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Biomedical subjects

N Rogers

Publications and source records attributed to N Rogers.

At least 19 recordsLinked to original sources
PubMed2003

Regulation of dendritic cell function by microbial stimuli.

Dendritic cells (DC) initiate T cell responses and produce cytokines and other molecules that can regulate the class adaptive immunity. It is increasingly clear that DC in vivo are in a "resting" state and require exogenous signals to transit into an "effector" state in which they can prime T cells. Much of this DC activation process appears to be regulated by infection. Exposure of murine DC to certain pathogens or their products triggers DC migration to T cell areas of secondary lymphoid tissues, improves MHC presentation and increases DC co-stimulatory potential. Pathogen recognition can also initiate cytokine production and/or condition DC to produce cytokines in response to subsequent T cell feedback signals delivered via CD40 and similar receptors. Recognition of pathogens by DC is largely dependent on Toll-like receptors (TLRs). Interestingly, mouse splenic CD8alpha+ and CDalpha-CD4- DC have the ability to produce either IL-12 p70 or IL-10 depending on the nature of the pathogen encountered. In contrast, CD4+ DC seem incapable of producing IL-12 p70. Thus, the nature of the pathogen can dictate the type of cytokine that is made by some DC subsets, allowing them to prime distinct types of immune responses. Overall, DC display significant plasticity in their ability to respond to infection and direct adaptive immunity.

Animals↗
PubMed2003

The development and evaluation of the UK national telepathology network.

AIMS: As technology advances and costs fall, it may be anticipated that soon every histopathologist will expect to be able to exchange electronic images with colleagues. Arguing that the value of a network increases as more people are connected, we sought to install a simple, low-cost telepathology system into any histopathology laboratory which requested it within the UK. METHODS AND RESULTS: We assumed that laboratories had microscopes, computers and internet access. We offered low-cost video cameras, video input cards, software and training to any histopathology department requesting installation, limited only by resources supplied by the UK government. We also established central servers and a website with 'help' files. After 1 year we studied system use and pathologists' opinions by circulating a questionnaire. Installations were completed in 35 laboratories; there are currently 66 registered users of the system, with 16 identified 'experts' covering most organ systems. Serious difficulties were caused by institutional firewalls and reluctance of local information technology (IT) staff to make changes to facilitate the installation or to help resolve subsequent network problems. After installation, many of the telepathology systems remain unused. Concerns were expressed about image quality, though mainly by pathologists who had not used the system for diagnostic work. The system remains available, but the level of use is low. CONCLUSIONS: This project has not achieved its aims. The reasons are complex, but mainly relate to human attitudes. Pathologists with excessive workloads were reluctant to use time to learn new skills which were not directed to reducing workload. IT staff did not perceive the project as part of their routine work. There were also numerous technological problems, but although image quality was cited by many, it was not a complaint of those who actively used the system. These problems have not been encountered by previous projects which involved small groups of committed enthusiasts.

Attitude of Health Personnel↗
PubMed2001

Comparison of pocket-computer memory aids for people with brain injury.

Two styles of pocket computer memory aid were compared as support for people who had sustained non-progressive, closed-head brain injury. A purpose-designed interface provided a diary with auditory alarms, a notebook and links between diary entries and specific notepages. One computer had a physical keyboard, the other did not. Twelve adult volunteers were loaned each computer for 2 months, with a 1 month gap between, in counterbalanced order. It was found that all participants could use the memory aids, and most (83%) found them useful. Little customizing was needed, but amount of use varied widely. Predictors of usage included use of other reminding systems before joining the project, and speed in calculator addition which may reflect working memory. High users preferred the computer with a physical keyboard; low users made more entries with the palm-size computer. These data highlight the need to distinguish ability to use from willingness to use.

Activities of Daily Living↗
PubMed2001

Resorbable mesh in the treatment of orbital floor fractures.

A variety of materials have been used to reconstruct defects of the orbital floor. Autogenous materials such as bone and cartilage have the obvious drawback of the necessary donor site, whereas alloplastic implants carry the potential risk of infection, particularly when in communication with the maxillary sinus. Consequently, there has been interest in the use of resorbable alloplastic material that acts as a barrier until completely degraded. In this series, a total of 12 patients with orbital defects larger than 1 cm2 were treated by the placement of a resorbable mesh plate of polyglycolic and polylactic acid (Lactosorb). Of the total of 12 patients treated, 3 were lost to follow-up. Of the remaining 9 patients, the mean follow-up was 6 months, with the longest follow-up being 15 months and the shortest 1 month. Two patients developed enophthalmos. In each case, this measured 2 mm using Hertel exophthalmometry, and was present in the early postoperative period (less than 1 month). The cause of the enophthalmos in both patients was found to be a technical error in placement of the mesh. One patient developed an inflammatory reaction along the infraorbital rim requiring implant removal. This occurred at 7 months. From the above series, it is concluded that resorbable mesh is an acceptable material for reconstruction of the orbital floor in selected patients. It is believed that larger floor defects are better suited for nonresorbable alloplastic reconstruction, and that placement of the mesh over the infraorbital rim is unnecessary and places the patient at risk for a local inflammatory reaction.

Absorbable Implants↗
PubMed2001

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

Appointments and Schedules↗
PubMed2000

Text entry on handheld computers by older users.

Small pocket computers offer great potential in workplaces where mobility is needed to collect data or access reference information while carrying out tasks such as maintenance or customer support. This paper reports on three studies examining the hypothesis that data entry by older workers is easier when the pocket computer has a physical keyboard, albeit a small one, rather than a touch-screen keyboard. Using a counter-balanced, within-subjects design the accuracy and speed with which adults over 55 years of age could make or modify short text entries was measured for both kinds of pocket computer. The keyboard computer was the Hewlett Packard 360LX (HP), but the touch-screen computers varied across studies (experiment 1: Apple Newton and PalmPilot; experiment 2: Philips Nino; experiment 3: Casio E10). All studies showed significant decrements in accuracy and speed when entering text via the touch-screen. Across studies, most participants preferred using the HP's small physical keyboard. Even after additional practice with the touch screen (experiments 2 and 3) many entries still contained errors. Experiment 3 showed that younger people were faster but not more accurate than older people at using the touch-screen keyboard. It is concluded that satisfactory text entry on palm-size computers awaits improvements to the touch-screen keyboard or alternative input methods such as handwriting or voice. Interface developments that assist older people typically benefit younger users too.

Aged↗
PubMed1999

Retinal function as a marker for cell membrane omega-3 fatty acid depletion in schizophrenia: a pilot study.

BACKGROUND: There is a growing body of evidence that abnormalities of the cell membrane, particularly depletion of n-3 essential fatty acids (EFA), are found in patients suffering from schizophrenia. These fatty acids particularly Docosohexaenoic acid (DHA) are found in particularly high concentrations in the photoreceptor cells of the retina and abnormalities of light sensitivity have been reported in patients with schizophrenia. Animal studies have demonstrated that reduced EFA levels are associated with changes in the electrophysiological response of the retina to light as measured by the electroretinogram (ERG). METHODS: We measured the ERG of 9 patients with schizophrenia and 9 age and sex matched control subjects. All but one of the patients was medicated. RESULTS: Schizophrenic subjects had significantly reduced a-wave amplitudes on the ERG when compared with control subjects and the a-wave amplitude was independent of the dose of antipsychotic agents being taken. The a-wave of the ERG is thought to reflect activity of the photoreceptor cells. CONCLUSIONS: These findings support the hypothesis that patients with schizophrenia have abnormalities of photoreceptor function, which may be a result of reduced levels of n-3 EFA in the cell membrane.

Adaptation, Ocular↗
PubMed1999

A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.

BACKGROUND: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). OBJECTIVE: To develop an equation to predict GFR from serum creatinine concentration and other factors. DESIGN: Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. PATIENTS: 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. METHODS: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. RESULTS: To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. CONCLUSION: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.

Age Factors↗
PubMed1999

Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology.

Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFNgamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFNgamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology.

Animals↗
PubMed1999

Tumor necrosis factor-alpha signals to the IFN-gamma receptor complex to increase Stat1alpha activation.

We describe a novel mechanism of signaling interaction through which tumor necrosis factor-alpha (TNF-alpha) treatment augments interferon-gamma (IFN-gamma)-induced Stat1alpha DNA-binding complexes and transcriptional activation of a Stat-binding element. In TNF-alpha-treated cells, IFN-gamma-induced phosphorylation of Jak2 kinase is increased, Jak2 kinase activity is enhanced, and genetic studies indicate that TNF-alpha requires Jak2 kinase activity to enhance Stat1alpha tyrosine phosphorylation. Increased Jak2 and Stat1alpha phosphorylation are observed within minutes of coexposure to TNF-alpha/IFN-gamma, suggesting a direct signaling interaction. IFN-gamma receptor chain 1 (IFNGR-1) tyrosine phosphorylation is markedly enhanced in cells treated with TNF-alpha/IFN-gamma without alteration in receptor levels. Thus, there exists a direct signaling interaction between TNF-alpha and IFN-gamma, independent of cooperating enhancer elements, that may be relevant for cytokine action during immune-mediated host defense and inflammatory processes.

DNA-Binding Proteins↗
PubMed1999

Urinary 6-sulfatoxymelatonin excretion and aging: new results and a critical review of the literature.

The apparent age-related decline in melatonin production has been thought to continue in a secular manner across the lifespan. While it is clear that melatonin levels in children and adolescents are elevated compared to older individuals, the question of whether there is a sudden or gradual change has not been adequately addressed. In this study, we report the excretion of the melatonin metabolite, 6-sulfatoxymelatonin in 253 subjects aged between 21 and 82 yr. The correlation with age was significant (r = -0.24; P < 0.05). When the data was analysed by ANOVA using 5-yr age spans, there was a significant effect of age, but post hoc analysis indicated that after 25 yr of age there was no significant decline in excretion of the metabolite. Thus, although the oldest subjects excreted 36% less melatonin metabolite than the youngest, the decrease occurred at a very early age. In the second part of the study, we re-evaluated the data from seven previous studies that measured plasma melatonin levels or metabolite excretion across a wide range of ages and 11 studies comparing young versus older subjects. Statistical analysis by ANOVA again suggested that the changes in melatonin occurring with age were essentially complete before 30 yr of age. The youngest subjects produced at the most twice the amount of melatonin as the oldest subjects. Finally, we evaluated the mean plasma melatonin levels in 144 groups of normal subjects reported in 137 separate publications with respect to age. Again, whereas there was a significant correlation with age, ANOVA showed that there was no difference between groups after 35 yr of age, and the oldest groups had levels that were only 43% of the youngest groups. We conclude that melatonin production is lower in older people, but that the change occurs very early in life, around 20-30 yr of age.

Adolescent↗
PubMed1998

6-Sulfatoxymelatonin excretion and self-reported sleep in good sleeping controls and 55-80-year-old insomniacs.

The pineal hormone melatonin is thought to play a role in sleep initiation and maintenance. This was examined in a large sample of good sleeping controls (n = 52) and sleep maintenance insomniacs (n = 56), aged 55-80 y. Subjects collected 5 d of self-reported sleep diary measures, and 12-h urine samples (08.00-20.00 and 20.00-08.00 h) for analysis of the urinary melatonin metabolite, 6-sulphatoxymelatonin (aMT.6S). Insomniacs reported a significantly greater amount of wake after sleep onset, less sleep in total, less efficient sleep and poorer quality sleep compared to controls. However, no significant differences in melatonin excretion were observed between controls and insomniacs, with both groups showing similar mean (SEM) 12-h night-time [30.9 (2.9) vs. 30.6 (3.3) nmoles, respectively] as well as 24-h total [38.7 (3.4) vs. 36.7 (3.8)] aMT.6S excretion levels. No significant correlations were observed with any sleep parameters nor any effects of medication (anti-inflammatory agents, hormone replacement therapy, and an undifferentiated group of medications). The present results do not support a simple relationship between total melatonin production and self-reported sleep quality and duration in the aged.

Age Factors↗
PubMed1998

Characterization of the bactericidal effects of sodium nitroprusside and other pentacyanonitrosyl complexes on the food spoilage bacterium Clostridium sporogenes.

The potent bactericidal activity of sodium nitroprusside (SNP; Na2[Fe(CN)5(NO)]) towards Clostridium sporogenes has been investigated. SNP inhibited cell growth in the concentration range of 10 to 40 microM. Concentrations above 80 microM caused irreversible loss of cell viability and cell lysis. Inhibition of cell growth was similar in complex and in defined media. SNP was found to be unreactive towards individual components of the defined medium, with the exception of cysteine. The chemical characteristics responsible for the potency of SNP were investigated by synthesizing analogs of SNP in which the Fe was replaced by different metals. The inhibitory potency of the pentacyanonitrosyl complexes decreased in the order Fe > Cr > V, which correlates with N-O stretching frequency (vNO). In contrast, the Ru complex which had a vNO comparable to that of Fe was a poor inhibitor. Electron paramagnetic resonance spectroscopy showed that SNP was rapidly reduced to the paramagnetic Fe(I) compound [Fe(CN)4(NO)](2-) on contact with cells. Analysis of fractions from SNP-treated cells showed 90% oxidation of thiols in the cell walls compared with those in control cells. The toxicity of SNP involves S-nitrosation and reduction, the lack of toxicity of the Ru analog being consistent with the fact that it has poor reactivity towards thiols. When C. sporogenes cells were exposed to sublethal concentrations of SNP and viewed under the electron microscope, they showed blisters on the surface. These results point to the cell wall surface as a primary point of attack of the nitrosyl complex.

Cell Fractionation↗
PubMed1997

Effect of melatonin and corticosteroid on in vitro cellular immune function in humans.

It is well accepted that the immune system shows circadian rhythmicity and that circadian disruption can significantly alter indices of immune function. Recently, a functional link between the endocrine and immune systems has been proposed to explain circadian rhythms in immune activity. Of particular interest is the finding that hormones such as melatonin and corticosteroid are able to exert modulating effects on lymphocyte proliferation. Previous research examining the effects of melatonin in vitro, however, has produced equivocal results. The aim of this study, therefore, was to examine the effects of melatonin and corticosteroid, both separately and together, on mitogen-stimulated human lymphocyte proliferation. Purified human lymphocytes were stimulated with concanavalin A (Con A, 4 micrograms/mL). Melatonin and/or corticosteroid were added to the culture medium during incubation. All cultures were done in quadruplicate. As expected, corticosteroid (25-1,000 ng/mL) significantly reduced proliferation by between 30 and 60% in a dose-related manner (P < 0.0001). Melatonin alone (10-1,000 fmol/mL) did not significantly affect lymphocyte proliferation. However, when lymphocytes were cultured in the presence of melatonin and corticosteroid, a significant decrease in proliferative function of 50-85% was observed (P < 0.0001). Hence, the effect of melatonin and corticosteroid combined was significantly greater than that observed with corticosteroid alone (P < 0.0001). Therefore, it appears that the in vitro effect of corticosteroid on immune function may be modulated by melatonin in physiological to pharmacological concentrations.

Adjuvants, Immunologic↗
PubMed1996

Ergonomic data of elderly people and their application in rehabilitation design.

The population of the First World is ageing, and as it does so elderly people are becoming an increasingly significant consumer group. This process has important ramifications for the ergonomics and design professions. The demand for products that have been developed with consideration for the elderly consumer will require designers to develop new skills and ergonomists to supply new data. This paper highlights the inadequacy of current design data pertaining to the elderly. Anthropometric studies which have been carried out within the fields of ergonomics and rehabilitation are reviewed, and their usefulness to the product designer discussed. Recommendations are made regarding future needs for the collection and dissemination of further data.

Activities of Daily Living↗
PubMed1995

A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6.

The protein tyrosine kinases JAK1, JAK2 and Tyk2 and STATs (signal transducers and activators of transcription) 1 and 3 are activated in response to interleukin-6 (IL-6) in human fibrosarcoma cells. In mutant cells lacking JAK1, JAK2 or Tyk2, the absence of one kinase does not prevent activation of the others; activation does not, therefore, involve a sequential three-kinase cascade. In the absence of JAK1, the phosphorylation of the gp130 subunit of the IL-6 receptor and the activation of STATs 1 and 3 are greatly reduced. JAK1 is also necessary for the induction of IRF1 mRNA, thus establishing a requirement for the JAK/STAT pathway in the IL-6 response. JAK2 and Tyk2 although activated cannot, in the absence of JAK1, efficiently mediate activation of STATs 1 and 3. A kinase-negative mutant of JAK2 can, however, inhibit such activation, and ancillary roles for JAK2 and Tyk2 are not excluded. A major role for JAK1 and the nonequivalence of JAK1 and JAK2 in the IL-6 response pathway are, nevertheless, clearly established for these cells.

Adolescent↗
PubMed1995

The application of an anthropometric database of elderly and disabled people.

We report on the development of an anthropometric database of elderly and disabled people for use by designers. The problems encountered by the designer in developing products for the elderly and disabled are highlighted. Reference is made to previous work carried out using computer modelling to simulate the human product interface, and the problems in specifying the anthropometric data are discussed. From a review of existing anthropometric databases we have noted the lack of data on the elderly and disabled. Not only is there insufficient dynamic anthropometric data available, but there are no standards for the measurement techniques to produce this data. We report briefly on parallel work by the group which is looking at anthropometric measurement techniques, and the computer modelling of the human product interface for elderly and disabled people. The lack of dynamic anthropometric data that is appropriate for use by designers and rehabilitation engineers is the major area to be addressed by the database. We investigate the use of existing medical data available as a possible solution to the problem. The database will also seek to address the problem through its methodology of interpretation and presentation.

Aged↗