decrease with age.

Adolescent↗
PubMed2004

Early genetic mechanisms underlying the inhibitory effects of endostatin and fumagillin on human endothelial cells.

A tumor needs to initiate angiogenesis in order to develop its own blood supply, to grow, to invade, and to spread. Angiogenesis, under normal conditions, is a tightly regulated balance between endogenous pro- and antiangiogenic factors. In this study, we investigated, by microarray analysis, the effects of two known antiangiogenic agents (endostatin and fumagillin) on the gene expression profiles of human umbilical vein endothelial cells (HUVEC) in order to elucidate pathways common to the effects of these agents. We observed a majority of gene expression changes within 1 and 2 h of treatment. The genes demonstrating these early expression changes are involved in cell proliferation, gene transcription, and a number have unknown functions. We selected four genes (DOC1, KLF4, TC-1, ID1) from the microarray profile that showed a similar pattern of expression for both of the antiangiogenic agents we tested. We then used small interfering RNAs (siRNA) in an attempt to better understand the role of these selected genes in the inhibitory activity of these agents. Because the gene expression changes occurred within 1 and 2 h of treatment, these genes might be involved in the initial pathways of angiogenesis inhibition.

Angiogenesis Inhibitors↗
PubMed2003

Balance in single-limb stance in healthy subjects--reliability of testing procedure and the effect of short-duration sub-maximal cycling.

BACKGROUND: To assess balance in single-limb stance, center of pressure movements can be registered by stabilometry with force platforms. This can be used for evaluation of injuries to the lower extremities. It is important to ensure that the assessment tools we use in the clinical setting and in research have minimal measurement error. Previous studies have shown that the ability to maintain standing balance is decreased by fatiguing exercise. There is, however, a need for further studies regarding possible effects of general exercise on balance in single-limb stance. The aims of this study were: 1) to assess the test-retest reliability of balance variables measured in single-limb stance on a force platform, and 2) to study the effect of exercise on balance in single-limb stance, in healthy subjects. METHODS: Forty-two individuals were examined for test-retest reliability, and 24 individuals were tested before (pre-exercise) and after (post-exercise) short-duration, sub-maximal cycling. Amplitude and average speed of center of pressure movements were registered in the frontal and sagittal planes. Mean difference between test and retest with 95% confidence interval, the intraclass correlation coefficient, and the Bland and Altman graphs with limits of agreement, were used as statistical methods for assessing test-retest reliability. The paired t-test was used for comparisons between pre- and post-exercise measurements. RESULTS: No difference was found between test and retest. The intraclass correlation coefficients ranged from 0.79 to 0.95 in all stabilometric variables except one. The limits of agreement revealed that small changes in an individual's performance cannot be detected. Higher values were found after cycling in three of the eight stabilometric variables. CONCLUSIONS: The absence of systematic variation and the high ICC values, indicate that the test is reliable for distinguishing among groups of subjects. However, relatively large differences in an individual's balance performance would be required to confidently state that a change is real. The higher values found after cycling, indicate compensatory mechanisms intended to maintain balance, or a decreased ability to maintain balance. It is recommended that average speed and DEV 10; the variables showing the best reliability and effects of exercise, be used in future studies.

Adult↗
PubMed2003

High defibrillation thresholds in transvenous biphasic implantable defibrillators: clinical predictors and prognostic implications.

The aim of this study was to identify clinical characteristics that distinguish patients with high DFTs and assess the prognostic implication. DFTs testing is a lengthy, potentially painful, and a hazardous process. Little information is available concerning the identification of patients with high DFT who undergo ICD surgery with transvenous leads and biphasic energy. This study analyzed 968 patients from two separate clinical studies who received a Medtronic cardioverter defibrillator from January 1995 through November 1999 and who had DFT testing measured by a binary search protocol. Compared to 865 patients with low defibrillation thresholds (< 18 J), the 103 patients with high thresholds (> or = 18 J) had a lower LVEF (34 +/- 16.7 vs 38.3 +/- 16.2%, P = 0.01), a worse NYHA functional class (23% Class I, 43% Class II, 29% Class III, 5% Class IV vs. 27% Class I, 55% Class II, 17% Class III, 1% Class IV, P < 0.0001), had bypass surgery less often (10.7 vs 27.5%, P < 0.0001), used amiodarone within the past 6 weeks (42.7 vs 27.2%, P = 0.002), and had a history of ventricular fibrillation more often (44.7 vs 33.1%, P = 0.02). Information concerning the number of shocks delivered was available in 345 (35%) patients; 23 were in the high DFT group and 322 were in the low DFT group. Twelve (52%) of the 23 patients in the high DFT arm received 3.6 +/- 2.7 shocks (median 2.5) and 106 (33%) of the 322 patients with low DFT received 4.9 +/- 9.5 shocks (median 2). After 6 months the mortality rate of patients with high thresholds was 11.7 vs 7.8% in patients with low thresholds (P = 0.118). Using a multivariate logistic regression model the significant predictors of death were older age, higher NYHA class, lower LVEF, amiodarone use, had a presenting arrhythmia of ventricular fibrillation and CHF but not initial high defibrillation thresholds. The study found that (1) 11% of patients have high DFTs, (2) clinical characteristics that identify high defibrillation thresholds are NYHA Class III, IV, low ejection fraction, no previous history of bypass surgery, prior amiodarone use preoperatively, and presenting with ventricular fibrillation, and (3) while high DFTs were associated with a more ill patient population, there was no difference in survival in a 6-month follow-up. Patients with a predicted low DFTs may be eligible for abbreviated ICD testing while high risk patients require formal testing.

Case-Control Studies↗